The Impact of Fasting on Major Metabolic Pathways of Macronutrients and Pharmacokinetics Steps of Drugs
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REVIEW ARTICLE
The Impact of Fasting on Major Metabolic Pathways of Macronutrients and Pharmacokinetics Steps of Drugs Reza Karimi1 · Anita Cleven1 · Fawzy Elbarbry1 · Huy Hoang1
© Springer Nature Switzerland AG 2020
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.
Key Points
1 Introduction
Fasting results in the mobilization of glucose, fatty acids, amino acids, ketone bodies, glucagon, and epinephrine in the plasma to meet the body’s daily energy demands.
Fasting has been a regular practice for many religions with different restrictions for food and water, and is commonly part of a spiritual ceremony with different goals and expectations. For instance, while Muslims completely abstain from food and drink from dawn to sunset during the holy month of Ramadan, Christians, Jews, Buddhists, and Hindus fast partially or completely on designated days of the week or year [1]. Fasting has also been used as a medical treatment that was practiced by ancient Chinese, Greek and Roman physicians [2]. From an evolutionary point of view, humans have adapted a few biochemical cross-talks to resist the threat of starvation. Consequently, fasting is an adaptive biochemical and physiological condition [3] that allows humans to utilize major energy sources to meet their energy needs. As a result, there is a growing body of interest in understanding the implications of fasting on healthy individuals [4]. There is a vast amount of literature describing the impact of fasting on animals and humans. While there are available data that indicate the impact of fasting on glucose and blood lipids among healthy individuals [5–7], we have focused on finding direct links between fasting and the four metabolic pathways that are actively engaged in the metaboli
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