Saturday, 24 January 2015

ClinicSpeak: vD supplements or sunshine

What is better; vD supplements or sunshine? #ClinicSpeak #MSBlog #MSResearch

"Chicken or egg; association vs. causation vs. reverse causation. There are a lot of believers out there when it comes to vitamin D and MS disease activity. At first glance it would look as if low vitamin D levels are the cause of MS and drive MS disease activity. This has led to the hypothesis that simply taking vD supplements will prevent a large proportion of MS and will work as a disease-modifying drug. Unfortunately the evidence that vD works as a DMT is very poor; we need large adequately powered studies to answer this question. I personally don't think the current trials are large enough and I am still not convinced we know what dose of vD will answer the question definitively."

"Reverse causation simply refers to the observation that virtually all diseases associated with inflammation have low vD levels. In other words the immune system consumes and uses vD. Therefore it is the immune activation that causes low vD levels and not the other way round; i.e. low vD does not cause immune activation. I refer to this as the consumptive hypovitaminosis D hypothesis. The epidemiologists call this reverse causation." 



"What about prevention? I personally think the case for low vD levels being linked to MS susceptibility is stronger that MS disease activity. The many migration and international case-control studies are very suggestive and indicate that we really need to do a prevention trial. The one major confounder is that low vD levels may simply be an indicator of low sunlight exposure. There is mounting evidence that sunlight affects immune function. As your immune cells pass through the skin they are being modified by ultraviolet light. If this is the case then vD supplements won't work. The following review paper below speculates on how sunlight works as a immunomodulator."

"What is clear is the field really needs a shake-up and some leadership to get the necessary trials off the ground to answer these questions. I fear that the next generation of MSers are going to look back at us and say: 'You knew about this latitude gradient for over 50 years and you did nothing about it. Why? If you had done what was so glaringly obvious I may not have developed MS'. This prediction haunts me. Based on the migration studies vD supplementation may be able to prevent over 75% of new cases of MS; then it again it may not. Without a major investment, and soon, we won't have an answer to this question in my lifetime."

"At Barts-MS we recommend vD supplements to all our patients with the aim of keeping them vD replete. We do this for bone health reasons and not because we believe vD is a DMT. You should be well aware of the data by now showing MSers are more likely to have thin bones and are high risk of falls and fractures. vD supplementation is based on this information. What doses do we recommend? Higher than the current RDA. We defer to the experts who run the Vitamin D council. However, I would prefer to supplement vD by treating to target, i.e. finding out how much vD each individual needs. At a population level this is very expensive as it require blood test to adjust levels of vD supplementation and hence is not cost-effective."


Epub: Marsh-Wakefield & Byrne. Photoimmunology and Multiple Sclerosis. Curr Top Behav Neurosci. 2015 Jan 22.

The ultraviolet (UV) radiation contained in sunlightSunlight is a powerful immune suppressant. While exposure to UV is best known for its ability to cause skin cancer, it is also associated with protection against a range of autoimmune diseases, particularly multiple sclerosis (MS). Although the precise mechanism by which sunlightSunlight affords protection from MS remains to be determined, some have hypothesised that UV immunosuppression explains the "latitude-gradient effect" associated with MS. By stimulating the release of soluble factors in exposed skin, UV activates immune suppressive pathways that culminate in the induction of regulatory cells. Regulatory cells in distant tissues. Each and every one of the immune suppressive cells and molecules activated by UV exposure are potential targets for treating and preventing MS. A thorough understanding of the mechanisms involved is therefore required if we are to realise the therapeutic potential of photoimmunology.

24 comments:

  1. Doc,

    If sunshine were indeed able to prevent MS, do you think the same mechanism of action would prevent MS from progressing in the early stages?

    So as a newly diagnosed MSer maybe I should go on semi annual vacations to hot countries to get me some sunshine?

    Or is it that once you pop, you can't stop? Pringles. That's the stuff.

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    1. Funny, I had my first symptoms when I was in Tenerife! Then, got worse 3 months later in sunny Italy. Had a lovely time though.

