Do v-3 PUFAs affect insulin resistance in a sex-specific manner? A systematic review and meta-analysis of randomized controlled trials

American Journal of Clinical Nutrition

Volumn 104, Issue 5, 2016, Pages 1470-1484

  Abbott, Kylie A ^a   Burrows, Tracy L ^b   Thota, Rohith N ^a   Acharya, Shamasunder ^c   Garg, Manohar L ^a  

^a Schools of Biomedical Sciences and Pharmacy   (Australia)

^b UNIVERSITY OF NEWCASTLE   (Australia)

^c JOHN HUNTER HOSPITAL   (Australia)

Author keywords

Adults; DHA; Diabetes; EPA; Insulin resistance; Insulin sensitivity; Omega 3 PUFAs

Indexed keywords

OMEGA 3 FATTY ACID;

ARTICLE; DIET SUPPLEMENTATION; HUMAN; INSULIN RESISTANCE; INSULIN SENSITIVITY; INTERVENTION STUDY; META ANALYSIS; OUTCOME ASSESSMENT; RANDOMIZED CONTROLLED TRIAL (TOPIC); SEX DIFFERENCE; SYSTEMATIC REVIEW (TOPIC); BODY MASS; DIABETES MELLITUS, TYPE 2; DIETARY SUPPLEMENT; FACTUAL DATABASE; FEMALE; MALE; OBESITY;

BODY MASS INDEX; DATABASES, FACTUAL; DIABETES MELLITUS, TYPE 2; DIETARY SUPPLEMENTS; FATTY ACIDS, OMEGA-3; FEMALE; HUMANS; INSULIN RESISTANCE; MALE; OBESITY; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SEX FACTORS;

EID: 84994234498     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.3945/ajcn.116.138172     Document Type: Article

References (70)

