Nuances of intermittent fasting and its effect on healthy lifespan

by | Dec 26, 2023

A neuroscientist and intermittent fasting expert weighs in on the potential health benefits of this diet that may go beyond just weight loss.
Fruits and vegetables.

Being able to survive without food for extended periods of time is an evolutionary adaptation. Our hunter–gatherer ancestors were sometimes forced to run on empty, as food sources were few and far between.

These days, abstaining from eating, or “fasting”, is usually done for health, spiritual, or ethical reasons, and for many who do voluntarily fast, food is usually within arm’s reach. If weight loss or health improvement is the goal, intermittent fasting or time-restricted eating is a less extreme alternative to longer-term, multi-day fasting.

“In addition to weight loss, intermittent fasting can improve mental clarity, reduce inflammation, and improve blood glucose regulation and cardiovascular health,” Mark Mattson, a professor of neuroscience at Johns Hopkins University and author of The Intermittent Fasting Revolution: The Science of Optimizing Health and Enhancing Performance, told us.  

“Evidence suggests that intermittent fasting may help prevent cancers, stroke, and dementia,” he added. Excessive calorie intake, particularly in midlife, has been linked to higher risks of stroke, Alzheimer’s disease, and Parkinson’s disease.

The potential cognitive benefits of fasting might be less obvious. “Dietary restriction can prevent cognitive decline by providing ketones (energy) to neurons, by enhancing the ability of neurons to cope with stress, and by increasing the number of synaptic connections between neurons,” Mattson explained. 

But there are a few things to keep in mind. For one, what you eat matters. Intermittent fasting should be paired with eating a healthy diet, including whole grains, fruits and vegetables, unsaturated fats, and healthy protein sources, while avoiding processed foods and sugar.  

In addition, although some intermittent fasting studies have involved humans, many are based on animal models. The anti-aging effects of intermittent fasting on mice are promising, but these results can’t be directly applied to humans given their metabolic differences.

Nutrition plays a role   

According to a study published this year by Mattson and his collaborators, weight reduction as a result of intermittent fasting does not automatically improve metabolic health.

This randomized, controlled trial, which included overweight participants, was divided into two parts. For the first six months, 21 participants (group A) fasted on alternate days (that is, for 24 hours at a time), but were allowed to eat a fasting-mimicking diet of non-starchy vegetables on fasting days to help minimize dropout, which is a common problem in fasting studies. Otherwise, they ate a standard Western diet. At the same time, the 20 participants in the control group (group B) ate their normal diet.   

In the second part of the study, 19 participants from group A continued to alternate-day fast for another six months (12 months in total), and 12 participants from group B, who had previously been controls, began fasting in the same manner. 

Although the participants lost, on average, 8% body weight and around 16% fat mass over the study period, changes in healthy aging indicators, such as inflammation, glucose tolerance, and insulin sensitivity, were negligible at best.

This finding is in contrast to intermittent fasting studies on rodents, where mice subjected to a 12-month alternate-day fasting protocol improved on all healthy aging indicators.

In their article, Mattson and his collaborators stressed that mice have an extremely high metabolism and will starve to death after only 48–60 hours of fasting, while humans can go 57–73 days without eating. Given this metabolic difference, a 24-hour fast for a mouse roughly equates to a five-day fast for a human, which explains why humans do not benefit in the same ways as mice from a 24-hour fast.

In intermittent fasting studies involving mice, the mice normally eat a nutritionally balanced meal during feeding times, while the participants in this study ate as they would normally, including processed, high-calorie foods. This discrepancy would account for the very slight increase in insulin sensitivity.  

Intermittent fasting myths

Given the popularity of intermittent fasting and wealth of information available, some misconceptions have arisen. Mattson says there are three major myths surrounding the practice.

For one, many people assume that the change will be difficult to incorporate into their lifestyle. But Mattson believes that fasting can be adopted like any other habit, and the irritability, hunger, and brain fog that might arise during the adjustment period will subside. “After an initial adaptation period of several weeks, intermittent fasting becomes easy,” he said.

