Here is my letter the corresponding author. He is part of the group in Berlin (Clinical and Experimental Research Center for Multiple Sclerosis, Charité - Universitätsmedizin Berlin) conducting a major study of the effectiveness of vitamin D supplementation in managing MS. Title:
Can we prevent or treat multiple sclerosis by individualised vitamin D supply?
Hello Herr Dr. Dörr,
I am pleased that you and your colleagues are close to recommending D3 minimum blood
level of 125nmol/L for people with Multiple Sclerosis. This is my recommendation, which
is widely read and supported on the internet:
http://www.thisisms.com/forum/chronic-c ... 5-345.html
My background concerning MS has been documented by a broadsheet UK newspaper:
http://www.telegraph.co.uk/health/78823 ... elief.html
http://www.telegraph.co.uk/health/83598 ... minds.html
I attach three abstracts which lead me to conclude that 125 nmol/L should be
the minimum blood level, rather than 75-100 nmol/L you suggest. I trust that
when you study these papers you will agree that the positive effect of vitamin
D3 in people with MS may reach a plateau at 110-120 nmol/L (Abstract 1).
Also that high blood (above 100nmol/L) levels are beneficial (Abstracts 2 & 3).
As an experienced pharmaceutical analyst, taking a pragmatical point of view
and considering available data on efficacy, safety, tolerability, and the very low
cost of vitamin D3. It seems to be rational to monitor and control 25(OH)VD
levels in MS patients to at least 125 nmol/L (50 ng/ml), either by appropriate
sun exposure or, for most Europeans and North Americans, adequate vitamin
D3 supplementation. This must happen forthwith and prior to further clinical
trials as the economic costs of MS far outweigh those of vitamin D3
supplementation and monoriting. The imperative of vitamin D3
supplementation in Scotland has been noted by Prof George Ebers on
the BBC (
http://www.bbc.co.uk/news/uk-scotland-16255661). I hope that
you and your colleagues will update your findings publically in the coming
weeks. Then your review may be cited as a pivitol paper for the addition
of vitamin D3 to the lives of people with Multiple Sclerosis.
In answer to your question:
We can mitigate multiple sclerosis relapses by individualised vitamin D
supply. I have developed a plan to target vitamin D supply to those at
increased risk of MS, in order to mitigate the rising incidence of MS.
However, that is a further step after the best minimum blood level of
25(OH)VD is agreed, which my goal in writing to you.
Kind Regards,
Mark
Mark Walker
Posted on 'This is MS' website.
CC: Prof George Ebers
ABSTRACT ONE -----------------------------------------------------------------------------------
Ther Adv Neurol Disord. 2012 Jul;5(4):187-98.
Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients
before and after vitamin D supplementation.
Pierrot-Deseilligny C, Rivaud-Péchoux S, Clerson P, de Paz R, Souberbielle JC.
Service de Neurologie 1, Hôpital de la Salpêtrière, Assistance Publique-Hôpitaux de
Paris, Université Pierre et Marie Curie (Paris VI), Paris, France.
Abstract
BACKGROUND:
Vitamin D could play a protective role in multiple sclerosis.
METHODS:
In an observational, uncontrolled study, vitamin D3 supplementation (3010 IU/day on
average) was given to 156 consecutive patients with relapsing-remitting multiple
sclerosis, under first-line immunomodulatory therapy and with initial 25-OH-D serum
level lower than 100 nmol/l (40 ng/ml). Relapses were determined for 29.1 ± 8.4 months
during vitamin D and 29.8 ± 10.1 months before supplementation. The 25-OH-D level
was measured before supplementation and several times during supplementation. The
incidence rate of relapses before and during supplementation was estimated using
negative binomial regression models with follow-up durations as offset terms. The
incidence rate and incidence rate ratio of relapses at various 25-OH-D levels were
also calculated using negative binomial regression models.
