Tuesday, 28 January 2014

Clinic speak: vitamin D levels as a predictor of MS disease activity

Chicken or egg: low vitamin D levels and MS. #MSBlog #MSResearch #ClinicSpeak

"Chicken or egg? Vitamin D and MS is another conundrum in need of a solution. We know  that low vD levels are a susceptibility factor for MS and  that MS incidence (number of new cases per year) and prevalence (total number of cases in the population) are strongly associated with latitude (distance from the equator) and in particular annual ultraviolet B light exposure (UVB). UVB is the spectrum of light required by your skin to synthesize vD. For  these reasons we believe that low vD levels are part of the causal pathway that leads to the development of MS. However, what happens once you have MS? Will low vD levels increase your chances of having a poor prognosis? Will vD supplements improve your disease course? The study below addresses the former; CISers with low vD levels were more likely to do poorly over the next 5-years than CISers/MSers with high vD levels. This study, however, does not show causation. It is possible that low vD levels are simply a marker of a more active disease. In other words inflammation consumes vD and hence the more inflammation you have the lower your vD levels are. This could be untangled by an adequate double-blind placebo controlled trial of vD supplementation trial in CIS. If vD supplements reduces MS disease activity then vD is a DMT. If on the contrary vD supplements don't reduce MS disease activity then low vD levels are likely to be a consequence of MS disease activity." ]

"The problem with treatment trials is that we in the field have yet to settle on what is an appropriate dose. Most vD experts suggest that you need to take enough vD to raise your blood levels above 100 nmol/L. At the moment this is much higher than the upper limit of the normal range. Why so high? At present the normal range is based on the vD levels in the normal population. If a large number of the normal population are vD deficient, or insufficient, then the normal range will be artificially low. They base their assumption on the vD levels of people living in outdoor environments with unlimited sun exposure, for example hunter-gatherers in Africa, farmers, life-guards, etc. These sorts of people have year round levels above 100 nmol/L. As we evolved as a species in these environments it is likely that these levels are physiological or normal. At present most studies are testing fixed doses of vD levels of 10,000U per day or lower. This may not be enough for MS. Some commentators suggest we need to adjust doses and  treat to a target blood level. Too late. There are several ongoing vD supplementation trials, which to the best of my knowledge are using a fixed-dose. Let's hope they provide answers."

"Should we treat low vD levels in MSers? Yes, I do. Why? Not because I think vD supplements will reduce MS disease activity; we don't have the evidence for this at present. I supplement low vD levels to maximise bone health. MSers are known to have thin bones, aka osteopaenia, and as a result are at increased risk of falls and fractures. Therefore, I recommend vD supplements to all the MSers under my care and I also recommend it to their family members. There is a theoretical possibility that by keeping your children and siblings vD replete that you will reduce their chances of getting MS."

"What now? We need to wait for the Australian CIS vD supplementation trial to report. It may show that vD supplements are disease-modifying. However, we still need to remind MSers that vD may be linked to MS disease activity and therefore there is a good reason to keep yourself vD replete, i.e. with a blood level of >100nmol/L. Do this you need to take more vD than the RDA. We recommend 5,000U vD3 per day for children older than 10 years and adults. This recommendation is based on the guidelines of the Vitamin D Council. For children less than 2 years of age we recommend 600U per day and for children 2-10 years of age 2,000U per day."

"Do I practice what I preach? Yes, I do. I personally take 5,000U per day as well as my family. The problem I have is getting my family to adhere to the supplements. That is the elephant in the room. It is easy to say take this, or do that, it is much more difficult to get people to take your advice and stick to it in the long-term. I hope having MS, or not wanting to have MS, is a big enough incentive not to forget your supplements." 

Epub: Ascherio et al. Vitamin D as an Early Predictor of Multiple Sclerosis Activity and Progression. JAMA Neurol. 2014 Jan.

IMPORTANCE: It remains unclear whether vitamin D insufficiency, which is common in individuals with multiple sclerosis (MS), has an adverse effect on MS outcomes. 

