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Black Cohosh Adulteration Herbs for Female US/CAN $6.95

Black Cohosh Adulteration Herbs for Female US/CAN $6.95

HerbalGram 98 • May - July 2013

Holy Profile • and Blood Pressure • 100+ Year-Old Phytomedicine Company Artichoke and Cholesterol • ABC Celebration • Chocolate and Stroke Risk Holy Basil Profile • Garlic and Blood Pressure • for Female Reproductive Health • 100+ Year-Old Phytomedicine Company • Herbal Insect Repellents • Chocolate and Stroke Risk Risk Stroke and Chocolate • Repellents Insect 100+ Herbal Year-Old • • PhytomedicineCompany Health Female forReproductive Herbs • Pressure Blood and Garlic • Profile Basil Holy

The Journal of the American Botanical Council Number 98 | May - July 2013

Black Cohosh Adulteration Herbs for Female US/CAN $6.95

Reproductive Health www.herbalgram.org

www.herbalgram.org Herbal Insect Repellents Profile Holy Basil tenuiflorum (syn. O. sanctum) Family: (formerly Labiatae)

INTRODUCTION or “pleasing basil”), is known as Forest or Vana Tulsi. Even Holy basil is a perennial or annual in the mint family though it is a different , O. gratissimum also is consid- ered sacred in and is used in the same ways as the O. that exhibits the square stem and volatile oils characteristic 2 of its family.1 It is erect, very branched, strongly aromatic, tenuiflorum varieties. and mildly hairy.2 Holy basil is native to India and parts of Tulsi is one of the principal herbs used in the Ayurvedic M I S S I O N D R I V E N : northern and eastern Africa, Island, and , medicine system, in which it is known alternately as “The Queen of Herbs,” “The Incomparable One,” and “The and grows wild throughout India and up to an altitude of 9 5,900 feet (1,800 meters) in the Himalayas.3-5 In , Mother Medicine of Nature.” It holds a supreme place in it occurs in dry, sandy areas of Hainan and , as the ancient Vedic scriptures and is integrated into daily life well as in , , , , Myan- by through religious worship. Hindu homes typi- mar, the , , and .6 Holy basil cally have a tulsi growing in an earthen pot in or is cultivated in Southeast and also grows abundantly around the home. In , it is believed that the best Educate in Australia, West Africa, and some Arab countries.1,3 In India, the dried , dried seed, and dried whole plant are used sepa- rately in the systems of Ayurveda, Siddha, and Unani, as well as & Inspire in Indian folk medicine. The materials of commerce are obtained mainly from culti- vated sources throughout India.7 HISTORY AND CULTURAL SIGNIFICANCE recognition of our work in the propagation and con- Making Outstanding Extracts The genus name, Ocimum, means “fragrant servation of endangered medicinal . lipped,” and the species name, tenuiflorum, Has Never Been Enough. means “slender” or “small flowers.” In India, It’s seen in our higher education scholarship fund, O. tenuiflorum is known by a variety of names, including: tulasi, ajaka, ramatulasi, Excellence in herbal extraction is at the heart of what which provides financial assistance to students of and vriddhatulasi in Sanskrit; tulsi, baranda, we do. But the soul of Herb Pharm’s mission is to lead naturopathic medicine and clinical herbalism. kalatulsi, and vranda in Hindi; tulsi, tulshi, people to embrace herbal healthcare by educating kalatulsi, and kural in Bengali; tulsi, tulasi, And it’s why we offer guided herb walks and educa- and talasi in Gujarati; tulasi, kalatulasi, kari- them on the safe and effective use of herbs, and tulasi, sritulasi, and vishnutulasi in Kannada; tional seminars to share our expertise with herbal inspiring a respect for plants and nature. tulsi in Konkani; tulasi, krishnatulasi, and enthusiasts and the herbally curious. trittavu in Malayam; tulasa and tulasi- That means standing shoulder-to-shoulder with aspiring chajadha in Marathi; tulsi and bantulsi in Educating, inspiring and offering Punjabi; tulasi in Tamil; and tulasi and krish- herbalists who attend our renowned HerbaCulture natulasi in Telegu.2,4,8 In some circles, the outstanding herbal Work-Study Program to experience traditional culti- previous Latin binomial, O. sanctum, is still healthcare products, preferred, as sanctum refers to the histori- vation and preparation of medicinal herbs. for more than 30 cal “holy” status of the plant. Sorting out the species that are referred to as holy basil It means that our organic farm is designated a years that’s been can be confusing. Ocimum tenuiflorum has Botanical Sanctuary by United Plant Savers in our secret formula. at least two varieties: or Shyama Tulsi (dark green-to-purple-leaved) and Sri or Tulsi (green-leaved).4,9 A third variety, Kapoor (or Kapur) Tulsi (also green-leaved), may or may not be O. tenuiflorum; some sources surmise that it is O. kilimandschari- For more information about Herb Pharm’s educational programs cum, native to East Africa.10,11 A separate visit us at www.herb-pharm.com/education.html species, O. gratissimum (“very grateful basil” or use your smart phone to scan the image to the left. Holy Basil Ocimum tenuiflorum. Photo ©2013 Steven Foster

www.herbalgram.org • 2013 • I SSUE 98 • 1 www.herbalgram.org • 2013 • I SSUE 98 • 1 way to take tulsi medicinally is in its raw, fresh, whole form CURRENT AUTHORIZED USES IN dial monograph include “traditionally used in Ayurveda cells and natural killer (NK) cells, showing holy basil’s as a hot-water infusion.9 COSMETICS, FOODS, AND MEDICINES (as an expectorant and/or demulcent) to help relieve cough immunomodulatory effects in humans.21 Tulsi is combined with various other herbs in Ayurvedic In countries where the Ayurvedic system of medicine is (Kasa) and colds,” “traditionally used in Ayurveda (as an Two double-blind pilot studies in 2009 investigated preparations to treat the following conditions and symp- e.g expectorant) to help relieve respiratory catarrh,” “tradition- holy basil and four other Ayurvedic herbs for their reputed recognized and practiced ( ., India, , , 22 toms: abscesses, abdominal pain, teething-related ailments, Malaysia, , and Sri Lanka), the powdered, dried leaf of ally used in Ayurveda as a cardiotonic (Hrdya),” and “tradi- immune-enhancing effect. The first study included 32 anemia, arthritis, boils, bronchial asthma, bronchitis, tionally used in Ayurveda to aid digestion (Dipani) and volunteers randomized to two treatment groups of 16 each holy basil is used therapeutically, depending on the formu- 17 catarrh (respiratory tract inflammation), constipation, lation, for treating the following conditions: acute rhini- stimulate appetite (stomachic).” who consumed three cups daily (over the course of two coryza (cold), cough, diarrhea due to giardiasis or amebia- tis (inflammation of the mucous membrane of the nose), The powdered dried seed may be labeled and marketed months) of regular tea or Natural Care tea (Hindustan Unile- sis (both caused by microscopic parasites), dysentery, eye asthma or dyspnea (shortness of breath), hiccups, cough, in Canada for the following uses: “traditionally used in ver Research Center, Bangalore, India), which contains holy diseases (topically), headaches, fever (including chronic tastelessness (inability to differentiate tastes, which may be Ayurveda (as a demulcent) to help relieve cough (Kasa),” basil (0.5%); ashwagandha (Withania somnifera, Solanaceae, and malarial fevers), filariasis (a parasitic disease caused by due to improper digestion or lack of desire for food), worm “traditionally used in Ayurveda as a cardiotonic (Hrdya),” 0.5%); licorice (Glycyrrhiza glabra, Fabaceae, 0.5%); nematodes), general debility or weakness, goiter, gonorrhea, and “traditionally used in Ayurveda to aid digestion (Zingiber officinale, Zingiberaceae, 1.5%); and infestation, skin diseases, 18 hernias, intestinal worms, intercostal neuralgia (pain (Dipani).” (Elettaria cardmomum, Zingiberaceae, 1.5%). NK cell activ- jaundice, leucoderma (loss in the tissue between the In the United States, holy basil is not listed as Generally ity was measured after one and two months of tea consump- of skin pigmentation; ribs), and pleurodynia (pain Recognized as Safe (GRAS) in the Code of Federal Regu- tion. While there were no significant changes in either applied topically), loose in the upper chest [pleu- lations (CFR) for use in conventional food products, nor group at the end of the first month, NK cell activity signifi- teeth (as a snuff or mouth ral cavity]). Similarly, the does holy basil appear in the US Food and Drug Admin- cantly increased after two months in the Natural Care tea lotion), loss of appe- dried whole plant (prepared istration’s (FDA) GRAS Notice Inventory database. Holy drinkers but not in the regular tea group. tite, lumbago (low back in juice form) is used to basil plant parts are permitted, however, as dietary supple- The second study was a larger, double-blind, crossover pain), memory enhance- ment components that require FDA notification within study in which 110 subjects (60 male, 40 female [sic]) were treat asthma or dyspnea, 22 ment, piles (inflamed hiccups, cough, worm infes- 30 days of marketing a product (if a “structure-function” assigned randomly to two groups. Each group consumed hemorrhoids), premature tation, and skin diseases, claim is made), and the product must be manufactured three cups of tea (Natural Care or regular [Camellia aging and graying of hair, as well as pleurisy, calculi according to dietary supplement GMPs. In 2012, the sinensis, Theaceae]) per day for two months. NK cell activ- pulmonary tuberculosis, (stones), vomiting, and eye United States Pharmacopeial Convention (USP) published ity was measured before a 15-day washout period when no rheumatism, ringworm diseases.14 proposed dietary supplement quality standards monographs tea was drunk. The groups then switched to the other tea (topically), syphilis, thin- The powdered seed also for “Holy Basil” (dried leaf) and “Powdered Holy Basil” for another two months, after which NK cell activity was ness of semen, strangury is used, depending on the (pulverized dried leaf) containing no less than 0.5% trit- measured again. NK cell activity increased in both groups (painful, frequent urina- formulation in which it erpenes, calculated as the sum of oleanolic acid and ursolic after two months, but the increase in the Natural Care tea tion in small volume), occurs, for treatment of acid, and a corresponding “Powdered Holy Basil Extract” drinking groups was approximately 4.2 times higher, while tubercular lymph nodes, acute rhinitis, asthma or monograph for public consultation and finalization in the NK cell activity in the regular tea group was about 2.9 tubercular leprosy, and dyspnea, hiccups, cough, 2013. The new USP monographs will be acceptable for use times higher. tumors.2,9,12 as holy basil leaf dietary supplement component specifica- Holy basil was investigated for its effect on generalized skin diseases, tasteless- 19 23 Ayurvedic medicine ness, intercostal neuralgia tions. anxiety disorder (GAD) in a 2008 study. The study was also has credited holy basil and pleurodynina, as well Concerning use of holy basil in cosmetic products, the conducted on 35 patients suffering from GAD from the with numerous actions, as inflammation, intestinal European Commission Health and Consumers Directorate outpatient clinics of the J. B. Roy State Ayurvedic Medical including the following: helminths (worm-like para- lists “Ocimum Tenuiflorum Extract” for skin-conditioning College and Hospital in Calcutta, India. Each subject was adaptogenic, antibacte- sites), dysuria or painful functions, and “Ocimum Tenuiflorum Oil” (wax obtained given 500 mg holy basil (70% ethanol extraction repeated rial, antiperiodic (prevents urination, foul smell, artifi- from the of O. tenuiflorum) for emollient (softens and three times, reduced in a rotary evaporator, then freeze- the recurrence of disease smooths the skin), hair-conditioning, and skin-condition- dried and packaged in gelatin capsules; manufacturer not cial poisons, hematological 20 symptoms), antipyretic/ diseases, and parasitic ing functions. stated) orally twice daily after a meal for 60 days. Base- febrifuge (reduces fever), line score index was 84.42±7.56 at the start, decreased to infections.15 MODERN RESEARCH antiseptic, antispasmodic, In countries where the 68.17±7.84 (-19.2%) at 30 days, and 55.54±7.20 (-34.2%) carminative (relieves Unani system of medicine Holy basil contains alkaloids, carbohydrates, fats, at 60 days. Stress index at baseline was 95.65±8.42 and intestinal gas), diapho- glycosides, phenols, proteins, saponins, tannins, and decreased to 84.32±9.08 (-11.5%) at 30 days and 68.45±9.60 is recognized and practiced 9 retic (promotes sweating), (e.g., Bangladesh, India, . Pharmacological and in vitro laboratory studies (-27.5%) at 60 days. Additionally, depression index declined expectorant, nervine, and have exhibited adaptogenic, anabolic, anti-asthmatic, anti- from 66.45±5.68 at baseline to 57.65±5.04 (-13.2%) at 30 2,9,12,13 Malaysia, Pakistan, and Sri stimulant. Lanka), holy basil (rehan) diabetic, antidiarrheal, anti-inflammatory, antioxidant, days and 45.97±6.27 (30.8%) at 60 days. There are O. tenuiflo- Holy Basil Ocimum tenuiflorum. Photo ©2013 Steven Foster leaf and whole plant are antipyretic, anti-radiation, anti-stress, calming, cardiac A 2001 open, prospective, multicenter clinical study rum standards mono- used therapeutically (in depressant, contraceptive, hepatoprotective, hypotensive, investigated the efficacy of an herbal eye drop containing graphs published in the immunomodulatory, neuro- and cardio-protective, and holy basil on various ophthalmic conditions.24 Ophthacare® dried or juice forms) to treat amenorrhea, cough, palpita- 9,13 Ayurvedic Pharmacopoeia of India (Vol. II, 1999, and Vol. tion, and weakness of the stomach.16 mosquito-repelling properties for the plant. is an aqueous extract of six plants and honey made by Hima- IV, 2004) and Unani Pharmacopoeia of India (Vol. V, 2008), In Canada, holy basil leaf and seed are classified as active Tulsi is believed to increase immunity when taken on laya Drug Co. (Makali, Bangalore, India). Ophthacare as well as Thai Herbal Pharmacopoeia (Vol. I, 1995), Viet- ingredients of licensed natural health products (NHPs) an empty stomach. In a 2011 double-blind, randomized, comprises 0.60% w/v ajowan seed (Trachyspermum ammi, namese Pharmacopoeia (1st ed., 1983), and World Health controlled trial, 24 healthy volunteers consumed 300 syn. Carum copticum, Apiaceae); 0.65% w/v belleric myrob- 2 that require pre-marketing authorization from the Natural Organization (WHO) Monographs (Vol. 2, 2002). The Health Products Directorate (NHPD) and must be manu- mg capsules of holy basil leaves (70% ethanolic extract; alan fruit (Terminalia bellerica, Combretaceae); 1.30% WHO monograph lists other uses that are described factured in compliance with NHP good manufacturing Dabur Pharmaceutical Ltd., Ghaziabad, India) or placebo w/v amla (Phyllanthus emblica, syn. Emblica officinalis, in pharmacopeias and in traditional systems of medi- practices (GMPs). Authorized uses for holy basil leaf prepa- on empty stomachs every day for four weeks, followed Euphorbiaceae); 1.30% w/v rhizome (Curcuma cine including treatment of arthritis, asthma, bronchitis, rations (powdered leaf, decoctions, infusions, and non-stan- by a three-week washout period before crossover to the longa, Zingiberaceae); 1.30% w/v holy basil leaf; 1.10% common cold, diabetes, fever, influenza, peptic ulcer, and dardized aqueous extracts) outlined in the NHPD compen- next intervention. The holy basil group had significantly w/v damask rose petals (Rosa damascena, Rosaceae); 0.5% rheumatism.3 increased levels of IFN-γ, IL-4, and percentages of T-helper w/v crystal (, Lauraceae);

2 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 3 and 3.70% w/v honey. Eye drops were applied at the rate the Institute for Market Ecology (IMO), as well as biody- 13. Khare CP. Indian Herbal Therapies Based on Latest Scientific community/sustainability/missionreport/pdfs/2012_Mission_ of two drops four times daily for 15 days on 100 patients namic certification from Demeter International.28,29 Research. New Delhi: Vishv Vijay Private Limited; 2000. Report.pdf. Accessed March 21, 2013. with acute conjunctivitis (allergic, bacterial, or viral) (n=35), Another US company, Davidson’s Organics (Sparks, 14. Ayurvedic Pharmacopoeia Committee. The Ayurvedic Phar- 28. Institut für Marktökologie (IMO). Certified Operators: Fair acute dacryocystitis (inflammation of the nasolacrimal sac) NV), now markets certified fair trade, biodynamic, and macopoeia of India, Part I, Volume II. New Delhi, India: for Life - Social & FairTrade Certification Programme. Wein- Government of India, Ministry of Health and Family Welfare, felden, Switzerland: IMO. Accessed: March 21, 2013. (n=20), conjunctival xerosis (dry eye) (n=7), degenerative organic tulsi leaf teas grown by certified operator Puthar- Department of Ayurveda, & Naturopathy, Unani, 29. Phalada Agro Research Foundation Pvt. Ltd. Certifications. 30 conditions such as pterygium/pinguecula (n=15), or who jhora Tea Garden Pvt. Ltd. Siddha and Homoeopathy (AYUSH). 1999. Bangalore, India: Phalada Agro. Available at: www.phaladaa- were postoperative cataract patients (n=23). Therapeutic Other big players in the marketing of sustainable tulsi 15. Ayurvedic Pharmacopoeia Committee. The Ayurvedic Phar- gro.com/certifications.html. Accessed March 21, 2013. responses occurred in most of the patients with the post- teas in North America include Choice Organic Teas (Seat- macopoeia of India, Part I, Volume IV. New Delhi, India: 30. Tulsi Tea. Sparks, Nevada: Davidson’s Organics. Available at: operative cataract patients experiencing the most benefit tle, WA), which specializes in fair trade, organic, and Non- Government of India, Ministry of Health and Family Welfare, www.davidsonstea.com/tulsi-tea.aspx. Accessed March 21, (95%), followed by dacryocystitis patients (88.2%), acute GMO-Project Verified teas; Pukka Herbs Ltd. (Bristol, Department of Ayurveda, Yoga & Naturopathy, Unani, 2013. conjunctivitis patients (87.5%), patients with degenera- UK), which specializes in fair trade, FairWild®, and organic Siddha and Homoeopathy (AYUSH). 2004. 31. FAQ: Are your products Fair Trade? Boulder, Colorado: tive conditions (76.9%), and conjunctival xerosis patients teas; and Organic India® (Boulder, CO). Organic India has 16. Unani Pharmacopoeia Committee. The Unani Pharmacopoeia Organic India USA. Available at: http://organicindiausa.com/ of India, Part I, Volume V, New Delhi, India: Government of faq/. Accessed March 21, 2013. (66.7%). decided not to pursue fair trade certification at this time, India, Ministry of Health and Family Welfare, Department of 32. Natural Health Products Directorate (NHPD). Ocimum In a 1996 randomized, single-blind, placebo-controlled, but states that its labor and trade practices go above and Ayurveda, Yoga & Naturopathy, Unani, Siddha and Homoe- tenuiflorum. In: Licensed Natural Health Products Database. crossover study, 40 type 2 diabetes patients were random- beyond what any certification requires, i.e., they provide opathy (AYUSH). 2008. Ottawa, Ontario: NHPD. Available at: http://webprod3. ized to consume holy basil leaf tea for four weeks followed their tulsi farmers and their families with health care, 17. Monograph: Holy Basil - Ocimum tenuiflorum - Leaf hc-sc.gc.ca/lnhpd-bdpsnh/start-debuter.do?lang=eng. Accessed by placebo leaf tea for four weeks or the reverse after a five- education, and a sustainable method of agriculture.31 (Under Consultation). Natural Health Products Directorate March 21, 2013. day run-in period in which they all consumed holy basil leaf Presently, in the Canadian market, there are 50 licensed (NHPD). Ottawa, Ontario: NHPD. August 18, 2012. Avail- tea.25 The authors concluded that consumption of the holy NHPs that contain holy basil leaf, leaf extract, or seed as able at: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/monoReq. basil tea resulted in significant reduction in fasting blood active ingredients, including, for example, Holy Basil 500 do?id=1938&lang=eng. Accessed March 21, 2013. 18. Monograph: Holy Basil - Ocimum tenuiflorum - Seed sugar and postprandial blood sugar, as well as a moderate mg Vegetarian Capsules (Organika Health Products Inc.), (Under Consultation). Natural Health Products Directorate ® reduction in cholesterol. However, the Jadad score for this Holy Basil Tea (St. Francis Herb Farm, Inc.), Perfect Calm (NHPD). Ottawa, Ontario: NHPD. August 18, 2012. Avail- study was 1 (on a scale of 0 [very poor] to 5 [rigorous]), tablets, Wholemega® Focus capsules, and Zyflamend® P.M. able at: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/monoReq. suggesting lack of adequate design and controls and that capsules (New Chapter Inc.).32 do?id=1937&lang=eng. Accessed March 21, 2013. further studies are necessary. 19. United States Pharmacopeial Convention. Holy Basil; A number of clinical studies were reported in the late —Gayle Engels and Josef Brinckmann Powdered Holy Basil; and Powdered Holy Basil Extract. 1900s, including ones for treatment of bronchial asthma, Pharmacopeial Forum. 2012;38(6). viral encephalitis, stress-related arterial hypertension, cell- References 20. European Commission Health & Consumers Directorate. 1. Mondal S, Mirdha BR, Mahapatra SC. The science behind Cosmetic Ingredients and Substances (CosIng®) Database. mediated and humoral immune response, and chronic Brussels, Belgium: European Commission. Available at: fatigue.9 While these studies suggested some positive bene- sacredness of tulsi (Ocimum sanctum Linn.). Indian J Physiol Pharmacol http://ec.europa.eu/consumers/cosmetics/cosing/. Accessed fit for the conditions studied, they were all small pilot stud- . 2009;58(4):291-306. 2. Parotta JA. Healing Plants of Peninsular India. New York: March 21, 2013. ies. CABI Publishing; 2001. 21. Mondal S, Varma S, Bamola VD, Naik SN, Mirdha BR, Padhi MM, et al. Double-blinded random- FUTURE OUTLOOK 3. World Health Organization. Folium Ocimi Sancti. In: WHO Monographs on Selected Medicinal Plants, Volume 2. Geneva, ized controlled trial for immunomodulatory Of the estimated 960 medicinal plant species that Switzerland: World Health Organization; 2002:206-216. effects of tulsi (Ocimum sanctum Linn.) leaf form the source of 1,289 botanical raw drugs traded in 4. Anonymous. Wealth of India 1991. Publication and Informa- extract on healthy volunteers. J Ethnophar- macol. 2011;136(3):452-456. ABC Board of Trustees India, O. tenuiflorum is among the top 117 species whose tion Directorate; New Delhi, India: CSIR; 1991:79-89. Michael J. Balick, PhD Thomas M. Newmark 5. Gupta AK, Tandon N, Sharma M (eds.). Ocimum sanctum 22. Bhat J, Damle A, Vaishnav PP, Albers R, VP and Director, Chairman, 6Pacific Group, San Isidro de annual domestic consumption exceeds 100 metric tons Joshi M, Banerjee G. In vivo enhancement (MT). Ranking sixth in terms of volume, Indian domes- Linn. In: Quality Standards of Indian Medicinal Plants, Volume Institute of Economic Botany, New York Peñas Blancas, Costa Rica 5. New Delhi, India: Medicinal Plants Unit, Indian Council of natural killer cell activity through tea Botanical Garden, Bronx, NY tic consumption of holy basil is estimated at 3,533 MT. In of Medical Research; 2008:275-284. fortified with Ayurvedic herbs. Phyto Res. Morris Shriftman terms of trade volume and consumption, annual demand 6. Li XY, Hedge IC. Lamiaceae. In: Wu ZY, Raven PH (eds.). 2010;24:129-135. Neil Blomquist CEO, Mozart, Inc., Petaluma, CA was estimated to be between 2,000 to 5,000 MT in 2008. , Vol. 17 (Verbenaceae through Solanaceae). 23. Bhattacharyya D, Sur TK, Jana U, President, Sustainable Solutions Consulting Debnath PK. Controlled programmed Margaret Wittenberg Most of the commercial supply is produced through culti- Beijing: Science Press, and St. Louis: Missouri Botanical Services, Sebastopol, CA Global VP of Quality Standards & Public 26 trial of Ocimum sanctum leaf on general- vation. Garden Press; 1994:296-297. Peggy Brevoort Affairs, Whole Foods Market, Inc., 7. Ved DK, Goraya GS. Demand and Supply of Medicinal Plants ized anxiety disorders. Nepal Med Coll J. Demand for holy basil with sustainability certifications 2008;10(3):176-179. President, Brevoort, LLC, Kapa'au, HI Austin, TX (e.g., organically grown, biodynamic, and/or fair trade) in India. Dehra Dun, India: Bishen Singh Mahendra Pal Singh. 2008. 24. Biswas NR, Gupta SK, Das GK, Kumar N, Steven Foster James A. Duke, PhD (emeritus) appears to be increasing, evidenced by the fact that Indian Mongre PK, Haldar D, et al. Evaluation of 8. McGuffin M, Kartesz JT, Leung AY, Tucker AO. American President, Steven Foster Group, Inc., Eureka Botanical Consultant, Economic Botanist farms are beginning to implement both ecological and Herbal Products Association’s Herbs of Commerce, 2nd ed. Silver Ophthcare® eye drops—a herbal formulation social standards for the growing export market, and US in the management of various ophthalmic Springs, AR (USDA, ret.), Herbal Vineyard Inc. / Green Springs, MD: American Herbal Products Association; 2000. Farmacy Garden, Fulton, MD companies are investing in the marketing of ecological and 9. Singh N, Hoette Y. Tulsi: The Mother Medicine of Nature. disorders. Phyto Res. 2001;15:618-620. Fredi Kronenberg, PhD socially responsible certified tulsi products. Two such exam- Lucknow, India: International Institute of Herbal Medicine; 25. Agrawal P, Rai V, Singh RB. Randomized Stanford University School of Medicine Mark Blumenthal ples are the Phalada Agro Research Foundation Pvt. Ltd. 2002. placebo-controlled single-blind trial of holy Palo Alto, CA (ex officio) 10. Kashyap CP, Ranjeet K, Vikrant A, Vipin K. Therapeutic basil leaves in patients with non-insulin- Founder & Executive (Bangalore, India) and the Putharjhora Tea Garden Pvt. dependent diabetes mellitus. Int J Clin Bernadette P. Marriott, PhD Ltd. (Calcutta, , India). potency of Ocimum kilimandscharicum Guerke – a review. Director Global Journal of Pharmacology. 2011;5(3):191-200. Pharmacol Ther. 1996;34:406-409. Professor, Department of Psychiatry On the American side of the trade, Honest Tea (Bethesda, 26. Ved DK, Goraya GS. Demand and Supply of MUSC College of Medicine American Botanical 11. Dolly G, Nidhi S, Bps S, Shweta R, Shikha A. Ocimum kili- Council MD) has worked closely with Fair Trade USA (Oakland, mandscharicum: a systematic review. Journal of Drug Delivery Medicinal Plants in India. Dehra Dun: India: Clinical Neuroscience Division CA) to help the Organic Tulsi Farm, part of the Phalada and Therapeutics. 2012;2(3):45-52. Bishen Singh Mahendra Pal Singh; 2008. Charleston, SC Austin, TX cooperative of 750 farms, obtain Fair Trade certification.27 12. Tirtha SSS. The Ayurveda Encyclopedia: Natural Secrets to 27. Goldman S. Keeping it Honest® 2012 Phalada’s tulsi producer group and processing unit also hold Healing, Prevention, and Longevity. Bayville, NY: Ayurveda Mission Report. Bethesda, MD: Honest Tea. Fair For Life Social and FairTrade Certification issued by Holistic Center Press; 1998. 2012. Available at: www.honesttea.com/

4 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 5 American Botanical Council Mark Blumenthal Founder, Executive Director, HerbalGram Editor-in-Chief dear reader Toby Bernal Adulteration of Black Cohosh Gardener From the moment we envisioned the establishment of Mary Ceallaigh the ABC-AHP-NCNPR Botanical Adulterants Program Executive Assistant more than two years ago, black cohosh was included Janie Carter on the list of herbs for which we had a confirmed basis Membership Coordinator for adulteration. Two published analytical papers by ABC Advisory Board member Professor Ed Kennelly Sara O'Connor at Lehman College at the City University of New York Communications & Marketing and his colleagues detected chemical marker compounds Coordinator characteristic of several widely suspected adulterant species Gayle Engels from China, i.e,. other species in the genus Actaea. The American Herbal Products Special Projects Director Association also has included black cohosh in its list of “Known Adulterants.” In this issue, we present author and botanical photographer Steven Foster’s exten- Lori Glenn sive review of the confusing nomenclature associated with the genus Actaea (syn. HerbClip Managing Editor Cimicifuga), of which Actaea racemosa (syn. Cimicifuga racemosa) — known most Ash Lindstrom commonly as black cohosh in North American and many English-speaking coun- HerbalGram Managing Editor tries) — is the only species that is legally permitted to be sold as “black cohosh” in the Lindsay Stafford Mader United States. HerbalEGram Managing Editor Black cohosh is used primarily to help middle-aged and older women manage HerbalGram Writer/Associate Editor symptoms associated with menopause. In the United States and elsewhere, black cohosh dietary supplements are self-selected by many women for such use, which is Matthew Magruder supported by a variety of published clinical trials. Also, in what appears to be increas- Art Director ing frequency, black cohosh preparations are being recommended by a growing body Denise Meikel of licensed healthcare practitioners. Development Director Consumers and practitioners need to be certain that the “black cohosh” root mate- rial (or its extract) in the capsules or tablets in their bottles of dietary supplements really Jenny Perez are what the labels purport them to be. While there are numerous responsible compa- Education Coordinator nies that produce high-quality, properly authenticated black cohosh products, there are Reaves some companies whose quality control programs are apparently inadequate, hence the HerbClip Assistant Editor detection of adulterants in some commercial products. It is past time for all members of the herb and dietary supplement industry in the United States, and the botanical prod- Perry Sauls ucts industry around the world, to institute and adhere to appropriate quality control Customer Service Coordinator measures related to properly identifying and authenticating black cohosh products, as Tyler Smith well as all herbal products. HerbalGram Writer/Assistant Editor With increased awareness of these problems associated with accidental and inten- tional adulteration of black cohosh, the old excuse used by some manufacturers — “We George Solis didn’t know to test for an adulterant in black cohosh” — and related excuses won’t Clerical Assistant fly anymore. It’s time to stop the errors caused by inadequate identity testing and the Cecelia Thompson possible intentional substitution of cheaper Chinese materials in order to ensure that Finance Coordinator consumers get what they want and what they think they’re buying. Margaret Wright This article is the latest in a series that ABC is publishing as part of the ABC-AHP- Accounting Coordinator NCNPR Botanical Adulterants Program, in which ABC is partnering with our good friends at the American Herbal Pharmacopoeia and the National Center for Natu- ral Products Research at the University of Mississippi. Previous articles in this series include Foster’s excellent historical review of botanical adulteration (HerbalGram 92), his article on adulteration of skullcap with germander (HerbalGram 93), John Cardel- lina’s review of analyses showing that many materials labeled “grapefruit seed extract” are adulterated with synthetic industrial disinfectants (HerbalGram 94), and Foster’s article on the adulteration of bilberry extract with various synthetic and natural mate- rials (HerbalGram 96). To date, the Botanical Adulterants Program is endorsed by more than 100 members 714-754-4372 of the international herb industry, third-party analytical laboratories, professional and trade organizations, media members, accredited schools of natural medicine, and many more. Also, of course, as is customary with articles in our adulterants series, this article has been peer reviewed extensively and carefully for accuracy by numerous highly qualified Mission: Provide education experts in the fields of botany and , chemistry and analytics, and the indus- using science-based and WWW.ALKEMIST.COM trial trade of authentic North American black cohosh raw materials. traditional information to promote responsible use of herbal medicine—serving the public, researchers, educators, healthcare professionals, industry, and media.

6 • I SSUE 98 • 2013 • www.herbalgram.org

ABCEach issue of HerbalGramAdvisory is peer reviewed Board by members of the ABC Advisory Board and other qualified experts before publication.