RESULTS:
In 76 patients, immunomodulatory therapy preceded vitamin D supplementation (by 4.2
± 2.7 years) and in 80 patients both treatments were started simultaneously. Under
supplementation, the 25-OH-D level increased from 49 ± 22 nmol/l to 110 ± 26 nmol/l
on average. Pooling data collected before and during supplementation, we found a
significant strong inverse relationship between the relapse incidence rate and the
25-OH-D level (p < 0.0001), suggesting that vitamin D did indeed influence the relapse
rate. Results of univariate, bivariate and multivariate analyses were analogous:
in the multivariate model adjusted for age, disease duration and previous use of
immunomodulatory therapy, every 10 nmol increase in 25-OH-D level was associated
with a reduction in the relapse incidence rate of 13.7%. Dividing iteratively the
population made up of pooled periods into two subgroups according to the 25-OH-D
levels, the relapse incidence rate ratio decreased as the 25-OH-D level increased
up to 110 nmol/l, but a plateau effect was observed beyond this limit.
CONCLUSION:
Further studies are warranted for accurate quantification of the vitamin D effect.
PMID: 22783368 [PubMed]
PMCID: PMC3388527
Free PMC Article
http://www.ncbi.nlm.nih.gov/pmc/article ... ool=pubmed
---------------------------------------------------------------------------------------------------------
ABSTRACT TWO ------------------------------------------------------------------------------------
Neurology. 2012 Jun 13. [Epub ahead of print]
Lower serum vitamin D levels are associated with a higher relapse risk in multiple
sclerosis.
Runia TF, Hop WC, de Rijke YB, Buljevac D, Hintzen RQ.
Source
From the Department of Neurology, MS Centre ErasMS (T.F.R., D.B., R.Q.H.), Department
of Biostatistics (W.C.J.H.), and Departments of Clinical Chemistry and Internal Medicine
(Y.B.d.R.), Erasmus MC, Rotterdam, the Netherlands.
Abstract
OBJECTIVE:
There is increasing evidence that vitamin D can be protective against the development
of multiple sclerosis (MS), but it may also be beneficial for the clinical course
of the disease. Our objective was to prospectively investigate if 25-hydroxy-vitamin
D (25-OH-D) levels are associated with exacerbation risk in MS in a study with frequent
serum measurements.
METHODS:
This was a prospective longitudinal study in 73 patients with relapsing-remitting
MS. Blood samples for 25-OH-D measurements were taken every 8 weeks. Associations
between 25-OH-D levels and exacerbation rates were assessed using Poisson regression
(generalized estimating equations) with the individual serum levels as time-dependent
variable.
RESULTS:
During follow-up (mean 1.7 years), 58 patients experienced a total of 139 exacerbations.
Monthly moving averages of 25-OH-D levels were categorized into low (<50 nmol/L),
medium (50-100 nmol/L), and high (>100 nmol/L) levels. Exacerbation risk decreased
significantly with higher serum vitamin D levels: respective relative exacerbation
rates for the medium and high-level category as compared to the low-level category
were 0.7 and 0.5 (p value for trend: p = 0.007). The association between 25-OH-D
concentrations and exacerbation rate was log linear without a threshold. With each
doubling of the serum 25-OH-D concentration the exacerbation rate decreased by 27%
(95% confidence interval 8%-42%, p = 0.008).
CONCLUSIONS:
Our finding that higher vitamin D levels are associated with decreased exacerbation
risk in relapsing-remitting MS suggests a beneficial effect of vitamin D on disease
course in MS. However, the possibility of reverse causality cannot be ruled out completely.
Randomized intervention studies are therefore needed to investigate the effect of
vitamin D supplementation in MS.
PMID: 22700811
-----------------------------------------------------------------------------------------------
ABSTRACT THREE ------------------------------------------------------------------------
Ann Neurol. 2012 Aug;72(2):234-40. doi: 10.1002/ana.23591.
Vitamin D status predicts new brain magnetic resonance imaging activity in multiple
sclerosis.
Mowry EM, Waubant E, McCulloch CE, Okuda DT, Evangelista AA, Lincoln RR, Gourraud
PA, Brenneman D, Owen MC, Qualley P, Bucci M, Hauser SL, Pelletier D.
