December 20, 2005
More Evidence For Fructose Obesity Link

Fructose fruit sugar is not a harmless substitute for glucose.

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."

An increase in uric acid is involved in creating the negative consequences from fructose consumption.

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.

Blocking of uric acid prevented the weight and blood sugar problems.

"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.

I love it when a scientific discovery suggests obvious practical ways to make use of the new information.

"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."

So how can one keep uric acid levels down? Anyone know?

Also see my previous post "Fructose Consumption May Lead To Obesity".

Share |      Randall Parker, 2005 December 20 10:11 PM  Brain Appetite

Alan Little said at December 21, 2005 3:01 AM:

So might fructose consumption in the form of fresh fruit be a problem, or just pure refined fructose? I would have thought other benefits of fresh fruit - fibre, vitamin C, heavy-duty antioxidants in berries etc. - might outweigh any negative impact from the fructose

Bob Badour said at December 21, 2005 7:47 AM:

How to avoid uric acid?

Avoid purines and don't get fat:

auntulna said at December 21, 2005 8:45 AM:

Allopurinol has been used for many years to lower uric acid to control gout. The problem there is high uric acid levels lead to crystal formation in joints, then pain. The drug blocks a step in the synthesis of uric acid.

Uric acid has been noted to be elevated in metabolic syndrome, but it hasn't been known if it is a cause or just an associated finding. Elevated uric acid hasn't been treated unless symptoms of gout occurred.

This report may change thinking toward more aggressive control of uric acid levels.

Other recommendations have included losing weight, avoiding purine containing foods, but these are weaker factors than the probable inherited tendency to make too much uric acid.

Zeuswood said at December 21, 2005 10:53 AM:

Others beat me to it. Uric acid is associated with gout, making this doubly fascinating. The whole "diet and exercise" thing has always been way too simplistic when it comes to people being often inexplicably overweight or obese.

Marvin said at December 21, 2005 1:25 PM:

I have always thought that using corn to make high fructose syrup was a terrible waste. Jack Daniels and George Dickel knew very well the correct use of corn. Funny that it has taken science so long to learn.

Fly said at December 21, 2005 7:29 PM:

Disturbing news on creatine:

"In an article in the November Journal of Biological Chemistry, a team of Canadian and American scientists reports the first-ever finding of elevated levels of creatine-the newly discovered agent of Alzheimer's-in brain tissue."

Randall Parker said at December 21, 2005 9:42 PM:

I'd love to see a study done on humans on uric acid levels as compared to obesity and incidence of type II diabetes.

So legumes, beans, and peas raise uric acid. I had no idea. Shell fish, fish roe, and scallops: Can't remember last I ate them. Don't eat much red meat or kidney or liver either. I'm already on a low uric acid diet except for the pineapples I love to eat. Darn. Oh, and Craisins (cherry flavored dried cranberries).

tc said at December 22, 2005 12:01 AM:

Fructose makes you feel hungrier? A little while back there was a story about this professor who lost 40 pounds by drinking fructose water because it made him less hungry. Is he off his rocker?

James Cook said at December 22, 2005 6:26 AM:

I would be surprised if the increase in Brain creatine levels seen in Alzheimer's patients wasn't the result of the disease rather than being a causal factor.

lindenen said at December 22, 2005 10:49 AM:

Well, drinking a lot of water and only water would probably make anyone lose weight.

Doug said at December 22, 2005 6:55 PM:

As I recall, one mechanism of uric acid increase is very simply intake of carbohydrates to the extent that the body becomes so "habituated" to metabolizing glucose and other sugars that when it runs low on sugars, it metabolizes protein--either dietary protein or the lean tissues of the muscles, internal organs, and bone matrix--into glucose and then metabolizes the glucose. The uric acid, if I remember, is produced as a byproduct of the conversion of the protein to glucose. Uric acid can also be raised if one consumes protein in excess of what the body needs for maintenance, repair, and growth. All this is my recollection of what I read in Ron Rosedale's book, The Rosedale Diet. Rosedale also considers fructose more dangerous than glucose, as well as less needful. He acknowledges the importance of eating fruits, but encourages people to focus on the ones that make the greatest vitamin and anti-oxidant contributions and to eat fruits sparingly. He considers the lactose and galactose in milk more dangerous than glucose, also. I think I should add that the most important measures for Rosedale are those of serum leptin and insulin, although I think uric acid is down the list somewhere.

jimcrack said at December 23, 2005 7:50 PM:

They should attack on the acne angle too. Dermatologists stand by the mantra that if you want clear skin, avoid tomatoes (ie tomato sauce) and chocolate. Amazing the common denominator of most brands of both is high fructose at work, as entirely artificial additives. Good chocolate never hurt me, and I never met anyone who had an allergic reaction to a tomato (peanuts, that's another story)

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