Gluten: Effect on Health and Cognition

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. 


  1. Biesiekierski, J. R. (2017). What is Gluten? Journal of Gastroenterology and Hepatology, 32 Suppl 1, 78–81.  
  1. 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.  
  1. 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.  
  1. Mohan, M., Chow, C.-E. T., Ryan, C. N., Chan, L. S., Dufour, J., Aye, P. P., Blanchard, J., Moehs, C. P., & Sestak, K. (2016). Dietary Gluten-induced Gut Dysbiosis is Accompanied by Selective Upregulation of MicroRNAs with Intestinal Tight Junction and Bacteria-binding Motifs in Rhesus Macaque Model of Celiac Disease. Nutrients, 8(11), 684.  
  1. Campagna, G., Pesce, M., Tatangelo, R., Rizzuto, A., Fratta, I. L., & Grilli, A. (2017). The Progression of Coeliac Disease: Its Neurological and Psychiatric Implications. Nutrition Research Reviews, 30(1), 25–35.  
  1. 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.  
  1. 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. 
  1. 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.  
  1. Jackson, J. R., Eaton, W. W., Cascella, N. G., Fasano, A., & Kelly, D. L. (2012). Neurologic and Psychiatric Manifestations of Celiac Disease and Gluten Sensitivity. Psychiatric Quarterly, 83(1), 91–102.  
  1. 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.  
  1. 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.  
  1. 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.  
  1. Corvaglia, L., Catamo, R., Pepe, G., Lazzari, R., & Corvaglia, E. (1999). Depression in Adult Untreated Celiac Subjects: Diagnosis by the Pediatrician. The American Journal of Gastroenterology, 94(3), 839–843.  
  1. 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.