THE SCIENCE OF FASTING

For most animals out in the wild, periods of feast and famine are the norm. Our remote ancestors did not often eat four or five meals a day. Instead they would kill, gorge, lie around and then have to go for long periods of time without having anything to eat. Our bodies and our genes were forged in an environment of scarcity, punctuated by the occasional massive blow-out.

These days, of course, things are very different. We eat all the time. Fasting – the voluntary abstaining from eating food – is seen as a rather eccentric, not to mention unhealthy, thing to do. Most of us expect to eat at least three meals a day and have substantial snacks in between. In addition to the meals and the snacks, we also graze; a milky cappuccino here, the odd biscuit there, or maybe a smoothie because it’s ‘healthier’.

Once upon a time parents told their children not to eat between meals. Those times are long gone. Recent research in the US, which compared the eating habits of 28,000 children and 36,000 adults over the last thirty years, found that the amount of time spent between what the researchers coyly described as ‘eating occasions’ has fallen by an average of an hour. In other words, over the last few decades the amount of time we spend ‘not eating’ has dropped dramatically.1 In the 1970s, people like my mother would go around four and a half hours without eating, while children like me would be expected to last about four hours between meals. Now it’s down to three and a half hours for adults and three hours for children, and that doesn’t include all the drinks and nibbles.

The idea that eating little and often is a ‘good thing’ has partly been driven by snack manufacturers and faddish diet books, but it has also had support from the medical establishment. Their argument is that it is better to eat lots of small meals because that way we are less likely to get hungry and gorge on high-fat junk. I can appreciate the argument, and there have been some studies that suggest there are health benefits to eating small meals regularly, as long as you don’t simply end up eating more. Unfortunately, in the real world that’s exactly what happens.

In the study I quoted above, they found that compared to 30 years ago, we not only eat around 180 calories a day more in snacks – much of it in the form of milky and fizzey drinks and smoothies – but we also eat more when it comes to our regular meals, up by an average of 120 calories a day.

In other words, snacking doesn’t seem to mean that we eat less at meal times; it just whets the appetite.

Eating throughout the day is now so normal, so much the expected thing to do, that it is almost shocking to suggest there is value in doing the absolute opposite. When I first started fasting I discovered some unexpected things about myself, my attitudes to food and about my beliefs.

I discovered that I often eat when I don’t need to. I do it because the food is there, because I am afraid that I will get hungry later, or simply from habit

I assumed that when you get hungry it builds and builds until it becomes intolerable, and so you bury your face in a vat of ice cream. I found instead that hunger passes and once you have been really hungry you no longer fear it

I thought that fasting would make me distractible, unable to concentrate. What I’ve discovered is that it sharpens my senses and my brain

I wondered if I would feel faint for much of the time. It turns out that the body is incredibly adaptable and many athletes I’ve spoken to advocate training while fasting

I feared it would be incredibly hard to do. It isn’t

Why I got started

Although most of the great religions advocate fasting (the Sikhs are an exception, though they do allow fasting for medical reasons), I have always assumed that this was principally a way of testing yourself and your faith. I could see potential spiritual benefits but I was deeply sceptical about the physical benefits.

I have also had a number of body-conscious friends who, down the years, have tried to get me to fast, but I could never accept their explanation that the reason for doing so was ‘to rest the liver’ or ‘to remove the toxins’. Neither explanation made any sense to a medically trained sceptic like me. I remember one friend telling me that after a couple of weeks of fasting his urine had turned black, proof that the toxins were leaving. I saw it as proof that he was an ignorant hippy and that whatever was going on inside his body as a result of fasting was extremely damaging. As I wrote in the introduction, what convinced me to try fasting was a combination of my own personal circumstances – in my mid-50s, high blood sugar, slightly overweight – and the emerging scientific evidence, which I list below.

That which does not kill us makes us stronger

There were a number of researchers who inspired me in their different ways, but one who stands out is Professor Mark Mattson of the National Institute on Aging in Baltimore. A couple of years ago he wrote an article with Edward Calabrese in New Scientist magazine, ‘When a little poison is good for you’,2 which really made me sit up and think.

‘A little poison is good for you’ is a colourful way of describing the theory of hormesis – the idea that when a human, or indeed any other creature, is exposed to a stress or toxin it can toughen them up. Hormesis is not just a variant of ‘join the army and it will make a man of you’; it is now a well-accepted explanation in biology of how things operate at the cellular level.

Take, for example, something as simple as exercise. When you run or pump iron, what you are actually doing is damaging your muscles, causing small tears and rips. If you don’t completely overdo it, then your body responds by doing repairs and in the process makes the muscles stronger.

Vegetables are another example. We all know that we should eat lots of fruit and vegetables because they are chock full of antioxidants – and antioxidants are great because they mop up the dangerous free radicals that roam our bodies doing harm.

