CLA

CLA/Drug Interactions:

  • AntibioticsAntibiotics: In animals, CLA had a lack of negative effects on antibiotic function (270). In dairy cows, monensin increased levels of CLA in milk fat (271; 272; 273). In in vitro research, CLA inhibited foodborne and pathogenic bacteria (274).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In humans, CLA had a lack of an effect on antithrombotic parameters, prothrombin time, activated partial prothrombin time, antithrombin III levels, or bleeding times (275). Decreased platelet aggregation has been shown in human study (109).
  • AntidepressantsAntidepressants: In a clinical trial, the rate of reported negative emotions was decreased in the CLA group (22). The effects of concurrent use of CLA and antidepressants are not well understood.
  • AntidiabeticsAntidiabetics: CLA-induced insulin resistance has been shown in various animal studies (195). Other animal and in vitro studies have demonstrated further antidiabetic effects (276; 277; 278; 279; 280). In humans and animals, CLA supplementation increased glucose levels (99; 96; 281; 282; 129). CLA decreased glucose levels in humans (149; 133). In animals, CLA improved glucose tolerance (11; 12; 13). Reduced blood sugar has been shown in other animal models (283; 284; 285). Other studies have shown a lack of an effect of CLA on plasma glucose (286; 148). However, CLA isomers may have opposing effects, with the t10,c12 CLA isomer promoting increased serum glucose concentrations (287).
  • AntihypertensivesAntihypertensives: In animals, t10,c12 CLA isomer reduced blood pressure, potentially due to decreased secretion of hypertensive adipocytokines (107). In Chinese patients with obesity-related hypertension, CLA supplementation enhanced the antihypertensive effect of ramipril (110). In animal research, a combination of telmisartan and CLA reduced various risk factors for cardiovascular disease, including blood pressure (111).
  • Anti-inflammatoriesAnti-inflammatories: In animals and in vitro, CLA had anti-inflammatory effects (288; 289; 290; 291; 292). Both the c9,t11 CLA and t10,c12 CLA isomers inhibited stimulated TNF-alpha production, although the t10,c12 isomer was more effective. However, in humans, CLA supplementation resulted in an increase in C-reactive protein and had a lack of an effect on TNF-alpha or vascular cell adhesion molecules (25). CLA as c9,t11 isomer for three months increased excretion of proinflammatory cytokines, possibly via fatty acid receptors (26). In vitro, CLA produced by probiotics exerted anti-inflammatory effects in gastric epithelial cells infected with Helicobacter pylori (293).
  • Antilipemic agentsAntilipemic agents: The effects of CLA on lipids are equivocal. In animal research, CLA-enriched diets improved plasma lipid profiles (294; 295; 296; 297; 298; 299; 284; 300; 177; 301; 285; 302; 303; 304). In animals, the c9,t11 CLA isomer improved levels of HDL cholesterol and the ratio of HDL cholesterol to LDL cholesterol (101). However, in other research, CLA had a lack of an effect on blood lipids or the ratio of LDL cholesterol to HDL cholesterol (188; 305) or increased total and LDL cholesterol (306; 307).
  • AntineoplasticsAntineoplastics: In epidemiological research, high dietary intake of CLA was associated with reduced incidence of colorectal cancer (308). In animals, CLA inhibited tumor growth and metastasis (3; 4; 5; 6; 7; 8; 9; 10). In vitro, CLA as mixed or individual isomers (t10,c12 and c9,t11) inhibited growth and proliferation, and induced apoptosis of various cancer cell lines (309; 310; 311; 312; 313; 314; 315; 316; 317; 318; 319). In animal and in vitro research, CLA may have enhanced efficacy when used with taxane chemotherapeutic agents including paclitaxel and docetaxel. In animal research, combined use of paclitaxel and CL showed greater antitumor effects than paclitaxel alone (320). A paclitaxel-incorporated CLA-coupled poloxamer thermosensitive hydrogel has been developed to enhance the antitumor activity of paclitaxel (321). In vitro, antitumor effects of docetaxel were potentiated by CLA (322).
  • Antiobesity agentsAntiobesity agents: Clinical trials and animal studies suggest that CLA induced weight or fat loss (100; 323; 324; 15; 139; 22). However, in some animal studies, CLA was found to increase appetite (17; 36; 37; 38). In animals, CLA reduced anorexia due to endotoxin injection (17). Thus CLA may have additive effects with antianorexic agents. In an animal model, CLA decreased cachectic symptoms of systemic lupus erythematosus (36; 37; 38).
  • CalciumsaltsCalciumsalts: In humans, a combination of calcium and CLA from weeks 18-22 of gestation to delivery decreased the incidence of pregnancy-induced hypertension (325; 326). In animal research, extra calcium in the diet improved CLA's effects on bone mass (327; 328).