Donald I. Abrams, MD Keith I. Block, MD Bevin Clare, M.S., R.H., CNS Mimi Guarneri, MD, FACC Richard Kingston, PharmD, CSPI Joe-Ann McCoy, PhD Ethan B. Russo, MD Roy Upton Professor of Clinical Medicine Medical and Scientific Director, Block Center for Interim Program Director of the Masters of Founder, Scripps Center for Integrative President, Regulatory and Scientific Affairs, Director, Medicinal Germplasm Repository GW Pharmaceuticals Group Senior Medical Executive Director, American Herbal University of California San Francisco, Integrative Cancer Treatment, Evanston, IL Science in Herbal Medicine Program Medicine, La Jolla, CA Safety Call™ International Poison Center; Bent Creek Institute / NCSU Advisor, GW Pharmaceuticals plc., Wiltshire, Pharmacopoeia, Scotts Valley, CA San Francisco, CA Tai Sophia Institute, Laurel MD Professor, Dept. of Experimental and Clinical Robert Alan Bonakdar, MD De-An Guo, PhD Asheville, NC United Kingdom Daniel T. Wagner, RPh, MBA, PharmD Pharmacology, University of Minnesota, Bharat (Bart) B. Aggarwal, PhD Director of Pain Management Ray Cooper, PhD Professor, Shanghai Research Center for TCM Dennis J. McKenna, PhD Ric Scalzo Owner, Nutri-Farmacy, Wildwood, PA Ransom Horne, Jr. Distinguished Professor Scripps Center for Integrative Medicine, La St. Louis, MO Modernization, Shanghai Institute of Materia Minneapolis, MN Senior Scientist, British Columbia Institute of President, CEO & Founder John Weeks of Cancer Research, Dept. of Experimental Jolla, California Medica, Shanghai, China Uwe Koetter, PhD Jerry Cott, PhD Technology, Burnaby, B.C., Canada Gaia Herbs, Inc., Brevard, NC Publisher-Editor, The Integrator Blog Therapeutics, The University of Texas Principal and Founder, Dr. Koetter Consulting Nancy L. Booth, Ph.D. Pharmacologist, Silver Spring, MD Prof. Ameenah Firdaus Gurib-Fakim Mark Messina PhD, MS Alexander G. Schauss, PhD, FACN, CFS Seattle, WA M. D. Anderson Cancer Center, Houston, TX Senior Science Director, Spherix Consulting, a Director, CEPHYR Ltd. (Centre for Phytotherapy Services, Switzerland Paul Alan Cox, PhD President, Nutrition Matters, Inc. Senior Research Director and CEO, Natural Andrew T. Weil, MD Lise Alschuler, ND division of ChromaDex, Inc., Rockville, MD & Research), Cyber City, Ebene, Mauritius David Kroll, PhD Executive Director, Institute for Ethnomedicine, Eau Claire, WI and Medicinal Products Research, AIBMR Life Author, Director of the Center for Integrative Naturopathic Specialists Director of Science Communications and Sciences, Puyallup, Washington Kerry Bone Jackson, WY Bill J. Gurley, PhD Marc S. Micozzi, MD, PhD Medicine and Associate Director of the Chicago, IL Investigator in the Laboratory of Microbiology Director, Research and Development, Integria Professor, College of Pharmacy, University of Private Practice in Forensic Medicine, and Paul Schulick Division of Social Perspectives in Medicine, Lyle E. Craker, PhD and Genomics, Nature Research Center of the Cindy K. Angerhofer, PhD Healthcare, Warwick, Australia Arkansas for Medical Sciences, Little Rock, AR Policy Institute for Integrative Medicine, Founder and Formulator, New Chapter, Inc., College of Medicine, University of Arizona, Professor, Dept. of Plant and Soil Sciences, North Carolina Museum of Natural Sciences, Executive Director of Botanical Research, Deni Bown University of Massachusetts, Amherst, MA Charlotte Gyllenhaal, PhD Bethesda, MD Brattleboro, VT Tucson, AZ Aveda, Minneapolis, MN Raleigh, NC Manager, International Institute of Tropical Adjunct Assistant Professor of Pharmacognosy, Simon Y. Mills Navindra Seeram, PhD David Winston, RH (AHG) Amanda McQuade Crawford Thomas L. Kurt, MD, MPH Wendy L. Applequist, PhD Agriculture Forest Project College of Pharmacy, University of Illinois at Senior Teaching Fellow, Peninsula Medical Associate Professor of Pharmacognosy Director, Herbal Therapeutics Research Library, Consultant Medical Herbalist, Solixir, Ojai, CA Clinical Professor, Dept. of Internal Medicine, Associate Curator, William L. Brown Center Ibadan, Nigeria Chicago; Research Program Manager, Block School, Exeter, England University of Rhode Island College of Herbalist & Alchemist, Inc., Washington, NJ University of Texas Southwestern, Dallas, TX Missouri Botanical Garden, St. Louis, MO Edward M. Croom, Jr., PhD Center for Integrative Cancer Care, Evanston, IL Pharmacy Thomas Brendler Daniel E. Moerman, PhD Jacqueline C. Wootton, MEd Adjunct Associate Professor of Pharmacognosy, Danna J. Leaman, PhD John Thor Arnason, PhD Founder/CEO, PlantaPhile Mary Hardy, MD William E. Stirton Emeritus Professor of Holly Shimizu President, Alternative Medicine Foundation, University of Mississippi, Oxford, MS Chair, Medicinal Plants Specialist Group, Professor, Dept. of Biology, University of Collingswood, NJ Medical Director, Simms/Mann-UCLA Center Anthropology, University of Michigan- Executive Director, US Botanic Garden, Inc., Wales, United Kingdom Species Survival Commission, International Ottawa, Ontario, Canada Alan M Dattner, MD for Integrative Oncology, Los Angeles, CA Dearborn, Dearborn, MI Washington, D.C. Josef Brinckmann Founder, HolisticDermatology.com Union for the Conservation of Nature, Ottawa, Peiying Yang Christopher Hobbs, LAc, AHG Gary N. Asher, MD, MPH VP of Sustainability, Traditional Medicinals, Inc. Manhattan and New Rochelle, NY Ontario, Canada William Morris, PhD, DAOM, LAc Victor Sierpina, MD Assistant Professor, Dept. of General Oncology, Assistant Professor of Family Medicine Sebastopol, CA Herbalist, botanist, licensed acupuncturist, President and CEO, AOMA Graduate School of Associate Professor of Family Practice Section of Integrative Medicine Roberta A. Lee, MD University of North Carolina Wade Davis, PhD Davis, CA Integrative Medicine, Austin, TX Medicine, University of Texas Medical Branch, University of Texas, M.D. Anderson Cancer Francis Brinker, ND Explorer-in-Residence, National Geographic Medical Director, Co-Director Integrative Chapel Hill, North Carolina Freddie Ann Hoffman, MD Galveston, TX Center, Houston, TX Clinical Assistant Professor, Dept. of Medicine, Society, Washington, D.C. Medicine, Continuum Center for Health and Susan Murch, PhD Dennis V. C. Awang, PhD, FCIC Arizona Center for Integrative Medicine, CEO and Managing Member, HeteroGeneity, Healing; Director of Medical Education and Associate Professor and Canada Research James E. Simon, PhD Eric L. Yarnell, ND MediPlant Natural Products Consulting University of Arizona, Tucson, AZ Steven Dentali, PhD LLC, Washington, D.C. Integrative Fellowship, Beth Israel Medical Chair in Natural Products Chemistry Professor, Director of the Center for New Assistant Professor, Bastyr University, Chief Science Officer, American Herbal Products Services, Surrey, B.C., Canada Donald J. Brown, ND David Hoffmann BSc, FNIMH Center, New York, NY University of British Columbia-Kelowna, BC, Use Agriculture and Natural Plant Products, Kenmore, WA Association, Silver Spring, MD Canada Rutgers University, Prof. Dr. K. Hüsnü Can Baser Natural Products Research Consultants, Medical herbalist, author, and research Susan Leopold, PhD New Brunswick, NJ Faculty of Pharmacy Seattle, WA Subhuti Dharmananda, PhD associate, Traditional Medicinals Executive Director, United Plant Savers Nicholas H. Oberlies, Ph.D. Director, Institute for Traditional Medicine Sebastopol, CA Anadolu University, Eskişehir, Turkey Paula N. Brown, PhD East Barre, Vermont Associate Professor, Dept. of Chemistry and Ed Smith Portland, OR Biochemistry, University of North Carolina at Co-founder and Co-owner of Herb Pharm Bruce Barrett, MD, PhD Director of Applied Research in Biosciences, BC Maurice M. Iwu, PhD Martha M. Libster, PhD, RN, CNS Greensboro, Greensboro, NC Williams, OR Associate Professor of Family Medicine, Institute of Technology, Burnaby, B.C., Canada Hardy Eshbaugh, PhD President, Bioresources Development and Director and Chair, Dept. of Nursing, University of Wisconsin-Madison Medical Professor of Botany & Assistant Curator, Conservation Program, Wusell, Abuja, Nigeria Humboldt State University William Obermeyer, PhD S. H. Sohmer, PhD Jane Buckle, PhD, RN Willard Sherman Turrell Herbarium, Miami School, Madison, WI Director, RJ Buckle Associates LLC. Tori Hudson, ND Arcata, CA VP of Research and Technology, President and Director, Botanical Research University, Oxford, OH Consumer Lab., Annapolis, MD Institute of Texas, Fort Worth, TX Marilyn Barrett, PhD London, England and Haslet, NJ Clinical Professor Tieraona Low Dog, MD Trish Flaster, MS National College of Naturopathic Medicine, Pharmacognosy Consulting Service, Mill Veronika Butterweck, PhD Director of the Fellowship, Arizona Center Joseph E. Pizzorno, Jr., ND Paul Stamets, D.Sc. Valley, CA Executive Director, Botanical Liaisons, LLC, Portland, OR for Integrative Medicine, Clinical Assistant President Emeritus, Bastyr University, Editor, Director of Research Associate Professor, School of Life Sciences Boulder, CO Prof. Dr. Rudolf Bauer Institute for Pharma Technology, Universtiy of Timothy Johns, PhD Professor, Dept. of Medicine, Integrative Medicine: A Clinician's Journal, Fungi Laboratories, Fungi Perfecti, LLC Department of Pharmacognosy Applied Sciences Northwestern Switzerland, Stefan Gafner, PhD Professor, School of Dietetics and Human University of Arizona Health Sciences Center, Seattle, WA Michael S. Tempesta, PhD Institute of Pharmaceutical Sciences, Muttenz, Switzerland Director, Analytical Chemistry Nutrition; Centre for Indigenous People’s Tucson, AZ Mark J. Plotkin, PhD Managing Partner and Founder, Phenolics, Tom's of Maine, Kennebunk, ME Nutrition and Environment, McGill University, Graz, Austria John H. Cardellina II, PhD Douglas “Duffy” MacKay Executive Director, Amazon Conservation LLC, El Granada, CA Montreal, Canada Ezra Bejar, PhD Distinguished Scientist—Chemistry Paula M. Gardiner, MD, MPH Vice President, Scientific & Regulatory Affairs Team, Arlington, VA Barbara N. Timmermann, PhD Founder, Latino Herbal, Redondo Beach, CA Technical Innovation Center Assistant Professor, Dept. of Family Medicine, Kenneth Jones Council for Responsible Nutrition, John Rashford, PhD Chairperson-Professor of Medicinal Chemistry, McCormick and Co., Inc. Boston University Medical School, Boston, MA President and Medical Writer, Armana Washington, DC Stacey J. Bell, DSc Professor of Anthropology University of Kansas, Lawrence, KS Hunt Valley, Maryland Research, Inc, Halfmoon Bay, B.C., Canada Nutritional Consultant, Belmont, MA Patricia Gerbarg, MD Robin J. Marles, PhD College of Charleston, Charleston, S.C. Arthur O. Tucker, PhD Thomas J.S. Carlson, MS, MD Kingston, NY Edward Kennelly, PhD Director of the Bureau of Research and Bradley C. Bennett, PhD Danica Harbaugh Reynaud, PhD Research Professor of Agriculture and Natural Associate Adjunct Professor, Associate Professor and Chair, Dept. of Science, Natural Health Products Directorate, Associate Professor of Biology, Florida Joe Graedon, MS Chief Executive Officer & Chief Science Officer, Resources, Delaware State University, Dept. of Integrative Biology; Director, Biological Sciences, Lehman College, City Health Canada, Ottawa, Canada International University, Miami, FL Author, syndicated columnist, radio host, AuthenTechnologies, Richmond, CA Dover, DE Center for Health, Ecology, Biodiversity, Durham, NC University of New York, Bronx, NY Rachel Mata, PhD Joseph M. Betz, PhD John M. Riddle, PhD Nancy Turner, PhD & Ethnobiology; Curator of Ethnobotany, Ikhlas Khan, PhD Professor of Pharmacognosy, Universidad Director, Analytical Methods and Reference Mindy Green, MS Professor, Dept. of History, Distinguished Professor and Ethnobotanist, University and Jepson Herbaria; University of Research Professor of Pharmacognosy, Nacional Autónoma de Mexico, Mexico City, Materials, Office of Dietary Supplements, US California, Berkeley, CA Green Scentsations North Carolina State University, Raleigh, NC Environmental Studies Program, University of Assistant Director, National Center for Natural Mexico Victoria, BC, Canada National Institutes of Health, Boulder, CO Aviva Romm, MD Chun-Tao Che, PhD Products Research, University of Mississippi, Will C. McClatchey, PhD Bethesda, MD Frank L. Greenway, MD Boston, MA Jay Udani, MD Norman R. Farnsworth Professor of Oxford, MS Professor of Botany, University of , John A. Beutler, PhD Medical Director and Professor CEO and Medical Director, Medicus Research Pharmacognosy Steven King, PhD Mânoa, HI Robert Rountree, MD Associate Scientist, Molecular Targets Pennington Biomedical Research Center of the LLC., Medical Director, Northridge Hospital University of Illinois at Chicago, College of VP, Sustainable Supply and Ethnobotanical Practitioner, Boulder Wellcare Inc., Boulder, CO Development Program, National Cancer Louisiana State University System Integrative Medicine Program, Northridge, CA Pharmacy, Chicago, IL Research, Napo Pharmaceuticals Inc., South Institute, Frederick, MD Baton Rouge, Louisiana San Francisco, CA

8 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 9 8 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 9 The Journal of the American Botanical Council

Number 98 • May - July 2013 departments Contributors 1 Herb Profile 70 Book Reviews Josef Brinckmann Exploring the Peripatetic Treating PCOS Naturally: Holy Basil (Ocimum tenuiflorum, Herbal Supplements and the Brain: 32 Maze of Black Cohosh 58 Clinical experience and scientific Lamiaceae) Understanding Their Health Benefits and Chun-Tao Che, PhD Adulteration: evidence support medicinal herbs, Hazards Jerry Cott, PhD A Review of the Nomen- nutritional supplements, and lifestyle 12 ABC News The Alphabet of Galen: Pharmacy from Paul Alan Cox, PhD clature, Market Econom- interventions to treat symptoms of this Antiquity to the Middle Ages — A Critical Shari Henson ics, Analytical Methods, common female endocrine disorder ABC Celebrates Employee of 25 Years, Edition of the Latin Text with English Margaret Wright Translation and Commentary Amy C. Keller, PhD Chemistry, and Safety By Lindsay Stafford Mader Steven R. King, PhD Implications ABC Welcomes New Advisory Board Medicinal Plants of China, Korea, and Members : Bioresources for Tomorrow’s Heather S. Oliff, PhD By Steven Foster Natural therapies can play an important role in the Drugs and Cosmetics John M. Riddle, PhD treatment of polycystic ovarian syndrome (PCOS), a More Than 100 Groups Support complex endocrine disorder that affects more than five ABC-AHP-NCNPR Botanical Adulterants Medicinal Plants and the Legacy of Risa Schulman, PhD Black cohosh root and rhizome and Richard E. Schultes their preparations (Actaea racemosa, syn. million women in the United States alone. Scientific Program research suggests that several herbs can help balance Palau Primary Health Care Manual: Cimicifuga racemosa; Ranunculaceae) have ABC Presents Annual Botanical hormones in women with PCOS, who typically exhibit Health Care in Palau — Combining been of considerable interest for more than Excellence Awards 60 years, particularly during the last 15 lower-than-normal levels of progesterone and higher- Conventional Treatments and years in the United States. The increased than-normal levels of testosterone (and sometimes Traditional Uses of Plants for Health and HerbalGram Staff prolactin). Other herbs, although not scientifically 26 Research Reviews Healing market demand, nomenclatural confu- Mark Blumenthal sion of related North American and Asian investigated for this specific condition, have been used in traditional medicine and clinical practice for many Review Supports Chaste Tree Berry Editor-in-Chief/Publisher species, along with case reports of liver Extracts for Female Reproductive 77 In Memoriam years to address the symptoms of PCOS, such as lack of Ash Lindstrom toxicity associated with products labeled as Conditions black cohosh, have led to both suspicion menstruation, excessive facial hair, acne, and infertility. Timothy J. Motley Managing Editor Likewise, several herbs and foods also have been shown and actual identification of economic Black Cohosh Actaea racemosa. Clinical Trial Shows Aged Garlic in scientific studies as well as clinical practice experi- Billy Joe Tatum Tyler Smith adulteration of black cohosh commercial Photo ©2013 Steven Foster Extract™ Supplementation Reduces Writer/Assistant Editor ence to improve insulin sensitivity, another common Blood Pressure supplies. A significant body of new analyti- 79 Classifieds cal chemical, pharmacognostic, pharmaco- condition associated with PCOS. Also crucial to PCOS Matthew Magruder Artichoke Leaf Extract Improves HDL Art Director logical, and clinical scientific literature has been published relative to the iden- management are various lifestyle changes, including weight loss for women who are overweight, a low-carb diet, exercise, and stress reduction Cholesterol Levels in Patients with 80 Photo Finish tity, pharmacology, toxicology, and clinical applications of black cohosh. In this Hypercholesterolemia Lindsay Stafford Mader feature, Steven Foster reviews issues associated with the complexities of black through practices like yoga, acupuncture, and consuming adaptogenic foetida () Writer/Associate Editor cohosh adulteration, including botanical and nomenclatural considerations; herbs. Because the conventional pharmaceuticals typically prescribed to Prospective Study and Meta-Analysis treat PCOS have many drawbacks, these herbal and natural medicine of Chocolate and Reduction of Stroke Steven Foster trade and economic issues; various identification, analytical, and authentication Contributing Editor challenges; alleged liver toxicity linked to adulterated products; and other data strategies serve as promising options. Risk on economic adulteration of products labeled as black cohosh. Gayle Engels Contributing Editor Dr. Willmar Schwabe Pharmaceuticals: An Herbal On the Cover Josef Brinckmann Plant-Based Insect Repellents Provide an Alternative Legacy Company Black Cohosh Actaea racemosa. Contributing Editor 66 Photo ©2013 Steven Foster 52 to Synthetic Formulas German Namesake’s Founding Values Continue to Lance Lawhon Guide Company Practices Advertising Sales By Tyler Smith 877-832-1881 By Tyler Smith [email protected] The US Centers for Disease Control and Prevention reported more than 5,300 cases of West Nile Virus in 2012 — the most in a decade — with In this second installment of HerbalGram’s “Legacy Herb Companies” nearly 250 deaths caused by the mosquito-borne virus. Experts recom- series, Tyler Smith profiles Dr. Willmar Schwabe Pharmaceuticals, a mend using repellents registered with the Environmental Protection German phytomedicine company founded in 1866 and still family-owned Agency (EPA), the most recognizable of which is DEET, a highly effective nearly a century-and-a-half later. At the time of its founding, the world chemical compound that has been in use since the 1950s. However, more was experiencing significant scientific advancements, including the use Published by the American Botanical Council, P.O. Box 144345, Austin, TX 78714-4345. consumers are turning to natural or plant-based products, which may be of early anesthetics such as ether and chloroform and the development Subscriptions to HerbalGram are a benefit of ABC membership at every level. One year memberships: more cosmetically appealing, can be sustainably produced, and, in some of aspirin. This article chronicles the history of the company, from the Individual $50; Academic $100; Professional $150; Organization $250; Retailer $250; HerbClip Service $600; cases, have shown similar efficacy to DEET. As a self-defense mechanism, launch of its first phytomedicinal product, Schwabe’s hamamelis ointment Corporate; Sponsor. Add $20 for memberships outside of the U.S. Student and Senior discounts are available. plants produce chemicals that act as natural deterrents to insects, which — a witch hazel (Hamamelis virginiana, Hamamelidaceae)-based hemor- For information about Corporate or Sponsor Memberships, contact Denise Meikel at [email protected] or 512-926-4900. make them appealing candidates for insect-repellent research. This article rhoid cream — to its current standing as an industry leader in natural © 2013 American Botanical Council. ISSN #0899-5648. Printed in the U.S.A. explores three popular plant-based mosquito repellents, including EPA- pharmaceutical research and development. Schwabe is generally acknowl- The information in HerbalGram® is intended for educational purposes only and is not a substitution for the advice of a qualified healthcare professional. Although we attempt to ensure that advertising in HerbalGram registered PMD, a derivative of oil of lemon eucalyptus (Corymbia citrio- edged as the leading manufacturer of clinically researched phytomedicines HerbalGram® is printed ® is truthful and not misleading, the publication of an ad for a product or company in HerbalGram does not dora, Mytaceae), hydrogenated catmint oil (Nepeta cataria, Lamiaceae), worldwide, including its most-recognized formulation, EGb 761 , derived on recycled paper at constitute an endorsement by ABC of the product or the company being advertised. Publication of an ad that and oil of citronella (obtained from nardus or C. winterianus, from the ancient Ginkgo biloba (Ginkgoaceae) tree. Craftsman Printers, Inc. makes a health claim or structure-function claim does not necessarily constitute an approval of that claim by Poaceae). Lubbock, Texas ABC. Further, ABC has not reviewed any manufacturer’s Good Manufacturing Practices.

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ABC Celebrates Employee of 25 Years, Margaret Wright Margaret Wright began working as a part-time employee for Bee Creek Botanicals, a company established by Ameri- Adopt-An-Herb is an exciting and mutually beneficial way to support ABC! can Botanical Council (ABC) Founder and Executive Director Mark Blumenthal, in January of 1988. Shortly thereaf- Each adopting organization helps ensure that the most current information on its adopted herb is avail- ter, in November of that year, she transitioned to the newly established ABC, where she has worked full-time ever since able in the powerful HerbMedPro database on ABC’s website. — with 17 co-workers — a departure from the more modest and upstart atmosphere she first encountered. This enables consumers, researchers, educators, media, health practitioners, government agencies, and “Back then, there were three people in the office: Mark, Before coming to Bee Creek and ABC, Margaret leased and members of industry to have easy access to abstracts of the latest scientific and clinical publications on who did his usual stuff except he didn’t travel nearly as much maintained plants for office buildings. Her initial title at ABC the many aspects, properties, and benefits of the adopted herb. as he does now; his secretary, Mary, who did sales calls for Bee was subscription coordinator, and she continued in that role Become an adopter today! Visit us at www.herbalgram.org Creek, payroll, and tried to keep Mark on track; and me, who until ABC relocated to Case Mill. She now serves as account- Contact Denise Meikel at 512-926-4900 extension 120 or by email at [email protected] did everything else,” Margaret wrote in 2000, in her reflec- ing coordinator, a vocation that provides her with opportuni- tion “Back in Time with ABC.” “Mark would come into my ties to engage with interesting people from around the world. office every day,” she wrote, “and ask if I still liked it here.” “One of the things I like about my job is I get to talk to In “Back in Time with ABC,” people in other states and countries,” ABC thanks its Founding Herbal Adopters Margaret recalls those early days with said Margaret. “Some of them I’ve been fondness. “We had fun,” she said. talking to for years and I kind of think “For our first Thanksgiving and holi- of them as my friends. If we’re having a day parties, we could all fit around particularly hot summer or I’ve heard that Devil's Claw Hibiscus the kitchen table. We would go out to it’s snowing extra hard in some commu- Harpagophytum procumbens Hibiscus sabdariffa lunch for people’s birthdays and all sit nity and I am on the phone asking about at one small table. We even went to a payment or membership, I’ll sometimes movie one time together after work.” ask them about the weather where they Turmeric PeppermintContinued on page 4 Over the course of 25 years, Marga- are. It’s kind of nice.” Curcuma longa ret traveled to Costa Rica through Another component of the job Marga- x piperita an ABC program and witnessed the ret enjoys most is sleuthing. “Cecelia and organization’s numerous technologi- I always say we like to play detectives,” Sceletium cal upgrades, such as ABC’s first fax Margaret Wright next to a memorial tree she said. “I like solving mysteries. Some- Bacopa machine. “We were all so excited,” she planted in memory of her mother, Muriel times I have to figure out a membership Sceletium tortuosum Bacopa monnieri said with a laugh. She also became Goddard Hull. ©2013 ABC that I can’t find in our system or a math- ABC’s official, much-lauded birthday- ematical question that requires a lot of cake baker. ABC employees look forward to monthly staff concentration. It’s fun when I figure it out.” Chocolate meetings as they almost always are coupled with a sumptuous It comes as no surprise, then, that Margaret is a trusted Theobroma cacao Cinnamomum verum dessert from Margaret to celebrate corresponding staff birth- connoisseur of BBC mystery series — and British television days. Popular options include her chocolate silk pie, fudge, series in general — and her consistently good taste is relied and of course her infamous and dangerously delicious carrot upon by many in the ABC offices. The same can be said in the Tea Black Cohosh cake — Mark’s personal favorite — which is in fact so good it area of literature as a result of her voracious appetite for books. Camellia sinensis Actaea racemosa has been known to convert carrot-cake detractors. Among all of her wonderful qualities and skills, Margaret is ABC’s work-culture values have remained consistent since perhaps most beloved for her cunning, wily, and effortless ’88. For Margaret, who had three children under the age of sense of humor, which she never neglects to bring to work. four when she joined ABC, part of the appeal of the organi- “Margaret is every employer’s dream,” said Blumenthal. Arnica Ginkgo zation was that it honored the importance of family above “I can never adequately express how much I appreciate and Arnica montana Ginkgo biloba all. “One of the things that I liked about ABC in the begin- respect her as an employee, and as a person. She is one of ning, and I started out working there when my kids were the most solidly consistent employees I’ve ever had in over very young… it was a good place to work for a family person 40 years of owning or running a business or organization. Olive Hawthorn because Mark always believed in putting family first.” Marga- She’s intensely responsible, totally reliable, incredibly loyal, Olea europaea ret’s daughter, Carrie, even worked at ABC for a short time. performs her duties virtually flawlessly, handles myriad details Crataegus spp. “She was 14, and we didn’t have a receptionist that summer effectively, has an excellent 25-year institutional memory, and for some reason, so she came to work there and was a recep- gets along exceedingly well with the rest of the staff. Who tionist, and Mark got a call one time, and whoever it was said could ask for anything more?” Neem Umckaloabo ‘It sounds like your receptionist is 14,’ and he said ‘She is!’” To the delight of everyone fortunate enough to work along- Azadirachta indica Pelargonium sidoides Margaret found friendship at ABC, as well, particularly side her, even after 25 years, Margaret is still going strong at with finance coordinator Cecelia Thompson, who was hired ABC. “Cecelia and I have a pact, and Mark wanted to join about six months after Margaret. “We became friends right in on our pact. He said he’s never quitting, so that means we Cranberry Lavender away, but we weren’t in the same office,” she said. That situa- can’t, so….” Vaccinium macrocarpon tion was remedied when ABC moved to its present location at its historic Case Mill Homestead headquarters. —Ash Lindstrom

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for the Clinician (Lippincott Williams & Wilkins, 2010). (Arnold Publishers, 1997) and Clinical Aromatherapy: Essen- ABC Welcomes New Advisory Board Members In 2004, he co-founded the renowned Scripps conference tial Oils in Practice (Churchill Livingstone, 2003) — Dr. The American Botanical Council (ABC) announces the addition of 17 new members to its Advisory Board. “Natural Supplements: An Evidence-Based Update,” which Buckle has taught thousands of nurses and other healthcare These esteemed individuals — with diverse academic backgrounds ranging from analytical chemistry, oncology, he still co-directs. practitioners the benefits of integrating essential oils into and pharmacognosy to environmental science, aromatherapy, and Traditional Chinese Medicine — are committed Nancy Booth, PhD, patient treatment. She created the United States’ first clini- to promoting healthier living through herbal and plant-based medicine. Advisory Board members volunteer their currently works for Spherix cal aromatherapy course for nurses, has lectured on comple- time to peer review articles that appear in HerbalGram, HerbalEGram, HerbClips, and other ABC publications. Health Sciences Consulting, mentary medicine at the University of West London, and Additionally, ABC staff and HerbalGram editors seek feedback and advice from Advisory Board members on issues a division of ChromaDex, as currently serves on the editorial boards of several peer- such as research questions, article ideas, ABC policies, book reviews, and much more. a senior science consultant. In reviewed journals. In 1994, Dr. Buckle patented her own The new Advisory Board members include an oncologist, ety of Integrative Oncology. that role, she counsels clients on gentle, structured touch method, known as the “M” Tech- a cardiologist, an endocrinologist, a dermatologist, a nurse/ Gary N. Asher, MD, is an product safety and regulation. nique. She received her PhD in health service management aromatherapist, a nutritionist, a doctor of acupuncture and assistant professor in the Univer- Her specialties include the areas and a post-doctorate diploma in biostatistics and epidemi- oriental medicine, a mycologist, a geneticist, two phar- sity of North Carolina (UNC) of dietary supplements, food ology as an NIH-funded Complementary and Alternative macognosists, two family practice physicians, two natural School of Medicine’s Depart- ingredients, pharmacognosy, Medicine Research Fellow at the University of Pennsylva- product chemists, and two environmentalists. ment of Family Medicine, medi- analytical method development, nia. “We are deeply grateful to include these experts on the cal director of Integrative Medi- chemistry, and biochemistry. Alan M. Dattner, MD, is ABC Advisory Board,” said ABC Founder and Executive cine Services at UNC’s Line- Dr. Booth earned her doctor- a pioneer in holistic derma- Director Mark Blumenthal. “For many of these individu- berger Comprehensive Cancer ate in pharmacognosy from the tology, a field that integrates als, receiving official ABC Advisory Board status simply Support Program, and a prac- esteemed College of Pharmacy at the University of Illi- nutrition, skin care, and natu- formalizes an already established, long-term relationship titioner of medical acupunc- nois – Chicago, and conducted her postdoctoral research ral products. He has served in which many of these friends and colleagues have been ture at UNC’s Family Medicine on botanical dietary supplements through a fellowship as a clinical cancer fellow contributing their time and expertise to ABC and many of Acupuncture Clinic. A graduate of Columbia University from NIH. Dr. Booth is also a member of the American at Albert Einstein College its publications as expert peer reviewers. The wide spectrum and Ben Gurion University in Israel, Dr. Asher also has a Chemical Society, the Institute for Food Technologists, of Medicine, a fellow of of scientific and clinical expertise held by these individuals Master of Public Health degree with a focus in health care the American Society of Pharmacognosy, and the Chemi- the American Academy of as a group reflects the increasing complexity and sophisti- and prevention from UNC. He has over 15 years of experi- cal Consultants Network. She is an American College of Dermatology (AAD), and as a cation of the modern herbal movement and of ABC’s vital ence working with botanical medicines, including clinical Nutrition Fellow. visiting scientist in the derma- nonprofit educational mission.” training and practice, and gained manufacturing and qual- Deni Bown serves as proj- tology branch of the National Following are the names and brief bio-sketches of the new ity control experience within the herbal industry during his ect manager of the Interna- Cancer Institute, where he ABC Advisory Board members. time as a lab manager for several small companies. His post- tional Institute of Tropical discovered important links Donald I. Abrams, MD, is doctoral fellowship at UNC included training in comple- Agriculture (IITA) Forest between environmental factors and inflammatory diseases. chief of the Hematology-Oncol- mentary and alternative medicine clinical research and clin- Project in Ibadan, Nigeria. Dr. Dattner graduated from the University of Rochester ogy Division at San Francisco ical pharmacology. Dr. Asher is a member of the Society for Her responsibilities comprise and obtained his medical degree from New York Univer- General Hospital, an integra- Integrative Oncology, the American Academy of Medical environmental education, sity, and was a founding member of the AAD’s Task Force tive oncologist at the Univer- Acupuncture, and the American Society for Clinical Phar- reforestation, natural resource for Nutrition and the Evaluation of Alternative Medicine. sity of California – San Fran- macology and Therapeutics. Currently, he is conducting management, and biodiver- He lectures and writes on holistic dermatology topics, oper- cisco (UCSF) Osher Center two clinical trials with curcumin, a component of turmeric sity monitoring, in addition ates a clinical practice in New Rochelle, New York, and for Integrative Medicine, and (Curcuma longa, Zingiberaceae). to the management of IITA’s also sees patients at the Healthy Tao Center for Wellbeing a professor of clinical medi- Robert Alan Bonakdar, MD, Nursery and Medicinal Plant in Manhattan. cine at UCSF. A graduate of has served as the director of pain Garden. Bown is the author Stefan Gafner, PhD, is the Brown University and Stanford management at Scripps Center for of several books, including the Herb Society of America’s director of analytical chemistry at University College of Medicine, Integrative Medicine since 2002. Encyclopedia of Herbs & Their Uses (1995), and has been a Tom’s of Maine, where he focuses Dr. Abrams worked in a UCSF Dr. Bonakdar focuses on herbal recipient of the British Broadcasting Corporation’s Wildlife on quality control of botanical retrovirology laboratory when the first cases of AIDS were medicine and natural product ther- Photographer of the Year award in the plants category. She raw materials and finished prod- being diagnosed. His current research, some of which is apies in integrative family medi- has chaired the UK’s Herb Society, served as regional chair ucts, as well as plant metabo- supported by grants from the National Institutes of Health cine, particularly for chronic pain of the UK’s Plant Heritage, and was the honorary president lites with antibacterial and anti- (NIH), involves cancer, nutrition, and HIV/AIDS. Dr. conditions. A member of several of the Herb Society of America. At present, Bown consults inflammatory properties for Abrams is a member of the American Medical Association, conventional and integrative medi- for Lagos State Urban Forest in applications in oral and personal the Society for Integrative Oncology, and a member and cal associations, he likewise serves Nigeria. care. After graduating with a BSc past president of the Gay and Lesbian Medical Associa- as a peer reviewer for a variety of Jane Buckle, RN, PhD, a regis- in pharmacy from the University tion. Currently, he is involved with clinical investigations medical journals, including Ameri- tered critical care nurse, specializes of Bern’s Institute of Pharmacy in integrative oncology with specific interests in medicinal can Family Physician and the Journal of Alternative and in holistic therapies for the nursing in 1992 and a PhD in pharma- mushrooms, (Cannabis spp., Cannabaceae), Tradi- Complementary Medicine. He also sits on the boards and profession. Through her consult- ceutical sciences from the University of Lausanne in 1997 tional Chinese Medicine interventions, and nutrition. He committees of several foundations and groups, including ing firm, R.J. Buckle Associates, — both located in Switzerland — Dr. Gafner moved to co-edited an Oxford University Press textbook, Integrative his current position as president of the American Academy LLC, many scholarly journal - the United States for his postdoctoral work on plant-based Oncology (2009), with Andrew Weil, MD, and serves on the of Pain Management. Dr. Bonakdar authors and edits many cles, mainstream media stories, cancer chemopreventative agents at the University of Illi- editorial boards of the Journal of AIDS, Integrative Medicine chapters and articles on integrative medicine, and was editor and two aromatherapy books — nois – Chicago. Dr. Gafner is a member of the American Insights, and as the associate editor of The Journal of the Soci- of The H.E.R.B.A.L. Guide: Dietary Supplement Resources Clinical Aromatherapy in Nursing Society of Pharmacognosy, the Society for Medicinal Plant

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Research (GA), and the Society of Europe. all UpS programs, including the Botanical Sanctuary Mai Dao: Path of the Pulse (2009) and Li Shi-Zhen Pulse lead scientist, Dr. Schauss has worked on projects in 44 He also serves on the editorial board of Natural Products Network, Partners in Education, UpS membership and Studies: An Illustrated Guide (People’s Medical Publishing countries for AIBMR to support research activities and deal Against Cancer and is a reviewer for the Journal of Natu- internships, garden grants, and the at-risk plant program. House, 2011). He serves as editor and regularly authors arti- with regulatory matters for over 500 companies or institu- ral Products, Phytochemistry, and Planta Medica. To date, She earned her PhD in environmental studies at Antioch cles for Acupuncture Today and American Acupuncturist, and tions. He earned his undergraduate, graduate, and doctoral Dr. Gafner has co-authored more than 30 peer-reviewed University – New England, for which she completed her lectures on pulse diagnosis, Chinese herbs, and other topics. degrees at the University of New Mexico at Albuquerque publications and book chapters and has been awarded three dissertation titled “Loss of Ethnobotanical Knowledge in Danica Taylor Harbaugh and California Coast University in Santa Ana, respectively. patents. the Bull Run Mountains.” For the seven years preceding Reynaud, PhD, is the founder Dr. Schauss is a Fellow of the American College of Nutri- Frank L. Greenway, MD, is her employment at UpS, Dr. Leopold was a librarian at the and CEO of AuthenTechnolo- tion, and a member of the American Society of Nutrition, the medical director and a profes- renowned Oak Spring Garden Library, home to — among gies LLC, the founder and exec- the Society for Experimental Biology in Medicine, and the sor at Louisiana State Univer- other treasures — the collection of rare botanical books and utive director of the nonprofit Association for African Medicinal Plants Standards, among sity’s (LSU) Pennington Biomed- manuscripts of Rachel Lambert Mellon. There, Dr. Leopold International Foun- others. In 2005, he received the Linus Pauling Lecture Award ical Research Center, a clini- entered the collection into a searchable database, established dation, and a visiting scholar and for contributions to the medical sciences from the American cal professor of medicine in the a digital photography lab, and oversaw graduate research. museum specialist at the Univer- College for the Advancement of Medicine. Dr. Schauss is the Department of Medicine at the Rachel Mata, PhD, is a sity and Jepson Herbaria at the author or co-author of over 200 publications, and the author State University Medical Center professor at the Universidad University of California – Berke- or co-author of 23 books in the fields of nutrition and botani- in New Orleans, and an adjunct Nacional Autónoma de México. ley, where she earned both her cal medicine. professor in LSU’s Human Ecol- Her research interests include bachelor’s and doctoral degrees Paul E. Stamets is the founder, ogy Department. Dr. Greenway natural product drug and agro- in integrative biology. She is a owner, and managing director of is a graduate of the University of chemical discovery and chem- geneticist and botanical taxono- Fungi Perfecti, LLC, founder and California – Los Angeles School of istry, biochemistry, and phar- mist whose focuses include the managing director of Agarikon Medicine and Stanford University, and served as a major macology of medicinal plants. development of DNA-technology-based botanical authen- Press and The Life Box Company, in the US Army National Guard’s Medical Corps. He is Among her 180 scientific publi- tication methods, as well as the study of and conservation as well as the owner and managing currently a member of the International Association for cations to date, Dr. Mata has strategies for (Santalum spp., Santalaceae). Dr. director of Mycopesticide, LLC. the Study of Obesity, the American Society for Nutri- authored a number of book Reynaud has served as a reviewer for academic journals such Widely acknowledged as North tional Sciences, and the American Association of Clinical chapters and respected journal as Molecular Phylogenetics and Evolution, Journal of Biogeogra- America’s premier advocate for Endocrinologists. Dr. Greenway’s current research involves articles as well as three books. phy, and the Botanical Journal of the Linnaean Society. medicinal mushrooms and fungi for health outcomes of weight loss, diabetes prevention, resve- She is a member of the editorial Navindra Seeram, bioremediation, Stamets has been a ratrol treatment for insulin sensitivity, and vitamin D for boards of the Journal of Natural PhD, is an assistant mycologist for more than 30 years, type 2 diabetes. He has authored more than 150 articles in Products and Current Topics in Medicinal Chemistry, and professor of pharmacog- during which he discovered four new peer-reviewed journals. she co-edited the book Phytochemistry of Medicinal Plants nosy at the University of species of mushrooms and pioneered techniques in the field Mimi Guarneri, MD, founded (Springer, 1995). She studied for her MSc and PhD in Rhode Island’s College of of edible and medicinal mushroom cultivation. A graduate the Scripps Center for Integra- medicinal chemistry at Purdue University in Indiana. She Pharmacy, where he runs of Kenyon College and The Evergreen State College, he is a tive Medicine in La Jolla, Califor- also held a teaching position at Universidad Central de the Bioactive Botanical member of the GMP/GAP Board on Standards for Produc- nia, where she served as medical Venezuela, where she earned her bachelor’s degree in phar- Research Laboratory. He tion of Medicinal Plants/Medicinal Mushroom Production director from 1999 to 2012 and macy. previously was the assis- for the US Pharmacopeia, on the editorial boards for The thereon as senior consultant in William Morris, PhD, tant director of the David International Journal on Medicinal Mushrooms and Mush- integrative medicine. Dr. Guarneri DAOM, LAc, president of the Geffen School of Medicine’s room, the Journal, and an advisor to the Program for Integra- — who is board-certified in cardi- Academy of Oriental Medicine Center for Human Nutrition at the University of Califor- tive Medicine at the University of Arizona Medical School. ology, holistic medicine, internal at Austin’s (AOMA) Graduate nia – Los Angeles. Dr. Seeram — who received his doctoral In 2008, Stamets received National Geographic Adven- medicine, and nuclear medicine School of Integrative Medicine, degree in natural products chemistry from the University of ture Magazine’s Green-Novator and Argosy Foundation’s — earned her doctoral degree is a leading figure within North the West Indies in Kingston, Jamaica — focuses his research E-chievement awards. Stamets is the author of six books on from the State University of New America’s Traditional Chinese on traditional medicines and botanical extracts, particularly mushroom cultivation and has presented a TED talk on the York Downstate Medical Center Medicine community. Morris examining how they might prevent or treat chronic illnesses. vast health and environmental benefits of mushrooms, titled in Brooklyn. Currently, Dr. Guarneri is an assistant clini- led the American Association He has been the recipient of several awards and honors, “Six Ways Mushrooms Can Save the World.” cal professor in the Department of Medicine at the Univer- of Acupuncture and Oriental including the American Chemical Society’s 2009 Young sity of California – San Diego, as well as director of the Medicine to become a single Scientist Award. Dr. Seeram publishes in numerous Integrative Cardiology Fellowship at Scripps Center for national association, and later scientific journals and helps Integrative Medicine and Depart- played an instrumental role in organize conferences for the ment of Cardiology. Her articles AOMA’s obtaining regional accreditation with the South- natural products commu- have appeared in respected jour- ern Association of Colleges and Schools as a level 5 doctoral nity. nals, including Annals of Internal granting institution. Prior to that, he spent more than a Alexander G. Schauss, Medicine and the Journal of Echo- decade of study examining the Ding family lineage of inter- PhD, is the senior cardiography. nal medicine and the Gu family lineage of external medi- research director at Natu- Susan Leopold, PhD, is execu- cine. He earned a doctorate in acupuncture and oriental ral and Medicinal Prod- tive director of the medicinal plant medicine, a PhD in transformative studies, and a Master ucts Research and CEO at conservation nonprofit United of Science in medical education. Morris has written several AIBMR Life Sciences in Plant Savers (UpS). She manages books on acupuncture and Chinese medicine — including Puyallup, Washington. As

