ESPEYB16 15 Editorsߣ Choice (1) (18 abstracts)
15.2. Vitamin D supplements and prevention of cancer and cardiovascular disease
Manson JE , Cook NR , Lee IM , Christen W , Bassuk SS , Mora S , Gibson H , Gordon D , Copeland T , D’Agostino D , Friedenberg G , Ridge C , Bubes V , Giovannucci EL , Willett WC & Buring JE
VITAL Research Group, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, the Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
To read the full abstract: N Engl J Med 2019;380:33–44
This paper describes a large randomized, placebo-controlled trial of vitamin D3 (cholecalciferol) 2000 IU per day in 25,871 US adults. After median follow-up of 5.3 years, supplementation with vitamin D did not alter the risk of the primary end points, invasive cancer of any type hazard ratio, 0.96; 95% confidence interval [CI], 0.88–1.06; P=0.47) or major cardiovascular events (hazard ratio, 0.97; 95% CI, 0.85–1.12; P=0.69).
We routinely (and should continue to) recommend that infants and young children receive vitamin D supplements in order to avoid effects of vitamin deficiency on bone and muscle health. In addition, observational studies have reported a very large number of other health benefits associated with higher circulating vitamin D levels, ranging from Type 2 diabetes, cardiovascular disease autoimmunity, inflammation, cancer and innate immunity. However, a major limitation of those observational studies is ‘residual confounding’. Vitamin D is lipophilic, accumulates substantially in adipose tissue, and therefore apparent associations with lower circulating vitamin D levels can be artificially created, or strengthened, by higher levels of adiposity. Statistical adjustments can be performed but are dependent on studies having collected accurate measures of adiposity. The current paper joins other growing trial evidence that such associations may not be causal (1). The trial was very large, well performed, tested a relatively high dose of vitamin D (equivalent to five-times the daily dose recommended in the UK) and found convincingly no benefit on the primary outcomes.
Some believers of widespread benefits of vitamin D supplementation might remain optimistic. In this US setting, 43% of participants were already taking a vitamin D supplement at baseline, so the majority may have been vitamin D replete.
Reference: 1. Pittas AG, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, et al. Vitamin D Supplementation and Prevention of Type 2 Diabetes. N Engl J Med 2019. Epub ahead of print Jun 7.
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ESPE Yearbook of Paediatric Endocrinology
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