

Grocery store aisles are awash in foods and beverages that contain high-fructose corn syrup. It is common in sodas and crops up in everything from ketchup to snack bars. This cheap sweetener has been an increasingly popular additive in recent decades and has often been fingered as a driver of the obesity epidemic.

These fears may be well founded. Fructose, a new study finds, has a marked affect on the brain region that regulates appetite, suggesting that corn syrup and other forms of fructose might encourage over-eating to a greater degree than glucose. Table sugar has both fructose and glucose, but high-fructose corn syrup, as the name suggests, contains a higher proportion of fructose.

To test how fructose affects the brain, researchers studied 20 healthy adult volunteers. While the test subjects consumed sweetened beverages, the researchers used fMRIs (functional magnetic resonance imaging) to measure the response of the hypothalamus, which helps regulate many hunger-related signals, as well as reward and motivation processing.

Volunteers received a 300-milliliter cherry-flavored drink sweetened with 75 grams (equivalent to about 300 calories) of fructose as well as the same drink sweetened with the same amount of glucose. These different drinks were given, in random order, at sessions one to eight months apart. The researchers also took blood samples at various time points and asked volunteers to rate their feelings of hunger and fullness.

Subjects showed substantial differences in their hypothalamic activity after consuming the fructose-sweetened beverage versus the one sweetened by glucose within 15 minutes. Glucose lowered the activity of the hypothalamus but fructose actually prompted a small spike to this area. As might be expected from these results, the glucose drink alone increased the feelings of fullness reported by volunteers, which indicates that they would be less likely to consume more calories after having something sweetened with glucose than something sweetened with more fructose.

Fructose and glucose look similar molecularly, but fructose is metabolized differently by the body and prompts the body to secrete less insulin than does glucose (insulin plays a role in telling the body to feel full and in dulling the reward the body gets from food). Fructose also fails to reduce the amount of circulating ghrelin (a hunger-signaling hormone) as much as glucose does. (Animal studies have shown that fructose can, indeed, cross the blood-brain barrier and be metabolized in the hypothalamus.) Previous studies have shown that this effect was pronounced in animal models.

The study, led by Kathleen Page, of Yale University School of Medicine and published online January 1 in JAMA, The Journal of the American Medical Association, was small and was not able to pinpoint precise neural circuits that might be affected by the sweeteners. But the results, along with other research, suggest that, thanks to the "advances in food processing and economic forces" that have boosted the intake of fructose, added sugar and high-fructose corn syrup are "indeed extending the supersizing concept to the population's collective waistlines," wrote Jonathan Purnell, of the Division of Endocrinology, Diabetes, and Clinical Nutrition, and Damien Fair, of the Department of Behavioral Neuroscience, both of Oregon Health & Sciences University in Portland, who coauthored an essay that appeared in the same issue of JAMA.

Could fructose consumption alone really be playing such an outsized role in expanding our pant sizes? "A common counterargument is that it is the excess calories that are important, not the food. Simply put: just eat less," Purnell and Fair noted. "The reality, however, is that hunger and fullness are major determinants of how much humans eat, just as thirst determines how much humans drink. These sensations cannot simply be willed away or ignored." In order to eat less (and consume fewer calories overall), they argued, then, one should avoid foods or ingredients that fail to satisfy hunger. And that, according to the results from the new study, would mean those fructose-sweetened foods--and drinks.







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