Vitamin D for tuberculosis or acute respiratory infections: lost in translation?

Purpose of review This review summarizes findings of recent Phase 3 randomized controlled trials (RCTs) and meta-analyses investigating effectiveness of vitamin D supplementation for prevention and treatment of tuberculosis or acute respiratory infections (ARI). It also considers why null results from these studies contrast with largely positive results from laboratory studies, observational epidemiology and early RCTs in the field. Recent findings The latest evidence from RCTs and meta-analyses does not support the use of vitamin D supplements to prevent ARI or tuberculosis infection, or to enhance response to standard antimicrobial therapy for tuberculosis disease. Summary Limited physiologic relevance of positive results from cell culture studies and animal models, noncausal associations from epidemiologic investigations, publication bias and citation bias may have contributed to an over-appreciation of potential benefits of vitamin D for prevention and treatment of respiratory infections prior to conduct of Phase 3 RCTs. Potential limitations of Phase 3 RCTs in the field – that could have undermined their ability to detect a true signal – include under-representation of participants with vitamin D deficiency at baseline, use of sub-optimal dosing regimens, contamination bias, type 2 error, operation of factors that may have masked, attenuated or antagonized vitamin D-inducible responses, redundancy and inadequate outcome ascertainment.