On Dec. 17, there was widespread coverage in the news media of an editorial that appeared in the Annals of Internal Medicine (Annals), under the title, "Enough is enough: stop wasting money on vitamin and mineral supplements."(1) The authors of the editorial concluded, "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." However, the editorial appears to be biased and to lack scholarship, as it is based on selective reporting and a superficial analysis of the vast and complex body research on the health effects of nutritional supplements.
The editorial focused mainly on three studies published in that issue of the Annals. The first study found that supplementing with large doses of vitamins and minerals after a heart attack reduced the recurrence rate of cardiovascular events (such as heart attack, stroke, or heart surgery) by 11 percent, compared with a placebo. (2) However, because this reduction was not statistically significant, the editorial concluded (incorrectly) that the treatment was ineffective. The failure to demonstrate that an effect is statistically significant is not the same as demonstrating the absence of an effect. The correct conclusion is that the nutritional supplement reduced the number of cardiovascular events by 11 percent, but because this reduction was not statistically significant, we are less than 95 percent certain that the effect was real (as opposed to being due to chance).
The second study in the Annals found that daily use of a low-potency multivitamin (Centrum Silver) for an average of 8.5 years had no effect on cognitive function in elderly men participating in the large Physicians' Health Study II. (3) However, two other recent double-blind trials (which were not mentioned in the editorial) found positive effects of vitamins. In one of those studies, daily supplementation with 400 mcg of folic acid and 100 mcg of vitamin B12 significantly improved cognitive function in elderly men. (4) The other study showed that daily supplementation with 800 mcg of folic acid, 500 mcg of vitamin B12, and 20 mg of vitamin B6 slowed the rate of brain atrophy in elderly individuals suffering from mild cognitive impairment. (5) There are two potentially important differences between these positive studies and the negative study cited in the editorial. One difference is that the amount of vitamin B12 in Centrum Silver (25 mcg) is much lower than the amount used in the positive studies (100 and 500 mcg, respectively). Loss of cognitive function is a well-known effect of vitamin B12 deficiency. Although all of the study supplements provided more than the Recommended Dietary Allowance for vitamin B12 (2.4 mcg per day), recent research has shown that many elderly people need unusually large amounts of this vitamin (500 mcg per day or more in some cases) to achieve optimal vitamin B12 nutritional status. (6) The other difference is that several aluminum-containing artificial coloring agents are present in Centrum Silver (FD&C Blue 2 Aluminum Lake, FD&C Red 40 Aluminum Lake, and FD&C Yellow 6 Aluminum Lake), and these chemicals have the potential to adversely affect cognitive function. Artificial coloring agents are known to have negative effects on the behavior of children, (7) although these chemicals have not been well studied in adults. Moreover, there is evidence that long-term aluminum exposure can contribute to the development of Alzheimer's disease.(8) The ineffectiveness of a low-potency supplement that contains extraneous and potentially harmful additives does not negate the beneficial effects of higher-potency supplements reported in other trials.
The third Annals study discussed in the editorial was a review of research examining whether vitamin and mineral supplements can prevent heart disease or cancer. (9) The editorial stated there is "no clear evidence" that taking a multivitamin can prevent cancer. However, the research review that was cited in the editorial actually found a statistically significant 7 percent reduction in cancer incidence in men, and no effect in women. While further research is needed to understand why the results differed between men and women, the findings certainly do not warrant the conclusion that the case is closed and to stop wasting money on supplements. With respect to heart disease prevention, the research review focused on two large studies that failed to find a beneficial effect. In one of those studies, Centrum Silver was given to men participating in the Physicians' Health Study II (mentioned above). In the other study, five nutrients were given (zinc, vitamin C, vitamin E, selenium, and beta-carotene). In both of these studies, zinc was not properly balanced with copper. Copper deficiency causes cardiovascular disease in experimental animals, and supplementing with large doses of zinc has been shown to induce copper deficiency in humans. It is possible that taking a moderate amount of zinc (15 to 20 mg per day, as used in these studies) for many years would also decrease copper status. Considering that the average copper content of various foods has declined substantially since around 1940,(10) a further decrease in copper status from long-term zinc supplementation could adversely affect the cardiovascular system. The study that included five nutrients gave 20 mg of zinc per day with no copper for 7.5 years. Centrum Silver does contain copper, but for approximately 70 percent of the 11-year study, the form of copper in the product was cupric oxide, (11) which cannot be absorbed by humans. (12)
Multivitamin-mineral preparations have been shown in published research to have a wide range of benefits, including increasing energy and stress tolerance, improving pregnancy outcomes, decreasing infection rates, slowing bone loss, and improving cognitive function in schoolchildren. Some studies have also demonstrated protection against cardiovascular disease and cancer, although the evidence is conflicting. Furthermore, various individual nutrients or combinations of nutrients have been used successfully for the prevention and treatment of many other health conditions, including migraines, congestive heart failure, rheumatoid arthritis, kidney stones, diabetes, and depression. (13)
Future research should attempt to understand the differences between studies that found positive results and those that did not, in order to maximize the benefits and minimize the risks of nutritional supplements. Simply dismissing a vast body of research because the results are conflicting is not useful. The case regarding vitamins and minerals is far from closed, and the public is not well served by shallow interpretations of complex issues.
References:
1. Guallar E, et al. Enough is enough: stop wasting money on vitamin and
mineral supplements. Ann Intern Med 2013;159:850-851.
2. Lamas GA, et al. Oral high-dose multivitamins and minerals after myocardial infarction: a randomized trial. Ann Intern Med 2013;159:797-804.
3. Grodstein F, et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann Intern Med 2013;159:806-814.
4. Walker JG, et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms - the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr 2012;95:194-203.
5. Smith AD, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One 2010;5(9):e12244.
6. Hill MH, et al. A vitamin B-12 supplement of 500 mcg/d for eight weeks does not normalize urinary methylmalonic acid or other biomarkers of vitamin B-12 status in elderly people with moderately poor vitamin B-12 status. J Nutr 2013;143:142-147.
7. McCann D, et al. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet 2007;370:1560-1567.
8. Gaby AR. Alzheimer's disease. In Gaby AR, Nutritional Medicine. 2011; Concord, NH, chapter 278. www.doctorgaby.com.
9. Fortmann SP, et al. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an update systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2013;159:824-834.
10. Worthington V. Nutritional quality of organic versus conventional fruits, vegetables, and grains. J Altern Complement Med 2001;7:161-173.
11. Personal communication, Pfizer Consumer Healthcare, December 7, 2012.
12. Baker DH. Cupric oxide should not be used as a copper supplement for either animals or humans. J Nutr 1999;129:2278-2279.
13 Gaby AR, Nutritional Medicine. 2011; Concord, NH. www.doctorgaby.com.