The idea that antioxidant vitamins provide a safe, convenient way to protect the heart from disease appears to have hit a snag. Instead of protecting the heart, a new study suggests that the vitamins, such as E, C, and beta carotene, could raise the liver's production of the so-called bad form of cholesterol, which transports cholesterol into artery walls.
The study, led by New York University School of Medicine researcher Edward A. Fisher, is published in the Journal of Clinical Investigation.
"It does appear that antioxidant vitamins may be potentially harmful for the heart based on their ability to increase the secretion of VLDL (very low density lipoprotein) in the liver cells and in the mice that we studied," says Dr. Fisher.
After its secretion from the liver, VLDL is converted in the bloodstream to low-density lipoprotein (LDL), the so-called bad form of cholesterol. The liver is the major source of atherosclerosis-causing lipoproteins. "However, our study is the first to document this association between antioxidant vitamins and VLDL cholesterol, and more studies are needed to back up our findings," says Dr. Fisher. "Until more data becomes available, we can't make any recommendations about whether people should not use these vitamins."
Antioxidants usually have been considered healthful. The vitamins scavenge "free radicals", which are highly reactive and damaging forms of oxygen produced by natural metabolic processes in the body and by external sources like the sun's UV rays, ozone, and toxins in pesticides. In the early 1990s, laboratory studies suggested that antioxidant vitamins prevented biochemical changes that made cholesterol form plaques that can block blood flow through the arteries. Although some subsequent clinical studies seemed to back up these findings, others did not.
The new study by Dr. Fisher and his colleagues provides a different perspective on antioxidants. Surprisingly, his group found that antioxidants hampered a process in the liver that prevents the production of harmful lipoproteins.
In further experiments, vitamin E, a well-known antioxidant, prevented the activation of the lipoprotein-breakdown pathway in rat and mouse liver cells. Thus, the liver destroyed fewer of the bad lipoproteins.
The study also explains why polyunsaturated fatty acids, the good fatty acids found in cold water fish, are healthy for the heart. In another series of experiments, the scientists show that omega-3 and omega-6 fatty acids activated the pathway in the liver that breaks down the bad lipoproteins. Dr. Fisher's group recently described this pathway, which they dubbed PERPP for post-ER presecretory proteolysis.
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."