Indian Journal of Pharmacy and Pharmacology · Oct 12, 2026

The vitamin D paradox: Strong associations, weak clinical benefits

By Bhardwaj K, Tripathi A, Srivastava D et al.

Vitamin D occupies a paradoxical position in contemporary medicine. Low circulating concentrations of 25-hydroxyvitamin D [25(OH)D] are consistently associated with numerous adverse health outcomes, including cancer, cardiovascular disease (CVD), fractures, and autoimmune and inflammatory rheumatic diseases (IRDs). Despite these epidemiological associations, large Randomized controlled trials and genetic-causal analyses have repeatedly failed to demonstrate substantial clinical benefits from vitamin D supplementation for several of these conditions. This discrepancy highlights the importance of distinguishing association from causation when interpreting observational evidence. This narrative review synthesises four landmark lines of evidence, including the VITAL trial (2019), which investigated the effects of vitamin D supplementation on cancer and cardiovascular outcomes, and Mendelian randomization studies examining potential causal relationships between vitamin D status and disease risk. Particular emphasis is placed on the 2026 International Osteoporosis Foundation review by Messina et al., which evaluates evidence concerning vitamin D and inflammatory rheumatic diseases. Collectively, these findings challenge assumptions about supplementation and suggest that low vitamin D status may frequently reflect underlying ill-health rather than an independently modifiable cause.

doi.org/10.18231/j.ijpp.18190.1788954376Open accessInterventions