Metabolomics of human fasting: new insights about old questions

Abstract

Since ancient days, human fasting has been performed for religious or political reasons. More recently, fasting has been employed as an effective therapy for weight reduction by obese people, and numerous studies have investigated the physiology of fasting by obese subjects. Well-established fasting markers (butyrates, BCAAs and carnitines) were considered essential energy substitutes after glycogen storage depletion. However, a recently developed metabolomic approach has unravelled previously unappreciated aspects of fasting. Surprisingly, one-third (44) of 120 metabolites investigated increase during 58 h of fasting, including antioxidative metabolites (carnosine, ophthalmic acid, ergothioneine and urates) and metabolites of entire pathways, such as the pentose phosphate pathway. Signalling metabolites (3-hydroxybutyrate and 2-oxoglutarate) and purines/pyrimidines may also serve as transcriptional modulators. Thus, prolonged fasting activates both global catabolism and anabolism, reprogramming metabolic homeostasis.

Whole Blood Metabolomics in Aging Research

“…Thus, our metabolomic approach to whole blood comprehensively captures complex changes with individual differences, suitable for human aging research. Indeed, whole blood metabolomics have revealed metabolites that serve as biomarkers relevant to aging, fasting, and frailty [ 53 , 54 , 55 , 56 ].…”

“…While little is known about the link between fasting and aging in humans, it is well known that humans can withstand 30–40 days of fasting if dehydration is avoided [ 55 ], in sharp contrast to the vulnerability of mice to hunger (average survival of only several days of starvation). For example, Gandhi experienced hunger strikes of up to 21 days, 14 times or more in his lifetime as a form of political protest [ 69 ].…”

Covid-19, Carnosine and Cognition

“…33 Carnosine also facilitates macrophage-mediated clearance of senescent cells. 34 It is likely that carnosine's effects are multifactorial, not only can the dipeptide affect metabolism, but it has recently been shown that prolonged fasting causes blood levels of carnosine (presumably intra-erythrocytic) to increase 35 along with a number of other anti-oxidants. A recent study has produced evidence suggesting that carnosine may act as an inhibitor of angiotensin-converting enzyme 2 (ACE2) which could then inhibit viral cellular entry via this protein.…”

Intermittent fasting: a strategy to counteract aging linked to oxidative stress

“…4 Fasting, considered the restriction of food and beverages in a specific time, has been practiced throughout human existence in some cultures as a religious practice by Muslims, Christians, Buddhists, and others. 5 Intermittent fasting (IF) is considered an eating pattern with little or no energy intake with intermediate periods of regular food intake regularly. There are two general types of intermittent fasting, alternate-day fasting (ADF) and time-restricted feeding (TRF).…”