Abstract
In rheumatoid arthris s various pro-inflammatory metabolites of arachidonic acid (AA), such as leukotriene B4 (LTB4) and prostaglandin E2 (PGE2), contribute to tissue destruction and pain. In contrast to AA, which is an omega-6 fatty acid, the omega-3 fatty acids, after having been liberated from the cell membrane phospholipids, are further converted into the non-or anti-inflammatory eicosanoids LTB5 and PGI3. AA concentration is an important regulatory step in the synthesis of both prostanoids and leukotriens. Dietary supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has therefore been used to decrease the ratio of AA to EPA or DHA to obtain beneficial clinical effects. EPA and DHA are found in animal fat and are quite expensive compared to their precursor alpha-linolenic acid (alpha-LNA) found in flaxseed oil. We, therefore, performed a placebocontrolled trial with alpha-LNA in 22 patients with rheumatoid arthritis, using a linoleic acid preparation as a placebo. After a 3-month follow-up, the treatment group showed an increased bleeding time, but the clinical, subjective (global assessment, classification of functional status, joint score index, visual analogue scale, pain tendereness score) and laboratory parameters (haemoglobin, erythrocyte sedimentation rate, C-reactive protein) did not show any statistical alterations. AA, EPA and DHA did not change either in spite of a significant increase in alpha-LNA in the treatment group. Thus, 3-month's supplementation with alpha-LNA did not prove to be beneficial in rheumatoid arthritis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Lewis RA (1989) Prostaglandins and leukotriens. In: Kelly WN, Harris ED Jr, Ruddy S, Sledge CB (eds) Textbook of rheumatology. Saunders, Philadelphia, pp 253–265
Ford-Hutchinson AW, Bray MA, Doig MV, Shipley ME, Smith MJH (1980) Leukotriene B4, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature 286:264–265
Borgeat P, Nadeau M, Salari H, Poubelle B, Fruteau de Laclos B (1985) Leukotrienes: biosynthesis, metabolism, and analysis. Adv Lipid Res 21:47–77
Lee TH, Hoover RL, Williams JD (1985) Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 19:1217–1224
Sperling RI, Weinblatt M, Robin J-L, Ravalese J, Hoover RL, House F, Coblyn JS, Fraser PA, Spur BW, Robinson DR, Lewis RA, Austen KF (1987) Effects of dietary supplementation with marine fish oil on leukocyte lipid mediator generation and function in rheumatoid arthritis. Arthritis Rheum 30:988–997
Kremer JM, Jubiz W, Michalek A, Rynes R, Bartholomew LE, Bigaoulette J, Timchalk M, Beeler D, Lininger (1987) Fish oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, cross-over study. Ann Intern Med 106:497–502
Leaf A, Weber PC (1988) Cardiovascular effects of n-3 fatty acids. N Engl J Med 318:549–557
Belch JJF, Ansell D, Madhok R, O'Dowd A, Sturrock RD (1988) Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study. Ann Rheum Dis 47:96–104
McCarthy G, Kenny D (1992) Dietary fish oil and rheumatic disease. Semin Arthritis Rheum 21:368–375
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA Jr, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324
Honkanen V, Lamberg-Allardt C, Letho J, Vesterinen M, Mussalo-Rauhamaa H, Metsä-Ketelä T, Westermarck T, Konttinen YT (1991) Plasma trace element levels in rheumatoid arthritis, the influence of dietary factors and disease activity. Am J Clin Nutr 54:1082–1086
Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolfe F (1992) The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum 35:498–502
Kaarela K (1985) Prognostic factors and diagnostic criteria in early rheumatoid arthritis (thesis). Scand J Rheumatol [Suppl] 57:1–54
Huskisson EC (1974) Measurement of pain. Lancet II:1127–1131
Yunus MB (1983) Fibromyalgia syndrome; a need for uniform classification. J Rheumatol 10:841–844
Konttinen YT, Honkanen V, Grönblad M, Keinonen M, Santavirta N, Santavirta S (1992) The relation of extra-articular tenderness to inflammatory joint disease and personality in patients with rheumatoid arthritis. J Rheumatol 19:851–855
Renaud S, Nordoy A (1983) Small is beautiful: alpha-linolenic acid and eicosapenaenoic acid in man. Lancet II:1169
Lorgelir de M, Renaud S, Mamelle N, Salen P, Martin J-L, Monjaud I, Guidollet J, Touboul P, Delaye J (1994) Mediterranean alpha-linolenic acid-rich diet in secondary prevention in coronary heart disease. Lancet II:1454–1459
Taiwo YO, Levine JD (1988) Characterization of arachidonic acid metabolites mediating bradykinin and noradrenalin hyperalgesia. Brain Res 458:402–406
Konttinen YT, Sorsa T, Santavirta S, Russel A (1994) Via dolorosa: from the first to the second station. J Rheumatol 21:783–787
Meydani SN, Dinarello CA (1993) Influence of dietary fatty acids on cytokine production and its clinical implications. Nutr Clin Pract 8:65–72
Fairburn K, Grootveld M, Ward RJ, Abiuka C, Kus M, Williams RB, Winyard PG, Blake DR (1992) Alpha-tocopherol, lipids and lipoproteins in knee-joint synovial fluid and serum from patients with inflammatory joint disease. Clin Sci 83:657–664
Adam O, Wolfram G, Zöllner N (1986) Effect of alpha-linolenic acid in the human diet on linolenic acid metabolism and prostaglandin biosynthesis. J Lipid Res 27:421–426
Belch J (1988) The effects of altering dietary essential fatty acid on requirement for nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis. Ann Rheum Dis 47:96–104
Leventhal LJ, Boyce EG, Zurier RB (1993) Treatment of rheumatoid arthritis with gammalinolenic acid. Ann Intern Med 119:867–873
Cunnane SC (1988) Role of zinc in lipid fatty acid metabolism and in membranes. Prog Nutr Sci 12:151–188
Cunnane SC, Yang J, Chen Z-Y (1993) Low zinc intake increases apparent oxidation of linoleic and alpha-linoleic acids in the pregnant rat. Can J Physiol Pharmacol 71:205–210
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nordström, D.C.E., Friman, C., Konttinen, Y.T. et al. Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed. Rheumatol Int 14, 231–234 (1995). https://doi.org/10.1007/BF00262088
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00262088