Editorial Note: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 32% of the global population. Without proper intervention, it can progress to metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). Currently, treatment options for MASH are limited, and the antioxidant vitamin E has been considered a potential therapeutic candidate.To explore this possibility, Dr. Junping Shi from the Affiliated Hospital of Hangzhou Normal University led a nationwide, multi-center, large-sample, randomized, double-blind, placebo-controlled clinical trial known as the VENS study (Vitamin E Versus Placebo for the Treatment of Non-Diabetic Patients with Nonalcoholic Steatohepatitis). This study aimed to evaluate the efficacy and safety of moderate-dose vitamin E (300 mg/day) in non-diabetic MASH patients. The findings were published on February 18, 2025, in Cell Reports Medicine (Impact Factor: 11.7) under the title “Vitamin E (300 mg) in the treatment of MASH: A multi-center, randomized, double-blind, placebo-controlled study.”
Study Overview
The VENS study enrolled 124 biopsy-confirmed non-diabetic MASH patients from 15 medical centers in China between January 2017 and July 2021. Participants were randomly assigned to receive either 300 mg of vitamin E daily or a placebo for 96 weeks. The primary endpoint was the improvement in liver histology, while secondary endpoints included improvements in steatosis, lobular inflammation, and fibrosis stage. Throughout the study, all participants received personalized lifestyle guidance.
Key Findings
After 96 weeks of treatment, the study demonstrated significant histological improvement in the vitamin E group. A total of 29.3% of patients in the vitamin E group achieved the primary endpoint, which was significantly higher than the 14.1% in the placebo group (OR = 2.5, 95% CI: 1.0–7.1, P = 0.04). Vitamin E treatment also led to significant improvements in multiple secondary endpoints, including reductions in steatosis, lobular inflammation, NAS score, and fibrosis stage, confirming its positive effects on liver histology.
There was no significant difference in adverse event rates between the vitamin E and placebo groups, and all reported adverse events were deemed unrelated to the study drug. The study also monitored biomarkers such as B-type natriuretic peptide (BNP) and prostate-specific antigen (PSA) in male participants, with results showing that these indicators remained within normal ranges before and after treatment. No cardiovascular events or prostate-related abnormalities were observed. These findings indicate that moderate-dose vitamin E exhibited a good safety and tolerability profile in this study.
Conclusions
The VENS study is the first liver biopsy-based randomized controlled trial on fatty liver disease conducted in mainland China. The results confirm that in non-diabetic MASH patients, a moderate dose of vitamin E (300 mg/day) for 96 weeks significantly improves liver histology while maintaining a good safety profile.
Research Team
This study was led by Professor Shi Junping from the Affiliated Hospital of Hangzhou Normal University, Professor Li Jie from Nanjing Drum Tower Hospital, Nanjing University Medical School, and Professor Zang Shufei from Shanghai Fifth People’s Hospital. The first authors include Dr. Song Yu from the Affiliated Hospital of Hangzhou Normal University, Dr. Ni Wenjing from Nanjing Drum Tower Hospital, Professor Zheng Minghua from the First Affiliated Hospital of Wenzhou Medical University, Professor Sheng Huiping from the General Hospital of Ningxia Medical University, and Professor Wang Jing from the Affiliated TCM Hospital of Southwest Medical University.
