Conjugated linoleic acid (CLA) is a naturally occurring polyunsaturated fatty acid. Nine different isomers of CLA have been identified, and their double bonds are conjugated at carbons 9 and 11 or 10 and 12 in the cis and trans configuration. CLA is found in low concentrations in blood and tissues, although the body does not synthesise CLA endogenously. CLA is readily absorbed from food and supplements.
CLA is present in small quantities in many foods, especially beef and dairy produce. Cooking has been shown to increase the CLA content of meat. Changes in the way beef and dairy animals have been reared in the last decades have reduced the amount of CLA in the diet.
CLA is essential for the delivery of dietary fat into cells. It transports glucose into cells, and helps glucose to be used to provide energy and build muscle rather than being converted to fat. It is this effect that lies behind the claims that CLA is useful for promoting weight loss. CLA is also an antioxidant and enhances the immune system.
CLA is being marketed for loss of body weight, and is also being investigated for prevention of cancer.
Body weight and energy expenditure
CLA is being promoted for control of body weight, and early evidence from animal studies was promising. In mice, CLA has been shown to reduce fat accumulation and increase protein accumulation without any change in food intake,1 to reduce energy intake, increase metabolism and reduce body fat,2 to reduce body fat and increase lean body mass without affecting body weight,3 and to reduce body fat and increase energy expenditure.4
Human clinical data are now appearing in the literature, but with somewhat conflicting results. A 12-week randomised double-blind study including 60 overweight or obese volunteers given various doses of CLA from 1.7 to 6.8 g daily found that CLA was associated with a significantly higher reduction in body fat mass than placebo. The reduction in body fat was significant for the groups taking 3.4 and 6.8 g CLA.5 A 4-week double-blind RCT in 25 obese men aged 39–64 with metabolic disorder found that CLA 4.2 g daily was associated with a significant reduction in abdominal fat but with no concomitant effects on overall obesity and other cardiovascular risk factors.6
A Dutch RCT in 54 men and women involved subjects being put on a very low-calorie diet (2.1 MJ/day) for 3 weeks, followed by 13 weeks on either low- or high-dose CLA (1.8 or 3.6 g daily) or placebo. Weight regain after the low-calorie diet was not significantly different between the active and placebo groups, but subjects on CLA did gain a significantly greater proportion of that weight as fat-free mass (4.6% vs 3.4%). The effect was similar for the low- and high-dose CLA.7 As part of this study, appetite and food intake was also measured. Appetite (hunger, satiety and fullness) was favourably, dose-dependently affected by consumption of both 1.8 and 3.6 g CLA daily. However, this did not affect energy intake at breakfast and did not improve body weight maintenance.8
A 12-month study investigated the effect of CLA in 180 healthy overweight adults. Body fat mass was significantly reduced in the CLA groups.9 As part of the same study, 134 of the participants were included in an open study for a further 12 months to evaluate the safety of CLA and assess its effect on body composition. The extended study found that CLA 3.4 g daily decreases body fat mass and may help maintain initial reductions in body fat mass and weight in the long term. The supplement was well tolerated.10
CLA has also been investigated in people who are exercising. A human study showed that 5.6–7.2 g of CLA daily produced non-significant gains in muscle size and strength in experienced and inexperienced training men.11 A double-blind 12-week RCT in 20 healthy people with body mass index <25 who did standardised exercise in a gym for 90 min three times weekly found that CLA 1.8 g daily reduced body fat but not body weight.12 A further study investigated the effect of CLA 6 g daily in 23 resistance-trained subjects. Results showed some statistical trends, but CLA did not significantly affect changes in total body mass, percentage body fat, bone mass or fat-free mass, indicating that CLA does not appear to possess significant ergogenic value for experienced resistance-trained athletes.13
There is some evidence that a specific isomer of CLA may be the bioactive component in relation to weight change. A US study in 21 adults with type 2 diabetes found that a CLA mixture of predominantly two isomers (c911t and t10c12) resulted in an increase in plasma CLA that was inversely correlated with body weight and serum leptin levels. However, these significant correlations were only seen with the t10c12-CLA.14
Animal research suggests an effect of CLA supplementation on preventing atherosclerosis,15,16 but one study has shown that CLA does not produce beneficial lipid profiles.17 One human study in 17 healthy female volunteers found that CLA 3.9 g daily for 2 months did not alter blood cholesterol or lipoprotein levels.18 In the same study, there were no effects of CLA on blood coagulation and platelet function.19 Another human RCT in 51 normolipidaemic patients found that an isomeric blend of CLA significantly reduced plasma triglycerides and VLDL cholesterol concentrations.20
Based on preliminary work in animals,21 there has been some hope that CLA could improve insulin resistance. An 8-week Canadian RCT in 16 normal weight, healthy young adults living a sedentary lifestyle found that an isomeric blend of CLA 4 g daily significantly improved insulin sensitivity by 27% compared with the control group. Insulin sensitivity improved in six out of 10 of the treated group while two deteriorated and two had no change.22
An Irish RCT in 32 overweight diabetic sub-jects found the opposite. Treatment consisted of 8 weeks of either placebo or an isomeric blend of CLA (3 g daily). CLA produced a 6.3% signif-icant increase in fasting glucose concentration and a reduction in insulin sensitivity.23 Two further studies from the same research group found that both of the common CLA isomers have a negative effect on insulin resistance in obese non-diabetics.24,25
Preliminary evidence from in vitro work and animals suggests that CLA may reduce the risk of cancer,26–28 but other studies have not confirmed this.29 Linoleic acid itself has been shown to promote tumorigenesis in some studies.