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  2. Actually when I look at the map particularly at France which has lower MS levels than Spain yet lies further north from the aquator I think the prevalence has as much to do with healthy living particularly not eating so much meat (red meat, processed meat) and also sugars.

    My point is, I lived in France for a while and know what they eat - they just never have eaten junk food - they value their regional cuisine too much for that. women also tend to smoke but I never believed in the causation of smoking and MS anyway.

    sadly, as soon as I moved away and started to stuck myself with sugars and meats the MS did not take long to show itself.

    also, the 'joie de vivre' in France meant a more relaxed way of living and less stress.

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    1. This is interesting, I was warned about sugar (or too much sugar) is not good for MS. The first time in my life I suffered from bad stress my MS decided to rear it's ugly head.
      My old flat mate is french and she said people grow up in France knowing how to cook healthy meals for themselves, with vegetables.

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    2. This doesn't explain why I developed MS I had healthy diet, all cooked from scratch by my grandmother. She shopped almost every day.

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    3. It's a combo of things - have you been outside in the sun a lot as a toddler/child/teenager? I mean for hours at a time? What about sunbathing? What did your granma cook - meats or veggies - how often? Was it fatty or too salty? What about your sugar intake?
      What about your stress levels?

      I meant diet but also lifestyle.

      MS is genetically encoded to some degree cos when I got MS my Mum got another autoimmune illness due to the same stressful events. So the organ to be attacked is in your genetic make-up but the outbreak of MS can be prevented cos you can turn around the pieces of your genes or make them sleep if you live a good lifestyle imho.

      but if I didn't have the stress and had eaten healthily and stopped sitting on my couch without seeing the sun for years things most likely would have been different now.

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    4. My primary school was in the middle of a food market. Fish, chicken, and red meat once or twice a week. Fresh vegetables and meals followed by fresh fruit not puddings. Did loads of walking so that we could keep the bus fare we saved and the two miles there and back to the not so local swimming pool. Always outside when the weather permitted. My lifestyle has been one that doctors keep telling us we should follow. It made no difference, I still got cancer a few times, but what I would say is that when I got it, I had the ammunition to fight it. I'm still here to tell the story. I still say it's got to be the genes.

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  3. How interesting that France appears to have lower prevalence. Any thoughts?

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    1. France supplements its infants at a higher IU per day than other countries. 1000IU to 1200IU + 400IU for dark skin.
      see: Recommendations for a National Policy on Vitamin D Supplementation for Infants in Ireland (it is in the tables at the end).
      https://www.fsai.ie/WorkArea/DownloadAsset.aspx?id=1222

      They have historically been less 'afraid' of vitamin d.

      As the saying goes, not a proof of causality but makes you thing.

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    2. The Committee on Nutrition of the French Society of Paediatrics positional paper, Arch Pediatr. 2012 Jan 25. , stated that:

      In the absence of any underlying risk of vitamin D deficiency, the recommendations are as follows:

      pregnant women: a single dose of 80,000 to 100,000IU at the beginning of the 7th month of pregnancy;
      breastfed infants: 1000 to 1200IU/day;
      children less than 18 months of age, receiving milk supplemented with vitamin D: an additional
      daily dose of 600 to 800 IU;
      children less than 18 months of age receiving milk not supplemented with vitamin D:
      daily dose of 1000 to 1200 IU;
      children from 18 months to 5 years of age: 2 doses of 80,000 to 100,000 IU every winter (November and February).

      which shows a difference in attitude between France and the rest of Europe.

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  4. It is worth pointing out again that the RDA for vitamin d calculated by the IOM in the USA is wrong

    Veugelers PJ, Ekwaru JP. A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D. Nutrients 2014;6(10):4472-4475. doi:10.3390/nu6104472

    and that the incorrectly calculated RDA recommended in the USA (600IU) is still higher than the UK (200IU). The RDA for an adult is half that recommended for a new born baby by the Royal College of Paediatrics and Child Health and one fifth of the RDA in Italy for an adult. None of these RDAs take an effect of body mass even though it has been shown that blood levels of 25(OH)D vs vitamin d intake are affected by body mass.

