Conjugated Linoleic Acid (CLA)

The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on cardiovascular risk factors in patients at risk of CVD. Relevant studies were obtained by searching the PubMed, SCOPUS and Web of Science databases (from inception to January 2023). Weighted mean differences (WMD) and 95% CI were pooled using a random-effects model. Heterogeneity, sensitivity analysis and publication bias were reported using standard methods. A pooled analysis of 14 randomised controlled trials (RCT) with 17 effect sizes revealed that CLA supplementation led to significant reductions in body weight (WMD: -0·72 kg, 95% CI: -1·11, -0·33, P < 0·001), BMI (WMD: -0·22 kg/m2, 95% CI: -0·44, -0·00, P = 0·037) and body fat percentage (BFP) (WMD: -1·32 %, 95% CI: -2·24, -0·40, P = 0·005). However, there was no effect on lipid profile and blood pressure in comparison with the control group. In conclusion, CLA supplementation may yield a small but significant beneficial effect on anthropometric indices in patients at risk of CVD. Moreover, CLA seems not to have adverse effects on lipid profiles and blood pressure in patients at risk of CVD. It should be noted that the favourable effects of CLA supplementation on anthropometric variables were small and may not reach clinical importance.

BACKGROUND: The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines, cytokines, malondialdehyde (MDA) and liver function enzymes in patients at risk of cardiovascular disease. METHODS: Relevant studies were obtained by searching the PubMed, SCOPUS and Web of Science databases (from inception to January 2023). Weighted mean differences (WMD) and 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods. RESULTS: A pooled analysis of 13 randomized controlled trials (RCTs) revealed that CLA supplementation led to a significant increment in fasting blood glucose (FBG) (WMD: 4.49 mg/dL; 95%CI: 2.39 to 6.59; P < 0.001), and aspartate aminotransferase (AST) (WMD: 2.54 IU/L; 95%CI: 0.06 to 5.01; P = 0.044). Moreover, CLA supplementation decreased leptin (WMD: -1.69 ng/ml; 95% CI: -1.80 to -1.58; P < 0.001), and interleukin 6 (IL-6) (WMD: -0.44 pg/ml; 95%CI: -0.86 to -0.02; P = 0.037). However, there was no effect on hemoglobin A1c (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and alanine aminotransferase (ALT) adiponectin compared to the control group. CONCLUSION: Our findings showed the overall favorable effect of CLA supplementation on the adipokines and cytokines including serum IL-6, and leptin, while increasing FBG and AST. It should be noted that the mentioned metabolic effects of CLA consumption were small and may not reach clinical importance. PROSPERO REGISTERATION COD: CRD42023426374. © 2023. BioMed Central Ltd., part of Springer Nature.

Prior meta-analytic investigations over a decade ago rather inconclusively indicated that conjugated linoleic acid (CLA) supplementation could improve anthropometric and body composition indices in the general adult population. More recent investigations have emerged, and an up-to-date systematic review and meta-analysis on this topic must be improved. Therefore, this investigation provides a comprehensive systematic review and meta-analysis of randomised controlled trials (RCT) on the impact of CLA supplementation on anthropometric and body composition (body mass (BM), BMI, waist circumference (WC), fat mass (FM), body fat percentage (BFP) and fat-free mass (FFM)) markers in adults. Online databases search, including PubMed, Scopus, the Cochrane Library and Web of Science up to March 2022, were utilised to retrieve RCT examining the effect of CLA supplementation on anthropometric and body composition markers in adults. Meta-analysis was carried out using a random-effects model. The I2 index was used as an index of statistical heterogeneity of RCT. Among the initial 8351 studies identified from electronic databases search, seventy RCT with ninety-six effect sizes involving 4159 participants were included for data analyses. The results of random-effects modelling demonstrated that CLA supplementation significantly reduced BM (weighted mean difference (WMD): -0·35, 95 % CI (-0·54, -0·15), P < 0·001), BMI (WMD: -0·15, 95 % CI (-0·24, -0·06), P = 0·001), WC (WMD: -0·62, 95% CI (-1·04, -0·20), P = 0·004), FM (WMD: -0·44, 95 % CI (-0·66, -0·23), P < 0·001), BFP (WMD: -0·77 %, 95 % CI (-1·09, -0·45), P < 0·001) and increased FFM (WMD: 0·27, 95 % CI (0·09, 0·45), P = 0·003). The high-quality subgroup showed that CLA supplementation fails to change FM and BFP. However, according to high-quality studies, CLA intake resulted in small but significant increases in FFM and decreases in BM and BMI. This meta-analysis study suggests that CLA supplementation may result in a small but significant improvement in anthropometric and body composition markers in an adult population. However, data from high-quality studies failed to show CLA's body fat-lowering properties. Moreover, it

BACKGROUND AND AIMS: Many studies have investigated the effect of conjugated linoleic acid (CLA) supplementation on inflammatory cytokines and adipokines. However, the results of these studies are not consistent. Therefore, this systematic review and meta-analysis were designed to comprehensively evaluate the effect of CLA supplementation on inflammatory cytokines and adipokines. METHODS: Randomized controlled trials (RCTs) examining the effects of CLA supplementation on C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), adiponectin, and leptin, published up to March 2022, were identified through PubMed, SCOPUS, and ISI Web of Science databases. A random-effects model was used to calculate weighted mean differences (WMDs) with 95% confidence intervals (CI) for 42 studies that included 1,109 participants. RESULTS: Findings from 42 studies with 58 arms indicated that CLA supplementation significantly decreased IL-6 and TNF-α levels and also slightly increased CRP levels. However, adiponectin and leptin levels did not change after CLA supplementation. A subgroup analysis found that CLA supplementation reduced adiponectin and leptin in women. CONCLUSION: Our results demonstrated that CLA supplementation increased CRP levels and decreased TNF-α and IL-6 levels. Therefore, it seems that CLA can have both proinflammatory and anti-inflammatory roles. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier (CRD42022331110).

