Saturday, 22 March 2014

MS is preventable: can we ignore the evidence?

Can vitamin D supplements prevent MS? I wish I knew the answer. #MSBlog #MSResearch
"Mouse Doctor posted on the observation that the latitudinal gradient of MS incidence and prevalence has disappeared in Norway. Why is this Important? Norway was the one country that was the exception to the rule. Exceptions to the rule are very important they can slay hypotheses unless they can be explained. A previous meta-analysis showed that MS prevalence actually decreased as you went further north in Norway. "
"Why the latitude reversal? The reversal in MS prevalence in Norway has been explained on dietary factors. Norwegians in the north of the country eat more fish, in particular fatty fish, and have higher vitamin D levels (see figure below). This observation has been used by me and others to support the vD MS hypothesis; i.e. higher levels vD protect you from getting MS. "

"The loss of this MS gradient suggests the underlying environmental factors, which underpin the causal pathway of MS, are changing. Unfortunately for Norwegians this appears to be for the worst as the incidence and prevalence of MS is increasing. If the incidence and prevalence can Increase due to environmental changes , surely we can decrease this trend by reversing these environmental changes. This would also prove that MS can be prevented. What are these factors? If they are linked to vD then something can be done about it."

"Sun exposure. It is well known that over the last 15-20 years dermatologists and the cosmetic industry have massively increased our consumption of sun blockers. Dermatologists tell us to avoid sunburn to prevent skin cancer and the cosmetic industry to prevent  sun damage that is a major cause of skin aging. Could sun blockers in female cosmetics underlie the increasing sex ratio in women? The scary for me is the targeting and increasing consumption of cosmetics with sub blockers by men, in particular the younger generation. Almost all of the new male cosmetics now include sun blockers badged as anti-aging agents. If the cosmetics industry, with their ubiquitous use of sun blockers, is partly responsible for the rising incidence of MS in woman, I predict that the ratio will normalise as males start using daily sun blockers. "

"Outdoor activities. Other behavioural changes has been the shift from outdoor activities to indoor activities. Children and teenagers now spend much less time in the sun. Why? This is the era of facebook and gaming. Young girls spend large amounts of time on social networks and boys playing computer games. There are several studies from the past that have demonstrated that outdoor activities in childhood protect against MS; reversing this trend is very worrying."
"Fish consumption. It is well known that fish consumption worldwide is going down. This is based on economic factors, as we deplete fish stocks prices have risen and consumption has dropped. We are also increasingly eating farmed fish which has about a third of the vD levels of wild fish; wild fish have higher vD levels because of their diet is higher in phytoplankton which provides the vD."
"Pollution and weather. Atmospheric pollution and cloud cover is another issue that is probably less of a problem in Norway. In heavily polluted areas of the world air pollution exacerbates vD deficiency as it acts a ultraviolet B filter."
"Cultural changes. I have mentioned before that covering up for cultural reasons is a massive problem for woman. Whether or not covering up is for religious or other cultural reasons it contributes to very low vD levels in some parts of the world that may underlie the increasing incidence of MS in woman."
"What can be done about the vD problem? You tell me."
"We now promote physiological vD supplementation in all children and relatives of MSers. Despite this we have found that adherenece to our advice is poor. Therefore we have started Digesting Science. This is a course to teach children of MSers about MS and the link between low vD and MS. The idea is to get children to be adherent to their vD supplementation regimen via education. Only one of the stations on our Digesting Science course is dedicated to vitamin D education the other stations teach children about MS and its impact on physical, emotional and cognitive functioning. Our pilots that ran last year went very well and we are now trying to expand the programme in the UK and want it to go global. Any one keen to help? As with all public health programmes we are trying to get data to show it works. We have a grant being assessed at present to do just this. Let's hope it gets funded."
"For those of you interested in the changing epidemiology of MS the following review is interesting as it discusses the changing latitudinal gradients across the world, the increasing incidence of MS and the changing sex ratio. We need to take these trends seriously; they are real and can be explained and tell us that MS is a preventable disease. Why are we not acting on this?"

