The Effect of Conjugated Linoleic Acid Supplementation on Densitometric Parameters in Overweight and Obese Women-A Randomised Controlled Trial.

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).

Topical application with conjugated linoleic acid ameliorates 2, 4-dinitrofluorobenzene-induced atopic dermatitis-like lesions in BALB/c mice.

Atopic dermatitis (AD) is a multifactorial chronic inflammatory skin disease characterized by skin barrier dysfunction, eczematous lesions, pruritus, and abnormal immune responses. In this study, we assessed the therapeutic effect of topical applied conjugated linoleic acid (CLA) on a murine AD model that was developed by repetitive applications of 2, 4-dinitrofluorobenzene (DNFB). 2% or 5% CLA could markedly ameliorate AD-like skin lesions, scratching behaviour and skin inflammation as evidenced by the reduced inflammatory blood cells, IgE and Th2-related cytokine levels, and the infiltration of mast cells and inflammatory cells to the dermal tissues. Moreover, topical application with CLA modulated skin barrier repair including maintaining a balanced skin pH and increasing skin hydration, partially mediated by upregulating skin barrier-related protein, filaggrin (FLG). In addition, topical CLA significantly dose-dependently inhibited pro-inflammatory cytokines including interleukin (IL)-6, IL-1ß, tumour necrosis factor (TNF)-α and pro-inflammatory enzyme expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in inflamed mice skin. Its anti-inflammatory effect was associated with the inhibition of DNFB-stimulated IκBα and NF-κB p65 phosphorylation in mouse skin. Taken together, our results suggest that locally applied CLA exerts potentially protective effects against AD lesional skin at least in part, due to regulation of skin barrier function and inflammatory response.

Different monocyte phenotypes result in proresolving macrophages in conjugated linoleic acid-induced attenuated progression and regression of atherosclerosis.

Monocytes/macrophages drive progression and regression of atherosclerosis. Conjugated linoleic acid (CLA), an anti-inflammatory lipid, mediates atheroprotective effects. We investigated how CLA alters monocyte/macrophage phenotype during attenuated progression and regression of atherosclerosis. Apolipoprotein E knockout (ApoE-/-) mice were fed a high-fat (60%) high-cholesterol (1%) diet (HFHCD) for 2 wk, followed by 6-wk 1% CLA 80:20 supplementation to investigate disease progression. Simultaneously, ApoE-/- mice were fed a 12-wk HFHCD with/without CLA for the final 4 wk to investigate regression. Aortic lesions were quantified by en face staining. Proteomic analysis, real-time quantitative PCR and flow cytometry were used to interrogate monocyte/macrophage phenotypes. CLA supplementation inhibited atherosclerosis progression coincident with decreased proinflammatory and increased anti-inflammatory macrophages. However, CLA-induced regression was associated with increased proinflammatory monocytes resulting in increased proresolving M2 bone marrow-derived macrophages, splenic macrophages, and dendritic cells in lesion-draining lymph nodes. Proteomic analysis confirmed regulation of a proinflammatory bone marrow response, which was abolished upon macrophage differentiation. Thus, in attenuation and regression of atherosclerosis, regardless of the monocyte signature, during monocyte to macrophage differentiation, proresolving macrophages prevail, mediating vascular repair. This study provides novel mechanistic insight into the monocyte/macrophage phenotypes in halted atherosclerosis progression and regression of atherosclerosis.-Bruen, R., Curley, S., Kajani, S., Lynch, G., O'Reilly, M. E., Dillon, E. T., Fitzsimons, S., Mthunzi, L., McGillicuddy, F. C., Belton, O. Different monocyte phenotypes result in proresolving macrophages in conjugated linoleic acid-induced attenuated progression and regression of atherosclerosis.

Conjugated linoleic acid supplements preserve muscle in high-body-fat adults: A double-blind, randomized, placebo trial.

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.

Effect of L-carnitine and conjugated linoleic acid supplements on haemoglobin levels and haptoglobin genotype in chronic kidney disease.

