Chapter 19

An Old Custom in New Clothes

When researchers do calorie restriction experiments, they usually feed their animals once a day. The animals are hungry, so they eat everything at once. Then they fast until the next day. This has led some researchers to suspect that it may be the fasting – and not the reduction in calorie intake – that is responsible for prolonging life. In an ingenious experiment that supports this idea, researchers put mice on calorie restriction in a different way. Instead of giving the mice small amounts of typical food, they were given a special kind of chow with a very low cal­orie content. The mice were allowed to eat all day – and they did – but they still ended up getting limited calories. In this way, the researchers created calorie restriction without fasting. Now, if eating fewer calories is what is beneficial to the mice, these mice should still have had prolonged lifespans. However, if fasting is actually the cause of life extension, the mice wouldn’t live longer, as they were eating throughout the day. The result was the latter: when mice are calorie-restricted without fasting, they don’t live longer than usual.

Other researchers have attacked the question from the opposite angle: they have made mice fast while not reducing their overall food intake. This can be done by only feeding the mice every other day. The mice will typically eat twice as much as usual on the days they are fed, so they don’t get fewer calories than normal, but they are fasting in between. And that is enough to prolong their life. In fact, their fasted mice live almost as long as calorie-restricted mice.

At this point, there is little doubt that fasting can mimic the effect of calorie restriction and extend lifespan in rodents. It makes good sense, too, and fits in with our previous discoveries. For example, fasting is a kind of hormesis: a stressor that ultimately makes us stronger. And just like calorie restriction, fasting also inhibits the growth promoter mTOR while increasing the activity of the cellular garbage collectors, autophagy.

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Fasting is a widespread phenomenon in most of the world. We see it in nearly every culture and religion. As far back as ancient Greece, Hippocrates – the father of modern medi­cine – recommended fasting for health-related reasons. And the historian Plutarch, who lived a few hundred years later, said: ‘Fast today instead of using medicine.’ To this day, fasting is part of all the major world religions. Orthodox Christians have fasting periods, including the forty days between Shrove Tuesday and Easter; Jews have regular fast days, including the holiest day, Yom Kippur, where you don’t eat from sundown one day until sundown the next day; Muslims celebrate the annual month of Ramadan, where neither food nor drink is allowed while the sun is up; Buddhists fast during periods of intense meditation; and Hindus too have a wide variety of fasts throughout the year. In fact, fasting is so common that you’d be hard pressed to find a culture or religion that doesn’t have a fasting tradition of some sort.

Now, of course, these religions don’t prescribe fasting to fight ageing, but religious texts do frequently describe fasting as something healthy. Whether it is about cleansing (autophagy?), strength through trials (hormesis?), mental clarity or self-reflection.

Fasting is implemented in a variety of different ways as well. Some people don’t eat anything at all, some just omit certain kinds of foods (especially meat), some eat much less than usual, and some refrain from eating during particular times.

Similarly, there are almost as many research-based ways of fasting as there are religious ones. Let’s take a look. A common way to fast is to restrict your eating window, which is known as time-restricted feeding. We all do this to some extent. Unless you’re one of those people who snack late at night or get up in the middle of the night to do it, you fast from dinner one day to breakfast the next. Some people experiment with extending this fasting period, for example by eating all their food within a window of four to eight hours, instead of the typical twelve to fourteen hours.

This approach has had some promising results in mice. For instance, studies show that time-restricted eating protects mice from the negative effects of an unhealthy diet, whether that diet is high in sugar or high in fat. To put it another way, in mice an unhealthy diet can – to some extent – be neutralised by time-restricted eating. I can imagine using a similar strategy during the holidays which is, in fact, the time period where people tend to put on most weight.

Beyond time-restricted eating, most other fasting methods involve undertaking all-day fasts for one or more days. This type of fasting is known as intermittent fasting, and is the kind of fasting we particularly see in religious texts.

The scientific history of intermittent fasting originated in the 1940s with the researchers Anton Carlson and Frederick Hoelzel of the University of Chicago. The two were something of an odd couple. Carlson was an eminent Swedish-American physiologist with a PhD from Stanford University who chaired the Department of Physiology at the University of Chicago for twenty-four years.

Hoelzel also ended up as a researcher, though his path there was a little more curious. As a teenager, he’d developed terrible stomach pains, and nothing made them go away. Eventually, he became convinced that the pain was caused by the food he was eating. His solution was simple: just don’t eat anything. That turned out to be too hard, so instead Hoelzel started eating ‘alternative’ foods to keep his hunger under control. He tried, among other things, coal, sand, hair, feathers and – his favourite – surgical cotton.

After Carlson and Hoelzel’s paths crossed, they became friends and ended up as a dynamic scientific duo. When they weren’t testing the passage time of the various objects Hoelzel ate (glass balls passed faster than gold flakes, for example), they also tested more legitimate physiological questions together.

In 1946, they carried out what is now a famous experiment involving fasting and mice. The two were inspired by Clive McCay’s study on life extension using calorie restriction. They thought, quite reasonably, that it wouldn’t be possible to carry over that method to humans in a pleasant way. Instead, they argued, inspiration should be drawn from the only similar phenomenon in the real world: religious fasting.

