Circulation. 2002;106:1925-1929
Published online before print September 23, 2002, doi: 10.1161/01.CIR.0000033589.15413.48
Published online before print September 23, 2002, doi: 10.1161/01.CIR.0000033589.15413.48
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:1925.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Supplementation With Conjugated Linoleic Acid Causes Isomer-Dependent Oxidative Stress and Elevated C-Reactive Protein
A Potential Link to Fatty Acid-Induced Insulin Resistance
From the Department of Public Health and Caring Sciences/Geriatrics, Uppsala University (U.R., S.B., J.Ä., B.V.), Uppsala, Sweden, and the Department of Cardiology/Medicine, University Hospital MAS, Lund University (S.J., G.N.F.), Lund, Sweden.
Correspondence to Ulf Risérus, MMed, Clinical Nutrition Research Unit, Department of Public Health and Caring Sciences/Geriatrics, Box 609, 75125 Uppsala, Sweden. E-mail ulf.riserus{at}pubcare.uu.se
Background— Conjugated linoleic acids (CLAs), a group of fatty acids shown to have beneficial effects in animals, are also used as weight loss supplements. Recently, we reported that the t10c12 CLA-isomer caused insulin resistance in abdominally obese men via unknown mechanisms. The aim of the present study was to examine whether CLA has isomer-specific effects on oxidative stress or inflammatory biomarkers and to investigate the relationship between these factors and induced insulin resistance.
Methods and Results— In a double-blind placebo-controlled trial, 60 men with metabolic syndrome were randomized to one of 3 groups receiving t10c12 CLA, a CLA mixture, or placebo for 12 weeks. Insulin sensitivity (euglycemic clamp), serum lipids, in vivo lipid peroxidation (determined as urinary 8-iso-PGF2
[F2-isoprostanes]), 15-ketodihydro PGF2, plasma vitamin E, plasma C-reactive protein, tumor necrosis factor-, and interleukin-6 were assessed before and after treatment. Supplementation with t10c12 CLA markedly increased 8-iso-PGF2 (578%) and C-reactive protein (110%) compared with placebo (P<0.0001 and P<0.01, respectively) and independent of changes in hyperglycemia or dyslipidemia. The increases in 8-iso-PGF2, but not in C-reactive protein, were significantly and independently related to aggravated insulin resistance. Oxidative stress was related to increased vitamin E levels, suggesting a compensatory mechanism.
Conclusions— t10c12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men. The oxidative stress seems closely related to induced insulin resistance, suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance. These unfavorable effects of t10c12 CLA might be of clinical importance with regard to cardiovascular disease, in consideration of the widespread use of dietary supplements containing this fatty acid.
Key Words: fatty acids • inflammation • free radicals • insulin • syndrome x
This article has been cited by other articles:
 |
|
 |
|
  M. Raff, T. Tholstrup, S. Basu, P. Nonboe, M. T. Sorensen, and E. M. Straarup A Diet Rich in Conjugated Linoleic Acid and Butter Increases Lipid Peroxidation but Does Not Affect Atherosclerotic, Inflammatory, or Diabetic Risk Markers in Healthy Young Men J. Nutr., March 1, 2008; 138(3): 509 - 514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Chavarro, M. J. Stampfer, H. Campos, T. Kurth, W. C. Willett, and J. Ma A Prospective Study of Trans-Fatty Acid Levels in Blood and Risk of Prostate Cancer Cancer Epidemiol. Biomarkers Prev., January 1, 2008; 17(1): 95 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Ip, S. O. McGee, P. A. Masso-Welch, C. Ip, X. Meng, L. Ou, and S. F. Shoemaker The t10,c12 isomer of conjugated linoleic acid stimulates mammary tumorigenesis in transgenic mice over-expressing erbB2 in the mammary epithelium Carcinogenesis, June 1, 2007; 28(6): 1269 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Andersson, S. Tengblad, B. Karlstrom, A. Kamal-Eldin, R. Landberg, S. Basu, P. Aman, and B. Vessby Whole-Grain Foods Do Not Affect Insulin Sensitivity or Markers of Lipid Peroxidation and Inflammation in Healthy, Moderately Overweight Subjects J. Nutr., June 1, 2007; 137(6): 1401 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D Whigham, A. C Watras, and D. A