FEATURE ARTICLES 7 Why Arginine Failed as a Heart Drug 32 Epidemic of Male Osteoporosis 42 Relief from Digestive Upsets 54 Beautify Skin from Within LifeExtension.com April 2020 65 Lactoferrin Promotes Bone Growth

Restore YOUTHFUL Arterial Function

PLUS: New Method to Boost Nitric Oxide

LEMAPR20pCVR.indd 1 2/14/20 11:34 AM ections Between Y Conn our N tore eur es Neuro-Mag® Magnesium L-Threonate ons R was specifically formulated by MIT scientists to be uniquely absorbable by brain and nerve cells.

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LEMAPR20pIFC.indd 1 2/19/20 2:08 PM CONTENTS

LifeExtension.com April 2020

REPORTS

22 ON THE COVER BOOST NITRIC OXIDE TO IMPROVE CIRCULATION An age-related decline in nitric oxide levels contributes to inner arterial wall dysfunction. A blend of aronia berries and a sus- 32 42 54 65 tainable form of L-arginine boosts the body’s production of nitric oxide, 32 EPIDEMIC OF OSTEOPOROSIS IN MEN helping to improve blood flow. Men are at a higher risk of osteoporosis than most realize. Healthy lifestyle choices, along with bone-building nutrients, can protect and restore bone density.

42 IMPROVE DIGESTION OF PLANT-BASED FOODS 22 The trend toward plant-based diets often requires special enzymes to digest the fiber in these foods to avoid gastrointestinal bloating, gas, diarrhea, and cramping.

54 IMPROVE SKIN APPEARANCE FROM THE INSIDE Oral intake of clinically effective doses of collagen peptides and hyaluronic acid restores skin hydration and elasticity, reducing eye wrinkle depth up to 20%.

65 LACTOFERRIN HELPS BUILD NEW BONES Lactoferrin provides vital signals that enables an increase in new bone formation. In one study, lactoferrin increased markers of bone-forming activity 24% more than placebo.

DEPARTMENTS

75 HEALTHY EATING Open-air markets called shuks sell the seasonal ingredients for Israeli home 7 WHY ARGININE FAILED cooking. Of the 140 recipes in Shuk, 7 AS A CARDIOVASCULAR DRUG we feature a flavorful four. Back in the 1980s, there was interest about using L-arginine for athero- 83 AUTHOR INTERVIEW sclerosis treatment. Arginine, however, In his book, The Switch, and in his 15 quickly degrades in the body. A new interview, James Clement outlines how sustained-release arginine offers to activate your body’s metabolic switch support for vascular health. to boost weight loss, cut disease risk, 83 and slow aging. 13 IN THE NEWS Oral hygiene reduces heart failure risk; 89 SUPER FOODS PEA alleviates knee discomforts; tea Hemp seeds are high in protein, can lower boosts brain health; blueberries cut the risk of heart disease, improve skin cardiovascular risk. health, and more. 75

APRIL 2020 | LIFE EXTENSION | 1

LEMAPR20p.indd 1 2/19/20 2:13 PM Volume 26 • Number Four LifeExtension.com April 2020 Publisher • LE Publications, Inc.

Editorial Editor-in-Chief • Philip Smith Executive Managing Editor • Renee Price Medical Editor • Hernando Latorre, MD, MSc Senior Editor • Dan Jewel Connect with Life Extension Online! Senior Staff Writer • Michael Downey Department Editor • Laurie Mathena Associate Editor • Rivka Rosenberger, EdD Creative Director • Robert Vergara Facebook.com/LifeExtension Twitter.com/LifeExtension Art Director • Alexandra Maldonado For instant access to special For up-to-the-minute health offers and promotions, product tips, breaking industry news, Chief Medical Officer Chief Scientific Officer news, and exclusive health and the latest updates in Steven Joyal, MD Andrew Swick, MS, PhD and wellness information. medical research. Scientific Advisory Board Örn Adalsteinsson, PhD • Richard Black, DO • John Boik, PhD Customer care is available to take your calls Aubrey de Grey, PhD • Deborah F. Harding, MD • Steven B. Harris, MD 24 hours a day, 7 days a week: 1-800-678-8989 Sandra C. Kaufmann, MD • Peter H. Langsjoen, MD, FACC • Dipnarine Maharaj, MD • L. Ray Matthews, MD, FACS • Ralph W. Moss, PhD Visit the Life Extension® Michael D. Ozner, MD, FACC • Jonathan V. Wright, MD • Xiaoxi Wei, PhD Nutrition Center Store East Cypress Creek Rd. Contributors N Life Extension Susan Cummings • Michael Downey • Laurie Mathena • Jacob Rose • The Most Complete Line of 2 Nutrition Center Life Extension Supplements cean ighway O Advertising • Blood Testing and Analysis l H Vice President of Marketing • Rey Searles • [email protected]

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LIFE EXTENSION (ISSN 1524-198X) Vol. 26, No. 4 ©2020 is published monthly except bi-monthly in April by LE Publications, Inc. at 3600 West Commercial Blvd., Fort Lauderdale, FL 33309-3338. LE Publications, Inc. All rights reserved. Published 13 times a year. Subscription rate: $40 per year in the United States. US $47 in Canada. US $60 in other countries. Mail subscriptions or address changes to: LE Publications, Inc., P.O. Box 407198, Fort Lauderdale, FL 33340-7198, USA. Or phone us toll-free at: 1-800-841-5433. Canada Subscriptions: Publications mail agreement num- ber 40028967. Return undeliverable Canadian addresses to PO Box 503, RPO West Beaver Creek, Richmond Hill, ON L4B4R6. You will be sent your first issue within six weeks after LE Publications, Inc. receives your subscription fee. Periodicals Postage paid at Fort Lauderdale, FL and at additional mailing offices. POSTMASTER: Send address changes to Life Extension, P.O. Box 407198, Ft. Lauderdale, Florida 33340-7198, USA. Printed in USA. The articles in this magazine are intended for informational purposes only. They are not intended to replace the attention or advice of a physi- cian or other health-care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a qualified health-care professional. LEGAL NOTICE: Health claims contained in articles and advertisements in this publication have not been approved by the FDA with the exception of FDA-approved, qualified health claims for calcium, antioxidant vitamins, folic acid and EPA and DHA omega-3 fatty acids, and selenium as noted where applicable. Life Extension ® Magazine does not endorse any of the businesses or the products and/or services that may appear in advertisements for non-Life Extension branded products or services contained in it, except to state that they are advertisers who may have paid Life Extension for placement of an advertisement in this publication. Life Extension disclaims any and all responsibilities or warranties as to the accuracy of information contained in advertisements for non-Life Extension branded products or services. For Canadian customers send change of address information and blocks of undeliverable copies to P.O. Box 1051, Fort Erie, ON L2A 6C7.

2 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 2 2/19/20 2:02 PM Highly Absorbable

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These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 3 2/14/20 11:14 AM MEDICAL ADVISORY BOARD

Gustavo Tovar Baez, MD, operates the Life Mitchell J. Ghen, DO, PhD, holds a doc- Herbert Pardell, DO, FAAIM, practices internal Extension Clinic in Caracas, Venezuela. He is torate in holistic health and anti-aging medicine at the Emerald Hills Medical Center the first physician in Caracas to specialize in and serves on the faculty of medicine in Hollywood, FL. He is a medical director of anti-aging medicine. at the Benemerita Universidad Autonoma the Life Extension Foundation®. Ricardo Bernales, MD, is a board-certified pedia- De Puebla, Mexico, as a professor of Lambert Titus K. Parker, MD, an internist and a trician and general practitioner in Chicago, IL, cellular hematopoietic studies. board- certified anti-aging physician, practices focusing on allergies, bronchial asthma, and Gary Goldfaden, MD, is a clinical dermatolo- integrative medicine from a human ecology immunodeficiency. gist and a lifetime member of the American perspective with emphasis on personalized Mark S. Bezzek, MD, FACP, FAARM, FAAEM, is Academy of Dermatology. He is the founder of brain health, biomarkers, genomics and total boardcertified in internal medicine, emergency Academy Dermatology of Hollywood, FL, and health optimization. He serves as the Medical medicine, and anti-aging/regenerative medi- COSMESIS Skin Care. Director of Integrative Longevity Institute of cine. He is the director of Med-Link Consulting, Miguelangelo Gonzalez, MD, is a certified Virginia, a 501(c)3 Non-Profit Medical Research which specializes in bioidentical hormone plastic and reconstructive surgeon at the Institute. He also collaborates on education replacement therapy, natural alternatives, anti- Miguelangelo Plastic Surgery Clinic, Cabo and research for Hampton Roads Hyperbaric aging, and degenerative diseases. He holds San Lucas. Therapy. U.S. patents for a multivitamin/mineral supple- Garry F. Gordon, MD, DO, is a Payson, Arizona- Ross Pelton, RPh, PhD, CCN, is scientific director ment, an Alzheimer’s/dementia compilation, based researcher of alternative approaches for Essential Formulas, Inc. and a diabetic regimen. to medical problems that are unresponsive Patrick Quillin, PhD, RD, CNS, is a clinical nutri- Thomas F. Crais, MD, FACS, a board-certified plas- to traditional therapies. He is president of the tionist in Carlsbad, CA, and formerly served as tic surgeon, was medical director of the micro- International College of Advanced Longevity vice president of nutrition for Cancer Treatment surgical research and training lab at Southern Medicine. Centers of America, where he was a consultant Baptist Hospital in New Orleans, LA, and cur- Richard Heifetz, MD, is a board-certified anesthe- to the National Institutes of Health. rently practices in Sun Valley, ID. siologist in Santa Rosa, CA, specializing in the Allan Rashford, MD, graduated from the William Davis, MD, is a preventive cardiologist delivery of anesthesia for office-based, plastic/ University of Iowa Medical School. Upon com- and author of Wheat Belly: Lose the Wheat, cosmetic surgery, chelation therapy, and pain pleting medical training, he became chief Lose the Weight and Find Your Path Back to management. of medicine at St. Francis Hospital in South Health. He is also medical director of the online Roberto Marasi, MD, is a psychiatrist in Brescia Carolina, and he was later named president of heart disease prevention and reversal program, and in Piacenza, Italy. He is involved in anti-ag- the Charleston Medical Society. Track Your Plaque (www.trackyourplaque.com). ing strategies and weight management. Marc R. Rose, MD, practices ophthalmology in Martin Dayton, MD, DO, practices at the Sunny Maurice D. Marholin, DC, DO, is a licensed chiro- Los Angeles, CA, and is president of the Rose Isles Medical Center in North Miami Beach, FL. practic physician and board-certified osteo- Eye Medical Group. He is on the staff of Pacific His focus is on nutrition, aging, chelation ther- pathic family physician.While training at the Alliance Medical Center, Los Angeles, and apy, holistic medicine, and oxidative medicine. University of Alabama, he completed fel- other area hospitals. John DeLuca, MD, DC, is a 2005 graduate of St. lowships in Clinical Nutrition and Behavioral Michael R. Rose, MD, a board-certified ophthal- George’s University School of Medicine. He Medicine. He is currently in private practice mologist with the Rose Eye Medical Group completed his internal medicine residency at in Clermont, FL. in Los Angeles, CA, is on the staff of the Monmouth Medical Center in Long Branch, NJ, Professor Francesco Marotta, MD, PhD, of University of Southern California and UCLA. in 2008 and is board-certified by the American Montenapoleone Medical Center, Milan, Italy, Ron Rothenberg, MD, is a full clinical profes- Board of Internal Medicine. Dr. DeLuca is is a gastroenterologist and nutrigenomics sor at the University of California San Diego a Diplomate of the American Academy of expert with extensive international university School of Medicine and founder of California Anti-Aging Medicine and has obtained certifi- experience. He is also a consulting profes- HealthSpan Institute in San Diego. cations in hyperbaric medicine, pain manage- sor at the WHO-affiliated Center for Biotech Roman Rozencwaig, MD, is a pioneer in research ment, nutrition, strength and conditioning, and & Traditional Medicine, University of Milano, on melatonin and aging. He practices in manipulation under anesthesia. Italy and honorary resident professor, Nutrition, Montreal, Canada, as research associate at Sergey A. Dzugan, MD, PhD, was formerly chief Texas Women’s University. He is the author of Montreal General Hospital, Department of of cardiovascular surgery at the Donetsk more than 130 papers and 400 lectures. Medicine, McGill University. Regional Medical Center in Donetsk, Ukraine. Philip Lee Miller, MD, is founder and medical Michael D. Seidman, MD, FACS, is the director Dr. Dzugan’s current primary interests are anti- director of the Los Gatos Longevity Institute of skull base surgery and wellness for the aging and biological therapy for cancer, cho- in Los Gatos, CA. Adventist Health System in Celebration, FL. lesterol, and hormonal disorders. Michele G. Morrow, DO, FAAFP, is a board-certified Ronald L. Shuler, BS, DDS, CCN, LN, is involved Patrick M. Fratellone, MD, RH, is the founder family physician who merges mainstream and in immunoncology for the prevention and and executive medical director of Fratellone alternative medicine using functional medicine treatment of cancer, human growth hormone Associates. He completed his internal med- concepts, nutrition, and natural approaches. secretagogues, and osteoporosis. He is board- icine and cardiology fellowship at Lenox Filippo Ongaro, MD, is board-certified in anti- certified in anti-aging medicine. Hill Hospital in 1994, before becoming the aging medicine and has worked for many medical director for the Atkins Center for Paul Wand, MD, Fort Lauderdale, FL, is a clinical years as flight surgeon at the European Complementary Medicine. neurologist with special expertise in treating Space Agency. He is a pioneer in func- and reversing diabetic peripheral neuropathy Norman R. Gay, MD, is proprietor of the Bahamas tional and anti-aging medicine in Italy and brain injuries from various causes. Anti-Aging Medical Institute in Nassau, where he also works as a journalist and Bahamas. A former member of the Bahamian a writer. Parliament, he served as Minister of Health and Minister of Youth and Sports.

4 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 4 2/14/20 2:53 PM SCIENTIFIC ADVISORY BOARD

Örn Adalsteinsson, PhD, is chairman of the Life Peter H. Langsjoen, MD, FACC, is a cardiologist Extension® Scientific Advisory board. He holds a specializing in congestive heart failure, primary and master’s and doctorate from the Massachusetts statin-induced diastolic dysfunction, and other heart Institute of Technology (MIT). He has specialized in diseases. A leading authority on coenzyme Q10, Dr. human therapeutics including vaccines, monoclonal Langsjoen has been involved with its clinical appli- antibodies, product development, nutraceuticals, cation since 1983. He is a founding member of the formulations, artificial intelligence, hormones, and executive committee of the International Coenzyme nutritional supplementation. He has also authored Q10 Association, a fellow of the American College of articles and contributed to peer-reviewed publica- Cardiology, and a member of numerous other medi- tionzs and served as an editor for the Journal of cal associations. Medicinal Food. Dipnarine Maharaj MD, MB, ChB, FRCP (Glasgow), FRCP (Edinburgh), FRCPath., FACP, is the Medical Director of Richard Black, DO, is a dedicated nuclear medicine the South Florida Bone Marrow Stem Cell Transplant physician practicing as an independent contractor Institute and is regarded as one of the world’s out of Cleveland, Ohio. Dr. Black is board certified foremost experts on adult stem cells. He received in internal medicine and nuclear medicine, and is his medical degree in 1978 from the University of licensed to practice medicine in multiple states Glasgow Medical School, Scotland. He completed throughout the United States. his internship and residency in Internal Medicine John Boik, PhD, is the author of two books on can- and Hematology at the University’s Royal Infirmary. cer therapy, Cancer and Natural Medicine (1996) L. Ray Matthews, MD, FACS, is a professor of surgery and Natural Compounds in Cancer Therapy (2001). and director of Surgical Critical Care at Morehouse He earned his doctorate at the University of Texas School of Medicine in Atlanta, GA, and a trauma and Graduate School of Biomedical Sciences with critical care surgeon at Grady Memorial Hospital. He research at the MD Anderson Cancer Center, focus- has published widely and is known as one of the top ing on screening models to identify promising new vitamin D experts. Dr. Matthews has spoken before anti-cancer drugs. He conducted his postdoctoral the U.S. Food and Drug Administration several times, training at Stanford University’s Department of presenting a recent update about clinical research Statistics. on vitamin D. Aubrey de Grey, PhD, is a biomedical gerontologist Ralph W. Moss, PhD, is the author of books such as and Editor-in-Chief of Rejuvenation Research, the Antioxidants Against Cancer, Cancer Therapy, world’s highest-impact, peer-reviewed journal Questioning Chemotherapy, and The Cancer focused on intervention in aging. He received his Industry, as well as the award-winning PBS doc- BA and PhD from the University of Cambridge in umentary The Cancer War. Dr. Moss has inde- 1985 and 2000 respectively. Dr. de Grey is a Fellow pendently evaluated the claims of various cancer of both the Gerontological Society of America and treatments and currently directs The Moss Reports, the American Aging Association and sits on the an updated library of detailed reports on more than editorial and scientific advisory boards of numerous 200 varieties of cancer diagnoses. journals and organizations. Michael D. Ozner, MD, FACC, FAHA, is a board-certi- fied cardiologist who specializes in cardiovascular Deborah F. Harding, MD, is founder of the Harding disease prevention. He serves as medical direc- Anti-Aging Center. She is double board-certified in tor for the Cardiovascular Prevention Institute of internal medicine and sleep disorder medicine. She South Florida and is a noted national speaker on also earned the Cenegenics certification in age man- heart disease prevention. Dr. Ozner is also author agement medicine. She is a faculty member of the of The Great American Heart Hoax,The Complete University of Central Florida Medical School. Mediterranean Diet and Heart Attack Proof. For Sandra C. Kaufmann, MD, is a fellowship-trained and more information visit www.drozner.com. board-certified pediatric anesthesiologist as well Jonathan V. Wright, MD, is medical director of the as the Chief of Anesthesia at the Joe DiMaggio Tahoma Clinic in Tukwila, WA. He received his MD Children’s Hospital in Hollywood, Florida. She is the from the University of Michigan and has taught founder of The Kaufmann Anti-Aging Institute and natural biochemical medical treatments since 1983. the author of the book The Kaufmann Protocol: Why Dr. Wright pioneered the use of bioidentical estro- we Age and How to Stop it (2018). Her expertise is gens and DHEA in daily medical practice. He has in the practical application of anti-aging research. authored or co-authored 14 books, selling more than 1.5 million copies. Steven B. Harris, MD, is president and director of Xiaoxi Wei, PhD, is a chemist, expert in supramolecular research at Critical Care Research, a company assembly and development of synthetic transmem- that grew out of 21st Century Medicine in Rancho brane nanopores with distinguished selectivity via Cucamonga, CA. Dr. Harris participates in ground- biomimetic nanoscience. She has expertise in ion breaking hypothermia, cryothermia, and ischemia channel function and characterization. She founded research. His research interests include antioxi- X-Therma Inc., a company developing a radical dant and dietary-restriction effects in animals and new highway towards non-toxic, hyper-effective humans. antifreeze agents to fight unwanted ice formation in regenerative medicine and reduce mechanical icing.

