By Robert Lamberts, M.D.
The supplement industry is a huge one – Over $14 Billion in US sales in 2004 (still small compared to the over $200 Billion spent on prescription drugs in the same year), but one study showed that 6 out of 10 Americans were taking a supplement of some kind.
A recent article in the Washington Post caught my eye, casting some questions about some of the more popular supplements:
Millions of Americans who regularly take vitamins and other popular dietary supplements have had their faith in those products challenged in the past year as the substances fared poorly in several large clinical trials and a federal panel’s scientific review.
The supplements tested are widely used but few had previously been put to large-scale, well-designed clinical trials. The findings showed that some of Americans’ most trusted supplements — including some, such as multivitamins and calcium, that doctors ave recommended for decades — failed to show the benefits they were believed to offer
The difference between drugs and dietary supplements lies mainly in how they are regulated by the FDA. While drug companies cannot make any claims that the FDA has not sanctioned, supplement manufacturers are able to be much more “creative” with their information. While they can’t make bold-faced lies, they can make claims that are unable to be disproven, such as “supports a healthy immune system,” or “supports prostate health.” The FDA has little say as to what claims are made (actually the Federal Trade Commission can step in for fraudulent advertising). The same is true for the content of the medications, which must meet stringent government requirements for prescription drugs, but can have a wide range of content in supplements.
The article goes on:
Loose regulation of dietary supplements by the Food and Drug Administration (FDA), noted in the federal panel’s May report on multivitamins, complicates the testing of products. Even if researchers know what constitutes an effective dose, formulas can vary from brand to brand, and even batch to batch, and what’s on the label isn’t always what’s in the bottle, tests have shown.
Yet the beat goes on, and many people are taking things that very little is known about. I had a patient today say she was taking Black Cohash for her hot flashes, so I looked it up in ePocrates to see if there was anything to worry about. It stated about 20 different possible uses for the supplement, but warned that this drug could be confused with white and blue cohash. Now, I wouldn’t know a cohash if it bit me in the face, and I was not aware there was such a rainbow of cohashes out there, but someone is getting people to believe that this stuff is safe and effective. The article concludes:
The year’s negative findings probably have had little impact on people’s habits or doctors’ recommendations, said Avins. Even he doesn’t advise people to stop taking the supplements in question. He urged patients to discuss the benefits and drawbacks of supplements with their doctors.
The Council for Responsible Nutrition, a trade group that represents dietary supplement makers, was critical of several of the studies and said the trials left unanswered questions that should be looked at in future research.
“Each one of those studies, for some reason, has been interpreted as the final word — when in fact it shouldn’t be,” said Andrew Shao, the council’s vice president of scientific and regulatory affairs. “That simply isn’t the case.” ?
Right. Science says that there is no such thing as the “final word.” If a claim is made, it is based on a finite number of observations, and so can be overturned by better evidence. This is the standard held to the pharmaceutical industry and one that should also appy to the supplement industry. Yet the same patient taking colorful cohash of unknown quantity is reluctant to treat their high cholesterol with a statin for fear of the safety.
Even doctors fall prey to medical fads. Most patients were recommended for a long time to take Vitamin E for reduction of heart disease (among other benefits). I googled vitamin E and found the following in the first site:
Vitamin E acts as a powerful antioxidant by neutralizing free radicals in the body that cause tissue and cellular damage. Vitamin E also contributes to a healthy circulatory system and aids in proper blood clotting and improves wound healing. Some studies have shown that vitamin E decreases symptoms of premenstrual syndrome and certain types of breast disease.
Other studies have shown that taking large doses of Vitamin E has decreased the risk of Coronary Artery Disease (CAD). Animal studies have suggested that vitamin E does slow the development of atherosclerosis, but the American Heart Association doesn’t recommend using supplements until the effects are proven in large-scale, carefully controlled clinical trials.
Yet looking at the science you see a different story. A recent article in the Annals of Internal Medicine showed that Vitamin E may increase all-cause mortality (death from any cause):
Background: Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed nonâ€“statistically significant increases in total mortality.
Purpose: To perform a meta-analysis of the doseâ€“response relationship between vitamin E supplementation and total mortality by using data from randomized, controlled trials.
Patients: 135 967 participants in 19 clinical trials. Of these trials, 9 tested vitamin E alone and 10 tested vitamin E combined with other vitamins or minerals. The dosages of vitamin E ranged from 16.5 to 2000 IU/d (median, 400 IU/d).
Data Sources: PubMed search from 1966 through August 2004, complemented by a search of the Cochrane Clinical Trials Database and review of citations of published reviews and meta-analyses. No language restrictions were applied.
Data Extraction: 3 investigators independently abstracted study reports. The investigators of the original publications were contacted if required information was not available.
Data Synthesis: 9 of 11 trials testing high-dosage vitamin E (400 IU/d) showed increased risk (risk difference > 0) for all-cause mortality in comparisons of vitamin E versus control. The pooled all-cause mortality risk difference in high-dosage vitamin E trials was 39 per 10 000 persons (95% CI, 3 to 74 per 10 000 persons; P = 0.035). For low-dosage vitamin E trials, the risk difference was â€“16 per 10 000 persons (CI, â€“41 to 10 per 10 000 persons; P > 0.2). A doseâ€“response analysis showed a statistically significant relationship between vitamin E dosage and all-cause mortality, with increased risk of dosages greater than 150 IU/d.
Limitations: High-dosage (400 IU/d) trials were often small and were performed in patients with chronic diseases. The generalizability of the findings to healthy adults is uncertain. Precise estimation of the threshold at which risk increases is difficult.
Conclusion: High-dosage (400 IU/d) vitamin E supplements may increase all-cause mortality and should be avoided.
This article is a meta-analysis – an analysis of multiple studies looking at vitamin E mortality. It shows that at even over 150 units/day mortality rises and continues to rise as you increase the dose.
Yet many of my patients are still taking 1000 units of Vitamin E per day. Most doctors are not aware of this data. We go on thinking that vitamin E must be healthy with little evidence to support it.
So where does this lead to? I agree with the authors of the Washington Post article that this will have little effect on people’s behavior when buying supplements. Overall, supplements are perceived to be safer than prescriptions (which they probably are – after all, you don’t have to be a licensed professional to prescribe and dispense supplements), but also equally efficacious (which they clearly are not). I always try to follow the evidence when it comes to prescribing. New drugs are usually suspect because there needs to be a base of evidence supporting the benefit of a drug, which is usually lacking early. We can easily fall prey to the Cheerleader Drug Rep that says we should prescribe this medication. Yet much of what is happening in the supplement market is little better than the modern equivalent of the “snake oil” salesmen of old West lore.
I warn my patients: yes, they may help. They may also help you lose a lot of weight…from your wallet.