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Vitamin E and metformin do not reduce liver enzyme levels in pediatric nonalcoholic fatty liver disease

Clinical Question:
Does vitamin E or metformin reduce elevated liver enzyme levels in children with nonalcoholic fatty liver disease?

Bottom Line:
Neither vitamin E nor metformin significantly reduces alanine aminotransferase (ALT) levels in children and adolescents with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD). Given the potential concern regarding an increased risk of all-cause mortality in adults treated with vitamin E, it seems prudent not to recommend this treatment for children and adolescents with NAFLD. (LOE = 1b)

Lavine JE, Schwimmer JB, Van Natta ML, et al, for Nonalcoholic Steatohepatitis Clinical Research Network. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents. The TONIC randomized controlled trial. JAMA 2011;305(16):1659-1668.  [PMID:21521847]

Study Design:
Randomized controlled trial (double-blinded)



Outpatient (any)

These investigators identified 173 children and adolescents, aged 8 years to 17 years, with biopsy-confirmed NAFLD and persistently elevated levels of ALT. All patients and their parents received standard instructions on diet and exercise. In addition, study patients randomly received (concealed allocation assignment) either (1) metformin 500 mg twice daily and placebo; (2) vitamin E 400 IU twice daily and placebo; or (3) double placebo. Patients underwent scheduled clinic visits 4 weeks and 12 weeks after randomization, and then every 12 weeks through 96 weeks total. Complete follow-up occurred for 87% of participants. Liver biopsy was performed on all remaining participants at 96 weeks. Individuals assessing outcomes remained masked to treatment group assignment. Using intention-to-treat analysis, the primary outcome of a sustained reduction in ALT level, defined as 50% or less of the baseline level or 40 U/L or less at each visit, occurred similarly in all 3 groups. No significant differences were found between the 3 groups regarding overall lipid or fasting glucose levels, changes in physical or emotional functioning, or quality of life. The study was 88% powered to detect a clinically relevant reduction in ALT level.


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