Conjugated Linoleic Acid

Health Care Professional Information

Scientific Name
cis-9,trans-11 conjugated linoleic acid; trans-10,cis-12 conjugated linoleic acid
Common Name

CLA

Clinical Summary

Conjugated Linoleic Acid (CLA) is commonly found in dairy products and beef. It has purported benefits for cancer prevention, weight control, and high cholesterol. Animal studies suggest that CLA may play a role in reducing tumor proliferation in certain cancer cell lines (2) (3) (4) and ameliorate inflammatory bowel disease (20).
Human studies of CLA for weight reduction are mixed: CLA showed a reduction in body fat mass in obese men (6) and body mass index (1). However, it had little effect on body composition in non-obese women (7) and healthy adults (8). In other studies, CLA supplementation resulted in insulin resistance (9), and reduction in glycemia and plasma leptin (1). CLA may affect total cholesterol levels (6) (9) (10) but does not significantly reduce proteolysis in muscles (10).
CLA improved airway hyper-reactivity in overweight individuals with mild asthma (21).

Reported adverse events include minor gastrointestinal symptoms (9) and severe fatigue (6).

Purported Uses
  • Cancer prevention
  • Cancer treatment
  • High cholesterol
  • Weight maintenance
Mechanism of Action

CLA is a strong antioxidant and is readily incorporated into cell membrane phospholipids. CLA has been shown to reduce the synthesis of prostaglandins, especially PGE2 (12) (13) and decrease stearoyl-CoA desaturase activity (14). CLA was also shown to cause apoptosis in white adipose tissue in mice (5). The trans-10, cis-12 isomer has been shown to decrease serum HDL cholesterol levels (9), inhibit the activity of stearoyl-CoA desaturase (12), inhibit insulin sensitive in new adipose cells (1) and decrease Insulin-Like Growth Factor-II secretion at both transcriptional and post-transcriptional levels (18).

It is thought that replacing other PUFAs with CLA may reduce oxidative stress and modulate intracellular signaling (11). These effects may inhibit carcinogenesis and affect the cellular response to tumor necrosis factor-alpha (TNF-alpha) (15). In vitro studies have shown that it inhibits the proliferation of MCF-7 breast cancer cells (3). The two major isomers of CLA, trans-10, cis-12 (t10c12) and cis-9, trans-11 (c9t11), have different physiological properties. The cis-9, trans-11 isomer, the principal dietary form, was shown to induce tissue inhibitor of metalloproteinase mRNA in SGC-7901 human gastric carcinoma cells. This may play a role in inhibiting the tumor metastasis cascade (2). The inhibition was thought to come from blocking of the cell cycle with reduced expressions of cyclin A, B1 and D1 and enhanced expressions of CDKI (17).

Pharmacokinetics

Absorption
Cooking or heating seems to increase rather than decrease CLA content in foods (1) (11). The trans-10, cis-12 isomer is metabolized more rapidly than the cis-9, trans-11 isomer (12). Although CLA may be generated from linoleic acid (LA) by intestinal microorganisms, consumption of excess LA does not appear to increase CLA concentrations in humans (19).
Distribution
In rats fed with CLA-containing diets, CLA accumulates in the mammary fat pad greater than in the liver or plasma (4).

Herb Lab Interactions
  • CLA may increase insulin resistance causing increase in blood glucose level (9).
  • CLA may affect cholesterol levels (9) as well as decrease creatinine, bilirubin, creatine-phosphokinase and platelets.
  • CLA may increase potassium levels (6).
Literature Summary and Critique

 


Riserus U, Arner P, Brismar K, Vessby B. Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care 2002;25:1516-21.Sixty obese Caucasian men with metabolic syndrome (abdominal obesity, insulin resistance, dyslipidemia and hypertension) participated in a trial of CLA. Subjects were randomly assigned to receive 3.4 grams per day of CLA (mixed isomers), trans-10, cis-12 CLA, or placebo for 12 weeks. Subjects taking the trans-10, cis-12 isomer had statistically significant increases in insulin resistance and glycemia as well as reduction in HDL cholesterol. Subjects receiving the mixed CLA had lowered HDL cholesterol only. No change in weight or body composition was observed. Researchers note that change in insulin resistance was unexpected.

Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O. Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr 2000;130:2943-8.
Sixty volunteers with body mass index values between 25 and 35 kg/m2 were randomized into five groups to receive either 1.7, 3.4, 5.1 or 6.8 grams of CLA or 9 g placebo per day for 12 weeks. A significantly higher reduction in body fat mass (BFM) was found in the CLA groups when compared with the placebo group, however no additional effects on BFM were observed with doses higher than 3.4 grams per day. No significant differences were observed in lean body mass, blood safety variables or blood lipids. Non clinically significant changes in blood lipids, potassium, creatinine, platelets and bilirubin were observed as well. One severe case of fatigue and some mild-to-moderate gastrointestinal symptoms were reported.

 

Smedman A,.Vessby B. Conjugated linoleic acid supplementation in humans—metabolic effects. Lipids 2001;36:773-81.
Fifty-three healthy men and women participated in a trial of CLA and reduction in body fat. Subjects were randomly assigned to supplementation with 4.2 grams per day of CLA or placebo for 12 weeks. Subjects in the treatment arm showed a significantly decreased proportion of body fat when compared with the control group. No changes were seen on body weight, body mass index, abdominal diameter, serum lipids or glucose metabolism in the treatment group as compared to the placebo group.

Dosage (Inside MSKCC Only)
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References
  1. D'Orazio N, Ficoneri C, Riccioni G, Conti P, Theoharides TC, Bollea MR. Conjugated linoleic acid: a functional food? Int J Immunopathol.Pharmacol. 2003;16:215-20.
  2. Chen BQ, Yang YM, Gao YH, Liu JR, Xue YB, Wang XL et al. Inhibitory effects of c9, t11-conjugated linoleic acid on invasion of human gastric carcinoma cell line SGC-7901. World J Gastroenterol. 2003;9:1909-14.
  3. Chujo H, Yamasaki M, Nou S, Koyanagi N, Tachibana H, Yamada K. Effect of conjugated linoleic acid isomers on growth factor-induced proliferation of human breast cancer cells. Cancer Lett. 2003;202:81-7.
  4. Ip MM, Masso-Welch PA, Ip C. Prevention of mammary cancer with conjugated linoleic acid: role of the stroma and the epithelium. J Mammary.Gland.Biol Neoplasia. 2003;8:103-18.
  5. Miner JL, Cederberg CA, Nielsen MK, Chen X, Baile CA. Conjugated linoleic acid (CLA), body fat, and apoptosis. Obes.Res 2001;9:129-34.
  6. Blankson H, Stakkestad JA, Fagertun H, Thom E, Wadstein J, Gudmundsen O. Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr 2000;130:2943-8.
  7. Petridou A, Mougios V, Sagredos A. Supplementation with CLA: isomer incorporation into serum lipids and effect on body fat of women. Lipids 2003;38:805-11.
  8. Smedman A,.Vessby B. Conjugated linoleic acid supplementation in humans—metabolic effects. Lipids 2001;36:773-81.
  9. Riserus U, Arner P, Brismar K, Vessby B. Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care 2002;25:1516-21.
  10. Mougios V, Matsakas A, Petridou A, Ring S, Sagredos A, Melissopoulou A et al. Effect of supplementation with conjugated linoleic acid on human serum lipids and body fat. J Nutr Biochem. 2001;12:585-94.
  11. Belury MA. Conjugated dienoic linoleate: a polyunsaturated fatty acid with unique chemoprotective properties. Nutr Rev. 1995;53:83-9.
  12. Pariza MW, Park Y, Cook ME. Mechanisms of action of conjugated linoleic acid: evidence and speculation. Proc Soc Exp.Biol Med 2000;223:8-13.
  13. Ma DW, Field CJ, Clandinin MT. An enriched mixture of trans-10,cis-12-CLA inhibits linoleic acid metabolism and PGE2 synthesis in MDA-MB-231 cells. Nutr Cancer 2002;44:203-12.
  14. Choi Y, Park Y, Storkson JM, Pariza MW, Ntambi JM. Inhibition of stearoyl-CoA desaturase activity by the cis-9,trans-11 isomer and the trans-10,cis-12 isomer of conjugated linoleic acid in MDA-MB-231 and MCF-7 human breast cancer cells. Biochem.Biophys.Res Commun. 2002;294:785-90.
  15. Pariza MW, Park Y, Cook ME. Conjugated linoleic acid and the control of cancer and obesity. Toxicol.Sci. 1999;52:107-10.
  16. Banni S, Angioni E, Casu V, Melis MP, Scrugli S, Carta G et al. An increase in vitamin A status by the feeding of conjugated linoleic acid. Nutr Cancer 1999;33:53-7.
  17. Liu JR, Li BX, Chen BQ, Han XH, Xue YB, Yang YM et al. Effect of cis-9, trans-11-conjugated linoleic acid on cell cycle of gastric adenocarcinoma cell line (SGC-7901). World J Gastroenterol. 2002;8:224-9.
  18. Cho HJ, Lee HS, Chung CK, Kang YH, Ha YL, Park HS et al. trans-10, cis-12 conjugated linoleic acid reduces insulin-like growth factor-II secretion in HT-29 human colon cancer cells. J Med Food 2003;6:193-9.
  19. Herbel BK, McGuire MK, McGuire MA, Shultz TD. Safflower oil consumption does not increase plasma conjugated linoleic acid concentrations in humans. Am J Clin Nutr 1998;67:332-7.
  20. Bassaganya-Riera J, Hontecillas R. Dietary conjugated linoleic acid and n-3 polyunsaturated fatty acids in inflammatory bowel disease. Curr Opin Clin Nutr Metab Care. 2010 Sep;13(5):569-73.
  21. MacRedmond R, Singhera G, Attridge S, et al. Conjugated linoleic acid improves airway hyper-reactivity in overweight mild asthmatics. Clin Exp Allergy. 2010 Jul;40(7):1071-8.