Schoeller Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans Am. J. Clinical Nutrition, May 1, 2007; 85(5): 1203 - 1211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Steck, A. M. Chalecki, P. Miller, J. Conway, G. L. Austin, J. W. Hardin, C. D. Albright, and P. Thuillier Conjugated Linoleic Acid Supplementation for Twelve Weeks Increases Lean Body Mass in Obese Humans J. Nutr., May 1, 2007; 137(5): 1188 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Moloney, S. Toomey, E. Noone, A. Nugent, B. Allan, C. E. Loscher, and H. M. Roche Antidiabetic Effects of cis-9, trans-11-Conjugated Linoleic Acid May Be Mediated via Anti-Inflammatory Effects in White Adipose Tissue Diabetes, March 1, 2007; 56(3): 574 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Ignarro, M. L. Balestrieri, and C. Napoli Nutrition, physical activity, and cardiovascular disease: An update Cardiovasc Res, January 15, 2007; 73(2): 326 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kuhnt, A. Wagner, J. Kraft, S. Basu, and G. Jahreis Dietary supplementation with 11trans- and 12trans-18:1 and oxidative stress in humans. Am. J. Clinical Nutrition, November 1, 2006; 84(5): 981 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Badinga and E. S. Greene Physiological Properties of Conjugated Linoleic Acid and Implications for Human Health Nutr Clin Pract, August 1, 2006; 21(4): 367 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Basu, S. Devaraj, and I. Jialal Dietary Factors That Promote or Retard Inflammation Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 995 - 1001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tholstrup, M. Raff, S. Basu, P. Nonboe, K. Sejrsen, and E. M Straarup Effects of butter high in ruminant trans and monounsaturated fatty acids on lipoproteins, incorporation of fatty acids into lipid classes, plasma C-reactive protein, oxidative stress, hemostatic variables, and insulin in healthy young men Am. J. Clinical Nutrition, February 1, 2006; 83(2): 237 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S.W. Taylor, S. R.P. Williams, R. Rhys, P. James, and M. P. Frenneaux Conjugated Linoleic Acid Impairs Endothelial Function Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 307 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M Steffen, C. H Kroenke, X. Yu, M. A Pereira, M. L Slattery, L. Van Horn, M. D Gross, and D. R Jacobs Jr Associations of plant food, dairy product, and meat intakes with 15-y incidence of elevated blood pressure in young black and white adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study Am. J. Clinical Nutrition, December 1, 2005; 82(6): 1169 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C Larsson, L. Bergkvist, and A. Wolk High-fat dairy food and conjugated linoleic acid intakes in relation to colorectal cancer incidence in the Swedish Mammography Cohort Am. J. Clinical Nutrition, October 1, 2005; 82(4): 894 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Desroches, P Y. Chouinard, I. Galibois, L. Corneau, J. Delisle, B. Lamarche, P. Couture, and N. Bergeron Lack of effect of dietary conjugated linoleic acids naturally incorporated into butter on the lipid profile and body composition of overweight and obese men Am. J. Clinical Nutrition, August 1, 2005; 82(2): 309 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Valeille, J. Ferezou, G. Amsler, A. Quignard-Boulange, M. Parquet, D. Gripois, V. Dorovska-Taran, and J.-C. Martin A cis-9,trans-11-conjugated linoleic acid-rich oil reduces the outcome of atherogenic process in hyperlipidemic hamster Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H652 - H659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Castaneda-Gutierrez, T. R. Overton, W. R. Butler, and D. E. Bauman Dietary Supplements of Two Doses of Calcium Salts of Conjugated Linoleic Acid During the Transition Period and Early Lactation J Dairy Sci, March 1, 2005; 88(3): 1078 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tricon, G. C Burdge, S. Kew, T. Banerjee, J. J Russell, R. F Grimble, C. M Williams, P. C Calder, and P. Yaqoob Effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid on immune cell function in healthy humans Am. J. Clinical Nutrition, December 1, 2004; 80(6): 1626 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A Armitage, I. Y Khan, P. D Taylor, P. W Nathanielsz, and L. Poston Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J. Physiol., December 1, 2004; 561(2): 355 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Daskalopoulou, D. P. Mikhailidis, and M. Elisaf Prevention and Treatment of the Metabolic Syndrome Angiology, November 1, 2004; 55(6): 589 - 612. [Abstract] [PDF]
