The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids
Open accessAbstract
Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose. Despite strong ties between fructose and disease, the metabolic fate of fructose in mammals remains incompletely understood. Here we use isotope tracing and mass spectrometry to track the fate of glucose and fructose carbons in vivo, finding that dietary fructose is cleared by the small intestine. Clearance requires the fructose-phosphorylating enzyme ketohexokinase. Low doses of fructose are ∼90% cleared by the intestine, with only trace fructose but extensive fructose-derived glucose, lactate, and glycerate found in the portal blood. High doses of fructose (≥1 g/kg) overwhelm intestinal fructose absorption and clearance, resulting in fructose reaching both the liver and colonic microbiota. Intestinal fructose clearance is augmented both by prior exposure to fructose and by feeding. We propose that the small intestine shields the liver from otherwise toxic fructose exposure.
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After intestinal absorption, fructose appears to be actively metabolized in the splanchnic area, whereas glucose appears to be largely transmitted passively from the splanchnic area into the systemic circulation.
“After intestinal absorption, fructose appears to be actively metabolized in the splanchnic area (i.e. intestine, liver and kidneys), whereas glucose appears to be largely transmitted passively from the splanchnic area into the systemic circulation (Gonzalez et al. 2017; Tappy & Rosset, 2017; Jang et al. 2018; Tappy, 2018; Fig. 1).”
From Fructose co‐ingestion to increase carbohydrate availability in athletes (2019) · cites this paper as Jang et al. 2018
The Results section (“Small Intestine Is a Primary Organ for Dietary Fructose Clearance”; page unavailable) says the small intestine largely passively transmits glucose into the body while actively metabolizing fructose. The claim extends that contrast to the whole splanchnic area, including the liver and kidneys; this passage does not establish that glucose passes largely unchanged through those organs into systemic circulation. (LLM, conf=0.86)
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- Authors
- Jang, C., Hui, S., Lu, W., Cowan, A. J., Morscher, R. J., Lee, G., Liu, W., Tesz, G. J., Birnbaum, M. J., & Rabinowitz, J. D.
- Affiliations
- Princeton University (US)
- Cornell University (US)
- Pfizer (United States) (US)
- Corresponding author
- Rabinowitz, Joshua D.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 27
- Issue
- 2
- Pages
- 351-361.e3
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC6032988
- OpenAlex
- W2787707131
- Cited by
- 639
- References
- 3
- Citations by year
- 2026: 50 · 2025: 77 · 2024: 76 · 2023: 83 · 2022: 69 · 2021: 97 · 2020: 84 · 2019: 58 · 2018: 44
- FWCI
- 57.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Pfizer
- National Institutes of Health (1DP1DK113643, P30 DK019525)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- dietary fructose, small intestine, ketohexokinase, fructose phosphorylation, lactate, glycerate, portal blood, colonic microbiota, liver, metabolic syndrome, isotope tracing
- MeSH terms
- Animals, Carboxylic Acids, Dietary Carbohydrates, Feeding Behavior, Fructose, Glucose, Intestine, Small, Isotope Labeling, Liver, Mice, Inbred C57BL, Models, Biological, Metabolome, Microbiota
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