OBJECTIVE: To investigate the efficacy of L-carnitine (LC) and conjugated linoleic acid (CLA) supplements on haemoglobin levels and inflammatory markers in chronic kidney disease (CKD) patients with different haptoglobin (HP) genotypes. METHODS: This clinical trial study was conducted at Imam Khomeini Hospital, Ardabil, and Labbafinejad Hospital, Tehran, Iran, from March 2014 to March 2015, and comprised male patients with CKD and anaemia. Anthropometric factors were recorded and demographic data was collected using general questionnaires. LC (1 g/day) and CLA (2.4 g/day) supplements were given to the patients for a month. Blood samples were taken to measure haematological and inflammatory markers at the beginning and end of the study. Haptoglobin genotypes were determined using polymerase chain reaction (PCR). SPSS 21 was used for data analysis. RESULTS: Among the 40 patients in the study, HP2-2 genotype was the most prevalent genotype (62.5%). The level of haemoglobin was significantly increased in the patients at the end of the study (p< 0.05). No significant changes were found in the weight, body mass index and serum levels of Interleukin-6, high-sensitivity C-reactive protein, ferritin, total iron-binding capacity and iron (p>0.05 each). CONCLUSIONS: Regular diet supplementation with LC plus CLA can improve haemoglobin levels in CKD patients with anaemia.

Obese Mice Losing Weight Due to trans-10,cis-12 Conjugated Linoleic Acid Supplementation or Food Restriction Harbor Distinct Gut Microbiota.

Background: trans-10,cis-12 Conjugated linoleic acid (t10,c12-CLA) is a dietary supplement that promotes weight loss by increasing fat oxidation and energy expenditure. We previously reported that in the absence of t10,c12-CLA, mice forced to lose equivalent body weight by food restriction (FR) do not exhibit increases in fat oxidation or energy expenditure but have improved glucose metabolism, consistent with FR as a metabolically healthy weight-loss method. Objective: Because diet is a primary determinant of gut bacterial populations, we hypothesized that the disparate metabolic effects accompanying weight loss from t10,c12-CLA or FR could be related to altered intestinal microbiota. Methods: Ten-week-old male LDL receptor-deficient (Ldlr-/-) mice were fed a high-fat, high-sucrose diet (HFHS; 36% lard fat, 36.2% sucrose + 0.15% cholesterol) for 12 wk (baseline), then switched to the HFHS diet alone (obese control), HFHS + 1% c9,t11-CLA (obese fatty acid control), HFHS + 1% t10,c12-CLA (weight-loss-inducing fatty acid), or HFHS + FR (weight-loss control group with 75-85% ad libitum HFHS food intake) for a further 8 wk. Fecal microbial content, short-chain fatty acids (butyrate, acetate), tissue CLA concentrations, and intestinal nutrient transporter expression were quantified. Results: Mice fed t10,c12-CLA or assigned to FR lost 14.5% of baseline body weight. t10,c12-CLA-fed mice had elevated concentrations of fecal butyrate (2-fold) and plasma acetate (1.5-fold) compared with HFHS-fed controls. Fecal α diversity decreased by 7.6-14% in all groups. Butyrivibrio and Roseburia, butyrate-producing microbes, were enriched over time by t10,c12-CLA. By comparing with each control group, we also identified bacterial genera significantly enriched in the t10,c12-CLA recipients, including Lactobacillus, Actinobacteria, and the newly identified Ileibacterium valens of the Allobaculum genus, whereas other taxa were enriched by FR, including Clostridiales and Bacteroides. Conclusion: Modalities resulting in equivalent weight loss but with divergent metabolic effects are associated with compositional differences in the mouse intestinal microbiota.

Nutrient Regulation: Conjugated Linoleic Acid's Inflammatory and Browning Properties in Adipose Tissue.