    Ekwaru J. P. et al. The importance of Body Weight for the Dose Response Relationship of Oral Vitamin D Supplementation and Serum 25-Hydroxyvitamin D in Healthy. PLoS One. 2014; 9(11):e111265.

    The IOM calculated that 600IU a day would lift 95% of the population above 20ng/ml and that was why it was chosen. It does not.

    Vitamin d deficiency is very bad for the body, it is part of the immune system, programmed cell death and calcium control. It operates in almost every cell in the body. It is so important that evolution selected the population of Europe to have white skin, even though it carries inherent risks, and that was for a population that lived outdoors.

    The problem is that even if people take notice of the publicity that almost everyone in the UK is short of vitamin d they will take the RDA and have almost no effect on their blood levels. Everyone agrees there is no evidence that no adult has ever reached toxic levels at 10,000IU a day, but there is a fear of raising the RDA, and I have no idea where it comes from.

    Whether it affects MS does not matter it should be taken for all the other effects.

    Is there high levels of MS in populations who see little sun but get vitamin d from fish?

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  5. so which one is it? supplementation or sunlight?

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    1. sunlight.

      just check it yourself - next time you have your symptoms e.g. fatique, pain etc. go and sit in the sun for 10-15 minutes and do it for two months - you'll see.

      I have to say that all my relapses have been stress-related - but sunlight can mediate that as well - so in a good way I can control my relapeses but unfortunately I am bad at facing stressful situations so the cycle goes on.

      I have stopped taking DMTs because I was very prone to infections and my blood levels were very low - I really am not ready to get PML or some other life-threatening illness on top of my MS. So the docs need to search for better drugs until they find a cure.

      I rely on herbal medication only - as I predicted my relapes and overall condition are the same as with DMTs (the newer ones but not the super strong ones) and I just know that my MRI will be the same as on medication. It's been the same in the past. The progression goes on but in a tortoise-like way really.

      I had my first relapse I can remember around 7 yrs. ago (the other one I suspect of being CIS was 2003) - I am on good days pretty much the same old me (minus jogging and walking fast but I never liked being that active anyways) - I stopped working now cos I hated the hassle.

      I am more anxious but that happened more due to my environment being super dramatic than myself, I sleep well, don't have any urinary problems, can climb the stairs fast, have learned a new language last year, can still outdo most of my peers in discussion, and can still ride my bike like always.

      There is life with MS not just doom and gloom - and I love the sun, so enjoy it cos it's good for many autoimmune diseases not just MS.

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    2. All very well, but some of us cannot afford to give up work.

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  6. Some populations of people in northern latitudes : Sami, Inuit, Central Asian countries such as Mongolia, Uzbekistan, Turkmenistan, etc. do not have high MS prevalence. Have vitD levels been measured in these groups?

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    1. Inuit eat alot of fish and whale so they get vit D from that.

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  7. Both the effects of sunlight and sun generated vitamin d will be affected by weather as well as latitude, as cloud cover modifies both. There will also be effects from height above sea level, pollution levels, time spent outdoors and the clothes worn. Mongolia is 46 degrees North (average height above sea level 1580m), Uzbekistan (the capital is at 500m) 41 degrees North & Turkmenistan 38 degrees North (capital is 200m above sea level).
    All these countries are further South than the UK (Glasgow is 56 degrees North) and they have hot dry summers. Ashgabat, Turkmenistan gets 2712 hours of sunlight per year, Glasgow 1243 hours of sunshine per year. London gets 1460.

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    1. Your ideas still don't explain the lower prevalence in France (plenty of sun at the Cote d'Azur) as well as the Baltics (Estonia, Lativia) which are high up north - the MS epidemics has to do with our unhealthy Western diet and lifestyle - chemically enriched food aka junk, not going outside, not much movement just sitting in front of a computer, high stress levels.

      I predict that granted non-Western countries will adopt our Western lifestyle and diet we will see MS going up multi-folds in the future.

