Hostname: page-component-7c8c6479df-5xszh Total loading time: 0 Render date: 2024-03-28T11:26:18.931Z Has data issue: false hasContentIssue false

Conjugated linoleic acid (CLA) and obesity

Published online by Cambridge University Press:  01 October 2007

Manuela-Belén Silveira*
Affiliation:
Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Diego de León, 62. 28006 Madrid, Spain
Raffaele Carraro
Affiliation:
Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Diego de León, 62. 28006 Madrid, Spain
Susana Monereo
Affiliation:
Sección de Endocrinología y Nutrición, Hospital Universitario de Getafe, Madrid, Spain
Javier Tébar
Affiliation:
Servicio de Endocrinología y Nutrición, Hospital Universitario Virgen de La Arrixaca, Murcia, Spain
*
Corresponding author: Email belensilveira@telefonica.net
Rights & Permissions [Opens in a new window]

Abstract

Background

The term conjugated linoleic acid (CLA) refers to several positional and geometric conjugated dienoic isomers of linoleic acid (LA), of which the trans-10,cis-12 isomer has been reported to reduce adiposity and increase lean mass in mice and other animals when included at ≤1% of the diet. However, most dietary CLA in humans is obtained from dairy products, accounting for the cis-9,trans-11 CLA isomer, also known as rumenic acid, for more than 90% of the total CLA intake. Commercial CLA preparations industrially produced, containing trans-10,cis-12 and cis-9,trans-11 CLA isomers in diverse proportions, are attracting consumers’ interest because of the purported body fat-lowering effects of CLA, coupled to the perception of a ‘natural’ compound devoid of harmful effects. Nevertheless, despite numerous studies on CLA effects on body composition for nearly a decade, the mechanisms by which CLA isomers elicit their effects remain largely unknown. The purpose of this paper is to provide an updated review of the studies performed on animals and humans, as well as to describe the potential mechanisms involved in CLA effects on body weight and composition and metabolism.

Method

Literature review.

Results

Experiments in humans have not been able to show a significant effect on body weight, body composition or weight regain related to either of the CLA isomers. In fact, some studies suggest a tendency towards a decrease in body fat mass and an increase in body lean mass, while some others raise concern about the possibility of deleterious effects of trans-10,cis-12 CLA on lipid profile, glucose metabolism and insulin sensitivity.

Conclusions

Evidence regarding effectiveness of CLA in humans is not concluding.

Type
Original Article
Copyright
Copyright © The Authors 2007

The term conjugated linoleic acid (CLA) refers to several positional and geometric conjugated dienoic isomers of linoleic acid (LA). LA, or cis,cis-9, 12-octadecadienoic acid, is an 18-carbon omega-6 fatty acid (18:2, 9c–12c) abundant in seed oils, such as sunflower oil. LA is converted to CLA when a chemical or microbial reaction shifts the double bonds to form alternating double and single bonds, hence the term conjugated. These double bonds can be located in different positions along the 18-carbon chain (7,9; 8,10; 9,11; 10,12; 11,13). This conjugation of the double bonds can alter the geometrical isomery of the acid, so that one or both double bonds can adopt trans isomery. The two isomers with known biological activity are cis-9,trans-11 and trans-10,cis-12 CLA.

CLA potential effects on health include anticarcinogenic, antiatherogenic, antidiabetogenic and immune modulating propertiesReference Belury1, Reference McLeod, LeBlanc, Langille, Mitchell and Currie2. CLA has also attracted interest in the scientific community because of its potential effects on body composition, reducing body fat mass and increasing the lean mass. Because of the increasing prevalence and incidence of obesity, a significant proportion of consumers are interested in CLA supplements with purported body fat-lowering effects, perceived as a ‘natural’ compound devoid of harmful effects.

Sources of conjugated linoleic acid

Rumiant animals are able to synthesise CLA through the microbial isomerisation (Butyrinvibrio fibrisolvens and other anaerobic bacteria) of dietary LA in their gastrointestinal tractsReference Kepler, Hirons, McNeill and Tove3. Rumiant meat (beef, veal, lamb) and dairy products are rich in cis-9,trans-11 CLA, also known as rumenic acid. Rumenic acid is the first intermediate step in the biohydrogenation of LA to stearic acid (C18:0).

CLA isomers can also be industrially produced by heating LA in the presence of alkali or by partial hydrogenation of LA. CLA that is typically produced for experimental purposes (MI-CLA) consists of the cis-9,trans-11 (40.8–41.1%), trans-10,cis-12 (43.5–44.9%) and trans-9,trans-11/trans-10,trans-12 (4.6–10%) isomersReference Pariza, Park and Cook4. It should be noted that some commercial CLA preparations contain additional isomers with conjugated double bonds at the 8,10 or 11,13 positionsReference Christie, Dobson and Gunstone5.

The major dietary sources of CLA for humans are beef and dairy products. Cis-9,trans-11 CLA is the principal CLA isomer in milkfatReference Pariza, Park and Cook4. Several factors influence CLA content of food products, such as animal’s diet, age, breed or seasonal factors, reaching the highest levels in cow’s milk during the spring and summer, as cows are allowed to graze in pasturesReference Rainer and Heiss6. CLA in milk or meat is a stable compound under normal cooking and storage conditionsReference Dhiman, Nam and Ure7.

