SupplementScience

F cusing on Brain Nutrients A Scientific & Regulatory Review By Gene Bruno, MS, MHS

n writing an article on brain nutri- elderly people with mild cognitive memory and cognition that were most ents, the choices of potential impairment (50-69 years old) were ran- improved by the treatment included for inclusion are domly assigned to take PS (100 mg or memorizing information, visual memory, almost endless. A partial list 300 mg/day) or placebo for six months. and memorizing numbers. Mood was includes (in alphabetical order) In the subjects with a relatively low also influenced. Winter mood changes acetyl-L-, alpha-GPC, score at baseline, the memory scores in (“winter blues”) did develop in the IBacopa monnieri, citicoline, DHA, the PS-treated groups were significantly placebo group but were entirely blocked DMAE, Ginkgo biloba, gotu kola, increased compared to the baseline, in those treated with PS. huperzine A, L-, phosphatidyl- while those of the placebo group A 12-week, placebo-controlled clinical , , vinpoce- remained unchanged. The memory trial4 conducted on 50 patients (mean tine, B12 and others. So, how to improvements in the PS-treated groups age of 60.5, 52 percent female) with choose which of them to write about? In were mostly attributed to the increase age-related cognitive decline examined order to do justice to the topic, I decid- in delayed verbal recall, a memory abili- the effects of 300 mg of soy derived PS ed to write about one amino acid, one ty attenuated in the earliest stage of daily. Learning and memory were herb and one vitamin. In this case, dementia. assessed at three, six, nine and 12 phosphatidylserine, ginkgo biloba and Another double-blind, placebo con- weeks using a clinically relevant com- vitamin B12. trolled study3 assessed the influence of puterized neuropsychological test bat- Phosphatidylserine PS on memory and mood in patients tery. Comparisons with PS and placebo The phosphatidylserine aged 60-80 years, and who reported are shown below. (PS) is active at membranes (includ- some memory difficulties that were veri- Other controlled trials were also con- ing synaptic membrane zones) and is a fied by a score of at least 25 out of 30 ducted on PS. In each case, the results major building block for nerve cells. A on the Mini Mental State Test, which showed significant improvements in significant amount of published clinical screens for cognitive impairment. cognitive performance over placebo in research has demonstrated that PS sup- Seventy-two subjects, randomly assigned patients with cognitive performance plementation supports various cognitive to placebo and therapy groups, were issues (300 mg/day),5 Alzheimer’s (300- parameters.1 treated for three months with 300 mg, 700 mg/day)6-8, and senile dementia An example is a double-blind, ran- PS daily. Results showed a large and sta- (300 mg/day).9 In addition, research with domized, controlled study2 to investi- tistically significant positive influence of PS supplementation has also shown gate the effects of PS on the cognitive treatment on both memory and mood, improvements in cognitive function in functions of elderly Japanese subjects whereas influence of placebo was small both patients with mild cognitive with memory complaints. Seventy-eight and non-significant. Components of impairment10 and mild dementia.11

33 VITAMIN RETAILER WWW.VITAMINRETAILER.COM ■ AUGUST 2013 SupplementScience that that ginkgo had mod- ciency cases, and repletion of the vita- Remembering names one hour est effects on improving min has positive results regardless of the symptoms of dementia other risk factors.25 In one clinician’s after introduction and cerebral insufficiency. experience, replenishment of vitamin Furthermore, they indicat- B12 can reverse 75 percent of B12 defi- 40% ed that the improvement ciency dementias when discovered early was equivalent to therapy enough.26 Other research also suggests 30% with ergoloid mesylates that dementia caused by vitamin B12 PS 20% (hydergine). deficiency can be reversed by vitamin Placebo 19 10% A meta-analysis includ- treatment, but reversibility seems to be ed four studies (with a total dependent upon the duration of the 0% 27 12 Weeks of 212 subjects in