Despite growing sales and a promising future, some sales of natural products are based upon consumer use of ineffective or inappropriate products that reap undeserved rewards upon the industry.

Examples of misdirected use of natural products abound: calcium for postmenopausal bone loss – but it is the loss of estrogen not a shortage of calcium that induces this problem;[i] red yeast rice to lower cholesterol – but cholesterol has never been shown to lower coronary artery disease mortality rates in healthy people and only marginally in high-risk individuals;[ii] vitamin E for heart disease– based upon two Canadian cardiologists who never provided convincing evidence in controlled trials and last wrote about the subject 40 years ago;[iii] or even niacin to raise HDL “good” cholesterol – but HDL cholesterol is no longer regarded as a desirable blood lipid.[iv] The natural products industry needs to keep up with rapidly changing science.

The natural products industry may be so busy counting its profits it may not be forced to do what it needs to do, which is to cease promoting products that don’t make a difference.

Science vs “pop” science

So what precisely should the natural products industry be doing?

An obvious though unfruitful answer is to scientifically validate all functional foods and dietary supplements. The problem here is that great science does not usually equate with sales.

As an example, look at Pycnogenol, a proprietary pine bark extract. To date there are 279 positive published papers about this natural molecule.[v] But Pycnogenol doesn’t even rank in the top 100 herbal products sold in the U.S.

Furthermore, the industry has gravitated toward gaining approval from Dr. Oz Laboratories Inc, an outfit that announces results of its testing on television. This “pop science” approach can create a greater flurry of sales than any published study.

That is how shark cartilage became so popular for a short time, after it was aired as a potential cure for cancer in 1993 on 60 Minutes.[vi] With publicity like that, who needs science? However, shark cartilage was later debunked and is no longer considered an anti-cancer agent.[vii]

I don’t foresee a day when the natural products industry can shed its reliance upon pop science. This is how retail stores gravitated into offering what sells (example: coral calcium) rather than what has been proven to work. If retail stores want to continue to serve the public in a meaningful way and develop customer retention, they will need to be a source of up-t0-date information, or find their customers have walked away to buy online.

Industry intimidation

With that said, allow me to characterize the natural products industry as being overly apologetic, weak-kneed, ignorant and capitulating.

For example, every time health authorities beat the drum for another imagined flu epidemic, the natural products industry is pressed upon by public health authorities to publicly say it has no remedies for the flu, leaving consumers to rely upon ineffective vaccines.[viii] Even if vaccination is effective, only a third of the population undergoes inoculation during the flu season.  

The natural products industry DOES have at least some proven and promising remedies for colds and the flu.[ix] Among them are garlic (allicin),[x] high-dose zinc lozenges,[xi] echinacea and vitamin D.[xii] While pharmaceutical-oriented public health agencies would lead consumers to believe seasonal colds and the flu are due to vaccine deficiency, a better explanation centers around lack of sun-generating vitamin D in wintertime.[xiii]

Drugs or natural products?

David Stouder, owner of Apple Health Foods in Redwood City, California, asks if you were forced to make a choice between two doors, both which had unlabeled bottles of pills behind them, and behind the first door were drugs and behind the second door were dietary supplements, and you then had to consume them, which door would you pick?

The point of this is drugs may be FDA approved but they don’t get anybody well. Drugs may artificially lower numbers (markers of disease like cholesterol, blood sugar, elevated blood pressure or PSA counts), but they may not address the cause of the problem, creating perpetual drug dependency.

For example, it was shown decades ago by France’s Dr. Serge Renaud that red wine addresses a primary cause of mortal heart attacks, which is inability of blood vessels to dilate (widen) with physical or emotional exertion.[xiv]

Dr. Renaud noted that the wine-drinking French paradoxically consumed meals with more fat and cholesterol and had higher circulating levels of cholesterol but had a far lower rate of mortality from coronary artery disease (90 per 100,000 in the early 1990s) than North Americans (240 per 100,000).

The inability of blood vessels to dilate is also a primary cause of hypertension. But treatment of high blood pressure has gravitated into being a statin, diuretic, beta blocker, ACE inhibitor drug deficiency, none of which singularly control blood pressure. What little effect these drugs have upon high blood pressure may simply be from their ability to produce a transient intra-arterial gas called nitric oxide that dilates blood vessels.[xv] Nitric oxide is activated by a number of natural molecules, and its precursor in nature is L-arginine, an amino acid.[xvi]

The problem with so many of these markers of disease like cholesterol and PSA counts is that they are not associated with mortality rates. They are bogus measures used to induce disease mongering.

