Correspondence
No changes occurred in markers of cardiovascular risk, glucose sensitivity, or inflammation (apart from a small change in apolipoprotein B100 that was of debatable clinical significance). Our study suggests that vitamin D status might not only be a marker of ill health, as concluded by Autier and colleagues,1 but also an indicator of other effects related to season or sunlight levels that might benefit long-term health. We declare that we have no competing interests.
*Helen M Macdonald, Adrian D Wood, William D Fraser, William G Simpson [email protected] School of Medicine and Dentistry University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK (HMM, ADW); Norwich Medical School, University of East Anglia, Norwich, UK (WDF); and Department of Clinical Biochemistry, Aberdeen Royal Infirmary, Foresterhill, UK (WGS) 1
2
3
4
5
Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2014; 2: 76–89. Jackson RD, LaCroix AZ, Gass M, et al, for the Women’s Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354: 669–83. Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women’s Health Initiative (WHI) limited-access data set. Am J Clin Nutr 2011; 94: 1144–49. Prentice RL, Pettinger MB, Jackson RD, et al. Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos Int 2013; 24: 567–80. Wood AD, Secombes KR, Thies F, et al. Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. J Clin Endocrinol Metab 2012; 97: 3557–68.
In their review,1 Philippe Autier and colleagues examined the evidence base relating vitamin D status and supplementation to various health outcomes, and concluded that available data are insufficient to deduce a causal role for vitamin D in such conditions. This conclusion is concordant with our own findings, which resulted from a similar approach with a systematic review and metaanalysis, in the examination of the role of vitamin D in pregnancy in terms of health of the mother and child. Funded by UK National Institute for e9
Health Research Health Technology Assessment, and with standard UK Centre for Reviews and Dissemination procedures, we identified 76 articles for review from 16 842 citations (excluding duplications).2 We noted evidence of positive associations between numerous health outcomes and maternal 25-hydroxyvitamin D (25[OH]D) status, including birthweight (the pooled regression coefficient after adjustment for potential confounding factors was 5·63 g [95% CI 1·11–10·16] change per 10% change in maternal 25[OH]D serum concentration in a meta-analysis of three observational studies), offspring cord blood or postnatal calcium concentrations (meta-analysis of six intervention studies, which were all deemed to be at high risk of bias, with concentrations a mean of 0·05 mmol/L (95% CI 0·02, 0·05) greater in offspring of mothers supplemented versus unsupplemented with vitamin D in pregnancy, and offspring bone mass (positive relationship with maternal serum 25(OH)D in pregnancy, in observational studies deemed to be of good quality, but which did not permit meta-analysis). Overall, we noted substantial heterogeneity between the studies and conflicting evidence for most outcomes. Indeed, we noted no convincing evidence for any association between maternal vitamin D status and conditions previously linked to vitamin D deficiency, such as offspring asthma, atopy, type 1 diabetes, or blood pressure. Our conclusion echoed that of both Autier and colleagues1 and the editors of The Lancet Diabetes & Endocrinology,3 in that insufficient evidence exists on which to base any clinical recommendations, and that high quality randomised trials are needed.4 Such trials are now ongoing, for example the vitamin D and omega-3 trial (VITAL) study in the USA, and our own randomised controlled trial in pregnant women (MAVIDOS),5 which aims to optimise offspring bone mass.
Investigations such as these should help to answer the questions posed by previous observational studies. Hopefully, in the next 5–10 years, the evidence supporting or refuting a role for vitamin D supplementation in human health will become much more clearly documented. We declare that we have no competing interests.
*Nicholas C Harvey, Cyrus Cooper [email protected] MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton SO16 6YD, UK (NCH, CC); NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK (NCH, CC); and NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK (CC) 1
2
3.
4 5
Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2014; 2: 76–89. Harvey NC, Holroyd C, Ntani G, et al. Vitamin D supplementation in pregnancy: a systematic review. HTA Journal (in press). The Lancet Diabetes & Endocrinology. Vitamin D: chasing a myth? Lancet Diabetes Endocrinol 2014; 2: 1. Harvey NC, Cooper C. Vitamin D: some perspective please. BMJ 2012; 345: e4695. Harvey NC, Javaid K, Bishop N, et al. MAVIDOS maternal vitamin D osteoporosis study: study protocol for a randomized controlled trial. Trials 2012; 13: 13.
In their Review,1 Philippe Autier and colleagues, point out several limitations related to studies linking vitamin D status and health outcomes and suggest that 25-hydroxyvitamin D (25[OH]D) concentrations might be a biological marker of deteriorating health instead of having a causal role. However, no mention is made that the studies reviewed did not take into account serum bioavailable concentrations of 25(OH)D, which might be a more appropriate marker of vitamin D status than total serum concentration. 2 Notably, Powe et al2 showed that some polymorphisms in the vitamin D-binding protein that are prevalent in black Americans, but also present in white Americans, could explain why some individuals with low serum concentrations of total 25(OH)D can show normal values of bioavailable 25(OH)D. These findings might
www.thelancet.com/diabetes-endocrinology Vol 2 April 2014
No changes occurred in markers of cardiovascular risk, glucose sensitivity, or inflammation (apart from a small change in apolipoprotein B100 that was of debatable clinical significance). Our study suggests that vitamin D status might not only be a marker of ill health, as concluded by Autier and colleagues,1 but also an indicator of other effects related to season or sunlight levels that might benefit long-term health. We declare that we have no competing interests.
