Supplements and CVD: Why Negative Data Don't Dampen Sales

Vitamins and supplements do not prevent cardiovascular disease (CVD). In any discussion regarding the use of dietary supplements, we need to begin with that salient point. There have been numerous studies using both individual supplements and multivitamins, and the evidence shows a resounding lack of benefit.

Negative Data Abound

Christopher Labos, MD CM, MSc, FRCPC

Back in 1996, the Physicians' Health Study randomly assigned 22,071 men to receive beta-carotene or placebo for 12 years and showed no difference in CVD, or for that matter in malignant neoplasms or overall mortality.^[1] In fact, other evidence showed that beta-carotene might actually increase the risk for lung cancer in smokers.^[2] The Women's Health Study of almost 40,000 women older than 45 years compared beta-carotene with placebo and also found no benefit in terms of stroke, myocardial infarction, or cardiovascular death.^[3]

The evidence for vitamin C and vitamin E has been equally disappointing, despite great hope that as antioxidants, they would have some benefit. The second Physicians' Health Study compared vitamin E, vitamin C, or both against placebo in over 14,500 men and found no reduction in stroke, myocardial infarction, or cardiovascular mortality.^[4] The Women's Antioxidant Cardiovascular Study tested beta-carotene, vitamin C, and vitamin E in 8171 women over 9 years of follow-up and also found no benefit.^[5] The ability of folic acid to lower homocysteine levels initially held promise, but subsequent reviews showed it was not associated with a reduction in CVD.^[6]

The extraskeletal benefits of vitamin D supplementation were all the rage for a while, but recently the VIDA study failed to show a cardiovascular benefit for vitamin D,^[7] and the VITAL study is presumably the final nail in the coffin for the sunshine vitamin.^[8] In their 2013 review of all the evidence, the US Preventive Services Task Force concluded that there was no benefit to vitamin supplementation,^[9] which prompted the editorial "Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements."^[10]

Sales Soar Regardless

And waste money on them we do. Supplements are a $133 billion industry globally, and their use is increasing. Omega-3 supplements are one of the fastest growing and most popular supplements on the market; fish oil sales increased 10-fold between 1999 and 2012, whereas vitamin D use merely quadrupled.^[11]

Negative trials, such as ASCEND,^[12] VITAL,^[8] and a large Cochrane Collaboration meta-analysis showing no cardiovascular benefit,^[13] are unlikely to dent sales. The recent positive findings in REDUCE-IT may boost them further, but it is worth noting that REDUCE-IT tested a 4-g/day dose of only eicosapentaenoic acid (EPA).^[14] This prescription product is not the same as the usual low-dose over-the-counter fish oil combinations of EPA and docosahexaenoic acid (DHA) that most consumers buy and for which the evidence is strongly negative.

The Worried Well

Which raises the question: Why do people continue to use vitamins and supplements? Surveys show that the public takes supplements for a variety of reasons. The National Health and Nutrition Examination Survey found that most people were using supplements to "improve" or "maintain" overall health.^[15] Some reported using products for medically justifiable reasons, such as calcium or vitamin D for bone health, or iron for anemia. But others reported taking fish oil for heart health or vitamin C to boost the immune system, reasons that are not justifiable given the existing data.^[16]

Ultimately, it seems that many people use vitamins and supplements because they believe that it will make them healthier. The irony, though, is that an analysis of the baseline data found that supplement users tended to be in very good health. Compared with nonusers, they have lower rates of obesity, exercise more, and smoke less than their counterparts who did not take vitamins.

Another inherent contradiction was illustrated by a survey of 2159 US adults.^[17] Nearly 90% of respondents agreed or strongly agreed with the statement, "Multivitamin and mineral supplements can help people meet nutrient needs that can't be met through food alone." But, paradoxically, 80% also agreed or strongly agreed with the statement, "Multivitamin and mineral supplements should not be used to replace healthy dietary and lifestyle habits," and 75% agreed or strongly agreed that "multivitamin and mineral supplements are not meant to cure disease." So even though nutrient deficiencies are very rare in the population, many people see supplements as a way to treat this problem while simultaneously acknowledging that they probably shouldn't do this and that vitamins will not treat any disease.

A survey of 770 Italian students surprisingly found that very few (2.9%) cited dietary deficiencies as the main reason for taking supplements. The most popular reason given (41.7% of respondents) was to enhance sport performance, and many did so on the advice of their coach.^[18] Clearly, the reasons people take these products may vary by age and may reflect the major preoccupation of that particular group. Older adults are concerned about their health; therefore, vitamins serve to promote health. Younger adults are concerned about performance; therefore, vitamins and supplements serve to boost sport performance, even though according to the National Institutes of Health fact sheet on dietary supplements for exercise and athletic performance, "little research supports the use as ergogenic aids of antioxidant supplements containing greater amounts than those available from a nutritionally adequate diet."

Unaware or Unpersuaded

This raises the question of why the many randomized trials, editorials, and statements from public health authorities have failed to curtail the growth in sales of these products. It is possible that the public is simply unaware of the medical evidence demonstrating a lack of effectiveness. However, a more worrying possibility is that they are aware of the evidence and use these products anyway.

A research letter published in JAMA Internal Medicine surveyed users' views of nonprescription dietary supplements and found that only 25% of respondents said they would cease using a supplement if public health authorities stated that it was ineffective.^[19] That means that three quarters of them do not seem to care whether their supplement actually works—a staggering statistic if it is indeed generalizable to the general population.

It may also be that many members of the public are using these products on the advice of their doctor. US survey data show that 31% of users said that a physician or nurse had recommended they take a supplement,^[19] whereas 50% of respondents in an Italian survey said they were taking a supplement because they were following a medical doctor's recommendation.^[18]

Harmless, Pricey Placebo?

Are physicians and other healthcare professionals unaware or simply disregarding the evidence? A 2008 survey of US internists and rheumatologists found that 38% had prescribed vitamins in the past year as a form of "placebo" and typically described them to patients as "potentially beneficial medicine."^[20]

This suggests that a significant number of healthcare professionals who seem to be aware of the lack of evidence recommend vitamins nonetheless. It's not surprising, then, that many patients disregard the advice of government regulators if their personal physicians recommend the products.

If most supplements are not harmful, should we be concerned that our patients take them? Isn't the bigger problem that only about one half of patients with CVD consistently take their evidence-based medicines?^[21,22]

When the medical community continues to ignore data that supplements don't prevent CVD, should we be surprised that many patients may ignore the evidence for their prescription meds? We need to keep reminding the public that the routine use of multivitamin supplementation is costly and unnecessary, we clearly need to remind our peers as well. Before engaging in more public education, we would do well to remember the old adage, "Physician, heal thyself!"

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