Intermittent fasting: diet trend, Silicon Valley practice, religious ritual, and now, maybe, long-term health regimen? Intermittent fasting (IF) has been around for centuries but only penetrated the mainstream in the past decade. Celebrities like Hugh Jackman and tech executives like Jack Dorsey have practiced the diet, along with almost 400,000 people on Reddit. Jackman credits IF with helping him build muscle and shred weight while prepping for The Wolverine. Dorsey, who eats just one meal a day, says the practice helps him focus and sleep better. But what does the science say? What do we know, and more importantly, not know about intermittent fasting?

The potential health benefits of intermittent fasting are long: accelerated weight loss, reduced inflammation, lower cholesterol, longer lifespan, blood sugar stabilization, and prevention of type 2 diabetes.

Emerging research suggests intermittent fasting may also lead to a healthier brain, longer life, and even aid cancer treatment. But such claims remain controversial.

While offering promising health gains, the research, primarily conducted in animal models and rodents, has significant limitations.

Scientists have made strides in determining how intermittent fasting impacts the mind and body, but there is still a long way to go.

How Intermittent Fasting Works

Each time we eat, the body releases insulin to help cells convert sugar (especially glucose) from the food into usable energy. If the glucose isn’t used immediately, insulin helps store the excess glucose in fat cells. But when we don’t eat food for extended periods, insulin is not released, and the body then starts breaking down fat cells for energy, leading to weight loss and triggering different signal pathways to the rest of the body.

Intermittent fasting facilitates this process. Basically, intermittent fasting (IF) means cycling through periods of abstaining from food (or drastically cutting food intake) with periods of normal eating. Fasts typically last from 12 hours to up to weeks at a time.

Some intermittent fasters gush about the 5:2 Diet, which involves eating normally for five days and consuming no food (or fewer than 500 to 600 calories) on two fasting days per week. Others limit their “feeding window”, squeezing all their meals into six- or eight-hour periods and fasting for the rest of the day or night. Some people rave about the “one meal a day” (OMAD) diet, where people fast for 23 hours a day, then squeeze all their eating into a single hour.

A plant-based diet will help you feel full during fasting periods. Unsplash / Edgar Castrejon

During fasting periods, dieters stave off hunger pangs and survive on black coffee, tea and water. On non-fasting days, people eat normally. Experts like Monique Tello, MD, MPH, a Harvard Medical School professor and internal medicine physician at Massachusetts General Hospital, suggest eating a plant-based diet and consuming protein and nutrient-rich food to feel full during fasting periods.

"I usually tell people that if you want to lose weight, intermittent fasting is probably the way to go. If you want to live a long time and be out of the hospital, a plant-based diet is the way to go.”

“Combine those two and you are good to go,” Tello explains to Inverse.

But, like most dietary approaches, intermittent fasting is not for everyone, and comes with potentially dangerous risks. IF can be uncomfortable, unsustainable, exacerbate disordered eating patterns, and may increase stress levels in fasters.

Your Brain on Intermittent Fasting

Intermittent fasting doesn’t just help you lose weight; it may also make you sharper and healthier as you age. In lab rats and mice, intermittent fasting shows the potential to help slow aging, extend lifespan, and counteract age-related disorders, including cardiovascular disease, cancers and neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and stroke.

The research dates back almost a century. The first widely recognized scientific study of restricted diets and their ability to extend lifespan was published by McCay et. al in 1935. Still, human studies are limited; most of the research has been conducted on rodents.

Mark Mattson, Ph.D., a professor of neuroscience at the Johns Hopkins University School of Medicine and former chief of the Laboratory of Neurosciences at the National Institute on Aging, has studied intermittent fasting and its impacts on aging and the brain since the ‘90s. Decades of his research have shown protective effects caused by intermittent fasting against neurological diseases.

“The bottom line is that, in the brain, intermittent fasting will increase the resistance of nerve cells to various types of stress,” Mattson tells Inverse. “It will enhance what we call synaptic plasticity or the formation of new synapses. And then, we recently published a couple papers that suggest that the intermittent fasting increases the number of mitochondria in individual nerve cells.”

Put simply, intermittent fasting can help trigger certain pathways in the brain that help cells become more equipped to deal with stress and resist disease.

A 2006 literature review published in Ageing Research Reviews, authored by Mattson, Bronwen Martin, MD, Ph.D., and Stuart Maudsley, found that intermittent fasting, along with calorie restriction, spurred the production of neurotrophic factors, antioxidant enzymes, proteins, and repair pathways that make the brain stronger, healthier, and more efficient. Studies on rodents also suggest that intermittent fasting can enhance learning and memory. A 2010 literature review published in Neuroscience Bulletin outlined how dietary restriction and intermittent fasting has been shown to improve health and slow the aging process in many species, such as improving learning and memory, delaying age-related cognitive decline, and reducing the risk of neurodegenerative disorders.

All signs point to more energy and a healthier brain. But it’s not just intermittent fasting that shows these potential benefits. Studies on good old dietary restriction — simply eating less than normal — appear to do the trick as well.

Furthermore, Tello is quick to point out that many of the promised neurological benefits of intermittent fasting have also been seen in a plant-based diet. “The World Health Organization actually just released official recommendations looking at all of the research,” she says. “Lower risk of dementia, improved memory, cognition, mood; I’ve seen the most studies on the plant-based diet. Intermittent fasting may or may not have effects on those areas. But I don’t think there’s enough evidence yet accumulated to incorporate that into any of the recommendations.”

