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Persistent overeating by the obese generates massive free radical load, initiating artery disease

University at Buffalo

Endocrinologists at the University at Buffalo have pinpointed one of the mechanisms that place the obese at higher risk of atherosclerosis and subsequent heart attack.

Their study, published in the January issue of The Journal of Clinical Endocrinology and Metabolism, shows that persistent overeating in the obese exposes them to excessive oxidative damage from free radicals, the hyperactive oxygen molecules that damage arterial walls and initiate the accumulation of fatty deposits that eventually inhibit or block blood flow to the heart.

Moreover, the researchers found that severely restricting caloric intake decreased the production of free radicals by more than 50 percent, lowering the risk of developing heart disease without medication.

"Our research has shown for the first time that the obese carry a massive oxidative load," said Paresh Dandona, M.D., UB professor of medicine and primary author on the study. "This oxidative load causes the kind of changes in the blood stream that make obese people prone to heart disease.

"We've also shown for the first time that diet restriction alone can change their risk," he said. "Taking a pill is easier, but lifestyle change is just as effective and should be considered."

Dandona and colleagues at the Diabetes-Endocrinology Center of Western New York at Kaleida Health, which Dandona heads, set out to determine whether the generation of free radicals and other indices of oxidative damage decrease as a result of short-term calorie restriction and weight loss.

Their study subjects were nine obese nondiabetic men and women who were taking neither antioxidant vitamins nor medication for heart disease. Their weight ranged from 183 lbs. to 360 lbs., with a mean body mass index (BMI) -- a ratio of weight to height -- of 40.7. An individual with a BMI over 30 is considered obese.

After taking fasting blood samples, researchers placed the participants on 1,000-calorie diets, consisting of a 200-calorie commercial liquid diet drink for breakfast and lunch and a home-cooked 600-calorie dinner. They remained on the diet for four weeks, returning to the clinic weekly to be weighed and provide fasting blood samples. Participants were asked to maintain their normal level of physical activity.

At the end of four weeks, participants had lost an average of 10 pounds. Analysis of blood samples showed a marked decrease in both markers of oxidative damage and the generation of free radicals. The more than 50 percent fall in free radical concentrations was accompanied by a significant decrease in markers of oxidative damage to lipids, proteins and amino acids.

"This finding is important because it represents a dramatic reversal in the cardinal processes affecting atherogenesis without the use of any drug or antioxidant," Dandona said. "Despite the wide variation in BMI, the changes were consistent and therefore are intrinsic to the process of dietary restriction and weight loss."

All participants gained weight after the four-week intervention, and at three months post-study, the concentration of free radicals and indices of oxidative damage were higher than at its inception, the researchers found.


Additional authors on the study are Ahmad Aljada, Ph.D., UB research assistant professor of medicine; Richard Browne, Ph.D., UB research instructor in the Department of Social and Preventive Medicine; and Priya Mohanty, Husam Ghanim, Wael Hamouda, Anu Prabhala, Aqeela Afzal and Rajesh Garg, doctoral students working with Dandona.

The study was supported in part by the William G. McGowan Charitable Fund.

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