Formation of Fructose-Mediated Advanced Glycation End Products and Their Roles in Metabolic and Inflammatory Diseases
Open accessAbstract
Fructose is associated with the biochemical alterations that promote the development of metabolic syndrome (MetS), nonalcoholic fatty liver disease, and type 2 diabetes. Its consumption has increased in parallel with MetS. It is metabolized by the liver, where it stimulates de novo lipogenesis. The triglycerides synthesized lead to hepatic insulin resistance and dyslipidemia. Fructose-derived advanced glycation end products (AGEs) may be involved via the Maillard reaction. Fructose has not been a main focus of glycation research because of the difficulty in measuring its adducts, and, more importantly, because although it is 10 times more reactive than glucose, its plasma concentration is only 1% of that of glucose. In this focused review, I summarize exogenous and endogenous fructose metabolism, fructose glycation, and in vitro, animal, and human data. Fructose is elevated in several tissues of diabetic patients where the polyol pathway is active, reaching the same order of magnitude as glucose. It is plausible that the high reactivity of fructose, directly or via its metabolites, may contribute to the formation of intracellular AGEs and to vascular complications. The evidence, however, is still unconvincing. Two areas that have been overlooked so far and should be actively explored include the following: 1) enteral formation of fructose AGEs, generating an inflammatory response to the receptor for AGEs (which may explain the strong association between fructose consumption and asthma, chronic bronchitis, and arthritis); and 2) inactivation of hepatic AMP-activated protein kinase by a fructose-mediated increase in methylglyoxal flux (perpetuating lipogenesis, fatty liver, and insulin resistance). If proven correct, these mechanisms would put the fructose-mediated Maillard reaction in the limelight again as a contributing factor in chronic inflammatory diseases and MetS.
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Fructose can increase AGE formation independently of glucose by increasing alpha-oxoaldehyde levels.
“Additionally, fructose can increase AGE formation independently of glucose by increasing 𝛼-oxoaldehydes levels.[5]”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [5]
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- Authors
- Gugliucci, A.
- Affiliations
- Touro University California (US)
- Corresponding author
- Gugliucci, Alejandro
- ORCID
- Gugliucci, Alejandro
- Venue
- Advances in Nutrition
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 8
- Issue
- 1
- Pages
- 54-62
- ISSN
- 2156-5376 (ISSN-L)
- 2161-8313
- PMC
- PMC5227984
- OpenAlex
- W2572954835
- Cited by
- 225
- References
- 105
- Citations by year
- 2026: 7 · 2025: 24 · 2024: 31 · 2023: 24 · 2022: 32 · 2021: 36 · 2020: 20 · 2019: 26 · 2018: 14 · 2017: 8 · 2016: 1
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Advances in Nutrition (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Touro Scholar (Touro College) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Agricultural and Biological Sciences › Food Science › Potato Plant Research
- Keywords
- fructose, advanced glycation end products, Maillard reaction, metabolic syndrome, non-alcoholic fatty liver disease, type 2 diabetes, hepatic insulin resistance, de novo lipogenesis, polyol pathway, methylglyoxal, AMPK, receptor for advanced glycation end products, inflammation, asthma, chronic bronchitis, arthritis, vascular complications
- MeSH terms
- Adenosine Triphosphate, Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Fructose, Humans, Obesity, Sorbitol, Uric Acid, Glycation End Products, Advanced, Metabolic Syndrome, Lipogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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