Obesity is the most widespread nutritional disease in the United States. Developing effective and safe strategies to manage excess body weight is therefore of paramount importance. One potential strategy to reduce obesity is to consume conjugated linoleic acid (CLA) supplements containing isomers cis-9, trans-11 and trans-10, cis-12, or trans-10, cis-12 alone. Proposed antiobesity mechanisms of CLA include regulation of (a) adipogenesis, (b) lipid metabolism, (c) inflammation, (d) adipocyte apoptosis, (e) browning or beiging of adipose tissue, and (f) energy metabolism. However, causality of CLA-mediated responses to body fat loss, particularly the linkage between inflammation, thermogenesis, and energy metabolism, is unclear. This review examines whether CLA's antiobesity properties are due to inflammatory signaling and considers CLA's linkage with lipogenesis, lipolysis, thermogenesis, and browning of white and brown adipose tissue. We propose a series of questions and studies to interrogate the role of the sympathetic nervous system in mediating CLA's antiobesity properties.

Systematic evaluation on the effectiveness of conjugated linoleic acid in human health.

The term CLA (conjugated linoleic acid) corresponds to a mixture of positional and geometric isomers of linoleic acid. Two of these isomers (9c, 11t and 10t, 12c) have biological activity. The milk and dairy products are the most abundant source of conjugated linoleic acid, which refers to a group of positional and geometric isomers of CLA (CLA 18:2 cis-9, cis-12). The following research aims to approach aspects regarding the CLA, as well as its relationship with diseases. Conjugated linoleic acids have been studied for their beneficial effects in the prevention and treatment of many diseases, including obesity, cancer, diabetes, and cardiovascular diseases. Scientific information put together the physiological properties of CLA, which serves as inputs to claim their potential as functional ingredients to be used in the prevention and control of several chronic metabolic disorders.

Evidences and perspectives in the utilization of CLNA isomers as bioactive compounds in foods.

Conjugated alpha linolenic acid (CLNA) isomers are promising lipids owing to their similarities with conjugated linoleic acid (CLA) but exerting their bioactivity at lower doses; some isomers also belong to omega 3 family. This review aims to summarize the state of the art about the utilization of CLNA as a functional ingredient. Indeed, in vitro and in vivo studies reported that CLNA exerted anticancer, anti-inflammatory, anti-obese, and antioxidant activities. However, CLNA has not been tested in humans. These compounds are naturally present in meat and milk fat from ruminants but the highest concentrations are found in vegetable oils. Their incorporation in foodstuffs is one of the most effective strategies to elaborate CLNA-enriched products together with the microbiological production. Lactobacilli, propionibacteria, and bifidobacteria strains have been assayed to produce CLNA isomers but at the current moment there are not high CLNA concentration products elaborated using these strains. Furthermore, it is known that CLNA isomers are highly prone to oxidation when compared with linoleic acid and CLA, but the possible effects of elaboration and storage on high CLNA productsare unknown.The utilization of CLNA as a functional compound still remains a challenge and requires more research to address all of its technological and bioactivity aspects.

Atheroprotective effects of conjugated linoleic acid.

Atherosclerosis, the underlying cause of heart attack and strokes, is a progressive dyslipidaemic and inflammatory disease where monocyte-derived macrophage cells play a pivotal role. Although most of the mechanisms that contribute to the progression of atherosclerosis have been identified, there is limited information on those governing regression. Conjugated linoleic acid (CLA) is a generic term denoting a group of naturally occurring isomers of linoleic acid (18:2, n6) that differ in the position or geometry (i.e. cis or trans) of their double bonds. The most predominant isomers in ruminant fats are cis-9, trans-11 CLA (c9,t11-CLA), which accounts for more than 80% of CLA isomers in dairy products and trans-10, cis-12 CLA (t10,c12-CLA). Dietary administration of a blend of the two most abundant isomers of CLA has been shown to inhibit the progression and induce the regression of pre-established atherosclerosis. Studies investigating the mechanisms involved in CLA-induced atheroprotective effects are continually emerging. The purpose of this review is to discuss comprehensively the effects of CLA on monocyte/macrophage function in atherosclerosis and to identify possible mechanisms through which CLA mediates its atheroprotective effects.