The trouble with this widely accepted explanation of how fruit and vegetables ‘work’ is that it is almost certainly wrong, or at least incomplete. The levels of antioxidants in fruits and vegetables are far too low to have the profound effects they clearly do. In addition, the attempts to extract antioxidants from plants and then give them to us in a concentrated form, as a health-inducing supplement, have been unconvincing when tested in long-term trials. Betacarotene, when you get it in the form of a carrot, is undoubtedly good for you. When they took betacarotene out of the carrot and gave it as a supplement to patients with cancer, it actually seemed to make them worse.

If we look through the prism of hormesis at the way vegetables work in our bodies, we can see that the reasons for their benefits may be quite different.

Consider this apparent paradox: bitterness is often associated in the wild with poisons, something to be avoided. Plants produce a huge range of so-called phytochemicals and some of them act as natural pesticides, to keep mammals like us from eating them. The fact that they taste bitter is a clear warning signal: keep away. So there are good evolutionary reasons why we should dislike and avoid bitter-tasting foods. Yet some of the vegetables that are particularly good for us, such as cabbage, cauliflower, broccoli and other members of the brassica family, are so bitter that even as adults many of us struggle to love them.

The resolution to this paradox is that these vegetables taste bitter because they contain chemicals that are potentially poisonous. The reason they don’t harm us is that these chemicals are present in them at low doses that are not toxic. Rather, they activate stress responses and switch on genes that protect and repair.

Once you start looking at the world in this way, you realise that many activities we initially find stressful – like eating bitter vegetables, going for a run, or Intermittent Fasting – are far from harmful. The challenge itself seems to be part of the benefit. The fact that prolonged starvation is clearly very bad for you does not imply that short periods of Intermittent Fasting must be a little bit bad for you. Indeed the reverse is true.

This point was vividly made to me by Professor Valter Longo, director of the University of Southern California’s Longevity Institute. His research is mainly into the study of why we age, particularly concerning approaches that reduce the risk of developing age-related diseases such as cancer and diabetes.

I went to see Valter, not just because he is a world expert, but also because he had kindly agreed to act as my fasting mentor and buddy, to help inspire and guide me through my first experience of fasting.

Valter has been studying fasting for many years, and he is a keen adherent of it. He lives by his research and thrives on the sort of low-protein, high-vegetable diet that his grandparents enjoy in southern Italy. Perhaps not coincidentally, his grandparents live in a part of Italy that has an extraordinarily high concentration of long-lived people.

As well as following a fairly strict diet, Valter skips lunch to keep his weight down. Beyond this, once every six months or so, he does a prolonged fast that lasts several days. Tall, slim, energetic, Italian, he is an inspiring poster boy for would-be fasters.

The main reason he is so enthusiastic about fasting is that his research, and that of others, has demonstrated the extraordinary range of measurable health benefits that you get from doing it. Going without food for even quite short periods of time switches on a number of ‘repair genes’, which, as he explained, can confer longterm benefits. ‘There is a lot of initial evidence to suggest that temporary periodic fasting can induce long-lasting changes that can be beneficial against ageing and diseases,’ he told me. ‘You take a person, you fast them, after 24 hours everything is revolutionised. And even if you took a cocktail of drugs, very potent drugs, you will never even get close to what fasting does. The beauty of fasting is that it’s all co-ordinated.’

Fasting and longevity

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.3

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.

Fasting and repair genes

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.4 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.

Experiencing a four-day fast

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.

Fasting and weight loss

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.

Alternate Day Fasting

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.5 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.

Krista has done a number of studies on ADF, and what surprised her is that, even when they are allowed to, people don’t go crazy on their feed days. ‘I thought when I started running these trials that people would eat 175% the next day; they’d just fully compensate and wouldn’t lose any weight. But most people eat around 110%, just slightly over what they usually eat. I haven’t measured it yet, but I think it involves stomach size, how far that can expand out. Because eating almost twice the amount of food that you normally eat is actually pretty difficult. You can do it over time; people that are obese, their stomachs get bigger to accommodate, you know, 5000 calories a day. But just to do it right off is actually pretty difficult.’

In her earlier studies, subjects were asked to stick to a low-fat diet, but what Krista wanted to know was whether ADF would also work if her subjects were allowed to eat a typical American high-fat diet. So she asked 33 obese volunteers, most of them women, to go on ADF for eight weeks. Before starting, the volunteers were divided into two groups. One group was put on a low-fat diet, eating low-fat cheeses and dairies, very lean meats and a lot of fruit and vegetables. The other group was allowed to eat high-fat lasagnes, pizza, the sort of diet a typical American might consume. Americans consume somewhere between 35 and 45% fat in their diet.

As Krista explained, the results were unexpected. The researchers and volunteers had assumed that the people on the low-fat diet would lose more weight than those on the high-fat diet. But, if anything, it was the other way around. The volunteers on the high-fat diet lost an average of 5.6kg, while those on the low-fat diet lost 4.2kg. They both lost about seven centimetres around their waists.

