Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid with attractive biological activities. Numerous studies have been conducted on the inflammation-lowering effects of CLA in in vitro and animal models. However, the effects of CLA treatment on the inflammatory markers in humans are controversial. Therefore, the objective of this study was to perform a systematic review and meta-analysis on controlled clinical trials (RCT) assessing the effects of CLA supplementation on the circulating inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α).
The literature search of RCTs was performed using Pubmed/Medline, Scopus, ScienceDirect, Web of science, Cochrane, and Google Scholar databases from inception to March 2017. Weighted mean differences were estimated and the pooled effect size was calculated by a random effects model.
Of the 427 identified studies, eleven RCTs, including 420 subjects were included in the statistical analysis. Findings suggested that CLA supplementation increased blood levels of CRP by 0.89 mg/l (95% CI: 0.11, 1.68; P = 0.025) and TNF-α levels by 0.39 pg/ml (95% CI: 0.23, 0.55; P < 0.0001). However, blood IL-6 levels were marginally decreased by 0.32 pg/ml (95% CI: −0.71, 0.07; P = 0.11) following CLA supplementation. There was a significant heterogeneity for the impact of CLA on CRP and IL-6, but not TNF-α.
This meta-analysis showed that CLA supplementation may increase inflammatory markers (CRP and TNF-α). There are concerns about using CLA supplementation as an anti-obesity agent among the obese population for at least a short duration.
Subscribe to Journal
Get full journal access for 1 year
only $41.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Chin S, Liu W, Storkson J, Ha Y, Pariza M. Dietary sources of conjugated dienoic isomers of linoleic acid, a newly recognized class of anticarcinogens. J Food Compos Anal. 1992;5:185–97.
Chin SF, Storkson JM, Liu W, Albright KJ, Pariza MW. Conjugated linoleic acid (9, 11-and 10, 12-octadecadienoic acid) is produced in conventional but not germ-free rats fed linoleic acid. J Nutr. 1994;124:694–701.
Pariza MW. Perspective on the safety and effectiveness of conjugated linoleic acid. Am J Clin Nutr. 2004;79:1132S–6S.
Park Y. Conjugated linoleic acid (CLA): Good or bad trans fat? J Food Compos Anal. 2009;22:S4–S12.
McLeod RS, LeBlanc AM, Langille MA, Mitchell PL, Currie DL. Conjugated linoleic acids, atherosclerosis, and hepatic very-low-density lipoprotein metabolism. Am J Clin Nutr. 2004;79:1169S–74S.
Navarro V, Zabala A, Macarulla M, Fernandez-Quintela A, Rodriguez V, Simon E, et al. Effects of conjugated linoleic acid on body fat accumulation and serum lipids in hamsters fed an atherogenic diet. J Physiol Biochem. 2003;59:193–9.
Noone 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. Br J Nutr. 2002;88:243–51.
Park 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;34:235–41.
West 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. J Nutr. 2000;130:2471–7.
Parodi PW. Conjugated linoleic acid: an anticarcinogenic fatty acid present in milk fat. Aust J Dairy Technol. 1994;49:93–7.
Basu S, Riserus U, Turpeinen A, Vessby B. Conjugated linoleic acid induces lipid peroxidation in men with abdominal obesity. Clin Sci. 2000;99:511–6.
Risérus 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.
Taylor JS, Williams SR, Rhys R, James P, Frenneaux MP. Conjugated linoleic acid impairs endothelial function. Arterioscler, Thromb, Vasc Biol. 2006;26:307–12.
US Department of Agriculture UDoH, Services H. Dietary guidelines for Americans, 2010. Washington, DC: US Government Printing Office; 2010.
Harizi H, Corcuff J-B, Gualde N. Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends Mol Med. 2008;14:461–9.
