Multiple Sclerosis – the developing link with Vitamin D

The 19th Century was the real heyday of discovery when it came to the enigmatic role that vital amines (or vitamins as they came to be known) play in human physiology. That our bodies could be so dependent on minute quantities of these mysterious substances was demonstrated profoundly in the cure of the dreaded disease of scurvy, by the simple provision of limes to sailors. The prevention of beriberi, rickets and other diseases of deficiency soon followed, and in the early 20th century all the scientists had left to do was to identify and purify the dietary compounds responsible.

We are never likely to cure a vitamin-related disease in one fell swoop in quite the same way again, but there is still much to be learnt about the role they play, and the possibility that a relative deficiency in a single vitamin might influence our risk of developing a particular disease. High on that list is multiple sclerosis (MS), a debilitating disease of the nervous system, and its relationship with Vitamin D. Although we do not know the cause of MS, we can be sure that it is not simply a matter of deficiency – many people have low Vitamin D levels and do not develop MS, while many of those who do develop it will have normal levels of the vitamin. Genetic factors and other environmental triggers will certainly play their part. The question is – does a low level of Vitamin D make you more susceptible?

Well, there is some compelling circumstantial evidence. One of the most striking reasons to think about Vitamin D in particular is the unusual geographical incidence of the disease. This is beautifully demonstrated on this map, based on WHO data. Whatever explanation we come up with for MS, it has to account for the remarkable predilection that the condition has for increasing latitude away from the equator – something that also makes it a pressing issue in the northern climes of the United Kingdom. That sunshine is our most potent source of Vitamin D is something I have already commented on in this blog, and this is clearly a commodity the equator has in abundance compared with the poles. There is also evidence of an association between low blood levels of Vitamin D and the development of MS, and only last week, new research was published from Oxford which suggested that at least some of the genetic link could be related to problems with Vitamin D.

The Oxford study was clever in its approach. They took about 1500 children with MS and looked at the genetics of their parents, to see if they were carriers for a genetic defect known to be linked to Vitamin D deficiency. If a child inherits two copies of the gene (one from each parent) then they develop a congenital form of rickets due to severe Vitamin D deficiency, but being a carrier for the genetic defect is not thought to be a problem. They discovered that of the 3000 parents, 35 of them were carriers for the gene. In itself that is not too remarkable. That means 2965 parents did not have the gene and yet had a child who developed MS – hardly evidence of a strong genetic cause. What was interesting, though, is that in all 35 cases the affected child inherited the genetic defect. Left to chance you would expect only 50% of the children to have inherited the gene – as the researchers say, it is like tossing a coin 35 times and getting heads every single time. Interesting indeed!

The problem is that all this evidence, good as it is, is circumstantial – there is no proof of cause and effect. It is rather like finding the candlestick that killed Colonel Mustard in the library with Miss Scarlett’s fingerprints on it – good, but not quite good enough to make a conviction – maybe she just liked polishing candlesticks? What we want to know is this: Would taking Vitamin D supplements help to prevent MS, or help avoid relapses in people who already have MS? To answer those questions we need a large, randomised study where thousands of people are given either the vitamin or placebo, and a second, similar study in people who already have MS.

The problems are these: The first study has to be large, and large means expensive. Vitamin D is cheap and generically available which means drug companies will not be interested in making an investment, leaving the cost to fall on research charities and governments in these austere times. The second study can be smaller, since episodes of relapse in people who have MS will be much more frequent than new episodes of MS in the general population, but how do you stop people with MS from taking Vitamin D on their own initiative? The placebo arm of the study will not be much of a placebo if everyone is also obtaining the vitamin from their local pharmacist. If I had MS would I take it? Well, yes. On the grounds that Vitamin D supplements (at normal levels) are safe and probably a good thing anyway, I think I could be convinced on even circumstantial evidence.

Forgotten where you put the vitamin pills? Don’t worry too much just yet!