Consumer Information

How It Works

Bottom Line: Conjugated Linoleic Acid (CLA) has been shown to reduce both good and bad levels of cholesterol. Its anticancer effects have not been studied in humans.

Conjugated Linoleic Acid (CLA) is made by microbes that live within the gut of certain animals. It is therefore found throughout the body was well as in dairy products and beef. The walls of all cells within the body contain a variety of fatty acids and CLA is readily incorporated into those cell walls upon ingestion. Because CLA is an antioxidant, it may help protect the body from some cancer causing substances. CLA is incorporated into the walls of cells and can modify the signaling between cells.

Two forms of CLA exist in nature. The form most often found in food, called cis-9, trans-11 is thought to help disrupt the replication of some cancer cells. The other form, which is called trans-10, cis-12, has been shown to reduce HDL (“good”) cholesterol levels as well as affect insulin reduction of glucose in the blood.

Purported Uses
  • To Prevent and Treat Cancer
    Animal studies have shown CLA to reduce cancer proliferation and to have antioxidant activities. Human data are lacking.
  • To Treat High Cholesterol
    Studies show that while CLA reduces total cholesterol levels, it reduces HDL, or good cholesterol level as well.
  • To Promote Healthy Weight
    CLA appears to improve body fat mass in very obese people, however results are mixed for non-obese people.
Research Evidence

Weight Maintenance:
A few studies have looked at CLA and its use in reducing weight in obese people. In one study, sixty volunteers with body mass index values (weight divided by height) between 25 and 35 kg/m2 were randomly assigned one of four dosages of CLA or placebo per day for 12 weeks. Volunteers taking the CLA were found to have a higher reduction in body fat mass than those taking placebo. Other measures of weight, such as lean body mass were unaffected.

Another study of fifty-three healthy men and women randomly assigned participants into two groups. One group received CLA for 12 weeks and the other received placebo for 12 weeks. Similar to the study above, subjects in the CLA group observed a significant reduction in proportion of body fat than those taking placebo. Body weight and body mass index were unaffected.

Cholesterol:
Sixty obese volunteers with health characteristics that put them in a high risk for heart disease (high blood pressure, insulin resistance, high cholesterol and obesity) participated in a study of CLA and cholesterol. Volunteers were randomly assigned to receive CLA or placebo for 12 weeks. Volunteers who took CLA observed a reduction in high density lipoprotein (“good”) cholesterol. Volunteers who took the trans-10, cis-12 form of CLA also observed an unexpected observation of a diminished ability of insulin to reduce glucose levels in their blood.

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