Total CLA content in milk or dairy products ranges from 0.34% to 1.07% of total fatReference Dhiman, Nam and Ure7, whereas in raw or processed beef it ranges from 0.12% to 0.68% of total fatReference Dhiman, Nam and Ure7. CLA daily intakes are 212 mg for men and 151 mg for women not consuming CLA commercial preparations. Most dietary CLA is obtained from dairy products, accounting for the cis-9,trans-11 CLA isomer for more than 90% of the total CLA intakeReference Ritzenthaler, McGuire, Falen, Schultz, Dasgupta and McGuire8.

Evidence of conjugated linoleic acid effects on body weight in animals

Interest in CLA started in 1987, when Ha et al. Reference Ha, Grimm and Pariza9 reported that CLA present in fried ground beef, also synthetically produced by base-catalysed isomerisation of LA, was an effective inhibitor of benzopyrene-initiated mouse epidermal neoplasia.

Regarding obesity and body composition, several studies in animals have shown the ability of CLA to reduce adiposity and increase lean mass. Park et al.Reference Park, Albright, Liu, Storkson, Cook and Pariza10 were the first to report that dietary CLA could alter body composition. A diet containing 0.5% MI-CLA administered to the ICR (Institute for Cancer Research) line of mice caused a 60% decrease in body fat, coupled with enhanced lean body mass, after about 4–5 weeks of feeding.

CLA has also been reported to lower fat mass in other lines of miceReference Pariza, Park and Cook4, as well as in Sprague–DawleyReference Yamasaki, Ikeda, Oji, Tanaka, Hirao and Kasai11 and Zucker ratsReference Sisk, Hausman, Martin and Azain12, though not reaching such impressive results as in mice. In swine, MI-CLA decreased fat deposition and increased lean tissue tooReference Dugan, Aalhus, Schaefer and Kramer13, Reference Ostrowska, Muralitharan, Cross, Bauman and Dunshea14. Interestingly, MI-CLA-supplemented diet increased fat deposition in obese Zucker ratsReference Sisk, Hausman, Martin and Azain12, while reducing insulin levels.

CLA does not reduce food intake in rodentsReference DeLany and West15, Reference West, Blohm, Truett and DeLany16 and its effects are independent of fat content of the dietReference DeLany and West15. Conversely, dietary protein source may alter the effects of CLA on adipocytes’ fat content and adipocytokine production, as rats fed with soy diet show more pronounced fat loss and different changes in leptin and adiponectin levels compared to their casein-fed counterpartsReference Akahoshi, Koba, Ichinose, Kaneko, Shimoda and Nonaka17.

There is substantial evidence that CLA reduces body fat gain in young growing animalsReference Park, Albright, Liu, Storkson, Cook and Pariza10, Reference Ostrowska, Muralitharan, Cross, Bauman and Dunshea14, Reference Bee18Reference Dugan, Aalhus and Kramer20 although some study results do not strongly confirm thisReference Weber, Schinckel, Houseknecht and Richert21. CLA supplementation during gestation and lactation elicits greater body weight and feed efficiency in weanling mice relative to control animalsReference Chin, Storkson, Albright, Cook and Pariza22. This effect on feed efficiency and growth seems to be exerted by the cis-9,trans-11 isomerReference Pariza, Park and Cook4.

Reported effects of CLA on body weight and composition in animals are summarised in Table 1.

Table 1 Effects of CLA isomers on body weight and composition

CLA – conjugated linoleic acid.↑ – increase; ↓ – decrease; ? – possible.

Evidence of conjugated linoleic acid effects on body weight in humans

Experiments in humans have not been able to show a significant effect on body weight related to either MI-, cis-9,trans-11 or trans-10,cis-12 CLAReference House, Cassady, Eisen, McIntosh and Odle23Reference Terpstra26. Published studies report contradicting results. Although in the majority of them there are no significant differences on body weight, body compositionReference Terpstra26 or weight regainReference Kamphuis, Lejeune, Saris and Westerterp-Plantinga27, Reference Larsen, Toubro, Gudmundsen and Astrup28 between controls and CLA-supplemented groups, some studies suggest that CLA might have a tendency to increase lean body massReference Kamphuis, Lejeune, Saris and Westerterp-Plantinga27, Reference Smedman and Vessby29, Reference Blankson, Stakkestad, Fagertun, Thom, Wadstein and Gudmundsen30. On one hand, one study carried out in overweight/obese adult volunteersReference Blankson, Stakkestad, Fagertun, Thom, Wadstein and Gudmundsen30 report a reduction in body fat mass with doses ≥3.4 g MI-CLA per day at week 12 (150–580 g more than placebo), with a significant increase in body lean mass in the group that received 6.8 g MI-CLA per day, measured by dual-energy X-ray absorptiometry; however, this group was also the only one with a significant increase in exercise level. Similar effects were detected in other human trials with MI- and trans-10,cis-12 CLAReference Riserus, Smedman, Basu and Vessby31.

On the other hand, another recent study designed to assess the effect of 1-year supplementation with 3.4 g day−1 CLA in body weight or body fat regain found no differences against placeboReference Larsen, Toubro, Gudmundsen and Astrup28, Reference Whigham, Watras and Schoeller32. In a recent meta-analysis at a dose of 3.2 g day−1, CLA was found to produce a slight reduction in fat mass peaking at 6 months, although confidence intervals were broad.