BACKGROUND: Previous research reported inconsistent findings regarding the effects of conjugated linoleic acid (CLA) supplementation on liver enzymes. This systematic review and meta-analysis was conducted to summarize data from available randomized clinical trials (RCTs) on the effect of CLA supplementation on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malondialdehyde (MDA) in adults. METHODS: Google Scholar, PubMed, Web of Science, Scopus, and the Cochrane databases were investigated to identify relevant articles up to July 2022. The weighted mean differences (WMD) and 95 % confidence intervals (CI) were calculated via a random-effects model to evaluate the effect size. Between studies, heterogeneity was evaluated by the Cochran's Q test and I2. RESULTS: 22 RCTs with 26 effect sizes were included. The effect size for ALT (IU/L), AST (IU/L), and MDA (µmol/L) were 19, 19 and 6 respectively. The pooled analysis demonstrated CLA decreases MDA (p = 0.003). However, ALT and AST levels did not change after CLA supplementation compared with control group. CONCLUSION: CLA supplementation may significantly reduce MDA levels as a marker of oxidative stress. However, supplementing with CLA failed to alter ALT and AST. Published by Elsevier Ltd.

CONTEXT: Conjugated linoleic acid (CLA) has been reported to have anti-obesity and antidiabetic effects. However, the benefits of CLA combined with exercise remain unclear, and studies report conflicting results. OBJECTIVE: A systematic review and meta-analysis were performed to investigate the synergistic effect of CLA and exercise on body composition, exercise-related indices, insulin resistance, and lipid profiles; and of the safety of CLA supplements. DATA SOURCES: In October 2021, the PubMed, Embase, and Cochrane Library databases were searched for reports on clinical trials of the combined intervention of CLA and exercise. DATA EXTRACTION: A total of 18 randomized controlled trials and 2 crossover trials were included. The methodological quality assessment was performed using the revised Cochrane risk-of-bias tool. Pooled effect sizes were reported as standardized mean difference (SMD) for continuous data and risk ratio for dichotomous data with their corresponding 95% confidence intervals (CIs). Heterogeneity was tested using the I2 statistic. DATA ANALYSIS: The combination of CLA and exercise resulted in significantly decreased body fat (SMD, -0.42 [95%CI, -0.70, -0.14]; P = 0.003; I2 = 65) and insulin resistance (SMD, -0.25 [95%CI, -0.44, -0.06]; P = 0.01; I2 = 0) than did exercise alone. In subgroup analysis, the following factors were associated with significant outcomes: (1) body mass index ≥25 kg/m2; (2) female sex; (3) follow-up time >4 weeks; and (4) intervention duration >4 weeks. Nevertheless, supplementation with CLA during exercise programs was not effective for body-weight control, exercise performance enhancement, or lipid-profile improvement. CLA in combination with exercise did not result in a higher risk of adverse events (risk ratio, 1.32 [95%CI, 0.94-1.84]; P > 0.05; I2 = 0). CONCLUSION: CLA combined with exercise is generally safe and can lower body fat and insulin resistance but does not reduce body weight, enhance exercise performance, or improve lipid profiles. © The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journ

BACKGROUND: Findings of studies investigating the effect of conjugated linoleic acid (CLA) supplementation on blood pressure (BP) and endothelial function are controversial. METHOD: This meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of CLA supplementation on BP and endothelial function. Two authors independently searched electronic databases using PubMed, Web of Science, and Scopus until March 2022, in order to find relevant RCTs. RESULTS: Eighteen RCTs with 20 effect sizes met the inclusion criteria and were eligible for meta-analysis. CLA supplementation did not significantly alter systolic blood pressure (SBP) (WMD: -0.48; 95% CI: -3.23, 2.27), diastolic blood pressure (DBP) (WMD: -0.71; 95% CI: -3.54, 2.12), and vascular cell adhesion molecule (VCAM) (WMD: -34.02; 95% CI: -88.08, 20.03) levels. However, CLA supplementation significantly reduced intercellular adhesion molecule (ICAM) (WMD: -8.02; 95% CI: -13.95, -2.09) level. CONCLUSION: This systematic review and meta-analysis showed CLA association with reduction of ICAM. The PROSPERO registration number: CRD42022331108.

