The Integrative Practice

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Is Gluten Making you Miserable?

Learning Goals:

  • What is coeliac disease?

  • Coeliac disease & your mental health

  • Coeliac VS non-coeliac gluten sensitivity (NCGS)

  • Understand testing & interventions for coeliac and NCGS

Reading time 20 minutes.

A sometimes overlooked cause of psychological or neurological concerns such as anxiety, depression, “brain fog”, or chronic exhaustion lies in the immune activation caused by gluten in affected people - AKA the autoimmune condition coeliac disease (CD). CD is a perfect example of the gut-brain connection where immune activity and damage to the small intestines impacts on the brain and nervous system functioning.

CD is a lifelong condition, with diagnosed rates of approximately 1% of the western population and these rates have been increasing for various reasons including the changing microbiome as well as better awareness and screening. However, undiagnosed rates are estimated to be much higher. Dr. Alessio Fasano, a gastroenterologist and coeliac/autoimmunity expert, describes the development of coeliac autoimmunity using a “three-legged stool” metaphor 1) genetic predisposition, 2) intestinal permeability (“leaky gut”), and 3) environmental trigger/s. Each leg of the stool must be present in order for the autoimmunity to turn on. While a genetic predisposition is present from birth, coeliac autoimmunity can develop any time after you start consuming gluten containing foods and develop “leaky gut”, which may occur from gluten itself or another environmental trigger (e.g., a gastrointestinal infection or Epstein Barr virus). These epigenetic changes are commonly described as “genetics loads the gun, environment pulls the trigger.”

Gluten is found in wheat, spelt, rye, barley, and often oats, and, in people who are predisposed, will cause an immune response that attacks the small intestine, destroying the villi and microvilli which line the intestines (see picture below). Gluten is an undigestible protein containing gliadin and glutenin, which triggers the release of zonulin in the gut (Fasano, 2011). Zonulin “opens the doors” to your intestinal barrier and in CD gluten is mistaken for a dangerous bacteria hence a systemic immune response is mounted. The intestines are lined with finger like protrusions covered in enterocytes and microvilli.

Intestinal villi vs flattened villi in coeliac disease

To the left of the intestines, you’ll see a zoomed in view of healthy villi “fingers“ protruding that are undamaged and are home to healthy microvilli. Microvilli are responsible for promoting nutrient absorption from foods, hence the overlap between CD and malabsorption resulting in nutrient deficiencies of essential vitamins and minerals. To the right, you’ll see a flattened intestinal landscape lacking healthy villi and microvilli. The malabsorption resulting from CD is one cause of psychological symptoms and fatigue, as micronutrients are all critical for optimal brain and nervous system health (Gariépy, 2015). Another reason is because there is a link between bodily inflammation - such as that which occurs after consuming gluten in CD - and depression or anxiety symptoms via the immune system and inflammation. Other reasons include the life-limiting result of having to constantly avoid gluten which can be challenging in a modern diet largely comprising processed foods and when eating out. The question for someone with CD is always “is this safe for me to eat or will I get sick?”

Coeliac disease is complicated in that some other foods can mimic the effects of gluten and result in an immune or inflammatory response, through a process called “molecular mimicry.” Examples can include oats, corn, and dairy (and the jury is still out on coffee). Both A1 and A2 milk can poses similar problems as gluten for people with CD (Gariėpy, 2015). There can be the need to eliminate these foods either temporarily during intestinal healing work in the recovery from CD, or permanently if reactions continue.

Suspect Coeliac Disease?

“The problem is that it’s such a clinical chameleon. Some people have no gastrointestinal symptoms whatsoever, and no one presents in the same way.”

Dr Allisio Fasano, Gastroenterologist

Possible indicators that warrant further investigation:

  • Unexplained nutrient deficiencies (or suboptimal levels) such as B12, folate, iron or zinc. These biomarkers can indicate a wider array of deficiencies and so are necessary but not sufficient to treat.

  • First degree family history of CD (1/10 increased risk if so).