  • CorticosteroidsCorticosteroids: In an animal model of Duchenne muscular dystrophy, a combination of corticosteroids, creatine, alpha-lipoic acid, beta-hydroxy-beta-methylbutyrate, and CLA increased strength and decreased fatigue (31). In young rats, CLA prevented growth attenuation induced by corticosteroid administration and increased bone mineral content (329).
  • Dermatologic agentsDermatologic agents: In animals, CLA modified fatty acid composition of skin and decreased thickness of subcutaneous tissue layers, with a lack of an effect on thickness of dermis layers (35). In in vitro research, CLA modulated ultraviolet radiation-induced IL-8 and prostaglandin E2, potentially resulting in photoprotection (330). In animal research, CLA improved the wound closure rate during the early stage of wound healing; oxidative stress and inflammatory markers were also reduced (331).
  • Drugs used for osteoporosisDrugs used for osteoporosis: In epidemiological research, dietary CLA was associated with increased bone mineral density in the forearm, and nonsignificantly associated with increased bone mineral density in the hip, lumbar spine, and whole body (33). In animal research, CLA increased bone mineral content and density (332; 333; 329; 334; 328). However, cis-10,trans-12 CLA was associated with a decreased bone mineral density (335). In animal research, extra calcium in the diet improved CLA's effects on bone mass (327; 328). In animals, depending on dietary fatty acid type, CLA increased or decreased insulin-like growth factor binding proteins, suggesting an influence on bone metabolism (34).
  • Fertility agentsFertility agents: In a multistudy analysis in dairy cows, CLA may have improved reproductive performance, as shown by decreased time to conception (261). The mechanism may involve improved ovarian follicular steroidogenesis and increased circulating concentrations of IGF-I (262). In late-stage chick embryos, maternal CLA negatively affected lipid uptake, which resulted in increased embryonic mortality and decreased hatchability (175). Leone et al. suggested that factors other than storage and egg yolk fatty acid composition played a role in CLA-induced embryonic mortality (253). In animal research, CLA decreased levels of FSH and LH (259).
  • HepatotoxinsHepatotoxins: Both positive and negative effects of CLA have been shown on the liver in animal studies, including liver enlargement, reduced or increased steatosis, reduced or increased lipid levels, and reduced fibrosis (336; 337; 338; 339; 340; 341; 306; 342; 343; 344; 201; 345).
  • Hormonal agentsHormonal agents: In animal research, CLA decreased levels of progesterone (259). In animal research, dietary cis-9,trans-11 CLA reduced parathyroid hormone in male, but not female, rats (335). CLA has been esterified to estrone and used to induce the mobilization of fat in animal research (346).
  • ImmunoglobulinsImmunoglobulins: In animals, CLA reduced tissue levels of immunoglobulins, such as IgE, IgA, IgG, and IgM (347; 348).
  • ImmunosuppressantsImmunosuppressants: In humans, regulation of inflammatory proteins suggested enhanced immune function following CLA supplementation (349). In animals, CLA increased antibody production and increased cellular immunity by influencing CD8+ T cell subsets (350; 347; 351; 352; 353; 354; 355). In animals, CLA reduced tissue levels of chemical mediators, such as leukotrienes and prostaglandins, and immunoglobulins, such as IgE, IgA, IgG, and IgM (347; 348).
  • Polyethylene glycolPolyethylene glycol: PEGylated CLA has been investigated for its anticancer effects in vitro (356). Apoptosis occurred. PEGylated CLA was also found to reduce lipid accumulation and attenuated insulin resistance due to a high-fat diet in animal research (357) and to induce lipolysis (358).
  • SurfactantsSurfactants: In in vitro research, CLA conjugated with Pluronic F127 had greater anticancer effects than CLA alone (359).

    • CLA/Herb/Supplement Interactions:

  • AjoeneAjoene: In in vitro research, CLA enhanced ajoene-induced apoptosis (360).
  • Alpha-lipoic acidAlpha-lipoic acid: In an animal model of Duchenne muscular dystrophy, a combination of corticosteroids, creatine, alpha-lipoic acid, beta-hydroxy-beta-methylbutyrate, and CLA increased strength and decreased fatigue (31).
  • Alpha-tocopherolAlpha-tocopherol: In animal research, CLA increased liver alpha-tocopherol and liver alpha-tocopherol transfer protein (361).
  • AntibacterialsAntibacterials: In animals, CLA had a lack of negative effects on antibiotic function (270). In in vitro research, CLA inhibited foodborne and pathogenic bacteria (274).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In humans, CLA had no effect on antithrombotic parameters, prothrombin time, activated partial prothrombin time, antithrombin III levels, or bleeding times (275). Decreased platelet aggregation has been shown in human study (109).
  • AntidepressantsAntidepressants: In a clinical trial, the rate of reported negative emotions was decreased in the CLA group (22).
  • Anti-inflammatoriesAnti-inflammatories: In animals and in vitro, CLA demonstrated anti-inflammatory effects (288; 289; 290; 291; 292). Both the c9,t11 CLA and t10,c12 CLA isomers inhibited stimulated TNF-alpha production, although the t10,c12 isomer was more effective. The effects of concurrent use of CLA and anti-inflammatory agents are not well understood.
