Clinical Review

Fish Oil and Osteoarthritis: Current Evidence

Am J Orthop. 2015 July;44(7):302-305

References

1. Jordan KM, Sawyer S, Coakley HE, Smith HE, Cooper C, Arden NK. The use of conventional and complementary treatments for knee osteoarthritis in the community. Rheumatology. 2003;43(3):381-384.

2. Vista ES, Lau CS. What about supplements for osteoarthritis? A critical and evidenced-based review. Int J Rheum Dis. 2011;14(2):152-158.

3. European Food Safety Authority Panel on Biological Hazards (BIOHAZ). Scientific opinion on fish oil for human consumption. Food hygiene, including rancidity. EFSA J. 2010;8(10):1874.

4. Berbert AA, Kondo CR, Almendra CL, Matsuo T, Dichi I. Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition. 2005;21(2):131-136.

5. Calder PC. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr. 2006;83(6 suppl):1505S-1519S.

6. Calder PC, Zurier RB. Polyunsaturated fatty acids and rheumatoid arthritis. Curr Opin Clin Nutr Metab Care. 2001;4(2):115-121.

7. Kremer JM. Effects of modulation of inflammatory and immune parameters in patients with rheumatic and inflammatory disease receiving dietary supplementation of n-3 and n-6 fatty acids. Lipids. 1996;31(suppl):S243-S247.

8. Kremer JM, Jubiz W, Michalek A, et al. Fish oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled, crossover study. Ann Intern Med. 1987:106(4):497-503.

9. Kremer JM, Lawrence DA, Jubiz W, et al. Dietary fish oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects. Arthritis Rheum. 1990;33(6):810-820.

10. Nielsen GL, Faarvang KL, Thomsen BS, et al. 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(10):687-691.

11. Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007;129(1-2):210-223.

12. van der Tempel H, Tulleken JE, Limburg PC, Muskiet FA, van Rijswijk MH. Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis. 1990;49(2):76-80.

13. Rosenbaum CC, O’Mathúna DP, Chavez M, Shields K. Antioxidants and antiinflammatory dietary supplements for osteoarthritis and rheumatoid arthritis. Altern Ther Health Med. 2010;16(2):32-40.

14. Sanghi D, Avasthi S, Srivastava RN, Singh A. Nutritional factors and osteoarthritis: a review article. Internet J Med Update. 2009;4(1).

15. Curtis CL, Hughes CE, Flannery CR, Little CB, Harwood JL, Caterson B. n-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation. J Biol Chem. 2000;275(2):721-724.

16. Curtis CL, Rees SG, Cramp J, et al. Effects of fatty acids on cartilage metabolism. Proc Nutr Soc. 2002;61(3):381-389.

17. Zainal Z, Longman AJ, Hurst S, et al. Relative efficacies of omega-3 polyunsaturated fatty acids in reducing expression of key proteins in a model system for studying osteoarthritis. Osteoarthritis Cartilage. 2009;17(7):896-905.

18. Hankenson KD, Watkins BA, Schoenlein IA, Allen KG, Turek JJ. Omega-3 fatty acids enhance ligament fibroblast collagen formation in association with changes in interleukin-6 production. Proc Soc Exp Biol Med. 2000;223(1):88-95.

19. Melanson KJ. Diet, nutrition and osteoarthritis. Am J Lifestyle Med. 2007;1(4):260-263.

20. Pritchett JW. Statins and dietary fish oils improve lipid composition in bone marrow and joints. Clin Orthop Relat Res. 2007;(456):233-237.

21. Roush JK, Cross AR, Renberg WC, et al. Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. J Am Vet Med Assoc. 2010;236(1):67-73.

22. Roush JK, Dodd CE, Fritsch DA, et al. Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs. J Am Vet Med Assoc. 2010;236(1):59-66.

23. Fritsch DA, Allen TA, Dodd CE, et al. A multicenter study of the effect of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. J Am Vet Med Assoc. 2010;236(5):535-539.

24. Fritsch DA, Allen TA, Dodd CE, et al. Dose-titration effects of fish oil in osteoarthritic dogs. J Vet Intern Med. 2010;24(5):1020-1026.

25. Curtis CL, Rees SG, Little CB, et al. Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids. Arthritis Rheum. 2002;46(6):1544-1553.

26. Shen CL, Dunn DM, Henry JH, Li Y, Watkins BA. Decreased production of inflammatory mediators in human osteoarthritic chondrocytes by conjugated linoleic acids. Lipids. 2004;39(2):161-166.

27. Hurst S, Zainal Z, Caterson B, Hughes CE, Harwood JL. Dietary fatty acids and arthritis. Prostaglandins Leukot Essent Fatty Acids. 2010;82(4-6):315-318.

28. Cleland LG, Hill CL, James MJ. Diet and arthritis. Baillieres Clin Rheumatol. 1995;9(4):771-785.

29. Maresz K, Meus K, Porwolik B. Krill oil: background and benefits. Int Sci Health Found. 2010;1-11.

30. Wang Y, Wluka AE, Hodge AM, et al. Effect of fatty acids on bone marrow lesions and knee cartilage in healthy, middle-aged subjects without clinical knee osteoarthritis. Osteoarthritis Cartilage. 2008;16(5):579-583.

31. Stammers T, Sibbald B, Freeling P. Efficacy of cod liver oil as an adjunct to non-steroidal anti-inflammatory drug treatment in the management of osteoarthritis in general practice. Ann Rheum Dis. 1992;51(1):128-129.