the associated neurologic complications. placebo and ginkgo In an initial, randomized, controlled groups) that met inclusion study28 on elderly subjects with criteria for adequate clini- increased dementia risk (mild cognitive Learning & remembering written cal design for examining impairment), researchers showed that information ginkgo’s effects on objec- treatment with 500 mcg vitamin B12, tive measures of cognitive combined with 800 mcg folic and 20 40% function in patients with mg vitamin B6, slowed shrinkage of the Alzheimer’s disease. The whole brain volume by 50 percent over 30% results were that a signifi- two years. In a follow up study29, the PS 20% cant overall effect in the same researchers found that the vitamin Placebo gingko groups was demon- B12 combination reduced, by as much 10% strated that was compara- as seven fold, the cerebral atrophy in 0% ble with the benefits of those gray matter (GM) regions specifi- 12 Weeks donepezil (Aricept). cally vulnerable to the Alzheimer’s dis- Likewise, a review20 of stud- ease process, including the medial tem- In laboratory tests on serum samples ies on ginkgo that lasted at least six poral lobe. of patients treated with PS, significant months in duration concluded that gink- A note on vitamin B12 absorption: reductions in uric acid and SGPT levels go extract was equally effective in mild The intestinal absorption of B12 is were noted (which may be considered to moderate Alzheimer’s dementia in dependent upon its binding with the beneficial), and all other serum parame- comparison to second-generation glycoprotein intrinsic factor (IF), secret- ters were unaffected.12 In addition, PS inhibitors. Other research ed from the parietal cells of the stom- has a favorable benefit-to-risk profile reviews on the use of ginkgo in treating ach. If the gastric juices of a person since, according to researchers, “its dementia have shown similar beneficial lacks IF, then there is little uptake of the benefits are often remarkable, adverse results to those previously discussed.21 vitamin (as little as one percent).30 This effects from its use are virtually never In a controlled trial of ginkgo extract, issue can be addressed through the use seen, and its compatibility with most LeBars et al. (1997) treated 309 patients of a vitamin B12 lozenge, which can be common drugs is established.”13 Most with mild to moderately severe forms of absorbed via the sublingual plexus and of the research on PS in the treatment dementia of the Alzheimer type (DAT) buccal cavity, thereby bypassing the of dementias and cognitive dysfunctions or multi-infarct dementia (MID), using issue with IF entirely. The result is a 90 indicated an effective daily dosage 120 mg/day or placebo. The evaluation percent increase in serum B12.31 range of 300-400 mg.14 of patients took place periodically, up through 52 weeks of therapy. The Conclusion Ginkgo biloba Extract results indicated that ginkgo extract was Although there are many nutraceuticals The research on Ginkgo biloba extract capable of stabilizing cognitive perform- that support brain health, PS, ginkgo in treating dementias and other cogni- ance and social functioning in patients and B12 are three very good ones with tive functions is vast. As a matter of with dementia. These changes were a history of safe and effective use. VR fact, there are hundreds of published objectively quantifiable and noticeable clinical studies on ginkgo.15 Conse- by caregivers, despite the fact that they References: quently, with the exception of a discus- were classified as modest. 1 Kidd PM. A review of nutrients and botanicals in the sion on one clinical trial, it was neces- integrative management of cognitive dysfunction. Altern sary to limit my presentation of the data Med Rev. 1999;4(3):144-61. Vitamin B12 2 Kato-Kataoka A, Sakai M, Ebina R, Nonaka C, Asano to reviews and meta-analyses on the Vitamin B12 deficiency is frequently T, Miyamori T. Soybean-Derived Phosphatidylserine topic. It should be noted that ginkgo is associated with neurological problems, Improves Memory Function of the Elderly Japanese used as a standardized preparation con- including memory loss and dementia.22 Subjects with Memory Complaints. J Clin Biochem Nutr. taining 24 percent ginkgo flavonoid gly- Individuals with Alzheimer’s disease 2010;47:246–255. 