Methylation analysis in fatty-acid-related genes reveals their plasticity associated with conjugated linoleic acid and calcium supplementation in adult mice.

PURPOSE: DNA methylation is one of the most extensively studied mechanisms within epigenetics, and it is suggested that diet-induced changes in methylation status could be involved in energy metabolism regulation. Conjugated linoleic acid (CLA) and calcium supplementation counteract body weight gain, particularly under a high-fat (HF) diet, in adult mice. The aim was to determine whether the modulation of DNA methylation pattern in target genes and tissues could be an underlying mechanism of action. METHODS: Mice (C57BL/6J) were divided into five groups according to diet and treatment: normal fat as the control group (12 % kJ content as fat), HF group (43 % kJ content as fat), HF + CLA (6 mg CLA/day), HF + calcium (12 g/kg of calcium) and HF with both compounds. Gene expression and methylation degree of CpG sites in promoter sequences of genes involved in fatty acid metabolism, including adiponectin (Adipoq), stearoyl-CoA desaturase (Scd1) and fatty acid synthase (Fasn), were determined by bisulphite sequencing in liver and epididymal white adipose tissue. RESULTS: Results showed that the methylation profile of promoters was significantly altered by dietary supplementation in a gene- and tissue-specific manner, whereas only slight changes were observed in the HF group. Furthermore, changes in specific CpG sites were also associated with an overall healthier metabolic profile, in particular for calcium-receiving groups. CONCLUSIONS: Both CLA and calcium were able to modify the methylation pattern of genes involved in energy balance in adulthood, which opens a novel area for increasing efficiency in body weight management strategies.

The effect of commercial conjugated linoleic acid products on experimental periodontitis and diabetes mellitus in Wistar rats.

OBJECTIVE: The aim of present study was to determine the effects of conjugated linoleic acid enriched milk on alveolar bone loss, hyperglycaemia, oxidative stress and apoptosis in ligature-induced periodontal disease in diabetic rat model. METHODS: Wistar rats were divided into six experimental groups: 1; non-ligated (NL, n = 6) group, 2; ligature only (LO, n = 6) group, 3; streptozotocin only (STZ, n = 8) group, 4; STZ and ligature (STZ + L, n = 8) group, 5; ligature and conjugated linoleic acid (CLA) (L + CLA, n = 8) group, 6; STZ, ligature and CLA group (STZ + L + CLA, n = 8) group. Diabetes mellitus was induced by 60 mg/kg streptozotocin. Rats were fed with CLA enriched milk for four weeks. Silk ligatures were placed at the gingival margin of lower first molars of mandibular quadrant. The study duration was four weeks after diabetes induction and the animals were sacrificed at the end of this period. Changes in alveolar bone levels were clinically measured and tissues were histopathologically examined. Inducible nitric oxide synthase (iNOS) and Bax protein expressions, serum interleukin-1ß (IL-1ß), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride levels and tartrate resistant acid phosphatase (TRAP)+ osteoclast numbers were also evaluated. RESULTS: At the end of four weeks, alveolar bone loss was significantly higher in the STZ + LO group compared to the other groups (p < .05). CLA decreased alveolar bone loss in L + CLA and STZ + L + CLA groups. CLA significantly decreased TRAP + osteoclast numbers and increased osteoblastic activity compared to the STZ + L group (p < .05). Diabetes and CLA increased Bax protein levels (p < .05) however CLA had no effect on iNOS expression (p > .05). CONCLUSION: Within the limits of this study, commercial CLA product administration in addition to diet significantly reduced alveolar bone loss, increased osteoblastic activity and decreased osteoclastic activity in the diabetic Wistar rats.

Lipid rafts, KCa/ClCa/Ca2+ channel complexes and EGFR signaling: Novel targets to reduce tumor development by lipids?