  • AntilipemicsAntilipemics: The effects of CLA on lipids are equivocal. In some animal research, CLA-enriched diets improved plasma lipid profiles (294; 295; 296; 297; 298; 299; 284; 284; 300; 177; 301; 285; 302; 303; 304). In animals, the c9,t11 CLA isomer improved levels of HDL cholesterol and the ratio of HDL cholesterol to LDL cholesterol (101). However, in other research, CLA had no effect on blood lipids or the ratio of LDL cholesterol to HDL cholesterol (188; 305), or increased total and LDL cholesterol (306; 307).
  • AntineoplasticsAntineoplastics: In epidemiological research, high dietary intake of CLA was associated with reduced incidence of colorectal cancer (308). In animals, CLA inhibited tumor growth and metastasis (3; 4; 5; 6; 7; 8; 9; 10). In vitro, CLA as mixed or individual isomers (t10,c12 and c9,t11) inhibited the growth and proliferation and induced the apoptosis of various cancer cell lines (309; 310; 311; 312; 313; 314; 315; 316; 317; 318; 319). The effects of concurrent use of CLA and antineoplastic agents are not well understood.
  • Antiobesity herbs and supplementsAntiobesity herbs and supplements: In humans, the combination of CLA with an "herbal anticellulite" pill had a beneficial effect on weight loss (362). Clinical trials and animal studies suggest that CLA induced weight or fat loss (100; 323; 324; 15; 139; 22). However, in some animal studies, CLA was found to increase appetite (17; 36; 37; 38). In animals, CLA reduced anorexia due to endotoxin injection (17). Thus CLA may have additive effects with antianorexic agents. In an animal model, CLA decreased cachectic symptoms of systemic lupus erythematosus (36; 37; 38)
  • AntioxidantsAntioxidants: In vitro, CLA isomers were unstable molecules (363). Jasmine green tea catechins exhibited protection to CLA. Oxidation of CLA was reduced by adding alpha-tocopherol as an antioxidant (364). In vitro, both CLA and beta-carotene inhibited growth of human cancer cells (310). In animals, CLA reduced superoxide production and nonenzymatic lipid peroxidation, and increased oxidative stability (288; 365; 366). In vitro, CLA acted as an antioxidant in various studies (367; 368; 369; 370; 371; 372). The effects of various plant antioxidants on oxidation of CLA have been studied; some were more effective than others (373).
  • ArginineArginine: In animal research, CLA and arginine modulated adipose tissue metabolism by separate, but not additive, effects (374).
  • Athletic performance enhancersAthletic performance enhancers: In animals, CLA increased fat oxidation during exercise, increasing endurance (375). In an animal model of Duchenne muscular dystrophy, a combination of corticosteroids, creatine, alpha-lipoic acid, beta-hydroxy-beta-methylbutyrate, and CLA increased strength and decreased fatigue (31). In animals, dietary CLA increased the endurance capacity of mice, possibly by increasing fat utilization and reducing the consumption of stored liver glycogen as substrates for energy metabolism (376). In human research, a combination of CLA, creatine monohydrate, and whey protein increased bench-press and leg press strength and lean body mass vs. creatine or whey protein in the absence of CLA (377). The use of a combination of creatine and CLA has been reviewed by Tarnopolsky (378) and has been shown to enhance training benefit in human study (379).
  • Beta-cyclodextrinBeta-cyclodextrin: Yang et al. discussed the use of an amylase-beta cyclodextrin complex to improve the delivery efficiency of CLA (380). Beta-cyclodextrin did not affect CLA levels in milk fat of pasteurized milk (381).
  • BetaineBetaine: In animal research, betaine and CLA had synergistic effects on growth and carcass composition (lean composition, decreased fat) (382).
  • Beta-lactoglobulinBeta-lactoglobulin: A self-assembled beta-lactoglobulin-CLA complex was formed for use as a colon cancer-targeted substance (383). This complex reduced viability of cancer cells in vitro.
  • Beta-sitosterol, sitosterolBeta-sitosterol, sitosterol: In animal research, use of CLA beta-sitosterol reduced total and LDL cholesterol, as well as triglycerides and liver lipids (384). HDL cholesterol was not decreased.
  • Black currant seedBlack currant seed: In animal research, CLA and black currant seed oil did not have additive effects in the treatment of canine atopic dermatitis (385).
  • CalciumCalcium: In humans, a combination of calcium and CLA from weeks 18-22 of gestation to delivery decreased the incidence of pregnancy-induced hypertension (325; 326). In animal research, extra calcium in the diet improved CLA's effects on bone mass (327; 328).
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: Compared to a control group, plasma c9,t11 CLA was reduced in a group of individuals who underwent an operation for atherosclerotic stenosis in the carotid arteries (386). In epidemiological research, cis-9,trans-11 CLA in adipose tissue was associated with decreased risk of myocardial infarction (387). In animals, c9,t11 CLA isomer had antiatherogenic effects (14; 388).