Krista thinks that the main reason this happened was compliance. The volunteers randomised to the high-fat diet were more likely to stick to it than those on the low-fat diet simply because they found it a lot more palatable. And it wasn’t just weight loss. Both groups saw impressive falls in low-density lipoprotein (LDL) cholesterol, the bad cholesterol, and in blood pressure. This meant that they had reduced their risk of cardiovascular disease, of having a heart attack or stroke.

Krista doesn’t want to encourage people to binge on rubbish. She would much rather that people on ADF ate healthily, increased their fruit and vegetable intake, and generally ate less. The trouble is, as she pointed out rather exasperatedly, doctors have been encouraging people to embrace a healthy lifestyle for decades, and not enough of us are doing it. She thinks dieticians should take into account what people actually do rather than what we would like them to do.

One other significant benefit to Intermittent Fasting is that you don’t seem to lose muscle, which you would on a normal calorie-restricted regime. Krista herself is not sure why that is and wants to do further research.

The two-day fast

One of the problems with ADF, which is why I am not so keen on it, is that you have to do it every other day. In my experience this can be socially inconvenient as well as emotionally demanding. There is no pattern to your week and other people, friends and family, find it hard to keep track of when your fast and feed days are. Unlike Krista’s subjects, I was not particularly overweight to start with, so I also worried about losing too much weight too rapidly. That is why, having tried ADF for a short while, I decided to cut back to fasting two days a week.

I now have my own experience of this to fall back on (see page 60), together with the experiences of hundreds of others who have written to me over the last few months. But what trials have been done on two-day fasts in humans?

Well, Dr Michelle Harvie, a dietician based at the Genesis Breast Cancer Prevention Centre at the Wythenshawe Hospital in Manchester, has done a number of studies assessing the effects of a two-day fast on female volunteers. In a recent study, she divided 115 women into three groups. One group was asked to stick to a 1500-calorie Mediterranean diet, and was also encouraged to avoid high-fat foods and alcohol.6 Another group was asked to eat normally five days a week, but to eat a 650-calorie, low-carbohydrate diet on the other two days. A final group was asked to avoid carbohydrates for two days a week, but was otherwise not calorie-restricted.

After three months, the women on the two-day diets had lost an average of 4kg, which was almost twice as much as the full-time dieters, who had lost an average of just 2.4kg. Insulin resistance had also improved significantly in the two-day diet groups (see more on insulin on page 54).

The focus of Michelle’s work is trying to reduce breast cancer risk through dietary interventions. Being obese and having high levels of insulin resistance are both risk factors. On the Genesis website (www.genesisuk.org), she points out that they have been studying Intermittent Fasting at the Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester NHS Foundation Trust, for over six years and that their research has shown that cutting down on your calories for two days a week gives the same benefits, possibly more, than by going on a normal calorie-reduced diet. ‘To date, our research has concluded that intermittent diets appear to be a safe, viable, alternative approach to weight loss and maintaining a lower weight, in comparison to daily dieting.’

Is it just calories?

If you eat 500 or 600 calories two days a week and don’t significantly overcompensate during the rest of the week, then you will lose weight in a steady fashion.

But is there any evidence that Intermittent Fasting does more than that? I recently came across one particularly fascinating study suggesting that when you eat can be almost as important as what you eat.

In this study, scientists from the Salk Institute for Biological Studies took two groups of mice and fed them a high-fat diet.7 The mice got exactly the same amount of food to eat, the only difference being that one group of mice was allowed to eat whenever they wanted, nibbling away when they were in the mood, rather like we do, while the other group of mice had to eat their food in an eight-hour time period. This meant that there were 16 hours of the day in which they were, involuntarily, fasting.

After 100 days, there were some truly dramatic differences between the two groups of mice. The mice who nibbled away at their fatty food had developed high cholesterol, high blood glucose and had liver damage. The mice that had been forced to fast for 16 hours a day put on far less weight (28% less) and suffered much less liver damage, despite having eaten exactly the same amount and quality of food. They also had lower levels of chronic inflammation, which suggests they had reduced risk of a number of diseases, including heart disease, cancer, stroke and Alzheimer’s.

The Salk researchers’ explanation for this is that all the time you are eating your insulin levels are elevated and your body is stuck in fat-storing mode (see the discussion of insulin on page 54). Only after a few hours of fasting is your body able to turn off the ‘fat storing’ and turn on the ‘fat burning’ mechanisms. So if you are a mouse and you are continually nibbling, your body will just continue making and storing fat, resulting in obesity and liver damage.

By now, I hope you are as convinced as I am that fasting offers multiple health benefits, as well as helping to achieve weight loss. I had been aware of some of these claims before I got really interested in fasting and, though initially sceptical, I was converted by the sheer weight of evidence.

But there was one area of study that was a complete surprise: research showing how fasting can improve mood and protect the brain from dementia and cognitive decline. This, for me, was something completely new, unexpected, and hugely exciting.