Mohammadzadeh M, Faramarzi E, Mahdavi R, Nasirimotlagh B, Asghari Jafarabadi M. Effect of conjugated linoleic acid supplementation on inflammatory factors and matrix metalloproteinase enzymes in rectal cancer patients undergoing chemoradiotherapy. Integr Cancer Ther. 2013;12:496–502.
Baghi AN, Mazani M, Nemati A, Amani M, Alamolhoda S, Mogadam RA. Anti-inflammatory effects of conjugated linoleic acid on young athletic males. J Pak Med Assoc. 2016;66:280–4.
Kuhnt K, Kraft J, Vogelsang H, Eder K, Kratzsch J, Jahreis G. Dietary supplementation with trans-11- and trans-12-18: 1 increases cis-9, trans-11-conjugated linoleic acid in human immune cells, but without effects on biomarkers of immune function and inflammation. Br J Nutr. 2007;97:1196–205.
MacRedmond R, Singhera G, Attridge S, Bahzad M, Fava C, Lai Y, et al. Conjugated linoleic acid improves airway hyper‐reactivity in overweight mild asthmatics. Clin Exp Allergy. 2010;40:1071–8.
Mullen A, Moloney F, Nugent AP, Doyle L, Cashman KD, Roche HM. Conjugated linoleic acid supplementation reduces peripheral blood mononuclear cell interleukin-2 production in healthy middle-aged males. J Nutr Biochem. 2007;18:658–66.
Riserus U, Basu S, Jovinge S, Fredrikson GN, Arnlov J, Vessby B. Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein: a potential link to fatty acid-induced insulin resistance. Circulation. 2002;106:1925–9.
Steck 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. J Nutr. 2007;137:1188–93.
Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:13.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.
Egger M, Davey-Smith G, Altman D. Systematic reviews in health care: meta-analysis in context. 2nd ed. (Wiley, London, 2008).
Moloney 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. Am J Clin Nutr. 2004;80:887–95.
Venkatramanan S, Joseph SV, Chouinard PY, Jacques H, Farnworth ER, Jones PJ. Milk enriched with conjugated linoleic acid fails to alter blood lipids or body composition in moderately overweight, borderline hyperlipidemic individuals. J Am Coll Nutr. 2010;29:152–9.
Griel AE, Kris-Etherton PM, Hilpert KF, Zhao G, West SG, Corwin RL. An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans. Nutr J. 2007;6:2.
Turpeinen AM, Ylonen N, von Willebrand E, Basu S, Aro A. Immunological and metabolic effects of cis-9, trans-11-conjugated linoleic acid in subjects with birch pollen allergy. Br J Nutr. 2008;100:112–9.
Zhao G, Etherton TD, Martin KR, Gillies PJ, West SG, Kris-Etherton PM. Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Am J Clin Nutr. 2007;85:385–91.
Tholstrup T, Raff M, Straarup EM, Lund P, Basu S, Bruun JM. An oil mixture with trans-10, cis-12 conjugated linoleic acid increases markers of inflammation and in vivo lipid peroxidation compared with cis-9, trans-11 conjugated linoleic acid in postmenopausal women. J Nutr. 2008;138:1445–51.
Smit LA, Katan MB, Wanders AJ, Basu S, Brouwer IA. A high intake of trans fatty acids has little effect on markers of inflammation and oxidative stress in humans. J Nutr. 2011;141:1673–8.
Olveira G, Olveira C, Acosta E, Espildora F, Garrido-Sanchez L, Garcia-Escobar E, et al. Fatty acid supplements improve respiratory, inflammatory and nutritional parameters in adults with cystic fibrosis. Arch Bronconeumol. 2010;46:70–7.
Liou YA, King DJ, Zibrik D, Innis SM. Decreasing linoleic acid with constant alpha-linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phospholipids in healthy men. J Nutr. 2007;137:945–52.
Dawczynski C, Massey KA, Ness C, Kiehntopf M, Stepanow S, Platzer M, et al. Randomized placebo-controlled intervention with n-3 LC-PUFA-supplemented yoghurt: effects on circulating eicosanoids and cardiovascular risk factors. Clin Nutr. 2013;32:686–96.