Based on findings in experimental animals and cells in culture that CLA can positively influence calcium and bone metabolism, research is now being conducted in humans. However, one double-blind RCT in 60 healthy adult men aged 39–64 found that CLA 3 g daily for 6 weeks had no significant effect on markers of bone formation or bone resorption or on serum or urinary calcium levels.30
CLA has also been investigated for effects on immune function. One study in humans found that CLA supplementation results in a dose-dependent reduction in mitogen-induced T-lymphocyte activation,31 while a further study showed that CLA had a minimal effect on the markers of human immune function.32
Until more is known, caution should be exer-cised in the use of CLA supplements because of potential problems with insulin resistance. Although this is not proven, people likely to use CLA will be overweight and most likely to suffer from insulin resistance.
Pregnancy and breast-feeding
No problems have been reported, but there have not been sufficient studies to guarantee the safety of CLA in pregnancy and breast-feeding.
No known toxicity or side-effects, apart from one report of gastrointestinal side-effects. How-ever, there are no long-term studies assessing the safety of CLA.
CLA is produced for supplements from sunflower oil and is available in the form of capsules.
The dose is not established. Animal research has used large doses, equivalent to several grams a day for humans. However, dietary supplements tend to provide a dose of 1–4 g daily.
Studies in animals suggest that CLA reduces body fat and increases lean body mass. Human clinical data are conflicting, with only limited evidence that CLA can influence lean body mass. CLA may also increase insulin resistance and overweight people are likely to be those with insulin resistance. Animal studies suggest that CLA may have beneficial effects on atherosclerosis, bone metabolism and immune function, but preliminary human studies have not demonstrated such beneficial effects.
- DeLany JP, Blohm F, Truett AA, et al. Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake. Am J Physiol 1999; 276 (part 2): R1172–1179.
- West DB, DeLany JP, Camet PM, et al. Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am J Physiol 1998 (part 2); 275: R667–672.
- Park Y, Allbright KJ, Liu W, et al. Effect of conjugated linoleic acid on body composition in mice. Lipids 1997; 32: 853–858.
- West DB, Blohm FY, Truett AA, DeLany JP. Conjugated linoleic acid persistently increases total energy expenditure in AKR/J mice without uncou-pling protein gene expression. J Nutr 2000; 130: 2471–2477.
- Blankson H, Stakkestad JA, Fagertun H, et al. Conjugated linoleic acid reduces body fat mass in overweight and obese humans. J Nutr 2000; 130: 2943–2948.
- Riserus U, Berglund L, Vessby B. Conjugated linoleic acid reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial. Int J Obes Relat Metab Disord 2001; 25: 1129–1135.
- Kamphuis MM, Lejeune MP, Saris WH, Westerterp-Plantenga MS. The effect of conjugated linoleic acid supplementation after weight loss on body weight regain, body composition and resting metabolic rate in overweight subjects. Int J Obes Relat Metab Disord 2003; 27: 840–847.
- Kamphuis MM, Lejeune MP, Saris WH, Westerterp-Plantenga MS. Effect of conjugated linoleic acid supplementation after weight loss on appetite and food intake in overweight subjects. Eur J Clin Nutr 2003; 57: 1268–1274.
- Gaullier JM, Halse J, Hoye K, et al. Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Am J Clin Nutr 2004; 79: 1118–1125.
- Gaullier JM, Halse J, Hoyce K, et al. Supplemen-tation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans. J Nutr 2005; 135: 778–784.
