Nutritional friend or foe? Vitamin E sends mixed messages

One of the most powerful antioxidants is truly a double-edged sword, say researchers at Ohio State University who studied how two forms of vitamin E act once they are inside animal cells.

In the past couple of decades, a slough of studies has looked at the benefits of vitamin E and other antioxidants. While a considerable amount of this research touts the advantages of consuming antioxidants, some of the studies have found that in certain cases, antioxidants, including vitamin E, may actually increase the potential for developing heart disease, cancer and a host of other health problems.

This study provides clues as to why this could happen, say Jiyan Ma, an assistant professor of molecular and cellular biochemistry, and his colleague David Cornwell, an emeritus professor of molecular and cellular biochemistry, both at Ohio State.

The two men led a study that compared how the two most common forms of vitamin E –– one is found primarily in plants like corn and soybeans, while the other is found in olive oil, almonds, sunflower seeds and mustard greens – affect the health of animal cells. The main difference between the two forms is a slight variation in their chemical structures.

In laboratory experiments, the kind of vitamin E found in corn and soybean oil, gamma-tocopherol, ultimately destroyed animal cells. But the other form of vitamin E, alpha-tocopherol, did not. (Tocopherol is the scientific name for vitamin E.)

“In the United States we tend to eat a diet rich in corn and soybean oil, so we consume much greater amounts of gamma-tocopherol than alpha-tocopherol,” Cornwell said. “But most of the vitamin E coursing through out veins is alpha-tocopherol – the body selects for this version. We want to know why that is, and whether the selection of the alpha-tocopherol confers an evolutionary benefit in animal cells.”

Cornwell and Ma explain their findings in this week’s Early Edition of the Proceedings of the National Academy of Sciences. They conducted the study with several colleagues from the departments of molecular and cellular biochemistry and chemistry at Ohio State.

The researchers conducted laboratory experiments on cells taken from the brains of mice. They treated some of the cells with metabolic end products, called quinones, of alpha- and gamma-tocopherol.

When the body breaks down vitamin E, these end products are what enter and act on our cells. However, Ma said that our bodies get rid of most gamma-tocopherol before it ever has a chance to reach its quinone stage.

Still, some nutritional supplement companies make and sell gamma-tocopherol supplements, promoting this version of vitamin E as a good antioxidant source. In theory, taking a vitamin supplement – a concentrated form of the vitamin – increases the amount of that substance in the body.

Using laboratory techniques that allowed them to detect the activity of the quinones inside the cells, the researchers found that the gamma-tocopherol quinone formed a compound which destroyed that cell. It did so by preventing proper protein folding in the cells, which causes a cellular response that is involved in a variety of human diseases, including diabetes and Parkinson’s disease.

However, the alpha-tocopherol quinone did not kill cells, nor did it interfere with protein folding. The researchers repeated their experiments on kidney cells cultured from monkeys and on skin cells cultured from mice and found similar results.

“We think that gamma-tocopherol may have this kind of damaging effect on nearly every type of cell in the body,” Ma said.

While the study doesn’t get into the possible effects on health, the researchers raise the point that there is still a great deal that isn’t known about how antioxidants act in the body. In order to get to that point, scientists must study how antioxidants and cells interact on their most fundamental levels.

This work was funded through grants from the National Science Foundation Environmental Molecular Science Institute and the Large Interdisciplinary Grants Program in the Office of Research at Ohio State.