Alzheimer’s Disease is a serious problem in the UK. Devastating for sufferers and family alike, it is destined to place an ever-increasing financial burden on our ailing state, as our ageing population inevitably leads to more elderly people succumbing to this most debilitating illness. As our society has at last started to be concerned about this historically neglected condition, a headline such as: “A 10p Vitamin B pill a day from middle age may ward off Alzheimer’s” on the front page of The Daily Mail this morning is bound to catch the eye. It was also reported by both The Telegraph and The Independent  if they are more your cup of tea, with the former actually bolder in its claims than The Mail, changing the word ‘may’ for the rather more definitive ‘can’.

As ever with these claims, we have to make the often disappointing journey beyond the headlines. Whenever I read about new health claims my first thought is: ‘Will it do any harm?’, followed by: ‘Will it do any good?’, and finally: ‘Is it worth the effort?’

So what of harm? Well the proposed treatment is with vitamins – doesn’t sound too bad does it? Probably not – except these are high dose vitamins. Very high dose in fact. The 10p pill in question involves B vitamins and folic acid, some in  doses of up to fifteen times the Recommended Daily Amount (RDA). Now that’s not necessarily harmful – the RDA is a minimum recommendation to ensure sufficient intake of a vitamin, not a maximum safe limit. Indeed, some vitamins seem very innocuous in large amounts (Vitamin C seems to be a mild laxative, but not much else) but we cannot assume they are all harmless – Vitamin A, for instance, is highly toxic to the liver in over-dose; the researchers in this study concede that high dose Vitamin B12 might accelerate cancer; while Vitamin B6 can  cause nerve damage (although this is only proven at doses 25 times higher still than in this study). So I don’t want to jump on this bandwagon without at least seeing some data on harms. The newspapers make no comment on whether or not this data is available, and unfortunately I don’t have access to the original paper, so for the moment I will have to be content with a word of caution.

On the positive, does it work? Well the research sounds promising – it reduced shrinkage of the brain (seen on brain scans) over a 2 year period by an average of 30%. We know that there is a correlation between brain shrinkage and Alzheimer’s so this is likely to be beneficial. What does a 30% reduction mean though? Well, it does not mean that  those who took the vitamins ended up with brains 30% larger than those who did not take them. It is the shrinkage that was reduced. This means, for instance, that if the brains in the placebo group shrank by 10% in the 2 year period, then those in the Vitamin group would have shrunk by 7% – or would have been 3% larger – which might still be significant, but does not sound quite so impressive.

The next question we need to ask is, does the reduction in brain shrinkage seen in this study mean a reduction in the development of Alzheimer’s? Well there is good reason to think it does, but we cannot assume so. The problem with brain shrinkage is that it is a proxy marker for Alzheimer’s. A proxy marker is something that is associated with a disease, but is not the disease itself. Put it another way – I don’t care what size my brain is, I want to know how well it is going to work. It may be that the reduction in brain shrinkage seen in this study is nothing to do with Alzheimer’s but due to some other cause. For instance, were high dose vitamins to actually damage brain cells in a way that made them swell, there would be a reduction of brain shrinkage due to the vitamins causing a problem in the patients taking them rather than preventing one. I have no reason to think this might be the case, but we cannot assume that the effects seen in this study are due to a delay in the development of Alzheimer’s Disease on the basis of scan results alone.

A second possibility is that the effect brain shrinkage is due to a delay in the onset of Alzheimer’s, but to an extent that is not clinically relevant. This is an important distinction. There may be a statistically proven delay in the onset of Alzheimer’s – but if it the onset of the disease by only a week, would it be worth taking vitamins every day for that? If the reduction in brain shrinkage means that I am slightly better at remembering a list of names and addresses, but still have trouble knowing what year it is, or how to use the bathroom, what use is that to me? There is some evidence for a clinically useful outcome from the study – a subset of those who were tested (those with a high blood level of a chemical called homocysteine) performed better in a word recall test. However, this effect was not seen in other patients in the trial, and it was not the primary purpose of the study to test memory. For this reason the scientists behind the study are launching a new, larger, investigation, which will look at more clinically relevant outcomes. So the study is promising, there is good reason to think that it may lead to a useful strategy for preventing Alzheimer’s, but it is far from proven.

