Impact of Polymorphisms in Genes Related to Vitamin D Metabolism on Serum Response to Supplementation in Adults and Elderly: A Systematic Review and Meta‐Analysis Protocol

ABSTRACT Background and Aims Vitamin D deficiency is a major public health issue, with varying individual responses to supplementation. Genetic factors, especially single‐nucleotide polymorphisms (SNPs) in Vitamin D metabolism genes, likely play a key role. This protocol proposes a systematic review to explore how genetic variability affects serum 25‐hydroxyvitamin D [25(OH)D] levels after supplementation. Methods This protocol adheres to the Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols (PRISMA‐P). The literature search will be conducted across MEDLINE, Scopus, Web of Science, and Embase, without restrictions on publication date or language. The study selection will be guided by Population, Exposure, Comparator, Outcomes, Study Design (PECOS) framework, focusing on randomized clinical trials that report pre‐ and post‐supplementation serum 25(OH)D levels alongside genotype data. Inclusion criteria comprise adults and elderly individuals, from both sexes and any ethnicity, who received Vitamin D supplementation and have SNPs data, while exclusion criteria reject studies with confounding factors such as pre‐existing conditions or use of medications affecting Vitamin D status. Data extraction will include study characteristics, participant demographics, intervention details, SNPs, and serum 25(OH)D data. Inter‐rater reliability will be assessed using Cohen's kappa coefficient. A descriptive synthesis will summarize the findings, and if feasible, a meta‐analysis will be conducted. The primary outcome will be changes in serum 25(OH)D concentrations. Heterogeneity among studies will be quantified using the I² statistic. The methodological quality of studies will be assessed using the Joanna Briggs Institute checklist, and the overall certainty of evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Conclusion By identifying genetic subgroups with differential responses to vitamin D supplementation, the findings are expected to contribute to the development of personalized supplementation strategies. These insights may enhance health interventions by optimizing supplementation protocols based on genetic predispositions, ultimately improving health outcomes. Trial Registration This protocol has been registered with International prospective register of systematic reviews (PROSPERO) ID: CRD42023449836.