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INSIDE HEALTH

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TX:听 02.04.13 2100-2130

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PRESENTER:听 MARK PORTER

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PRODUCER:听 ERIKA WRIGHT

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Porter

Hello, coming up in today's programme:听 Obesity and cancer - the heavier you are, the greater the risk. I will be learning more about one factor that might explain the link.

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People who have IGF levels in their blood at the top end of normal, not abnormally high but just at the top end of what's normal, those people are at higher risk of getting some of the common cancers like breast cancer, colon cancer, lung cancer adjusting of course for the known risk factors like cigarette smoking.

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Porter

And from weight to the latest darling of the burgeoning diet industry- so called two day diets. The answer to our weight loss prayers or just another passing fad? We examine the evidence.

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But first, the return to work after Easter was supposed to herald the launch of the NHS 111 service across England - it replaces NHS Direct and is designed to help the public access medical help fast, when the problem's urgent but not urgent enough to dial 999.听 The free, 24 hour, seven day a week care service was designed to ensure - and I quote - "that people receive the right care, from the right person, in the right place, at the right time." But the introduction of 111 has been plagued with problems - ranging from lengthy delays to a huge increase in workload for the emergency services -听 and it has not been rolled out as planned. Here's BMA spokesman Dr Richard Vaughtry on the Today programme just before the bank holiday weekend.

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Vaughtry - Today Programme

We've been warning the government for the last two years that their plans were too rushed, that they didn't take time to properly learn and evaluate the pilots, there wasn't enough capacity to handle the expected increase in calls, the IT didn't work properly and worst of all they planned to introduce it on a long bank holiday weekend at exactly the same time as the biggest reorganisation of the NHS was taking place - it was a recipe for disaster and we predicted that it would happen, sadly it is happening - patients are trying to get through, they're finding it difficult to get through, calls are being answered inappropriately, patients are being given the wrong advice - that is happening now.

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Porter

Dr Richard Vaughtry on the Today programme.

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Jeanette Turner is Senior Research Fellow at the University of Sheffield and part of a team that has been assessing the 111 service since it was first piloted nearly three years ago.

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Turner

We looked at the first four sites of NHS 111 that went live and overall they were quite favourable.听 We asked a lot of people who'd used that service what they thought of it and they were very satisfied, there were certain aspects that they liked, particularly things like getting appointments made for them directly without people having to phone them back and generally thought it was quite an efficient and friendly service.听 We did find a problem that there was a small increase in the number of calls going to the 999 ambulance service, which we'd not quite expected, that was about 3%, because one of the ideas of 111 is to try and reduce calls to 999.听 But overall we thought it was a well-functioning service.

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Porter

Which is very different though, Jeanette isn't it, from the experience we've had over the last week or so, I mean people have been talking about 40% increase in calls to the urgent services, long waits, people unhappy, so why - why has the pilot done better than the real thing?

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Turner

I think one of the problems with the newer sites is they've had far less time to prepare and get all those things in place and also in some places, although not all, NHS Direct is starting to get turned off.听 And one of the things we did say in our report was that some serious consideration needed to be given to what the impact would be once those NHS Direct calls started going to 111 because obviously the call volumes are going to be much higher then.

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Porter

One of the problems that seems to have happened in the last few months leading up to this launch is that the general public don't seem to know how to use this number, so let's cover a few basics - who should be using this and for what?

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Turner

The reason 111 came about was because over quite a long period of time, the last 20 years, there's been various consultations done with the general public and one of the things that they've always said they've found really confusing is how to access emergency and urgent care.听 NHS Direct was one of the things that was put in place to try and rectify that but it didn't seem to have worked and of course other services have come online, so people have got more and more confused.听 And one of the ideas of 111 was really to try and just have two numbers - 999 for emergencies and 111 for urgent calls or where people weren't quite sure what to do.听 And the idea of it was that their calls would be assessed straightaway, so they wouldn't have to wait for someone to call them back although that's not what happened in reality quite recently obviously and they would essentially be signposted to the right service and if they needed an ambulance one would be sent straightaway there would be no need to make another call.听 Depending on what was available locally there may be facilities in place to actually make an appointment for people at things like urgent care centres while they're on the phone, so no need for a second phone call.听 So it was really to try and streamline that whole process.