APRIL 2020 | LIFE EXTENSION | 5

LEMAPR20p.indd 5 2/19/20 1:49 PM B D 12

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These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.

LEMAPR20p.indd 6 2/14/20 11:19 AM AS WE SEE IT Why Arginine Failed as a Cardiovascular Drug

L-arginine increases nitric oxide, With age, the activity of arginine- degrading enzymes increases in which enables arteries to many tissues, most notably the expand with youthful elasticity.1 cardiovascular system.4,5 I was pleased to learn of a novel method to protect L-arginine from degrading in the stomach and Back in the 1980s, there was enhance nitric oxide availability. excitement about using the amino acid L-arginine to prevent and treat This new formula utilizes a low-dose atherosclerosis. arginine compound to sustain higher arginine plasma levels, plus a berry Boosting nitric oxide improves extract that helps stabilize endo- circulation throughout the body.2 thelial nitric oxide. A drug company obtained a patent The berry extract alone was shown to sell an L-arginine powder to to increase a validated measure of cardiologists for coronary heart WILLIAM FALOON circulation.6 disease patients. Low-dose, sustainable L-arginine Others promoted the sex-enhanc- combined with aronia berry extract ing effects of improved blood flow offers intriguing potential to support ARGININE to male and female genitalia. circulatory health. L-arginine, however, has some Cardiologists may eventually pre- major limitations. scribe this novel approach now that Much of it gets degraded by longer-acting, low-dose arginine enzymes before being converted plus aronia polyphenols can be to nitric oxide in the arterial wall.3 conveniently taken together. ARONIA BERRY

HUMAN ARTERY

APRIL 2020 | LIFE EXTENSION | 7

LEMAPR20p.indd 7 2/19/20 2:01 PM AS WE SEE IT

Nitric Oxide: Discovering Nitric Oxide’s L-arginine has demonstrated “Molecule of The Year” Health Effects other benefits, such as accelerat- In 1992, the journal Science In 1987, scientists were seeking to ing wound healing, and helping to nominated nitric oxide as the “relax” the inner wall of arteries, called maintain kidney function.16-18 “Molecule of the Year.”7 the endothelium. 11 After more than four decades Not only does nitric oxide A major advance occurred when of study, it appears that the most support the inner arterial wall to nitric oxide was found to be released important role of L-arginine is its enable healthy circulation, but it is from the endothelium. ability to produce nitric oxide, and also a neurotransmitter.8,9 The release of nitric oxide induces thus protect against endothe- Over the past three decades, relaxation of the lining of the lial dysfunction (and subsequent nitric oxide has demonstrated value artery.8,12 atherosclerosis).19-21 through its diverse applications Nitric oxide is now understood The elderly often suffer from in medicine. Dr. Solomon Snyder, to be a principal regulator of blood accelerated atherosclerosis.22 founder of the Solomon H. Snyder pressure. One reason is that nitric oxide- Department of Neuroscience at blocking compounds in the body Johns Hopkins Medical School increase with age, thus causing dis- Arginine Needed wrote: ruption to the artery’s endothelial to Make Nitric Oxide lining. “In my 25 years of research, Nitric oxide is synthesized It is encouraging to know that I have never seen a in the body from the amino acid arginine is able to help reverse this 13 molecule [nitric oxide] L-arginine. particular atherogenic event.20 that so pervasively Since the mid-1980s, arginine has been a popular supplement for influences normal and body builders,14,15 along with aging Reversing 10 abnormal body functions.” people wanting to protect against Arterial Stiffness nitric oxide deficit. The age-related decline in L-arginine bioavailability reduces nitric oxide production.4,5 The result is a disruption of healthy endothelial function and structure.22 Endothelial dysfunction inhibits the ability of arteries to expand and contract (vasodilation). This contrib- utes to hypertension.23 Arginase is an enzyme present in multiple tissues in the body.24 In the intestinal tract, the arginase enzyme degrades about 40% of ingested arginine before it can be absorbed into the bloodstream. Once in the bloodstream, L-arginine is further degraded by three other enzymes with only a small amount remaining that can be converted to nitric oxide.3,25 In one study, when the argi- nase enzyme was blocked in rat arteries, L-arginine levels went up.

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LEMAPR20p.indd 8 2/14/20 11:19 AM AS WE SEE IT

Nitric oxide is one important factor required for the endothelium to function properly. The amino acid L-arginine serves as a precursor to nitric oxide in the body.

Challenge of Obtaining Arginine Benefits A major drawback to L-arginine supplementation has always been that, in order to achieve a sustained blood level, people had to take high doses throughout the day. It was difficult to comply with this rigorous dosing requirement and there may be side effects with ingesting this much arginine on a consistent basis. A more troublesome shortcom- ing of L-arginine is the age-related increase in the activity of the argi- nase enzyme that rapidly degrades While arterial dilation increased vascular disorders, and how fast arginine. This means that little only modestly in young animals, they sometimes accelerate after ingested arginine is available to pro- it increased an astounding 680% initial diagnosis. mote nitric oxide synthesis.3,24 in old animals!26 One problem up to now has For people with increased Even more impressive was that been that people could not obtain arginase activity, supplemental the arteries of old rats (23 months) arginine’s benefits because of its L-arginine may not provide ade- regained the same vasodilation rapid enzymatic degradation in the quate nitric oxide synthesis to pro- as young rats (three months) in intestines and blood.3 tect against endothelial dysfunction. response to blocking the L-arginine- degrading enzyme called arginase. This rat study provides evidence Protect Against of the adverse effects that aging Endothelial Dysfunction inflicts on the endothelium, including Aging people can slow the break- elevated blood pressure. down of their delicate endothelium This study demonstrated that (inner artery wall linings). aged arteries can be rejuvenated Folate, vitamin C, fish oil, lipoic by providing the vascular system acid, and pomegranate are a few with more L-arginine. of the nutrients that help maintain healthy endothelial function.29-36 It is no coincidence that these Human Data same nutrients have been shown More recent studies show that in some studies to reduce the inci- 70-to-80-year-old humans lose up dence of cardiovascular pathology to 75% of their endothelial nitric in animals and humans.37-42 Statin oxide compared to healthy 20 year drugs and agents that suppress olds.27,28 This helps explain why chronic inflammation also help so many elderly people suffer protect the endothelium.43-46

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Dual Combination to Boost Nitric Oxide In a significant advance, a form of arginine has been shown to decrease the arginase enzyme, allowing L-arginine to remain pres- ent in the plasma for a greater length of time.47 In a preclinical study, polyphe- nols from aronia berries dem- onstrate the ability to increase activation of an enzyme called endothelial nitric oxide synthase that is responsible for producing nitric oxide from arginine.48 In addition, these polyphenols have been shown, in another pre- clinical study, to stimulate nitric oxide formation in coronary arteries.49 This means that lower doses of L-arginine can be used to enable References more sustained nitric oxide synthe- Atherosclerosis is usually associ- 1. Brooks JR, Oketch-Rabah H, Low Dog T, sis needed for healthy endothelial ated with heart attack risk, but many et al. Safety and performance benefits of function. of the disorders of aging, including arginine supplements for military person- kidney impairment and memory nel: a systematic review. Nutr Rev. 2016 Nov;74(11):708-21. loss, are related to circulatory Support for 2. Boger RH, Bode-Boger SM. The clinical disorders.52-54 pharmacology of L-arginine. Annu Rev Aging Arteries Pharmacol Toxicol. 2001;41:79-99. Sales of sex-enhancing drugs are 3. Wu G, Bazer FW, Davis TA, et al. Argi- People who follow a healthy life- strong mainly because so many men nine metabolism and nutrition in growth, health and disease. Amino Acids. 2009 style often develop a false sense suffer from endothelial dysfunction May;37(1):153-68. of security that they will not suffer that causes erectile dysfunction.55 4. Moretto J, Girard C, Demougeot C. The role ® of arginase in aging: A systematic review. the circulatory disorders that are In this issue of Life Extension , Exp Gerontol. 2019 Feb;116:54-73. the leading killers in the Western we describe a novel approach to 5. Santhanam L, Christianson DW, Nyhan D, help prevent and/or partially reverse et al. Arginase and vascular aging. J Appl world. Physiol (1985). 2008 Nov;105(5):1632-42. One reason for this optimism is endothelial dysfunction. 6. Istas G, Wood E, Le Sayec M, et al. Effects that heart disease death rates have Life Extension® readers take of aronia berry (poly)phenols on vascular function and gut microbiota: a double-blind 50 declined dramatically since 1980. aggressive steps to maintain healthy randomized controlled trial in adult men. Much of this can be attributed to circulation, but haven’t had access Am J Clin Nutr. 2019 Aug 1;110(2):316-29. 7. Koshland DE, Jr. The molecule of the year. reduced tobacco use, improved to a slowly released, continuous flow Science. 1992 Dec 18;258(5090):1861. diets and medical treatments, better of L-arginine to boost nitric oxide. 8. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 Dec control of hypertension, along with For longer life, 30;329(27):2002-12. increased use of supplements, and 9. Snyder SH, Bredt DS. Biological roles of 51 nitric oxide. Sci Am. 1992 May;266(5):68- drugs that lower heart attack risk. 71, 4-7. A lot of people who would have 10. Talan J. The healing powers of nitric oxide. suffered from blocked coronary Montreal Gazette. September 26, 1993: C5. 11. Ignarro LJ, Buga GM, Wood KS, et al. arteries or a heart attack around William Faloon, Co-Founder Endothelium-derived relaxing factor pro- age 50 are delaying this problem Life Extension Buyers Club duced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987 until later in life. Dec;84(24):9265-9.

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LEMAPR20p.indd 10 2/14/20 11:19 AM AS WE SEE IT

12. Hurlimann D. The relationship between 30. Tardif JC, Rheaume E. Lipoic acid supple- 45. Ellulu MS. Obesity, cardiovascular the endothelium and the vessel wall. mentation and endothelial function. Br J disease, and role of vitamin C on inflam- European Heart Journal Supplements. Pharmacol. 2008 Apr;153(8):1587-8. mation: a review of facts and underlying 2002;4(suppl_A):A1-A7. 31. Wang D, Ozen C, Abu-Reidah IM, et al. mechanisms. Inflammopharmacology. 2017 13. Wilson G, Garthwaite J. Nitric Oxide. In: Vasculoprotective Effects of Pomegranate Jun;25(3):313-28. Squire LR, ed. Encyclopedia of Neurosci- (Punica granatum L.). Front Pharmacol. 46. Santos-Parker JR, Strahler TR, Bassett CJ, ence. Oxford: Academic Press; 2009:1151-6. 2018;9:544. et al. Curcumin supplementation improves 14. L-arginine. Monograph. Altern Med Rev. 32. Zehr KR, Walker MK. Omega-3 polyunsatu- vascular endothelial function in healthy 2005 Jun;10(2):139-48. rated fatty acids improve endothelial func- middle-aged and older adults by increas- 15. Available at: https://www.essentialnutrition. tion in humans at risk for atherosclerosis: A ing nitric oxide bioavailability and reducing com.br/media/artigos/crealift/23.pdf. Ac- review. Prostaglandins Other Lipid Mediat. oxidative stress. Aging (Albany NY). 2017 cessed January 17, 2020. 2018 Jan;134:131-40. Jan 3;9(1):187-208. 16. Gould A, Naidoo C, Candy G. Arginine me- 33. Zanetti M, Gortan Cappellari G, Barbetta D, 47. Komorowski J, Perez Ojalvo S, Sylla S, et tabolism and wound healing. Wound Heal et al. Omega 3 Polyunsaturated Fatty Acids al. Arginase inhibition by inositol-stabilized South Afr. 2009 01/01;1:48-50. Improve Endothelial Dysfunction in Chronic arginine silicate (ASI; Nitrosgine); a novel 17. Ghasemi M, Nematbakhsh M, Daneshmand Renal Failure: Role of eNOS Activation and mechanism by which ASI enhances argi- F, et al. Role of nitric oxide in kidney and of Oxidative Stress. Nutrients. 2017 Aug nine bioavailability. American Society for liver (as distance organ) function in bilateral 18;9(8):895. Nutrition’s Annual Meeting 2018; 2018; renal ischemia-reperfusion: Effect of L- 34. Fahs CA, Yan H, Ranadive S, et al. The Boston, MA. Arginine and NG-nitro-L-Arginine methyl effect of acute fish-oil supplementation on 48. Varela CE, Fromentin E, Roller M, et ester. Adv Biomed Res. 2015;4:233. endothelial function and arterial stiffness al. Effects of a natural extract of Aronia 18. Tirani SA, Pezeshki Z, Nematbakhsh M, following a high-fat meal. Appl Physiol Nutr Melanocarpa berry on endothelial cell nitric et al. Effect of L-arginine and L-NAME on Metab. 2010 Jun;35(3):294-302. oxide production. J Food Biochem. 2016 Kidney Tissue Damage in Rats after 24 h 35. Stanhewicz AE, Kenney WL. Role of folic Aug;40(4):404-10. of Bilateral Ureteral Obstruction. Int J Prev acid in nitric oxide bioavailability and vas- 49. Kim JH, Auger C, Kurita I, et al. Aronia Med. 2015;6:60. cular endothelial function. Nutr Rev. 2017 melanocarpa juice, a rich source of poly- 19. Strohle A, von Bibra H, Hahn A. L-Arginine Jan;75(1):61-70. phenols, induces endothelium-dependent and vascular health. Med Monatsschr 36. Ashor AW, Lara J, Mathers JC, et al. Ef- relaxations in porcine coronary arteries via Pharm. 2016 Dec;39(12):515-20. fect of vitamin C on endothelial func- the redox-sensitive activation of endothelial 20. Gornik HL, Creager MA. Arginine and tion in health and disease: a systematic nitric oxide synthase. Nitric Oxide. 2013 endothelial and vascular health. J Nutr. 2004 review and meta-analysis of randomised Nov 30;35:54-64. Oct;134(10 Suppl):2880S-7S; discussion 95S. controlled trials. Atherosclerosis. 2014 50. Weir HK, Anderson RN, Coleman King SM, 21. Heffernan KS, Fahs CA, Ranadive SM, et Jul;235(1):9-20. et al. Heart Disease and Cancer Deaths - al. L-arginine as a nutritional prophylaxis 37. Mohammad A, Ali N, Reza B, et al. Effect of Trends and Projections in the United States, against vascular endothelial dysfunction ascorbic acid supplementation on nitric ox- 1969-2020. Prev Chronic Dis. 2016 Nov with aging. J Cardiovasc Pharmacol Ther. ide metabolites and systolic blood pressure 17;13:E157. 2010 Mar;15(1):17-23. in rats exposed to lead. Indian J Pharmacol. 51. Mensah GA, Wei GS, Sorlie PD, et al. De- 22. Wang JC, Bennett M. Aging and ath- 2010 Apr;42(2):78-81. cline in Cardiovascular Mortality: Possible erosclerosis: mechanisms, functional 38. Cui S, Li W, Lv X, et al. Folic Acid Supple- Causes and Implications. Circ Res. 2017 consequences, and potential therapeutics mentation Delays Atherosclerotic Lesion Jan 20;120(2):366-80. for cellular senescence. Circ Res. 2012 Jul Development by Modulating MCP1 and 52. Dubois B, Hampel H, Feldman HH, et al. 6;111(2):245-59. VEGF DNA Methylation Levels In Vivo and Preclinical Alzheimer’s disease: Definition, 23. Konukoglu D, Uzun H. Endothelial Dysfunc- In Vitro. Int J Mol Sci. 2017 May 5;18(5). natural history, and diagnostic criteria. Al- tion and Hypertension. Adv Exp Med Biol. 39. Graham IM, O’Callaghan P. The role of zheimers Dement. 2016 Mar;12(3):292-323. 2017;956:511-40. folic acid in the prevention of cardiovas- 53. Kooman JP, van der Sande FM, Leunissen 24. Ming X-F, Yang Z. Functions and Mecha- cular disease. Curr Opin Lipidol. 2000 KM. Kidney disease and aging: A recipro- nisms of Arginase in Age-Associated Car- Dec;11(6):577-87. cal relation. Exp Gerontol. 2017 Jan;87(Pt diovascular Diseases. Current Translational 40. Jain AP, Aggarwal KK, Zhang PY. Omega-3 B):156-9. Geriatrics and Experimental Gerontology fatty acids and cardiovascular disease. Eur 54. Chade AR, Lerman A, Lerman LO. Kidney Reports. 2013 2013/12/01;2(4):268-74. Rev Med Pharmacol Sci. 2015;19(3):441-5. in early atherosclerosis. Hypertension. 2005 25. Wu G, Morris SM, Jr. Arginine metabolism: 41. Aviram M, Rosenblat M. Pomegranate Jun;45(6):1042-9. nitric oxide and beyond. Biochem J. 1998 for your cardiovascular health. Rambam 55. Stein RA. Endothelial dysfunction, erectile Nov 15;336 ( Pt 1):1-17. Maimonides Med J. 2013 Apr;4(2):e0013. dysfunction, and coronary heart disease: 26. Berkowitz DE, White R, Li D, et al. Arginase 42. Zhang WJ, Bird KE, McMillen TS, et al. the pathophysiologic and clinical linkage. reciprocally regulates nitric oxide synthase Dietary alpha-lipoic acid supplementation Rev Urol. 2003;5 Suppl 7(Suppl 7):S21-7. activity and contributes to endothelial dys- inhibits atherosclerotic lesion develop- function in aging blood vessels. Circulation. ment in apolipoprotein E-deficient and 2003 Oct 21;108(16):2000-6. apolipoprotein E/low-density lipoprotein 27. Torregrossa AC, Aranke M, Bryan NS. receptor-deficient mice. Circulation. 2008 Nitric oxide and geriatrics: Implications in Jan 22;117(3):421-8. diagnostics and treatment of the elderly. J 43. Oz HS. Chronic Inflammatory Diseases and Geriatr Cardiol. 2011 Dec;8(4):230-42. Green Tea Polyphenols. Nutrients. 2017 28. Egashira K, Inou T, Hirooka Y, et al. Effects Jun 1;9(6):561. of age on endothelium-dependent vaso- 44. Margaritis M, Channon KM, Antoniades dilation of resistance coronary artery by C. Statins as regulators of redox state in acetylcholine in humans. Circulation. 1993 the vascular endothelium: beyond lipid Jul;88(1):77-81. lowering. Antioxid Redox Signal. 2014 Mar 29. Heinisch BB, Francesconi M, Mittermayer 10;20(8):1198-215. F, et al. Alpha-lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo-controlled randomized trial. Eur J Clin Invest. 2010 Feb;40(2):148-54.

