Janis C. Kelly
June 23, 2017
Eating fish two or more times per week is associated with lower disease activity in patients with rheumatoid arthritis (RA), according to a cross-sectional analysis published online June 21 in Arthritis Care & Research.
Whereas randomized controlled trials have shown that dietary supplements of fish oil improved tender joint counts and increased remission rates in patients with RA, the new findings suggest similar benefit could come from increasing the amount of fish consumed in regular diet.
"Our observed difference in [28-joint disease activity score with C-reactive protein (DAS28-CRP)] of 0.49 between the highest and lowest categories of fish consumption is approximately one-third the magnitude of previously reported pre- and post-treatment differences in DAS28 among methotrexate users," the authors write.
As with the dietary supplements, the benefits from fish consumption are thought to be from the anti-inflammatory effects of omega-3 fatty acids, according to Sara K. Tedeschi, MD, MPH, from Brigham and Women's Hospital, Division of Rheumatology, Immunology and Allergy, and Harvard Medical School, both in Boston, Massachusetts, and colleagues.
Fish Consumption and Changes in RA Disease Activity
The cross-sectional dietary analysis used data from 176 participants in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in RA (ESCAPE-RA) cohort study. Patients were excluded if they had a prior cardiovascular event or weighed more than 300 pounds. Subjects had a median DAS28-CRP of 3.5, indicating moderate RA disease activity.
Frequency of fish consumption was assessed by a baseline food frequency questionnaire assessing usual diet in the past year. Fish consumption was stratified as never to less than one serving/month, one serving/month to less than one serving per week, one serving per week, and two or more servings per week. Fish consumption was defined as "tuna fish, salmon, sardines (cooked or raw including sashimi or sushi)," and "other broiled, steamed, baked or raw fish (trout, sole, halibut, poke, grouper, etc.)."
The authors explain that previous studies had shown that plasma omega-3 fatty acid levels were significantly correlated with nonfried fish consumption, but not with consumption of fried fish, nonfried shellfish, or fish in mixed dishes (such as "stir-fried shrimp or fish with vegetables"), so those items were not included in the assessment of fish intake.
The researchers analyzed the association between frequency of fish consumption and baseline DAS28-CRP, a measure of RA disease activity. They also estimated the difference in DAS28-CRP associated with increasing fish consumption by one serving per week. Adjustment for possible confounding factors included age, sex, race, and body mass index.
The authors write, "We report a statistically and clinically significant reduction in DAS28-CRP among subjects with rheumatoid arthritis who consumed fish ≥2 times/week compared to those who consumed fish never or <1/month, after adjustment for confounders."
After adjusting for demographic factors as well as use of biologic disease-modifying antirheumatic drugs, fish oil supplements, and smoking, linear regression analysis showed a 0.49 lower DAS28-CRP in participants consuming fish two or more times/week compared with those who ate fish never to less that once a month (95% confidence interval, -0.97 to -0.02).
Moreover, each additional serving of fish per week was associated with an additional 0.18 reduction in DAS28-CRP (95% confidence interval, -0.35 to -0.004).
Among the 160 subjects not using fish oil supplements, DAS28-CRP was lower by an average of 0.41 among those who had fish two or more times/week compared with those who ate fish never to less than one time month. The authors note that doses of omega-3 fatty acids in fish oil supplements used in previous studies exceed the omega-3 content in one serving of fish.
Is Fish Consumption a Cause or a Marker?
The authors caution against drawing causal inferences from the cross-sectional, nonrandomized study.
"Our observation that baseline consumption of fish ≥2 times per week was associated with lower DAS28-CRP at the same point in time may either reflect a generally healthier lifestyle among those who eat fish most often, or may reflect an effect of consuming fish as a whole food that contains various macronutrients and micronutrients in addition to omega-3 fatty acids," they write.
The researchers conclude that higher intake of fish "may be associated with lower disease activity in RA patients."
Too Soon for Recommendations
Daniela Di Giuseppe, PhD, from the Department of Medicine, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News, "I have read with pleasure the paper from Tedeschi et al. I think that it is a well-written and comprehensive paper, and that they have considered all limitations and have been careful in the interpretation of the results."
Dr Di Giuseppe, who was not involved in the study, reiterates the authors' caution that a cross-sectional study can only establish association, not causation. As such, the data from Tedeschi et al are not sufficient to support recommending that patients with RA eat more fish.
Further, Dr Di Giuseppe and the authors warn about the risk for "reverse causation" bias. She said, "The association found could be due to the fact that patients have increased their fish consumption due to the diagnosis of their disease." Prospective studies would be needed to minimize this potential source of bias.
The authors and Dr Di Giuseppe have disclosed no relevant financial relationships.