Correlation of Ion: A Systematic Analysis of Molecular and Clinical Mechanisms of Vitamin D Deficiency in Obesity

• Fathia Faaid

  faculty of Health Sciences, Misurata, Libya

  Author

Background: Accumulating epidemiological evidence demonstrates a consistent inverse relationship between obesity and serum 25-hydroxyvitamin D [25(OH)D] concentrations. However, the direction of causality and the underlying biological mechanisms remain subjects of active investigation. Objectives: This systematic review aims to (1) elucidate the causal direction between obesity and vitamin D deficiency using Mendelian randomization evidence, (2) analyze the molecular and physiological mechanisms involved, (3) evaluate the efficacy of supplementation strategies in obese populations, and (4) provide evidence-based clinical recommendations using the GRADE framework. Methods: A systematic literature search was conducted in PubMed, Scopus, and the Cochrane Library from inception through January 2026. Studies were included if they reported serum 25(OH)D measurements in relation to body mass index (BMI), Mendelian randomization analyses, or randomized controlled trials (RCTs) of vitamin D supplementation stratified by adiposity. A total of 87 studies encompassing 145,000 participants were included in the final analysis. Results: Mendelian randomization analyses confirmed a unidirectional causal relationship, whereby obesity causes vitamin D deficiency (β = −4.2% per 10% increase in BMI; p = 0.005), but not vice versa (p = 0.57). Biological mechanisms include adipose sequestration, volumetric dilution, impaired hepatic hydroxylation (reduced CYP2R1 expression by 30–40%), chronic low-grade inflammation, and altered gut microbiome composition. Obese individuals require 2–3 times higher vitamin D doses to achieve target serum levels, yet supplementation does not produce clinically meaningful weight loss (I² = 67% heterogeneity). Conclusions: Obesity causally drives vitamin D deficiency through multiple convergent mechanisms. Weight-adjusted supplementation protocols are recommended for obese patients presenting with clinical indications of deficiency. However, weight reduction remains the primary strategy for restoring vitamin D homeostasis.

1. Fathia Faaid, faculty of Health Sciences, Misurata, Libya

    faculty of Health Sciences, Misurata, Libya 

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