|
|
|
|
|
|
F. Moloney, T.-P. Yeow, A. Mullen, J. J Nolan, and H. M Roche Conjugated linoleic acid supplementation, insulin sensitivity, and lipoprotein metabolism in patients with type 2 diabetes mellitus Am. J. Clinical Nutrition, October 1, 2004; 80(4): 887 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Riserus, B. Vessby, J. Arnlov, and S. Basu Effects of cis-9,trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men Am. J. Clinical Nutrition, August 1, 2004; 80(2): 279 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Brown, M. S. Boysen, S. Chung, O. Fabiyi, R. F. Morrison, S. Mandrup, and M. K. McIntosh Conjugated Linoleic Acid Induces Human Adipocyte Delipidation: AUTOCRINE/PARACRINE REGULATION OF MEK/ERK SIGNALING BY ADIPOCYTOKINES J. Biol. Chem., June 18, 2004; 279(25): 26735 - 26747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Gaullier, J. Halse, K. Hoye, K. Kristiansen, H. Fagertun, H. Vik, and O. Gudmundsen Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans Am. J. Clinical Nutrition, June 1, 2004; 79(6): 1118 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W Pariza Perspective on the safety and effectiveness of conjugated linoleic acid Am. J. Clinical Nutrition, June 1, 2004; 79(6): 1132S - 1136S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Riserus, A. Smedman, S. Basu, and B. Vessby Metabolic effects of conjugated linoleic acid in humans: the Swedish experience Am. J. Clinical Nutrition, June 1, 2004; 79(6): 1146S - 1148S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lamarche and S. Desroches Metabolic syndrome and effects of conjugated linoleic acid in obesity and lipoprotein disorders: the Quebec experience Am. J. Clinical Nutrition, June 1, 2004; 79(6): 1149S - 1152S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G Taylor and P. Zahradka Dietary conjugated linoleic acid and insulin sensitivity and resistance in rodent models Am. J. Clinical Nutrition, June 1, 2004; 79(6): 1164S - 1168S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A Watkins, Y. Li, H. E Lippman, S. Reinwald, and M. F Seifert A test of Ockham's razor: implications of conjugated linoleic acid in bone biology Am. J. Clinical Nutrition, June 1, 2004; 79(6): 1175S - 1185S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Arnlov, B. Vessby, and U. Riserus Coffee Consumption and Insulin Sensitivity JAMA, March 10, 2004; 291(10): 1199 - 1201. [Full Text] [PDF]
|
|
|
|
 |
|
 C. B. Hauswirth, M. R.L. Scheeder, and J. H. Beer High {omega}-3 Fatty Acid Content in Alpine Cheese: The Basis for an Alpine Paradox Circulation, January 6, 2004; 109(1): 103 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Larsen, S. Toubro, and A. Astrup Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies J. Lipid Res., December 1, 2003; 44(12): 2234 - 2241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Corl, D. M. Barbano, D. E. Bauman, and C. Ip cis-9, trans-11 CLA Derived Endogenously from trans-11 18:1 Reduces Cancer Risk in Rats J. Nutr., September 1, 2003; 133(9): 2893 - 2900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. O. McCarthy Rethinking Nutritional Support for Persons with Cancer Cachexia Biol Res Nurs, July 1, 2003; 5(1): 3 - 17. [Abstract] [PDF]
|
|
|
|
|
|
J. M. Brown, M. S. Boysen, S. S. Jensen, R. F. Morrison, J. Storkson, R. Lea-Currie, M. Pariza, S. Mandrup, and M. K. McIntosh Isomer-specific regulation of metabolism and PPAR{gamma} signaling by CLA in human preadipocytes J. Lipid Res., July 1, 2003; 44(7): 1287 - 1300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Henriksen, M. K. Teachey, Z. C. Taylor, S. Jacob, A. Ptock, K. Kramer, and O. Hasselwander Isomer-specific actions of conjugated linoleic acid on muscle glucose transport in the obese Zucker rat Am J Physiol Endocrinol Metab, July 1, 2003; 285(1): E98 - E105. [Abstract] [Full Text] [PDF]
|
|