Membrane lipid rafts are distinct plasma membrane nanodomains that are enriched with cholesterol, sphingolipids and gangliosides, with occasional presence of saturated fatty acids and phospholipids containing saturated acyl chains. It is well known that they organize receptors (such as Epithelial Growth Factor Receptor), ion channels and their downstream acting molecules to regulate intracellular signaling pathways. Among them are Ca2+ signaling pathways, which are modified in tumor cells and inhibited upon membrane raft disruption. In addition to protein components, lipids from rafts also contribute to the organization and function of Ca2+ signaling microdomains. This article aims to focus on the lipid raft KCa/ClCa/Ca2+ channel complexes that regulate Ca2+ and EGFR signaling in cancer cells, and discusses the potential modification of these complexes by lipids as a novel therapeutic approach in tumor development. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

Effects of a dietary intervention with conjugated linoleic acid on immunological and metabolic parameters in children and adolescents with allergic asthma--a placebo-controlled pilot trial.

BACKGROUND: Circumstantial evidence suggests that conjugated linoleic acid (CLA) beneficially modulates immune function in allergic subjects. C9,t11-CLA, naturally occurring in ruminant fats, is suggested to be the effective isomer. In contrast, for the t10,c12-CLA isomer, which is naturally found only in traces but usually constitutes a relevant part in commercial CLA mixtures, adverse effects have been reported. Aim of this study was to assess putative immunomodulatory effects of highly enriched c9,t11-CLA in allergic subjects. To our best knowledge, our study is the first in that a CLA preparation was used for such purpose which was free of t10,c12-CLA. DESIGN: Twenty-nine asthmatic children and adolescents (age 6-18 y) with diagnosed allergic sensitization against grass pollen, house dust mite, or cat hair/epithelia consumed daily a portion of yoghurt containing either 3 g CLA (75 % c9,t11-CLA, 87 % purity) or placebo (safflower oil) over a period of 12 weeks. At study start and end, lung function parameters, specific IgE, in vitro allergen-induced cytokine production in peripheral blood mononuclear cells (PBMC), plasma ECP, urinary 8-oxodG as marker of oxidation, fatty acid profiles of erythrocytes, and routine haematological parameters were determined. Prior to blood samplings, 3-days dietary records were requested. Throughout the study, the participants documented daily their peak expiratory flow and kept protocol about their allergy symptoms and usage of demand medication. RESULTS: In contrast to the CLA group, PBMC-produced IFN-γ and IL-4 increased significantly and by trend, respectively, in the placebo group. Moreover, plasma ECP tended to increase in the placebo group. In the pollen subgroup, FEV1 improved upon both CLA and placebo oil supplementation. In both intervention groups, the n-6/n-3 PUFA ratio in red blood cells decreased, mainly due to an increase in n-3 PUFA. Moreover, 8-oxodG excretion increased in both groups. No changes occurred regarding specific IgE concentrations, allergy symptoms, and volume parameters. CONCLUSION: Our results indicate that CLA modestly dampens the inflammatory response on the cellular level. A clinically relevant amelioration of the symptoms could not be proved in atopic manifest patients. TRIAL REGISTRATION: NCT01026506.

Conjugated linoleic acid improves glycemic response, lipid profile, and oxidative stress in obese patients with non-alcoholic fatty liver disease: a randomized controlled clinical trial.

