Vitamin D: Shedding light on diabetes, MS and cancer

As we recently reported here on Naked Scientists, fifteen new species were recently discovered on the seabed of the Southern Ocean in Antarctica. And one of them, nicknamed the Hoff crab because it had a hairy chest like David Hasselhoff, even went viral making headline news around the world.

The new species were all found on the East Scotia Ridge, an area on the ocean floor that is littered with hydrothermal vents.

The UK-led project involved universities, the National Oceanography Centre and the British Antarctic Survey, as well as a collaboration with Woods Hole

Oceanography Centre in the United States. Planet Earth podcast presenter

has been speaking to two of the team - marine biologist Dr Katrin Linse* and

geologist Dr Ali Graham - both from the British Antarctic Survey...

Katrin -   What I have brought out today are samples of the animals we collected.  For example, the 'hoff crab'.

Sue -   That could easily fit in the palm of my hand.  They're white and pale, presumably because there's no light down there.

Katrin -   Yeah.  This is a small female.  She is about 6 cm tall, the large males were up to 12 cms tall and they had big claws, but also the females you can clearly see a really hairy chest and along the bottom of their legs.

Sue -   So it's not just the males then that have the hairy chests it's the females too?

Katrin -   No, the females have it too.

Sue -   Ali, tell me a little bit about where these creatures were found because they're beside some very unusual structures called hydrothermal vents.

Ali -   The East Scotia Ridge itself is an area where the seafloor - the lithosphere - which is the hard outer shell of the earth is actually extending and stretching and where this happens, magma from the mantel actually up wells and along the ridge itself you get volcanic activity.  And because the crust has a lot of water in it that water is heated geothermally, like geysers, and eventually through fissures and through fractures and faults in the crust, this hot water finds its way out and it finds its way out through vents.

Sue -   And these vents look almost like a termites nest - tall tapering structures but with these enormous plumes of smoke coming out which, I assume, are sulphurous.

Ali -   Exactly, that's a very good description.  They are tall conical chimneys formed of precipitates that come out of the water, emerging from the ocean floor.

Sue -   You've got a couple of other little jars here.

Katrin -   The piece I personally love the most is in this large top bag, because here, what you actually now see emerging is the top of the chimney and in the top here you see a hole of about 4mm, this is where the smoky hot water would come out at temperatures of up to 380 degrees.

Sue -   Wow! So that's the top of a hydrothermal vent?

Katrin -   Yes.  Next to it are the barnacles and then all the other creatures.

Sue -   Ali, you were also involved as a geologist in mapping the ocean floor itself.

Ali -   That's right, yes.  Over the past few years we've had two research trips to the East Scotia Ridge.  The first one we aimed to actually map out the regional sea floor just using sonar from the underside of our ship.  On our second, we took the remotely operated vehicle, Isis, down to areas where we knew there were vents and we did even more detailed mapping of the sea floor with a smaller sonar.

Sue -   What resolution then did you produce?

Ali -   Initially our maps were, maybe, down to say a 20 metre size, so we could see things that were larger than around 20 metres on the sea floor.

Sue -   But not necessarily a hydrothermal vent.

Ali -   Well, the vents themselves were only less than a metre in width so we would have totally missed them even from our ship mapping, the first initial mapping we did.  The second trip we could actually make maps down to things that were almost the size of a shoebox.  So we actually started picking up blips on our map and when we looked at them in detail in three dimensions we could see these were the actual individual chimneys themselves, so the geophysics actually directed us straight to where these vents were.

Sue -   It's an obvious question.  For scientists it's like, well, new species, wow, but is it important on the grand scheme of things?

Katrin -   We know from some Antarctic deep-water species that they seem to be the origin of life of the deep-sea fauna globally.  We don't know this about the hydrothermal vents.  We know that in the last 30 million years the Antarctic marine fauna was almost buried off from the non-Antarctic through the cold water and the circum-Antarctic current; these are specially adapted animals.  We have lots of hydrothermal vents north of the Antarctic, these were first found in the Antarctic.  How do our species link in to the global ones?  Are they the ancestors of everything or not?  We don't know.  And then the big question is, where did life on Earth originate at the start, could it have been in the deep waters in very - nowadays - toxic, sulphuric environments.  This is why this research is so exciting and important.

Chris -   There is confusing and contradictory evidence about the link between vitamin D and cancer.  Scientists now need to find out what the precise nature of that link is.  Professor Sir John Burn is a Clinical Geneticist in Newcastle University and for the last 20 years, he's been leading an international consortium looking at cancer prevention in groups of people with a genetic predisposition to develop bowel cancers.  Last year, they confirmed that aspirin can protect these individuals.  Now they're turning their attention to vitamin D.  Hello, John.  So, who are these patients that you're looking at?

