Adjunctive vitamin E treatment in Wilson disease and suggestions for future trials
Authors: Liang Shen, Hong-Fang Ji
Journal: Hepatology (2010)

Wilson disease (WD) is a genetic disorder involving copper accumulation in various tissues, and oxidative stress plays a central role in its pathogenesis. We read with great interest the article by Linn et al.1 in which they report that long-term exclusive zinc monotherapy in patients with symptomatic WD generally led to a good outcome for neurological disease, whereas the results were less satisfactory in cases of hepatic disease. However, because of (1) the significantly lower serum vitamin E levels in WD patients treated with zinc2 and (2) the beneficial effects of vitamin E reported in WD animal models and also occasionally in WD patients, it is reasonable to assume the potential of vitamin E as an adjunctive treatment to further improve zinc treatment in WD, and rigorous trials should be conducted as suggested recently.3 More importantly, because of the disappointing trials of vitamin E in many oxidative stress–related diseases, including chronic liver diseases,4 Alzheimer's disease (AD),5, 6 cardiovascular diseases, and cancer,7 we suggest that the potential factors leading to the negative trials in these diseases should be taken into consideration when future trials of vitamin E in WD are conducted. For example, similarly to WD, both oxidative stress and excessive transition-metal ions (e.g., Cu2+) have been proved to play crucial roles in the pathogenesis of AD. However, among the numerous trials of vitamin E conducted for the prevention and treatment of AD, many have shown disappointing results.5, 6 For instance, it was recently reported that vitamin E was ineffective in preventing oxidative stress, did not prevent loss of cognition in AD patients, and may even have been detrimental.6 Moreover, the beneficial effects of vitamin E are still controversial, and many trials have failed to confirm any protective effect of vitamin E for either cardiovascular diseases or cancer.7 Therefore, the disappointing trials of vitamin E in many other diseases should be paid full attention, and future trials of vitamin E in WD will benefit from these disappointing trials. Besides the intrinsic limitations of antioxidants and the heterogeneity of biological systems attenuating the reactive oxygen species–scavenging capacity proposed by us,8 many other important factors have been suggested to be responsible for the disappointing trials of vitamin E.9, 10 Brewer9 recently analyzed why vitamin E is ineffective for the treatment of AD, and the reasons, including inappropriate doses, inappropriate timing, and unbalanced monotherapy in the trials, were presumed. In addition, Steinhubl10 provided several possibilities for the negative trials of vitamin E in atherosclerosis, such as the wrong form of vitamin E (a synthetic form instead of a natural form comprising eight different isoforms used in the trials), inadequate durations, and the wrong patients. All these aspects should be taken into account when rigorous trials of vitamin E in WD are conducted. In addition, the rational suggestions proposed by Lu4 for the antioxidant treatment of chronic liver diseases have important implications for future trials of vitamin E in WD. Liang Shen Ph.D.*, Hong-Fang Ji Ph.D.*, * Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Shandong University of Technology, Zibo, People's Republic of China.