Grain field on a wheat farm

Read the final 2 facts 9-10 about Chronic Fatigue Syndrome (ME/CFS) and gluten sensitivity below.

FACT 9  – Research on Dietary Intervention in ME/ CFS is Mainly Based  on the Classical IgE Mediated Approach to Food Allergy Which is Outdated

Despite clear evidence for non-IgE mediated food sensitivities such as IgG and IgA delayed sensitivities to foods like gluten, studies on CFS continue to ignore the research.

In the Scandinavian Journal of Gastroenterology in Sept 2012   in the paper called “Functional bowel symptoms, fibromyalgia and fatigue: a food-induced triad?” researchers reported:

“In a prospective study, 84 patients referred to our outpatient clinic for investigation of perceived food hypersensitivity were enrolled consecutively……Neither IgE-mediated food allergy nor organic pathology could explain the patients’ symptoms.”

The above paper did not test for CD, or NCGS nor IgG or IgA cross-sensitised foods, and reflects what Manu et al concluded back in 1993 below, which is essentially that  if IgE mediated allergies are not identified, CFS patients’ assertions that they have sensitivities to food is mental or emotional in origin.

 “Intolerance to various foods is reported often by patients seeking evaluation for chronic fatigue. To assess the prevalence and significance of this phenomenon we studied 200 consecutive patients with chronic fatigue who were given a comprehensive medical and psychiatric evaluation…

These data suggest that intolerance to multiple foods is probably not a cause or the effect of chronic fatigue, but rather one of the manifestations of the somatization trait expressed in these patients.

The food intolerances in the above study were assessed simply by asking patients which foods they were intolerant to. In classical IgE allergy, foods cause immediate and obvious reactions which can easily be self-identified, unlike IgG and IgA reactions where identification of the offending food is much more difficult due to the delayed reaction.

We know that people with Celiac disease (CD) may not improve just on a gluten-free diet but may need gut healing work as well. We know that in the most sensitive 1/90th of a piece of bread can cause symptoms for 6-8 weeks, and that people may have developed cross-sensitization to non-gluten foods such as instant coffee, all dairy and milk chocolate as was discussed in part 2 of these series of articles.

In the studies quoted below, ME/CFS patients may have failed to improve from restricting gluten because all gluten or cross-sensitized foods were not adequately restricted, and no specific intervention were done to heal the gut and reduce inflammation.

 “A 24-week randomized intervention study was conducted with 52 individuals diagnosed with CFS. Patients were randomized to either a low sugar low yeast (LSLY) or healthy eating (HE) dietary interventions…In this randomized control trial, a LSLY diet appeared to be no more efficacious on levels of fatigue or QoL compared to HE.”

In the 2012 Trabal et al study in the Spanish Journal Nutrición Hospitalaria a cross sectional pilot study with 28 ME/CFS patients assessed their dietary eating habits with food frequency questionnaires. They reported that the digestive symptoms of the 15 patients restricting gluten and 22 restricted dairy did not improve and  concluded:

“Dietary restrictions should be based on a proven food allergy or intolerance. Dietary counseling should be based on sound nutritional knowledge.”

Despite these negative studies, Logan and Wong reported on several studies where dietary restrictions made a large improvement in ME/CFS:

Nisenbaum et al presented an abstract at the American Association for Chronic Fatigue Syndrome conference in Seattle in January 2001, showing that 54 percent of a sample of CFS patients had attempted unspecified dietary modifications. Of these individuals who modified their diet, 73 percent reported dietary changes were beneficial in reducing fatigue.

 In an Australian study, CFS patients eliminated wheat, milk, benzoates, nitrites, nitrates, and food colorings and other additives from their diet…Of the CFS patients who complied, the results were remarkable: 90 percent reported improvement in the severity of symptoms across multiple body symptoms, with significant reduction in fatigue, recurrent fever, sore throat, muscle pain, headache, joint pain, and cognitive dysfunction. Furthermore, the elimination protocol resulted in a marked improvement in IBS-like symptoms among allpatients; a significant finding because CFS patients have a high rate of IBS.

 The results of this study support the findings of Borok published in the South African Medical Journal over a decade ago.Borok cited a strong correlation between CFS and the presence of food intolerance. He reported alleviation of chronic fatigue among CFS patients (n=20) after removing certain foods from the diet, with milk, wheat, and corn among the top offenders. Alternative Medicine Review 2001

No studies to date have adequately assessed the presence of Celiac disease or Non-Celiac-Gluten Sensitivity (NCGS) in ME/CFS. Nor have studies tested the effectiveness of  a strict gluten-free diet and with a gut healing anti-inflammatory intervention. These studies are needed before we can assess the impact gluten and gut inflammation has on this and other related disorders.

Stethoscope lying on an ECG chartFACT 10  – Every Person With Chronic Fatigue Syndrome Should Be Screened for Coeliac Disease and Non Celiac Gluten Sensitivity (NCGS) as Part of the Differential Diagnosis of the Condition

Several factors suggest CD and NCGS should be part of the differential diagnosis for chronic fatigue syndrome (ME/CFS).