Differences in doses (ranging from 0.7 to 6.8 g day−1)Reference Blankson, Stakkestad, Fagertun, Thom, Wadstein and Gudmundsen30Reference Mougios, Matsakas, Petridou, Ring, Sagredos and Melissopoulou33, treatment compliance, type and/or proportion of the administered isomer/s, length of the study, characteristics of the study population, energy expenditure and nutrient and energy intakes are possible explanations for the observed discrepancies in the results. Noteworthy, there is no clear dose–response related to the body fat-lowering effect of trans-10,cis-12 CLA and in most of the studies that reported a significant decrease of body fat mass or in those suggesting an increase in lean mass, the participants were also involved in a training programme or did a considerable amount of exerciseReference Blankson, Stakkestad, Fagertun, Thom, Wadstein and Gudmundsen30, Reference Mougios, Matsakas, Petridou, Ring, Sagredos and Melissopoulou33. Therefore, exercise might enhance the body fat lowering and/or lean mass increasing effect of CLA.

The effects of CLA on body weight and composition in humans are summarised in Table 1.

Effects of conjugated linoleic acid on adipocytes

Although the mechanisms by which CLA exerts its action on body weight have not been fully elucidated yet, it seems clear that trans-10,cis-12 CLA is the isomer involved in the changes of body composition.

Trans-10,cis-12 CLA and/or its metabolites is/are able to reduce lipid uptake by adipocytes due to the inhibitory effects on gene expression and enzymatic activity of stearoyl-CoA desaturase (SCD)Reference Choi, Kim, Han, Park, Pariza and Ntambi34, Reference Park, Storkson, Ntambi, Cook, Sih and Pariza35 and lipoprotein lipase (LPL)Reference Park, Albright, Liu, Storkson, Cook and Pariza10, Reference Park, Storkson, Albright, Liu and Pariza36, Reference Brown, Boysen, Jensen, Morrison, Storkson and Lea-Currie37. Trans-10,cis-12 CLA also inhibits the expression of glucose transporter-4 (GLUT-4)Reference Brown, Boysen, Jensen, Morrison, Storkson and Lea-Currie37, Reference Brown, Boysen, Chung, Fabiyi, Morrison and Mandrup38 and increases the activity of carnitine palmitoyltransferase (CPT), enhancing fatty acid oxidationReference Park, Albright, Liu, Storkson, Cook and Pariza10. Trans-10,cis-12 CLA reduces lipogenesis in humanReference Brown, Boysen, Jensen, Morrison, Storkson and Lea-Currie37 and mice adipocytes, decreasing sterol regulatory element-binding protein-1 (SREBP-1) expression in vivo Reference Tsuboyama-Kasaoka, Takahashi, Tanemura, Kim, Tange and Okuyama39. Trans-10,cis-12 CLA also induces adipocyte apoptosis in miceReference Tsuboyama-Kasaoka, Takahashi, Tanemura, Kim, Tange and Okuyama39Reference Hargrave, Meyer, Li, Azain, Baile and Miner43, perhaps mediated by an increase in tumour necrosis factor alpha (TNFα)Reference Tsuboyama-Kasaoka, Takahashi, Tanemura, Kim, Tange and Okuyama39, but the effects of CLA on lipolysis in vivo and in vitro are conflictingReference Park, Albright, Liu, Storkson, Cook and Pariza10, Reference Brown, Boysen, Chung, Fabiyi, Morrison and Mandrup38. Data regarding its effects on preadipocyte differentiation are inconclusive, possibly depending on species, CLA isomer and experimental conditionsReference Pariza, Park and Cook4, Reference Brown, Boysen, Jensen, Morrison, Storkson and Lea-Currie37. Chronic treatment with trans-10,cis-12 CLA significantly reduces the expression of several adipocyte-specific genes, including PPARα and PPARγ target genes, partly due to an increase in nuclear factor kappa B (NFκB) activity and subsequent induction of interleukin-6Reference Chung, Brown, Provo, Hopkins and McIntosh44, therefore explaining at least part of its effects on glucose and lipid metabolism. Trans-10,cis-12 CLA inhibits insulin-stimulated glucose uptake and oxidation, reduces fatty acid uptake and alters fatty acid metabolism in differentiating human preadipocytesReference Brown, Boysen, Jensen, Morrison, Storkson and Lea-Currie37.

MI-CLA appears to increase energy expenditure in rodents by several mechanisms that are not fully understood, although an increase in uncoupling protein UCP1 and UCP3 gene expression does not seem to be involvedReference Pariza, Park and Cook4, Reference DeLany and West15, Reference West, Blohm, Truett and DeLany16, Reference West, Delany, Camet, Blohm, Truett and Scimeca45, Reference Ohnuki, Haramizu, Oki, Ishihara and Fushiki46. However, some studies show an increase in UCP2 expression (mostly with trans-10,cis-12 CLA supplementation) in brown and white adipose tissue and skeletal muscleReference Tsuboyama-Kasaoka, Takahashi, Tanemura, Kim, Tange and Okuyama39, Reference Ealey, El Sohemy and Archer47, Reference Takahashi, Kushiro, Shinohara and Ide48.

