Daily Vitamin E Achieves Liver Histology Improvements in Patients With MASH

Key Takeaways

Vitamin E significantly improved liver histology in MASH patients, with 29.3% showing improvement versus 14.1% in the placebo group.
Significant reductions in steatosis, lobular inflammation, and fibrosis scores were observed with vitamin E treatment compared to placebo.
Hepatocyte ballooning did not show significant improvement between the vitamin E and placebo groups.
Adverse events were more frequent in the vitamin E group but were not considered treatment-related.

Patients with metabolic dysfunction-associated steatohepatitis (MASH) receiving 300 mg of vitamin E daily presented improved steatosis, lobular inflammation, and fibrosis stages.

Findings from a clinical trial published in Cell Reports Medicine indicate that 300 mg of vitamin E daily can achieve sound improvements in liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH). Additionally, serious adverse events (AEs) that were observed were not believed to be related to treatment, according to the authors.¹

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VENS was a multicenter, randomized, double-blinded, placebo parallel-controlled clinical trial (NCT02962297)² that assessed the efficacy and safety of treatment with vitamin E softgels in adult patients without diabetes and who have MASH (referred to as non-alcoholic steatohepatitis in the trial). The investigators screened and enrolled a total of 122 participants between January 2017 and November 2018, who were then randomly assigned to receive either 300 mg of vitamin E or placebo. Doses were administered in 100-mg oral softgels 3 times per day over a 96-week period.^1,2

The primary outcome measure was improvement in hepatic histology. This was assessed after 96 weeks of treatment and defined by histologic improvement, which required the following: either improvement in nonalcoholic fatty liver disease (NASH) activity score (NAS) by at least 2 points or post-treatment NAS of 3 points or less; at least 1 point improvement in the score for ballooning or lobular inflammation; and no worsening of fibrosis stages.²

According to the investigators, all participants received personalized lifestyle advice from dietitians during the trial’s timeframe. All groups were balanced for demographic and clinical characteristics. The mean ages were about 37.9 and 39.0 years in the vitamin E and placebo groups, respectively, and men accounted for approximately 72.4% (n = 42) and 75.8% (n = 50) of their respective groups. The corresponding mean body mass indexes (BMIs) were 26.7 kg/m² ²and 25.4 kg/m².^1,2

According to the investigators, hepatic histological parameters were well balanced between the 2 groups, with approximately 79.3% and 80.3% of participants in the vitamin E and placebo groups, respectively, presenting a NAS of at least 4 at the final central reading. Additionally, alanine aminotransferase and aspartate aminotransferase levels in the vitamin E group were 60.4 U/L and 33.6 U/L, respectively, compared with placebo, which were 60.1 U/L and 36.0 U/L. The liver stiffness measurement was 7.7 kPa in the vitamin E group and 6.5 kPa in the placebo group.¹

More participants had improved liver histology in the vitamin E group (29.3%) compared with the placebo group (14.1%; OR: 2.5, 95% CI [1.0–7.1]; P = .04). Additionally, similar results were seen in sensitivity analyses when baseline biopsy specimens were at local reading and post-96-week specimens were at central reading. Differences between the groups regarding fibrosis improvement by at least 1 stage without worsening of steatohepatitis after 96 weeks were not considered statistically significant (25.9% vs 15.6%, respectively; OR: 1.9, 95% CI [0.7–5.2]; P = .16). The composite end point of fibrosis improvement by at least 1 stage or steatohepatitis resolution without fibrosis worsening had also failed to achieve statistical significance (vitamin E: 37.9%; placebo: 32.8%; OR: 1.2, 95% CI [0.7–1.9]; P = .56).¹

About the Trial

Trial Name: Vitamin E Versus Placebo for the Treatment of Non Diabetic Patients With Nonalcoholic Steatohepatitis

ClinicalTrials.gov ID: NCT02962297

Sponsor: Zhejiang Medicine Co., Ltd.

Completion Date: December 17, 2021

Further, patients receiving vitamin E showed significant reductions in steatosis (win ratio [WR]: 2.5, 95% CI [1.3–5.0], P = .01), lobular inflammation (WR: 2.0, 95% CI [1.0–4.0]; P = .04), fibrosis score (WR: 2.1, 95% CI: [1.0–4.0], P = .04), and total NAS score (WR: 1.9, 95% CI [1.1–3.4], P = .03) when compared with placebo. Hepatocyte ballooning did not achieve significant improvement between the 2 groups, according to the investigators.¹

As far as safety, there were 11 AEs, of which 7 (12.07%) were in the vitamin E group. Within the 96-week intervention period, the incidence rate of AEs was about 7.17 cases and 4.21 cases per 100 person-years in the vitamin E and placebo groups, respectively. These AEs, however, were not considered to be related to treatment.¹

REFERENCES

1. Song Y, Ni W, Zheng M, et al. Vitamin E (300 mg) in the treatment of MASH: A multi-center, randomized, double-blind, placebo-controlled study. Cell Rep. 2025;6(2):101939. doi:10.1016/j.xcrm.2025.101939

2. Vitamin E Versus Placebo for the Treatment of Non Diabetic Patients With Nonalcoholic Steatohepatitis. ClinicalTrials.gov identifier: NCT02962297. Updated April 3, 2023. Accessed February 18, 2025. https://clinicaltrials.gov/study/NCT02962297