Health enthusiasts, including many of our LIFE Fasting Tracker users, have long practiced intermittent fasting for its reported ability to not only improve insulin sensitivity and tap the brakes on the cellular growth promoter called mTOR, but “clean up” our cells and improve tissue function through autophagy.

Autophagy is a process of cellular recycling. During autophagy, components inside of cells, including proteins, are degraded and recycled. For example, autophagy can protect brain cells against accumulation of “bad” protein clumps that cause neurodegeneration.

Autophagy activity has been shown to increase during intermittent fasting in animal models, with health benefits including clearance of harmful, dysfunctional or “sticky” aggregating proteins in the brain. But autophagy is difficult to measure in human beings. It has never been studied as a direct impact of intermittent fasting in humans. That is, until now.

“Autophagy is an important biological process that is essential for the removal of damaged organelles and toxic or aggregated proteins by delivering them to the lysosome for degradation.”  –  Martin et al. 2015

A new study conducted by researchers at the Pennington Biomedical Research Center in Louisiana and the University of Alabama at Birmingham suggests that just 16 hours of daily intermittent fasting can upregulate cellular recycling processes. In the study, 11 overweight adults who practiced early time-restricted eating, or who fasted from 2pm to 8am for four consecutive days, collectively had evidence of increased autophagy-related gene expression!

What is Early Time-Restricted Eating?

Early time-restricted eating is one form of daily intermittent fasting. If you are a regular at LIFEApps, you know that intermittent fasting is an approach to eating that involves taking regular breaks, from periods of 12 hours to several days, to allow the body to essentially rest and repair.

The average American eats at least over a 12-hour period. In fact, one study conducted via Satchidananda Panda’s My Circadian Clock app found that more than half of the adults using the app ate over the course of 15 hours or longer every day! This type of eating schedule can lead to chronically elevated levels of glucose and insulin that push cells to grow instead of recycle their components, reduce and clean up harmful waste products of metabolism, and repair damage. Around the clock eating raises our risk of weight gain, obesity, insulin resistance, inflammation and chronic disease.

“In humans, data on [intermittent fasting] is limited but suggests that it decreases body weight, insulin levels, blood pressure, inflammation, and appetite, and that it improves insulin sensitivity and lipid profiles..” – Peterson et al., 2019

Early time-restricted eating is a special flavor of intermittent fasting that combines the “rest and repair” benefits of a period of strict calorie restriction with the benefits of eating in tune with our biological clock. Our evolution on earth has led our bodies and the cells that make up our bodies to be metabolically active during daylight hours. In other words, our bodies and brains were built to eat during the day while fasting in the early evening and overnight (if not longer).

Circadian rhythms in our body’s activities, from the expression of our genes to the levels of our stress, hunger and sleep hormones, ideally reflect the rise and setting of the sun. Eating by the sun has a range of health benefits. It improves the profile of healthy microbes in your gut, sleep quality and blood sugar control.

“Time-restricted feeding (TRF) is a novel form of intermittent fasting that improves cardiometabolic health, slows tumor progression, delays aging, and increases lifespan in rodents.” – Peterson et al., 2019

To date, researchers have investigated the impacts of time-restricted eating in humans in a total of nine trials. Although these trials have typically involved relatively small sample sizes, time-restricted eating has been observed to naturally restrict calories and promote weight loss, reduce body fat, reduce inflammation and improve insulin sensitivity in individuals with prediabetes. Time-restricted eating also improved muscular endurance in young men performing endurance training, compared with eating around the clock.

Early time-restricted eating takes daily fasting to the next level by pushing the majority of your calorie intake into the morning and early afternoon. While any form of daily fasting typically comes with health benefits, earlier is typically better. Evening-only meals may promote weight loss, fat loss and reductions in insulin levels, but may increase blood pressure, cholesterol and even morning fasted glucose levels.

Our bodies are most insulin sensitive some time after we wake up in the morning and into the early afternoon, based on our circadian rhythms of glucose and fat metabolism. Typically, eating during daylight hours is associated with improved weight loss and metabolic health. Based on preliminary studies, early time-restricted eating improves insulin sensitivity, lowers blood pressure, increases fat oxidation, reduces the hunger hormone ghrelin and improves subjective appetite.

Eating by the sunlight can reduce risk of weight gain and insulin resistance.
Eating by the sunlight can reduce risk of weight gain and insulin resistance.

A New Trial of Early Time-Restricted Eating in Humans

The new study on early time-restricted eating published in Nutrients involved of a four-day randomized crossover trial. Participants were randomly (by the toss of a coin) assigned to eat on a typical American eating schedule (12 hours of eating between 8am and 8pm) or on an early time-restricted eating schedule (18:6 fasting, between 8am and 2pm). The participants on one schedule then switched to the other schedule after a few weeks of normal eating. Thus, all participants practiced a total of four days of intermittent fasting during the study period.

The research participants included seven men and four women. The average age was 32, the average BMI was approximately 30 kg/m2 (at the boundary between normal weight and overweight), and the average fasting glucose level was 92 mg/dl (normal range).

