Some antioxidants promote oxidation of `bad' cholesterol

Under certain circumstances, antioxidants don't act like the arterial plaque-fighting supermen they've been touted as being, reported Emory researchers in the June issue of the Journal of Clinical Investigation. In fact, antioxidants can become villains, promoting the dangerous oxidation of low-density lipoproteins (LDLs, the "bad" cholesterol) that initiates the clogging of arteries, the researchers said.

Antioxidants have been revered for their ability in animal studies to rein in the free radicals involved in oxidation. But the Emory researchers found that some antioxidants, including vitamin E, produce their own radicals in certain circumstances.

"Despite vast interest in the oxidative processes that may be involved in atherogenesis, the specific nature of the involvement is poorly understood," reported Nalini Santanam and Sampath Parthasarathy. "On the one hand there is increased urgency to validate the hypothesis in humans. On the other hand, a detailed understanding of the mechanism(s) of the oxidative pathways is warranted, as such an understanding would lead to the development of more specific inhibitors. Furthermore, an understanding of the malfunctioning of the oxidative pathway would help to devise preventive strategies.

"The findings of the epidemiological studies and prospective studies may suggest beneficial effects of long-term consumption of antioxidants in normal humans. On the other hand, the deleterious effects of beta carotene and the lack of effect of vitamin E observed in smokers in preventing cancer deaths would suggest that small doses of antioxidants may be ineffective in oxidatively challenged humans. The results presented in our study confirm the findings of Bowry et al. which suggest that, when antioxidant radicals are generated, they may participate and promote further oxidation. Adequate availability of free antioxidants to inhibit the propagation of lipid peroxidation or the choice of an antioxidant that does not generate a propagating radical may afford better protection."

Paradoxically, the pro-oxidant effects themselves may be helpful in oxidizing and clearing LDL from plasma, Parthasarathy said.

He is professor and director of research for the Department of Gynecology and Obstetrics (GYN/OB), and a professor of medicine (cardiology) at the School of Medicine. Santanam is a post-doctoral researcher in the GYN/OB laboratory. The study was funded by the Department of GYN/OB.

-- Lorri Preston