Vitamin E dosing study (VEDS) in patients with metabolic dysfunction-associated steatotic liver disease with elevated aminotransferases: A multicenter, randomized, placebo-controlled trial.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) is a leading cause of liver disease. Despite recent drug approvals, there is a need for low-cost therapies. Potential safety concerns regarding higher doses of vitamin E led to this study.

APPROACH: Adults with suspected MASH, controlled attenuation parameter (CAP) score >280 dB/m on vibration-controlled transient elastography, and serum alanine aminotransferase (ALT) ≥60 U/L were randomized to 200, 400, or 800 IU of natural vitamin E (d-alpha tocopherol) or placebo once daily for 24 weeks. The primary aim was to determine the lowest effective dose of vitamin E that resulted in the greatest reduction in ALT levels from baseline to 24 weeks. Secondary aims were to assess improvements in other biomarkers of MASH, including liver fat and stiffness.

RESULTS

Two hundred participants (age 47.0+13.9 y; 62% male) completed protocol-based visits. Serum ALT levels decreased similarly compared with placebo with all 3 doses of vitamin E: -38% (200 IU), -36% (400 IU), and -36% (800 IU) compared with -12% with placebo ( p ≤0.001 for all). ALT levels normalized in more patients taking vitamin E (49%, 37%, and 50%) than with placebo (22%). AST levels also decreased significantly. Mean reduction in CAP and liver stiffness was non-significantly greater in vitamin E-treated groups. Adverse events were mild to moderate, with no life-threatening events, and similar between vitamin E and placebo.

CONCLUSIONS

Vitamin E administered at 200 IU/day was as effective as other doses tested in patients with MASLD and elevated aminotransferases. No safety signals were noted.