Applied Evidence

Vitamin supplementation in healthy patients: What does the evidence support?

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Multivitamins are often defined as a supplement containing 3 or more vitamins and minerals but without herbs, hormones, or drugs.132 Many multivitamins do contain additional substances, and some include levels of vitamins that exceed the RDA or even the established tolerable upper intake level.133

Safe medication storage should be practiced, as multivitamins with iron are a leading cause of poisoning in children.

A 2013 systematic review found limited evidence to support any benefit from multivitamin supplementation.41 Two included RCTs demonstrated a narrowly significant decrease in cancer rates among men, but saw no effect in women or the combined population.134,135 This benefit appears to disappear at 5 years of follow-up.136 RCT data have shown no benefit of multivitamin use on cognitive function,95 and high-quality data suggest there is no effect on all-cause mortality.137 Given this lack of supporting evidence, the USPSTF has concluded that there is insufficient evidence (grade I) to recommend vitamin supplementation in general to prevent cardiovascular disease or cancer.41

The use of prenatal multivitamins is generally recommended in the pregnancy and preconception period and has been associated with reduced risk of autism spectrum disorders, pediatric cancer rates, small-for-gestational-age infants, and multiple birth defects in offspring; however, studies have not examined if this benefit exceeds that of folate supplementation alone.138-140 AAP does not recommend multivitamins for children with a well-balanced diet.141 Of concern, children taking multivitamins were often found to have excess levels of potentially harmful nutrients such as retinol, zinc, and folic acid.142

The takeaway: There is limited evidence to support any benefit from multivitamin supplementation. Prenatal multivitamins are generally recommended in the pregnancy and preconception period. Overall, the risks of multivitamins are minimal, although that risk is dependent on the multivitamin’s constituent components.143 Components such as vitamin K may interact with a patient’s medications, and multivitamins have been shown to reduce the circulating levels of antiretrovirals.144 Specifically, multivitamins with iron should be avoided in men and postmenopausal women, and safe medication storage should be practiced as multivitamins with iron are a leading cause of poisoning in children.2


Vitamin supplementation in the developed world remains common despite a paucity of RCT data supporting it. Supplementation of folate in women planning to conceive, vitamin D in breastfeeding infants, and vitamin K in newborns are well supported by clinical evidence. Otherwise, there is limited evidence supporting clinically significant benefit from supplementation in healthy patients with well-balanced diets—and in the case of vitamins A and E, there may be outright harms.

Joel Herness, MD, 4700 North Las Vegas Boulevard, Nellis AFB, NV 89191;


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