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studies published in international journals demonstrat- More Than 100 Groups Support ABC-AHP-NCNPR Botanical ing that samples of GFSE were adulterated with various synthetic chemicals, including the disinfectant triclo- Adulterants Program san. The article concludes that a significant amount of The American Botanical Council-American Herbal Pharmacopoeia-National Center for Natural Products GFSE is adulterated, or at least was at the time the 10 Research (ABC-AHP-NCNPR) Botanical Adulterants Program announces that it has reached the milestone of analyses occurred over a 20-year period, and that GFSE’s having more than 100 underwriters and endorsers. They include some of the biggest names in the botanical and promoted antimicrobial activity may be due to the pres- dietary supplement community, including botanical dietary ingredient suppliers, supplement manufacturers, trade ence of these synthetic antimicrobial adulterants, rather and professional associations, colleges and universities, analytical laboratories, contract research organizations, than the extract itself. media companies, and law firms. The most recent article in the series, “The Adulteration Leading nonprofit organizations ABC, mixed or packed therewith so as to increase of Commercial Bilberry Extracts,” also written by Foster, AHP, and NCNPR initiated this ongoing its bulk or weight, or reduce its quality or was published in the winter 2012 issue of HerbalGram. program in 2011 to educate members of the strength, or make it appear better or of greater Bilberry fruit (Vaccinium myrtillus, Ericaceae) is a popular herbal and dietary supplement industry and value than it is.” food in Europe where it grows wild throughout Scandina- Formerly Tai Sophia Institute numerous other stakeholders in the The primary intention of the ABC- via and Eastern Europe. It is also a best-selling supplement herb, dietary supplement, and natural AHP-NCNPR Botanical Adulterants ingredient in the US marketplace. In a probable exam- medicine arenas about ingredient and Program is to help protect consum- ple of economically motived adulteration, it seems that product authenticity and adulteration. ers and responsible members of the many bilberry extracts are adulterated with a “confus- “We are deeply gratified by the huge herb and dietary supplement industry, ing morass” of ingredients, including black soybean hull extract, amaranth dye (also known as Red Dye No. 2), GROW outpouring of support that we have as well as other manufacturers, from received on this vitally needed educa- purchasing adulterated raw materials. charcoal, and various other fruits. tional program,” said Mark Blumenthal, This is done by the Program’s publishing With more than 100 underwriters and endorsers of Passion. Knowledge. founder and executive director of ABC, and a series of detailed articles that serve as an authori- the ABC-AHP-NCNPR Botanical Adulterants Program, Program manager. “Wherever we have gone to tative source of information on botanical adulter- Blumenthal says that this widespread support will Career. continue to bring the global problem of adulteration to solicit financial, technical, and other types of ants. These articles contain references to published Master of Science in Therapeutic Herbalism support, we have almost always received a posi- official and unofficial analytical methods for the attention of members of the herbal and dietary supple- tive response. This reflects the high level of company and/or third-party quality control labo- ment community. Integrates modern scientific knowledge with concern that many responsible elements in the herb and ratories to consider using to detect the presence (or absence) “We will continue to invite more companies, organiza- traditional wisdom to build a deep understanding natural health community — including, but not limited of known adulterants. tions, and others — both in the US and internationally of the principles and practice of herbal medicine. to, the herb and dietary supplement industry — have about To date, four papers on the topic of botanical adultera- — to join with us in this educational quest to increase The nation’s only graduate degree in the field. the quality and reliability of herbal supplements, teas, etc. tion have been published in HerbalGram. The first of these, knowledge about authenticity and adulteration problems,” Even though it’s apparent that there are many authentic, “A Brief History of Adulteration of Herbs, , and said Blumenthal. “Adulteration is an ancient and global problem. With increased education through an effective Graduate Certificate in Herbal Studies high-quality, reliable ingredients and products, the fact Botanical Drugs,” written by noted botanical expert Steven Provides broad knowledge and practical skills remains that there are identity and quality problems that Foster, appeared in the winter 2011 issue (#92). The article program, we believe we can significantly reduce, perhaps have persisted far too long, and now many of us are circling provides a history of accidental and intentional adulteration even eliminate, some of the problems in the market.” in the use of common herbs to support self and the wagons to reduce and hopefully of botanical ingredients spanning In addition to the series of articles, the Adulterants family care. eliminate some of the errors and “We are deeply gratified the past two millennia. Program includes contributions and consultations from fraud that exist in this field.” In the spring of 2012, HerbalGram some of the leading independent third-party laboratories Graduate Certificate in Medical Herbalism The ABC-AHP-NCNPR Botani- by the huge outpouring featured another article by Foster, with experience in quality control and botanical identifi- Offers healthcare professionals the opportunity cal Adulterants Program focuses on covering the adulteration of skull- cation issues. The editorial committee, which advises on of support that we have all technical publications, includes expert scientists from to gain practical knowledge of the most popular both accidental adulteration that cap with American germander. The herbs on the U.S. market. may occur due to inadequate quality received on this vitally herb skullcap (Scutellaria lateriflora, various universities, government agencies, and third-party control procedures, as well as inten- Lamiaceae), has been used as a mild analytical laboratories with extensive knowledge of herbal tional adulteration of plant-based needed educational sedative for more than a century, quality control. The Program also is being supported Post-Master’s Certificate in Clinical Herbalism ingredients for financial gain. In an but, in the early 1980s, it became by leading trade associations in the dietary supplement Assists skilled herbalists in building a successful, industry that saw sales rise 4.5% in program.” erroneously implicated as a possible industry, including the Consumer Healthcare Products safe, and effective clinical practice. 2011 to an estimated figure of nearly source of liver toxicity, likely due to Association, the Council for Responsible Nutrition, the Natural Products Association, and the United Natural $5.3 billion in herbal dietary supple- adulteration with or substitution of Maryland University of Integrative Health, an ment product retail sales in the United States alone, docu- American germander (Teucrium canadense, Lamiaceae). Products Alliance. A complete list of ABC-AHP-NCNPR Botanical Adul- accredited graduate university, also offers programs mented cases of adulteration of raw materials, i.e., problems The third feature in the series is “The Adulteration of in Nutrition & Integrative Health, Health Promotion, related to ingredient authenticity and quality, is a matter of Commercial ‘Grapefruit Seed Extract’ with Synthetic Anti- terants Program supporters can be found at http://abc. herbalgram.org/site/PageServer?pagename=Adulterants. Health & Wellness Coaching, Health Education, Yoga growing concern. microbial and Disinfectant Compounds,” written by John Therapy, and Acupuncture & Oriental Medicine. Title 21 of the US Code of Federal Regulations defines H. Cardellina II, PhD, and published in HerbalGram #94. adulteration as the “[a]ddition of an impure, cheap, or A popular ingredient in natural products, grapefruit seed —Sara O’Connor unnecessary ingredient to cheat, cheapen, or falsify an extract (GFSE; Citrus x paradisi, Rutaceae) has appeared Online courses begin Fall 2013 ingredient or preparation.” The Code also deems a prod- in cosmetics and dermatological preparations as well as www.muih.edu 800-735-2968 uct adulterated “if any substance has been added thereto or dietary supplements. The article reviews 10 analytical

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ABC Presents Annual Botanical Excellence Awards ABC James A. Duke Excellence in Botanical Literature Crowd of ABC supporters enjoying the presentations made at the 2013 ABC Celebration. The American Botanical Council held the 8th Annual ABC Botanical Celebration and Awards Ceremony on Photo ©2013 ABC March 7, 2013, in Anaheim, California. As in previous years, ABC’s event was held in conjunction with the Natu- The ABC James A. Duke Excel- ral Products Expo West trade show and Nutracon scientific conference. lence in Botanical Literature Award was created in 2006 in honor of The event, held at the Marriott Anaheim, was attended noted economic botanist and author, by approximately 300 ABC Sponsor Members, Corporate James A. Duke, PhD. It is given Members, members of the ABC Board of Trustees, Advi- annually to books that provide a sory Board, and Director’s Circle (a group of supporters who significant contribution to litera- assist ABC’s executive director with fundraising and educa- ture in the fields of botany, taxon- tional efforts), and other supporters of ABC’s nonprofit omy, ethnobotany, pharmacognosy, educational mission from academia and the natural prod- phytomedicine, herb safety, and ucts community. The evening was filled with dynamic other disciplines related to the vast conversations, opportunities to renew old relationships field of medicinal plants. Among his and establish new ones, delectable food and drink, and, of ous ABC Norman R. Farnsworth Excellence in Botanical prestigious career achievements in course, the honored award recipients. Research Award recipient Joseph M. Betz, PhD, presented economic botany and ethnobotany The awards program itself began with one of ABC the ABC Farnsworth award to Professor De-An Guo, PhD, at the United States Department Founder and Executive Director Mark Blumenthal’s signa- who traveled from Shanghai especially to accept the award of Agriculture (USDA), Dr. Duke ture slide shows of entertaining cartoons, which brought in person. has authored more than 30 refer- smiles and laughter to the crowd. ABC Board of Trustees ABC also presented, for the first time, its newly created ence and consumer books. He is also Chairman Steven Foster announced the ABC James A. Mark Blumenthal Herbal Community Builder Award. The a co-founding member of ABC’s Duke Excellence in Botanical Literature Award recipients, inaugural recipient was celebrated herbalist, educator, and Board of Trustees and currently including Martin A. Lee’s Smoke Signals: A Social History of author Gladstar, who accepted the award via a serves as Director Emeritus. Marijuana in the Consumer/Popular category, and Rainer delightful pre-recorded video. “I have been hesitant to insti- In 2011, due to the diversity of the impressive scientific data, mainly based on pre-clinical Bussmann, PhD, and Bruce Ponman’s Medicinal Plants and tute an award named after myself, of course, but the ABC quality books related to medicinal plants, ABC created two research, that powerfully validates the experience of many the Legacy of Richard. E. Schultes in the Reference/Techni- Board of Trustees insisted,” said Blumenthal. “I finally distinct categories for the James A. Duke Award. The recipi- medical marijuana users,” said Lee. “Public attitudes reflect cal category. acquiesced because I have long wanted to honor Rosemary, ent of the Consumer/Popular books category award was conflicting claims about marijuana’s potential benefits and Blumenthal presented Horphag Research, producer of and others like her (if there are any like her!), whose vital Healing Spices: How to Use 50 Everyday and Exotic Spices risks. There has been a deliberate effort to create uncer- Pycnogenol®, with the ABC Varro E. Tyler Commercial contributions fall outside of the previously existing ABC to Boost Health and Beat Disease by Bharat B. Aggarwal, tainty about what the science says about cannabis. I would Investment in Phytomedicinal Research Award. Previ- award categories.” PhD, and Debora Yost (Sterling Publishing, 2011). The compare it to corporate-driven efforts to create scientific same year, the American Herbal Pharmacopoeia’s Botani- uncertainty with respect to climate change. The public cal Pharmacognosy: Microscopic Characterization of Botani- discussion about marijuana continues to be haunted by the cal Medicines (CRC Press) received the Reference/Technical ghosts of Reefer Madness,” he said, referring to the 1936 books category award. American propaganda film that heavily distorted the physi- cal, psychological, and social effects of smoking cannabis. Smoke Signals: A Social History of Marijuana – Foster explained the importance of public education and Medical, Recreational, and Scientific debate in a time when cannabis is still viewed by many as Martin A. Lee, who spent three-and-a-half years research- taboo. “We don’t get to the next stage of understanding ing and writing the book, is an award-winning investigative the phytochemistry, pharmacology, and medical potential, journalist and co-author of Acid Dreams: A Complete Social unless we go through a period of social revolt against the History of LSD – The CIA, The 60s, and Beyond (Grove way things are and have been for far too long,” he said. “And Press, 1985). The publication of Smoke Signals by Scrib- we don’t get there as a society unless we do understand the ner, a division of Simon & Schuster, Inc., coincided with social history. That is the only way that we as a society are a robust public discussion of going to move the science forward in a rational way.” medicinal cannabis (Cannabis “My exciting, sometimes dangerous, and always interest- spp., Cannabaceae) during the ing career has seen me in the coca fields of Latin America, 2012 election season. Currently, poppy fields in Laos, and ganja fields in Jamaica,” said Dr. 18 states and the District of Duke, who worked for several years on a USDA collabo- Columbia have legalized medic- ration with the Drug Enforcement Agency’s anti-narcotic inal cannabis, and, last Novem- program, referring to frequently controversial and often- ber, Colorado and Washing- abused medicinal plants coca (Erythroxylum coca, Eryth- ton became the first states to roxylaceae), poppy (Papaver somniferum, Papaveraceae), decriminalize the possession of and cannabis. “Their programs targeted cannabis, the up to an ounce of cannabis for coca bush, and the opium poppy, each with long histories personal use by adults. of major medicinal activities. [Smoke Signals] is histori- “When I began writing about cally important, but my greater interest is in the medicinal Mark Blumenthal, ABC’s Founder and Executive Director, hosts the 2013 ABC Celebration in Anaheim, CA. Photo ©2013 ABC cannabis, I had no idea about bullets that Lee presents.”

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The meticulously researched book aims to help educate botanist of our time, or possibly of any era,” said ABC’s Horphag Research was founded in Berlin in 1925 as has resulted in more than 100 published clinical studies readers to understand the long, often-contentious history Blumenthal. “His students were profoundly inspired by HormopharmaAG by Charles Haimoff. In the 1960s, and 300 scientific publications in total (chemistry, in vitro of cannabis, including its use as medicine. According to his teachings, and many have embraced ethnobotany and Haimoff’s vision of “healthy aging” led to the develop- laboratory studies, animal pharmacology and toxicology the publisher’s website, Smoke Signals “draws attention to related fields as their primary passion and inspiration for ment of the antioxidant French maritime pine bark extract, studies, review articles, etc). Horphag Research’s bibliog- underreported scientific breakthroughs that are reshaping their careers.” Pycnogenol. Research on the product began in 1965, and, raphy includes studies on a diverse group of topics, includ- the therapeutic landscape.” Medicinal cannabis has been Many of Schultes’ former students are part of ABC, either just two years later, the first preparations were being sold in ing antioxidant properties, cardiovascular health, skin care, studied as a potential treatment for a wide variety of health as members of the ABC Advisory Board or friends of the Europe. By 1987, Horphag was awarded its first US patent, joint health, sports nutrition, and more. Recently published conditions including chronic pain, cancer and chemother- herbal community. These include, but are not limited to, and in 2003 Pycnogenol was self-affirmed to be GRAS clinical studies show the abilities of Pycnogenol to reduce apy side effects, and heart disease, among many others. the following scholars, authors, educators, and conserva- (Generally Recognized as Safe) for use in food products. perimenopausal symptoms, improve skin hydration and “I’m very pleased that the American Botanical Council tion botanists, among numerous others: Michael J. Balick, Sales of Pycnogenol products to consumers now exceed elasticity, reduce asthma symptoms, and improve endothe- recognizes the importance of clear, incisive reporting about PhD, of the New York Botanical Garden; Wade Davis, $500 million annually and are sold in more than 80 coun- lial function. cannabis,” said Lee. “The plant deserves it.” PhD, explorer-in-residence at the National Geographic tries around the world. This proliferation of research and the popularity of Society and best-selling author; Djaja D. Soejarto, PhD, “For 40 years, Horphag has invested in extensive research Pycnogenol products are likely what caught the eye of cele- Medicinal Plants and at the College of Pharmacy at the University of Illinois - to ensure the safety and efficacy of Pycnogenol as a brated surgeon and TV host Mehmet Oz, MD, who spent a the Legacy of Richard E. Chicago; Steven King, PhD, of Napo Pharmaceuticals; premium ingredient,” said Frank Schönlau, PhD, scientific segment of his “Dr. Oz” show in December 2012 discussing Schultes Mark Plotkin, PhD, director of the Amazon Conservation director for Horphag Research. “For more than a decade, I the benefits of Pycnogenol for younger-looking skin. The This book, a collection Team; Paul Alan Cox, PhD, executive director of the Insti- have personally overseen much of the research as we have effects extolled by Oz are perfectly in line with the compa- of essays published by the tute for Ethnomedicine; Robert Bye, PhD, director emeri- built upon that commitment. I am extremely proud to see ny’s motto of helping people “look, feel, and live better.” Missouri Botanical Garden, tus of the Botanical Garden of the Institute of Biology of the team recognized for its dedication to making Pycno- Previous recipients of ABC’s Tyler Award include Schwabe is based on the proceed- the National Autonomous University of Mexico; and the genol one of the most well-researched natural health supple- Pharmaceuticals (2008), Indena SpA (2009), Bionorica AG ings of the 2011 symposium iconic integrative medicine pioneer and best-selling author ments available today.” (2010), New Chapter Inc. (2011), and Bioforce (2012). held in honor of the great Andrew Weil, MD. “ABC congratulates Horphag Research for this most well- ethnobotanist and Harvard Dr. Bussmann and Mr. Ponman were grateful to be deserved and probably overdue honor,” said Blumenthal. Norman R. Farnsworth Excellence in Botanical University Professor Rich- chosen for the Excellence in Botanical Literature award, “Horphag Research is the epitome of a research-based natu- Research Award ard E. Schultes, PhD (1915- praising its namesake. “James Duke is one of the most ral products company, investing millions of dollars in scores Over the course 2001), on the 10th anniver- respected colleagues in our field, and has for decades of clinical research trials on its key product, Pycnogenol. of his career, ABC sary of his death. been the leader of the systematization and publication of “Professor Varro Tyler was one of my key mentors for Farnsworth Award “If anybody could be ethnobotanical information and the phytochemical data about 20 years. He repeatedly emphasized his desire to see recipient Professor named as the father of ethno- associated with it,” said Dr. Bussmann. “He is also one of herb companies invest in scientific and clinical research on De-An Guo’s research botany, it would be Richard E. Schultes,” said co-editor the most prolific and widely read authors in the field. To their herb and phytomedicinal products. I have no doubt has centered on Tradi- Dr. Bussmann. “No researcher has ever done more field receive the James Duke Award is an exceptional honor to us that if he were alive today, he would fully endorse ABC’s tional Chinese Medi- research, more to promote the discipline, and has encour- both as editors and the Missouri Botanical Garden.” choosing Horphag this year to receive his eponymous cine (TCM) quality aged more students to become ethnobotanists, with almost award,” continued Blumenthal. control, biochemistry, every senior scientist in the field acknowledging some Varro E. Tyler Commercial Investment in The late Professor Tyler — who has been described as and metabolism; his connection to Schultes.” Phytomedicinal Research Award one of the most respected men in late 20th century herbal phytochemical inves- The book chronicles the influence of Dr. Schultes on The recipient of ABC’s 2012 Varro E. Tyler Commercial medicine and pharmacognosy (the study of medicines of tigations of traditional former students and colleagues and sheds light on his illus- Investment in Phytomedicinal Research Award, Switzer- natural origin, usually from plants) — was an early trustee Chinese herbal medi- trious career and the lasting effects of the pioneering ethno- land-based Horphag Research, is the producer of Pycno- of ABC, dean of the College of Pharmacy and Pharmaceu- cines have resulted in Professor De-An Guo, PhD botanist. “I am increasingly of the belief that Richard Evans genol® French maritime pine bark (Pinus pinaster, Pinaceae) tical Sciences at Purdue University, and vice-president of the identification of 100 new chemical entities. In addition Schultes’ impact has yet to be fully realized in terms of his extract, which is used in hundreds of brands and formulas academic affairs at Purdue. He was the senior author of six to his professorship, Dr. Guo serves as director of the State historical importance,” said ABC Board of Trustees Presi- of dietary supplements, as well as in cosmetics, functional editions of the leading textbook in the field, formerly used Engineering Laboratory for TCM Standardization Tech- dent Steven Foster. “Roughly half of the chapter authors foods, and beverages. in every college of pharmacy in the United States. nology and as director of the Shanghai Research Center for of the book were his students. Schultes’ careful, conserva- “Horphag Research and its entire team are, of course, Professor Tyler urged his students and colleagues “not TCM Modernization at the Shanghai Institute of Materia tive, high-quality scholarship quietly affected the social and very honored to receive this prestigious award,” said Victor only to seek the truth but, after finding it, to discard any Medica of the Chinese Academy of Sciences. He earned political history of the last half of the twentieth century.” Ferrari, CEO of Horphag Research. “It is an important preconceived ideas which it may reveal as untrue.” He his doctorate in pharmacognosy from Beijing Medical According to Dr. Bussmann, Dr. Schultes published recognition for the scientific work that has been established encouraged scientific and product integrity and envisioned University’s School of Pharmaceutical Sciences in 1990, roughly two dozen books and 500 papers, collected over over so many years on one single and unique product — a rational herbal healthcare sector that valued the proper and conducted his postdoctoral studies in the department 30,000 plant samples, and conducted continuous fieldwork Pycnogenol.” evaluation of products’ quality, safety, and efficacy. of chemistry and biochemistry at Texas Tech University in in the Amazon for more than 14 years. “[He] created what “Receiving the American Botanical Council’s Tyler Lubbock, Texas. can only be called the golden age of Economic Botany,” he Award provides not only credibility to our scientific work, Among his many accomplishments, including more than said. but also a tremendous motivation to our team to continue 430 published scientific papers to date, Dr. Guo acted as “The symposium volume, like Schultes himself, is providing scientific evidence on a multitude of health bene- the vice-editor-in-chief of the 2005 edition of the Pharma- an ethnobotanical treasure,” said Dr. Duke. “My thanks fits of Pycnogenol,” said Ferrari. “We are not only blessed copoeia of the People’s Republic of China and editor-in-chief and congratulations to the editors and contributors for a with one of the most versatile and well-documented prod- of the 2010 edition. At present, he sits on the editorial notable symposium we can treasure forever.” ucts in this industry, but also with the most professional and boards of several highly respected international scientific “There is no doubt among those in the fascinating field of dedicated team.” journals, including Planta Medica and Phytomedicine. Dr. ethnobotany that Professor Schultes was the greatest ethno- According to Horphag, the extensive study of Pycnogenol Guo is an expert committee member of the United States

22 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 23 ABC NEWS ABC NEWS

Pharmacopeia and a member of the ABC Advisory Board. community in the United States, Gladstar founded several ally focused Plant Lovers Journeys since 1986. Gladstar’s and lovable. She gave a big leg up to herbalists of current “Professor Guo is not only an established scientist, he schools of herbal education, founded and organizes annual several books on herbs — including Herbal Healing for renown, helping them to achieve success and grow their has provided leadership in the modernization of TCM,” herbal conferences, leads international herb-focused jour- Women, Rosemary Gladstar’s Family Herbal, and the 2012 reputations. [She also] is a brilliant business woman. All of said past recipient of ABC’s Farnsworth Award, Professor neys, and has authored or co-authored about a dozen books Rosemary Gladstar’s Medicinal Herbs: A Beginner’s Guide — her businesses, even when she has moved on, continue to Ikhlas Khan, PhD, a research professor of pharmacognosy on topics ranging from herbal medicine recipes to medicinal regularly sell well and receive glowing reviews from her flourish in some form. To achieve such success, and to be so and associate director of the National Center for Natural plant conservation. herbal peers and loyal readers. The United Plant Savers, well loved by colleagues and students alike, is remarkable. Products Research at the University of Mississippi. “He is a “I know of no other herbalist who has done more to which Gladstar founded in 1994, remains the project that Her trustworthiness shines because it is legitimate emanat- deserving recipient and I am proud to call him my friend.” create a sense of relationship, community, and identity she is most passionate about due to its focus on preserving ing from an open heart and mind with roots entwined deep The Excellence in Botanical Research Award’s namesake among herbalists and others with a strong interest in herbs and conserving native North American medicinal plants in Mother Earth. By walking her talk, Rosemary’s achieved is ABC’s co-founding Board of Trustees member, the late and herbal healing than Rosemary,” said Blumenthal. “Her and their habitats from unsustainable wild-collection. She incredible energy that she has generously shared.” Professor Norman R. Farnsworth, PhD, a research profes- energy, enthusiasm, passion, creativity, love, and generous continues to serve on the group’s Board of Directors as Ever humble and modest, Gladstar gives much credit sor of pharmacognosy and senior university scholar in the spirit are bountiful and contagious. There is no one like founding president. to her herbal peers. “We help each other grow,” she said, College of Pharmacy at the University of Illinois – Chicago. her.” “For Rosemary, the linking of herbs to humans is only “either by pushing, pulling, encouraging, tugging, or just When Professor Farnsworth died in 2011 at the age of 81, Gladstar, the daughter of Armenian immigrants, first a mechanism for people to bring awareness to Mother pure nourishing love. At this point in time, the herbal the medicinal plant community lost one of its greatest learned plant medicine during informal garden walks Earth from whom we all originate,” said Steven Foster. community is really comprised of many communities, all champions. ABC will continue to present this award each with her grandmother, Mary Abelian Egitkanoff. She was “Rosemary laid the foundation for the rise of traditional interlinking through our love of plants. But as extraordi- year to a person or institution that has made significant instantly interested in the plant world, which was apparent herbalism, which has blossomed into touching the hearts of nary as the plants that bring us together and unite us as an contributions to ethnobotanical and/or pharmacognostic in the middle school projects she chose to do on medicinal and teaching tens of thousands of people. Small gatherings herbal community, are the people who love plants. They are research. herbs. In the early 1970s, Gladstar opened her own herb of a couple dozen folks of like mind grew into international an amazing group of diverse, bright, eccentric, talented, and “We are most pleased to be able to recognize and honor shop, Rosemary’s Garden, in Sonoma County, California. conferences, symposia, classes, and retreats that were key amazing individuals. I count my lucky stars to be amongst Professor Guo for his outstanding achievements in the Then, in 1974, she co-founded the tea company Traditional to the rise of two generations of practicing herbalists in the them…. Again, I am humbled and honored by this award.” chemistry and pharmacology of many traditional Chinese Medicinals with Drake Sadler and created many of the modern herbal renaissance.” ABC members are welcome to nominate persons, books, medicinal plants,” said Blumenthal. “He is clearly one of teas’ original formulations, including the popular Smooth “Rosemary Gladstar introduced herbalists to each other, and companies for the respective awards for consideration the leading figures in scientific medicinal plant research Move®, Throat Coat®, and Mother’s ®. In 1978, she and to the world,” said fellow herbalist, the late Cascade by the ABC Board of Trustees. Nominations can be made in China, a country with a vast spectrum of traditionally founded the California School of Herbal Studies (CSHS), Anderson Geller. “She gave herbalism a face, approachable by emailing [email protected]. used medicinal plants that are undergoing modern scientific which is still in operation today as the country’s oldest research and validation.” herbal school. In the following years, she founded the Breit- “I am very pleased and honored to receive the high enbush Herbal Conference, the International Herb Sympo- distinction of ABC’s Norman R. Farnsworth Excellence in sium, and the New England Women’s Herbal Conference Stock Photography that doesn’t look like Stock Botanical Research Award. I would like to thank ABC and — the latter two of which she still directs. the nominating committee who selected me for this award,” “In those early days,” said Gladstar, “when herbalism said Dr. Guo. “This reflects the world-wide coverage of and herbalists were first peeking up from ‘underground’ — ABC’s Farnsworth Award,” he continued. where they had rested quite contentedly, it seems to me, for Previous recipients of ABC’s Norman R. Farnsworth a number of decades — there really wasn’t very much going Excellence in Botanical Research Award include Dr. Betz, on herbally at all. We were rather isolated; there weren’t of the Office of Dietary Supplements at the US National newsletters, gatherings, or schools that I know of in the US Institutes of Health (2006); Professor Edzard Ernst, MD, that served to bring us together. [So,] these early gather- PhD, formerly of the Peninsula Medical School at the ings were revolutionary, really, and had a lot to do, I think, University of Exeter in the United Kingdom (2007); Profes- with nourishing and creating an herbal community. When I sor Hildebert Wagner, PhD, of the Institute for Pharma- look at plant communities, they thrive together. The greater pecializing in medicinal and aromatic ceutical Biology in Munich, Germany (2008); Dr. Khan the diversity in the garden (or meadow or woodland), the (2009); Professor Rudolf Bauer, PhD, head of the Institute better the health of the community. And it’s certainly true plants, along with the places they grow, of Pharmaceutical Sciences at the Karl-Franzens University of herbalists, as well.” ourS stock photo fi les include more than of Graz in Austria (2010); Professor A. Douglas Kinghorn, In the 1980s, Gladstar PhD, chair of the department of medicinal chemistry and created Sage Mountain Herbal 120,000 images shot around the world pharmacognosy in the College of Pharmacy at Ohio State Retreat Center, a 500-acre for over 30 years. University (2011); and Professor Djaja D. Soejarto, PhD, botanical sanctuary in of the College of Pharmacy at the University of Illinois – Vermont where she currently Contact us at our NEW location in the heart of the Chicago (2012). lives and hosts educa- Ozarks in Eureka Springs, Arkansas tional events and programs. Mark Blumenthal Herbal Community Builder Additionally, she runs her Photography, Consulting, Publications Award commended herbal home- The first Mark Blumenthal Herbal Community Builder study course, “The Science Award recipient, Rosemary Gladstar, is a renowned herbal- & Art of Herbology,” and has StevenSteven FFosteroster GrGroup,oup, Inc. • SSteventeven FFoster,oster, PPresidentresident • PP.O..O. BoBoxx 191 • EurEurekaeka SSprings,prings, AR 72632 ist, teacher, and author known to many as the Godmother been leading the internation- Phone:Phone: 479-253-2629 • Fax:Fax: 479-253-2693 • email: [email protected]@stevenfoster.com of American Herbalism. Among her many accomplish- ments and efforts that have helped grow a rich herbal Rosemary Gladstar Visit our website: www.stevenfoster.com

24 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 25 RESEARCH REVIEWS RESEARCH REVIEWS

and well-tolerated for the relief of mild-to-moderate PMS References Review Supports Chaste Tree Berry Extracts for Female symptoms. It also was superior to pyridoxine in one study 1. Zamani M, Neghab N, Torabian S. Therapeutic effect of Vitex (105 subjects).8 In the study comparing the use of VAC agnus castus in patients with premenstrual syndrome. Acta Med to magnesium (82 subjects), PMS symptoms were more Iran. 2012;50(2):101-106. Reproductive Conditions 2. Ma L, Lin S, Chen R, Wang X. Treatment of moder- Reviewed: van Die MD, Burger HG, Teede HJ, Bone KM. Vitex agnus-castus extracts for female reproductive improved in the VAC group than in the magnesium group ate to severe premenstrual syndrome with Vitex agnus disorders: a systematic review of clinical trials. Planta Med. November 2012; [epub ahead of print]. doi: 10.1055/s- for all variables (back pain, menstrual pain, breast fullness, castus (BNO 1095) in Chinese women. Gynecol Endocrinol. 0032-1327831. headache, asthenia, irritability, and sleep disturbances).7 2010;26(8):612-616. Chaste tree (Vitex agnus-castus, Lamiaceae) berry (VAC) Google Scholar, and Web of Science. They searched for Regarding PMDD, one study with 38 subjects reported 3. He Z, Chen R, Zhou Y, et al. Treatment for premenstrual is used for a range of female reproductive conditions, RCTs, including crossover trials, of VAC versus placebo or a clinical improvement in both the VAC and fluoxetine syndrome with Vitex agnus castus: a prospective, randomized, including premenstrual syndrome (PMS) and associated comparator treatment, with no language restrictions. They groups, with 57.9% of subjects responding to VAC, and multi-center placebo controlled study in China. Maturi- tas. 2009;63(1):99-103. cyclic mastalgia (breast pain), premenstrual dysphoric extracted details of trial design, duration and setting, condi- 68.4% responding to fluoxetine.10 The authors proposed that “fluoxetine may be more effective for psychological 4. Pakgohar M, Moradi M, Jamshidi AH, Mehran A. Assess- disorder (PMDD; severe PMS), lactation difficulties, low tion under investigation, sample size, participants, outcome ment of Vitex agnus-castus L. extract effect on treatment fertility, and menopause-related complaints. These authors measures, adverse events, and results. The Jadad scale and symptoms while VAC may be more effective for physical of premenstrual syndrome. Journal of Medicinal Plants. conducted a systematic review to evaluate the evidence of the Cochrane risk of bias were used to measure the trials’ symptoms.” In the other PMDD study, with 57 subjects, 2009;8(32):98-107,185. the efficacy and safety of VAC extracts from randomized, methodological quality. fluoxetine outperformed VAC on all endpoints — depressed 5. Schellenberg R. Treatment for the premenstrual syndrome controlled trials (RCTs) investigating the effects of various Thirteen trials were identified; twelve trials met the mood, work interests, psychic anxiety, and general somatic with agnus castus fruit extract: prospective, randomised, VAC preparations on women’s health. inclusion criteria for this review. Three of the trials contin- symptoms; simultaneously, the VAC group significantly placebo controlled study. BMJ. 2001;322(7279):134-137. The authors searched the following electronic data- ued for two menstrual cycles or months, one continued for improved on all endpoints. 6. Turner S, Mills SY. A double-blind clinical trial on a herbal remedy for premenstrual syndrome: a case study. Complement bases from earliest publication to 2012: Medline, PubMed, six cycles, and eight lasted for three cycles or months; one of Of the LHP studies, one trial reported VAC to be supe- rior to placebo in treating luteal phase defects due to LHP, Ther Med. 1993;1(2):73-77. EMBASE, The Cochrane Library, CINAHL, Ovid, them, after a two-month washout, re-administered the same 7. Di Pierro F, Prazzoli R, Candidi C, Attolico M. Premenstrual extract treatment on only the last seven days as evidenced by its role in reducing thyrotropin-releasing syndrome: controlled clinical trial with a fast acting form of a of the luteal phase for another three-month hormone-stimulated prolactin secretion, normalizing a highly standardized extract of Vitex agnus castus. Giorn It Ost period. Of the 12 RCTs, eight investigated shortened luteal phase, and increasing mid-luteal proges- Ginecol. 2009;31:153-157. the effects of VAC extracts in women suffer- terone and 17β-estradiol levels. In another study, VAC was 8. Lauritzen C, Reuter HD, Repges R, Böhnert KJ, Schmidt ing from PMS,1-8 two examined VAC in comparable to bromocriptine in reducing serum prolactin U. Treatment of premenstrual tension syndrome with Vitex PMDD,9,10 and the other two investigated levels and ameliorating cyclic mastalgia.11 agnus castus controlled, double-blind study versus pyridox- Because of the “range of conditions under investigation, ine. Phytomedicine. 1997;4(3):183-189. latent hyperprolactinemia (LHP) with or 9. Ciotta L, Pagano I, Stracquadanio M, Di Leo S, Andò A, 11,12 outcome measures, and expression of results,” the authors without mastalgia. Formuso C. Psychic aspects of the premenstrual dysphoric Six of the PMS studies were placebo- could perform a meta-analysis on only two of the PMS disorders. New therapeutic strategies: our experience controlled; one compared the effects of VAC studies. Combining the results of the multicenter study with Vitex agnus castus. [Article in Italian]. Minerva Ginecol. reporting total PMS symptoms on the PMSD and PMTS with those of pyridoxine (vitamin B6); and 2011;63(3):237-245. another one compared VAC with magne- scales3 (including 217 subjects) with the outcome reported 10. Atmaca M, Kumru S, Tezcan E. Fluoxetine versus Vitex agnus sium. Both RCTs on PMDD compared on the Penn Daily Symptom Report4 (with 116 subjects), castus extract in the treatment of premenstrual dysphoric VAC extracts with fluoxetine (Prozac®, Eli VAC showed a greater benefit than placebo. disorder. Hum Psychopharmacol. 2003;18(3):191-195. 11. Kilicdag EB, Tarim E, Bagis T, et al. Fructus agni casti and Lilly & Co.). Of the two trials investigat- Adverse events associated with VAC were mild, generally infrequent, and less severe than those reported with fluox- bromocriptine for treatment of hyperprolactinemia and ing LHP, one was placebo-controlled and mastalgia. Int J Gynaecol Obstet. 2004;85(3):292-293. the other compared VAC with bromocrip- etine or bromocriptine. 12. Milewicz A, Gejdel E, Sworen H, et al. Vitex agnus tine (a conventional drug used to treat LHP, The methodological quality of the included studies varied, castus extract in the treatment of luteal phase defects due to among other conditions). but was generally moderate to high. Even with the method- latent hyperprolactinemia. Results of a randomized placebo- Five studies reported sample-size calcu- ological limitations, the RCTs to date appear to support the controlled double-blind study. [Article in German]. Arzneimit- lation estimates ranging from 55 to 120 efficacy and tolerability of VAC extracts in the treatment of telforschung. 1993;43(7):752-756. subjects per arm. Six studies included data PMS, PMDD, and LHP. “However, lack of transparency in from more than 100 subjects (ranging from the reporting of some studies limits assessment of trial 110 to 217). design and, in some cases, results. Future research Eight different outcome measures were into Vitex extracts for these conditions would benefit ® used in the RCTs investigating PMS and from use of tightly defined patient populations and PMDD. Symptoms were measured by the common endpoints,” concluded the authors. premenstrual tension syndrome (PMTS) Agnucaston® (Bionorica; Neumarkt, Germany), Ze self-rating scale and the premenstrual 440 (Zeller AG; Romanshorn, Switzerland), Agnolyt® syndrome diary (PMSD), as well as visual (Madaus GmbH; Cologne, Germany), and Monose- analogue scales and the Hamilton Rating lect Agnus® (PharmExtracta; Pontenure, Italy) were Scale for Depression. among the commercial products used in the trials in The authors reported that for PMS, VAC which products were specified. extract was superior to placebo in five of the six studies (with a total of 1067 subjects), —Shari Henson Custom Contract Manufacturing Since 1980. Chase Tree Berry Vitex agnus-castus. leading most of the investigators of those Photo ©2013 Steven Foster studies to conclude that VAC was effective 360-253-3197 www.pacnut.com

