A meta-analysis of 17 randomized, controlled trials suggests that supplementation with oral n-3 fatty acids improves patient-assessed pain, duration of morning stiffness, and number of painful and/or tender joints in patients with rheumatoid arthritis (RA) [Bahadori B et al. JPEN J Parenter Enteral Nutr 2010; Kremer JM. Am J Clin Nutr 2007; Goldberg RJ, Katz J. Pain 2007]. Joel M. Kremer, MD, Albany Medical College and the Center for Rheumatology, Albany, New York, USA, reviewed studies on the efficacy of fish oil in the treatment of RA and its cardiovascular (CV) benefits.

A 24-week, prospective, double-blind, randomized trial of high and low doses of fish oil and olive oil showed significant improvements from baseline in the number of tender joints (p=0.05 for the high dose; p=0.04 with the low dose) and morning stiffness (p≤0.01) and significant decreases in leukotriene B4 and macrophage IL-1 production, especially in the high-dose n-3 fatty acid group [Kremer JM et al. Arthritis Rheum 1990].

A 12-month, double-blind, randomized study [Geusens P et al. Arthritis Rheum 1994] compared supplementation with either 2.6 mg of n-3 fatty acids or 1.3 gm of n-3 fatty acids+3 gm of olive oil. Findings indicated that 2.6 gm/day of n-3 fatty acids led to significant clinical benefit and may have reduced the need for concomitant antirheumatic medication.

According to Dr. Kremer, more than 20 peer-reviewed, blinded studies have demonstrated a consistent amelioration of tender joints in patients who have been given n-3 fatty acids versus controls of corn or olive oil. All but two studies added n-3 fatty acids to existing RA treatment regimens.

The minimal effective dose of n-3 fatty acids per day appears to be 3 to 5 g, or at least 10 capsules per day of most over-the-counter fish oil supplements. These contain about 300 mg of n-3, but “high-potency” capsules with 500 to 950 mg of n-3 are now available.

The finding that fish oil decreases CV risk is well established [Mozaffarian D. Am J Clin Nutr 2008; Albert CM et al. N Engl J Med 2002]. A protective effect seems evident at doses of long-chain n-3 fats >250 mg, much lower than those needed for symptomatic relief in RA [James M. Proc Nutr Soc 2010].

Fish oil may reduce CV events in RA via direct myocardial and, possibly, antithrombotic actions [Cleland LG et al. J Rheumatol 2006] and may also induce a favorable vascular response to ischemia [DiGiacomo RA et al. Am J Med 1989].

In a double-blind prospective study, 32 patients with primary or secondary Raynaud phenomenon were randomly assigned to olive oil placebo or fish oil groups. Data indicated that the ingestion of fish oil improved tolerance to cold exposure and delayed the onset of vasospasm in patients with primary (p=0.05), but not secondary, Raynaud phenomenon. The improvements were associated with significantly increased digital systolic blood pressures in cold temperatures [DiGiacomo RA et al. Am J Med 1989].

Dr. Kremer recommended three high-potency fish oil capsules (approximately 3 g n-3/day) in young patients with primary Raynaud, with at least 6 weeks of observation. He noted that the potential of n-3 fatty acids in the amelioration of CV comorbidity in inflammatory diseases, like RA, is worthy of further study.