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Growth Horm IGF Res 18 5 , — Download references. We are grateful to Lilian Bengtsson, Diane Jackson and Ian Matheson for expert assistance in the project. We thank all of the volunteers that took part in the study.

The work was supported by Scottish Government Rural and Environment Research and Analysis Directorate RERAD in the United Kingdom and EC Framework V Grant QLK, the Swedish Research Council Grant no.

Division of Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. Metabolic Unit, Institute of Biomedical Engineering ISIB CNR , Padova, Italy. Obesity and Metabolic Health Division and Vascular Health Division, Rowett Research Institute, Aberdeen, UK. School of Life Sciences, The Robert Gordon University, Aberdeen, UK.

You can also search for this author in PubMed Google Scholar. Correspondence to B Ahrén. Reprints and permissions. Ahrén, B. et al. Effects of conjugated linoleic acid plus n -3 polyunsaturated fatty acids on insulin secretion and estimated insulin sensitivity in men.

Eur J Clin Nutr 63 , — Download citation. Received : 10 March Revised : 15 July Accepted : 30 July Published : 03 September Issue Date : June Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content Thank you for visiting nature. nature european journal of clinical nutrition original article article. Results: The combination was well tolerated. Access through your institution. Buy or subscribe. Change institution.

Learn more. Figure 1. Figure 2. Data are based on 57 subjects with complete follow-up data. Supplements were generally well tolerated, with only minor transient gastrointestinal problems reported.

No adverse events occurred, and no changes in liver enzymes occurred data not shown. Compliance capsule count did not significantly differ between groups No significant changes in dietary intake occurred during the study Table 4. There were no significant differences between groups in body weight, BMI, body fat, lean body mass, or waist girth at 12 weeks Table 2.

CLA preparations did not decrease weight or change body fat, BMI, or waist girth compared with placebo, although these variables significantly decreased within the t 10 c 12 CLA group, whereas SAD and body fat decreased within the CLA group paired t test.

Insulin sensitivity M decreased significantly in the t 10 c 12 CLA group compared with placebo but not compared with CLA Table 3. The significant reduction in M after t 10 c 12 CLA treatment was not affected by adjustment for age or changes in glucose levels, body fat, BMI, or abdominal fat.

Of all variables, only adjustment for changes in VLDL TG abolished the significant change in M after t 10 c 12 CLA treatment. This randomized placebo-controlled trial has revealed unexpected metabolic actions by conjugated fatty acids in humans—actions that seem isomer-specific.

The t 10 c 12 CLA isomer, but not a CLA mixture, significantly increased insulin resistance, fasting glucose, and dyslipdemia in abdominally obese men. Such men are prone to develop type 2 diabetes and are considered a possible target group for the putative beneficial effect of CLA.

Commercial CLA had no metabolic benefit, which is consistent with previous data 7 , 9 , Instead, t 10 c 12 CLA might be diabetogenic in the metabolic syndrome.

However, unlike other studies, diet and physical activity were controlled using metabolic suites in that study, and the relative amount of c 11 t 13 CLA was higher and c 9 t 11 CLA was lower, which should be taken into account when comparing that study with our data.

Whether insulin resistance in CLA-fed mice shares a common mechanism with the t 10 c 12 CLA-induced insulin resistance is unclear. Thus, the mechanism of current insulin resistance is unknown, but some animal data are worth considering.

An intriguing speculation is that CLA induces adipocyte apoptosis as shown in mice 6 and in vitro 6 , 25 , 26 , and by the t 10 c 12 isomer in particular t 10 c 12 CLA might also inhibit the formation of new, small, and insulin-sensitive fat cells 27 , possibly via downregulated peroxisome proliferator-activated receptor PPAR -γ 6.

Other mechanisms for a t 10 c 12 CLA-induced insulin resistance might involve impaired cell membrane function 28 , possibly via increasing intramuscular fat content Insulin resistance appeared to occur mainly in the peripheral tissues rather than in the liver, as serum IGF binding protein IGFBP -1, a marker of hepatic insulin sensitivity 30 , did not change unpublished data.