According to all these data, it seems that trans-10,cis-12 CLA elicits its de-lipidative activity through both metabolism and cell cycle control. More research is necessary to clarify conflicting results and differences between species.

Potential effects of CLA on adipocytes are summarised in Table 2.

Table 2 Effects of trans-10,cis-12 CLA on adipocytes

CLA – conjugated linoleic acid; SCD – stearoyl-CoA desaturase; LPL – lipoprotein lipase; GLUT4 – glucose transporter-4; CPT – carnitine palmitoyltransferase; SREBP-1 – sterol regulatory element-binding protein-1; TNFα – tumour necrosis factor alpha; UCP2 – uncoupling protein 2; NFκB – nuclear factor kappa B; PPAR – peroxisome proliferator-activated receptor. ↑ – increase; ↓ – decrease; ? – possible.

Effects of conjugated linoleic acid on the liver and skeletal muscle

Several in vivo and in vitro studies in mice have reported an increase in both liver fatty acid synthesis and oxidation in response to MI-CLA supplementationReference Tsuboyama-Kasaoka, Takahashi, Tanemura, Kim, Tange and Okuyama39, Reference Clement, Poirier, Niot, Bocher, Guerre-Millo and Krief49Reference Peters, Park, Gonzalez and Pariza51. CLA may mediate its effects through PPARα and PPARβ/δ (both trans-10,cis-12 and cis-9,trans-11 CLA isomers are their ligandsReference Moya-Camarena, Vanden Heuvel, Blanchard, Leesnitzer and Belury52), a decrease in SCD-1Reference Lee, Pariza and Ntambi53 expression and other alternative pathways, as suggested by studies on knockout miceReference Kang, Miyazaki, Ntambi and Pariza54, Reference Peters, Park, Gonzalez and Pariza51. However, there seem to be differences between species, as hamstersReference de Deckere, van Amelsvoort, McNeill and Jones55 on a CLA-supplemented diet developed liver hypertrophy but not lipid accumulation, and rats or pigs fed with CLA-enriched diets showed no changes in weight or lipid content in the liverReference Pariza, Park and Cook4.

There is evidence of the anabolic properties of CLA on lean mass in miceReference Park, Albright, Liu, Storkson, Cook and Pariza10, and probably in other speciesReference Ostrowska, Muralitharan, Cross, Bauman and Dunshea56, Reference Ostrowska, Suster, Muralitharan, Cross, Leury and Bauman57. However, the effects of CLA on the skeletal muscle are still unclear. CLA-fed mice showed an increase of CPT activity on skeletal muscle, improving β-oxidationReference Park, Albright, Liu, Storkson, Cook and Pariza10 and, as previously indicated, an enhancement in UCP2 expression is also evident in some studies.

Metabolic effects of conjugated linoleic acid

The effects on lipid metabolism of trans-10,cis-12 CLA, the active isomer involved in fat mass loss, are currently objects of concern. Administration of trans-10,cis-12 CLA to humans results in an increase of the LDL/HLDL ratioReference Tricon, Burdge, Kew, Banerjee, Russell and Jones24, some studies reflecting an increase in LDL-cholesterolReference Smedman and Vessby29, while others showing a decrease in HDL-cholesterolReference Smedman and Vessby29, Reference Blankson, Stakkestad, Fagertun, Thom, Wadstein and Gudmundsen30, Reference Mougios, Matsakas, Petridou, Ring, Sagredos and Melissopoulou33, Reference Riserus, Arner, Brismar and Vessby58; however, such effects are just marginal and not statistically significant compared to the control group in some of the studiesReference Smedman and Vessby29, Reference Mougios, Matsakas, Petridou, Ring, Sagredos and Melissopoulou33. These deleterious effects are not evident with the administration of MI-CLA or the cis-9,trans-11 isomerReference Tricon, Burdge, Kew, Banerjee, Russell and Jones24, Reference Tricon, Burdge, Jones, Russell, El-Khazen and Moretti25, Reference Riserus, Smedman, Basu and Vessby31, Reference Riserus, Arner, Brismar and Vessby58Reference Moloney, Yeow, Mullen, Nolan and Roche60. Moreover, cis-9,trans-11 CLA actually appears to decrease LDL cholesterol in humansReference Tricon, Burdge, Kew, Banerjee, Russell and Jones24, Reference Blankson, Stakkestad, Fagertun, Thom, Wadstein and Gudmundsen30. A 6.4 g day−1 MI-CLA doses for 12 weeks produced a modest increase in lean mass (0.6 kg) but significant decrease in serum HDL-cholesterol, sodium, hemoglobin, and hematocrit, and significant increases in serum alkaline phosphatase, C-reactive protein, and K-6, and white blood cells.

Plasma triacylglycerides (TAG) did not significantly change or decrease compared to placebo in some studies with MI-CLA supplementationReference Mougios, Matsakas, Petridou, Ring, Sagredos and Melissopoulou33, Reference Noone, Roche, Nugent and Gibney59, Reference Petridou, Mougios and Sagredos62, Reference Benito, Nelson, Kelley, Bartolini, Schmidt and Simon63. Nevertheless, in another study mean plasma TAG concentration was higher during supplementation with a mixture 85% trans-10,cis-12 CLA than with another mixture 80% cis-9,trans-11 CLAReference Tricon, Burdge, Kew, Banerjee, Russell and Jones24.

