University of Florida scientists find sugar may have a sour side

Public Release Date 6-December-05

Fructose may trick you into thinking you are hungrier than you should be.
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."

Contact: Melanie Fridl Ross
ufcardiac@aol.com
352-690-7051
University of Florida