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Vitamin D – BBC Radio 4 Case Notes With Dr Mark Porter

Transcript of Programme : Programme no 3 Vitamin D

CASE NOTES Programme no. 3 Vitamin D

RADIO 4 TUESDAY 20TH APRIL 2010 -2130 – PRESENTER: Mark Porter
CONTRIBUTORS: Oliver Gillie, Veronica Warrell,Elina Hypponen, Nick Bishop, Minoo Irani, Adrian Martineau, Chris Griffiths, Kay-Tee Khaw

PRODUCER: Erika Wright

PORTER : It’s unusual for Case Notes to devote a whole programme to a single nutrient, but today’s subject vitamin D warrants it. In recent years it has taken a back seat to higher profile vitamins like A, C and E, but new evidence suggesting that it has a much wider role than previously thought, looks set to drag it back into the limelight.

GILLIE : You have to think back to the 19th Century and the purification of water supplies and then you think back to the 20th Century when housing was improved. The next frontier that we’re coming to is vitamin D. If we get that right we’ll make a major, major improvement in our health because so many diseases are linked with insufficient vitamin D.

PORTER : Medical researcher and journalist Oliver Gillie, one of a growing band of vitamin D evangelists. But what is all the excitement about?

WARRELL : Using my hands was really painful. Everyday things like, you know, putting the washing in the washing machine, having a scratch if I had a little itch, all sorts of things was really, really painful writing, using a keyboard I mean I was in constant pain all the time, everything I’d done. So much so that I had to reduce my hours at work I couldn’t function and do it.

PORTER : Vitamin D helps the body make proper use of calcium the basic building block of bones which is why interest in it has traditionally centred on bone conditions like rickets that result from severe deficiency. But we now understand that vitamin D does far more than maintain the skeleton, and that milder degrees of deficiency may predispose to a range of other illnesses including diabetes, lung disease, multiple sclerosis, rheumatoid arthritis, various cancers, and even Alzheimer’s disease.

And mild deficiency is extremely common in the UK. Nearly all of our vitamin D is manufactured in the skin when we’re exposed to sunlight, but our northern latitude and short summers mean that for six months of the year UV levels are so low that most of us don’t make enough of the vitamin to meet basic requirements. Underexposure that’s likely to be compounded if you have darker skin (because it blocks more of the sun’s rays), cover up when you’re outside or spend most of your time indoors.

Veronica Warrell works nights as a nursing assistant, so sees much less sun than she would like but never dreamt that her aching joints could have anything to do with a vitamin deficiency.

WARRELL : I started to experience this pain in my ankle, it was predominantly when I was sitting and I got up again. I couldn’t walk properly, I had quite intense pain. It would last for a few minutes and then disappear. I didn’t really pay any attention to it, I just kind of thought well it’s one of those things and just carried on with it. And then I’d say around about June ’09 I started to experience this pain in my knuckles and it really did feel like I would imagine an arthritis pain every time I moved my hands it hurt. I didn’t pay much attention then, I just thought well it’s one of those things. But it progressed to all my knuckles. So eventually I went to my GP and my GP was under the same impression as I was that I had osteoarthritis. I was convinced, I was totally yes that’s what I’ve got, I’m going to have to put up with it. And he sent me for an x-ray on my ankle and a blood screen. My x-ray was actually clear there was no sign of any arthritis. And my blood test showed that I had quite a bad vitamin D deficiency I was about a level 28. And they straightaway put me on vitamin D supplements twice a day. Within about two to three weeks the pain disappeared in my hands, it really was like a miracle, it was just like just disappeared.

PORTER : Cases like Veronica’s are thought to represent the tip of a much larger iceberg in the UK. Dr Elina Hypponen is a reader in epidemiology and public health at the Institute of Child Health.

