Harvard health letter's anti-vitamin advice to men constitutes premature conjecture based on thin evidence 03/03/2008
More than one in three Americans takes a multivitamin supplement... pills that constitute a major portion of the $23 billion spent on dietary supplements annually in the U.S.
But an increasing body of evidence supports the notion that whole foods provide superior nutrition and preventive health benefits (See “Whole Foods Seen Superior to Supplements”).
While few Americans show signs of outright vitamin-mineral deficiency disease, there's ample evidence that their generally nutrient-poor, “empty-calorie” diets fail to provide optimal levels of some essential nutrients, including omega-3s and vitamins D and E.
Vitamin D deficiency and insufficiency are common in American women and their newborns (Bodnar LM et al. 2007). And insufficient maternal intake of the B-vitamin folic acid (folate) causes birth defects in children—a risk that was ameliorated by folate-fortification of foods only recently.
So when the editors of the Harvard Men's Health Watch newsletter advised men to stop taking multivitamin supplements, the suggestion created quite a stir.
They cited the results of a recent epidemiological study by the National Cancer Institute (NCI), and indications that higher dietary intake of folic acid may promote or exacerbate prostate cancer in men with certain genetic profiles.
Folate plays important roles in the synthesis, repair, and modification of DNA, and higher intake appears to reduce the risk of some cancers (Stevens VL et al. 2005).
Higher intake of this B-vitamin—which occurs in virtually all multivitamin supplements—lowers blood levels of homocysteine (a risk factor for cardiovascular disease) and may reduce the risk of Alzheimer's disease.
What the vitamin-prostate studies actually show
The Harvard health letter's advice was based on the outcome of a study conducted by an NCI team based at the agency's headquarters in Bethesda, Maryland (Lawson KA et al 2007).
The NCI group investigated the association between multivitamin use and risk of early-stage (localized), advanced, and fatal prostate cancer in 295,344 men enrolled in the NIH-AARP Diet and Health Study.
All the men were cancer free when they enrolled in 1995 and 1996.
Five years later, the data showed an increased risk of advanced and fatal prostate cancers among men who reported taking multivitamins more than seven times a week—which the authors characterized as “excessive multivitamin use”—compared with men who never took multivitamins.
The supplement-takers risk of being diagnosed with advanced or fatal prostate cancers were 32 and 98 percent higher than for non-takers, respectively (Lawson KA et al 2007).
However, the supplement-takers' risk of being diagnosed with early-stage prostate cancer was no greater than the risk among non-takers.
The link between “excessive” multivitamin use and prostate cancer risk was strongest in two subgroups:
- Men with a family history of prostate cancer.
- Men who took individual vitamin/mineral supplements, including selenium, beta-carotene, or zinc.
Because of the limitations of the NCI study, its authors could not determine whether multivitamins actually caused cancer nor ascertain which multivitamins were taken. Nor did they detect any connection between the doses of folate men consumed and their risk of prostate cancer.
And the results of three other recent studies found no risk from taking multivitamins frequently, or from having higher blood levels of folic acid as a (presumed) result of this habit:
- An 18-year-long study in 475,726 men—the Cancer Prevention Study II—found no statistically significant increase in prostate cancer deaths among men who took multivitamins 15 or more times a month, compared with vitamin abstainers (Stevens VL et al. 2005).
- A European study in 869 men with prostate cancer and 1,174 cancer-free controls found that having higher blood levels of folic acid did not increase a man's risk of prostate cancer (Johansson M et al. 2008).
- An American Cancer Society analysis of data from 65,836 men found a slight (statistically insignificant) reduction in risk among men with higher folate intakes (Stevens VL et al. 2006).
Multivitamins display mixed preventive health record
The supplement industry's reaction to the Harvard letter's warning was predictable, but probably on target.
Andrew Shao, vice-president for regulatory and scientific affairs at industry trade group the Council for Responsible Nutrition (CRN) made these critiques of the Harvard advice:
“The issue raised on folic acid from a scientific standpoint is one that warrants follow-up, but it is not something isolated to multivitamins. [People get folate from fortified foods, too.] The majority of Americans don't eat well… and multivitamins are an important component to the diet.”
In an effort to provide guidance to the public, the National Institutes of Health (NIH) conducted a conference in 2006, at which a panel reviewed the evidence on health outcomes among people who take multivitamin supplements.
The panel came to the same unclear conclusions reached by other recent reviews of the medical literature:
- “…we found few rigorous studies on which to base clear conclusions and recommendations.”