OBJECTIVES: To determine whether serum concentrations of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, predict disease activity and prognosis in patients with a first event suggestive of MS (clinically isolated syndrome). 

DESIGN, SETTING, AND PARTICIPANTS: The Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment study was a randomized trial originally designed to evaluate the impact of early vs delayed interferon beta-1b treatment in patients with clinically isolated syndrome. Serum 25(OH)D concentrations were measured at baseline and 6, 12, and 24 months. A total of 465 of the 468 patients randomized had at least 1 25(OH)D measurement, and 334 patients had them at both the 6- and 12-month (seasonally asynchronous) measurements. Patients were followed up for 5 years clinically and by magnetic resonance imaging. 

MAIN OUTCOMES AND MEASURES: New active lesions, increased T2 lesion volume, and brain volume on magnetic resonance imaging, as well as MS relapses and disability (Expanded Disability Status Scale score). 

RESULTS: Higher 25(OH)D levels predicted reduced MS activity and a slower rate of progression. A 50-nmol/L (20-ng/mL) increment in average serum 25(OH)D levels within the first 12 months predicted a 57% lower rate of new active lesions (P <001), 57% lower relapse rate (P = .03), 25% lower yearly increase in T2 lesion volume (P< .001), and 0.41% lower yearly loss in brain volume (P = .07) from months 12 to 60. Similar associations were found between 25(OH)D measured up to 12 months and MS activity or progression from months 24 to 60. In analyses using dichotomous 25(OH)D levels, values greater than or equal to 50 nmol/L (20 ng/mL) at up to 12 months predicted lower disability (Expanded Disability Status Scale score, -0.17; P = .004) during the subsequent 4 years. 

CONCLUSIONS AND RELEVANCE: Among patients with MS mainly treated with interferon beta-1b, low 25(OH)D levels early in the disease course are a strong risk factor for long-term MS activity and progression.


  1. Prof G - are there any risks attached to taking Vit D? Like clogged arteries or so?

    I was told by my neuro lately that I should not take my Vit D (1000ie) too often just 2-3 times a week because it's 'not good to take it often'.

    That surprised me because I used to take it daily and now am confused.

    1. funny....my neuro takes 4000 iu a day and advises me to do the same. is it safe or not?!!

    2. The 4,000U per day comes from EFSA. We have had the 5,000 vs. 4,000 debate before it makes little difference the 5,000U dose (1 tablet) is simply cheaper than 4,000U (4 x 1,000U or 2 x 2,000U), Please see the following post; http://multiple-sclerosis-research.blogspot.co.uk/2013/03/survey-results-vitamin-d.html

    3. Re: "I was told by my neuro lately that I should not take my Vit D (1000ie) too often just 2-3 times a week because it's 'not good to take it often'.

      This may be appropriate if your vD levels are very high. If not then 1,000 per day is fine.

    4. The value of 4000IU a day was got by dividing 10,000IU a day by 2.5. If you look at the paper there is no rational for choosing 2.5 as compared to 1.5 except 4000IU a day matched the USA.

    5. I have been taking Vitamin d for years but despite this my level is usually between 35-60. I also go away in the winter. Despite this my ms has progressed very quickly and, Im now in a wheelchair. I've tried to get my children to take Vitamin d without worrying them. My daughters was very low and despite supplements it gets nowhere near 100. My son has now had an episode of blurred vision and is awaiting results of brain scan. My worst nightmare my be happening. Could you tell me do you only tend to use gadolinium if something is seen.?He fought so hard to get to University and its affecting his exams. Please help Prof. G

    6. The 4000IU upper tolerable limit means what most of the general population can take with no risk and without any medical supervision. Once you are monitoring vitamin d levels then you increase the dose until you get the required 25(OH)D level in the blood. It is worth pointing out there are 2 sets of units used for vitamin d. So toxicity seems to set in at about 750 nmol/L, which is 300ng/mL. As you can see the units are important. It is not known if vitamin d3 and vitamin d2 behave differently in MS, but there was a paper published last week showing in a double blind test that d2 is possibly damaging to muscle repair, while d3 is not. As vitamin d3 is cheap and what the sun makes on the skin buy that, Amazon has lots.