Systematic review of the research confirms Tello’s assertion. Currently, there is no direct evidence from a human study showing the protective effect of either short-term or long-term dietary restriction on cognition, such as memory, attention, processing speed, and concentration. So, maybe, Dorsey is wrong.

Fasting to Age Better

For millenia, people have searched for the secret to staying young, healthy, and fit. In 2018, the global anti-aging industry was worth 42.51 billion US dollars, and is estimated to reach 55 billion US dollars by 2023. Despite ample money funneling into research and high consumer spending, no one has found that magic cure to warding off dementia, weight gain, joint pain, and all the other not so fun side effects of getting older.

In addition to a healthy diet, it's critical to keep moving as you age: walking, jogging, hiking, and swimming are all great options. Unsplash / sk

Intermittent fasting has well-documented age-related benefits, in addition to potential positive effects on the brain.

There are multiple ways in which intermittent fasting seems to slow down aging, Mattson explains. The first is reduced inflammation. Mattson’s lab has shown that IF is linked to reduced inflammation in the brain, and other researchers have seen the effect in other tissues.

Inflammation is a biological defense mechanism that occurs naturally when the immune system detects threats, like a damaged molecule, toxic compound, or pathogen. However, if inflammation kicks up too often or gets out of control, it can lead to chronic inflammation throughout the body, contributing to tissue damage or disease. A 2016 literature review analyzing how inflammation is caused and resolved showed that too much can cause cardiovascular diseases, atherosclerosis, type 2 diabetes, rheumatoid arthritis, and some cancers. In short, keeping inflammation in check using IF can keep us healthier for longer.

The second mechanism by which IF seems to slow aging, Mattson says, is through reduced accumulation of molecules damaged by free radicals. Free radicals are unstable molecules that can damage cells, causing aging and illness.

“There seems to be a stimulation of the cells own intrinsic antioxidant defenses, and there is quite a bit of evidence that the cells are able to better remove damaged molecules,” Mattson explains.

Cells get rid of damaged molecules through a regenerative process called autophagy — what Mattson calls your body’s “garbage disposal.” Cells degrade or break down and recycle themselves.

“During aging, the cell’s ‘garbage disposal system’ becomes progressively worse. And intermittent fasting maintains the ability to remove the molecular garbage.”

Could Intermittent Fasting Prevent or Help Treat Cancer?

Although the research is nowhere near conclusive, studies do suggest that intermittent fasting could help prevent and even aid treatment in cancer patients.

Mattson says there’s been a large increase in the number of clinical trials of intermittent fasting, some focused on cancer.

“There’s a pretty strong scientific rationale for why intermittent fasting when getting chemo or radiation therapy may be a benefit,” Mattson says. “That’s started in animal studies, and intermittent fasting was showing a slow in tumor growth in various cancer models.”

Most cancer cells cannot use ketones for their energy, Mattson explains. Ketones are produced from using fat stores instead of glucose, and are triggered during intermittent fasting and other dietary approaches like the keto diet. Cancer cells use glucose almost exclusively.

“The idea is if you have to have a patient when they’re getting chemo or radiation, which are very harsh on cells, including your normal cells, that if the person has low glucose and ketones are up, the cancer cells will be more vulnerable to being killed by the drugs or radiation. Since the normal cells do use ketones, and because the intermittent fasting protects them against stress, the side effects of the treatment may be less.”

A 2012 review of decades of animal studies by Michelle Harvie, Ph.D., and Anthony Howell at the University of Manchester also showed potential benefit of habitual energy restriction or intermittent fasting on reducing breast cancer tumor growth.

But again, a few promising studies, even in humans, do not imply certainty. The relationship between intermittent studies and cancer needs to be studied far more extensively.

Tello agrees. When asked about Harvie’s research, Tello replied: “That’s going to be under the category of one study that is interesting. But really, you can’t say anything about it because it’s just one study.”

"The most evidence we have is around the plant-based diet, and not only cancer prevention but also cancer recurrence prevention."

Most of the studies Tello is referencing focus on breast cancer. “Women who have a history of breast cancer who are able to follow either a plant-based diet or a more active lifestyle or both have a lower risk of recurrence of their breast cancer. We know that applies to other cancers as well. Prostate cancer in particular.”

IF's health benefits may also result from combined dietary approaches like the Mediterranean diet. Pexels

Is Fasting Good for You or Just Weight Loss?

It is important to note that many of the health benefits tied to intermittent fasting also result from other dietary approaches like the plant-based diet, Mediterranean diet, or even just from weight loss. It is not clear yet which benefits result from the fasting itself, or from the weight loss that the fasting causes.

“There really is no one weird trick for the perfect diet for everyone,” John Newman, MD, Ph.D., a geriatrician at the University of California, San Francisco and researcher with the Buck Institute for Research on Aging, tells Inverse. “If anything, I would say that the science is leading us more towards the idea that we want to maintain some flexibility in our body’s metabolism, and it’s probably a good idea to be doing different things at different times. And this might be one of the reasons why intermittent fasting, for example, is metabolically helpful, because it forces your body to switch how it is using a fuel for energy.”

While the potential health benefits are impressive, health professionals stress that intermittent fasting could exacerbate disordered eating patterns like anorexia, bulimia, or orthorexia. People with a history of this behavior should consult a doctor to see if intermittent fasting is a healthy approach to eating for them.

Intermittent fasting’s impacts on the brain, aging, and disease are still in question. But if research in human subjects confirms the potential benefits of carefully incorporating fasting into a normal diet, then skipping breakfast or nighttime snacking may become as common as lunch and dinner.