Advertisement

Rheumatology International

, Volume 14, Issue 6, pp 231–234 | Cite as

Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed

  • D. C. E. Nordström
  • C. Friman
  • Y. T. Konttinen
  • V. E. A. Honkanen
  • Y. Nasu
  • E. Antila
Original Article

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.

Key words

Dietary intervention Alpha-linolenic acid Rheumatoid arthritis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lewis RA (1989) Prostaglandins and leukotriens. In: Kelly WN, Harris ED Jr, Ruddy S, Sledge CB (eds) Textbook of rheumatology. Saunders, Philadelphia, pp 253–265Google Scholar
  2. 2.
    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 286:264–265Google Scholar
  3. 3.
    Borgeat P, Nadeau M, Salari H, Poubelle B, Fruteau de Laclos B (1985) Leukotrienes: biosynthesis, metabolism, and analysis. Adv Lipid Res 21:47–77Google Scholar
  4. 4.
    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 19:1217–1224Google Scholar
  5. 5.
    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 30:988–997Google Scholar
  6. 6.
    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 106:497–502Google Scholar
  7. 7.
    Leaf A, Weber PC (1988) Cardiovascular effects of n-3 fatty acids. N Engl J Med 318:549–557Google Scholar
  8. 8.
    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 47:96–104Google Scholar
  9. 9.
    McCarthy G, Kenny D (1992) Dietary fish oil and rheumatic disease. Semin Arthritis Rheum 21:368–375Google Scholar
  10. 10.
    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 31:315–324Google Scholar
  11. 11.
    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 54:1082–1086Google Scholar
  12. 12.
    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 35:498–502Google Scholar
  13. 13.
    Kaarela K (1985) Prognostic factors and diagnostic criteria in early rheumatoid arthritis (thesis). Scand J Rheumatol [Suppl] 57:1–54Google Scholar
  14. 14.
    Huskisson EC (1974) Measurement of pain. Lancet II:1127–1131Google Scholar
  15. 15.
    Yunus MB (1983) Fibromyalgia syndrome; a need for uniform classification. J Rheumatol 10:841–844Google Scholar
  16. 16.
    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 19:851–855Google Scholar
  17. 17.
    Renaud S, Nordoy A (1983) Small is beautiful: alpha-linolenic acid and eicosapenaenoic acid in man. Lancet II:1169Google Scholar
  18. 18.
    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:1454–1459Google Scholar
  19. 19.
    Taiwo YO, Levine JD (1988) Characterization of arachidonic acid metabolites mediating bradykinin and noradrenalin hyperalgesia. Brain Res 458:402–406Google Scholar
  20. 20.
    Konttinen YT, Sorsa T, Santavirta S, Russel A (1994) Via dolorosa: from the first to the second station. J Rheumatol 21:783–787Google Scholar
  21. 21.
    Meydani SN, Dinarello CA (1993) Influence of dietary fatty acids on cytokine production and its clinical implications. Nutr Clin Pract 8:65–72Google Scholar
  22. 22.
    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 83:657–664Google Scholar
  23. 23.
    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 27:421–426Google Scholar
  24. 24.
    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 47:96–104Google Scholar
  25. 25.
    Leventhal LJ, Boyce EG, Zurier RB (1993) Treatment of rheumatoid arthritis with gammalinolenic acid. Ann Intern Med 119:867–873Google Scholar
  26. 26.
    Cunnane SC (1988) Role of zinc in lipid fatty acid metabolism and in membranes. Prog Nutr Sci 12:151–188Google Scholar
  27. 27.
    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 71:205–210Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • D. C. E. Nordström
    • 1
    • 2
  • C. Friman
    • 1
  • Y. T. Konttinen
    • 1
  • V. E. A. Honkanen
    • 2
  • Y. Nasu
    • 2
  • E. Antila
    • 2
  1. 1.Fourth Department of Medicine, Division of RheumatologyHelsinki University Central HospitalFinland
  2. 2.Musculoskeletal Diseases and Inflammation Research Group, Institute of Biomedicine, Department of AnatomyUniversity of HelsinkiFinland

Personalised recommendations