When antioxidants go bad

Antioxidants are good for your health in many ways. But too much of them can lead to disease, new research shows.

People with an inherited mutation of a gene called alpha-B crystallin can suffer progressive heart failure, but nobody has known why. Now it appears that the mutation leads to an excess of natural antioxidants that damage heart cells.

Researchers led by Ivor J. Benjamin of the University of Utah in Salt Lake City inserted the mutant human gene into the DNA of mice. As in people with the disease called protein-aggregation cardiomyopathy, the mice developed enlarged hearts and abnormal clumps of the alpha-B crystallin protein in their heart cells. The mice eventually died of heart failure.

The mouse cells responded to the clumps by producing a natural antioxidant called glutathione, the team reports in the Aug. 10 Cell. Chronic overproduction of the compound changed the chemical environment in the cell from oxidative to the opposite, a reductive state.

“If you change to a reductive state, then the whole protein-folding mechanism is affected,” explains coauthor Namakkal S. Rajasekaran, also of the University of Utah. Impairment of the cells’ ability to make new proteins could be the reason that the inherited mutation causes heart failure, he says.