AIM: To investigate if conjugated linoleic acid supplementation (CLA) affects metabolic factors and oxidative stress in non-alcoholic fatty liver disease (NAFLD). METHODS: The study was a randomized, controlled clinical trial conducted in specialized and subspecialized clinics of Tabriz University of Medical Sciences from January 2014 to March 2015. 38 obese NAFLD patients were randomly allocated into either the intervention group, receiving three 1000 mg softgel of CLA with a weight loss diet and 400 IU vitamin E, or into the control group, receiving only weight loss diet and 400 IU vitamin E for eight weeks. Dietary data and physical activity, as well as anthropometric, body composition, metabolic factors, and oxidative stress were assessed at baseline and at the end of the study. RESULTS: Weight, body composition, and serum oxidative stress, insulin, and lipid profile significantly improved in both groups, while hemoglobin A1c (HbA1c) levels (P=0.004), total cholesterol to high density lipoprotein ratio (P=0.008), low density lipoprotein to high density lipoprotein ratio (LDL/HDL) (P=0.002), and alanine aminotransferase to aspartate aminotransferase (ALT/AST) ratio (P=0.025) significantly decreased in the intervention group. At the end of the study, fat mass (P=0.001), muscle mass (P=0.023), total body water (P=0.004), HbA1c (P<0.001), triglycerides (P=0.006), LDL/HDL ratio (P=0.027), and ALT/AST ratio (P=0.046) were significantly better in the CLA group than in the control group. CONCLUSION: CLA improved insulin resistance, lipid disturbances, oxidative stress, and liver function in NAFLD. Therefore, it could be considered as an effective complementary treatment in NAFLD.

The effect of conjugated linoleic acids (CLA) supplementation on the activity of enzymes participating in the formation of arachidonic acid in liver microsomes of rats--probable mechanism of CLA anticancer activity.

The aim of the present research was to examine the effect of conjugated linoleic acids (CLA) supplementation on the activity of enzymes that take part in the synthesis of arachidonic acid (AA) and also to investigate the relation between their activity and the neoplastic process. The enzyme activities were established indirectly, because their measure was the amount of AA formed in vitro, being developed from linoleic acid as determined in liver microsomes of Spraque-Dawley rats. In addition, the indices of Δ6-desaturase (D6D) and Δ5-desaturase (D5D) were determined. To this aim, the method of high per-formance liquid chromatography with UV/VIS detection was used. Between the examined groups, statistically significant differences were observed in the activities of enzymes as well as D6D. The carcinogenic agent applied (DMBA) was found to significantly increase the activity of the examined enzymes. Negative correlation was found between the activities of desaturases and CLA supplementation, whereas the activity of those enzymes was a little higher in the group of rats with chemically induced cancer process. The neoplastic process has a stimulating effect on the activity of D6D. The decrease of D6D activity, resulting from the presence of CLA in the animals' diet, may confirm the anticancer properties of these isomers.

Comparison of shock wave therapy and nutraceutical composed of Echinacea angustifolia, alpha lipoic acid, conjugated linoleic acid and quercetin (perinerv) in patients with carpal tunnel syndrome.

Even though the initial treatment of carpal tunnel syndrome (CTS) is conservative, knowledge of the clinical effects of supplements and of some methods of physiotherapy is still preliminary. Many biological mechanisms can support the administration of shock wave therapy (ESWT) or of alpha lipoic acid (ALA) based nutraceutical, conjugated linoleic acid (GLA), anti-oxidants and Echinacea angustifolia for CTS. The shock waves reduce the nerve compression, produce an anti-inflammatory action, and accelerate the regeneration of neuropathy. ALA and GLA induce antioxidant protective actions, reduce inflammation, promote neuroregeneration, and decrease pain. The Echinacea modulates the endogenous cannabinoid system.The aim of study is to verify the efficiency of shock wave therapy versus nutraceutical composed of ALA, GLA, and Echinacea in CTS. Sixty patients were enrolled in this study and they were randomly assigned to one of two treatments. Both groups showed significant improvements in pain, symptoms' severity and functional scores, and electrodiagnostic results until the sixth month. We verified a trend to a better pain regression in the nutraceutical group. The presence of the medicinal Echinacea represents an added value to the antioxidant effect in ALA and GLA, which can justify this result. ESWT or the association of ALA, GLA, and Echinacea proved to be two effective treatments for controlling symptoms and improving the evolution of CTS.

Effect of conjugated linoleic acid on blood pressure: a meta-analysis of randomized, double-blind placebo-controlled trials.