HYPPONEN : The situation is pretty bad I would say. The worst situation is during late winter, early spring when about 90% of white Caucasians have a concentrations which are sub-optimal and 15% have concentrations that are severely deficient, so that if that type of concentrations continue over prolonged periods of time they will start to have severe problems with their bone health such as softening of the bone tissue, which is the classical vitamin D deficiency syndrome.

PORTER : Let’s look at the other half of the year, when the sun is out, and some of us do get an opportunity to go out in it. Do all of us have normal vitamin D levels then?

HYPPONEN : Well it’s better but still about 60% of the white Caucasians have sub-optimal concentrations. So you can take that the 60% of us will never reach optimal concentrations throughout the year.

PORTER : So what you’re saying is that more than half of the UK population never have optimal levels of vitamin D that’s more than 30 million people?

HYPPONEN : That’s correct.

BISHOP : We do have an image of a typical vitamin D deficient person as perhaps being a veiled mum or somebody with very dark coloured skin.

PORTER : Nick Bishop is professor of paediatric bone disease at the University of Sheffield, and looked at vitamin D levels in the cord blood of babies born in Sheffield at the end of spring a time when their mothers’ stores were likely to be at their lowest.

BISHOP : We found in this study where 90% of the women were white Caucasian folk that 70% of the babies had low vitamin D levels and none of those mums were coming forward and saying gosh I’ve got really achy bones or I’ve got pain in my hip or I’ve got a waddling gait which are some of the more traditional ways in which people might suspect that you were vitamin D deficient. So those signs of what in adults is called osteomalacia weren’t clinically evident in those mums at all.

ADVERT CLIP : Yes the baby’s here, mother’s delighted, father’s anguish is over poor father. And the baby, well it looks just like other babies but don’t tell mother that and it needs its extras its cod liver oil and orange juice unless of course you want a rickety child a bandy knock kneed large headed pale and rickety article. Cod liver oil prevents all this.

IRANI : Rickets, as a term, comes from apparently an old English word called wrickken, meaning to twist.

PORTER : Dr Minoo Irani is a consultant paediatrician in Berkshire East and has a special interest in public health.

IRANI : It is defined as the disease of growing bones. In practise we can identify rickets either by the classical skeletal manifestations, like the bowed legs, the knock knees, the widened wrists and ankles and other signs like the large prominent forehead or a sign called craniotabes which is a sensation of ping pong, a sensation of the skull when you press the bones I’ve never done that really.

PORTER : Like a ping pong ball, it moves in and out?

IRANI : Absolutely, except I don’t know how many paediatricians would have done that. But those are the sort of skeletal manifestations. There are other rather subtle manifestations of vitamin D deficiency which can also be seen in children with rickets. And one of them is a child who’s just generally failing to thrive, is irritable, miserable, could have vitamin D deficiency.

BISHOP : We moved when my son was three months old to Canada and my wife was feeding him herself and we didn’t think about vitamin D, which is pretty foolish, considering I’m a bone doctor. But we got through to the point in January, February time, in Montreal the winters are very long and hard, where she wasn’t feeling very well, went off to the doctor and had a blood test, was found to be vitamin D deficient and we looked at him and realised that the edge of his rib cage was starting to tilt upwards, so that he’d got signs of bone softening. And he had been well exposed to a lot of sunlight, just before we went off we’d had a holiday in Portugal with some friends and so his vitamin D certainly hadn’t lasted him the winter and neither had my wife’s.

WARRELL : As far as I’m concerned you know I’m quite a healthy person. And I thought I take everything that I’m supposed to have, you know, in a day I have my five a day, I have cereal, I have all the things that you’re supposed to have, I have my annual holiday like everybody else. I was completely thought I was up to date with all my vitamins and that, I didn’t in no circumstances would I have thought I had any deficiencies in that area.

PORTER : Veronica responded rapidly to vitamin D supplements, but there is much more to vitamin D than maintaining a healthy skeleton it acts more like a hormone than a nutrient. Which may explain a recently discovered role in diabetes.

