Plasma Alkylresorcinols

Plasma Alkylresorcinols Reflect Gluten Intake and Distinguish between Gluten-Rich and Gluten-Poor Diets in a Population at Risk of Metabolic Syndrome

Mads V Lind,4,5,9* Mia L Madsen,6,9 Ju¨ ri J Rumessen,7 Henrik Vestergaard,6,8 Rikke J Gøbel,6 Torben Hansen,6 Lotte Lauritzen,4 Oluf B Pedersen,6 Mette Kristensen,4 and Alastair B Ross5

4Department of Nutrition, Exercise, and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark; 5Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; 6The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, and 7QD-Research Unit and Department of Gastroenterology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; and 8Steno Diabetes Center, Gentofte, Denmark


Background: Many patients with celiac disease experience difficulties in adherence to a gluten-free diet. Methods for testing compliance to a gluten-free diet are costly and cumbersome. Thus, a simple biomarker of gluten intake is needed in a clinical setting and will be useful for epidemiologic studies investigating wider effects of gluten intake.

Objective: The aim was to evaluate plasma total alkylresorcinol concentrations as a measure of gluten intake.

Methods: In this randomized, controlled, crossover intervention study in 52 Danish adults with features of the metabolic syndrome, we compared 8 wk of a gluten-rich and gluten-poor diet separated by a washout period of $6 wk. We measured fasting plasma concentrations of alkylresorcinols to determine if they reflected differences in gluten intake as a secondary
outcome of the original study. In addition, we investigated in 118 Danish adults the cross-sectional association between selfreported gluten intake and plasma alkylresorcinols in the same and a similar study at baseline.We used mixed-model ANCOVA for examining treatment effects, a classification tree to determine compliance to the gluten-poor diet, and linear regression
models for examining baseline correlation between plasma alkylresorcinol concentrations and gluten intake.

Results: Plasma total alkylresorcinols decreased more during the gluten-poor period (geometric mean: –124.8 nmol/L; 95% CI: –156.5, –93.0 nmol/L) than in the gluten-rich period (geometric mean: –31.8 nmol/L; 95% CI: –63.1, –0.4 nmol/L) (P < 0.001). On the basis of the plasma alkylresorcinol profile, we built a classification tree to objectively determine
compliance and found an overall participant misclassification error of 3.9%. In the cross-sectional study we found a 5.6% (95% CI: 2.4%, 8.9%) increase in plasma total alkylresorcinols per 1-g increase in reported gluten intake (P < 0.001).

Conclusion: We propose the use of plasma alkylresorcinols to monitor compliance to a gluten-free diet as well as to help investigations into the possible effects of gluten in the wider population. This trial was registered at as NCT017119913 and NCT01731366.

J Nutr doi: 10.3945/jn.116.236398.
20 JUNE 2024