APRIL 2020 | LIFE EXTENSION | 11

LEMAPR20p.indd 11 2/14/20 11:19 AM Most Complete Omega-3 FISH OIL FORMULA

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LEMAPR20p.indd 12 2/14/20 11:20 AM IN THE NEWS

In the News

Atrial Fibrillation and Heart Failure Risk are Lower with Better Oral Hygiene

How well you take care of your teeth is linked to your risk of atrial fibrillation and heart failure, a study published in the European Journal of Preventive Cardiology* reported. Better oral hygiene is associated with a lower risk of atrial fibrillation and heart failure, researchers concluded. The study subjects were 161,286 men and women from the National Health Insurance System-Health Screening Cohort in Korea, aged 40 to 79, with no prior history of atrial fibrillation, heart fail- ure, or cardiac valvular diseases. They were examined by dentists to note the presence of periodontal disease, con- dition of teeth, and missing teeth, and they completed a questionnaire about their oral hygiene behavior and dental symptoms. The median follow-up was 10.5 years, during which there were 4,911 (3%) cases of atrial fibrillation and 7,971 (4.9%) cases of heart failure. Brushing teeth three times a day or more was associated with a 10% reduced risk of atrial fibrillation and a 12% reduced risk of heart failure.

Editor’s Note: “Poor oral hygiene can provoke transient bacteremia and systemic inflammation, a mediator of atrial fibrillation and heart failure,” the authors stated. * Eur J Prev Cardiol. 2019 Dec 1.

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LEMAPR20p.indd 13 2/14/20 11:46 AM IN THE NEWS

PEA Safe, Effective for In comparison with the placebo group, participants who Knee Osteoarthritis received PEA experienced significant reductions in pain (up to 57.6%) and stiffness (up to 53.7%) scores. Function The journal Inflammopharmacology reported the out- significantly improved among those who received 600 mg come of a randomized, double-blind trial that revealed of PEA. Both doses of PEA were associated with improve- the safety and efficacy of supplementation with PEA ments in pain intensity scores and anxiety. (palmitoylethanolamide) for individuals with knee osteo- By week eight, the number of participants reporting arthritis.* no pain had increased by more than two and a half times The trial included 111 men and women with mild to in both groups, while decreasing slightly among the pla- moderate osteoarthritis in one or both knees who were cebo group compared to the beginning of the study. given either a placebo, 300 mg of PEA or 600 mg of Editor’s Note: Palmitoylethanolamide is a fatty acid that is naturally PEA daily for eight weeks. Pain, stiffness and other fac- produced in the body as part of a healthy immune response. tors were evaluated at the beginning and end of the trial. * Inflammopharmacology. 2019 Jun;27(3):475-485.

14 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 14 2/14/20 11:47 AM IN THE NEWS

Drinking Tea Supports a Healthy Brain

Research reported in the jour- nal Aging revealed a brain benefit in association with regularly drink- ing tea.* Acting on the results of previous research that found a reduction in the risk of cognitive decline among daily tea drinkers, the current study compared 15 tea drinkers aged 60 and older to 21 participants in the same age group who did not regu- larly consume tea. Neuropsychological tests evalu- ated cognitive function and mag- netic resonance imaging assessed brain connectivity. Participants who regularly consumed tea had better organized brain regions and cogni- tive function compared to those who were not tea drinkers. The authors noted that, “Tea has been a popular beverage since antiquity, with records referring to consumption dating back to the dynasty of Shen Nong (approxi- mately 2700 BC) in China.” They went on to say that drinking tea has become increasingly popular in western countries today. The study was led by Research Assistant Professor Feng Lei, of the National University of Singapore School of Medicine, with collabora- tors from the University of Essex and University of Cambridge.

Editor’s Note: “Our results offer the first evi- dence of positive contribution of tea drinking to brain structure and suggest that drinking tea regularly has a protective effect against age-related decline in brain organization,” said Dr. Feng Lei. * Aging (Albany NY). 2019 Jun 14;11(11): 3876-3890.

APRIL 2020 | LIFE EXTENSION | 15

LEMAPR20p.indd 15 2/14/20 11:47 AM IN THE NEWS

Blueberry Intake May Reduce Cardiovascular Disease Risk

A study reported in the American Journal of Clinical Nutrition found a lower risk of cardiovascular dis- ease among men and women with metabolic syndrome who con- sumed the equivalent of a cup of blueberries daily for six months.* A total of 138 participants were randomized to groups that received 26 grams of powdered blueberries (equivalent to a cup of fresh blueberries), 13 grams of powdered blueberries plus ½ cup of a mock blueberry placebo, or 26 grams of the placebo. Insulin resistance, flow mediated dilatation (a measure of endothe- lial function), augmentation index (which measures arterial stiffness), cholesterol, and other factors were measured before and after the intervention. The researchers observed an improvement in endothelial func- tion and arterial stiffness in the group that received 26 grams of blueberry powder.

Editor’s Note: “The simple and attainable message to consume one cup of blueber- ries daily should be given to those aiming to improve their cardiovascular health,” the authors concluded. * Am J Clin Nutr. 2019 Jun 1;109(6):1535- 1545.

16 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 16 2/19/20 2:09 PM STRONGER BONES STRONGER YOU

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LEMAPR20p.indd 18 2/14/20 11:26 AM Enhance Arginine to Boost NITRIC OXIDE

When L-arginine is ingested, about 40% is degraded in the digestive tract by the arginase enzyme. Mix one (1) stick pack of NitroVasc™ Boost in 8 oz of water for a tasty, berry- flavored drink. Drink on an empty After absorption, arginine encounters further stomach, or as recommended by a degradation, leaving little for conversion into health care professional.

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LEMAPR20p.indd 19 2/19/20 2:07 PM Promote Oral Health with Targeted

Probiotic Blend Item #02120࠮30 lozenges 1 bottle $15 4 bottles $13 each FLORASSIST® Oral Hygiene provides the S. salivarius BLIS M™ oral probiotic that colonizes the mouth and inhibits the growth of unwanted bacteria.- References 1. Oral Microbiol Immunol. 2009 Apr;24(2):152-61. This product also contains beneficial Immuno-LP®. 2. J Med Microbiol. 2013 Jun;62(Pt 6):875-84. 3. Benef Microbes. 2011 Jun;2(2):93-101. Just one mint cherry lozenge of FLORASSIST® Oral 4. IADR/AADR/CADR 89th General Session and Exhibition, 16–19 March 2011, San Diego, CA, USA. Paper no. 150126. Hygiene a day maximizes oral hygiene by supporting healthy bacterial colonization throughout the mouth.- BLIS™ and BLIS M18™ are trademarks of Blis Technologies Limited and the subject of USA patent no. 7226590. Immuno- LP20® is a registered trademark of House Foods Group Inc.

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LEMAPR20p.indd 20 2/19/20 2:09 PM Blueberry EXTRAC T

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LEMAPR20p.indd 21 2/14/20 11:53 AM SAFELYSSAAAFFELLYLY AALALLEVIATELLEVLELEVEVIAIATIAATTEE1 11111S SSYMPTOMSYYMPYMMMPPTOTOMTOOMMSSO OOFFFM MMENOPAUSEENOENENONOPAUPAPAAUUSESE

22 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 22 2/14/20 11:54 AM Boost Nitric Oxide to Reduce Cardiovascular RISK

BY JACOB ROSE

Nitric oxide is a substance your body naturally produces. It signals blood vessels to widen, allowing blood to flow through freely. But nitric oxide production decreases with age.1 This contributes to endothelial dysfunction that leads to the initiation and progression of arterial disease.2-5

The consequences of endothelial dysfunction are: 1. Diminished circulation 2. High blood pressure 3. Throm bosis (clots inside blood vessels)

4. Atherosclerosis

These are major causes of stroke and heart attack.5-8 We can’t get nitric oxide directly from diet or supplements. The good news is that L-arginine and aronia berries help the body make more of it.

APRIL 2020 | LIFE EXTENSION | 23

LEMAPR20p.indd 23 2/14/20 11:55 AM BOOST NITRIC OXIDE TO REDUCE CARDIOVASCULAR RISK

Endothelial Dysfunction and How L-Arginine Helps Cardiovascular Disease Unfortunately, we can’t simply take nitric oxide as The endothelium is the inner lining of blood ves- a supplement. It has an extremely short half-life, which sels, and it plays a critical role in regulating the flow of means it’s too quickly metabolized and eliminated from blood.2-4 the bloodstream to be useful. It does this by producing nitric oxide, which signals To work properly, blood vessels must make nitric blood vessels to dilate (widen). That allows greater oxide for themselves. To do so, they need a precur- blood flow to tissues, including the heart and brain. sor compound. This precursor is an amino acid called But as we age, our body makes less nitric oxide.1 L-arginine. That can lead to endothelial dysfunction, which means Aware of this link between L-arginine and nitric the blood vessels are unable to dilate and constrict as oxide production, researchers evaluated whether needed, reducing blood flow.2-4 increasing intake of L-arginine improves blood vessel This condition, referred to as arterial stiffness, con- dilation, lowering risk for disease.13-17 tributes to high blood pressure, formation of athero- One of the main ways to test this is to measure how sclerotic plaque, and inflammation in the arteries—all much a blood vessel widens in response to an increase of which can lead to cardiovascular disease.9 in blood flow, something called flow-mediated dilation. It also greatly increases the risk of abnormal clotting, In a landmark clinical trial published in the which can block blood vessels, leading to heart attack, International Journal of Cardiology, scientists gave stroke, and sudden cardiac death.10,11 patients with high blood pressure a single dose of either Endothelial dysfunction is surprisingly common; L-arginine or a placebo.15 While the placebo group had one study showed it affected about one third of people no change in their blood vessel function, those receiv- without any prior history of cardiovascular disease.12 ing L-arginine had an improvement in their flow-medi- The elderly, diabetics, the obese, smokers, people with ated dilation from an average of 1.7% to 5.9%. cardiovascular disease, and those with high cholesterol Considering that each 1% improvement in flow- or high blood pressure have a higher risk.2-4 mediated dilation correlates with a 12% lower risk of But if we can increase the amount of nitric oxide in cardiovascular events like heart attacks and strokes,18,19 our blood vessels, it may stop, and even reverse endo- this would suggest a 50% reduction in risk of cardio- thelial dysfunction. vascular events if the effect is sustained over time. Other longer-term clinical studies have shown that taking L-arginine can lower blood pressure and reduce symptoms associated with coronary artery disease.16,20

A New, Better Form of L-Arginine Life Extension® has written about L-arginine for the past 38 years. But in the last few years, scientists have developed and tested a new form. Known as inositol-stabilized arginine silicate, this novel form is more bioavailable, which means more of it is absorbed into the bloodstream after ingestion. Studies show that L-arginine blood levels increase within one hour after supplementation with inositol- stabilized arginine silicate and stay there for many hours.21,22 It appears to do this by inhibiting the enzyme argi- nase, which breaks down L-arginine in the digestive tract, allowing more of the L-arginine to enter and cir- culate in the blood longer.23

24 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 24 2/14/20 11:55 AM BOOST NITRIC OXIDE TO REDUCE CARDIOVASCULAR RISK

WHAT YOU NEED TO KNOW

Boost Nitric Oxide to Support Endothelial Function

Q The endothelium is a layer of cells lining Aronia Berry Improves Endothelial Function the inside of blood vessels. It produces Aronia berries are small, dark purple berries native nitric oxide, a gas that signals the to North America. They’re high in anthocyanins, ben- vessel to dilate, allowing blood to flow eficial polyphenols. through and preventing abnormal Scientists discovered that like L-arginine, aronia can clotting. improve endothelial function. Q With age and other risk factors, nitric While L-arginine provides the precursor needed oxide production declines, contribut- to form nitric oxide, polyphenols from aronia berries ing to endothelial dysfunction. This appear to increase the activity of the enzyme that con- increases risk for the development of verts the L-arginine into nitric oxide. cardiovascular disease events, includ- It does this by inducing the modification of the ing heart attack and stroke. enzyme, called endothelial nitric oxide synthase, in a way that turns the enzyme “on.”24 Q L-arginine is a precursor the body In one randomized, controlled trial, daily supplemen- needs to make nitric oxide. A new form, tation with 500 mg of aronia whole fruit berry for 12 inositol-stabilized arginine silicate, weeks resulted in improved flow-mediated dilation.25 improves its bioavailability and supports Subjects taking the aronia had a 0.9% improvement higher levels in the bloodstream for a in flow-mediated dilation compared to those taking a longer time. placebo. Q Aronia berries help activate the That may sound small, but bear in mind that each 1% enzyme that converts L-arginine into improvement in flow-mediated dilation correlates with a nitric oxide. 12% lower risk of cardiovascular events,18,19 suggesting that this corresponds to a nearly 11% reduction in risk Q These two ingredients work to boost for cardiovascular events. nitric oxide production, helping blood The enhanced bioavailability of inositol-stabilized vessels dilate more efficiently. This may arginine silicate coupled with the increased endothe- significantly reduce risk for heart attack, lial nitric oxide synthase activity from aronia berries stroke, and other cardiovascular events. make this a potent duo in the production of nitric oxide.

APRIL 2020 | LIFE EXTENSION | 25

LEMAPR20p.indd 25 2/14/20 11:55 AM BOOST NITRIC OXIDE TO REDUCE CARDIOVASCULAR RISK

Summary 17. Melik Z, Zaletel P, Virtic T, et al. L-arginine as dietary supplement for improving microvascular function. Clin Hemorheol Microcirc. Our bodies produce nitric oxide, which signals 2017;65(3):205-17. blood vessels to dilate. With age, its production 18. Matsuzawa Y, Kwon TG, Lennon RJ, et al. Prognostic Value of Flow-Mediated Vasodilation in Brachial Artery and Fingertip Artery declines, contributing to endothelial dysfunction. for Cardiovascular Events: A Systematic Review and Meta-Analy- Endothelial dysfunction increases the risk of cardio- sis. J Am Heart Assoc. 2015 Nov 13;4(11). 19. Shimbo D, Grahame-Clarke C, Miyake Y, et al. The association vascular disease, including heart attacks and strokes. between endothelial dysfunction and cardiovascular outcomes Two ingredients, L-arginine and aronia berries, in a population-based multi-ethnic cohort. Atherosclerosis. 2007 boost the body’s production of nitric oxide. May;192(1):197-203. 20. McRae MP. Therapeutic Benefits of l-Arginine: An Umbrella Review Human studies show that they improve the flow of of Meta-analyses. J Chiropr Med. 2016 Sep;15(3):184-9. blood through the vessels, which can reduce the risk 21. Kalman DS, Feldman S, Samson A, et al. A clinical evaluation to determine the safety, pharmacokinetics, and pharmacodynam- for cardiovascular disease. • ics of an inositol-stabilized arginine silicate dietary supplement in healthy adult males. Clin Pharmacol. 2015;7:103-9. 22. Komorowski J, Perez Ojalvo S. A pharmacokinetic evaluation of If you have any questions on the scientific the duration of effect of inositol-stabilized arginine silicate and content of this article, please call a Life Extension® arginine hydrochloride in healthy adult males. FASEB J. 2016;30 Wellness Specialist at 1-866-864-3027. (1_suppl). 23. Komorowski J, Perez Ojalvo S, Sylla S, et al. Poster Presentation presented at the American Society for Nutrition’s Annual Meeting 2018. Arginase inhibition by inositol-stabilized arginine silicate References (ASI; Nitrosigine); a novel mechanism by which ASI enhances arginine bioavailability. Current Developments in Nutrition. 2018. 1. Torregrossa AC, Aranke M, Bryan NS. Nitric oxide and geriatrics: 24. Varela CE, Fromentin E, Roller M, et al. Effects of a natural extract Implications in diagnostics and treatment of the elderly. J Geriatr of Aronia Melanocarpa berry on endothelial cell nitric oxide pro- Cardiol. 2011 Dec;8(4):230-42. duction. J Food Biochem. 2016 Aug;40(4):404-10. 2. Davignon J, Ganz P. Role of endothelial dysfunction in atherosclero- 25. Istas G, Wood E, Le Sayec M, et al. Effects of aronia berry (poly) sis. Circulation. 2004 Jun 15;109(23 Suppl 1):III27-32. phenols on vascular function and gut microbiota: a double-blind 3. Widlansky ME, Gokce N, Keaney JF, Jr., et al. The clinical impli- randomized controlled trial in adult men. Am J Clin Nutr. 2019 Aug cations of endothelial dysfunction. J Am Coll Cardiol. 2003 Oct 1;110(2):316-29. 1;42(7):1149-60. 4. Widmer RJ, Lerman A. Endothelial dysfunction and cardiovascular disease. Glob Cardiol Sci Pract. 2014;2014(3):291-308. 5. Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial function in humans. Clin Sci (Lond). 2011 May;120(9):357-75. 6. Fordjour PA, Wang Y, Shi Y, et al. Possible mechanisms of C-reac- tive protein mediated acute myocardial infarction. Eur J Pharmacol. 2015 Aug 5;760:72-80. 7. Eelen G, de Zeeuw P, Simons M, et al. Endothelial cell metabo- lism in normal and diseased vasculature. Circ Res. 2015 Mar 27;116(7):1231-44. 8. Huveneers S, Daemen MJ, Hordijk PL. Between Rho(k) and a hard place: the relation between vessel wall stiffness, endothe- lial contractility, and cardiovascular disease. Circ Res. 2015 Feb 27;116(5):895-908. 9. Namba T, Masaki N, Takase B, et al. Arterial Stiffness Assessed by Cardio-Ankle Vascular Index. Int J Mol Sci. 2019 Jul 26;20(15). 10. Aykan AC, Hatem E, Kalaycioglu E, et al. Assessment of arterial stiffness in patients with venous thromboembolism: Separate or continuous circuits? Phlebology. 2017 Jun;32(5):316-21. 11. Cooper JN, Evans RW, Mori Brooks M, et al. Associations between arterial stiffness and platelet activation in normotensive overweight and obese young adults. Clin Exp Hypertens. 2014;36(3):115-22. 12. Toggweiler S, Schoenenberger A, Urbanek N, et al. The prevalence of endothelial dysfunction in patients with and without coronary artery disease. Clin Cardiol. 2010 Dec;33(12):746-52. 13. Cooke JP, Singer AH, Tsao P, et al. Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit. J Clin Invest. 1992 Sep;90(3):1168-72. 14. Hambrecht R, Hilbrich L, Erbs S, et al. Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation. J Am Coll Cardiol. 2000 Mar 1;35(3):706-13. 15. Lekakis JP, Papathanassiou S, Papaioannou TG, et al. Oral L- arginine improves endothelial dysfunction in patients with essential hypertension. Int J Cardiol. 2002 Dec;86(2-3):317-23. 16. Lerman A, Burnett JC, Jr., Higano ST, et al. Long-term L-arginine supplementation improves small-vessel coronary endothelial func- tion in humans. Circulation. 1998 Jun 2;97(21):2123-8. ARONIA BERRIES

26 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 26 2/14/20 11:57 AM Maintain Youthful HOMOCYSTEINE LEVELS FOR BRAIN, HEART, AND HEARING HEALTH

Homocysteine Resist supports healthy levels of homocysteine, an unfavorable amino acid that can increase with normal aging.

