Feature Article: Intermittent Fasting and Human Metabolic Health by Patterson et al. - an Overview

1 - Moores UCSD Cancer Center, University of California, San Diego, La Jolla, CA, USA  2 - Department of Family & Preventive Medicine, University of California, San Diego, La Jolla, CA, USA 3 - Department of Medicine, Division of Endocrinology and Metabolism, University of California, La Jolla, California, USA 4 - Graduate School of Public Health, San Diego State University, San Diego, CA, USA 5 - Department of Psychology, San Diego State University, San Diego, CA, USA

INTRODUCTION

Periods of voluntary abstinence from food and drink (i.e., intermittent fasting) has been practiced since earliest antiquity by peoples around the globe. Books on ethnology and religion describe a remarkable variety of fasting forms and practices.1 Renewed interest in fasting regimens is evidenced by a plethora of popular press publications and diet recommendations. For example, in 2013, Mosley and Spencer published a best-selling book titled “The Fast Diet,” which touts the benefits of restricting energy intake severely for two days a week while eating normally the rest of the week.2 Dozens of books promote various fasting dietary patterns and the web offers hundreds of fasting-related sites. However, scientific evidence for the health benefits of intermittent fasting in humans is often extrapolated from animal studies, based on observational data on religious fasting (particularly Ramadan), or derived from experimental studies with modest sample sizes.

The overall objective of this paper is to provide an overview of intermittent fasting regimens (Table 1) and summarize the evidence on the health benefits of intermittent fasting with a focus on human intervention studies. Because much of the data on intermittent fasting is from research in animal models, we briefly summarize key rodent studies and reviews. Health outcomes of interest are changes in weight and metabolic parameters associated with type 2 diabetes, cardiovascular disease, and cancer. We also present an overview of the major mechanisms hypothesized to link fasting regimens with human health: (1) circadian biology, (2) the gastrointestinal microbiota, and (3) modifiable lifestyle behaviors such as diet, activity, and sleep. Finally, we present conclusions regarding the evidence-base for intermittent fasting as an intervention for improving human health and propose a research agenda.

This paper provides a uniquely broad synthesis of the scientific evidence linking intermittent fasting with human health and a framework for future research on this topic.

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The publisher's final edited version of this article is available at J Acad Nutr Diet

 CONCLUSIONS

It is well known that in humans, even a single fasting interval (e.g., overnight) can reduce basal concentrations of metabolic biomarkers associated with chronic disease such as insulin and glucose. For example, patients are required to fast for 8–12 hours before blood draws to achieve steady-state fasting levels for many metabolic substrates. Therefore the important clinical and scientific question is whether adoption of a regular intermittent fasting regimen is a feasible and sustainable population-based strategy for promoting metabolic health. In addition, research is needed to test whether these regimens can complement or replace energy restriction and if so, whether they support long-term weight management. Below, we briefly summarize the major conclusions that can be drawn based on

Periods of voluntary abstinence from food and drink (i.e., intermittent fasting) has been practiced since earliest antiquity by peoples around the globe. Books on ethnology and religion describe a remarkable variety of fasting forms and practices.1 Renewed interest in fasting regimens is evidenced by a plethora of popular press publications and diet recommendations. For example, in 2013, Mosley and Spencer published a best-selling book titled “The Fast Diet,” which touts the benefits of restricting energy intake severely for two days a week while eating normally the rest of the week.2 Dozens of books promote various fasting dietary patterns and the web offers hundreds of fasting-related sites. However, scientific evidence for the health benefits of intermittent fasting in humans is often extrapolated from animal studies, based on observational data on religious fasting (particularly Ramadan), or derived from experimental studies with modest sample sizes.

The overall objective of this paper is to provide an overview of intermittent fasting regimens (Table 1) and summarize the evidence on the health benefits of intermittent fasting with a focus on human intervention studies. Because much of the data on intermittent fasting is from research in animal models, we briefly summarize key rodent studies and reviews. Health outcomes of interest are changes in weight and metabolic parameters associated with type 2 diabetes, cardiovascular disease, and cancer. We also present an overview of the major mechanisms hypothesized to link fasting regimens with human health: (1) circadian biology, (2) the gastrointestinal microbiota, and (3) modifiable lifestyle behaviors such as diet, activity, and sleep. Finally, we present conclusions regarding the evidence-base for intermittent fasting as an intervention for improving human health and propose a research agenda.

