Intermittent fasting: Trying it out for science

[Demi]

From BBC News Online
London, UK
1 January, 2014

Intermittent fasting: Trying it out for science

If losing weight is on your January wish-list, you're not alone - it's one of the most common New Year resolutions. But diets can be hard to stick to at any time of year. In the first of a three-part series, the BBC's Peter Bowes steeled himself for the task by joining a clinical trial for an experimental fasting diet.

Knowing which diet advice to follow can be perplexing and frustrating. Hardly a day goes by without news of a new scientific study. Fad diets come and go.

Sales of high-protein shakes have surged in recent years, but the scientific evidence suggests that most people are consuming too much protein. Low-fat diets were once all the rage; now they seem to have fallen out of favour.

"People do get confused," says Dr Lawrence Piro, CEO and President of The Angeles Clinic and Research Institute, a private medical facility in Los Angeles.

People receive mixed messages about what to eat, Piro acknowledges.

"Eat fish and don't eat red meat," he says, listing some of the medical advice he's seen doing the rounds in recent years. "But then don't eat farm-raised fish because it may be too high in various minerals that are toxic. So now don't eat any fish at all and switch to vegetables - be vegan..."

The popularity of intermittent fasting has grown over the past year or so. The 5:2 diet, which involves dramatically reducing your calorific intake on certain days of the week, is one example.

But more clinical data is needed to confirm the benefits of such regimes. Doctors are generally reluctant to recommend them. The UK's National Health Service questions how sustainable intermittent fasting is in the long term.

Curious about the scientific research that goes into devising a new diet, I decided to volunteer as a subject in a five-month clinical trial at the University of Southern California (USC).

As a human guinea pig, I signed up to test a strict diet regime and subject myself to a battery of clinical tests to evaluate its effect on my body.

It involved surviving, for five consecutive days, on a narrow range of foods that contained as little as 500 calories per day - about a quarter of the average person's consumption. There was to be no cheating, no falling off the wagon and no treats. It was an opportunity to be part of study that may help scientists unravel the complex relationship between food and the human body.

The clinical trial, which is still ongoing, is designed to investigate the feasibility, safety, potential benefits and psychological changes associated with a calorie-restricted diet. It is based on previous experiments, at a number of institutions, which have shown that mice live longer and healthier lives if their food intake is cut by up to 30%.

Research at USC's Longevity Institute has also shown, in rodents, that short-term fasting before chemotherapy can prevent some of the toxic side-effects of the treatment. There is a growing body of opinion that fasting has a potent, beneficial effect on organisms and that it is potentially extendable to humans.

But it is still unlikely that a doctor would put a patient on a restricted diet because of the potential risk of nutritional deficiencies. Also, fasting regimes are tough to follow through, for most of us at least.

This is why the current USC diet does not involve a complete fast and is designed to be repeated in short bursts over a number of months.

"I don't think there is a solid data-supported study to show that cycles of low-calorie diet will actually have a beneficial effect, so that's what we are trying to achieve," explains Dr Min Wei, the study's lead investigator.

There was an enthusiastic response from members of the public when the university appealed for volunteers.

"California people are especially conscious of diet, exercise and health," says Wei, "especially in the environment where obesity is a huge problem, as well as diabetes and cancer."

Since fasting can be dangerous, I sought the advice of my family doctor, who confirmed that it was "medically safe" for me to participate.

The food, during the period of the restricted diet, was designed to be highly nutritious. It consisted of plant-based soups, kale chips, a nutty bar, a herbal tea and an energy drink. The total number of calories, in five days, was about 2,500 - a little more than the average person consumes in one day. No additional food was allowed. For the rest of the month we were allowed a normal diet. The regime was repeated three times, followed by a control period, when we could eat anything.

During the test and control periods, blood samples were taken; body weight and composition (bone density and body fat) were measured using a Dexa (dual X-ray absorptiometry) machine. Brain activity was recorded during one-hour MRI (magnetic resonance imaging) sessions, to determine whether the diet had any impact on cognitive abilities.

