Gluten Intolerance & Rheumatoid Arthritis

The story on gluten and rheumatoid arthritis (RA) began almost 50 years ago when Australian physician Dr. Ray Shatin of Alford Hospital in Melbourne published several reports on his successful treatment of RA with a gluten-free, high protein diet including supplements. His findings introduced a concept that in RA patients – as in celiac – the primary culprit, which triggers a systemic inflammatory response, is found in the small intestine.

Dr. Shatin’s point of view was based on the premise that historically, man changed from a food-gatherer to a food-producer, which paralleled the transition from animal flesh, milk, nuts, berries, fruits, and roots to domesticated cereals obtained by culturing and farming the seeds of grasses. Shatin proposed that celiac disease was very common in ancient times but was lethal before most of the affected individuals had reached the age of reproduction, resulting in a natural elimination of a large pool of dominant celiac associated genes. However, genes responsible for non-lethal gluten intolerance have broadly penetrated into the modern human genome.

Shatin proposed a hypothesis that a majority of patients with RA have low grade gluten-driven inflammation in the gut different from that of celiac disease, but significant enough to cause malabsorption of metabolites essential for connective tissue – causing imbalance and inflammation in the joints.

Based on his hypothesis, he started 18 patients with RA on a gluten-free diet, which resulted in a universal symptom improvement in all of the treated patients. However, his discovery was accepted with skepticism and became almost forgotten for several decades.

The revival of this topic occurred around 10-15 years ago based on:

• Development of genetic tests identifying individuals at risk of celiac disease

• Improvement of serological (serum) testing for celiac disease and gluten intolerance

• Better understanding of molecular mechanisms of gluten-driven inflammation

In 2001, a group of Scandinavian rheumatologists from Sweden and Finland published clinical data on the use of a gluten-free, vegan diet in patients with RA. It showed that 35-40% of patients benefited from this diet. In 2008, another group of Swedish rheumatologists presented data indicating that a gluten-free, vegan diet in RA induces changes that are anti-inflammatory and protects patients from atherosclerosis.

So where do we stand in 2014?

Genetic research is making enormous progress, showing that patients with gluten intolerance, celiac disease, and other autoimmune diseases (including RA) share common traits such as:

• Functional abnormality of the intestinal lining (increased intestinal permeability, known as leaky gut syndrome)

• Abnormal proline (an amino acid determining a rigid structure of gluten)

• Abnormal glutamine (a vital amino acid controlling gut permeability)

• Abnormal metabolism, causing hyperactivation of immune cells and the initiation of autoimmune responses

• Abnormal epigenetic regulation (non-genetic cellular memory, which records developmental and environmental signals) of the immune responses

Currently, it is well recognized that the population of RA patients is a very diverse one. In some, gluten and other food molecules are the main inflammatory triggers, while in others the inflammation is driven by chronic infectious processes, neuroendocrine imbalance, heavy metal overload, stress, and other factors.

In my clinic, somewhere between 20-30% of patients with RA benefit from a gluten-free diet. The benefits are much more obvious when the diet starts at the early stages of the disease.

How do we define who may and may not benefit from eliminating gluten? Although we rely heavily on laboratory tests in our decision making process, the ultimate answer is based upon a patient’s response to a three month gluten-free diet with a subsequent gluten challenge. If their symptoms return or are heightened after eating gluten, remaining gluten-free is the optimal path.

Based on our personal observation, we believe that RA patients with a dominant inflammation of the wrists have a positive response to a gluten-free diet. Similarly, patients with a history of RA and Sjogren’s syndrome (an autoimmune disease manifesting in the form of eye and mouth dryness), Hashimoto thyroiditis (an autoimmune disease affecting thyroid glands), and rapidly progressing osteoporosis (loss of bone mass) have higher chances of benefiting from a gluten-free diet.

In general, it takes 2-3 months to notice the benefits from the diet. People with RA who experience a partial response to the diet are likely to have a broader intolerance to prolamines. Prolamines, which are found in the seeds of cereal grains, are a group of plant proteins that have a high content of an amino acid known as proline. These include wheat (gliadin), barley (hordein), rye (secalin), corn (zein), sorghum (kafirin), and – as a minor protein – avenin in oats.

Eliminating these prolamines as well as eliminating cross-reactive foods such as soy, cow’s milk-based dairy products, and eggs will benefit those with an incomplete response to gluten elimination.

Another important issue directly related to RA patients is drug tolerance. Clinical data indicates that patients with RA and gluten intolerance have a high rate of complications when using certain anti-rheumatic drugs. For example, a frequently used disease modifying drug, methotrexate, is poorly tolerated by gluten-intolerant RA patients when it is used by mouth, but well tolerated when administered via injection. Our clinical experience also indicates that patients with RA and gluten-intolerance demonstrate better response to rituximab, a biologic agent to treat advanced cases of RA, compared to other biologic drugs.

While the evidence has shown that people with RA benefit from a gluten-free diet, monitoring the response to gluten elimination should be performed under strict supervision of a rheumatologist or other qualified health care practitioner.

Resources:
Elkan AC, Sjöberg B, Kolsrud B, Ringertz B, Hafström I, Frostegård J. Gluten-free vegan diet induces decreased LDL and oxidized LDL levels and raised atheroprotective natural antibodies against phosphorylcholine in patients with rheumatoid arthritis: a randomized study. Arthritis Res Ther. 2008;10(2):R34.
Hafström I, Ringertz B, Spångberg A, von Zweigbergk L, Brannemark S, Nylander I, Rönnelid J, Laasonen L, Klareskog L. A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford). 2001 Oct;40(10):1175-9.
Östensson M1, Montén C, Bacelis J, Gudjonsdottir AH, Adamovic S, Ek J, Ascher H, Pollak E, Arnell H, Browaldh L, Agardh D, Wahlström J, Nilsson S, Torinsson-Naluai Å. A possible mechanism behind autoimmune disorders discovered by genome-wide linkage and association analysis in celiac disease. PLoS One. 2013 Aug 2;8(8):e70174.
Shatin R. Gluten, the small intestine and rheumatoid arthritis. Rheumatism. 1966 Apr;22(2):48-52.
Stenberg P, Roth B, Wollheim FA. Peptidylarginine deiminases and the pathogenesis of rheumatoid arthritis: a reflection of the involvement of transglutaminase in celiac disease. Eur J Intern Med. 2009 Dec;20(8):749-55.
Volta U, De Angelis GL, Granito A, Petrolini N, Fiorini E, Guidi M, Muratori P, Bianchi FB. Autoimmune enteropathy and rheumatoid arthritis: a new association in the field of autoimmunity. Dig Liver Dis. 2006 Dec;38(12):926-9.

Written by Dr. Alexander Shikman

Gluten Free & More magazine, by Edgewater Park Media Inc. (EPM) is publishing this article for purposes of medical topic, however no warranty is made that the article is accurate and there is no assurance that any statement contained or cited in the article touching on medical matters is correct, or up to date. EPM also states that nobody in EPM takes responsibility for the results of any attempt to use any information in the article. Always seek the advice of a medical professional before starting any new protocol.