Food, Diet, Nutrition & Rheumatic Diseases—Are They Really Related?

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“‘I didn’t say there was nothing better,’ the King replied. ‘I said there was nothing like it.’” —Lewis Carroll,
Through the Looking Glass

“Why did I get this? Was it because of my diet? What should I eat now? What diet should I follow? Are there any natural treatments I can take instead of medications?”

We are all familiar with these frequent questions asked by our newly diagnosed patients with rheumatic disease. For years our response was to deny a relationship between rheumatic diseases and food, diet and nutrition—or, perhaps more generously, to concede that we don’t know.

We offer our perspectives about certain aspects of this topic—one of us (i.e., Dr. Cerk) has systematically reviewed this topic during fellowship and the other of us (Dr. Panush) has studied, thought about and written on this over the years.^1-6

History

The belief that diet can remedy many health conditions dates back to ancient times. Hippocrates is alleged to have said, “Let food be thy medicine and medicine be thy food.” Although this notion has become relevant for some disorders, such as diabetes, heart disease and celiac disease, a role of nutrition in rheumatic diseases remains elusive.

Finding a relationship between diet and rheumatic disease was of considerable interest in the early 20th century. However, those early attempts to study this issue largely failed to find a convincing or consistent association, and this came to be labeled quackery by the rheumatology community.⁵

An informational handout for patients from the Arthritis Foundation, The Truth About Diet and Arthritis, stated, “no food has anything to do with causing arthritis, and no food is effective in treating or ‘curing’ it.”^5,7

Toward the end of the 20th century, quackery was replaced by complementary or alternative medicine or, even more euphemistically, as integrative medicine. With these changes came renewed attention on the relationship of diet, food and nutrition with rheumatic diseases. The topic is now generally perceived as a legitimate area of inquiry in mainstream rheumatology and has attracted credible and respected investigators.⁵

The widespread popularity of complementary and alternative medicine tells us, in part, that we need to be more “sensitive, responsive and empathetic to our patients and their needs” and is also a reminder that we need to do better at finding causes and cures for rheumatic diseases.³

Regardless of one’s own beliefs on this topic, it is important to keep an open mind and an open dialogue with our patients. Further, we must not dismiss ideas beyond our usual paradigms just because we may not understand them. Many scientific breakthroughs would not have occurred if we had not balanced healthy skepticism with a mind open to new ideas.⁴

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 Appeal^3,8,9

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

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

Interest & Influence

Although the role of diet in the management of rheumatic disease appears to be modest at best, significant interest in this topic remains, likely reflecting the inadequacies of our current understanding and management of rheumatic disease.³

Recent developments have provided some novel insights into the possible etiopathogenesis of rheumatic disease. Monoclonal anti-citrullinated protein antibodies (ACPA) have been shown to cross-react with numerous plant and microbial proteins; this would be consistent with the possibility that environmental factors, such as microbes or food antigens, may trigger the generation of ACPAs, which then leads to rheumatoid arthritis by cross-reacting with various citrullinated human autoantigens though molecular mimicry.¹⁸

Eating a generally healthier diet may reduce the risk of developing rheumatoid arthritis.¹⁹ Erythrocyte levels of the n-6 polyunsaturated fatty acid, linoleic acid, may be inversely associated with risk of rheumatoid arthritis, and omega-3 fatty acids may potentially lower the risk of transition from ACPA positivity to inflammatory arthritis.^20,21 Immunoregulatory mRNAs in bovine milk may influence the onset of arthritis (see Table 2, p. 37, and Table 3).²²

Table 3: Selected Studies

One particularly interesting way in which diet may affect rheumatic disease could be through an effect on the microbiome. Microbiomics is an emerging field, and our understanding of it is increasing dramatically. The hope is, that with increased understanding, it may be possible to one day develop treatments that target the microbiome to manage or even prevent rheumatic disease.²³

New data also suggest a possible role for fasting in the management and prevention of chronic medical conditions, including rheumatic disease. In one study, subjects who participated in five consecutive days of fasting per month experienced beneficial effects on body mass index, blood pressure, fasting glucose, IGF-1, triglycerides, cholesterol and C-reactive protein.²⁴ It will be interesting to see if a beneficial regimen for a fasting or nutritional elimination diet can be developed for and tolerated by patients with rheumatic disease.

Importance

The relationship between nutrition and rheumatic disease is of continued interest and has possible implications for the etiopathogenesis of rheumatic disease. However, it is unlikely that diet has more than a marginal role in the current treatment of rheumatic disease, even with recent reports and developments. Although there may be a benefit when used in conjunction with DMARDs, diet will not replace or substitute for DMARDs.^3,5,6,10,25

We expect that any role for diet, food or nutrition in the treatment of rheumatic disease will become further diminished as our science improves and therapies become better and safer (see Table 4).^3,5,6,10,25 Nonetheless, as Camus said, “There is no sun without shadow, and it is essential to know the night.” We respect the enthusiasm and persistence of those colleagues who continue to study nutrition in the treatment and understanding of rheumatic disease.³

Table 4: Conclusions

“Science requires an almost complete openness to all ideas. On the other hand, it requires the most rigorous and uncompromising skepticism.” —Carl Sagan

Brendan Cerk, MD, is a post-doctoral fellow in the Division of Rheumatology of the Department of Medicine, the Keck School of Medicine, University of Southern California, and Los Angeles County + University of Southern California (LAC+USC) Medical Center.

Richard S. Panush, MD, MACP, MACR, is a professor in the Division of Rheumatology of the Department of Medicine, the Keck School of Medicine, University of Southern California, and Los Angeles County + University of Southern California (LAC+USC) Medical Center.

References

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