Metabolic syndrome (MetS) is a cluster of conditions increasing the risk of cardiovascular disease and type 2 diabetes. Insulin resistance is a key feature. Low levels of 25-hydroxyvitamin D [25(OH)D] are associated with MetS, with vitamin D deficiency impacting various MetS components like central obesity (waist circumference), hypertension, hyperglycemia, elevated triglycerides (TG) and cholesterol, and reduced high-density lipoproteins (HDL-c). Vitamin D receptors in various tissues suggest extraskeletal effects, influencing lipid metabolism, glucose homeostasis, and blood pressure regulation. Studies have shown inverse associations between vitamin D levels and abdominal obesity, cholesterol, triglycerides, HDL-c and LDL-c. Vitamin D's potential to improve glucose metabolism involves enhancing insulin secretion, modulating immune responses, reducing inflammation, and improving insulin sensitivity. Its antihypertensive properties might stem from reduced expression of angiotensinogen and aldosterone synthase genes. However, the vitamin D obtained from diet or sun exposure may be insufficient for individuals with MetS, as metabolic disorders can disrupt vitamin D activation. This review aimed to determine if VDS effectively controls dyslipidemia, fasting glucose, blood pressure, HDL-c, and central obesity in adults diagnosed with MetS, using a rigorous methodology that focuses on RCTs simultaneously evaluating all five MetS components, unlike previous reviews which had limitations such as analyzing only a subset of MetS components or including non-RCT studies.

Existing systematic reviews on vitamin D supplementation and MetS have yielded conflicting results due to varying methodologies, doses, types of vitamin D supplements, and study durations. Some reviews focused on only two MetS components (HDL-c and TG) and reported no significant effect of VDS, while others, incorporating observational studies, reported positive effects on blood pressure, abdominal obesity, and glucose metabolism. The heterogeneity across studies, discrepancies in effect measures, and the lack of a confirmed MetS diagnosis in some studies, necessitated this review which aimed for more comprehensive analysis using a strict protocol focusing on RCTs, using the GRADE tool for assessing the certainty of evidence, and assessing all five components of MetS simultaneously in participants with confirmed MetS diagnoses.

This systematic review followed PRISMA and SWiM guidelines, registered in PROSPERO (CRD42019123212). The PICOS criteria included adults >18 years with MetS diagnosed using NCEP-ATP III or IDF criteria; intervention was oral VDS (vitamin D3 or D2); comparison was placebo; primary outcome was lipid profile (TG and HDL-c); secondary outcomes were fasting glucose, blood pressure, and waist circumference; and study type was RCTs. RCTs combining vitamin D with other supplements, those using fortified foods, and those using 1,25(OH)2D3 were excluded. Databases searched from 1998 to April 2023 included EMBASE, MEDLINE, Web of Science, LILACS, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar. Rayyan software was used for study selection. Two researchers independently screened abstracts, with discrepancies resolved by a third reviewer. Data extraction used Cochrane forms. Due to heterogeneity, a meta-analysis was not performed; a narrative synthesis was used. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool, and certainty of evidence was evaluated using GRADE guidelines for each outcome.

The search identified 13,644 articles, resulting in seven RCTs included in the final analysis. High heterogeneity among the included studies prevented a meta-analysis. All seven studies reported a significant increase in serum 25(OH)D levels after VDS. Two studies showed significant decreases in triglyceride (TG) levels (one with a daily dose of 7142 IU for 4 months) and waist circumference (one with a daily dose of 8571 IU for 6 months). However, the certainty of evidence for TG reduction was very low and low for WC reduction. The certainty of evidence for the effect of VDS on fasting glucose, blood pressure, and HDL-c was moderate, indicating the findings were not strong enough to make definitive conclusions. Three studies had a low risk of bias, three had some concerns, and one had a high risk of bias. Different VDS protocols (dose, frequency, duration) were used in the included studies, and the lack of standardized therapeutic goals for serum 25(OH)D level made it difficult to draw strong conclusions about the optimal dose of VDS for improving MetS parameters. Many studies originated from Eastern countries, limiting the generalizability of the results.

This review is the first to assess RCTs examining the effects of VDS on all five components of MetS simultaneously. Although two studies reported significant improvements in TG and WC, the low certainty of evidence does not support the widespread use of VDS for these parameters in individuals with MetS. The observed benefits in a few components, coupled with the risk of bias and low certainty of evidence, suggest caution in recommending VDS for MetS. The varied supplementation protocols, lack of uniform target 25(OH)D levels and the predominantly Eastern study origins, hinder firm conclusions. The mechanisms underlying the potential positive effects of vitamin D on lipid profile might involve the regulation of lipogenic genes and improved lipoprotein lipase activity. The relationship between vitamin D and MetS remains complex; while observational studies show inverse associations, RCTs haven't consistently demonstrated improvement in MetS components with VDS.

Significant improvements were observed only in triglyceride levels and waist circumference in some studies, but low certainty of evidence limits recommendations for VDS to treat MetS. Further well-designed RCTs are needed, addressing all components simultaneously, standardizing protocols and exploring different phenotypes to provide more robust evidence for clinical decision-making.

The limitations of this review include the small number of RCTs assessing all five MetS components concurrently, the high heterogeneity in VDS protocols, the predominantly Eastern study origins, and significant sources of bias in some included studies, leading to low certainty of evidence for most outcomes. The baseline vitamin D status of participants was not always consistently reported across studies.