An international team of researchers found that antioxidants commonly promoted as being good for our health may speed up early onset of Type 2 diabetes by mopping up Reactive Oxygen Species (ROS) that may play a protective role in the early stages of Type 2 diabetes by enhancing insulin action.

The study was led by Professor Tony Tiganis from the Department of Biochemistry and Molecular Biology at Monash University in Victoria, Australia and is published in the 7 October issue of the journal Cell Metabolism. Other members of the team included 12 researchers from Monash, and colleagues from the Baker IDI Heart and Diabetes Institute, University of Melbourne, and Cold Spring Harbor Laboratory in the US.

The sales pitch of promoters of antioxidant vitamin and other supplements is that they prevent the damage that “free radicals” or Reactive Oxygen Species (ROS) can do to us by causing “oxidative stress” to our cells. This is based on evidence that antioxidants in healthy foods like fruits and vegetables protect us from cancer and other diseases like insulin resistance and type 2 diabetes thought to result from cells producing too much ROS.

But there is now mounting evidence that the situation is not as straightforward as it may seem, and like many things in biology, it is all about balance, and that small amounts of seemingly harmful substances actually play vital roles in preserving health.

For instance, studies in worms have suggested that antioxidants can reduce lifespan, and some studies in humans have suggested the same. Other research has also shown that antioxidants may counteract the longer term benefits of exercise training by lowering the activity of certain genes involved in ROS defence.

In this study, Tiganis and colleagues showedd that low levels of ROS — and hydrogen peroxide in particular — might actually protect us from diabetes, by improving our sensitivity to insulin signals.

Tiganis told the press that:

“Our studies indicate that ‘physiological’ low levels of ROS may promote the insulin response and attenuate insulin resistance early in the progression of type 2 diabetes, prior to overt obesity and hyperglycemia.”

“In a way, we think there is a delicate balance and that too much of a good thing – surprise, surprise – might be bad,” he added.

Tiganis and colleagues found that mice specially bred so they could not eliminate physiological ROS didn’t develop insulin resistance when fed a high-fat diet, as they otherwise would have.

But when these mice were given antioxidants, which “mopped up” ROS, the improved insulin response was lost and the mice showed more signs of diabetes.

“ROS molecules, such as hydrogen peroxide, are important for normal cell function”, said Tiganis.

“We have shown that ROS present in muscle enhance insulin action and help lower blood sugar levels,” he added.

Tiganis suggested that perhaps state of health influences whether antioxidants do people harm or good.

“In the case of early type 2 diabetes and the development of insulin resistance, our studies suggest that antioxidants would be bad for you,” he said, explaining that under some conditions, treatments that selectively increase ROS in muscle might even help, if they could be developed.

He said it will be necessary to work out at what stage ROS turns from a benefit into a harm.

“There’s a ‘yin and yang’ relationship that takes place, wherein ROS are beneficial in the early stages of Type 2 diabetes and shift to being harmful at later stages of the disease,” explained Tiganis, suggesting it may also depend on how much ROS are around where they came from. (ROS are made in two places: on cell surfaces and also by mitochondria, the energy-producing centres inside cells.)

Tiganis was also of the opinion that it is probably not a good idea to take daily antioxidant supplements if you are healthy.

“Although we need to undertake further studies in humans, our results indicate that the widespread use of antioxidants by the general public as a preventative measure is something that should be discouraged, particularly if you are otherwise healthy,” said Tiganis.

He said healthy people should stick to a healthy diet and do exercise because this is a natural way of making ROS that promotes insulin action.

“Reactive Oxygen Species Enhance Insulin Sensitivity.”
Kim Loh, Haiyang Deng, Atsushi Fukushima, Xiaochu Cai, Benoit Boivin, Sandra Galic, Clinton Bruce, Benjamin J. Shields, Beata Skiba, Lisa M. Ooms, Nigel Stepto, Ben Wu, Christina A. Mitchell, Nicholas K. Tonks, Matthew J. Watt, Mark A. Febbraio, Peter J. Crack, Sofianos Andrikopoulos and Tony Tiganis.
Cell Metabolism, Volume 10, Issue 4, 260-272, 7 October 2009

Source: Cell Press, Monash University.

Written by: Catharine Paddock, PhD