Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways
Open accessAbstract
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.
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Previous studies have typically limited the duration of observation to ≤1 h after food consumption, when glucose absorption peaks and a high-GI meal may transiently appear to provide benefits to brain function.
“Previous studies have typically limited the duration of observation to #1 h after food consumption, when glucose absorption peaks and a high-GI meal may transiently appear to provide benefits to brain function (33).”
From Effects of dietary glycemic index on brain regions related to reward and craving in men (2013) · cites this paper as [33]
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- Authors
- Page, K. A., Chan, O., Arora, J., Belfort-DeAguiar, R., Dzuira, J., Roehmholdt, B., Cline, G. W., Naik, S., Sinha, R., Constable, R. T., & Sherwin, R. S.
- Affiliations
- Yale University (US)
- University of Southern California (US)
- Corresponding author
- Sherwin, Robert S.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2013-01-02
- Volume
- 309
- Issue
- 1
- Pages
- 63
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC4076145
- OpenAlex
- W2114918553
- Cited by
- 379
- References
- 39
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 9 · 2023: 18 · 2022: 27 · 2021: 20 · 2020: 34 · 2019: 20 · 2018: 48 · 2017: 38 · 2016: 29 · 2015: 42 · 2014: 43 · 2013: 24
- FWCI
- 24.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- National Institutes of Health (P30 DK, DK 20495)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK45735, DK20495, R01DK020495, T32 DK-07058, R37DK020495, T32DK007058, P30DK045735)
- National Center for Research Resources (UL1RR024139)
- Yale Center for Clinical Investigation, Yale School of Medicine (UL1RR024139)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- fructose, glucose, regional cerebral blood flow, hypothalamus, appetite, reward pathways, thalamus, striatum, functional connectivity, satiety hormones, insulin, obesity, weight gain, brain glucose metabolism, sugar consumption, appetite regulation, reward processing, brain insulin signaling
- MeSH terms
- Adult, Animals, Appetite, Beverages, Blood-Brain Barrier, Brain, Female, Fructose, Glucose, Humans, Hunger, Hypothalamus, Insulin, Magnetic Resonance Imaging, Male, Regional Blood Flow, Reward, Single-Blind Method, Cross-Over Studies, Rats, Glucagon-Like Peptide 1
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