No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial

This was a single-center, randomized, double-blind, placebo-controlled trial conducted at a diabetes outpatient clinic in Rome, Italy. Adults 25 to 70 years old with type 2 diabetes and non-alcoholic fatty liver disease were enrolled; for the cholecalciferol arm, 29 participants were randomized and 26 completed the study in a 1:1 allocation.

Participants in the active arm received oral cholecalciferol 2000 IU/day, given as eight drops daily for 24 weeks, compared with placebo. The study used high-dose vitamin D supplementation without additional active cointerventions.

Vitamin D supplementation did not improve hepatic steatosis or related metabolic and cardiovascular outcomes over 24 weeks. Change in hepatic fat fraction was not significantly different between groups (beta, 0.63; 95% CI, -1.6 to 2.8; P = 0.57), and active-arm hepatic fat fraction remained similar from baseline to 24 weeks (6.8 [3.9-14.8] to 7 [4.4-12.9]). Liver injury markers, insulin resistance measures, adiponectin, inflammatory markers, and vascular measures also showed no meaningful benefit; an ABI difference of -0.10 (-0.18 to -0.01) reached P = 0.03 but was not significant after correction. Overall, the trial found no evidence that 24 weeks of oral vitamin D improved NAFLD in patients with type 2 diabetes.

The active arm was small, single-center, and only 24 weeks in duration, limiting power to detect modest effects and limiting generalizability. Secondary and subgroup analyses were likely underpowered, and the corrected interpretation of one ABI signal did not support a clear benefit.