Even with growing sales and many successes, the natural products industry has generally fallen short of achieving goals of prolonging the human health span while realizing envious profitability. There are many reasons for this industry shortfall. Misdirection, overlooked discoveries, failure to understand the opportunity posed by nutrigenomics, and the need to focus on nutrient delivery systems come to mind.
Misdirection: time for a natural medicine about-face
Modern medicine is the envy of those who are deprived of its availability. Despite avid interest and adoption of natural remedies and food supplements into the daily regimen of many Americans, increased health-care costs are largely driven by introduction of high tech.1 In fact, most Americans believe their health insurance companies deny access to many advanced, albeit costly, therapies. The demand for the most modern diagnostics and treatments is ravenous.
So it comes as no surprise that the natural products industry often seeks to emulate conventional medicine, despite its misdirection. After all, the public is clamoring for ways to live healthier, such as controlling cholesterol and maintaining bone strength with advancing age.
Take the case of cardiovascular health. Alternative medicine is quick to say it has natural versions of statin molecules that inhibit liver synthesis of cholesterol, or that drive circulating cholesterol numbers down,2 and it certainly participates alongside conventional medicine in the provision of supplemental calcium for menopausal bone loss. Yet upon review, following in the footsteps of conventional medicine does not stand up to scrutiny. The most telling fact is that a review of the major clinical trials of statin cholesterol-lowering drugs does not show evidence for a reduction in coronary heart disease mortality. Circulating cholesterol numbers drop, but the death rate for coronary heart disease is unaffected with the use of these drugs.3
Barking up the wrong tree
But is allopathic medicine (and by extension, the natural products industry) aiming at the wrong target? It appears that cholesterol is not the major cause of sudden mortal heart attacks, calcium is.4 If the coronary calcium score is zero, the risk for a mortal heart attack is near zero. About 50 percent of arterial plaque is comprised of calcium, only 3 percent of cholesterol. Population studies bear this out – countries that consume the most calcium-rich dairy products (Scandinavia, Ireland, New Zealand and North America) have the highest rates of coronary artery disease.5
There is also a follow-on connection between arterial disease and age-related bone loss. As middle-aged women enter menopause and begin to lose calcium from bone, there is a 360 percent increased risk for sudden mortal heart attack. The lost calcium is being deposited in arteries and is stiffening them. In fact, a human clinical trial in New Zealand found menopausal women faced a 45 percent increased risk for coronary heart disease mortality with the use of calcium supplements!6
Consumption of supplemental calcium for menopausal women is like pouring calcium into a barrel with a hole in the bottom. It would be better to restore the estrogen signal to hold calcium in bones, employing phytoestrogens like flaxseed lignans and red wine resveratrol, than to supplement with calcium.7 Encouragingly, natural medicine offers many anti-calcifying agents – magnesium (natural calcium blocker), vitamin D,8 vitamin K,9 and rice bran-derived phytate (IP6), which dissolves calcifications.5
The above evidence requires a re-think among those who design and formulate foods and supplements.
Re-direction: Darwinian evolution or epigenetics?
With the cataloging of the human genome almost a decade ago, and the surprising discovery that humans have only ~25,000 genes (far less than some less advanced forms of life), coupled with the realization that maybe 12,000 of these genes are defunct or duplicate genes, it is foreseeable that technologies can be developed that would beneficially influence genetic mechanisms in health, aging and disease.
There is much talk about individualized gene testing for the masses, but this would not only be unaffordable, but would also address only rare genetic disorders. Individualized testing for genetic mutations does not need to be done for mutations that are widespread.
For example, all humans lost their ability to naturally synthesize vitamin C in their liver many generations ago. Most animals have not suffered this same fate. Due to this genetic flaw, humans must therefore solely rely upon the diet or supplements for vitamin C.10 Furthermore, Asians produce less haptoglobin, a protein that mops up loose iron, and therefore experience greater degradation of vitamin C, suggesting Asian populations need to further fortify their diets with this vitamin.11
Another example is dark-skinned populations that require about 10 times more solar radiation to produce the same amount of natural vitamin D in their skin as Caucasians. Supplementation is, once again, suggested here,to overcome a genetic characteristic (greater melanin in the skin).12
We may fail to realize the full potential to put nutrigenomics into daily practice because Darwinian biology, which is fast losing credence, distracts from the viable opportunity to influence the human genome via epigenetics, which refers to the “on” and “off” switching of genes.