Source
Multiple Sclerosis Center, Department of Neurology, University of California at San
Francisco, San Francisco, CA.
emowry1@jhmi.edu.
Abstract
OBJECTIVE:
We sought to determine whether vitamin D status is associated with developing new
T2 lesions or contrast-enhancing lesions on brain magnetic resonance imaging (MRI)
in relapsing multiple sclerosis (MS).
METHODS:
EPIC is a 5-year longitudinal MS cohort study at the University of California at San
Francisco. Participants had clinical evaluations, brain MRI, and blood draws annually.
From the overall cohort, we evaluated patients with clinically isolated syndrome
or relapsing-remitting MS at baseline. In univariate and multivariate (adjusted for
age, sex, ethnicity, smoking, and MS treatments) repeated measures analyses, annual
25-hydroxyvitamin D levels were evaluated for their association with subsequent new
T2-weighted and gadolinium-enhancing T1-weighted lesions on brain MRI, clinical relapses,
and disability (Expanded Disability Status Scale [EDSS]).
RESULTS:
A total of 2,362 3T brain MRI scans were acquired from 469 subjects. In multivariate
analyses, each 10ng/ml higher 25-hydroxyvitamin D level was associated with a 15%
lower risk of a new T2 lesion (incidence rate ratio [IRR], 0.85; 95% confidence interval
[CI], 0.76-0.95; p = 0.004) and a 32% lower risk of a gadolinium-enhancing lesion
(IRR, 0.68; 95% CI, 0.53-0.87; p = 0.002). Each 10ng/ml higher vitamin D level was
associated with lower subsequent disability (-0.047; 95% CI, -0.091 to -0.003; p
= 0.037). Higher vitamin D levels were associated with lower, but not statistically
significant, relapse risk. Except for the EDSS model, all associations were stronger
when the within-person change in vitamin D level was the predictor.
INTERPRETATION:
Vitamin D levels are inversely associated with MS activity on brain MRI. These results
provide further support for a randomized trial of vitamin D supplementation. ANN
NEUROL 2012;72:234-240.
Copyright © 2012 American Neurological Association.
PMID: 22926855
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http://www.epmajournal.com/content/4/1/4#B128
Conclusions
In this review article, which follows the recommendations of the “EPMA White Paper”
[128], we summarise and discuss available data on the role of VD for the development
and disease course of MS. Many lines of evidence, in particular epidemiologic data,
preclinical investigations, animal studies, and association studies on VD status
and disease activity, suggest that higher serum concentrations of VD are beneficial
in terms of the risk to develop MS as well as the further course of the disease in
already-established MS. Moreover, VD supplementation is safe, cheap, and convenient
to perform. Therefore, it is intriguing to hypothesise that boosting the VD serum
levels would be an option to both prevent and treat MS. Despite the inherent methodological
drawbacks of epidemiologic studies, existing data on the preventive capacity of higher
VD levels are quite compelling. Final proof of this hypothesis would be reached by
large-scale prospective epidemiological studies which will probably not be available
in the near future, for obvious reasons. With respect to the therapeutic efficacy,
an association between higher VD serum concentrations and a favourable disease course
has been conclusively shown. Unfortunately, the so-far performed interventional trials,
though not negotiating this hypothesis, also do not unambiguously support the idea
that raising patients' VD levels would be favourably in terms of disease outcome.
Hopefully, ongoing (Table 2) and future trials will shed more light on this aspect.
But, how are we going to deal with this issue in the meantime? From a pragmatical
point of view and considering available data on efficacy, safety, tolerability, and
last but not least costs, it seems to be reasonable to regularly control 25(OH)VD
levels in MS patients, especially during winter months. In patients with inadequate
VD, levels should be raised to at least 30–40 ng/ml (75–100 mmol/l), either by appropriate
sun exposure and/or adequate VD supplementation. As a rule of thumb, supplementary
1 μg (40 IU) cholecalciferol will increase 25(OH)VD levels by 1 ng/ml (2.5 nmol/l).
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