What’s the Appeal?
Nearly one-quarter of patients with longstanding rheumatoid arthritis (RA) believe that diet affects their disease symptoms, as do many patients with other rheumatic diseases.8,9 What could be more appealing than an inexpensive, safe, accessible, empowering treatment for rheumatic disease? What could be simpler than understanding being unwell today as a consequence of something patients did (i.e., ate) yesterday? For many patients, too, the concept of natural or holistic is both attractive and conducive to a lifestyle view (see Table 1).3
Nearly one-quarter of patients with longstanding rheumatoid arthritis believe that diet affects their disease symptoms, as do many patients with other rheumatic diseases.
Table 1: The Appeal3,8,9
• Simple; understandable • Inexpensive • Safe • Accessible • Empowering to patients • Natural; conducive to certain lifestyles |
The Rationale
Historically, two main mechanisms for a diet–rheumatic disease link have been considered (see Table 2). First, nutritional factors may alter immune and inflammatory responses, thereby affecting rheumatic disease manifestations. EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in fish oil, for example, suppress the synthesis of leukotrienes and prostaglandins—eicosanoids involved in the inflammatory response.5 Another example is caloric restriction, which may inhibit the NLRP3 inflammasome.10
Table 2: The Rationale
- Nutritional factors may alter immune and inflammatory responses • Fish and plant oils' effects on disease susceptibility, risk, emergence, and inflammatory and immunologic events5,10,15,20,21 • Immunoregulatory RNAs in milk (or in other nutrients)22 • Effects on the microbiome and then on rheumatic disease23 • Effects of fasting on the inflammasome and C-reactive protein10,24 - Food-related antigens may induce an immunologic response and lead to rheumatologic symptoms5,11,12 • “Allergic” arthritis2,14 • Autoantibodies (e.g., ACPAs) may cross-react with food antigens18 |
Second, food-related antigens may induce an immunologic response that may lead to rheumatic symptoms.5 Food antigens are known to cross the gastrointestinal barrier and circulate both as antigens and immune complexes, and it is, therefore, not unreasonable to consider they may interact with effector or intermediary cells in the immune system.5,11,12
Limited Evidence
Studies on food, diet and nutrition are very difficult to do well. Proper controls, assurances of compliance and adequate blinding and randomization are all daunting challenges in these kinds of investigations.5,6,13 Many studies rely on patients being able to accurately recall what they consumed in the distant past.5,6 Further, most rheumatoid arthritis patients now take disease-modifying anti-rheumatic drugs (DMARDs), which are likely to be significantly more efficacious than diet. It is, therefore, difficult for trials to detect the relatively small differences in disease activity caused by dietary changes.10
Convincing, consistent, reproducible evidence for nutrition having a clinically significant role in the management of rheumatic disease remains sparse. Selected examples follow.
A 10-week, controlled, double-blind, randomized trial of 26 patients with active rheumatoid arthritis compared a popular diet—free of additives, preservatives, fruit, red meat, herbs and dairy—thought to help control rheumatoid arthritis with a placebo diet; 183 variables were analyzed and no clinically important differences were noted between the two groups.1
Interestingly, two patients in the experimental group did improve and noted exacerbations after consuming foods outside the experimental diet; this suggested that although this diet had no overall clinical benefit for rheumatoid arthritis patients, the possibility exists that some patients could benefit from dietary manipulation.1 Some rheumatic disease patients may have an immunologic sensitivity to specific foods, with inflammatory synovitis developing after consuming these offending nutrients.2,14
Although of interest, this food-induced arthritis does not seem to play a role in the vast majority of patients. We don’t think that not making diet/nutrition recommendations deprives patients of demonstrably clinically important benefit.3
However, for those who are so inclined, evidence exists for a modest role for fish (or plant) oil supplementation and for the Mediterranean diet. A 12-week, placebo-controlled, double-blind study of patients with new-onset rheumatoid arthritis found that patients taking fish oil supplementation had a reduced rate of failure of triple therapy and a higher rate of remission based on the ACR criteria.15
Although supplements cannot replace DMARDs for the treatment of rheumatoid arthritis, patients may experience some slight improvement in their symptoms with 3 g EPA plus DHA daily, in addition to DMARDs.10
Similarly, adherence to a Mediterranean diet has been shown to possibly reduce inflammatory activity in rheumatoid arthritis patients.16 Although larger randomized clinical trials are still needed, the Mediterranean diet is a well-balanced diet that also has benefits for comorbidities of rheumatic diseases, such as heart disease and may, therefore, be a salutary recommendation for patients wishing to implement dietary changes for their rheumatoid arthritis in addition to DMARDs.17