The Impact of Fasting on Major Metabolic Pathways of Macronutrients and Pharmacokinetics Steps of Drugs

Abstract

In this review, we have investigated how fasting promotes an adaptive cross-talk between different hormones and metabolic pathways to supply and meet the body's daily energy demands. We highlight in biochemical terms and mechanisms how fasting impacts four metabolic pathways-glycogenolysis, gluconeogenesis, amino acid oxidation, and fatty acid β-oxidation-that are actively engaged in the metabolism of carbohydrates, proteins, and lipids. Fasting results in reduced insulin secretion and increased glucagon and epinephrine release to prevent or stimulate metabolic reaction(s). Fasting stimulates glycogenolysis, amino acid and glucose oxidation, aminotransferase reactions in skeletal muscle, and promotes gluconeogenesis and urea production in the liver. In addition, fasting promotes gene expression of lipid metabolism in skeletal muscle, the synthesis of ketone bodies in the liver, and intracellular hormone-sensitive lipase activity in adipose tissue. Furthermore, the impact of fasting on reducing cellular damage by mitochondrial reactive oxygen species is discussed. Lastly, we briefly describe the impact of fasting on the four steps of pharmacokinetics-the absorption, distribution, metabolism, and excretion of a few select drugs-with an emphasis on the elimination of drugs related to the cytochrome-P450 family of enzymes.