  • Chromium picolinateChromium picolinate: In human research, chromium picolinate and CLA did not synergistically influence changes in body composition (389).
  • CobaltCobalt: In animal research, ruminal infusion of cobalt-EDTA decreased milk levels of CLA (390).
  • Coconut oilCoconut oil: In animals, coconut oil diet plus CLA had additive effects on weight reduction (391).
  • Conjugated linolenic acid (CLNA)Conjugated linolenic acid (CLNA): In animals, conjugated linolenic acid (CLNA) reduced adipose tissue weight (392). In animals, CLNA inhibited tumor development (316).
  • CreatineCreatine: In an animal model of Duchenne muscular dystrophy, a combination of corticosteroids, creatine, alpha-lipoic acid, beta-hydroxy-beta-methylbutyrate, and CLA increased strength and decreased fatigue (31). The use of a combination of creatine and CLA has been reviewed by Tarnopolsky (378) and has been shown to enhance training benefit in human research (379). Creatine, CLA, and resistance training have been discussed in a review (393).
  • Dermatologic agentsDermatologic agents: In humans, the combination of CLA with an "herbal anticellulite" pill had a beneficial effect on skin appearance (362). In animals, CLA modified fatty acid composition of skin and decreased thickness of subcutaneous tissue layers, with a lack of an effect on thickness of dermis layers (35). In in vitro research, CLA modulated ultraviolet radiation-induced IL-8 and prostaglandin E2, potentially resulting in photoprotection (330). In animal research, CLA improved the wound closure rate during the early stage of wound healing; oxidative stress and inflammatory markers were also reduced (331).
  • Fatty acidsFatty acids: Feeding hens CLA in addition to other unsaturated fatty acids improved the parameters of egg quality, which was reduced when CLA was fed alone (394). Feeding swine monounsaturated fatty acids in addition to CLA balanced the increase in the ratio of saturated to unsaturated fats in back fat seen when CLA was given alone (395). In in vitro research, inhibition of stearoyl-CoA desaturase, using trans-10,cis-12 CLA augmented saturated fatty acid-induced endoplasmic reticulum stress and apoptosis (396).
  • Fertility agentsFertility agents: In a multistudy analysis in dairy cows, CLA may improve reproductive performance, as shown by decreased time to conception (261). The mechanism may involve improved ovarian follicular steroidogenesis and increased circulating concentrations of IGF-I (262). The mechanism may involve improved ovarian follicular steroidogenesis and increased circulating concentrations of IGF-I (262). In late-stage chick embryos, maternal CLA negatively affected lipid uptake, which resulted in increased embryonic mortality and decreased hatchability (175). Leone et al. suggested that factors other than storage and egg yolk fatty acid composition played a role in CLA-induced embryonic mortality (253). In animal research, CLA decreased levels of FSH and LH (259).
  • GlutamineGlutamine: In animal research, infusion of glutamine increased plasma levels of cis-9,trans-11 CLA (397).
  • HepatotoxinsHepatotoxins: Both positive and negative effects of CLA have been shown on the liver in animal studies, including liver enlargement, reduced or increased steatosis, reduced or increased lipid levels, and reduced fibrosis (336; 337; 338; 339; 340; 341; 306; 342; 343; 344; 201; 345).
  • Hormonal herbs and supplementsHormonal herbs and supplements: In animal research, CLA decreased levels of progesterone (259). In animals, CLA supplementation during early pregnancy had no effect on intrauterine synthesis of prostaglandins (258). In animal research, dietary cis-9,trans-11 CLA reduced parathyroid hormone in male, but not female, rats (335). CLA has been esterified to estrone and used to induce the mobilization of fat in animal study (346).
  • HypoglycemicsHypoglycemics: CLA-induced insulin resistance has been shown in various animal studies (195). Other animal and in vitro studies have demonstrated further antidiabetic effects (276; 277; 278; 279; 280). In humans and animals, CLA supplementation increased glucose levels (99; 96; 281; 282; 129). CLA decreased glucose levels in humans (149; 133). In animals, CLA improved glucose tolerance (11; 12; 13). Reduced blood sugar has been shown in other animal models (283; 284; 285). Other studies have shown a lack of an effect of CLA on plasma glucose (286; 148). However, CLA isomers may have opposing effects, with the t10,c12 CLA isomer promoting increased serum glucose concentrations (287).
  • HypotensivesHypotensives: In animals, t10,c12 CLA isomer reduced blood pressure, potentially due to decreased secretion of hypertensive adipocytokines (107). Theoretically, concurrent use of CLA and antihypertensive agents may cause additive blood pressure-lowering effects.
  • ImmunomodulatorsImmunomodulators: In humans, regulation of inflammatory proteins suggested enhanced immune function following CLA supplementation (349). In animals, CLA increased antibody production and increased cellular immunity by influencing CD8+ T cell subsets (350; 347; 351; 352; 353; 354; 355). In animals, CLA reduced tissue levels of chemical mediators, such as leukotrienes and prostaglandins, and immunoglobulins, such as IgE, IgA, IgG, and IgM (347; 348).
