Validating the effects of correcting vitamin D deficiency; time for reappraisal of clinical trial design

Goreyet al.1 report many reasons for vitamin D [VitD] supplementation trials producing disparate results. Additionally, investigating causality for the inverse associations consistently seen between VitD status and health risks,2 and suggested by many specific mechanistic effects, requires randomized controlled trial (RCT) designs suitable for nutrients, not pharmaceuticals. Rises in serum 25 hydroxyvitamin D3 (25(OH)D) concentrations and in the biological effectiveness of VitD when supplementing deficiency are both ‘S-shaped’. This means that failure to increase deficient 25(OH)D values up onto the steep part of these dose–response curves will have no noticeable health benefits and neither does the supplementation of replete subjects as increases in their serum 25(OH)D will usually be small as they will be on the flat upper part of the S-shaped curves.3 The common practice of giving single doses of vitamin D3 without adjustment so as to achieve repletion perpetuates these effects, whilst very high dosages, often given at long intervals, frequently lead to detrimental health effects, as the authors point out.1 However, RCT data analyses for initially deficient subjects [using ‘Individual Participant Data’] overcomes these major problems and are revealing significant health benefits with reductions, e.g. in upper respiratory tract infections [by −70%],4 and significant reductions also in acute asthma exacerbations, in overall mortality [by 25% when supplementing su...
Source: QJM - Category: Internal Medicine Source Type: research