John -   I've been working for 20 years with people with hereditary predisposition to bowel cancer in particular. They have a problem with genes called mismatch repair genes.  They cannot fix spelling mistakes in their DNA.

If they inherit that gene they have about a 50% chance of developing cancer, mainly of the bowel and also of the womb, and obviously, they're very keen to help with attempts to find ways to reduce the risk of cancer which is of relevance to them and their families.  But also, it's relevant to the rest of us because about 1 in 20 of us will develop a colon cancer in our lifetime and about a 6th of those have a problem with the mismatch repair genes.  It's just that they acquire it during their lifetime rather it being an inherited problem. 

These [people] are a model group in which we can study interventions that you couldn't really test in a rigorous way in the general population, because cancer happens so slowly in general population.  You'd have to do vast studies over decades.  And as you say, what we showed with the aspirin study, where we gave people aspirin for two years, was that after five years we had reduced their bowel cancer risk by over 60%, and that was on top of the benefits of giving regular colonoscopies and removing polyps.  

That was a huge boost for our idea of these genetically targeted trials.  So in the next five years or so, in addition to comparing different doses of aspirin to see if we can get away with less, we'd also like to see if we can give people vitamin D and whether that would give us the rigorous randomised control trial data which would justify us giving these patients and their families vitamin D on a regular basis.

Chris -   Before we dwell on the vitamin D, could we just have a look at what you think the mechanism is for why aspirin protected those people because that's a dramatic difference - a 60% reduction?

John -   It is and in fact, that evidence has been building over 25 years.  In fact, that story is very parallel to vitamin D in a way because it's the observational studies of people who were using a lot of aspirin-like drugs that demonstrated that there was a massive effect, but we couldn't get randomised data until we did our study which has really nailed it.  

The answer is that aspirin again, somewhat like vitamin D, is probably an essential nutrient, something you need from the outside, and it has a wide range of effects.  One of them is to promote programmed cell death or apoptosis, again [this is] like vitamin D.  Plants make salicylate, which is the core of aspirin, in order to trigger programmed cell death when they develop infections.  It's their way of defending themselves.

Interestingly, up until 100 years ago, we would have had quite a lot of salicylate in our diet because of eating wilder foods.  Now that we grow everything under control, they don't get exposed to infection, so the salicylate never forms.

There are reasons we have seen in the laboratory, lots of evidence in the lab that says aspirin has a number of other effects particularly blocking inflammation which is a part of the cancer process.  So that might also be part of it.

Chris -   And what sort of dose of the aspirin do you need in order to get these effects?  Would the same doses that are effective in preventing or reducing the risk of heart attacks and strokes also be effective in the prevention of bowel cancer, or do you need a bigger dose?

John -   That's the $64,000 question.  We used two aspirins a day and got this big effect.  Peter Rothwell did some wonderful studies over the last few years, looking at people who took part in the very early aspirin studies back in the '80s and found that those people had fewer cancers 10 years later when he checked them on the cancer registries.

Just last week, I was on the BBC talking with Professor Ray from St. Georges who had not found an effect.  He had looked by meta analysis, which we're going to talk about in a moment, by pooling all the data on aspirin and cancer, and heart attacks to see whether people at low risk should take it.  He didn't see a benefit, but that was because those studies only followed people for 6 years.  The problem with these sorts of studies is you have to follow them for a very long time to see the benefit.  In our high risk patients, they developed cancer much faster.  That's why we were able to see the effect in only 5 years, but in the general population, you'd have to wait 10 years to see the benefit. 

That, of course, has general relevance to this evening's conversation because when you do preventive work, you might have to wait a decade to see the benefit.  You can't actually see the people who didn't get the disease.  They never knew they were going to get it and they were "saved", so to speak.  So all we ever see are the side effects. 

A lot of the preoccupation has to be with, "Is it safe?"  And I was interested in George's observation that vitamin D does seem to be an extremely safe supplement.  The body can handle it extremely well.  So although there is a little bit of evidence to suggest people on very high dose of vitamin D might have a slightly increased risk of cancer, certainly at any sensible dose, the evidence does seem to be building that vitamin D is very clearly beneficial.

Chris -   And how is it first spotted that vitamin D does seem to have this protective effect in bowel cancer?

John -   People have been looking for clues to explain the strange distribution of cancer for many years.

We should at this point by way just say, a word for Casimir Funk who, 100 years ago, actually coined the term 'vitamins' or vital amines he derived it from, when he discovered thiamine.  And I learned that from reading Bill Bryson by the way!  