Finland has a high rate of Type 1 Diabetes, and even darker winters than the UK, and recent research suggests that the two may be linked lack of vitamin D appears to predispose a baby to developing diabetes later in life.

Dr Elina Hypponen and colleagues followed over 12,000 woman who gave birth in Finland during the late ’60s and compared rates of diabetes between the children who were given vitamin D supplements, with those who weren’t. The results were striking.

HYPPONEN : When we compared the children that had been receiving this recommended dosage of vitamin D regularly their risk of developing Type 1 Diabetes was reduced by 80% in that population. For that study we followed the children up until they were 30 years of age and we are certain that they actually had developed Type 1 Diabetes.

PORTER : Eighty percent, I mean that is a massive difference, a very significant protective effect, it must have struck you when you first looked at the data?

HYPPONEN : It did indeed. And when one is thinking about vitamin D it’s important to think that it’s not actually a nutrient or vitamin per se but it’s a pro-hormone. And for me I’m able to conceptualise the possibility of such wide ranging health effects through the fact that vitamin D receptors they are really present all over the body. So they are not just in the bone, which is the classical target tissue but they are in brain, heart, pancreas, immune cells they are everywhere in the body. And if there is a receptor for a hormone in a certain target tissue that hormone must have a function.

PORTER : And those receptors on cells of the immune system are another area that is attracting a lot of interest, particularly in relation to the body’s response to tuberculosis TB. Dr Adrian Martineau, from Barts and The London Medical School is involved in a number of trials looking at vitamin D.

MARTINEAU : The first was a study in healthy TB contacts that is people who’ve lived with the person who’s got infectious TB but haven’t fallen ill themselves. And we showed in that study, which was published in 2007, that giving a single dose of vitamin D enhanced the ability of those people’s blood to contain growth of micro bacteria, which are the bacteria which cause TB.

The second study was the first to investigate the possibility that giving extra vitamin D to patients with active TB that is TB disease and seeing whether it might enhance their response to antibiotic treatment. And that second study was a dose finding study and showed that we need to give TB patients greater doses of vitamin D than healthy people, possibly because the TB antibiotics breakdown vitamin D.

The third study, just complete, shows that giving a high dose of vitamin D to patients with infectious lung TB can in the early stages of treatment reduce infectiousness to a certain extent. And we’ve also shown that giving that higher dose of vitamin D on top of antibiotic treatment can have wide ranging effects on the immune system. Basically enhancing the ability of the immune system to kill bugs, while at the same time dampening down inflammatory responses which damage the lung.

PORTER : When you talk about high doses of vitamin D are these much more than people would expect to get through normal sun exposure and diet?

MARTINEAU : Yes these are doses that you would attain using vitamin D as a drug. So to give you an example: we use 1,000 units given every two weeks, that compares with say 400 units given daily, which is the recommendation from the government to prevent profound deficiency in the general population. So this is using high dose vitamin D as a drug.

PORTER : So it looks like it helps as a drug, is there evidence to suggest that having sub-optimal doses makes you more prone to these sorts of infections because TB globally is a huge problem?

MARTINEAU : Yes there’s very compelling evidence that that may be the case. This hypothesis was first raised by Professor Peter Davis up at Liverpool who demonstrated in case control studies that low vitamin D levels were found in patients with active TB compared to higher levels in controls. And he hypothesised that what was going on was that patients migrating from areas where TB’s highly prevalent, such as southern Africa or southern Asia, and moving to the UK, became vitamin D deficient as a result of their having much less sun exposure. Those patients had latent TB infection, just as one third of the world’s population does, and after arriving in the UK the lack of sunshine meant that their vitamin D level dropped and their immune response to the TB bug was weakened and therefore the bacteria were able to divide and cause disease.

PORTER : And by latent infection, these are people who’ve got the TB bacterium inside them but it’s not actually causing any disease, it’s just lying dormant?