  • Anxiety, depression, or lasting fatigue that hasn’t resolved from expected therapies (e.g., psychological approaches, lifestyle change such as sleep intervention, exercise, yoga or meditation).

  • “Brain fog” - a sluggish or hazy brain with difficulty focusing or concentrating and accessing thoughts or memories.

  • Gastrointestinal symptoms such as abdominal pain, bloating, diarrhoea and/or constipation.

  • Other autoimmune health problems such as hashimoto’s thyroiditis or unexplained chronic health symptoms.

  • Autism spectrum disorders and schizophrenia have also been associated with CD in some cases.

  • Note. There are cases of “silent coeliac disease” which as the name suggests involves no indications whatsoever although mucosal damage to the intestines is occurring. Gluten and autoimmunity expert Dr Fasano recommends a low threshold for testing CD for this very reason.

Coeliac Disease and Psychological Wellbeing

As a clinical psychologist I regularly screen clients for CD whenever someone has chronic experiences of anxiety or depression, unexplained fatigue, brain fog or neurological symptoms, or any chronic physical health presentation.

Testing and Diagnosis

There are currently two forms of diagnostic testing include CD antibody testing and genetic testing which you can request as a blood test via your GP (note: there may be a cost). A subsequent biopsy of the small bowel may be ordered if these tests are positive. (Note. the nature of the IGA-tTG test means that a negative test doesn’t automatically rule out issues with gluten).

Specific genetic tests:

  • HLA DQ2

  • HLA DQ8

Note: Gene testing alone is not diagnostic but is useful if someone can’t do the 4-6 week gluten challenge required the antibodies tests. Gene testing can rule out coeliac disease, as if you have neither gene then you can be 95-99% sure you do not have CD.

Specific antibody tests:

  • IGA-tTG (tissue transglutaminase),

  • +/- Endomysial antibodies,

  • and +/- Deamidated gliadin peptide antibodies.

Note: Antibody testing requires that you consume gluten (minimum 4 slices of bread per day for 4-6 weeks) in order to get an accurate result (e.g., if you are no longer eating gluten, you may have no longer show an antibody response although you could still have CD).

A small bowel biopsy is the gold standard for confirming a diagnosis after someone has completed genetic and blood testing. So, if you have coeliac signs or symptoms, either or both genes, positive antibodies, damage to the intestines and your symptoms go away after a gluten-free diet and re-occur with exposure to gluten, then CD can be confirmed.

But whether or not to go through this full process required for a diagnosis is an individual choice. The gluten challenge and biopsy can be extremely undesirable or debilitating for many people already benefitting from a gluten-free diet. It depends what your aim is, as if you have either of the genes and feel better on a gluten-free diet and worse if you consume gluten, than that is often enough for many people to commit to long-term avoidance of gluten.

What if it’s Not Coeliac Disease?

Some people have no biomarkers for CD yet still react to gluten and will do better on a gluten-free diet. These cases could involve a specific wheat allergy (requiring only removal of gluten in wheat) as well as non-coeliac gluten sensitivity (NCGS). A 2016 study on NCGS found that there was a subset of individuals without CD or a wheat allergy who experienced a gluten sensitivity with immune activation and “leaky gut” (Uhde et al., 2016). Wheat allergy can be tested for with food allergy screening while NCGS may be a proposed explanation if wheat allergy and CD has been ruled out.

Recommendations for Coeliac Disease or NCGS

  • Anticipate a stage of adjustment with many thoughts and feelings about what it means for you and your life. There can be grief and loss, embarrassment or shame, and real world implications in needing to learn how to eat, shop, travel and socialise differently.

  • The ability to communicate your dietary needs to friends, partners, family and hospitality staff takes practice and assertiveness skills. Acceptance takes time and occurs when you have fully comes to terms with the need to cease gluten.

  • Lifelong avoidance of gluten containing foods, medicines and care products (gluten can hide in a lot of unexpected places!). This is the only effective treatment available to prevent chronic immune activation and further intestinal damage.