1. Westphal SA. Obesity, abdominal obesity, and insulin resistance. Clin Cornerstone 2008;9:23-9; discussion 30-1.
2. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes. Diabetes Care 2004;27:1047-53.
3. World Health Organisation. Global report on diabetes. Geneva (Switzerland): World Health Organisation; 2016.
4. Lamping KG, Nuno DW, Coppey LJ, Holmes AJ, Hu S, Oltman CL, Norris AW, Yorek MA. Modification of high saturated fat diet with n-3 polyunsaturated fat improves glucose intolerance and vascular dysfunction. Diabetes Obes Metab 2013;15:144-52.
5. Flachs P, Rossmeisl M, Kopecky J. The effect of n-3 fatty acids on glucose homeostasis and insulin sensitivity. Physiol Res 2014;63(Suppl 1):S93-118.
6. Jafari T, Fallah AA, Azadbakht L. Role of dietary n-3 polyunsaturated fatty acids in type 2 diabetes: a review of epidemiological and clinical studies. Maturitas 2013;74:303-8.
7. Abbott KA, Veysey M, Lucock M, Niblett S, King K, Burrows T, Garg ML. Sex-dependent association between erythrocyte n-3 PUFA and type 2 diabetes in older overweight people. Br J Nutr 2016;115: 1379-86.
8. Lohner S, Fekete K, Marosvölgyi T, Decsi T. Gender differences in the long-chain polyunsaturated fatty acid status: Systematic review of 51 publications. Ann Nutr Metab 2013;62:98-112.
9. Harris WS, Pottala JV, Varvel SA, Borowski JJ, Ward JN, McConnell JP. Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: observations from 160,000 patients. Prostaglandins Leukot Essent Fatty Acids 2013;88:257-63.
10. Giltay EJ, Gooren LJ, Toorians AW, Katan MB, Zock PL. Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects. Am J Clin Nutr 2004;80:1167-74.
11. Phang M, Sinclair AJ, Lincz LF, Garg ML. Gender-specific inhibition of platelet aggregation following omega-3 fatty acid supplementation. Nutr Metab Cardiovasc Dis 2012;22:109-14.
12. Phang M, Scorgie FE, Seldon M, Garg ML, Lincz LF. Reduction of prothrombin and Factor V levels following supplementation with omega-3 fatty acids is sex dependent: a randomised controlled study. J Nutr Biochem 2014;25:997-1002.
13. Moher D, Liberati A, Tetzlaff J, Altman DG,PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med 2009;6:e1000097.
14. American Dietetic Association. Evidence analysis manual. Chicago: Academy of Nutrition and Dietetics; 2012.
15. Higgins J, Green S, editors. Cochrane Handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collection; 2011. Available from: www.handbook.cochrane.org.
16. Katan MB, Deslypere JP, van Birgelen AP, Penders M, Zegwaard M. Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study. J Lipid Res 1997;38:2012-22.
17. Bloedon LT, Balikai S, Chittams J, Cunnane SC, Berlin JA, Rader DJ, Szapary PO. Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial. J Am Coll Nutr 2008;27:65-74.
18. Brinton EA, Ballantyne CM, Bays HE, Kastelein JJ, Braeckman RA, Soni PN. Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200-500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study. Cardiovasc Diabetol 2013;12:100.
19. Browning LM, Krebs JD, Moore CS, Mishra GD, O'Connell MA, Jebb SA. The impact of long chain n-3 polyunsaturated fatty acid supplementation on inflammation, insulin sensitivity and CVD risk in a group of overweight women with an inflammatory phenotype. Diabetes Obes Metab 2007;9:70-80.
20. Chan DC,Watts GF, Barrett PH, Beilin LJ, Mori TA. Effect of atorvastatin and fish oil on plasma high-sensitivity C-reactive protein concentrations in individuals with visceral obesity. Clin Chem 2002;48:877-83.
21. Crochemore IC, Souza AF, de Souza AC, Rosado EL. v-3 polyunsaturated fatty acid supplementation does not influence body composition, insulin resistance, and lipemia in women with type 2 diabetes and obesity. Nutr Clin Pract 2012;27:553-60.
22. Dasarathy S, Dasarathy J, Khiyami A, Yerian L, Hawkins C, Sargent R, McCullough AJ. Double-blind randomized placebo-controlled clinical trial of omega 3 fatty acids for the treatment of diabetic patients with nonalcoholic steatohepatitis. J Clin Gastroenterol 2015;49:137-44.
23. Derosa G, Cicero AF, Fogari E, D'Angelo A, Bonaventura A, Romano D, Maffioli P. Effects of n-3 PUFAs on postprandial variation of metalloproteinases, and inflammatory and insulin resistance parameters in dyslipidemic patients: evaluation with euglycemic clamp and oral fat load. J Clin Lipidol 2012;6:553-64.
24. Griffin MD, Sanders TA, Davies IG, Morgan LM, Millward DJ, Lewis F, Slaughter S, Cooper JA, Miller GJ, Griffin BA. Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity, lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45-70 y: the OPTILIP Study. Am J Clin Nutr 2006;84:1290-8.
25. Hutchins AM, Brown BD, Cunnane SC, Domitrovich SG, Adams ER, Bobowiec CE. Daily flaxseed consumption improves glycemic control in obese men and women with pre-diabetes: a randomized study. Nutr Res 2013;33:367-75.
