Effects of vitamin D supplementation on liver fibrogenic factors, vitamin D receptor and liver fibrogenic microRNAs in metabolic dysfunction-associated steatotic liver disease (MASLD) patients: an exploratory randomized clinical trial

Exploratory randomized clinical trial in adults aged 20 to 60 years with MASLD and NASH confirmed by ultrasound and FibroScan, who were overweight or obese and not taking vitamin D supplements at baseline. In the vitamin D arm, 23 participants were randomized and 22 completed; the study used intention-to-treat analysis across 46 participants.

Vitamin D was given as oral tablets at 4000 IU daily with the main meals for 12 weeks. The active regimen was compared with placebo in a randomized trial.

Vitamin D supplementation showed a favorable effect on several surrogate markers of liver injury and fibrogenesis in MASLD. Serum 25(OH)D increased and VDR rose significantly, while HDL-C improved and ALT, AST, fasting glucose, LDL-C, and total cholesterol decreased versus placebo. Key between-group differences were reported for 25(OH)D (p < 0.001), VDR (p = 0.008), HDL-C (p < 0.001), ALT (p < 0.001), AST (p = 0.001), fasting glucose (p < 0.001), LDL-C (p = 0.01), and total cholesterol (p = 0.03). Fibrogenic markers laminin and hyaluronic acid were also reduced, and MiR-21 and MiR-122 decreased, whereas MiR-34a did not change significantly (p = 0.22).

This was an exploratory study with a small active arm and short 12-week duration, so findings are hypothesis-generating rather than confirmatory. Outcomes were based on surrogate biomarkers instead of direct liver fibrosis measures or histology, limiting certainty about clinical antifibrotic benefit. Generalizability is also limited to similar overweight or obese MASLD patients from this setting.