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Can fasting for five days once per month improve your health?

Fasting has shown health benefits in both humans and animals. But fasting is very, very hard for most people. So what about a diet that isn't quite fasting, but may have similar benefits?

Study under review: Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease

Introduction

Our bodies are well equipped to go for long periods of time without food. Generally, a bout of feeding and digestion is followed by an episode of digestive quiescence (i.e., fasting). In the modern day, feeding is rather frequent and fasting tends to be limited to our sleep, no more than 8-12 hours for most people. However, extended episodes of fasting are characterized[1] by an extensive repertoire of physiological changes that promote the use of stored energy to prolong survival. Importantly, fasting is distinct from starvation[2], which is the ultimate endpoint at which survival is compromised due to the loss of organ function.

Extended bouts of fasting can be categorized into three chronological phases[3] (depicted in Figure 1), with the duration of each phase depending on various lifestyle and environmental factors. Phase I is relatively short (a couple days at most) and encompasses the transition from digestion and absorption of nutrients to digestive inactivity and the mobilization of stored energy as a fuel source. Glycogen stores are being depleted and the use of bodily protein as a substrate to create glucose has increased. Phase II is the longest phase where the body begins to rely more heavily on fatty acids and ketone bodies as an energy source, thus limiting its need for glucose and therefore minimizing the breakdown of bodily protein to make glucose. Phase III is the critical period of fasting during which fat stores have been depleted and the breakdown of bodily protein accelerates, eventually leading to organ failure and death (i.e., starvation).

Figure 1: Phases of fasting

Source: Secor and Carey. Compr Physiol. 2016 Mar 15.

As the body literally feeds on itself, numerous physiological adaptations occur to reduce energy requirements, including those central for growth and reproduction, with the focus shifting towards repair and maintenance. Notably, there is a suppression of the the growth hormone/insulin-like growth factor-1 (IGF-1) axis and mTOR-S6K pathway. Many of the interventions that extend lifespan in animals have the effect of reducing mTOR signaling[4], and using drugs to inhibit mTOR[5] in mice without any other intervention increases lifespan by more than 20%.

A renewed interest in longevity has spurred the creation of many types of fasting regimens. Some of the most well known are variations of intermittent fasting, or consuming little to no calories for 12 to 24 hours on a regular basis. Intermittent fasting has been investigated in controlled trials for weight loss[6] and reducing the risk[7] of metabolic diseases such as type 2 diabetes[8], especially in comparison[9] to daily energy restriction. However, the length of fasting may not be long enough to elicit the physiological changes related to life extension.

Of course, going for days without food is impractical for many in the modern world, not to mention probably very difficult. As such, fasting mimicking diets (FMDs) have recently emerged as a potential diet regimen that allows for eating while eliciting similar metabolic effects as complete abstinence from food. The expert consensus[10], based primarily on animal studies[11], is that FMDs are one of the more promising strategies for promoting longevity due to their ability to suppress the growth hormone/IGF-I axis and mTOR-S6K pathway.

To this end, a group of researchers published data in 2015[12] about a very low calorie and low protein FMD that caused physiological changes in mice that were similar to those caused by complete fasting. This publication also contained data on a pilot trial in 38 humans showing that the FMD was safe and feasible. The study under review is a follow-up randomized controlled trial of 100 participants evaluating the effects of the FMD on biomarkers and risk factors for metabolic syndrome and longevity.

Numerous physiological changes occur in response to fasting that have been shown in animals to extend lifespan. Accordingly, various fasting regimens have been developed and tested to promote longevity. One of these regimens is a fasting mimicking diet, which allows for food intake while still leading to similar physiological effects as complete fasting. The current study sought to test its effects on biomarkers and risk factors for metabolic syndrome and longevity in humans.

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