So what does the natural products industry do? It follows the misdirection of conventional medicine and says it too has an array of natural molecules that control cholesterol (red yeast rice, niacin, garlic, plant sterols).

Fear sells, not health promotion

Conventional medicine preys upon fears to sell its products and services. The fear of what will happen if a person stops taking their prescription drugs. The fear they may die of the same malady that killed their forefathers. Or the fearful demand something must be done if cancer is diagnosed despite there being no cure. Fear drives consumers to stick with so-called FDA-approved drugs, and insurance coverage reduces price resistance. In contrast, safer and often more effective nutraceuticals are not FDA approved and are not covered by insurance.

The natural products industry is limited by government mandate to produce and market products that “support healthy…” body structures (examples: bone, heart, liver, etc.) or functions (examples: blood pressure, cholesterol, etc.). Health promotion doesn’t prey upon fear. Prevention is not a big seller.

Even though dietary supplements do in fact help “diagnose, prevent or treat disease,” no such claims can be made without adequate scientific substantiation, and even then, the product will, for regulatory purposes, become a drug at that point.

Of course, it’s absurd that consumers cannot learn on a product label that vitamin C prevents and treats scurvy and its accompanying symptoms – anemia, weak capillaries and resultant swelling as blood serum leaks into surrounding tissues, hemorrhages, bleeding gums, irritability, celiac, gallstones, hemorrhoids, sluggish immune response, vein varicosity, poor bile flow and accompanying cholesterol buildup, poor wound healing and a mortal form of arterial plaque.

Any brand of vitamin C would have to conduct human trials to make any of the above claims, and then it would ludicrously become an over-priced drug as Lovaza pharma brand fish oil concentrate did to treat high triglycerides.[xvii] Fish oil concentrates provide a similar amount of fish oil at far less cost.[xviii]

The natural products industry is seemingly complacent in accepting this untenable requirement.

Highest and best use

So to ask the question again, what would be a primary objective for the natural products industry? The singular purpose of the industry is to produce a healthier population. Drugs don’t do that. The industry should insist it no longer be a stepchild of the drug industry.

“We are not fighting for our rightful position,” says Stouder. “In reality, Mother Nature will always trump Big Pharma.”

What natural products advocates need to be fighting for is a free market, not the rigged market that exists today.

The highest and best application of natural products today would be to demonstrate how natural products can be used to reduce healthcare costs (not just by billions but trillions of dollars) at a critical point in time when healthcare funding is in a state of collapse.

The Affordable Care Act only ensures doctors, hospitals and pharmaceutical companies get paid, and it enrolls more people in the ranks of the insured. Why can’t we give natural products an even footing with Rx drugs, so they can both compete in the open market on a level playing field?

The FDA should evaluate safety and accuracy of label claims and the Federal Trade Commission accuracy of advertising claims. Effectiveness would be judged by consumers themselves.

What becomes obvious here is that the whole process of gaining FDA drug approval has gravitated into an anticompetitive effort to protect pharmaceutical industry profits rather than ensure the public is using safe and effective remedies.

Running the FDA gauntlet

FDA regulations pose another barrier for natural products. Recently the company I manage attempted to run the FDA gauntlet to see if a resveratrol-based nutraceutical could be utilized to treat a particular eye disease on a waiver basis. The situation involved hopeless senior adults facing a devastating form of legal blindness called wet macular degeneration. In this disease abnormal blood vessels invade the visual center of the eye (the macula) and destroy it. The disease is caused by lack of oxygen in the retina that signals new blood vessels to form.

Injectable drugs are effective at quelling these abnormal blood vessels about 85 percent of the time. But about 15,000 senior Americans annually don’t respond to treatment and progress to irreversible registered blindness.

Dr. Stuart Richer OD, PhD, utilized a nutraceutical I formulated (Longevinex) and demonstrated it caused abnormal blood vessels at the back of the eyes to recede when injectable drugs did not work.[xix] (It was doing what shark cartilage pretended to do.)