Damsgaard CT, Frokiaer H, Andersen AD, Lauritzen L. Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men. J Nutr. 2008;138:1061–6.
Cappa M, Bizzarri C, Petroni A, Carta G, Cordeddu L, Valeriani M, et al. A mixture of oleic, erucic and conjugated linoleic acids modulates cerebrospinal fluid inflammatory markers and improve somatosensorial evoked potential in X-linked adrenoleukodystrophy female carriers. J Inherit Metab Dis. 2012;35:899–907.
Baril-Gravel L, Labonte ME, Couture P, Vohl MC, Charest A, Guay V, et al. Docosahexaenoic acid-enriched canola oil increases adiponectin concentrations: a randomized crossover controlled intervention trial. Nutr Metab Cardiovasc Dis. 2015;25:52–9.
Paschos GK, Zampelas A, Panagiotakos DB, Katsiougiannis S, Griffin BA, Votteas V, et al. Effects of flaxseed oil supplementation on plasma adiponectin levels in dyslipidemic men. Eur J Nutr. 2007;46:315–20.
Bemelmans WJ, Lefrandt JD, Feskens EJ, van Haelst PL, Broer J, Meyboom-de Jong B. et al. Increased alpha-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis. Eur J Clin Nutr. 2004;58:1083–9.
Asp ML, Collene AL, Norris LE, Cole RM, Stout MB, Tang S-Y, et al. Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized, double-masked, crossover study. Clin Nutr. 2011;30:443–9.
Raff M, Tholstrup T, Toubro S, Bruun JM, Lund P, Straarup EM, et al. Conjugated linoleic acids reduce body fat in healthy postmenopausal women. J Nutr. 2009;139:1347–52.
Wallace FA, Miles EA, Calder PC. Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects. Br J Nutr. 2003;89:679–89.
Ulven SM, Leder L, Elind E, Ottestad I, Christensen JJ, Telle-Hansen VH, et al. Exchanging a few commercial, regularly consumed food items with improved fat quality reduces total cholesterol and LDL-cholesterol: a double-blind, randomised controlled trial. Br J Nutr. 2016;116:1383–93.
Nugent AP, Roche HM, Noone EJ, Long A, Kelleher DK, Gibney MJ. The effects of conjugated linoleic acid supplementation on immune function in healthy volunteers. Eur J Clin Nutr. 2005;59:742–50.
Penedo LA, Nunes JC, Gama MA, Leite PE, Quirico-Santos TF, Torres AG. Intake of butter naturally enriched withcis9, trans11 conjugated linoleic acid reduces systemic inflammatory mediators in healthy young adults. J Nutr Biochem. 2013;24:2144–51.
Sofi F, Buccioni A, Cesari F, Gori AM, Minieri S, Mannini L, et al. Effects of a dairy product (pecorino cheese) naturally rich in cis-9, trans-11 conjugated linoleic acid on lipid, inflammatory and haemorheological variables: a dietary intervention study. Nutr Metab Cardiovasc Dis. 2010;20:117–24.
Peterson KM, O’Shea M, Stam W, Mohede IC, Patrie JT, Hayden FG. Effects of dietary supplementation with conjugated linoleic acid on experimental human rhinovirus infection and illness. Antivir Ther. 2009;14:33–43.
Smedman A, Basu S, Jovinge S, Fredrikson GN, Vessby B. Conjugated linoleic acid increased C-reactive protein in human subjects. Br J Nutr. 2005;94:791–5.
Hassan Eftekhari M, Aliasghari F, Babaei-Beigi MA, Hasanzadeh J. Effect of conjugated linoleic acid and omega-3 fatty acid supplementation on inflammatory and oxidative stress markers in atherosclerotic patients. ARYA Atheroscler. 2013;9:311–8.
