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Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials

BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g2035 (Published 01 April 2014) Cite this as: BMJ 2014;348:g2035

Re: Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials

Dear Editor,

We read with interest the study by Theodoratou and colleagues [1]. Their comprehensive umbrella review of an impressive number of systematic reviews and meta-analyses did not find convincing evidence of a clear role of vitamin D on the vast majority of health outcomes. Interestingly, vitamin D supplementation did not reduce the risk of fractures and falls in older people.

Some comments might be of interest. Before shifting to the other edge of underestimating the value of vitamin D supplementation, it is prudent to recognize that these findings cannot be generalized. First, the anti-fracture and protective role of vitamin D against falls, when it is co-administered with calcium [2], should not be neglected. This has also been shown for fracture risk reduction [3]. Second, baseline 25-hydroxy-vitamin D [25(OH)D] levels may also be an issue, since vitamin D deficient subjects seem to present a greater response in fall risk reduction compared with those with vitamin D sufficient levels [2]. Third, the anti-fracture benefit of vitamin D seems to be dose-dependent, as shown by another recent meta-analysis, in which patients with doses >800 IU/d seem to benefit more than those with lower doses [4]. Fourth, institutionalized patients may also benefit more than community-dwelling patients from vitamin D [3,4].

Regarding the non-skeletal effects of vitamin D, they are difficult to be proven yet with current data, since most studies are of a relatively short duration to show a reduction in outcomes, such as cancer or cardiovascular disease (CVD). It must be also emphasized that most studies had the effect of vitamin D supplementation on bone health as the primary outcome. However, a recent study by Chowdhury and colleagues [5] showed that vitamin D deficiency is associated with a modest but significant increased all-cause and disease-specific mortality, mainly from CVD, compared with 25(OH)D concentrations ≥30 ng/ml. Perhaps greater doses of vitamin D, especially vitamin D3 (i.e. >2,000 IU/d) are needed [5] and the response may depend also on the baseline levels. These questions may be answered by upcoming trials, such as the VITAL study.

We suggest that the need for vitamin D supplementation must be individualized, taking account the patient’s age and status (institution or community), fracture risk, baseline 25(OH)D levels and it should be also co-administered with calcium.

References
1.Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 2014;348:g2035. doi: 10.1136/bmj.g2035.
2.Murad MH, Elamin KB, Abu Elnour NO, Elamin MB, Alkatib AA, Fatourechi MM, et al. Clinical review: The effect of vitamin D on falls: a systematic review and meta-analysis. J Clin Endocrinol Metab 2011;96:2997-3006.
3.Chung M, Lee J, Terasawa T, Lau J, Trikalinos TA. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med 2011;155: 827-38.
4.Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 2012; 367: 40-9.
5.Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903. doi: 10.1136/bmj.g1903.

Competing interests: No competing interests

29 April 2014
Panagiotis Anagnostis
Endocrinologist
Spyridon N. Karras
Division of Endocrinology, Police Medical Center of Thessaloniki, Greece
Sarantaporou 10, Thessaloniki, 54640, Greece