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-MTHF (activated folate) , mcg Methylcobalamin (activated vitamin B) , mcg Pyridoxal ’-phosphate (activated vitamin B)  mg Riboflavin (vitamin B)  mg

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LEMAPR20p.indd 27 2/14/20 11:58 AM LLow-Costow-Cost Enzymatically Active Vitamins BioActive Complete B-Complex provides BBiologicallyiologically enzymatically active forms of meaningful AActivective potencies of each B vitamin. This includes the pyridoxal ’-phosphate form of vitamin B shown to protect lipids and proteins against glycation and the most biologically active form of folate called -methyltetrahydrofolate (-MTHF), which is up to  times more bioavailable than folic acid.*

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Reference * Br J Pharmacol. 2004 Mar;141(5):825-30.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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Item #01993࠮60 softgels References 1. JAMA Ophthalmol. 2015;133(12):1415-24. 6. Evid Based Complement Alternat Med. 1 bottle $33 2. Nutrients. 2013 April;5(4):1169-85. 2012;2012:429124. 3. Nutrition. 2011 Sep;27(9):960-6. 7. Invest Ophthalmol Vis Sci. 2010;51(12):6118-24. 4 bottles $30 each 4. Free Radic Biol Med. 2012;53(6):1298-307. 8. J Agric Food Chem. 2003 Jun 4;51(12):3560-3. 5. J Ophthalmol. 2015;2015:523027. 9. Altern Med Rev. 2011 Dec;16(4):355-64. Each bottle lasts for two months.

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LuteinPlus® and Mz® are registered trademarks of NutriProducts Ltd., UK, licensed under U.S. Patent 8,623,428.

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LEMAPR20p.indd 31 2/14/20 12:01 PM SAFELYSAFSAFELYEEL ALALLEVIATELEVL IATTEE1 1111 SSYMPTOMSYMYMPMPPTTOTOMOMOMS OOFF MMENOPAUSEENOPAUAUSE

How Men Can Fight OSTEOPOROSIS

32 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 32 2/14/20 2:22 PM BY SUSAN CUMMINGS

Osteoporosis has long been viewed as a disease that primarily affects women, turning their bones weak and prone to fractures as they age. But men are at a far higher risk of osteoporosis than most realize. About one-third of all hip fractures worldwide occur in men.1 And while women do get osteoporosis more fre- quently, fractures in men result in more severe, and deadly complications.2-4 The rate of bone loss in osteoporosis is closely asso- ciated with increased mortality.5-8 And all men can strengthen bones and help pre- vent fractures with a few simple measures, including increased physical activity, weight-bearing exercises, resistance training, and ensuring proper intake of nutrients including magnesium, calcium, vitamin D, vitamin K, and more. Together, these actions can help maintain healthy bones well into advanced age.

APRIL 2020 | LIFE EXTENSION | 33

LEMAPR20p.indd 33 2/19/20 2:12 PM HOW MEN CAN FIGHT OSTEOPOROSIS

Osteoporosis in Men Assessing Fracture Risk Healthy bone is constantly being remodeled. This Osteoporosis in men usually results from a combina- means that old bone is broken down and new bone is tion of risk factors, rather than from a single cause (like formed. menopause in women).2 For people with osteoporosis, bone loss outweighs The most frequent causes of osteoporosis in men bone growth. The result is low bone mass, deterioration are alcohol abuse, excessive use of corticosteroids of bone tissue, and bone fragility that leads to increased (medications often used to treat inflammatory disorders), fracture risk.9,10 and low testosterone and estrogen from aging, or from Osteoporosis usually produces no symptoms until androgen-deprivation therapy for prostate cancer.2 a fracture occurs,2,11-13 so it remains underdiagnosed Once osteoporosis has developed, many factors and undertreated. Many men, in particular, believe raise the risk of bone fractures in men, including:1,2,9,12 osteoporosis affects mostly aging women and ignore • Increasing age, their own risks.14 But rates in men are striking: • Low body mass index,

• Up to 1/3 of all hip fractures worldwide • A history of fragility fractures in the occur in men.1 individual or a parent,

• Half of male hip fractures occur before • Low testosterone and estrogen, the age of 80.1,15 • Prolonged immobilization or inactivity,

Hip fractures are the most serious of all broken • High alcohol intake, bones resulting from osteoporosis.2 In a study in men aged 60 and over, the mortality • Smoking, 3 rate at one year from hip fractures was 37.5%, while • Glucocorticoid treatment, another study found that men are more than twice as likely as women to die from infection during the first • Type I diabetes, two years after a hip fracture.4 • Rheumatoid arthritis, Fractures of the spinal vertebrae are much harder to detect than hip fractures. They may cause little pain • Thyroid disorders, and at first, but can gradually lead to severe discomfort and • Chemotherapy treatment for cancer. risk of serious spinal cord injury.2,16

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LEMAPR20p.indd 34 2/14/20 2:23 PM HOW MEN CAN FIGHT OSTEOPOROSIS

Weight-bearing and resistance exercises help build strong bones.17 And there are a variety of nutrients that can help slow bone loss and prevent fractures.

Nutrients to Promote Bone Strength The standard nutritional “building blocks” of bone are calcium and vitamin D3.18 Calcium provides the bulk of the mineral content of bones, and vitamin D promotes calcium uptake from the gut. But bones aren’t simple structures that can be built and left alone. They’re dynamic, living tissue, with all the vulnerabili- ties to damage as any other tissue. It’s now recognized that healthy bones require additional nutritional support.

• Magnesium regulates calcium movement into and between bone cells, increasing bone min- eral density.19 Q • Zinc stimulates new bone formation and helps calcium consolidate in bone.20 WHAT YOU NEED TO KNOW

• Manganese functions as an essential cofactor (helper molecule) for enzymes that promote Building and Protecting the growth of bone and prevent damaging oxi- dative stress.21 Strong Bones

• Silicon improves the quality of bone matrix (the Q Osteoporosis is no longer thought non-mineral part of bone composed of collagen of as a disease that just affects older and other proteins) and facilitates the bone- women. About one-third of all hip building process known as mineralization.22 fractures worldwide occur in men.

• Boron regulates the proper metabolism of Q Men have a higher death rate from calcium and other bone-forming minerals and hip fractures than women, and higher influences the metabolism of vitamin D.23-25 rates of bone loss are associated with higher mortality. • Vitamin K is essential for activating a bone hormone (osteocalcin) needed to maintain Q All men can benefit from ensuring bone strength.26,27 Low vitamin K status is adequate intake of vitamins and min- associated with decreased bone density and erals that build up bone strength and increased fracture risk.28 help minimize risk of fracture, includ- ing calcium, vitamin D3, vitamin New evidence is also emerging for two other com- K, magnesium, manganese, zinc, pounds that support bone health. silicon, and boron. 1. Curcumin, an extract of the turmeric plant, Q The nutrients curcumin and PQQ has powerful anti-inflammatory properties. also play important roles in reducing Chronic systemic inflammation is now being the oxidative stress and inflammation recognized as a contributor to osteoporosis that contribute to bone loss. risk.29,30

APRIL 2020 | LIFE EXTENSION | 35

LEMAPR20p.indd 35 2/14/20 2:24 PM HOW MEN CAN FIGHT OSTEOPOROSIS

• Newer studies have found that curcumin acts If you have any questions on the scientific in multiple ways to increase bone mineral content of this article, please call a Life Extension® density and boost resistance to fractures.31-35 Wellness Specialist at 1-866-864-3027. In one human study, curcumin in combination with calcium added to the effects of a pre- References scription osteoporosis drug, alendronate.34 1. Herrera A, Lobo-Escolar A, Mateo J, et al. Male osteoporosis: A review. World J Orthop. 2012 Dec 18;3(12):223-34. 2. PQQ (pyrroloquinoline quinone) is a vita- 2. Giusti A, Bianchi G. Male osteoporosis. Reumatismo. 2014 Jul min-like nutrient with anti-aging properties 28;66(2):136-43. related to its ability to help mitochondria (the 3. Jiang HX, Majumdar SR, Dick DA, et al. Development and initial validation of a risk score for predicting in-hospital and 1-year “powerhouses” of the cells) use energy more mortality in patients with hip fractures. J Bone Miner Res. 2005 efficiently.36 Mar;20(3):494-500. 4. Wehren LE, Hawkes WG, Orwig DL, et al. Gender differences in • Studies of PQQ in osteoporosis-prone mice mortality after hip fracture: the role of infection. J Bone Miner Res. 2003 Dec;18(12):2231-7. show that it enhances the activity of bone- 5. Lee P, Ng C, Slattery A, et al. Preadmission Bisphosphonate and forming osteoblast cells while reducing the Mortality in Critically Ill Patients. J Clin Endocrinol Metab. 2016 May;101(5):1945-53. activity of bone-destroying osteoclast cells, 6. Lenchik L, Register TC, Russell GB, et al. Volumetric bone mineral resulting in increased bone mass and density of the spine predicts mortality in African-American men 36-39 with type 2 diabetes. Osteoporos Int. 2018 Sep;29(9):2049-57. density. 7. Masunari N, Fujiwara S, Kasagi F, et al. Height loss starting in middle age predicts increased mortality in the elderly. J Bone Ensuring adequate daily intake of all these nutrients Miner Res. 2012 Jan;27(1):138-45. can minimize the risk of developing osteoporosis and 8. Bliuc D, Tran T, van Geel T, et al. Reduced Bone Loss Is Associ- ated With Reduced Mortality Risk in Subjects Exposed to Nitrogen related fractures. Bisphosphonates: A Mediation Analysis. J Bone Miner Res. 2019 Nov;34(11):2001-11. 9. Pisani P, Renna MD, Conversano F, et al. Major osteoporotic fragil- ity fractures: Risk factor updates and societal impact. World J Summary Orthop. 2016 Mar 18;7(3):171-81. Osteoporosis is a progressive loss of bone density and strength, leading to sharply raised risk of fractures. It was once thought mostly to affect older women. But about one-third of all hip fractures worldwide occur in men. And because of the high osteoporosis risk, all men should regularly exercise to strengthen their bones, and should ensure they are getting the nutrients required to build and maintain strong bones. Those include calcium, vitamin K, and vitamin D3, along with the minerals magnesium, manganese, zinc, silicon, and boron. Further bone support can be obtained from cur- cumin and PQQ, which fight inflammation, improve bone cell energy use, and produce stronger bones. •

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10. Kanis JA, McCloskey EV, Johansson H, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2013 Jan;24(1):23-57. 11. Nih Consensus Development Panel on Osteoporosis Prevention D, Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001 Feb 14;285(6):785-95. 12. Drake MT, Khosla S. Male osteoporosis. Endocrinol Metab Clin North Am. 2012 Sep;41(3):629-41. 13. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993 Jun;94(6):646-50. 14. Dy CJ, Lamont LE, Ton QV, et al. Sex and gender considerations in male patients with osteoporosis. Clin Orthop Relat Res. 2011 Jul;469(7):1906-12. 15. Chang KP, Center JR, Nguyen TV, et al. Incidence of hip and other osteoporotic fractures in elderly men and women: Dubbo Osteopo- rosis Epidemiology Study. J Bone Miner Res. 2004 Apr;19(4):532-6. 16. Khosla S, Amin S, Orwoll E. Osteoporosis in men. Endocr Rev. 2008 Jun;29(4):441-64. 17. Available at: https://www.bones.nih.gov/health-info/bone/bone- health/exercise/exercise-your-bone-health. Accessed January 27, 2020. 18. Moyer VA, Force* USPST. Vitamin D and calcium supplementa- tion to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013 May 7;158(9):691-6. 19. Mammoli F, Castiglioni S, Parenti S, et al. Magnesium Is a Key Regulator of the Balance between Osteoclast and Osteoblast Dif- ferentiation in the Presence of Vitamin D(3). Int J Mol Sci. 2019 Jan 17;20(2). 20. Yamaguchi M. Role of nutritional zinc in the prevention of osteopo- rosis. Mol Cell Biochem. 2010 May;338(1-2):241-54. 21. Available at: https://lpi.oregonstate.edu/mic/minerals/manganese. Accessed January 23, 2020. 22. Price CT, Koval KJ, Langford JR. Silicon: a review of its potential role in the prevention and treatment of postmenopausal osteoporo- sis. Int J Endocrinol. 2013;2013:316783. 23. Devirian TA, Volpe SL. The physiological effects of dietary boron. Crit Rev Food Sci Nutr. 2003;43(2):219-31. 24. Naghii MR, Samman S. The role of boron in nutrition and metabo- lism. Prog Food Nutr Sci. 1993 Oct-Dec;17(4):331-49. 25. Nielsen FH. Studies on the relationship between boron and mag- nesium which possibly affects the formation and maintenance of bones. Magnes Trace Elem. 1990;9(2):61-9. 26. Fujita Y, Iki M, Tamaki J, et al. Association between vitamin K intake from fermented soybeans, natto, and bone mineral density in elderly Japanese men: the Fujiwara-kyo Osteoporosis Risk in Men 33. French DL, Muir JM, Webber CE. The ovariectomized, mature rat model (FORMEN) study. Osteoporos Int. 2012 Feb;23(2):705-14. of postmenopausal osteoporosis: an assessment of the bone sparing 27. Bullo M, Estruch R, Salas-Salvado J. Dietary vitamin K intake is effects of curcumin. Phytomedicine. 2008 Dec;15(12):1069-78. associated with bone quantitative ultrasound measurements but 34. Khanizadeh F, Rahmani A, Asadollahi K, et al. Combination therapy not with bone peripheral biochemical markers in elderly men and of curcumin and alendronate modulates bone turnover markers and women. Bone. 2011 Jun 1;48(6):1313-8. enhances bone mineral density in postmenopausal women with 28. Rodriguez-Olleros Rodriguez C, Diaz Curiel M. Vitamin K and osteoporosis. Arch Endocrinol Metab. 2018 Aug;62(4):438-45. Bone Health: A Review on the Effects of Vitamin K Deficiency 35. Li G, Bu J, Zhu Y, et al. Curcumin improves bone microarchitecture and Supplementation and the Effect of Non-Vitamin K Antagonist in glucocorticoid-induced secondary osteoporosis mice through the Oral Anticoagulants on Different Bone Parameters. J Osteoporos. activation of microRNA-365 via regulating MMP-9. Int J Clin Exp 2019;2019:2069176. Pathol. 2015;8(12):15684-95. 29. Al-Daghri NM, Aziz I, Yakout S, et al. Inflammation as a contributing 36. Huang Y, Chen N, Miao D. Effect and mechanism of pyrrolo- factor among postmenopausal Saudi women with osteoporosis. quinoline quinone on anti-osteoporosis in Bmi-1 knockout mice- Medicine (Baltimore). 2017 Jan;96(4):e5780. Anti-oxidant effect of pyrroloquinoline quinone. Am J Transl Res. 30. Fang H, Zhang H, Wang Z, et al. Systemic immune-inflammation 2017;9(10):4361-74. index acts as a novel diagnostic biomarker for postmenopausal 37. Geng Q, Gao H, Yang R, et al. Pyrroloquinoline Quinone Prevents osteoporosis and could predict the risk of osteoporotic fracture. J Estrogen Deficiency-Induced Osteoporosis by Inhibiting Oxidative Clin Lab Anal. 2020 Jan;34(1):e23016. Stress and Osteocyte Senescence. Int J Biol Sci. 2019;15(1):58-68. 31. Chen Z, Xue J, Shen T, et al. Curcumin alleviates glucocorticoid-in- 38. Wen H, He Y, Zhang K, et al. Mini-review:Functions and Action duced osteoporosis by protecting osteoblasts from apoptosis in vivo Mechanisms of PQQ in Osteoporosis and Neuro Injury. Curr Stem and in vitro. Clin Exp Pharmacol Physiol. 2016 Feb;43(2):268-76. Cell Res Ther. 2018 Dec 10. 32. Chen Z, Xue J, Shen T, et al. Curcumin alleviates glucocorticoid- 39. Wu X, Li J, Zhang H, et al. Pyrroloquinoline quinone prevents testos- induced osteoporosis through the regulation of the Wnt signaling terone deficiency-induced osteoporosis by stimulating osteoblastic pathway. Int J Mol Med. 2016 Feb;37(2):329-38. bone formation and inhibiting osteoclastic bone resorption. Am J Transl Res. 2017;9(3):1230-42.

APRIL 2020 | LIFE EXTENSION | 37

LEMAPR20p.indd 37 2/14/20 2:25 PM KSUPER Comprehensive Vitamin K Formula!

Item #02334 • 90 softgels Just one daily softgel of 1 bottle $22.50 Super K provides: 4 bottles $20.25 each Vitamin K1 1,500 mcg For full product description and Vitamin K2 (MK-4) 1,000 mcg to order Super K, call 1-800-544-4440 Each bottle lasts for three months. Vitamin K2 (trans MK-7) 100 mcg or visit www.LifeExtension.com

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 38 2/14/20 2:29 PM YOUR BONE HEALTH ... NOW

Bone Restore with Vitamin K2 combines skeletal-strengthening nutrients in one highly absorbable formula.

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For full product description and to order Bone Restore with Vitamin K2, call 1-800-544-4440 or visit LifeExtension.com

Note: Those taking the anticoagulant drug Coumadin® (warfarin) should use Bone Restore without vitamin K2. Fruitex B® and OsteoBoron® are registered trademarks of VDF Futureceuticals, Inc. U.S. patent #5,962,049. DimaCal® and TRAACS® are registered trademarks of Albion Laboratories, Inc., U.S. patent 6,706,904.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 39 2/14/20 2:31 PM Road Trip!N O NSTO P

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LEMAPR20p.indd 40 2/14/20 2:33 PM EFEND YOUR HEALTH

Item # • , IU •  softgels  bottle $. VITAMIN D3  bottles $. each Systemic support for For full product description youthful cell function, bone and to order Vitamin D, health, and normal insulin and call --- or visit www.LifeExtension.com blood-sugar levels.

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LEMAPR20p.indd 41 2/19/20 2:15 PM 42 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 42 2/14/20 2:16 PM Improve DIGESTION of Plant- Based Foods

BY MICHAEL DOWNEY

Digestion is a complicated process.

Enzymes are needed to break down each of the major food groups: carbohydrates, proteins, and fats.

