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SYNOPSIS: A cross-sectional analysis using baseline data from participants in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis (ESCAPE-RA) cohort study demonstrated biweekly consumption of fish significantly decreased pain and progression of RA sufferers.
SOURCE: Tedeschi SK, Bathon JM, Giles JT, et al. Relationship between fish consumption and disease activity in rheumatoid arthritis. Arthritis Care Res (Hoboken) 2018;70:327-332.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation leading to pain, functional impairment, and joint erosions. Disease-modifying anti-rheumatic drugs (DMARDs) are the standard of care and significantly decrease inflammation, improve symptoms, and decrease erosions. Omega-3 fatty acids decrease pro-inflammatory cytokines and have been studied in the form of orally dosed fish oil in several randomized, controlled studies.1,2 In double-blind, placebo-controlled studies, subjects ingesting fish oil had reduced pain in joints and higher rates of remission on DMARD therapy.3,4 Since the benefits of eating fish had not been studied in relationship to reducing RA signs and symptoms, Tedeschi et al sought to investigate the benefits of eating fish for those with RA.
A total of 176 participants in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis (ESCAPE-RA) study were included in this analysis. The majority were middle-aged, college-educated, white females taking DMARDs for seropositive, long-standing RA. These participants were enrolled in the ESCAPE-RA study from October 2004 to May 2006, were 45 to 84 years of age, and lived near Baltimore. Subjects with a previous cardiovascular event or weighing > 300 pounds were excluded.
In this study, baseline signs and symptoms were evaluated using the Disease Activity Score in 28 joints (DAS28) and C-reactive protein (CRP). The DAS28 includes examination of the joints for swelling and tenderness in 28 joints, global scores of pain and overall status, and questionnaires to assess function (HAQ). The median DAS28-CRP score at baseline was 3.5 (interquartile range, 2.9-4.3), reflecting moderate disease activity. A DAS28-CRP of > 5.1 implies active disease, < 3.2 low disease activity, and < 2.6 remission.
Dietary intake was measured using a baseline food frequency questionnaire assessing usual diet in the past year. Fish consumption was recorded in four categories: never to < 1 time/month, 1 time/month to < 1 time/week, 1 time per week, and ≥ 2 times per week. Fish included in the study were tuna, salmon, sardines, and “other broiled, steamed, baked, or raw fish (trout, sole, halibut, poke, grouper, etc.).” These fish were selected because of higher omega-3 content. Excluded were fried fish, non-fried shellfish, or fish mixed into dishes. The serving size was not recorded, as these data focused on frequency of consumption rather than quantity. Future studies could investigate serving size of fish and specific types of fish consumed and their individual effect on DAS-CRP.
Confounding variables in this study include age, gender, body mass index, depression, marital status, DMARD therapy, and fish oil use. A linear regression model adjusted to these variables was used to test the relationship between frequency of fish consumption and DAS-CRP. After adjusting for these confounders, subjects consuming fish more than two times per week had a significantly lower DAS28-CRP compared to subjects who ate fish never to less than one time per month (difference, -0.49; 95% confidence interval [CI], -0.97 to -0.02). To test for trends across categories of fish consumption, the authors calculated the difference in DAS28-CRP associated with increasing fish consumption (an increase of one serving per week). For each additional serving of fish per week, DAS28-CRP was reduced significantly by 0.18 (95% CI, -0.35 to -0.004). (See Table 1.)
Epidemiological data have shown the benefits of eating fish and decreased cardiovascular mortality, decreased rates of diabetes, lower rates of depression, and decreased risk of dementia.5-8 To date, much research has been conducted on the benefits of supplementing with omega-3 rich fish oil. A recent randomized, controlled trial of fish oil supplementation among patients with RA included those with disease duration of 12 months and taking triple DMARD therapy. Subjects were divided into two categories: treatment with high-dose fish oil (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA], 5.5 g/day) and treatment with low-dose fish oil (EPA and DHA, 0.4 g/day). There was no significant difference between the groups in the DAS28-ESR over 12 months. However, at 12 months, both groups had significant decrease in DAS28-ESR.
Now, with this current analysis, we can start to see a greater benefit with eating fish instead of simply supplementing with fish oil. Those in the highest fish consumption group (more than twice per week) consumed < 5.5 g EPA + DHA per day. A 1 ounce serving of fatty fish provides 2 to 4 g of EPA and DHA.9 Whole fish provides a host of additional micronutrients and macronutrients that may account for the additional beneficial effect. Oily fish are good sources of vitamin B12, vitamin D, vitamin A, selenium, zinc, iodine, iron, potassium, and calcium. Seeing the added value of fish compared to fish oil, future studies could explore the benefit of these other nutrients in RA. However, one drawback to eating fish is the increased intake of mercury and PCBs present in fish. Fish oil often is purified to remove such contaminants. These contaminants may interfere with the anti-inflammatory effect of the omega-3s present in the fish. Future studies comparing therapeutic effectiveness of fish low in mercury and PCB contaminants with those that are higher also could yield useful information.
Ideally, clinicians want patients to adopt healthy, low-inflammatory lifestyles. In patients who live a more inflammatory lifestyle (i.e., smoking), there still is a benefit in eating oily fish regularly. Foods high in omega-3s have a direct anti-inflammatory effect and can offset the negative effects of a high inflammatory, standard American lifestyle. Interestingly, pack years were highest and depression scores were lowest among those who ate fish more than two times per week. It is impressive to note in smokers with a high inflammatory state that there is a significant benefit from eating fish. It also is important to note that consuming fish may have the additional beneficial effect on mood. Healthier mood encourages greater motivation for self-care and healthier lifestyle choices.
Encouraging consuming oily fish on a regular basis is wise clinical advice. The greatest anti-inflammatory benefit comes from eating oily fish at least twice per week. However, it is important to be especially careful with this recommendation for pregnant women and young children. In the most recent recommendation from the Environmental Protection Agency,10 pregnant women and women who intend to become pregnant should consume only lower-mercury containing fish and a maximum of three servings per week. It is also recommended children eat fish once or twice per week, choosing lower-mercury fish. These include shrimp, pollock, salmon, canned light tuna, tilapia, catfish, and cod. The omega-3s in fish are very important for the development of a healthy nervous system, but the mercury in some fish is neurotoxic. The seven types of fish with higher levels of mercury that should be avoided include tilefish from the Gulf of Mexico, shark, swordfish, orange roughy, bigeye tuna, marlin, and king mackerel. One should consider the environmental effect of more people eating fish on a regular basis. Some fish are severely over harvested and are at risk of becoming endangered. Seafood Watch (http://www.seafoodwatch.org) is a good resource for patients to learn which fish are safe to consume and which fish are sustainably harvested.
Financial Disclosure: Integrative Medicine Alert’s Executive Editor David Kiefer, MD; Peer Reviewer Suhani Bora, MD; AHC Media Executive Editor Leslie Coplin; Editor Jonathan Springston; and Editorial Group Manager Terrey L. Hatcher report no financial relationships relevant to this field of study.