Neurological symptoms in CD are common (as was discussed in part 1 of this blog series). Back in 1999, Luostarinen et al, in European Neurology, stated that CD should be considered in all patients presenting with neurological disturbances such as memory deficits and ataxia of unknown etiology, two symptoms  that commonly occur in ME/CF.

In their paper “Gut inflammation in chronic fatigue syndrome” in Nutrition and Metabolism in 2010, Lakhan et al discuss the evidence for leaky gut and inflammation in CFS at length. Citing studies by Maes et al, Logan et al, Sullivan et alRao et al and Sheedy et al they concluded imbalanced gut bacteria linked with gut inflammation and gut permeability is common in ME/CFS.

Small-fibre neuropathy may be common in ME/CFS/FM and muscle pain is. Symptoms of small-fibre neuropathy including tingling, burning pain and tightness, stabbing pain, pins and needles, itchiness and intermittent numbness in different parts of the body, are commonly experienced in ME/CFS and gluten triggered autoimmune ganglioside antibodies can produce all these symptoms.

The Rituximab studies with CFS patients and other studies suggest autoimmunity is likely to be present in a subgroup of CFS/ME patients.  Celiac disease and Non-Celiac-Gluten-Sensitivity (NCGS) may be able to trigger autoimmune processes by triggering B Lymphocyte activation. Rituximab’s reversal of (gluten-triggered) B-lymphocyte activation could, therefore, account for some of the progress some ME/CFS patients make on that drug.

 The landmark 2000 Lancet study on non-IgE mediated food sensitivities (“Relation between food provocation and systemic immune activation in patients with food intolerance”) indicates that people with non-IgE mediated food intolerances experience significant elevations in inflammatory cytokines (interleukin-4, interferon gamma, TNF-α) when given a dietary challenge of dairy and wheat. 

The authors noted that cytokine elevations could account for the post-food challenge symptoms experienced such as headache, myalgia, joint pain, and gastrointestinal disturbance – all of which are common in ME/CFS.

“We found that food provocation in food intolerant patients was characterised by a general and systemic immune activation accompanied by an increase in systemic symptoms. Our findings might be important for the understanding of the mechanisms involved in the pathogenesis of food intolerance.”  Lancet July 2000

Other more direct links to coeliac disease and chronic fatigue syndrome exist. Skowera et al found a high prevalence of markers of Celiac disease in 100 CFS patients in 2001.  Empson’s 1998 critique of the diagnostic criteria for ME/CFS asked why ruling out CD was not included.

“given our prevalence of 2%, and the fact that there is a treatment for CD, we now suggest that screening for CD should be added to the relatively short list of mandatory investigations in suspected cases of CFS.”Skowera et. al. 2001

As we have discussed, sensitivity to gluten is likely much higher than 2% in the CFS population, as the diagnosis of CD requires total villous atrophy and thus misses out on gluten-sensitive individuals with partial or no villous atrophy in the non-celiac gluten-sensitive group.

A preliminary paper in the International Journal of clinical practice in 2001, found no link between CD and Chronic Fatigue Syndrome, but again the standard CD test used in this study completely misses the NCGS group with partial villous atrophy and gut inflammation. As we pointed out in Part 2 of this series of articles, people with NCGS may have no overt gut involvement at all but still test positive for gluten antibodies. 

The standard CD antibody test may, because it doesn’t test for all twelve gluten peptides,  underdiagnose gluten sensitivity by as much as 50%. 

Wheat in a fieldWhy Are so Many  More People Sensitive to Gluten Than Thought?  

A popular reason given for sensitivity to gluten is due to genetics. The “Paleo” diet movement has often pointed to research suggesting pre-agriculture Stoneage man may have been free of many of the complex chronic illnesses we face today. Some evidence suggesting increased rates of chronic illness occurred in the post-agricultural era, suggests the human genome was not fully equipped to deal with the agricultural revolution and the consumption of grains.

A recent study of the genetics of 2500 Australians published on BioMed Central in August this year found that over 50% of the Australian population have the genetic propensity to develop celiac disease. Researchers are now looking to find out why some people develop the disease and others don’t.

However, a remarkable study from the Mayo Clinic in 2009 suggests a different kind of genetic issue may be in play. This study cites genetic Modification (GM) of wheat as one of ten factors that may account for the 400% increase in undiagnosed CD since the 1950s.

 “The prevalence of undiagnosed CD seems to have increased dramatically in the United States during the past 50 years.” Gastroenterology June 2009

In this study over 9000 blood samples gathered at the Warren Air Force Base in Wyoming between 1948 and 1954, were tested for autoantibodies to gluten, and then compared to age or birth-year matched recently collected from Olmsted County, Minn. Researchers found that young people today are 4.5 times more likely to have celiac disease than young people were in the 1950s, while those whose birth years matched the Warren AFB participants were four times more likely to have celiac disease

Joseph Murray, M.D., the Mayo Clinic gastroenterologist who led the study stated:

Celiac disease is unusual, but it’s no longer rare…Something has changed in our environment to make it much more common. Until recently, the standard approach to finding celiac disease has been to wait for people to complain of symptoms and to come to the doctor for investigation. This study suggests that we may need to consider looking for celiac disease in the general population, more like we do in testing for cholesterol or blood pressure.”

