BMJ 2014;348:g2923 doi: 10.1136/bmj.g2923 (Published 29 April 2014)
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Letters
LETTERS VITAMIN D AND MULTIPLE OUTCOMES
Causal link between vitamin D deficiency and ill health still possible Barbara J Boucher honorary professor Blizard Institute, Bart’s and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK
The two BMJ articles suggest that vitamin D supplementation has limited benefits.1 2 However, their findings could be compromised by non-adjustment for several factors—inclusion of the same study data in several meta-analyses reviewed; benefits only at higher intakes (fracture reduction in older women) or with baseline deficiency (muscle strength); “thresholds” for detectable benefits (insulin resistance when final 25 hydroxyvitamin D ≥80 nmol/L); and non-exclusion of high dose interval studies with initial worsening, despite discussing this problem. Failure to achieve repletion, or pre-supplementation repletion, affects the outcomes of nutritional randomised controlled trials (RCTs). Calcium intake affects vitamin D efficacy, but vitamins A and K and magnesium also interact with vitamin D. Vitamin A deficiency is common in developing countries but intake is often excessive in Western countries (34% of Europeans have potential toxicity). Thus, confounding of vitamin D trial findings by non-adjustment for vitamin A intakes is likely.3 Furthermore, the degree of irreversible tissue damage at trial baseline affects outcomes—for example, rickety bone deformities are non-correctable, as defective insulin secretion may also be. This concept is now supported for target tissues in general, and genetic data suggest that vitamin D’s health benefits may require adequate lifelong repletion.4
Ioannidis and colleagues1 did not allow for the difficulties in nutritional research that Ioannidis discussed earlier, when he identified different problems from those in RCTs of drugs, and
explained why RCTs of single nutrient intakes produce small (
Page 1 of 1
Letters
LETTERS VITAMIN D AND MULTIPLE OUTCOMES
Causal link between vitamin D deficiency and ill health still possible Barbara J Boucher honorary professor Blizard Institute, Bart’s and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK
The two BMJ articles suggest that vitamin D supplementation has limited benefits.1 2 However, their findings could be compromised by non-adjustment for several factors—inclusion of the same study data in several meta-analyses reviewed; benefits only at higher intakes (fracture reduction in older women) or with baseline deficiency (muscle strength); “thresholds” for detectable benefits (insulin resistance when final 25 hydroxyvitamin D ≥80 nmol/L); and non-exclusion of high dose interval studies with initial worsening, despite discussing this problem. Failure to achieve repletion, or pre-supplementation repletion, affects the outcomes of nutritional randomised controlled trials (RCTs). Calcium intake affects vitamin D efficacy, but vitamins A and K and magnesium also interact with vitamin D. Vitamin A deficiency is common in developing countries but intake is often excessive in Western countries (34% of Europeans have potential toxicity). Thus, confounding of vitamin D trial findings by non-adjustment for vitamin A intakes is likely.3 Furthermore, the degree of irreversible tissue damage at trial baseline affects outcomes—for example, rickety bone deformities are non-correctable, as defective insulin secretion may also be. This concept is now supported for target tissues in general, and genetic data suggest that vitamin D’s health benefits may require adequate lifelong repletion.4
Ioannidis and colleagues1 did not allow for the difficulties in nutritional research that Ioannidis discussed earlier, when he identified different problems from those in RCTs of drugs, and
explained why RCTs of single nutrient intakes produce small (