They tested that idea and found that, yes indeed, periodic fasting was beneficial for rats in an experimental setting. Carlson and Hoelzel’s results added this kind of fasting to the – at the time – very short list of ways to extend the life of rats.

The method Carlson and Hoelzel used on their rats is called alternate-day fasting, an approach that involves fasting every other day and otherwise eating normally. Today, it has become a popular method in health circles and among people who want to lose weight. The method is quite simple: days of fasting are alternated with days of eating normally to satiety. Some people don’t fast entirely, but eat a small amount of food, for example 500–600 calories, to keep hunger at bay. A slightly gentler alternative is the 5:2 diet, which is also popular. The principles are like those of alternate-day fasting, but you only fast for two days a week.

We’re still collecting evidence of the effects of intermittent fasting in humans. One caveat when translating the mouse studies to humans is that a whole day of fasting is a lot longer for a mouse than a person. A mouse lives a few years at best, while humans live for decades. So some scientists think we will have to undertake longer fasts to get the same benefits as the laboratory mice.

One of the proponents of longer fasts is the renowned researcher Valter Longo. Longo and his colleagues found that many of the beneficial effects of a fast only appear after three days. The problem with that, of course, is that fasting for three days is not very pleasant or convenient, especially if you have a normal life that needs to be held together (and there are probably very few people who want to spend their vacations or weekends fasting).

The solution Longo and his colleagues have come up with is the so-called fasting-mimicking diet which they envision healthy people occasionally using. As the name suggests, this diet simulates a complete fast without actually being one. The fast lasts five days, in which participants eat very small meals with a low calorie content. The meals are high in fat and are designed to trick the body into thinking that it is fasting because that normally involves burning our own body fat for fuel.

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Some people might get nervous at the thought of longer fasts, and not without reason. Obviously, there are people who shouldn’t fast for long periods, like children, pregnant women, sick people and the elderly. But for healthy adults, fasting for a few days is fine, as long as you remember to drink plenty of water. The general rule is that humans can survive three ­minutes without oxygen, three days without water and three weeks without food. But the last one isn’t always accurate; if you have enough fat for your body to burn, you can go ­significantly longer.

The world record for the longest fast is held by the Scotsman Angus Barbieri. As a twenty-seven-year-old, Barbieri weighed 207kg (456lb). He knew that he was facing an early death and desperately wanted to lose weight. Back then, in the 1960s, there was a lot of research into using fasting for weight loss. The logic was basically that you should stop eating until you reached your desired weight.

Barbieri was willing to give fasting a try, so he showed up at Maryfield Hospital in Dundee near his hometown. He told doctors he was ready to give up food to lose weight and feeling his determination, the doctors agreed to monitor Barbieri while he fasted.

To begin with, Barbieri hadn’t planned to fast for ­anything more than a short period of time. But as time went on, he became more and more focused on reaching his ideal weight. Doctors agreed to let him continue, but started ­giving him a multivitamin pill to make sure he didn’t become deficient in anything. Besides that, though, the heavily overweight Barbieri didn’t need much – his body had enough fuel to sustain itself.

Weeks turned into months as Barbieri stubbornly chased his ideal weight of 82kg (181lb). When he finally reached his goal, he had been fasting for 382 days. That’s a year and seventeen days without eating. Incredibly, Barbieri managed to maintain his weight loss. When the doctors caught up with him again five years later, he’d put on only 7kg (15lb).

A fast of that duration obviously isn’t something that I’d recommend for anyone, no matter how overweight they might be. The reason we don’t use Barbieri’s method today is that some people who attempted it after him ended up dying.

In addition to the safety issue, the most common objection to fasting is that you go into a state of starvation and begin to break down muscles if you do not eat constantly. It is true that if you fast for a long time, your body slows down your metabolism and will eventually start burning muscle for fuel. However, this isn’t something that would happen during a day or two of fasting. Studies show that metabolism doesn’t decrease if, for example, a person fasts every other day. In fact, metabolism and fat burning increases. This makes sense evolutionarily; when an animal lacks food, it must go out to find it, and this means that its activity should increase, not decrease.

In addition, research shows that people who start strength training and, at the same time, eat within a restricted ­window gain the same amount of muscle mass as people who eat ­regularly. And in one study where subjects fasted every other day for eight weeks, their fat mass dropped, but their muscle mass didn’t.

Feel free to have another cup of coffee

Studies suggest that people who drink a few cups of coffee a day (between two and four) have a lower mortality rate than those who don’t drink coffee at all. Now, this doesn’t mean the coffee drinking causes this difference, but there are some aspects of coffee that we could at least imagine to be beneficial. For one, caffeine is an appetite suppressant, and we know eating less can be beneficial. Some people even use coffee when fasting, as it can help keep hunger at bay and is calorie-free when no milk, sugar or cream is added. However, even drinking decaf coffee is correlated to a longer life, so it is possible the health benefits of coffee comes from something else as well.