At the last medical conference I gave a speech at, I asked an informal poll of the audience: “How many of you, with a show of hands, takes a vitamin/mineral or other supplement?” The results were surprising. Well over 90% of the audience raised their hands, simultaneous with a wry smile as though they were catching themselves doing something that they would advise against.

The supplement industry in the U.S. is estimated at $35 billion last year, according to Statista, and is expected to reach $278 billion worldwide by 2024 based on data from Grand View Research, Inc. This worldwide growth also includes the medical foods market. Recently, Nestlé announced groundbreaking strategies to approach fortified medical foods—a market estimated at $15 billion—banking on the segment to the tune of $500 million, which is the budget to 2021 at Nestlé’s Institute of Health Science (NIHS) in Lausanne, Switzerland.

The nutraceutical and medical foods industries are in an interesting place at the moment. Dietary supplements represent a market that has defied all analysts’ expectations and has grown even when competitor markets have shrunk. The interesting thing about these markets is that they represent a forward-looking advancement philosophy to the foods and nutrients we eat (‘improving on nature’), which is in stark contrast to the majority of popular media about foods—the messages which espouse whole foods, unprocessed foods, raw foods, and organic or non-GMO foods. So the public has a bit of an identity crisis within itself. Do people want raw, organic, unprocessed foods in all practical cases? Or do we want to put our faith in nutraceutical supplements to give us high-dose specific micronutrients that we may be lacking?

The real science
Of course, I’ll give you the real science, which suggests in-aggregate that nutraceuticals aren’t very effective for people. For example, curcumin, which has been touted for everything from treatment for Alzheimer’s disease to bone loss to baldness has recently shown to be less-effective than previously thought. Perhaps it’s due to assay confounding. The authors of this research on curcumin chemistry noted, “Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful.”³

Let’s look at the multivitamin/mineral market. It is estimated to be worth about $12 billion annually, and about 53% of American adults (>70% of those 65 and older) take these supplements. Similarly, Larry Appel, director of the Johns Hopkins Welch Center for Prevention, Epidemiology, and Clinical Research noted that, “Pills are not a shortcut to better health and the prevention of chronic diseases.” Appel was co-author of an article² in the Annals of Internal Medicine (2013), which looked at various studies of vitamin/mineral supplements. Here’s some of what the researchers found:

• An analysis of several research papers involving 450,000 people found that multivitamins did not reduce risk for heart disease or cancer;
• A study that tracked the multivitamin use of 5,947 men for 12 years found that multivitamins/minerals did not improve overall cognitive performance or verbal memory; and
• A study of 1,708 heart attack survivors who took a high-dose multivitamin or placebo were followed for up to 55 months. Rates of later heart attacks, heart surgeries and deaths were similar in the two groups. The authors noted, “After a median follow-up of 4.6 years, there was no significant difference in recurrent cardiovascular events with multivitamins compared with placebo—hazard ratio, 0.89 (95% CI, 0.75 to 1.07).”

They also reported that, “Evidence involving tens of thousands of people randomly assigned in many clinical trials shows that β-carotene, vitamin E, and possibly high doses of vitamin A supplements increase mortality, and that other antioxidants, folic acid and B vitamins, and multivitamin supplements have no clear benefit.” It should be noted that the exception is folic acid for women of child bearing potential, where it has been shown to prevent neural tube defects in babies when women take it before and during early pregnancy. Ergo, Guallar and his colleagues showed that there was no specific reason to take multivitamins, and that they didn’t confer any health benefits to those who took them. In fact, researchers found certain cancers more often in people who were taking vitamins, though I’ll leave that as a simple correlation and not draw any causality links to it here.

Counterpoint
However, most nutritional supplements, nutraceuticals, and medical foods are measured by a very crude yardstick. There often aren’t mechanistic biological studies of nutraceuticals and what they’re doing at a cellular and molecular level to elicit biological and physiological effects, but instead they are measured by extraordinarily low resolution clinical measures such as, “did _____(symptom) resolve?” Unfortunately, like any other clinical measure, there are innumerable factors in whether a patient’s headache or rash or other issue has abated, and these ‘other’ factors can, and often do, totally overwhelm the ability to detect effects from the supplements. It could have been their sleep status the night before the clinical appointment, whether or not they had breakfast or lunch, personal stress, etc.

We know that many real effective drugs on the market are derived from natural plant sources. There’s no equivocation that molecules within plants and foods do have medical effects. But that’s also a long way from saying, “All foods have compounds with nutraceutical properties.” Said in another way, just because some powerful drugs, such as aspirin and digoxin, are derived from plants doesn’t mean that there are miraculous and effective compounds in all plant sources. To look for medically active compounds, it requires a bit of smarts, and empirical study above all else.

As far as the clinical data referenced, remember, while we get strong directional evidence from large clinical trials and well conducted scientific studies, they don’t tell us what a specific individual will experience from a particular intervention. For certain nutrient deficiencies, which are very real, and in particular individuals, there can be unequivocally real effects from nutraceutical and medical food supplementation. As even Guallar and his co-authors from the Annals of Internal Medicine article observe, “Available evidence does not rule out small benefits or harms or large benefits or harms in a small subgroup of the population [from vitamin and mineral supplements].” After all, this team is the first to admit, “Clinical trials are not well-suited to identify very small effects.” This is especially the case in multiple smaller studies meta-analytically reviewed together. In fact, John Michael Gaziano, a researcher at Brigham and Women’s Hospital and the VA Boston Healthcare System and co-author of one of the studies referenced by the Annals piece said frustratingly, “It drives me crazy that they [Guallar and colleagues] say ‘enough is enough,’ [about studying vitamins and minerals] when there’s only been one large study of (standard) multivitamins and it’s ours.”

Science is about reproducibility. Evidence trumps opinion and hope. And as the Nobel laureate Richard Feynman noted, “It doesn’t matter how beautiful your theory is, it doesn’t matter how smart you are. If it doesn’t agree with experiment, it’s wrong.” The more we continue to research supplements, nutraceuticals, and medical foods, the more we’ll know about their benefits. 

References

1. Dar W.R., Najeebullah, S., Dar, I., Sofi, P., & Changal, K.H. (2016). Moving beyond conventional heart failure treatment – Does micronutrient supplementation have a role? Journal of Nutraceuticals and Food Science, 1(1).
2. Guallar, E., Stranges, S., Mulrow, C., Appel, L.J., Miller, E.R. (2013). Enough is enough: Stop wasting money on vitamin and mineral supplements. Annals of Internal Medicine.
3. Nelson, K.M., Dahlin, J.L., Bisson, J., Graham, J. Pauli, G.F., & Walters, M.A. (2017). The essential medicinal chemistry of curcumin. Journal of Medicinal Chemistry.

---

Ben Locwin

Ben Locwin, PhD, MBA, MS heads a healthcare consultancy, advises on clinical practice, and frequently speaks on nutraceutical, nutritional, and food-based research. He was formerly a steering committee member for the American Association of Pharmaceutical Scientists’ (AAPS) Nutraceuticals and Natural Products focus group, and works on making connections in the best practices of health, medical care, science, behavior, and patient-centricity to improve the healthcare industry.