  • Stopping gluten can include cravings for certain foods and a struggle to stay off these for some - this often comes to an end when there is enough discomfort and health consequences to no longer make the “minute on the lips” worth it.

  • Commit to the time required to heal your intestinal lining and “leaky gut” - encourage microvilli to thrive so you can absorb nutrients optimally. Things can improve in time.

  • Monitor levels of B12, folate and iron through routine blood tests with you GP or whenever you notice psychological or chronic health symptoms returning.

  • Ensure adequate dietary intake through iron and zinc rich foods (e.g., red meats) and B vitamin containing foods (e.g., eggs). However, diet alone may not be sufficient to ensure you are receiving optimal nutrients, especially in the coeliac recovery phase of restoring your villi (minimum 2 years) and so plugging any gaps with a high quality multi-nutrient is recommended.

  • To support accidental “gluten-ing”, there are acute interventions to respond and support your intestinal health including 1) anti-inflammatory agents such as curcumin or fish oil, 2) immune system supporting vitamins and minerals such as Vitamin D, Vitamin A, and zinc, 3) products that help the intestinal lining such as glutamine, and aids such as digestive enzymes and specific strains of probiotics (e.g., lactobacillus rhamnosus) that may be beneficial. Working with a health professional that can advise and prescribe is recommended where possible. (Note. there is no “free lunch” with getting glutened and choosing to eat gluten because of these interventions is not advised - damage to your intestines will be occurring each time).

When it comes to dietary change for CD there is “gluten-free” and gluten-free. Plenty of gluten-free food is highly processed and low in nutrients. A good framework can be to follow more ancestral diets, including whole foods like fresh fruits and vegetables, nuts and seeds, animal products including eggs, red meat, poultry and sea food as well as dairy if you tolerate this (Note. many with CD need to go diary-free short- or long-term due to molecular mimicry). The Mediterranean diet is one example of a whole food diet that also has research support as a mental health therapy for depression (Jacka et al., 2017). However, some people with “leaky gut” from gluten may not tolerate the legumes and pulses or non-gluten containing grains of the Mediterranean diet, and so it often advisable to work with a nutrition specialist who has expertise in CD for a personalised nutritional plan, as tailoring a diet that suits your needs is recommended.

You can heal and recover if you have CD/NCGS and you remove gluten from your diet long term. Gluten elimination does not have to be viewed as a life sentence to be endured - instead it’s an opportunity to discover all the real food that makes your health thrive and to focus on what you can eat and enjoy that!

Check out Coeliac New Zealand for more information on CD.



References

  1. Clappison, E., Hadjivassiliou, M., & Zis, P. (2020). Psychiatric manifestations of coeliac disease, a systematic review and meta-analysis. Nutrients12(1), 142.

  2. Campagna, G., Pesce, M., Tatangelo, R., Rizzuto, A., La Fratta, I., & Grilli, A. (2017). The progression of coeliac disease: its neurological and psychiatric implications. Nutrition research reviews30(1), 25-35.

  3. Fasano, A. (2011). Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiological reviews.

  4. Fasano, A., & Catassi, C. (2012). Celiac disease. New England Journal of Medicine367(25), 2419-2426.

  5. Gariépy, C. (2015). Dietary peptides and the spectrum of food hypersensitivities. In J.M Greenblatt & K. Brogan. (Eds.). Integrative therapies for depression: Redefining models for assessment, treatment and prevention (pp. 223 - 240). CRC Press.

  6. Jacka, F. N., O’Neil, A., Opie, R., Itsiopoulos, C., Cotton, S., Mohebbi, M., ... & Berk, M. (2017). A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’trial). BMC medicine, 15(1), 1-13.

  7. Uhde, M., Ajamian, M., Caio, G., De Giorgio, R., Indart, A., Green, P. H., ... & Alaedini, A. (2016). Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut65(12), 1930-1937.

  8. Sapone, A., Bai, J. C., Ciacci, C., Dolinsek, J., Green, P. H., Hadjivassiliou, M., ... & Fasano, A. (2012). Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC medicine10(1), 1-12.