26. Kabir M, Skurnik G, Naour N, Pechtner V, Meugnier E, Rome S, Quignard-Boulange A, Vidal H, Slama G, Clement K, et al. Treatment for 2 mo with n 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr 2007;86:1670-9.
27. Kelley DS, Adkins Y, Woodhouse LR, Swislocki A, Mackey BE, Siegel D. Docosahexaenoic acid supplementation improved lipocentric but not glucocentric markers of insulin sensitivity in hypertriglyceridemic men. Metab Syndr Relat Disord 2012;10:32-8.
28. Koh KK, Quon MJ, Shin KC, Lim S, Lee Y, Sakuma I, Lee K, Han SH, Shin EK. Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia. Atherosclerosis 2012;220:537-44.
29. Krysiak R, Gdula-Dymek A, Okopien B. The effect of bezafibrate and omega-3 fatty acids on lymphocyte cytokine release and systemic inflammation in patients with isolated hypertriglyceridemia. Eur J Clin Pharmacol 2011;67:1109-17.
30. Krysiak R, Gdula-Dymek A, Okopien B. Hemostatic effects of bezafibrate and omega-3 fatty acids in isolated hypertriglyceridemic patients. Pharmacol Rep 2011;63:763-71.
31. Lee TC, Ivester P, Hester AG, Sergeant S, Case LD, Morgan T, Kouba EO, Chilton FH. The impact of polyunsaturated fatty acid-based dietary supplements on disease biomarkers in a metabolic syndrome/diabetes population. Lipids Health Dis 2014;13:196.
32. Luo J, Rizkalla SW, Vidal H, Oppert JM, Colas C, Boussairi A, Guerre-Millo M, Chapuis AS, Chevalier A, Durand G, et al. Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study. Diabetes Care 1998;21:717-24.
33. Maki KC, Lawless AL, Kelley KM, Dicklin MR, Schild AL, Rains TM. Prescription omega-3-acid ethyl esters reduce fasting and postprandial triglycerides and modestly reduce pancreatic beta-cell response in subjects with primary hypertriglyceridemia. Prostaglandins Leukot Essent Fatty Acids 2011;85:143-8.
34. Mohammadi E, Rafraf M, Farzadi L, Asghari-Jafarabadi M, Sabour S. Effects of omega-3 fatty acids supplementation on serum adiponectin levels and some metabolic risk factors in women with polycystic ovary syndrome. Asia Pac J Clin Nutr 2012;21:511-8.
35. Mostad IL, Bjerve KS, Bjorgaas MR, Lydersen S, Grill V. Effects of n-3 fatty acids in subjects with type 2 diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation. Am J Clin Nutr 2006;84:540-50. Erratum in: Am J Clin Nutr 2007;85:1668.
36. Navas-Carretero S, Perez-Granados AM, Schoppen S, Vaquero MP. An oily fish diet increases insulin sensitivity compared to a red meat diet in young iron-deficient women. Br J Nutr 2009;102:546-53.
37. Nelson TL, Stevens JR, Hickey MS. Adiponectin levels are reduced, independent of polymorphisms in the adiponectin gene, after supplementation with alpha-linolenic acid among healthy adults. Metabolism 2007;56:1209-15.
38. Pelikánová T, Kohout M, Valek J, Kazdova L, Base J. Metabolic effects of omega-3 fatty acids in type 2 (non-insulin-dependent) diabetic patients. Ann N Y Acad Sci 1993;683:272-8.
39. Rajkumar H, Mahmood N, Kumar M, Varikuti SR, Challa HR, Myakala SP. Effect of probiotic (VSL#3) and omega-3 on lipid profile, insulin sensitivity, inflammatory markers, and gut colonization in overweight adults: a randomized, controlled trial. Mediators Inflamm 2014;2014:348959.
40. Rhee Y, Brunt A. Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: A randomized crossover design. Nutr J 2011;10.
41. Rivellese AA, Maffettone A, Iovine C, Di Marino L, Annuzzi G, Mancini M, Riccardi G. Long-term effects of fish oil on insulin resistance and plasma lipoproteins in NIDDM patients with hypertriglyceridemia. Diabetes Care 1996;19:1207-13.
42. Spencer M, Finlin BS, Unal R, Zhu B, Morris AJ, Shipp LR, Lee J, Walton RG, Adu A, Erfani R, et al. Omega-3 fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance. Diabetes 2013;62:1709-17.
43. Tardivo AP, Nahas-Neto J, Orsatti CL, Dias FB, Poloni PF, Schmitt EB, Nahas EAP. Effects of omega-3 on metabolic markers in postmenopausal women with metabolic syndrome. Climacteric 2015;18: 290-8.
44. Taylor CG, Noto AD, Stringer DM, Froese S, Malcolmson L. Dietary milled flaxseed and flaxseed oil improve N-3 fatty acid status and do not affect glycemic control in individuals with well-controlled type 2 diabetes. J Am Coll Nutr 2010;29:72-80.
45. Toft I, Bonaa KH, Ingebretsen OC, Nordoy A, Jenssen T. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. Ann Intern Med 1995;123:911-8.
46. Woodman RJ, Mori TA, Burke V, Puddey IB, Watts GF, Beilin LJ. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 2002;76:1007-15.
47. Zhang J, Wang C, Li L, Man Q, Meng L, Song P, Frøyland L, Du Z-Y. Dietary inclusion of salmon, herring and pompano as oily fish reduces CVD risk markers in dyslipidaemic middle-aged and elderly Chinese women. Br J Nutr 2012;108:1455-65.
