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

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.

Increase in Ischemic Stroke Incident Hospitalizations Among Bedouin Arabs During Ramadan Month

“…The high risk during the first 2 weeks of the Ramadan may possibly be explained by habituation of homeostatic mechanisms to the changes in water and dietary consumption after the initial period of fast. 37 In addition, a previous study from our institution demonstrated a similar phenomenon of increasing frequency in renal colic admissions during the first fortnight of Ramadan. 38 Our study has several limitations.…”

“…During Ramadan, signs of dehydration, such as increased hematocrit, hemoglobin, and plasma osmolality were observed,6 probably because of a reduction of fluid intake, increasing blood viscosity and possibly contributing to the risk of thrombosis. The high risk during the first 2 weeks of the Ramadan may possibly be explained by habituation of homeostatic mechanisms to the changes in water and dietary consumption after the initial period of fast 37. In addition, a previous study from our institution demonstrated a similar phenomenon of increasing frequency in renal colic admissions during the first fortnight of Ramadan 38…”

Comparing metabolite profiles of habitual diet in serum and urine

“…Associations between dietary variables and metabolites were estimated with the use of a partial Pearson correlation while adjusting for factors previously associated with metabolites and dietary intake (27)(28)(29)(30)(31)(32)(33)(34)(35), including age (years), sex, smoking (never, past, or current), fasting status at time of blood draw (fasting or nonfasting), case-control status, BMI (kg/m 2 ), physical activity index (weekly frequency of moderate-intensity leisure activity plus 2 3 weekly frequency of vigorous-intensity leisure activity), education (#12 y, vocational or 1-3 y college, $4 y college, or graduate), and daily caloric intake (kcal/d). Analyses of single vitamin and nutrient supplement use were adjusted for multivitamin use.…”

Evidence for Chronic Kidney Disease-Mineral and Bone Disorder Associated With Metabolic Pathway Changes

“…Unfortunately, the mechanisms underlying it have not been well characterized. Small-molecule metabolites have an important role in biological system 1 , 2 and represent attractive biomarkers to understand CKD. In the present study, we employed mass spectrometry-based metabolomics to analyze small molecules in patient serum using a ultra performance liquid chromatography (UPLC)-Quadrupole Time-of-Flight (Q-TOF)/mass spectrometry (MS) system.…”