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Supplementation With Conjugated Linoleic Acid Causes Isomer-Dependent Oxidative Stress and Elevated C-Reactive Protein: A Potential Link to Fatty Acid-Induced Insulin Resistance
Abstract
BACKGROUND: Conjugated linoleic acids (CLAs), a group of fatty acids shown to have beneficial effects in animals, are also used as weight loss supplements. Recently, we reported that the t10c12 CLA-isomer caused insulin resistance in abdominally obese men via unknown mechanisms. The aim of the present study was to examine whether CLA has isomer-specific effects on oxidative stress or inflammatory biomarkers and to investigate the relationship between these factors and induced insulin resistance. METHODS AND RESULTS: In a double-blind placebo-controlled trial, 60 men with metabolic syndrome were randomized to one of 3 groups receiving t10c12 CLA, a CLA mixture, or placebo for 12 weeks. Insulin sensitivity (euglycemic clamp), serum lipids, in vivo lipid peroxidation (determined as urinary 8-iso-PGF(2alpha) [F2-isoprostanes]), 15-ketodihydro PGF(2alpha), plasma vitamin E, plasma C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 were assessed before and after treatment. Supplementation with t10c12 CLA markedly increased 8-iso-PGF(2alpha) (578%) and C-reactive protein (110%) compared with placebo (P<0.0001 and P<0.01, respectively) and independent of changes in hyperglycemia or dyslipidemia. The increases in 8-iso-PGF(2alpha), but not in C-reactive protein, were significantly and independently related to aggravated insulin resistance. Oxidative stress was related to increased vitamin E levels, suggesting a compensatory mechanism. CONCLUSIONS: t10c12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men. The oxidative stress seems closely related to induced insulin resistance, suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance. These unfavorable effects of t10c12 CLA might be of clinical importance with regard to cardiovascular disease, in consideration of the widespread use of dietary supplements containing this fatty acid.
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“past and emerging evidence indicates that chronic low-grade inflammation is associated with poor Fe status in obese persons (716 -721) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [720]
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Metadata
- Authors
- Risérus, U., Basu, S., Jovinge, S., Fredrikson, G. N., Ärnlöv, J., & Vessby, B.
- Affiliations
- From the Department of Public Health and Caring Sciences/Geriatrics, Uppsala University (U.R., S.B., J.Ä., B.V.), Uppsala, Sweden, and the Department of Cardiology/Medicine, University Hospital MAS, Lund University (S.J., G.N.F.), Lund, Sweden.
- Uppsala University (SE)
- ORCID
- Jovinge, Stefan
- Venue
- Circulation
- Published
- 2002-10-08
- Volume
- 106
- Issue
- 15
- Pages
- 1925-1929
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2164592152
- Cited by
- 292
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 2 · 2017: 4 · 2016: 10 · 2015: 7 · 2014: 9 · 2013: 20 · 2012: 9
- FWCI
- 20.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- conjugated linoleic acid, CLA isomers, oxidative stress, lipid peroxidation, C-reactive protein, inflammation, insulin resistance, metabolic syndrome, obesity, weight loss supplements, vitamin E, 8-isoprostane
- MeSH terms
- Adult, Aged, Blood Glucose, C-Reactive Protein, Double-Blind Method, Humans, Inflammation, Insulin Resistance, Isomerism, Kinetics, Linoleic Acids, Lipoproteins, VLDL, Male, Middle Aged, Triglycerides, Lipid Peroxidation, Biomarkers, Cytokines, Oxidative Stress, Anti-Obesity Agents, Metabolic Syndrome, F2-Isoprostanes
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