26 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 27 ChromaDex® Provides a RESEARCH REVIEWS RESEARCH REVIEWS Are You Confi dent Your Wide Range of Contract Raw Materials Are Contaminant Free? and Analytical Services was superior to placebo in lower- were selected based on their SBP. Clinical Trial Shows Aged Garlic ing SBP in patients with uncon- Currently, it is thought that for cGMPs. trolled hypertension. The two- DBP is an important predictor Extract™ Supplementation Reduces capsule dose was effective and well of cardiovascular disease and may tolerated. The authors wrote that be a more important determinant Blood Pressure the effect was clinically significant than SBP. The authors should Reviewed: Ried K, Frank OR, Stocks NP. Aged Garlic Extract reduces because the 10 percent improve- re-examine the two-capsule dose blood pressure in hypertensives: a dose-response trial. Eur J Clin Nutr. ment in SBP is known to be in a patient sample powered to 2013;67(1):64-70. associated with a decreased risk determine whether AGE has an in cardiovascular disease. The effect on DBP. Standard hypertension treatment The primary outcome measures authors stated that the study was with medication that lowers high were SBP and diastolic blood pres- not powered to detect a differ- —Heather S. Oliff, PhD blood pressure is ineffective in some sure (DBP) at four, eight, and ence in DBP because the patients people. Studies show that aged 12 weeks compared to baseline. garlic (Allium sativum, Liliaceae) The baseline characteristics were Garlic Allium sativum. Photo ©2013 Steven Foster supplements can lower blood pres- similar between groups. Patients sure. Aged Garlic Extract™ contains took an average of two different S-allylcysteine, a bioavailable and types of antihypertensive medica- stable water-soluble organosulfur tions. At 12 weeks, the two-capsule compound. The purpose of this (480 mg) group showed a signifi- randomized, double-blind, placebo- cant reduction in SBP compared controlled study was to evaluate the to placebo (P=0.03). There was ® effect and tolerability of different no change in DBP. The authors ChromaDex doses of Aged Garlic Extract as an conducted an additional analysis Contaminant Screening adjunct treatment for patients with that excluded five patients from uncontrolled hypertension. the data set who had blood pres- Seventy-nine patients (mean age: sure medication changes or poor 70 years) with uncontrolled hyper- compliance. In this additional anal- From vouchered reference materials tension (systolic blood pressure ysis, the two-capsule group had to complete analytical testing services, › Identity testing [SBP] ≥ 140 mmHg in the past six a significant reduction in SBP ChromaDex offers unique analytical months) from two general prac- compared to placebo at both eight methods to identify: › Potency analysis tices in Adelaide, South Austra- and 12 weeks (P=0.006). There lia, participated in this study was no significant improvement › Contaminant screening conducted from August 2011 to in the one-capsule or four-capsule › Microbiological contamination › Finished product testing March 2012. Included patients had group compared with placebo at taken prescription antihyperten- any point in either analysis. Across › Heavy metals › Stability studies sive medication for two months or all groups, blood pressure changed longer, and their general practitio- from -40 to +5 mmHg. SBP did › Adulterants › Risk management ners did not intend to change the not change by > 5 mmHg in one- medication plan during the trial. third of the participants. This find- › Steroid analogs › Master fi le development Excluded patients had an unstable ing was unassociated with sex, age, › Sildenafi l analogs or serious illness or already were body mass index, smoking status, › Reference standards/materials taking garlic supplements. Patients or number of blood pressure medi- › Pesticides received one, two, or four capsules cations. One-third of the patients › cGMP compliance consulting per day of Kyolic® High Potency correctly guessed their treatment › Herbicides Everyday Formula 112 (Wakunaga/ allocation. › Residual solvents Wagner; Sydney, Australia; Kyolic® Participants in the garlic groups Aged Garlic Extract is produced in reported minor complaints in Japan by Wakunaga), containing the first week of the trial, includ- Contact a ChromaDex representative to 240, 480, or 960 mg of Aged Garlic ing constipation, bloating, flatu- fi nd out how we can help you with your Extract (AGE) and 0.6, 1.2, or lence, reflux, garlic taste, and diffi- phytochemical and service needs. 2.4 mg Sallylcysteine, respectively, culty swallowing the capsules (23 or placebo, for 12 weeks. Sachets percent). The difference in reported Contact ChromaDex for more information on with a drop of liquid Kyolic were minor adverse side effects between our cGMP Services. +1.949.419.0288 | [email protected] added to the placebo containers those taking garlic capsules and www.chromadex.com as a method of blinding. Patients those taking the placebo was not +1.949.419.0288 | [email protected] were instructed to take their usual statistically significant. www.chromadex.com prescription medication. The authors concluded that AGE

28 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 29 RESEARCH REVIEWS RESEARCH REVIEWS

Artichoke Leaf Extract Improves HDL Cholesterol Levels in Prospective Study and Meta-Analysis of Chocolate and Patients with Hypercholesterolemia Reduction of Stroke Risk Reviewed: Rondanelli M, Giacosa A, Opizzi A, et al. Beneficial effects of artichoke leaf extract supplementation Reviewed: Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of stroke: a prospective cohort of men on increasing HDL-cholesterol in subjects with primary mild hypercholesterolaemia: a double-blind, randomized, and meta-analysis. Neurology. 2012;79(12):1223-1229. placebo-controlled trial. Int J Food Sci Nutr. February 2013;64(1):7-15. Much evidence has accumulated to show that cocoa of total stroke by 17 percent (95% confidence interval [CI]: Cardiovascular disease (CVD) is a prevalent worldwide cial HDL cholesterol levels, the primary endpoint, signifi- (Theobroma cacao, Sterculiaceae) and chocolate may have 1-30) after adjustment for age and stroke risk factors, includ- threat to health. Nutritional modifications, such as low- cantly increased in the ALE group (P<0.001), but remained benefits for cardiovascular health through antioxidant, ing blood pressure. This association was similar across stroke fat diets, typically are used to prevent or lessen CVD risk. unchanged in the placebo group. No significant changes were antiplatelet, anti-inflammatory, and blood pressure-lower- types. There was an inverse relationship between chocolate However, diets targeting the reduction of harmful low-density observed in blood glucose concentrations in either group. Total ing effects. In this paper, effects on stroke have been exam- consumption and risk of total stroke observed in men without lipoprotein (LDL) cholesterol also may reduce the concentra- cholesterol was significantly lower in both the supplemented ined in four studies, with two having statistically significant hypertension (relative risk [RR]: 0.76; 95% CI: 0.62-0.93), tion of beneficial high-density lipoprotein (HDL) cholesterol. (P<0.001) and control (P<0.010) groups; the change in this results. However, none of these studies examined exclusively but not in men with a history of hypertension (RR: 1.04; 95% Thus, interventions that reduce LDL while promoting higher parameter in the supplemented group was significantly greater male populations, and only one made its evaluation based on CI: 0.77-1.41; P for interaction = 0.04). The age-standardized concentrations of HDL are necessary for the alleviation of than in the control group (P=0.012). stroke type. The prospective study assessed the association incidence rates of stroke were 85 per 100,000 person-years CVD. Artichoke (Cynara scolymus, Asteraceae) leaf extract In addition, the total cholesterol-to-HDL cholesterol ratio between chocolate consumption and risk of stroke and stroke among men in the lowest quartile of chocolate consumption (ALE) has been shown to lower cholesterol in previous stud- at the end of the study was significantly lowered in the subtypes in a cohort of Swedish men. In addition, the authors and 73 per 100,000 person-years among men in the highest ies. This randomized, double-blind, placebo-controlled study supplemented group as compared to baseline (P<0.001); no conducted a meta-analysis of prospective studies involving quartile. investigated the effects of eight weeks of ALE supplementation change was observed in the placebo group. The LDL choles- chocolate and stroke risk. For the meta-analysis, the databases PubMed and EMBASE on HDL, LDL, and total cholesterol concentrations in subjects terol concentrations also were significantly lowered in both The study used data from the 1997 Cohort of Swedish were searched up to January 13, 2012, with no restrictions with hypercholesterolemia. the supplemented and placebo groups (P<0.001 and P<0.05, Men (aged 45 to 79 years). Questionnaires with 350 items imposed. Four prospective studies examining the association The 92 study participants were “mildly” hypercholesterolemic respectively). In the supplemented group, the LDL cholesterol- on diet and lifestyle were gath- between chocolate consumption (5.4-7.0 mmol/l), 18 to 60 years of age, had a body mass index to-HDL cholesterol ratio significantly decreased (P<0.001), but ered from 48,850 men who were a and stroke were identified, plus (BMI) range from 19 to 30 kg/m2, and were recruited from the remained unchanged in the placebo group. Triglycerides were good representation of the general the current study, making a total University of Pavia in Pavia, Italy. They did not have CVD or not significantly altered in either group. Compliance was rated population with respect to age of five. These studies included a chronic diseases and were not on medicine that targeted choles- as “excellent,” and no adverse side effects were reported. In addi- distribution, relative body weight, total of 4,260 stroke cases over terol concentrations. The study excluded those who smoked tion, blood chemistry was normal in all subjects both at baseline and education level, compared a range of eight to 16 years of tobacco, consumed excessive amounts of alcohol or weight-loss and endpoint of the study. with representative data from follow-up. Highest and lowest drugs, or were pregnant, lactating, or in menopause. Subjects In conclusion, this study reports a significant increase in the Official Statistics of Sweden. consumption of chocolate were were instructed to maintain their normal level of exercise and a HDL cholesterol with a concurrent decrease in LDL choles- After excluding questionnaires compared, and dose response three-day baseline dietary assessment was taken. This informa- terol in patients with hypercholesterolemia after eight weeks of that were not completely filled in, also was analyzed. tion was used to standardize subjects’ diets to total caloric levels supplementation with ALE. The authors note that an inverse and patients who had died or had The RR of stroke in the high- similar to American Heart Association recommendations; diet relationship exists between HDL cholesterol and CVD risk, a history of cancer, cardiovascular est compared to the lowest quar- also was evaluated at the end of the study. with a three percent reduction in death risk or myocardial disease, diabetes, or an implau- tiles of chocolate consumption Blood pressure, body weight, and BMI, as well as skinfold infarction for every one percent increase in HDL cholesterol. sible total energy intake, 37,103 was 0.81 (95% CI: 0.73-0.90), Cocoa Theobroma cacao. Photo ©2013 Steven Foster thickness and abdominal diameter, were measured both at the Therefore, the clinical applications of ALE for this purpose may men remained. with no heterogeneity. Dose beginning and at the end of the study. Treatments consisted of be beneficial, but warrant further study. Consumption of chocolate was response could be assessed in 250 mg tablets of either ALE or “a matching placebo” (excipi- Possible mechanisms for the observed bioactivity include the assessed using a self-administered food-frequency question- four out of five of the studies; for a 50 g increment per week, ents without ALE) administered before lunch and dinner (500 modulation of various enzymatic activities by ALE compounds. naire that included 96 foods and beverages. Consumption in the RR was 0.86 (95% CI: 0.76-0.97), with no heterogeneity mg total daily dosage) for eight weeks. ALE was standardized For example, previous studies have shown that the ALE grams was computed by multiplying the frequency of choco- among studies (P=0.21; I2=34.1%). to contain more than 20% caffeoylquinic acids, 5% flavonoids, compounds chlorogenic acid and luteolin possibly attenuate late consumption by four age-specific portion sizes (43-54 The highest levels of chocolate consumption were associated and 5% cynaropicrin. [Note: No description of the placebo LDL cholesterol oxidation and related damage. Luteolin, in years, 42 g; 55-63 years, 34 g; 64-71 years, 27 g; 72-77 years, with a decreased risk of stroke in men, and this was confirmed is given.] Both the ALE and placebo tablets were supplied by addition, inhibits coenzyme A reductase activity, which is a key 26 g), which were obtained from the authors’ validation study by the meta-analysis. The results can be extrapolated to men Indena SpA; Milan, Italy. Leftover tablets were used to gauge enzyme in the liver cholesterol synthesis pathway. Finally, chlo- in Swedish men. Approximately 90 percent of chocolate in general because of the wide representation of men pres- compliance. rogenic acid could favor the HDL cholesterol increase through consumption during the time frame of the study was in the ent in the sample population. Though the exact mechanism Fasting LDL, HDL, total cholesterol, and glucose concen- the agonistic effect on paraxonase-1, which is involved in the form of milk chocolate. of action for the stroke benefit has not been elucidated, it is trations were measured from blood samples taken at baseline protection of HDL cholesterol from oxidation. Incidence of stroke was identified via the Swedish Hospital likely due to the pleiotropic (producing multiple effects from and the study endpoint. Fasting HDL cholesterol also was One important avenue of future research into ALE is the Discharge Registry and was classified as cerebral infarction one gene) cardiovascular benefits of chocolate, including the assessed eight weeks after the study’s conclusion. Tolerability investigation of gender-related effects, as certain parameters (ICD-10 [International Statistical Classification of Diseases lowering of blood pressure. The strengths of the study are of the treatments was estimated by blood pressure and blood measured — HDL cholesterol, in particular — have shown and Related Health Problems 10th Revision] code I63), intra- its large population and its nearly complete data regarding chemistry at baseline and at the end of the study. Any adverse differences when data is stratified by gender. This suggests cerebral hemorrhage (I61), subarachnoid hemorrhage (I60), stroke incidence. Its limitations include a lack of differen- side effects were inquired about by investigators and reported potential variable responses to ALE supplementation. Further- and unspecified stroke (I64). tiation between types of chocolate consumed, self-reporting by subjects. more, given the marked sensory properties of cynaropicrin In 10.2 years of follow-up, 1,995 cases of first-time stroke of consumption, and evidence of small study effects in the Of the subjects enrolled, there were no dropouts reported (bitter) and cynarin (sweet aftertaste), more information on the were identified, including 1,511 cerebral infarctions, 321 meta-analysis. The authors caution that chocolate should be and all participants — 46 in each group — completed the nature of the placebo should have been included in the publi- hemorrhagic strokes (254 intracerebral hemorrhages and 67 consumed in moderation because of its high fat and sugar study. Blood pressure measurements of both groups were within cation. subarachnoid hemorrhages), and 163 unspecified strokes. content. a normal range at baseline and endpoint, and BMI did not Patients in the highest quartile of chocolate consump- —Risa Schulman, PhD significantly change in either group during the study. Benefi- —Amy C. Keller, PhD tion (62.9 g/week) had a statistically significantly lower risk

30 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 31 Editor’s note: This paper is part of the series published under the aegis of the ABC-AHP-NCNPR Botanical Adul- terants Program, an educational program led by the American Botanical Council, the American Herbal Pharma- copoeia, and the National Center for Natural Products Research at the University of Mississippi. The Program is Exploring the financially supported and/or endorsed by an international coalition of more than 100 herb and dietary supplement industry members, third-party analytical laboratories, professional and trade associations, nonprofit educational groups including accredited schools of natural medicine, industry media organizations, law firms, contract research Peripatetic Maze of organizations, and others. Summary active constituents, elucidating mechanisms of action, and 1 Black cohosh root and rhizome and their preparations conducting phase I and phase II clinical studies. Research BLACK COHOSH (Actaea racemosa, syn. Cimicifuga racemosa; Ranunculaceae) interest in black cohosh also was emphasized by many have been of considerable international market, scientific, other research groups, such as the group led by Edward J. and consumer interest for more than 60 years, particularly Kennelly, PhD, at the Department of Biological Sciences, ADULTERATION during the last 15 years in the United States. The increased Lehman College and the Graduate Center, City University market demand, nomenclatural confusion of related North of New York, and others too numerous to name. In addi- A Review of the Nomenclature, American and Asian species, tion, various herb companies, commercial analytical labo- along with case reports of ratories, trade organizations, Distribution, Chemistry, Market Status, liver toxicity associated with non-governmental organiza- products labeled as black tions, and regulatory agencies Analytical Methods, and Safety cohosh, have led to both have focused on contributing suspicion of and actual to the general knowledge and Concerns of this Popular Herb identification of economic understanding of all aspects adulteration of black cohosh of black cohosh. This article By Steven Foster commercial supplies. From reviews issues associated with the mid-1950s through the complexities of black the 1990s, a voluminous cohosh adulteration, includ- body of literature on black ing botanical and nomen- cohosh was published based clatural considerations; trade on market experience and and economic issues; various clinical use of black cohosh identification, analytical, and in Germany. Since the late- authentication challenges; 1990s, a significant body alleged liver toxicity linked of new analytical chemi- to adulterated products; and cal, pharmacognostic, other data on economic adul- pharmacological, and clini- teration of products labeled cal scientific literature has as black cohosh. been published relative to Introduction the identity, pharmacol- ogy, toxicology, and clin- The root and rhizome ical applications of black of black cohosh are sold as cohosh. In 1999, the Depart- whole, semi-whole, chopped, ment of Medicinal Chem- cut and sifted, dry powders, istry and Pharmacognosy and liquid and dry extracts. at the College of Phar- They are widely available macy, University of Illinois in dietary supplement and - Chicago (UIC), under phytomedicinal formulations the direction of the late Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster in the United States, Canada, Norman R. Farnsworth, Europe, Australia, and else- PhD, received funding from US National Institutes of where. In modern phytother- Health (NIH) to establish the Center for Botanical Dietary apy, black cohosh preparations are used primarily for the Supplements Research. The emphasis of the Center’s treatment of menopausal symptoms, including hot flashes, research focused on botanical dietary supplements that heart palpitations, nervousness, irritability, sleep distur- may improve women’s health, especially in the areas of bances, tinnitus, vertigo, excessive perspiration, and depres- sive states associated with menopause, as well as for premen- menopause, premenstrual syndrome and persistent urinary 2 tract infections. Black cohosh became one of the Center’s strual discomfort and painful menstruation. Historically, primary research subjects. That collective research serves as the botanical was specifically considered to have an affilia- a model for overcoming challenges associated with research tion with the nervous system and uterus, and was used for a host of nervous system disorders and as a uterine tonic and on botanicals (as dietary supplements), including acquir- 3 ing and identifying plant species, isolating and identifying antispasmodic. Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster

32 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 33 Product forms with the most market experience and eval- blooming in mid-to-late June. Toward the northern part of with electrospray ionization time-of-flight mass spectrome- nation enclosed in single quotes. For example, one cultivar uation in clinical studies are Remifemin®, an oral formula- its range, blooming begins as late as early August.14 try (HPLC-TOF-ESI-MS). The study states that in addition is Cimicifuga ramosa ‘James Compton,’ named for botanist tion, standardized to triterpene glycosides, of an isopropa- to A. racemosa, there are eight more North American species and taxonomist James Compton, PhD, recent monographer nolic black cohosh extract,4 and Menopret® (Klimadynon®), Voucher Specimens and Identification of Actaea. However, the authors include both A. podocarpa of the genus Actaea.12 To further confuse matters, many an ethanolic extract. Remifemin has been manufactured Bennett and Balick (2008) emphasize the fact that in and “A. americana,” the latter a of no botanical nurseries offer “Actaea ramosa” bronze-foliage cultivars, even by Schaper & Brümmer GmbH & Co. KG (Salzgitter- the field of medicinal plant research, unless a plant can be standing for A. podocarpa. Actaea podocarpa formerly was though the name “Actaea ramosa” never was published as a Ringelheim, Germany) since 1956. Bionorica (Neumarkt, unambiguously identified, reproducibility — the funda- known as Cimicifuga americana, and it appears that in this scientific name for any plant. Here, the genus name “Actaea” Germany) produces Menopret (Klimadynon).5* mental underpinning of science — is uncertain. To aid case the genus name “Actaea” was erroneously substituted simply has been used to replace the genus name Cimicifuga Black cohosh raw materials and their extracts are widely reproducibility, a preserved herbarium specimen to which for Cimicifuga. Fortunately, the chemical profiles for A. with no attempt to determine the correct botanical name for known in the herb industry to be adulterated with related the correct scientific name has been applied should be podocarpa and the purported “A. americana” in the species of Actaea (syn. Cimicifuga) from China. The Ameri- deposited in a properly curated collection. Two common study are virtually identical. Therefore, there are can Herbal Products Association (AHPA) provides infor- problems, they note, are the frequent misuse of binomials in only eight North American Actaea species, rather In the case of black cohosh and mation and links to analytical tools and methods to help medicinal plant publications, and the lack of author citations than nine, as suggested by C. Ma et al.21 its relatives, researchers must be identify adulteration of raw materials and ingredients for binomials. In a PubMed search of 100 titles or abstracts Furthermore, when exploring the historical through its Botanicals Authentication Program6 and its on medicinal plants, they found that 20% contained errors record, the reader should be aware of additional cognizant of relevant synonyms in Known Adulterants recommendations incorporated into in the botanical name, emphasizing that the misspelling of nomenclature complexities. The genus name AHPA’s Guidance Policies.7 According to AHPA, “The binomials is an inexcusable error.15 For example, a PubMed “Macrotrys,” established by C.S. Rafinesque in retrieving scientific papers published economic adulteration of black cohosh root and rhizome search for the misspelled “Actea” (rather than the correctly 1808 as a new designation for Cimicifuga racemosa, with other species is well established.”8 spelled Actaea) retrieves three citations. was subsequently misspelled “Macrotys” (omitting in the last 15 years. A detailed microscopic identification of A. racemosa as A practice in the medicinal plant literature, which is often the second “r”) in several of the eight editions of Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster well as closely related species are provided by the Ameri- not followed, is that every study should reference the rele- the popular Manual of Botany by Amos Eaton can Herbal Pharmacopoeia (AHP) in its recently published vant scientific specimen and indicate where the specimen is (1776-1842), published from 1817-1840, and Microscopic Characterizations of Botanical Medicines (CRC curated for reference. The voucher itself is more important widely used as a standard field reference until the Press, 2011).3 AHP also published a comprehensive review than the correct identification, as an erroneous scientific mid-19th century. Black cohosh was adopted as of quality control and authentication specifications of black name attributed to a voucher can be corrected or amended a drug by the Eclectic medical movement in the cohosh and its adulterants in its Black Cohosh Rhizome at a later date. mid-19th century, and the Eclectics nearly univer- monograph (2002), which provides comprehensive guid- In accordance with the International Code of Botanical sally referred to the drug under the misspelled ance on known adulterants that includes the botanical, Nomenclature, there is only one accepted scientific name genus name “Macrotys,” perpetuating the error microscopic, and chemical analyses of black cohosh.9 for a taxon. However, Bennett and Balick use black cohosh of Eaton. The common name black cohosh did as a well-known example to which synonyms are applied. not come into widespread use until the late Botanical, Taxonomic and Nomenclatural The choice of the scientific name depends on the interpre- 19th century. Macrotys and black snakeroot were Considerations tation of taxonomic data by a given specialist. For example, widely used as common names for black cohosh The genus Actaea includes 28 species from the Northern in the treatment of the Ranunculaceae (buttercup family) in until about 1900.14,22 Hemisphere.10 Compton et al.11-13 analyzed morphologi- Flora of North America, separation of the genera Actaea and cal and genetic data and supported the combination of the Cimicifuga is maintained.16,17 Comments on Names of Source Plants of genus concepts of Actaea, Cimicifuga, and Souliea — essen- Similarly, in the 2001 treatment of the Ranunculaceae Chinese Extracts tially reverting to Linnaeus’s 1753 concept of the genus in Flora of China, Actaea, Cimicifuga, and Souliea18-20 are Various Chinese species of Actaea are source Actaea. Previously, the major morphological basis for sepa- treated separately with the caveat, “Elsewhere (Compton plants of the traditional Chinese medicine sheng- rating Cimicifuga from Actaea was fruit type. Actaea has a et al., Taxon 47:593-634. 1998), Cimicifuga has been trans- ma (shengma). Three Actaea/Cimicifuga species berry-like fruit and Cimicifuga has a dry follicle. ferred to Actaea. However, for the present account, as in are official source plants of sheng-ma: A. heracle- Black cohosh is an erect, smooth-stemmed perennial that FRPS [Flora Reipublicae Popularis Sinicae], one of us (Li) ifolia (C. heracleifolia, aka da-san-ye sheng-ma), A. grows from four-to-eight feet (75-250 cm) in height. The prefers to maintain Cimicifuga as distinct.”19 dahurica (C. dahurica, C. dahurica var. simplex, large, alternate, triternately compound leaves are borne on In the case of black cohosh and its relatives, researchers aka xin-gan sheng-ma), and A. cimicifuga (C. short, clasping petioles. The ovate, acute leaflets, two-to- must be cognizant of relevant synonyms in retrieving scien- foetida, aka sheng-ma). Actaea simplex (A. cimicif- three inches (3-8 cm) in length, are thin, smooth, and two- tific papers published in the last 15 years. uga var. simplex, C. simplex, C. foetida var. simplex) to-three-lobed with sharply double-serrate margins. The Plant names associated with black cohosh and its relatives is known as ye-sheng-ma. long, wand-like, white inflorescence, about one inch (2.5 are easily confused in the scientific literature. Some research Actaea simplex is the most commonly cultivated cm) in diameter, are borne on a terminal branching spike- groups refer to studied species under the taxonomic concept Asian species related to black cohosh in Ameri- like raceme. The main feature of the flowers are the numer- of Cimicifuga, while others embrace the broader generic can horticulture and an excellent example of the ous showy stamens, consisting of slender filaments with concept of Actaea as defined by Compton and colleagues confused nomenclature of black cohosh relatives white anthers. Four or five small, concave, greenish-white in their 1998 reclassification.12 The practical application of in commercial trade, extending beyond sourc- sepals are larger than the nearly inconspicuous, stamen- the taxonomy is not as easy as simply replacing the genus ing of botanical dietary supplement ingredients. like petals. The solitary white pistil is smooth to somewhat name “Actaea” for “Cimicifuga” when referring to species Actaea simplex is known by numerous botanical pubescent and sessile (attached at the base without a stalk under either genus name. synonyms, including “Cimicifuga ramosa,” which or ). The fruit is a dry, oval-ribbed follicle that splits For example, C. Ma et al. (2011) provide methods for is not a misspelling of “C. racemosa.” “Cimicifuga along a ventricle suture with eight-to-10 triangular brown authentication and differentiation of Actaea species using ramosa” cultivars are widely available as perennials seeds in two rows. In the southern United States, it begins high-performance liquid chromatography (HPLC) coupled in American horticulture, particularly selections in the “atropurpurea group” which have purple- * There are varying levels of evidence from clinical trials that may be used to support many of these health uses; mention of these uses here is merely for the purpose of acknowledging the range of use of black cohosh preparations and is not an endorsement or state- to-bronze foliage. Cultivar names are expressed as ment of support by the author or publisher of confirmed efficacy. the scientific name, followed by the cultivar desig-

34 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 35 the plant at hand. A simple Google search for “Cimicifuga specifications, and differing species listed as “black cohosh China) at $5-60/kg.31 Naturalin Bio-Resources small lots, mostly to small manufacturers at about $8.00/ ramosa” will return numerous sites listing bronze-foliaged extract” from Chinese sources require that the daunted Co., Ltd. (Changsa, Hunan, China), offered 2.5% triter- lb ($17.80/kg), but is not believed to represent a significant cultivars of A. simplex as “Cimicifuga racemosa” or “Actaea buyer attempting to source black cohosh work closely with pene glycosides “black cohosh extracts” from “Cimicifuga percentage of the wholesale black cohosh supply. (Fletcher ramosa.” This example is highly indicative of the confused a qualified analytical lab to authenticate black cohosh foetida L.”32 Xi’an Aladdin Biological Technology Co., Ltd. E., email to S. Foster and M. Blumenthal, April 2-5, 2013). understanding and application of binomials in the Actaea/ extracts before securing any supply source. (Xi’an, , China) offered “Black Cohosh Extract,” Cultivated wholesale black cohosh root for the medici- Cimicifuga genus nomenclatural complex. citing the Latin name Vernonia aspera (Roxb.) Buch.- nal herb trade is not economically feasible to produce, at The root of Vernonia aspera (Asteraceae; also known as Sampling of Names from Chinese Wholesale Ham.33 This illustrates the myriad offerings encountered in least not at the present time. The time frame for growth roughleaf ironweed) is an obscure Chinese folk medicine “Black Cohosh Extract Sources” a simple search and represents random samples of 18 differ- from seed to production of roots of large enough size for known as hei-sheng-ma,23 which translates to “black cohosh” According to the nomenclature reference AHPA’s Herbs ent supply source site links out of 38 suppliers listed on just the medicinal market is estimated at six-to-eight years, (hei=black). It occurs on open grassy slopes in mountains of Commerce,28 the only acceptable species to which the one of 47 pages returned on the alibaba.com website search which would require at least doubling and perhaps tripling above 3,000 feet in south China (Guizhou, Hainan, and common name “black cohosh” applies is Actaea racemosa of “black cohosh root extract.” The names mentioned above the price compared with wild-harvested material to recoup provinces), as well as India, Laos, , Nepal, (syn. Cimicifuga racemosa). Herbs of Commerce is formally — “Cimicifuga romose,” the investment in time Thailand, and Vietnam, and is known by at least 12 botani- recognized in Title 21 of the US Code of Federal Regu- Cimicifuga foetida, and Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster and inputs. At this cal synonyms in six genera.24,25 A PubMed search using all lations (CFR)29 as a primary reference for the appropri- Vernonia aspera — were point, cultivated mate- 13 names in the botanical literature returned no results on ate labeling of herbal products in the US, and, therefore, observed on more than one rial — compared with scientific studies published on Vernonia aspera or any of the non-compliance with this text — unless otherwise scien- page in this very limited the relative abundance synonyms. This author located no reference to Vernonia tifically warranted — is a violation of dietary supplement random sample. A follow- and much lower price of aspera in any of the chemical good manufacturing practices up search for “Cimicifuga wild-harvested material analytical studies on Actaea/ The sheer volume of (GMPs), and other regulations romose” (an apparent and — provides little incen- Cimicifuga adulteration. There pertaining to product label- often repeated misspelling) tive to commercial growers is a virtual dearth of scientific offerings, prices ranges, ing. According to the same returned a list of 387 prod- except in vertically inte- literature on Vernonia aspera, varied specifications, and text, Chinese species of Actaea ucts from 53 suppliers.34 grated operations with a yet multiple listings as a source (syn. Cimicifuga) are required A search for “Cimicifuga desire or need to control plant of “black cohosh extract” differing species listed as to be identified by the standard foetida” returned 121 supply sources. (Fletcher on wholesale Chinese websites “black cohosh extract” from common name “Chinese cimi- products from 24 suppli- E., email to S. Foster and are common. Is the plant actu- cifuga.” This name is subse- ers, most of which also M. Blumenthal, April 2-5, ally used as a base-material Chinese sources require quently required in finished- called the products offered 2013). for extract, spiked with triter- product labeling, thus clearly “black cohosh extract.”35 Chinese sources sell penes to make it appear to be that the daunted buyer distinguishing between Asian A follow-up search of powdered material or a black cohosh extract? Or is attempting to source black and North American species “Vernonia aspera extract” extract to the US market, this simply yet another case contained in a product. Any returned a list of 17 prod- rather than crude raw mate- of confused nomenclature lost cohosh work closely with designation of a botanical mate- ucts from 11 suppliers.36 In rial. Authenticated black in translation from Chinese to a qualified analytical lab to rial or finished product in the all 17 instances, the name cohosh extract at $50.00/ English on Internet sites? United States by the common “Vernonia aspera extract” kg can be expected to be The AHP monograph on authenticate black cohosh name of “black cohosh” on was associated with prod- three-to-four times the black cohosh makes refer- product labels (and presum- ucts labeled as “black price of Chinese-supplied ence to guang-dong sheng-ma extracts before securing ably in the supply chain) is cohosh extract.” As stated, extract (averaging around as a common substitute for any supply source. required to be Actaea racemosa none of the aforementioned $15.00/kg), depend- sheng-ma in the Asian market.9 and no other species. To apply Chinese species are accept- ing upon quantities. Serratula chinensis (Chinese the name “black cohosh” to able as “black cohosh” and Prices paid for Chinese- sawwort root, syn. Rhaponticum chinense, Centaurea missio- any other species violates the CFR and results in adultera- clearly are represented as supplied black cohosh nis; Asteraceae) is found on grassy slopes, thickets, and tion of the finished product offered to consumers. adulterated products under ranged from $6-$8.50/ forest edges in western , , southeast , Much of the material offered from wholesale sources of Title 21 of the CFR.† kg (including shipping) north and northeast , Guizhou, , , Chinese origin appear to be offered as “black cohosh” rather while US-supplied black Hunan, , , south Shaanxi, Sichuan, Yunnan, than “Chinese cimicifuga,” as listed in Herbs of Commerce. The Price of Authentic cohosh ranges from and south provinces in China.26 According to An Internet search conducted on Google with the simple North American Black $14.50-$16.50/kg. Obvi- Professor De-An Guo, PhD, director of the Shanghai search phrase “Black Cohosh Wholesale China” led to a Cohosh ously, prices vary consid- Center for Traditional Chinese Medicine Modernization, first hit at alibaba.com, which returned 2,440 black cohosh Price differences between erably based on root hei sheng-ma also refers to Serratula chinensis, which may be herbal extracts on 77 pages. Searching the landing page for authenticated North Ameri- quality, form (whole, cut, collected by Chinese exporters since it has the same name “black cohosh root extract”30 returned 1,670 herbal extracts can black cohosh and Chinese species sold labeled as “black powdered), and quantities purchased, but the overall trend (in Chinese) as black cohosh. He noted that as far as he can listed on 47 pages. Random price ranges for extracts were cohosh” provide the obvious incentive for economic adul- shows an economic adulteration incentive with the price determine, there is no commercial cultivation of A. racemosa between $1.00-$300.00/kg, with ranges of availability teration. Estimates suggest that between 300,000-380,000 of Chinese material running at about 25-30 percent, or in China (personal communication to S. Foster and M. from various suppliers offered at as little as a few grams per lbs (136,078-172,365 kg) of wild-harvested crude, dried, in some cases, much less, of that of authenticated black Blumenthal, March 25, 2013). The scientific literature on week up to five tons per week. Several plant species under whole black cohosh root enter the wholesale trade from the cohosh in wholesale trade (Fletcher E., email to S. Foster Serratula chinensis also is exceedingly sparse. A PubMed various correct or incorrect spellings of common and or US (as of the 2011 season) with prices from supplier/dealer and M. Blumenthal, April 2-5, 2013; Wanzer C., email to search retrieved only one citation — a 2007 study in which technical names were listed as the source of “black cohosh to manufacturers/processors ranging from $4.50-$7.50/ M. Blumenthal, April 4 and 5, 2013). Ling et al. reported on the isolation and structure of a new extract(s).” For example, “ISO9000 & Kosher certificate lb ($9.92-$16.54/kg). Some cultivated material is sold in cerebroside from the species, the first report of the occur- black cohosh extract,” 2.5% triterpenoides (HPLC) of 27 † Per 21 CFR 101.4(h): “The common or usual name of ingredients of dietary supplements that are botanicals (including fungi and algae) rence of cerebrosides in the genus Serratula. “Cimicifuga romose (L) Nutt.” was offered by Sanyuan shall be consistent with the names standardized in [the American Herbal Products Association’s] Herbs of Commerce, 1992 edition, The sheer volume of offerings, prices ranges, varied Jinrui Natural Ingredients Co., Ltd. (Xi’an, Shaanxi, which is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51.”

