Regression of non-alcoholic fatty liver by vitamin D supplement: A double-blind randomized controlled clinical trial

Objective: Evidence indicates that NAFLD patients are vitamin D deficient. Vitamin D has new roles in lipid and glucose metabolism. The aim of this study was to examine the effects of calcitriol supplementation on the NAFLD progression based on liver lipid accumulation, serum lipid profile and insulin resistance. Methods: We randomly assigned 73 patients with NAFLD-confirmed by ultra-sonography to 12 weeks of treatment with hypocaloric diet (reduction of 500 kcal per day) plus 25 μg of calcitriol supplement or a hypocaloric diet plus placebo. Before and after treatment, we assessed anthropometric parameters, grade of fatty liver, serum lipoproteins, liver enzymes and insulin level. Result: Baseline variables were not significantly different between groups. A statistically significant reduction in anthropometric measures was observed over the 12 weeks in both groups. However, no significant differences were seen between groups after intervention. Compared with the placebo, reductions in triglyceride and an increase in HDL cholesterol were seen over the 12 weeks of intervention in the calcitriol group (P = 0.002 and P = 0.004). AST level was decreased in the calcitriol group (-4.2 ± 4.3 μmol/L, P < 0.001), but increased in the placebo group (12.6 ± 6.1 μmol/L, P = 0.02) after 12 weeks. Reductions in mean difference of ALT, insulin and HOMA were significantly higher in the calcitriol than placebo group (P = 0.01, P = 0.007 and 0.01). Conclusions: Calcitriol supplementation combined with weight loss diet showed no significant effects on anthropometric measures in NAFLD patients. However, it may have positive effects on lipid profile, liver enzyme tests and insulin sensitivity during a weight-loss program. © 2016, Academy of Medical Sciences of I.R. Iran. All rights reserved

Effect of daily calcitriol supplementation with and without calcium on disease regression in non-alcoholic fatty liver patients following an energy-restricted diet: Randomized, controlled, double-blind trial

Background & aims: Despite evidence for beneficial effects of vitamin D, to our knowledge, no study has compared the effects of calcium supplementation with vitamin D on non-alcoholic fatty liver disease (NAFLD) regression during a hypo-energetic program. We compared the effect of the vitamin D supplementation with and without calcium on anthropometric measures and biochemical parameters in NAFLD patients during a weight-loss program. Methods: A 12-week, randomized, controlled, double-blind trial was conducted in 120 NAFLD patients randomly assigned to receive 25 μg calcitriol (n = 37), 500 mg calcium carbonate + 25 μg calcitriol (n = 37), or placebo (n = 36) every day with their lunch meals while following a weight-loss program. Results: Weight, BMI and fat mass reduction were significant in each group after 12 wk of intervention (p < 0.001), but differences among the groups was not significant after 12 wk of the study, adjusted to the baseline measurements. Significant reduction in fasting plasma glucose (FPG), insulin, insulin resistance (by HOMA-IR) and TG concentrations and an increase in HDL.C was seen over the 12 wk of study in each group (p < 0.001). Adjusting to the baseline measurements, there was significant difference in FPG (p < 0.001), HOMA-IR (p < 0.001), serum insulin (p = 0.01), TG (p = 0.01) and HDL.C (p < 0.001) among the groups after 12 wk of the study. The calcium plus calcitriol group showed a significant decrease in ALT and FPG and increase in HDL.C level compared with the calcitriol group, adjusted to the baseline measures (p < 0.001). Conclusions: Our results suggest that calcium plus calcitriol supplementation for 12 weeks may be potentially effective for biochemical parameters in NAFLD patients. Further additional larger controlled trials are needed to confirm these findings. Registration: Registered under ClinicalTrials.gov Identifier no. IRCT201408312709N29. © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolis

Effect of daily calcitriol supplementation with and without calcium on disease regression in non-alcoholic fatty liver patients following an energy-restricted diet: Randomized, controlled, double-blind trial

Background & aims: Despite evidence for beneficial effects of vitamin D, to our knowledge, no study has compared the effects of calcium supplementation with vitamin D on non-alcoholic fatty liver disease (NAFLD) regression during a hypo-energetic program. We compared the effect of the vitamin D supplementation with and without calcium on anthropometric measures and biochemical parameters in NAFLD patients during a weight-loss program. Methods: A 12-week, randomized, controlled, double-blind trial was conducted in 120 NAFLD patients randomly assigned to receive 25 μg calcitriol (n = 37), 500 mg calcium carbonate + 25 μg calcitriol (n = 37), or placebo (n = 36) every day with their lunch meals while following a weight-loss program. Results: Weight, BMI and fat mass reduction were significant in each group after 12 wk of intervention (p < 0.001), but differences among the groups was not significant after 12 wk of the study, adjusted to the baseline measurements. Significant reduction in fasting plasma glucose (FPG), insulin, insulin resistance (by HOMA-IR) and TG concentrations and an increase in HDL.C was seen over the 12 wk of study in each group (p < 0.001). Adjusting to the baseline measurements, there was significant difference in FPG (p < 0.001), HOMA-IR (p < 0.001), serum insulin (p = 0.01), TG (p = 0.01) and HDL.C (p < 0.001) among the groups after 12 wk of the study. The calcium plus calcitriol group showed a significant decrease in ALT and FPG and increase in HDL.C level compared with the calcitriol group, adjusted to the baseline measures (p < 0.001). Conclusions: Our results suggest that calcium plus calcitriol supplementation for 12 weeks may be potentially effective for biochemical parameters in NAFLD patients. Further additional larger controlled trials are needed to confirm these findings. Registration: Registered under ClinicalTrials.gov Identifier no. IRCT201408312709N29. © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolis

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 P-values 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