Vitamin D Supplementation and Increased Risk of Falling: A Cautionary Tale of Vitamin Supplements Retold.

The randomized clinical trial (RCT) by Bischoff-Ferrari et al1 in this issue of JAMA Internal Medicine shows that vitamin D supplementation is associated with the risk of falls. Two “high” doses (60 000 IU of vitamin D3 per month or 24 000 IU vitamin D3 plus 300 mg of calcifediol per month) achieved a serum 25-hydroxyvitamin D (25[OH]D) level of 30 ng/mL in 80% of participants, a level that has been recommended as best for reducing the risk of fractures and for other health benefits (to convert 25[OH]D to nanomoles per liter, multiply by 2.496).2,3 However, compared with a dose of 24000 IU of vitamin D3 per month (equivalent to 800 IU per day), the higher doses had no effect on lower extremity physical performance and increased the risk of falls. A previous RCT4 in women of the same age showed that 500000 IU of vitamin D per year achieved serum 25(OH)D levels of at least 30 ng/mL in most participants but significantly increased risk of falls by 15% and fractures by 26%. A theoretical possibility has been raised that periodic administration of high doses of vitamin D accounts for the increased risk of falls and fractures.5 That hypothesis should be tested by placebo-controlled trials showing that a daily dose of 2000 IU, for example, reaching serum 25(OH)D levels of at least 30 ng/mL reduces the risk of falls and fractures. The trial in this issue1 had no placebo group and, therefore, could not test the effects of supplementation with 800 IU of vitamin D per day. However, a recent placebocontrolled trial by Uusi-Rasi et al6 found that an 800 IU per day supplement had no effect on physical function or risk of falls or injurious falls, whereas an exercise program reduced the risk of injurious falls by about half. Another trial found that 800 IU daily had no effect on lower extremity function or risk of falls in postmenopausal women 75 years or younger.7 It is uncertain whether any dose of vitamin D supplementation reduces the risk of falls or fractures in communitydwelling older adults. Previous meta-analyses of RCTs had differed about whether vitamin D supplements reduce the risk of falls8-11 or fractures8,12-14 in community-dwelling elderly individuals. In contrast meta-analyses15-17 have shown that 800 IU of vitamin D and 1200 mg of calcium reduced the risk of hip fracture and mortality for patients dwelling in institutions. These patients should receive calcium and vitamin D supplements. Clinicians should not recommend vitamin D supplements for other putative health benefits. There is no evidence frommeta-analyses ofRCTs that vitaminDsupplementation reduces the risk of cardiovascular disease or cancer.13,18 In addition, a recent trial19 found that 1000 IUof vitaminDper day, with or without calcium, did not decrease the risk of coloncanceror recurrent adenomas in thosewithahistoryof colon adenomas. The vitamin D story seems to be following the familiar pattern observed with antioxidant vitamins. Enthusiasm for the health benefits of vitamin supplements is coupled with the belief that “vitamins” are inherently safe and reinforced by observational studies showing, essentially, that healthy people have higher vitamin levels. Then RCTs and meta-analyses20 proved that the supplements in fact increase mortality (β-carotene, vitamin E), or have no health benefits (vitamin A, vitamin C). The strategy of supplementation with vitamin D to achieve serum levels of at least 30 ng/mL has not been established by RCTs to reduce the risk of falls and fractures. It may increase the risk of falling. Until that approach is supported by randomized trials with updated meta-analyses, it would be prudent to follow recommendations21 from the Institute of Medicine (IOM) that people 70 years or older have a total daily intake of 800 IU of vitamin D without routine measurement of serum 25(OH)D levels. It is prudent to get recommended intakes of vitamin D and other vitamins from a balanced diet with foods that naturally contain what is manufactured into supplements.