MARTINEAU : Exactly. I, for example, have latent TB infection as a result of sitting in TB clinics over many years but as you can see I’m a perfectly healthy person.

PORTER : And what mechanism is actually involved, how are vitamin D levels affecting our response to infection, in this case TB?

MARTINEAU : Well the effects of vitamin D on the immune system are legion but to summarise a few. Vitamin D switches on the production of natural antibiotic substances in white blood cells and in the lining of the lung, which can kill the TB bacteria. Vitamin D also down regulates or switches off the production of immune messengers, if you like, which are implicated in lung damage in tuberculosis.

PORTER : So would it be fair to say that the millions of people in the UK who have sub-optimal levels of vitamin D, albeit not frank deficiency, could have weakened immune systems as a result of that?

MARTINEAU : I think that’s a hypothesis that has yet to be proven. And this brings me on to the ongoing series of trials which we have at Barts and the London Medical School, the first a trial in patients with asthma, looking to see whether or not a high dose of vitamin can prevent colds, coughs and exacerbations. A second study in patients with chronic bronchitis, looking at the same outcomes and a third study among people living in sheltered accommodation to see whether vitamin D supplementation can prevent colds and flu.

PORTER : You say these studies are ongoing, obviously we can’t pre-empt what’s going to happen in the results but you started the studies for a reason, is there a suggestion that vitamin D may play an important role in all of those diseases?

MARTINEAU : There is a suggestion. First from the laboratory studies, which I’ve described but also interestingly from clinical trials of vitamin D, which were looking at primary outcomes other than infection. So studies, for example, with vitamin D supplementation for prevention of fractures have shown, as a by product, a secondary outcome, that the patients who received vitamin D in the fracture study had much lower incidence of colds and flu.

GRIFFITHS : Vitamin D has the potential to affect the way that our immune systems function and there’s a theory, a hypothesis, that lack of vitamin D has been responsible or contributed to the increase in allergic disorders like eczema, hay fever and asthma that’s been seen over the last 20 years or so. Now if you have asthma or COPD, that’s chronic obstructive pulmonary disease, used to be called chronic bronchitis, then infections can trigger asthma attacks. So if someone had insufficient levels of vitamin D then they may be less able to fight off these germs and bugs that trigger asthma attacks and exacerbations of COPD.

PORTER : Chris Griffiths professor of primary care at Barts and the London.

Vitamin D’s role in immunity is exciting, but it’s a possible protective effect against cancer that has caught the media’s imagination in recent months. A large European study published earlier this year found that high levels of vitamin D are associated with a lower risk of bowel cancer. Kay-tee Khaw is professor of clinical gerontology at the University of Cambridge and one of the team behind the trial.

KHAW : Well the story about vitamin D and cancer of the colon has been around for several decades. It was noted by many observers, particularly Cedric Garland and his brother in the States, several decades ago that there is a latitude gradient for colorectal cancer. That is countries that are in the more northern areas tend to have higher rates of colon cancer than countries near the equator. Now his idea was that because vitamin D is made in the skin in the presence of sunlight people in northern latitudes have lower levels of vitamin D, compared to people who live in more tropical or equatorial regions and that this might explain why there is such a gradient for bowel cancer. What we did was in a large European study of nearly half a million people, who were healthy initially, we stored blood samples and later on followed up for new cases of colon cancer occurring. We were able to measure the blood samples that we’d taken originally and compare the blood levels of vitamin D in people who developed colon cancer and people who didn’t and we found that there was a strong relationship in that the people who had the highest blood levels of vitamin D had the lowest rates of subsequent colon cancer, compared to people who had the lowest levels. And that was an apparent gradient across the whole range of vitamin D levels.

PORTER : So that confirms what’s already gone before but it doesn’t necessarily mean that the vitamin D is protecting against cancer of the bowel does it?

