Frame Magazine


The serious science of not eating, according to three prominent scientists studying it, and how it may change the way you think about food. We’ve decided to keep this story focused on the science of fasting, as explained by the experts, rather than providing advice. (And any advice you do take from articles should be discussed with your healthcare practitioner.) But readers will inevitably wonder what it’s like to do these fasting regimens. In our experience they do present some challenges. For instance, cutting calories can be uncomfortable, and continuing to exercise (during the 5:2 diet) probably requires careful planning. The biggest challenges tend to be social, though: If your eating window has closed or you’ve consumed your allotted calories, how do you go out for an impromptu happy hour with colleagues or dinner with friends? As more human data emerges supporting the positive health benefits of fasting, it will be important to have a clear and public discussion about the potential gains to be accrued in exchange for changing our relationship with food. When it comes to diet, the questions that concern scientists are no longer simply “What should we eat?” and “How much should we eat?” Now, it is when we should eat and whether we should eat at all — at least for certain periods of time. The relationship between health and longevity, and fasting (i.e., not eating), was as recently as 20 years ago, seen as the scientific backwater. But this is changing. Longevity research has entered the mainstream, and with it a wide body of research that significant calorie reduction over specific periods of time may actually improve long-term health. In lab studies, three types of calorie restriction — time-restricted feeding, calorie restriction and periodic fasting diets — have demonstrated benefits to healthspan (the healthy, functional years of one’s life), reducing the risk of age-related diseases. Mice, for instance, have shown protection from obesity (and the associated chronic diseases), improved fitness, and lower risk of metabolic diseases. Now, recent studies are confirming that at least some of these benefits translate to humans. More conclusive studies are in the works that will shed vital light on fasting and long-term health. We spoke with three leading scientists pursuing research on this topic: Dr. Satchidananda Panda, an expert in circadian rhythms and time-restricted feeding; Dr. Michelle Harvie, a research dietitian and specialist in calorie restriction (often called intermittent fasting); and Dr. Valter Longo, a fasting and longevity specialist, who focuses on cellular health and periodic fasting.


Time-Restricted Feeding:

Scientist: Satchidananda Panda

Education: Ph.D., The Scripps Research Institute, La Jolla, CA

Role: Professor, Regulatory Biology Laboratory, Salk Institute for Biological Studies

Recent Paper: A camera-phone based study reveals erratic eating pattern and disrupted daily eating-fasting cycle among adults in India

Area of Study: The genes, molecules and cells that keep the whole body on the same circadian clock

What It Means: Time-restricted feeding (TRF) is the practice of limiting calorie intake to a certain time period, somewhere between eight and 12 hours per day. It’s based on Panda’s research on circadian rhythms and how our adherence to patterns of sleep, physical activity, and eating, affect them. Panda noted that existing diet advice focuses on what and how much one eats, often leaving out the crucial third component of when one eats. Based on animal and human studies, Panda’s general conclusion is humble yet practical: “Spreading calories over a long period of time may not be the best idea.”

How it Works: Like any good expert, Panda explains complex concepts with analogies. His first: the stoplight. According to Panda, the body does not have one circadian clock, but a series of circadian clocks (“a clock in the gut, a clock in the kidney, a clock in the liver”) that make up the whole of our biological rhythm. Each of these is turned off and on at certain times, and can be imagined as stoplights. The system works best when the stoplights are in sync, to keep traffic rolling smoothly. The digestive system works on a particular sequence throughout a day, turning on when we first consume calories in the morning. That kicks the system in gear. As food moves through the system, each organ does its work, then moves into “standby” mode, then kicks on again when we eat next, and so on until we eat our last meal. When the system finishes its work, it does a bit of self-maintenance. If you toss in an outlier (say, a quick half-pint of ice cream in the middle of the night), the system’s maintenance process is thrown off, which hurts overall proficiency. Said another way, if you eat from 6:00 a.m. until 11:00 p.m., you’re only giving the body a seven hour window to repair, which, Panda has found, is not an optimal amount of time. In Panda’s studies (here, here, and here, all of which are available for download on his lab’s website), he restricted mice to different feeding intervals, (8, 9, 12, and 15 hours) and offered one group access to food at all times of the day (24 hours). Interestingly, mice consumed a comparable amount of calories provided they were allowed to eat for at least 8 hours. Generally speaking, the mice that had more restricted eating periods performed better on fitness tests than mice that ate for a longer period of time. Likewise, the mice that were restricted to feeding 12 hours or less were protected from obesity (a risk factor for many chronic diseases), metabolic diseases, and inflammation, compared to mice that were not on a TRF regimen. Having good genes is huge,” Panda says. “And the composition of your diet matters. But the third part is the timing of your eating.”

The Takeaway: Eating during consistent time periods each day is helpful for keeping biological rhythms in sync, which can help with preventing metabolic diseases and chronic diseases related to obesity. Importantly, this research on TRF is mostly limited to animal models, so it will be necessary to demonstrate efficacy in human studies. For those convinced by the existing data, Panda says, “What is optimal depends on someone’s goal, but if the goal is to improve overall health, then 8–9 hours might be better to begin with, but in terms of sticking with it long term, maybe 10–12 hours is practical.” If you want to learn about how your daily behaviors may impact your health, consider participating in Dr. Panda’s ongoing study myCircadianClock.


