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Cited by 668Advanced Glycation End Products researchPotato Plant ResearchAdipokines, Inflammation, and Metabolic Diseases

Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy

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Vlassara, Helen, Cai, Weijing, Crandall, Jill, Goldberg, Teresia, Oberstein, Robert, Dardaine, Veronique, Peppa, Melpomeni, Rayfield, Elliot J.·2002·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.242407999PMC PMC137762
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Abstract

Diet is a major environmental source of proinflammatory AGEs (heat-generated advanced glycation end products); its impact in humans remains unclear. We explored the effects of two equivalent diets, one regular (high AGE, H-AGE) and the other with 5-fold lower AGE (L-AGE) content on inflammatory mediators of 24 diabetic subjects: 11 in a 2-week crossover and 13 in a 6-week study. After 2 weeks on H-AGE, serum AGEs increased by 64.5% (P = 0.02) and on L-AGE decreased by 30% (P = 0.02). The mononuclear cell tumor necrosis factor-alphabeta-actin mRNA ratio was 1.4 +/- 0.5 on H-AGE and 0.9 +/- 0.5 on L-AGE (P = 0.05), whereas serum vascular adhesion molecule-1 was 1,108 +/- 429 and 698 +/- 347 ngml (P = 0.01) on L- and H-AGE, respectively. After 6 weeks, peripheral blood mononuclear cell tumor necrosis factor-alpha rose by 86.3% (P = 0.006) and declined by 20% (P, not significant) on H- or L-AGE diet, respectively; C-reactive protein increased by 35% on H-AGE and decreased by 20% on L-AGE (P = 0.014), and vascular adhesion molecule-1 declined by 20% on L-AGE (P < 0.01) and increased by 4% on H-AGE. Serum AGEs were increased by 28.2% on H-AGE (P = 0.06) and reduced by 40% on L-AGE (P = 0.02), whereas AGE low density lipoprotein was increased by 32% on H-AGE and reduced by 33% on L-AGE diet (P < 0.05). Thus in diabetes, environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury. Restriction of dietary AGEs suppresses these effects.

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  • Adiponectin overexpression in apoE2/2 mice reduces lesion size after acute ischaemic myocardial infarction, increases angiogenesis and reduces atheromatous plaque size.

    “Overexpression of adiponectin results in diminished size of the lesions observed following acute ischaemic myocardial infarction, increased angiogenic properties and reduced size of atheromatous plaques in the genetically predisposed apoE 2/2 mouse (103) .”

    From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [103]

  • Restriction of dietary AGEs is associated with reductions in inflammation and an increase in vascular function in humans.

    “Nonetheless the restriction of dietary AGEs has been associated with reductions in inflammation and an increase in vascular function in humans, [96,97]”

    From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [96]

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Authors
Vlassara, H., Cai, W., Crandall, J., Goldberg, T., Oberstein, R., Dardaine, V., Peppa, M., & Rayfield, E. J.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • Division of Experimental Diabetes and Aging, Department of Geriatrics, and Division of Endocrinology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029
ORCID
Crandall, Jill
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2002-11-12
Volume
99
Issue
24
Pages
15596-15601
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.242407999
PMC
PMC137762
OpenAlex
W2159634370
Cited by
668
References
54
Citations by year
2026: 9 · 2025: 12 · 2024: 20 · 2023: 25 · 2022: 29 · 2021: 12 · 2020: 28 · 2019: 27 · 2018: 24 · 2017: 24 · 2016: 34 · 2015: 46 · 2014: 29 · 2013: 36 · 2012: 32
FWCI
15.48
Type
journal article
Language
en
Update notices
correction (2003-01-21)
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (AG09453, R01AG009453)
  • National Center for Research Resources (MO1RR00071, M01RR000071)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Potato Plant Research
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
advanced glycation end products, dietary AGEs, diabetic vascular disease, inflammation, TNF-α, C-reactive protein, mononuclear cells, diabetes mellitus, dietary intervention
MeSH terms
C-Reactive Protein, Diabetes Mellitus, Diabetic Angiopathies, Diet, Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Female, Food Analysis, Food, Formulated, Gene Expression Regulation, Humans, Lysine, Male, Middle Aged, Pyruvaldehyde, Risk Factors, Tumor Necrosis Factor-alpha, Lipid Peroxidation, Biomarkers, Glycation End Products, Advanced, Cross-Over Studies, Inflammation Mediators, Vascular Cell Adhesion Molecule-1, Diabetes Complications

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