Fasting and the brain

The brain, as Woody Allen once said, is my second favourite organ. I might even put it first, as without it nothing else would function. The human brain, around three pounds of pinkish greyish gunk with the consistency of tapioca, has been described as the most complex object in the known universe. It allows us to build, write poetry, dominate the planet and even understand ourselves, something no other creature has succeeded in doing.

It is also an extremely efficient energy-saving machine, doing all that complicated thinking and making sure our bodies are functioning properly while using the same amount of energy as a 25-watt light bulb. The fact that our brains are normally so flexible and adaptable makes it even more tragic when they go wrong. I am aware that as I get older my memory has become more fallible. I’ve compensated by using a range of memory tricks I’ve picked up over the years, but even so I find myself occasionally struggling to remember names and dates. Far worse than this, however, is the fear that one day I may lose my mind entirely, perhaps developing some form of dementia. Obviously I want to preserve my brain in as good a shape as possible and for as long as possible. Fortunately fasting seems to offer significant protection.

The man I went to discuss my brain with was Professor Mark Mattson.

Mark Mattson, a professor of neuroscience at the National Institute on Aging, is one of the most revered scientists in his field: the study of the ageing brain. I find his work genuinely inspiring – suggesting, as it does, that fasting can help combat diseases like Alzheimer’s, dementia and memory loss.

Although I could have taken a taxi to his office, I chose to walk. I’m a fan of walking. It not only burns calories, it also improves the mood, and it may also help retain your memory. Normally as we get older our brain shrinks, but one study found that in regular walkers the hippocampus, an area of the brain essential for memory, actually expanded.8 Regular walkers have brains that in MRI scans look, on average, two years younger than the brains of those who are sedentary.

Mark, who studies Alzheimer’s, lost his own father to dementia. He told me that although it didn’t directly motivate him to go into this particular line of research – when he started work on Alzheimer’s disease his father had not yet been diagnosed – but it did give him insight.

Alzheimer’s affects around 26 million people worldwide and the problem will grow as the population ages. New approaches are desperately needed because the tragedy of Alzheimer’s disease and other forms of dementia is that once you’re diagnosed it may be possible to delay, but not prevent, the inevitable deterioration. You are likely to get progressively worse to the point where you need constant care for many years. By the end you may not even recognise the faces of those you once loved.

Can fasting make you clever?

Just as Valter Longo had, Mark took me off to see some mice. Like Valter’s mice, Mark’s mice are genetically engineered, But they have been modified to make them more vulnerable to Alzheimer’s. The mice I saw were in a maze, which they had to navigate in order to find food. Some of the mice perform this task with relative ease; others get disorientated and confused. This task, and others like it, are designed to reveal signs that the mice are developing memory problems; a mouse that is struggling will quickly forget which arm of the maze it has already travelled down.

The genetically engineered Alzheimer’s mice will, if put on a normal diet, quickly develop dementia. By the time they are a year old, the equivalent of middle age in humans, they normally have obvious learning and memory problems. The animals put on an intermittent fast, something Mark prefers to call ‘intermittent energy restriction’, often go up to 20 months without any detectable signs of dementia.9 They only really start deteriorating towards the end of their lives. In humans that would be the equivalent of developing signs of Alzheimer’s at the age of 80 rather than at 50. I know which I would prefer.

Disturbingly, when these mice are put on a typical junk-food diet, they go downhill much earlier than even normally fed mice. ‘We put mice on a high-fat and high-fructose diet,’ Mark said, ‘and that has a dramatic effect; the animals have an earlier onset of the learning and memory problems, more accumulation of amyloid and more problems with finding their way in a maze test.’

In other words, junk food makes these mice fat and stupid.

One of the key changes that occur in the brains of Mark’s fasting mice is increased production of a protein called brain-derived neurotrophic factor. BDNF has been shown to stimulate stem cells to turn into new nerve cells in the hippocampus. As I mentioned earlier, this is a part of the brain that is essential for normal learning and memory.

But why should the hippocampus grow in response to fasting? Mark points out that from an evolutionary perspective it makes sense. After all, the times when you need to be smart and on the ball are when there’s not a lot of food lying around. ‘If an animal is in an area where there’s limited food resources, it’s important that they are able to remember where food is, remember where hazards are, predators and so on. We think that people in the past who were able to respond to hunger with increased cognitive ability had a survival advantage.’

We don’t know for sure if humans grow new brain cells in response to fasting; to be absolutely certain researchers would need to put volunteers on an intermittent fast and then kill them, take their brains out and look for signs of new neural growth. It seems unlikely that many would volunteer for such a project. But what they are doing is a study where volunteers fast and then MRI scans are used to see if the size of their hippocampi changes over time.

