Too many antioxidants may play role in type 2 diabetes, new theory

US researchers believe they may have discovered a new cause of insulin resistance, the condition that leads to the increasingly prevalent type 2 diabetes. They say that high amounts of antioxidants may promote the disease, contradicting the general belief that antioxidants can improve insulin function.

Type 2 diabetes is one of the fastest growing and most costly disorders worldwide. There are currently more than 194 million people with diabetes worldwide, according to the International Diabetes Federation, and this number could reach 333 million by 2025.

Dietary factors have been cited as possible factors behind this rise. Obesity is known to impact insulin regulation but there is also research into the impact of different nutrients on insulin function. A study earlier this year suggested increased levels of iron could interfere with organ functions, particularly the body's ability to produce insulin.

Many studies have also looked at nutrients that protect against type 2 diabetes, including magnesium and vitamin D.

But now researchers at Cornell University report that higher-than-normal amounts of a selenium-containing enzyme could promote type 2 diabetes. The researchers found that mice with elevated levels of the antioxidant enzyme develop the precursors of diabetes at much higher rates than did control mice.

The trace mineral selenium is an antioxidant, a compound that is thought to fight the molecules that can damage cell membranes and genetic material and contribute to the development of cancer and heart disease. Many of the benefits of selenium are related to its role in the production of glutathione peroxidase, an antioxidant enzyme that helps detoxify the body.

"Although free radicals are known to be harmful and antioxidants helpful, our study suggests that we actually need some free radicals to regulate insulin sensitivity," said Xingen Lei, an author of the study published online and in the 15 June issue of the Proceedings of the National Academy of Sciences.

The researchers found that mice that were bred to overexpress glutathione peroxidase to up to three times above normal developed hyperglycemia, hyperinsulinemia and elevated plasma leptin. They also became 36 per cent heavier and twice as fat as did control mice. These conditions precede the development of type 2 diabetes.

Glutathione peroxidase, which holds about 60 per cent of the selenium in the body, is the most abundant selenium-containing protein in mammals. Lei noted that this is the first study to show that an antioxidant actually promotes insulin resistance, a precursor of type 2 diabetes.

"Although antioxidants are beneficial for health, too many may be harmful and we need to be much more cautious in making recommendations to supplement the diet with them," he said.

"Most people believe that both selenium and the selenium-containing enzyme are good for health by protecting cells and tissues from oxidation. However, this study suggests that they are a double-edged sword," Lei continued.

"Antioxidants can be harmful by neutralizing too many free radicals and interfering with insulin signaling, which results in promoting obesity, insulin resistance and possibly diabetes."

He added that these findings are consistent with a recent study of pregnant women that reported on a link between high levels of glutathione peroxidase, insulin resistance and gestational diabetes.

"Before people blindly supplement their diets with antioxidants, such as selenium and vitamins E and C, more research is needed," Lei concluded.

The researcher plans to put the obese mice from this study on a diet to see if weight loss and fat loss can prevent or improve the mice's insulin sensitivity.

The study was presented to the Experimental Biology 2004 meeting in Washington DC in April.