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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

Riserus, U; Basu, S; Jovinge, Stefan LU ; Nordin Fredrikson, Gunilla LU ; Arnlov, J and Vessby, B (2002) In Circulation 106(15). p.1925-1929
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... (More)
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-a, 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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
inflammation, fatty acids, insulin, free radicals, syndrome x
in
Circulation
volume
106
issue
15
pages
1925 - 1929
publisher
Lippincott Williams and Wilkins
external identifiers
  • wos:000178610600020
  • pmid:12370214
  • scopus:0037044425
ISSN
1524-4539
DOI
10.1161/01.CIR.0000033589.15413.48
language
English
LU publication?
yes
id
9c842e25-e32e-4e36-9e98-d21a6258a250 (old id 325754)
date added to LUP
2007-11-12 11:22:11
date last changed
2017-12-10 04:24:28
@article{9c842e25-e32e-4e36-9e98-d21a6258a250,
  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-a, 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&lt;0.0001 and P&lt;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.},
  author       = {Riserus, U and Basu, S and Jovinge, Stefan and Nordin Fredrikson, Gunilla and Arnlov, J and Vessby, B},
  issn         = {1524-4539},
  keyword      = {inflammation,fatty acids,insulin,free radicals,syndrome x},
  language     = {eng},
  number       = {15},
  pages        = {1925--1929},
  publisher    = {Lippincott Williams and Wilkins},
  series       = {Circulation},
  title        = {Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein - A potential link to fatty acid-induced insulin resistance},
  url          = {http://dx.doi.org/10.1161/01.CIR.0000033589.15413.48},
  volume       = {106},
  year         = {2002},
}