Aryaeian N, Djalali M, Shahram F, Djazayery A, Eshragian MR. Effect of conjugated linoleic Acid, vitamin e, alone or combined on immunity and inflammatory parameters in adults with active rheumatoid arthritis: a randomized controlled trial. Int J Prev Med. 2014;5:1567–77.
Joseph SV, Jacques H, Plourde M, Mitchell PL, McLeod RS, Jones PJ. Conjugated linoleic acid supplementation for 8 weeks does not affect body composition, lipid profile, or safety biomarkers in overweight, hyperlipidemic men. J Nutr. 2011;141:1286–91.
de Gaetano M, Dempsey E, Marcone S, James WG, Belton O. Conjugated Linoleic Acid Targets β2 Integrin Expression To Suppress Monocyte Adhesion. J Immunol. 2013;191:4326–36.
O’Shea M, Bassaganya-Riera J, Mohede IC. Immunomodulatory properties of conjugated linoleic acid. Am J Clin Nutr. 2004;79:1199S–206S.
Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim H-J, Tange T, Okuyama H, et al. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes. 2000;49:1534–42.
Miller JR, Siripurkpong P, Hawes J, Majdalawieh A, Ro H-S, McLeod RS. The trans-10, cis-12 isomer of conjugated linoleic acid decreases adiponectin assembly by PPARγ-dependent and PPARγ-independent mechanisms. J Lipid Res. 2008;49:550–62.
Brandebourg T, Hu C. Isomer-specific regulation of differentiating pig preadipocytes by conjugated linoleic acids. J Anim Sci. 2005;83:2096–105.
Martinez K, Kennedy A, West T, Milatovic D, Aschner M, McIntosh M. trans-10, cis-12-Conjugated linoleic acid instigates inflammation in human adipocytes compared with preadipocytes. J Biol Chem. 2010;285:17701–12.
Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler, Thromb, Vasc Biol. 2011;31:986–1000.
Arbonés-Mainar JM, Navarro MA, Guzmán MA, Arnal C, Surra JC, Acín S, et al. Selective effect of conjugated linoleic acid isomers on atherosclerotic lesion development in apolipoprotein E knockout mice. Atherosclerosis. 2006;189:318–27.
Zulet M, Marti A, Parra M, Martinez J. Inflammation and conjugated linoleic acid: mechanisms of action and implications for human health. J Physiol Biochem. 2005;61:483–94.
Risérus U, Vessby B, Ärnlöv J, Basu S. Effects of cis-9, trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men. Am J Clin Nutr. 2004;80:279–83.
Basu S. Radioimmunoassay of 15-keto-13, 14-dihydro-prostaglandin F2α: an index for inflammation via cyclooxygenase catalysed lipid peroxidation. Prostaglandins Leukot Essent Fat Acids. 1998;58:347–52.
Moloney F, Toomey S, Noone E, Nugent A, Allan B, Loscher CE, et al. Antidiabetic effects of cis-9, trans-11–conjugated linoleic acid may be mediated via anti-inflammatory effects in white adipose tissue. Diabetes. 2007;56:574–82.
Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci. 2013;110:3507–12.
Lear SA, Chen MM, Birmingham CL, Frohlich JJ. The relationship between simple anthropometric indices and C-reactive protein: ethnic and gender differences. Metabolism. 2003;52:1542–6.
Chen K, Li F, Li J, Cai H, Strom S, Bisello A, et al. Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nat Med. 2006;12:425.
Galletti F, D’Elia L, De Palma D, Russo O, Barba G, Siani A, et al. Hyperleptinemia is associated with hypertension, systemic inflammation and insulin resistance in overweight but not in normal weight men. Nutr, Metab Cardiovasc Dis. 2012;22:300–6.
Escrich E, Moral R, Grau L, Costa I, Solanas M. Molecular mechanisms of the effects of olive oil and other dietary lipids on cancer. Mol Nutr Food Res. 2007;51:1279–92.
