ORIGINAL ARTICLE Plasma alkylresorcinols C17:0/C21:0 ratio, a biomarker of relative whole-grain rye intake, is associated to insulin sensitivity: a randomized study OK Magnusdottir 1,2 , R Landberg 3,4 , I Gunnarsdottir 1,2 , L Cloetens 5 , B Åkesson 5,6 , M Landin-Olsson 7 , F Rosqvist 8 , D Iggman 8,9 , U Schwab 10,11 , K-H Herzig 12,13 , MJ Savolainen 14,15 , L Brader 16 , K Hermansen 16 , M Kolehmainen 10,17 , K Poutanen 10,17 , M Uusitupa 10,18 , I Thorsdottir 1,2 and U Rise ´ rus 8 BACKGROUND/OBJECTIVES: Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism. We aimed to investigate the association between plasma alkylresorcinols (AR), a biomarker of whole-grain rye and wheat intake, and glucose metabolism in individuals with metabolic syndrome (MetS). SUBJECTS/METHODS: Participants were 30–65 years of age, with body mass index 27–40 kg/m 2 and had MetS without diabetes. Individuals were recruited through six centers in the Nordic countries and randomized to a healthy Nordic diet (ND, n ¼ 96), rich in whole-grain rye and wheat, or a control diet (n ¼ 70), for 18–24 weeks. In addition, associations between total plasma AR concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake, and glucose metabolism measures from oral glucose tolerance tests were investigated in pooled (ND þ control) regression analyses at 18/24 weeks. RESULTS: ND did not improve glucose metabolism compared with control diet, but the AR C17:0/C21:0 ratio was inversely associated with fasting insulin concentrations (P ¼ 0.002) and positively associated with the insulin sensitivity indices Matsuda ISI (P ¼ 0.026) and disposition index (P ¼ 0.022) in pooled analyses at 18/24 weeks, even after adjustment for confounders. The AR C17:0/C21:0 ratio was not significantly associated with insulin secretion indices. Total plasma AR concentration was not related to fasting plasma glucose or fasting insulin at 18/24 weeks. CONCLUSIONS: The AR C17:0/C21:0 ratio, an indicator of relative whole-grain rye intake, is associated with increased insulin sensitivity in a population with MetS. European Journal of Clinical Nutrition (2014) 68, 453–458; doi:10.1038/ejcn.2014.12; published online 19 February 2014 Keywords: alkylresorcinols; insulin sensitivity; whole grain; rye INTRODUCTION Whole-grain and cereal fiber consumption has been inversely associated with the risk of type 2 diabetes and insulin sensitivity in observational studies, 1–5 but findings have been inconsistent in intervention studies. 6–11 A possible reason for the inconclusive results seen in intervention studies may be inadequate dietary compliance. Nutritional science relies on accurate dietary information to assess compliance to dietary interventions and to investigate diet–disease associations. However, most dietary assessment instruments rely to some extent on self-reporting, which is prone to measurement errors. 12,13 The use of dietary biomarkers could be one way to improve the validity of dietary assessment in combination with, or as an alternative for, self- reports or as a tool for secondary analysis, where noncompliant individuals can be excluded on the basis of the biomarker measurements. Alkylresorcinols (AR) have been proposed as biomarkers for whole-grain and bran intake of wheat and rye 14–16 and for cereal fiber intake in populations with a high intake of whole-grain wheat and rye. 17 AR are almost exclusively present in the outer parts of wheat and rye grains and not in refined white flour. 18,19 Controlled whole-grain and bran intervention studies show that plasma AR concentration increases proportionally with AR and whole-grain intake 16,20–24 and can be used as a biomarker of compliance to a whole-grain diet. 15,25 Previously, we have demonstrated that AR are useful biomarkers for whole-grain wheat and rye intake as part of a healthy Nordic diet (ND). 26 Total plasma AR have been associated with lower body mass index 1 Unit for Nutrition Research, Landspitali-The National University Hospital of Iceland, Reykjavı ´k, Iceland; 2 Faculty of Food Science and Nutrition and School of Health Sciences, University of Iceland, Reykjavı ´k, Iceland; 3 Department of Food Science, BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden; 4 Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 5 Biomedical Nutrition, Pure and Applied Biochemistry, Lund University, Lund, Sweden; 6 Department of Clinical Nutrition, Skåne University Hospital, Lund, Sweden; 7 Department of Endocrinology, Skåne University Hospital, Lund, Sweden; 8 Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden; 9 Center for Clinical Research Dalarna, Falun, Sweden; 10 Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 11 Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Kuopio, Finland; 12 Department of Physiology and Biocenter of Oulu, Institute of Biomedicine, Oulu University, Oulu, Finland; 13 Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland; 14 Department of Internal Medicine and Biocenter Oulu, Institute of Clinical Medicine, University of Oulu, Oulu, Finland; 15 Clinical Research Center, Oulu University Hospital, Oulu, Finland; 16 Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 17 VTT, Technical Research Centre of Finland, Espoo and Kuopio, Kuopio, Finland and 18 Research Unit, Kuopio University Hospital, Kuopio, Finland. Correspondence: OK Magnusdottir, Unit for Nutrition Research, Landspitali-The National University Hospital of Iceland, Reykjavik IS-101, Iceland. E-mail: olakally@landspitali.is Received 4 October 2013; revised 6 December 2013; accepted 4 January 2014; published online 19 February 2014 European Journal of Clinical Nutrition (2014) 68, 453–458 & 2014 Macmillan Publishers Limited All rights reserved 0954-3007/14 www.nature.com/ejcn