  • L-carnitineL-carnitine: In a solvent-free system CLA was esterified to L-carnitine using lipase-catalyzed esterification (398).
  • Oleic acidOleic acid: In in vitro research, oleic acid prevented apoptotic cell death induced by trans-10,cis-12 CLA (399).
  • Omega-3 fatty acidsOmega-3 fatty acids: In humans, CLA had a lack of an effect on conversion of alpha-linolenic acid to docosahexaenoic acid (DHA) (400; 401), although in one study conversion to eicosapentaenoic acid (EPA) was increased (400). In animals, fish oil was found to referee physiological changes induced by dietary CLA (402). In humans, CLA and omega-3 fatty acids prevented increased abdominal fat and increased fat-free mass in obese individuals (403). In animal research, DHA and flaxseed oil, but not EPA, prevented CLA induced insulin-resistance (404; 405), and a combination of DHA and CLA reduced CLA-induced hepatic lipid accumulation (406). In animals, fish oil and CLA had an additive effect on increased serum insulin (402). Insulin was reduced as fish oil levels were further increased. In animals, fish oil reduced CLA-induced increases in triglycerides (402). In animals, both fish oil and t10,c12 CLA lowered total cholesterol and increased insulin (407). Also, fish oil and CLA had opposing effects on triglyceride levels. In sea bass, CLA increased levels of omega-3 polyunsaturated fatty acids (408). A combination of CLA with fish oil prevented age-associated bone marrow adiposity in C57Bl/6J mice (332). In animals, both CLA and fish oil omega-3 fatty acids induced apoptosis of cancer cells (409).
  • Osteoporosis herbs and supplementsOsteoporosis herbs and supplements: In epidemiological research, dietary CLA was associated with increased bone mineral density in the forearm and nonsignificantly associated with increased bone mineral density in the hip, lumbar spine, and whole body (33). In animal research, CLA increased bone mineral content and density (332; 333; 329; 334; 328). However, cis-10,trans-12 CLA was associated with a decreased bone mineral density (335). In animal research, extra dietary calcium in the diet improved CLA's effects on bone mass (327; 328). In animals, depending on the dietary fatty acid type, CLA increased or decreased insulin-like growth factor binding proteins, suggesting an influence on bone metabolism (34).
  • ProbioticsProbiotics: Bifidobacterium and Lactobacillus probiotic bacterial strains commonly found in humans and animals synthesize CLA (410; 411; 412; 413; 414; 415; 416; 417; 418; 419; 420; 421; 422; 423; 424; 425; 426; 427; 428; 429; 430; 431).
  • Propionic acidPropionic acid: In animal research, trans-10,cis-12 CLA and propionic acid had additive effects on milk fat content and composition in dairy cows (228).
  • ResveratrolResveratrol: In in vitro research, resveratrol attenuated CLA-mediated inflammation and insulin resistance in human adipocytes (432).
  • Selenized yeastSelenized yeast: In animal research, a combination of CLA and selenized yeast increased CLA in heart and muscle lipids and increased body weight gain (433).
  • SesaminSesamin: In animals, sesamin in the diet had additive effects with CLA in terms of weight loss (434).
  • SoySoy: In animals, a combination of high levels of isolated soy protein and CLA increased tumor volume (435). High concentrations of CLA alone had a lack of such an effect, whereas the increased tumor volume continued with high doses of isolated soy protein.
  • Vaccenic acidVaccenic acid: In animal research, bovine milk fat enriched in CLA (cis-9,trans-11) and vaccenic acids attenuated allergic airway disease in mice (436). In animal research, a combination of cis-9,trans-11 CLA with trans-11 vaccenic acid had increased hypolipidemic and weight loss benefit (298).
  • Vitamin AVitamin A: The effect of dietary vitamin A restriction on marbling and CLA content in Holstein steers was examined (437). Further details are lacking.

    • CLA/Food Interactions:

  • NoteNote: In vitro, conjugated linoleic acid (CLA) increased calcium transport in human intestinal-like cells (438; 439).
  • Antioxidant-rich dietsAntioxidant-rich diets: In vitro, CLA isomers were unstable molecules (363). Jasmine green tea catechins exhibited protection to CLA. Oxidation of CLA was reduced by adding alpha-tocopherol as an antioxidant (364). In vitro, both CLA and beta-carotene inhibited growth of human cancer cells (310). In animals, CLA reduced superoxide production and nonenzymatic lipid peroxidation and increased oxidative stability (288; 365; 366). In vitro, CLA acted as an antioxidant in various studies (367; 368; 369; 370; 371; 372).
  • BeefBeef: In animals and in vitro, beef fatty acids had anticancer effects, and in animals, anticancer effects were additive to those of CLA (440; 441).
