Unravelling the health effects of fasting: a long road from obesity treatment to healthy life span increase and improved cognition

Figures & data

Table 1. Main forms of fasting and related diets.

Fasting and related diets	Calorie intake	Length
Calorie Restriction (CR)	∼70 % of normocaloric intake without malnutrition (with possible variations)	Optional
Intermittent Fasting (IF)
Alternate Day Fasting (ADF)	0 kcal/alternating with ad libitum (with possible variations)	Optional; alternation of fasting and ad libitum food intake every other day
Time Restricted Feeding/Eating (TRF/TRE) 16:8	Ad libitum with possible variations	Optional; daily food intake is reduced to a time window of 8 h (with possible variations)
Periodic Fasting (PF)
5:2 diet (5:2)	600 kcal/2 days per week/ad libitum	Two consecutive or independent days of calorie restriction every week
Long-term (LF) or prolonged Fasting
Buchinger Wilhelmi fasting	200–250 kcal/day	>2 days to weeks according to baseline nutritional and health status
Water-only fasting	0 kcal/day
Zero calorie diet	0 kcal/day	Weeks to months. Weight-loss program practiced between the 1960s and the 1970s
Very Low Calorie Diet* (VLCD)	800–1000 kcal	High protein formula weight-loss program with reduced calorie intake for 6 -12 weeks
Fasting Mimicking Diet* (FMD)	800–1100 kcal	5 days of calorie reduced low protein diet (1 to 6 cycles per year)

* Diets derived from fasting strategies.

Figure 1. Metabolic switch from carbohydrates to fatty acids and ketones induced by 10 days of fasting (daily energy intake of about 250 kcal and multidisciplinary programme). A regression spline was fitted on individual acetoacetic values to show the variations in ketosis during the course of the study. T: transition to the fasting mode; RF: progressive reintroduction of food [40].

Figure 2. Representationof signalling pathways modulated fasting. The reduced levels of circulating amino acids and of IGF-1 consequent to fasting repress the activity of mTOR and its downstream effector leading to an inhibition of global protein synthesis and promote recycling of macromolecules by autophagy stimulation. There is a rise in the AMP-to-ATP ratio leading to the activation of AMPK. SIRT1-driven deacetylation of PGC-1α and FOXO1 transcription factors provides a mechanism by which mitochondrial and lipid oxidation genes can be dynamically controlled in response to energy demand. AMPK: AMP-activated protein kinase; FOXO1: forkhead box O1; IGF: insulin-like growth factor; NAD+: nicotinamide adenine dinucleotide; PGC-1α: peroxisome proliferator–activated receptor γ coactivator 1α; mTOR: mammalian target of Rapamycin; SIRT: sirtuin.

Mesnage R, Grundler F, Schwiertz A, et al. Changes in human gut microbiota composition are linked to the energy metabolic switch during 10 d of Buchinger fasting. J Nutr Sci. 2019;8:e36.

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