As I mentioned above, these techniques have been used in humans to show that regular exercise, such as walking, increases the size of the hippocampus. Hopefully similar studies will show that two days a week of Intermittent Fasting is good for learning and memory. On a purely anecdotal level, and using a sample size of one, it seems to work. Before starting the Fast Diet, I did a sophisticated memory test online. Two months in I repeated the test and my performance had, indeed, improved. If you are interested in doing something similar then I suggest you go to www.cognitivefun.net/test/2. Do let us know how you get on.

Fasting and mood

One of the things that Professor Valter Longo and others told me before I began my four-day fast was that it would be tough initially, but that after a while I would start to feel more cheerful, which was indeed what happened. Similarly, I was surprised to discover how positive I have felt while doing Intermittent Fasting. I expected to feel tired and crabby on my fasting days, but not at all. So is this simply a psychological effect, that people who do Intermittent Fasting and lose weight feel good about themselves, or are there also chemical changes that are influencing mood?

According to Professor Mark Mattson, one of the reasons people may find Intermittent Fasting relatively easy to do due to its effects on BDNF. BDNF not only seems to protect the brain against the ravages of dementia and age-related mental decline, but it may also improve your mood.

There have been a number of studies going back many years that suggest rising levels of BDNF have an antidepressant effect, at least in rodents. In one study, they injected BDNF directly into the brains of rats and found this had similar effects to repeated use of a standard antidepressant.10 Another paper found that electric shock therapy, which is known to be effective in severe depression, seems to work, at least in part, because it stimulates the production of higher levels of BDNF.11

Mark Mattson believes that within a few weeks of starting a two-day-a-week fasting regime, BDNF levels will start to rise, suppressing anxiety and elevating mood. He doesn’t currently have the human data to fully support this claim, but he is doing trials on volunteers which involve, among other things, collecting regular samples of cerebrospinal fluid (the liquid that bathes the brain) in order to measure the changes that occur during intermittent fasts. This is not a trial for the faint-hearted as it requires regular spinal taps, but as Mark pointed out to me, many of his volunteers are already undergoing early signs of cognitive change, so they are extremely motivated.

Mark is keen to study and promote the benefits of Intermittent Fasting as he is genuinely worried about the likely effects of the current obesity epidemic on our brains and our society. He also thinks if that if you are considering Intermittent Fasting you should get going sooner rather than later: ‘The age-related cognitive decline in Alzheimer’s disease, the events that are occurring in the brain at the level of the nerve cells and the molecules in the nerve cells, those changes are occurring very early, probably decades before the subject starts to have learning and memory problems. That’s why it’s critical to start dietary regimes early on, when people are young or middle-aged, so that they can slow down the development of these processes in the brain and live to be 90 with their brain functioning perfectly well.’

Like Mark, I’m convinced the human brain benefits from short periods abstaining from food. This is an exciting and fast-emerging area of research that many will watch with great interest. Beyond the brain, though, Intermittent Fasting also has measurable, beneficial effects on other areas of the body – on your heart, on your blood profile, on your risk of cancer. And that’s where we’ll turn now.

Fasting and the heart

One of the main reasons I decided to try fasting was that tests had suggested I was heading for serious problems with my cardiovascular system. Nothing has happened yet, but the warning signs were flashing amber. The tests showed that my blood levels of LDL (low-density lipoprotein, the ‘bad’ cholesterol) were disturbingly high, as were the levels of my fasting glucose.

To measure ‘fasting glucose’ you have to fast overnight, then give a sample of blood. The normal, desirable range is 3.9-5.8mmol/l. Mine was 7.3mmol/l. Not yet diabetic, but dangerously high. There are many reasons why you should do all you can to avoid becoming a diabetic, not least the fact that it dramatically increases your risk of having a heart attack or stroke.

Fasting glucose is an important thing to measure because it is an indicator that all may not be well with your insulin levels.

Insulin – the fat-making hormone

When we eat food, particularly food rich in carbohydrates, our blood glucose levels rise and the pancreas, an organ below the ribs and near the left kidney, starts to churn out insulin. Glucose is the main fuel that our cells use for energy, but the body does not like having high levels of it circulating in the blood. The job of insulin, a hormone, is to regulate blood glucose levels, ensuring that they are neither too high nor too low. It normally does this with great precision. The problem comes when the pancreas gets overloaded.

Insulin is a sugar controller; it aids the extraction of glucose from blood and then stores it in places like your liver or muscles in a stable form called glycogen, to be used when and if it is needed. What is less commonly known is that insulin is also a fat controller. It inhibits something called lipolysis, the release of stored body fat. At the same time, it forces fat cells to take up and store fat from your blood. Insulin makes you fat. High levels lead to increased fat storage, low levels to fat depletion.

The trouble with constantly eating lots of sugary, carbohydrate-rich foods and drinks, as we increasingly do, is that this requires the release of more and more insulin to deal with the glucose surge. Up to a point, your pancreas will cope by simply pumping out ever-larger quantities of insulin. This leads to greater fat deposition and also increases the risk of cancer. Naturally enough, this can’t go on forever. If you continue to produce ever-larger quantities of insulin, your cells will eventually rebel and become resistant to its effects. It’s rather like shouting at your children; you can keep escalating things, but after a certain point they will simply stop listening.

