Gluten Intake Is Positively Associated with Plasma α2-Macroglobulin in Young Adults

J Nutr. 2015 Jun;145(6):1256-62. doi: 10.3945/jn.115.212829. Epub 2015 Apr 8.


Background: Gluten-free foods have increased in popularity over the past decade and are now being consumed by individuals without celiac disease. However, the physiologic effects of gluten intake in individuals without celiac disease remain unknown. High-abundance plasma proteins involved in inflammation, endothelial function, and other physiologic pathways may represent potential biomarkers of biological effects of gluten intake.

Objective: The objective was to examine the association between gluten intake and plasma proteomic biomarkers in a population of adults without clinically diagnosed celiac disease.

Methods: Subjects (n = 1095) were participants of the Toronto Nutrigenomics and Health Study, a cross-sectional examination of young adults aged 20-29 y. Dietary gluten intake was estimated by using a 1-mo, 196-item semiquantitative food-frequency questionnaire. The concentrations of 54 plasma proteins were measured simultaneously by liquid chromatography/multiple-reaction monitoring mass spectrometry. The association between gluten intake and each proteomic biomarker was examined by using general linear models. Analyses were then conducted in individuals who do not have the human leukocyte antigen (HLA)-DQ2 or DQ8 risk variants required for the development of celiac disease to determine whether any associations observed could have been due to undiagnosed cases of celiac disease.

Results: Increased gluten intake was associated with increased concentrations of plasma α2-macroglobulin (P = 0.01), a marker of inflammation and cytokine release. The association remained after adjusting for age, sex, BMI, ethnicity, physical activity, energy intake, fiber intake, and hormonal contraceptive use among women. This relation was not modified by HLA risk variants.

Conclusion: Gluten consumption is associated with increased plasma α2-macroglobulin in young adults, which appears to be independent of celiac disease, suggesting possible effects of gluten on inflammation.

Keywords: alpha-2-macroglobulin; gluten; human leukocyte antigen; plasma proteins; proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Proteins / metabolism
  • Body Mass Index
  • Celiac Disease / blood
  • Cross-Sectional Studies
  • Energy Intake
  • Female
  • Glutens / administration & dosage*
  • Glutens / adverse effects*
  • HLA-DQ Antigens / blood
  • Humans
  • Male
  • Motor Activity
  • Nutrition Assessment
  • Proteomics
  • Surveys and Questionnaires
  • Waist Circumference
  • Young Adult
  • alpha-Macroglobulins / metabolism*


  • Biomarkers
  • Blood Proteins
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • HLA-DQ8 antigen
  • alpha-Macroglobulins
  • Glutens