  • Black currant seedBlack currant seed: In animal research, CLA and black currant seed oil did not have additive effects in the treatment of canine atopic dermatitis (385).
  • ButterButter: In animal research, butter high in trans 18:1 had detrimental effects on cardiovascular disease risk factors, which were neutralized when the butter was also higher in cis-9,trans-11 CLA (442).
  • Calcium-rich dietsCalcium-rich diets: In humans, a combination of calcium and CLA from weeks 18-22 of gestation to delivery decreased the incidence of pregnancy-induced hypertension (325; 326).
  • CheeseCheese: Addition of probiotics to cheese increased CLA levels in the cheese (50). When goats were supplemented with CLA, the properties of semihard goat cheese produced from the lower-fat milk were investigated (225). CLA supplementation increased the hardness, springiness, and chewiness, and decreased the cohesiveness and adhesiveness of cheeses, and there was a lack of obvious defects. In human research, pecorino cheese, naturally rich in cis-9,trans-11 CLA reduced inflammatory parameters such as IL-6, IL-8, and TNF-alpha; the erythrocyte filtration rate was improved and there was a reduction in the extent of platelet aggregation induced by arachidonic acid (109).
  • Coconut oilCoconut oil: In animals, coconut oil diet plus CLA had additive effects on weight reduction (391).
  • EggsEggs: Dietary CLA in layers increased CLA in the egg yolk; feed intake, egg weight, and yolk weight were decreased (443). In animal research, feeding of eggs enriched in CLA had better antiatherosclerotic effects than feeding eggs plus supplemental CLA (444).
  • Essential fatty acid-deficient dietEssential fatty acid-deficient diet: In animals, an essential fatty acid-deficient diet in combination with CLA had additive effects on weight reduction (324).
  • FiberFiber: In animal research, there was a lack of an interaction of CLA and fiber in terms of body composition (445).
  • Flaxseed oilFlaxseed oil: In animal research, flaxseed oil prevented CLA induced insulin-resistance (405).
  • Lipid-lowering dietsLipid-lowering diets: In animals, the c9,t11 CLA isomer improved levels of HDL cholesterol and the ratio of HDL cholesterol to LDL cholesterol (101). In general in animal models, CLA-enriched diets improved plasma lipid profiles (294; 295; 296; 297).
  • Low-protein dietsLow-protein diets: In animal research, the addition of both low-protein diets and CLA reduced the number of bulls presenting swollen joints (446).
  • MilkMilk: In animal research, CLA-induced body fat mass was enhanced with nonfat milk (447).
  • Omega-3 fatty acidsOmega-3 fatty acids: In humans, CLA had a lack of an effect on conversion of alpha-linolenic acid to docosahexaenoic acid (DHA) (400; 401), although in one study conversion to eicosapentaenoic acid (EPA) was increased (400). In humans, CLA and omega-3 fatty acids prevented increased abdominal fat and increased fat-free mass in obese individuals (403). In animal research, DHA and flaxseed oil, but not EPA, prevented CLA induced insulin-resistance (404; 405), and a combination of DHA and CLA reduced CLA-induced hepatic lipid accumulation (406). In animals, fish oil and CLA had an additive effect on increased serum insulin (402). Insulin was reduced as fish oil levels were further increased. In animals, fish oil reduced CLA-induced increases in triglycerides (402). In animals, both CLA and fish oil omega-3 fatty acids induced apoptosis of cancer cells (409). In animals, both fish oil and t10,c12 CLA lowered total cholesterol and increased insulin (407). Also, fish oil and CLA had opposing effects on triglyceride levels.
  • ProbioticsProbiotics: Bifidobacterium and Lactobacillus probiotic bacterial strains commonly found in humans and animals synthesized CLA (410; 411; 412; 413; 414; 415; 416; 417; 418; 419; 420; 421; 422; 423; 424; 420; 425; 426; 427; 428; 429; 430; 431).
  • Pine nut oilPine nut oil: In animal research, a dietary combination of CLA and pine nut oil prevented CLA-induced fatty liver in mice (448).
  • SesaminSesamin: In animals, sesamin in the diet had additive effects with CLA in terms of weight loss (434).
  • SoySoy: In animals, a soy-based diet led to increased weight-reducing effects of CLA (449; 434). In animals, a combination of high levels of isolated soy protein and CLA increased tumor volume (435). High concentrations of CLA alone had a lack of such an effect, whereas the increase tumor volume continued with high doses of isolated soy protein.

    • CLA/Lab Interactions:

  • 3-methylhistidine3-methylhistidine: Following exercise, conjugated linoleic acid (CLA) resulted in smaller increases in 3-methylhistidine in humans (135).
  • 8-iso-prostaglandin F2alpha8-iso-prostaglandin F2alpha: In human research, CLA increased levels of 8-iso-prostaglandin F2alpha in healthy young men (450) and women (184). In animal studies, CLA was found to increase urinary F(2a) isoprostane concentration (451).
