Background: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases that result in chronic inflammation of the joints. n-3 polyunsaturated fatty acids (PUFAs) have been suggested to play a role in the pathogenesis and clinical course of RA. The purpose of the present study was to investigate whether erythrocyte levels of n-3 PUFA are associated with an increased risk of RA and whether this could potentially serve as an indicator of RA disease activity in Korean women. Methods: A total of 100 female RA patients and 100 healthy women were enrolled into this study. Erythrocyte fatty acid composition and RA disease activity were evaluated in all patients. Results: Erythrocyte levels of α-linolenic acid (ALA; 18:3n3), eicosapentaenoic acid (EPA; 20:5n3), and the omega-3 index [EPA + docosahexaenoic acid (DHA)] were significantly lower in RA patients than in healthy controls. Multivariable-adjusted regression analysis showed that the levels of ALA, EPA, and the ratio of EPA to arachidonic acid were negatively associated with the risk of RA after adjusting for body weight and smoking status. Additionally, the concentration of prostaglandin E2 was significantly decreased with increased levels of erythrocyte DHA among RA patients. Conclusions: Erythrocyte levels of EPA and ALA were negatively associated with the risk of RA in Korean women, which may be related to eicosanoid metabolism.

Keywords:
Eicosanoids, Erythrocyte, Korean women, n–3 polyunsaturated fatty acids, Rheumatoid arthritis
1.
Firestein GS: Evolving concepts of rheumatoid arthritis. Nature 2003;423:356-361.
2.
Lesuis N, Befrits R, Nyberg F, van Vollenhoven RF: Gender and the treatment of immune-mediated chronic inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease and psoriasis: an observational study. BMC Med 2012;10:82.
3.
Goto M: Inflammaging (inflammation + aging): a driving force for human aging based on an evolutionarily antagonistic pleiotropy theory? Biosci Trends 2008;2:218-230.
4.
Stavropoulos-Kalinoglou A, Metsios GS, Koutedakis Y, Kitas GD: Obesity in rheumatoid arthritis. Rheumatology (Oxford) 2011;50:450-462.
5.
Cleland LG, Hill CL, James MJ: Diet and arthritis. Baillieres Clin Rheumatol 1995;9:771-785.
6.
Simopoulos AP: Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr 1991;54:438-463.
7.
Sperling RI: Dietary omega-3 fatty acids: effects on lipid mediators of inflammation and rheumatoid arthritis. Rheum Dis Clin North Am 1991;17:373-389.
8.
Kromann N, Green A: Epidemiological studies in the Upernavik district, Greenland: incidence of some chronic diseases 1950-1974. Acta Med Scand 1980;208:401-406.
9.
Miles EA, Calder PC: Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis. Br J Nutr 2012;107:S171-S184.
10.
Adam O, Beringer C, Kless T, Lemmen C, Adam A, Wiseman M, Adam P, Klimmek R, Forth W: Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int 2003;23:27-36.
11.
Kremer JM, Jubiz W, Michalek A, Rynes RI, Bartholomew LE, Bigaouette J, Timchalk M, Beeler D, Lininger L: Fish-oil fatty acid supplementation in active rheumatoid arthritis: a double-blinded, controlled, crossover study. Ann Intern Med 1987;106:497-503.
12.
van der Temple H, Tulleken JE, Limburg PC, Muskiet FA, van Rijswijk MH: Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis 1990;49:76-80.
13.
Kremer JM, Lawrence DA, Jubiz W, DiGiacomo R, Rynes R, Bartholomew LE, Sherman M: Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis: clinical and immunologic effects. Arthritis Rheum 1990;33:810-820.
14.
Sköldstam L, Börjesson O, Kjällman A, Seiving B, Akesson B: Effect of six months of fish oil supplementation in stable rheumatoid arthritis: a double blind, controlled study. Scand J Rheumatol 1992;21:178-185.
15.
Nielsen GL, Faarvang KL, Thomsen BS, Teglbjaerg KL, Jensen LT, Hansen TM, Lervang HH, Schmidt EB, Dyerberg J, Ernst E: The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial. Eur J Clin Invest 1992;22:687-691.
16.
Geusens P, Wouters C, Nijs J, Jiang Y, Dequeker J: Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis: a 12-month, double blind, controlled study. Arthritis Rheum 1994;37:824-829.
17.
Volker D, Fitzgerald P, Major G, Garg M: Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. J Rheumatol 2000;27:2343-2346.
18.