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Porter

And there doesn't seem to be much of a national awareness campaign either directed at the people who are going to be using the service.

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Turner

No I've not seen one.

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Porter

So what's the difference between something that's urgent and something that's an emergency?

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Turner

It's a good question, it's one that a lot of people can't answer - I can't - the only thing I would say is that essentially people have already been doing it for a long time, so if they've got a health problem they've been making a decision whether to call 999, whether to call NHS Direct, whether to call out of hours GPs and for a lot of the time, not always, but a lot of the time people are actually very sensible about those things.听 At the moment someone might think do I call the out of hours GP or do I call NHS Direct first and check - in theory now they just need to deal one number - 111 - and that question would be answered for them.

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Porter

One of the criticisms that's come out of the recent launches is that the staff simply aren't qualified enough to advise people - they're following - presumably they're following some sort of algorithm, some set of instructions that they follow, and actually they can't really interpret it because they're not healthcare professionals.

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Turner

That's a fair criticism, certainly it's not something we encountered a problem with.听 I think one of the problems with 111 is because it's been rolled out so quickly and lots of services have tried to get going at the same time over the last few months is there's been very little time for people to actually recruit people, train them and make sure that's all working really well before they've got going.

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Porter

Jeanette Turner.听 And you will find an overview of the NHS 111 service, including a link to find out if it's up and running in your area, on our website. Go to bbc.co.uk/radio4 and click on I for Inside Health.

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Most people are aware that being overweight increases the risk of problems like heart attack, stroke and diabetes, but the link with cancer is not so well appreciated. Yet obesity is an important risk factor for a number of common cancers - including cancer of the bowel, breast and kidney - and it's now thought to be responsible for around one in 15 of all deaths from the disease in the UK. 听And although it's making the headlines these days the relationship's never really explained.听

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There are likely to be a number of factors responsible for the link, but it is becoming increasingly clear that changes in the levels of some hormones and related chemicals play an important role. Hormones like insulin - which controls blood sugar levels - and a related compound called IGF1.

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Terry Wilkin is Professor of endocrinology and metabolism at the University of Exeter Medical School.

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Wilkin

Nature is very parsimonious, it doesn't waste anything.听 Now it happens that insulin has a very close proximity to IGF1, in fact it's one of what we call a super family.听 From the mists of time of evolutionary time one hormone has become a number with slightly different functions and the insulin super family produces insulin, which we're familiar with, but also a series of other hormones which have very similar structure, slightly different, but very similar structure to insulin called IGFs - the insulin like growth factors.

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Porter

And it these factors that attracted the attention of cancer researchers like Dr Val Macaulay - medical oncologist at the Weatherall Institute of Molecular Medicine in Oxford where she studies cancer cells in the lab. They require special culture mediums to grow but one set of lung cancer cells seemed to thrive without much help from Dr Macaulay. So she sent the culture to a colleague for analysis, and the results were rather unexpected.

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Macaulay

I remember the day that he phoned me up and he said to me - Well done, I've tested this liquid for the X and Y proteins that you asked me to and they were negative but I can tell you, Val, that this stuff is absolutely packed full of growth factor.听 Now at that point I didn't know much about growth factors but I knew that there was more than one and I said to him - Which one is it?听 And he said - It's insulin like growth factor.听 And that was the first time I'd ever heard the word and it just seemed to me that it was an incredibly powerful thing that could help cancer cells to grow.

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Porter

And what do we know about IGF1 now?

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Macaulay

So IGF1 has been recognised for a while as being an important reason for the body to grow.听 So we all know about growth hormone - growth hormone makes us grow.听 And the reason that it does that is it makes the liver produce IGF1.听 So when you have growth hormone production by the brain that causes the liver to make IGF1 and that causes your bones and muscles to grow.