Interestingly, there is no clear dose–response relationship in the relative hyperlipidemic properties of trans-10,cis-12 CLA and hypolipidemic properties of cis-9,trans-11 CLA in humansReference Tricon, Burdge, Kew, Banerjee, Russell and Jones24, suggesting that this influence could be exerted even at low dosesReference Tricon, Burdge, Kew, Banerjee, Russell and Jones24. Moreover, in apolipoprotein E knockout mice, supplementation with trans-10,cis-12 CLA had a profound pro-atherogenic effect, whereas cis-9,trans-11 CLA impeded the development of atherosclerosisReference Benito, Nelson, Kelley, Bartolini, Schmidt and Simon64.

In a similar way, there are conflicting results related to carbohydrate metabolism in humans. Although several studies show that neither cis-9,trans-11 CLA nor trans-10,cis-12 CLA supplementation significantly modify plasma glucose or insulin levels or alter insulin sensitivity (revised QUICKI) or insulin resistance (HOMA-IR)Reference Tricon, Burdge, Kew, Banerjee, Russell and Jones24, Reference Smedman and Vessby29, Reference Noone, Roche, Nugent and Gibney59, Riserus et al.Reference Riserus, Smedman, Basu and Vessby31, Reference Riserus, Arner, Brismar and Vessby58, Reference Arbones-Mainar, Navarro, Guzman, Arnal, Surra and Acin65 repeatedly report marginal but detrimental effects of both trans-10,cis-12 CLA (3.4 g day−1) and cis-9,trans-11 CLA (3 g day−1) on insulin sensitivity (measured as the insulin sensitivity index with the euglycemic clamp) and lipid peroxidation in obese subjects with metabolic syndrome. Another study in type 2 diabetic patients supplemented with MI-CLA (3 g day−1) also shows unfavourable effects on fasting glucose, insulin resistance (HOMA) and oral glucose insulin sensitivityReference Moloney, Yeow, Mullen, Nolan and Roche60. These results are in agreement with those of CLA-fed miceReference Tsuboyama-Kasaoka, Takahashi, Tanemura, Kim, Tange and Okuyama39, but not with the reported improvement on insulin sensitivity of some other studies in genetically obese miceReference Riserus, Vessby, Arner and Zethelius66 or Zucker rats supplemented with CLAReference Sisk, Hausman, Martin and Azain12.

Conclusions

Although there is evidence in animals of the ability of trans-10,cis-12 CLA to reduce adiposity and increase lean mass, such unequivocal data supporting the efficacy of either of the CLA isomers in humans are not available.

Moreover, contradictory results raise concern about the possibility of the deleterious effects of trans-10,cis-12 CLA on the lipid profile, glucose metabolism and insulin sensitivity. Therefore, it is advisable to consider with caution the use of CLA supplements containing high quantities of trans-10,cis-12 CLA, especially in obese patients with type 2 diabetes or metabolic syndrome, which constitutes a considerable proportion of the whole overweight/obese population.

Before CLA supplementation is recommended, further research on human effectiveness and safety of the different isomers of CLA is required.

Acknowledgements

Conflict of interest declaration: The authors had no conflicts of interest to report.

Authorship contributions: All the authors (M.B.S., R.C., S.M., J.T.) declare that they participated sufficiently in the work to take full and public responsibility for its content..

