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

Correspondence

explain why some individuals or ethnic groups with low total serum 25(OH)D concentrations who carry such genetic variants might not show clinical effects associated with vitamin D deficiency, such as reduced bone-mineral density3 or increased risk of coronary heart disease.4 Thus, a low serum 25(OH)D concentration alone should not be regarded uniformly as a marker of ill health but the result, at least in some individuals, of relatively common genetic variants not necessarily linked to deteriorating health. Accordingly, a clinical benefit from vitamin D supplementation cannot be anticipated in healthy individuals with genetically determined low serum total 25(OH)D concentrations, but normal bioavailable 25(OH)D levels. In our opinion, the emerging role of serum bioavailable 25(OH)D underscores the complexity of vitamin D metabolism and the limitations of assessing the effects of its supplementation on health outcomes on the basis of surrogate markers of vitamin D status, which might be poorly related to its true biological activity in some individuals. We declare that we have no competing interests.

*Jaime García de Tena, Laura Abejón-López, Cristina Hernández-Gutiérrez, David Bernal-Bello, Manuel Rodríguez-Zapata [email protected] Servicio de Medicina Interna, Hospital Universitario de Guadalajara, Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Guadalajara 19002, Spain (JGdT, LA-L, CH-G, MR-Z); and Servicio de Medicina Interna, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain (DB-B) 1

2

3

4

Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol 2014; 2: 76–89. Powe CE, Evans MK, Wenger J, et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med 2013; 369: 1991–2000. Aloia JF. African Americans, 25-hydroxyvitamin D, and osteoporosis: a paradox. Am J Clin Nutr 2008; 88 (suppl): 545–50. Robinson-Cohen C, Hoofnagle AN, Ix JH, et al. Racial differences in the association of serum 25-hydroxyvitamin D concentration with coronary heart disease events. JAMA 2013; 310: 179–88.

We are disappointed that the Review 1 by Philippe Autier and colleagues omitted geographical evidence suggesting that increased levels of solar ultraviolet B radiation, the controlling factor in vitamin D biosynthesis, is associated with a substantially reduced incidence of many diseases, including some common cancers.2 The number of studies supporting the theory that vitamin D prevents these cancers has been growing for decades. Most major advances in understanding of the mechanism behind the protective effects of vitamin D have resulted from epidemiological studies. The first disease associated with vitamin D deficiency was identified by Jędrzej Śniadecki in 1832, who noticed a strikingly increased incidence of rickets in dark central Warsaw compared with sunnier rural districts, and Theobald Palm, who published a map that identified sunlight deficiency as the main cause of rickets. Moreover, incidence of colon cancer3 and adenocarcinoma of the female breast4 were first identified as being related to vitamin D deficiency from mapping of disease rates with maps developed for the US War on Cancer. Such maps showed that cancers that are mainly due to vitamin D deficiency have a characteristic signature in their geographical distribution. When the incidence rates are plotted according to ultraviolet B radiation, with such radiation in the southern hemisphere denoted as negative values, the parabolic curve that results corresponds exactly to the distinctive geographical signature of solar irradiance.5 Stated technically, the incidence rate is directly proportional to the inverse of the cosine of the latitude of the country. This definition is identical to the formula for solar irradiance by latitude. The strong geographical association between high latitude and high risk of cancer argues strongly against reverse causation. It provides

www.thelancet.com/diabetes-endocrinology Vol 2 April 2014

compelling evidence that vitamin D is the major factor accounting for the latitude gradient in several cancers. Prospective cohort and nested-case control studies have confirmed this association in cohorts such as the Harvard (for breast cancer) and Johns Hopkins University (for colon cancer) cohorts. Reduced risk of disease in association with increased 25-hydroxyvitamin D concentrations is well established based on the Hill criteria for disease causation that include temporal sequence and dose-response gradient. The inverse associations of serum 25-hydroxyvitamin D concentrations with colon cancer and adenocarcinoma of the female breast are well documented, and the negative studies that exist do not nullify the results of many positive studies. These discoveries have great potential for major advances to be made in prevention of some cancers. The opinions expressed in Autier and colleagues’ Review and the accompanying editorial are particularly ill-timed in view of the sad resurgence of rickets and the high rates of colon cancer and other diseases related to vitamin D deficiency in the UK and other countries distant from the equator. We declare that we have no competing interests.

*Cedric F Garland, Edward D Gorham, Heather E Hofflich, Sharif B Mohr [email protected] University of California, San Diego, La Jolla, CA 92093, USA (CFG, EDG, HEH, SBM) 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. Garland C, Garland F, Gorham E, et al. The role of vitamin D in cancer prevention. Am J Public Health 2006; 96: 252–61. Garland CF, Cornstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham ED. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet 1989; 18: 1176–78. Mohr SB, Gorham ED, Alcaraz JE, et al. Serum 25-hydroxyvitamin D and prevention of breast cancer: pooled analysis. Anticancer Res 2011; 31: 2939–48. Jacobson MZ. Fundamentals of atmospheric modeling. Cambridge: Cambridge University Press, 2000; 280–95.

e10

Vitamin D status and ill health.

Vitamin D status and ill health. - PDF Download Free
45KB Sizes 0 Downloads 5 Views