Conjugated linoleic acids as functional food: an insight into their health benefits

This review evaluates the health benefits of the functional food, conjugated linoleic acids (CLA) - a heterogeneous group of positional and geometric isomers of linoleic acid predominantly found in milk, milk products, meat and meat products of ruminants. During the past couple of decades, hundreds of reports - principally based on in vitro, microbial, animal, and of late clinical trials on humans - have been accumulating with varying biological activities of CLA isomers. These studies highlight that CLA, apart form the classical nuclear transcription factors-mediated mechanism of action, appear to exhibit a number of inter-dependent molecular signalling pathways accounting for their reported health benefits. Such benefits relate to anti-obesitic, anti-carcinogenic, anti-atherogenic, anti-diabetagenic, immunomodulatory, apoptotic and osteosynthetic effects. On the other hand, negative effects of CLA have been reported such as fatty liver and spleen, induction of colon carcinogenesis and hyperproinsulinaemia. As far as human consumption is concerned, a definite conclusion for CLA safety has not been reached yet. Parameters such as administration of the type of CLA isomer and/or their combination with other polyunsaturated fatty acids, mode of administration (eg., as free fatty acid or its triglyceride form, liquid or solid), daily dose and duration of consumption, gender, age, or ethnic and geographical backgrounds remain to be determined. Yet, it appears from trials so far conducted that CLA are functional food having prevailing beneficial health effects for humans

The antiobesity mechanism of conjugated linoleic acid

Given the steady rise in obesity worldwide, it is important to identify dietary compounds that prevent adiposity. One dietary strategy is supplementation with conjugated linoleic acid (CLA), which has been demonstrated to reduce body fat mass. However, side effects associated with CLA supplementation include inflammation, insulin resistance, and dyslipidemia. Elucidation of the antiobesity mechanism of CLA is critical for evaluating its efficacy and safety as a dietary supplement for treating obesity. Therefore, this research examined the upstream mechanism by which CLA induced inflammation, insulin resistance, and delipidation of human adipocytes. Our research group has previously demonstrated that trans-10, cis-12 (10,12) CLA causes delipidation of human adipocytes via activating nuclear factor kappa B (NF?B) and mitogen-activated protein kinase / extracellular signal-regulated kinase kinase (MEK/ERK) signaling, leading to inflammation and the suppression of peroxisome proliferator activated receptor (PPAR?) and decreased glucose and fatty acid uptake. Based on these findings, the following questions were addressed using primary cultures of newly differentiated human adipocytes as a cell model 1) How does CLA impact PPAR? activity?, 2) What upstream mechanisms activate ERK, NF?B and induce inflammation?, and 3) Does resveratrol, a phenolic phytochemical with antioxidant properties, attenuate CLA-induced inflammation, insulin resistance, and delipidation? Answers to these questions were as follows. 1) 10,12 CLA antagonized ligand-dependent PPAR? activity, possibly via PPAR? phosphorylation by ERK. 10,12 CLA suppression of PPAR? and insulin-stimulated glucose uptake, along with delipidation were partially rescued by co-supplementation with the PPAR? agonist BRL, further supporting CLA antagonizing PPAR?. 2) Cultures treated with TMB-8, an inhibitor of calcium release from the endoplasmic reticulum or KN-62, an inhibitor of calcium/calmodulin-dependent kinase II (CAMKII) attenuated 10,12 CLA-mediated reactive oxygen species (ROS) production, mitogen-activated protein kinase (MAPK) activation, inflammatory gene induction, and insulin resistance. These data suggested that 10,12 CLA-mediated inflammation and insulin resistance are dependent on calcium release from the endoplasmic reticulum or CAMKII. 3) Treatment with resveratrol prevented 10,12 CLA-mediated inflammation and insulin resistance by attenuating intracellular calcium, ROS, and inflammation, by increasing PPAR? activity. Collectively, these data suggest that one of the antiobesity mechanisms of 10,12 CLA is inducing cellular stress and inflammation which antagonize PPAR?, leading to insulin resistance and delipidation of human adipocytes

Effect of conjugated linoleic acid, vitamin E and their combination on lipid profiles and blood pressure of Iranian adults with active rheumatoid arthritis

The aim of this study was to assess the impact of conjugated linoleic acids (CLAs), vitamin E, and combination of these nutrients on serum lipid profiles and blood pressure (BP) in patients with active rheumatoid arthritis (RA). In a randomized, double-blind, placebo-controlled trial, 87 patients with active RA were divided into four groups receiving one of the following daily supplements for three months: Group C: CLAs 2.5 g equivalent to 2 g mixture of cis 9-trans 11 and trans 10-cis12 CLAs in a rate of 50/50; Group E: vitamin E: 400 mg; Group CE: CLAs and vitamin E at above doses: Group P: placebo. After supplementation, SBP levels decreased significantly in the group C in comparison with groups E and P and mean arterial pressure reduced significantly in groups C and CE. There weren’t significant differences in the levels of prostaglandin E2 (PGE2), triglycerides, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL/HDL, cholesterol/HDL, fasting blood sugar, C-reactive protein (CRP), arylestrase activity, platelet count and body mass index between groups. CRP dropped nonsignificantly in groups P, C, E and CE (19%, 24%, 55%, and 39%, respectively). Erythrocytes sedimentation rate levels decreased in groups C, E and CE (P ≤ 0.05, P ≤ 0.05, P ≤ 0.001, respectively). It is concluded that supplementation of CLAs decreased BP and vitamin E decreased CRP. Therefore cosupplementation of CLAs and vitamin E might be profitable for heart disease prevention in RA patients