  2. There are no known cases of vitamin d toxicity below 10,000IU a day. The EU and the USA set the max tolerable dose at 4,000IU a day. The EU paper is here
    www .efsa .europa .eu /en /efsajournal /doc /2813.pdf
    you will have to take the spaces out for the address to work.

    Low levels of vitamin d are more likely to cause clogged arteries due to secondary hyper-parathyroidism. Given that the body naturally produces vitamin d3 and d3 is cheap to buy as a supplement take that instead of d2.

  3. For additional reporting and some skeptical views on this interesting vitamin D study, please see our news article at the MS Discovery Forum (MSDF): http://www.msdiscovery.org/news/new_findings/9392-serum-vitamin-d-levels-predict-severity-ms

    I've taken the liberty of excerpting some of Dr. G's comments above following the MSDF article.

  4. Personally I am very pro Vitamin D. In the first part of 2013 up until May, I had 6 relapses in as many months, 1 really bad one followed by optic neuritis which fast tracked my MS diagnosis. I have no idea what my vit D levels were at this time but my reckoning is that they were very low as being fair skinned, I rarely ventured outside without a sun block.

    Whilst waiting for the official diagnosis, I googled everything I could about MS and began taking regular Vitamin D3 supplements, By Aug my levels were 113 nmo/L and I now maintain my levels between 150 and 200 nmo/L. Since the increase in Vit D levels I have not had another relapse. As I am not currently on any DMT's either, I find this to be more than a coincidence.

  5. Vitamin D is garbage. The circumstantial evidence (month of birth effect, maternal effect) have now fallen by the wayside. It's all hype and no substance. Do people seriously believe taking a vitamin will prevent unremitting neurological disability?

    1. The evidence that geographical location is the greatest risk factor in MS is proven. White Europeans near the Equator in places that are sunny have much lower risk (best to worst is about 6x). African who move North or South away from the equator massively increase their risk. Is this vitamin d, we do not know but it is one of the things that has changed. However, vitamin d is NOT a vitamin, it is the precursor to a powerful hormone, immune system moderator and compound which is implicated in many genetic functions. But a lack of vitamin B12 does permanent damage to the nervous system.

  6. 100nmol/l serum levels is very low, who wrote the article is confusing 100nmol/l with ng/ml may be but even in this case 100ng/ml is still in the normal range...
    maybe you have to go an study a little medicine before writing article dont you?

    vitd25oh normal range is 30-100ng/ml.using the old unit nmol/l 74-250nmol/l

    to treat MS vitd25oh stable at 160ng/ml is used on no diary diet and calcium lowers instead of rising despite these blood levels.this happens because calcium absorption in the gut has been found to correlate to vitd1.25oh levels which are not correlated to vitd25oh.some cases of calcium rising have been observed with vitd25oh>300ng/ml

  7. "Not because I think vD supplements will reduce MS disease activity; we don't have the evidence for this at present. I supplement low vD levels to maximise bone health. MSers are known to have thin bones, aka osteopaenia, and as a result are at increased risk of falls and fractures."

    I wonder about this because I have PPMS, have never broken any bone in my body all my life (I'm in my late 30s) and I have excellent, highly caries resistant teeth - only one small filling and the other teeth are pretty much in perfect condition.

  8. I have oily fish a few times a week which helps keep my vit D up, also mushrooms and eggs quite a bit. I take 2000iu a day of vit D3. My levels are 100 now and have been told I am doing sonething right to keep it there in normal range. I'm on Tecfidera and have another blood test in six weeks time so will ask to be checked vit D again. Calcium was in normal range too. I was thinking of asking to check my uric acid, vit B12 and iron. I do have new activity though seen on a recent MRI of my brain. I had a relapse, I was stressed abit and also had ear symptom, so could have been triggered by either.


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