Conjugated Linoleic Acid (CLA) are thought to pose beneficial effects on inflammatory responses and oxidative stress (OS). Thus, the present systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to assess the net effects of CLA supplementation on various OS parameters and antioxidant enzymes. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched for publications on CLA supplementation effects on OS parameters up to March 2021. The data extracted from eligible studies were expressed as standardized mean difference with 95% confidence intervals and then combined into meta-analysis using the random-effects model. Overall, 11 RCTs (enrolling 586 participants) met the inclusion criteria and were included in meta-analysis; however, since those trials evaluated different OS parameters, meta-analysis was carried out considering different sets for each parameter separately. According to our results, CLA supplementation significantly increases 8-iso-PGF2α urinary concentration (SMD: 2; 95% CI: 0.74, 3.27; I2 = 87.7%). On contrary, the intervention does not seem to change 15-keto-dihydro-PGF2α urinary concentration, nor the serum levels of CAT, SOD, GPx and MDA. Taken all together, CLA supplementation does not appear to have substantial effects on OS markers in general; albeit due to relatively small sample size and high level of heterogeneity between studies, the obtained findings should be interpreted with caution. Further large well-designed RCTs, investigating the impact of CLA and including various groups of patients, are still needed.

BACKGROUND & AIMS: Recent trial studies have found that conjugated linoleic acid (CLA) supplementation beneficially reduces oxidative stress markers but, there is no definitive consensus on this context. The present systematic review and meta-analysis aimed to investigate the effect of CLA supplementation on oxidative stress parameters. METHODS: We searched PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases until September 2021 to identify randomized controlled trials (RCTs) assessing CLA supplementation effects on oxidative markers including malondialdehyde (MDA), 8-isoprostanesF2α (8-iso-PGF2α), and glutathione peroxidase (GPx). Summary estimates and corresponding 95% confidence intervals (CI) were derived via the DerSimonian and Laird method using a random-effects model. RESULTS: A total of 11 RCTs were included. The obtained results show that CLA supplementation caused a significant decrease in MDA concentrations (Hedges's: -0.35; 95% CI: -0.70 to -0.01, P = 0.04, I2 = 62.1%, n = 7), and also significantly increased 8-iso-PGF2α levels (Hedges's: 1.45; 95% CI: 0.98 to 1.91, P˂0.001, I2 = 42.9%, n = 4). However, the results showed that supplementation with CLA did not significantly change the concentrations of GPx (Hedges's: 0.30; 95% CI: -0.04 to 0.64, P = 0.08, I2 = 0.0%, n = 3). CONCLUSION: It seems this supplement can be used as a dietary supplement to improve oxidative stress parameters. However, further studies are required to demonstrate present results.

Clinical trials have indicated conflicting results on the effects of conjugated linoleic acid (CLA) on obesity. The present study aimed to systematically review controlled clinical trials examining the effects of CLA on anthropometric indices and body composition in overweight and obese subjects. Pubmed, Scopus, Web of science, and Cochrane databases were searched between 2000 and December 2017 with no language restriction. Placebo-controlled clinical trials that reported anthropometric indices and body composition in overweight and obese subjects were included. Random-effect model was used to pool the effect estimates. Of 4032 publications, 13 trials were included for the meta-analysis. Pooled effect sizes indicated that CLA significantly reduced body weight (WMD: -0.52 kg, 95% CI: -0.83, -0.21; I2: 48.0%, p = 0.01), BMI (WMD: -0.23 kg/m2, 95% CI: -0.39, - 0.06; I2: 64.7%, p = 0.0001), FM (WMD: -0.61 kg, 95% CI: -0.98, -0.24; I2: 53.8%, p = 0.01) and increased LBM (WMD: 0.19 kg, 95% CI: 0.04, 0.34; I2: 81.4%, p = 0.0001) compared to the placebo group. However, the effects of CLA on WC (WMD: 0.05 cm, 95% CI: -0.01, 0.1; I2: 0%, p = 0.93) was not significant. Additionally, its impact on body weight in subjects older than 44 year (WMD: -1.05 kg, 95% CI: -1.75, -0.35; I2: 57.0%, p = 0.01), with longer duration (more than 12 weeks) (WMD: -1.29 kg, 95% CI: -2.29, -0.29; I2: 70.3%, p = 0.003) and dosage more than 3.4 g/day (WMD: -0.77 kg, 95% CI: -1.28, -0.25; I2: 62.7%, p = 0.004) were greater than comparative groups. Supplementation with CLA can slightly reduce body weight and FM and increase LBM in overweight and obese subjects. However, its efficacy was not clinically considerable. Further studies with high methodological quality are needed to shed light on the effects of CLA on anthropometric indices in overweight and obese subjects.

Whether conjugated linoleic acid (CLA) improves body composition by altering de novo lipogenesis (DNL) and related pathways in human remains unclear. The study aimed to investigate CLA-induced changes in DNL-derived fatty acids, and related metabolic pathways via plasma metabolome. Erythrocyte fatty acids of 65 participants with elevated body fat percentage before and after a 12-week CLA intervention were analyzed by gas chromatography. Compared with placebo, CLA supplementation decreased erythrocyte C16:1n7 and C18:1n9 while increased C18:3n3 levels (all p < 0.05). The C16:1n7 change was positively correlated with the triglycerides (TG) change, while the C18:3n3 change was negatively correlated with the low-density lipoprotein cholesterol (LDL-C) change. The optimal metabolite panels and metabolite scores predictive of fatty acid changes were identified and generated. TG and visceral adiposity index changes were positively correlated with the metabolite scores of the C16:1n7 change and C18:1n9 change, while metabolite score of the C18:3n3 change was negatively correlated with LDL-C change. Furthermore, DNL fatty acid changes were related to KEGG pathways, including the citrate cycle and butanoate metabolism. In adults with high body fat, 12-week CLA supplementation suppressed DNL activity, associated with changes in plasma and liver lipids, involving energy metabolism pathways. Trial Registration: ClinicalTrials.gov identifier: NCT03915808. © 2025 Wiley‐VCH GmbH.