The recent trend toward eating more plant-based foods has brought along with it the need for additional enzymes to break down hard-to-digest, fiber-rich foods.

As we age, internal production of digestive enzymes declines.1 As a result, undigested foods may pass into the large intestine,2,3 causing bloating, gas, diarrhea, and cramping.

Researchers have identified additional enzymes that specifically promote digestion of high-fiber plant foods.

When combined with a specific probiotic, these benefits can be further enhanced.

APRIL 2020 | LIFE EXTENSION | 43

LEMAPR20p.indd 43 2/19/20 1:48 PM IMPROVE DIGESTION OF PLANT-BASED FOODS

Common Causes of Digestive Problems digestion of foods in the stomach. Since then, studies Many health problems plaguing aging adults, includ- have validated the beneficial effects of digestive enzyme ing digestive discomfort like gas and diarrhea, impaired supplementation.7-9 immunity, and nutritional deficiencies, can often be Optimal digestion of major food types, including pro- attributed to poor digestion. teins, fats, dairy, and plant cellulose (fiber), requires dif- Two important causes of digestive problems are:1-5 ferent digestive enzymes, such as:

1. Age-related declines in production of endogenous • Protease, digestive enzymes, and • Lipase, 2. Imbalances in the gut microbiota. • Lactase, Digestive enzymes are needed to break down the foods we eat and extract essential nutrients from them. • Cellulase, and And a proper balance of bacteria must be present in the gut to prevent bloating, gas, and other unpleasant • Bromelain. digestive symptoms. Drugs such as Alka-Seltzer® and Pepto-Bismol® can temporarily relieve some symptoms but do nothing to The Challenge of Plant-Based Diets address the underlying problem. In recent years, diets have changed. More people are reducing their meat and other animal-derived food intake and increasing their intake of plant-based foods. The Power of Digestive Enzymes The cell walls of these foods contain complex poly- To help break down food more completely by the saccharides and fibers. While fiber is an important part time it reaches the end of our small intestine, substantial of a healthy diet, it may also bind to minerals and other amounts of all required digestive enzymes are needed. nutrients, blocking their bioavailability and preventing This helps prevent undigested food from passing into their absorption. the colon and causing gastrointestinal problems. Humans do not produce the enzymes required to About 70 years ago, scientists first discovered6 that break down fiber and depend on enzymes produced taking digestive enzymes orally leads to more complete by intestinal microorganisms.10,11

44 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 44 2/14/20 2:16 PM IMPROVE DIGESTION OF PLANT-BASED FOODS

Protease 3.0 is an enhanced form of the protease enzyme that helps digest gliadin found in wheat. To properly break down other plant-based foods requires:

• Alpha-galactosidase,

• Hemicellulase,

• Cellulase,

• Xylanase, and

• Pectinase.

General Purpose Enzymes The enzymes described next have long been used to improve digestion. Each has a specific, targeted func- tion that helps break down complex foods into nutrient components that can be readily absorbed. WHAT YOU NEED TO KNOW

Protease Protease breaks down proteins. Research shows Boost Digestion that giving protease to animals enhances their digestion.12 Q Poor digestion can result in bloating, Aging individuals may receive tremendous poten- gas, and discomfort, and compromises tial benefits from supplementing with protease the absorption of key nutrients. enzymes in order to increase the efficiency of protein digestion. Q Digestive problems can be caused by an age-related decline in digestive enzymes Lactase and an imbalance in the all-important gut microbial ecosystem. Lactase breaks down lactose, or milk sugar. Older people are often deficient in this enzyme,13 resulting in Q Increasing your intake of plant-based cramps, bloating, gas, and diarrhea after consuming foods creates special challenges to your dairy products.14 But avoiding dairy can cause calcium digestion but special enzymes that spe- deficiency, increasing the risk of osteoporosis and bone cifically target these high-fiber foods can fractures.15-18 help your body better handle a plant- Studies show that taking lactase reduces or elimi- based diet. nates post-meal abdominal cramping, belching, flatu- lence, bloating, and diarrhea in people with lactase Q Digestive enzymes can help break down insufficiency. It also promotes better overall nutrition.19 and digest food while preventing gastro- intestinal distress and promoting better Lipase overall health. Lipase breaks down fat into individual fatty acids Q Adding Bacillus coagulans to a broad and related substances. It helps the body absorb vital range of digestive enzymes may provide fat-soluble nutrients, such as omega-3 fatty acids, protection against several gastrointesti- carotenoids like lycopene and lutein, and vitamins A, nal discomforts. D, K, and E.20

APRIL 2020 | LIFE EXTENSION | 45

LEMAPR20p.indd 45 2/14/20 2:16 PM IMPROVE DIGESTION OF PLANT-BASED FOODS

Without sufficient lipase, incompletely digested better at promoting the digestion of proteins in acidic fats can cause greasy, fatty stools and cramping. conditions such as those found in the stomach. Inadequate fat digestion also blocks absorption of key This enzyme may also help some people with gluten vitamins, leading to deficiencies. sensitivity or intolerance since it specifically promotes Taking oral lipase promotes fat digestion.21,22 In one digestion of gliadin, a protein found in gluten in wheat, study, pancreatic lipase enzymes were given to sub- and some other grains. jects eating a high-fat meal, resulting in significant reductions in bloating and gas.22 Alpha-Galactosidase Alpha-galactosidase is a digestive enzyme that Bromelain breaks down oligosaccharides, carbohydrates found in Bromelain is extracted from pineapple stem and fruit. plant foods including beans and cruciferous vegetables It helps with digestion of proteins.23,25 (such as cauliflower, broccoli, and cabbage). Scientists studied adults with an inability to fully Taking this enzyme substantially reduces bloating, digest and absorb fats and proteins. Taking an enzyme discomfort, and flatulence associated with eating these mix containing bromelain improved digestion and foods.26,27 absorption of both these food groups.25 In one study, scientists recruited volunteers with irri- table bowel syndrome (IBS). For three days they ate a diet high in a type of oligosaccharide that triggers IBS Digestive Enzymes to Plant-Based symptoms. The group that took oral alpha-galactosi- Support Diets dase had a clinically significant reduction in gastro- The enzymes described so far support basic digestion. intestinal symptoms compared to a placebo group.28 But the trend toward plant-based foods means additional enzymes can help improve the breakdown of Cellulase hard-to-digest types of plant fibers. Cellulase is not produced naturally in the human The following digestive enzymes deliver potent body. It allows humans to digest most cellulose, or support for high-fiber, plant-based diets. plant fiber. This allows for smoother digestion of tough vegetable Protease 3.0 fiber and minimizes the excessive flatulence that deters Traditional protease breaks down most proteins. But many people from eating healthy, high-fiber foods like a specialized protease known as protease 3.0 is even broccoli and beans.

46 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 46 2/14/20 2:17 PM IMPROVE DIGESTION OF PLANT-BASED FOODS

Hemicellulase, Xylanase, and Pectinase One particular probiotic, Bacillus coagulans strain Additional digestive support is found in three MTCC 5856, has been shown to effectively treat both enzymes specific for the breakdown of plant foods constipation and diarrhea, along with other symptoms high in fiber: of irritable bowel syndrome.30,31 In a double-blind, placebo-controlled study, patients • Hemicellulase breaks down hemicellulose, with irritable bowel syndrome took tablets containing a complex carbohydrate that is a major 2 billion spores of Bacillus coagulans strain MTCC component of cell walls in plants. 5856 daily. This led to a significant decrease in bloat- ing, vomiting, diarrhea, abdominal pain and discomfort, and stool frequency.31 • Xylanase breaks down xylan, another complex Addition of this probiotic strain to a broad range of sugar found in plant cell walls. When undigested, digestive enzymes may provide comprehensive protec- xylan can impair nutrient absorption.29 tion against several types of gastrointestinal discomfort.

• Pectinase breaks down pectin, a naturally occurring substance found in pears, apples, Summary guavas, plums, oranges, and other fruits. As we age, the levels of digestive enzymes in our bodies decline. This triggers digestive problems, includ- An optimal selection of enzymes should include: ing bloating, gas, and diarrhea, and prevents absorp- tion of nutrients. • The full range of traditional digestive enzymes, The recent shift toward eating more plant-based and additional enzymes that target high-fiber foods can increase this problem, because the increased and gas-producing plant foods. amount of difficult-to-digest plant fiber components requires specialized enzymes. A Probiotic for Digestive Health Digestive enzymes can boost the body’s ability to fully break down food and may prevent gastrointestinal Even greater digestive health is possible with the distress and promote better overall health. addition of a targeted probiotic. Addition of the probiotic Bacillus coagulans to a Probiotics are microorganisms that, taken in ade- broad range of digestive enzymes may provide a high quate amounts, have a health benefit. Like enzymes, level of protection against several gastrointestinal they are vital to the digestion process. discomforts. •

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LEMAPR20p.indd 47 2/14/20 2:17 PM IMPROVE DIGESTION OF PLANT-BASED FOODS

If you have any questions on the scientific content 17. Di Stefano M, Veneto G, Malservisi S, et al. Lactose malabsorp- of this article, please call a Life Extension® tion and intolerance and peak bone mass. Gastroenterology. 2002 Wellness Specialist at 1-866-864-3027. Jun;122(7):1793-9. 18. Hodges JK, Cao S, Cladis DP, et al. Lactose Intolerance and Bone Health: The Challenge of Ensuring Adequate Calcium Intake. Nutri- ents. 2019 Mar 28;11(4):718. References 19. Sanders SW, Tolman KG, Reitberg DP. Effect of a single dose of lactase on symptoms and expired hydrogen after lactose challenge 1. Remond D, Shahar DR, Gille D, et al. Understanding the gastroin- in lactose-intolerant subjects. Clin Pharm. 1992 Jun;11(6):533-8. testinal tract of the elderly to develop dietary solutions that prevent 20. Layer P, Keller J. Lipase supplementation therapy: standards, alter- malnutrition. Oncotarget. 2015 Jun 10;6(16):13858-98. natives, and perspectives. Pancreas. 2003 Jan;26(1):1-7. 2. Di Stefano M, Veneto G, Malservisi S, et al. Lactose malabsorp- 21. Dominguez-Munoz JE, Iglesias-Garcia J, Iglesias-Rey M, et al. Effect tion and intolerance in the elderly. Scand J Gastroenterol. 2001 of the administration schedule on the therapeutic efficacy of oral Dec;36(12):1274-8. pancreatic enzyme supplements in patients with exocrine pancre- 3. Laugier R, Bernard JP, Berthezene P, et al. Changes in pancreatic atic insufficiency: a randomized, three-way crossover study. Aliment exocrine secretion with age: pancreatic exocrine secretion does Pharmacol Ther. 2005 Apr 15;21(8):993-1000. decrease in the elderly. Digestion. 1991;50(3-4):202-11. 22. Suarez F, Levitt MD, Adshead J, et al. Pancreatic supplements 4. Bures J, Cyrany J, Kohoutova D, et al. Small intestinal bacte- reduce symptomatic response of healthy subjects to a high fat meal. rial overgrowth syndrome. World J Gastroenterol. 2010 Jun Dig Dis Sci. 1999 Jul;44(7):1317-21. 28;16(24):2978-90. 23. Pavan R, Jain S, Shraddha, et al. Properties and therapeutic appli- 5. Lin HC. Small intestinal bacterial overgrowth: a framework for under- cation of bromelain: a review. Biotechnol Res Int. 2012;2012:976203. standing irritable bowel syndrome. JAMA. 2004 Aug 18;292(7):852-8. 24. Available at: https://nccih.nih.gov/health/bromelain. Accessed Janu- 6. Howell E, National Enzyme Company C. The status of food enzymes ary 9, 2019. in digestion and metabolism. Chicago, Ill.: National Enzyme Co.; 1946. 25. Knill-Jones RP, Pearce H, Batten J, et al. Comparative trial of 7. Roxas M. The role of enzyme supplementation in digestive disorders. Nutrizym in chronic pancreatic insufficiency. Br Med J. 1970 Oct Altern Med Rev. 2008 Dec;13(4):307-14. 3;4(5726):21-4. 8. Glade MJ, Kendra D, Kaminski MV, Jr. Improvement in protein utili- 26. Di Stefano M, Miceli E, Gotti S, et al. The effect of oral alpha-galac- zation in nursing-home patients on tube feeding supplemented with tosidase on intestinal gas production and gas-related symptoms. an enzyme product derived from Aspergillus niger and bromelain. Dig Dis Sci. 2007 Jan;52(1):78-83. Nutrition. 2001 Apr;17(4):348-50. 27. Zhang S, Song J, Deng Z, et al. Effects of combined alpha-galac- 9. Karani S, Kataria MS, Barber AE. A double-blind clinical trial with a tosidase and xylanase supplementation on nutrient digestibility digestive enzyme product. Br J Clin Pract. 1971 Aug;25(8):375-7. and growth performance in growing pigs. Arch Anim Nutr. 2017 10. Supplier Educational Articles. Enzymes 101. Data on File. 2020. Dec;71(6):441-54. 11. Supplier Educational Articles. Probiotics 101. Data on File. 2020. 28. Tuck CJ, Taylor KM, Gibson PR, et al. Increasing Symptoms in Irri- 12. Eun JS, Beauchemin KA. Effects of a proteolytic feed enzyme on table Bowel Symptoms With Ingestion of Galacto-Oligosaccharides intake, digestion, ruminal fermentation, and milk production. J Dairy Are Mitigated by alpha-Galactosidase Treatment. Am J Gastroen- Sci. 2005 Jun;88(6):2140-53. terol. 2018 Jan;113(1):124-34. 13. Lee MF, Krasinski SD. Human adult-onset lactase decline: an up- 29. Polizeli ML, Rizzatti AC, Monti R, et al. Xylanases from fungi: proper- date. Nutr Rev. 1998 Jan;56(1 Pt 1):1-8. ties and industrial applications. Appl Microbiol Biotechnol. 2005 14. Available at: https://www.medicinenet.com/script/main/art. Jun;67(5):577-91. asp?articlekey=6201. Accessed January 9, 2019. 30. Lactobacillus sporogenes. Altern Med Rev. 2002 Aug;7(4):340-2. 15. Newcomer AD, Hodgson SF, McGill DB, et al. Lactase deficiency: 31. Majeed M, Nagabhushanam K, Natarajan S, et al. Bacillus coagu- prevalence in osteoporosis. Ann Intern Med. 1978 Aug;89(2):218-20. lans MTCC 5856 supplementation in the management of diarrhea 16. Birge SJ, Jr., Keutmann HT, Cuatrecasas P, et al. Osteoporosis, predominant Irritable Bowel Syndrome: a double blind randomized intestinal lactase deficiency and low dietary calcium intake. N Engl J placebo controlled pilot clinical study. Nutr J. 2016 Feb 27;15:21. Med. 1967 Feb 23;276(8):445-8.

48 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 48 2/14/20 2:17 PM Clinical trials demonstrate that the plant extracts in once-daily ArthroMax® Elite help: • Support a healthy inflammatory response • Maintain healthy connective cartilage tissue • Promote comfortable joint function Take advantage of the benefits of Mobile-Ease™ Chinese skullcap, cutch tree and white mulberry TODAY!

For full product description and to order ArthroMax® Elite, call --- or visit www.LifeExtension.com

Item # •  vegetarian tablets  bottle $.  bottles $ each

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 49 2/14/20 2:37 PM Maintain a Healthy Post-Inflammatory Response PRO-RESOLVING MEDIATORS

Specialized Pro-Resolving Mediators (SPMs) support a healthy relationship with inflamma- tory factors for whole-body health. SPMs help: • REMOVE: Support the body’s natural process for clearing cellular debris. • RESTORE: Help balance cytokines in the body. • RENEW: Promote the regeneration of healthy tissues. Specialized Pro-Resolving Mediators (SPMs) are derived from polyunsaturated fatty acids found in highly refined, marine-oil concentrate.

Item # •  softgels  bottle $  bottles $ each

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These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 50 2/14/20 2:39 PM OPTIMIZE DIGESTION and INTESTINAL BALANCE

The body’s production of digestive enzymes decreases with age, leading to diminished nutrient absorption and bloating, as well as other intestinal discomforts—especially after eating a large meal.

Enhanced Super Digestive Enzymes and Probiotics provides a broad range of enzymes required to help break down proteins, fats, carbohydrates, and other food nutrients—including enzymes that specifically target the cell structures of plant-based foods.

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Enhanced Super Digestive For full product description and toto ororderder Enzymes and Probiotics Enhanced Super Digestive Enzymess and Probiotics, Item #02022 • 60 vegetarian capsules callcall 1-800-544-44401-800-544-4440 or visitvisit www.LifeExtension.comwwww.LifeExtension.com 1 bottle $21 2 bottles $18 each

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These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat,reat, ccurcure,e, or ppreventrevent anyanyy disease.disease.

LEMAPR20p.indd 51 2/14/20 1:38 PM LEMAPR20p.indd 52 2/14/20 2:28 PM RESTORE YOUTHFUL COGNITIVE HEALTH

Dopamine is a neurotransmitter that regulates mood and cognition. As we age, dopamine levels in our brain decline due to excess levels of the MAO-B enzyme. Wild green oat extract inhibits the MAO-B enzyme to promote healthy dopamine levels.- The wild green oat extract in Dopa-MindTM is for aging individuals who wish to: • Maintain youthful mental performance • Revive cognitive health • Support longevity

Item #02006࠮60 vegetable tablets 1 bottle $33 4 bottles $28 each

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These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 53 2/14/20 2:42 PM 54 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 54 2/14/20 11:31 AM COLLAGEN PEPTIDES Reverse Skin Aging from the Inside

BY MICHAEL DOWNEY

As we age, our skin loses two natural compounds that keep it smooth, moisturized, and youthful looking: 1. Collagen and 2. Hyaluronic acid.1,2

The loss of these skin components leads to wrinkles, sagging, and dryness. 1,2

But there’s a way to prevent and even reverse these changes. Scientists have clinically demonstrated that: • Oral use of a collagen peptide improves skin elasticity by an average of 7%3 and reduces the volume of eye wrinkles by 20%.4

• Oral use of hyaluronic acid significantly increases skin moisture in those with chronically dry, rough skin after just 3-6 weeks.1

Researchers have now devised a way to deliver clinically effective doses of these two nutrients together in a tasty, fruit-flavored gummy. Working from the inside out, they can rejuvenate the skin and return it to optimal health.