3 Gindin J, Novikov M, Dedar D, Walter- Ginzburg A, cosides and six percent terpene lac- often have low levels of vitamin B12 in Naor S, Levi S. The effect of plant phosphatidylserine on tones, in a typical range of 120-240 mg the blood and/or low cerebrospinal age-associated memory impairment and mood in the daily, taken in two to three doses.16 fluid.23 In fact, vitamin B12 deficiency functioning elderly. The Geriatric Institute for Education To begin with, eight randomized, affects 10-15 percent of adults over the and Research, and Department of Geriatrics, Kaplan Hospital, Rehovot, Israel. Unpublished report; 2009. double-blind, placebo-controlled stud- 24 age of 60. According to some 4 Crook TH. Treatment of Age-Related Cognitive ies on ginkgo extract were systematical- researchers, many cases of Alzheimer’s Decline: Effects of Phosphatidylserine. In Klatz RM (ed). ly reviewed.17,18 The reviewers concluded dementia are actually missed B12 defi- Anti-Aging Medical Therapeutics, Vol II. Chicago: Health

34 VITAMIN RETAILER WWW.VITAMINRETAILER.COM ■ AUGUST 2013 Anti-Aging Medical Therapeutics, Vol II. Chicago: Health 14 Phosphadidylserine. Altern Med Rev. acid, biotin, and choline. Washington, D.C.: National Quest Publications; 1998:20-29. 1999;4(2):115-17. Academy Press; 1998:306-356. 5 Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi 15 Sierpina VS, Wollschlaeger B, Blumenthal M. 28 Smith AD, Smith SM, de Jager CA, Whitbread P, G, et al. Cognitive decline in the elderly: A double-blind, Ginkgo biloba. American Family Physician. Johnston C, et al. Homocysteine-Lowering by B placebo-controlled multicenter study on efficacy of phos- 2003;68(5):923-6. Slows the Rate of Accelerated Brain Atrophy in Mild phatidyiserine administration. Aging Clin Exp Res. 16 Sierpina VS, Wollschlaeger B, Blumenthal M. Cognitive Impairment: A Randomized Controlled Trial. 1993;5:123-133. Ginkgo biloba. American Family Physician. PLoS ONE. 2010;5(9): e12244. 6 Engel RR, Satzger W, Gunther W, Kathmann N, Bove 2003;68(5):923-6. 29 Douauda G, Refsum H, de Jager CA, Jacoby R, D, Gerke S, Munch U, Hippius H. Double-blind cross-over 17 Kleijnen J, Knipschild P. Ginkgo biloba for cerebral Nichols TE, Smith SM, Smith AD. Preventing Alzheimer’s study of phosphatidylserine vs. placebo in patients with insufficiency. Br J Clin Pharmacol. 1992;34:352-8. disease-related gray matter atrophy by B-vitamin treat- early dementia of the Alzheimer type. European 18 Kleijnen J, Knipschild P. Ginkgo biloba. ment. PNAS. 2013; Published online before print May Neuropsychopharmacology. 1992;2(2):149-55. Lancet.1992;340:1136–1139. 20, 2013, doi: 10.1073/pnas.1301816110. 7 Funfgeld EW, Baggen M, Nedwidek P, Richstein B, 19 Oken BS, Storzbach DM, Kaye JA. The efficacy of 30 Whitney EN, Cataldo CB, Rolfes SR: Understanding Mistlberger G. Double-blind study with phosphatidylser- Ginkgo biloba on cognitive function in Alzheimer disease. Normal and Clinical . Belmont, CA: ine (PS) in parkinsonian patients with senile dementia of Arch Neurol. 1998;55:1409-15. Wadsworth/Thompson Learning; 2002. Alzheimer’s type (SDAT). Progress in Clinical and 20 Wettstein A. Cholinesterase inhibitors and Ginkgo 31 Libby AF, Starling CR, Josefson FH, Ward SA. The Biological Research. 1989;317:1235-46. extracts — are they comparable in the treatment of Junk Food Connection: A Study Reveals and Drug 8 Rabboni M, Maggioni FS, Giannelli A, Beinat L. dementia? Comparison of published placebo-controlled Life Styles Adversely Affect Metabolism and Behavior. Neuroendocrine and behavioural effects of phos- efficacy studies of at least six months’ duration. Orthomolecular Psychiatry 1982;11(2):116-127. phatidylserine in elderly patients with abiotrophic or vas- Phytomedicine. 2000;6: 393-401. cular dementia or mild depression. A preliminary trial. 21 Sierpina VS, Wollschlaeger B, Blumenthal M. Clin Trials J. 1990;27(3):230-240. Ginkgo biloba. American Family Physician. Gene Bruno, MS, MHS, the dean of 9 Delwaide PJ, Gyselynck-Mambourg AM, Hurlet A, 2003;68(5):923-6. academics for Huntington College Ylieff M. Double-blind randomized controlled study of 22 Healton EB, Savage DG, Brust JC, Garrett TJ, of Health Sciences, is a nutritionist, phosphatidylserine in senile demented patients. Acta Lindenbaum J. Neurologic aspects of cobalamin deficien- herbalist, writer and educator. For Neurologica Scandinavica. 