The misuse of intended use when interpreting dietary supplement research

Dietary supplements have become a mainstream part of self-care in the U.S.; however, people are confused about which supplements are right for them. There is no shortage of conflicting information about supplements and people are starving for credible advice. Even scientists find it difficult to evaluate the diverse opinions espoused by medical and scientific thought leaders. At the core of the confusion is the grey area between products “intended” to treat a disease, as compared to products “intended” to keep people healthy. The key nuance is the concept of “intended use.”

In certain sub-populations, the benefits of supplementation with essential nutrients are not up for debate. These include pregnancy, lactation, filling nutrient shortfalls, illnesses that result in nutritional malabsorption, drug-induced nutrient depletions, or when individuals choose a restricted diet. However, there is a healthy debate about the appropriate role of a vast array of dietary supplements that make claims to support health and prevent disease. One camp embraces the value of supplements and the other debunks the entire category as hocus pocus. There is a scientific dialogue that occurs among nutrition experts and health care providers, which spills unfiltered to the media, resulting in conflicting reports about the benefits of supplements.

A common oversight in scientific research and reporting on non-drug interventions is the appreciation of the product’s intended use. Supplements are intended to support health and wellness and, in a few cases, reduce the risk of disease. Supplements may often be integrated into disease management, but this is done under the care of a qualified provider who has evaluated the benefits and risks for the individual patient.

Even though supplements are intended to support health, it is common for them to be erroneously researched and expected to work as a replacement for drugs. When researched and compared with this false head-to-head expectation (often funded by the drug makers), supplements not surprisingly fail to show the same effects attributed to the drug comparator. And the research outcome—severely biased and handicapped from the initial research objective and design—often translates to juicy headlines that disparage supplements, or worse, yields a commentary in a high-impact medical journal that tosses the entire category under the bus. This unfortunate reality is despite numerous sources of evidence showing that doctors recognize most consumers are using supplements, and that many doctors are already directing their patients to use supplements as well.

The Journal of the American Medical Association (JAMA), one of the highest impact medical journals in the world, published an editorial that questions the value of multivitamins (MVMs) and dietary supplements, “Multivitamins and Supplements – Benign Prevention or Potentially Harmful Distraction?” (2022;327:2294-2295). While it is respectable for the authors to conclude the available scientific evidence is not adequate to make a public health recommendation that MVMs prevent cancer or heart disease, it is over-reach to discredit supplements broadly based on the meta-analysis of a single narrow scientific question looking only for disease treatment effects for products that do not make disease treatment claims.

Significant scientific challenges impact clinical studies done on nutrient interventions in chronic disease. A randomized controlled trial (RCT) is a model designed to evaluate the effects of drugs, not nutrients. Variables like a subject’s daily diet, nutrient status, absorption and nutrient metabolism (Am J Clin Nutr. 2006;84[3]:471-472) are just a few of the confounders that complicate results when studying nutrition. These significant differences are critical when designing, conducting and interpreting dietary supplement research.

When trusted medical journals question the value of the entire supplement category, they should take care not to unintentionally discourage people who take supplements prudently to stay healthy—like the millions of older Americans that follow the Dietary Guidelines for Americans and supplement with vitamin B12 to protect their cognitive function because science has demonstrated B12 absorption decreases with age.

A similar oversight of the importance of “intended use” was on display when a high-profile study compared the cholesterol-lowering effects of a prescription statin drug to six heart health non-nutrient dietary supplements, such as fish oil, cinnamon and garlic. The authors did a keynote presentation at the 2022 American Heart Association (AHA) scientific meeting while simultaneously releasing the manuscript in the Journal of the American College of Cardiology. There was also a press release blitzed to major media.

As a result, dozens of consumer articles parroted their message that a cholesterol medication (statin) lowered bad cholesterol in a clinically meaningful way in 28 days and dietary supplements did not. It is not surprising that a drug works faster and better than a supplement to treat cholesterol, but we need to remember dietary supplements are not meant to treat elevated cholesterol. Predictably, the media coverage focused on discrediting all supplements and skipped important context like:

- the fact that the American Heart Association (AHA) recommends supplements, like fish oil, for heart health (Arterioscler Thromb Vasc Biol. 2003;23:151-152);

- and the Journal of the American College of Cardiology previously published a more appropriately designed systematic review and meta-analysis of 884 randomized controlled trials that evaluated 27 dietary supplement ingredients and found omega-3, omega-6, L-arginine, L-citrulline, folic acid, vitamin D, magnesium, zinc, alpha lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanols, genistein and quercetin all showed moderate to high-quality evidence for reducing cardiovascular disease risk factors (J Am Coll Cardiol 2022;80:2269-2285), which is part of keeping healthy people healthy and exactly what supplements are intended to do.

Medical authorities continue to share mixed recommendations, in part, because the concept of “intended use” is, at best, under-appreciated, or, at worst, completely ignored by those who approach dietary supplement research with a negative bias prima facie. It is not as simple as asking the AHA if fish oil works. If you ask if fish oil treats elevated cholesterol, the answer is NO. If you ask if fish oil is good for heart health, the answer is YES. And this is true for most supplements. Do MVMs prevent cancer and heart disease? NO. Do MVMs fill nutrient gaps with a less than perfect diet? YES.

When the next headline reads, “Study proves dietary supplements don’t work,” the first question should always be, “For what intended use?”

Naturopathic doctor Duffy MacKay is the senior vice president of dietary supplements at the Consumer Healthcare Products Association (CHPA), where he leads the association’s dietary supplement scientific, policy and legislative initiatives. His career in supplements spans over 25 years and includes serving as a senior executive and scientist at leading dietary supplement companies, including CV Sciences, Nordic Naturals and Thorne Research.