Grand Rounds: The Role of Omega-3 fatty Acids in Rheumatoid Arthritis

May 6, 2009

Grand Rounds ImageMichael Owen MD

Please also see the clinical vignette presented before Grand Rounds on the 15th of April.

Grand rounds on April 15th was presented by Dr. Joel Kremer, Pfaff Family Professor of Medicine at Albany Medical College and Director of Research at the Center for Rheumatology. Dr. Kremer informed the NYU community about the role of omega-3 fatty acid supplementation in rheumatoid arthritis.

Dr. Kremer began with an overview of fatty acid biochemistry including saturated, mono-unsaturated, and polyunsaturated fatty acids. Omega-3 fatty acids are in the polyunsaturated group and include alpha-linolenic acid, EPA, and DHA. Alpha-linolenic acid was the highest omega-3 in the diet of pre-industrial humans. It is found in some plants and in livestock that are grass-fed. It is less common in modern diets because most livestock are grain-fed. Alpha-linolenic acid is the predominant omega-3 in flax seed oil supplements. On the other hand, EPA and DHA mostly come from cold water fish, such as wild salmon, tuna, and mackerel. Similar to the difference between grass-fed vs. grain-fed livestock, farm-raised salmon contains less EPA and DHA than wild salmon.

Dr. Kremer reviewed data that the amount of omega-3 fatty acids in the average diet since the advent of industrial agriculture has declined, while the content of omega-6 and saturated fats has dramatically increased. Alterations in the ratio of omega-3 to omega-6 can change the metabolism of these fatty acids and increase or decrease the ratio of the final metabolic products including thromboxane and prostaglandins and thereby alter the inflammatory cascade. Dr. Kremer reviewed evidence and hypotheses that increasing the proportion of omega-3 relative to omega-6 can increase red blood cell deformability, decrease platelet adhesion and aggregation, decrease blood pressure, decrease the incidence of arrhythmias, decrease the size and density of lipoproteins, and decrease the production of interleukin 1. These findings correlate with epidemiological studies that have shown decreased rates of cardiovascular mortality in populations with increased dietary intake of omega-3, such as in Crete and Greenland.

Next, Dr. Kremer discussed evidence of benefit from omega-3 in clinical and basic science research. One study showed an increased time to induction of symptoms from cold exposure in patients with Raynauld’s after 6 weeks of supplementation with 3 g/day of fish oil. Also, omega-3 was shown to decrease proteinuria and mortality in a mouse model of SLE. Finally, Dr Kremer commented on the implications of the Jupiter study with regard to the role of inflammation in cardiovascular disease.

The core of the presentation was Dr. Kremer’s review of the literature on omega-3 supplementation in rheumatoid arthritis. In all, he said that there have been 20 published clinical trials testing the hypothesis that omega-3 could be beneficial in rheumatoid arthritis. Most of these studies were published in the 1980’s and 1990’s. All 20 showed a reduction in the number of painful joints after supplementation with at least 3 g/day of fish oil for at least 12 weeks. Some also showed a reduction in morning stiffness and reduced levels of leukotriene B4. Several of the studies were limited by small numbers and flawed study design, including a crossover study with a washout period that was too short.

Dr. Kremer ended by saying that the potential role of omega-3 fatty acids in decreasing cardiovascular morbidity and mortality in patients with rheumatoid arthritis deserves further study.

Dr. Owen is a second year resident in internal medicine at NYU Medical Center.