Vitamin E Significantly Improves Liver Health in MASH Patients, New Studies Find

Vitamin E Significantly Improves Liver Health in MASH Patients, New Studies Find

New research shows that vitamin E therapy significantly improves liver function and reduces inflammation in MASH patients, providing a safer and effective treatment option in the fight against metabolic liver disease.

Study: Vitamin E (300 mg) in the treatment of MASH: A multicenter, randomized, double-blind, placebo-controlled trial

In a study recently published in the journalCell Reports MedicineA group of researchers examined the effectiveness and safety of 300 mg of vitamin E in improving liver histology and biochemical markers in participants with metabolic dysfunction-associated steatohepatitis (MASH).

background

Did you know that almost 30% of the world's population is affected by metabolic dysfunction associated steatotic disease (MASLD)? This silent epidemic increases the burden of liver-related complications, including cirrhosis and liver cancer. Mash, the progressive form of Masld, is characterized by hepatocellular damage and inflammation driven by oxidative stress and metabolic dysfunction. Despite lifestyle interventions, effective pharmacological options remain limited. Selective thyroid hormone receptor-β agonist resmetirome was recently approved for moderate to advanced fibrotic pulp, but treatment gaps remain.

Vitamin E, a natural antioxidant, has shown potential in reducing liver inflammation, but its optimal dosage, long-term effects and safety profiles require further evaluation. Identifying a safe and effective vitamin E dosage for MASH treatment could transform patient outcomes worldwide. Further research is needed to establish definitive treatment regimens.

About the study

Minimal adverse effects with no safety red flags: Vitamin E was well tolerated over 96 weeks, with no cases of prostate cancer, cardiovascular events, or hemorrhagic stroke addressed in previous concerns associated with high-dose vitamin E.

A multicenter, double-blind, randomized, placebo-controlled study was conducted in 14 clinical centers in China. Participants diagnosed with biopsy-proven MASH were recruited and randomly assigned in a 1:1 ratio to receive either vitamin E (300 mg per day) or placebo for 96 weeks. All participants received nutritional and exercise recommendations throughout the study period.

Baseline and posttreatment liver biopsies were reviewed centrally by independent hepatopathologists blinded to treatment assignment. The primary endpoint was histologic improvement, defined as a reduction in nonalcoholic fatty liver disease activity (NAS) score of at least 2 points, with no worsening of fibrosis. The study followed a modified intention-to-treat (MITT) approach, with sensitivity analyzes performed to confirm robustness.

Secondary endpoints included regression of fibrosis, resolution of steatohepatitis, and changes in liver enzymes, inflammatory markers, and metabolic parameters. Fibroscan-based liver stiffness measurement (LSM) was also assessed to provide additional insight into fibrosis progression.

Biochemical parameters were assessed at regular intervals, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting plasma glucose, and proinflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and interleukin-6 [IL-6]). Statistical analyzes were performed using SAS 9.4 and R 4.2.3 with analysis of covariance models (ANCOVA) used for continuous variables and logistic regression for binary outcomes. The study adhered to strict ethical guidelines and all participants provided informed consent.

Study results

The personalized lifestyle guideline was an essential part of the trial: all participants received individual dietary and exercise recommendations, monitored through a mobile app, to ensure a consistent approach to lifestyle management alongside supplementation.

A total of 124 participants were enrolled with 58 in the vitamin E group and 66 in the placebo group. Baseline characteristics, including age, sex distribution, and metabolic parameters, were comparable between groups. The average age was approximately 38 years, with male participants (72.4% in the vitamin E group and 75.8% in the placebo group).

Statistically significant 29.3% of participants who received vitamin E [OR]: 2.5; 95% confidence interval [CI]: 1.0-7.1; p = 0.04). Subgroup analyzes showed greater improvement in men, participants younger than 40 years, and those with baseline NAS scores of 5 to 8.

Fibrosis regression of at least one stage without worsening of steatohepatitis was observed in 25.9% of the vitamin group in the placebo group, but this difference was not statistically significant (OR: 1.9; 95% CI: 0.7-5.2; p = 0.16). However, Fibroscan liver stiffness (LSM) measurement showed significant improvement in the vitamin E group (P = 0.04), indicating potential long-term benefits, although biopsy-based fibrosis results did not reach statistical significance.

Steatohepatitis resolution without worsening fibrosis was observed in 12.1% of the vitamin E group compared with 17.2% in the placebo group (OR: 0.7; 95% CI: 0.2-2.0; P = 0.43). Nevertheless, a significant reduction in steatosis (P = 0.01), lobular inflammation (P = 0.04), fibrosis score (P = 0.04) and total NaS score (P = 0.03) were observed in the vitamin E group.

Liver enzyme levels improved significantly in the vitamin E group, with ALT and AST reductions of 20% and 18%, respectively. Serum proinflammatory cytokine levels, including TNF-α and IL-6, also showed a significant reduction in the treatment group compared to placebo (IL-6, p = 0.04).

Security and additional insights

Minimal adverse effects with no safety red flags: Vitamin E was well tolerated over 96 weeks, with no cases of prostate cancer, cardiovascular events, or hemorrhagic stroke addressed in previous concerns associated with high-dose vitamin E.

A comprehensive safety analysis revealed no significant differences in adverse events between groups. The most commonly reported events were mild gastrointestinal symptoms, which occurred in 12% of the vitamin E group and 6% of the placebo group. Importantly, no participants developed prostate cancer, cardiovascular events or a hemorrhagic stroke during the study, addressing previous concerns about high-dose vitamin E supplementation.

Exploratory analyzes showed that vitamin E was associated with improved metabolic parameters, including the Nasten Insulin and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). However, no significant differences in lipid profiles or body mass index (BMI) were found between groups.

Genetic analysis of the participants revealed a dominance of the HP 2-2 haptoglobin genotype, which was associated with the regulation of oxidative stress. Although preliminary, this finding suggests a possible genetic influence on vitamin E responsiveness in MASH patients.

Sensitivity analyzes confirmed the accuracy of the results and reinforced the potential of vitamin E as a promising treatment for MASH.

Conclusions

The study showed that 96 weeks of treatment with 300 mg of vitamin E significantly improved liver histology and inflammatory markers in participants with biopsy-proven MASH. While fibrosis regression did not reach statistical significance, improvements in steatosis, lobular inflammation, liver stiffness and enzyme levels suggest a potential therapeutic role for vitamin E.

The treatment was well tolerated with no safety concerns identified. Notably, no concerns about prostate cancer, cardiovascular risk, or hemorrhagic stroke associated with high-dose vitamin E were observed in this study.

These findings have significant implications for individuals facing liver disease with a noninvasive, accessible treatment option. At the community level, improved liver health could reduce healthcare burdens, while globally, effectively controlling MASH may help address the rising incidence of liver-related complications.

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