32. Jacquet A, Girodet PO, Pariente A, Forest K, Mallet L, Moore N. Phytalgic, a food supplement, vs placebo in patients with osteoarthritis of the knee or hip: a randomised double-blind placebo-controlled clinical trial. Arthritis Res Ther. 2009;11(6):R192.

33. Gruenwald J, Petzold E, Busch R, Petzold HP, Graubaum HJ. Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis. Adv Ther. 2009;26(9):858-871.

34. Baker KR, Matthan NR, Lichtenstein AH, et al. Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study. Osteoarthritis Cartilage. 2012;20(5):382-387.

35. Christensen R, Bliddal H. Is Phytalgic® a goldmine for osteoarthritis patients or is there something fishy about this neutraceutical? A summary of findings and risk-of-bias assessment. Arthritis Res Ther. 2010;12(1):105.

Literature Review

In the PubMed database, we targeted the subject of fish oils and OA by using search terms that included omega-3, DHA, EPA, and alpha-linolenic acid. The MedLine and Google Scholar databases were searched as well. Results were limited to those reported in English and involving human subjects and clinical trials; results were excluded if they primarily involved patients with RA. Studies cited or mentioned in articles found through the PubMed search were evaluated according to the criteria mentioned, such that all relevant articles available at time of search are thought to be included, and these articles represent a reasonable presentation of the available evidence.

Findings

Our search revealed 6 clinical trials in which omega-3–containing supplements were used in the treatment of human OA with differing endpoints. We reviewed these trials in detail. One study, which used alteration of bone marrow lipids as an endpoint, was included for completeness of the evaluation of the relevant evidence.²⁰ In addition, the study by Wang and colleagues,³⁰ who assessed patients without clinical evidence of OA for development of bone marrow lesions, was reviewed. This study was deemed relevant to examine the process by which n-3 fatty acids alter knee structure, as subsequent risk of OA has not been elucidated, and effects on bone marrow lesions may indeed have a direct impact on the OA process. Results of the trials that were identified were varied between no significant difference in OA symptoms between treatment and control groups, implied benefits, and substantial benefits.

The first clinical study of omega-3 supplementation in OA treatment was conducted in 1992.³¹ The study compared 10 g of cod liver oil (containing 786 mg of EPA) with 10 g of olive oil, both taken daily over 24 weeks by 86 patients with OA. Effects were assessed by NSAID use (recorded in patient diary) and pain score (evaluated by clinician) every 4 weeks. The trial found no significant difference in effects between the oils.

Wang and colleagues³⁰ used a food questionnaire to measure the n-3 intake of 293 healthy adults and quantified their bone marrow lesions after 10 years in an effort to describe how n-3 intake correlates with development of OA or pre-OA lesions. Higher intake of n-6 fatty acids was positively associated with presence of bone marrow lesions; n-3 intake had no association.

In a study of 84 patients who had joint replacement, Pritchett²⁰ evaluated lipid alterations resulting from a regimen of 3 g of fish oil containing 11% DHA daily for a 6-month trial period, measuring lipids before and after the trial period. Pritchett²⁰ found a 20% increase in long-chain fatty acids and a corresponding decrease in saturated fatty acids, as measured in bone marrow.

The supplement Phytalgic (Phythea Laboratories), which is advertised for OA, includes n-3 fatty acids, n-6 fatty acids, extract from Urtica dioica (the common nettle), zinc, and vitamin E. In a study by Jacquet and colleagues,³² this supplement was given 3 times daily over 3 separate 4-week periods to 81 patients with knee or hip OA. Measuring NSAID use with patient diaries and assessing pain with the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index every 4 weeks for 12 weeks, the authors found a significant decrease in NSAID use and, according to WOMAC results, a more than 50% reduction in pain and stiffness, and improved function.

One study compared the effects of glucosamine with and without omega-3 fatty acids in 182 patients with knee or hip OA.³³ Each day, patients took 500 mg of glucosamine plus 3 capsules each containing either 444 mg of omega-3 fatty acids or 444 mg of an oil mixture. Pain was assessed with visual analog scale and the WOMAC scale 3 times over the 26-week study. More than 90% reductions in morning stiffness and pain were found for the combination of fish oil and glucosamine.

The Multicenter Osteoarthritis Study (MOST), published in February 2012, demonstrated that plasma levels of n-3 and n-6 polyunsaturated fatty acids (PUFAs) may be related to knee structural findings.³⁴ This study confirmed that dietary modification of n-3 and n-6 PUFAs altered plasma concentration predictably. Higher DHA intake was associated with less evidence of OA on patellofemoral cartilage, though no association was found on tibiofemoral cartilage.³⁴

Discussion

The lack of human clinical trials detailing the effects of fish oil supplementation in patients with OA is arguably the most significant hindrance to fish oil being routinely recommended. Since 1992, only 6 studies have addressed this topic, and their endpoints and results were inconsistent. These interventional trials had their limitations, including short duration, insufficient dosage, inappropriate n-3 choice, dietary interactions, genotype, and medication interactions.¹⁸ The present review is limited as well, by the quantity of evidence on the topic and by the focus (of the majority of the studies) on short-term alterations in pain and mobility instead of on disease-modifying potential. Short-term evaluation is unlikely to capture such an effect, which may require long-term supplementation to become evident.