Effects of Oral Vitamin C Supplementation on Liver Health and Associated Parameters in Patients With Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial

Frontiers in Nutrition

Sep 2021

DOI: 10.3389/fnut.2021.745609

Citations:45

Influential Citations:2

Interventional (Human) Studies

Enhanced Details

Methods

Double-blind, randomized controlled trial in adults with NAFLD aged 18-60 years (mean age 40.6; 58.3% female). 98 participants enrolled, 84 completed. Stratified randomization by gender, age, weight, BMI, and waist circumference. Conducted at Xi'an Jiaotong University and Xianyang Central Hospital, Xi'an, Shaanxi, China.

Intervention

Vitamin C supplementation at 250 mg/day (Low), 1,000 mg/day (Medium), or 2,000 mg/day (High) taken orally before meals for 12 weeks.

Results

12 weeks of vitamin C supplementation improved liver function and glucose metabolism in NAFLD, with 1,000 mg/day showing the strongest liver enzyme reductions (AST and ALT) compared with 2,000 mg/day. Other liver markers improved similarly across groups. Fasting insulin and fasting glucose improved; HOMA-IR decreased. Plasma vitamin C and adiponectin (total and high-molecular-weight) increased. Fecal microbiota alpha diversity rose in the 250 mg/day and 1,000 mg/day groups, suggesting potential gut-liver axis involvement. Overall, daily VC supplementation, especially 1,000 mg/day, can help promote liver function recovery and glucose homeostasis in NAFLD.

Limitations

No placebo control; relatively small sample size per group; stool samples available for only a subset; not all liver-function markers showed significant between-group differences; short duration.

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. show less