References

1Belury, MA. Inhibition of carcinogenesis by conjugated linoleic acid: potential mechanisms of action. Nutrition 2002; 132 (10): 29952998.Google ScholarPubMed
2McLeod, RS, LeBlanc, AM, Langille, MA, Mitchell, PL, Currie, DL. Conjugated linoleic acids, atherosclerosis, and hepatic very-low-density lipoprotein metabolism. American Journal of Clinical Nutrition 2004; 79: 1169S1174S.CrossRefGoogle ScholarPubMed
3Kepler, CR, Hirons, KP, McNeill, JJ, Tove, SB. Intermediates and products of the biohydrogenation of linoleic acid by Butyrinvibrio fibrisolvens. The Journal of Biological Chemistry 1966; 241 (6): 13501354.CrossRefGoogle ScholarPubMed
4Pariza, MW, Park, Y, Cook, ME. The biologically active isomers of conjugated linoleic acid. Progress in Lipid Research 2001; 40 (4): 283298.CrossRefGoogle ScholarPubMed
5Christie, WW, Dobson, G, Gunstone, FD. Isomers in commercial samples of conjugated linoleic acid. Lipids 1997; 32 (11): 1231.Google Scholar
6Rainer, L, Heiss, C. Conjugated Linoleic Acid: health implications and effects on body composition. Journal of the American Dietetic Association 2004; 104: 936938.Google Scholar
7Dhiman, TR, Nam, SH, Ure, AL. Factors affecting conjugated linoleic acid content in milk and meat. Critical Reviews in Food Science and Nutrition 2005; 45 (6): 463482.CrossRefGoogle ScholarPubMed
8Ritzenthaler, KL, McGuire, MK, Falen, R, Schultz, TD, Dasgupta, N, McGuire, MA. Estimation of conjugated linoleic acid intake by written dietary assessment methodologies underestimates actual intake evaluated by food duplicate methodology. Journal of Nutrition 2001; 131: 15481554.CrossRefGoogle ScholarPubMed
9Ha, YL, Grimm, NK, Pariza, MW. Anticarcinogens from fried ground beef: heat-altered derivatives of linoleic acid. Carcinogenesis 1987; 8: 18811887.CrossRefGoogle ScholarPubMed
10Park, Y, Albright, KJ, Liu, W, Storkson, JM, Cook, ME, Pariza, MW. Effect of conjugated linoleic acid on body composition in mice. Lipids 1997; 32: 853858.CrossRefGoogle ScholarPubMed
11Yamasaki, M, Ikeda, A, Oji, M, Tanaka, Y, Hirao, A, Kasai, M, et al. . Modulation of body fat and serum leptin levels by dietary conjugated linoleic acid in Sprague–Dawley rats fed various fat-level diets. Nutrition 2003; 19: 3035.CrossRefGoogle ScholarPubMed
12Sisk, MB, Hausman, DB, Martin, RJ, Azain, MJ. Dietary conjugated linoleic acid reduces adiposity in lean but not obese Zucker rats. Journal of Nutrition 2001; 131: 16681674.Google Scholar
13Dugan, MER, Aalhus, JL, Schaefer, AL, Kramer, JKG. The effect of conjugated linoleic acid on fat to lean repartitioning and feed conversion in pigs. Canadian Journal of Animal Science 1997; 77: 723725.CrossRefGoogle Scholar
14Ostrowska, E, Muralitharan, M, Cross, RF, Bauman, DE, Dunshea, FR. Dietary conjugated linoleic acids increase lean tissue and decrease fat deposition in growing pigs. Journal of Nutrition 1999; 129: 20372042.CrossRefGoogle ScholarPubMed
15DeLany, JP, West, DB. Changes in body composition with conjugated linoleic acid. Journal of the American College of Nutrition 2000; 19: 487S493S.Google Scholar
16West, DB, Blohm, FY, Truett, AA, DeLany, JP. Conjugated linoleic acid persistently increases total energy expenditure in AKR/J mice without increasing uncoupling protein gene expression. Journal of Nutrition 2000; 130: 24712477.CrossRefGoogle ScholarPubMed
17Akahoshi, A, Koba, K, Ichinose, F, Kaneko, M, Shimoda, A, Nonaka, K, et al. . Dietary protein modulates the effect of CLA on lipid metabolism in rats. Lipids 2004; 39: 2530.CrossRefGoogle ScholarPubMed
18Bee, G. Dietary conjugated linoleic acids affect tissue lipid composition but not de novo lipogenesis in finishing pigs. Animal Research 2001; 50: 383399.CrossRefGoogle Scholar
19Wiegand, BR, JrParrish, FC, Swan, JE, Larsen, ST, Baas, TJ. Conjugated linoleic acid improves feed efficiency, decreases subcutaneous fat, and improves certain aspects of meat quality in stress-genotype pigs. Journal of Animal Science 2001; 79 (8): 21872195.CrossRefGoogle ScholarPubMed
20Dugan, ME, Aalhus, JL, Kramer, JK. Conjugated linoleic acid pork research. American Journal of Clinical Nutrition 2004; 79 (6 Suppl.): 1212S1216S.CrossRefGoogle ScholarPubMed
21Weber, TE, Schinckel, AP, Houseknecht, KL, Richert, BT. Evaluation of conjugated linoleic acid and dietary antibiotics as growth promotants in weanling pigs. Journal of Animal Science 2001; 79 (10): 25422549.Google Scholar
22Chin, SF, Storkson, JM, Albright, KJ, Cook, ME, Pariza, MW. Conjugated linoleic acid is a growth factor for rats as shown by enhanced weight gain and improved feed efficiency. Journal of Nutrition 1994; 124: 23442349.CrossRefGoogle ScholarPubMed
23House, RL, Cassady, JP, Eisen, EJ, McIntosh, MK, Odle, J. Conjugated linoleic acid evokes de-lipidation through the regulation of genes controlling lipid metabolism in adipose and liver tissue. Obesity Reviews 2005; 6 (3): 247258.CrossRefGoogle ScholarPubMed