This paper provides a uniquely broad synthesis of the scientific evidence linking intermittent fasting with human health and a framework for future research on this topic.

Studies in rodents and other nocturnal mammals support the hypothesis that intermittent fasting and restricting the availability of chow to the normal nighttime feeding cycle improves metabolic profiles and reduces the risk of obesity, obesity-related conditions such as non-alcoholic fatty liver disease, and chronic diseases such as diabetes and cancer. 

In healthy, normal weight, overweight, or obese adults, there is little evidence that intermittent fasting regimens are harmful physically or mentally (i.e., in terms of mood).

 It appears that almost any intermittent fasting regimen can result in some weight loss. Among the 13 intervention trials included in this review, 11 (84.6%) reported statistically significant weight loss ranging from 1.3% in a cross-over trial with a 2 week intervention23 to 8.0% in a 1-arm trial of 8 weeks duration.13

 Based on only 3 studies, alternate day fasting appears to results in weight loss as well as reductions in glucose and insulin concentrations. However, this pattern may not be practical because of intense hunger on fasting days.

 Modified alternate day fasting regimens result in reduced weight, ranging from 3.2% in comparison to a control group16 over a 12 week period to 8.0% in a one-arm trial over an 8 week period.13 There was limited and mixed evidence for reductions in insulin concentrations, improvements in lipids or reductions in inflammatory factors.

 Research to date has not demonstrated that alternate day fasting regimens produce superior weight loss in comparison to standard, continuous calorie restriction weight loss plans.

 There are limited data from human studies to support the robust rodent data regarding the positive impacts of time-restricted feeding (i.e., eating patterns aligned with normal circadian rhythms) on weight or metabolic health.

 There are considerable observational data on various forms of religious fasting, most of which suggests that these regimes result in transitory weight loss with mixed impacts on other biomarkers.

 Data are lacking regarding the impacts of intermittent fasting on other health behaviors such as diet, sleep, and physical activity.

 There are little or no published data linking intermittent fasting regimens with clinical outcomes such as diabetes, cardiovascular disease, cancer, or other chronic diseases such as Alzheimer’s.

 A Research Agenda on Intermittent Fasting

Intermittent fasting regimens attempt to translate the positive effects of fasting regimens in rodents and other mammals into a practical eating pattern for reducing the risk of chronic

disease in humans. Below we give suggestions for a future research agenda investigating intermittent fasting and metabolic health.

Modified fasting regimens appear to promote weight loss and may improve metabolic health. However, there are insufficient data to determine the optimal fasting regimen, including the length of the fasting interval, the number of “fasting” days per week, degree of energy restriction needed on fasting days, and recommendations for dietary behavior on non-fasting days.

Several lines of evidence support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals could result in sustained improvements in human health. While this hypothesis has not been tested in humans, support from animal research is striking and data from human time-restricted feeding studies are suggestive. Prolonged nightly fasting may be a simple, feasible, and potentially effective disease prevention strategy at the population level.

Large-scale randomized trials of intermittent fasting regimens in free-living adults are needed and should last for at least a year to see if behavioral and metabolic changes are sustainable and whether they have long term effects on biomarkers of aging and longevity. Future studies should incorporate objective measures of energy intake, sleep, and energy expenditure; assess numerous markers of disease risk; and enroll diverse populations who disproportionately suffer from obesity and related health maladies.

Current recommendations for weight loss frequently include advice to eat regular meals to avoid becoming hungry. Some guidelines also advise the consumption of regular snacks throughout the day. However, it is not clear that periods of fasting (i.e., hunger) necessarily lead to periods of over-eating. This overview suggests that intermittent fasting regimens may be a promising approach to lose weight and improve metabolic health for people who can tolerate intervals of not eating, or eating very little, for certain hours of the day or days of the week. If proven to be efficacious, these eating regimens may offer promising nonpharmacologic approaches to improving health at the population level with multiple public health benefits.