48. Akinkuolie AO, Ngwa JS, Meigs JB, Djousse L. Omega-3 polyunsaturated fatty acid and insulin sensitivity: a meta-analysis of randomized controlled trials. Clin Nutr 2011;30:702-7.
49. Wallin A, Di Giuseppe D, Orsini N, Patel PS, Forouhi NG, Wolk A. Fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes: systematic review and meta-analysis of prospective studies. Diabetes Care 2012;35:918-29.
50. Alsaleh A, Crepostnaia D, Maniou Z, Lewis FJ, Hall WL, Sanders TA, O'Dell SD. team Ms. Adiponectin gene variant interacts with fish oil supplementation to influence serum adiponectin in older individuals. J Nutr 2013;143:1021-7.
51. Titos E, Clària J. Omega-3-derived mediators counteract obesityinduced adipose tissue inflammation. Prostaglandins Other Lipid Mediat 2013;107:77-84.
52. Im DS. Functions of omega-3 fatty acids and FFA4 (GPR120) in macrophages. Eur J Pharmacol 2016;785:36-43.
53. Williams-Bey Y, Boularan C, Vural A, Huang NN, Hwang IY, Shan-Shi C, Kehrl JH. Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting NF-kB activation and enhancing autophagy. PLoS One 2014;9.
54. González-Périz A, Horrillo R, Ferre N, Gronert K, Dong B, Moran-Salvador E, Titos E, Martinez-Clemente M, Lopez-Parra M, Arroyo V, et al. Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J 2009;23:1946-57.
55. Clària J, González-Périz A, Lopez-Vicario C, Rius B, Titos E. New insights into the role of macrophages in adipose tissue inflammation and fatty liver disease: modulation by endogenous omega-3 fatty acidderived lipid mediators. Front Immunol 2011;2:49.
56. Oliver E, McGillicuddy FC, Harford KA, Reynolds CM, Phillips CM, Ferguson JF, Roche HM. Docosahexaenoic acid attenuates macrophage-induced inflammation and improves insulin sensitivity in adipocytes-specific differential effects between LC n-3 PUFA. J Nutr Biochem 2012;23:1192-200.
57. Rodina AV, Severin SE. [The role of adiponectin in the pathogenesis of the metabolic syndrome and approach to therapy] Patol Fiziol Eksp Ter 2013;1:15-26 (in Russian).
58. Grygiel-Ǵorniak B. Peroxisome proliferator-activated receptors and their ligands nutritional and clinical implications-a review. Nutr J 2014;13;17.
59. Belchior T, Paschoal VA, Magdalon J, Chimin P, Farias TM, Chaves-Filho AB, Gorjao R, St.-Pierre P, Miyamoto S, Kang JX, et al. Omega-3 fatty acids protect from diet-induced obesity, glucose intolerance, and adipose tissue inflammation through PPARg-dependent and PPARgindependent actions. Mol Nutr Food Res 2015;59:957-67.
60. Carmina E. Obesity, adipokines and metabolic syndrome in polycystic ovary syndrome. Front Horm Res 2013;40:40-50.
61. González M, del Mar Bibiloni M, Pons A, Llompart I, Tur JA. Inflammatory markers and metabolic syndrome among adolescents. Eur J Clin Nutr 2012;66:1141-5.
62. Fernández-Bergés D, Consuegra-Sanchez L, Penafiel J, Cabrera de Leon A, Vila J, Felix-Redondo FJ, Segura-Fragoso A, Lapetra J, Guembe MJ, Vega T, et al. Metabolic and inflammatory profiles of biomarkers in obesity, metabolic syndrome, and diabetes in a Mediterranean population. DARIOS Inflammatory study. Rev Esp Cardiol (Engl Ed) 2014;67:624-31.
63. von Frankenberg AD, Silva FM, de Almeida JC, Piccoli V, do Nascimento FV, Sost MM, Leitao CB, Remonti LL, Umpierre D, Reis AF, Canani LH, de Azevedo MJ, Gerchman F. Effect of dietary lipids on circulating adiponectin: a systematic review with meta-analysis of randomised controlled trials. Br J Nutr 2014;112:1235-50.
64. Bakewell L, Burdge GC, Calder PC. Polyunsaturated fatty acid concentrations in young men and women consuming their habitual diets. Br J Nutr 2006;96:93-9.
65. Burdge GC, Calder PC. alpha-Linolenic acid metabolism in adult humans: the effects of gender and age on conversion to longer-chain polyunsaturated fatty acids. Eur J Lipid Sci Technol 2005;107:426-39.
66. Damsgaard CT, Harsløf LBS, Andersen AD, Hellgren LI, Michaelsen KF, Lauritzen L. Fish oil supplementation from 9 to 18 months of age affects the insulin-like growth factor axis in a sex-specific manner in Danish infants. Br J Nutr 2016;115:782-90.
67. Palmer BF, Clegg DJ. The sexual dimorphism of obesity. Mol Cell Endocrinol 2015;402:113-9.
68. Samaras K, Botelho NK, Chisholm DJ, Lord RV. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity (Silver Spring) 2010;18:884-9.
69. Sedlmeier EM, Brunner S, Much D, Pagel P, Ulbrich SE, Meyer HH, Amann-Gassner U, Hauner H, Bader BL. Human placental transcriptome shows sexually dimorphic gene expression and responsiveness to maternal dietary n-3 long-chain polyunsaturated fatty acid intervention during pregnancy. BMC Genomics 2014;15:941.
70. Hartweg J, Perera R, Montori V, Dinneen S, Neil HA, Farmer A. Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus. Cochrane Database Syst Rev 2008; (1):CD003205.