We then proceeded to petition the FDA to allow us to proceed with human studies with real-time reporting to the FDA of any side reactions, knowing any delay would result in thousands more patients joining the ranks of the near-blind.[xx]

Upon hearing this, a regulatory affairs officer of a natural products industry group fired back and said one cannot skirt around the FDA regulations. A new drug application (NDA) must be filed. However, financial justification for an NDA would not be warranted given the market was only 15,000 patients. A human clinical trial would take around 2 years and cost an estimated $4-5 million. And an NDA would not be timely. During that time another 30,000 would go blind.

Attempt to break a monopoly

What the industry failed to see is that we were trying to break the stranglehold the FDA has over nutraceuticals. There was little risk for patients as the nutraceutical had been in common use for nearly a decade without report of serious side effects, and toxicity tests had even been completed,[xxi] a requirement for drugs.

In effect what the industry was saying is: “Let them go blind. Natural products aren’t drugs. Our products are solely confined to promoting health.” The natural products industry was retreating into its closet once again.

Unfortunately, we couldn’t gain industry or public support to apply pressure to the FDA, and the petition was predictably rejected by the FDA. Someday the stranglehold the FDA has over nutraceuticals must be broken.

If you are still standing on the fence and remain reticent to take action after reading my outspoken opinion, would you take action if your job was threatened?

The FDA is out to destroy the natural products industry and turn functional foods and nutraceuticals into drugs.[xxii] It has been attempting to do this since the 1970s.[xxiii]

Only for the popularity of dietary supplements has the FDA relented because of political reasons. The natural products industry has its head in the guillotine and it’s about to be chopped off.

If the industry can’t develop enough gumption to stand up to a government-backed monopoly that is not in service of the public, would the industry at least stand up and fight for its very livelihood?

It’s time to stand up and fight for a free market where natural products are given a fair opportunity to inform consumers about their attributes.

Natural products trump card

The natural products industry holds a trump card that nature has provided. The human body has an epigenetic switch that is triggered when biological stress occurs, such as lack of oxygen, food and exposure to mild radiation.[xxiv]   The biological trump card is called the Nrf2 transcription factor.[xxv] (Transcription factors are proteins that switch various downstream genes on or off via their ability to bind to DNA.)

Nature provides molecules that mimic biological stress and activate Nrf2, which in turn activates internal antioxidant enzymes catalase, glutathione, heme oxygenase and superoxide dismutase.

This is now arguably recognized as the most powerful health force in the human body.[xxvi] A growing body of evidence indicates Nrf2 activation results in unparalleled health and longevity. The effect is dose dependent, and too much negates, even worsens, the effect.

Small natural molecules activte Nrf2 – polyphenols[xxvii] and bioflavonoids, provided in the rind of citrus, the skin of fruit and berries, seeds of pomegranate,[xxviii] skin and seed of grapes and more so in wine, as well as in spices such as garlic[xxix] and turmeric, and herbs such as angelica, bacopa[xxx], danshen, Ginkgo biloba[xxxi], ginseng[xxxii], and cruciferous vegetables such as broccoli, seaweed[xxxiii], Lingzhi mushroom[xxxiv], among others.

These molecules are resveratrol[xxxv], quercetin, curcumin[xxxvi], magnesium lithospermate (danshen),[xxxvii] decursin (angelica),[xxxviii] sulforaphane,[xxxix] and allicin[xl] and hydrogen sulfide gas[xli] from fresh-crushed garlic.

So far, the natural products industry has all the molecules to activate Nrf2. The pharmaceutical industry has none.

The pharmaceutical industry has taken note and has expressed interest in developing Nrf2-activating drugs.[xlii] Pharmaceutical researchers will be attempting to create look-alike molecules called synthetic analogs to cash in on this biological pathway. Some of these attempts have been almost laughable, as resveratrol analogs after liver metabolism revert these “drugs” back to plain resveratrol.[xliii] (Nature is so kind.) Recognize, analogs will be excessively priced and may not work in a superior manner to natural un-patentable molecules.

The anti-aging pill trap

The natural products industry is advised to not fall into the anti-aging pill trap. A Pew Research study reveals most consumers would pass on this idea.[xliv] The promise of living longer by taking various natural elixirs does not generally resonate with the public. Not only because there have been so many snake-oil salesmen in the anti-aging arena in the past, but also because generally people fear living longer, running out of retirement money and spending more years in a wheelchair in a debilitated state. Consumers want a “fountain of youth,” not longevity. They want to look in the mirror and appear youthful again.

