Cross-sectional study ties fish with diminished disease activity

by Judy George, Contributing Writer, MedPage Today June 26, 2017

Action Points
• Eating fish high in omega-3 fatty acids may help reduce joint pain and inflammation, according to a new study among mostly middle-aged, white, college-educated females taking disease-modifying anti-rheumatic drugs (DMARDs) for seropositive, longstanding rheumatoid arthritis (RA).
• The disease activity difference between the highest and lowest categories of fish consumption was of clinically important magnitude and was approximately one-third the magnitude of previously reported pre- and post-treatment differences in disease activity among methotrexate users.
Eating fish — tuna, salmon, sardines, trout, sole, halibut, poke, and grouper — may help reduce joint pain and inflammation in rheumatoid arthritis (RA) patients, according to a new study in Arthritis Care & Research.

RA patients who ate baked, steamed, broiled, or raw fish 2 or more times per week had a significantly lower Disease Activity Score in 28 Joints with C-Reactive Protein (DAS28-CRP) — a score that measures tender and swollen joints, subjective disease activity, and C-reactive protein — than those who never ate fish or ate it less than once a month. The difference in DAS28-CRP between these two groups was -0.49 (95% CI, -0.97 to -0.02), according to Sara Tedeschi, MD, MPH, of Brigham and Women’s Hospital in Boston, and colleagues. With each additional serving of fish per week, DAS28-CRP dropped significantly by 0.18 (95% CI -0.35 to -0.004).
“This is a novel analysis of the relationship between consuming fish as a whole food, rather than consuming fish oil supplements, and rheumatoid disease activity,” the authors wrote. “Our observed difference in DAS28-CRP of 0.49 between the lowest and highest categories of fish consumption is approximately one-third the magnitude of previously reported pre- and post-treatment differences in DAS28 among methotrexate users.”
In their analysis, the Tedeschi team looked at baseline data from 176 rheumatoid arthritis patients who enrolled in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis (ESCAPE-RA) cohort study from October 2004 to May 2006. Patients who had a prior cardiovascular event or who weighed over 300 pounds were not part of this sample.
The investigators studied the results of a 120-item food frequency questionnaire that participants completed at baseline, which assessed their usual diet over the past year. They defined fish consumption as cooked or raw sardines, tuna, or salmon (including sashimi and sushi), and broiled, steamed, baked, or raw fish like trout, sole, halibut, poke, grouper, and others, selecting those foods because of their higher omega-3 fatty acid content. They did not include fried fish, non-fried shellfish, or fish in mixed dishes, such as stir-fried fish with vegetables.
Participants recorded the frequency in which they ate fish on a 9-point scale ranging from “never to <1/month” to “≥2/day,” and indicated each serving size as small, medium, or large. If frequency was missing on a questionnaire, the researchers assigned it to “never to <1/ month.” If the serving size was missing, they assigned it medium.
The majority of people who participated in this study were middle-aged, white, college-educated females taking disease-modifying anti-rheumatic drugs (DMARDs) for seropositive, longstanding RA. Of the 176 participants, 19.9% were infrequent fish eaters (never to <1/month) while 17.6% were frequent eaters (≥2 times/week).
The researchers analyzed the association between how much fish participants ate and their baseline DAS28-CRP, adjusting for factors like age, gender, biologic DMARD use, fish oil supplement use, depression, smoking, and body mass index (BMI).
After adjusting for confounders, the researchers found that DAS28-CRP was 0.49 lower in individuals who ate fish ≥2 times/week than those who ate fish never to <1/month. Each additional serving of fish per week was associated with 0.18 lower DAS28-CRP.
The DAS28 difference between the highest and lowest categories of fish consumption is of clinically important magnitude, the authors observed, especially compared to results from recent trials.
“During the SWEFOT [Swedish Farmacotherapy] trial run-in period, mean DAS28 decreased by 1.2 among 258 subjects after 3-4 months with methotrexate,” they wrote. “In a cohort of 307 longstanding RA patients with moderate-to-high disease activity treated with methotrexate (without biologic DMARDs), mean DAS28 decreased by 1.6 after 6 months.” The DAS28 difference found in this study of fish consumption is about one-third the size of the methotrexate findings, the researchers noted.
The group that ate fish most frequently had some baseline traits that might be associated with improved disease activity, like lower BMI and higher socioeconomic status, but they also had the highest prevalence of smoking and the longest disease duration, making it difficult to see how confounders might affect the relationship between fish consumption and RA disease activity.
While the magnitude of difference in DAS28-CRP was striking, the researchers cautioned that this study was a cross-sectional analysis, so they could not draw firm conclusions about fish consumption and RA disease activity. Reverse causation might be one explanation for the association between fish intake and disease activity, they noted, and a randomized controlled trial may provide firm evidence that greater fish consumption lowers RA disease activity. Moreover, they added, the ESCAPE-RA cohort consisted of predominantly white, well-educated married women with longstanding RA, so the results of this study might not apply to other populations.

The study was supported by grants from the National Institutes of Health.