FACT 5 – Autoimmune Disorders Occur Ten Times More Commonly in People with Celiac Disease (CD) Than in the Normal Population.
“Autoimmune diseases are the third leading cause of morbidity and mortality in the industrialized world, surpassed only by cancer and heart disease.”Annals of the rheumatic diseases Sept 2007
Autoimmune disorders are believed to affect approximately 8 percent of the US population or 24 million people. That’s more people than are affected by heart disease (22 million) or cancer of all forms (9 million). This suggests autoimmune disorders may be the number one cause of death in the U.S.
Autoimmune disorders occur 10 times more commonly in CD than in the general population“with type 1 diabetes and autoimmune thyroiditis leading the list. The presence of celiac disease in type I diabetes, for instance, is approximately twenty-times higher than in the general population. The autoimmune antibodies associated with CD include anti-endocrine, anti-gastrointestinal, anti-nuclear, anti-cytoskeleton and anti-neurological antibodies.
CD is believed to trigger autoimmunity through a variety of mechanisms including HLA and non-HLA genes, mimicry, altered intestinal permeability, epitope spreading and others. One study suggested long duration exposure to gluten products is associated with higher rates of autoimmunity in celiacs.
The longer celiacs are exposed to gluten the greater the risk they have of developing an autoimmune disorder.
“Our data show for the first time that the prevalence of autoimmune disorders in Celiac disease is related to the duration of exposure to gluten Gastroenterology August 1999
The age the patient was Diagnosed with CD
The presence of other autoimmune condition in addition to CD
Unfortunately most celiacs spend 5-10 years going from doctor to doctor before a correct diagnosis is made.
Immune, Liver and Cardiovascular Affects
CD is linked with many other diseases including liver and heart diseases, osteoporosis, myopathies, schizophrenia, small- fibre neuropathy and more: Celiac disease was associated with an 8-fold increased risk of death from liver cirrhosis. One study found osteoporosis in 50% of celiac patients. In fact, the rate of celiac disease in osteoporosis is high enough that some recommend all osteoporosis patients undergo CD screening.
CD triggered inflammation appears may be to cause or contribute to myopathy, a muscle disorder characterized by muscle weakness. A large epidemiological study involving almost 80,000 individuals suggested that every type of cardiovascular disease (heart attack, heart failure, stroke, etc.) is increased in patients with untreated celiac disease.
The Nervous System
IgG antibodies were present in 34% and biopsy demonstrated villi destruction (celiac disease) in 9% of people with idiopathic peripheral neuropathy including small-fiber neuropathy. (Another study, however, concluded the two were not linked, but a large Swedish study involving 14,000 people with celiac disease and 70,000 healthy controls found increased risk of peripheral neuropathy (but not increased risks of neurological disorders such as Parkinson’s, Alzheimer’s, multiple sclerosis, Huntington’s disease, myasthenia gravis.)
The study authors suggested people with peripheral neuropathy get tested for CD. Recent studies suggest a form of peripheral neuropathy called small fiber neuropathy is common in fibromyalgia.
Gluten sensitivity was present in a third of patients with sensory ganglionopathy (SG), a disorder characterized by damage to the cranial and spinal ganglia, usually by autoimmune processes. Autopsy’s of the three gluten sensitive, SG patients indicated damage to the dorsal ganglia.
Large Swedish Studies Highlight Risk
Sweden’s large medical databases have helped to elucidate the remarkable impact celiac disease can have on the body.
Adult celiac disease was associated with increased risk of pancreatitis. A large Swedish study found celiac disease to be associated with increased risk of a raft of liver diseases including hepatitis, liver failure, primary biliary cirrhosis, liver cirrhosis and fibrosis and fatty liver.
Immune dysfunction and inflammation is believed behind the increased rates of sarcoidosis in people with celiac and kidney disease. Even fractures got in the act with the Swedes finding increased risk of hip and other fractures in people with CD. Increased risks were also found in diabetes (relatively low risk), thyroid disease and adrenal disease (greatly increased).
Not surprisingly, given the impact Celiac disease can have on the body rates of depression are increased after celiac disease (but not before it).
