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
What this study found
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…
- Study & population
- 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.
- Intervention
- Vitamin D was given as oral tablets at 4000 IU daily with the main meals for 12 weeks.
- Key limitation
- This was an exploratory study with a small active arm and short 12-week duration, so findings are hypothesis-generating rather than confirmatory.
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Open PDFOriginal abstract
Background and aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global metabolic problem which can lead to irreversible liver fibrosis. It has been shown that vitamin D and its receptors contribute to fibrogenic pathways in the liver. However, the effect of vitamin D supplementation on liver fibrosis related factors have not been examined. This double blinded placebo controlled clinical trial was designed to investigate the effects on vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients. Methods Forty six MASLD patients after block matching for sex and BMI were randomly assigned to receive 4000 IU/d vitamin D or placebo for 12 weeks. Weight, height and waist circumference were measured. Serum fibrogenic microRNAs, laminin, collagen type IV, hyaluronic acid, vitamin D, VDR, PTH, blood fasting glucose, serum fasting insulin, lipid profile, ALT and AST were determined at the baseline and at the end of the trial. Insulin resistance and insulin sensitivity were calculated using the HOMA-IR and QUICKI equation. Results Supplementation with vitamin D for 12 weeks led to the significant increases in serum 25(OH) vitamin D, VDR and HDL-C compared to placebo ( P < 0.001, P = 0.008 and P < 0.001). There were significant decreases in ALT, AST, FBS and LDL-C levels in the vitamin D group as compared to the placebo ( P < 0.05). Laminin and hyaluronic acid concentrations were significantly decreased in the vitamin D group as compared to the placebo group, by -10.6 and − 28.7 ng/mL, respectively. Supplementation with vitamin D for 12 weeks resulted in a significant lower MiR-21 and MiR-122 gene expressions compared to the placebo group ( P = 0.01 and P < 0.001, respectively). Discussion As the first randomized controlled trial on the effect of vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients, we found a significant reduction in some liver fibrogenic factors, in liver transaminases and corresponding changes in some fibrosis-related MiRs and some metabolic factors. Further clinical trials with larger sample sizes and direct measures of liver fibrosis are needed to confirm these findings. Trial registration number (available at: http://www.irct.ir , identifier: IRCT201405251485N13), Registration date: 14-03-2017.