Gluten and The Brain

Gluten & the Brain | The Paleo Diet

With the plethora of benefits supported by scientific evidence,1 Gluten-free diets have been gaining in popularity in recent years.2 Studies range from gastrointestinal symptom improvement,3 to possible correlations with autism,4 and diabetes.5 However, there may not be a more fascinating area of gluten study than how the protein composite can be related to cognitive function.6 One study shows large changes in brain tissue, specifically, white matter, in those who are sensitive to gluten.7

Gluten MRI

Gluten and White Matter in the Brain

Why is this an important discovery? White matter is actively involved in neurogenesis, or “the growth of new neurons.”8, 9, 10 If gluten is possibly disrupting this process, like chemotherapy has been studied to do,11 then its effects may not be just temporary and transient. Instead they may be both long lasting and potentially damaging.12

Stress, sleep disruption, exercise and inflammation have all been linked with regulating hippocampal neurogenesis and implicated in the pathophysiology of mood disorders.13 But can gluten be linked to mood disorders? The science says yes.14

Many reports evidence unexpected resolution of long-term schizophrenic symptoms, when eliminating gluten from the diet.15 Interestingly, one study of Pacific Islanders who consumed almost no grains (or dairy) showed that only 2 in 65,000 subjects presented with overtly psychotic cases of schizophrenia.16, 17 However, since there are oftentimes confounding variables in these studies, it is not yet mechanistically clear on what may be causing remission of symptoms.18

In regards to cognitive function, as far back as 2004, scientists have shown improvements in the frontal region of the brain, in subjects consuming a gluten-free diet.19 Other research shows gluten’s effects are clearly not limited to gastrointestinal issues alone.20

Mapping of α-gliadin motifs

 

Gluten-Related Algorithm

Proposed algorithm for the differential diagnosis of gluten-related disorders, including celiac disease, gluten sensitivity and wheat allergy.

To whom does this apply21 and how exactly does gluten cause cognitive impairment? Definitively, we can seem to say that removing gluten from the diet improves cognitive functioning in many individuals.22, 23 Gluten elicits an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 genes.24

The “foggy brain” symptoms, as reported by non-celiac disease subjects, are intriguing. In these subjects, we see an up-regulation of claudin-4, which is associated with an increased expression of toll-like receptor-2 and a significant reduction of the T-regulatory cell marker FoxP3.25 This is part of why an innate immune system response seems to be involved in these subjects, rather than an adaptive immune system response.

Gluten sensitivity as a neurological illness

However, individuals diagnosed with celiac disease, α-amylase/trypsin inhibitors (ATIs) are strong activators of innate immune system responses in macrophages, monocytes and dendritic cells, via toll-like receptor-4.26 Despite these details, however, we cannot yet definitively say that gluten causes cognitive impairment,27, 28 no matter how likely it may seem in the scientific literature.

Brain MRI: Gluten Ataxia

Brain MRI of a patient with gluten ataxia showing rapid onset of cerebellar atrophy over a period of 15 months before the diagnosis of gluten ataxia.

The distinction is very important. A much-publicized study29 from early 2014 suggested it might not be gluten itself that causes issues, but instead it may agglutinins, FODMAPs, prodynorphins, deamidated gliadin and/or gliadorphins.

These findings illustrate more studies need to be done in order to show, mechanistically, what is causing physiologic disruptions, changes in white matter. Furthermore, research may determine distinct populations that should avoid gluten, if indeed the protein composite is causing these issues.

“Early diagnosis and removal of the trigger factor, by the introduction of a gluten-free diet, is a promising therapeutic intervention,” said researchers in a study published in the Journal of Neurology.30 A promising intervention – that needs much more research.31

I do not dismiss anecdotal improvements seen in individuals adopting gluten-free diets, such as the Paleo Diet. And with that said, we need instead maintain scientific rigor and provide the best, most accurate, recommendations possible.

The negative effects of gluten and other gluten-like compounds have been well-documented for many years.32, 33, 34, 35 Just because a specific mechanism for neurologic dysfunction hasn’t yet been identified – doesn’t mean gluten is doing anyone any favors.36, 37

We must also remember that although the human genome has remained primarily unchanged since the agricultural revolution 10,000 years ago, our diet and lifestyle have become progressively more divergent from those of our ancient ancestors.38, 39 A Paleo Diet still provides the best defense against neurologic impairment, as well as providing favorable changes in risk factors, such as weight, waist circumference, C-reactive protein, glycated haemoglobin (HbAlc), blood pressure, glucose tolerance, insulin secretion, insulin sensitivity and lipid profiles.40



References

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23. Bürk K, Bösch S, Müller CA, et al. Sporadic cerebellar ataxia associated with gluten sensitivity. Brain. 2001;124(Pt 5):1013-9.

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