The Link Between Gluten and Cognitive Function

by Oscar Jan MS, RDNNews

Introduction

The topic of gluten is often highly controversial. Gluten free diets have gained popularity over the years and are frequently touted as tools for weight loss and cures for a variety of ailments. Others are quick to label the gluten-free diet as a fad and believe that this way of eating should be reserved only for those with celiac disease, a condition that produces a severe reaction to gluten (1). While the benefits of going gluten-free can definitely be exaggerated at times, evidence does suggest that even those without celiac disease may experience clinical symptoms when consuming gluten. This condition is referred to as nonceliac gluten sensitivity (NCGS). Although NCGS tends to produce milder symptoms than celiac disease, both conditions can result in impaired gut functioning and overactivation of the immune system, and these pathologies may have a significant impact on cognitive function (2).

What is Gluten?

Gluten refers to a family of proteins that are found in certain grains such as wheat, barley and rye (3). In particular, glutenin and gliadin are the two main proteins found in gluten. Gluten is responsible for the elastic property of dough, and it is what gives bread and pasta its chewy texture. For most people, the proteins found in gluten are difficult to digest and may cause problems when they reach the small intestine.

Celiac Disease

Celiac disease (CD) affects approximately one percent of the population (1). CD is an autoimmune disease, or a condition in which the body attacks its own tissues. When celiac patients ingest gluten, the gliadin protein found in gluten triggers the immune system to attack the villi, or fingerlike projections that protrude out of the small intestine. These fingerlike projections provide more surface area for the small intestine to absorb nutrients, so damage to the villi can impair nutrient absorption.

If left untreated, CD may have a significant impact on cognitive function (2). There are a number of proposed mechanisms that link celiac disease pathology to cognitive impairment. Since a majority of the nutrients we ingest is absorbed in the small intestine, damage to the intestinal lining can prevent our bodies from obtaining adequate nutrients to support healthy brain functioning. Additionally, the immune response triggered by gluten in CD patients can result in systemic inflammation, and this inflammation can also make its way to the brain. Lastly, gluten may increase the permeability of the intestinal lining, and this process may exacerbate the inflammatory response (more on this in a bit!).

Nonceliac Gluten Sensitivity

Nonceliac gluten sensitivity (NCGS) refers to the presence of clinical symptoms that occur after gluten consumption and disappear once gluten is eliminated from the diet (1). However, unlike in celiac disease, NCGS is not triggered by an autoimmune response and does not result in direct damage to the intestinal lining. Rather, NCGS is classified as a food sensitivity, or an immune response to a food-based antigen that can result in intestinal symptoms such as gas, bloating, diarrhea and constipation. NCGS may also result in extraintestinal symptoms such as headache, fatigue, joint pain, and “brain fog,” or a mild transient form of cognitive impairment (2). These symptoms often disappear when gluten is eliminated from the diet. While the exact causes of NCGS are not clear, evidence suggests that they may be related to the effects of gluten on intestinal permeability.

Zonulin, Gut Permeability and the Brain

In addition to nutrient absorption, the small intestine also defends us against antigens, or foreign or toxic substances (4). Enterocytes, the cells that line the inner surface of the small intestine, work closely with immune cells to either promote tolerance to a recognized substance or to trigger an immune response to an antigen. These intestinal cells form tight junctions with each other that regulate the movement of antigens through the intercellular space. These tight junctions are controlled by zonulin, a protein that is released in the presence of gluten and bacteria overgrowth. Studies have found that those with CD and NCGS tend to release higher levels of zonulin as a result of gluten exposure. Zonulin can trigger the opening of these tight junctions, causing the intestinal lining to become more permeable to toxic substances in the gut.

Such toxins include bacteria-derived lipopolysaccharides (LPS), which can trigger the production of pro-inflammatory cytokines if they escape the digestive tract and into circulation, resulting in systemic inflammation (5). Once these toxins reach the brain, they can induce neuroinflammation, or inflammation in the brain. Chronic neuroinflammation is implicated in a number of brain-related disorders including depression, anxiety, Parkinson’s disease, and Alzheimer’s disease.

Who Should Eliminate Gluten from the Diet?

Individuals who test positive for celiac disease should absolutely eliminate gluten from the diet. Those without celiac disease who experience intestinal and extraintestinal symptoms should consider eliminating gluten and observing whether those symptoms subside. It is important to note that gluten consumption can result in transient increases in intestinal permeability in all individuals, which may not be a problem for most individuals (4). However, for those who are at increased risk of inflammatory Alzheimer’s disease, avoiding gluten may be one strategy to reduce these risks. Gluten avoidance is one of the key aspects of the Bredesen Protocol and may be one of the factors that have contributed to its effectiveness. Be sure to consult with a dietitian before starting a gluten-free diet.


References:

Leonard, M.M., Sapone, A., Catassi, C. & Fasano, A. (2017). Celiac Disease and Nonceliac Gluten Sensitivity: A Review. JAMA, 18(7):647-656. doi:10.1001/jama.2017.9730.

Makhlouf, S., Messelmani, M., Zaouali, J. & Mrissa, R. (2017). Cognitive impairment in celiac disease and non-celiac gluten sensitivity: review of literature on the main cognitive impairments, the imaging and the effect of gluten free diet. Acta Neurol Belg, 118(1):21-27. doi:10.1007/s13760-017-0870-z.

Shewry, P. (2019). What Is Gluten-Why Is It Special? Front Nutr, 6:101. doi:10.3389/fnut.2019.00101

Fasano, A. (2020). All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Res, 9.pii:F1000 Faculty Rev-69. doi:10.12688/f1000research.20510.1

Sartori, A.C., Vance, D.E., Slater, L.Z., Crowe, M. (2012). The Impact of Inflammation on Cognitive Function in Older Adults: Implications for Health Care Practice and Research. J Neurosci Nurs, 44(4):206-217. doi:10.1097/JNN.0b013e3182527690