Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Nutrient supplementation with polyunsaturated fatty acids and micronutrients in rheumatoid arthritis: clinical and biochemical effects

European Journal of Clinical Nutrition volume 58, pages 839–845 (2004)Cite this article

Abstract

Objective: To investigate in a double-blind placebo-controlled, parallel group study, the effects of a nutrient supplement, containing, among other ingredients, the omega-3 fatty acids eicosapentaenoic acid (1.4 g EPA), docosahexaenoic acid (0.211 g DHA), omega-6 fatty acid gamma-linolenic acid (0.5 g GLA) and micronutrients in patients with active rheumatoid arthritis (RA).

Design, subjects and intervention: RA patients were randomized to receive either daily liquid nutrient supplementation or placebo for 4 months. The primary end point was the change in tender joint count at 2 and 4 months. Other clinical variables included swollen joint count, visual analogue scales for pain and disease activity, grip strength, functionality score and morning stiffness. Biochemical parameters included plasma concentrations of PUFA and vitamins C and E.

Setting: Outpatient university clinic.

Results: In all, 66 patients enrolled, 55 completed the study. No significant change from baseline in tender joint count or any of the other clinical parameters was detected in either group. Patients receiving nutrient supplementation, but not those receiving placebo, had significant increases in plasma concentrations of vitamin E (P=0.015), and EPA, DHA and docosapentaenoic acid concomitant with decreases of arachidonic acid (P=0.01). Intergroup differences for PUFA and vitamin E were significantly different (P=0.01 and 0.03, respectively).

Conclusions: This double-blind, placebo-controlled study in RA patients did not show superior clinical benefit of daily nutrient supplementation with EPA, GLA and micronutrients at the doses tested as compared to placebo. The study adds information regarding doses of omega-3 fatty acids, below which anti-inflammatory effects in RA are not seen.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  • Belch JJ & Hill A (2000): Evening primrose oil and borage oil in rheumatologic conditions. Am. J. Clin. Nutr. 71, 352S–356S.

    Article  CAS  Google Scholar 

  • Bligh EG & Dyer WT (1959): A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911–920.

    Article  CAS  Google Scholar 

  • Burkhardt H, Schwingel M, Menninger H, Macartney HW & Tschesche H (1986): Oxygen radicals as effectors of cartilage destruction. Arthritis Rheum. 29, 379–387.

    Article  CAS  Google Scholar 

  • Calder PC & Kew S (2002): The immune system: a target for functional foods? Br. J. Nutr. 88(Suppl 2), 5165–5177.

    Google Scholar 

  • Chilton FH, Patel M, Fonteh AN, Hubbard WC & Triggiani M (1993): Dietary n-3 fatty acid effects on neutrophil lipid composition and mediator production. Influence of duration and dosage. J. Clin. Invest. 91, 115–122.

    Article  CAS  Google Scholar 

  • Cleland LG, James MJ, Neumann MA, D'Angelo M & Gibson RA (1992): Linoleate inhibits EPA incorporation from dietary fish-oil supplements in human subjects. Am. J. Clin. Nutr. 55, 395–399.

    Article  CAS  Google Scholar 

  • Cleland LG, James MJ & Proudman SM (2003): The role of fish oils in the treatment of rheumatoid arthritis. Drugs 63, 845–853.

    Article  CAS  Google Scholar 

  • Darlington LG & Stone TW (2001): Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. Br. J. Nutr. 85, 251–269.

    Article  CAS  Google Scholar 

  • del Rincon ID, Williams K, Stern MP, Freeman GL & Escalante A (2001): High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 44, 2737–2745.

    Article  CAS  Google Scholar 

  • de Vries JHM, Jansen A, Kromhout D, van de Bovenkamp P, van Staveren WA, Mensink RP & Katan MB (1997): The fatty acid and sterol content of food composites of middle-aged men in seven countries. J. Food Compos. Anal. 10, 115–141.