Look at how much money consumers spend to look younger (cosmetics, hair dyes, wigs, contact lenses, plastic surgery) versus so-called anti-aging pills that promise a 120-year lifespan. Most consumers are driven to look younger than live longer. Someone once said to me: “What the public wants is thick hair, smooth skin and Viagra, baby!”

Of course the natural products industry can deliver on those consumer desires, too (hyaluronic acid for thicker hair, carotenoids[xlv] like lutein, lycopene[xlvi] and beta carotene[xlvii] as well as hyaluronic acid[xlviii] for skin wrinkles, and red ginseng[xlix] for Viagra-like effects), but due to lack of published studies, such claims cannot be presently made for any particular brand.

Don't rock the boat?

There are those within the natural products industry who want it to stay in its designated place, to not rock the boat, certainly not when industry growth is bullish. The pharmaceutical industry is an $880 billion monopoly[l] with sales expected to exceed $1.2 trillion by 2016.[li] The natural products industry is a $91 billion pipsqueak (all distribution channels; $37 billion through natural and independent distribution channels[lii]; $32 billion of that in the vitamin, mineral and supplements sector, according to Forbes online[liii]) that only meekly meets the nation’s challenge to stay healthy.

Sadly, it is not the needless loss of life or avoidable human suffering that will finally break the stranglehold the pharmaceutical/government cabal has held over the American people, but rather financial default on their obligations to provide health care.

Patents on blockbuster prescription drugs are expiring. Newer drugs aren’t working as well as older drugs. Pharmaceutical companies are beginning to acquire nutraceutical food and supplement companies, but maybe only to create those previously mentioned analogs. (That is what has happened to resveratrol.[liv]) Or to simply shelve unique natural products altogether (also happened to resveratrol[lv]).

The natural products industry is on an unavoidable collision course with conventional medicine whether it likes it or not. How can the natural products industry in good conscience stand on the sidelines and allow needless deaths and misery to continue when it holds the keys to health?

Bill Sardi is a consumer advocate in San Dimas, California, and president of Resveratrol Partners LLC, manufacturer of Longevinex brand supplements.

References

[i] Ongphiphadhanakul B, Piaseu N, Tung SS, et al, Prevention of postmenopausal bone loss by low and conventional doses of calcitriol or conjugated equine estrogen.Maturitas, 2000 Feb 15; 34(2):179-84.

[ii] Carey J, Do cholesterol drugs do any good? Business Week, Jan 16, 2008 at BloombergBusinessweek.com

[iii] Wannamethee SG, Bruckdorfer KR, Shaper AG, Plasma vitamin C, but not vitamin E, is associated with reduced risk of heart failure in older men. Circulation Heart Failure2013 Jul; 6(4):647-54.

[iv] Kolata G, Doubt Cast on the ‘Good’ in ‘Good Cholesterol’, New York Times, May 16, 2012.

[v]National Library of Medicine, Pubmed.gov, searched Sept. 29, 2013

[vi]Dr. Charles Simone on 60 Minutes with Mike Wallace, CBS-TV, YouTubeposted April 26, 2012.

[vii]Finkelstein JB, Sharks Do Get Cancer: Few Surprises in Cartilage Research, J. Natl Cancer Institute, 2005 Nov: 97(21); 1562-63.

[viii] Industry Coalition Advises Against Use of Dietary Supplements
as Swine Flu Remedy, Cure, Council For Responsible Nutrition, May 1, 2009.

[ix]Nahas R, Balla A, Complementary and alternative medicine for prevention and treatment of the common cold. Can Family Physician2011 Jan; 57(1):31-6

[x]Nantz MP, Rowe CA, Muller CE, et al, Supplementation with aged garlic extract improves both NK and γδ-T cell function and reduces the severity of cold and flu symptoms: a randomized, double-blind, placebo-controlled nutrition intervention. Clinical Nut2012 Jun;31(3):337-44.

[xi]Eby GA, Zinc lozenges as cure for the common cold--a review and hypothesis. Medical Hypotheses2010 Mar; 74(3):482-92

[xii]Cannell JJ, Hollis BW, Use of vitamin D in clinical practice. Alt Med Rev2008 March; 13(1): 6-20

[xiii] Cannell JJ, Zasloff M, Garland CF, et al, On the epidemiology of influenza, Virology JournalFeb 25; 5:29.