Górska A, Nawrocki A, Urban M, Florys B: Composition of phospholipid fatty acids in erythrocyte membranes of children with chronic juvenile arthritis: clinical and biochemical correlations. Med Sci Monit 2000;6:30-39.
19.
Jacobsson L, Lindgärde F, Manthorpe R, Akesson B: Correlation of fatty acid composition of adipose tissue lipids and serum phosphatidylcholine and serum concentrations of micronutrients with disease duration in rheumatoid arthritis. Ann Rheum Dis 1990;49:901-905.
20.
Nogi A, Yang J, Li L, Yamasaki M, Watanabe M, Hashimoto M, Shiwaku K: Plasma n-3 polyunsaturated fatty acid and cardiovascular disease risk factors in Japanese, Korean and Mongolian workers. J Occup Health 2007;49:205-216.
21.
Moon HJ, Kim TH, Byun DW, Park Y: Positive correlation between erythrocyte levels of n-3 polyunsaturated fatty acids and bone mass in postmenopausal Korean women with osteoporosis. Ann Nutr Metab 2012;60:146-153.
22.
Korea Institute for Health and Social Affairs, Korean Ministry of Health and Welfare: Korean National Health and Nutrition Examination Survey, report on 2007. Seoul, Korean Ministry of Health and Welfare, 2009.
23.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovský J, Wolfe F, Hawker G: 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569-2581.
24.
Bae SC, Cook EF, Kim SY: Psychometric evaluation of a Korean Health Assessment Questionnaire for clinical research. J Rheumatol 1998;25:1975-1979.
25.
Pottala JV, Espeland MA, Polreis J, Robinson J, Harris WS: Correcting the effects of -20°C storage and aliquot size on erythrocyte fatty acid content in the Women's Health Initiative. Lipids 2012;47:835-846.
26.
Shapiro JA, Koepsell TD, Voigt LF, Dugowson CE, Kestin M, Nelson JL: Diet and rheumatoid arthritis in women: a possible protective effect of fish consumption. Epidemiology 1996;7:256-263.
27.
Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ: The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 1996;63:116-122.
28.
Bruderlein H, Daniel R, Boismenu D, Julien N, Couture F: Fatty acid profiles of serum phospholipids in patients suffering rheumatoid arthritis. Prog Lipid Res 1981;20:625-631.
29.
Prior P, Symmons DP, Scott DL, Brown R, Hawkins CF: Cause of death in rheumatoid arthritis. Br J Rheumatol 1984;23:92-99.
30.
Zhao G, Etherton TD, Martin KR, Vanden Heuvel JP, Gillies PJ, West SG, Kris-Etherton PM: Anti-inflammatory effects of polyunsaturated fatty acids in THP-1 cells. Biochem Biophys Res Commun 2005;336:909-917.
31.
Gu Y, Lu C, Zha Q, Kong H, Lu X, Lu A, Xu G: Plasma metabonomics study of rheumatoid arthritis and its Chinese medicine subtypes by using liquid chromatography and gas chromatography coupled with mass spectrometry. Mol Biosyst 2012;8:1535-1543.
32.
Kennedy A, Martinez K, Chuang CC, LaPoint K, McIntosh M: Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications. J Nutr 2009;139:1-4.
33.
Hayashi H, Satoi K, Sato-Mito N, Kaburagi T, Yoshino H, Higaki M, Nishimoto K, Sato K: Nutritional status in relation to adipokines and oxidative stress is associated with disease activity in patients with rheumatoid arthritis. Nutrition 2012;28:1109-1114.
34.
Bendsen NT, Stender S, Szecsi PB, Pedersen SB, Basu S, Hellgren LI, Newman JW, Larsen TM, Haugaard SB, Astrup A: Effect of industrially produced trans fat on markers of systemic inflammation: evidence from a randomized trial in women. J Lipid Res 2011;52:1821-1828.
35.
Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N, Stampfer MJ, Willett WC, Hu FB: Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction. J Nutr 2005;135:562-566.
36.
Okuda Y, Yamada T, Matsuura M, Takasugi K, Goto M: Ageing: a risk factor for amyloid A amyloidosis in rheumatoid arthritis. Amyloid 2011;18:108-111.
37.
Giles JT, Ling SM, Ferrucci L, Bartlett SJ, Andersen RE, Towns M, Muller D, Fontaine KR, Bathon JM: Abnormal body composition phenotypes in older rheumatoid arthritis patients: association with disease characteristics and pharmacotherapies. Arthritis Rheum 2008;59:807-815.
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