- “Most of the studies we examined do not provide strong evidence for beneficial health-related effects of supplements taken singly, in pairs, or in combinations of three or more.”
- “Within some studies or subgroups of the study populations, there is encouraging evidence of health benefits, such as increased bone mineral density and decreased fractures in postmenopausal women who use calcium and vitamin D supplements.”
Likewise, the authors of two recent evidence reviews—including one conducted especially for the NIH panel—found it hard to come to clear conclusions concerning the presumed benefits of taking multivitamin pills.
They found only some mild indications that multivitamin supplements might help prevent cancer in poorly nourished people, and might help prevent advanced age-related macular degeneration in high-risk individuals.
As the evidence-review team concluded, “Evidence is insufficient to prove the presence or absence of benefits from use of multivitamin and mineral supplements to prevent cancer and chronic disease” (Huang HY et al. 2006).
In other words, the jury remains out.
The challenge of deciding whether multivitamin supplements help prevent disease flows in part from the fact that most vitamin takers are already healthier than their peers.
The NIH panel put the analytical problem this way: “In general, MVMs [multivitamins] are used by individuals who practice healthier lifestyles, thus making observational studies of the overall relationship between MVM use and general health outcomes difficult to interpret” (NIH 2006).
To us, the takeaway lesson seems clear. For a preventive health edge, eat a balanced diet of whole, unrefined fare, rich in plant foods and fish.
And despite what the Harvard letter said, it still seems to make sense to take a daily multivitamin supplement as low-cost, low-risk health insurance.
- Bodnar LM, Simhan HN, Powers RW, Frank MP, Cooperstein E, Roberts JM. High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. J Nutr. 2007 Feb;137(2):447-52.
- [No authors listed] NIH State-of-the-Science Conference Statement on Multivitamin/Mineral Supplements and Chronic Disease Prevention. NIH Consens State Sci Statements. 2006 May 15-17;23(2):1-30.
- Harvard Health Publications, October 1, 2007. High doses of multivitamins may raise prostate cancer risk, from Harvard Men's Health Watch. Accessed online march 1, 2008 at http://www.health.harvard.edu/press_releases/multivitamins-and-prostate-cancer-risk.htm
- Huang HY, Caballero B, Chang S, Alberg A, Semba R, Schneyer C, Wilson RF, Cheng TY, Prokopowicz G, Barnes GJ 2nd, Vassy J, Bass EB. Multivitamin/mineral supplements and prevention of chronic disease. Evid Rep Technol Assess (Full Rep). 2006 May;(139):1-117. Review.
- Huang HY, Caballero B, Chang S, Alberg AJ, Semba RD, Schneyer CR, Wilson RF, Cheng TY, Vassy J, Prokopowicz G, Barnes GJ 2nd, Bass EB. The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference. Ann Intern Med. 2006 Sep 5;145(5):372-85. Epub 2006 Jul 31. Review.
- Johansson M, Appleby PN, Allen NE, Travis RC, Roddam AW, Egevad L, Jenab M, Rinaldi S, Kiemeney LA, Bueno-de-Mesquita HB, Vollset SE, Ueland PM, Sánchez MJ, Quirós JR, González CA, Larrañaga N, Chirlaque MD, Ardanaz E, Sieri S, Palli D, Vineis P, Tumino R, Linseisen J, Kaaks R, Boeing H, Pischon T, Psaltopoulou T, Trichopoulou A, Trichopoulos D, Khaw KT, Bingham S, Hallmans G, Riboli E, Stattin P, Key TJ. Circulating concentrations of folate and vitamin B12 in relation to prostate cancer risk: results from the European prospective investigation into cancer and nutrition study. Cancer Epidemiol Biomarkers Prev. 2008 Feb;17(2):279-85.
- Lawson KA, Wright ME, Subar A, Mouw T, Hollenbeck A, Schatzkin A, Leitzmann MF. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst. 2007 May 16;99(10):754-64.
- Stevens VL, McCullough ML, Diver WR, Rodriguez C, Jacobs EJ, Thun MJ, Calle EE. Use of multivitamins and prostate cancer mortality in a large cohort of US men. Cancer Causes Control. 2005 Aug;16(6):643-50.
- Wright ME, Weinstein SJ, Lawson KA, Albanes D, Subar AF, Dixon LB, Mouw T, Schatzkin A, Leitzmann MF. Supplemental and dietary vitamin E intakes and risk of prostate cancer in a large prospective study. Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1128-35.