Participants underwent continuous glucose monitoring and had their blood drawn twice between days 3 and 5 of their assigned 4-day eating schedules. Researchers used these blood samples to measure a range of health metrics. They measured cardiometabolic risk factors such as blood glucose, insulin and lipid levels, as well as levels of hormones like cortisol and the brain cell growth factor BDNF. They also measured expression or activity of genes related to circadian (biological clock) rhythms, longevity and autophagy.

Perhaps most intriguingly, when the overweight research participants were eating from only 8am to 2pm every day for four days, their morning levels of mRNA (a template for making proteins that is created from a gene, or DNA) reflected heightened activity of healthy circadian rhythms and autophagy.

Specifically, early time-restricted eating increased expression of LC3A, a gene that creates a protein that helps to form the structures inside of cells where recycling takes place, called autophagosomes. LC3A expression increased by nearly a quarter, or by 22%, in the morning at the end of an 18-hour fast. LC3A is commonly expressed in brain tissue and fat, as well as other tissues.

“Autophagy has been shown to play a major role in protecting against multiple chronic diseases such as diabetes, heart disease, cancer, and neurodegenerative diseases, by recycling damaged and used proteins and organelles. Increasing autophagy may have anti-aging or rejuvenating effects. Although no previous studies examining TRF as a meal timing intervention have investigated autophagy in either animals or humans, other studies on intermittent fasting conclude that several of the benefits of intermittent fasting are mediated through enhanced autophagy.” – Peterson et al., 2019

Autophagy is a complex process that requires the activation of many different genes and proteins. But substantially increased levels of LC3A gene expression in the morning after an 18-hour fast is a good indication that prolonged overnight fasting activates cellular recycling more than an eating schedule that includes late-night snacking.

Our bodies naturally activate autophagy at night, when our levels of glucose and insulin are ideally at their lowest. Glucose and insulin levels that increase after we eat signal mTOR, which acts as a strong “brake” on autophagy activities. Learn more about that here. This is part of the reason why eating late at night, along with sleep disruption, is associated with increased risk for a range of chronic diseases. Late night eating can lead to abnormally elevated levels of glucose and insulin as you sleep and lowered sleep quality, both of which can blunt autophagy aka cellular recycling.

“[E]ating dinner at 8 pm leads to a prolonged elevation of glucose levels while asleep and may have adverse metabolic consequences, such as impairing fat oxidation.” – Peterson et al., 2019

In the new study, early time-restricted eating also increased expression levels of the SIRT1 – the “longevity” gene – in the morning, decreased cortisol (stress hormone) levels in the evening and slightly increased levels of brain-derived neurotrophic factor (BNDF), a nerve cell growth factor.

“BNDF promotes neuronal growth, development, and survival and is widely known to be increased by intermittent fasting in rodents. Our study is one of the first trials to demonstrate that intermittent fasting can increase BDNF levels in humans.” – Peterson et al., 2019

SIRT1 codes for a special protein called a deacetylase that is known to protect our cells against inflammation, oxidative stress, telomere shortening and DNA damage. Greater SIRT1 gene expression is even associated with longevity in humans, while lower expression levels are associated with Alzheimer’s disease. Learn more about how fasting can activate SIRT1 here.

“The increase in SIRT1 expression in the morning suggests that eTRF may also promote longevity in humans, as it does in animals.” – Peterson et al., 2019

Finally, early time-restricted eating also doubled morning blood ketone levels compared to a normal eating schedule, lowered overnight and morning fasted glucose levels by several milligrams per deciliter (mg/dl), reduced periods of very high or low glucose levels, and lowered morning insulin levels. This overnight fasting schedule increased expression of a gene that creates insulin receptor substrate-2, a signaling molecule that communicates the presence of insulin within a cell. This suggests an increase in insulin sensitivity.

Early time-restricted eating did slightly increase the research participants’ lipid levels in the morning. This may be normal and reflective of fat burning during a longer fasting window, but more studies are needed to ensure that prolonged daily fasting doesn’t pathologically elevate cholesterol in healthy individuals.

Going out to dinner with friends while on a time-restricted eating schedule? Just order some tea!
Going out to dinner with friends while on a time-restricted eating schedule? Just order some tea!

Takeaways

Studies of time-restricted eating schedules that involve early day eating are still limited. We need more of these studies that look at impacts in far greater numbers of people, including normal weight, healthy individuals. However, to date early time-restricted eating appears to help with weight loss and blood sugar control.

We also now have evidence for the first time that 18 hours of daily fasting can activate the expression of genes related to autophagy in humans! That’s really good news for those of us practicing occasional 24-hour fasting to reach cellular recycling for health and potentially even healthy aging benefits.

To be safe, check in with your physician to monitor your blood lipid levels and markers of insulin sensitivity over time as you practice any form of intermittent fasting.


Paige Jarreau

I am the Director of Social Media and Science Communication for LifeOmic and an avid blogger. I'm interested in how scientists use social media to promote public engagement and health behaviors.

LifeOmic is the software company that leverages the cloud, machine learning and mobile devices to offer disruptive solutions to healthcare providers, researchers, health IT companies and patients.

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