October 5, 2018

expert reaction to study on vitamin D supplementation and bone health in adults

Research published in the Lancet Diabetes & Endocrinology suggests that vitamin D supplementation does not prevent fractures or falls.

Dr Robert Clarke, Professor of Epidemiology and Public Health, University of Oxford, said:

“The report included all available trials of vitamin D, but such trials included too few participants, used an insufficient dose of vitamin D, and had an insufficient duration of treatment.  Hence, the study lacked the ability to reliably test the effects of vitamin D on risk of hip fracture.  So, it is too soon to suggest making changes to health recommendations on vitamin D for bone health based on this study.  We should wait until the results of the five ongoing trials of vitamin D, involving total of 57,000 adults, that will be available in the next year or so.”

Prof Adrian Martineau, Clinical Professor of Respiratory Infection and Immunity, Queen Mary University of London, said:

“A major limitation of this study is that people with low vitamin D levels (i.e. 25-hydroxyvitamin D <25 nmol/L) – who potentially stand to benefit the most from supplementation – were in a small minority in the trials that were included in the analysis.  Moreover, the authors failed to obtain data from individual trial participants for their meta-analysis.  This limited their ability to determine whether individuals with low baseline vitamin D levels benefit more from vitamin D supplementation than those with higher baseline levels.

“We know from meta-analyses that have managed to obtain individual participant data that the health benefits of vitamin D supplementation tend to be most marked in people who have the lowest vitamin D levels to start with.  While it’s easy to pool published summary statistics relating to treatment effects to come up with a negative overall answer, this simplistic ‘one-size-fits-all’ approach is a blunt tool that has limited ability to explore whether the effects of a given intervention vary according to key characteristics of individuals who take part in clinical trials, such as whether or not they are deficient in a micronutrient at baseline.

“The authors of this study acknowledge that “trials of vitamin D supplementation in individuals with marked vitamin D deficiency … might produce different results”.  This caveat has important implications, since more than 1 in 5 of the UK population is vitamin D deficient.  The potential for vitamin D supplementation to reduce risk of fractures and falls should not be discounted until further trials in populations with 25-hydroxyvitamin D levels <25 nmol/L have been conducted.

“Public Health England’s recommendation that everyone needs 10 micrograms (400 international units) of vitamin D per day are designed specifically to elevate vitamin D levels out of the deficient range (i.e. to bring them over 25 nmol/L).  Achieving this target in the whole UK population would save lives by preventing the most extreme manifestations of vitamin D deficiency (seizures and heart failure in infants), which occur every year in the UK.  The findings of the new paper do not provide any reason to revisit or reconsider this sound advice.”

Prof Martin Hewison, member of the Society for Endocrinology, professor of molecular endocrinology and deputy director of the Institute of Metabolism and Systems Research at The University of Birmingham, said:

“Almost all trials for vitamin D supplementation have shown that supplementation is only effective if you are vitamin D-deficient to begin with.  In the UK, guidelines for bone health by the Science Advisory Council on Nutrition and other organisations such as the National Osteoporosis Society, indicate vitamin D supplementation for individuals with serum 25-hydroxyvitamin D levels below 25 nmol/L.

“In the study to be published in Lancet Diabetes and Endocrinology very few of the subjects assessed in this meta-analysis would be considered vitamin D-deficient according to UK guidelines, only 4 of the 81 studies assessed (6%) had mean baseline 25-hydroxyvitamin D levels less than 25 nmol/L.  As such the benefits of vitamin D supplementation are difficult to determine from the current study even though it involves a large number of individuals.

“Much of the data in the meta-analysis reflect subjects who already had adequate levels of vitamin D.  Many individual vitamin D supplementation trials do not screen for baseline vitamin D deficiency and this may account for disappointing results.  Where stratification has been used to identify baseline vitamin D-deficiency (<25 nmol/L 25-hydroxyvitamin D), results are often stronger, notably the work by Adrian Martineau and colleagues on acute respiratory infection (BMJ 2017;356:i6583).

“What the current study in Lancet Diabetes and Endocrinology illustrates is that more studies are required that target vitamin D supplementation where it is needed – in people with vitamin D-deficiency – repeated expansive meta-analyses will not achieve this.”

‘Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis’ by Mark J Bolland et al. was published in The Lancet Diabetes & Endocrinology at 23:30 UK time on Thursday 4 October 2018.

Declared interests

Prof Robert Clarke: “I have worked on vitamin D for several years but I have no conflicts of interest about this meta-analysis.”

Prof Adrian Martineau: “I am in receipt of funding from the UK Medical Research Council and the US National Institutes of Health to support on-going clinical trials of vitamin D supplementation to improve bone mineral density and prevent fractures in children.  I have conducted meta-analyses of individual participant data from clinical trials showing benefits of vitamin D supplementation for respiratory health outcomes that are strongest in, or restricted to, people with low baseline levels of vitamin D.”

Prof Martin Hewison: “No conflicts.”