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Porter

So IGF1 is actually the delivery boy, it's actually what makes growth hormone work?

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Macaulay

Exactly, in fact the first name for IGF1 was somatomedin, it was mediating the effects of growth on the growth of the body.听 And as we're getting better nourished we're kind of setting our IGF'o'stat, as it were, at a higher level.

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Porter

And is so often the case in medicine, it was a rare disease that first pointed scientists to a possible link between cancer and raised IGF1 levels.听 In this case it was Acromegaly - a condition where the pituitary gland goes into overdrive and produces too much growth hormone.

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Wilkin

People with Acromegaly have got heavy facial features, have got very thick fingers, protuberant bellies - the tissues are generally being stimulated to grow due to the production of excess growth hormone by the pituitary gland.听 And there was some 20 years ago I suppose noted to be an association between colon cancer and Acromegaly and this is really due to the pituitary gland making too much of the hormone that then makes the IGF1 from the liver and it's the IGF1 that is believed to be responsible for the increased risk of colon cancer.

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Porter

So these people with Acromegaly have high levels of growth hormone and IGF1?

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Wilkin

Indeed.

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Porter

And they're more prone to cancer?

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Wilkin

And they're more prone to cancer and it was that recognition, that realisation, that led to clinical practice changing insofar as any endocrinologist dealing with a patient with Acromegaly would nowadays, and indeed has for some time, include in the list of his work a colonoscopy to ensure that the patient didn't have cancer.

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Porter

Because that increased risk is of what sort of magnitude?

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Wilkin

Four fold and more.

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Porter

Significant.

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Wilkin

Oh very.

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Macaulay

What IGF may be doing is that if someone has a tiny cancer or a few cells that are thinking about becoming abnormal and making a cancer may be in someone whose IGF levels are relatively high that may allow the persistence and growth of that cancer to the point where it's clinically evident and starting to cause problems for the person.

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Porter

So going back to your lung cancer cells that were grown in the lab it was the IGF1 that was boosting them along, the same thing might be happening actually in vivo - in our bodies?

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Macaulay

Exactly, so IGFs are not only made by the liver but they're made by a lot of other cells and tissues.听 And the way that they work is that they stick on to a special molecule on the surface of cells and most of our cells in our body have got these special molecules and they're called receptors, it's a bit like if you think about a key going into a lock, the key will only fit into the lock that it's been designed to fit and when you turn that key you open the lock, you activate the receptor and that gives a signal into the cell.听 In the case of the IGF that signal is to grow and to develop, maybe to divide to produce more cells and in particular not just to produce more cells but to be resistant to killing.听 And this is something that really characterises cancers - what they are very good at is surviving, they're very good at not being killed.听 And IGFs is one of the factors that helps them to survive.

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Wilkin

Every cell you have is in the process of living and dying at some point and the process of programmed or natural cell death is called apoptosis.听 And this is very, very important because if you reduce the rate of apoptosis you will increase the likelihood of cancer because we're all of the time producing cancers in our bodies which never get anywhere because they just die...

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Porter

Some of our cells turn cancerous but they have this pre-programmed death?

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Wilkin

Absolutely, the switch is thrown and the cells just die a natural programme cell death.听 But if you are to interrupt that system whereby the switch wasn't thrown, the cells didn't die, they'd multiply and they'd multiply very quickly because that is the nature of a cancer.听 Now what is happening with high insulin levels and with high IGF1 levels is that these two hormones reduce the rate at which this switch is thrown, so they permit or facilitate the growth of a cancer.听

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Porter

The link between cancer and obesity may not be听 widely appreciated - yet - but the link with diabetes is. The more overweight you are the more likely you are to develop something called insulin resistance - where the blood lowering properties of insulin are no longer enough to control your blood sugar levels, so you produce even more. And not only does that increase your odds of developing diabetes, it may encourage cancers too. Val Macaulay.

