Robert Sherwin, MD, of Yale University, and colleagues reported that, in a brain imaging study, participants who had a drink sweetened with glucose had significant reductions in cerebral blood flow in the hypothalamus, while those who drank a fructose-sweetened drink saw a slight increase in activity (P=0.01).
Glucose also reduced activation in the insula and striatum, other brain regions that regulate appetite, motivation, and reward processing, while fructose did not, the researchers wrote.
In an accompanying editorial, Jonathan Purnell, MD, and Damien Fair, PhD, of Oregon Health & Science University in Portland, said the findings "support the conceptual framework that when the human brain is exposed to fructose, neurobiological pathways involved in appetite regulation are modulated, thereby promoting increased food intake."
As the obesity epidemic has grown, so too has consumption of fructose in the American diet, the researchers explained in their article. Fructose is found in both sucrose, or table sugar, and in high-fructose corn syrup, another common sweetener. It is valued because it’s sweeter than glucose.
But studies show fructose may have different metabolic effects than glucose. For instance, fructose only weakly stimulates secretion of insulin, a hormone that can increase satiety, and attenuates levels of the satiety hormone glucagon-like peptide-1 (GLP-1) — so researchers are concerned that it could possibly increase food-seeking behavior and intake.
To assess those effects, Sherwin and colleagues conducted functional MRIs (fMRIs) in 20 normal-weight, healthy adults who were given 75 grams of either glucose or fructose in a cherry-flavored drink, and then crossed over to a drink with the other sweetener. Participants rated their feelings of hunger, satiety, and fullness before and after the scan, and the researchers took blood to assess circulating hormone levels.
Overall, the researchers found that glucose significantly reduced cerebral blood flow in the hypothalamus, while fructose did not. Specifically, blood flow fell 5.45 mL/g per minute from baseline with glucose, compared with an increase of 2.84 mL/g per minute with fructose, for a mean difference of 8.3 ml/g per minute, they reported (P=0.01).
They also found that glucose reduced cerebral blood flow in the thalamus, insula, anterior cingulate, and striatum — "regions that act in concert to ‘read’ the metabolic state of an individual and drive motivation and reward" — compared with baseline (P<0.05).
In contrast, fructose reduced blood flow in the hippocampus, posterior cingulate cortex, fusiform, and visual cortex — but also in the thalamus (P<0.05).
In terms of connectivity between brain regions, glucose upped the links between the hypothalamus and the thalamus and striatum, while fructose only increased connectivity between the hypothalamus and thalamus, but not the striatum — the latter of which also de-activates once a person is sated, the researchers said.
"These findings suggest that ingestion of glucose, but not fructose, initiates a coordinated response between the homeostatic-striatal network that regulates feeding behavior," they wrote.
They also found that glucose, but not fructose, had effects on circulating "hunger" hormone levels. Glucose elevated levels of insulin and GLP-1 compared with fructose (P<0.001 and P=0.01, respectively).
Leptin and ghrelin levels, however, weren’t significantly different between the two sugars, the researchers found.
The differences in brain effects between glucose and fructose also appeared to coordinate with ratings of hunger, since there was a significant difference from baseline in terms of fullness and satiety when participants drank glucose, but not fructose (P=0.005 and P=0.03, respectively).
Sherwin and colleagues cautioned that the study was limited because fMRI doesn’t provide a direct measure of neuronal activity, and thus any clinical implications can’t yet be determined.
Editorialists Purnell and Fair noted that while some researchers and clinicians warn that the total amount of calories is more important than the type of food when it comes to losing weight, the "reality … 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."
"The remedy remains eating less," they wrote, "but the means involve reducing the food element, if possible."
- This study demonstrates that fructose consumption, compared with glucose consumption, resulted in a distinct pattern of regional cerebral blood flow and a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels.
- High-fructose diets compared to glucose are thought to promote weight gain and insulin resistance.