36 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 37 Habitat and Conservation try in which assistance in controlling trade is sought from Black cohosh occurs in moist, mixed deciduous eastern other CITES Parties, in which case trade would be permit- North American forests and forest margins, often in moun- ted only among CITES Parties if the member country that tainous terrain from Massachusetts south to Georgia, west listed the species issued an appropriate export permit and to northwest and north central Arkansas and the adjacent certificate of origin. However, no action was taken at the Ozarks of Missouri, north through the Ohio River Valley to CITES Conference of the Parties (COP 12) held in Santi- southern Ontario. Although not of significant conservation ago, Chile, in November of 2002. As of March 2006, active concern at the national level, at the extremities of the plant’s consideration to list black cohosh and its relatives was with- drawn by the USFWS, though the agency has been moni- natural range it may be considered rare at the state level. 40 Conservation concerns expressed by various groups toring and will continue to monitor status. including the US National Park Service, World Wildlife The information provided by AHPA in response to Fund, United Plant Savers, and others prompted the US the initial request for information and recommendations Fish and Wildlife Service (USFWS) to request information appears largely responsible for the lack of action taken to and recommendations for species to consider for changes to list black cohosh to a CITES Appendix. In the past decade, CITES (Convention on International Trade in Endangered Remifemin-manufacturer Schaper & Brümmer GmbH & Species of Wild Fauna and Flora) in the US Federal Regis- Co. KG has established large-scale commercial production ter in June of 2001.37 At the time, USFWS was consider- of black cohosh in Germany in order to better control and ing recommending black cohosh for a CITES Appendix II secure its supply source. The company’s production quan- listing, which may have monitored and/or restricted black tity is unknown and not reflected in trade data, though this cohosh in international trade. commercial production may contribute to an overall trend AHPA responded to the USFWS request for information of stabilization in wild-harvested tonnage and decreased with a detailed commentary on the suspected over-harvest conservation concerns from wild harvest. of black cohosh root for export.38 Subsequently, USFWS Ed Fletcher of Strategic Sourcing Inc., an experienced published a notice in the Federal Register in April of 2002 trader and consultant on North American medicinal stating that it would not seek an Appendix II listing, but plants and a supplier of wild-harvested and cultivated black that it intended to review and consider listing US native cohosh rhizomes/roots, observes that habitat depletion is species of Cimicifuga (Actaea) in Appendix III.39 CITES the most detrimental factor to current wild populations Appendix III includes species listed by one member coun- of black cohosh. He believes that managed stands of wild black cohosh regenerate adequately to be self-sustaining. Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster

Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster Population sustainability is achieved in part by high seed production in wild populations and Table 1. Black Cohosh Estimated Annual Trade Quantities in North America relatively high germination rates, which helps Dry Weight in kg to ensure the ability of populations to recover 1997-2010 from harvest impacts (personal communication, September 6, 2011). Year Estimated quantity (kg) Estimated quantity (kg) from cultivation from wild-collection Trade Data on Black Cohosh 1997 0 102,967 In a detailed analysis of black cohosh rhizome 1998 16,071 329,304 trade from the US, Brinckmann (2010)41 provided information on production scenarios, 1999 1,179 65,938 conservation status, trade volume, and market 2000 68 53,453 prices, along with information on quality expec- 2001 2,958 80,596 tations and pharmacopeial definitions. One of the problems in monitoring international trade 2002 128 76,856 in black cohosh is that the commodity does 2003 186 144,309 not have a unique 10-digit tariff code assigned 2004 1,502 144,575 to it under the Harmonized Tariff Schedule of the United States (HTSUS). The only esti- 2005 3,143 61,857 mates of annual trade volume and percentage 2006 925 139,478 of cultivated and wild-harvested black cohosh 2007 1,012 155,932 come from AHPA’s annual tonnage surveys of 2008 724 129,809 member companies that are primary raw mate- rial producers (direct buyers from point of 2009 629 76,509 origin) with data on up to 26 wild-harvested 2010 4,473 142,743 botanical commodities collected from 1997 to Source: Aggregate data from AHPA tonnage surveys as reported by 2010 (Table 1). Brinckmann (to 2005)48 and AHPA.49 Retail sales ranking of black cohosh products in the food, drug, and mass market channel as

38 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 39 well as the health and natural foods Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster channel in the US have remained rela- Table 2. Black Cohosh Dietary Supplement Product Sales Ranking, Sales tively stable over the past six years, as Estimates, and Percent of Change over Previous Years in Food, Drug, reflected in trade data summarized Mass Market (FDM) Channel in US in HerbalGram’s annual Herb Market 2006-2011 Reports (Tables 2 and 3). Year Sales Rank Retail Sales % ± Over Previous Year Potential Confusion of North 2011 8 $10,319,990 +9.85 American Actaea/Cimicifuga 2010 8 $9,303,047 +14.34 Species 2009 10 $8,123,878 +0.29 Accidental A. racemosa adulteration or inadvertent admixture to commer- 2008 10 $8,122,758 -7.07 cial lots may occur with several North 2007 7 $8,641,608 -0.47 American Actaea species that share the 2006 8 $8,682,563 0 same habitat and whose ranges overlap. Actaea podocarpa (syn. C. americana, Data do not include sales in WalMart stores. Information supplied for Food, Drug, and A. americana) occurs in a narrow range Mass Market retail stores, as compiled by Symphony IRI and published in the American in the central Appalachian mountains Botanical Council’s annual Herb Market Report in HerbalGram.50-54 from Pennsylvania south to Geor- gia. Appalachian bugbane (A. cordi- folia, syn. C. cordifolia, C. rubifolia, Table 3. Black Cohosh Dietary Supplement Product Sales Ranking, Sales C. racemosa var. cordifolia, A. rubifo- Estimates, and Percent of Change over Previous Years in Health and lia) has a narrow range limited to a Natural Foods Channel in US few counties in Pennsylvania, Virginia, 2008-2011 Tennessee, Alabama, Kentucky, and southern Illinois and Indiana. Actaea Year Sales Rank Retail Sales % ± Over Previous Year pachypoda and A. rubra also share over- 2011 19 $3,848,203 +2.5 lapping ranges with A. racemosa. All 2010 - (not ranked in five species are known to occur in the top 20) same habitat, often in sterile popula- tions, with few distinguishing features 2009 17 $3,645,883 +3.23 if flowers and/or fruits are not avail- 2008 18 $4,915,972 -4.11 able. This could result in uninten- Source: American Botanical Council’s annual Herb Market Report in tional admixture of one or more of the HerbalGram. 51-54 above species in commercial lots of A. racemosa.14 Fletcher noted that, in practical terms diversity in the genus. in Appalachia, A. podocarpa (yellow cohosh) is the species In a comprehensive paper explaining DNA barcoding as that most closely resembles black cohosh. Wildcrafters pass it relates to accuracy of identification of medicinal plants over other Actaea species because the roots/rhizomes are published in HerbalGram 97, Y.C. Ma et al. of the Cana- smaller, and they know that buyers will not purchase other dian Phytopharmaceutical Corporation,48 suggest that Actaea species. However, once the roots are dry they become DNA barcoding is emerging as a useful methodology in visually more difficult to differentiate (personal communi- the quality control toolbox to help reduce misidentifica- cation, September 6, 2011). tion and adulteration of medicinal plants. The practical In the AHP Black Cohosh Rhizome monograph, Upton et application of DNA barcoding to plant identification is an al. (2002) suggest that yellow cohosh (A. podocarpa) is unin- evolving field, circumscribed by key limiting factors such tentionally but commonly mixed with A. racemosa based on as standardization minimalism and scalability. In animals, similarities of above-ground morphological features. The a fragment of a single gene (cytochrome c oxidase 1) is AHP monograph provides a table showing unique visual the accepted standard for ease of species differentiation. features that provide distinction between A. racemosa and However, no single region of plant DNA provides univer- A. podocarpa fruit, seed, pistils, pedicels, bracts, and stami- sal sequence quality and species discrimination of plants, nodea. When fresh, black cohosh root is black and yellow leading to development of various proposed methods or a cohosh root is yellow, though once dried they are more combination of methods to correctly identify plants based difficult to differentiate. Also, A. podocarpa blooms about on their DNA barcodes. three weeks later than A. racemosa.9 Y.C. Ma et al. explain that a short region of DNA is used to identify species in DNA barcoding. First, a small sample DNA Analysis and Barcoding of DNA has to be extracted from the specimens. Second, Several DNA studies on Actaea have been published the selected barcode region undergoes polymerase chain distinguishing A. racemosa from other Actaea species, as reaction (PCR) amplification. The PCR result is purified well as increasing awareness of geographical and chemical and sequenced; then, the DNA sequence is compared to a

40 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 41 library/database to identify the species. as “black cohosh” arbitrarily purchased on the Internet In addition, they reported — for the first time — the of polyphenolic constituents. Replication of the method Researchers in China at the Institute of Medicinal Plant and from New York metropolitan-area stores, the research- presence of six additional phenolic compounds including could be applied to more collections of North American Development (IMPLAD) in Beijing and the Institute of ers found that of 36 samples sequenced, 27 (75%) exactly protocatechuic acid, protocatechualdehyde, p-coumaric Actaea species.57 Chinese Medicine at The Chinese University of Hong matched black cohosh. Nine samples (25%) had sequences acid, 1-isoferuloyl-β-D-glucopyranoside, ferulate-1-methyl Kong have taken the lead internationally in developing identical to three Asian Actaea species (A. cimicifuga, A. ester, and cimicifugic acid D. They also isolated two new Further Analytical Tools and Methods for DNA barcoding of botanical ingredients including medici- dahurica, and A. simplex). As noted above, Actaea simplex is compounds, a lignin — actaealactone — and a phenyl- Authentication nal plants and their adulterants. The Medicinal Materials widely available in American horticulture, but often misla- propanoid ester derivative — cimicifugic acid G — with The analytical tools and methods to assure that black DNA Barcode Database,49 for example, covers 1,658 plant beled, adding to potential confusion. structures determined based on nuclear magnetic resonance cohosh (A. racemosa syn. C. racemosa) is properly identified species. The 2015 Pharmacopoeia of the People’s Republic Significantly, none of the samples studied contained any (NMR) spectrometry analysis.56 are numerous, precise, and widely known to experts in the of China likely may be the first national pharmacopeia North American Actaea species other than A. racemosa, In 2007, Nuntanakorn et al. published a method to herb trade and the natural products research community. A to contain detailed DNA protocols for authentication of suggesting that wild collectors, buyers of wild-collected distinguish among various eastern North American Actaea combination of the use of several analytical methods may be herbal medicines. North American material, and their customers’ quality species based on phenolic component fingerprints. A necessary for proper authentication of black cohosh and to In order to distinguish among sympatric eastern North control procedures are achieving success at maintaining reversed-phase high-perfor- rule out economic adultera- American species of Actaea, several research groups have correct identity of authentic A. racemosa in North Ameri- mance liquid chromatog- tion or inadvertent admix- effectively applied DNA fingerprinting methods. Xu et al. can-sourced black cohosh supplies. raphy (RP-HPLC) method ture of related species. (2003) found that random amplified polymorphic DNA Four dietary supplements could not be identified using with diode array detection In its black cohosh guid- (RAPD) analyses could distinguish A. racemosa, A. podo- the lab’s PCR amplification protocol, presumably because (DAD) is useful for distin- ance document, AHPA carpa, and A. cordifolia when no powdered plant materials the DNA was degraded, possibly when heat was applied guishing the eastern North advocates the relatively were available.50 during processing. Nevertheless, the method described in American Actaea species A. inexpensive method of Zerega et al. (2002) used Amplified Fragment Length the Baker et al. paper using matK sequence supplemented by pachypoda, A. podocarpa, high-performance thin- Polymorphism (AFLP) DNA fingerprinting to analyze nrITS2 can consistently and unambiguously differentiate A. racemosa, and A. rubra layer chromatography black cohosh in relationship to its relatives with overlap- black cohosh, assuming that the DNA is not degraded.53‡ based on polyphenolic (HPTLC), citing the ping ranges. The method was applied to commercial black components. Described methodology of Verbitski cohosh products, and, in two products, verification of the Chemical Differentiation of Actaea species as a simple, reliable, and et al. (2008)58 for authen- presence of A. racemosa was confirmed along with the Various studies on the chemical constituents of black convenient method less tication of black cohosh absence of other eastern North American Actaea species. cohosh reveal that the two principal compound groups in complex than distinguish- in comparison to other However, use of this method was unable to verify the pres- the plant are triterpene glycosides (at least 43 reported to ing triterpene glycoside North American species ence or absence of Actaea species in black cohosh tea bags date) and polyphenolic derivatives, which have been the fingerprints, the method of Actaea/Cimicifuga. The and coated tablets. Variables such as rhizome temperature major focus of analysis and characterization of black cohosh provides qualitative and HPTLC methods of Ankli drying, storage conditions, processing techniques, age, and products. However, in an effort to conclusively identify quantitative polyphenolic et al. (2008) of CAMAG storage quality of finished products could have individu- standardization methods based on active compounds and fingerprints to reliably Laboratories59 in Swit- ally or collectively contributed to the degradation of DNA, biological activity, the late Professor Farnsworth’s research distinguish these four zerland are suggested with loss of AFLP markers, highlighting the limitation of group at UIC reported new potential bioactive compounds species. The method was for detecting adultera- the method.51 The results also supported the uniting of from black cohosh. Fabricant et al. (2005), as part of an validated with respect to tion of black cohosh from Cimicifuga with Actaea by Compton et al.,12 and suggest effort to produce a standardized, definable extract for use sensitivity, linearity, preci- Chinese species of Actaea/ that the morphologically dissimilar A. racemosa and A. in the UIC black cohosh clinical trials, reported on the sion, accuracy, and recov- Cimicifuga. Members of pachypoda are the most closely related eastern North Ameri- isolation and characterization of a new cyclic guanidine ery. the HPTLC Association can Actaea species in terms of genetics. alkaloid, cimipronidine, the first guanidine isolated from The eight polyphenolic can access further details of Pate et al. (2012) applied isolating microsatellite DNA a plant in the Ranunculaceae.54 Gödecke et al. (2009) compounds detected these methods through the loci to develop molecular markers for A. racemosa from isolated and characterized three new guanidine alkaloids included caffeic acid, feru- organization’s website (no living specimens throughout the plant’s geographical range. including cylo-cimipronidine and cimipronidine methyl lic acid, isoferulic acid, open access).60 The aim of the research was to measure genetic diversity ester (both congenors of cimipronidine), and a new alkaloid fukinolic acid, and cimici- C. Ma et al. (2011)21 across the species’ range as a tool to examine potential given the trivial name dopargine, a derivative of dopamine. fugic acids A, B, E, and F. provide further methods for genetic depletion in the southeastern United States, and These and other compounds, including 3-hydyroxytyrosol Actaea racemosa contains authentication and differ- provide a context for detecting possible genetic variations in 3-O-glucoside, may contribute significant biological activ- all eight polyphenolic entiation of Actaea species, Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster triterpene glycoside production. The characteristics of seven ity in polar fractions of an extract produced for use in clini- compounds. Actaea rubra using HPLC coupled with microsatellite regions provide a comparative genetic library cal trials, and they are being researched further for their has a similar phenolic the HPLC-TOF-ESI-MS for use in the future assessment of population structure serotonin receptor pathways, and possible central nervous profile to A. racemosa, but different ratios of polyphe- technique. They identified 15 chemical markers including and genetic relationships, which also could aid in assessing system and antioxidant activity.55 nols with higher levels of cimicifugic acids A and B as the three marker compounds that were unambiguously identi- genetic variables for active compound production.52 With respect to polyphenolic compounds, in 2006, predominant polyphenols, while fukinolic acid is the most fied using authentic standards, and an additional 12 marker Baker et al. (2012) applied another method of iden- Nuntanakorn et al. reported on the identity of 17 polyphe- abundant polyphenol in A. racemosa. Cimicifugic acid F compounds tentatively identified by fragmentation patterns tifying two matK nucleotides from the DNA sequences nols including hydroxycinnamic acid derivatives (caffeic was not found in A. rubra. In A. pachypoda, isoferulic acid when compared with previously reported data. (barcodes) of black cohosh that consistently and unambigu- acid, ferulic acid, and isoferulic acid); fukiic acid deriva- and cimicifugic acid A are the only two predominant poly- The analytical methods described in the paper that distin- ously distinguishes black cohosh from all related species. tives (fukinolic acid and cimicifugic acids A and B); and phenols. Actaea podocarpa contains cimicifugic acids A and guish 15 marker compounds inform differences among four In a sampling of 40 dietary supplement products labeled piscidic acid ester derivatives (cimicifugic acids E and F). B as the only two predominant polyphenols. The sympat- types of Actaea classified as follows: (1) species other than ric eastern North American species A. cordifolia (syn. C. A. racemosa, (2) Asian species of Actaea, (3) Actaea racemosa, ‡Those readers interested in a better understanding of the value and limitations of DNA barcoding are encouraged to visit the Barcode cordifolia, C. racemosa var. cordifolia, C. rubifolia) does not and (4) North American species other than A. racemosa. of Life website (www.barcodeoflife.org), which contains both introductory and technical details, along with many additional informa- seem to have been tested. An additional eight populations Of note, three cimifugin derivatives and a 16,23-dike- tion resources on species identification via DNA barcoding, with links to the Barcode of Life Database (maintained by the University of Guelph in Ontario). See, for example: Wallace LJ, Boilard SMAL, Eagle SHC, Spall, JL, Shokralla S, Hajibabaei M. DNA barcodes for every- of black cohosh from New York to North Carolina and toshengmanol class triterpene marker were found useful to day life: Routine authentication of Natural Products. Food Research International. 2012;49(1):446-452. Tennessee were examined, all of which had similar profiles differentiate species other than A. racemosa. For example,

42 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 43 the cimifugin derivative prim-O-cimifugin was present in it was difficult to determine identification of A. racemosa The workshop brought together experts active in multi- Beck v. Pharmavite and Nutraceutical Corporation involved Asian and North American species except for A. laciniata, by HPTLC alone. HPLC-UV showed distinct differences disciplinary research on black cohosh to gain a better a case of a 50-year-old woman who claimed to take 500 mg A. podocarpa, and A. racemosa; therefore, the presence of between A. racemosa and the Chinese Actaea species, but understanding of reported hepatotoxicity in humans and daily of a black cohosh product before the onset of jaun- that compound in a “black cohosh” product would indicate there was little distinction between A. racemosa and A. focused on issues relative to NIH-funded studies on black dice, leading to a diagnosis of autoimmune hepatitis. The adulteration. podocarpa, plus A. rubra and A. pachypoda exhibited almost cohosh. The late Professor Farnsworth, citing research patient required a liver transplant. The case was reported The alkaloid cimicifugaine (syn. cimicifine A) was found exactly the same HPLC-UV trace. However, HPLC-ELSD from his laboratory at UIC, underscored that there was by Levitsky et al. in a 2005 issue of Digestive Diseases and to be unique to Asian species of Actaea (including A. heracle- coupled with HPLC-MS provided unambiguous identifica- increasing concern that some of the black cohosh prod- Sciences.79 An erratum to the paper was published in the ifolia, A. mairei, A. dahurica, and A. yunnanensis). The pres- tion of A. racemosa, according to the authors. None of the ucts marketed in the US may not be genuine black cohosh same journal in 2008.80 One of the authors, Michael F. ence of this alkaloid is useful for identifying the presence of techniques were able to unambiguously distinguish between but one (or more) of the Chinese Actaea species instead. Sorrell, MD, a gastroenterologist, was one of the treating Asian Actaea species, and if found in a product labeled as the two closely-related North American species A. rubra Consensus was expressed that, given variables in prepara- physicians of co-plaintiff Susan M. Grant, and was retained containing “black cohosh,” would again indicate adultera- and A pachypoda.66 tions and possible adulteration and/or contamination, NIH as an expert witness. According to court documents, only tion. Dr. Kennelly’s research group at Lehman College at the grant recipients should have allowable budget costs for veri- after Dr. Sorrell was retained as an expert witness did he A single compound, 12 β,21-dihydroxycimigenol-3-O- City University of New York, with collaborating research- fication of research materials. One of the 40 participants at submit a report on Grant’s case for publication, which alleg- L-arabinoside, was found in high concentration in A. ers at various institutions, has published a series of papers the workshop, Wolfgang Wuttke, MD, of the University edly linked her liver disease to black cohosh. The published racemosa, but was absent from all other North American on the identity of black cohosh components and authen- of Göttingen in Germany — and principle investigator on case report included a statement that the patient “did not and Asian Actaea species tested; therefore, it is useful in tication.§ Remarkably, Jiang et al. (2005) found that an several clinical trials on Klimadynon — expressed that his drink alcohol or use illicit drugs, and was not taking any detecting unadulterated A. racemosa product.21 85-year-old black cohosh specimen collected in 1919 by reviews of the black cohosh clinical literature found few if medications, including other herbal medications, acet- Another compound, cimigenol-3-O-a-L-arabinoside H.H. Rusby had comparable quality and quantities of any effects on the liver, and was surprised at the level of aminophen [and] nonsteroidal anti-inflammatory drugs.”81 (syn. cimiracemoside C, cimicifugoside M), was reported four triterpene glycosides and six phenolic constituents, concern about black cohosh-associated hepatotoxicity in However, the plaintiff’s testimony did reveal that she regu- by He et al. (2000) to be unique to A. racemosa and hence compared with modern plant material, confirming the the US.74 larly consumed wine, used ibuprofen (an NSAID) on a reported to be a useful marker compound for A. racemosa.61 potential stability of those constituents in storage.67 Jiang Australia’s Therapeutic Goods Administration (TGA) regular basis, and was prescribed the antiviral drug vala- However, Ma et al., using the highly sensitive methods in et al. (2006), analyzed 11 commercial products from the was the first regulatory agency to require a warning label for cyclovir, all of which may contribute to liver disease. The the time-of-flight mass spectrometry analysis, detected the US labeled as black cohosh using HPLC-PDA+LS(SIM) black cohosh products. In 2005, TGA reviewed the safety court granted the defendants a summary judgment result- compound in three additional North American species and found that three products contained the marker of black cohosh in relation to possible cases of liver toxicity ing in dismissal.81,82 and one variety of Actaea, as well as three Asian species of compound cimifugin (and not cimiracemoside C), indicat- that at the time included 47 international case reports — A June 26, 2007 press release from the USP announced Actaea. ing they contained Asian Actaea species rather than authen- nine of which were from Australia. As of February 2006, that the USP Dietary Supplements Information Expert In addition, other published analytical methods for tic black cohosh, and one product contained a mixture of TGA required black cohosh products to include the follow- unambiguous identification of black cohosh include the black cohosh and an Asian Actaea species.68 A more recent ing label statement: “Warning: Black cohosh may harm the Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster HPLC method of Avula et al. (2007).62 Avula et al. (2009) paper (Jiang et al., 2011) from this same group used HPLC/ liver in some individuals. Use under the supervision of a provide a UPLC/UV/ELSD (ultra performance liquid chro- LC-MS analysis to distinguish HPLC fingerprints for both healthcare professional.” Following the initial safety review, matography/ultra-violet/evaporative light scattering detec- polyphenols and triterpene glycosides from samples of 15 TGA convened an expert advisory group that concluded tion) method and identification by UPLC-MS (ultra perfor- Actaea species including eight North American species and that there appears to be an association with products labeled mance liquid chromatography/mass spectrometry).63 The seven Asian species. Of note, cimifugin was detected in all as “black cohosh” and liver disease, but it was very rare.75 HPLC-photodiode array (PDA)/mass spectrometric (MS/ Asian species tested as well as three American species of A revised warning stated, “In very rare cases, black cohosh ELSD) method of He and colleagues (2006) provides more Actaea, but was absent from A. racemosa, as well as three has been associated with liver failure. If you experience guidance.64 A LC/TIS/MS (liquid chromatography/turbo closely related North American species (A. podocarpa, A. yellowing of the skin or eyes, dark urine, nausea, vomiting, ion spray/mass spectrometry method) developed by Wang pachypoda, and A. rubra).69 unusual tiredness, weakness, stomach or abdominal pain, et al. (2006) presents fingerprints of six commercial black In addition, the United States Pharmacopeial Conven- and/or loss of appetite, stop using this product and see your cohosh products along with six related Asian species. The tion (USP) has published authentication methods for black doctor.”76 method produces LC/MS fingerprints that provide reli- cohosh.70 Health Canada’s monograph,71 the EC European In July of 2006, the UK’s Medicines and Healthcare able and reproducible methods useful for identification of Medicines Agency monograph,72 and related documents all Products Regulatory Agency (MHRA) followed with a Actaea/Cimicifuga species and validation of commercial provide further guidance for quality assessment, authentica- suggested product-label warning in conjunction with a products.65 tion, and use guidance for black cohosh products. public statement by the European Agency for the Eval- Gafner et al. (2006) noted that the evaluation of chemical uation of Medicinal Products/Herbal Medicinal Prod- fingerprinting using a combination of techniques is espe- Products Labeled “Black Cohosh” and Alleged ucts Committee (EMEA/HMPC) advising patients and cially useful in the quality control of black cohosh, since the Liver Toxicity healthcare professionals to be aware of the liver toxicity majority of triterpene glycosides of A. racemosa also occur Since 2002, beginning with several case reports from linked to black cohosh-labeled products. Of the 42 poorly in several other Actaea species. An identification procedure Australia, presumed herb-induced liver injury has been documented case reports evaluated in the world literature, based on a few marker compounds may not be enough linked to products labeled as containing black cohosh. a temporal causality association was made in four cases.77 to rule out every adulterant. They compared HPLC-UV, Reactive alerts by regulatory bodies, when assessing causal- Health Canada issued a brief notice in a July 2005 issue HPLC-MS, HPLC-ELSD, and HPTLC fingerprints of ity, gave preference to quantity of cases over quality of of the Canadian Adverse Reaction Newsletter encouraging five Actaea species (A. racemosa, A. rubra, A. pachypoda, A. case data.73 On November 22, 2004, the NIH, NIH healthcare providers, manufacturers, and the public to be podocarpa, and a Chinese Actaea species sold as A. heracle- National Center for Complementary and Alternative Medi- aware of international reports of liver toxicity associated ifolia by the supply source). HPTLC gives good separation cine (NCCAM), and the NIH Office of Dietary Supple- with black cohosh.78 A follow-up consumer advisory about of phenolics and triterpene glycosides, but A. rubra, A. ments (ODS) convened a workshop on the safety of black a possible link between health products containing the podocarpa, and A. pachypoda showed very similar finger- cohosh in clinical studies in response to the case reports of herbal medicine black cohosh and liver damage was issued prints to A. racemosa, leading the authors to conclude that hepatotoxicity. on August 18, 2006. Continued media reports and regulatory agency warn- §A collaborating botanist who co-authored many papers with Dr. Kennelly’s group, Timothy Motley, PhD, the J. Robert Stiffler Professor ings regarding the possible association of black cohosh and of Botany at Old Dominion University, died at age 47 on March 28, 2013. A tribute article is available on page 77. hepatotoxicity led to the inevitable — lawsuits. Grant and

44 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 45 Committee (DSI-EC) voted to require new labeling at least 78 natural health products (NHPs) containing problems in any of the trials. In two cases, mildly elevated suggesting a potential link between black cohosh and liver black cohosh and that an unknown number of additional liver enzymes were reported but judged to be clinically damage. A proposed Interim Revision Announcement with unauthorized products on the market had yet to come into insignificant.88 the cautionary statement for black cohosh was released in compliance with NHP regulations. In a detailed, vigorous causality assessment — using a Pharmacopeial Forum 33(5), for a 60-day public comment Dr. Marles and colleagues obtained the same lots of black diagnostic algorithm — of the four cases of alleged black period.83 cohosh products from retail outlets and from the manufac- cohosh liver toxicity suspected by EMEA/HMPC, Teschke In a press release dated January 11, 2008, AHPA urged turer of four products of the same brand of black cohosh- et al. (2009) found no evidence for the causal association USP to drop label cautions on black cohosh, noting the labeled products, including a product labeled as containing between black cohosh and liver injury.89 An analysis and following: (1) “USP has not considered the full range of only black cohosh, along with three additional combina- review of the quality and causality of all published case products that may contain a variety of different forms tion products produced by the manufacturer. The products reports plus spontaneous reports of alleged black cohosh of black cohosh or that the proposed caution is actually had been linked to probable adverse liver reactions. Actein, toxicity assessed by the scale of the Council for the Inter- warranted for all dosages and use patterns,” and (2) “That 23-epi-26-doexyactein, and black cohosh powder reference national Organizations of Sciences (CIOMS) showed lack the need for a cautionary statement was based on an inap- standards were obtained from USP. Cimiracemoside C and of causality for black cohosh in all cases. In this review, propriately narrow review of case reports, which without cimifugin were purchased from ChromaDex (Santa Ana, Teschke and colleagues concluded that true black cohosh supportive data are insufficient to justify the proposed CA). LC-MS (liquid chromatography-mass spectrometry) may not produce an overt risk of hepatotoxicity, but quality cautionary labeling.”84 with a photodiode array detector (PDA) was used to analyze problems in some products may require additional regula- In 2008, the USP DSI-EC published a thorough review the products. Health Canada’s analysis of three products, tory quality specifications. They wrote that the focus should of alleged black cohosh hepatotoxicity case reports, and and the manufacturer’s analysis of a fourth product, all be on quality specifications to ensure that any problems of regulatory actions and reactions. The extensive review of showed there was no authentic black cohosh in the prod- impurities, misidentifications, and adulteration of black adverse event reports (AERs) by Mahady et al.82 stated that ucts when compared with chemical reference standards. cohosh products are identified.73,89 the DSI-EC observed that the link between black cohosh The probable adulterant was reported to be A. cimicifuga A review of adverse events associated with black cohosh and liver damage reports (C. foetida), but their raw products was conducted by Borrelli and Ernst (2008),90 were weak and of uncer- All of the identification and material supplier reportedly which found that clinical studies suggest black cohosh to tain causality. Weaknesses of believed it to be A. dahurica be safe; the authors noted that case reports for which causal reviewed data found incom- authentication scientific tools (C. dahurica) based on adja- attribution is problematic require urgent further investiga- plete case information and cent warehouse storage of tion. unknown products, poten- necessary to distinguish the two Chinese species. tially confounding variables Again, these products were Conclusions such as the use of alcohol and authentic black cohosh from associated with cases of Numerous monographs such as those produced by AHP, Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster other medications, and preex- any other plant materials of any probable adverse liver reac- USP, Health Canada, and other authoritative official and isting liver disease risk factors. tions. non-official organizations provide the details necessary for phytochemist. A 2010 report by Dr. Marles and colleagues Despite these and other limi- After the testing was unambiguous authentication of genuine North American origin are readily available. at Health Canada linked known cases of hepatotoxicity tations on available data, completed, Dr. Marles et black cohosh (Actaea racemosa, syn. Cimicifuga racemosa) to black cohosh-labeled “natural health products” (as they DSI-EC decided to reclassify al. reported that Health using relatively simple organoleptic, macroscopic, and are termed in Canada) that contained Asian relatives of black cohosh as “Class 2” for the purposes of a USP black Canada contacted all licensees for black cohosh products, of microscopic classical pharmacognosy methods, coupled black cohosh, thereby more closely implicating the Asian cohosh monograph, requiring a label caution stating the which 52 were found to have used an appropriate authenti- with relatively inexpensive and widely available chemical adulterant(s) with some of the recent cases of hepatotox- following: “Discontinue use and consult a healthcare prac- cation method [not characterized in the poster in relation to analytical methods such as HPTLC. AHPA offers a guid- icity associated with products labeled as containing black titioner if you have a liver disorder or develop symptoms of the licensees’ method(s)], seven licensees requested cancella- ance document on its website with suggestions to industry cohosh. liver trouble, such as abdominal pain, dark urine, or jaun- tion of their license, five did not provide enough informa- of reliable, dependable methods with references to readily Commercial Chinese websites offering “black cohosh dice.” The label caution applies only to products that are tion to determine compliance, and two did not respond. available literature. In addition, AHPA provides sources extract” in tonnage at prices that vary by 300-fold list botan- represented as conforming to specifications of an official There were 11 licensees using the same third-party labora- for the availability of reference compound standards, as ical source species for extract as an Actaea or Cimicifuga USP-NF monograph.82,85 tory that was reported to be using an non-validated method well as member companies that can supply chemical refer- species, or sometimes as Vernonia aspera (hei shengma). returning false positive results.86 ence standards, botanical voucher specimens, or commer- Another member of the Asteraceae, Serratula chinensis, also Hepatotoxicity of Commercial Products Labeled Painter et al. (2010) reported on Canadian products linked cial labs with proven and known expertise to unambigu- may be sourced as hei-shengma (black cohosh), but is usually as Containing “Black Cohosh” Linked to Plant to six cases of liver toxicity associated with products labeled ously authenticate black cohosh raw material and extracts. seen under the Chinese name guang-dong shengma. Analyti- Species Misidentification as black cohosh. The products were analyzed according to Depending upon the condition of raw material, DNA cal methods were not found for distinguishing these species Despite numerous cases reports of hepatotoxicity linked methods described by Dr. Marles and colleagues and were authentication methods also are available. In addition, more in the supply chain. to products labeled as containing black cohosh, with at found to contain Actaea species other than black cohosh. expensive, sophisticated, and perhaps less widely available To comply with appropriate current Good Manufactur- least 82 cases reported worldwide as of early 2010, causal- In two other cases of purported black cohosh liver toxic- chemical analytical methods using the latest technologies ing Practices (cGMPs) as required by law in the United ity has remained controversial. A report associating hepa- ity connected with products unlicensed by Health Canada, delivering unambiguous information, identification, and States and many other countries requires only the will to do totoxicity from commercial products labeled as containing the products connected with the cases were not obtained authentication have been published in the chemical analyti- so and the subsequent access to appropriate quality control black cohosh linked to plant species misidentification was for chemical analysis. They suggested greater vigilance in cal literature in the last 15 years, especially since 2006. resources. Mislabeling or confusion may be due to simple presented in a poster session by Robin J. Marles, PhD, and reporting liver reactions of products labeled as containing Beginning in 2002, case reports, many of which are language and translation variations, or, in some cases, the colleagues of various branches of Health Canada, on March black cohosh.87 inadequately documented, have appeared in the medical actual intent to sell a lower-cost material that is not an 23, 2010, at a symposium titled “Developments in Botani- In June 2007, the NIH ODS convened a workshop on literature associating potential hepatotoxicity to products acceptable substitute for authentic North American black cal Dietary Supplements Research from 1994 to Today,” the current state of knowledge for black cohosh in Gaith- labeled as containing black cohosh. Suspicions arose that cohosh. However, these are possibly moot points as all of organized by the UIC College of Pharmacy, in honor of ersburg, Maryland. A summary of workshop results by Betz those cases may be associated with adulteration (perhaps the identification and authentication scientific tools neces- the late Professor Farnsworth’s 80th birthday.86 By March, et al. (2009) noted that in contrast to adverse event reports, with Asian species of Actaea/Cimicifuga), but in a vast sary to distinguish authentic black cohosh from any other 2010, Dr. Marles and colleagues at Health Canada reported clinical trials and other human studies involving more than majority of such reports, the alleged offending product was plant materials of any origin are readily available. that the agency under Canadian regulations had licensed 3,000 subjects, there was not a single report of serious liver not retained nor were its contents analyzed by a competent