Background and Objectives: Conjugated linoleic acid (CLA) can improve bone health in animals, yet the effects on humans have not been consistent. Therefore, this parallel randomised controlled trial aimed to assess the effect of CLA supplementation on bone mineral density (BMD) and content (BMC) in overweight or obese women. Materials and Methods: The study population included 74 women who were divided into the CLA (n = 37) and control (n = 37) groups. The CLA group received six capsules per day containing approximately 3 g of cis-9, trans-11 and trans-10, cis-12 CLA isomers in a 50:50 ratio. The control group received the same number of placebo capsules that contained sunflower oil. BMC and BMD at total body, lumbar spine (L1-L4), and femoral neck were measured before and after a three-month intervention. Results: The comparison of BMC and BMD for the total body, lumbar spine (L1-L4), and femoral neck before and after the intervention showed no differences between the groups. However, a within-group analysis demonstrated a significant increase in BMC (p = 0.0100) and BMD (p = 0.0397) at lumbar spine (L1-L4) in the CLA group. Nevertheless, there were no significant differences between the CLA and placebo groups in changes in all analysed densitometric parameters. Conclusions: Altogether, three-month CLA supplementation in overweight and obese women did not improve bone health, although the short intervention period could have limited our findings, long-term intervention studies are needed. The study protocol was registered in the German Clinical Trials Register database (ID: DRKS00010462, date of registration: 4 May 2016).

CONTEXT: Conjugated linoleic acid (CLA) may optimize body composition, yet mechanisms underlining its benefits are not clear in humans. OBJECTIVE: We aimed to reveal the CLA-induced changes in the plasma metabolome associated with body composition improvement and the predictive performance of baseline metabolome on intervention responsiveness. METHODS: Plasma metabolome from overnight fasted samples at pre- and post-intervention of 65 participants in a 12-week randomized, placebo-controlled trial (3.2 g/day CLA vs 3.2 g/day sunflower oil) were analyzed using untargeted LC-MS metabolomics. Mixed linear model and machine learning were applied to assess differential metabolites between treatments, and to identify optimal panel (based on baseline conventional variables vs metabolites) predicting responders of CLA-derived body composition improvement (increased muscle variables or decreased adiposity variables) based on dual-energy x-ray absorptiometry. RESULTS: Compared with placebo, CLA altered 57 metabolites (P < 0.10) enriched in lipids/lipid-like molecules including glycerophospholipids (n = 7), fatty acyls (n = 6), and sphingolipids (n = 3). CLA-upregulated cholic acid (or downregulated aminopyrrolnitrin) was inversely correlated with changes in muscle and adiposity variables. Inter-individual variability in response to CLA-derived body composition change. The areas under the curves of optimal metabolite panels were higher than those of optimal conventional panels in predicting favorable response of waist circumference (0.93 [0.82-1.00] vs 0.64 [0.43-0.85]), visceral adiposity index (0.95 [0.88-1.00] vs 0.58 [0.35-0.80]), total fat mass (0.94 [0.86-1.00] vs 0.69 [0.51-0.88]) and appendicular fat mass (0.97 [0.92-1.00] vs 0.73 [0.55-0.91]) upon CLA supplementation (all FDR P < 0.05). CONCLUSION: Post-intervention metabolite alterations were identified, involving in lipid/energy metabolism, associated with body composition changes. Baseline metabolite profiling enhanced the prediction accuracy for responsiveness of CLA-induced body composition benefits. © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights rese

Linoleic acid (LA) is an omega-6 polyunsaturated fatty acid. Conjugated linoleic acid (CLA) is a family of LA isomers that includes both a trans fatty acid and a cis fatty acid. Both fatty acids play a nutritional role in maintaining health. Inflammation is critical in the pathogenesis of many diseases, including cancer. This study found that the combination of LA and CLA (LA/CLA), each of which had no effect, had a strong anti-synergistic effect on inflammatory macrophage RAW264.7 cells in vitro. Cells were cultured in a DMEM containing fetal bovine serum with or without either LA, CLA, or a combination of LA/CLA. The composition of LA and CLA at a comparatively lower concentration synergistically suppressed cell growth, resulting in a reduction in cell number. The underlying mechanism of this effect was based on reduced levels of Ras, PI3K, Akt, MAPK, and mTOR and elevated levels of p21, p53, and Rb, which are associated with cell growth. In addition, the combination of LA and CLA at a lower concentration stimulated potential cell death associated with increased caspase-3 and cleaved caspase-3 levels. Notably, this composition synergistically suppressed the production of TNF-α, IL-6, and PGE2, which are a major mediator of inflammation, with lipopolysaccharide stimulation in RAW264.7 cells This effect was associated with decreased levels of COX-1, COX-2, and NF-κB p65. This study may provide a useful tool for treating inflammatory conditions with the composition of LA and CLA.