KHAW : No of course not. There are many possible explanations for this association, including the fact that vitamin D may be just a marker of other factors that may be causal, for example it may be a marker of spending more time in physical activity, which has been related to lower risk of bowel cancer, it may be a marker for certain other dietary patterns that have been implicated in colorectal cancer risk, for example people who have high vitamin D levels may have different patterns of meat intake or dietary fibre intake. So one of the things that we were able to do, because we’d measured many of the other dietary factors and other known risk factors for cancer, was that we were able to control for these but even after controlling for these and including obesity as well the relationship with vitamin D and bowel cancer still held.

PORTER : This may have a sense of deja vu for some people I remember at the beginning of the ’90s there was a lot of observational work suggesting that anti-oxidants were going to be the next great breakthrough, and the subsequent intervention trials proved to be disappointing, particularly protecting against heart disease for instance using supplements like vitamin C and E. Are you more hopeful that D may prove helpful?

KHAW : I think you’re absolutely right about the anti-oxidant supplement trials and I think perhaps the jump to having single supplements from the observational studies was perhaps too large a leap. And it was actually very important to have these trials to demonstrate whether they did or did not have an effect. I think with vitamin D there is much more promise in that there has been a lot of preliminary work suggesting a lot of biological plausibility for vitamin D and a wealth of evidence but clearly we still need the supplement trials.

PORTER : But given that so many people in the UK have lower than ideal levels of vitamin D should we all be taking supplements? If so, at what sort of dose? Professor Nick Bishop

BISHOP : There is a school of thought that says all of us should take vitamin D everyday and if you look at the American Association of Paediatrics guidance they believe that every single human being should take 200 units a day from birth to the day that you’re shuffling off the mortal coil.

PORTER : If I wanted to be scientific about it and wanted to be sure that I needed a vitamin D supplement and managed to persuade my doctor to do a blood test, what sort of levels would I be looking at to know that I was taking an optimal intake?

BISHOP : If you’ve got a level that’s 75 nanomole per litre or over, I think anyone would agree that that is good and you don’t need to take anything more at that stage. If your value is below 25 then I think most people would agree that that is low and you should be having some kind of supplementation. The difficulty is the very large grey area in between 25 to 75 there is at the present time no data on functional outcomes, that is does it do you any harm to have a level between those values. And if you are measured as having a value between 25 and 75 how long does it have to be at that level for? What are the other factors that might exacerbate the effects of vitamin D deficiency? You know for instance if you have a diet that’s very low in calcium would you be at risk of developing complications from having vitamin D deficiency than if you have a diet that’s very rich in calcium? Is it more important when you’re growing quickly? Are there other factors, such as pregnancy, that would make you feel that you needed to put a supplement in place? So all of those factors still are at the present time not properly clarified and established to make very firm recommendations about.

PORTER : While there is still some debate about whether we should all be considering supplements, it is agreed that the following groups are those most likely to benefit:

Women who are pregnant or breastfeeding
Children under five, particularly those who are breastfed
The over 50s
Vegetarians and people who don’t eat oily fish
Anyone who is housebound or who covers up when outside and
Those who are dark-skinned.

The current recommended dose for an adult in the UK is 10 micrograms a day, that’s 400 units. You can get vitamin D in your diet it’s added to some margarines and cereals and good natural sources include oily fish and eggs but most people only get a very small amount this way.

Conventional wisdom has it that during the summer we manufacture enough vitamin D by exposing our face and arms to the sun for just an hour or two across the week. You don’t have to sunbathe, just accumulate 10 15 minutes a day while going about your normal business assuming you are not wearing a sunscreen, or a moisturiser that contains one. But recent research suggests that it may take much more than this to get the sort of levels associated with optimum health.

Easier said than done particularly when we all being encouraged to cover up in the sun because of the risk of skin cancer. So supplements look a sensible way forward but at the moment they are only officially recommended during pregnancy and breastfeeding. Dr Minoo Irani:

IRANI : Do remember it’s just 10% of the body’s vitamin D requirements which we can get from the diet.