APRIL 2020 | LIFE EXTENSION | 55

LEMAPR20p.indd 55 2/14/20 11:31 AM COLLAGEN PEPTIDES REVERSE SKIN AGING FROM THE INSIDE Collagen Fiber

Collagen Keeps Skin Youthful The word collagen comes from the Greek kola, “glue.” Essentially, collagen—the most abundant protein in the human body—is the glue that holds the entire body together. It’s the main component of most connective tissues, like tendons and muscle, and makes up 70% of the inner layer of skin by weight.5,6 Collagen provides strength and resilience and is inte- grated with elastin fibers, the protein that gives skin flex- ibility and elasticity. Elastin allows the skin to return to its original shape after it’s been stretched.7 But collagen production begins to decline around age 25. The cells that produce collagen fibers slow down, and the remaining fibers can stiffen, break, and lose proper shape over time. Elastin fibers also begin to fray and lose elasticity. It is no coincidence that visible skin aging occurs in Cross-section of human skin many people around age 25, which is when collagen production begins to drop. 8 Adults lose about 1% of their skin collagen each year. received 2.5 grams of oral collagen daily, one received While this may not seem like a lot, after several decades, 5 grams daily, and a third received a placebo.3 we may have lost half the skin collagen we had at age After eight weeks, both groups taking the oral colla- 8,9 18. gen had an average 7% improvement in skin elasticity. This decline accelerates faster in women after meno- Remarkably, those subjects retained higher elasticity pause. Factors such as smoking, high blood sugar, and than the placebo group even four weeks after the last 10-14 sun exposure also decrease collagen levels. dose. The improvement in skin elasticity was found to Reduced collagen production has a devastating effect be greater in women over age 49.3 8,9 on the skin, resulting in thinning, sagging, and wrinkles. Next, researchers tested collagen on skin wrinkles. To solve this problem, scientists developed collagen In a double-blind, placebo-controlled trial, they gave peptides that provide the building blocks for collagen. oral collagen peptides to 114 women, aged 45 to 65, in Taken orally, they stimulate the production of new daily doses of 2.5 grams.4 collagen and elastin in the skin. This leads to increased suppleness and elasticity and reduces wrinkles.4 Results from Human Study Oral Collagen Research After four weeks, the volume of eye wrinkles for the collagen group had decreased by 7.2%, compared with In animal studies, scientists showed that hydrolyzed placebo recipients. After the full eight-week trial, those (or partially broken-down) collagen peptides boosted taking oral collagen peptides showed a stunning 20.1% 15 the creation and activity of collagen. This produces reduction in the size of eye wrinkles.4 stronger, more supple skin. In the same trial, scientists studied how collagen Collagen peptides also decreased the activity of a peptides affected the synthesis of the dermal matrix, “protein-melting” enzyme (matrix metalloproteinase 2) the structural framework responsible for skin renewal that degrades collagen and hastens skin aging.15 and vitality. They did so by measuring structural proteins Human trials have now demonstrated that an oral in the matrix. The more proteins, the healthier and more collagen peptide is clinically effective in improving skin youthful the skin appears.4 appearance.3,4 The study found that subjects taking collagen had a Scientists evaluated the effectiveness of collagen 65% increase in essential type-I pro-collagen and an peptides on skin elasticity. One group of volunteers 18% increase in elastin fibers.4

56 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 56 2/14/20 11:31 AM COLLAGEN PEPTIDES REVERSE SKIN AGING FROM THE INSIDE

Hyaluronic Acid Oral Hyaluronic Acid Rehydrates Skin Moisturizes Skin Scientists conducted an in-depth analysis of several Hyaluronic acid is equally critical for maintaining and previous studies of hyaluronic acid. In most, volunteers restoring youthful-looking skin. had been diagnosed with “chronically rough and dry It’s a carbohydrate present in most body tissues. skin,” which was not substantially improved by mois- More than 50% of it is found in the skin, where it helps turizers or other treatments.1 hold in moisture.1,16 In fact, hyaluronic acid can hold up But hyaluronic acid made a radical difference. to 1,000 times its weight in water.17 Compared to volunteers who received a placebo, those Hyaluronic acid is an essential part of the extracel- taking oral hyaluronic acid had a significant increase lular matrix, a network that provides structural integrity in skin moisture after just three to six weeks. And the and cohesion to skin.18 It supports skin hydration,19 stim- moisturizing effects continued for a full two weeks after ulates synthesis of collagen and elastin,20-22 promotes they stopped taking it.1 tissue repair,23-26 and combats the effects of ultraviolet Hyaluronic acid also reduced itching that comes radiation.26 with dry skin.1 In other words, the skin needs hyaluronic acid to maintain a healthy and youthful appearance. But the body produces less of it as we age. This problem is worsened by environmental stress, particu- WHAT YOU NEED TO KNOW larly chronic sun exposure.27-30 The result is wrinkling, dryness, and sagging. In a dramatic finding, however, scientists have dem- Get Healthier, onstrated that oral hyaluronic acid can slow—and Younger-Looking Skin even reverse—these effects. Q Collagen and hyaluronic acid are two nutrients vital to the health and youthful appearance of our skin. The body pro- duces less of them as we age, causing wrinkling, sagging, and dryness.

Q Taking oral collagen peptides spurs the synthesis of new collagen, improving skin elasticity, boosting essential struc- tural proteins, and reducing the size of eye wrinkles by as much as 20%.

Q Hyaluronic acid taken orally has been shown to reverse the loss of moisture in aging skin, effectively treating dry, itchy skin and helping to restore a more youthful appearance.

Q Taking these two nutrients together at Collagen peptides Hyaluronic acid clinically effective doses can lead to healthier, smoother, and younger-looking skin.

APRIL 2020 | LIFE EXTENSION | 57

LEMAPR20p.indd 57 2/14/20 11:31 AM COLLAGEN PEPTIDES REVERSE SKIN AGING FROM THE INSIDE

Summary Collagen and hyaluronic acid keep our skin smooth, supple, moisturized and youthful looking. But, as we age, we lose both these nutrients. Taking oral collagen peptides boosts the synthesis of new collagen in the skin. That improves skin struc- ture and elasticity, reduces eye wrinkle depth up to 20%, and increases levels of proteins that provide strength and resilience to the dermal matrix. Oral hyaluronic acid also protects and nourishes skin by boosting moisture content. That can help treat dry, itchy skin, and make it healthier and younger looking. Both of these nutrients can now be taken together in clinically effective doses, quickly providing noticeable improvements in the appearance of aging skin. •

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References 1. Kawada C, Yoshida T, Yoshida H, et al. Ingested hyaluronan moistur- izes dry skin. Nutr J. 2014 Jul 11;13:70. 2. Rittie L, Fisher GJ. Natural and sun-induced aging of human skin. Cold Spring Harb Perspect Med. 2015 Jan 5;5(1):a015370. 3. Proksch E, Segger D, Degwert J, et al. Oral supplementation of In fact, the scientists concluded that skin dryness is specific collagen peptides has beneficial effects on human skin caused by a decrease in hyaluronic acid due to aging, physiology: a double-blind, placebo-controlled study. Skin Pharma- col Physiol. 2014;27(1):47-55. sun exposure, smoking, and other factors. Their study 4. Proksch E, Schunck M, Zague V, et al. Oral intake of specific bioac- found that hyaluronic acid safely and effectively mois- tive collagen peptides reduces skin wrinkles and increases dermal turizes the skin and improves its health.1 matrix synthesis. Skin Pharmacol Physiol. 2014;27(3):113-9. 5. Available at: https://www.ncbi.nlm.nih.gov/books/NBK507709/. Ac- You can now orally replenish the skin’s diminishing cessed January 20, 2020. supplies of both collagen and hyaluronic acid. These 6. Available at: https://emedicine.medscape.com/article/1294744- overview#showall. Accessed January 20, 2020. two nutrients have been shown to: 7. Available at: https://www.ncbi.nlm.nih.gov/books/NBK21582/. Ac- cessed January 24, 2020. 8. Ganceviciene R, Liakou AI, Theodoridis A, et al. Skin anti-aging • Increase skin moisture, strategies. Dermatoendocrinol. 2012 Jul 1;4(3):308-19. 9. Available at: https://www.scientificamerican.com/article/why-does- skin-wrinkle-wit/. Accessed January 18, 2019. • Improve elasticity, 10. Gautieri A, Passini FS, Silvan U, et al. Advanced glycation end-prod- ucts: Mechanics of aged collagen from molecule to tissue. Matrix Biol. 2017 May;59:95-108. • Decrease wrinkle depth, 11. Uitto J. The role of elastin and collagen in cutaneous aging: intrinsic aging versus photoexposure. J Drugs Dermatol. 2008 Feb;7(2 Suppl):s12-6. • Boost levels of the skin’s structural proteins, and 12. Danby FW. Nutrition and aging skin: sugar and glycation. Clin Der- matol. 2010 Jul-Aug;28(4):409-11. 13. Knuutinen A, Kokkonen N, Risteli J, et al. Smoking affects collagen • Provide more youthful-looking skin. synthesis and extracellular matrix turnover in human skin. Br J Der- matol. 2002 Apr;146(4):588-94.

58 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 58 2/14/20 11:32 AM COLLAGEN PEPTIDES REVERSE SKIN AGING FROM THE INSIDE

14. Bosch R, Philips N, Suarez-Perez JA, et al. Mechanisms of Photo- 23. Jiang D, Liang J, Noble PW. Hyaluronan in tissue injury and repair. aging and Cutaneous Photocarcinogenesis, and Photoprotective Annu Rev Cell Dev Biol. 2007;23:435-61. Strategies with Phytochemicals. Antioxidants (Basel). 2015 Mar 24. Noble PW. Hyaluronan and its catabolic products in tissue injury and 26;4(2):248-68. repair. Matrix Biol. 2002 Jan;21(1):25-9. 15. Zague V, de Freitas V, da Costa Rosa M, et al. Collagen hydrolysate 25. Teriete P, Banerji S, Noble M, et al. Structure of the regulatory intake increases skin collagen expression and suppresses matrix hyaluronan binding domain in the inflammatory leukocyte homing metalloproteinase 2 activity. J Med Food. 2011 Jun;14(6):618-24. receptor CD44. Mol Cell. 2004 Feb 27;13(4):483-96. 16. Laurent UB, Dahl LB, Reed RK. Catabolism of hyaluronan in rabbit 26. Wang Y, Lauer ME, Anand S, et al. Hyaluronan synthase 2 protects skin takes place locally, in lymph nodes and liver. Exp Physiol. 1991 skin fibroblasts against apoptosis induced by environmental stress. Sep;76(5):695-703. J Biol Chem. 2014 Nov 14;289(46):32253-65. 17. Mateo Orobia AJ, Saa J, Ollero Lorenzo A, et al. Combination of 27. Dai G, Freudenberger T, Zipper P, et al. Chronic ultraviolet B irradia- hyaluronic acid, carmellose, and osmoprotectants for the treatment tion causes loss of hyaluronic acid from mouse dermis because of of dry eye disease. Clin Ophthalmol. 2018;12:453-61. down-regulation of hyaluronic acid synthases. Am J Pathol. 2007 18. Nusgens BV. [Hyaluronic acid and extracellular matrix: a primitive Nov;171(5):1451-61. molecule?]. Ann Dermatol Venereol. 2010 Apr;137 Suppl 1:S3-8. 28. Ghersetich I, Lotti T, Campanile G, et al. Hyaluronic acid in cutane- 19. Masson F. [Skin hydration and hyaluronic acid]. Ann Dermatol Vene- ous intrinsic aging. Int J Dermatol. 1994 Feb;33(2):119-22. reol. 2010 Apr;137 Suppl 1:S23-5. 29. Matuoka K, Hasegawa N, Namba M, et al. A decrease in hyaluronic 20. Beasley KL, Weiss MA, Weiss RA. Hyaluronic acid fillers: a compre- acid synthesis by aging human fibroblasts leading to heparan sulfate hensive review. Facial Plast Surg. 2009 May;25(2):86-94. enrichment and growth reduction. Aging (Milano). 1989 Sep;1(1):47- 21. McKee CM, Penno MB, Cowman M, et al. Hyaluronan (HA) 54. fragments induce chemokine gene expression in alveolar mac- 30. Rock K, Grandoch M, Majora M, et al. Collagen fragments inhibit rophages. The role of HA size and CD44. J Clin Invest. 1996 Nov hyaluronan synthesis in skin fibroblasts in response to ultraviolet B 15;98(10):2403-13. (UVB): new insights into mechanisms of matrix remodeling. J Biol 22. Bukhari SNA, Roswandi NL, Waqas M, et al. Hyaluronic acid, a Chem. 2011 May 20;286(20):18268-76. promising skin rejuvenating biomedicine: A review of recent updates and pre-clinical and clinical investigations on cosmetic and nutricos- metic effects. Int J Biol Macromol. 2018 Dec;120(Pt B):1682-95.

SKIN AGING AND COLLAGEN LEVELS

APRIL 2020 | LIFE EXTENSION | 59

LEMAPR20p.indd 59 2/14/20 11:32 AM MAGNESIUM CRITICAL FOR WHOLEBODY HEALTH

Magnesium is a critically important mineral, yet most Americans do not obtain enough from their diet. Magnesium helps: , • Keep heart rhythm steady. • Promote normal blood pressure. • Maintain normal muscle and nerve function. • Support a healthy immune system. • Keep bones strong. • Maintain blood sugar levels already within normal range. The recommended intake of magnesium to maintain vascular health is  mg or more a day. Each Life Extension® Magnesium Cap provides  mg of elemental magnesium for  cents a day! Item # •  vegetarian capsules For full product description and to order Magnesium Caps,  bottle $ call --- or visit www.LifeExtension.com  bottles $. each

References Caution: If taken in high doses, magnesium . Am J Clin Nutr. ;:-. may have a laxative effect. If this occurs, divide . Clinica Chimica Acta. ;:-. dosing, reduce intake, or discontinue product.

TRAACS® is a registered trademark of Albion Laboratories, Inc.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 60 2/14/20 3:00 PM REJUVENATE YOUR SKIN FROM WITHIN

Restore Collagen AND Hyaluronic Acid WITH DELIGHTFUL GUMMIES

Oral ingestion of collagen peptides and hyaluronic acid boosts these rejuvenating factors in normal, aging skin.

Clinical results reveal improved skin elasticity, increased moisture, and a % reduction in the appearance of eye wrinkles.

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These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 61 2/14/20 3:00 PM Restore Smoother, Youthful-Looking Skin from the Inside Out Wrinkling, dryness, and loss of firmness are outward signs of normal aging. One reason is loss of ceramides that are required for skin to retain its moisture and youthful suppleness. Skin Restoring Ceramides contains wheat-derived ceramide lipids in an oral capsule that hydrate the skin and smooth the appearance of fine lines and wrinkles.

Item # •  liquid vegetarian capsules  bottle $.  bottles $. each

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Contains wheat. Gluten free.

Ceratiq® is a registered joint-trademark of PLT Health Solutions and Arco, Robertet Group, France.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 62 2/14/20 3:03 PM Advanced Probiotic-Fermented Eye Serum

FRESHER, YOUNGER-LOOKING SKIN

Skin around the eye area is delicate and more sensitive than the skin on the rest of your face.

Advanced Probiotic-Fermented Eye Serum contains Lactobacillus ferment to promote a healthy balance of skin flora.

In a clinical study, Lactobacillus ferment increased skin moisture by 10%.*

Apply a small quantity around your eye area, tapping gently until absorbed.

For full product description and tto order Advanced Probiotic-Fermented Eye Serum, call 1-800-544-4440 or visit www.LifeExtension.com

0[LT ࠮5L[>[6aTS IV[[SL$29.25࠮IV[[SLZ LHJO

*Product Monograph: Leucidal® Liquid SF. Active Micro Technologies. 2019.

Not tested on animals.

Keep out of reach of children. For external use only. Avoid contact with eyes. If product contacts eyes, rinse thoroughly with water. If rash or irritation occurs, please discontinue use.

LEMAPR20p.indd 63 2/14/20 3:04 PM GEROPROTECT ®

Stem ® This new GEROPROTECT formula supports stem cell health and function.

Life Extension® scientists developed this proprietary Cell formula in collaboration with the Deep-Learning AI Technology at Insilico Medicine.

Three plant-based nutrients (garcinol, piceatannol, and resveratrol) were selected for activating key cell-signaling pathways that support stem cell health.

Item #02401࠮60 vegetarian capsules For full product description and to order 1 bottle $36 GEROPROTECT® Stem Cell, call 4 bottles $33 each 1-800-544-4440 or visit www.LifeExtension.com

Livinol™ is a trademark of Sabinsa Corporation.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 64 2/14/20 3:08 PM RESEARCH UPDATE

Lactoferrin Promotes Bone Growth and Strength

BY RICHARD RYAN

Osteoporosis plagues millions of older adults, weakening bones and leading to fractures.