What is frustrating is the tendency for the scientists behind studies like this to get carried away with their own enthusiasm, and make claims that are beyond the evidence in their research. In this case, Dr Celeste de Jager of Oxford University, who led the trial, is quoted as saying that ‘the trial had “definitively” shown that the vitamins were a good way of preventing mental decline’. If this is an accurate quote and not a media distortion, then it is distinctly misleading.

So, is it worth the effort? Well, if it was the simple matter of taking standard doses of a vitamin tablet then it might well be worth it – I would have no concerns about harms, and it might just help – so why not? However, I would need a bit more persuading before taking the very high doses in this study – and there is no evidence that standard doses will make any difference at all, so for the moment I won’t be recommending that anyone heads for the health food shop just yet. Let’s wait for more research, and – no doubt – another eye-catching headline!

 

The Sunshine Vitamin

I was fortunate enough over Easter to be able to spend three weeks in Australia. I’m sure I’m not the only one who spends much of their time abroad noticing every tiny difference to life at home – yes the water really does flow anticlockwise down the plughole! – perhaps not everyone, though, would be quite so interested in the finer details on the side of a packet of Kellogg’s corn flakes. It might seem a bit sad to find my inspiration from a table marked Nutrition Information, but it does tell an interesting story if you care to look.

My UK packet of Corn Flakes proudly boasts to be The Sunshine Breakfast – a source of Vitamin D, the only vitamin that is made in our skin by the action of sunlight. It is not an idle boast, as there is only one other packet of cereal among the extensive range in my kitchen cupboard that contains Vitamin D, and that is also made by Kellogg’s (it’s Bran Flakes and, interestingly, it contains the same amount of Vitamin D as Corn Flakes, but makes no comment about this other than in the small print). It seems that Kellogg’s are the only cereal company to have been keeping an eye on the medical journals – because Vitamin D is the in thing in medical research at the moment.

When the British Medical Journal arrives on my doorstep every week, there is at least a 50/50 chance that there will be an article on Vitamin D. We’ve  known since the 1920’s how important Vitamin D is in bone formation – it is the key vitamin in the metabolism of calcium and so vital for making good bones – but we are only just learning about what else it might do. People with adequate Vitamin D levels live longer than those without – we don’t know why this might be, but it seems to be a good thing to have enough of it. There are suggestions that it may reduce the risk of cancer, and that deficiency could be linked to the development of multiple sclerosis. It may have a role in our immune system (could it explain part of the reason why influenza is more common in the winter when Vitamin D levels are lower?) and it seems that deficiency is linked with a higher risk of heart disease and circulatory problems. Much of this is uncertain, but one thing is clear – and that is that many of us in the United Kingdom are short of this important vitamin – perhaps as many as 2 out of every 3 people aged over 65, a fair few younger people and almost everyone in a nursing home are deficient in Vitamin D.

So what about Australia? Well Kellogg’s clearly think the Sunshine Breakfast is not such a marketing winner Down Under – no bold claims on the packet, and no Vitamin D in the packet. Who can blame them? Sunshine is not exactly in short supply in that part of the world. But maybe they need it more than they think? The problem in this modern world is that much medical advice is mutually exclusive. For instance, if you want strong bones then you should drink plenty of milk as it’s the best source of calcium, but if you want a healthy heart then you need to avoid dairy and all its bad cholesterol – how can you do both? And so with sunshine. To avoid skin cancer it’s so important to cover up and cream up, but is this leading to a generation growing up without enough Vitamin D? Nowhere has this message got through more effectively than the melanoma centre of the world – Australia – and what an important public health message to get through!

So what should we advise our Antipodean friends? Well they probably won’t solve this quandary by importing British Corn Flakes. Noble as it is to put Vitamin D into their cereals, the amount of Vitamin D in a typical bowl of Corn Flakes is probably the equivalent of only a few seconds of exposure to Noon-Time sun. The answer, as it so often is, has to be moderation. Get some exposure to the sun every day that you can – about 15 minutes of full sun is plenty to get a good daily top-up if you have your arms and legs on show – but cover or cream up after that, and don’t ever get burnt. And in the UK now is the time to get going – our British sun is too weak from October to April to do much good, so we have to make the most of our summer!