Intermittent time-restricted eating may increase autophagic flux in humans: an exploratory analysis.

Autophagy slows age-related pathologies and is stimulated by nutrient restriction in animal studies. However, this has never been shown in humans. We measured autophagy using a physiologically relevant measure of autophagic flux (flux of MAP1LC3B isoform II/LC3B-II in peripheral blood mononuclear cells in the context of whole blood) in 121 humans with obesity who were randomised to standard care (SC, control condition), calorie restriction (CR) or intermittent fasting plus time-restricted eating (iTRE) for 6 months. While the differences in change from baseline between groups was not significant at 2 months, we observed a significant difference in change from baseline between iTRE compared to SC at 6 months (P = 0.04, post hoc analysis). This effect may be driven partly by a tendency for autophagy to decrease in the SC group. The difference in change from baseline between CR and SC was not significant. Uncorrected analysis of correlations showed a negative relationship between change in autophagy and change in blood triglycerides. Data on the specificity and performance of the methods used to measure human autophagy are also presented. This shows autophagy may be increased by intermittent nutrient restriction in humans. If so, this is a demonstration that nutrient restriction can be used to improve a primary hallmark of biological ageing and provides a mechanism for how fasting could delay the onset of age-related disease. KEY POINTS: Autophagy slows biological ageing, and dysfunction of autophagy has been implicated in age-related disease - an effective way of increasing autophagy in cells and animal models is nutrient restriction. However, the impact of different types of nutrient restriction on physiological autophagic flux in humans has not been extensively researched. Here we measure the effect of intermittent time-restricted eating (iTRE) and calorie restriction on physiological autophagic flux in peripheral blood mononuclear cells. After 6 months, there was a significant difference in change from baseline between the iTRE and the standard care control group, with flux being higher in the iTRE group at this timepoint. However, there was no significant increase from baseline within the iTRE group, showing that although autophagy may be modified by nutrient restriction in humans, further studies are required.