Vitamin D offered negligible benefits on skeletal, nonskeletal outcomes

Among individuals living in non-institutional community settings, supplemental vitamin D with or without calcium appears to provide limited benefits to skeletal and nonskeletal health, according to study findings.

Researchers utilized a conventional meta-analysis of existing studies to evaluate the data from randomized controlled trials of effects of vitamin D, with or without calcium, on cardiovascular events, cerebrovascular events, cancer, fracture and mortality. Subsequently, they conducted a trial sequential analysis, which was designed to determine potential changes to risk estimates in future trials.

In the conventional meta-analysis, the researchers evaluated data from 40 randomized controlled trials. Using this data, the researchers evaluated the effect of vitamin D, vitamin D with calcium, and vitamin D with or without calcium. In 80% of the 40 trials, the participants had baseline 25-hydroxyvitamin D concentrations, and in 72% of these trials, the average 25-(OH)D level was lower than 50 nmol/L.

The analysis found that vitamin D, with or without calcium, had no effect on myocardial infarction, ischemic heart disease, stroke or cerebrovascular disease, or cancer. When the researchers separately assessed outcomes for MI (five trials, n=43,116; RR=1.04; 95% CI, 0.91-1.17) and ischemic heart or CVD (four trials, n=5,571; RR=1.12; 95% CI, 0.78-1.62) and outcomes for stroke (six trials, n=43,418; RR=1; 95% CI, 0.88-1.13) and cerebrovascular disease (two trials, n=3,013; RR=1.05; 95% CI, 0.82-1.34), the results were similar to the pooled analyses.

The trial sequential analysis revealed that the effect estimate of vitamin D with or without calcium fell within the futility boundary for most study endpoints, meaning that vitamin D changed the RR of these outcomes by at least 15%. Although supplementation with vitamin D alone did not decrease hip fracture by 15% or more (12 trials, n=27,834), vitamin D and concomitant calcium yielded a decrease in hip fracture among institutionalized individuals (two trials, n=3,853). In community residents, vitamin D combined with calcium did not affect the RR of hip fracture by at least 15% (seven trials, n=46,237). The effect of vitamin D with or without calcium on mortality was found to be inconclusive (38 trials, n=81,173).

The researchers also concluded that similarly designed studies are unlikely to reveal significantly different findings.

In an accompanying commentary, Karl Michaëlsson, MD, of the department of surgical sciences at Uppsala University, said these findings contradict many popular beliefs about the benefits of vitamin D.

“Existing evidence does not lend support to the commonly held belief that vitamin D supplementation in general prevents osteoporosis, fractures, and nonskeletal diseases,” Michaëlsson wrote. “Without stringent indications — ie, supplementing those without true insufficiency — there is a legitimate fear that vitamin D supplementation might actually cause net harm.”

For more information:

Bolland MJ. Lancet Diabetes Endocrinol. 2014;doi:10.1016/S2213-8587(13)70212-2.

Michaëlsson K. Lancet Diabetes Endocrinol. 2014;doi:10.1016/S2213-8587(14)70008-7.

Disclosure: The researchers report no relevant financial disclosures.