PORTER : So even if you eat a vitamin D rich diet oily fish etc. the sort of thing children aren’t going to eat you’re still likely to be deficient?

IRANI : Yes you still require the remaining 90% from sunshine for your body to produce the vitamin D. The current recommendations are that all pregnant and breastfeeding women should receive at least 10 micrograms, which is 400 international units of vitamin D. Especially important is to target those women who are at highest risk of vitamin D deficiency and those would be from ethnic minority groups like the south Asians, the Africans and Caribbeans and the Middle Eastern population.

PORTER : But everybody, irrespective of their ethnic background, should be taking a supplement if they’re pregnant or breastfeeding. Now breastfeeding that might seem strange to some people because it’s supposed to be the ultimate nutrition for a developing baby.

IRANI : Yes we know that breast milk is not all that rich in vitamin D as a nutrient. At the same time I think we need to remember that breast milk is far the best source of nutrition for infants. But yes mothers who are breastfeeding will require that extra vitamin D to produce that extra calcium in the breast milk to be able to pass on to the infant, along with the vitamin D. The woman requires the vitamin D to produce high quality breast milk and herself to make the stores of vitamin D in the body. The baby is also supplemented at the same time to ensure that the baby is not deficient in vitamin D.

PORTER : And the reason why why formula fed babies are okay is because we artificially reinforce formula milks?

IRANI : Formula milk is fortified in this country yes.

PORTER : Now it’s recommended but do we know how many parents or children are taking it?

IRANI : I think few are taking it and that is a reality.

PORTER : And I think very few mums are actually told by their midwife or doctor that they should be on these drops do you think that’s the case?

IRANI : I think that’s true and we need an awareness campaign and we have been doing it nationally and locally to increase the awareness of the public about the importance of vitamin D supplements. The other point is that over a period of time the medical profession have become less aware of the importance of vitamin D, especially for pregnant and breastfeeding women and children.

PORTER : The Food Standards Agency also suggest that vitamin D supplements should be considered by older people who spend a lot time indoors and therefore tend to have very low levels. Professor Kay-tee Khaw has looked at the benefits.

KHAW : I think the controversy is what is an optimum level of vitamin D. We were particularly interested in investigating this, which is why we did a randomised trial about 10 years ago in giving vitamin D supplement to see whether in healthy normal older people we could prevent fractures.

PORTER : And what did you find?

KHAW : Well in our trial we found that after five years of a quite a low dose supplement it was 100,000 units once every four months, we found a 22% reduction in fractures, which was quite substantial, considering it was not a very big dose of vitamin D. Now the difficulty with just this single trial that we published is that not all trials that have used vitamin D supplementation have shown a benefit.

PORTER : But if I’m listening as an elderly person living in the UK now should I be considering supplementation for my bones, I mean is there a downside?

KHAW : The big concern and why people are so worried about recommending vitamin D supplementation to all old or all people in the population is that at very, very high levels, blood levels, of vitamin D we can get toxicity with things like renal stones or nausea and vomiting. I think what we can safely say is that in northern hemisphere most people in this country we are nowhere near toxic levels, mainly because most old people first of all don’t get out in the sunlight and when we do get out in the sunlight we don’t make vitamin D as well as younger people.

PORTER : So the trust would probably be for them that even taking supplements they’re unlikely even to get to the optimum level?

KHAW : Yes. I think if most people take a 400 international unit or 1,000 international unit the trials that have been done, that we’ve done, show that their blood levels go up to about 50-60, high levels perhaps 80 but not much beyond that. So I think we can certainly say it’s safe to take a supplement of 1,000 international units a day and probably will get people up to an optimum level.

WARRELL : You use your hands constantly and within a couple of weeks, two or three weeks, of taking those tablets the pain in my knuckles almost completely disappeared. Never would I ever have thought that deficiency in a vitamin could cause so much pain.


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