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

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.