The diet had unexpected consequences for everyone, including extreme hunger in some cases - and an aversion to the limited amount of food in others. On the positive side, volunteers, including myself, reported a heightened feeling of mental well-being.

Our stomachs may have been grumbling but we experienced a surprising sense of alertness and sharpness of the mind.

This is the first of a three-part series. Tomorrow: Surviving on 500 calories. Friday: How my body changed.



The trial

Why? To find out if a specially designed calorie-restricted diet for a short time is feasible and safe
Where? The School of Gerontology, University of Southern California (gerontology is the study of biological and psychological aspects of ageing)
Who? 64 healthy adults between the ages of 18 and 65 (no pregnant women) - no payment for taking part
What? Three five-day cycles over three months, when volunteers ate only low-calorie food supplied by the research team, followed by a two-to-three month control period on a "normal" diet

Conflict of interest?

The study is funded by USC and sponsored by L-Nutra, a spin-off company from USC, which makes the food. The company's founder, Dr Valter Longo, is the Director of USC's Longevity Institute.

He is not allowed to have anything to do with the collection and analysis of data during the study, although under the university's ethics rules, he is permitted to be a "co-investigator".

"The conflict of interest is handled above of me (by USC's Conflict of Interest Review Committee) meaning that every year I get reviewed as a founder of the company and as a professor," says Longo.

The company produces food, designed in a clinical setting, which can be relied upon for a clinical trial.

"Our idea is to figure this out scientifically and clinically here at USC and then let the company sell it for a fairly reasonable price," Longo says.

http://www.bbc.co.uk/news/magazine-25498742

[Demi]

From BBC News Online
2 January 2014

Intermittent fasting: Enduring the hunger pangs

Scientists in California are conducting a clinical trial to test a diet that may help people lose weight while also boosting resistance to some diseases. One of their guinea pigs was the BBC's Peter Bowes, who reports here on his experience of fasting for five days per month.

It's been tried on mice and now it's being tried on humans - a diet that involves multiple five-day cycles on an extremely low-calorie diet. Each of those five days is tough, but the upside is that for much of the time - about 25 days per month - people eat normally, although not excessively.

The low-calorie period includes small amounts of food to minimise the negative effects of a total fast. Designed by scientists to provide a minimum level of essential vitamins and minerals, the diet consists of:

vegetable-based soups
energy bars
energy drinks
dried kale snacks
chamomile tea

These meals are extremely low in calories - about 1,000 on day one and 500 for each of the next four days.

With the exception of water and black coffee, nothing else is consumed.

The limited selection of food (with no choice of flavours) means that everything has to be eaten. It's monotonous... but at least it makes meal planning easy for five days.

"The reason why diets don't work is because they are very complicated and people have an interpretation problem," says Dr Valter Longo, director of the University of Southern California (USC) Longevity Institute.

"The reason I think these diets work is because you have no interpretation. You either do it or you don't do it. And if you do it you're going to get the effect."

Dr Longo established a company to manufacture the food, based on research in his department at USC. He has shown in mice that restricting calories leads to them living longer with less risk of developing cancer.

The food used during the trial is the result of years of experimenting. The idea is to develop a diet that leads to positive cellular changes of the same kind seen in mice that have been made to fast.

"It turned out to be a low-protein, low-sugar-and-carbohydrate diet, but a high-nourishment diet," explains Longo.

"We wanted it to be all natural. We didn't want to have chemicals in there and did not want to have anything that is associated with problems - diseases. Every component has to be checked and tested. It's no different to a drug."

Longo stresses that the experimental food could not be made in your kitchen.

But it is a big leap from laboratory mice to human beings. Restricting the diets of rodents is easy, but people have minds of their own - and face the culinary temptations of the modern world.

I knew the diet cycles would be difficult.

