Apr 3, 1991 - Correspondence: Gunnar h u g e Nielsen, Carsten Hauchsvej I 1,. DK-9000 ..... 4 Cathchart ES, Gonnerman WA, Leslie CA, Hayes KC. Dietary.
European Journal of Clinical Znoestigation ( I 992) 22, 687-69 1
The effects of dietary supplementation w i t h n-3 polyunsaturated fatty acids in patients w i t h rheumatoid arthritis: a randomized, double blind trial G. L. NIELSEN*, K. L. FAARVANG?, B. S. THOMSENf, K. L. TEGLBJiERG*, L. T. JENSENf, T. M. HANSEN?, H. H. LERVANGS, E. B. SCHMIDT§, J. DYERBERG7 & E. ERNSTS; *Department of Rheumatology, Aalborg Hospital; ?Department of Rheumatology, Herlev Hospital; $Department of Rheumatology, Hvidovre Hospital; $Department of Clinical Chemistry, Aalborg Hospital and YMedi-Lab a s., Copen hagen Received 18 February 1992 and in revised form 19 June 1992; accepted 24 June I992
Abstract. Study objective: To determine the effect of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) on disease variables in patients with rheumatoid arthritis. Design: Multicenter, randomized, placebo controlled, double blind. Setting: Three Danish hospital Departments of Rheumatology. Patients: Fifty-one patients with active rheumatoid arthritis. Intervention: Random allocation to 12 weeks of treatment with either six n-3 PUFA capsules (3.6 g) or six capsules with fat composition as the average Danish diet. Main results: Significant improvement of morning stiffness and joint tenderness. No significant effect on the four other assessed clinical parameters. No serious side effects. Conclusions: Dietary supplementation with n-3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters. Further studies are needed to clarify the more precise role of n-3 PUFA in the treatment of rheumatoid arthritis.
has proven to be beneficial in experimentally induced arthritis and systemic lupus erythematosus in animal models [4,5]. Previously published clinical studies of supplementation with n-3 PUFA in patients with rheumatoid arthritis support a real, although modest, beneficial effect of fish oil supplementation on clinical disease variables [6-I 31. We have studied the clinical effect of dietary supplementation with six capsules of fish oil (3.6 g n-3 PUFA), a dose likely to be acceptable for continued use, in patients with active rheumatoid arthritis. In addition to the conventional parameters of disease activity (ESR and CRP), we measured serum procollagen type I carboxyterminal propeptide (PICP) and serum procollagen type 111 aminoterminal propeptide (PIIINP), serological markers of the type I collagen synthesis and the type 111 collagen turn-over, supposed to reflect the inflammatory processes in the joints [14,15]. Patients and methods
Keywords. -3 PUFA, rheumatoid arthritis. Introduction Eskimos have a lower incidence of chronic inflammatory diseases e.g. rheumatoid arthritis, ulcerative colitis and psoriasis compared to inhabitants in most Western countries [I]. This has been ascribed to a high consumption of seafood rich in long chained n-3 polyunsaturated fatty acids (n-3 PUFA) [2]. In a recent study from the Faroe Islands, a society with a high dietary intake of fish, it was reported that rheumatoid arthritis takes a milder course in this population than seen in other Nordic countries [3]. Furthermore dietary supplementation with n-3 PUFA The main clinical results from the study were presented at the 25th annual meeting of the European Society for Clinical Investigation, Pisa, 3 -6 April 1991, abstract no. 375. Correspondence: Gunnar h u g e Nielsen, Carsten Hauchsvej I 1 , DK-9000 Aalborg. Denmark.
Design
A double blind, randomized design with a 12-week treatment period was used. The protocol was in accordance with the Helsinki Deklaration I1 and approved by the local Ethical Committees. Informed consent was obtained. Patients
A total of 57 patients with rheumatoid arthritis were included in the study from the outpatient clinics at the Departments of Rheumatology at the hospitals in Aalborg, Herlev and Hvidovre. All patients fulfilled the ARA-criteria for rheumatoid arthritis [I 61. Actual disease activity was secured by the presence of at least three swollen joints in combination with two out the following three criteria: ( I ) a minimum of six tender joints; (2) duration of morning stiffness > 60 min and (3) erythrocyte sedimentation rate (ESR) > 3 0 mm hk'. Median age was 61 years (range 33-78 years), duration of arthritis 5 years (range 1-41 years). 687
688
G . L. NIELSEN et al. Table 1. Fatty acids contents of n-3 PUFA and control capsules (‘%weight/totalweight) n-3 PUFA control Total n-3 fatty acids Eicosapentanoic acic (20:5) Docosapentaenoic acid (22: 5) Docosahexanoic acid (22:6) Total n-6 fatty acids Saturated fatty acids Polyunsaturated fatty acids Free fatty acids
68.3 34.0 3.5 19.0
0
5.0
41.1 59.7