Our bones are constantly remod- eled by removing old bone and replacing it with new bone. It’s how bones stay strong and youthful. But as we age, the creation of new bone doesn’t always keep up with the destruction of old bone. That’s osteoporosis, and it causes bones to become brittle, weak, and prone to fractures that can be fatal.1 It’s alarmingly common, striking 30% of women aged 50 or older and more than 77% of women over 80. In men, about 16% of those 50 or above have osteoporosis, and more than 46% of those over 80 have it.2 Many people are careful to ensure they get enough of the build- ing blocks of bone, including cal- cium, vitamins D3 and K, and other essential bone nutrients.3-8 However, building new bones is a complex operation. Research shows that a protein called lactofer- rin gives bones the instructions they need to both reduce bone loss and increase the building of new bone. The results can be dramatic. In one study, a lactoferrin combination product increased markers of bone- forming activity by 24% more than a placebo.9

APRIL 2020 | LIFE EXTENSION | 65

LEMAPR20p.indd 65 2/14/20 3:12 PM RESEARCH UPDATE

Lactoferrin and Osteoporosis These signaling molecules In one study, researchers gave increase the activity of cells called healthy, postmenopausal women To create and maintain strong osteoclasts that absorb bone and either a placebo or 125 mg/day of bones, we need certain nutrients decrease the activity of bone-form- lactoferrin coupled with an enzyme as building blocks and cofactors (or ing cells called osteoblasts. The from milk called ribonuclease.9 “helper molecules”). result: Our bones become weaker, Both groups also received 100% Calcium and vitamin D3 are the more porous, and prone to fractures. of the recommended daily allowance best known. We also need sufficient But lactoferrin, a protein found of calcium.9 vitamin K (which turns on bone- in milk,11 has the power to activate After 180 days, women who took building proteins) and the minerals bone-building signals that normally the lactoferrin-ribonuclease combi- magnesium, boron, zinc, manga- shut down or weaken with age.12-18 nation had a decrease in a marker of nese, and silicon.3-8 These vitamins When it comes to bone strength, bone-resorption osteoclast activity and minerals provide the raw mate- one lactoferrin combination product by 15.6% compared with placebo rial for healthy bones. was shown to counter the kinds of recipients, and an increase in mark- But rebuilding weak bones signals that result in weakened bone, ers of bone-forming osteoblast activ- caused by osteoporosis requires meaning lactoferrin could reduce ity by 7%-33%.9 something more. bone breakdown and increase Another study examined the As we age, senescent cells new bone formation.9 effect of direct application of lac- accumulate in our bones and toferrin alone in a rare but trou- bling side effect of bisphosphonate throughout our bodies. These are Results of Human Studies old, unhealthy cells that can no lon- drugs used to build bone. This ger divide and refuse to die off to bone-destroying side effect is called make way for new, healthy cells. Human studies show how effec- osteonecrosis of the jaw.19 Worst of all, they secrete harm- tively lactoferrin can restore a proper, In this condition, bone in the ful signaling molecules that actively healthy balance between bone lower jaw dies for unknown reasons, weaken bones and hasten body resorption and new bone production. often poking through the gums and aging.10 skin and allowing infection to set in.20 Generally, dead bone has to be removed surgically. Then a gauze dressing is applied while the wound heals.19 In this study, researchers satu- rated the gauze dressing with lac- toferrin and applied it after surgery, exposing the healing bone directly to lactoferrin.19 The surgical wounds healed in just one to two weeks, compared with two to three months under usual treatment,19 a dramatic demonstra- tion of the powers of lactoferrin to drive healthy, new bone formation. Animal studies also show that lactoferrin promotes stronger, frac- ture-resistant bones with increased mineral density.18,21-24 These bones have a more youthful structure, with more of the tiny “I-beams” called trabeculae that internally support bone.18,22

66 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 66 2/14/20 3:12 PM RESEARCH UPDATE

How Lactoferrin Strengthens Bones

Lactoferrin is a natural component of milk, nature’s baby food. Many of its properties promote cell growth and differentiation (when stem cells mature and develop into special- ized cell types), which is required in infancy and early childhood. Lactoferrin can promote bone health by:

• Preserving bone mass and improving bone micro- architecture,22

• Preventing the stress-induced death of bone-building osteo- blast cells,25-27

• Promoting the differentiation of stem cells into bone-build- ing osteoblast cells, while Summary suppressing their differen- tiation into bone-resorption Osteoporosis plagues millions of If you have any questions on the osteoclasts,15,25-29 older adults, weakening bones and scientific content of this article, please ® • Enhancing the growth of new leading to fractures. call a Life Extension Wellness Specialist at 1-866-864-3027. cartilage cells in-vitro, poten- It’s vital to get enough of the nutri- tially benefiting joint health,26 ents the body uses to make strong bones, including calcium, vitamins References • Activating youthful signaling D3 and K, as well as essential bone that stimulates growth of new minerals. 1. Available at: https://www.bones.nih.gov/ bone, suppresses the death But we can also correct the health-info/bone/osteoporosis/overview. of bone cells, and promotes signals that drive osteoporosis. Accessed January 24, 2020. differentiation leading to new 2. Wright NC, Saag KG, Dawson-Hughes B, Lactoferrin, a protein derived from et al. The impact of the new National Bone 13,18,21,24,27 bone, and milk, may do just that: It can reduce Health Alliance (NBHA) diagnostic criteria on signals that promote bone loss, and the prevalence of osteoporosis in the USA. • Activating transforming Osteoporos Int. 2017 Apr;28(4):1225-32. boost signals that promote bone 3. Boyacioglu O, Orenay-Boyacioglu S, growth factor-beta (TGF- growth. Yildirim H, et al. Boron intake, osteocalcin beta), a signaling protein most polymorphism and serum level in post- As research into this important active in youth, which pro- menopausal osteoporosis. J Trace Elem compound continues, lactoferrin Med Biol. 2018 Jul;48:52-6. motes new bone formation.12 4. Claro da Silva T, Hiller C, Gai Z, et al. may well take a prominent place Vitamin D3 transactivates the zinc and Researchers are continuing to among the more familiar bone-build- manganese transporter SLC30A10 via the Vitamin D receptor. J Steroid Biochem Mol investigate additional benefits of lac- ing nutrients. Biol. 2016 Oct;163:77-87. toferrin in promoting youthful cellular In case you do not know, the 5. Gurban CV, Mederle O. The OPG/RANKL system and zinc ions are promoters of activity. But it’s already shown great primary benefit of lactoferrin is to bone remodeling by osteoblast prolif- promise in fighting against the bone enhance healthy immune responses. eration in postmenopausal osteoporosis. The bone-building effect is an Rom J Morphol Embryol. 2011;52(3 loss that has too often been consid- Suppl):1113-9. ered an inevitable part of aging. added bonus. •

APRIL 2020 | LIFE EXTENSION | 67

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6. Huang ZB, Wan SL, Lu YJ, et al. Does 14. Li Q, Zhao J, Hu W, et al. Effects of Recom- 22. Guo HY, Jiang L, Ibrahim SA, et al. Orally vitamin K2 play a role in the prevention and binant Human Lactoferrin on Osteoblast administered lactoferrin preserves bone treatment of osteoporosis for postmeno- Growth and Bone Status in Piglets. Anim mass and microarchitecture in ovariecto- pausal women: a meta-analysis of random- Biotechnol. 2018 Apr 3;29(2):90-9. mized rats. J Nutr. 2009 May;139(5):958-64. ized controlled trials. Osteoporos Int. 2015 15. Cornish J, Naot D. Lactoferrin as an ef- 23. Amini AA, Nair LS. Lactoferrin: a biologi- Mar;26(3):1175-86. fector molecule in the skeleton. Biometals. cally active molecule for bone regeneration. 7. Mederle OA, Balas M, Ioanoviciu SD, et al. 2010 Jun;23(3):425-30. Curr Med Chem. 2011;18(8):1220-9. Correlations between bone turnover mark- 16. Chen XW, Li YH, Zhang MJ, et al. Lac- 24. Li W, Zhu S, Hu J. Bone Regeneration Is ers, serum magnesium and bone mass toferrin ameliorates aging-suppressed Promoted by Orally Administered Bovine density in postmenopausal osteoporosis. osteogenesis via IGF1 signaling. J Mol Lactoferrin in a Rabbit Tibial Distraction Clin Interv Aging. 2018;13:1383-9. Endocrinol. 2019 Jul;63(1):63-75. Osteogenesis Model. Clin Orthop Relat 8. Price CT, Koval KJ, Langford JR. Silicon: a 17. Malet A, Bournaud E, Lan A, et al. Bovine Res. 2015 Jul;473(7):2383-93. review of its potential role in the prevention lactoferrin improves bone status of ovariec- 25. Cornish J. Lactoferrin promotes bone and treatment of postmenopausal osteopo- tomized mice via immune function modula- growth. Biometals. 2004 Jun;17(3):331-5. rosis. Int J Endocrinol. 2013;2013:316783. tion. Bone. 2011 May 1;48(5):1028-35. 26. Cornish J, Callon KE, Naot D, et al. Lac- 9. Bharadwaj S, Naidu AG, Betageri GV, et 18. Hou JM, Xue Y, Lin QM. Bovine lactoferrin toferrin is a potent regulator of bone cell al. Milk ribonuclease-enriched lactoferrin improves bone mass and microstructure activity and increases bone formation in induces positive effects on bone turnover in ovariectomized rats via OPG/RANKL/ vivo. Endocrinology. 2004 Sep;145(9): markers in postmenopausal women. Os- RANK pathway. Acta Pharmacol Sin. 2012 4366-74. teoporos Int. 2009 Sep;20(9):1603-11. Oct;33(10):1277-84. 27. Naot D, Grey A, Reid IR, et al. Lactoferrin- 10. Farr JN, Fraser DG, Wang H, et al. Iden- 19. Calvani F, Cutone A, Lepanto MS, et al. -a novel bone growth factor. Clin Med Res. tification of Senescent Cells in the Bone Efficacy of bovine lactoferrin in the post- 2005 May;3(2):93-101. Microenvironment. J Bone Miner Res. 2016 surgical treatment of patients suffering from 28. Montesi M, Panseri S, Iafisco M, et al. Nov;31(11):1920-9. bisphosphonate-related osteonecrosis of Coupling Hydroxyapatite Nanocrystals with 11. Available at: https://www.sciencedirect. the jaws: an open-label study. Biometals. Lactoferrin as a Promising Strategy to Fine com/topics/food-science/lactoferrin. Ac- 2018 Jun;31(3):445-55. Regulate Bone Homeostasis. PLoS One. cessed January 30, 2020. 20. Payne KF, Goodson AM, Tahim AS, et 2015;10(7):e0132633. 12. Li Y, Wang J, Ren F, et al. Lactoferrin al. Why worry about bisphosphonate- 29. Cornish J, Palmano K, Callon KE, et al. Promotes Osteogenesis through TGF-beta related osteonecrosis of the jaw? A guide Lactoferrin and bone; structure-activity Receptor II Binding in Osteoblasts and to diagnosis, initial management, and relationships. Biochem Cell Biol. 2006 Activation of Canonical TGF-beta Signaling referral of patients. Br J Gen Pract. 2017 Jun;84(3):297-302. in MC3T3-E1 Cells and C57BL/6J Mice. J Jul;67(660):330-1. Nutr. 2018 Aug 1;148(8):1285-92. 21. Fan F, Shi P, Liu M, et al. Lactoferrin 13. Liu M, Fan F, Shi P, et al. Lactoferrin pro- preserves bone homeostasis by regulat- motes MC3T3-E1 osteoblast cells prolifera- ing the RANKL/RANK/OPG pathway of tion via MAPK signaling pathways. Int J osteoimmunology. Food Funct. 2018 May Biol Macromol. 2018 Feb;107(Pt A):137-43. 23;9(5):2653-60.

68 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 68 2/14/20 3:12 PM HEALTHY BONES HEALTHY HEART

Vitamin K helps support calcium balance in bones, heart valves, and arteries. Super K Elite introduces two new forms of vitamin K called MK- and MK-. Super K Elite provides clinically studied doses of vitamin K. Plus four subtypes of vitamin K:

Vitamin K , mcg Vitamin K (MK) , mcg Vitamin K (MK-)  mcg Vitamin K (MK-)  mcg KEEP CALCIUM Vitamin K (MK-)  mcg IN YOUR BONES AND OUT OF YOUR Item # •  softgels  bottle $ BLOOD VESSELS  bottles $ each

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BROADSPECTRUM VITAMIN K

Caution: If you are taking anticoagulant or antiplatelet medications, or have a bleeding disorder, consult with your healthcare provider before taking this product.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 69 2/14/20 3:14 PM EUROPEAN MILK THISTLE

Ultimate Protection For Your Liver

European Milk Thistle contains standardized, top-grade potencies of silymarin, silybin, isosilybin A, and isosilybin B, providing a full spectrum of liver-supportive compounds.

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SILIPHOS® is a registered trademark of Indena S.p.A., Italy.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 70 2/14/20 3:17 PM ACTIVATE BONE-BUILDING SIGNALS

WHILE SUPPORTING HEALTHY IMMUNE FUNCTION

Lactoferrin, a component of whey protein, is best known for its immune benefits. New data reveal how lactoferrin turns on bone-building signals in the body. This enables better utilization of calcium, magnesium, and other skeletal structural components.

Item #01681࠮TNJHWZ\SLZ For full product description and to order 1 bottle $45 Lactoferrin Caps, call 1-800-544-4440 IV[[SLZ LHJO or visit www.LifeExtension.com (Two-Month Supply) Bioferrin® is a registered trademark of Glanbia.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 71 2/14/20 3:51 PM BORON

Promotes Healthy Prostate Function and Healthy Bones

Each capsule provides  mg of boron divided in three bioavailable different forms:

• Boron citrate • Boron aspartate • Boron glycinate

There are  mg of boron in the daily dose of each of the following Life Extension™ formulas: • Two-Per-Day • Bone Restore • Ultra Prostate Formula Item # •  vegetarian capsules • Life Extension Mix™  bottle $.  bottles $. each The suggested daily dose for most adults is - mg of boron., If you are already obtaining this potency References in your multi-nutrient formulas, you may not need 1. Open Orthop J. 2012;6:143-9. additional boron. 2. Altern Med Rev. 2004 Dec;9(4):434-7.

For full product description and to order Life Extension® Boron, call --- or visit www.LifeExtension.com

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 72 2/19/20 2:17 PM LEMAPR20p.indd 73 2/14/20 2:34 PM Maintain Healthy Muscle Mass

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LEMAPR20p.indd 74 2/14/20 3:20 PM HEALTHY EATING

Shuk: From Market to Table, the Heart of Israeli Home Cooking

BY EINAT ADMONY AND JANNA GUR

True Israeli home cooking doesn’t start in the home. It starts in the shuk—the local open-air market. Dotted throughout Israel’s towns and cities, shuks are lively mazes of stalls that sell the freshest seasonal ingredients, including fruit and vegetables, meats and fish, nuts and spices, fresh herbs, cheeses and yogurts, and everything in between. The shuk is a feast for your senses as much as it is for your appetite. What makes Israeli food unique is its fusion of Middle Eastern cuisine, combined with the recipes of immigrants from many countries. Celebrating this melting pot of culture and cuisine, Shuk: From Market to Table, the Heart of Israeli Home Cooking contains 140 Israeli dishes that have roots in Persia, Yemen, Libya, the Balkans, and more—and includes favorites such as hummus, tab- boulehs, shakshukas, chopped salad, and couscous. All of the recipes are based on fresh ingredients that could be found in any local shuk. In this issue, Life Extension® Magazine features four flavorful recipes that bring the heart of the shuk into your own kitchen.

—LAURIE MATHENA

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LEMAPR20p.indd 75 2/14/20 3:22 PM HEALTHY EATING

Cauliflower Tabbouleh with Fry the pumpkin and sunflower Add the lemon juice, oil, salt, and Crunchy Seeds seeds in the same manner; transfer some energetic twists of pepper and them to the paper towels as well. toss to combine. Taste and adjust the seasoning, adding more salt, SERVES 4 TO 6 Pulse the cauliflower florets in a food pepper, lemon juice, and/or oil as processor until they are broken down 3 tablespoons sesame seeds needed to make the salad yummy to couscous-size crumbles. Transfer and bright. Olive oil, for frying the cauliflower to a large bowl. If 3 tablespoons pine nuts there are any large pieces left, return Sprinkle the pomegranate seeds on them to the food processor and top (if using) and serve promptly. 3 tablespoons hulled pumpkin pulse until they reach the desired seeds (pepitas) size, then add them to the bowl. Add 3 tablespoons hulled sunflower the sesame seeds, pine nuts, pump- seeds kin seeds, sunflower seeds, nigella 1 medium cauliflower, cored and seeds, cilantro, mint, and parsley to cut into large florets the bowl with the cauliflower. 1 tablespoon nigella seeds 2 tablespoons finely chopped fresh cilantro 2 tablespoons finely chopped fresh mint 2 tablespoons finely chopped fresh parsley 3 tablespoons fresh lemon juice, plus more as needed 3 tablespoons extra-virgin olive oil, plus more as needed 1 teaspoon kosher salt, plus more as needed Freshly ground black pepper

1/3 cup (60 g) fresh pomegranate seeds, for garnish (optional)

Toast the sesame seeds in a dry medium skillet over medium heat, stirring continuously, for a couple of minutes, until golden. Transfer to a small plate and let cool.

Line a plate with paper towels. Heat a thin layer of oil in the same skillet over medium-low heat. Add the pine nuts and sauté, shaking the skillet frequently, until they just turn light golden, 3 to 4 minutes. Use a slot- ted spoon to transfer them to the paper towels.

76 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 76 2/14/20 3:22 PM HEALTHY EATING

Masabacha

Whole Chickpeas in Warm, Spicy Tahini Sauce

SERVES 6 TO 8

2 cups (370 g) dried chickpeas ½ teaspoon baking soda ¼ cup (60 ml) boiling water ¾ cup (180 ml) best-quality raw tahini 1 teaspoon kosher salt

DRESSING ¼ cup (60 ml) extra-virgin olive oil 3 medium garlic cloves, minced or grated ½ jalapeño chili, cored, seeded, and finely chopped ¼ cup (60 ml) fresh lemon juice 1 teaspoon ground cumin Kosher salt and freshly ground black pepper

FOR GARNISH Chopped fresh parsley Extra-virgin olive oil

Pick through the dried chickpeas ¼ teaspoon baking soda. Bring to a Meanwhile, make the dressing: and discard any little stones (yes, boil over high heat, reduce the heat Whisk together the oil, garlic, jalapeño, that can happen) or peas that look to medium, and cook at a lively sim- lemon juice, and cumin in a small very irregular in color or in shape. mer, uncovered, for 1 to 1½ hours. bowl and season with salt and pepper. Rinse the chickpeas thoroughly Use a slotted spoon to skim off Ladle the warm chickpea mixture under cold water. Transfer the chick- any skins that float to the surface. into a large serving bowl or individual peas to a large bowl and add cold The chickpeas are ready when they plates and pour the dressing over water to cover them by 3 to 4 inches are completely soft, slightly broken the top. Garnish with chopped pars- (7.5 to 10 cm). Add ¼ teaspoon of down, and can easily be smooshed ley and a generous drizzle of oil and the baking soda. Soak for at least 12 with your fingers. Drain the chick- serve at once. and up to 24 hours. peas thoroughly and return them to the pot. TIP Drain and rinse the soaked chick- Masabacha is delicious only when it is peas under cold water until the water Add the boiling water, tahini, and salt. really warm, so many hummus makers runs clear. Transfer the chickpeas Cook over medium heat for a couple keep the cooked chickpeas and tahini over to a large pot, pour in 3 quarts (3 L) of minutes, just until the chickpeas a double boiler until serving and add the cold water, and add the remaining are warmed through. dressing at the last moment.