46 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 47 Solving the problem of economic adulteration of black 17. Ford BA. Actaea. In: Committee FoNAE, ed. Flora of North cohosh products is within reach. Many in the herb indus- America North of Mexico: Magnoliophyta: Magnoliidae and Hamamelidae. Vol. 3. New York, NY: Oxford University Press; try are acutely aware of the need for fulfillment of cGMPs 1997;181-183. as FDA increases cGMP inspections, compliance, and the 18. Li LQ, Tamura M. Actaea. In: Wu ZY, Raven PH. Flora of China: issuance of 483s warning letters.|| Clearly, the crux of the Caryophyllaceae through Lardizabalaceae. Vol. 6. Beijing and St. problem of black cohosh adulteration lies squarely on the Louis: Science Press and Missouri Botanical Garden; 2001;147. 19. Li LQ, Brach AR. Cimicifuga. In: Wu ZY, Raven PH. Flora of doorstep of intentional economic adulteration with less China: Caryophyllaceae through Lardizabalaceae. Vol. 6. Beijing expensive materials from China. and St. Louis: Science Press and Missouri Botanical Garden; 2001;144-147. References 20. Li LQ, Tamura M. Souliea. In: Wu ZY, Raven PH. Flora of China: 1. Farnsworth NR, Mahady GB. Research highlights from the UIC/ Caryophyllaceae through Lardizabalaceae. Vol. 6. Beijing and St. NIH Center for Botanical Dietary Supplements Research for Louis: Science Press and Missouri Botanical Garden; 2001;143. Women’s Health: Black cohosh from the field to the clinic. Phar- 21. Ma C, Kavalier AR, Jiang B, Kennelly EJ. Metabolic profil- maceutical Biology. 2009;47(8):755-760. ing of Actaea species extracts using high performance liquid 2. Blumenthal M, Hall T, Goldberg A, et al. (eds.). ABC Clinical chromatography coupled with electrospray ionization time-of- Guide to Herbs. Austin, TX: American Botanical Council; 2003. flight mass spectrometry. Journal of Chromatography. Mar. 18 3. Upton R, Graff A, Jolliffe G, Länger R, Williamson E (eds). 2011;1218(11):1461-1476. Botanical Pharmacognosy—Microscopic Characterization of Botani- 22. Lloyd JU, Lloyd CG. Drugs and Medicines of North America Vol. cal Medicines. Boca Raton, Florida: CRC Press; 2011. 1. Ranunculaceae Cincinnati: J.U. & C.G. Lloyd, 1884-1885. 4. Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, 23. Jiangsu New Medical College, eds. Dictionary of Traditional Riggins CW, et al. (eds.), Klein S, Rister RS. Trans. The Complete Chinese Medicine. (Zhong Yao Da Ci Dian). 3 vols. Shanghai: German Commission E Monographs: Therapeutic Guide to Herbal Shanghai Science and Technology Publishing Co., 1977–1979; Medicines. Austin, TX: American Botanical Council; Boston, MA: 1978; Vol. 2, #4943. Integrative Medicine Communications; 1998. 24. Vernonia aspera. In: Wu ZY, Raven PH. Flora of China Asteraceae. 5. Liske E. 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Accessed March 22, 2013. 15. Bennett B, Balick M. Phytomedicine 101: Plant taxonomy for 36. Vernonia aspera extract Internet search. www.alibaba.com/trade/ preclinical and clinical medicinal plant researchers. Journal of the search?fsb=y&IndexArea=product_en&CatId=&SearchText=Vern Society for Integrative Oncology, 2008;6(4):150-157. onia+aspera+extract. Accessed March 22, 2013. 16. Ramsey GW. Cimicifuga. In: Committee FoNAE, ed. Flora of 37. United States Fish and Wildlife Service (USFWS). 66 FR 31686 North America North of Mexico: Magnoliophyta: Magnoliidae and – Request for information and recommendations on species to Hamamelidae. Vol. 3. New York, NY: Oxford University Press; consider for changes to the CITES Appendices. Federal Register. 1997;177-181. June 12, 2001;66(113):31686-31690. || The Director of FDA’s Dietary Supplement Programs within the Center for Food Safety and Applied Nutrition, Daniel S. Fabricant, received his PhD in Pharmacognosy from the University of Illinois at Chicago under the tutelage of major and dissertation advisor the late Norman R. Farnsworth. Dr. Fabricant’s dissertation was “Pharmacognostic Investigation of Black Cohosh (Cimicifuga racemosa (L.) Nutt.)”.91 Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster

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Rockville, 45. Cavaliere C, Rea P, Lynch ME, Blumenthal M. Herbal supple- cultural and Food Chemistry. 2005;53(5):1379-1386. 74. NIH Workshop on the Safety of Black Cohosh in Clinical Stud- MD:United States Pharmacopeial Convention; sJune 26, 2007. ment sales rise in all channels; sales rise in 2009. HerbalGram. 66. Gafner S, Sudberg S, Sudberg EM, Villinski JR, Gauthier R, ies. NIH, Bethesda, MD, November 22, 2004. 40 pp. Available 84. American Herbal Products Association. AHPA urges USP to drop 2010;86:62-65. Bergeron C. Chromatographic fingerprinting as a means of qual- at: http://nccam.nih.gov/sites/nccam.nih.gov/files/news/blackco- label cautions on black cohosh and green tea. AHPA Update. 46. Blumenthal M, Lindstrom A, Lynch ME, Rea P. Herbs sales ity control: distinction between Actaea racemosa and four different hosh_mtngsumm.pdf. Accessed March 13, 2013. January 1, 2008. continue growth – up 3.3% in 2010. HerbalGram. 2011;90:64- 85. United States Pharmacopeial Convention. Black Cohosh. In: USP 67. 34-NF 29. Rockville, MD: United States Pharmacopeial Conven- 47. Blumenthal M, Lindstrom A, Ooyen C, Lynch ME. Herb supple- Black Cohosh Actaea racemosa. Photo ©2013 Steven Foster tion. 2012;1083-1085. ment sales increase 4.5% in 2011. HerbalGram. 2012;95:60-64. 86. Marles RJ, Omar S, Jordan S, Murty M, Perwaiz S, Bertrand R 48. Ma YC, Chen SL, Thibault ME, Ma J. Enhancing quality control and Lacroix P. Species misidentification of black cohosh products of botanical medicine in the 21st century from the perspective of in Canada. Developments in Botanical Dietary Supplements industry: the use of chemical profiling and DNA barcoding to Research from 1994 to Today. College of Pharmacy, University of ensure accurate identity. HerbalGram. 2013;97:58-67. Illinois at Chicago. Scientific Poster Session. March 23, 2010. 49. Medicinal Material DNA Barcode Database. Institute of Chinese 87. Painter D, Perwaiz S, Murty M. Black cohosh products and Medicine, The Chinese University of . Available at: liver toxicity: update. Canadian Adverse Reaction Newsletter. Jan. www.cuhk.edu.hf/icm/mmdbd.htm. 2010;20(1):12. 50. Xu H, Fabricant DS, Piersen CE, et al. A preliminary RAPD-PCR 88. Betz JM, Andersen L, Avigan MI, Barnes J, Farnsworth NR, et al. analysis of Cimicifuga species and other botanicals used for women’s Issues for the 2010 Dietary Guidelines: black cohosh consider- health. Phytomedicine. Dec 2002;9(8):757-762. ations of safety and benefit. Nutrition Today. 2009:44(4):155-162. 51. Zerega NJC, Mori S, Lindqvist C, Zhen QY, Motley, TJ. Using 89. Teschke R, Schwarzenboeck A. Suspected hepatotoxicity by amplified fragment length polymorphisms (AFLP) to identify black Cimicifugae racemosae rhizoma (black cohosh, root): criti- cohosh (Actaea racemosa). Economic Botany. 2002;56(2):154-164. cal analysis and structured causality assessment. Phytomedicine. 52. Pate SJ, Clement JA, McCoy JA, Lance SL, Mathews KG. Devel- 2009;16(1):72-84. opment and characterization of microsatellite markers for Actaea 90. Borrelli F, Ernst E. Black cohosh (Cimicifuga racemosa): a system- racemosa (black cohosh, Ranunculaceae). American Journal of atic review of adverse events. American Journal of Obstetrics and Botany. 2012;99(7):e274-276. Gynecology. 2008;199(5):455-466. 53. Baker DA, Stevenson DW, Little DP. DNA barcode identification 91. Fabricant DS. 2005. Pharmacognostic Investigation of Black of black cohosh herbal dietary supplements. Journal of AOAC Inter- Cohosh (Cimicifuga racemosa (L.) Nutt.). Ph.D. Dissertation. national. 2012;95(4):1023-1034. Graduate College of the University of Illinois at Chicago. 2005; 54. Fabricant DS, Nikolic D, Lankin DC et al. Cimipronidine, a cyclic 210 pp. guanidine alkaloid from Cimicifuga racemosa. Journal of Natural Products. 2005;(68):1266-1270. 55. Gödecke T, Lankin DC, Nikolic D, et al. Guanidine alkaloids and Pictet—Spengler adducts from black cohosh (Cimicifuga racemosa). Journal of Natural Products. 2009;(72):443-437. 56. Nuntanakorn P, Jiang B, Einbond LS, Yang H, Kronenberg F, Weinstein IB, Kennelly EJ. Polyphenolic constituents of Actaea racemosa. Journal of Natural Products. 2006;69(3):314-318. 57. Nuntanakorn P, Jiang B, Yang H, Cervantes-Cervantes M, Kronenberg F, Kennelly EJ. Analysis of polyphenolic compounds and radical scavenging activity of four American Actaea species.

50 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 51 By the end of 2012, the US Centers for Disease Control and Prevention (CDC) had reported nearly 250 West Nile virus-related deaths in the United States. With more than 5,300 reported cases in 2012 — the most in nearly a decade1 — health officials are urging individuals to take certain precautions to avoid being bitten by mosquitoes, which can carry the virus. In addition to ensuring properly fitting screens on windows and doors, wearing pants and long-sleeved clothing when outdoors, and avoiding pools of stagnant water where mosquitoes lay eggs, the CDC recommends using an insect repellent with an active ingredient registered by the Environmental Protection Agency (EPA).2 Of EPA-registered active ingredients, the most widely personal preference plays a role in repellent selection as well. recognized and studied synthetic compound is DEET “There is a strong perception that natural actives are safer (N,N-Diethyl-3-methylbenzamide), an insect repellent than synthetics,” said Sarah J. Moore, PhD, a lecturer in the developed by the US Department of Agriculture (USDA) Department of Disease Control at the London School of in 1952 and approved for public use in the late 1950s.3 Hygiene and Tropical Medicine, and a co-author of a 2011 Extensive testing supports the use of DEET as an effective review of plant-based insect repellents published in Malaria Plant-Based method of preventing mosquito and tick bites, but mild Journal (email, September 21, 2012). “Plant-based odours skin and eye reactions have been reported, as well as several are scents that people feel comfortable with as they are natu- cases of seizures in individuals who frequently used DEET. EPA requires all DEET-containing products to contain detailed instructions for safe use, which includes avoiding Catnip Nepeta cataria. Photo ©2013 Steven Foster Insect over-application of the repellent and washing any treated skin or clothing after use. According to the EPA’s 1998 reregistration eligibility decision, “DEET is not believed to be acutely toxic nor carcinogenic, significantly develop- mentally toxic nor mutagenic at the doses tested.” Further, Repellents the EPA concluded that the “available data do not support a direct link between exposure to DEET and reported seizure incidences (14 cases).”4 In recent years, however, much research has been conducted on plant-based alternatives to synthetic formu- Provide an las, which may be preferable to consumers with chemical sensitivities or those who wish to avoid synthetics. “[Plant-based insect repellents] may be more cosmetically appealing, more widely available or producible, including in tropical countries where the public health value of repellents Alternative is especially important,” said Scott P. Carroll, PhD, a scien- tist affiliated with the Department of Entomology at the University of California-Davis (email, September 25, 2012). “Plants are great biochemical synthesists, and we are well to Synthetic adapted to plants, so it’s obviously functionally prosperous for investigation.” Appeal of Plant-Based Insect Repellents Plants produce chemicals that act as natural deterrents to Formulas pests, and they have been used since ancient times to repel insects, most commonly by burning plant material.5 The By Tyler Smith established use of plants as insect repellents in part contrib- utes to their acceptability among consumers. “There are quite a few natural products (oils and single compounds) that demonstrate repellent efficacy,” said Ulrich R. Bernier, PhD, a research chemist in the Mosquito and Fly Research Unit at the USDA’s Center for Medical, Agricultural, and Veterinary Entomology (email, Septem- ber 21, 2012). “One advantage of using a plant-based botan- ical is user acceptability. People tend to favor natural prod- ucts over synthetics.” Plant-based active ingredients also are thought by some to pose fewer risks to users. And since repellents are often applied directly to the skin, consumers tend to favor prod- ucts without harsh chemical smells. Although, according to some experts, an effective active ingredient is the most important consideration when choosing an insect repellent,

Catnip Nepeta cataria. Photo ©2013 Steven Foster 52 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 53 contain more than 100 approved biopesticide active ingre- use as a food ingredient by the general public without any dients; however, only a small fraction of this number are reported adverse effects on human health.” Further, in the specifically plant-based insect repellents. environmental risk section of the fact sheet, they concluded that “it is not likely to accumulate in drinking water,” nor Hydrogenated Catmint (Catnip) Oil is it “expected to occur or pose a threat to non-target organ- In December 2008, the EPA approved hydrogenated isms.”13 catmint oil (Nepeta cataria, Lamiaceae), a species of the mint family. Catmint, or catnip as it is more commonly Repellents Derived from the Lemon Eucalyptus referred to*, is best known for its ability to produce behav- Tree ioral changes when given to cats, which typically last In April 2005, the CDC approved botanically based para- only a few minutes. The chemical believed to be respon- menthane-3,8-diol, or PMD, as an effective insect repel- sible for this intoxication-like behavior in cats is known as lent.14 PMD, which is derived from leaves of the lemon nepetalactone, a mild hallucinogen.8 eucalyptus tree (Corymbia citriodora, Myrtaceae), was “[Catmint oil] is in the pipeline for becoming available discovered in the 1960s by researchers conducting chemical as a consumer product, and [has] better lasting properties screenings for potential insect-repelling properties of plants than citronella,” said Dr. Carroll (email, October 1, 2012). used in Traditional Chinese Medicine. In fact, as plants are According to the American Mosquito Control Associa- occasionally named in accordance with their traditional tion (AMCA), “Catnip has been noted for years as possess- uses, the Chinese name for lemon eucalyptus, quwenling, ing repellency against mosquitoes. However, only recently translates roughly to “effective mosquito repeller.”15 has its efficacy been demonstrated to the extent it could be Although there are multiple plant-based active ingredi- registered by the EPA.”9 ents registered with the EPA, researchers have reported that The EPA has registered four formulations of catmint oil, PMD is “the only plant-based repellent that has been advo- including liquids and lotions with various percentages of the cated for use in disease endemic areas by the CDC, due to active ingredient. Each of these products is currently made its proven clinical efficacy to prevent malaria and is consid- by DuPont and exhibit protection times between seven and ered to pose no risk to human health. [PMD] provides very 15 hours.10 AMCA points out that “A commercial version is high protection from a broad range of insect vectors over not yet available, though. Catnip products currently avail- several hours.”5 able through internet suppliers do not possess an EPA regis- PMD is not to be confused with what is frequently tration that validates its efficacy.”9 referred to as “oil of lemon eucalyptus.” In distilling the In 2007, Spero et al. published the results of repellency from leaves of the lemon eucalyptus tree, PMD activity of hydrogenated catmint oil against mosquitoes and is left over as a waste product.5 It is this waste product Catnip Nepeta cataria. Photo black flies in the Journal of Medical Entomology. According that has been shown to be effective in repelling mosqui- ©2013 Steven Foster to the authors, “Iridoid monoterpenoids such as nepetalac- toes, more so than the oil itself. Although insect repellent Lemon Eucalyptus Tree Corymbia citriodora tone have long been known to be repellent to some insect products containing oil of lemon eucalyptus are available, Photo ©2013 Steven Foster ral. My research on [multiple] continents (North and South species.… The related compound dihydronepetalactone Dr. Moore cautions against using anything but CDC- and America, South-east Asia and Africa) has highlighted this (DHN) is also an effective repellent of a number of biting EPA-recommended active ingredients, such as PMD, in past 6 years in a highly malarious area where we use PMD same perception.” insect species.”11 areas with disease risk. every evening in conjunction with long clothing, and we Perhaps more importantly, insect repellents derived Although DHN comprises only a small percentage of Depending on the concentration, PMD formulas can last screen our home and use an insecticide-treated bed net as from plants can be an inexpensive, sustainable method of the oils of N. cataria, the authors explained that it can be up to eight hours,15 and have been shown to be almost as recommended best practise. I have never had a negative skin preventing disease in high-risk regions of the world. “If produced by a chemical process known as catalytic hydro- effective as those containing DEET. In some cases, PMD reaction or a vector-borne disease. Malaria is a preventable plant-based repellents are ethically sourced and produced genation of the nepetalactones in the oil, hence the name has been shown to be more effective than DEET in repelling disease and we have effective tools, both synthetic and natu- then they can bring trade [to] developing countries and are “hydrogenated” catmint oil.11 certain species of mosquitoes. ral, to combat it.” less damaging to the environment,” said Dr. Moore. Spero et al. reported that hydrogenated catmint oil “[Some plant-based ingredients can] better repel certain In 1996, the EPA began compiling annual lists of newly Citronella-Based Insect Repellents 6 (HCO) offered protection for more than four hours, with a vectors, as in the case of PMD’s evident superiority to approved biopesticide active ingredients. Biopesticides are 15% lotion providing protection of more than eight hours. DEET in repelling Anopheles malaria vectors,” said Dr. Although PMD is a widely studied natural insect repel- defined as “naturally occurring substances that control pests They concluded that their results “indicate strongly that Carroll. In a 2006 study published in the Journal of the lent, the plant-based ingredient citronella is arguably more (biochemical pesticides), microorganisms that control pests HCO in different topical formulations offers an effective American Mosquito Control Association, of which Dr. Carroll recognized as a mosquito repellent. Citronella oil has been (microbial pesticides), and pesticidal substances produced alternative to existing natural and synthetic insect repel- was a co-author, he wrote that “PMD has shown unprec- shown to be less effective than DEET, but it still can be a by plants containing added genetic material (plant-incorpo- 11 15 useful tool for repelling mosquitoes in areas without disease 7 lents.” edented repellency and consistency for a botanical.” rated protectants) or PIPs.” In the following year, Polsomboon et al. examined two Similarly, Dr. Moore, who conducts field research around risk. However, before being marketed, the Federal Insecti- separate categories of behavioral responses of mosquitoes the world, has found that PMD is consistently effective. “Citronella has found its way into many commercial cide, Fungicide, and Rodenticide Act requires the EPA to to catmint oil — contact irritancy and non-contact repel- Although her research primarily concerns the prevention of preparations through its familiarity, rather than its effi- conduct rigorous testing of the ingredient to ensure that it cacy,” said Dr. Moore. “Citronella-based repellents only 7 lency — in a paper published in the Journal of the American malaria, the same mosquito-repelling properties will protect does not pose a risk to human health or the environment. Mosquito Control Association. Using two species of mosqui- against other mosquito-borne diseases such as West Nile protect from host-seeking mosquitoes for about 2 hours.” The first year records were available, six ingredients were toes, the researches determined that “catnip oil has strong fever and encephalitis, dengue fever, and yellow fever.16 Citronella was first registered by the EPA in 1948 and 4 addressed, including a German cockroach pheromone and irritant and repellent actions on mosquito test populations “I can attest to the fact that PMD repellents are highly was originally used in perfumes for its pleasant scent. multiple bacteria-derived ingredients. In 2010, the most as indicated by the comparatively low escape time.”12 effective from both my research where they demonstrate Today, citronella candles are ubiquitous in American recent year for which records are available, the list included In its fact sheet on HCO, the EPA cited that “no risks good efficacy and the research of others who all show a backyards, although it also is used in creams, lotions, and 17 approved active ingredients, almost three times as many to human health will be expected from the use of Hydro- consistently good effect in preventing bites from disease- sprays. According to the EPA, citronella is classified as a as were first approved in 1996. Combined, the annual lists genated Catmint Oil based on its low toxicity and current vector insects,” she said. “I have lived in Tanzania for the biopesticide and registered as an insect repellent or feeding

54 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 55 molecules that evaporate more slowly. Vanillan, a relatively 6. New biopesticide active ingredients – 1996. EPA website. large molecular component of the bean (Vanilla Available at: www.epa.gov/oppbppd1/biopesticides/product_ spp., Orchidaceae), has been added with some success to lists/new_ai_1996.htm. Accessed April 16, 2013. botanical insect repellent formulas to reduce the formulas’ 7. Regulating biopesticides. EPA website. Available at: www.epa. 5 gov/pesticides/biopesticides/index.htm#factsheet. Accessed volatility. And in recent years, advances in nanotechnol- April 16, 2013. ogy have provided even more options to increase the dura- 8. What is catnip? Feline Advisory Bureau website. Available at: tion of plant-based repellents. These techniques have been www.fabcats.org/behaviour/other/catnip.html. Accessed April used in some citronella formulas. For example, “[e]ncapsu- 16, 2013. lated citronella oil nanoemulsion [can be] prepared by high- 9. Repellents. American Mosquito Control Association website. pressure homogenization … to create stable droplets that Available at: www.mosquito.org/repellents. Accessed April 19, increase the retention of the oil and slow down release.”5 2016. To counteract the high volatility of some plant-based 10. “Nepeta cataria” - Insect repellents: use and effectiveness. EPA website. Available at: http://cfpub.epa.gov/oppref/insect/ active ingredients, some mosquito repellents contain higher search_results.cfm?Rangetime=&hidSelected=1&ProductNam concentrations of these ingredients. And as with any e=&Ingredient=Catnip+Oil&Company=null&Registration=& dermatological applications of chemicals — plant-based or Submit=Search. Accessed April 16, 2013. synthetic — there is some risk of a reaction. 11. Spero NC, Gonzalez YI, Scialdone MA, Hallahan DL. Repel- “Some essential oils can cause skin irritation,” said Dr. lency of hydrogenated catmint oil formulations to black flies Moore. “Read the label — if there are high concentrations and mosquitoes in the field. Journal of Medical Entomology. of essential oils they are unlikely to be suitable for those 2008;45(6):1080-1086. with sensitive skin. If you have a reaction, immediately 12. Polsomboon S, Grieco JP, Achee NL et al. Behavioral responses of catnip (Nepeta cataria) by two species of mosqui- discontinue use and consult a physician if you have a derma- toes, Aedes aegypti and Anopheles harrisoni, in Thailand. titis that does not resolve after a few days.” Journal of the Mosquito Control Association. 2008;24(4):513- As consumer interest in plant-based products grows, 519. scientists will continue to study plants to learn more about 13. Hydrogenated catmint oil fact sheet. EPA website. Available their insect-repelling properties. Botanical formulas, when at: www.epa.gov/oppbppd1/biopesticides/ingredients/fact- used properly, provide an alternative to synthetic repellents. sheets/factsheet_004801.htm. Accessed April 19, 2013. Although plant-based insect repellents often are not as 14. CDC adopts new repellent guidance for upcoming mosquito effective as DEET, in time, this may change. season [press release]. Atlanta, GA: Centers for Disease Control and Prevention; April 28, 2005. Available at: www. “As technology improves so that formulations make cdc.gov/media/pressrel/r050428.htm. Accessed September 21, Citronella Cymbopogon nardus essential oils and other plant based molecules remain on the 2012. Photo ©2013 Steven Foster skin for as long as DEET, then we will see more effective 15. Carroll SP, Loye J. PMD, a registered botanical mosquito plant-based repellents that can be used to prevent disease. I repellent with DEET-like efficacy. J Am Mosquito Contr. am certainly keen to see this happen if it means that prod- 2006;22(3):507-514. Available at: www.ncbi.nlm.nih.gov/ ucts can be made in a more environmentally sustainable pubmed/17067054. Accessed September 26, 2012. depressant and also as an animal repellent. Oil of citronella Issues Associated with Plant-Based Repellents way through fair trade,” said Dr. Moore. “It will hopefully 16. Infectious disease information: mosquito-borne diseases. comes from 2 species of aromatic grasses, Ceylon citro- As a scientific term, volatility refers to a chemical’s help make repellents such as citronella and PMD more Centers for Disease Control and Prevention website. Available at: www.cdc.gov/ncidod/diseases/list_mosquitoborne.htm. nella (Cymbopogon nardus, Poaceae) and Java citronella (C. tendency to evaporate. Bruised or damaged plants will accessible to those living in disease endemic countries of the winterianus). Citronella is regarded as a highly safe repel- Accessed September 27, 2012. release volatile odors into the environment, which can offer tropics because they often cannot afford to purchase repel- 17. R.E.D. facts: oil of citronella. Environmental Protection lent; in a 1997 reregistration memo, the EPA concluded protection from pests at a distance.4 However, when these lents imported from outside. I am keen to see more manu- that “based on available data, the use of currently registered Agency website. Available at: www.epa.gov/oppsrrd1/REDs/ chemicals are formulated into insect repellents that are facturers taking on this challenge.” factsheets/3105fact.pdf. Accessed September 26, 2012. products containing oil of citronella in accordance with applied to the skin, volatility becomes a problem. 18. Henson S. Re: Using herbal medicines to prevent and treat their approved labeling will not pose unreasonable risks or malaria. HerbClip. April 15, 2005 (No. 010253-278). Austin, 17 PMD is unique in that it has an especially low vapor pres- *Catnip is the Standardized Common Name (SCN) accord- adverse effects to humans or the environment.” sure, which causes it to evaporate slower than other plant- ing to the American Herbal Products Association’s Herbs of TX: American Botanical Council. Botanical prevention and Hydrogenated catmint oil, citronella, and PMD are just based insect repellents. Citronella, however, upon initial Commerce, 2nd edition. Catmint is the Other Common Name treatment of malaria - Part 1 by Yarnell E, Abascal K. Altern three of the hundreds of plants or plant-based ingredients Complement Ther. 2004;206-210. application, is just as effective as DEET, but its high volatil- (OCN). 19. Bissinger BW, Apperson CS, Sonenshine DE, Watson DW, that have been studied for their insect-repelling proper- ity quickly decreases its effectiveness. ties. In addition to hydrogenated catmint oil, citronella, Roe RM. Efficacy of the new repellent BioUD® against three “Some plant-based molecules are incredibly effective in References Exp Appl Acarol PMD, and DEET, Health Canada — the governmental species of ixodid ticks. . 2009:48:239-250. the short term but quickly evaporate and for this reason 1. Division of Vector-Borne Diseases: West Nile Virus. Centers 20. Polsomboon S, Grieco JP, Achee NL, et al. Behavioral body responsible for national public health in Canada — they don’t last as long as the synthetic molecules,” explained for Disease Control website. Available at: www.cdc.gov/ responses of catnip (Nepeta cataria) by two species of mosqui- has approved products containing soybean (Glycine max, Dr. Moore. ncidod/dvbid/westnile/index.htm. Accessed January 7, 2013. toes, Aedes aegypti and Anopheles harrisoni, in Thailand. J Am Fabaceae) oil for mosquito-repelling purposes for up to 2. West Nile virus: What you need to know. Centers for Disease Mosquito Contr. 2008:24(4):513-519. According to Dr. Bernier, volatility is one of the chal- Control website. Available at: www.cdc.gov/ncidod/dvbid/ 3.5 hours, although less research has been conducted on lenges to formulating an effective and long-lasting botanical this particular ingredient. Other commonly-cited botani- westnile/wnv_factSheet.htm. Accessed September 26, 2012. insect repellent. “One the greatest problems with naturally 3. The insect repellent DEET. Environmental Protection Agency cals used to repel mosquitoes include species in the mint based repellents is the volatility of those oils or compounds website. Available at: www.epa.gov/opp00001/factsheets/ family (basil [Ocimum basilicum] and [Mentha within oils that contribute to the observed repellency,” he chemicals/deet.htm. Accessed September 25, 2012. x piperita]), 2-undecanone (an extract from tomato plants said. “There are a number of natural compound repellents 4. Reregistration eligibility decision (RED): DEET. Environ- [Solanum lycopersicum, Solanaceae]), neem oil (Azadi- on the market and some of these do repel for a short time.” mental Protection Agency website. Available at: www.epa.gov/ rachta indica, Meliaceae), lemongrass (Cymbopogon citratus, However, there are some ways to mitigate the effects of oppsrrd1/REDs/0002red.pdf. Accessed September 28, 2012. 5. Maia MF, Moore SJ. Plant-based insect repellents: a review Poaceae), (Foeniculum vulgare, Apiaceae), and rue the high volatility of plant-based active ingredients. One (, Rutaceae).18-20 of their efficacy, development and testing. Malaria Journal. option is to combine plant-based chemicals with larger 2011;10(Suppl 1):S11. Available at: www.ncbi.nlm.nih.gov/ pmc/articles/PMC3059459/. Accessed September 21, 2012.

56 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 57 Chase Tree Berry Vitex agnus-castus. Polycystic ovarian syndrome (PCOS) — a hormonal Photo ©2013 Steven Foster endocrine disorder that affects more than 5 million women in the United States alone — manifests itself through a spectrum of symptoms, including irregu- lar or absent menstruation (known as amenorrhea), lack of ovulation, multiple cysts on the ovaries, acne, excessive facial hair (hirsutism), and obesity.1 (Many women with PCOS are of normal weight — referred to as “lean” PCOS.) PCOS is one of the leading reasons behind female infertility, and it also increases the likeli- hood of miscarriage and infant death during or shortly after birth. Additionally, PCOS can lead to serious health issues, including endometrial cancer, osteoporo- sis, heart disease, and diabetes.1 While the cause of PCOS is uncertain, complex, and variable, several conditions are present within the bodies of women with PCOS that lead to their often-distressing symptoms. These typically include higher-than-normal levels of male hormones — particularly testosterone — lower-than-normal levels of the female hormone progester- one, elevated levels of the hormone prolactin in some cases, and abnormal insulin regulation.1 Drugs prescribed for PCOS include oral contraceptives, which decrease male hormone levels and may normalize a woman’s menstrual cycle, and metformin (brand name Glucophage®), a drug commonly used to treat type 2 diabe- tes that has been found to help PCOS patients regulate insulin levels and support conception.1 Women with PCOS who are trying to conceive are sometimes prescribed clomi- phene (Clomid,™ Serophene®), a fertility drug that stimu- lates ovulation. These pharmaceuticals, unfortunately, are not without significant drawbacks. Oral contraceptive pills often produce myriad side effects (increased appetite, mood swings, weight gain, nausea, etc.), cannot be used by women with PCOS who are trying to conceive, and frequently worsen insulin resistance in PCOS patients.2 Clomid can lead to undesired multiple-birth pregnancies,2 and the US Food and Drug Administration (FDA) warns that it increases the risk of major birth defects and should not be used in pregnancy.3 Although metformin is showing potential to help manage PCOS symptoms and perhaps boost conception chances, some women experience discouraging gastrointestinal side effects from the drug,4 which has not been approved by FDA to treat PCOS.1 “Herbs are important as there are few truly effective phar- maceutical options,” said Jillian Stansbury, ND, a Washing- ton state-based naturopathic physician and author of The PCOS Health and Nutrition Guide (Robert Rose, 2012). “Herbs are a safe and nutritive option to support ovarian function, endocrine feedback loops, thyroid function, and blood sugar regulation and metabolism. I have had a great many patients with PCOS over the years, and can report Treating PCOS Naturally overall good success in treating the various forms and presentations of PCOS: helping women lose weight, restor- Clinical experience and scientific evidence support medicinal ing normal menses, helping infertile women to conceive and carry the pregnancy, and improve metabolic function and herbs, nutritional supplements, and lifestyle interventions to treat prevent diabetes” (email, February 11, 2013). symptoms of this common female endocrine disorder Integrative medicine physician, herbalist, and midwife By Lindsay Stafford Mader Aviva Romm, MD, agrees that herbs play a significant role

58 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 59 in PCOS treatment. “Weight loss is the most effective inter- ity, acne, and excessive facial hair. Women who have been vention, and metformin is actually not a bad option, but of diagnosed with PCOS or those who think they might have course herbs are natural and generally safe so a great option PCOS should obtain a blood test in order to determine to at least try for folks wanting to avoid pharmaceuticals,” if their testosterone and/or prolactin levels are increased. said Dr. Romm (email, February 10, 2013). “They might be If they are, Dr. Stansbury suggests chaste tree berry, lico- particularly helpful in the insulin resistance aspects of the rice root, and the Traditional Chinese Medicine (TCM) condition, as well as stress hormone mediation.” herb dong quai (Angelica sinensis, Apiaceae) root to restore The PCOS section in Dr. Romm’s 2010 book, Botanical normal menses. (For herb use during pregnancy, please see Medicine for Women’s Health (Churchill Livingstone), illus- the “Conclusion” section on page 63.) trates the potential that herbs offer for this complex condition “I have seen many amenorrheic women be able to regain by presenting a successful case report. Author of the section, their menses — some of them quite quickly,” said Dr. Stans- Angela Hywood, ND, writes that the PCOS patient took six bury. “I remember one case with a woman who hadn’t had herbs* — chaste tree berry (Vitex agnus-castus, Lamiaceae), a menses for more than three years begin to menstruate licorice (Glycyrrhiza glabra, Fabaceae), white peony (Paeo- after two weeks on an herbal tincture of chaste tree, saw nia lactiflora, Paeoniaceae), gymnema (Gymnema sylves- palmetto, and licorice. And then we did some trial-and- tre, Apocynaceae), echinacea error, and when we stopped (Echinacea spp., Asteraceae), the formula, her menses and schisandra (Schisan- Because PCOS is an endocrine would stop again.”5 dra chinensis, Schisandraceae) Chaste tree has been used — in addition to eating a low- disorder, herbs that balance for thousands of years for carbohydrate diet. According numerous women’s health to the report: hormone levels can be very helpful issues, including menstrual After five months on disorders. Although no the herbal protocol, the existing studies have patient’s cycle regulated in improving most PCOS symptoms, directly examined its effects to a 32-day length…. in PCOS patients, a small Problematic symptoms including amenorrhea, infertility, collection of published such as mastalgia [breast scientific and clinical pain], acne, and hirsutism acne, and excessive facial hair. evidence supports its ability diminished significantly to treat some of the condi- during the five-month tion’s symptoms.6 Several program. The lipid profile has improved to within older clinical trials reportedly found chaste tree to result normal ranges…. She lost a total of 12 percent body in normal menstrual cycles,6 and more recent research has weight in the five months. The client became pregnant shown that it is successful at decreasing elevated prolactin in her second month of actively trying to conceive.2 levels and improving fertility and the body’s progesterone- Natural treatment plans formulated for PCOS patients by producing process.7 NDs, herbalists, and integrative physicians typically focus Licorice, a well-researched medicinal plant in the legume on addressing three main types of PCOS manifestations: family, contains compounds that exhibit estrogenic activ- (1) hormonal imbalances; (2) insulin, blood sugar, and ity. Some studies have found licorice to reduce testoster- metabolic sensitivities and/or irregularities; and (3) stress one levels in healthy women, suggesting that it might also response and management. be useful for women with PCOS.8 Dong quai also exhib- “My general approach has emphasized diet and exer- its estrogenic activity, and has been used for many years cise as a foundational therapy,” said Dr. Stansbury, “and I to treat gynecological conditions. While more research is create specific herbal and nutritional protocols for individ- warranted to support its traditional uses, limited evidence ual patients. Because PCOS has many presentations, there has found that it can successfully treat amenorrhea.9 could be a variety of different approaches to address specific For women whose PCOS-related hormone imbalances presentations.” are making conception difficult, Dr. Stansbury recom- The following herbs and other natural approaches for mends several herbs, including chaste tree berry, dong quai, treating PCOS and its symptoms are based on practitioners’ Indian kudzu (Pueraria spp., Fabaceae) leaf, and knotweed experience in treating women with PCOS, as well as several (Polygonum multiflorum, Polygonaceae) root. Although controlled human studies. The numerous medicinal plants, these herbs have been shown in her clinical practice to help substances, and techniques discussed herein represent a women with PCOS to conceive, Dr. Stansbury notes that broad overview of this mixed-source data, and are not being success varies and can take longer when working toward suggested for comprehensive or concurrent use. this more complex outcome, and thus several herbal combi- nations are often formulated and tried on each individual Balancing Hormones patient. In her 1999 book Women’s Encyclopedia of Natural Because PCOS is an endocrine disorder, herbs that Medicine (Keats Publishing), Tori Hudson, ND, suggests balance hormone levels can be very helpful in improving that chaste tree be taken for at least three or four months.6 most PCOS symptoms, including amenorrhea, infertil- Additional menstruation-normalizing/hormonal-balanc- Red Clover Trifolium pratense. Photo ©2013 Steven Foster