Intermittent Calorie Restriction: 

Scientist: Michelle Harvie

Education: Ph.D. 2000, University Hospital South Manchester Trust

Role: Research Dietitian, Nightingale Centre, University Hospital South Manchester Trust

Recent Paper: Intermittent energy restriction induces changes in breast gene expression and systemic metabolism

Area of Study: Lifestyle prevention of breast cancer and its recurrence

What It Means: Calorie restriction is exactly what it sounds like: reducing calories consumed in a day, in this case by half or a quarter, to around 800–1,000 calories. Dr. Harvie has focused on what’s called a 5:2 or 2-day diet, a calorie-restricted, low-carbohydrate diet for two consecutive days each week. This model is sometimes called “intermittent energy restriction” or “intermittent fasting.” It should be noted that Dr. Harvie is a research dietician and a breast cancer researcher, and her work primarily focuses on weight loss to help reduce the risk of breast cancer. For instance, her epidemiological study with the Iowa Women’s Health Study showed that weight loss can reduce the risk of breast cancer. She believes the selling point of 5:2 is its adoptability, spinning the diet as similar to exercise: “You’re putting your body through a short, intermittent, intensive therapy.”

How it Works: “Total fasting diets [with zero calorie consumption] are not a good idea for a couple reasons,” Harvie says. “You’re more likely to start losing lean body mass. You will get, potentially, big fluctuations in fatty acids, which could lead to insulin resistance. And you’re going to get increased hunger.” Plus, no one is going to do them. Harvie wanted to find something she believed to be more practical to help people lose weight. She wanted to get people consuming fewer calories. “People are eating constantly,” Harvie says. “They’re not taking breaks from food — which I think is an issue.” The 5:2 diet is a way to remind people that they don’t have to consume constantly. It can be done without limiting exercise (she highly recommends continuing exercise), and can encourage more balanced, healthy eating habits. Harvie recommends on the restricted calorie days to avoid carbohydrates and focus on proteins, which can help reduce hunger pains. And on the normal days, to maintain healthy habits learned from the restricted days. Harvie and other scientists have completed short-term human studies on the diet (read them here and here), which showed benefits including weight loss and improvement in metabolic disease disk markers, and longer-term studies are in the works. She is also pursuing the connection between weight loss and chemotherapy, particularly how cells on a calorie-restricted diet may be better protected from the treatments’ toxic side effects.

The Takeaway: The 5:2 diet is a practical and effective option for weight loss, which in turn can help prevent chronic diseases associated with aging. It is not yet proven to support health in normal weight people, nor does she recommend the diet for healthy people (because there isn’t data to support that recommendation).


Periodic Fasting and Fasting Mimicking Diet

Scientist: Valter Longo

Education: Ph.D. 1997, UCLA

Role: Director of the USC Longevity Institute; Edna Jones Professor in Gerontology and Professor in Biological Science; Senior Group Leader at IFOM Cancer Institute in Milan

Recent Paper: Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease

Area of Study: Fundamental mechanisms of aging; molecular pathways that can be modulated to protect against multiple stresses and treat or prevent cancer, Alzheimer’s Disease and other diseases of aging

What It Means: Periodic fasting requires limiting calories for between three and five days, such that cells deplete glycogen stores (glucose from food stored as energy) and begin ketogenesis (breaking down fatty acids for energy). While this could theoretically be done without food, scientists and doctors don’t consider it a safe option, particularly if there are existing malnourishments or dysfunctions. As an alternative, Dr. Longo has developed a “fasting mimicking diet” (FMD) called ProLon, a five-day program in which total caloric intake is limited to between 770 and 1,100 calories per day. This helps with the mental and physical rigors of fasting by providing nutrients to the body without stopping the fasting process at the cellular level.”You destroy when you are starving and you rebuild when you refeed,” he says. “Destruction is as important as the rebuilding.” Longo’s analogy is the construction of a new building. First you implode the existing structure, then you build the new one. “You destroy when you are starving and you rebuild when you refeed,” he says. “Destruction is as important as the rebuilding.” To do this on a cellular level, cells must consume all existing glycogen stores and begin consuming ketones stored in fat, after the readily available glucose has been depleted. After three to five days of ketosis, you return to a normal range of calories again and the cells receive glucose to build back up, fresh and rejuvenated. “It’s much more about the feeding than it is about the restriction,” Longo says. “This combination can cause the destruction of damaged cells and replace them with functional ones.” What does this destruction and rebuilding lead to? In Longo’s human study, published in February 2017, the FMD group experienced a significant improvement in body weight, waist circumference and BMI, absolute total body and trunk fat, as well as risk factors for aging and disease, including systolic blood pressure and insulin-like growth factor 1 (IGF-1). In animal models, the results of the FMD protocol were even more profound. It extended longevity, lowered visceral fat, reduced cancer incidence, rejuvenated the immune system, improved cognitive performance, and decreased risk factors/biomarkers for aging, diabetes, and cardiovascular disease. Longo also advocates for Dr. Panda’s time-restricted feeding as a good life practice. He also suggests that while the hard rules on what constitutes fasting have yet to be written, intermittent energy restriction for only two days a week (the 5:2 diet) would not allow cells to enter into a fasting state. “The beginning of ketogenesis and the depletion of glycogen is the beginning of fasting,” he says. And for that one must follow a guided low calorie intake for at least three days, preferably supervised by a doctor — and without exercising.

The Takeaway: This is the most rigorous proposition, with the highest potential benefits. Periodic fasting can do the most comprehensive destruction and rebuilding of the cells, giving the greatest health benefits, but the process needs to be moderated carefully.

The Truth About Juice Cleanses: Is the popular idea of a “juice cleanse” a mainstream version of fasting?  “A juice cleanse does not mean anything,” Longo says. “It could work, it could be terrible, it could be deadly — based on who uses it and what’s in there. Who tested it? What are the animal tests on it? What are the human tests on it? What are the results?” In other words, unless there are scientific studies, a juice cleanse is a combination of drinking juice and clever marketing. (Source: Endpoints – a science publication by Elysium Health)