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Macaulay

If you think of someone who's having repeated high carbohydrate meals that means the pancreas is producing a lot of insulin most of the time and what effect that has is that initially the insulin is doing its job but over time the insulin receptor starts to care less about insulin.听 If I can maybe make the analogy - if you're listening to loud music, cranked up really loud, and after a while it starts to knacker your ears a little bit and you have to turn up the music louder in order to get the same enjoyment, finally you're cranking up the music louder and louder until you really knacker your hearing.听 It's the same sort of effect with insulin - if the pancreas is constantly turning out high levels of insulin eventually the insulin receptor stops caring.听 So at that point the insulin receptor doesn't respond to insulin, the level of blood sugar rises and the person becomes a Type 2 diabetic.听 That has several consequences for cancer risk and the behaviour of cancers in cells.听 One is that it can increase the active amount of IGF in the blood, it doesn't actually change the amount of IGF in the blood but it reduces the levels of special binding proteins that stop the IGF being active all the time - so you've effectively got more active IGF1 in your blood if you have high insulin levels and if you're Type 2 diabetic.听 And the other thing it does is obviously you've got very high blood sugar levels - cancers are well recognised to like to use a lot of glucose in their metabolism, this is something that's been recognised since the 1920s that cancers use a lot of glucose.听 And all those things are the sort of environment that really favour the growth of cancers.

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Porter

But it's not just how much we eat that influences insulin and IGF1 levels - it is where we store the excess nutrients as fat too. Terry Wilkin.

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Wilkin

We're all born with a number of specialist fat cells whose job it is to store fat.听 You eat a meal it contains fat in the meal these fat cells are there to store that fat immediately until it's needed.听 And insulin does its job taking fat in and out of the cells as and when it's needed but if, as is so commonly the case in our modern environment, you begin to eat just too much, whether it's fat or whether it's carbohydrate, then the excess is always converted into fat but where do you store it?听 Well if you've filled up your specialist fat cells then you've got to find somewhere else and the place you find is in the gut and most harmfully perhaps in the liver and in the muscles.

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Porter

So looking at our fat stores from a long term health point of view, in terms of diabetes and risks of cancer, would it be fair to differentiate our stores into normal healthy fat stores, the ones under the skin, but harmful ones that occur inside the abdominal cavity - in the liver, around the gut?

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Wilkin

Absolutely and I think the useful analogy would be that of overflow and people use - they talk about overflow, the overflow hypothesis is one of the explanations for what is happening, that people are born with different capacities, different sump sizes if you like, to absorb their dietary fat.听 And at a particular point it will overflow into tissues where fat shouldn't be and that's when it begins to cause the problems.

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Porter

Is there a correlation between IGF1 levels and where you store your fat?

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Wilkin

Yes there is.听 The IGF1 levels are higher in people who are inappropriately storing fat in the liver or in muscle or in their gut cavity.

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Porter

And equally is there a correlation between people who store that fat inside their abdomen and their risk of getting cancer - weight for weight - compared to somebody who stores their fat elsewhere?

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Wilkin

Yes there is, you're looking at the same metabolic dysfunction that is in any other language pre-diabetes, it's pre-cardiovascular disease, these are the beginnings of a process which is affecting any number of different tissues amongst them cancer growth.

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Porter

So some types of fat are okay, other types are potentially toxic to the body, can you tell by looking at a patient which is which?

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Wilkin

Yes you can and the first usage of the terminology apples and pears was in fact French and it was a Professor Vargue [phon.] from Marseilles who first looked at his metabolic patients in his clinic in the South of France in the 1940s and said aha, you're at risk but you're not and I can tell the difference between the two of you because one of your fat distribution is low in the body and the other one is high in the body, one of you is a pear distribution - butts and thighs if you like - and the other is an apple distribution - it's all abdominal.听 And he recognised and he published that the apple distribution had a much greater metabolic risk, not to do with cancer in those days but he was looking at diabetes and cardiovascular disease, but he saw the risk just by looking at the patient.

