Is there enough evidence for clinical recommendations?
While vitamin D deficiency is defined by the presence of bone disease (either rickets or osteomalacia), the term "insufficiency" has been used to describe suboptimal levels of vitamin D that are often associated with other skeletal and nonskeletal health outcomes. Interest in the nonskeletal effects of vitamin D has grown since the discovery of vitamin D receptors and the
1α-hydroxylase enzyme in multiple tissues, including cells of the pancreas, immune system, macrophages, vascular endothelium, stomach, epidermis, colon, and placenta. However, unlike the well-established skeletal benefits of vitamin D, the evidence for other presumed effects is based mainly on observational studies.1
A study published in the January issue of Mayo Clinic Proceedings examined the evidence for making clinical decisions based on the strongest research to date for the potential benefits of vitamin D associated with numerous outcomes.1 These included lower mortality rate; lower cardiovascular mortality; less musculoskeletal pain; and reduced risk of diabetes mellitus, cancer, multiple sclerosis, allergy and asthma, infection, mental illness, and renal disease.
The level of evidence was assessed with the following hierarchy: meta-analyses of randomized controlled trials (RCTs), RCTs, nonrandomized intervention studies, meta-analyses of observational studies (cohort and case-control studies), and observational studies. For the available RCTs, the authors reported the following data:
Mortality: There was a 7% lower risk of mortality in postmenopausal women who received supplemental vitamin D (meta-analysis of 18 RCTs). However, mortality assessment was not the primary aim of these trials, and trials that showed such an effect would be more likely to report this outcome, leading to potential reporting bias that could negate the findings.
Colorectal or breast cancer: Two separate RCTs that were part of the Women's Health Initiative trial found no significant effect of combined supplementation with calcium and vitamin D on the risk of colorectal or breast cancer.
Depression: One randomized, double-blind trial showed that high-dose vitamin D (20,000 or 40,000 IU) weekly for 1 year significantly improved depression scores in overweight or obese patients vs placebo.
Musculoskeletal pain: Two RCTs were examined. One found no benefit of vitamin D supplementation vs placebo for reducing musculoskeletal pain (including pain due to osteoarthritis). Another double-blind RCT found that patients with vitamin D levels of 10-25 ng/mL who received high-dose vitamin D (50,000 IU) weekly for 8 weeks showed improvement on fibromyalgia scores vs placebo.
Overall, the authors concluded that most of the current data on vitamin D is mainly based on observational, epidemiological outcomes, which are "useful for generating hypotheses but not for proving causality." Therefore, the evidence for benefits beyond bone health is not strong. The authors also noted that, based on current data, patients 60 years and older may benefit from supplemental vitamin D (800-2,000 IU/day) to reduce the risk of falls and fractures.
Reference
Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011;86(1):50-60.
