Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein: a potential link to fatty acid-induced insulin resistance.
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.


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.
Risérus
Ulf
U
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden. ulf.riserus@pubcare.uu.se
Basu
Samar
S
Jovinge
Stefan
S
Fredrikson
Gunilla Nordin
GN
Arnlöv
Johan
J
Vessby
Bengt
B
D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis*; D016207:Cytokines / Q000032:analysis; D004311:Double-Blind Method; D028441:F2-Isoprostanes / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D007536:Isomerism; D007700:Kinetics; D008041:Linoleic Acids / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008079:Lipoproteins, VLDL / Q000032:analysis; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D018384:Oxidative Stress; D014280:Triglycerides / Q000032:analysis
D019440:Anti-Obesity Agents; D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D028441:F2-Isoprostanes; D008041:Linoleic Acids; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D002097:C-Reactive Protein