Barone R, Macaluso F, Catanese P, Gammazza AM, Rizzuto L, Marozzi P, et al. Endurance exercise and conjugated linoleic acid (CLA) supplementation up-regulate CYP17A1 and stimulate testosterone biosynthesis. PloS ONE. 2013;8:e79686.
Bellido T, Jilka RL, Boyce BF, Girasole G, Broxmeyer H, Dalrymple SA, et al. Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor.J Clin Investig. 1995;95:2886
Maggio M, Basaria S, Ble A, Lauretani F, Bandinelli S, Ceda GP, et al. Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men. J Clin Endocrinol Metab. 2006;91:345–7.
Khosla S, Atkinson EJ, Dunstan CR, O’fallon W. Effect of estrogen versus testosterone on circulating osteoprotegerin and other cytokine levels in normal elderly men. J Clin Endocrinol Metab. 2002;87:1550–4.
Chung HY, Kim HJ, Kim KW, Choi JS, Yu BP. Molecular inflammation hypothesis of aging based on the anti‐aging mechanism of calorie restriction. Microsc Res Tech. 2002;59:264–72.
Iwakiri Y, Sampson D, Allen K. Suppression of cyclooxygenase-2 and inducible nitric oxide synthase expression by conjugated linoleic acid in murine macrophages. Prostaglandins Leukot Essent Fat Acids. 2002;67:435–43.
Viladomiu M, Hontecillas R, Bassaganya-Riera J. Modulation of inflammation and immunity by dietary conjugated linoleic acid. Eur J Pharmacol. 2016;785:87–95.
Mestas J, Hughes CC. Of mice and not men: differences between mouse and human immunology. J Immunol. 2004;172:2731–8.
Larsen TM, Toubro S, Gudmundsen O, Astrup A. Conjugated linoleic acid supplementation for 1 y does not prevent weight or body fat regain. Am J Clin Nutr. 2006;83:606–12.
Chung S, Brown JM, Provo JN, Hopkins R, McIntosh MK. Conjugated linoleic acid promotes human adipocyte insulin resistance through NFκB-dependent cytokine production. J Biol Chem. 2005;280:38445–56.
Basu S, Smedman A, Vessby B. Conjugated linoleic acid induces lipid peroxidation in humans. FEBS Lett. 2000;468:33–6.
Onakpoya IJ, Posadzki PP, Watson LK, Davies LA, Ernst E. The efficacy of long-term conjugated linoleic acid (CLA) supplementation on body composition in overweight and obese individuals: a systematic review and meta-analysis of randomized clinical trials. Eur J Nutr. 2012;51:127–34.
Malpuech‐Brugère C, Verboeket‐van de Venne WP, Mensink RP, Arnal MA, Morio B, Brandolini M, et al. Effects of two conjugated linoleic acid isomers on body fat mass in overweight humans. Obesity. 2004;12:591–8.
BFNMG conceived the study, carried out the literature search and data extraction. FH performed data analysis. BFNMG and FH wrote the manuscript and both authors read and confirmed the final version of manuscript.
This work received no grant from any funding agency in the public, commercial and academic sectors.
Conflict of interest
The authors declare that they have no conflict of interest.
About this article
Cite this article
Haghighatdoost, F., Nobakht M. Gh, B.F. Effect of conjugated linoleic acid on blood inflammatory markers: a systematic review and meta-analysis on randomized controlled trials. Eur J Clin Nutr 72, 1071–1082 (2018). https://doi.org/10.1038/s41430-017-0048-z
High-fat diets are detrimental of the lipid profile, glucose metabolism and body composition of Wistar rats: the role of fatty acid type and consumption duration
Nutrition & Food Science (2020)
Beneficial Effects of a Low-dose of Conjugated Linoleic Acid on Body Weight Gain and other Cardiometabolic Risk Factors in Cafeteria Diet-fed Rats
Frontiers in Nutrition (2020)
Frontiers in Immunology (2019)
International Journal of Molecular Sciences (2019)