Fructose Does Not Cause Weight Gain in Isocaloric Diet

Kate Johnson

December 06, 2011

December 6, 2011 (Dubai, United Arab Emirates) — In a meta-analysis that promises to generate a spectacular debate, Canadian researchers have challenged what they call "the fructose-centered view of obesity" with the finding that fructose does not cause weight gain in the setting of a calorie-controlled diet.

The results were reported here at the International Diabetes Federation World Diabetes Congress 2011 by John Sievenpiper, MD, PhD, from McMaster University in Hamilton, Ontario, and his colleagues.

In presenting the findings, Dr. Sievenpiper added fuel to the fructose debate, which has already sparked inflammatory headlines, lively letters to journal editors, and impassioned YouTube lectures that have gone viral, elevating some of his opponents to almost "rock star status," he said.

Richard Johnson, MD, professor of medicine at the University of Colorado, Denver, and author of The Sugar Fix: The High-Fructose Fallout That Is Making You Fat and Sick, said he has concerns about the Canadian findings.

"The way fructose stimulates weight is by causing leptin resistance; hence, it will not be observed with short-term studies or with isocaloric diets. Understanding physiology is required," he told Medscape Medical News.

Although he acknowledged that the studies in the meta-analysis were short, Dr. Sievenpiper countered that criticism. "In terms of leptin, I'm not sure how much time one needs. The only data I'm aware of are animal data, and I have a lot of issues with animal data being used to underpin this debate."

Dr. Sievenpiper's study involved a systematic review and meta-analysis of controlled fructose feeding trials in humans.

Of 1984 articles on plain fructose (not high-fructose corn syrup) identified through database searches, 31 isocaloric trials (635 subjects) and 10 hypercaloric trials (119 subjects) met the criteria of being at least 7 days in duration, and thus were included in the study.

The meta-analysis showed that fructose feeding had no significant effect on body weight, even at "extreme doses" (104 to 250 g/day) across the isocaloric trials (median follow-up, 4 weeks).

"It should be noted that the median dose in these studies is well above what is generally consumed, certainly in the United States. If you look at the National Health and Nutrition Examination Survey data, the median intake is about 49 g," he said.

The hypercaloric trials tell a different story, showing a significant increase in body weight — about 0.5 kg over as little as 1.5 weeks.

"The problem with these studies is that it's very difficult to disentangle the relative contributions of excess energy from fructose," he said.

Only 5 of the isocaloric trials and none of the hypercaloric trials lasted longer than 12 weeks, which is a limitation of the analysis, Dr. Sievenpiper acknowledged, adding that about 60% of the studies were also of poor quality.

"There's a need for larger, longer, and higher-quality trials under real-world doses to confirm these results," he said.

Dr. Sievenpiper and colleagues presented other data at the meeting, which suggested that low "catalytic" doses of fructose actually have a beneficial metabolic impact because they blunt the glycemic response to high-glycemic meals.

Cochair of the session, Dana Dabelea, MD, PhD, associate professor at the Colorado School of Public Health in Aurora, told Medscape Medical News that Dr. Sievenpiper "provided evidence that the wealth of studies that we have so far is not conclusive, and I don't disagree with that, based on what he presented."

"I do know the pathophysiologic discussion on the effects of fructose that have been seen in animals and humans in small populations. It seems like the evidence is not there, and it's not there because we don't have the right studies that ask the right questions, enroll a large enough population, and follow them for enough time. I think we need those studies to formulate those conclusions at the clinical trial level," Dr. Dabelea explained.

"In the absence of a study that is conclusive, his presentation of the results of this a meta-analysis: How useful is that? I'm not sure it's that useful. I'm sure it's controversial and that's why he presented it — because it raises discussion," she observed.

"When one controls caloric intake, it is hard to show weight gain, as most weight gain requires a positive energy balance. We reported that fructose stimulates leptin resistance in rats, which might be how fructose stimulates weight gain. This also likely takes a long time, and might not be observed in short-term studies," said Dr. Johnson.

Dr. Sievenpiper reports receiving several unrestricted travel grants to present research at meetings from the Coca-Cola Company; being a coinvestigator on an unrestricted research grant from the Coca-Cola Company; receiving travel funding and honoraria from Archer Daniels Midland and the International Life Sciences Institute North America; and receiving research support, consultant fees, and travel funding from Pulse Canada. Dr. Johnson and Dr. Dabelea have disclosed no relevant financial relationships.

International Diabetes Federation (IDF) World Diabetes Congress 2011: Abstract O-0476. Presented December 6, 2011.

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