Bolland et al state that there is no clinical trial evidence that increasing vitamin D levels impacts favourably on non-skeletal outcomes.1 This is not true. In our paper,2 we referenced Lappe et al which showed that improving calcium and vitamin D status substantially reduces all-cancer risk in postmenopausal women.3 This was a rigorously conducted 4-year population-based, double-blind, randomised placebo-controlled clinical trial in which mean serum 25-hydroxyvitamin D was raised from 72 to 96 nmol/L.

More recently, a meta-analysis4 of 18 independent randomised controlled trials, including 57,311 participants, showed a relative risk for all-cause mortality of 0.93 (95% CI 0.87–0.99). Daily doses of vitamin D supplements varied from 300 to 2000 IU. The trial size-adjusted mean daily vitamin D dose was 528 IU.

In 9 trials, there was a 1.4- to 5.2-fold difference in serum 25-hydroxyvitamin D between the intervention and control groups. There was neither indication for heterogeneity nor indication for publication biases. Moreover, the summary relative risk did not change according to the addition of calcium supplements in the intervention.

Three other randomised controlled clinical trials give some pointers to the reasons for the reduced mortality. A single dose of vitamin D significantly enhanced tuberculosis contacts’ antimycobacterial immunity in vitro.5 Trials of vitamin D for the prevention of infections6 and falls,7 while failing to show statistically significant effects; did, consistent with hypotheses, observe fewer infections (by 20%) and fewer fallers (by 18%) in the vitamin D-treated groups.

Regarding expert consensus on the optimal serum 25-hydroxyvitamin D concentration, the median of the values favoured by each member of the panel of six experts8 referred to by Bolland et al was 75 nmol/L. This is the same value we used.2

It is emerging that vitamin D has a greater role than maintenance of skeletal integrity9 and that the clinical community needs to broaden its field of view away from the sharp skeletal focus of Bolland et al. Supportive evidence-based medicine is already present in the literature.3–7

John Livesey
Scientific Officer
Christchurch Hospital, Christchurch

Peter Elder
Scientific Officer
Christchurch Hospital, Christchurch

M Jane Ellis
Scientific Officer
Christchurch Hospital, Christchurch

Chris Florkowski
Chemical Pathologist
Christchurch Hospital, Christchurch

Richard McKenzie
Research Scientist
National Institute of Water & Atmospheric Research (NIWA)
Lauder, Central Otago

Ben Liley
Research Scientist
National Institute of Water & Atmospheric Research (NIWA)
Lauder, Central Otago