Vulnerability to Fructose Varies, Health Study Finds

By ANAHAD O’CONNOR OCTOBER 13, 2014 9:20 PM

Fructose, a sugar widely consumed in the form of high-fructose corn syrup, may promote obesity and diabetes by overstimulating a hormone that helps to regulate fat accumulation, researchers reported on Monday.

The study, carried out at Harvard Medical School, marks the first time that scientists have identified a hormone that rises sharply and consistently in response to eating fructose. The finding suggests that people may vary in their sensitivity to the sugar, and that eventually it may be possible to test an individual for susceptibility to illnesses linked to weight gain.

Fructose stimulated the sharpest rise in the hormone in people who were obese, an increase that the researchers believe may trigger resistance to its effects, according to the study, which was published in the journal Molecular Metabolism. But even among lean people, there was wide variation in this response.

“This shows us that different people for whatever reasons have differences in their fructose metabolism,” said Dr. Mark A. Herman, an assistant professor of medicine at Harvard and an author of the study. “It suggests that fructose may be relatively safer for some people than others.”

Most researchers agree that no single factor is responsible for the nationwide obesity epidemic, but the rise in sugar consumption that began several decades ago is considered a likely contributor. Between 1970 and 2000, the amount of added sugars in the food supply rose 25 percent.

Some of this was in the form of table sugar, or sucrose — a molecule of fructose bound to a molecule of glucose. But much of the increase stemmed from the introduction of high-fructose corn syrup, a cheaper sweetener that usually contains slightly more fructose than glucose.

When these sweeteners are consumed, glucose is absorbed into the bloodstream and ushered into tissues like fat and muscle with assistance from insulin. But fructose takes a different route.

The vast majority of it goes to the liver, where it stimulates the production of triglycerides, some of which are packaged into lipoproteins with cholesterol and secreted into the bloodstream.

A buildup of these triglycerides in the liver itself leads to nonalcoholic fatty liver diseasean increasingly common metabolic disorder that affects about 10 percent of children and as many as a third of all adults. Fatty liver often coincides with insulin resistance, a precursor to Type 2 diabetes, and it is a strong risk factor for heart disease.

“There’s no question that fructose is a sugar that promotes fat storage in the liver,” said Christopher B. Newgard, the director of the Sarah W. Stedman Nutrition and Metabolism Center at Duke University School of Medicine, who was not involved in the study. “In that sense, it’s a sugar that is a bad actor in the development of metabolic syndrome and Type 2 diabetes.”

Metabolic syndrome refers to a constellation of cardiovascular risk factors that often occur together: abdominal fat, high blood levels of triglycerides and sugar, low levels of high-density lipoprotein, and elevated blood pressure.

In the new study, Dr. Herman and his colleagues recruited 21 adults, and then looked at what happened when they drank different solutions of sugars on different mornings. About half the people were lean and seemingly healthy; the other half were obese and at high risk of developing diabetes.

On one morning, the subjects drank 75 grams of glucose and then had their blood sugar measured over the next five hours. Doctors can diagnose diabetes with this procedure, known as a glucose tolerance test, by looking at whether blood sugar returns to normal levels over time or remains elevated, a sign that insulin is not properly clearing glucose from the bloodstream.

Some mornings the subjects were given the test with 75 grams of fructose instead of glucose. At other times, they were given a 75-gram mixture of fructose and glucose, similar to the sugar content of a 20-ounce bottle of Pepsi.

Glucose had only a minimal impact on the hormone, called fibroblast growth factor 21, or FGF21. But fructose increased its levels; the largest dose increased hormone levels fourfold within two hours on average.

The obese subjects had higher levels of FGF21 to begin with. And after they ate fructose, their peak levels of the hormone rose much higher than in the lean subjects.

FGF21 appears to be largely produced in the liver, and some researchers suspect that it helps to burn fat stores there and elsewhere in the body. But as fat accumulates and more of the hormone is released, the body may become desensitized to its effects.

“One of the reasons FGF21 could be so high in people with fatty liver disease is to try and clear fat out of the liver,” said another author of the paper, Dr. Eleftheria Maratos-Flier, a professor of medicine at Harvard.

But Dr. Newgard thinks there may be more to the story. He pointed out that in other studies, FGF21 seemed to play a very positive role, causing weight loss and lowering blood sugar in animals.

“What they’ve done here is opened up a whole new area that we have to sort out,” he said. “Why is fructose able to stimulate FGF21, and how does that relate to the known effects of fructose to be a bad actor in metabolic syndrome?”

The researchers said they planned to look at whether ethnicity and other factors influence the response to fructose. And they cautioned that some foods would likely have less of an impact on FGF21, like fresh fruit, which has fiber that slows the rate at which its fructose is metabolized.

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