Cross-reactivity: why gluten free isn't always enough

As I've discussed before, gluten has long been implicated in the onset of numerous neurological and neuropsychiatric illnesses, yet no one has ever managed to formally establish a causal relationship, and research still relies on statistical correlation to imply a tenuous link. For example, if you are schizophrenic you’re 50-100 times more likely to develop coeliac disease, or if you have coeliac disease you're 10 times more likely to develop schizophrenia, or if you have an autoimmune disease you’re 40% more likely to develop psychosis. Moreover, while limited research does exist that has shown an improvement in symptoms in patients with schizophrenia when following a gluten and diary free diet, or that anti gliadin antibodies have been linked to bipolar, not to mention the occasional anecdote of miraculous recovery that surfaces in weight loss or autism patient groups that seem to link a whole plethora of brain diseases with diet, there just is no evidence to suggest undertaking any form of dietary change as a treatment for mental illness.

The only glimmer of an alternative treatment for some cases of psychosis comes from the growing body of research that demonstrates that in around 9% of cases, the actions of the immune system is the cause of these illnesses, and that treatment with an immuno-suppressive medication is therefore indicated. However, as Prof Hadjivassiliou lamented during my last consultation with him, this research is not looking for anti gliadin antibodies and therefore no link with diet is being established.

The good news is there is now a new area of research that might be about to open up a whole new direction of treatment for these illnesses. Researchers at Harvard Medical School are exploring the clinical indications that an immune reaction to a particular food, for example wheat gluten, can also be triggered by another food protein that shares a similar sequence of amino acids. What this means they say, is that if a patient consumes a different food that contains that same sequence of amino acids then they will still have a reaction, even if they no longer consume the food to which they originally had the reaction.

Immuno detection of anti-cerebellar and anti-gliadin binding
to cerebellar peptides, brain, egg and soy antigens.
© Nutritional Neuroscience
The research showed how anti cerebellar antibodies, these are the ones that cause ataxia, reacted to gliadin, the protein in wheat. Specifically, these antibodies to gliadin cross reacted with the Purkinje cells in the cerebellum as there were shared epitopes that would trigger the antigen to attack it, causing the patient to develop brain damage. While this is an incredible discovery in itself, it was the discovery that similar protein structures to the one found in gliadin existed in dairy, egg and soy protein, and that they could also trigger an antigen that would then attack the cerebellar tissue. This cross reactivity is also confirmed in research into the molecular mimicry of food and human aquaporins.

What it means is that once the antigen to gliadin has been been produced in a genetically predisposed person, and stage 3 autoimmunity has been reached where significant symptoms have appeared, then if the patient stops eating gluten, but continues to eat foods that cross react (ie they contain the same piece of amino acid chain that causes an antigen to be produced), then the patient will continue to experience symptoms.

So in other words, a patient with an autoimmune disease of the brain, or indeed anywhere, may need to stop eating all cross reactive foods in order to recover.

These discoveries are summarised in this video webinar by Dr Datis Kharazzian that I was fortunate enough to attend.

Approximate rate of clinical reactivity to
at least 1 other related food
© Journal of Allergy & Clinical Immunology
However, not all people react to all cross reactive foods. Testing does exist to establish if an antigen is produced, and numerous cross-reactive foods have been identified, but as I learned, the best test is to stop eating all potentially cross reactive food groups and reintroduce them one at a time and look for a reaction.

This discovery was the eureka moment for me, as it explains why I didn’t get well when I went on a gluten free diet, and why I experience symptoms every time a I try and go onto the celiac diet. It’s because there is something else I am eating that is causing me to produce an antigen to an epitope in the amino acid chain in a different food, one that mimics the amino acid chain in gliadin. I’m still not exactly sure which other foods I react to, but I believe that cows milk, soy and corn are very probably culprits based on my symptoms when I eat them.

So it leaves me wondering about those people with schizophrenia, autism, bipolar and psychotic depression. Could it be that some of those cases are due to an antibody to something they are eating, but removing the main trigger, which may very well be gluten, won’t make any noticeable difference because other foods still provoke the immune system to produce the same antibody? It certainly appears to be true for me. What it means though is recovery could be very difficult, as not only does the patient have to go to extremes to avoid gluten as it appears that even amounts ‘safe for celiac’ can trigger a reaction, but that they must also adopt an incredibly strict autoimmune paleo diet for many months to avoid all other possible cross reactive foods in order to get well.

But when you’re as sick as I was, an incredibly strict diet was by far the preferable option.

I hope this research yields further discoveries and the autoimmune protocol diet becomes a treatment option for anyone suffering with psychosis. It can’t happen soon enough.