…When the finely tuned trafficking of macromolecules is dysregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune disorders can occur… Nature clinical practice. Gastroenterology & hepatology Sept 2005
Although research has yet to confirm the link between autoimmunity and non-celiac gluten sensitivity (NCGS), the largest study ever completed on gluten sensitivity suggests mortality rates are higher for people with NCGS than Coeliac disease (CD). That suggests it’s probably just a matter of time before similar correlations regarding autoimmunity are made.
Indeed, the study found that people with gut inflammation (which is characteristic of NCGS) are also highly likely to suffer from “leaky gut” – which is strongly associated with the onset of autoimmune disorders – and appears to be common in ME/CFS/FM.
The GI track regulates the flow of macromolecules between the gut and the rest of the body. Some researchers believe the introduction of harmful macromolecules into the blood stream commonly triggers autoimmune processes, both inside and outside of the gut.
It is also important to understand that even if your gut exhibits no villous atrophy (celiac disease), and no intraepithelial lymphocytosis (inflammation), gluten sensitivity (positive IgA and IgG blood tests to gluten), may still be triggering an autoimmune process that’s attacking other organs in your body.
“Antigenic mimcry” is one way CD is believed to cause autoimmunity outside the gut. As the body becomes sensitized to gluten, it can mistakenly attack molecules similar to gluten, such as those associated with the thyroid gland.
The common immunogenetic theories ….are sharing common HLA and non-HLA genes, antigenic mimicry, damage-induced neoantigen exposure, altered intestinal permeability, idiotype network dysregulation and epitope spreading”
The below autoantibodies have been associated with CD; notice that most involve the gut.
According to the latest textbook: Advancing Medicine with Food and Nutrients 2nd Edition, correlations between the illnesses below and NCGS have been confirmed:
- Cereballar Ataxis
- Peripheral Neuropathy
- Brain atrophy
- Irritable bowel syndrome
Where CD/NCGS has affected the gut, taking gluten out of the diet may NOT be enough for clinical improvement. The fire of inflammation in the gut must be put out, and intestinal permeability MUST be healed to restore absorption. Taking gluten out stops feeding the fire, but the inflammatory cascade has a life of its own, and unless there is a specific healing intervention gut permeability may continue.
Less than half of patients with coeliac disease on a gluten-free diet have complete normalization of intestinal biopsies, intestinal permeability defects, and antibody levels (after a mean of 9.7 years on a GFD) Digestive diseases and sciencesApril 2010
It is important to understand that children with CD had a 3 fold increase of long-term mortality – whether they were on a gluten-free diet or not.
This suggests taking gluten out of the diet is not enough. Although the villi of CD patients does grow back after 1 year on a gluten-free diet, the evidence suggests that increased intestinal permeability and poor absorption – both linked with autoimmunity – is still present. So the gut must be healed and any inflammatory cascade dealt with even after gluten is removed.
The difficulty of adhering to a gluten-free diet can make prognosis difficult. Strict adherence to a GFD does greatly improve nutritional status but one study found it did not completely normalize ‘body composition’. Metabolizing B-vitamins, in particular, may still be reduced even after a gluten-free diet. Hallert et al. found that celiac patients on long-term gluten-free diets with normal gut villi, had reduced plasma B-vitamin (homocysteine) levels. Forty-five percent of celiac disease patients on a gluten free diet for decades had reduced bone mineral density (osteoporosis).
Increased rates of peripheral neuropathy even in ‘well treated coeliac disease’ indicate that neurological problems can manifest themselves even when ‘overt malabsorption’ is not present. While substantial improvement in gut mucosa and other factors did occur 2-4 years after beginning a gluten-free diet, lactase activity was still reduced. One study suggested ‘leaky gut’ was still common a year after beginning a gluten-free diet.
Finally, quality of life measures that improve after initiating a gluten-free diet but are still somewhat reduced relative to the general population also suggest that simply removing gluten, while beneficial, is often not sufficient to return one to full health.
FACT 7 – The Cross-sensitization Factor: Taking Gluten Out of the Diet May Not Be Enough if You’ve Become Sensitized to Other Foods As Well
Even minute traces of gliadin or their cross-reactive foods are capable of triggering a state of heightened immunological activity in gluten sensitive people Journal of neurology, neurosurgery, and psychiatry.Dec 1997
Cross-sensitization refers to a process whereby a person becomes sensitized to new substances. For instance, people sensitive to the gluten proteins called gliadins found in cereals in the Triticum genus (wheat, rye and barley) can become sensitized to other types of foods.
