Vitamin D and human health: evidence from Mendelian randomization studies.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational Mendelian randomization studies
PubMed 38214845 · doi:10.1007/s10654-023-01075-4
What was done
Authors searched PubMed and Embase through September 1, 2022, for original Mendelian randomization (MR) studies examining linear causal associations between vitamin D status and any health outcome. Non-linear MR studies were excluded. Study-specific estimates were meta-analyzed after removing overlapping samples, and quality was assessed using the STROBE-MR checklist.
What was found
A total of 133 publications examining 275 individual outcomes were included (no exact effect sizes or confidence intervals were reported in the abstract). Genetically higher 25-hydroxyvitamin D was associated with reduced risk of multiple sclerosis (incidence and relapse), non-infectious uveitis and scleritis, psoriasis, femur and leg fractures, amyotrophic lateral sclerosis, anorexia nervosa, delirium, heart failure, ovarian cancer, non-alcoholic fatty liver disease, dyslipidemia, and bacterial pneumonia. It was associated with increased risk of Behçet's disease, Graves' disease, kidney stone disease, radius/ulna fracture, basal cell carcinoma, and cataracts. Only the multiple sclerosis protective association remained consistent across all genetic instrument selections; most other outcomes were significant only when instruments included variants outside the core vitamin D pathway.
Why it matters
This review provides robust genetic epidemiology evidence supporting a causal protective role of vitamin D in multiple sclerosis. It also demonstrates that many other previously reported associations may reflect genetic pleiotropy rather than direct effects of vitamin D.
Limits
The abstract provides no effect sizes, p-values, or confidence intervals. Methodological quality across the 133 studies was substantially heterogeneous, non-linear effects were not analyzed, and most associations weakened when genetic instruments were restricted to specific vitamin D pathway variants.
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- supports Vitamin D deficiency increases the risk of developing multiple sclerosis.