[xiv] Renaud S, de Lorgeril M, Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet June 20; 339 (8808) 1423-26.

[xv] Desouza CV, Does drug therapy reverse endothelial progenitor cell dysfunction in diabetes? Journal Diabetes Complications2013 Sep-Oct; 27(5):519-25.

[xvi] Yetik-Anacak G, Catravas JD, Nitric oxide and the endothelium: history and impact on cardiovascular disease. Vascular Pharmacology2006 Nov; 45(5): 268-76.

[xvii] Lovaza Pricing & Ordering Comparisons, PharmacyChecker.com

[xviii] ConsumerLab.com Answers, ConsumerLab.com.

[xix] Richer S, Stiles W, Ulanski L, et al, Observation of human retinal remodeling in octogenarians with a resveratrol based nutritional supplement. Nutrients2013 June; 5(6): 1989-2005.

[xx] Petition to the US Food & Drug Administration, Resveratrol Partners LLC, Longevinex.com, 2013.

[xxi] Sangeetha MK, Eazhisai Vallabi D, Sali VK, Thanka J, Vasanthi HR,Sub-acute toxicity profile of a modified resveratrol supplement. Food Chem Toxicology2013 Sept; 59: 492-500.

[xxii] New dietary ingredients in dietary supplements- background for industry, Food & Drug Administration, August 28, 2013, online.

[xxiii] Harper AE, Nutritional regulations and legislation--past developments, future implications. J Am Dietetic Assn, 1977 Dec; 71(6): 601-09.

[xxiv]McDonald JT, Norris KK, Vlashi E, et al, Ionizing radiation activates the Nrf2 antioxidant response. Cancer Research2010 Nov 1; 70 (21): 8886-95.

[xxv] Magesh S, Chen Y, Hu L, Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents. Medicinal Research Reviews2012 Jul; 32(4):687-726.

[xxvi]Lewis KN, Mele J, Hayes JD, Buffenstein R, Nrf2, a guardian of healthspan and gatekeeper of species longevity. Integrative Comp Biology2010 Nov; 50 (5): 829-43

[xxvii]Bhullar KS, Rupasinghe HP, Polyphenols: multipotent therapeutic agents in neurodegenerative diseases. Oxidative Med Cell Longevity2013 June; 2013: 891748.

[xxviii]Bishayee A, Bhatia D, Thoppil RJ, et al, Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms. Carcinogenesis2011 June; 32(6): 888-96.

[xxix]Ho CY, Cheng YT, Chau CF, Yen GC, Effect of diallyl sulfide on in vitro and in vivo Nrf2-mediated pulmonic antioxidant enzyme expression via activation ERK/p38 signaling pathway. J Agric Food Chem2012 Jan 11: 60 (1): 100-7.

[xxx]Prisila DC, Singh HK, Preethi J, Rajan KE, Standardized extract of Bacopa monniera (BESEB CDRI-08) attenuates contextual associative learning deficits in the aging rat's brain induced by D-galactose. J Neurosci Res2012 Oct; 90(10): 2053-64.

[xxxi]Chen JS, Huang PH, Wang CH, et al, Nrf-2 mediated heme oxygenase-1 expression, an antioxidant-independent mechanism, contributes to anti-atherogenesis and vascular protective effects of Ginkgo biloba extract. Atherosclerosis2011 Feb; 214(2): 301-9.

[xxxii]Li J, Ichikawa T, Jin Y, et al, An essential role of Nrf2 in American ginseng-mediated anti-oxidative actions in cardiomyocytes. J Ethnopharmacology2010 July; 130(2): 222-30.

[xxxiii]Wang R, Paul VJ, Luesch H, Seaweed extracts and unsaturated fatty acid constituents from the green alga Ulva lactuca as activators of the cytoprotective Nrf2-ARE pathway. Free Radical Biology Med2013 Apr; 57: 141-53.

[xxxiv]Li B, Lee DS, Kang Y, et al, Protective effect of ganodermanondiol isolated from the Lingzhi mushroom against tert-butyl hydroperoxide-induced hepatotoxicity through Nrf2-mediated antioxidant enzymes. Food Chem Toxicology2013 March; 53: 317-24.

[xxxv]Kumar A, Singh CK, Lavoie HA, et al, Resveratrol restores Nrf2 level and prevents ethanol-induced toxic effects in the cerebellum of a rodent model of fetal alcohol spectrum disorders. Molecular Pharmacology2011 Sept; 80(3):446-57.