Murray suggested genetic modifications to produce hardier, shorter, and better-growing plants may have contributed to recent increases in gluten sensitivity. In an interview in the Mayo Clinic newsletter in 2010 Dr. Murray listed several other possible environmental causes of increased celiac disease. The “hygiene hypothesis” suggests our modern emphasis on cleanliness confuses an immune system adapted to a less clean environment so much that it accidentally turns on the body.  Another potential culprit is a 21st century diet that features novel ways of processing wheat.  “Many of the processed foods we eat were not in existence 50 years ago” Murray said.

View detailsWhat About GMOs, the modern form of Genetic Modification?

Genetically modified organisms (GMOs) are plants or animals that have been genetically engineered with DNA from bacteria or viruses or other plants and animals. Some researchers are concerned with the immune reactions foods that are “new to nature” may cause. 

The vast majority of wheat grown in the US and Europe is not GMO but the the majority of corn (maize)  (88%) and 93 percent of soy grown in the US is GM. Although Europe rejected GMO for direct human consumption, the increasing use of GMO in animal feeds suggests GMO products are making their way into the diets there.

Given that old-fashioned forms of genetic modification of wheat have created a “new-to-nature” food which the Mayo Clinic site as one likely cause of increased immune system sensitivity, is it possible we will find increased immune system sensitivity to GMO corn and soy as well, and that reactions to these foods are not just due to cross-sensitivity to gluten?

The ongoing debate on health concerns about GMO is controversial and will be covered in a separate blog post.

I Have Chronic Fatigue Syndrome – What Can I Do To Determine if I have Celiac Disease or Non-Celiac-Gluten Sensitivity?

Science lab test tubesHow Do I Get Tested?

Antibody Testing – First, have the antibody blood test done for CD. If that comes back negative, check for NCGS first by Array #3 antibody testing from Cyrex Labs in the USA or Regenerus Labs in the UK. If that’s not available, a trial period of eliminating gluten is rational.

Endoscopy – If you are having an endoscopy/biopsy done request that an IEL (Intraepithelial lymphocytes)  count be done to assess inflammation in the gut. Most pathologists don’t do it but it’s easy and inexpensive (about $40). This test will determine if you fall into the inflammatory sub-clinical group of NCGS patients.

Cross-sensitized foods – If the Array 3 comes back positive, you can then request Array 4 from Cyrex labs to test for cross-sensitized foods. The lab automatically saves the original blood sample for 3 months so another blood sample is not needed.

You may already know you have some form of gluten sensitivity; to confirm this, do the same test as above. Note: don’t worry if you have not eaten gluten before doing the test and DO NOT go back on gluten for the test because it can have very adverse effects on some patients. Much of the time, even if you thought you were gluten-free, you’ve probably still been exposed, unknowingly and this testing will confirm that.

Slice taken from a loaf of bread, close-upHow Do I Follow a Gluten-Free Diet?

An important fact is that mortality rates rise after the first year of going gluten-free possibly due to gluten withdrawal and because blood sugar problems arise as some people start to skip meals.

Cardiovascular disease was the most common cause of death in Coeliac disease, followed by malignancy. The highest HRs were seen in the first year after biopsy, with an HR of 3.78 for death due to malignancy and 1.86 for CV death.

Journal of the American Medical Association.

Dr O’Bryan recommends a “Modified gluten-free” diet, which is essentially a gluten-free diet designed to manage blood sugar imbalances and the crashes which often occur in the early withdrawal phase from gluten. A low sugar diet, eating five meals a day, and other standard recommendations to manage blood sugar levels are needed to prevent blood sugar falling too low or rising too quickly.

Following a gluten-free diet when even a crouton in your salad can cause problems takes time to master. (Did you know gluten is present in cosmetics and personal hygiene products too? That gluten doesn’t go through your skin;  instead it gets inhaled,and in the very sensitive can cause adverse effects.)

Dr  O’ Bryan’s DVD for patients, where he works with an experienced gluten-free chef, an be very helpful. Sharing the same toaster as one used for bread containing gluten has been found to affect people with celiac disease, so it would be best if the entire family goes gluten free. Hence Dr O’Bryan recommends the entire family sits and watches the DVD for patients together.

I have provided a short summary of these series of 3 articles on my blogsite and a full set of initial guidelines to transition successfully off gluten for free on my blogsite here: How and Why to go Gluten Free.

Many free resources for living gluten-free can be found online; a short list is provided below.

View detailsHow Do I Heal My Gut?

It is clear that even people with confirmed cases of CD often do not completely recover after going on a gluten-free diet, and that  gut healing and anti-inflammatory intervention with follow up testing  may be required as well. This is a topic that will be covered in the next series of articles. So stay tuned folks!


Free Info For Patients

Read the First Two Part’s of Niki’s Gluten Intolerance Blogs





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