*Helen M Macdonald, Adrian D Wood, William D Fraser, William G Simpson [email protected] School of Medicine and Dentistry University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK (HMM, ADW); Norwich Medical School, University of East Anglia, Norwich, UK (WDF); and Department of Clinical Biochemistry, Aberdeen Royal Infirmary, Foresterhill, UK (WGS) 1
2
3
4
5
Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2014; 2: 76–89. Jackson RD, LaCroix AZ, Gass M, et al, for the Women’s Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354: 669–83. Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women’s Health Initiative (WHI) limited-access data set. Am J Clin Nutr 2011; 94: 1144–49. Prentice RL, Pettinger MB, Jackson RD, et al. Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos Int 2013; 24: 567–80. Wood AD, Secombes KR, Thies F, et al. Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. J Clin Endocrinol Metab 2012; 97: 3557–68.
In their review,1 Philippe Autier and colleagues examined the evidence base relating vitamin D status and supplementation to various health outcomes, and concluded that available data are insufficient to deduce a causal role for vitamin D in such conditions. This conclusion is concordant with our own findings, which resulted from a similar approach with a systematic review and metaanalysis, in the examination of the role of vitamin D in pregnancy in terms of health of the mother and child. Funded by UK National Institute for e9
Health Research Health Technology Assessment, and with standard UK Centre for Reviews and Dissemination procedures, we identified 76 articles for review from 16 842 citations (excluding duplications).2 We noted evidence of positive associations between numerous health outcomes and maternal 25-hydroxyvitamin D (25[OH]D) status, including birthweight (the pooled regression coefficient after adjustment for potential confounding factors was 5·63 g [95% CI 1·11–10·16] change per 10% change in maternal 25[OH]D serum concentration in a meta-analysis of three observational studies), offspring cord blood or postnatal calcium concentrations (meta-analysis of six intervention studies, which were all deemed to be at high risk of bias, with concentrations a mean of 0·05 mmol/L (95% CI 0·02, 0·05) greater in offspring of mothers supplemented versus unsupplemented with vitamin D in pregnancy, and offspring bone mass (positive relationship with maternal serum 25(OH)D in pregnancy, in observational studies deemed to be of good quality, but which did not permit meta-analysis). Overall, we noted substantial heterogeneity between the studies and conflicting evidence for most outcomes. Indeed, we noted no convincing evidence for any association between maternal vitamin D status and conditions previously linked to vitamin D deficiency, such as offspring asthma, atopy, type 1 diabetes, or blood pressure. Our conclusion echoed that of both Autier and colleagues1 and the editors of The Lancet Diabetes & Endocrinology,3 in that insufficient evidence exists on which to base any clinical recommendations, and that high quality randomised trials are needed.4 Such trials are now ongoing, for example the vitamin D and omega-3 trial (VITAL) study in the USA, and our own randomised controlled trial in pregnant women (MAVIDOS),5 which aims to optimise offspring bone mass.
Investigations such as these should help to answer the questions posed by previous observational studies. Hopefully, in the next 5–10 years, the evidence supporting or refuting a role for vitamin D supplementation in human health will become much more clearly documented. We declare that we have no competing interests.
*Nicholas C Harvey, Cyrus Cooper [email protected] MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton SO16 6YD, UK (NCH, CC); NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK (NCH, CC); and NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK (CC) 1
2
3.
4 5
Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2014; 2: 76–89. Harvey NC, Holroyd C, Ntani G, et al. Vitamin D supplementation in pregnancy: a systematic review. HTA Journal (in press). The Lancet Diabetes & Endocrinology. Vitamin D: chasing a myth? Lancet Diabetes Endocrinol 2014; 2: 1. Harvey NC, Cooper C. Vitamin D: some perspective please. BMJ 2012; 345: e4695. Harvey NC, Javaid K, Bishop N, et al. MAVIDOS maternal vitamin D osteoporosis study: study protocol for a randomized controlled trial. Trials 2012; 13: 13.
In their Review,1 Philippe Autier and colleagues, point out several limitations related to studies linking vitamin D status and health outcomes and suggest that 25-hydroxyvitamin D (25[OH]D) concentrations might be a biological marker of deteriorating health instead of having a causal role. However, no mention is made that the studies reviewed did not take into account serum bioavailable concentrations of 25(OH)D, which might be a more appropriate marker of vitamin D status than total serum concentration. 2 Notably, Powe et al2 showed that some polymorphisms in the vitamin D-binding protein that are prevalent in black Americans, but also present in white Americans, could explain why some individuals with low serum concentrations of total 25(OH)D can show normal values of bioavailable 25(OH)D. These findings might
www.thelancet.com/diabetes-endocrinology Vol 2 April 2014
