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Treatment of Rheumatoid Arthritis with Gammalinolenic Acid

Lawrence J. Leventhal, MD; Eric G. Boyce, PharmD; and Robert B. Zurier, MD
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From the University of Pennsylvania, The Graduate Hospital, Presbyterian Medical Center, and the Philadelphia College of Pharmacy and Science, Philadelphia, Pennsylvania; the University of Massachusetts Medical Center, Worcester, Massachusetts. Requests for Reprints: Robert B. Zurier, MD, Division of Rheumatology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655. Acknowledgments: The authors thank Drs. Peter Callegari, Bruce Freundlich, and Joan vonFeldt for assisting in patient enrollment and Mrs. Carol Mader for preparation of the manuscript. Grant Support: National Institutes of Health grant RO1-38501, grant SP57945 from the Commonwealth of Pennsylvania, and Food and Drug Administration grant FD-R000756.

Copyright 2004 by the American College of Physicians

Ann Intern Med. 1993;119(9):867-873. doi:10.7326/0003-4819-119-9-199311010-00001
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Objective: To assess the clinical efficacy and side effects of gammalinolenic acid, a plant-seed-derived essential fatty acid that suppresses inflammation and joint tissue injury in animal models.

Design: A randomized, double-blind, placebo-controlled, 24-week trial.

Setting: Rheumatology clinic of a university hospital.

Patients: Thirty-seven patients with rheumatoid arthritis and active synovitis.

Intervention: Treatment with 1.4 g/d gammalinolenic acid in borage seed oil or cotton seed oil (placebo).

Measurements: Physicians' and patients' global assessment of disease activity; joint tenderness, joint swelling, morning stiffness, grip strength, and ability to do daily activities.

Results: Treatment with gammalinolenic acid resulted in clinically important reduction in the signs and symptoms of disease activity in patients with rheumatoid arthritis (P < 0.05). In contrast, patients given a placebo showed no change or showed worsening of disease. Gammalinolenic acid reduced the number of tender joints by 36%, the tender joint score by 45%, swollen joint count by 28%, and the swollen joint score by 41%, whereas the placebo group did not show significant improvement in any measure. Overall clinical responses (significant change in four measures) were also better in the treatment group (P < 0.05). No patients withdrew from gammalinolenic acid treatment because of adverse reactions.

Conclusion: Gammalinolenic acid in doses used in this study is a well-tolerated and effective treatment for active rheumatoid arthritis. Gammalinolenic acid is available worldwide as a component of evening primrose and borage seed oils. It is usually taken in far lower doses than used in this trial. It is not approved in the United States for the treatment of any condition and should not be viewed as therapy for any disease. Further controlled studies of its use in rheumatoid arthritis are warranted.


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Figure 1.
Metabolic pathway of omega-6 (n-6) fatty acids.33441111

The pathway is one of progressive desaturation alternating with elongation (addition of two carbons). 18:2 = 18 carbons, 2 double bonds; (150H) DGLA = 15 hydroxy dihomogamma linolenic acid; LTC = leukotriene C ; LTB = leukotriene B ; PGE = prostaglandin E ; TXA = thromboxane A .

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Figure 2.
Joint tenderness scores in patients completing the study.nn

Mean percentage change from baseline at each evaluation for placebo (open squares; = 13) and gammalinolenic acid (GLA) treatment (closed squares; = 14) groups. Error bars are 1 standard error of the mean.

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Figure 3.
Joint swelling scores in patients completing the study.nn

Mean percentage change from baseline at each evaluation for placebo (open squares; = 13) and gammalinolenic acid (GLA) treatment (closed squares; = 14) groups. Error bars are 1 standard error of the mean.

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