MIAMI BEACH, FL — A high-dose regimen that includes 28 vitamins and minerals given to stable patients with a history of MI does not reduce their future risk of cardiovascular events, according to the results of a new analysis.
The results, from the second arm of the 2x2 factorial Trial to Assess Chelation Therapy (TACT), funded by the National Heart, Lung, and Blood Institute (NHLBI) and National Center for Complementary and Alternative Medicine (NCCAM), were first presented at the American College of Cardiology 2013 Scientific Sessions and are now published online December 16, 2013 in the Annals of Internal Medicine.
The trial showed no benefit of multivitamin therapy in 1708 patients who received the supplements.
"I'm a completely conventional cardiologist," Dr Gervasio Lamas (Mount Sinai Medical Center, Miami Beach, FL), the lead investigator of TACT, told heartwire . "I don't prescribe vitamins, and I tell my patients not to waste their money on them. But when I think of vitamin, I think of a microgram or a milligram, a nutritional supplement, which is used to replete a nutritional deficiency. But when you get these vitamins and minerals and you bring these up to very high dosages, and then you mix them, I think you do have unpredictable effects that can't be judged based on first principles."
For Dr Eliseo Guallar (Johns Hopkins Bloomberg School of Public Health, Baltimore, MD), Dr Saverio Stranges (University of Warwick, Coventry, UK), Dr Cynthia Mulrow (Annals of Internal Medicine, Philadelphia, PA), and Drs Lawrence Appel and Edgar Miller (Johns Hopkins School of Medicine, Baltimore, MD), the addition of the TACT data to the literature provides yet more evidence that the time has come to "stop wasting money on vitamin and mineral supplements."
"Although available evidence does not rule out small benefits or harms or large benefits or harms in a small subgroup of the population, 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," state the editorialists. "These vitamins should not be used for chronic disease prevention. Enough is enough."
Studying Mega Doses of Vitamins Used With Chelation
As reported by heartwire , the other, more controversial arm of the TACT trial found investigators and other experts at a bit of a loss when the study showed chelation therapy, an alternative-medicine mainstay, modestly improved clinical outcomes in patients after an acute MI. The difference in the primary end point—a composite of all-cause mortality, MI, stroke, coronary revascularization, and hospitalization for angina—reached the trial's specified threshold for statistical significance.
In this study, the TACT investigators randomized patients 50 years of age or older who had an MI at least six weeks prior to treatment with high-dose multivitamins and multiminerals, including vitamins A, C, and E, as well as selenium and magnesium, or to placebo.
Lamas explained that the multivitamins and multiminerals used in their analysis were standard doses used by centers practicing chelation therapy. Patients undergoing the controversial treatment were given large doses of oral vitamins and minerals, nearly all of which exceed the daily recommended values. For example, 1200 mg of vitamin C, 25 000 IU of vitamin A, 400 IU of vitamin E, 200 mg of niacin, and 800 µg of folate were prescribed, and these amounts all exceed the daily recommended dosages.
Adherence rates were low in the trial, however, with 46% of patients discontinuing the treatment during the study. In total, 76% of participants completed one year of treatment and only 47% of participants in the active-treatment arm completed three years. Dropout rates were also high, with 17% of patients withdrawing from the study.
The primary end point occurred in 27% of patients in the multivitamin arm and 30% of patients in the placebo group. In terms of risk reduction, there was a nonsignificant 11% reduction in the primary end point (TACT was powered for a 25% reduction in risk). Based on the data, Lamas said patients should not be taking vitamin or mineral supplements for cardiovascular-disease prevention.
"It was not exactly clear to me that there would be no null effect, or no spillover effect, on some other system when used at these higher doses," said Lamas. "And when you mix it, it's hard to say if there would have been an ill effect or a beneficial effect. Probably the most important contribution of all of these vitamin studies is that we're fairly certain that the majority of these vitamins are probably harmless even when given at very high doses. And that's important."
Lamas said that while data suggest that patients are not harming themselves with multivitamins, the American public is being pushed along by the vitamin industry to purchase and take the supplements. As noted in the accompanying editorial, sales of nutritional supplements reached $28 billion in 2010 and overall use of dietary supplements increased from 42% in 2003 to 53% in 2006.
Vitamins A, C, E as well selenium, ß-carotene, and folic acid have been the most tested, and evidence suggests these are either harmful or ineffective for chronic disease prevention. In addition, the Physicians' Health Study (PHS) showed that taking a daily multivitamin had no effect on rates of cardiovascular disease.
"I have an active cardiology practice, and I tell my patients every session: 'What are you doing? Why don't you give the money to orphans, or if you don't like people, the [Society for the Prevention of Cruelty to Animals] SPCA, because you're not doing anything.' At the end of it all, that's the clinical message I give. From the scientific point of view, am I willing to close the door on vitamins? I think it's still open maybe a few millimeters. . . . With these things you have to judge with your feet, and I'm not planning any vitamin studies."
Lamas reports grant support from the National Heart, Lung, and Blood Institute and National Center for Complementary and Alternative Medicine. Disclosures for the coauthors are listed here. Disclosures for the editorialists are listed here.
Heartwire from Medscape © 2013
Cite this: Michael O'Riordan. TACT: No CVD Benefit With High-Dose Multivitamins - Medscape - Dec 16, 2013.