  • AdipocytokinesAdipocytokines: In animals, CLA reduced the serum adipocytokine adiponectin and resistin (406; 102; 402; 282; 284). Higher levels of adiponectin were also shown in animal research (306). A lack of an effect of CLA on adiponectin was shown in human study (94).
  • AlbuminAlbumin: In animals, CLA reduced serum albumin (202).
  • Alpha-1 acylglicoproteinAlpha-1 acylglicoprotein: In animals, CLA reduced levels of serum alpha-1 acylglicoprotein (249).
  • ApoproteinsApoproteins: In humans, CLA had a lack of an effect on levels of apolipoprotein A-1 (apoA-1) or apoB (149). In vitro, CLA promoted hepatic secretion of small apoB-containing lipoproteins (106).
  • Blood pressureBlood pressure: In animals, t10,c12 CLA isomer reduced blood pressure, potentially due to decreased secretion of hypertensive adipocytokines (107). In humans, CLA decreased blood pressure (127) or had a lack of an effect (150).
  • Bone markersBone markers: In humans, supplementation with CLA had a lack of an effect on markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) or bone resorption (serum C-telopeptide-related fraction of type 1 collagen degradation products, urinary N-telopeptide-related fraction of type 1 collagen degradation products, urinary pyridinoline and deoxypyridinoline) (452). In humans, bone mineral content was not affected (151). In animal research, CLA increased bone mineral content and density (332; 333; 329; 334; 328). However, cis-10,trans-12 CLA was associated with a decreased bone mineral density (335).
  • Calcium levelsCalcium levels: In humans, CLA treatment had a lack of an effect on serum or urinary calcium levels (452).
  • CholesterinCholesterin: In animal studies, CLA decreased levels of cholesterin (277). In animals, CLA influenced CD8+ T cell subsets (352; 353; 354; 355).
  • CLACLA: In humans and animals, CLA supplementation resulted in increased CLA in plasma phospholipids and cholesteryl ester, as well as peripheral blood mononuclear cell lipids, and other tissues (453; 137; 454; 452; 455; 105; 243; 188). CLA in adipose tissue was not affected (137). In animal studies, the trans,trans CLA isomers were preferentially incorporated into lipids (456; 457).
  • Coagulation panelCoagulation panel: In humans, CLA had a lack of an effect on antithrombotic parameters, prothrombin time, activated partial prothrombin time, antithrombin III levels, or bleeding times (275). Decreased platelet aggregation has been shown in human study (109).
  • C-reactive proteinC-reactive protein: In humans, CLA increased levels of C-reactive protein (25; 97; 184; 153). Other human studies have shown a lack of an effect on C-reactive protein (99; 349).
  • CreatinineCreatinine: In animal research, CLA increased serum creatinine in females (458).
  • CytokinesCytokines: Studies in humans and animals have shown a lack of an effect on IL-6, IL-1beta, TNF-alpha, IFN-gamma, IL-2, or IL-4 (99; 142; 349; 25; 459), or have shown decreases in proinflammatory cytokines, TNF-alpha, and IL-1beta, and increases in IL-10 (460; 109) or increases in proinflammatory cytokines (461; 153). Peripheral blood mononuclear cell interleukin-2 production was reduced in healthy middle-aged males supplemented with CLA (462). In animals, CLA reduced levels of TNF-alpha (463). In animals, CLA increased expression of IL-10 and IL-2 (289; 455). In vitro, CLA increased secretion of IL-6 and IL-8 (196). In vitro, CLA reduced levels of TNF-alpha, IL-1 beta, and IL-6 (291).
  • Fatty acidsFatty acids: In humans, CLA altered fatty acid levels in plasma and tissues (148). In humans, CLA had a lack of an effect on level of free fatty acids (149).
  • Fecal contentsFecal contents: In human research, drinking milk containing CLA had a lack of an effect on fecal pH, ammonia, bacterial evaluation, or enzyme activities over milk alone (464).
  • FibrinogenFibrinogen: In humans, CLA reduced fibrinogen concentrations (99) or increased concentrations (184).
  • GlucoseGlucose: CLA-induced insulin resistance has been shown in various animal studies (195). Other animal and in vitro studies have demonstrated further antidiabetic effects (276; 277; 278; 279; 280). In humans and animals, CLA supplementation increased glucose levels (99; 96; 281; 282; 129). CLA decreased glucose levels in humans (149; 133). In animals, CLA improved glucose tolerance (11; 12; 13). Reduced blood sugar has been shown in other animal models (283; 284; 285). Other studies have shown a lack of an effect of CLA on plasma glucose (286; 148). However, CLA isomers may have opposing effects, with the t10,c12 CLA isomer promoting increased serum glucose concentrations (287).
  • Hemoglobin/hematocritHemoglobin/hematocrit: In humans, CLA has been found to decrease hemoglobin and hematocrit levels (153; 139; 153).
