Article

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

Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden.
Circulation (Impact Factor: 14.95). 10/2002; 106(15):1925-9.
Source: PubMed

ABSTRACT 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.
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.
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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    • "Despite the small structural differences between them, c9,t11 and t10,c12 CLA isomers have distinct cellular and physiological actions [6] [7]. The c9,t11 isomer exhibits anti-inflammatory and antiatherogenic effects, whereas t10,c12 CLA has antiadipogenic properties as well as possible harmful effects such as hyperinsulinaemia, hepatic steatosis, and adipose tissue inflammation [8] [9]. "
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    ABSTRACT: A conjugated linoleic acid (CLA) depletion-repletion study was carried out to investigate the effects of dietary c9,t11 CLA on C-reactive protein, transcription factor NFκB, metalloproteinases 2 and 9, inflammatory mediators (adiponectin, TNFα, IL-2, IL-4, IL-8, IL-10), body composition, and erythrocyte membrane composition in healthy normal-weight human adults. CLA depletion was achieved through an 8-week period of restricted dairy fat intake (depletion phase; CLA intake was 5.2±5.8 mg/day), followed by an 8-week period in which individuals consumed 20 g/day of butter naturally enriched with c9,t11 CLA (repletion phase; CLA intake of 1020±167 mg/day). The participants were 29 healthy adult volunteers (19 women and 10 men, aged 22 to 36 years), with body mass index between 18.0 and 29.9 kg m(-2). Blood samples were collected at baseline and at the end of both depletion and repletion phases. The content of CLA in erythrocytes decreased during CLA-depletion and increased during CLA-repletion. Intake of CLA-enriched butter increased the serum levels of anti-inflammatory IL-10 but reduced transcription factor NFκB in blood and serum levels of TNFα, IL-2, IL-8 and inactive metalloproteinase-9. Moreover, reduced activity of metalloproteinases 2 and 9 in serum was observed during the CLA-repletion period. In contrast, intake of CLA-enriched butter had no effects on body composition (DXA analysis) as well as on serum levels of adiponectin, C-reactive protein, and IL-4. Taken together, our results indicate that the intake of a c9,t11 CLA-enriched butter by normal-weight subjects induces beneficial changes in immune modulators associated with sub-clinical inflammation in overweight individuals.
    The Journal of nutritional biochemistry 12/2013; 24(12):2144-2151. DOI:10.1016/j.jnutbio.2013.08.006 · 4.59 Impact Factor
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    • "But what is clear, in patients with normal BMI or overweight, CLA has no or a little effect on improvement of blood glucose, insulin and insulin sensitivity [10,33]. So, it is likely that in obese individuals, CLA causes a small increase in insulin resistance [9,34]. However in our study, CLA supplementation did not change weight and glycemic indicators. "
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    ABSTRACT: The healthy properties of conjugated linoleic acid (CLA) such as weight loss, reducing cardiovascular risk factors and inflammation have been reported. The trans-10, cis-12 CLA isomer is related to increasing insulin resistance, but the effects of cis-9, trans-11 isomer is not clear. The aim of this study was to investigate the effects of CLA with and without Vitamin E on body weight, body composition, glycemic index, inflammatory and coagulation factors, lipid profile, serum leptin and adiponectin, malondialdehyde (MDA), and blood pressure in type2 diabetes. 56 patients with type2 diabetes were included in 8 week double-blind control trial that used metformin. They randomly divided into three groups: CLA + VitE, CLA + VitE placebo, CLA placebo + VitE placebo. All variables, anthropometric measurements, and body composition were evaluated at the beginning and the end of study. Statistical analysis and analysis of dietary data were performed using SPSS and nutritionist IV software, respectively. There were not any significant differences in variable changes among three groups. However, there was a trend to increase in MDA and decrease in apoB100 among CLA consumers. The results of this study showed that administration of CLA supplementation for 8 weeks does not affect any indicators of metabolic control in overweight type2 diabetic patients.
    07/2013; 12(1):42. DOI:10.1186/2251-6581-12-42
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    • "It seems that t10,c12 CLA isomer, and not the CLA mixture, is responsible for the increased insulin resistance, fasting blood glucose levels, and dislipidemia in humans (Riserus et al. 2002b). The insulin resistance may be induced by an enhancement of oxidative stress (Riserus et al. 2002b) or by an increase in the lipolytic rate and free fatty acid levels associated with supplementation (DeLany et al. 1999). There are evidences , as much from studies on rats as on humans, that this isomer probably promotes liver hypertrophy and insulin resistance through redistribution of body fat (Riserus et al. 2002a). "
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