Suddenly sugar isn't looking so sweet

University of Florida researchers have identified one possible reason for rising obesity rates, and it all starts with fructose, found in fruit, honey, table sugar and other sweeteners, and in many processed foods.

Fructose may trick you into thinking you are hungrier than you should be, say the scientists, whose studies in animals have revealed its role in a biochemical chain reaction that triggers weight gain and other features of metabolic syndrome - the main precursor to type 2 diabetes. In related research, they also prevented rats from packing on the pounds by interrupting the way their bodies processed this simple sugar, even when the animals continued to consume it.

The findings, reported in the December issue of Nature Clinical Practice Nephrology and in this month's online edition of the American Journal of Physiology-Renal Physiology, add to growing evidence implicating fructose in the obesity epidemic and could influence future dietary guidelines. UF researchers are now studying whether the same mechanism is involved in people.

"There may be more than just the common concept that the reason a person gets fat is because they eat too many calories and they don't do enough exercise," said Richard J. Johnson, M.D., the J. Robert Cade professor of nephrology and chief of nephrology, hypertension and transplantation at UF's College of Medicine. "And although genetic predispositions are obviously important, there's some major environmental force driving this process. Our data suggest certain foods and, in particular, fructose, may actually speed the process for a person to become obese."

Physical inactivity, increased caloric intake and consumption of high-fat foods undoubtedly account for part of the problem, Johnson said. But Americans are feasting on more fructose than ever. It's in soft drinks, jellies, pastries, ketchup and table sugar, among other foods, and is the key component in high fructose corn syrup, a sugar substitute introduced in the early 1970s.

Since then, fructose intake has soared more than 30 percent, and the number of people with metabolic syndrome has more than doubled worldwide, to more than 55 million in the United States alone, Johnson said. The condition, characterized by insulin resistance, obesity and elevated triglyceride levels in the blood, is linked to the development of type 2 diabetes and hypertension.

"If you feed fructose to animals they rapidly become obese, with all features of the metabolic syndrome, so there is this strong causal link," Johnson said, "And a high-fructose intake has been shown to induce certain features of the metabolic syndrome pretty rapidly in people."

Now UF research implicates a rise in uric acid in the bloodstream that occurs after fructose is consumed, Johnson said. That temporary spike blocks the action of insulin, which typically regulates how body cells use and store sugar and other food nutrients for energy. If uric acid levels are frequently elevated, over time features of metabolic syndrome may develop, including high blood pressure, obesity and elevated blood cholesterol levels.

Researchers from UF and the Baylor College of Medicine studied rats fed a high-fructose diet for 10 weeks. Compared with rats fed a control diet, those on the high-fructose diet experienced a rise in uric acid in the bloodstream and developed insulin resistance.

"When we blocked or lowered uric acid, we were able to largely prevent or reverse features of the metabolic syndrome," Johnson said. "We were able to significantly reduce weight gain, we were able to significantly reduce the rise in the triglycerides in the blood, the insulin resistance was less and the blood pressure fell."

UF researchers are now studying the uric acid pathway in cell cultures in the laboratory, in animals and in people, and are also eyeing it as a possible factor in the development of cardiovascular and kidney diseases because of its effects on blood vessel responses. They are conducting a National Institutes of Health-funded trial to determine if lowering uric acid in blacks with hypertension improves blood pressure control and are collaborating with scientists at Baylor to determine if lowering uric acid will reduce blood pressure in adolescents with hypertension.

"We cannot definitively state that fructose is driving the obesity epidemic," said Johnson. "But we can say that there is evidence supporting the possibility that it could have a contributory role - if not a major role. I think in the next few years we'll have a better feel for whether or not these pathways that can be shown in animals may be relevant to the human condition."

Findings to date suggest certain sugar carbohydrates are actually better than others, he added, because some do not activate the uric acid pathway.

"It may well be we don't need to cut out carbohydrates but just certain types of carbohydrates," Johnson said. "So this may be an alternative to the Atkins type of approach, which cuts out carbohydrates indiscriminately."

As scientists learn more about the pathway, Johnson said, and as studies are completed in people, the findings may influence how to make wise choices about the foods we eat.

"With the caveat that people are different from rodents in many ways, the link between urate levels, blood pressure elevation and insulin resistance demonstrated in rats fed fructose is extremely provocative," said Brian F. Mandell, M.D., Ph.D., vice chairman of medicine for education and a professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. "Whether the fructose supplementation to the diet in the United States is partially responsible for the 'epidemic' of obesity remains to be proven - but this is an association which can be tested, and the work of Dr. Johnson and his collaborators makes the evaluation of the fructose-metabolic link in people an academic and public health imperative."