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Gluten Intake Does Not Influence Cognitive Function in People Without Celiac Disease

Key findings

  • This study investigated whether long-term gluten intake is associated with current cognitive function, using data on 13,494 women who did not have celiac disease and provided dietary data over two decades
  • Estimated gluten intake was not associated with the psychomotor speed and attention score, learning and working memory score or global score on the Cogstate Brief Battery
  • The associations between gluten intake and cognitive scores remained null in multiple sensitivity analyses
  • Patients can be advised that restricting dietary gluten for the purpose of maintaining or improving cognition is not warranted in the absence of celiac disease or established gluten sensitivity

The immune reaction to gluten in people with celiac disease has been linked to multiple neuropsychiatric symptoms, including cognitive impairment, depression and anxiety. There is no epidemiologic evidence that gluten harms people without celiac disease. However, the best-selling book Grain Brain and other sources have popularized the notion that gluten has a harmful effect on cognition.

Yiqing Wang, PhD, research fellow at Massachusetts General Hospital, Andrew T. Chan, MD, MPH, director for Cancer Epidemiology in the Mass General Cancer Center, chief of the Clinical and Translational Epidemiology Unit in the Department of Medicine and vice chief in the Division of Gastroenterology, and colleagues investigated using 24 years of data from the Nurses' Health Study II. Their results, which do not support the claim, are published in JAMA Network Open.

Study Methods

The Nurses' Health Study II is a nationwide longitudinal study of female nurses who were 25 to 42 years old when enrolled in 1989. The participants have been asked to complete a validated 131-item semiquantitative food frequency questionnaire every four years since 1991.

This analysis involved 13,494 participants who did not have a diagnosis of celiac disease or stroke and completed the Cogstate Brief Battery online when the average age of the cohort was 61.

Primary Analyses

In a multivariable-adjusted model, there were no differences across quintiles of gluten intake in (1) psychomotor speed and attention score, (2) learning and working memory score or (3) global cognition score.

Sensitivity Analyses

The associations between gluten intake and cognitive scores remained null:

  • When additionally adjusting for servings per day of refined grains and whole grains
  • When modeling gluten intake as a continuous variable or by decile categories
  • In stratified analyses by age, smoking, body mass index, current depression status, and history of diabetes, hypertension or hypercholesterolemia
  • When analyzing gluten intake by each four-year questionnaire interval and when analyzing the change in gluten intake from the distant past (12–24 years) to the recent past (4–12 years)
  • When additionally excluding participants who had ever reported cancer diagnosis, had every reported dementia diagnosis, or had not completed all dietary assessments preceding the cognitive assessment

Counseling Patients

Patients can be advised that restricting dietary gluten for the purpose of maintaining or improving cognition is not warranted in the absence of celiac disease or established gluten sensitivity.

Gluten-free diets have also been touted for effects on weight loss, metabolic syndrome and intestinal symptoms. However, these putative benefits lack consistent evidence. Moreover, several studies have raised nutritional concerns, given that some gluten-free foods may contain less protein and fiber but higher saturated lipids and sodium than non–gluten-free foods.

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