Metabolomics of Ramadan fasting: an opportunity for the controlled study of physiological responses to food intake

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Metabolomics of Ramadan fasting: an opportunity for the controlled study of physiological responses to food intake Sweety Mathew1†, Susanne Krug2†, Thomas Skurk2,3†, Anna Halama1,4†, Antonia Stank5, Anna Artati4, Cornelia Prehn4, Joel A Malek6, Gabi Kastenmüller5, Werner Römisch-Margl5, Jerzy Adamski4,7,8, Hans Hauner2,3 and Karsten Suhre1,5*

Abstract High-throughput screening techniques that analyze the metabolic endpoints of biological processes can identify the contributions of genetic predisposition and environmental factors to the development of common diseases. Studies applying controlled physiological challenges can reveal dysregulation in metabolic responses that may be predictive for or associated with these diseases. However, large-scale epidemiological studies with well controlled physiological challenge conditions, such as extended fasting periods and defined food intake, pose logistic challenges. Culturally and religiously motivated behavioral patterns of life style changes provide a natural setting that can be used to enroll a large number of study volunteers. Here we report a proof of principle study conducted within a Muslim community, showing that a metabolomics study during the Holy Month of Ramadan can provide a unique opportunity to explore the pre-prandial and postprandial response of human metabolism to nutritional challenges. Up to five blood samples were obtained from eleven healthy male volunteers, taken directly before and two hours after consumption of a controlled meal in the evening on days 7 and 26 of Ramadan, and after an over-night fast several weeks after Ramadan. The observed increases in glucose, insulin and lactate levels at the postprandial time point confirm the expected physiological response to food intake. Targeted metabolomics further revealed significant and physiologically plausible responses to food intake by an increase in bile acid and amino acid levels and a decrease in long-chain acyl-carnitine and polyamine levels. A decrease in the concentrations of a number of phospholipids between samples taken on days 7 and 26 of Ramadan shows that the long-term response to extended fasting may differ from the response to short-term fasting. The present study design is scalable to larger populations and may be extended to the study of the metabolic response in defined patient groups such as individuals with type 2 diabetes. Keywords: Metabolomics, Nutritional challenging, Ramadan fasting, Study design, Clinical research

Introduction The accurate diagnosis of a diseased state relies on the integration of best research evidence with clinical expertise and patient data [1]. Clinical parameters that are used to describe the health condition of a patient are often defined as concentrations of specific metabolites and (regulatory) * Correspondence: [email protected] † Equal contributors 1 Department of Physiology and Biophysics, Weill Cornell Medical College – Qatar, Doha, Qatar 5 Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Germa