    Article  CAS  Google Scholar 

  • Edmonds SE, Winyard PG, Guo R, Kidd B, Merry P, Langrish-Smith A, Hansen C, Ramm S & Blake DR (1997): Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial. Ann. Rheum. Dis. 56, 649–650.

    Article  CAS  Google Scholar 

  • Felson DT, Anderson JJ, Boers M, Bombardier C, Chernoff M, Fried B, Furst D, Goldsmith C, Kieszak S, Lightfoot R, Paulus H, Tugwell P, Weinblatt M, Widmark R, Williams HJ & Wolfe F (1993): The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum. 36, 729–740.

    Article  CAS  Google Scholar 

  • Geusens P, Wouters C, Nijs J, Jiang Y & Dequeker J (1994): Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12-month, double-blind, controlled study. Arthritis Rheum. 37, 824–829.

    Article  CAS  Google Scholar 

  • Johnson MM, Swan DD, Surette ME, Stegner J, Chilton T, Fonteh AN & Chilton FH (1997): Dietary supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy humans. J. Nutr. 127, 1435–1444.

    Article  CAS  Google Scholar 

  • Jikimoto T, Nishikubo Y, Koshiba M, Kanagawa S, Morinobu S, Morinobu A, Saura R, Mizuno K, Kondo S, Toyokuni S, Nakamura H, Yodoi J & Kumagai S (2002): Thioredoxin as a biomarker for oxidative stress in patients with rheumatoid arthritis. Mol. Immunol. 38, 765–772.

    Article  CAS  Google Scholar 

  • Kaluzny MA, Duncan LA, Merritt MV & Epps DE (1985): Rapid separation of lipid classes in high yield and purity using bonded phase columns. J. Lipid Res. 26, 135–140.

    CAS  PubMed  Google Scholar 

  • Kheir-Eldin AA, Hamdy MA, Motawi TK, Shaheen AA & Abd el Gawad HM (1992): Biochemical changes in arthritic rats under the influence of vitamin E. Agents Actions 36, 300–305.

    CAS  PubMed  Google Scholar 

  • Kremer JM (2000): n-3 fatty acid supplements in rheumatoid arthritis. Am. J. Clin. Nutr. 71, 349S–351S.

    Article  CAS  Google Scholar 

  • Kremer JM, Lawrence DA, Jubiz W, DiGiacomo R, Rynes R, Bartholomew LE & Sherman M (1990): Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects. Arthritis Rheum. 33, 810–820.

    Article  CAS  Google Scholar 

  • Kris-Etherton PM, Harris WS & Appel LJ (2002): Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106, 2747–2757.

    Article  Google Scholar 

  • Laidlaw M & Holub BJ (2003): Effects of supplementation with fish oil-derived n-3 fatty acids and γ-linolenic acid on circulating plasma lipids and fatty acid profiles in women. Am. J. Clin. Nutr. 77, 37–42.

    Article  CAS  Google Scholar 

  • Liau LS, Lee BL, New AL & Ong CN (1993): Determination of plasma ascorbic acid by high-performance liquid chromatography with ultraviolet and electrochemical detection. J. Chromatogr. 612, 63–70.

    Article  CAS  Google Scholar 

  • Lunec J, Halloran SP, White AG & Dormandy TL (1981): Free radical oxidation (peroxidation) products in serum and synovial fluid in rheumatoid arthritis. J. Rheumatol. 8, 233–244.

    CAS  PubMed  Google Scholar 

  • Morrison WR & Smith LM (1964): Preparation of fatty acids methyl esters and dimethylacetals from lipids with boron fluoride methanol. J. Lipid Res. 5, 600–607.

    CAS  Google Scholar 

  • Peretz A, Siderova V & Neve J (2001): Selenium supplementation in rheumatoid arthritis investigated in a double blind, placebo-controlled trial. Scand. J. Rheumatol. 30, 208–212.

    Article  CAS  Google Scholar 

  • Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB & van Riel PL (1995): Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 41, 44–48.