Eventually the cells stop responding to insulin; your blood glucose levels now stay permanently high and you will find you have joined the 285 million people around the world who have type 2 diabetes. It is a massive and rapidly growing problem worldwide. Over the last 20 years, numbers have risen almost tenfold and there is no obvious sign that this trend is slowing.

Diabetes is associated with an increased risk of heart attack, stroke, impotence, going blind and losing your extremities due to poor circulation. It is also associated with brain shrinkage and dementia. Not a pretty picture.

One way to prevent the downward spiral into diabetes is to cut back on the carbohydrates and instead start eating more vegetables and fat, since these foods do not lead to such big spikes in blood glucose. Nor do they have such a dramatic effect on insulin levels. The other way is to try Intermittent Fasting.

How Intermittent Fasting affects insulin sensitivity

In a study from 2005, eight healthy young men were asked to fast every other day, 20 hours a day, for two weeks.12 On their fasting days they were allowed to eat until 10pm, then not eat again until 6pm the following evening. They were also asked to eat heartily the rest of the time to make sure they did not lose any weight.

The idea behind the experiment was to test the so-called ‘thrifty hypothesis’, the idea that since we evolved at a time of feast and famine the best way to eat is to mimic those times. At the end of the two weeks, there were no changes in the volunteers’ weight or body-fat composition, which is what the researchers had intended. There was, however, a big change in their insulin sensitivity. In other words, after just two weeks of Intermittent Fasting, the same amount of circulating insulin now had a much greater effect on the volunteers’ ability to store glucose or break down fat.

The researchers wrote jubilantly that, ‘by subjecting healthy men to cycles of feast and famine we changed their metabolic status for the better’. They also added that, ‘to our knowledge this is the first study in humans in which an increased insulin action on whole body glucose uptake and adipose tissue lipolysis has been obtained by means of Intermittent Fasting.’

I don’t know what impact Intermittent Fasting has had on my insulin sensitivity – it’s a test that is hard to do and extremely expensive – but what I do know is that the effects on my blood sugar have been spectacular. Before I started fasting, my blood glucose level was 7.3 mmol/l, well above the acceptable range of 3.9 – 5.8 mmol/l. The last time I had my level measured it was 5.0 mmol/l, still a bit high but well within the normal range.

This is an incredibly impressive response. My doctor, who was preparing to put me on medication, was astonished at such a dramatic turnaround. Doctors routinely recommend a healthy diet to patients with high blood glucose, but it usually only makes a marginal difference. Intermittent Fasting could have a revolutionary, game-changing effect on the nation’s health.

Fasting and cancer

My father was a lovely man but not a particularly healthy one. Overweight for much of his life, by the time he reached his 60s he had developed not only diabetes but also prostate cancer. He had an operation to remove the cancer that left him with embarrassing urinary problems. Understandably, I am not at all keen to go down that road.

My four-day fast, under Professor Valter Longo’s supervision, had shown me that it was possible to dramatically cut my IGF-1 (Insulin-like Growth Factor 1) levels and by doing so, hopefully, my prostate cancer risk. I later discovered that Intermittent Fasting had a similar effect on my IGF-1 levels. The link between growth, fasting and cancer is worth unpacking.

The cells in our bodies are constantly multiplying, replacing dead, worn-out or damaged tissue. This is fine as long as cellular growth is under control, but sometimes a cell mutates, grows uncontrollably and turns into a cancer. Very high levels in the blood of a cellular stimulant, like IGF-1, are likely to increase the chance of this happening.

When a cancer goes rogue, the normal options are surgery, chemotherapy or radiotherapy. Surgery is used to try to remove the tumour; chemotherapy and radiotherapy are there to try and poison it. The major problem with chemotherapy and radiotherapy is that they are not selective; as well as killing tumour cells they will kill or damage surrounding healthy cells. They are particularly likely to damage rapidly dividing cells such as hair roots, which is why hair commonly falls out following therapy.

As I mentioned above, Valter Longo has shown that when we are deprived of food for even quite short periods of time, our body responds by slowing things down, going into repair and survival mode until food is once more abundant. That is true of normal cells. But cancer cells follow their own rules. They are, almost by definition, not under control and will go on selfishly proliferating whatever the circumstances. This ‘selfishness’ creates an opportunity. If you fast just before chemotherapy, at least in theory, you create a situation where your normal cells are hibernating while the cancer cells are running amok and therefore more vulnerable.

In a paper published in 2008, Valter and colleagues showed that fasting ‘protects normal but not cancer cells against high-dose chemotherapy’.13 They followed this with another paper in which they showed that fasting increased the efficacy of chemotherapy drugs against a variety of cancers.14

Again, as is so often the case, this was a study done with mice. But the implications of Valter’s work were not missed by an eagle-eyed judge called Nora Quinn, who saw a short article about it in The LA Times.

