The scientists also found that the polyunsaturated fatty acids increased the generation of lipid peroxidation products (these compounds produce the nasty smell of rancid fish) and stimulated the PERPP pathway. In addition to the studies with liver cells in laboratory dishes, they also demonstrated the relationship between lipid peroxidation and reduced production of bad lipoproteins in living mice.

Dr. Fisher plans to conduct further experiments in mice to confirm these findings. Direct experimentation in people to explore the inner workings of the liver is difficult, says Dr. Fisher, "but there are already observational studies in normal people showing that a diet enriched in polyunsaturated fats increases blood levels of lipid peroxides and decreases levels of VLDL and LDL."

Antioxidants may still have beneficial affects on other parts of the body, says Dr. Fisher. The molecules, for example, have been shown in some animal studies to protect the arteries from atherosclerosis and the pancreas and other organs from damage caused by diabetes. "In other words, oxidant stress is damaging in some contexts, but probably beneficial in others," he says. "In terms of the risk of cardiovascular disease," he adds, the previous view that all oxidant stress is bad is probably an oversimplification.

In an editorial accompanying the study titled "Hold the antioxidants and improve plasma lipids?," Ronald Krauss of Children's Hospital Oakland Research Institute in California, writes, "Thus, although there is considerable evidence for the involvement of oxidative stress in many disease processes, including atherosclerosis, the potential for unintended outcomes of oxidant therapy should serve as a warning against proceeding with such treatment in the absence of clinical-trial evidence of benefit and safety."

The new study was supported by grants from the National Institutes of Health and the American Diabetes Association.