It's interesting to realise that up until 100 years ago, we didn't realise that it was just not the fact that you ate a lot of food.  It was what was in the food that mattered.  Of course, we knew about scurvy long before, but it was only generalised in the 20th century that there are these series of elements that we needed that would be beneficial to us.  

How vitamin D affects cancer?  Again, I mentioned earlier about programmed cell death.  Vitamin D might well have a key part to play there.  But the point is that vitamin D is a crucial component of our body.  It's not truly a vitamin, as George said earlier, because we do manufacture it or in fact, we should manufacture it from exposure to light.  

It gets into the cells where it meets the vitamin D receptor and it has an impact on a whole range of genetic mechanisms and cellular mechanisms.  So it's not at all surprising that if you're deficient in it, then you might see all manner of side effects or effects on the body in the same ways if you take away vitamin C, people's teeth fall out and all sorts of things happen.  

These chemicals are an integral part of our body which we expect to be there and when they're missing, all sorts of things fall apart, the immune system being one of the most obvious ones.  There's lots of interest in the fact that vitamin D deficiency might be a factor in people developing infections in the winter, for example.  So, you can see it's a story building that vitamin D could well be playing in a whole series of different scenarios where it could have an impact on our ability to either prevent cancer or destroy cancer.

Chris -   You obviously don't know the answer yet, but what are you now setting up to try to find out whether vitamin D is going to make a difference?

John -   Essentially, what we now know from the beautiful study of two colleagues during the meta analysis last year is that there's about 5% cut in cancer per 100 units per litre of vitamin D in your blood stream.  So we can work with that and do power analyses, and that will tell us how many thousand people we need to treat for how many years.  We're working on that at the moment.  But with the aspirin dose-finding study, we're going to be looking for 3,000 gene carriers, we'll supplement them and then follow them for 5 to 10 years.  That is the only way we'll absolutely nail to the ground whether vitamin D can prevent cancer at a sufficient level to justify supplementing the population.  But in the meantime, I think clearly there's a strong evidence for self-medication for those who - certainly those who are not exposed to sun and those with darker skin who are living now a long way from the equator.

John - If you take very large volumes or quantities of vitamin D, you'll get hypercalcaemia and that can have adverse effects and indeed can cause kidney failure if you really overdo it. But as George was saying, in fact, it's very hard to get anywhere near those levels. You have to really work quite hard at it and for the general population, the sort of supplements that we will get from our diet and from adding a tablet of vitamin D to our routine is not going to take you anywhere near that level.

George:: I agree. The safety here has been demonstrated in volunteers. So, the institute of medicine's recommendation was up to 4,000 units a day for adults. The safety factor is huge so that volunteers have been given over 100,000 units a day when it's been gradually increased over time, which is you know, let's say 25 times the Institute of medicine maximum recommendation and no ill-effects were seen. So if you increase the amount of water you took a day by 25-fold, then it would be fatal, but you can increase the amount of vitamin D slowly and in fact, no side effects have been found. I'm not recommending people to take that, but there's a big safety factor.

Well I think there are a variety of different kinds of light boxes, but I think just light unless it's got an awful lot of radiation, it's not going to generate any vitamin D so that I mean, people can go to - you know, they go to tanning salons and so forth and that will in fact generate vitamin D, but the downside of this of course is it may have the consequences of being exposed to sun. So, the way around the dilemma, it seems to be, is if you want to increase your vitamin D content, then just simply take it by mouth as a regular vitamin D3.

I think that everything needs to be considered in a balance and there is a very good reason why sunblocks are recommended but common sense should be applied in using those as well.

I don't put the sunblock on before I go outside but I go first outside and only after being there for 10 or 15 minutes I apply the sunblock. I allow both some vitamin D synthesis in the skin as well as protecting myself from any excess in sunlight.

George - Well chemically, it's a very simple molecule and it's identical really to what you make in your skin, so I don't think there's any reason to think that it would be any different. But I think the issue of supplementing the population is awkward. Despite the fact there's a control study showing that folate prevents neural tube defects, it's not added to the food and one can only compare what happened in America now. I'm a Canadian, but I'd have to say, the way they dealt with this was the way it probably should've been done which is that they supplemented their food within a couple of years that the results coming available and they were able to show that as much as 80% of neural tube defects were prevented. Here, I think these issues have been more controversial and just the fact that people want to put supplements then doesn't mean that it's bad. There are lots of examples where supplementation is very useful. Iodine and salt is a good example. No one argues about that and I think in a few years, nobody is going to be arguing about this as well.