Exploring the synergistic effect of docosahexaenoic acid (DHA) or conjugated linoleic acid (CLA) with caffeic acid (CA) on ameliorating oxidative stress, thereby introducing CA to DHA or CLA will contribute significantly to enhance the bioactivity. We observed that DHA or CLA with CA promoted the recovery of intact individual morphology and the decline of cavities inside the nucleus and apoptosis under the observation of confocal laser scanning microscopy and fluorescent inverted microscope. The activity of intracellular antioxidant enzymes catalase (CAT) and glutathione peroxidase (GSH-Px), lactate dehydrogenase (LDH) leakage, pyruvate and malondialdehyde and reactive oxygen species (ROS), cellular morphology, and cell cycle were analyzed. Our results showed that DHA or CLA with CA enhanced the activity of CAT and GSH-Px, decreased LDH leakage and the number of apoptotic, significantly inhibited (ROS-induced cellular injury. Cell arrest in G1 and G2 phase during cell mitosis was reduced by the measurement of flow cytometry. DHA or CLA combined with CA could markedly strengthen the free radical scavenging and endogenous antioxidant defense capacity on HepG2 cells. This study provides a new direction in the application of synergies to antioxidant compounds. PRACTICAL APPLICATION: Caffeic acid (CA) can synergize with docosahexaenoic acid (DHA) or conjugated linoleic acid (CLA) to enhance antioxidant capacity. This study highlighted an effect of ameliorating oxidative stress injury DHA or CLA with CA on HepG2 cells. The data indicated that DHA or CLA with CA might be used to relieve oxidative stress damage. © 2021 Institute of Food Technologists®.

During biohydrogenation-induced milk fat depression, adipose tissue lipogenesis may be increased through nutrients spared from milk fat synthesis. However, the direct effect of trans-10,cis-12 conjugated linoleic acid (CLA) and the indirect effect of spared nutrients on adipose tissue lipogenesis during milk fat depression is not clear. The objective of this study was to determine the direct effect of CLA, spared acetate, and their interaction on adipose tissue lipogenesis using nonlactating dairy cows as an experimental model, which allows separation of the effect of CLA and nutrient sparing. Eight ruminally cannulated, multiparous nonlactating and pregnant Holstein cows were randomly assigned to treatments in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Factors were CLA and acetate, and treatments were control (CON), rumen acetate infusions (Ac; continuous infusion of 7 mol/d adjusted to pH 6.1 with sodium hydroxide), abomasal infusion of trans-10,cis-12 CLA (CLA; 10 g/d of both trans-10,cis-12 CLA and cis-9,trans-11 CLA), and Ac + CLA (Ac + CLA). Dry matter intake was not affected by Ac, but tended to decrease by CLA. Plasma trans-10,cis-12 CLA concentration as a percentage of fatty acids was increased by 0.3 percentage points by CLA. No treatment effect was observed on plasma glucose and β-hydroxybutyrate, but an interaction was observed of CLA and Ac on plasma insulin and nonesterified fatty acids. Insulin was increased 24% by CLA, but not by Ac + CLA, and nonesterified fatty acids were increased 55% by Ac + CLA, but not by CLA alone. Lipogenesis and oxidation capacity of adipose tissue explants were not affected by treatments. Adipose expression of key lipogenic factors (peroxisome proliferator-activated receptor γ2 and sterol response element binding protein 1c) were reduced by CLA, by the interaction of Ac and CLA (sterol response element binding protein 1c), and tended to be reduced with Ac (S14 and peroxisome proliferator-activated receptor γ1). Expression of several adipose lipogenic enzymes (fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase 1) was reduced by CLA and Ac. An interaction was observ

The aim of this study was to determine in vitro synergistic efficacy of conjugated linoleic acid (CLA), oleic acid (OLA), safflower oil and taxol (Tax) cytotoxicity on human prostate cancer (PC3) cell line. To determine synergistic efficacy of oil combinations, PC3 treated with different doses of compounds alone and combined with 10 μg/mL Tax. The MTT results indicated that OLA-Tax combinations exhibited cytotoxicity against PC3 at doses of 30 nM+10 μg-Tax, 15 nM+5 μg-Tax and 7.5 nM+2.5 μg-Tax. The treatment of OLA or Tax did not show significant inhibition on PC3, while OLA-Tax combinations showed effective cytotoxicity at treated doses. CLA-Tax combinations demonstrated the same effect on PC3 as combined form with 45.72% versus the alone form as 74.51% viability. Cytotoxic synergy between Tax, OLA and CLA shows enhanced cytotoxicity on PC3 which might be used in the therapy of prostate cancer.

Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR-α and RXR heterodimer. We also present preliminary data that may position PPAR-α at the crossroads between the metabolism of lipids and vitamin A.

PURPOSE: The combination of resveratrol + conjugated linoleic acid (RSV + CLA) did not show the body fat-lowering effect exhibited by these molecules when administered separately. This study aimed to find metabolic explanations for this situation in an experimental model of diet-induced obesity. METHODS: Thirty-six male Wistar rats were divided into four groups: rats treated with saline (control), resveratrol (RSV), conjugated linoleic acid (CLA) and a combination of these molecules (RSV + CLA). RESULTS: Rats treated with RSV + CLA did not show the reduction in heparin-releasable lipoprotein lipase (HR-LPL) and fatty acid synthase activities observed in RSV group or the increased HSL expression found in RSV and CLA groups. These animals showed reduced sirtuin 1 expression and CLA isomer amounts in adipose tissue. Finally, intracellular Ca(2+) concentration was increased. CONCLUSION: The attenuation of the effects induced in adipose tissue triacylglycerol metabolism by RSV and CLA separately, such as the decrease in lipogenesis and fatty acid uptake and the increase in lipolysis, contributes to explain the lack of body fat-lowering effect of the combination RSV + CLA.