The uneven distribution of MS across Populations can be attributed to differences in genes and the environment and Their Interaction. Prevalence and incidence surveys Could be affected by inaccuracy of diagnosis and ascertainment, and prevalence Also depends on survival. These sources of error might play a part in the Geographical and temporal variations. Our literature search and meta-regression analyzes indicated an almost universal Increase in prevalence and incidence of MS over time ; They challenge the well accepted theory of a latitudinal gradient of incidence of MS in Europe and North America, while this gradient is still apparent for Australia and New Zealand, and suggest a general, although not ubiquitous, Increase in incidence of MS in females . The latter observation should prompt epidemiological studies that focus on changes in lifestyle in females . New insights into gene-environment and gene-gene interactions complicate interpretations of demographic epidemiology and have made ​​obsolete the idea of simple associations Between causative genes or the environment and MS.

28 comments:

  1. I agree about Vitamin D and think the level should be checked as a matter of routine when ms is diagnosed or suspected. I asked for mine to be checked years ago and as a result started to take a supplement. Unfortunately this was only 10 iu. Following current advice, I increased this to 5000 iu daily two weeks ago. I now sleep very well too!

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  2. Very interesting post, Don Giovannoni . You’re probably thinking my compliment is full of subtext and sarcasm, but you’re wrong; the issues you’ve flagged are of the utmost importance. You are advocating better living and that is something Britain fails to take seriously. Heck, even our Chancellor poses with burger and fries to make himself more relatable to the mindless troglodytes of Britain.

    I read that our proliferating junk food diets are leading to premature puberty in kids as young as eight. Added with sheltered lifestyles, overworked parents fearful of sensational misreporting by the tabloid press regarding paedophiles looking to abuse children that play outdoors, and a general lackadaisical malaise of exercising, what you have is a ticking time bomb that will cause insurmountable future problems.

    I agree that MS is likely an avoidable malady, as are a host of other diseases. Vitamin D, a product we can attain freely and artificially manufacture at low cost, remains overlooked by successive health policy overlords.

    Although we disagree in the large, I’m totally with you on this one, Don Giovannoni . The problem is that you are not powerful as the fast food giants, social media billionaires, and religious zealots fighting for the rights of women covering up. You ain’t got the Government’s ear like they do.

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    1. Vitamin D production in the skin is blind to vanity (staying young, staying pale), preventing skin cancer, playing indoors, covering up for religious reasons, or air pollution. I am simply saying we should recognise the problem, adopt the science on vD biology and get the government to raise the recommended daily allowance (RDA) of vD and/or allow the food industry to address the problem with additives. Can you imagine how the next generation of MSers will view us when they find out in 50 years time that their disease could have been prevented by a simple public health policy that should have been be taken today?

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    2. There is little point in the UK on using sunshine to keep your vitamin d levels up as we are still in the vitamin d winter that started last September and vitamin d has a half life in the body of 20 to 30 days. Use supplements at a suitable level.

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    3. The Norwegian study gives no proof that vitamin D is involved in MS and actually goes against it. Given that there a number of large RCTs that are negative for vitamin D why don't you prove some causality before giving recommendations?

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    4. If the influence of vitamin D is in utero, have the right RCT been done

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    5. Re: "..why don't you prove some causality before giving recommendations?"

      My vD recommendations to people with MS are based on bone health and not disease modification. I think most will accept that MSers have a high incidence of osteopaenia, osteoporosis and bone fractures. Most of us in the field accept low vD levels causes, or contributes to the cause, of thin bones. If you want to be laggard be my guest.

      The higher RDA is based on the vitamin D council's recommendation, not my own. The vD Council have been lobbying for years to get the current RDA increased. The current 400IU per day RDA that is based on rickets prevention from the cod liver oil era. The sad thing is that rickets has returned and is now endemic in many European countries, including Norway (http://www.ncbi.nlm.nih.gov/pubmed/10327858). Why?

      As far as prevention goes the community has been trying for years to get funding to do the trial. Unfortunately, their requests have fallen on deaf ears. I agree we need a trial, but that is easier said than done. I attended a task force meeting 2 years ago on this topic and there was no consensus on the best trial to test whether or not vD supplementation could prevent MS and other autoimmune diseases. May be in my lifetime a trial will be started; it will take 20-30 years to read-out. I may not be around to when the results become apparent.

