The Fast Diet: The secret of intermittent fasting � lose weight, stay healthy, live longer (3 page)

Most of the early long-term studies on the benefits of fasting were done in rodents. They also gave us important insights into the molecular mechanisms that underpin fasting.

In one early study from 1945, mice were fasted for either one day in four, one day in three or one day in two.
The researchers found that the fasted mice lived longer than a control group, and that the more they fasted the longer they lived. They also found that, unlike
calorie-restricted
mice, the fasted mice were not physically stunted.
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Since then numerous studies have confirmed, at least in rodents, the value of fasting. But why does fasting help? What is the mechanism?

Valter has access to his own supply of genetically engineered mice, known as dwarf or Laron mice, which he was keen to show me. These mice, though small, hold the record for longevity extension in a mammal. In other words, they live for an astonishingly long time.

The average mouse doesn’t live that long, perhaps two years. Laron mice can live twice that, many for over four years when they are also calorie-restricted. In a human, that would be the equivalent of reaching almost 170.

The fascinating thing about Laron mice is not just their longevity, but the fact that they stay healthy for most of their very long lives. They simply don’t seem to be prone to diabetes or cancer, and when they die, more often than not, it is of natural causes. Valter told me that on autopsy they are often unable to find a cause of death. They just seem to drop dead.

The reason these mice are so small and so long-lived is that they are genetically engineered so that their bodies do not respond to a hormone called IGF-1,
Insulin-Like
Growth Factor 1. IGF-1, as its name implies, has
growth-promoting effects on almost every cell in your body. It keeps your cells constantly active. You need adequate levels of IGF-1 and other growth factors when you are young and growing, but high levels later in life appear to lead to accelerated ageing and cancer. As Valter put it, it’s like driving along with your foot flat down on the accelerator, pushing the car to continue to perform all the time. ‘Imagine, instead of occasionally taking your car to the garage and changing parts and pieces, you simply kept on driving it and driving it and driving it. Well, the car, of course, is going to break down.’

Valter’s work is focused on trying to figure out how you can go on driving as much as possible, and as fast as possible, while enjoying life. He thinks the answer is periodic fasting. Because one of the ways fasting works is by making your body reduce the amount of IGF-1 it produces.

The evidence that IGF-1 plays a key role in many of the diseases of ageing comes not just from rodents like the Laron mice but also from humans. For the last seven years, Valter has been studying villagers in Ecuador with a genetic defect, also called Laron syndrome. This is an extremely rare condition which affects fewer than 350 people in the world. People with Laron syndrome have bodies which don’t seem to be able to respond to IGF-1. There’s a specific mutation in the growth hormone receptor, causing a deficiency that is very
similar to that in the Laron mouse.

The villagers with Laron syndrome are normally quite short; many are less than four feet tall. The thing that is most surprising about them, however, is that, like the Laron mice, they simply don’t seem to develop common diseases like diabetes and cancer. In fact, Valter says that, though they have been studied for many years, there is not a single case he has come across of someone with Laron dying of cancer. Yet their relatives, who live in the same household but who don’t have Laron syndrome, get cancer like everybody else.

Disappointingly, for anyone hoping that IGF-1 will provide the secrets of immortality, people with Laron syndrome, unlike the mice, are not exceptionally
long-lived
. They certainly lead long lives, but not
super-long
lives. Valter thinks one reason for this may be that they tend to enjoy life rather than worry about their lifestyle. ‘They smoke, eat a high-calorie diet, and then they look at me and they say, “Oh it doesn’t matter, I’m immune.”’

Valter thinks they prefer the idea of living as they want and dying at 85, rather than living more carefully and perhaps going beyond 100. He would like to persuade some of them to take on a healthy lifestyle and see what happens, but knows he wouldn’t live long enough to see the outcome.

As well as reducing circulating levels of IGF-1, fasting also appears to switch on a number of repair genes. The reason this happens is not fully understood, but the evolutionary argument goes something like this. As long as we have plenty of food, our bodies are mainly interested in growing, having sex and reproducing. Nature has no long-term plans for us. She does not invest in our old age. Once we have reproduced we become disposable.

So what happens if you decide to fast? Well, the body’s initial reaction is one of shock. Signals go to the brain reminding you that you are hungry, urging you to go out and find something to eat. But you resist. The body now decides that the reason you are not eating as much and as frequently as you usually do must be because you are now in a famine situation. In the past this would have been quite normal.

In a famine situation there is no point in expending energy on growth or sex. Instead the wisest thing the body can do is spend its precious store of energy on repair, trying to keep you in reasonable shape until the good times return once more. The result is that, as well as removing its foot from the accelerator, your body takes itself along to the cellular equivalent of a garage. There, all the little gene mechanics are ordered to start doing some of the urgent maintenance tasks that have been put off till now.

One of the things that calorie restriction does, for example, is to switch on a process called autophagy.
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Autophagy, meaning ‘self eat’, is a process by which the body breaks down and recycles old and tired cells; just as with a car, it is important to get rid of damaged or ageing parts if you are going to keep things in good working order.

Valter thinks that the majority of people with a BMI over 25 would benefit from fasting, but he also thinks that if you plan to do it for more than a day it should be done in a proper centre. As he put it, ‘a prolonged fast is an extreme intervention. If it’s done well, it can be very powerful in your favour. If it’s done improperly, it can be very powerful against you.’ With a prolonged fast lasting several days, you also get a drop in blood pressure and some fairly profound metabolic re-programming. Some people faint. It’s not common but it happens.

One of Valter’s areas of research is into the effects of fasting on cancer (see more on pages 56-7 below) and this seems to be optimised by prolonged rather than Intermittent Fasting. As he pointed out, the first time you try fasting for a few days it can be a bit of a struggle. ‘Our bodies are used to high levels of glucose and high levels of insulin, so it takes time to adapt. But then eventually it’s not that hard.’