Whole fat milk and dairy products (although providing more energy compared to low- or non-fat products), are good sources of α-linolenic acid (ALA), conjugated linoleic acid (CLA) and calcium, which may be favorable in modulating bone and adipose tissue metabolism. We examined individual and/or synergistic effects of ALA, CLA and calcium (at levels similar to those in whole milk/dairy products) in regulating bone and adipose cell growth. ST2 stromal, MC3T3-L1 adipocyte-like and MC3T3-E1 osteoblast-like cells were treated with: (a) linoleic acid (LNA):ALA ratios = 1-5:1; (b) individual/combined 80-90 % c9, t11 (9,11) and 5-10 % t10, c12 (10,12) CLA isomers; (c) 0.5-3.0 mM calcium; (d) combinations of (a), (b), (c); and (e) control. Local mediators, including eicosanoids and growth factors, were measured. (a) The optimal effect was found at the 4:1 LNA:ALA ratio where insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) production was the lowest in MC3T3-L1 cells. (b) All CLA isomer blends decreased MC3T3-L1 and increased MC3T3-E1 cell differentiation. (c) 1.5-2.5 mM calcium increased ST2 and MC3T3-E1, and decreased MC3T3-L1 cell proliferation. (d) Combination of 4:1 LNA:ALA + 90:10 % CLA + 2.0 mM calcium lowered MC3T3-L1 and increased MC3T3-E1 cell differentiation. Overall, the optimal LNA:ALA ratio to enhance osteoblastogenesis and inhibit adipogenesis was 4:1. This effect was enhanced by 90:10 % CLA + 2.0 mM calcium, indicating possible synergism of these dietary factors in promoting osteoblast and inhibiting adipocyte differentiation in cell cultures.

Conjugated linoleic acid (CLA), a dietary lipid, has been proposed as an antidiabetic agent. However, studies specifically addressing the molecular dynamics of CLA on skeletal muscle glucose transport and differences between the key isomers are limited. We demonstrate that acute exposure of L6 myotubes to cis-9, trans-11 (c9,t11) and trans-10, cis-12 (t10,c12) CLA isomers mimics insulin action by stimulating glucose uptake and glucose transporter-4 (GLUT4) trafficking. Both c9,t10-CLA and t10,c12-CLA stimulate the phosphorylation of phosphatidylinositol 3-kinase (PI3-kinase) p85 subunit and Akt substrate-160 kDa (AS160), while showing isomer-specific effects on AMP-activated protein kinase (AMPK). CLA isomers showed synergistic effects with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR). Blocking PI3-kinase and AMPK prevented the stimulatory effects of t10,c12-CLA on AS160 phosphorylation and glucose uptake, indicating that this isomer acts via a PI3-kinase and AMPK-dependent mechanism, whereas the mechanism of c9,t11-CLA remains unclear. Intriguingly, CLA isomers sensitized insulin-Akt-responsive glucose uptake and prevented high insulin-induced Akt desensitisation. Together, these results establish that CLA exhibits isomer-specific effects on GLUT4 trafficking and the increase in glucose uptake induced by CLA treatment of L6 myotubes occurs via pathways that are distinctive from those utilised by insulin.

BACKGROUND: The pathophysiology of cellulite involves changes in the subcutaneous adipose layer and the extracellular matrix (ECM) that supports it together with overlying dermal layer. Cellular mechanisms governing cellulite are not fully understood. However, it is accepted that changes include enhanced lipogenesis, decreased lipolysis, and increased lipid storage within the adipocytes as well as changes in the dermal architecture. AIM: In our studies the ability of cosmetic agents Furcellaria lumbricalis, Fucus vesiculosus, retinoid, conjugated linoleic acid (CLA), and a glaucine mixture to stimulate in vitro 1) lipolysis in human adipocytes and 2) production of pro-collagen I by fibroblasts was investigated in vitro. The ability of these ingredients to improve cellulite condition in vivo was also determined. PATIENTS/METHODS: Mature adipocytes and 'aged' fibroblasts were used for in vitro studies. The assessment of cellulite in vivo was performed by dermatological grading and ultrasound measurements. RESULTS: Mature adipocytes treated with combined actives resulted in a significant synergistic increase in free glycerol release. On "aged" fibroblasts, combined treatment of F. vesiculosus and F. lumbricalis stimulated pro-collagen I production. CLA increased pro-collagen I production, but the glaucine mixture had no effect. The clinical study demonstrated a significant improvement in cellulite grading by a dermatologist after 8 and 12 weeks vs. vehicle, and ultrasound imaging showed a significant decrease in fat thickness compared with placebo after 12 weeks. CONCLUSIONS: Our studies revealed a potent cocktail of ingredients that when combined together can act in vitro to markedly improve lipolysis mechanisms and by way of stimulating pro-collagen I can also have an effect on the surrounding extracellular matrix. The in vitro actions of the ingredients were translated in vivo, where a clinical improvement of cellulite condition was observed. © 2012 Wiley Periodicals, Inc.

