Gluten-Free Diet Curbs Pain in Gluten Neuropathy

Pauline Anderson

March 05, 2018

A strict gluten-free diet is associated with a significant reduction in peripheral neuropathic pain in patients with neuropathy due to gluten sensitivity, new research suggests.

"Gluten neuropathy is common and can be painful, but a gluten-free diet can reduce this pain," lead author, Panagiotis Zis, consultant neurologist/honorary senior lecturer, Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom, told Medscape Medical News.

It has already been shown that strict adherence to a gluten-free diet improves neuropathy in patients with gluten neuropathy (GN), a peripheral neuropathy due to gluten sensitivity. This is the first study to show that such a diet also reduces neuropathic pain in these patients.

The research will be presented April 23 at the upcoming American Academy of Neurology (AAN) 2018 Annual Meeting in Los Angeles, California.

The study aimed to establish the prevalence and determinants of pain in patients with GN.

GN, said Zis, is defined as peripheral neuropathy with serologic presence of gliadin, transglutaminase, and/or endomysial antibodies, in the absence of other risk factors for neuropathy, such as diabetes. In addition to these antibodies, the diagnosis of GN relies on the presence of neurophysiologic evidence of neuropathy, he added.

Serologic Evidence

For the study, researchers recruited 60 people, mean age 70 years, who were attending the gluten sensitivity/neurology clinic at the Sheffield Teaching Hospitals NHS Trust and who had serologic evidence of gluten sensitivity.

Clinic patients diagnosed with GN are asked to go for a gluten-free diet. They were seen by an experienced dietitian and given advice on avoiding gluten, which is found in grains such as wheat (in all its forms, including wheat starch, wheat bran, wheat germ, cracked wheat), rye, oats, and barley.

Foods that are naturally gluten-free include rice, corn, soy, potato, and beans.  

Patients who managed to normalize the titers of the antibodies while on the diet were considered as being on a strict gluten-free diet, and the rest as not being on this diet.

To assess pain in the study, researchers used the 10-item Douleur Neuropathique 4 (DN4) questionnaire, a useful tool to detect neuropathic pain. The DN4 includes questions that patients answer related to pain quality and others that are based on clinician assessment of reduced sensitivity. Researchers also used the visual analogue scale to measure pain intensity.

The analysis showed that 55% of study patients had pain with their neuropathy. This is about typical; on average, 50% to 60% of patients with peripheral neuropathy have pain, said Zis.

Common Misconception

A common misconception is that some forms of neuropathy, for example, diabetic neuropathy, are more painful, he said. "However, this study along with other studies from our group and others have shown that any peripheral neuropathy can be painful."

This new study showed that participants with painless GN were more likely to follow a gluten-free diet than those with painful GN (55.6% vs 21.2%; P = .006.)

The study also looked at the participants' overall quality of life. This included their mental health status, assessed by using the validated Mental Health Index (MHI), a short questionnaire that is part of the Quality of Life Short-Form 36 questionnaire.

Pain perception is often altered when patients face mental health issues, such as anxiety and depression, explained Zis.

The analysis showed that those with painful GN scored significantly worse on the MHI than  those with painless GN (average score, 75.9 of 100 vs 87.4).

After adjustment for age, sex, and mental health status, strict adherence to the gluten-free diet was associated with a reduction in the risk for peripheral neuropathic pain by 88.7% (95% confidence interval [CI], 47.2% - 97.6%).

"We wanted to see whether the increased pain in patients with gluten neuropathy is because of worse mental health," but the analysis showed this not to be the case, said Zis.

Immune Reaction

Gluten sensitivity is thought to be an autoimmune disease in which the ingestion of gluten causes an immune reaction that affects nerve endings, explained Zis.

"Damage of the nerve endings can be associated with pain. A strict gluten-free diet removes the main factor causing the inflammation — gluten — alleviating the neuropathic symptoms, including pain."

It has been shown that patients with GN who follow a gluten-free diet experience less disease progression or improved neuropathy.  

"Our advice to patients with gluten neuropathy is that they will benefit from being on a strict gluten-free diet," said Zis.

But not all patients opt to embark on this diet, and some who do are not as strict as they should be, he said. "We know this because the antibodies are still there, whereas for those who are strict, the antibodies are eliminated."

Research shows that up to 50% of patients with celiac disease — the classic gastrointestinal presentation of sensitivity to gluten — are not strict with their diet, said Zis.

It can take up to a year after initiation of the diet for blood antibodies to normalize, he noted. In some cases, even traces of gluten might be enough to stimulate the immune system and produce antibodies.  

While celiac disease is typically more common in women, about three quarters (76.7%) of the study participants were male.

"The total number of patients assessed in this study was relatively small and therefore it would be difficult to derive any firm conclusions about this observation," said Zis.

He recommends that all patients with neuropathy be tested for gluten sensitivity, which he said is probably one of the most common causes of peripheral neuropathy.

"It's important for physicians to appreciate that gluten neuropathy can exist even in the absence of small bowel inflammation seen in celiac disease."

He stressed the importance of patients being tested with the appropriate serologic markers. In the current study, antigliadin antibodies were used "as they define the presence of sensitivity to gluten," said Zis.

He and his colleagues don't advocate that all patients with neuropathy go on a gluten-free diet,  just those with a sensitivity to gluten.

The Sheffield Institute of Gluten related Diseases has been involved in research into the neurologic manifestations of gluten sensitivity for over 20 years, said Zis.

Ongoing projects are looking at the entire spectrum of neurologic manifestations, for example, gluten ataxia and gluten encephalopathy. As well, laboratory work is examining novel biomarkers that may allow better diagnosis of gluten-related neurologic manifestations.

Zis and his team are now looking at the presence of small fiber dysfunction in patients with gluten sensitivity.

Intriguing Results

Asked to comment, Charles E Argoff, MD, professor, Albany Medical College; director, Comprehensive Pain Management Center, Albany Medical Center, New York, and member of the American Academy of Neurology, called the findings "intriguing."

"Given that one of the causes of painful small fiber neuropathy is celiac disease, the observations in this new study are especially interesting," Argoff said.  

Armin Alaedini, PhD, assistant professor of medicine, Department. of Medicine & Institute of Human Nutrition, and scientific director, Celiac Disease Center, Columbia University Medical Center, New York City, also commented on the results. Alaedini's lab has long been involved in studies of gluten sensitivity/celiac disease and the potential link to neurologic or psychiatric manifestations, including neuropathy and ataxia. 

The new study findings could be "very significant" because they suggest that ingestion of wheat and related cereals may be linked to certain symptoms in a subset of patients with neuropathy, said Alaedini.

"If the results are replicated in further studies, there could be a substantial impact on patient care."

However, several details weren't clear from the abstract, said Alaedini.

"More information about how long the study participants were on the restricted diet — and the potential link between the duration and symptoms — would be very helpful in interpreting the results and designing follow-up studies."

Zis, Argoff, and Alaedini have disclosed no relevant financial relationships.

American Academy of Neurology (AAN) 2018 Annual Meeting. Abstract 2356 P2.091. To be presented April 23, 2018.

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