"You should consider eliminating all gluten and dairy from your diet for 3 months."
Those words hung in the air like an alien spacecraft hovering between us.
When I had the good sense to consult a naturopath after my diagnosis with postpartum thyroiditis, this was the backbone of her recommendation to me. To me, as a psychiatric fellow, 9 years into my medical training, gluten had no relevance to the non-celiac population.
Celiac disease was a rare and unfortunate affliction that made living a "normal" life impossible because of the strict prohibition on, what seemed to me at the time, all food. Raised on classic Italian pastas, lasagnas, and paninis, and a NYC pizza and bagel-ophile, I honestly couldn't conceive of what I would eat. Fast-forward five years, several hundred medical journal articles, conferences, seminars, and a personal health revolution later, and I am now convinced of the imperative for all people to eliminate this inflammatory food from their lives. I plan to detail – be forewarned: science to follow – the information that made me change my tune on this seemingly innocuous, but quite ubiquitous "food". Here's the goods in 1500 words:
We Know Why and How it Hurts You
Sometimes, as I read a medical paper, I get this euphoric rush that makes time seem to slow down (nerd alert). I grip the pages a bit tighter and I savor what is to come because I know that I am experiencing paradigm-shifting information, first hand. When I read this paper by Alessio Fasano in 2011, I knew the processed food industry was going to have to think fast to get out from under this knowledge. In a feat of scientific brilliance, he connected the dots for us and explained the following:
- The gut does more than absorb food – it is the barrier determinant of self and non-self that educates the immune system. Here is where our bodies learn about what to attack, and where they can be miseducated about attacking themselves (autoimmunity).
- The trafficking of macromolecules across the gut barrier requires a facilitator – a doorman who lets them through. This agent is called zonulin and opens the spaces or tight junctions between gut cells.
- Zonulin is triggered by gliadin which is the protein found in the grains wheat, rye, and barley. This triggering occurs in 80% of the population based on hereditary haplotypes.
- There is reason to suspect that prolamine grains including the above and corn, sorghum, and oats (called this because of their high proline and glutamine content) may all play a role in triggering these dynamic gut changes. Cross-reactivity and stimulation of alpha gliadin by foods like dairy, oats, corn, millet, and even instant coffee was examined in this study suggesting that those with limited clinical improvement on a gluten free diet (but with positive antibodies) should also consider broader eliminations.
- Immune activation is mediated by changes in gut permeability and blood brain permeability. Essentially, once local inflammation is kicked off and the door to the blood stream is opened, the immune system responds. This permeability also allows for the passage of toxins from bacteria called lipopolysaccharide that may play a significant role in depression as discussed here.
Inflammation and Immune Stimulation
The nature of this immune response is becoming better elucidated. Here are some important conceptual players:
This is an immunologic concept that appears to lie at the root of a lot of what ails us in this world full of foreign particles. The immune system reacts to unknown/novel compounds through the innate system, which is mediated by white blood cells including macrophages and dendritic cells, complement cascades, natural killer cells, and cytokines. This arm of the immune system instructs the "learned" or adaptive system, which employs B cells and T cells to build antibodies that continues to re-recognize the offending agent.
Once gliadin peptides in gluten have breached the gut mucosa, they can stimulate production of an array of antibodies and other tissue impairing agents:
- Alpha/beta, gamma, and omega gliadin antibodies
- Endomesial tissue antibodies
- Tissue transglutaminase: Tissue transglutaminase is an enzyme that plays an important role in presenting gliadin to B and T cells to be marked for antibody production. This enzyme is tagged as part of the complex with gluten and becomes a target of the immune system. Importantly, transglutaminase 6 is active in the central nervous system and appears to mediate the neurologic effects of gluten intolerance including depression, seizures, headaches, multiple sclerosis/demyelination, anxiety, ADHD, ataxia, neuropathy as discussed here and here. Importantly, transglutaminase deposits accumulate in blood vessels including the blood brain barrier.
- Synapsin, GAD (glutamic acid decarboxylase), and gangliodise: 51% of the Celiac population develops neurologic or psychiatric dysfunction, and significant percentages of neurologic diseases such as ataxia, seizures, and neuropathy are found to be driven by and resolved by gluten exposure as discussed here. One study found that 27% of schizophrenics had gliadin antibodies. Once again, molecular mimicry is at the foundation of gliadin-reactive antibodies that target cellular components of the nervous system influencing neurochemical transmission. Neurological manifestations most often present in the absence of any report of gastrointestinal symptoms.
- Thyroid autoantibodies: Autoimmune thyroid disease occurs in unexpected frequency in Celiac patients leading researchers to identified shared pathology to these two conditions. Molecular mimicry and amino acid motif overlap in gliadin and the thyroid enzyme peroxidase and protein thyroglobulin may trigger cross-reactivity in the setting of intestinal permeability and immune response to gluten. Tissue transglutaminase antibodies also bind thyroid tissue causing gland destruction and recruitment of the immune system for repair. The inflammatory cytokine IL-15 is a shared mechanism for immune reactivity in Celiac disease and Hashimoto's thyroiditis thought to drive inflammation that is furthered by poor selenium absorption when the gut lining is compromised (as discussed here). Selenium is not only integral for thyroid hormone function, but is also an antioxidant that does damage control in the setting of oxidative stress.