Effects of butter from mountain-pasture grazing cows on risk markers of the metabolic syndrome compared with conventional Danish butter: a randomized controlled study.

BACKGROUND: There is considerable interest in dairy products from low-input systems, such as mountain-pasture grazing cows, because these products are believed to be healthier than products from high-input conventional systems. This may be due to a higher content of bioactive components, such as phytanic acid, a PPAR-agonist derived from chlorophyll. However, the effects of such products on human health have been poorly investigated. OBJECTIVE: To compare the effect of milk-fat from mountain-pasture grazing cows (G) and conventionally fed cows (C) on risk markers of the metabolic syndrome. DESIGN: In a double-blind, randomized, 12-week, parallel intervention study, 38 healthy subjects replaced part of their habitual dietary fat intake with 39 g fat from test butter made from milk from mountain-pasture grazing cows or from cows fed conventional winter fodder. Glucose-tolerance and circulating risk markers were analysed before and after the intervention. RESULTS: No differences in blood lipids, lipoproteins, hsCRP, insulin, glucose or glucose-tolerance were observed. Interestingly, strong correlations between phytanic acid at baseline and total (P<0.0001) and LDL cholesterol (P=0.0001) were observed. CONCLUSIONS: Lack of effects on blood lipids and inflammation indicates that dairy products from mountain-pasture grazing cows are not healthier than products from high-input conventional systems. Considering the strong correlation between LDL cholesterol and phytanic acid at baseline, it may be suggested that phytanic acid increases total and LDL cholesterol. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0134358

Conjugated linoleic acid modulation of risk factors associated with atherosclerosis

Conjugated linoleic acid (CLA) has been the subject of extensive investigation regarding its possible benefits on a variety of human diseases. In some animal studies, CLA has been shown to have a beneficial effect on sclerotic lesions associated with atherosclerosis, be a possible anti-carcinogen, increase feed efficiency, and act as a lean body mass supplement. However, the results have been inconsistent, and the effects of CLA on atherogenesis appear to be dose-, isomer-, tissue-, and species-specific. Similarly, CLA trials in humans have resulted in conflicting findings. Both the human and animal study results may be attributed to contrasting doses of CLA, isomers, the coexistence of other dietary fatty acids, length of study, and inter-and/or intra-species diversities. Recent research advances have suggested the importance of CLA isomers in modulating gene expression involved in oxidative damage, fatty acid metabolism, immune/inflammatory responses, and ultimately atherosclerosis. Although the possible mechanisms of action of CLA have been suggested, they have yet to be determined

The development of new methods for the assessment of oxygen radical-mediated oxidative damage to biomolecules with special reference to lipids

The involvement of chemically-reactive oxygen radical species (RORS) in the pathogenesis of inflammatory joint diseases has been well documented. Much of the toxicity produced by increased superoxide ion (O2.-) and hydrogen peroxide (H2O2) generation has been attributed to the production of the highly reactive hydroxyl radical (.OH) which is mediated by low-molecular-mass iron chelates such as iron-citrate complexes. The .OH radical is extremely reactive and proving its formation in vivo is very difficult. Hence, assays for the assessment of .OH radical activity in the inflamed rheumatoid joint have involved identification and/or quantification of ‘unnatural’ chemical species produced by the attack of OH radical on a range of endogenous or, alternatively, therapeutically-administered exogenous 'target' molecules. This study involves: (1) An investigation of the precise chemical nature of intermediates in and so called 'endproducts' of the process of lipid peroxidation. Second-derivative (2D) electronic absorption spectrophotometry has been applied to the analysis of isomeric conjugated hydroperoxydienes, hydroxydienes and ketodienes and also to thiobarbituric acidreactive material in synovial fluid (SF) obtained from patients with inflammatory joint diseases. (2) A method for determining the extent of RORS-dependent peroxidation of polyunsaturated fatty acids (PUFAs) has been further developed for application to biological samples. This technique involves the conversion of conjugated hydroperoxydienes and compounds derived therefrom, i.e. oxodiene and hydroxydienes, to strongly chromophoric conjugated triene and tetraene species. The chromophore(s) produced are measured by their absorbance in the ultra-violet or near ultra-violet regions of spectra using 2D spectrophotometry. (3) An evaluation of the chemical nature of non-transferrin-bound iron in inflammatory synovial fluid is investigated by high-resolution, high-field proton (1H) nuclear magnetic resonance (NMR) spectroscopy, combined with the use of powerful iron(III) chelators (desferrioxamine and nitrilotriacetate), and the iron(lII)-binding protein apotransferrin in order to 'speciate' catalytic, low-molecular-mass iron complexes present in inflammatory SF samples. (4) The application of high field proton NMR spectroscopy to evaluate the abilities of the antioxidant thiol drug N-acetylcysteine and exogenous cysteine to protect metabolites present in intact inflammatory SF samples against oxidative damage arising from reactive oxygen radical species generated via gamma-radiolysis (5.00 kGy) in the presence of atmospheric oxygen