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    2. They are not ideas they are statements about what the weather is like where, and that latitude is not the only factor controlling sun exposure. I make no statement of how these affect MS. The problem with your statements about lifestyle is that MS existed at approximately the same level before computers and modern diets and the gradient in risk has not significantly changed over time. The reduction in MS in Europeans moving to Northern Australia, existed before computers and has remained the same ever since. It was first observed in the 1940s. The French as it says in one of the other comments have and still use much higher levels of vitamin d supplementation in their children. I looked up Estonia they supplement vitamin d at 400IU a day for the first 2 years of life. I cannot find data for Latvia.

      To quote Latvia travel "Summers in Latvia are sunny, but not so hot as to cause discomfort." unlike Scotland which are often cloudy, wet and cold. As you move away from the Atlantic the summers become hotter and sunnier for the same latitude. Although these places are dark in the winter they are very sunny in the summer.

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    3. I don't believe MS existed at the same levels before 1940s or even 1950s - do you have any reliable data to back that up? As far as I heard MS is steadily growing in women which is too fast to be explained by better diagnostic tools only.
      Since I never used contraceptive pills I doubt that is the reason - diet is a far more likely explanation and there are people around who turned their diseases around with a change of diet, not only MS but other diseases as well - it makes sense to look at what people eat.

      Also, how do you explain the relatively recent MS prevalence in Middle-Eastern countries (eg Saudi-Arabia I think it was)? Exposure to a more western diet and not getting into the sun due to extreme heat in the day spring to mind. Also they had a different lifestyles before with a slower pace of living - now it's the same stressful business-like one which could be a reason as well.

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    4. There is a difference between prevalence (the number of people with MS) and the incidence. What you are referring to is prevalence, and prevalence has increased significantly. It has increased because people with MS live longer. In 1957 in Switzerland the life expectancy at diagnosis was 12.6 years, in the 1980's it was 30 years *. So there are at least 17 years more people with MS, assuming no change in incidence, or quality of treatment since the 1980's. About 6,000 people are diagnosed each year so that is at least an extra 102,000 people with MS. The data for incidence that I can find quickly only covers 1990 to 2010 and that shows a decrease in incidence. It is reviewed here http://multiple-sclerosis-research.blogspot.com/2013/09/prevalence-of-ms-in-uk.html

      * http://www.journalslibrary.nihr.ac.uk/__data/assets/pdf_file/0018/65043/FullReport-hta6100.pdf

      What is not shown on the map is the difference in prevalence of MS in different regions of Australia. The prevalence in Tasmania is 5 times that in Queensland and they will eat approximately the same diet and are genetically similar (white European).**

      Saudi Arabia and surrounding areas have such a significant vitamin d deficiency problems that there is a very high incidence of rickets ***

      ** http://www.msra.org.au/overview-multiple-sclerosis
      *** http://www.ijpeonline.com/content/2010/1/410502

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    5. Before the 1980s there was no access to MRi scanners. Some of us were told we were neurotic and not even referred. How many people went undiagnosed?

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  8. Re "need to do a prevention trial"
    The PrevANZ trial is currently recruiting participants in six states of Australia plus New Zealand. See details on the MS Research Australian website on the following link.
    http://www.mstrials.org.au/PrevANZ-Trial

    Also - full details of the trial, described as a "Phase IIb Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Trial to determine the safety and efficacy of Vitamin D3 in preventing the risk of MS in Patients with a first demyelinating event" can be found on the Australian & New Zealand Clinical Trials Register:
    https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363026&isClinicalTrial=False

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  9. Re "By stimulating the release of soluble factors in exposed skin, UV activates immune suppressive pathways" - I have seen references before to the possibility that sunlight exposure has benefits on the immune system which are not necessarily generated by taking Vit D3 supplements. However, for some of us with very fair freckled skin the recommended exposure is not a good idea as you get older and have already accumulated some sun damage over your lifetime, especially if you live in an area with very low pollution and consequently very savage UV. I have in the past even suffered from solar urticaria on a few occasions when the UV has been particularly savage and I have not been able to seek shade quickly enough after feeling my skin starting to prickle (different from sunburn).

    So - the supplementation option is the only one really available for me.

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