60 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 61 ing herbs recommended by various naturopathic doctors clomiphene rates of ovulation were higher at 93.5 percent.15 she said. “Lentils, split pea soup, hummus, baked beans, • ashwagandha (Withania somnifera, Solanaceae) and herbalists based on their clinical experience and tradi- black bean soup, kidney beans in salads, refried beans.... • American ginseng (Panax quinquefolium, Araliaceae) tional history include the following: Improving Insulin Regulation There are unlimited possibilities.” She additionally recom- and Asian ginseng (P. ginseng) • red raspberry (Rubus idaeus, Rosaceae) leaf Many women with PCOS have insulin resistance, mends prickly pear (Opuntia ficus-indica, Cactaceae) fruit • licorice • saw palmetto (Serenoa repens, Arecaceae) berry also known as metabolic syndrome, which presents itself for improving insulin resistance,5 an action that has been • rhaponticum (Rhaponticum carthamoides, Asteraceae) • ginger (Zingiber officinale, Zingiberaceae) root/ through weight gain, high blood pressure, high blood sugar, supported by years of use in traditional Mexican medicine • rhodiola (Rhodiola rosea, Crassulaceae) rhizome and high cholesterol. Others experience insulin resistance- as well as in preliminary animal and human studies, which • schisandra • rosemary (Rosmarinus officinalis, Lamiaceae) herb related hyperinsulinemia, which is higher-than-normal found the fruit to lower high blood sugar.22 Additional in In Integrative Women’s Health, Dr. Bongaard recom- • feverfew (Tanacetum parthenium, Asteraceae) leaf levels of insulin in the blood that can cause hyperglycemia vitro and animal studies found prickly pear to lower triglyc- mends various mind-body therapies, including yoga, guided • partridge berry (Mitchella repens, Rubiaceae)* as well as hypoglycemia (low blood sugar), the latter of eride, low-density lipoprotein cholesterol, and total choles- visualization, hypnosis, biofeedback, and aromatherapy • (Artemisia vulgaris, Asteraceae) herb which produces symptoms such as lightheadedness, nausea, terol levels — all of which can be a concern for women with for decreasing stress hormones and improving blood pres- • false unicorn (Chamaelirium luteum, Melanthia- shaking hands, and confusion. A woman who has been PCOS. Dr. Stansbury suggests using several tablespoons of sure and blood sugar. In fact, a recent controlled study ceae) root — a North American herb with an at-risk diagnosed with PCOS or who thinks she might have the prickly pear fruit juice in smoothies or sparkling water, or conducted in India and published in the July 2012 issue of conservation status. condition should have her blood tested for insulin sensitiv- using a splash with vinegar and oil for salad dressing or as the International Journal of Yoga found that a daily, hour- The following phyto-estrogenic herbs also are recom- ity. If she is found to exhibit full or partial manifestations, a marinating sauce.5 long yoga and meditation program improved anxiety symp- mended: the pharmaceutical metformin usually is prescribed, and Vitamin D, which enhances the action of insulin, also toms in teenage girls with PCOS.23 • black cohosh (Actaea racemosa, Ranunculaceae) root/ several herbs and foods exhibit similar therapeutic actions. can be helpful, as well as the mineral chromium.5 Accord- rhizome Due to their inositols and related compounds, Dr. Stans- ing to the PCOS section in the 2010 book Integrative Conclusion • red clover (Trifolium pratense, Fabaceae) flower bury noted that legumes are especially good for women Women’s Health, “accumulating evidence” supports chro- Additional supportive therapies for PCOS include nurtur- • alfalfa (Medicago sativa, Fabaceae) herb with PCOS-related insulin concerns. mium for enhancement of “the metabolic action of insu- ing a healthy liver — an organ crucial to the breaking down • flax (Linum usitatissimum, Linaceae) seed “These compounds work together to treat insulin resis- lin and decreasing total cholesterol and LDL…. It has the • soy (Glycine max, Fabaceae) bean, and tance,” she said. “They support signal transduction, the greatest benefit on obese, insulin-resistant individuals.”4 Red Raspberry Leaf Rubus idaeus. Photo ©2013 Steven Foster • hops (Humulus lupulus, Cannabaceae) stro- ability of a cell to receive insulin and then tell the nucleus Integrative medicine physician and author of this section, biles.2,5,6,10,11 of the cell to respond to it.” Bridget Bongaard, MD, recommends 200 to 1,000 mcg of Although little human clinical research has been Not only have inositols garnered positive clinical chromium picolinate per day,4 and the mineral also can be conducted on herbs specif- outcomes among herbalists found in brewer’s yeast, hibiscus (Hibiscus sabdariffa, Malva- ically for PCOS treat- and NDs, but their use in ceae) flowers and calyx, dandelion (Taraxacum officinale, ment, some new studies Not only have inositols garnered treating PCOS also has been Asteraceae) leaves, (, Asteraceae), present promising possi- supported by clinical trials. and lemongrass (Cymbopogon citratus, Poaceae).5 bilities. A traditional - A randomized, controlled Dr. Bongaard additionally advises PCOS patients to nese formulation of licorice positive clinical outcomes among clinical trial published in a consider ingesting moderate amounts of tea (Camellia and white peony — called 2010 issue of the journal sinensis, Theaceae) and/or coffee (Coffea arabica, Rubiaceae) Shakuyaku-Kanzo-To — Gynecological Endocrinology due to caffeine’s well-documented ability to improve insulin has been shown in trials on herbalists and NDs, but their use found that a daily dosage of sensitivity, taking 1 to 6 grams daily of cinnamon (Cinna- women with and without 4 grams myo-inositol and momum verum, Lauraceae) for its ability to improve insu- PCOS to decrease testoster- in treating PCOS also has been 400 mcg folic acid signif- lin resistance and reduce fasting blood glucose — activi- one levels, stimulate ovula- icantly increased ovula- ties exhibited in human trials — or 200 to 400 mg of tion, and promote concep- tion and conception rates alpha-lipoic acid to reduce insulin resistance and oxida- tion.2 supported by clinical trials. in infertile PCOS women tive stress.4 Dr. Hywood writes in Botanical Medicine for A 2013 Iranian study on compared with 1,500 mg Women’s Health that the traditional anti-diabetic Indian dried aerial parts of wood daily of metformin.16 herb gymnema has been shown in experimental models to betony (Stachys lavandulifolia, Lamiaceae) found that this Another inositol form — D-chiro-inositol — also has been lower blood sugar levels by preventing glucose absorption, mint-family herb ameliorated abnormal uterine bleeding in shown in earlier human studies to be very effective at treat- and that fish oil may also benefit PCOS patients due to its PCOS patients as well as the synthetic progesterone, and ing PCOS,17 and more recent research suggests a combina- reduction of serum triglycerides.2 that it lowered testosterone levels and improved ovarian tion of the two forms may be just as effective.18,19 Stud- condition more than the progesterone.12 ies are currently comparing the two against each other.20 Stress Response and Management Similarly, a study on the black cohosh root extract Klima- (Furthermore, a small, controlled, randomized clinical trial An important yet perhaps less-recognized aspect of dynon® (an ethanolic extract produced by German company has shown myo-inositol to be superior to D-chiro-inositol PCOS treatment is managing a patient’s stress level. As Bionorica) found that it increased PCOS patients’ proges- in improving embryo quality and pregnancy rates.21) Good Dr. Hywood explains, “In response to stress, the adre- terone levels, significantly reduced luteinizing hormone sources of inositols are brown rice (Oryza sativa, Poaceae); nals release cortisol, inducing an elevation in prolactin … levels, and improved ovulation and endometrial thickness legume family (Fabaceae) plants including soy, kidney and increased androgen synthesis, which in turn leads to more than Clomid.13 Although pregnancy rates were higher beans (Phaseolus vulgaris), garbanzo beans (Cicer arietinum), menstrual cycle dysregulation, especially anovulation, char- in the black cohosh group, the difference was not statisti- carob (Ceratonia siliqua) — available in powder form or in acteristic of PCOS.” In fact, Dr. Hywood notes that botani- cally significant. supplements — astragalus (Astragalus membranaceus), and cal PCOS treatments should first address stress and that A 2010 controlled trial on 80 women with PCOS found alfalfa; and legume-family herbs such as licorice. Small adaptogenic herbs “should be given primary consideration” that a maitake mushroom (Grifola frondosa, Polyporaceae) amounts of D-chiro-inositol are found in buckwheat (Fago- because they “improve resistance to stress through [modu- extract significantly increased ovulation when used alone pyrum esculentum, Polygonaceae). Inositol supplements also lation] at the adrenal level.” She lists the following herbs and in combination with clomiphene.14 While subjects are available over-the-counter at many health food stores. as helpful adaptogens for PCOS treatment (plant parts not taking the maitake had approximately 77 percent ovula- Dr. Stansbury recommends eating as much beans as specified): tion — which Dr. Hudson noted as “quite impressive” — possible. “As much one can stand, thus a cup or more daily,”

62 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 63 Prickly Pear Fruit Opuntia ficus-indica. Photo ©2013 Steven Foster Carob Ceratonia siliqua. Photo ©2013 Steven Foster of excess hormones — particularly through limiting alcohol intake review of clinical trials. Planta Med. November 2012; [epub ahead and ingesting liver-supportive herbs such as milk thistle (Silybum of print]. doi: 10.1055/s-0032-1327831. marianum, Asteraceae).5 Dr. Stansbury highlighted the signifi- 8. Armanini D, Mattarello MJ, Fiore C, Bonanni G, Scaroni C, cant role that alcohol plays in women with PCOS, for whom she Sartorato P, Palermo M. Licorice reduces serum testosterone in healthy women. Steroids. 2004;69(11-12):763-766. recommends limiting consumption to just a few alcoholic drinks 9. Dong quai (Angelica sinensis). Mayo Clinic website. Available at: per week, if any at all. www.mayoclinic.com/health/dong-quai/NS_patient-Dongquai. “Alcohol has one of the biggest glycemic indices of any food- Accessed March 20, 2013. stuff, more than eating a spoonful of sugar.5 So if anyone is prone 10. Hobbs C, Keville K. Women’s Herbs, Women’s Health. Loveland, CO: to insulin resistance, quantities of alcohol will just challenge Botanica Press; 1998. your blood sugar regulation. Alcohol also challenges the liver, of 11. Gladstar R. Herbal Healing for Women. New York, NY: Fireside; course, and if your liver is busy detoxifying alcohol, then it has less 1993. enzymes or less power and reserves to metabolize your hormones.” 12. Jalilian N, Modarresi M, Rezaie M, Ghaderi L, Bozorgmanesh M. Phytotherapeutic management of Polycystic Ovary Syndrome: role Regular and moderate exercise and resultant weight loss is para- of aerial parts of wood betony (Stachys lavandulifolia). Phytother Res. mount for overweight PCOS patients as it reduces insulin and 2013. doi: 10.1002/ptr.4921. testosterone levels — often providing dramatic relief of most PCOS 13. Kamel HH. Role of phyto-oestrogens in ovulation induction in symptoms.2,4 “Weight loss alone,” writes Dr. Hywood, “has led to women with polycystic ovarian syndrome. Eur J Obstet Gynecol achievement of pregnancy in 60% of cases without other medical Reprod Biol. 2013. doi: 10.1016/j.ejogrb.2012.12.025. intervention.” Likewise, low-carb, whole foods diets also have been 14. Chen J, Tominaga K, Sato Y, et al. Maitake mushroom (Grifola shown in clinical experience and human studies to reduce insu- frondosa) extract induces ovulation in patients with polycystic ovary lin resistance and testosterone levels in women with PCOS.5,24 syndrome: a possible monotherapy and a combination therapy after failure with first-line clomiphene citrate. J Altern Complement Med. Additionally, a small controlled clinical trial recently found that 2010;12(12):1295-1299. acupuncture increased the frequency of ovulation in women with 15. Hudson T. Maitake mushroom extract and polycystic ovarian PCOS.25 syndrome. March 31, 2011. Dr. Tori Hudson, N.D. blog. Available Although women with PCOS are understandably eager to at: http://drtorihudson.com/botanicals/maitake-mushroom-extract- improve their symptoms, enjoy an improved quality of life, and, and-polycystic-ovarian-syndrome/. Accessed March 19, 2013. often times, to start a family, they must keep in mind that herbal, 16. Raffone E, Rizzo P, Benedetto V. Insulin sensitiser agents alone nutritional, and lifestyle therapies can take time. In fact, Dr. Stans- and in co-treatment with r-FSH for ovulation induction in PCOS bury recommends that PCOS women hoping to have children women. Gynecol Endocrinol. 2010;26(4):275-280. 17. Nestler J, Jakubowicz D, Reamer P, Gunn R, Allan G. Ovulatory “take several months, even a year, to prepare yourself, improve your and metabolic effects of d-chiro-inositol in the polycystic ovary fertility, and decrease the chance of miscarriage by improving your syndrome. N Engl J Med. 1999; 340:1314-1320. diet and by taking key supplements.”5 18. Nordio M, Proietti E. The combined therapy with myo-inositol “[Women] might notice improvement as early as a month or and D-chiro-inositol reduces the risk of metabolic disease in PCOS two,” said Dr. Stansbury, “but since this is shifting your whole overweight patients compared to myo-inositol supplementation hormonal balance and acting on the liver and adrenals and ovarian alone. Eur Rev Med Pharmacol Sci. 2012;16(5):575-581. function and pituitary feedback loops, I give women a six-month 19. Galletta M, Grasso S, Vaiarelli A, Roseff SJ. Bye-bye chiro-inositol- to 12-month game plan.” myo-inositol: true progress in the treatment of polycystic ovary syndrome and ovulation induction. Eur Rev Med Pharmacol Sci. If a woman with PCOS conceives a child, most of the herbs 2011;15(10):1212-1214. mentioned above should not be used during pregnancy, unless 20. Myo-inositol versus D-chiro-inositol in the treatment of polycys- recommended by the patient’s healthcare provider.2 A few — includ- tic ovary syndrome and insulin resistance: evaluation of clinical, ing ginger, red raspberry leaf, echinacea, and partridge berry — metabolic, endocrine and ultrasound parameters. ClinicalTrials.gov. have safe pregnancy profiles.10 As in most cases, readers are advised Available at: www.clinicaltrials.gov/ct2/show/study/NCT01514942? to consult their healthcare provider for more information. term=inositol+pcos&rank=2. Accessed March 27, 2013. 21. Unfer V, Carlomagno G, Rizzo P, Raffone E, Roseff S. Myo-inositol References rather than D-chiro-inositol is able to improve oocyte quality in 1. Polycystic ovarian syndrome (PCOS) fact sheet. Office on Women’s intracytoplasmic sperm injection cycles. A prospective, controlled, Health website. Available at: http://womenshealth.gov/publica- randomized trial. Eur Rev Med Pharmacol Sci. 2011;15(4):452-457. tions/our-publications/fact-sheet/polycystic-ovary-syndrome.cfm#b. 22. Fengang JM, Konarski P, Zou D, Stintzing FC, Zou C. Nutritional Accessed February 15, 2013. and medicinal use of cactus pear (Opuntia spp.) cladodes and 2. Romm A. Botanical Medicine for Women’s Health. St. Louis, MO: fruits. Frontiers in Bioscience. 2006;11:2574-2589. Churchill Livingstone; 2012. 23. Nidhi R, Padmalatha V, Nagarathna R, Amritanshu R. Effect of 3. Goodman B. Infertility treatments may raise birth defect risk. holistic yoga program on anxiety symptoms in adolescent girls with WebMD Health News. May 5, 2012. Available at: www.webmd.com/ polycystic ovarian syndrome: A randomized control trial. Int J Yoga. infertility-and-reproduction/news/20120505/infertility-treatments- 2012;5(2):112-117. doi: 10.4103/0973-6131.98223. may-raise-birth-defect-risk. Accessed February 15, 2013. 24. Mavropoulos JC, Yancy WS, Hepburn J, Westman EC. The effects 4. Maizes V, Low Dog T (eds.). Integrative Women’s Health. New York, of a low-carbohydrate, ketogenic diet on the polycystic ovary NY: Oxford University Press; 2010. syndrome: A pilot study. Nutr Metab. 2005;2:35. 5. Stansbury J. The PCOS Health & Nutrition Guide. Toronto, Ontario, 25. Johansson J, Redman L, Veldhuis PP, Sazonova A, Labrie F, Holm Canada: Robert Rose; 2012. G, Johannsson G, Stener-Victorin E. Acupuncture for ovulation 6. Hudson T. Women’s Encyclopedia of Natural Medicine: Alternative induction in polycystic ovary syndrome: A randomized controlled Therapies and Integrative Medicine. Los Angeles, CA: Keats Publishing; trial. Am J Physiol Endocrinol Metab. 2013 Mar 12. [Epub ahead of 1999. print]. 7. van Die MD, Burger HG, Teede HJ, Bone KM. Vitex agnus-castus extracts for female reproductive disorders: a systematic

64 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 65 witch hazel (Hamamelis virginiana, Hamamelidaceae)-based hemorrhoid cream. In 1917, Dr. Schwabe’s son, Willmar Legacy Herb Companies Schwabe II, inherited the company. Today, Schwabe Phar- maceuticals maintains its status as an independent, family- owned business and is currently in its fifth generation.3 “Schwabe always has been a family-owned company,” said Uta Hülsermann, PhD, Schwabe’s official spokes- person (email, January 10, 2013). “There have been three Willmar Schwabes over the generations.” One of the original Willmar Schwabe’s most significant contributions to herbal medicine was the 1872 publication of Pharmacopoeia Homeopathica Polyglotta, a homeopathic pharmaceutical reference guide that has largely withstood the test of time. “Dr. Willmar Schwabe’s Pharmacopoeia Homeopathica Polyglotta received a lot of attention in its time because up to then, [there] existed a multitude of different Pharmacopoeiae and this publication was regarded as standard publication that finally ‘cleared the mess,’” said Dr. Hülsermann (email, February 6, 2013). By 1872, it had been published in English, German, and French, and it remains an indispensable reference in all German pharma- cies, she added. Today, the company has expanded far beyond its original roots in Leipzig, Germany. Dr. Willmar Schwabe Pharma- ceuticals, now headquartered in Karlsruhe, Germany, has more than 20 subsidiaries and joint ventures around the world, employing more than 3,500 people on five conti- nents and in more than 60 countries.4 Schwabe North America, which operates in the United States and Canada, comprises the well-known brands Nature’s Way®, Enzy- matic Therapy®, and Integrative Therapeutics®.4 Michael Devereux, chief executive officer of Schwabe North America, said it was Schwabe’s commitment to improving the lives of individuals through natural products Historic photo of Schwabe Pharmaceuticals analytical laboratory. that led him to the company. Photo ©2013 Schwabe “What truly attracted me, though, was the mission of Schwabe's first phytopharmaceutical product, "Schwabe's Hamamelis the business, and frankly of the industry, which is to focus ointment," today's Hametum®. Image ©2013 Schwabe on products and solutions tied into people improving their health and wellness,” said Devereux (email, February 14, lar systems, as well as urological and respiratory conditions. 2013). “Natural products that have existed from decades of The company’s research division is responsible for numer- Dr. Willmar Schwabe Pharmaceuticals: studies on ingredients for safety and efficacy seems to me to ous processes, from screening new plants for potential medicinal activity to conducting clinical trials of finished be a great way to start on the path to improving your health, 3 An Herbal Legacy Company before introducing something that is not natural. They are products. a first-line solution.” “Schwabe’s clinical research on phytomedicines … has German Namesake’s Founding Values Continue to Guide Company Practices significantly contributed to the acceptance of science-based A History of Evidence-Based Natural Medicine phytotherapy in the medical community,” the company By Tyler Smith The success of Schwabe’s global operations stems from a states on its website. “Looking back on the long in-house commitment to values put forth by Dr. Willmar Schwabe: tradition of such studies, Schwabe Pharmaceuticals may be Editor’s note: This is the second article in a derived from the bark of the white willow regarded as the inventor of evidence-based phytomedicine. series on legacy herbal businesses that have been tree (Salix alba, Saliaceae).1,2 Almost a reliability, innovation, quality, and responsibility.3 “He already was dedicated to prove scientifically the effi- Our dedication to proving the efficacy and safety of our operating for more than 100 years. century and a half later, Dr. Willmar phytomedicines through rigid pharmacological and clinical In 1866, just three years after receiving Schwabe Pharmaceuticals has become an cacy of the plant extracts and to set quality standards for the extraction and production process,” Dr. Hülsermann studies is unique.” his doctorate in pharmaceutics, Willmar industry leader in natural pharmaceutical In 2008, Schwabe was awarded the American Botani- Schwabe founded the company that still research and development, and is generally explained. “As a global leader in natural health, Schwabe strives to enhance the quality of life through innovative, cal Council’s inaugural Varro E. Tyler Commercial Invest- bears his name. At the time, the world was acknowledged as the leading manufacturer ment in Phytomedicinal Research Award. According to experiencing significant scientific advance- of phytomedicines worldwide.3 safe, and efficacious products.” Schwabe’s products are tested extensively for efficacy an HerbalEGram article about the award, “Many of the ments, including the use of early anesthet- A little over a decade after Dr. Willmar scientific methods and techniques developed and used ics such as ether and chloroform, and the Schwabe Pharmaceuticals was founded, the and safety in scientific studies and clinical trials. In total, Schwabe holds more than 800 registrations worldwide for by Schwabe during the past century have had a signifi- development of aspirin, based on a synthetic company launched its first phytomedicinal cant influence on today’s pharmaceutical and biochemical chemical modeled after salicin, originally product, Schwabe’s hamamelis ointment, a its phytomedicines, most of which focus on four key thera- peutic areas, including the central nervous and cardiovascu- research.”

66 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 67 One of the scientific methods Dr. Willmar Schwabe “High-quality raw plant materials are mandatory for the Dirk Reischig, PhD, Schwabe’s chairman and CEO, developed for quality control was capillary analysis, a production of our unique phytomedicines,” the website explained how the company’s founding values will continue technique used to separate the components of a substance states. “Apart from the quality aspect, this also helps to to sustain the 147-year-old company.3 “We believe that into its various phases using special absorbent paper. avoid over-exploitation of wild populations of these medici- innovative phytomedicines will become increasingly impor- “Nowadays, this technique is obsolete, but was the basis nal plants and contributes to the conservation of biodiver- tant over the next few decades,” he stated. “In the future, for modern techniques, as for example, capillary electro- sity.” phytomedicines will help people, worldwide, to lead a phoresis or gas chromatography,” said Dr. Hülsermann Schwabe’s environmental stewardship is a value that sustainable, productive, and healthy life.” (email, March 28, 2013). “Those techniques are widely remains an integral component of the company’s opera- For a company that started with one man committed to used in research, development, quality control and all tions. “As a company with a strong tradition and dedication harnessing and verifying the healing power of plants for other fields of analytics. Gas chromatography is used in to research, cultivation, and sustaining … nature’s valu- consumer use, Schwabe’s motto is particularly appropriate: our company as well.” able resources, we are still following our founding father’s “From Nature. For Health.” Of all of Schwabe’s products, the most-recognized is philosophy,” said Dr. Hülsermann. “So the sustainability formulated from the ancient Ginkgo biloba (Ginkgoaceae) of plants and their growing and harvesting are of utmost References tree. “The most important and most popular product of importance for us and our current and future business.” 1. Timeline of important dates and events in the development of Schwabe is EGb 761®, a special Ginkgo biloba extract,” While the sustainable production of ingredients is key to anaesthesia. History of Anaethesia website. Available at: www. said Dr. Hülsermann. “EGb 761® is marketed worldwide securing future supplies, ensuring that affordable products histansoc.org.uk/timeline.html. Accessed January 8, 2013. 2. Willow bark. University of Maryland Medical School in more than 60 countries. Depending on the market, it is reach as many consumers as possible is equally as impor- website. Available at: www.umm.edu/altmed/articles/willow- used in the therapy of cognitive disorders such as demen- tant. bark-000281.htm. Accessed January 9, 2013. tia and cognitive impairment, vertigo and tinnitus, and “An objective we all need to focus on within the herb 3. About us. Dr. Willmar Schwabe Pharmaceuticals website. PAOD (peripheral arterial occlusive disease).” and dietary supplement industry is to keep these products Available at: www.schwabepharma.com/international/about-us/ Other key Schwabe products include Prostagutt®, a saw affordable and available wherever people are looking for index.php. Accessed January 4, 2013. palmetto [Serenoa repens, Arecaceae] berry extract product them,” said Devereux of Schwabe North America. “Our 4. A legacy of quality. Schwabe North America website. Available used in benign prostate hyperplasia therapy; Prostagutt® strategy is developing to serve not just the 300 million at: www.schwabenorthamerica.com/. Accessed January 4, 2013. forte, a combination of saw palmetto extract and nettle people in America, but worldwide, so we are learning every (Urtica dioica, Urticaceae) root extract; Venoplant®, a day more about consumer wants and needs in countries all horse chestnut [Aesculus hippocastanum, Sapindaceae] over the world and how to create affordable solutions that seed extract used in chronic venous insufficiency; and support those wants and needs.” the latest development, Lasea®, a lavender [Lavandula angustifolia, Lamiaceae] flower essential oil-based product for subsyndromal anxiety disorder. The importance of phytomedicines for consumers is a driving factor for Schwabe’s continued research and devel- opment of new plant-based medicines. “In many cases, phytomedicines offer an additional therapeutic alterna- tive in the treatment of patients,” said Dr. Hülsermann. “With phytomedication, compliance is often better since [adverse] side-effects and drug-to-drug interactions occur in [fewer] cases and are generally less serious than with synthetic [pharmaceutical] agents.” Commitment to Quality and Sustainability In addition to its focus on research, Schwabe controls virtually every other aspect of the development of its phytomedicines, from raw material production to phar- maceutical-grade manufacturing, as well as marketing and sales.4 “Schwabe ‘owns’ the production process of many of its phytomedicines from the cultivation to the harvesting of the plants and the whole production cycle,” Dr. Hülser- mann explained. Currently, the company has plantations in Europe, South Africa, and the United States, where plants are grown under controlled conditions that follow Good Agricultural Practice guidelines. To ensure maximum potency, Schwabe monitors the levels of plants’ key active constituents throughout the growing season in order to harvest at the ideal time. Top photo: Ginkgo plantation Middle photo: Entrance of Schwabe headquarters in Karlsruhe, Schwabe quality assurance. Germany. Photos ©2013 Schwabe Photo ©2013 Schwabe

68 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 69 BOOK REVIEWS BOOK REVIEWS

Herbal Supplements and the a section on Hippocrates, there was tion by a plant) that (1) has been used kudzu (Pueraria montana, Fabaceae), the molecular level, it does not mean “every medicine derived from miner- Brain: Understanding Their Health discussion of how his humoral theory for this purpose for hundreds of years, daffodil (Narcissus pseudonarcissus, that one is inherently free of bias, or als, as well as aromatics, and from Benefits and Hazards by S.J. Enna of disease held back the progress of and (2) that shows sedative effects in Amaryllidaceae), passion flower (Passi- that another’s truth on a different level every species of plants” — in all, some and Stata Norton. Upper Saddle medicine for hundreds of years. There animals, unless and until we have posi- flora incarnata, Passifloraceae), and tea of organization is somehow less useful. 220 plants, 61 minerals, and 19 animal River, NJ: FT Press; 2012. Hardcover, was no mention of his statement that tively identified a single component (Camellia sinensis, Theaceae), as well Learning what questions to ask and in drug products. This treatise is one of 272 pages. ISBN: 978-0132824972. we should “let food be thy medicine that reaches the brain in sufficient as selected caffeinated beverages. I what order to ask them is a useful skill the more important pharmaceutical $34.99. and medicine be thy food.” There quantities and binds to a known brain found the coverage of these to be very and can be practiced while reading texts from the early Middle Ages, with Herbal Supplements and the Brain was also no mention of his famous receptor that could account for the uneven. This was especially the case this book. But again, it leads to a pre- surviving manuscripts from the 7th is a rather unique book. While the contributions on the ethics of medi- pharmacologic property. for phytomedicines that are the subject specified end, i.e., a single compound through 11th centuries. This important subject matter is common to readers of cine including the physician’s oath “to The next chapter drives this point of thousands of publications such as binding to a known receptor. work has been little known until Nich- HerbalGram, the fact that it’s written abstain from doing harm.” home by discussing the brain as a ginkgo and St. John’s wort. The vast Mechanism of action is a highly olas Everett’s thorough, competent by two leading main- Chapter 3 is about “target” for medication. In covering literature was not evenly reviewed, and interesting and useful tool. But I think study and English translation. The stream pharmacolo- “thinking like a phar- the topic of neurotransmission, they there were many missing references we can expect that the pharmacologic earliest manuscript, Everett finds, is gists is, I believe, a macologist.” While I suggest that a psychoactive drug must (that is, relevant statements were made effects (and mechanisms of action) of probably from the region of Ravenna, first. S.J. Enna, PhD, have used this phrase be shown to produce a measurable without literature citations). Entire dietary supplements are going to be Italy. Manuscript copies vary consider- is a particularly well- myself, I must say that effect on a neurotransmitter receptor. areas of relevant research and well- much more subtle than the ever more ably, but the critical text is thorough known neurophar- it felt uncomfortable My concern with this strategy is that it known research papers were unmen- potent and selective world of synthetic and skillfully presented. macologist who has to see the hubris pres- will produce only more drugs like the tioned for these two herbs. While pharmaceutics. If we are patient and First, even though the treatise been the editor of ent, and to read some ones we already have. In a discussion this is not surprising for authors who keep an open mind, exploring these was published in the Kühn edition several pharmacol- of the tenants that I of clinical trials, the authors propose are not deeply experienced in this fascinating natural compounds will of “complete works” by Galen (20 ogy journals and is no longer hold to be that the crossover study is clearly the subject area, it was still disappointing surely lead us to undreamed of systems, volumes in 22 parts; Leipzig, Germany, a past president of “self-evident.” In refer- best design. In actuality, this is not the as conclusions were being drawn with- substrates, homeostatic processes, and 1821-1833), the text is not by Galen. the American Soci- ence to modern drug case, because crossover designs suffer out a basis in the available literature. epigenetic effects. The latter may The sources that the unknown author ety for Pharmacol- development and from carryover effects and other prob- On the other hand, the chapters deal- begin to tell us what the things we eat employed are as mysterious as the ogy and Experimen- regulation, for exam- lems of interpretation that limit their ing with lesser-researched plants (for are doing to us or for us. author’s obscurity. Harnessing linguis- tal Therapeutics. the ple, the authors state usefulness. Drs. Enna and Norton fail which available literature could much tics and the best tools available to late Stata Norton, that “… it is not neces- to mention the importance of an active more easily be grasped as a whole) —Jerry Cott, PhD modern scholars, Everett postulates PhD, was a profes- sary for consumers to control comparison in drug stud- seemed more comprehensive and thus Pharmacologist, toxicologist that the author was learned in Greek as sor emeritus in the be concerned about ies. If there is only placebo and test more useful. Silver Spring, MD well as Latin and utilized sources that University of Kansas the safety and effec- drug, the results cannot be interpreted The title suggests that the purpose are now lost. The unknown author Medical Center’s Department of Phar- tiveness of prescription or over-the- unless there is a significant difference of the book is to understand the health The Alphabet of Galen: Phar- employed neither the Greek nor Latin macology, Toxicology, and Therapeu- counter medications.” Wow... I’m not between the two groups. If neither benefits and hazards of plants acting macy from Antiquity to the Middle works of the 1st century CE Greek tics. As a pharmacologist myself, I was sure I ever believed that. I certainly treatment works, it is just as likely that on the central nervous system. I don’t Ages – A Critical Edition of the physician and herbalist Dioscorides looking forward to the pharmacologi- don’t believe it now, after 15 years of the study design was poor as it is that know of any book that has been able Latin Text with English Transla- (an unexpected observation by Ever- cal perspective on these herbs. experience reviewing the safety and the drug actually didn’t work. A posi- to accomplish this. It’s a very tall order. tion and Commentary by Nicho- ett), nor closely followed any surviving The authors begin by reviewing efficacy of prescription drugs. While tive control that works and a negative For this purpose, there are other refer- las Everett. Toronto, Canada: Univer- classical texts. Everett also postulates the history of plants used as medi- there is much reductionist thinking control that doesn’t (placebo) suggests ences that better review the literature, sity of Toronto Press; 2012. Softcover, (persuasively to this reviewer) that cine, offering critiques along the way. in this chapter, there is useful infor- you have a good study design that is especially for ginkgo and St. John’s 445 pages. ISBN: 978-0802098126. similarities to Dioscorides, Galen, and Some inconsistencies nagged me from mation about how to approach the capable of measuring the endpoint wort. I do think the book has a niche, $95.00. the Roman naturalist Pliny the Elder early on. In the history section, the study of identifying useful chemi- of interest. This is especially true for however. Readers with an advanced Galen (129–post 215 CE), also (23–79 CE) drew upon texts that prob- authors claim that few botanical medi- cals in a plant. A particularly useful drugs that work on the central nervous degree in the life sciences will be much referred to as Galen of Pergamon (a ably included Sextius Niger’s lost work cines were used by early humans for strategy that persists throughout the system, where placebo rates as high as happier with this book and will be Greek city-state in what is modern-day on pharmacy, which Dioscorides and purposes similar to modern-day uses. book is the importance of determining 50 percent are not uncommon. able to relate to it. In my opinion, the western Turkey), was a 2nd century Pliny used as well. Thus, this popu- Yet on the next page they acknowledge whether bioactive molecules in a plant Subsequent chapters deal with pharmacologic detail will be out of naturalist philosopher and lar work in Late Antiq- that a 30,000-year-old Neanderthal actually are absorbed into the body selected herbal medicines by review- reach for most laypeople and consum- physician to the Roman uity and the early Latin grave in Iraq revealed a medicine bag after oral administration. This simple ing their history, known chemistry, ers. emperors Marcus Aurelius Middle Ages preserves with flowers from six plants that are exercise often can eliminate many of pharmacodynamics (drug action), Those looking for a general refer- and Commodus. Galen plant and drug lore from all used today for purposes that would the potential candidates for active and pharmacokinetics (drug absorp- ence guide or introduction to herbs is credited with numer- “the ancient and most have been very relevant to the cave constituents of a plant that were iden- tion, distribution, metabolism, etc.). will want to look elsewhere. And the ous writings as well as popular authorities,” to man. They additionally assert that, tified previously by in vitro test results. The chapters include the herbs Ginkgo sometimes condescending language the development of alco- quote from the epilogue in many cases, the active constituents The authors go on to say that one must biloba (Ginkgoaceae), St. John’s wort that has found its way onto most pages hol (wine)-based botanical (which itself may have of the plants are unknown, and that demonstrate the presence of the - (, Hyperica- may put off serious students of natural extracts (later known as been added to the text). this makes it impossible to determine cule in the brain as well. This seems a ceae), valerian (Valeriana officinalis, medicine. I absolutely agree that one “galenicals” in pharmacy), Most of the chap- their effects in humans. This was a bit of a stretch since this is not required Valerianaceae), (Melissa must seek truth (if such a thing really among many other accom- ters’ formats on plants disappointing beginning and gave me of synthetic compounds. The authors officinalis, Lamiaceae), kava (Piper exists in medicine) in an unbiased plishments. have the following: (1) a the feeling that this viewpoint might appear to suggest that a good scientist methysticum, Piperaceae), lavender manner. But the scientist must realize The Alphabet of Galen’s brief description, origin, carry on throughout the book. In should deny evidence (e.g., for seda- (Lavandula angustifolia, Lamiaceae), that just because one explores truth on prologue claims to present or location (with India

