Vitamin D for treatment of non‐alcoholic fatty liver disease detected by transient elastography: A randomized, double‐blind, placebo‐controlled trial

Abstract

Aim: To evaluate the effects of vitamin D on transient elastography (TE, FibroScan) indices of liver steatosis (controlled attenuation parameter [CAP]) and fibrosis (liver stiffness measurement [LSM]) in adults with non-alcoholic fatty liver disease (NAFLD). Patients and Methods: In this randomized (2:1), double-blind, single-centre, 12-month trial, patients with NAFLD were treated with vitamin D (1000 IU/day) (n = 201) or a matching placebo (n = 110). Two co-primary outcomes were changes in CAP and LSM after 360 days of treatment versus baseline. Two main secondary outcomes were CAP/LSM changes after 180 days of treatment. Results: Both CAP and LSM gradually decreased in vitamin D-treated patients and slightly increased in the placebo arm. Vitamin D was superior to placebo for both primary outcomes (mean differences in CAP and LSM changes (−49.5 dB/m [95% CI −59.5 to −39.4] and −0.72 kPa [95% CI −1.43 to 0.00], respectively) and both secondary outcomes (−22.1 dB/m [−32.1 to −12.1] and −0.89 kPa [−1.61 to −0.17], respectively). Of a number of exploratory outcomes (change at 12 months vs. baseline), vitamin D reduced serum uric acid (−17.9 μmol/L [−30.6 to −5.2]), gamma-glutamyltransferase (−8.9 IU/L [−15.5 to −2.3)] and fasting serum insulin levels (−5.1 pmol/L [−9.3 to −0.8]) as well as the homeostatic model assessment of insulin resistance index (−1.6 [−3.1 to −0.2]) (false discovery rate [5%]-adjusted Pvalues between .0572 and .0952). Conclusion: Low-medium dose supplementation of vitamin D (1000 IU/day) over 12 months reduces TE indices of liver steatosis (CAP) and fibrosis (LSM) in NAFLD patients.

Vitamin D3 enhances the effects of omega‐3 oils against metabolic dysfunction‐associated fatty liver disease in rat

“…Concomitantly, the hepatic concentrations of adiponectin alongside the antioxidants and anti‐inflammatory markers increased significantly, while leptin with the pro‐inflammatory and pro‐oxidative stress molecules diminished in the VD and OM groups than the PC group. Our results are aligned with many reports that have advocated the potential therapeutic values of VD 3 26–28,48–50 and omega‐3 oils 17,21–25 against MAFLD, plausibly by enhancing insulin sensitivity, reducing lipogenesis alongside antioxidative and anti‐inflammatory actions.…”

“…In contrast, VD 3 therapy reduced obesity, enhanced insulin sensitivity, modulated hepatic lipid metabolizing molecules, and mitigated inflammation and oxidative stress 26–28 . Although VD 3 also attenuated liver steatosis, deregulations of adipokines, inflammation, and oxidative stress in MAFLD patients, 48–50 other randomized clinical trials (RCTs) failed to detect significant beneficial anti‐steatotic effects for the hormone 51,52 . On the other hand, omega‐3 oils also abated MAFLD in murine by lowering insulin resistance, lipogenesis, inflammation, oxidative stress, and apoptosis 17,21,22 .…”

Heart failure with preserved ejection fraction and non‐alcoholic fatty liver disease: new insights from bioinformatics

“…A case–control study of 3023 subjects in a community in Nanjing, China, found that an elevated serum vitamin D level decreased the risk of NAFLD 81 . In a 12 month randomized controlled trial, low and moderate doses of vitamin D (1000 IU/day) reduced hepatic steatosis and fibrosis in NAFLD patients 82 . A meta‐analysis of 544 NAFLD subjects from 10 trials also showed that vitamin D supplementation improved glycaemic control and insulin resistance in NAFLD patients 83 .…”

Higher Serum 25-Hydroxyvitamin D Is Associated with Lower All-Cause and Cardiovascular Mortality among US Adults with Nonalcoholic Fatty Liver Disease

“…Dasarathy et al found that a low vitamin D level can independently predict the severity of NAFLD [ 31 ]. Some clinical trials also demonstrated that vitamin D supplementation has therapeutic effects on patients with NAFLD, including a reduction in liver enzymes, weight, and BMI and an improvement in lipid profile, glycemic control, insulin resistance, and hepatic steatosis and fibrosis [ 32 , 33 , 34 , 35 ]. However, a few studies reported insignificant relationships between vitamin D status and histological severity of NAFLD [ 36 ].…”