The time window of eating can also be adjusted according to a person’s lifestyle, and intermittent fasting eliminates the need to count calories since you’re effectively skipping a meal—as long as those calories aren’t crammed into the shorter eating period. 

The second myth is that eating numerous small meals throughout the day is superior to eating a few larger meals. For most people, the norm is to consume three meals a day plus snacks, but the metabolic shift that accompanies intermittent fasting cannot be tapped into by following this eating schedule.

“Spacing meals throughout the day prevents the metabolic switching (from glucose to fats and ketones) that is important for the health benefits of intermittent fasting,” Mattson explained. Metabolic switching typically begins around 10 to 12 hours after the onset of fasting. 

Normally, the body uses glucose stored in the liver for energy, but this energy source is eventually exhausted during fasting. The body instead resorts to fat, which is stored in fat tissue in the form of molecules called triglycerides that are broken down into fatty acids and glycerol. These serve as alternative energy sources, and the liver converts these fatty acids into “ketone bodies”, which not only supply energy to the brain and body but are involved in major cellular pathways associated with health and aging.

Some research has also suggested that intermittent fasting comes with the tradeoff of reduced muscle mass, but this also somewhat of a myth. Muscle mass loss is normal for any weight-loss diet and seems to only be the case if a person who is intermittently fasting is sedentary. 

Mattson emphasized the importance of exercise while fasting, stating that “intermittent fasting can facilitate (with exercise) muscle strength and endurance.”   

Human trials have shown that lean muscle mass is at least conserved when intermittent fasting is paired with regular exercise. For example, one study found that 21 overweight and obese adults who completed aerobic and resistance training while following a time-restricted eating regimen lost fat mass but actually gained lean mass.

Kinesiology researchers at the University of Toronto have also stated that pairing intermittent fasting with resistance exercise is particularly important for preserving muscle mass.

Fasting for longevity

Although how much a person benefits from intermittent fasting depends on diet and exercise, fasting on its own can initiate a specific process linked to longevity. 

Over time, the components of cells, such as proteins and organelles, undergo wear and tear and accumulate as junk. During autophagy, which means “self-eating” in Greek, cells dispose of this so-called “molecular garbage” and recycle the salvageable pieces into new cell parts. The regular occurrence of this process is important in protecting against chronic diseases such as diabetes, heart disease, cancer, and neurodegenerative disease.

“Autophagy promotes longevity by preventing the accumulation of damaged/toxic proteins and mitochondria in cells,” Mattson explained. “Impaired autophagy is implicated in Alzheimer’s disease and Parkinson’s disease. By stimulating autophagy, intermittent fasting can slow the aging process.”  

Until recently, scientists believed that liver cells were solely responsible for initiating autophagy.

Researchers at the Max Planck Institute for Metabolism Research found that the brain triggers liver autophagy in mice, even after four hours of nutrient deprivation. A group of neurons in the hypothalamus, the part of the brain that controls hunger, trigger the release of the hormone corticosterone, which induces liver autophagy.

In humans, however, it’s unclear exactly how long a person has to fast before significant autophagy sets in.

A research team in Germany recently measured the levels of autophagy markers in healthy young males who fasted for one month, from dawn to dusk each day. After two weeks of following this protocol, participants had higher levels of several proteins associated with autophagy activation, suggesting that prolonged intermittent fasting may induce autophagy.    

Although the research indicates that intermittent fasting has some health and longevity benefits, the safety and efficacy of the practice cannot be generalized to everyone and depends on sex, diet, and genetic factors.

For those who are underweight, have certain medical conditions, are taking certain medications, are pregnant or breastfeeding, or are recovering from illness, fasting isn’t recommended. It’s also important to stay well-hydrated during the fasting period. To safely fast — or to determine whether you should fast at all — a healthcare provider should be consulted before making any extreme changes.

Feature image credit: Jakub Kapusnak on Unsplash

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