Nora’s story

I met Nora in Los Angeles. She is a feisty woman with a terrific, dry sense of humour. Nora first noticed she had a problem when, one morning, she put her hand on her breast and felt a lump the size of a walnut under her skin. After indulging, as she put it, in the fantasy that it was a cyst, it was removed and sent to a pathologist.

‘The reality of your life always comes out in pathology,’ she told me. When the pathology report came back it said that she had invasive breast cancer. She had a course of radiotherapy and was about to start chemotherapy when she read about Professor Longo’s work with mice.

She tried to speak to Valter, but he wouldn’t advise her because none of the trials he had run, up to that point, had been done with humans. He didn’t know if it was safe for someone about to undergo chemo to fast and he certainly wasn’t going to encourage people like Nora to give it a go.

Undeterred, Nora did her own research and decided to try fasting for a seven-and-a-half-day, water-only fast; it would cover before, during and after chemotherapy. Having discovered how tough it can be to do even a four-day fast while fully healthy, I’m surprised she was able to go through with it, though Nora says it’s not so hard and I’m just a wimp. The results were mixed: ‘After the first chemo I didn’t get that sick, but my hair fell out.’

So next time she didn’t fast, and she was only medium sick. ‘I thought it wasn’t working. I thought, seven and a half days of fasting to avoid being medium sick, this is a really bad deal. I am so not doing that again.’

When it was time for her third course of chemo, she didn’t fast. That, she now feels, was a mistake.

‘I got sick. I don’t have words for how sick I was. I was weak, felt poisoned, and I couldn’t get up. I felt like I was moving through jello. It was absolutely horrible.’

The cells that line the gut, like hair root cells, grow rapidly because they need to be constantly replaced. That’s one reason why chemotherapy can make people feel really ill.

By the time Nora had to undergo her fourth course of chemo she had decided once again to try fasting. This time things went much better and she made a good recovery. She is currently cancer free.

Nora is convinced she benefitted from fasting but it’s hard to be sure because she wasn’t part of a proper medical trial. Valter and colleagues at University of Southern California did, however, study what happened to her and 10 other patients with cancers who had also decided to put themselves on a fast.15 All of them reported fewer and less severe symptoms after chemotherapy and most of them, including Nora, saw improvements in their blood results. The white cells and platelets, for example, recovered more rapidly when they had chemo in a fasted state than when they did not. But why did Nora go rogue? Why didn’t she fast under proper supervision?

‘I decided to fast based on years of information from animal testing. I do agree that if you are going to do crazy things like I do you should have medical supervision. But how? None of my doctors would listen to me.’

Nora’s self-experiment could have gone wrong, which is just one reason why such maverick behaviour is not recommended. Her experience, however, and that of the other nine cancer patients, helped inspire further studies.

For example, Professor Valter Longo and his colleagues have recently completed Phase I of a clinical trial to see if fasting around the time of chemotherapy is safe, which it seems to be. The next thing is to assess whether it makes a measurable difference. At least ten other hospitals around the world are either doing or have agreed to do clinical trials. Go to our website for the latest updates.

Intermittent Fasting: my personal journey

As you’ve read, I started out by trying the four-day fast under Professor Valter Longo’s supervision. But despite the improvements in my blood biochemistry and his obvious enthusiasm, I could not imagine doing lengthy fasts on a regular basis for the rest of my life. So what next? Well, having met Dr Krista Varady and learnt all about ADF (Alternate Day Fasting) I decided to give that a go.

After a short while, however, I realised that it was just too tough, physically, socially and psychologically. I need some pattern in my life and not being able to tell without a calendar and lengthy calculations whether I could meet friends for dinner on a particular night was irksome. I also found fasting every other day just a little too challenging. I realise that many of Krista’s volunteers do manage to stick to it, but they are in a trial situation and highly motivated. It is undoubtedly an effective way to lose weight rapidly and to get powerful changes to your biochemistry, but it was not for me. So I decided to try eating 600 calories for two days a week. It seemed a reasonable compromise and, more importantly, doable.

I tried eating all my food in one meal, as Krista does in her studies, but I discovered that if I skipped breakfast I started to feel hungry and irritable well before lunch. So I split my food in two: a moderate breakfast, miss lunch, a light supper. And I did it twice a week. This I found extremely manageable.

After experimenting with different versions of fasting, I found the 5:2 approach is the most effective and workable way for me to get the benefits of fasting and still retain a long-term commitment to a dietary plan. A 5:2 Fast Diet is a realistic synthesis of the current thinking on Intermittent Fasting, and the best way I know to guarantee success.

Before embarking on the diet, I decided to get myself properly tested, to see what effects it would have on my body. The following are the tests I did. Most are straightforward. The blood tests are, with one exception, tests your doctor should be happy to do for you.

