December 16th, 2013

Case Closed: Multivitamins Should Not be Used

The editorialists are fed up: “Enough is enough.” Writing about three new papers in the Annals of Internal Medicine that find no benefits for the use of multivitamins — only the latest in a long line of negative findings — Eliseo Guallar and colleagues write:

…we believe that the case is closed — supplementing the diet of well-nourished adults with (most) mineral or vitamin supplements has no clear benefit and might even be harmful. These vitamins should not be used for chronic disease prevention. Enough is enough.”

In the first paper, Stephen Fortmann and colleagues performed an updated systematic evidence review of vitamin and mineral supplements for the U.S. Preventive Services Task Force (USPSTF). They found “no evidence of an effect of nutritional doses on CVD, cancer, or mortality in healthy individuals without known nutritional deficiencies for most supplements we examined.” However, they were unable to rule out a benefit for vitamin D, and they called for improved studies to better assess both potential harms and potential benefits.

In the second paper, investigators from the Physicians Health Study II randomized nearly 6,000 physicians 65 years of age or older to  a multivitamin or a placebo. Over 12 years the physicians underwent as many as four assessments of global cognition, verbal memory, and category fluency. There were no significant differences between the groups in any of the test scores at any time.

In the third paper, Gervasio Lamas and his fellow investigators in the NIH’s Trial to Assess Chelation Therapy (TACT) randomized 1,708 patients who had had a heart attack to a multivitamin supplement or placebo. They found no significant difference in outcomes between the two groups after 4.6 years of followup. The results were less robust because the nonadherence rate was much higher than anticipated.

It should be noted that patients in TACT were also randomized to chelation therapy or placebo. Last year the results of that arm of the trial sparked an enormous controversy by suggesting that chelation therapy might be beneficial. Last month the TACT investigators reported that all the benefits observed in the main trial occurred in the large subgroup of patients who also had diabetes. At the American Heart Association meeting last month they also presented results showing that, although multivitamins did not have an independent effect, when added to chelation there was an additional 10% reduction in events. These findings have not yet been published.


4 Responses to “Case Closed: Multivitamins Should Not be Used”

  1. Gervasio Antonio Lamas, MD says:

    As the PI of TACT, I wanted to comment further on our oral vitamin comparison study. I fear that the nuances in the TACT vitamin results were really missed by the scientific reporting community in their rush to finally have a clearcut article after the CHL guideline, controversial TACT chelation results, etc. Admittedly it has been a rough year for our reporter friends. Especially with regards to TACT chelation, they were badly misled by the loudest, least informative voices. So we should try to prevent a repeat.

    Still, for the record, I have to admit that Larry Husten is the only one who listened when I enumerated the complexities of the results, so I will list them all here.

    As background, TACT was a factorial trial of IV chelation v placebo and oral high-dose vitamins v placebo. The study in question is the Annals publication comparing oral vitamins v oral placebo.

    1. TACT vitamins were, by far, the highest doses ever used in a randomized clinical trial. I contend that such high doses of 28 chemicals will have unpredictable effects that cannot be predicted based on first principles. This is not dietary supplementation of a nutritionally depleted patient. Think of the differences in effect between baby aspirin (anti-platelet), 650 mg ASA (analgesic antipyretic), and 3 grams daily for rheumatoid arthritis in the old days (anti-inflammatory). So change your mindset here. This is not vitamin supplementation.

    2. TACT enrolled a secondary prevention population.

    3. TACT had 85% power to detect a 25% difference. We showed an 11% difference between treatment groups with a non-significant p. But we were not powered for an 11% difference. Thus, while the study was not positive, it is inaccurate to call it negative.

    4. If you look at the components of the primary endpoint, you will note that the point estimate for each is <1.0-coincidence?

    5. We reported at ACC and AHA this year, but not yet published, that there is a greater difference in events when the 2 extreme cells of the factorial design and compared (active-active vs placebo-placebo) than when chelation is compared to placebo infusions.

    6. So the conclusion that the door is closed on ultra high-dose "vitamins" for secondary prevention is, in my estimation, not quite true. That door is open a few millimeters, but not yet closed.

    Hope our next publication helps.


  2. Regina Druz, MD says:

    As someone who is interested in combining nutritional and supplemental approaches with the mainstream cardiology practice,, and creating an integrative model of sorts, I wonder if we are measuring the right outcomes. Mega-doses of multi-vitamins may not improve signficantly on the hard end-points (although modest improvement has been detected by TACT investigators). Instead, multi-vitamins cocktails may decrease medication-related side-effects, improve medication adherence, lower rates of discontinuation, or improve quaity of life for the study participants. Is it possible that there is more “pep” associated with the vitamin “pop”?

  3. Before we flush all the multivitamins, I think it’s important to note that they may have positive effects outside the cardiovascular arena. For example, Wassertheil-Smoller, et al. recently
    found that certain groups of women with invasive breast cancer had a 30% higher survival rate if they were using multivitamins with minerals than if they were not. Other studies have shown that MVMs
    reduce the growth of cataracts and lower the risk of colorectal cancer. Until we can develop a more general and integrative knowledge of the potential value of these supplements, we should proceed with caution in speaking for or against their use.

  4. Gervasio Antonio Lamas, MD says:

    Barry and Regina,

    Ultimately, these potential claims will have to be subject to RCTs. And vitamin RCTs are even harder than chelation RCTs because the ingredients are many, and we do not know which are active, or whether it is the mixture. In mu mind I am comfortable with the following conclusions:

    1] Centrum Silver does not reduce the risk of initial cardiovascular events.

    2] The trials of single to few vitamins have been negative for a cardiovascular effect in large-scale meta-analyses (A, C, E).

    3] Secondary prevention with TACT vitamins has a faint, non-significant signal of possible benefit, but must not be considered as standard post-MI care.

    4] Ultra-high dose vitamins and minerals, like the TACT mixture, have not been sufficiently studied to to close the door on a cardiovascular effect.