The big news is that our genes are not locked – they can be altered. We are not doomed to a predetermined genetic destiny.13 This was recently demonstrated in an experiment conducted at Duke University where a golden-coated female rodent that was bred to overeat was mated with a brown-coated male that does not overeat, and given folic acid and vitamin B12 during conception and development of offspring in the womb. The animal’s litter began to produce progeny that ate normally and were brown coated. This is an example of genetic imprinting via epigenetics.14
Environmental or external factors, such as solar radiation, temperature, food or lack of food can signal a gene to make proteins (known as gene expression) or not make proteins (gene silencing). It is now realized that small molecules that can pass through cell walls are also able to influence genetic machinery.15 In this regard, a class of small molecules found in nature called polyphenols are gaining attention from biologists. Polyphenols are found in grapes (resveratrol, quercetin, ferulic acid, catechin, proanthocyanidins), olives (hydroxytyrosol), pomegranates (ellagic acid), and green tea (EGCG).
The potential for epigenetics to promote health and slow and even reverse aging and its concomitant diseases is just now gaining attention and creates a formidable opportunity for the natural products industry.16
Better direction: nutrient delivery systems
There is not a person in the natural products industry who hasn’t been confronted with a news broadcast about some negative study involving a natural product. Those who embrace natural remedies and healthy foods are taken aback at the suggestion that, for example, high-dose vitamin E could in any way be as harmful as some studies suggest.
But on second look, there may be reasons why dietary supplements don’t work in controlled studies. Insufficient dosage, inappropriate selection of subjects, lack of demonstrated cause and effect, and skewed statistics (science has a way of juxtaposing data so that the difference between 0.5 percent and 1 percent is a 50 percent increased risk) often explain away many null or negative studies involving nutraceuticals.
But to lay those obvious false arguments against nutraceuticals aside, there are other more common reasons why nutraceuticals don’t work – namely poor absorption, abnormal storage and impaired bioavailability.
For example, only about 4 percent of magnesium oxide is absorbed, yet it is the most economical and commonly sold form of this mineral supplement. In the oxide form it is almost useless.17 It is a wonder why it is even offered for sale.
A common reason for poor gastric absorption of nutrients is lack of stomach acid, particularly among senior adults.18 A revealing study conducted many years ago showed that older adults who took supplemental B vitamins often remained in a deficient state due to malabsorption from impaired secretion of stomach acid.19 Minerals like calcium and magnesium are also dependent upon stomach acid for absorption.20
An often errant advertising claim for some branded nutraceuticals is that they are absorbed faster. But there is no race to absorb nutrients faster. In fact, the slower the absorption the greater the amount that enters the blood circulation. This can be accomplished in many ways, such as adding bioflavonoids to vitamin C to slow transit time.21 Or by slow-release mechanisms in liposomes or micro-encapsulates.
A tremendous problem with fat-soluble nutrients that is just now being realized is that they tend to be stored in fat (adipose). Fat-soluble vitamins A,D,E and K and the carotenoids (beta-carotene, lutein, lycopene) may end up being stored in fatty tissue rather than reaching target tissues in the brain, eyes and internal organs.22 Impaired bile flow may also inhibit nutrient availability. This has been demonstrated for vitamin D.23
Once absorbed in the blood circulation, the liver has an array of detoxification systems that stand in the way of many nutrients achieving what is called bioavailability. Bioavailability can be enhanced by employing natural molecules, such as those found in grapefruit (quercetin), that inhibit detox liver enzymes and which in turn makes other companion nutrients more bioavailable.24
The bottom line is there may be good reason why nutraceuticals sometimes don’t work. Better design and formulation of nutraceutical molecules and delivery systems may produce natural products that are truly beneficial.
Bill Sardi is a health journalist, author of more than a dozen health and nutrition books and formulator and spokesperson for dietary-supplements companies. His latest book is titled Downsizing Your Body (Bill Sardi, 2009).