    Article  Google Scholar 

  • Rosenstein ED & Caldwell JR (1999): Trace elements in the treatment of rheumatoid arthritis. Rheum. Dis. Clin. North Am. 25, 929–935.

    Article  CAS  Google Scholar 

  • Sakai A, Hirano T, Okazaki R, Okimoto N, Tanaka K & Nakamura T (1999): Large-dose ascorbic acid administration suppresses the development of arthritis in adjuvant-infected rats. Arch. Orthop. Trauma Surg. 119, 121–126.

    Article  CAS  Google Scholar 

  • Simopoulos AP (2002): The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed. Pharmacother. 56, 365–379.

    Article  CAS  Google Scholar 

  • Sköldstam L, Börjesson O, Kjällman A, Seiving B & Åkesson B (1992): Effect of six months of fish oil supplementation in stable rheumatoid arthritis. A double-blind, controlled study. Scand. J. Rheumatol. 21, 178–185.

    Article  Google Scholar 

  • Stone SJ, Doube A, Dudson D & Wallace J (1997): Inadequate calcium, folic acid, vitamin E, zinc, and selenium intake in rheumatoid arthritis patients: results of a dietary survey. Semin. Arthritis Rheum. 27, 180–185.

    Article  CAS  Google Scholar 

  • Stump DD, Roth Jr EF & Gilbert HS (1984): Simultaneous determination by high-performance liquid chromatography of tocopherol isomers, alpha-tocopherol quinone, and cholesterol in red blood cells and plasma. J. Chromatogr. 306, 377–382.

    Article  Google Scholar 

  • Tarp U, Overvad K, Thorling EB, Graudal H & Hansen JC (1985): Selenium treatment in rheumatoid arthritis. Scand. J. Rheumatol. 14, 364–368.

    Article  CAS  Google Scholar 

  • Taysi S, Polat F, Gul M, Sari RA & Bakan E (2002): Lipid peroxidation, some extracellular antioxidants, and antioxidant enzymes in serum of patients with rheumatoid arthritis. Rheumatol. Int. 21, 200–204.

    Article  CAS  Google Scholar 

  • Tsuji F, Miyake Y, Aono H, Kawashima Y & Mita S (1999): Effects of bucillamine and N-acetyl-L-cysteine on cytokine production and collagen-induced arthritis (CIA). Clin. Exp. Immunol. 115, 26–31.

    Article  CAS  Google Scholar 

  • Venkatraman JT & Chu WC (1999): Effects of dietary omega-3 and omega-6 lipids and vitamin E on serum cytokines, lipid mediators and anti-DNA antibodies in a mouse model for rheumatoid arthritis. J. Am. Coll. Nutr. 18, 602–613.

    Article  CAS  Google Scholar 

  • Zurier RB, Rossetti RG, Jacobson EW, DeMarco DM, Liu NY, Temming JE, White BM & Laposata M (1996): Gamma-linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum. 39, 1808–1817.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr M Froelich (LUMC) and Dr J van den Berg (Numico Research) for laboratory analyses. This study was supported by a research grant from Senter/Dutch Ministry of Economic Affairs (BTS-99036).

Author information

Authors and Affiliations

  1. Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands

    P H J Remans, W M Zuijderduin, A Jongma, F C Breedveld & J M van Laar

  2. Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands

    J K Sont

  3. Numico Research, Wageningen, The Netherlands

    L W Wagenaar & W Wouters-Wesseling

Authors
  1. P H J Remans
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J K Sont
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L W Wagenaar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W Wouters-Wesseling
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W M Zuijderduin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Jongma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F C Breedveld
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J M van Laar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J M van Laar.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Remans, P., Sont, J., Wagenaar, L. et al. Nutrient supplementation with polyunsaturated fatty acids and micronutrients in rheumatoid arthritis: clinical and biochemical effects. Eur J Clin Nutr 58, 839–845 (2004). https://doi.org/10.1038/sj.ejcn.1601883

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601883

Keywords

This article is cited by

Search

Advanced search

Quick links