24Tricon, S, Burdge, GC, Kew, S, Banerjee, T, Russell, JJ, Jones, EL, et al. . Opposing effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on blood lipids in healthy humans. American Journal of Clinical Nutrition 2004; 80 (3): 614620.Google Scholar
25Tricon, S, Burdge, GC, Jones, EL, Russell, JJ, El-Khazen, S, Moretti, E, et al. . Effects of dairy products naturally enriched with cis-9,trans-11 conjugated linoleic acid on the blood lipid profile in healthy middle-aged men. American Journal of Clinical Nutrition 2006; 83 (4): 744753.CrossRefGoogle ScholarPubMed
26Terpstra, AH. Effect of conjugated linoleic acid on body composition and plasma lipids in humans: an overview of the literature. American Journal of Clinical Nutrition 2004; 79 (4): 352361.CrossRefGoogle ScholarPubMed
27Kamphuis, MMJW, Lejeune, MPGM, Saris, WHM, Westerterp-Plantinga, MS. The effect of conjugated linoleic acid supplementation after weight loss on body weight regain, body composition, and resting metabolic rate in overweight subjects. International Journal of Obesity and Related Metabolic Disorders 2003; 27: 840847.CrossRefGoogle ScholarPubMed
28Larsen, TM, Toubro, S, Gudmundsen, O, Astrup, A. Conjugated linoleic acid supplementation for 1 y does not prevent weight or body fat regain. American Journal of Clinical Nutrition 2006; 83 (3): 606612.Google Scholar
29Smedman, A, Vessby, B. Conjugated linoleic acid supplementation in humans – metabolic effects. Lipids 2001; 36: 773778.CrossRefGoogle ScholarPubMed
30Blankson, H, Stakkestad, JA, Fagertun, H, Thom, E, Wadstein, J, Gudmundsen, O. Conjugated linoleic acid reduces body fat mass in overweight and obese humans. Journal of Nutrition 2000; 130: 29432948.Google ScholarPubMed
31Riserus, U, Smedman, A, Basu, S, Vessby, B. Metabolic effects of conjugated linoleic acid in humans: the Swedish experience. American Journal of Clinical Nutrition 2004; 79: 1146S1148S.CrossRefGoogle ScholarPubMed
32Whigham, LD, Watras, AC, Schoeller, DA. Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. American Journal of Clinical Nutrition 2007; 85 (5): 12031211.CrossRefGoogle Scholar
33Mougios, V, Matsakas, A, Petridou, A, Ring, S, Sagredos, A, Melissopoulou, A. Effect of supplementation with conjugated linoleic acid on human serum lipids and body fat. The Journal of Nutritional Biochemistry 2001; 12: 585594.Google Scholar
34Choi, Y, Kim, YC, Han, YB, Park, Y, Pariza, MW, Ntambi, JM. The trans-10,cis-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes. Journal of Nutrition 2000; 130 (8): 19201924.Google Scholar
35Park, Y, Storkson, JM, Ntambi, JM, Cook, ME, Sih, CJ, Pariza, MW. Inhibition of hepatic stearoyl-CoA desaturase activity by trans-10,cis-12 conjugated linoleic acid and its derivatives. Biochimica et Biophysica Acta 2000; 1486 (2-3): 285292.Google Scholar
36Park, Y, Storkson, JM, Albright, KJ, Liu, W, Pariza, MW. Evidence that the trans-10,cis-12 isomer of conjugated linoleic acid induces body composition changes in mice. Lipids 1999; 34 (3): 235241.Google Scholar
37Brown, JM, Boysen, MS, Jensen, SS, Morrison, RF, Storkson, J, Lea-Currie, R, et al. . Isomer-specific regulation of metabolism and PPARγ signalling by CLA in human preadipocytes. Journal of Lipid Research 2003; 44: 12871300.CrossRefGoogle ScholarPubMed
38Brown, JM, Boysen, MS, Chung, S, Fabiyi, O, Morrison, RF, Mandrup, S, et al. . Conjugated linoleic acid (CLA) induces human adipocyte delipidation: autocrine/paracrine regulation of MEK/ERK signaling by adipocytokines. The Journal of Biological Chemistry 2004; 279: 2673526747.Google Scholar
39Tsuboyama-Kasaoka, N, Takahashi, M, Tanemura, K, Kim, HJ, Tange, T, Okuyama, H, et al. . Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes 2000; 49 (9): 15341542.CrossRefGoogle ScholarPubMed
40Nelson-Dooley, C, Della-Fera, MA, Hamrick, M, Baile, CA. Novel treatments for obesity and osteoporosis: targeting apoptotic pathways in adipocytes. Current Medicinal Chemistry 2005; 12 (19): 22152225.CrossRefGoogle ScholarPubMed
41Miner, JL, Cederberg, CA, Nielsen, MK, Chen, X, Baile, CA. Conjugated linoleic acid (CLA), body fat, and apoptosis. Obesity Research 2001; 9: 129134.Google Scholar
42Evans, M, Geigerman, C, Cook, J, Curtis, L, Kuebler, B, McIntosh, M. Conjugated linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3T3-L1 preadipocytes. Lipids 2000; 35: 899910.CrossRefGoogle ScholarPubMed
43Hargrave, KM, Meyer, BJ, Li, C, Azain, MJ, Baile, CA, Miner, JL. Influence of dietary conjugated linoleic Acid and fat source on body fat and apoptosis in mice. Obesity Research 2004; 12 (9): 14351444.CrossRefGoogle ScholarPubMed
44Chung, S, Brown, JM, Provo, JN, Hopkins, R, McIntosh, MK. Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production. The Journal of Biological Chemistry 2005; 280 (46): 3844538456.Google Scholar