Foods known to cross react with purified gliadins (wheat proteins) make up the first line (rye, barley, spelt, cow’s milk, whey protein plus milk chocolate and coffee) of the chart above. The other foods on the chart (most grains, soy, egg, potato, yeast, coffee, sesame, buckwheat) are foods people often turn to on gluten-free diets but which they may have become sensitive to. Some foods such as oats are prepared in facilities where gluten contamination is common. Even small traces of gliadin can trigger an immune response in very gluten sensitive people.
FACT 8 – The Current CD Test Does Not Test for Gluten Proteins People Can React to or Cross-Sensitized Foods.
Also there are at least 24 celiac-associated auto-antibodies that could be tested for, not just gut related autoantibodies
The Standard coeliac test is made up of three elements:
Two antibodies to parts of the BODY i.e.; AUTOIMMUNITY in the gut:
- To the endomysium – the sheath which encloses the villi
- To transglutaminase – an enzyme inside the endomysium
Plus antibodies to gluten.
- Antibodies to the gluten protein gliadin. Recently this has changed to deamidated gluten which has been found to be more accurate to diagnose CD, but not NCGS.
Problems With The Current Testing Protcols
( Antibodies to endomysium and transglutaminase are EXECELLENT markers for TOTAL VILLUS ATROPHY (ie celiac disease) but are highly unreliable diagnostic markers for the partial villous atrophy or increased epithelial lymphocytes found in non-celiac gluten sensitivity (NCGS). Only between 30% and 24% of patients with partial villous atrophy (NCGS) and coeliac disease were diagnosed correctly using antibody tests in two studies.
The antibody test to the gluten protein ONLY checks for one TYPE of gluten (called the 33-mer peptide.) If all you do is check the gluten 33-mer (the standard test) you’ll miss gluten sensitivity 50% of the time. Studies consistently show that most people with CD react to a range of gluten peptides, some as strongly as the gluten-33 mer that is typically tested for.
Note that gluten is found in ALL grains, however a subset of gluten proteins particularly toxic to some humans are found in wheat, rye and so on. An assay that includes IgA and IgG antibodies for a range of gluten peptides ( see www.CyrexLabs.com), therefore, is desirable;
Our present results indicate that CD patients are capable of responding to a large array of gluten peptides. We found that 50% of these patients do not respond to the alpha-GLIA peptide but to a diverse set of gliadin and glutenin peptides, including 6 novel epitopes.”
Gastroenterology June 2002
Niki to find referenced paper link for the above.
If we take into account that gluten sensitivity doesn’t just cause CD, but also partial villous atrophy and gut inflammation, AND probably triggers many disorders outside the gut including autoimmune disorders, AND the fact that people react to a range of gluten molecules, not just the one in the standard CD , it begs the question how much of the population is sensitive to some form of gluten?
Dr. O’Bryan believes between 10 and 35% of the population.
“Gluten Sensitivity (GS) is a state of heightened immunological responsiveness to ingested gluten in genetically susceptible people. It represents a spectrum of diverse manifestations, of which, the gluten sensitive enteropathy known as CD is one of many. Adverse reactions to the toxic family of gluten proteins found in wheat, barley, rye, and their derivatives may trigger a heterogeneous set of conditions, including wheat allergy (IgE), NCGS, and CD, that, combined, affect between 10 – 35% of the population.”
- Read Part 1 of this article covering a epidemic of misdiagnosis, comorbidity and mortality.
- Read Part 3 which focuses on the direct link between CFS and Gluten Sensitivity and next steps
- Dr. O’ Bryan’s 1 day Doctors training on Gluten on DVD for US Practitioner
- Dr O’Bryan’s 1 Day Training on Gluten for Practitioners in the UK
- Dr O’Bryan’s DVD on Gluten for patients in the US
- Dr. O’Bryan’s 1 day seminar on Autoimmunity
Keep Health Rising….RISING
After years of work it’s time to attempt what we’ve never been able to do before – get Congress to force the NIH to double its funding for ME/CFS. Support the historic bill to increase research funding, add new ME/CFS research centers, require the development of a strategic plan, etc.. It will take less than 5 minutes.