BACKGROUND: Numerous studies on animals evidenced that conjugated linoleic acid (CLA) could decrease blood pressure (BP) in several rat models. However, such beneficial effect is not completely supported by studies on humans. METHODS: We searched the Pubmed, Cochrane Library, and the ClinicalTrials.gov databases for relevant randomized, double-blind placebo-controlled trials up to August 2014 to perform a meta-analysis. A random-effects model was used to calculate the combined treatment effects. RESULTS: Eight studies with nine trials, which involved 638 participants with CLA supplementation ranging from 2.0 g/day to 6.8 g/day, were included in this meta-analysis. Compared with placebo, the pooled estimate of change was -0.03 mm Hg (95% CI: -2.29, 2.24, P=0.98) and 0.69 mm Hg (95% CI: -1.41, 2.80, P=0.52) in systolic and diastolic BPs, respectively. No significant heterogeneity across studies for systolic BP; however, substantial heterogeneity for diastolic BP was identified. Publication bias was not found for both systolic and diastolic BPs. CONCLUSION: The findings of this meta-analysis did not support the overall favorable effect of CLA supplementation on BP regulation.

Diet-induced metabolic change induces estrogen-independent allometric mammary growth.

Lifetime breast cancer risk reflects an unresolved combination of early life factors including diet, body mass index, metabolic syndrome, obesity, and age at first menses. In parallel, the onset of allometric growth by the mammary glands around puberty is widely held to be estrogen (E)-dependent. Here we report that several physiological changes associated with metabolic syndrome in response to a diet supplemented with the trans-10, cis-12 isomer of conjugated linoleic acid lead to ovary-independent allometric growth of the mammary ducts. The E-independence of this diet-induced growth was highlighted by the fact that it occurred both in male mice and with pharmacological inhibition of either E receptor function or E biosynthesis. Reversal of the metabolic phenotype with the peroxisome proliferator-activated receptor-γ agonist rosiglitazone abrogated diet-induced mammary growth. A role for hyperinsulinemia and increased insulin-like growth factor-I receptor (IGF-IR) expression during mammary growth induced by the trans-10, cis-12 isomer of conjugated linoleic acid was confirmed by its reversal upon pharmacological inhibition of IGF-IR function. Diet-stimulated ductal growth also increased mammary tumorigenesis in ovariectomized polyomavirus middle T-antigen mice. Our data demonstrate that diet-induced metabolic dysregulation, independently of ovarian function, stimulates allometric growth within the mammary glands via an IGF-IR-dependent mechanism.

c9,t11-Conjugated linoleic acid ameliorates steatosis by modulating mitochondrial uncoupling and Nrf2 pathway.

Oxidative stress, hepatic steatosis, and mitochondrial dysfunction are key pathophysiological features of nonalcoholic fatty liver disease. A conjugated linoleic acid (CLA) mixture of cis9,trans11 (9,11-CLA) and trans10,cis12 (10,12-CLA) isomers enhanced the antioxidant/detoxifying mechanism via the activation of nuclear factor E2-related factor-2 (Nrf2) and improved mitochondrial function, but less is known about the actions of specific isomers. The differential ability of individual CLA isomers to modulate these pathways was explored in Wistar rats fed for 4 weeks with a lard-based high-fat diet (L) or with control diet (CD), and, within each dietary treatment, two subgroups were daily administered with 9,11-CLA or 10,12-CLA (30 mg/day). The 9,11-CLA, but not 10,12-CLA, supplementation to CD rats improves the GSH/GSSG ratio in the liver, mitochondrial functions, and Nrf2 activity. Histological examination reveals a reduction of steatosis in L-fed rats supplemented with both CLA isomers, but 9,11-CLA downregulated plasma concentrations of proinflammatory markers, mitochondrial dysfunction, and oxidative stress markers in liver more efficiently than in 10,12-CLA treatment. The present study demonstrates the higher protective effect of 9,11-CLA against diet-induced pro-oxidant and proinflammatory signs and suggests that these effects are determined, at least in part, by its ability to activate the Nrf2 pathway and to improve the mitochondrial functioning and biogenesis.