Abstract

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent hepatic disorder worldwide, and an unhealthy lifestyle is the leading risk factor for its occurrence. Vitamin C (VC) has been suggested to protect NAFLD, whereas evidence from randomized controlled trials (RCTs) is sparse. In this study, we aimed to investigate the potential benefits of VC supplementation daily on liver health and associated parameters in patients with NAFLD. In this double-blind, RCT, 84 patients with NAFLD, aged 18–60 years old, were assigned to 12 weeks of oral treatment with either low (250 mg/day, n = 26), medium (1,000 mg/day, n = 30), or high (2,000 mg/day, n = 28) doses of VC supplements. After the intervention, the Medium group had a more significant decrease in aspartate aminotransferase [Medium, −5.00 (−10.25, −1.75) vs. High, −2.50 (−7.75, 0.00), P = 0.02] and alanine aminotransferase [Medium, −8.00 (−18.00, −1.75) vs. High, −3.50 (−13.75, 4.25), P = 0.05; Medium vs. Low, −3.00 (−9.00, 5.50), P = 0.031]. The levels of other indicators of liver health, such as gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, and direct bilirubin were decreased after the intervention but comparable among the three groups and so did the parameters of glucose metabolism, such as fasting insulin, fasting glucose, and homeostasis model assessment for insulin resistance. The plasma level of VC in patients and total adiponectin and high molecular weight (HMW) adiponectin levels were also elevated but not in a dose-dependent manner. Meanwhile, analysis of fecal microbiota composition showed an increase in the alpha diversity (Abundance-based Coverage Estimator (ACE), Shannon, chao1, and Simpson) both in the Low and the Medium groups. A total of 12 weeks of VC supplementation, especially 1,000 mg/day, improved liver health and glucose metabolism in patients with NAFLD. The elevated plasma levels of VC, total and HMW adiponectin, and the improvement of intestinal microbiota may have made some contributions.

Highlights

  • Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common chronic liver disease globally, with almost 25% prevalence in the general population [1]

  • Vitamin C (VC), as an effective water-soluble antioxidant, has a scavenging effect on excessive free radicals in the body and a protective effect on tissue damage caused by oxidative stress, and it probably plays a protective role against NAFLD [8, 9]

  • Han et al revealed a significant positive association between low VC intake and NAFLD in the male population in a cross-sectional study [11]. Another small sample cross-sectional study suggested that both dietary VC intake and plasma VC concentration were of similar levels between patients with NAFLD and healthy controls [12]

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Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common chronic liver disease globally, with almost 25% prevalence in the general population [1]. Han et al revealed a significant positive association between low VC intake and NAFLD in the male population in a cross-sectional study [11]. Another small sample cross-sectional study suggested that both dietary VC intake and plasma VC concentration were of similar levels between patients with NAFLD and healthy controls [12]. A recent meta-analysis investigating VC supplementation and insulin resistance found that doses of ≥200 mg/day VC significantly reduced glucose concentrations in patients with T2DM, mainly if the intervention was for more than 30 days and in older individuals [20]

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