Acylpeptide hydrolase (APEH), one of the four members of the prolyl oligopeptidase class, catalyses the removal of N-acylated amino acids from acetylated peptides and it has been postulated to play a key role in protein degradation machinery. Disruption of protein turnover has been established as an effective strategy to down-regulate the ubiquitin-proteasome system (UPS) and as a promising approach in anticancer therapy.Here, we illustrate a new pathway modulating UPS and proteasome activity through inhibition of APEH. To find novel molecules able to down-regulate APEH activity, we screened a set of synthetic peptides, reproducing the reactive-site loop of a known archaeal inhibitor of APEH (SsCEI), and the conjugated linoleic acid (CLA) isomers. A 12-mer SsCEI peptide and the trans10-cis12 isomer of CLA, were identified as specific APEH inhibitors and their effects on cell-based assays were paralleled by a dose-dependent reduction of proteasome activity and the activation of the pro-apoptotic caspase cascade. Moreover, cell treatment with the individual compounds increased the cytoplasm levels of several classic hallmarks of proteasome inhibition, such as NFkappaB, p21, and misfolded or polyubiquitinylated proteins, and additive effects were observed in cells exposed to a combination of both inhibitors without any cytotoxicity. Remarkably, transfection of human bronchial epithelial cells with APEH siRNA, promoted a marked accumulation of a mutant of the cystic fibrosis transmembrane conductance regulator (CFTR), herein used as a model of misfolded protein typically degraded by UPS. Finally, molecular modeling studies, to gain insights into the APEH inhibition by the trans10-cis12 CLA isomer, were performed.Our study supports a previously unrecognized role of APEH as a negative effector of proteasome activity by an unknown mechanism and opens new perspectives for the development of strategies aimed at modulation of cancer progression.

BACKGROUND AND AIMS: Conjugated linoleic acid (CLA) has been used to improve body composition in weight management. However, clinical trial results are inconsistent and limited among Asians. We aimed to investigate the effect of CLA on body composition of Chinese adults with elevated body fat percentage. METHODS AND RESULTS: In this double-blind, randomized, placebo-controlled trial, 66 Chinese adults (aged 18-45 years old, 37.9% male) with elevated body fat percentage were provided with 3.2 g/day CLA (n = 33) or 3.2 g/day placebo (sunflower oil; n = 33) for 12 weeks. Both groups received lifestyle counseling, featured with low fat and low sugar diet, and moderate physical activity. Body composition was measured using dual-energy X-ray absorptiometry at the baseline and end of the trial. Sixty-four participants finished this study. Compared with the placebo group, the CLA group showed increased trunk muscle mass (MM) (0.6 ± 1.7 vs. -0.3 ± 1.2 kg, P = 0.019). Among those with an adherence score higher than 0.80 (n = 56, 87.5%), a greater increase in both total and trunk MM was observed in the CLA group (both P < 0.05). Moreover, the effect on MM appeared to be more evident in men, those with a body mass index <25 kg/m2, or those with higher self-rated physical activity. CONCLUSIONS: In Chinese adults with elevated body fat percentage, 3.2 g/day CLA supplementation may be effective in preserving MM, especially in the trunk region. REGISTRATION: This study was registered at ClinicalTrials.gov as NCT03915808 on April 9, 2019.

OBJECTIVE: Conjugated linoleic acid (CLA) has several benefits, including body fat reduction, as proved in animals. However, the results of CLA-induced body composition alterations in humans are inconsistent, and no related data are available for Chinese populations. This study aimed to determine whether CLA affects body weight (BW) loss and body composition of overweight and obese Chinese subjects. METHODS: In this randomized, double-blind, placebo-controlled trial, subjects with a body mass index (BMI) of 24 to 35 kg/m(2) randomly received 1.7 g of cis-9,trans-11 and trans-10,cis-12 CLA (n = 30) or placebo (salad oil; n = 33) in 200 mL of sterilized milk twice daily for 12 wk. Changes in body composition were determined by bioimpedance measurements. RESULTS: Sixty-three subjects completed the study (CLA, n = 30). After 12 wk, compared with the baseline, the BW, BMI, total fat mass, fat percentage, subcutaneous fat mass, and waist-to-hip ratio decreased in the CLA group (P < 0.05). The CLA group was stratified by BMI and gender. The BW, BMI, subcutaneous fat mass, and waist-to-hip ratio decreased in 27 subjects with a BMI ≥ 27, and these indices, except subcutaneous fat mass, were lower in female subjects. The levels of total cholesterol, triacylglycerol, low-density lipoprotein, and plasma fasting glucose increased, whereas those of high-density lipoprotein decreased after 3 mo of CLA treatment. The changes were not significantly different from the baseline values. CONCLUSION: The supplementation of CLA for 12 wk in overweight and grade I obese Chinese subjects yielded lower obesity indices, with no obvious adverse effects. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

We hypothesized that increasing ruminal pH would lead to enrichment of adipose tissue with conjugated linoleic acid (CLA). Twenty-four Korean native (Hanwoo) steers were used to investigate the additive effects of monensin (30ppm, SO-BM) and/or fish oil (0.7%, SO-BMF) in the diets along with soybean oil (7%) and sodium bicarbonate (0.5%, SO-B) on cis-9, trans-11 and trans-10, cis-12 CLAs in adipose tissue. The steers were assigned to randomly four groups of six animals each based on body weight. The control group (CON) was fed a commercial concentrate for the late fattening stage. Supplementation of oil and sodium bicarbonate reduced feed intake and daily gain, and fish oil further decreased feed intake (P<0.001) and daily gain (P<0.087) compared to steers fed other diets. Total CLA and CLA isomers in M.longissimus dorsi were not affected when steers were fed SO-B and SO-BM diets compared with those of steers fed CON and SO-BMF diets. However, total poly unsaturated fatty acids were higher (P=0.03) in steers fed SO than in CON steers. Published by Elsevier Ltd.