- Ferreira M, Krieder R, Wilson M. Effects of CLA supplementation during resistance training on body muscle and strength. J Strength Cond Res 1998; 11: 280.
- Thom E, Wadstein J, Gudmundsen O. Conjugated linoleic acid reduces body fat in healthy exercising humans. J Int Med Res 2001; 29: 392–396.
- Kreider RB, Ferreira MP, Greenwood M, et al. Effects of conjugated linoleic acid supplementation during resistance training on body composition, bone density, strength and selected haematological markers. J Strength Cond Res 2002; 16: 325–334.
- Belury MA, Mahon A, Banni S. The conjugated linoleic acid (CLA) isomer, t10c12-CLA, is inversely associated with changes in body weight and serum leptin in subjects with type 2 diabetes mellitus. J Nutr 2003; 133: S257S–S260.
- Lee KN, Kritchevsky D, Pariza MW. Conju-gated linoleic acid and atherosclerosis in rabbits. Atherosclerosis 1994; 108: 19–25.
- Nicolosi RJ, Rogers EJ, Kritchevsky D, et al. Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters. Artery 1997; 22: 266–277.
- Kritchevsky D, Tepper SA, Wright S, et al. Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits. J Am Coll Nutr 2000; 19: S472S–S477.
- Benito P, Nelson GJ, Kelley DS, et al. The effect of conjugated linoleic acid on plasma lipoproteins and tissue fatty acid composition in humans. Lipids 2001; 36: 229–236.
- Benito P, Nelson GJ, Kelley DS, et al. The effect of conjugated linoleic acid on platelet function, platelet fatty acid composition and blood coagulation in humans. Lipids 2001; 36: 221–227.
- Noone EJ, Roche HM, Nugent AP, Gibney MJ. The effect of dietary suppelementation using iso-meric blends of conjugated linoleic acid on lipid metabolism in healthy human subjects. Br J Nutr 2002; 88: 243–251.
- Houseknecht KL, Vanden Heuvel JP, Moya-Camarena SY, et al. Dietary conjugated linoleic acid normalises impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat. Biochem Biophys Res Commun 1998; 244: 678–682.
- Eyjolfson V, Spriet LL, Dyck DJ. Conjugated linoleic acid improves insulin sensitivity in young, sedentary humans. Med Sci Sports Exerc 2004; 36: 814–820.
- Moloney F, Yeow TP, Mullen A, et al. Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus. Am J Clin Nutr 2004; 80: 887–895.
- Riserus U, Vessby B, Amlov J, Basu S. Supplemen-tation with trans10cis12-conjugated linoleic acid induces hyperproinsulinaemia in obese men: close association with impaired insulin sensitivity. Diabetologia 2004; 47: 1016–1019.
- Riserus U, Vesby B, Amer P, Zethelius B. Effects of cis-9, trans-11 conjugated linoleic acid supplemen-tation on insulin sensitivity, lipid peroxidation and proinflammatory markers in obese men. Am J Clin Nutr 2004; 80: 279–283.
- Cesano A, Visonneau S, Scimeca JA, et al. Opposite effects of linoleic acid and conjugated linolenic acid on human prostatic cancer in SCID mice. Anticancer Res 1998; 18 (3A): 1429–1434.
- Thompson H, Zhu Z, Banni S, et al. Morphological and biochemical status of the mammary gland influenced by conjugated linoleic acid: implication for a reduction in mammary cancer risk. Cancer Res 1997: 57: 5067–5072.
- Parodi PW. Cow’s milk fat components as potential carcinogenic agents. J Nutr 1997; 127: 1055–1060.
- Petrik MB, McEntee MF, Johnson BT, et al. Highly unsaturated (n-3) fatty acids, but not alpha linolenic, conjugated linoleic or gamma-linolenic acids, reduce tumourigenesis in Apc(Min/+) mice. J Nutr 2000; 130: 2434–2443.
- Doyle C, Jewell C, Mullen A, et al. Effect of dietary supplementation with conjugated linoleic acid on markers of calcium and bone metabolism in healthy adult men. Eur J Clin Nutr 2005; 59: 432–440.
- Tricon S, Burdge GC, Kew S, et al. Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid on immune cell function in healthy humans. Am J Clin Nutr 2004; 80: 1626–1633.
- Nugent AP, Roche HM, Noone EJ, et al. The effects of conjugated linoleic acid supplementation on immune function in healthy volunteers. Eur J Clin Nutr 2005; 59: 742–750.