[xxxvi]He HJ, Wang GY, Gao Y, et al, Curcuminattenuates Nrf2 signaling defect, oxidative stress in muscle and glucose intolerance in high fat diet-fed mice. World J DiabetesMay 15; 3(5):94-104.

[xxxvii]Hur KY, Kim SH, Choi MA, et al, Protective effects of magnesium lithospermate B against diabetic atherosclerosis via Nrf2-ARE-NQO1 transcriptional pathway. Atherosclerosis 2010 July; 211 (1): 69-76.

[xxxviii]Decursin Isolated from Angelica gigas Nakai Rescues PC12 Cells from Amyloid β-Protein-Induced Neurotoxicity through Nrf2-Mediated Upregulation of Heme Oxygenase-1: Potential Roles of MAPK. Li L, Du JK, Zou LY, et al, Evidence Based Complement Alternat Med2013 May; 2013-467245.

[xxxix]Tarozzi A, Angeloni C, Malaguti M, et al, Sulforaphane as a Potential Protective Phytochemical against Neurodegenerative Diseases. Oxidative Molecular Cell Longevity2013 July; 2013-415078

[xl]Li XH, Li CY, Xiang ZG, et al, Allicin ameliorates cardiac hypertrophy and fibrosis through enhancing of Nrf2 antioxidant signaling pathways. Cardiovascular Drugs Therapy2012 Dec; 26(6): 457-65.

[xli]Das DK, Hydrogen sulfide preconditioning by garlic when it starts to smell. Am J Physiology Heart Circul Physiol2007 Nov; 293(5): H2629-30.

[xlii]Baer-Dubowska W, Cancer chemopreventive agents-drugs for the 21st century? Acta Pol Pharm2006 Sep-Oct; 63(5):369-73

[xliii] Mattarei A, Azzolini M, Carraro M, et al, Acetal Derivatives as Prodrugs of Resveratrol. Molecular PharmacologyJune 17, 2013.

[xliv] Neergaard L, Live to 120? Most say no thanks, ABC News(Associated Press), August 6, 2013.

[xlv]Palombo P, Fabrizi G, Ruocco V, et al, Beneficial long-term effects of combined oral/topical antioxidant treatment with the carotenoids lutein and zeaxanthin on human skin: a double-blind, placebo-controlled study. Skin Pharmacology Physiology2007 April; 20(4): 199-210.

[xlvi]Darvin M, Patzelt A, Gehse S, et al, Cutaneous concentration of lycopene correlates significantly with the roughness of the skin. Euro J Pharm Biopharm2008 Aug; 69(3): 943-47.

[xlvii]Cho S, Lee DH, Won CH, et al, Differential effects of low-dose and high-dose beta-carotene supplementation on the signs of photoaging and type I procollagen gene expression in human skin in vivo. Dermatology2010 June; 221(2): 160-71.

[xlviii]Ascher B, Fanchon C, Kanoun-Copy L, A skincare containing retinol adenosine and hyaluronic acid optimizes the benefits from a type A botulinum toxin injection. J Cosmet Laser Therapy2012 Oct; 14(5):234-38.

[xlix]Price A, Gazewood J, Korean red ginseng effective for treatment of erectile dysfunction. J Family PracticeJan. 2003, 52(1): 20-1.

[l]Alazraki M, Global Pharmaceutical Sales Expected to Rise to $880 Billion in 2011, Daily Financeonline, Oct 7, 2010

[li]Research and Markets: The Global Pharmaceutical Industry Is Expected To Reach $1,241 Billion By 2016, Growing At A CAGR Of 5.7%. Yahoo Finance Research & Markets, May 3, 2013.

[lii]NFM Market Overview 2012: Natural stays on perennial path to growth, Natural Foods Merchandiser, May 29, 2012.  

[liii]Lariviere D, Nutritional Supplements Flexing Muscles As Growth Industry, Forbes.com, April 18, 2013.

[liv] Pezzuto J, Kondratyuk TP, Ogas T, Resveratrolderivatives: a patent review (2009 - 2012). Expert Opinion Therapy Therapeutic Patents, 2013, Sept. 16 online.

[lv] Timmerman L, GlaxoSmithKline Shuts Down Sirtris, Five Years After $720M Buyout, Xconomy.com, March 13, 2013.