I wasn’t keen to hear ‘eventually’, but by then I knew I would have to give it a go. It was a challenge, and one I thought I could win. Brain against stomach. No contest.

I don’t think it is either necessary or particularly desirable to do a prolonged fast before embarking on the Fast Diet. While there are few known risks involved in fasting for less than 24 hours, the same is not true of prolonged fasts. I decided to start with a four-day fast because I knew I was in safe hands. I had also had my IGF-1 levels measured just before I met Valter and they were high. Not super-high, as he kindly put it, but at the top end of the range (my levels of IGF-1 or somatomedin-C, as it’s also known, were 28.0nmol/l. The healthy range is 11.3–30.9nmol/l).

High levels of IGF-1 are associated with a range of cancers, among them prostate cancer which had troubled my father. Would a four-day fast change anything?

I had been warned that the first few days might be tough, but after that I would start feeling the effects of a rush of what Valter termed ‘wellbeing chemicals’. Even better, the next time I fasted it would be easier because my body and brain would have a memory of it and understand what I was going through.

Having decided that I would try an extended fast, my next decision was how harsh to make it. A number of different countries have a tradition of fasting. The Russians seem to prefer it tough. For them, a fast consists of nothing but water, cold showers and exercise. The Germans, on the other hand, prefer their fasts to be
considerably gentler. Go to a fasting clinic in Germany and you will probably be fed around 200 calories a day in comfortable surroundings.

I wanted to see results, so I went for a British
compromise
. I would eat 25 calories a day, no cold showers and just try working as normal.

So on a warm Monday evening, I enjoyed my last meal, a filling dinner of steak, chips and salad washed down with beer. I felt a certain trepidation as I realised that for the next four days I would be drinking nothing but water, sugarless black tea and coffee, and one measly cup of
low-calorie
soup a day.

Despite what I’d been told and read, before I began my fast I secretly feared that hunger would grow and grow, gnawing away inside me until I finally gave in and ran amok in a cakeshop. The first 24 hours were quite tough, just as Valter had predicted, but as he had also predicted things got better, not worse. Yes, there were hunger pangs, sometimes quite distracting, but if I kept busy they went away.

During the first 24 hours of a fast, there are some quite profound changes going on inside the body. Within a few hours, glucose circulating in the blood is consumed. If that’s not being replaced by food then the body turns to glycogen, a stable form of glucose that is stored in the muscles and liver.

Only when that’s gone does it really switch on fat burning. What actually happens is that fatty acids are
broken down in the liver, resulting in the production of something called ketone bodies. The brain uses these ketone bodies as a source of energy, instead of glucose.

The first two days of a fast can be uncomfortable because your body and brain are having to cope with the switch from using glucose and glycogen as a fuel to using ketone bodies. The body is not used to them so you can get headaches, though I didn’t. You may find it hard to sleep. I didn’t. The biggest problem I had with fasting is hard to put into words; it was sometimes just feeling ‘uncomfortable’. I can’t really describe it more accurately than that. I didn’t feel faint; I just felt out of place.

I did, occasionally, feel hungry, but most of the time I was surprisingly cheerful. By day three the feel-good hormones had come to my rescue.

By Friday, day four, I was almost disappointed that it was ending. Almost. Despite Valter’s warning that it would be unwise to gorge immediately on breaking a fast, I got myself a plate of bacon and eggs and settled down to eat. After a few mouthfuls I was full. I really didn’t need any more and in fact skipped lunch.

That afternoon I was tested again and discovered I had lost just under three pounds of body weight, a significant portion of which was fat. I was also happy to see that my blood glucose levels had fallen substantially and that my IGF-1 levels, which had been at the top end of the recommended range, had gone right down. In fact, they had almost halved. This was all good news.
I had lost some fat, my blood results were looking good, and I had learnt that I can control my hunger. Valter was extremely pleased with these changes, particularly the fall in IGF-1 that he said would significantly reduce my risk of cancer. But he also warned me that if I went back to my old lifestyle these changes would not be permanent.

Valter’s research points towards the fact that high levels of protein, the amounts found in a typical western diet, help keep IGF-1 levels high. I knew that there is protein in foods like meat and fish, but I was surprised that there is so much in milk. I used to like drinking a skinny latte most mornings. I had the illusion that because it is made with skimmed milk it is healthy. Unfortunately, though low in fat, a large latte comes in at around 11g of protein. And Valter recommends that you don’t eat more than 0.8g of protein per kg of body weight per day. For someone like me, that would be around 64g a day. The lattes would have to go.

One way to lose weight would be to go on a prolonged fast. I did the four-day fast, as described above, mainly because I was curious. I would not recommend it as a weight-loss regime because it is completely unsustainable. Unless they combine it with a vigorous exercise regime,
people who go on prolonged fasts lose muscle as well as fat. Then, when they stop, as they must eventually do, the risk is they will pile the weight right back on.

Fortunately less drastic, Intermittent Fasting – the subject of this book – leads to steady and sustainable weight loss and does not cause muscle loss.

One of the most extensively studied forms of short-term fasting is Alternate Day Fasting (ADF). As its name implies, it means you get no food, or relatively little food, every other day. One of the few researchers to have done human studies in this area is Dr Krista Varady of the University of Illinois at Chicago.

Krista is slim, charming and very amusing. We met in an old-fashioned American diner where I guiltily ate burgers and fries while Krista told me about one of the recent studies she has been carrying out with human volunteers.
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On fasting days the volunteers were allowed 25% of their normal energy needs, so men were allowed around 600 calories a day, women 500 calories a day. On fast days they ate all their calories in one go, at lunch. On their feed days they were asked to consume 125% of their normal energy needs.