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    6. There are no RCTs for vitamin d, an RCT requires control over the dose, this is easy for drugs because there is only one source that you control. With vitamin d you are not in control because there is food and there is the sun. These other sources and possibly differences in efficiency in production and consumption create a wide distribution of 25(OH)D level for a given supplement level. See figure 2 in Anticancer Res. 2011 Feb;31(2):607-11. "Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention." Garland CF, French CB, Baggerly LL, Heaney RP. This shows that although a daily intake of 400IU raises the mean 25(OH) by 4ng/ml the 25(OH)D ranges of the two arms completely overlap. You therefore will not detect an effect. To see an effect would require the 25(OH)D range of the treatment arm to be significantly modified, say 10,000IU a day. NB from work on muscle function there may be differences in behaviour between D2 and D3.

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  3. There is no evidence that Vitamin D is toxic even at 20,000 IU/day which is what your body produces from adequate exposure from sunlight. When I had a ADEM attack 4 yes ago my vitamin D level was zero. I started taking 40kiu/day to get my levels up and am at 20kiu/day to maintain this level. Now after being dxed with ms I am on Copaxone and Vitamin D. I imagine MS could be prevented if the Vitamin D levels were raised to realistic values and the DMD'S may be more effective. The current vitamin D recommendations are rediculous:

    http://ajcn.nutrition.org/content/69/5/842.full

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    1. or suggested levels of supplementation please read
      http://multiple-sclerosis-research.blogspot.co.uk/2014/01/clinic-speak-vitamin-d-levels-as.html

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  4. Prof G, I'd appreciate your comments on this http://www.ncbi.nlm.nih.gov/pubmed/24119980

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    1. Re: "Prof G, I'd appreciate your comments on this http://www.ncbi.nlm.nih.gov/pubmed/24119980"

      This was a meta-analysis of studies in a relatively elderly general population with no risk factors of osteoporosis. They concludes "continuing widespread use of vitamin D for osteoporosis prevention in community-dwelling adults without specific risk factors for vitamin D deficiency seems to be inappropriate". This does not apply to MSers as MS is a well-defined risk factor for osteopaenia and osteoporosis. In at risk populations vD supplements have been shown to of benefit.

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    2. Anonymous Sunday, March 23, 2014 10:24:00 am. I assume you are on a mission to stop people with MS taking vitamin D supplements. Why? If you don't agree with the policy you don't need to take supplements. A very good website that goes into these issues is www.vitamindcouncil.org. I think you will realise that most of the studies done on this topic are flawed due to the fact that they use too low a dose of vD. Therefore if you do a meta-analysis of flawed data you get a flawed or spurious result. The same applies to the meta-analyses of vD supplementation and cancer prevention; all of them are using a dose that is too low. The vitamin D council are lobbying for studies to be done with doses that are physiologically meaningful and get blood levels into a range that they consider normal (>100nmol/L).

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    3. They are not flawed. Vitamin D is supposed to be for good bones right? But it doesn't even help that. Why recommend vitamin D to the general population if it doesn't do anything? I am an advocate of evidence based medicine, and I get frustrated when Prof G advocates things with no evidence. There is no evidence that taking MSers taking vitamin D have any benefits. This post is an example of bad science.

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    4. What is your evidence that vitamin D is no good for bone health?
      Read the number of posts on broken bones.

      Advocates things with no real evidence.....yep otherwise there would be no trials.

      You can make up any story you like, this gives evidence in your own mind, is that universal evidence...

      The story for the statins was that it affects blood vessel function is this true? Maybe maybe not. Others would say effects on Th1/Th2 other would say if affects growth cones others would say it is all artefact.

      ProfG has a passion for VitD and other things like viruses. To think that this Blog has no bias is wrong because we all have opinions and opinions change. However do we do nothing about it or try and bring change.

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    5. Some evidence based medicine on vitamin supplements and bone health:

      http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000952/abstract

      http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006944.pub2/abstract

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    6. http://www.ncbi.nlm.nih.gov/pubmed/23299607

      http://www.ncbi.nlm.nih.gov/pubmed/21266418

      thanks, all negative

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    7. What dose? I suspect too low to normalise blood levels. Crap in crap out as the saying goes.

