Gluten is a protein that stores important nutrients and is technically a mixture of complex proteins; similar storage proteins are found in a variety of foods, including rye, barley, and oats, and are collectively referred to as “gluten.” Because it can be a binding and extending agent, it is often added to processed foods for improved texture and flavor [1]. Chewier bread products are high in gluten, such as pizza dough and other leavened bread. Historically, gluten has been associated with the development of gastrointestinal symptoms; it is also the root cause of the immune response in celiac disease [2]. Gluten is also thought to have negative effects on cognition.
Celiac disease (CD) is an illness causing certain cells in the intestine to die, leading to inflammation and nutritional deficiencies [3]. The only currently available treatment for CD is abstinence from gluten. An imbalanced gut microbiome (dysbiosis) is thought to be an important factor in causing CD [4]. On a molecular level, exposure to gliadin, one of the proteins in gluten, indirectly increases the passage of antigens into the gut mucus membranes. Undigested fragments from gluten-containing foods trigger an increase in T-cell response against some of the body’s own tissues, creating most of the secondary symptoms associated with CD [5]. A clinical study demonstrated CD patients showed increased activity in a type of cell that is involved in cell death [6]. Another feature of CD pathology is the upregulation of the pro-inflammatory cytokine IL-15, which promotes the destruction of intestinal epithelial cells [5]. Gluten is known to have a detrimental effect on health for patients with celiac disease, however, it may also be linked to negative effects on cognition in the general population.
A recent systematic review closely examined 13 studies (n = 526) and compared the association between gluten intake and cognitive function, looking specifically at depression, anxiety, autism, schizophrenia, or memory impairment [7]. The researchers concluded restricting gluten may be helpful in reducing cognitive impairment in people with IBS, CD, schizophrenia and fibromyalgia; however, in the case of patients with autism disorder, a gluten-free diet did not significantly enhance cognition [8]. Other research studies have also examined the association between gluten intake and neurological/psychological impairment through symptoms of peripheral neuropathy, depression, anxiety, and ataxia [9]. Ataxia is the most common neurological complication related to gluten intake; this is characterized by cerebellum dysfunction, increased production of certain antibodies, and ataxic symptomology [10]. Furthermore, one study showed CD patients were more likely to have anxiety but exhibited a significant improvement in these scores after one year on a gluten-free diet [11]. Similarly, a Scandinavian population study showed elderly patients with gluten sensitivities were twice as likely to have depressive symptoms than controls [12], but this difference improved after a gluten-free diet was imposed [13]. In mouse macrophages treated with gliadin, there was a significant increase in pro-inflammatory genes such as TNF-α, IL-12, IL-15 and IFN-β iNOS, suggesting gliadin and other gluten components may be capable of inducing excessive inflammation, interfering with brain signaling and contributing to neurological and cognitive impairments [9,14].
Accumulating evidence indicates the gluten-mediated immune response is detrimental to overall health but especially to cognition. In many cases, neurological and psychiatric manifestations may arise from gluten-related illnesses. Additional research is needed to determine what the exact link between gluten, health, and cognition is.
References
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- Alun Jones, V., Shorthouse, M., Mclaughlan, P., Workman, E., & Hunter, J. O. (1982). Food Intolerance: A Major Factor in the Pathogenesis of Irritable Bowel Syndrome. The Lancet, 320(8308), 1115–1117. https://doi.org/10.1016/S0140-6736(82)92782-9
- Hill, I. D., Fasano, A., Guandalini, S., Hoffenberg, E., Levy, J., Reilly, N., & Verma, R. (2016). NASPGHAN Clinical Report on the Diagnosis and Treatment of Gluten-related Disorders. Journal of Pediatric Gastroenterology & Nutrition, 63(1), 156–165. https://doi.org/10.1097/MPG.0000000000001216
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- Meresse, B., Chen, Z., Ciszewski, C., Tretiakova, M., Bhagat, G., Krausz, T. N., Raulet, D. H., Lanier, L. L., Groh, V., Spies, T., Ebert, E. C., Green, P. H., & Jabri, B. (2004). Coordinated Induction by IL-15 of a TCR-independent NKG2D Signaling Pathway Converts CTL into Lymphokine-activated Killer Cells in Celiac Disease. Immunity, 21(3), 357–366. https://doi.org/10.1016/j.immuni.2004.06.020
- Rouvroye, M. D., Zis, P., Van Dam, A.-M., Rozemuller, A. J. M., Bouma, G., & Hadjivassiliou, M. (2020). The Neuropathology of Gluten-related Neurological Disorders: A Systematic Review. Nutrients, 12(3), 822. https://doi.org/10.3390/nu12030822
- Aranburu, E., Matias, S., Simón, E., Larretxi, I., Martínez, O., Bustamante, M. Á., Fernández-Gil, M. del P., & Miranda, J. (2021). Gluten and FODMAPs Relationship with Mental Disorders: Systematic Review. Nutrients, 13(6), 1894. https://doi.org/10.3390/nu13061894
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- Bhatia, K. P., Brown, P., Gregory, R., Lennox, G. G., Manji, H., Thompson, P. D., Ellison, D. W., & Marsden, C. D. (1995). Progressive Myoclonic Ataxia Associated with Coeliac Disease: The Myoclonus is of Cortical Origin, but the Pathology is in the Cerebellum. Brain, 118(5), 1087–1093. https://doi.org/10.1093/brain/118.5.1087
- Addolorato, G. (2001). Anxiety but not Depression Decreases in Coeliac Patients after One-year Gluten-free Diet: A Longitudinal Study. Scandinavian Journal of Gastroenterology, 36(5), 502–506. https://doi.org/10.1080/00365520119754
- Ruuskanen, A., Kaukinen, K., Collin, P., Huhtala, H., Valve, R., Mäki, M., & Luostarinen, L. (2010). Positive Serum Antigliadin Antibodies Without Celiac Disease in the Elderly Population: Does it Matter? Scandinavian Journal of Gastroenterology, 45(10), 1197–1202. https://doi.org/10.3109/00365521.2010.496491
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- Thomas, K. E., Sapone, A., Fasano, A., & Vogel, S. N. (2006). Gliadin Stimulation of Murine Macrophage Inflammatory Gene Expression and Intestinal Permeability are MYD88-dependent: Role of the Innate Immune Response in Celiac Disease. The Journal of Immunology, 176(4), 2512–2521. https://doi.org/10.4049/jimmunol.176.4.2512