Sunday, 3 July 2016

ResearchSpeak: what's in a date?

How much vitamin D should I take during pregnancy? #ResearchSpeak #MSBlog #MSResearch

"Tomorrow is the Fourth of July, Independence Day of the United States, a holiday commemorating the adoption of the Declaration of Independence on July 4, 1776, which declared America a new nation and no longer part of the British Empire. Isn't it amazing that the Brexiteers are claiming the 24th June as Independence Day for Britain from the EU. Why do we put so much significance on a dates? Well if you have MS you may want to analyse your date of birth. The study below, which includes data from Barts-MS, confirms previous observations that date of birth is linked to the risk of getting MS. There have been past criticisms of this observation based on seasonal variations in birth rates of the general population, which we controlled for in this current analysis. In summary if you were born in April you have a 24% greater chance of developing MS compared to someone born in November. Some people may say this is not a big deal, but I think this study is crucial in telling us that a component of MS risk is attributable to events that occur in around birth, i.e. congenital factors."

"One theory is that if your mother was pregnant with you in winter, particularly toward the middle and end of winter, when her vitamin D levels were most likely to be low, then your vD levels in the womb would have also have been low. We have hypothesised that low vD levels in the womb affects how the immune system develops in particular the education of your T cells in the thymus and this allows more potentially auto-reactive T-cells to escape from the thymus into the periphery (blood, lymph nodes and spleen). These escaped T-cells then lie dormant with the potential of triggering MS in later life. If this hypothesis is correct then many more 'autoimmune diseases' would also have a month of birth effect. This appears to be the case with most autoimmune diseases studied to date showing a month-of-birth effect."

"Please note if this hypothesis is correct then the month-of-birth effect should flip 180-degrees from the Northern to the Southern hemisphere. As predicted this is exactly what has been described. Data from Australia and Argentina show that November, rather than April, is the high risk month in the southern hemisphere."

"Does this data have implications for you if you have MS? That depends on what burden of proof you require before you act on scientific data. If the month-of-birth effect is due to low vD levels in pregnancy then pregnant women should make sure they are vD replete during pregnancy. This is why we recommend that our patients planning a pregnancy, or who are pregnant, take vD supplements. At present we recommend the Vitamin D Council's recommendation of at least 5,000U per day. The latter is not only based on new data, but science from more than 60 years ago. On some occasions science, or the adoption of science, moves at a glacial pace. The following is a quote from a paper published in 1947 in the BMJ (OBERMER E. Vitamin-D requirements in pregnancy. Br Med J. 1947 Dec 6;2(4535):927)."

'Until further experimental evidence, adequate and incontrovertible, is made available, I submit that we should play for safety. In a climate like that of Britain every pregnant woman should be given a supplement of vitamin D in doses of not less than 10,000 IU per day in the first 7 months, and 20,000 IU (per day) during the 8th and 9th months.'


Obermer, 1947


Rodríguez Cruz et al. Time- and Region-Specific Season of Birth Effects in Multiple Sclerosis in the United Kingdom. JAMA Neurol. 2016 Jun 27. doi: 10.1001/jamaneurol.2016.1463. 

IMPORTANCE: The reports of seasonal variation in the births of people who later develop multiple sclerosis (MS) have been challenged and attributed to the background pattern in the general population, resulting in a false association.


OBJECTIVE: To study the seasonality of MS births after adjusting for temporal and regional confounding factors.

DESIGN, SETTING, AND PARTICIPANTS: A study was conducted using case-control data from 8 MS-specialized centers from the United Kingdom, MS cases from a population-based study in the Lothian and Border regions of Scotland, and death records from the UK Registrar General. Participants included 21 138 patients with MS and control data from the UK Office of National Statistics and the UK government office regions. The seasonality of MS births was evaluated using the Walter and Elwood test, after adjusting for temporal and regional variations in the live births of the UK population. The study was conducted from January 16, 2014, to September 2, 2015.

RESULTS: Analysis of the general population indicated that seasonal differences are present across time and region in the United Kingdom, with both factors contributing to the monthly distribution of live births. We were able to demonstrate that, when adjusting for the temporal and regional variations in the live births of the UK population, there was a significant season of birth effect in patients with MS, with an increased risk of disease in the peak month (April) compared with the trough month (November) (odds ratio, 1.24; 95% CI, 1.10-1.41) and 15.68% fewer people who developed MS being born in November (observed to expected birth ratio, 0.840; 95% CI, 0.76-0.92).

CONCLUSIONS AND RELEVANCE: Season of birth is a risk factor for MS in the United Kingdom and cannot be attributed to the background pattern in the general population. The reasons for the variations in birth rates in the general population are unclear, but not taking them into consideration could lead to false-positive associations.

COI I an co-author

9 comments:

  1. Wow, that quote from 1947 is akin to Nostradamus when you consider things.

    Prof G, how essential is vitamin K2 whilst taking D3? My teacher says it is essential for MSers.

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    1. A recommendation from 1947 and nothing from our public health England since then. We should be ashamed of ourselves. Even if this strategy reduces the incidence of MS by say 5% imagine how many fewer people with MS there would be today?

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  2. The effect of low mother vitamin d may be epigenetic rather than a direct effect on T cells, it may modify how the immune system uses vitamin d. It would be an evolutionary advantage to be able to conserve vitamin d if you are going to be born where low levels occur. This may then up regulate other parts of the immune system.

    Also you really should point out the evidence showing that the RDA was incorrectly calculated.

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  3. I was born in India in the month of July, in a part of the country with very mild winters. May and June are the summer months there and monsoon starts in July; it always rained on my b'day. I am sure that my mom had plenty of vit d in her body. Still got struck with MS. I had measles, mumps, chicken pox as a child; never heard of mono till I moved to the US.

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    1. At the individual level such articles are meaning less because the risk incease is small so there are always exceptions but at a group level it points towards possiblg prognosis

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    2. It does not matter how mild the winters are. It matters how much cloud cover there is in spring/summer/autumn, the latitude, air pollution and how much of the skin is covered when out in the midday sun. It is the amount of UVB hitting the skin that matters for vitamin d and very little else. And you still can be unlucky it is not a cure it just appears to reduce the risk. Low vitamin d levels are reported to be very common for women in India.

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  4. Professor G - your advice please
    Taking Vitamin D3 with a glass of milk (fat soluble) Now know you recommend NOT with calcium

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    1. Vitamin D, as well as A and E, is fat-soluble, so always eat with fat, not with calcium (do not know where they got it, if I had to be involved would have to be with vitamin K, particularly its form D2).
      I take Vitamin D3 always at lunch or dinner ...

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  5. I have read reports on benefits of very high dose vitamin therapy with no calcium allowed in diet. I would love to try this but realise it needs to be done with medical supervision.

    Also, what dose of vitamin D should adult children of an MSer take - and vitamin k. - without the need to avoid calcium.

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