In the report of Manning et al. (1), patient’s plasma peroxides were decreased by 29% at 6 months with a transient reduction in insulin resistance. Consequently, they postulate that vitamin E improves oxidative stress and hepatocellular function in overweight patients and suggest that “vitamin E could have a role to play in delaying the onset of diabetes in at-risk individuals (1).”
The rationale for vitamin E supplements protecting against diabetes is based on the assumption that it becomes depleted by reactive oxygen species and the expectation that vitamin E prevents the oxidative stress events linked to such oxidation. However, administered antioxidants could fail to intercept radical generation from discrete sources (cytoplasm, nucleus, and interstitial space). For example, myeloperoxidase is a major source of reactive oxygen species generation in inflammatory syndromes. However, myeloperoxidase-catalyzed lipid peroxidation is resistant to inhibition by vitamin E (2). Moreover, α-tocopherol may act as a prooxidant drug during lipid oxidation in vivo (2,3).
But theoretical considerations vanish against ethical concerns. Overweight patients have endothelial dysfunction and are “at-risk individuals” not only for diabetes but also for atherosclerosis. In clinical trials with antioxidants, it has been suggested that high-dose vitamin E has an acute toxic effect, and coronary heart disease can be expected (4) with its administration. Other studies (5) have also reported a nonsignificant excess in coronary deaths among those with a history of myocardial infarction who were receiving vitamin E.
In the Manning et al. article, were patients informed in detail before randomization to receive vitamin E that as a consequence of their overweight they could have increased mortality risks from coronary heart disease? Does the transient improvement in insulin resistance justify the authors’ suggestion that “vitamin E could have a role to play in delaying the onset of diabetes in at-risk individuals (1)” without alerting them about possible dangers associated with this approach? Scientific advances are difficult to obtain, but ethical constraints should not be forgotten.