I love to eat. I enjoy a big, healthy breakfast, exercise a lot and - left to my own devices - snack all day before digging in to a hearty evening meal. At 51, I am in good shape. I weigh 80kg (12 stone 8lbs / 176lbs) but like most middle-aged men, I struggle with belly fat. I have never tried any kind of fasting regime before.

The diet meals were better than I expected - at least initially. I was so hungry I would practically lick the soup bowl and shake the last kale crumb from its bag, to tide me over to the next feeding time.

Note: it is no longer lunch or dinner. It is a feeding opportunity. It is certainly not a social occasion.

Headaches, a typical side effect of fasting, started on Day 2 but they waned within 24 hours, leaving me in a state of heightened alertness. During the day - and especially in the morning - I was more alert and productive. Hunger pangs came and went - it was just a matter of sitting them out. But they did go.

By the evening - especially on Day 5, I was exhausted. Tiredness set in early. But I made it through the five days - for three cycles - without deviating from the regime. I lost an average of 3kg (6.6lbs) during each cycle, but regained the weight afterwards.

All participants keep a diary, noting their body weight, daily temperature reading, meals and mood. The feedback - positive and negative - is vital to the integrity of the study, which is partly designed to establish whether the diet could work in the real world.

For me, and for all but about 5% of the volunteers who have completed all three cycles, the diet was do-able - although opinions vary about the taste of the food.

"It is not an experience for the faint of heart. It was extremely difficult because the little bit of food that you're offered gets very tiresome as time wears on," says Angelica Campos, aged 28.

"I had to isolate myself because my family were constantly offering me food. They thought I was crazy."

She would not want to go through the experience again, but says she would if it were proven to have long-term benefits.

Her boyfriend, Alex de la Cruz, aged 29, says the fasting made him very tired, but when he woke up he was "as alert as could be".

"My overriding memory of the experience is that the food was horrible, but the results were totally positive," he says.

Lead investigator Dr Min Wei says that for some people the diet is a greater wrench than for others, depending on their lifestyle. The absence of carbohydrates and desserts, can hit some people hard, for example, and also the restriction to black coffee alone. "We are fairly strict," he says. "We recommend people stick to the regimen. If people enjoy special coffee - lattes for example - they won't be able to enjoy them."

Data from the volunteers is still being collected and analysed. The early signs are that the diet is safe and could be adopted by most healthy people, providing they are suitably motivated to endure the periods of hunger.

But the full effect can only be measured over the long term. Initial changes in the body may not tell the full story.

"Having dietary factors influence your body sometimes takes years and years," explains Dr Lawrence Piro, a cancer specialist at the Angeles Clinic and Research Institute.

This particular trial now moves into the laboratory. Based on blood tests, has anything changed inside my body to suggest extreme dieting improves my chances of avoiding the diseases of old age?

Tomorrow: My results. http://www.bbc.co.uk/news/magazine-25498743

[Demi]

Intermittent fasting: The good things it did to my body

By Peter Bowes
BBC News, Los Angeles

Many of the changes in my body when I took part in the clinical trial of an intermittent fasting diet, were no surprise. Eating very little for five days each month, I lost weight, and I felt hungry. I also felt more alert a lot of the time, though I tired easily. But there were other effects too that were possibly more important.

During each five-day fasting cycle, when I ate about a quarter the average person's diet, I lost between 2kg and 4kg (4.4-8.8lbs) but before the next cycle came round, 25 days of eating normally had returned me almost to my original weight.

But not all consequences of the diet faded so quickly.

"What we are seeing is the maintenance of some of the effects even when normal feeding resumes," explains Dr Valter Longo, director of USC's Longevity institute, who has observed similar results in rodents.

"That was very good news because that's exactly what we were hoping to achieve."

Clinical tests showed that during the diet cycles my systolic blood pressure dropped by about 10%, while the diastolic number remained about the same. For someone who has, at times, has borderline hypertension, this was encouraging. However, after the control period (normal diet), my blood pressure, like my weight, returned to its original - not-so-healthy - state.

