Intermittent fasting from dawn to sunset for 30 consecutive days is associated with anticancer proteomic signature and upregulates key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system and cognitive function in healthy subjects

Abstract

Murine studies showed that disruption of circadian clock rhythmicity could lead to cancer and metabolic syndrome. Time-restricted feeding can reset the disrupted clock rhythm, protect against cancer and metabolic syndrome. Based on these observations, we hypothesized that intermittent fasting for several consecutive days without calorie restriction in humans would induce an anticarcinogenic proteome and the key regulatory proteins of glucose and lipid metabolism. Fourteen healthy subjects fasted from dawn to sunset for over 14 h daily. Fasting duration was 30 consecutive days. Serum samples were collected before 30-day intermittent fasting, at the end of 4th week during 30-day intermittent fasting, and one week after 30-day intermittent fasting. An untargeted serum proteomic profiling was performed using ultra high-performance liquid chromatography/tandem mass spectrometry. Our results showed that 30-day intermittent fasting was associated with an anticancer serum proteomic signature, upregulated key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system, and cognitive function, and resulted in a serum proteome protective against cancer, metabolic syndrome, inflammation, Alzheimer's disease, and several neuropsychiatric disorders. These findings suggest that fasting from dawn to sunset for 30 consecutive days can be preventive and adjunct therapy in cancer, metabolic syndrome, and several cognitive and neuropsychiatric diseases. SIGNIFICANCE: Our study has important clinical implications. Our results showed that intermittent fasting from dawn to sunset for over 14 h daily for 30 consecutive days was associated with an anticancer serum proteomic signature and upregulated key regulatory proteins of glucose and lipid metabolism, insulin signaling, circadian clock, DNA repair, cytoskeleton remodeling, immune system, and cognitive function, and resulted in a serum proteome protective against cancer, obesity, diabetes, metabolic syndrome, inflammation, Alzheimer's disease, and several neuropsychiatric disorders. Importantly, these findings occurred in the absence of any calorie restriction and significant weight loss. These findings suggest that intermittent fasting from dawn to sunset can be a preventive and adjunct therapy in cancer, metabolic syndrome and Alzheimer's disease and several neuropsychiatric diseases.

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no conflict of interest.

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1.

Test of different sample preparation methods. A. Comparison of the effect of Top 12 abundant protein depletion, direct in-solution digestion and S-Trap aid in column digestion method. B. Comparison of the fractionation method between high pH STAGE tip method and SDS-PAGE. Recovered protein (shown in Gene Protein Product, GPs) and Peptide Spectrum Matches (PSMs) numbers are representative results from triple repeat. C. Schematic illustration of established workflow in the serum profiling process. S-Trap aided trypsin digestion, high pH STAGE tip method for preparation of serum samples was used.

Figure 2.

A. Distribution of normalized relative gene protein product (GP) amount and location of significantly changed selected proteins in serum samples taken at the end of 4th week during 30-day intermittent fasting shown in GP name and rank order. B. Volcano plot shows GPs that had an equal to or greater than 4-fold significant change (blue and red colors represent a significant decrease and increase in the levels of GPs, respectively) at the end of 4th week during 30-day intermittent fasting compared with the levels before 30-day intermittent fasting. C. Distribution of normalized relative GP amount and location of significantly changed selected proteins in serum samples taken one week after 30-day intermittent fasting shown in GP name and rank order. D. Volcano plot shows GPs that had an equal to or greater than 4-fold significant change (blue and red colors represent a significant decrease and increase in the levels of GPs, respectively) one week after 30-day intermittent fasting compared with the levels before 30-day intermittent fasting.

Figure 3.

Change (logiFOT X 105) in the levels of 13 selected GPs that significantly increased at the end of 4th week during 30-day intermittent fasting (30-day fasting) or one week after 30-day intermittent fasting (After) compared with the levels before 30-day intermittent fasting (Before).

Figure 4.

Change (logiFOT X 105) in the levels of 14 selected GPs that significantly decreased at the end of 4th week during 30-day intermittent fasting (30-day fasting) or one week after 30-day intermittent fasting (After) or both at the end of 4th week during 30-day intermittent fasting and one week after 30-day intermittent fasting compared with the levels before 30-day intermittent fasting (Before).