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    8. Low dose vitamin d studies are like testing how drinking 200mL of water a day affects kidney stones. You do an RCT with half getting the water and the other not. But there is a tap in the corner that everyone can drink from as much or little as they want. Why would you expect to see an effect as you have failed to control the dose.

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    9. http:// www.ncbi.nlm.nih.gov/pubmed/23299607
      has the title "knee pain and cartilage volume loss in patients with symptomatic osteoarthritis:..." It is not about osteoporosis.

      http:// www.ncbi.nlm.nih.gov/pubmed/21266418
      states "It is unlikely that vitamin D supplements are beneficial in children and adolescents with normal vitamin D levels. The planned subgroup analyses by baseline serum vitamin D level suggest that vitamin D supplementation of deficient children and adolescents could result in clinically useful improvements, particularly in lumbar spine bone mineral density and total body bone mineral content, but this requires confirmation." Note the second sentence.

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    10. The problem with meta analysis is without assessing quality control or fully understanding what is being done then the studies can show very little.

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  5. From Nordland and upwards in Norway there is a proportion Sami population with genes that are said to be less prone to MS. Finnmark far up north, with the lowest MS-prevalence, is the Sami main area.

    Denmark to the south has even more MSers registered than Norway:
    Denmark 220-100.000
    Norway 160-100.000

    Denmark is nation nr. 2 (after Canada) on the list “MS Top 10” from Multiple Sclerosis International Federation.

    The Italian island Sardinia is another well-known exception to the north-south gradient.

    Could there be genes with sun/heat intolerance involved…?

    A study from 2010 suggests that MS-relapses are more frequent in spring and summer: http://www.medpagetoday.com/clinical-context/MultipleSclerosis/21951

    I allow myself to add some personal experience: Diagnosis and hyperactive MS and after IVF treatments. MS-relapse on day 1-3 when going vitamin D-hunting on the Canary Islands in winter. A certain degree of sun intolerance (sun excema). Possible sensitivity to hormonal fluctuation (when estrogen levels are sky high?). Constantly lurking herpes simplex-infection.

    Greetings from a MSer in Norway

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    1. The UV index in Fuerteventura (Canaries) in December is 3 on a clear day so you can only make vitamin d for a short time either side of midday. Raise your levels with supplements. Vitamin d levels in summer are controlled by tendency to expose skin at midday and summer cloud cover so I would expect Scotland to be worse than Norway. I do not know how Denmark and Norway compare for sun and behaviour.

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  6. Prof G and Mouse Doc it appears that you are getting doctors reading this blog. Even if they are sceptics this is brilliant. May be with some persistence you can change a few minds and get them to be more proactive. I am really enjoying the banter this post has generated regarding vitamin D. I have been on vitamin D supplements for over 6 years - I take 4000U per day.

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    1. Yes we do and they are not just called Dre.

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  7. Apologies, for not being as responsive as normal in relation to this post. I note this post has generated a lot of discussion. I suggest we invite one of the wise men or women from the Vitamin D Council to do a guest post to help address these issues. I seem to be taking stick for promoting the recommendations of these experts.

    I was with George Ebers this afternoon and discussed this post with him and the response it generated and he informed me that he has done an analysis of major public health interventions and found that they usually occur 50 years after the scientists make a call for their adoption, e.g. folate supplementation for prevention of neural tube defects, the smoking ban, water fluoridation, etc. He said don't expect public health officials to make any changes to the vD RDA any time soon; they still have another 30-40 years to go on his clock.

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    1. You may also wish to consider inviting the good people at Grassrootshealth http:// www. grassrootshealth.net/ as they have generated most of the data relating supplement intake to 25(OH)D levels, showing basically it is not a linear relationship.

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  8. Here are two early trials of high dose vitamin D (up to 40,000 IU/day):

    http://www.ncbi.nlm.nih.gov/pubmed/20427749
    http://www.ncbi.nlm.nih.gov/pubmed/21179201

    No one died and it appears to shift the immune profile to anti-inflamitory. The theory that Vitamin D is a factor in MS has been around for decades. What is the hold-up on running a trial to show if it is beneficial? Low dose trials are useless. You should get some of these scientists on here to discuss their viewpoints.

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