APRIL 2020 | LIFE EXTENSION | 77

LEMAPR20p.indd 77 2/14/20 3:22 PM HEALTHY EATING

Green Shakshuka with Chard, Kale, Spinach, and Feta

SERVES 4 TO 6

¼ cup (60 ml) extra-virgin olive oil 2 leeks, white parts chopped, and green tops very thinly sliced 3 medium garlic cloves, thinly sliced 1 small jalapeño chili, cored, seeded, and thinly sliced 5 or 6 Swiss chard leaves, leaves coarsely chopped, stems thinly sliced 1 small bunch Tuscan kale (also called lacinato or dino- saur), stemmed, leaves coarsely chopped stirring often, until wilted and soft, 3 Spicy Fish in Cherry Tomato 3 cups baby spinach or trimmed to 4 minutes. Add the caraway and and Harissa Sauce and coarsely chopped regular cumin, and season very lightly with spinach salt (the feta is quite salty) and sev- SERVES 6 1 teaspoon ground caraway eral twists of pepper. 1 teaspoon ground cumin 1/3 cup (80 ml) vegetable oil Add the stock and the lemon juice Kosher salt and freshly ground and cook for 5 to 7 minutes, then 10 garlic cloves, smashed black pepper reduce the heat to low and cook ¼ cup tomato paste ½ cup (120 ml) homemade or for another few minutes, until the 1 jalapeño chili, cored, seeded, low-sodium store-bought chicken greens meld into a thick, dark green, and thinly sliced stock or vegetable stock or water stewy sauce. Taste and adjust the 1 tablespoon harissa, store-bought seasoning. 1 tablespoon fresh lemon juice or homemade 6 to 8 large eggs Use a large spoon to create little 3 tablespoons sweet paprika wells in the greens’ mixture. Carefully 1 teaspoon ground caraway TO SERVE break 1 egg into a cup or ramekin, 1½ teaspoons ground cumin 5 ounces (140 g) feta cheese, then slip it into one of the wells; coarsely crumbled repeat with the remaining eggs. 2 pints (910 g) cherry tomatoes (Cracking the egg into a cup first Extra-virgin olive oil Kosher salt lets you inspect it for any runaway Crusty bread or challah bits of shell.) Cover and simmer until ½ cup (120 ml) water the egg whites are set but the yolks 1 large bunch fresh cilantro are still a little runny, about 7 minutes. Heat the oil in a large skillet over Freshly ground black pepper Remove the skillet from the heat. medium heat. Add the leeks, garlic, 6 (7 to 9 ounce/200 to 255 g) jalapeño, and chard stems and sauté Sprinkle the shakshuka with the fillets flaky white-fleshed fish until softened and lightly caramelized, feta, drizzle with oil, and sprinkle (grouper, bass, snapper, and 10 to 12 minutes (take care not to generously with za’atar. Serve the halibut are all nice), skin-on, if brown the garlic). Add the kale, spin- shakshuka directly from the skillet, possible ach, and the chard leaves and cook, with plenty of crusty bread or challah. Challah or couscous, for serving

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LEMAPR20p.indd 78 2/14/20 3:23 PM HEALTHY EATING

Pour the vegetable oil into a rela- Remove about 3 tablespoons is cooked through, 7 to 8 minutes. tively deep, large skillet. Immediately of whole leaves from the cilantro Thicker fillets, like halibut, will need add the smashed garlic cloves and bunch and reserve them for garnish. 2 to 3 minutes more. To check the cook over very low heat just until Tear up the rest of the bunch and fish for doneness, make a small inci- fragrant, 3 to 4 minutes. Watch the toss into the pan. Give it a minute sion in the thickest part of the fish pan closely to make sure the gar- to blend with the sauce, then taste and make sure the flesh is opaque lic doesn’t brown, or it will become and adjust the seasoning with salt, and flaky. bitter. pepper, and the remaining jalapeño and 1½ teaspoons harissa if you Serve straight out of the pan, gar- Increase the heat to medium-high, want more heat. Bear in mind that nished with the reserved whole add the tomato paste, half the jala- once you add the fish, you won’t be cilantro leaves, with a lot of bread alongside or with couscous. peño, 1½ teaspoons of the harissa, able to stir the sauce and play with and all the paprika, caraway, and the seasonings—make sure the fla- cumin and stir for a minute or two, vor and level of spiciness are to your until fragrant. Add 1½ pints (680 g) liking. If you have any questions on the of the cherry tomatoes (reserve the scientific content of this article, please rest for later) and season with salt. Add the fish fillets, skin-side up, call a Life Extension® Wellness Reduce the heat to medium and tucking them gently into the sauce. Specialist at 1-866-864-3027. cook, stirring occasionally, until the Sprinkle the remaining ½ pint (225 g) Excerpted from Shuk by tomatoes start to break down, 7 to cherry tomatoes on top of the fish. Einat Admony and Janna Gur 8 minutes. Pour in the water, bring to Bring to a simmer over medium heat. (Artisan Books). Copyright © 2019. a simmer, cover, and cook over low Reduce the heat to low, cover, and Photographs by Quentin Bacon. heat for about 30 minutes, or until simmer, without stirring, until the fish thick and saucy. To order a copy of Shuk, call 1-800-544-4440 or visit www.LifeExtension.com Item #34168 Price: $26.25

APRIL 2020 | LIFE EXTENSION | 79

LEMAPR20p.indd 79 2/14/20 3:23 PM Dual-Layer Tablet for Optimal Cruciferous Benefits Cruciferous Vegetable Extracts

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LEMAPR20p.indd 80 2/14/20 3:24 PM COMBAT Senescent Cells and AGING

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LEMAPR20p.indd 81 2/14/20 3:25 PM Regain Yournergy Youth ful E Energize every cell in your body with carnosine, R-lipoic acid, benfotiamine, taurine, PQQ, and more.

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LEMAPR20p.indd 82 2/14/20 3:26 PM AUTHOR INTERVIEW The Switch

Calorie restriction [is] now established to be the most powerful intervention to delay aging and increase longevity in diverse species, from yeast to mammals.

Wouldn’t it be great if losing weight, easing chronic conditions, and staying healthier, longer was as simple as flipping a switch? As James Clement reveals in his new book, The Switch, it is. Our bodies contain a metabolic switch that, when activated, initiates fat burning, removes damaged and dysfunctional cells, and dampens inflammation. As a result, activating this switch can help promote weight loss, reduce the risk of major diseases, and slow down the aging process. In this interview with Life Extension®, Clement shares a few of the specific details from his highly acclaimed book on how to activate PHOTO BY DAVID STEELE PHOTO BY DAVID your body’s anti-aging switch. © JAMES CLEMENT, J.D., LL.M —Laurie Mathena

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LE: What would you say is the secret growths, and preventing metabolic LE: What is the connection between to living a long, healthy life? disorders such as obesity and diabe- this switch and lifespan? tes—which means that by boosting Clement: In your own grasp of the your body’s autophagy, you dampen Clement: Virtually all health-extend- “secrets” of living a good, long life, inflammation, slow down the aging ing and lifespan-extending inter- what comes to mind? My bet is that process, reduce your risk of devel- ventions that we know of have their you think of blood sugar balance, oping certain diseases, and optimize effects because of their actions to healthy weight, and physical fitness. your biological function. suppress this switch. Those are all appropriate goals Much of [my] book [details] how to achieve, but they miss the main LE: How can autophagy be turned these various interventions, some of point—they are merely a means of on in the body? which you may have heard of and sparking a prominent antiaging pro- others of which you haven’t, act on cess: autophagy. Clement: Autophagy can be trig- this pathway and ultimately regulate [Autophagy is] how the body gered when a certain complex, called this important switch, periodically removes and recycles dangerous, mTOR, within cells is turned down. I turning on autophagy in the process. damaged organelles and particles, refer to the mTOR complex as “the The information is meant to help as well as pathogens, from inside Switch.” reverse this hastening of aging and cells, thus aiding your immune sys- mTOR is the switch that nearly put us back onto a more natural tem and greatly reducing your risk every cell (except blood cells) has, path of consumption and exercise of developing cancer, heart disease, and it either activates your cell’s that keeps the Switch (mTOR and chronic inflammation, osteoarthri- self-cleaning mode (autophagy), rid- autophagy) in balance and prevents tis, and neurological disorders from ding the body of toxic materials and the age-related diseases that were depression to dementia. fomenting cancers, as well as burn- rare centuries ago but are wide- Autophagy makes us more physi- ing fat, or allows the body to produce spread now. ologically efficient by getting rid of more proteins, store as much energy defective parts, promoting healthy (glucose and fat) as possible, and LE: In your book, you talk about a metabolism, stopping cancerous build more cells. few specific ways to change the These anabolic processes, when direction of this metabolic switch: taken to an extreme level, which our calorie restriction, intermittent fast- modern lifestyle practices do, can ing, and very-low-carb diets. trigger illness. Think of this switch like a dimmer Clement: Researchers discovered for your lights: turning it toward one nearly 80 years ago that both calo- end to increase light and the other rie restriction and intermittent fast- direction to decrease it. ing greatly extended the lives of Although we evolved to have this test animals, often by reducing their biological switch move back and vulnerability to cancer and heart forth continuously between growth disease. (mTOR) and repair (autophagy, and A ketogenic (very-low-carbo- sometimes repair for prolonged hydrate) diet, widely used for the periods), the lifestyles of mod- treatment of neurological diseases, ern humans keep it turned toward showed somewhat similar antican- growth constantly and seldom or cer and anti-heart-disease benefits, never in the repair direction. although it has been investigated And when it’s in the growth stage, much less than calorie restriction or internal cell cleansing comes to a intermittent fasting. halt and our ability to clear out the After three months of reading biological debris—misfolded pro- through more than 500 scientific teins, pathogens, and dysfunctional papers, it finally dawned on me that organelles—falters. all of the papers I’d been reading

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LEMAPR20p.indd 84 2/14/20 3:28 PM AUTHOR INTERVIEW

LE: Another way to encourage autophagy is through calorie restric- tion. Can you explain that in more detail?

Clement: By definition, calorie restriction involves the consumption of fewer calories without malnutrition or deprivation of essential nutrients. Although the molecular mecha- nisms that control the effects of cal- orie restriction are still being studied and debated, there is more wide- spread acceptance of the hypothesis that calorie restriction and lifespan extension involve a dialing down of insulin signaling and a dialing up of autophagy. about life-extending, disease-pre- When you give your body food, Calorie restriction [is] now estab- venting genes, therapies, drugs, vita- your insulin level rises and your lished to be the most powerful inter- mins/supplements, lifestyles, and glucagon level decreases. But the vention to delay aging and increase so on had one thing in common: opposite happens when you don’t longevity in diverse species, from they turned down the mTOR cellular eat: your insulin level goes down and yeast to mammals. It is also the most mechanism and thereby turned up your glucagon level rises. potent and reproducible physiologi- the autophagy process. When your glucagon level rises, it cal intervention to protect against I spent another three months read- triggers autophagy. This is why tem- cancer specifically in mammals. ing 600 more papers focused on porarily denying your body nutrients mTOR and autophagy and confirmed through the safe practice of intermit- LE: What happens in the body when my suspicion. tent fasting is one of the best ways it’s deprived of an abundance of to boost the integrity of your cells. calories? LE: What is intermittent fasting, and Aside from maintaining your cells’ how does it trigger autophagy? youth, research has shown that inter- Clement: The effects of calorie mittent fasting promotes greater restriction on growth hormone, and Clement: Intermittent fasting (a form energy, increased fat burning, and in turn, levels of insulin and IGF-1, of which is called time-restricted decreased risk of developing dis- are certainly important to keeping eating) works because it activates eases such as diabetes and heart your “growth” switch (mTOR) turned the hormone glucagon, which func- disease, all due to its ability to acti- down so that your self-cleaning pro- tions opposite of insulin to keep your vate autophagy. cess (autophagy) is tuned up. blood glucose levels balanced. With less growth hormone around, Here’s a visual to really grasp this LE: How do you put intermittent fast- there’s increased autophagy to clean concept. Picture a seesaw: when ing into practice? house. And what’s the relationship one person goes up, the other goes between calorie restriction and down. This analogy is frequently Clement: You can start with a autophagy? used to explain the biological insu- very comfortable 12-hour fast just When you put mild stress on the lin-glucagon relationship. In your by avoiding eating after 7 p.m. (No body in the form of calorie restric- body, if the insulin level goes up, the midnight snacking!) Then you can tion, it turns up the autophagy dial. glucagon level goes down and vice stretch it to 16 hours and eventually As that happens, there’s an increase versa. forgo “break-fast” (breakfast) the in protein turnover and cellular repair. next morning, so your first meal of In other words, your body is the day is around 11 a.m. forced to renovate itself!

APRIL 2020 | LIFE EXTENSION | 85

LEMAPR20p.indd 85 2/14/20 3:28 PM AUTHOR INTERVIEW

One of insulin’s jobs is to send You’ll want to dial up autophagy amino acids from broken-down pro- for eight months of the year and teins into lean tissues such as mus- dial it down during the other four cle. But here’s the difference: protein months. It doesn’t really matter how doesn’t supply glucose rapidly, as you break up those months (e.g., you carbohydrate does. can do two months with autophagy on and one month off, then repeat for LE: How does this relate to autoph- a full calendar year). agy? Remember, autophagy is an action plan or tool for cellular self- Clement: When you reduce your fortification, but it also demands a protein intake, especially animal pro- balance as with so many other things teins, you will lower your insulin levels in life: too much or not enough can and in turn boost your glucagon level be harmful to the cell, and thus to and activate autophagy. This explains you. • why protein cycling, or reducing your protein intake in cyclical fashion, has an effect similar to that of fasting. In addition to enhancing autoph- If you have any questions on LE: How does protein restriction agy, protein cycling alongside calorie the scientific content of this article, factor in? restriction and intermittent fasting will please call a Life Extension® Wellness help reduce your risk of developing Specialist at 1-866-864-3027. Clement: Another key dietary strat- the diseases I’ve covered: diabetes, From THE SWITCH by James W. egy that is often ignored is protein cancer, and heart disease. Clement. Copyright © 2019 by James restriction. That’s right: you don’t Remember, these are the diseases W. Clement. Reprinted by permission want to be eating too much protein. of civilization, also known as dis- of Gallery Books, an Imprint of Although the practice of general eases of overconsumption. Simon & Schuster, Inc. calorie restriction has benefits for Protein cycling could become your body weight, it’s really the protein most powerful tool for making over To order a copy of The Switch, restriction that creates the health your metabolism and increasing your call 1-800-544-4440 or visit benefits. chances of living a long, disease-free www.LifeExtension.com If cutting way back on your calo- life. This is especially helpful for peo- rie consumption sounds like a hor- ple who find it unrealistic to commit Item #: 34167 rendous proposition and you don’t to the rigors of calorie restriction and Price: $20.24 need to lose weight, I’ve got good fasting. news for you: restriction of protein consumption—without restricting LE: These sound like great ways to calories—is among the most promis- keep the Switch turned off. Is this ing interventions that have emerged something that should be practiced to promote healthy aging in humans. all the time? And it’s not going to feel as though you’re “restricting” yourself, which Clement: As with most everything is why it’s better to call it protein in life, you’ll want to strike a balance cycling. between your Switch being on and I cannot emphasize the following being off. The body needs periods of enough: protein stimulates insulin rest from its internal cleansing mech- release as much as carbohydrate anisms so you can more easily build does! We often don’t think about that tissues, keep your weight in check because we tend to relate insulin (not lose too much), and maintain release with only sugar. your immune system.

86 | LIFE EXTENSION | APRIL 2020

LEMAPR20p.indd 86 2/14/20 3:28 PM Increase AMPK to Lower mTOR

Most people today consume too many excess calories. This results in mTOR constantly running at high gear, which is a factor in unwanted fat storage. Studies show that increasing AMPK activity turns down excess mTOR. Reduce Cell Fat Storage Scientific studies show that increasing AMPK activity can encourage cells to store less fat and burn it as energy.,

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LEMAPR20p.indd 87 2/14/20 3:30 PM THE VERSATILE BENEFITS OF ®

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LEMAPR20p.indd 88 2/14/20 3:31 PM SUPERFOODS

Hemp Seeds

BY LAURIE MATHENA

Hemp seeds, with their mild, nutty flavor, have been used in China for more than 3,000 years, as both food and medicine. More recently, hemp seeds (also called hemp hearts) have experi- enced a resurgence in the West because of their unique nutrient pro- file, which boasts an abundance of protein, healthy fats, and minerals. A Top Source of Plant-Based Protein About 25% of the total calories in hemp seeds are from protein. Just two to three tablespoons of the seeds provide about 11 grams of protein.1 In addition, hemp seeds are con- sidered a complete protein source, meaning they contain all nine essen- tial amino acids. Reduces Heart Disease Risk Hemp seed consumption can help reduce the risk of heart dis- ease. Animal studies have shown that hemp seeds can lower blood pressure,2 decrease cholesterol- induced platelet aggregation,3 and help the heart recover after a heart attack.4 Improves Skin Health

Dietary hemp seed oil has been According to Life Extension®, References shown to help improve clinical symp- the optimal ratio of omega-6 to 1. Available at: https://nutritiondata.self.com/ facts/custom/629104/2. Accessed January toms in patients with atopic derma- omega-3 consumption is about 4 28, 2020. titis.5 Researchers attributed these to 1. In fact, hemp seeds boast a 3 2. Eur J Nutr. 2014 Aug;53(5):1237-46. 3. Can J Physiol Pharmacol. 2008 improvements to the abundance of to 1 ratio. Apr;86(4):153-9. polyunsaturated fatty acids found in You can enjoy hemp seeds sprin- 4. Am J Physiol Regul Integr Comp Physiol. 2007 Mar;292(3):R1198-203. hemp seed oil, which include both kled on salads, in smoothies, or as 5. J Dermatolog Treat. 2005 Apr;16(2):87-94. omega-3 and omega-6 fats. a topping on oatmeal.

APRIL 2020 | LIFE EXTENSION | 89

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PRODUCTS P M HIGHER POTENCY CARNOSINE

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*Bio-Enhanced® is a registered trademark of Geronova Research, Inc.

These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.

LEMAPR20p.indd 96 2/14/20 3:35 PM Higher Potency at Discount Pricing TM + NAD Cell Regenerator TURN ON YOUR CELLULAR ENERGY NAD+ levels plummet with age but increase in response to nicotinamide riboside. Optimized NAD+ Cell Regenerator™ combines  mg of nicotinamide riboside with resveratrol and other plant extracts. For those already taking resveratrol, we also offer NAD+ Cell Regenerator™ that provides  mg of nicotinamide riboside. The only online source of these NAD+ formulas is LifeExtension.com (or by calling ---).

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IN THIS EDITION OF LIFE EXTENSION® MAGAZINE

7 WHY ARGININE FAILED AS A CARDIOVASCULAR DRUG L-arginine rapidly degrades in the body. This caused it to fall out of favor with cardiologists. A new low-dose, sustainable L-arginine offers support for circulatory health.

22 BOOST NITRIC OXIDE TO REDUCE CARDIOVASCULAR RISK A blend of aronia berries and an innovative form of L-arginine 7 22 boosts production of nitric oxide, helping to improve blood flow.

32 HOW MEN CAN FIGHT OSTEOPOROSIS Men are at a higher risk of osteoporosis than most realize. Healthy lifestyle choices, along with appropriate nutrients and hormone balance promotes bone formation and strength.

42 IMPROVE DIGESTION OF PLANT-BASED FOODS The trend toward eating plant-based diets often requires special enzymes to digest fiber-rich foods to avoid bloating, 32 42 gas, and diarrhea.

54 IMPROVE SKIN APPEARANCE FROM THE INSIDE Oral intake of collagen peptides and hyaluronic acid reduces 65 eye wrinkle depth up to 20%.

65 LACTOFERRIN HELPS BUILD NEW BONES Adding lactoferrin to your bone-building supplements helps reduce bone loss and increase new bone formation.

54 VISIT US ONLINE AT LIFEEXTENSION.COM

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