Vitamin D and probiotic/synbiotic co-supplementation in cardiometabolic disorders: a systematic review and meta-analysis targeting the gut-immune-metabolic axis.

BACKGROUND AND AIM: Vitamin D deficiency and gut microbiota dysregulation are both implicated in the pathophysiology of cardiometabolic disorders. The aim was to systematically evaluate and quantitatively synthesize the effects of vitamin D combined with probiotic or synbiotic supplementation on cardiometabolic outcomes in adults. METHODS AND RESULTS: A systematic search of PubMed/MEDLINE, Scopus, and Web of Science was conducted from inception to March 2026. Randomized controlled trials investigating combined vitamin D and probiotic or synbiotic interventions in adults with cardiometabolic conditions were included. Primary outcomes comprised glycemic parameters (fasting glucose, insulin, HOMA-IR), lipid profile, and anthropometric measures. Secondary outcomes included inflammatory and metabolic biomarkers. When at least three studies reported comparable outcomes, pooled analyses were performed using a random-effects model. Seven randomized controlled trials, including 470 participants, met the inclusion criteria. Interventions were administered as both capsule-based supplements and food-based formulations, particularly vitamin D-fortified probiotic dairy products. Pooled analyses demonstrated a significant reduction in fasting insulin concentrations, whereas HOMA-IR, fasting glucose, lipid profile, anthropometric parameters, and circulating 25(OH)D concentrations were not significantly affected. Most pooled analyses showed low or no statistical heterogeneity, although substantial between-study heterogeneity was observed for circulating 25(OH)D concentrations. CONCLUSIONS: Combined vitamin D and probiotic or synbiotic supplementation is associated with modest improvements in selected cardiometabolic parameters, particularly insulin resistance. These findings support a potential interaction between vitamin D signaling and gut microbiota; however, the current evidence remains limited and heterogeneous. Larger, well-designed randomized controlled trials are needed to confirm these effects and clarify underlying mechanisms.