Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite and Reward Pathways
JAMA. 2013;309(1):63-70. doi:10.1001/jama.2012.116975.
Importance Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety.
Objective To study neurophysiological factors that might underlie associations between fructose consumption and weight gain.
Design, Setting, and Participants Twenty healthy adult volunteers underwent 2 magnetic resonance imaging sessions at Yale University in conjunction with fructose or glucose drink ingestion in a blinded, random-order, crossover design.
Main Outcome Measures Relative changes in hypothalamic regional cerebral blood flow (CBF) after glucose or fructose ingestion. Secondary outcomes included whole-brain analyses to explore regional CBF changes, functional connectivity analysis to investigate correlations between the hypothalamus and other brain region responses, and hormone responses to fructose and glucose ingestion.
Results There was a significantly greater reduction in hypothalamic CBF after glucose vs fructose ingestion (−5.45 vs 2.84 mL/g per minute, respectively; mean difference, 8.3 mL/g per minute [95% CI of mean difference, 1.87-14.70]; P = .01). Glucose ingestion (compared with baseline) increased functional connectivity between the hypothalamus and the thalamus and striatum. Fructose increased connectivity between the hypothalamus and thalamus but not the striatum. Regional CBF within the hypothalamus, thalamus, insula, anterior cingulate, and striatum (appetite and reward regions) was reduced after glucose ingestion compared with baseline (P < .05 significance threshold, family-wise error [FWE] whole-brain corrected). In contrast, fructose reduced regional CBF in the thalamus, hippocampus, posterior cingulate cortex, fusiform, and visual cortex (P < .05 significance threshold, FWE whole-brain corrected). In whole-brain voxel-level analyses, there were no significant differences between direct comparisons of fructose vs glucose sessions following correction for multiple comparisons. Fructose vs glucose ingestion resulted in lower peak levels of serum glucose (mean difference, 41.0 mg/dL [95% CI, 27.7-54.5]; P < .001), insulin (mean difference, 49.6 μU/mL [95% CI, 38.2-61.1]; P < .001), and glucagon-like polypeptide 1 (mean difference, 2.1 pmol/L [95% CI, 0.9-3.2]; P = .01).
Conclusion and Relevance In a series of exploratory analyses, consumption of fructose compared with glucose resulted in a distinct pattern of regional CBF and a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels.
Fructose Ingestion and Cerebral, Metabolic, and Satiety Responses
JAMA. 2013;309(1):85-86. doi:10.1001/jama.2012.190505.
COMMENT: These are intriguing studies suggesting that fructose and sucrose have differing effects on hypothalamic centers controlling satiety and hormonal responses. If substantiated, these differences would explain why fructose ingestion could result in excess calorie intake. As the editorialists point out this is not a trivial issue. We generally think of high fructose corn syrup as a key ingredient of soft drinks, however;
“Products containing fructose are preferred by consumers and cooks over those containing only glucose, owing to the intrinsically greater sweetness of fructose and its ability to improve the appearance and texture of baked goods. As a result, sucrose and high-fructose corn syrup are added not just to sodas, energy drinks, and sports drinks favored by adolescents and adults but also to juice drinks consumed by infants and toddlers and to snacks, processed meats, sauces, and many other foods consumed by people of all ages.” Stay tuned.