Polycystic ovary syndrome is the most common endocrine disorder in women. Today, medicinal plants have been considered by women, especially in the reproductive and pregnancy ages. Multiple drug treatments and the length of the treatment period often lead to incomplete treatment by patients. Therefore, due to the side effects of chemical drugs, this study was conducted to assess investigate the effect of pomegranate seed oil on polycystic ovary syndrome. The prevalence of polycystic ovary syndrome is increasing by 15 to 20% and clinically includes oligomenorrhea or amenorrhea, hirsutism, and often infertility. Databases such as Cochran library, Medline, PubMed, SID, and Science Direct were used to access the related articles. To collect the required information, first, the articles that had one of the keywords of medicinal plants, polycystic ovary syndrome, plant, pomegranate extract, and menstrual irregularities in their text were searched in databases. All studies from 1985 to 2021 are included in the study. Conjugated linolenic acid (CLN) is a group of geometric and positional isomers of linolenic acid in which double bonds are conjugated. CLN has been reported to have a very strong cytotoxic effect on tissue tumor cells in the body, preventing cancer, reducing the accumulation of triacylglycerol in the liver, polycystic ovary syndrome, and LDL cholesterol in the blood. So far, seven CLN isomers have been identified, including ponic acid in pomegranate seed oil. Conjugated linoleic acid (CLA) is a group of situational and geometric isomers of linoleic acid in which double bonds are conjugated. The positive effects of the two main CLA isomers (cis-9, trans-11, and trans-10, cis-12) include inhibiting the growth of cancer, reducing the risk of atherosclerosis, and reducing body fat.

The results of human clinical trials examining the effects of conjugated linoleic acid (CLA) on leptin concentration are inconsistent. Our objective was to elucidate the role of conjugated linoleic acid supplementation on leptin through a systematic review and a meta-analysis of available randomized placebo-controlled trials (RCTs). We searched the PubMed, SCOPUS, and ISI web of science up to February2017, in English, to identify RCTs investigating the effect of CLA supplements on plasma leptin concentrations. Weighted mean differences (WMDs) and their respective 95% confidence intervals (CIs) were calculated to assess the efficacy of CLA on leptin concentration by using random effects. Statistical heterogeneity, study quality, meta-regression and publication bias were used based on standard methods. Nineteen RCTs (comprising 26 treatment arms) with 1045 subjects were included in this meta-analysis. Random-effect meta-analysis found a slight but not significant reduction in plasma leptin concentrations (WMD: -0.38 ng/ml, 95% CI: -1.08, 0.32, p=0.286); I2=53.24%, p=0.001), following CLA supplementation. The pooled effect size was robust and remained non-significant in the leave-one-out sensitivity analysis. Subgroup analysis based on BMI status showed that the CLA supplementation significantly reduces leptin when used for obese subjects (WMD: -1.47 ng/ml, 95% CI: -2.15, -0.79, p<0.001) and in the subset of trials lasting<24 weeks of duration (WMD: -0.76 ng/ml, 95% CI: -1.40, -0.12, p=0.019). CLA supplementation might moderately decrease circulatory leptin levels only among obese adults for shorter than 24 weeks. Additional high-quality studies are needed to replicate our results. © Georg Thieme Verlag KG Stuttgart · New York.

BACKGROUND/OBJECTIVES: Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid with attractive biological activities. Numerous studies have been conducted on the inflammation-lowering effects of CLA in in vitro and animal models. However, the effects of CLA treatment on the inflammatory markers in humans are controversial. Therefore, the objective of this study was to perform a systematic review and meta-analysis on controlled clinical trials (RCT) assessing the effects of CLA supplementation on the circulating inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). SUBJECTS/METHODS: The literature search of RCTs was performed using Pubmed/Medline, Scopus, ScienceDirect, Web of science, Cochrane, and Google Scholar databases from inception to March 2017. Weighted mean differences were estimated and the pooled effect size was calculated by a random effects model. RESULTS: Of the 427 identified studies, eleven RCTs, including 420 subjects were included in the statistical analysis. Findings suggested that CLA supplementation increased blood levels of CRP by 0.89 mg/l (95% CI: 0.11, 1.68; P = 0.025) and TNF-α levels by 0.39 pg/ml (95% CI: 0.23, 0.55; P < 0.0001). However, blood IL-6 levels were marginally decreased by 0.32 pg/ml (95% CI: -0.71, 0.07; P = 0.11) following CLA supplementation. There was a significant heterogeneity for the impact of CLA on CRP and IL-6, but not TNF-α. CONCLUSIONS: This meta-analysis showed that CLA supplementation may increase inflammatory markers (CRP and TNF-α). There are concerns about using CLA supplementation as an anti-obesity agent among the obese population for at least a short duration.