1. Lubitz J. Health, technology, and medical care spending. Health Aff (Millwood). 2005;24 Suppl 2:W5R81-5. PMID: 16186154
2. McGowan MP, Proulx S, Nutritional supplements and serum lipids: does anything work? Curr Atheroscler Rep. 2009 Nov;11(6):470-6. PMID: 19852889
3. Abramson J, Wright JM, Are lipid-lowering guidelines evidence-based? Lancet. 2007 Jan 20;369(9557):168-9. PMID: 17240267
4. Blaha M, Budoff MJ, Shaw LJ, et al. Absence of coronary artery calcification and all-cause mortality. JACC Cardiovasc Imaging. 2009 Jun;2(6):692-700. PMID: 19520338
5. Seely S, Is calcium excess in western diet a major cause of arterial disease? Int J Cardiol. 1991 Nov;33(2):191-8. PMID: 1743778
6. Bolland MJ, Barber PA, Doughty RN, et al, Vascular events in healthy older women receiving calcium supplementation: randomized controlled trial. BMJ. 2008 Feb 2;336(7638):262-6. Epub 2008 Jan 15. PMID: 18198394
7. Li X, Phillips FM, An HS, et al, The action of resveratrol, a phytoestrogen found in grapes, on the intervertebral disc. Spine (Phila Pa 1976). 2008 Nov 15;33(24):2586-95. PMID: 19011540
8. Zitterman A, Schleithoff SS, Koerfer R, Vitamin D and vascular calcification, Curr Opin Lipidol. 2007 Feb;18(1):41-6. PMID: 17218831
9. Shea MK, O’Donnell CJ, Hoffman U, et al, Vitamin K supplementation and progression of coronary artery calcium in older men and women, Am J Clin Nutr. 2009 Jun;89(6):1799-807. PMID: 19386744
10. Addison WN, McKee MD, Inositol hexakisphosphate inhibits mineralization of MC3T3-E1 osteoblast cultures. Bone. 2010 Apr;46(4):1100-7. PMID: 20079473
11. Stone I, Homo sapiens ascorbicus, a biochemically corrected robust human mutant. Med Hypotheses. 1979 Jun;5(6):711-21. PMID: 491997
12. Delanghe JR, Langlois MR, De Buyzere ML, Torck MA., Vitamin C deficiency and scurvy are not only a dietary problem but are codetermined by the haptoglobin polymorphism. Clin Chem. 2007 Aug;53(8):1397-400. PMID: 17644791
13. Weaver SP, Passmore C, Collins B, Fung E. Vitamin D, sunlight exposure, and bone density in elderly African American females of low socioeconomic status. <http://www.ncbi.nlm.nih.gov/pubmed/20063223> Fam Med. 2010 Jan;42(1):47-51.PMID: 20063223
14. Cloud J, Why Your DNA Isn't Your Destiny. Time Magazine Wednesday, Jan. 06, 2010.
15. Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL, Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect. 2006 Apr;114(4):567-72. PMID: 16581547
16. Mariappan D, Winkler J, Parthiban V, Dietary small molecules and large-scale gene expression studies: an experimental approach for understanding their beneficial effects on the development of malignant and non-malignant proliferative diseases. <http://www.ncbi.nlm.nih.gov/pubmed/16787199> Curr Med Chem. 2006;13(13):1481-9. Review.PMID: 16787199
17. Ingram DK, Anson RM, de Cabo R, Development of calorie restriction mimetics as a prolongevity strategy. <http://www.ncbi.nlm.nih.gov/pubmed/15247056> Ann N Y Acad Sci. 2004 Jun;1019:412-23. Review.PMID: 15247056
18. Firoz M, Graber M, Bioavailability of US commercial magnesium preparations. Magnes Res. 2001 Dec;14(4):257-62. PMID: 11794633
19. Schubert ML. Gastric Secretion, Curr Opin Gastroenterol. 2003 Nov;19(6):519-25. PMID: 15703599
20. Source: CRC Critical Review Food Science Nutrition 27: 189-218, 1988
21. Sipponen P, Härkönen M. Hypochlorhydric stomach: a risk condition for calcium malabsorption and osteoporosis? Scand J Gastroenterol. 2010;45(2):133-8. PMID: 19958055
22. Vinson JA, Bose P. Comparative bioavailability to humans of ascorbic acid alone or in a citrus extract. Am J Clin Nutr. 1988 Sep;48(3):601-4.PMID: 3414575
23. Yeum KJ, Ahn SH, Rupp de Paiva SA, Correlation between carotenoid concentrations in serum and normal breast adipose tissues of women with benign breast tumor or breast cancer. J Nutr. 1998 Nov;128(11):1920-6. PMID: 9808643
24. Schmidt DR, Holmstrom SR, Fon Tacer K, et al, Regulation of bile acid synthesis by fat-soluble vitamins A and D.