Creatine Monohydrate and Conjugated Linoleic Acid Improve Strength and Body Composition Following Resistance Exercise in Older Adults

Aging is associated with lower muscle mass and an increase in body fat. We examined whether creatine monohydrate (CrM) and conjugated linoleic acid (CLA) could enhance strength gains and improve body composition (i.e., increase fat-free mass (FFM); decrease body fat) following resistance exercise training in older adults (>65 y). Men (N = 19) and women (N = 20) completed six months of resistance exercise training with CrM (5g/d)+CLA (6g/d) or placebo with randomized, double blind, allocation. Outcomes included: strength and muscular endurance, functional tasks, body composition (DEXA scan), blood tests (lipids, liver function, CK, glucose, systemic inflammation markers (IL-6, C-reactive protein)), urinary markers of compliance (creatine/creatinine), oxidative stress (8-OH-2dG, 8-isoP) and bone resorption (Ν-telopeptides). Exercise training improved all measurements of functional capacity (P<0.05) and strength (P<0.001), with greater improvement for the CrM+CLA group in most measurements of muscular endurance, isokinetic knee extension strength, FFM, and lower fat mass (P<0.05). Plasma creatinine (P<0.05), but not creatinine clearance, increased for CrM+CLA, with no changes in serum CK activity or liver function tests. Together, this data confirms that supervised resistance exercise training is safe and effective for increasing strength in older adults and that a combination of CrM and CLA can enhance some of the beneficial effects of training over a six-month period. Trial Registration. ClinicalTrials.gov NCT0047390

Serum Conjugated Linoleic Acid and Risk of Incident Heart Failure in Older Men: The British Regional Heart Study.

BACKGROUND: Evidence largely from animal studies suggests that conjugated linoleic acid (CLA) may have cardiovascular health benefits. However, few prospective studies have examined the association between CLA and cardiovascular disease. We have prospectively examined the association between serum CLA and incident coronary heart disease and heart failure (HF) in older men. METHODS AND RESULTS: Prospective study of 3806 men, aged 60 to 79 years, without prevalent HF followed up for an average of 13 years, during which there were 295 incident HF cases. A high-throughput serum nuclear magnetic resonance metabolomics platform was used to measure CLA concentration in serum, expressed as a percentage of total fatty acids (CLA%). CLA% was adversely associated with cholesterol and high-density lipoprotein cholesterol but was inversely associated with C-reactive protein and NT-proBNP (N-terminal pro-B-type natriuretic peptide; a marker of ventricular stress). No association was seen between CLA% and incident coronary heart disease. High CLA% was associated with significantly reduced risk of HF after adjustment for HF risk factors and C-reactive protein (hazard ratio [95% confidence interval], 0.64 [0.43-0.96]; quartile 4 versus quartile 1). Elevated CLA% was associated with reduced HF risk only in those with higher dairy fat intake, a major dietary source of CLA (test for interaction P=0.03). The reduced risk of HF was partially explained by NT-proBNP. High dairy fat intake was not associated with incident coronary heart disease but was associated with reduced risk of HF, largely because of the inverse effect of CLA. CONCLUSIONS: The finding that high CLA% is associated with lower risk of incident HF in older men requires confirmation in larger studies

Bovine milk in human nutrition – a review

Milk and milk products are nutritious food items containing numerous essential nutrients, but in the western societies the consumption of milk has decreased partly due to claimed negative health effects. The content of oleic acid, conjugated linoleic acid, omega-3 fatty acids, short- and medium chain fatty acids, vitamins, minerals and bioactive compounds may promote positive health effects. Full-fat milk has been shown to increase the mean gastric emptying time compared to half-skimmed milk, thereby increasing the gastrointestinal transit time. Also the low pH in fermented milk may delay the gastric emptying. Hence, it may be suggested that ingesting full-fat milk or fermented milk might be favourable for glycaemic (and appetite?) regulation. For some persons milk proteins, fat and milk sugar may be of health concern. The interaction between carbohydrates (both natural milk sugar and added sugar) and protein in milk exposed to heat may give products, whose effects on health should be further studied, and the increasing use of sweetened milk products should be questioned. The concentration in milk of several nutrients can be manipulated through feeding regimes. There is no evidence that moderate intake of milk fat gives increased risk of diseases