The researchers will be looking at whether repeated cycles of the diet could be used to help manage blood pressure in people over the longer term.

Arguably, the most interesting changes were in the levels of a growth hormone known as IGF-1 (insulin-like growth factor). High levels of IGF-1, which is a protein produced by the liver, are believed significantly to increase the risks of colorectal, breast and prostate cancer. Low levels of IGF-1 reduce those risks.

"In animals studies we and others have shown this to be a growth factor that is very much associated with ageing and a variety of diseases, including cancer," says Longo.

Studies in mice have shown that an extreme diet, similar to the one I experienced, causes IGF-1 levels to drop and to stay down for a period after a return to normal eating.

My data showed exactly the same pattern.

"You had a dramatic drop in IGF-1, close to 60% and then once you re-fed it went up, but was still down 20%," Longo told me.

Such a reduction could make a significant difference to an individual's likelihood of developing certain cancers, he says. A study of a small population of people in Ecuador, who have much lower levels of IGF-1, because they lack a growth hormone receptor, showed that they rarely develop cancer and other age-related conditions.

My blood tests also revealed that the major inhibitor of IGF-1, which is called IGFBP-1, was significantly up during the fasting period. Even when I resumed a normal diet, the IGFBP-1 level was elevated compared with my baseline. It is, according to Longo, a sign that my body switched into a mode that was much more conducive to healthy ageing.

Data from other participants in the study is still being analysed, but if they also show lower levels of IGF-1 and higher levels of IGFBP-1, it could help scientists develop an intermittent fasting regime that allows people to eat a normal diet for the vast majority of the time, and still slow down the ageing process.

One idea being explored by Longo is that a five-day intervention every 60 days may be enough to trigger positive changes in the body.

"This is exactly what we have in mind to allow people, for let's say 55 every 60 days, to decide what they are going to eat with the help of a good doctor, and diet in the five days. They may not think it is the greatest food they have ever eaten, but it's a lot easier, let's say, than complete fasting and it's a lot safer than complete fasting and it may be more effective than complete fasting."

The very small meals I was given during the five-day fast were far from gourmet cooking, but I was glad to have something to eat. There are advocates of calorie restriction who promote complete fasting.

My blood tests also detected a significant rise in a type of cell, which may play a role in the regeneration of tissues and organs.

It is a controversial area and not fully understood by scientists.

"Your data corresponds to pre-clinical data that we got from animal models that shows that cycles of fasting could elevate this particular substance, considered to be stem cells," said Dr Min Wei, the lead investigator.

The substance has also been referred to, clumsily, as "embryonic-like".

"At least in humans we have a very limited understanding of what they do. In animal studies they are believed to be 'embryonic-like' meaning... they are the type of cells that have the ability to regenerate almost anything," says Longo.

It would be highly beneficial if intermittent fasting could trigger a response that enhances the body's ability to repair itself, but much more research is required to confirm these observations.

This diet is still at the experimental stage and data from the trial are still being studied. Other scientists will eventually scrutinise the findings independently, and may attempt to replicate them.

"We generally like to see not only an initial discovery in a trial but we like to see confirmatory trials to be sure that in the broadest kind of sense, in the general population that these findings are going to be applicable," says Dr Lawrence Piro, a cancer specialist at The Angeles Clinic and Research Institute.

"I do believe fasting to be a very effective mechanism. They are pieces of a puzzle, that puzzle is not fully revealed yet, the picture isn't clear yet but there's enough of the picture clear. I think we can be really excited that there is some substantial truth here, some substantial data coming forward and something that we can really be hopeful about."

Future clinical trials will focus on "at-risk" members of community - those who are obese - to gauge their response to a severely restricted diet.

But if this diet, or another intermittent fasting diet, is eventually proven be effective and sustainable, it could have profound implications for weight loss and the way doctors fight the diseases of old age.http://www.bbc.co.uk/news/magazine-25549805