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Porter

And it's the apple who is more likely to get diabetes and all the metabolic problems including raised IGF1 levels and therefore at risk of increased cancer.

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Wilkin

Because the apple is storing fat in a place where it shouldn't be stored in the abdominal cavity, the pear is storing it in specialised fat cells in the butt and the thighs.

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Porter

Professor Terry Wilkin extolling the virtues of maintaining a healthy figure, as well as a healthy weight.听

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But what is the best way of losing those extra pounds if your fat stores have overflowed into areas they shouldn't have? Well if you believe the latest fad it is all about fasting - the current vogue being for intermittent diets that centre around the two/five formula. The exact protocol depends upon which type you follow.

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On the one extreme is the feast and famine approach which advocates two days fasting (that's generally less than 650 calories a day for a man) followed by five days of eating whatever you like.

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While at the other you will be urged to restrict carbohydrates for two days (a sort of Atkin's approach) followed by five days on a normal, albeit healthy Mediterranean type diet. But do any of them work?

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Inside Health's Margaret McCartney has been taking a look - so have you found much good evidence Margaret?

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McCartney

Absolutely not.听 I think this is what I'm really pretty shocked about - there's been so much publicity saying that this is the new way forward, you can revolutionise your life, even some people saying that you can live a longer life, that your lifespan will extend, some people have even been putting out quite dramatic numbers on this when actually the evidence base for it is absolutely slight - slender if anything, really not the long term studies that we really need before we know that this diet is any better than any of the other miracle diets that have been sold to us over the last few decades.

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Porter

But we've had a Horizon documentary on it, it's difficult to pick a paper up...

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McCartney

Yeah and I think this is the problem that we have about science in general and how much we're able to be susceptible I think by stories - quite dramatic stories sometimes - and certainly I've had friends of friends who say they've lost lots of weight.听 But of course we never really hear the same stories from people who've been on a diet for two, three years, these are the kind of stories that really appeal far more to me because it's the long term weight that's the issue rather than short term weight loss.听 My fear is that we really have been given this big headline without being given any of the uncertainties behind it.听 And actually there's minimal evidence where the fast diet - where you have two days off and five days of eating whatever you like - very small studies in America, very short term, really not enough, I would say, to be writing any books or documentaries about.听 But there is some evidence for the intermittent fasting, low carbohydrate diet, but again these studies are about 100 patients or so, a maximum of six months - really not enough, I think, to be pinning on this the revolutionary diet for this year.

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Porter

Well we're joined by dietitian Dr Michelle Harvie from the Genesis Breast Cancer Prevention Centre in Manchester, and the co-author of the "the two day diet" which advocates two consecutive days on a low carbohydrate diet followed by five days of normal healthy eating. Michelle, what is your take on the current explosion in the feast/famine approach?

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Harvie
We've been researching these diets for about seven years and the current spin on it is a real over-simplification.听 We know that these diets will have health benefits but people think you can just fast and then feast on the other days and get all the health benefits and weight loss that you want and we know that that's just not the case.

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Porter

Well first of all is there any evidence that that has ever been the case?

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Harvie

No all the animal studies and our research has always been based on restricted periods interspersed with sort of healthier eating in between.

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Porter

So explain to me what's different about your diet?

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Harvie

On our diet we ask people to have two consecutive days of a low carbohydrate diet and on the other five days of the week they have a healthy Mediterranean diet, they're not restricted in the amount they can eat but we ask them to try and eat healthily.

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Porter

So basically yours is an intermittent diet, it's not a feast and famine?

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Harvie

Exactly.

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McCartney

When it comes to Michelle's diet, Dr Harvie's diet, about intermittent and carbohydrate restriction again the evidence is actually fairly slender.听 There's two papers I think Dr Harvie's group has produced, one from the International Journal of Obesity in 2011 and just 107 women took part in that one and didn't show any difference really between the intermittent carbohydrate restriction and the normal daily diet that we all know about - just eat a bit less and move a bit more.听 And the more recent paper that was a poster presentation, so the full data's not in the public domain, had 115 women in it and so for me the jury is definitely still out on this one.