1986;73(2):136-40. cy. Medicine (Baltimore). 1991;70(4):229-245. more than 30 years he has educat- 10 Sinforiani E, Agostinis C, Merlo P, Gualteri S, Mauri 23 Nourhashemi F, Gillette-Guyonnet S, Andrieu S, et M, Mancuso A. Cognitive decline in ageing brain. al. Alzheimer disease: protective factors. Am J Clin Nutr. ed and trained natural product Therapeutic approach with phosphatidylserine. Clin Trials 2000;71(2):643S-649S. retailers and health care profes- J. 1987; 24(1):115-124. 24 Baik HW, Russell RM. Vitamin B12 deficiency in sionals, has researched and formu- 11 Puca FM, Savarese MA, Minervini MG. Exploratory the elderly. Annu Rev Nutr. 1999;19:357-377. lated natural products for dozens trial of phosphatidylserine efficacy in mildly demented 25 Hattersley JG. High-dose vitamin B12 in the treat- of companies, patients. Clin Trials J. 1987;24(1): 94-98. ment of dementia. Nexus. 2007; Oct.-Nov.:25-28, 79. and has written articles on nutri- 12 Cenacchi T, Baggio C, Palin E. Human tolerability of 26 Dommisse JV. Subtle vitamin-B12 deficiency and oral phosphatidylserine assessed through laboratory psychiatry: An often unnoticed but devastating relation- tion, , nutraceuti- examinations. Clin Trials J. 1987;24(1):125-130. ship. Med Hypotheses. 1991;34(2):131-140. cals and integrative health issues 13 Kidd PM. A review of nutrients and botanicals in 27 Food and Nutrition Board, Institute of Medicine. for trade, consumer magazines and the integrative management of cognitive dysfunction. Vitamin B12. Dietary reference intakes for thiamin, peer-reviewed publications. Altern Med Rev. 1999;4(3):144-61. riboflavin, niacin, vitamin B6, vitamin B12, pantothenic 2013 Retailer of the Year (Continued from page 23) ing new stores in under-served parts of study released in July by the Centers for the state, Down to Earth has also had Disease Control and Prevention (CDC), to address major workplace safety which noted that Aloha State residents issues and workers compensation prob- 65 years old can expect another 16.2 lems. “We dealt with this by introduc- years of healthy living. But even ing a team member safety program Hawaiians have their share of health that has been very successful,” issues. “Our customers have a lot of the Fergusson said. usual needs for a good , And being located in Hawaii brings bone support, immune support, diges- geographic obstacles. “We are chal- tion (fiber, , enzymes) and lenged by shipping problems as getting omega-3s,” said Wolf. “Unfortunately, our orders takes 10 days from order to as people throughout our nation have receipt. It makes it more difficult to reduced healthy lifestyles and gained Wellness Manager Carmela Wolf receive orders in a timely way, and weight, we see a lot of new customers increases our out-of-stocks,” he added. coming in looking for products that can issues. Eating a healthy diet, exercising Despite the challenges, Fergusson help support healthier blood pressure, regularly and managing their stress are said there’s more work to be done at cholesterol, blood sugar and weight truly the foundations to good health. We Down to Earth. “We will grow and loss. And with the modern lifestyle show them what we have that can sup- expand, opening more stores in Hawaii comes a need for stress and mood sup- port or ‘supplement’ a healthy lifestyle, and one day possibly the mainland or port, as well as energy and sleep aids. and offer the best options.” even internationally.” VR “Many customers want to try a natural approach and avoid going on medica- Island Issues Extra! Extra! tions if possible. We show them what is While Whole Foods Market’s arrival to Visit www.vitaminretailer.com available to support their body’s needs,” Hawaii posed a steep challenge, one to learn about Down To Earth’s workplace she added. “We always remind them that the store meets with store renova- Safety Program. that these are lifestyle-driven health tions, customer service and by introduc-

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