Antioxidants — magic bullet for some, live grenade for others

Vitamins could worsen atherosclerosis in some women with diabetes, depending on their haptoglobin genotype

By Owen Dyer

There's been a sharp debate rumbling for some time about the benefits of vitamins in heart disease. Some studies suggest that antioxidants can prevent the progress of atherosclerosis, others have shown no benefit, and a few have suggested that vitamins can speed the disease's course by interfering with cholesterol levels and the effect of cholesterol lowering drugs.

Recent research has found that a simple blood test that's already on the market could help determine whether vitamins that prevent heart disease will help or harm older women with diabetes. The research was conducted jointly in Canada, Israel and the US, and published in the April issue of Diabetes Care.

In fact, said the researchers, a woman's response to antioxidant therapy depends partly on her genes for haptoglobin, the protein that binds free hemoglobin. Postmenopausal women with diabetes who carry two copies of the variation known as haptoglobin-2 actually increase their risk of atherosclerosis if they take vitamins C and E, said lead researcher Dr Andrew Levy.

The effects of antioxidants were studied in 299 postmenopausal women with at least partial blockage in one coronary artery. The women were randomly assigned to take either 400IU of vitamin E and 500mg of vitamin C twice a day, or placebos.

The effects of the vitamin therapy differed depending on the women's haptoglobin type. The researchers found that a three-year course of vitamin therapy slowed down atherosclerosis in women with a pair of haptoglobin-1 genes. Antioxidants were especially beneficial in women who suffered from diabetes with haptoglobin-1 genes.

But antioxidants seemed to accelerate the disease in women with diabetes carrying a pair of haptoglobin-2 genes. Women without the diabetes, however, experienced no negative effects from the antioxidants even if they carried a double dose of haptoglobin-2.

Fortunately, the test for haptoglobin type is commercially available. As a result of this research, Dr Levy believes all diabetics should be screened for haptoglobin type.

Researchers think that lesions in the arteries are caused in part by an oxidative process that attacks good cholesterol. So, antioxidants may protect arteries by blocking this oxidative process. Haptoglobin is itself an antioxidant protein, but some types are better than others. The haptoglobin-2 type is associated with high levels of iron that can convert antioxidants into pro-oxidants that actually increase the degradation of good cholesterol. The oxidative effect of high iron and sugar levels might explain why the findings were so much more pronounced in the diabetic subjects.

"The results will help not only determine how aggressively we should treat the person with regard to targets for blood pressure, cholesterol and blood sugar, but also determine whether antioxidant therapy is appropriate or inappropriate," said Dr Levy.

The team is now beginning a much larger study that will test their hypothesis in men and also in patients with child-onset diabetes.