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mentioned most frequently for more science,” although some “seem to have a reference for researchers who are medicinal uses and traditional and/or ing features. In numerous cases, exotic plants); (2) a simple statement no biological or physiological basis looking for new leads from Chinese folkloric applications, pharmacology partially highlighted chemical struc- for most of the plants’ general “prop- and remain puzzling,” he writes. An medicinal plants for pharmaceutical (brief description of selected in vitro tures appear side-by-side with other erties” or virtues (such as “sharp, heat- example of what to us is rational, and cosmetic studies. Though Profes- and/or in vivo biological effects of the structures bearing similar highlights. ing, and loosening properties” for gum (Pistacia lentiscus, Anacar- sor Stephen J. Hill, PhD, wrote in the plant extract or its chemical constitu- While the author never explains the cardamom [Elettaria cardamomum, diaceae), according to this book, “is preface that these plants “have been ents; in some cases, the structures of meaning of these features, my suspi- Zingiberaceae]); and (3) uses and styptic…It is good for those coughing carefully selected for their novelty one or two major bioactive chemical cion is that he intended to illustrate other applications primarily for medi- up blood,” whereas only recently have and pharmacological importance,” no constituents are provided); and finally, the structural similarities between a cal afflictions. The author avoided our laboratories proved it useful for further explanation is provided in the bioresources that includes promising plant constituent and a known active (but not completely) what we would peptic ulcer disease. text on why or how the plants were bioactivity for further research. Major compound. For example, under the call superstition or magic, even more With an unknown author living in chosen for this work. Furthermore, references are provided at the end of entry of Illigera luzoniensis (Hernan- so than rational classical authorities an unknown time and place and using the book contains no introduction, each chapter. The book concludes with diacea), which contains actinodaph- such as Dioscorides and Galen. To many unknown sources, the Alpha- nor does it feature any concluding five indices: common names, medici- nine and N-methyl-actinodaphnine, us, verdigris (a green pigment) might bet of Galen is an important, largely remarks. nal uses, natural products, pharmaco- the latter is recommendeded for in or might not be good as an eye-salve, overlooked, and certainly unstudied The bulk of the book consists of nine logical terms, and plants. vitro study for its effect on alope- but it is bizarre when “some” mix it treatise whose popularity mostly was chapters organized using the “Superor- At first glance, I was attracted to cia, while the chemical structure of with an infant boy’s urine, according confined to Late Antiquity and the der” system proposed by the Angio- this book’s subtitle, “Bioresources for phenylephrine is given side-by-side. In to the text. Similarly, donkey dung early Latin Medieval West. Despite sperm Phylogeny Group (APG) clas- Tomorrow’s Drugs and Cosmetics,” my opinion, additional information mixed with vinegar “relives tooth- its title, it is not connected to Galen, sification. They are Austrobaileyanae because, as a researcher in the area and an expansion of the Bioresource Available in the ABC Online Bookstore aches.” These examples withstanding, which is a characteristic of the peri- (ICBN family name: Austrobaileya- of natural drug discovery, choosing section certainly would make the text the Alphabet of Galen is notable in the od’s contrivance to lend authority to ceae), Magnolianae (Magnoliaceae), which plants to study is critical to more complete and useful. Moreover, Medicinal Plants and the Legacy absence of what appears to us as truly the composition. The original treatise Lilianae (Liliaceaea), Ranunculanae success. As the subtitle implies, the it would be preferable if the author of Richard E. Schultes edited by irrational uses. was written in Latin, using “simple, (Ranunculaceae), Rosanae (Rosaceae), most interesting and useful informa- presented his views with sound scien- Bruce E. Ponman and Rainer W. The book’s alphabetical order served technical language;” Everett’s compe- Saxifraganae (Saxifragaceae), Santa- tion that a reader might look for is tific evidence. Bussmann. St. Louis, MO: Missouri ease of use. Everett provides an excel- tent English translation achieves the lanae (Santalaceae), Caryophylla- the pharmacological potential of each On the back cover of the book, the Botanical Garden; 2012. Softcover, lent analysis of pharmacy in what he same. The Latin and translation are on nae (Caryophyllaceae), and Astera- plant species. Indeed, the book’s back author claims that “detailed photo- 138 pages. ISBN: 978-0984841523. describes as “self-medicating in late facing pages. Nicholas Everett’s study nae (Asteraceae). Under each Super- cover asserts that “critical analyses graphs and hand-made botanical $24.95. Antiquity” and an implicit theory for is important for two primary reasons: order are sections on selected orders of peer-reviewed articles provide the plates enable quick and reliable identi- In the fall of 1977, as a new student associating properties with specific to elucidate an important Western and families. In each family section, basis for Bioresource sections in each fication of each plant species.” Unfor- at Harvard, I received some disturb- medicinal actions. For example, opium medical work on pharmacy, and — brief morphological characteristics are chapter wherein readers are advised, tunately, no such plates can be found ing advice from a professor as I was (derived from Papaver somniferum, especially for HerbalGram readers — given, followed by individual species. engaged, and guided toward excit- in the book. Each species is accompa- attempting to select my PhD advisor. Papaveraceae) has a “cooling” prop- to establish a significant young scholar The layout for each plant species is ing pharmaceutical and cosmetologi- nied only by a hand-drawn line sketch “Whatever you do, stay away from erty that “alleviates earaches, reduces who can provide technical and linguis- consistent, providing information on cal research proposals.” Unfortunately, of selected plant parts (not necessar- Richard Evan Schultes. He spent a all types of fatigue in the body, and tic skills to help us understand early history (citation of the first botani- the Bioresource section turns out to be ily showing the medicinal part), from decade alone in the Amazon, he is a for this same reason it also induces herbal medicine. cal description of the plant), common one of the shortest sections in the text, which minimal morphological infor- dinosaur, and he is dangerous to other- sleep” (italics supplied). Similarly, lico- names (mainly Malay, Chinese, Japa- containing only short phrases, such mation can be obtained for identifica- wise good students.” rice (Glycyrrhiza glabra, Fabaceae) —John M. Riddle, PhD nese, and/or Korean names), basionym as “In vitro pharmacological study of tion purposes. Of course, the next morning I found has “moistening properties…therefore Professor Emeritus of History (original Latin binomial), synonyms alisol B monoacetate for its effect on Eight color pictures of plants appear myself in Professor Schultes’ office at quenches thirst, and relieves pain in North Carolina State University (Latin binomial), habitat in China and/ cancer,” or even as simple as “Antima- in the middle of the book with no the Harvard Botanical Museum on the kidneys and bladder.” The connec- Raleigh, NC or , diagnosis (morpho- larial agent(s).” I find it disappointing elucidation. Oxford Street. I found Dr. Schultes to tion between properties and specific logical descriptions of the plant species), that neither detailed explanations nor Overall, I am disappointed to find be a highly cultured Boston Brahmin medicinal applications is inconsistent, references are given to support these that the most important data I was who was more proud of his graduation thus, for example, a cooling action statements. In many cases, there are no looking for are missing from this book. from Boston Latin School than any of rarely points to a specific medicinal Available in the ABC Online Bookstore clues at all to help a reader understand If the author would consider a revision his Harvard accolades. His knowledge affliction. Many plants have no prop- why a particular suggestion is made. of this work, I suggest a substantial of plants and botanical literature was erties specified. For example, folicanthine from Chimo- expansion of the Bioresource section encyclopedic, and he was deeply inter- The opium account delivers an Medicinal Plants of China, Korea, nanthus praecox (Calycanthaceae) is by the inclusion of detailed explana- ested in the success of students. He objective, succinct description about and Japan: Bioresources for Tomor- proposed for study on Alzheimer’s tions and literature citations. certainly is one of the most extraordi- harvesting, preparation, and adul- row’s Drugs and Cosmetics by Chris- disease without any explanation. In nary people that I have ever met in my teration, but omits the assertion by tophe Wiart. Boca Raton, FL: CRC another case, under the Illigera appen- —Chun-Tao Che, PhD entire life, and is universally consid- Dioscorides that “when too much of Press; 2012. Hardcover, 454 pages. diculata (Hernandiaceae) entry, the Norman R. Farnsworth Professor ered to be the 20th-century pioneer of it is drunk, it plunges into a coma ISBN: 978-1439899113. $149.95. author suggests “In vitro pharmaco- of Pharmacognosy modern ethnobotany. and it is deadly.” “Uniquely,” Everett Medicinal Plants of China, Korea, logical study of actinodaphnine for College of Pharmacy Although I cannot strictly claim finds, the Alphabet of Galen claims the and Japan is a compilation of botani- its effect on acne,” yet this compound University of Illinois at Chicago the distinction of being a “Schultes best opium comes from Spain. Many cal, chemical, and pharmacological never was mentioned as being present Chicago, IL student,” having taken my PhD in therapeutic uses “hold up remark- information on roughly 200 selected in this plant species. evolutionary biology rather than ably well against the finds of modern plant species and is intended to be The book seems to be full of confus- ethnobotany, Professor Schultes

72 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 73 BOOK REVIEWS You are joyfully invited to attend this outstanding event

constantly encouraged me to pursue Richard E. Schultes is divided into 11 tion on Biodiversity had been conceived. ethnobotanical studies in chapters. Michael Balick, PhD, begins Neil Schultes, PhD, Professor th INTERNATIONAL during my other fieldwork there. Fortu- with a deeply personal account of his Schultes’ son, shares some personal nately, I was accepted by his real students introduction to Professor Schultes and experiences about what it was like to HERB SYMPOSIUM and regularly attended his seminars at documents the mentorship of the young grow up in the shadow of his famous 11 the Botanical Museum. Dr. Schultes’ Schultes as a student by Harvard Profes- father and to pursue a distinguished students were an amazing lot, and nearly sor Oakes Ames. Rainer Bussmann, career in plant biology himself. He JUNE 28 ~ 30, 2013 all of them went on to extraordinarily PhD — a co-editor of the book — now perpetuates the pioneering Schultes distinguished careers. The late Timo- documents the voluminous herbarium spirit in his careful analysis of photosyn- thy Plowman, PhD, of Chicago’s Field collections of Professor Schultes and his thesis at the Connecticut Agricultural “Celebrating the Healing Museum and the late Calvin Sperling, publication of 500 papers. My favorite Experiment Station. PhD, of the US Department of Agri- part of his chapter is a photograph of Distinguished plant explorer and Power of Plants” culture (USDA) were, in my opinion, the young Schultes in Oaxaca in 1938. expert in Asian ethnobotany, Doel Held at beautiful Wheaton two of the finest field botanists of the Looking at the photographs, one can see Soejarto, PhD, reflects on the legacy College, Norton, MA A symposium to touch your heart and soul as well as mind and spirit, this gathering is century. how the dashing, brilliant, and compas- of Richard Evan Schultes, sharing a for all people enraptured by the healing essence of herbs. Professor Schultes’ surviving students sionate young Schultes became a model marvelous photograph of himself and A Benefit Conference The International Herb Symposium offers herbal enthusiasts an incredible opportunity have collaborated to produce a gem of for Hollywood characters ranging from Professor Schultes in the Amazon in for a book, Medicinal Plants and the Legacy Sean Connery’s Medicine Man to Harri- 1963. Dr. Soejarto, last year’s recipi- United Plant Savers to learn from the world’s leading experts in botanical medicine and herbal lore. of Richard E. Schultes, which includes son Ford’s portrayal of Indiana Jones. ent of the American Botanical Coun- personal anecdotes, ethnobotanical An extremely tight chapter on cil’s Norman R. Farnsworth Excellence   research, and a great deal of biographical Chácabo ethnobotany in Bolivia follows, in Botanical Research Award, humbly INSPIRING EDUCATIONAL ENTERTAINING information. Reading this volume takes written by Dr. Bussmann and Narel links his own remarkable achievements me back to my student days, when his Zambrana. Distinguished ethnobota- in exploring for new medicines from The Symposium Features: Keynote address graduate students — with me as a spare nist Robert Bye, PhD, ensues with an plants in Southeast Asia — includ- Tieraona Low Dog M.D. wheel — modestly divided up the entire excellent analysis of Dr. Schultes’ contri- ing his discovery of the anti-HIV drug * An Extraordinary selection of Speakers from 13 countries Author of planet into our own private research butions to ethnotaxonomy, including an Calanolide A — to lessons he learned “Life is Your Best Medicine” realms. On special occasions, Professor examination of his undergraduate work from Professor Schultes. * Over 90 Workshops for all levels of interest Published by National Geographic Books Schultes would show his 8 mm home on the sacred plants of Mexico. Rodrigo The penultimate chapter by Robert & experience movies of first contact with Amazonian Cámara-Leret, Zambrana, and Manuel Voeks, PhD, Leaa Short, and Aline tribes. Other days, we would discuss Macía, PhD, continue with an excel- Gregorio evaluates the legacy of the * Herbal Intensives for in depth study, Learn from an extraordinary gathering of press reports of a real zombie walking lent chapter on ethnobotanical tech- journal Economic Botany, which was panel discussions & case studies herbal teachers, elders, and healers from into a hospital in Port-au-Prince, Haiti. niques for the study of palms. Prospec- championed by Professor Schultes since * Hands on Demonstrations & around the world representing diverse Sometimes Albert Hofmann, PhD, tive students of ethnobotany would its inception in 1947, illustrating how it backgrounds and experiences. inventor of LSD-25, would lecture us in be well-advised to read this chapter has become increasingly international- wild plant identification walks organic chemistry. It was a heady experi- carefully, including the appendices, as ized and rigorous through the years. * An Herbal Marketplace, Over 40 highly respected teachers ence. (For the record, Professor Schultes they prepare for their own field studies. The volume concludes with a magnif- Evening Entertainment and Dancing had no patience with fellow Harvard Andrés Gerique contributed a chapter icent chapter by James L. Zarucchi, including Kathleen Harrison, David professor Timothy Leary, hippies, or on the ethnobotany of the Ecuadorian PhD, of the Missouri Botanical Garden, * CNE for Nurses and Hoffmann, Marcela Ibieta (Chile), Matthew recreational exploitation of indigenous Andes with fascinating analyses of plant which is replete with remarkable color Wholistic Veterinary Track Wood, Rosemary Gladstar, Dr. Edward psychoactive plants.) use by the indigenous Shuar, the Sara- photographs of Professor Schultes in Thompson (England), Phyllis Light, Paulo Luzzi The day that Professor Schultes guros, and the Mestizos, which reveals Columbia. Deeply moving to me is (Italy), David Winston, Dr. Dawa Ridak (Tibet), discussed the molecular biology of the significant insights into land use and his photograph of Professor Schultes Registration Information Susun Weed, Rocio Alarcon, (Ecuador), ayahuasca vine (Banisteriopsis caapi, land tenure by different cultures. and Arthur Sledge in England, at the and many more Malpighiaceae) and chacruna (Psychotria Steven King, PhD, part of a company grave of the 19th century Amazonian Early Bird Registration until March 30th: $275 Regular viridis, Rubiaceae) in seminar was life- that recently scaled the Mount Everest ethnobotanical explorer Richard Spruce. Tuition: $325. Sponsors of The changing for me, and is the reason of ethnobotany — successfully navi- Every student of ethnobotany, every Inexpensive lodging and meal packages why I have devoted my career to the gating a new botanical drug through firm that compounds plant medicines, International Herb Symposium (delicious vegetarian and non/vegetarian options) ethnobotanical search for new drugs. I the USDA (i.e., the antidiarrheal drug and, indeed, every field biologist, should available on campus. realized that if indigenous people had crofelemer derived from the latex of have a copy of Medicinal Plants and the discovered that level of sophisticated the South American sangre de drago Legacy of Richard E. Schultes. I pinch To register and for further information neurochemistry, somewhere a tradi- tree [Croton lechleri, Euphorbiaceae]) myself that I was so lucky to have had visit the IHS website at tional healer just might hold the cure for — devotes his chapter to how Profes- him as one of my mentors. By adding cancer. Professor Schultes’ deep respect sor Schultes inspired the creation of a to this compilation the masterful biog- www.internationalherbsymposium.com for the dignity of indigenous peoples major conservation effort, The Healing raphy of Dr. Schultes by Wade Davis, and his awe at their pharmacological Forest Conservancy, and pioneered the PhD, One River (Touchstone, 1996), or contact achievements was inspiring. concepts of benefits-sharing with indig- any of Dr. Balick’s books on ethnobot- Sage Mountain, Medicinal Plants and the Legacy of enous people, long before the Conven- any or palm systematics, and perhaps P.O. Box 420, E. Barre, VT 05649 802.479.9825 • [email protected]

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one of the popular books by Mark authors and 36 local experts cited in root, or plant part that is used in ethno- Timothy J. Motley Molecular Systematics Studies — a research body Plotkin, PhD, you will be able to come the front of the volume — at least 54 medicine. Information on a particu- that focuses on “addressing questions of plant very close to the wonderful experi- people who collaborated to produce this lar plant used in traditional medicine classification, historical , plant- 1965–2013 1 ence I had as a student with Professor publication. The institutional sponsor- typically includes local and scientific animal interactions, and character evolution.” Schultes. ship includes the New York Botani- names, a description of the plant, habi- Timothy Motley, PhD, “I started working [at NYBG] as a postdoc but cal Garden, the Ministry of Health of tat ranges of the plant, traditional use, described by his friends, [didn’t] meet Tim for six months or so because — Paul Alan Cox, PhD the Republic of Palau, the Continuum and pharmacological properties and colleagues, and family as a gifted he spent a lot of time in the field,” said Tatyana. Institute for Ethnomedicine Center for Health and Healing service toxicology. and well-loved tropical botanist “Later it turned out that we were living in the Jackson Hole, WY of Beth Israel Medical Center in New A list of voucher specimens linked to and explorer, passed away on same apartment building near the Garden. He York City, and the Belau National the plants also is provided. I was espe- March 28, 2013, at the age of 47. was an amazing person — very kind, generous, Palau Primary Health Care Museum in Palau. cially impressed by the 21-page bibli- Motley was the J. Robert Stiffler funny, and very honest and reliable.” Manual: Health Care in Palau - As the back cover of Palau Primary ography, which will be useful to any Distinguished Professor of Plant Scott Mori, PhD, the Nathaniel Lord Britton Combining Conventional Treat- Health Care Manual states so elegantly, specialist interested in following up on Science at Old Dominion Univer- Curator of Botany at NYBG, first met Dr. Motley ments and Traditional Uses of Plants “The Republic of Palau in the Caroline any of the information presented. sity (ODU) in Norfolk, Virginia, in 1996 and became friends with him and Taty- for Health and Healing by Stephen Islands has a traditional medical system Overall, this is an excellent book where he taught a popular ethno- ana. “I was impressed with the breadth of Tim’s M. Dahmer, Michael J. Balick, Ann developed over many generations. The that hopefully will inspire other local botany course, along with four interest. He was not only a … botanist but also Hillman Kitalong, et al. Charleston, Palau Primary Health Care Manual and international research consortiums other plant science courses, in the a plant systematist who specialized in Rubiaceae. SC: CreateSpace Independent Publish- compiles traditional ethnomedical to produce similar volumes. There same department as his wife, Tatyana Lobova, PhD. Dr. He used both morphological and molecular data to study ing Platform; 2012. Softcover, 220 information about plants and presents has been a great deal of focus and Motley also served as the director of science at the Norfolk the phylogeny of this family [and] was a botanical explorer pages. ISBN: 978-1477446355. $40.95. it within the context of Western medi- concern in many sectors about the Botanical Garden (NBG). [who] headed the American side of a collaborative project This book is the second healthcare cine.” The book covers common health inappropriate use of traditional medical “Tim was not only a gifted scientist, field botanist, and with China,” said Dr. Mori (email, April 9, 2013). manual produced by a multidisci- conditions, including knowledge in the past collaborator, but also a friend who loved life, work, his During his time at ODU, Dr. Motley became known for plinary team of traditional healers, some of specific inter- decade. This publica- family, and plants,” wrote Edward J. Kennelly, PhD — a his course on ethnobotany and for his contagious passion Western-trained healthcare workers, est to Palauan peoples, tion represents the oppo- collaborator of Dr. Motley’s and a professor at Lehman for botany. medical doctors, botanists, ethnobota- and provides informa- site: a highly integrated College, City University of New York — in an email to “Tim’s ethnobotany course always filled as soon as regis- nists, and local people — all engaged tion on approximately applied focus on enhanc- colleagues shortly after Dr. Motley’s passing. “In our field- tration opened,” said Dr. Lytton John Musselman, the in the integration of conventional and 80 plant species. ing and managing health work that took us from nearby Pound Ridge, New York to Mary Payne Hogan Professor of Botany at ODU, and a traditional treatments and medicinal According to the back of communities utilizing collect black cohosh [Actaea racemosa, Ranunculaceae], to colleague of Dr. Motley’s (email, April 9, 2013). “He had a plants in Palau, Micronesia. The first cover, the healthcare the best of all medical remote areas of Yunnan, China (to collect anything), I grew gift for linking the use of a plant with its biology and did volume, Pohnpei Primary Health Care manual “is intended traditions and knowl- to know Tim better, and I valued greatly our time together, it in a clear, effective and challenging manner. … A clear Manual, was a groundbreaking book as an educational edge. I would love to see both for the science and camaraderie.” reflection of this botanical magnetism was the establish- developed by some of the same vision- manual for Palau and ethnobotanists, tradi- In 2006, Drs. Motley and Kennelly received a grant from ment of a botany club on our campus. Few campuses have ary authors of this volume. This work the Pacific region, an tional healers, medical the National Institutes of Health’s National Center for this claim.” and its predecessor are products of the area where traditional doctors, nurses, public Complementary and Alternative Medicine to study black Whether Dr. Motley was studying plants of remote New York Botanical Garden's Biodiver- medicine and some of health workers, commu- cohosh and its related species. The same year, Dr. Motley Pacific islands, teaching students at ODU, or conducting sity and Human Health in Micronesia the plants used in its nity health specialists, joined ODU’s Department of Biological Sciences and research with colleagues, Dr. Motley’s colleagues said that Program. practice, are endangered resources.” graduate students, government agen- became the director of science at NBG. he will be remembered as a loving husband, father, and an This Palau-focused volume is another The book is divided into 12 chapters cies, and international funding agencies Aside from being a professor and research scientist, Dr. accomplished scientist and mentor. gem of a book. It is so refreshing to read that describe various health conditions focus on the production of manuals like Motley had a passion for the flora of the Pacific islands and “He said many times that his professors were very good this book and to know that it is being and combine current Western medical this to assist countries and communi- regularly traveled to remote regions of the world to study to him and he wanted to help [his students] as much as he distributed to communities as a tool to knowledge with traditional Palauan ties in both the conservation and utili- plants. His research took him to exotic locales including the could,” said Tatyana. “All of Tim’s former students are also provide careful, respectful, and practi- botanical treatments; pharmacological zation of their biocultural diversity and Kingdom of Tonga, Tahiti, New Caledonia, Pohnpei, Rapa his good friends. I think that friendship was very important cal guidance on the application of some efficacy and toxicity of each species management of community health. It is Iti, Fiji, Papua New Guinea, Mauritius, and the Galápa- to him. I think he was exactly the same in any setting — of the best therapeutic approaches to also are included if such data exists in then that people working in the above- gos archipelago, among many others. His love of botanical just himself — kind, easy going, and funny.” cross-cultural health and healing. I the literature. mentioned disciplines and organiza- exploration began while he was still in school. In addition to his wife, Dr. Motley is survived by his two- consider this book and approach to be The specific chapters focus on the tions will want to own this book. This “Tim got interested in botany and especially ethnobotany year-old son, Anton. A memorial service for Dr. Motley was the next step in the evolution of applied following: preventive medicine in Palau volume could be employed to stim- when he was an undergrad at Eastern Illinois University. held at the Norfolk Botanical Gardens on May 17, 2013. botany, ethnomedicine, ethnobotany, (which is quite profound and well-artic- ulate discussion among communities … Later, at the University of Hawaii, he was working on healthcare, and conservation. The ulated); chronic diseases (such as heart and governments in other geographic [his] PhD with Dr. Gerald Carr and he fell in love with Republic of Palau is the westernmost disease, cancer, and diabetes); bites and regions of the world about what sort of the Pacific island flora,” noted his wife, Tatyana, in an email —Tyler Smith archipelago of the Caroline Islands in stings; gastrointestinal disorders; skin manual would be most effective for that (April 16, 2013). “His advisors played a very important role Micronesia, which are north of Irian disorders; cuts, wounds and broken culture and region. in defining his botanical interests and shaping his research, Reference and he was very grateful how generous they were with shar- 1. International plant science center — collaborative programs. Jaya and east of the Philippines in the bones; stress; pain; women’s health; The New York Botanical Garden website. Available at: http:// geographic region of Oceania. men’s health; colds and flu; and finally, —Steven R. King, PhD ing time and knowledge.” Dr. Motley met Tatyana while they were working at the sciweb.nybg.org/science2/CullmanProgram.asp.html. Accessed The people and institutions that ear, nose, and throat issues. Each chap- Sr. Vice President, Sustainable April 12, 2013. created this book are a model for the ter contains multiple color photographs Harvesting and Ethnobotanical New York Botanical Garden (NYBG). From 1998 until future of integrated public health in of the plants described, including, in Research 2006, Dr. Motley held various positions at NYBG, includ- biodiversity-rich nations. There are 18 most cases, details of the flower, fruit, Napo Pharmaceuticals, Inc. ing assistant curator, acting department chair, and associate curator of The Lewis B. and Dorothy Cullman Program for

76 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 77 IN MEMORIAM

Publications Billy Joe Tatum home, “Wildflower,” they raised American Herb Association Quarterly Newsletter: $20/yr. AHA, P.O. Box 1673, Nevada City, CA 96969. five children. Australian Journal of Medical Herbalism: Quarterly publication of the National Herbalists Association of Australia (founded in 1920). Dr. Tatum noted home reme- Deals with all aspects of Medical Herbalism, including latest medicinal plant research findings. Regular features include Australian medici- 1932–2012 Classifieds dies on his patients’ charts, nal plants, conferences, conference reports, book reviews, rare books, case studies, and medicinal plant reviews. AUD/$96 plus AUD/$15 Wild foods expert, international epicu- and eventually he and Billy Joe if required by airmail. National Herbalists Association of Australia, 33 Reserve Street, Annandale, NSW 2038, Australia. Medical Herbalism: Subtitled “A Clinical Newsletter for the Herbal Practitioner.” Edited by Paul Bergner. $36/yr, $60/2 yrs. Canada rean gourmand, herbalist, and author, collected over 2,500 of these from $39/yr. Overseas $45/yr. Sample/$6. Medical Herbalism, P.O. Box 20512, Boulder, CO 81308. Billy Joe Tatum of Melbourne, Arkan- community members. Until the sas, passed away on March 26, 2012, at mid-1970s, even state highways in the age of 80. She was born February 15, this remote Ozark location were Other 1932. Billy Joe won a reputation as the gravel roads. Home remedies were successor to Euell Gibbons (1911-1975), normal medical practice. American College of Healthcare Sciences, ACHS.edu is a DETC accredited, fully online college offering Graduate and Undergraduate degrees, diplomas, and career-training certificates in holistic health and herbal medicine. ACHS is committed to exceptional online education who generated interest in wild foods with “One of my first remembrances and is recognized as an industry leader in holistic health education worldwide. Federal financial aid available to those who qualify. Visit www. popular books such as Stalking the Wild of learning remedies from a patient achs.edu, call (800) 487-8839, or stop by the College campus located at 5940 SW Hood Ave., Portland OR 97239. Asparagus (Alan C. Hood & Co., Inc., is the day I trekked into Harold’s Interns, get hands-on experience before you graduate! If you’re a future pharmacist or dietitian, you can choose a rotation through ABC’s 1962). office with all four kids in tow,” internship program. You’ll get a comprehensive introduction to phytomedicines, researching the medicinal, culinary and cosmetic uses of herbs, Billy Joe’s 1976 bestseller, Billy Joe Billy Joe once shared. “I was just answering ABC members’ questions, working with medicinal plants in ABC’s 2.5 acres of herbal gardens, and preparing herbal salves, tinctures Tatum’s Wild Foods Cookbook & Field absolutely worn to a frazzle by or meals. For more information, call 512-926-4900x114 or e-mail [email protected]. Guide (Workman Publishing Co., Inc.), having a houseful of kids with Stock Photography that doesn’t look like Stock: Steven Foster Group, Inc. Photography, Consulting, Publications. Specializing in medici- Photo ©2013 Nick Kelsh nal and aromatic plants, along with the places they grow, our stock photo files include more than 120,000 images shot around the world for elevated Gibbons’ wild food foray from colds and runny noses.” over 30 years. Contact us at our location in the heart of the Ozarks in Eureka Springs, Arkansas. Visit our website: www.Stevenfoster.com or the campfire to the gourmet kitchen, Her husband was so tired each email: [email protected]. raising the perception of wild edibles from day after practicing medicine that Considering supplying herbal products in Europe? Ann Godsell Regulatory can offer consulting advice on regulatory strategy, and data simple survival food to epicurean art. She hosted numerous she didn’t want to bother him with their own children’s requirements. Services for dossier preparation & submission also available. For more information email [email protected]. gourmet wild food dinners. For example, the late Winthrop runny noses. Colorado School of Clinical Herbalism (formerly NAIMH). Now accepting applications for Introductory, Advanced, Clinical, Nutri- P. Rockefeller, Jr., won the winning bid on a Billy Joe Tatum “But that day, feeling so frazzled, I decided I would try tion, and Flower Essence programs in the Vitalist Tradition. In-depth training in the theory & practice of Western Herbalism and Nutrition. wild foods feast at a 1979 arts fundraising auction. Guests a trick of the doctor’s wifery; I would just go and sit in the Courses begin in August and January. Contact Lisa Ganora 720-722-4372. www.ClinicalHerbalism.com included Arkansas notables such as Bill and Hillary Clin- front of the office and wait for an appointment. And that was ton — Arkansas governor and first lady, at that time — who the day I happened to meet up with Aunt Tenny. This little were treated to elderberry and blackberry aperitifs followed old lady started talking to me and invited me to her house by watercress soup, apple- salad, pheasant liver and made me a wonderful cup of soothing tea. Before long, paté, elderberry capers, hickory-nut-stuffed eggs, and veni- she had convinced me that I should drink calming teas, give son Wellington. the children catnip [Nepeta cataria, Lamiaceae] for sleepless- Soon after publication of her first book, Billy Joe and ness and dittany [tea; Cunila origanoides, Lamiaceae] to lower her physician husband, Harold “Hally” Tatum, MD, were temperature..., but Aunt Tenny made me realize that it was featured in the first chapter of the 1977 National Geographic very important to put children’s tea in a beautiful, little china Watch your inbox for ABC’s newest publication classic Nature’s Healing Arts.1 An inexhaustible bouquet of cup with a pretty picture on it. She knew all the secrets.”3 energy and ideas, Billy Joe’s vivacious writing was inspired Billy Joe became the acknowledged expert on Ozark folk by her philosophy that “the only way to make life fun is to medicines in addition to being an internationally recognized make it a game. I found excitement in the endless possibili- specialist in wild foods. She is survived by her husband, her Herbal News & Events! ties of wild foods.”2 five children, nine grandchildren, five great grandchildren, Her fame grew with several appearances on “The Johnny three siblings, and two generations of artists, dancers, musi- ABC’s newest e-newsletter provides weekly insight Carson Show” and with TV host Dinah Shore. Personality cians, writers, photographers — the famous and the obscure profiles featuring Tatum appeared in numerous magazines — whom she generously entertained and often housed at the into upcoming events and conferences of interest to including People, National Geographic, and Gourmet. She Tatums’ Ozark home. This writer is among those who expe- took on the persona of an Ozark granny-herbalist (though rienced that expansive generous spirit. the herbal community, plus a members-only Media just in her 40s), with a gray-flecked, waste-length braid deco- Watch with the latest headlines in herbal news. rated with an ever-present buzzard feather, while sporting a —Steven Foster corncob pipe. Billy Joe graduated from Ouachita Baptist University in References Are you an ABC member, but haven’t received your Arkadelphia, Arkansas, with a degree in music. She eschewed 1. Aikman L. Nature’s Healing Arts: From Folk Medicine to Modern Herbal News & Events yet? Make sure you we have your Drugs. Washington, D.C: National Geographic Society; 1977. a Julliard scholarship and career track toward the Metropoli- correct email address. Go to www.herbalgram.org and click tan Opera to marry in 1951. In 1958, after several years in 2. Foster S. Billy Joe Tatum: A Seasoned Herbalist and Woman for All Seasons. Diversions for Physicians at Leisure. January 1983. on “Edit My Profile” at the top of the page. Detroit, the couple decided to return to their native Arkan- 3. Conrow R, Hecksel A. Herbal Pathfinders: Voices of the Herb sas. They took out a map, closed their eyes and randomly Renaissance. “Billy Joe Tatum.” Santa Barbara, CA: Woodbridge pointed a finger toward the Ozarks. The finger landed on the Press; 1983. Not an ABC member yet? Join or register (FREE) at www.herbalgam.org. map near Melbourne, in Izard County, Arkansas, an Ozark You can also call us at 1-800-373-7105. hamlet in need of a physician. In 1958, Dr. Tatum opened a rural practice there. At their famed Ozark mountaintop

78 • I SSUE 98 • 2013 • www.herbalgram.org www.herbalgram.org • 2013 • I SSUE 98 • 79 Individuals, organizations, and companies support ABC through membership Paederia foetida (Rubiaceae) This climbing liana grows as a weed on several Indian Ocean islands, including Comoros, Madagascar, and the Mascarenes. Despite P. foetida’s sulphur-fecal-like odor, similar to that of other species in its genus, it is commonly ingested and applied to the body for its anti-inflammatory properties. In the traditional medicine systems of these islands, leaf prep- The arations are rubbed on wounds to stop bleeding as well as ingested to treat eczema and to prevent indigestion and upper abdominal pain. The whole plant is consumed for gastric pain and bladder and digestive complaints in addition to being administered as a bath to heal skin irritations and venereal diseases.

Adapted from Medicinal and Aromatic Plants of Indian Ocean Islands by Ameenah Gurib-Fakim and Thomas Brendler (MedPharm, 2004). Photo ©2013 Gurib-Fakim. Invites You To Join Us The American Botanical Council is the leading nonprofit education and research organization using science-based and traditional information to promote the responsible use of herbal medicine. Founded in 1988, the member-supported American Botanical Council: SERVES members in more than 81 countries worldwide EDUCATES consumers, healthcare professionals, researchers, educators, industry and the media on the safe and effective use of medicinal plants ADVOCATES responsible herbal production and use ADVISES the media on emerging herbal science PROMOTES a healthier world through responsible herbal use.

Join Us! In return, you’ll receive access to a wealth of herbal data via: ABC’s acclaimed quarterly journal, HerbalGram 7 online databases of herbal information (depending on membership level) Regular electronic updates on herbal news that matters to you • 12 Monthly HerbalEGrams, 51 Weekly Herbal News & Events updates, and 360 HerbClips per year, plus other Member Advisories And much more. Learn more at www.herbalgram.org or contact Denise Meikel at [email protected] or (512) 926-4900 ext. 120. 80 • I SSUE 98 • 2013 • www.herbalgram.org How we help your products grow.

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