  • Immune panelImmune panel: In humans, CLA had a lack of an effect on natural killer cell activation, lymphocyte proliferation, levels of IL-6, IL-8, or TNF-alpha, or phagocytosis (142; 465). In animal and human research, CLA increased immunoglobulins, such as IgA, IgG, and IgM (347; 460) and decreased IgE (466). In animals, CLA increased antibody production (351).
  • InsulinInsulin: In humans, CLA supplementation reduced insulin sensitivity, increased insulin resistance, increased proinsulin levels, and increased the ratio of proinsulin to insulin (99; 97; 96; 129; 133; 136). In humans and animals, CLA has been found to increase insulin levels (152; 102; 402; 467; 282). In prediabetic animals, CLA improved hyperinsulinemia and reduced plasma insulin levels (13; 468; 277). Other studies have shown a lack of an effect of CLA on plasma insulin (286). However, CLA isomers may have opposing effects, with the t10,c12 CLA isomer promoting insulin resistance and increased serum insulin concentrations (287).
  • Insulin-like growth factorInsulin-like growth factor: In animals, CLA had a lack of an effect on insulin-like growth factor (IGF) (459). In vitro, CLA reduced insulin-like growth factor II secretion (469).
  • LeptinLeptin: In humans and animals, CLA supplementation decreased serum leptin (118; 139; 406; 102; 470; 402; 471; 463; 472; 282; 473; 474; 301; 277). Other animal and human studies have not shown an effect of CLA on leptin levels or suggest an increase in leptin (157; 149; 475; 162; 94).
  • Lipid profileLipid profile: In humans and animals, CLA reduced fasting triglyceride, VLDL cholesterol, total cholesterol, and LDL cholesterol, and ratios of total cholesterol to HDL cholesterol, and LDL cholesterol to HDL cholesterol (476; 104; 471; 477; 105; 475; 101; 294; 295; 296; 297; 468; 277; 136; 110). In human research, dairy products naturally enriched with cis-9,trans-11 CLA and trans-11 18:1 did not appear to have a significant negative or positive effect on the blood lipid profile (478). In humans and animals, CLA increased HDL cholesterol levels (99; 101; 164). Other studies have shown a lack of an effect or adverse effects of CLA on plasma lipids such as triglycerides, LDL cholesterol, and HDL cholesterol (476; 104; 139; 138; 148; 149; 402; 477; 105; 188; 305; 479; 306; 184; 150; 163; 480; 140; 109; 113). In humans, c9,t11 CLA was more effective in lowering triglyceride levels (104). In animals, t10,c12 CLA increased LDL cholesterol to a greater extent than c9,t11 CLA (481).
  • Liver function testsLiver function tests: One individual in a clinical trial withdrew due to increased gamma-glutamyl transpeptidase (112). In a case report, CLA was reported to have induced toxic hepatitis in a 46 year-old woman (170). Increased liver enzymes were found in two subjects in a clinical trial (163), and increased alkaline phosphatase occurred in one clinical trial (153). Decreased alanine aminotransferase has also occurred (164), as has a lack of changes (182).
  • Milk fat (in breast milk)Milk fat (in breast milk): In human studies, CLA supplementation decreased milk fat content in breastfeeding women (207). Other studies have found a lack of an effect of CLA on milk fat in breast milk (208; 209; 210). Decreased milk fat has also been observed in animal studies (211; 212; 213; 214; 215; 216; 217; 218; 219; 220; 221; 222; 223; 224; 225; 226; 227; 228; 229), although the majority of the studies do not support an effect of CLA on milk yield, protein, or lactose.
  • Nitric oxide.Nitric oxide: In vitro, CLA reduced levels of nitric oxide (291).
  • Parathyroid hormoneParathyroid hormone: In animal research, dietary cis-9,trans-11 CLA reduced parathyroid hormone in male, but not female, rats (335).
  • Plasminogen activator inhibitor-1 (PAI-1)Plasminogen activator inhibitor-1 (PAI-1): In humans, CLA had a lack of an effect on PAI-1 levels (148) or increased levels (184). In animals, CLA decreased PAI-1 levels (306).
  • SodiumSodium: Decreased sodium occurred in one clinical trial (153).
  • SomatolactinSomatolactin: In sea bream (Sparus aurata), CLA decreased levels of somatolactin (482).
  • Thiobarbituric acid reactive substances (TBARS)Thiobarbituric acid reactive substances (TBARS): In animal research, dietary CLA decreased TBARS in raw meat (483).
  • Thyroid function testsThyroid function tests: In piglets, CLA increased serum thyroxine (T4) (255).
  • TocopherolTocopherol: In humans, CLA treatment increased serum gamma-tocopherol (205). In animals, CLA had an alpha-tocopherol-sparing effect (296).
  • Triglycerides (liver)Triglycerides (liver): In animals, CLA increased liver triglyceride levels (338; 339; 340; 343; 345).
  • WeightWeight: In clinical trials, CLA has been found to reduce weight (100; 323; 324; 15; 139; 22).
  • White blood cell countWhite blood cell count: In animals and humans, CLA increased white blood cell counts (153; 200).