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Porter

Michelle, on the front of your book it's revolutionary and clinically proven and presumably the clinical proven aspect refers to that data that Margaret's talking about?

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Harvie

Yeah to our two trials and we've - the important thing about our two day diet is we've actually conducted what we call randomised trials where we've taken a group of women, randomly asked them to follow a two day diet or the normal daily diet and we've shown that the two day diet, about 65% of people, are successful with that, compared to about 40% of daily dieters, which is what you'd expect for a daily diet.听 So we've really upped that.

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Porter

Michelle, is there something clever about restricting intake, whether it be calories or whether it be carbohydrates on a couple of days a week that helps weight loss other than simple calorie restriction across the whole week, is it a fact - I mean do we know for a fact that these people just aren't simply eating less across the whole week?

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Harvie

Yeah, you get the benefit of losing fat on the two days but it actually seems to retrain people's appetites and a lot of our serial dieters found that they actually wanted to eat less on the other days.听 So partly how it works is people will naturally want to self-restrict on the other days.听 In fact in our studies people feel better for doing the two days and it buys them into it.

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McCartney

But looking back at your other study that was published in the International Journal of Obesity in 2011 there was actually very little difference between weight loss in the groups using your diet compared with a normal calorie restrictive diet, so again I'm unsure about how we can say that this diet is more successful and that is the only study that's fully in the public domain and yet the book out that sort of says it's revolutionary on the front cover.

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Harvie

Well - actually we're about to hopefully embark on some big sort of national studies.

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Porter

But in terms of how this diet is working I mean there's nothing magical going on here, what you're suggesting or the impression that I'm getting is that by making people restrict their carbohydrate on two days a week and that has then, in your experience, a knock on effect on what they consume for the rest of the week and that is how the diet's working, in your opinion?

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Harvie

That's right but there's also a very intriguing greater reduction in some of the markers of disease, such as insulin, which actually seems to go down more with these two day dieting - that's what we showed in our previous study, even though the weight differences were not that great.听 And we think that maybe there's something about having a sort of lower calorie, lower carbohydrate diet on two days a week which - we need to do more work on this - but it may actually preferentially mean that we lose fat from places in the body where they cause harmful effects like the liver and it certainly reduces insulin levels, both on restricted days and the unrestricted days and that may be really important in terms of health.

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Porter

And听 Margaret from your point of view is the fasting element of this at all important?

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McCartney

I don't think we really know to be absolutely honest with you, I don't think we have the data to tell us...

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Porter

That's what makes it different isn't it from every other plan?

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McCartney

Absolutely, absolutely, absolutely and I don't think we've got the data to tell us how many calories it is that people consume and do they gradually reduce their calories over their five good days, as it were, in the longer term.听 So unless we've got that data I don't really know how we can understand what's going on.

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Porter

Because every new diet plan says this is not calorie counting, it's not about calorie counting, there's another way round it and yet it would appear that it all comes down to calorie intake - as we would expect, the rules of thermodynamics.

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McCartney

Yes I mean - absolutely, this is the ultimate problem, I think, that no matter what diet you look at any diet that works is going to be about reduction of calories, that's the bottom line.

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Porter

Well guess what if you eat fewer calories you lose weight, if you eat more calories - surprise, surprise - it goes back on.

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McCartney

That's it.

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Porter

Margaret McCartney and Dr Michelle Harvie thank you both very much.听 And you will find some links to Dr Harvie's research on our website - go to bbc.co.uk/health and head for the Inside Health page.

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Just time to tell you about next week's programme when, among other things, I will be learning more about a surprisingly common, and often missed, complication of head injuries. So if you have ever been knocked out - even for a relatively short time - make sure you join us to find out more.

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ENDS