To the Editor:

Antioxidants are considered a promising tool for obese individuals with nonalcoholic steatohepatitis (NASH) who are unable to lose weight. However, a beneficial effect of these drugs needs still to be proven, since it has hitherto been inferred only from few pilot studies.1 Therefore we read with interest the paper of Kugelmas et al.,2 who evaluated in patients with NASH the effects of diet and exercise ± antioxidant vitamin E (800 IU daily) on cytokines profile and liver function tests. Regarding the latter aspect, they concluded that this dose of vitamin E provided no apparent added benefit upon serum transaminase levels. In our opinion, this conclusion did not take into sufficient consideration the eclipsing of vitamin E effects by patients' unpredictable extent of lifestyle modifications and/or adherence to drug prescription itself.

On this subject, we recently compared in a single-blind, randomized study the effect of vitamin E (α-acetate tocopherol, 400 IU/day) versus placebo on transaminase values and ultrasonographic bright liver in 28 children with obesity-related nonalcoholic fatty liver disease (NAFLD) treated with low-calorie diet and exercise.3 Baseline liver biopsy was available only in 10 patients. In line with Kugelmas et al., variations in transaminase levels and percentage of patients who normalized transaminase values were comparable in the two groups. However, looking at the subgroup of patients adherent to vitamin E intake (as shown by a twofold increase of vitamin serum levels) but unable to lose weight, we found that all of them normalized transaminase levels. Changes of their transaminase values were comparable to those obtained in children of the placebo group who lost weight (differences between means of baseline alanine aminotransferase values and alanine aminotransferase values after 2 months of treatment were −26 U/L and −31 U/L, respectively; P = 0.54). However, vitamin E was not effective upon ultrasonographic liver brightness. Our results are in keeping with data from two uncontrolled pilot studies in adolescents4 and adults5 with NASH, where comparable doses of vitamin E had been used. Interestingly, in our study also, compliance to vitamin E itself was variable: Only 10/14 patients reached serum values compatible with a correct taking of the drug.

Compliance to vitamin E therapy, based on blood levels, unfortunately could not be evaluated in the Kugelmas et al. paper. However, we believe that reevaluation of their results after stratifying the two patient groups on the basis of their veritable compliance to a diet leading to substantial weight reduction might better define the distinct effects of lifestyle modification and vitamin E supplementation on liver function tests.

Regarding the Kugelmas et al. conclusion about the need of pilot trials to evaluate effectiveness of higher doses of vitamin E, one should consider that the amount of the drug chosen in their study is comparable to that successfully prescribed by others in NASH/NAFLD.3–5 It corresponds to several times (on average, 50 times) the vitamin E daily requirements, and it has been considered adequate to expect an antioxidant effect in controlled studies regarding other oxidative stress-related diseases.6–7


  1. Top of page