	ME	RECOMMENDED
HEIGHT	5’ 11”
WEIGHT	187lb
BODY MASS INDEX	26.4	19-25
BODY FAT	28%	Less than 25% for men
WAIST SIZE	36 “	Less than half your height
NECK SIZE	17 “	Less than 16.5“

I wasn’t obese, but both my BMI and my body-fat percentage told me that I was overweight. I knew from doing an MRI scan that much of my fat was collected internally, wrapping itself in thick layers around my liver and kidneys, disturbing all sorts of metabolic pathways.

Clearly, the fat wasn’t all inside my abdomen. Quite a bit had collected around my neck. This meant that I was snoring. Loudly. Neck size is a powerful predictor of whether you will snore or not.16 A neck size above 16.5” for men or 16 inches for women means you are in the danger zone.

	MY RESULTS in mmol/l	RECOMMENDED
DIABETES RISK: FASTING GLUCOSE	7.3	3.9–5.8
HEART DISEASE FACTORS: TRIGLYCERIDES HDL CHOLESTEROL LDL CHOLESTEROL	1.4 1.8 5.5	Less than 2.3 0.9–1.5 Up to 3.0
HEART DISEASE RISK HDL % of total	23%	20% and over
CANCER RISK Somatomedin-C (IGF-1)	28.6 nmol/l	11.3–30.9nmol/l

According to this data, my fasting glucose was worryingly high. I was not yet a diabetic but I had signs of what is called impaired glucose tolerance, pre-diabetes. My LDL was far too high, but I was to some extent protected by the fact that my triglycerides were low and my HDL high. This is not a good picture, though.

My IGF-1 levels were also too high, suggesting rapid turnover of cells and increased cancer risk.

After three months on the Fast Diet there were some remarkable changes.

	ME	RECOMMENDED
HEIGHT	5’ 11”
WEIGHT	168lb
BODY MASS INDEX	24	19-25
BODY FAT	21%	Less than 25% for men
WAIST SIZE	33 inches	Less than half your height
NECK SIZE	16 inches	Less than 16.5 inches

I had lost about 19lb, almost one and a half stone. My BMI and body-fat percentage were now respectable. I had to go out and buy smaller belts and tighter trousers. I could fit into a dinner jacket I hadn’t worn for ten years. I had also stopped snoring, which delighted my wife and quite possibly the neighbours. Even better, my blood indicators had improved in a spectacular fashion.

	MY RESULTS in mmol/l	RECOMMENDED
DIABETES RISK: FASTING GLUCOSE	5.0	3.9–5.8
HEART DISEASE FACTORS: TRIGLYCERIDES HDL CHOLESTEROL LDL CHOLESTEROL	0.6 2.1 3.6	Less than 2.3 0.9–1.5 Up to 3.0
HEART DISEASE RISK HDL % of total	37%	20% and over
CANCER RISK Somatomedin-C (IGF-1)	15.9nmol/l	11.3–30.9nmol/l

My wife Clare, who is a doctor, was astonished. She regularly sees overweight patients with blood chemistry like mine had been and she said that none of the advice she gives has anything like the same effect.

For me, the particularly pleasing changes were in my fasting glucose levels and the huge drop in my IGF-1 levels, which matched the changes I had seen after doing a four-day fast.

Clare, however, felt I was losing weight too fast, that I should consolidate for a while. That is why I decided to go on a maintenance dose of fasting just one day a week. Unless it’s the weekend, holidays or a special occasion, I also, regularly, skip lunch.

What has happened is that my weight has stayed steady at 12 stone and my bloods remain in good shape. I do, however, think there is room for improvement and will shortly restart a two-day regime and blog about it. If you are interested then do visit our website, www.thefastdiet.co.uk.

So, what is the best way to go about an Intermittent Fast?

Let’s recap on what we’ve learnt. The reason for Intermittent Fasting – briefly but severely restricting the amount of calories you consume – is that by doing so you are hoping to ‘fool’ your body into thinking it is in a potential famine situation and that it needs to switch from go-go mode to maintenance mode.

The reason our bodies respond to fasting in this way is that we evolved at a time when feast and famine were the norm. Our bodies are designed to respond to stresses and shocks; it makes them healthier, tougher. The scientific term is hormesis – that which does not kill you makes you stronger. The benefits of fasting include:

Weight loss

A reduction of IGF-1, which means that you are reducing your risk of a number of age-related diseases, such as cancer

The switching-on of countless repair genes in response to this stressor

Giving your pancreas a rest, which will boost the effectiveness of the insulin it produces in response to elevated blood glucose. Increased insulin sensitivity will reduce your risk of obesity, diabetes, heart disease and cognitive decline

An overall enhancement in your mood and sense of wellbeing. This may be a consequence of your brain producing increased levels of neurotrophic factor, which will hopefully make you more cheerful, which in turn should make fasting more doable

So much for the science. In the next chapter Mimi discusses what to eat and how to go about starting life as an Intermittent Faster. How do you put the theory into practice?