Vitamin E is one of the first lines of defense in human lung tissue against the ravages of cigarette smoke

A new study has found that supplements of vitamin C can largely stop the serious depletion of vitamin E that occurs in smokers, demonstrating for the first time in humans a remarkable interaction between these two antioxidants as they work together.

The research also suggests a possible mechanism by which smoking can cause cancer.

The findings are published in Free Radical Biology and Medicine, a professional journal, by scientists from the Linus Pauling Institute at Oregon State University.

The results of the research were based on a placebo-controlled, double-blind clinical study with smokers and non-smokers, and showed that supplements of 1000 milligrams of vitamin C per day could reduce by up to 45 percent the rate of disappearance of one form of vitamin E in smokers. In general, vitamin C supplements helped protect the function and plasma levels of vitamin E, so that smokers who took supplements had about the same level of antioxidant protection as non-smokers.

"A lot of nutrition research in the past has been done by studying one nutrient or another in isolation, sometimes with conflicting results," said Maret Traber, a professor of nutrition at OSU and lead researcher in the Linus Pauling Institute. "What this and other studies like it are showing is that the protection we get from proper diet or supplements often comes from combinations of nutrients working together. This has implications not only for smokers but also for many other people."

Vitamin E is one of the first lines of defense in human lung tissue against the ravages of cigarette smoke, Traber said, which creates destructive free radicals. If the body has adequate levels of vitamin E, this protective antioxidant can interact with the peroxyl radicals created by cigarette smoke and prevent the destruction of lung membranes.

In this process, however, vitamin E can itself be made into a destructive radical. If adequate levels of vitamin C are present, it can help the vitamin E return to non-radical form and continue its protective role. But in the absence of adequate vitamin C, this process breaks down. The new study is one of the first to ever demonstrate this phenomenon in humans.

This and other studies at the Linus Pauling Institute have also shown that in smokers, vitamin E is being depleted from tissue concentrations in order to keep up its levels in the blood.

"We've known for some time that smokers are under oxidative stress, because the smoke itself is an oxidant that creates free radicals and cell mutations," Traber said. "The immune response of the body also tends to cause inflammation, and this inflammation is one reason that smoking relates not only to lung cancer but other serious health problems such as diabetes, hypertension and heart disease."

By having a more rapid loss of protective antioxidants, Traber said, smokers face special challenges.

"Think of a bucket that's filled with water but has holes in it," she said. "If you want to keep the water level, you have to keep adding water. But with smokers, the holes in the bucket are bigger and the water level goes down faster. In the case of nutrition, you have to add more and more nutrients to stay even."

With smokers, she said, that rarely happens. In the general population, research has shown that only 8 percent of men and 2.4 percent of women have adequate dietary intake of vitamin E. And studies indicate that smokers often have a diet with lots of meat but low intakes of the fruits and vegetables that provide most antioxidants. So although smokers require higher levels of antioxidants to gain their protective benefits, their diets usually contain even lower dietary intakes than most people - and nearly 50 million Americans smoke cigarettes.

For antioxidant vitamins to play a role in disease prevention, experts say, they usually have to be present in advance. They are less successful in addressing existing disease. According to Traber, many of the studies showing "no benefit" from improved nutrition or vitamin supplements have been done in people with existing disease, or studying one nutrient at a time rather than combinations.

In this research, participants were asked to eat a diet low in fruits and vegetables for three months so they had low levels of vitamin C. Some members were then given vitamin C supplements, and others a placebo. Smokers who got vitamin C supplementation had a plasma vitamin E disappearance rate about the same as non-smokers. But smokers who were still deficient in vitamin C lost alpha vitamin E about 25 percent faster than non-smokers, and gamma vitamin E about 45 percent faster.

Other collaborators on this research were from Columbia University, The Ohio State University, the University of Washington, and Brock University in Canada. Richard Bruno, a doctoral student at The Ohio State University, was also a co-author. The research was funded by the National Institutes of Health.

"What this clearly shows is that to perform their vital roles, vitamins C and E work together," Traber said. "They have a synergistic effect that will not be gained just by intake of one or the other, and adequate levels of these nutrients is especially important for people who smoke."