45West, DB, Delany, JP, Camet, PM, Blohm, F, Truett, AA, Scimeca, J. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. The American Journal of Physiology 1998; 275 (3 Pt 2): R667R672.Google ScholarPubMed
46Ohnuki, K, Haramizu, S, Oki, K, Ishihara, K, Fushiki, T. A single oral administration of conjugated linoleic acid enhanced energy metabolism in mice. Lipids 2001; 37: 583587.CrossRefGoogle Scholar
47Ealey, KN, El Sohemy, A, Archer, MC. Effects of dietary conjugated linoleic acid on the expression of uncoupling proteins in mice and rats. Lipids 2002; 37: 853861.Google Scholar
48Takahashi, Y, Kushiro, M, Shinohara, K, Ide, T. Dietary conjugated linoleic acid reduces body fat mass and affects gene expression of proteins regulating energy metabolism in mice. Comparative Biochemistry and Physiology 2002; 133: 395404.Google Scholar
49Clement, L, Poirier, H, Niot, I, Bocher, V, Guerre-Millo, M, Krief, S, et al. . Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. Journal of Lipid Research 2002; 43: 14001409.Google Scholar
50Degrace, P, Demizieux, L, Gresti, J, Chardigny, JM, Sébédio, JL, Coulet, P. Hepatic steatosis is not due to impaired fatty acid oxidation capacities in C57BL/6j mice fed the conjugated trans-10,cis-12-isomer of linoleic acid. Journal of Nutrition 2004; 134: 861867.CrossRefGoogle Scholar
51Peters, JM, Park, Y, Gonzalez, FJ, Pariza, MW. Influence of conjugated linoleic acid on body composition and target gene expression in peroxisome proliferator-activated receptor alpha-null mice. Biochimica et Biophysica Acta 2001; 1533: 233242.Google Scholar
52Moya-Camarena, SY, Vanden Heuvel, JP, Blanchard, SG, Leesnitzer, LA, Belury, MA. Conjugated linoleic acid is a potent naturally occurring ligand and activator of PPARalpha. Journal of Lipid Research 1999; 40: 14261433.Google Scholar
53Lee, KN, Pariza, MW, Ntambi, JM. Conjugated linoleic acid decreases hepatic stearoyl-CoA desaturase mRNA expression. Biochemical and Biophysical Research Communications 1998; 248 (3): 817821.Google Scholar
54Kang, K, Miyazaki, H, Ntambi, JM, Pariza, MW. Evidence that the anti-obesity effect of conjugated linoleic acid is independent of effects on stearoyl-CoA desaturase1 expression and enzyme activity. Biochemical and Biophysical Research Communications 2004; 315: 532537.Google Scholar
55de Deckere, EA, van Amelsvoort, JM, McNeill, GP, Jones, P. Effects of conjugated linoleic acid (CLA) isomers on lipid levels and peroxisome proliferation in the hamster. British Journal of Nutrition 1999; 82 (4): 309317.Google Scholar
56Ostrowska, E, Muralitharan, M, Cross, RF, Bauman, DE, Dunshea, FR. Dietary conjugated linoleic acids increase lean tissue and decrease fat deposition in growing pigs. Journal of Nutrition 1999; 129 (11): 20372042.CrossRefGoogle ScholarPubMed
57Ostrowska, E, Suster, D, Muralitharan, M, Cross, RF, Leury, BJ, Bauman, DE, et al. . Conjugated linoleic acid decreases fat accretion in pigs: evaluation by dual-energy X-ray absorptiometry. British Journal of Nutrition 2003; 89 (2): 219229.Google Scholar
58Riserus, 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: 15161521.Google Scholar
59Noone, EJ, Roche, HM, Nugent, AP, Gibney, MJ. The effect of dietary supplementation using isomeric blends of conjugated linoleic acid on lipid metabolism in healthy human subjects. British Journal of Nutrition 2002; 88: 243251.Google Scholar
60Moloney, F, Yeow, TP, Mullen, A, Nolan, JJ, Roche, HM. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. American Journal of Clinical Nutrition 2004; 80 (4): 887895.Google Scholar
61Steck, SE, Chalecki, AM, Miller, P, Conway, J, Austin, GL, Hardin, JW, et al. . Conjugated linoleic acid supplementation for twelve weeks increases lean body mass in obese humans. Journal of Nutrition 2007; 137 (5): 11881193.Google Scholar
62Petridou, A, Mougios, V, Sagredos, A. Supplementation with CLA: isomer incorporation into serum lipids and effect on body fat of women. Lipids 2003; 38 (8): 805811.Google Scholar
63Benito, P, Nelson, GJ, Kelley, DS, Bartolini, G, Schmidt, PC, Simon, V. The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans. Lipids 2001; 36: 229236.CrossRefGoogle ScholarPubMed
64Arbones-Mainar, JM, Navarro, MA, Guzman, MA, Arnal, C, Surra, JC, Acin, S, et al. . Selective effect of conjugated linoleic acid isomers on atherosclerotic lesion development in apolipoprotein E knockout mice. Atherosclerosis 2006; 189 (2): 318327; Epub 2006 Mar 13.CrossRefGoogle ScholarPubMed
65Riserus, U, Vessby, B, Arner, P, Zethelius, B. Supplementation with trans10, cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity. Diabetologia 2004; 47 (6): 10161019.Google Scholar
66Wargent, E, Sennitt, MV, Stocker, C, Mayes, AE, Brown, L, O’Dowd, J, et al. . Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation. Lipids in Health and Disease 2005; 4 (1): 3.Google Scholar
Figure 0

Table 1 Effects of CLA isomers on body weight and composition

Figure 1

Table 2 Effects of trans-10,cis-12 CLA on adipocytes