To elucidate the mechanism, it is probably necessary to investigate insulin-sensitive tissue directly, which is more complicated in humans than in mice.

Our primary goal, however, was to investigate the clinical effects of CLA in an insulin-resistant phenotype. Neither CLA preparation decreased weight or changed body composition compared with placebo. SAD tended to decrease after CLA treatment, but the difference was not significant versus placebo.

The standard deviations for changes in anthropometrics were large, and the measurement errors for SAD, BIA, and waist girth have to be considered when interpreting the data.

Adjustment for several variables did not affect the t 10 c 12 CLA-induced insulin resistance, with one exception. Adjusting for VLDL TG abolished statistical significance, reflecting the well-known tight relation between these two variables It is likely that impaired insulin action after t 10 c 12 CLA treatment preceded dyslipidemia 31 , but this remains to be proven.

HDL cholesterol decreased after treatment with both CLA forms, although the effect was more pronounced with t 10 c 12 CLA. This was also observed in overweight, normolipidemic subjects using a CLA mixture 10 , but not in normal-weight subjects 9 , Because low HDL cholesterol is an independent cardiovascular risk factor 33 , the current reduction of 0.

Interestingly, the current changes in HDL cholesterol were not related to insulin resistance, but were positively related to leptin levels. Further, the t 10 c 12 CLA-induced insulin resistance is impressive.

However, more clinical trials are needed to make firm conclusions regarding the clinical safety of CLA isomers and mixtures in obese patients. In summary, t 10 c 12 CLA increased insulin resistance and dyslipidemia in men with the metabolic syndrome, in agreement with data in CLA-fed mice 6 , 24 but unlike data in ZDF rats 4 , suggesting important isomer-specific metabolic effects of CLA in humans.

Data are means ± SD unless noted otherwise. There were no significant differences between the groups ANOVA. Data are means ± SD. There were no differences between the groups.

All P values indicate within-group differences;. P values represent paired t tests. This study was supported by the Swedish Medical Research Council no.

We thank Natural Lipids Ltd. AS, Norway, for supplying the CLA preparations. E-mail: ulf. riserus pubcare. A table elsewhere in this issue shows conventional and Système International SI units and conversion factors for many substances.

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Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 25, Issue 9. Previous Article Next Article. RESEARCH DESIGN AND METHODS. Article Information. Article Navigation. Treatment With Dietary trans 10 cis 12 Conjugated Linoleic Acid Causes Isomer-Specific Insulin Resistance in Obese Men With the Metabolic Syndrome Ulf Risérus, MMED ; Ulf Risérus, MMED.

This Site. Google Scholar. Peter Arner, MD, PHD ; Peter Arner, MD, PHD. Kerstin Brismar, MD, PHD ; Kerstin Brismar, MD, PHD. Bengt Vessby, MD, PHD Bengt Vessby, MD, PHD. Diabetes Care ;25 9 — Get Permissions.

toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Table 1— Baseline characteristics. n 19 19 19 Age years 53 ± View Large. Table 2— Change in body composition from baseline to 12 weeks. n 19 19 19 Weight kg 0. Table 3— Absolute and relative changes in glucose and lipid metabolism from baseline to 12 weeks.

Table 4— Changes in dietary intake during the study period. Dietary intake. Whigham LD, Cook ME, Atkinson RL: Conjugated linoleic acid: implications for human health. Pharmacol Res. Park Y, Albright KJ, Liu W, Storkson JM, Cook ME, Pariza MW: Effect of conjugated linoleic acid on body composition in mice.

West DB, Delany JP, Camet PM, Blohm F, Truett AA, Scimeca J: Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse.

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Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O: Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice.

Riserus U, Berglund L, Vessby B: Conjugated linoleic acid CLA reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial.

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