Vitamin D for Multiple Sclerosis

by Jeffrey Dach MD

Many of the old time clinicians have known for decades that Multiple Sclerosis is caused by Vitamin D deficiency and MS patients benefit from taking Vitamin D.  Perhaps some MS patients have been cured simply by taking sufficient quantities of Vitamin D.

Above left image: Multiple Sclerosis. wikimedia commons.(2)

Abram Hoffer MD and Vitamin D

Years ago, I attended a medical meeting in which another attendee, a Canadian nurse, had confided in me during lunch that her son had been cured of Multiple Sclerosis by Abram Hoffer MD with Vitamin D3 as described in his book, Orthomolecular Medicine For Everyone: Megavitamin Therapeutics for Families and Physicians.  So, it is no surprise we are seeing mainstream neurology journal articles like this one from Dr. Charles Pierrot-Deseilligny of Paris France, demonstrating the benefits of Vitamin D3 for MS patients.(1)(3)

Vitamin D3 and MS Relapse Rate. 
How Much of a Reduction in Relapse Rate ?

The authors found a linear relationship between Vitamin D3 level and MS relapse rate. For every 10 nmol increase in 25-OH-D level, this was associated with a reduction in the relapse incidence rate of 13.7%. (Note: 25 ng/ml =   10 nmol/l Vitamin D)

How Much Vitamin D3 ?

They doubled the Serum Vitamin D3 levels from about 50 nmol/l before vitamin D3 supplementation to about 110 nmol/l.

Here is the data from the article: (Table 2 Data ) Table 2.

Relapse incidence rate and       incidence rate ratio.
IR1 (before D)      IR2 (after D)               IRR
Whole population   0.70 [0.62–0.79]     0.18 [0.14–0.22]      0.25 [0.20–0.32]
Group  1               0.50 [0.41–0.61]      0.16 [0.11–0.22]      0.32 [0.24–0.43]
Group 2                  0.89 [0.78–1.02]    0.20 [0.14–0.28]     0.22 [0.15–0.32]

IR,  relapse incidence rate;
IR1, before vitamin D supplementation;
IR2, under vitamin D supplementation;
IRR, incidence rate ratio, results are expressed with two-sided 95% confidence interval;

Group 1, IMT started prior to vitamin D supplementation;
Group 2, IMT started concomitantly with vitamin D supplementation;

IMT= immunomodulatory treatment.

Analysis of Data Table

Group 2 patients,  before vitamin D and before IMT ,had the highest relapse incidence rate of 0.89. These are the patients prior to any therapy at all.

Group 1 patients, on  mainstream treatment with IMT (prednisone and other drugs) had a relapse incidence rate reduced to 0.50.  This is not a bad result for mainstream treatment with prednisone and other immune suppressing drugs.

However, when vitamin D supplements are given, there is a further significant reduction in relapse incidence rate into the area of 0.16-0.20 for all patients.

Note: all patients on Vitamin D were also on IMT (immune modulating drugs, such as prednisone).  This study shows that Vitamin D reduced the relapse rate far beyond the rates achieved with IMT (mainstream treatment with prednisone (called IMT).

One might wonder about the outcome and data for Vitamin D alone, or Vitamin D and B12 injections without the (IMT) prednisone?

Vitamin B12 for MS

I should add here that MS patients may have a deficiency in B12, and may respond to B12 supplements or B12 injections with a good clinical outcome.(4-6)  Since many MS patients are treated with prednisone, which may cause gastric ulceration, there is a common practice to add various types of antacid drugs which are known to cause B12 malabsorption and B12 deficiency.  This iatragenic form of B12 deficiency may worsen the MS symptoms and MS relapse rate. (6)  In my opinion, the hydroxycobalamin or the methylcobalamin forms of B12 are superior and these should be used.   I advise against using the cyanocabalamin form of B12 since the biologically active form does not contain cyanide.  Sublingual methylcobalamin tablets are readily available in 5000 mcg dosage at the vitamin store.

More Studies on Vitamin D level and MS

Additional studies from the University of California at San Fransisco, and from Turku Finland also highlight the importance of Vitamin D levels for Multiple Sclerosis (7-8)

From U. of California study: 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. (7)

From the Finland study: “Vitamin D3 add on treatment to IFNB reduces MRI disease activity in MS”(8)

Our Program for MS patients:

1) Vitamin D3 supplementation given to reach the upper end of the normal range for serum vitamin D3.(80-100)  Do not use vitamin D2, the wrong vitamin.  Use D3.

2) Low Dose Naltrexone (4.5 mg capsule Qhs)

3) Vitamin B12 (methyl cobalamin) injections preferably 1000 mcg Im or SQ weekly.  Hydroxycobalamin is also OK.  Do not use the cyanocobalamin form, as this is less effective.

4) Gluten Free diet.- Gluten consumption has now been firmly linked to a long list of autoimmune diseases, including MS. A gluten free diet is essential for the recovery of any MS patient. See my four part article on gluten sensitivity and autoimmune disease.

Articles on Gluten: Part One, Part Two, Part Three, Part Four

Links and References

1) Ther Adv Neurol Disord. 2012 July; 5(4): 187–198.

Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation

Charles Pierrot-Deseilligny,corresponding author Sophie Rivaud-Péchoux, Pierre Clerson, Raphaël de Paz, and Jean-Claude Souberbielle
Charles Pierrot-Deseilligny, Service de Neurologie 1, Hôpital de la Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie (Paris VI), Paris, France;

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.

(2) Image Illustration at top of page by Waglione (Image:Monthly multiple sclerosis MRI.gif) [GFDL or CC-BY-SA-3.0-2.5-2.0-1.0], via Wikimedia Commons

3) http://www.ncbi.nlm.nih.gov/pubmed/20556546
Curr Neurol Neurosci Rep. 2010 Sep;10(5):389-96.
Multiple sclerosis and vitamin D: a review and recommendations. Solomon AJ, Whitham RH. Department of Neurology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, CR 120, Portland, OR 97239, USA.

A relationship between vitamin D and several diseases, including multiple sclerosis (MS), has recently received interest in the scientific community. Vitamin D appears to have important actions beyond endocrine function, particularly for the immune system. Risk of development of MS, as well as disease severity, has been associated with vitamin D in a variety of studies. There remains a need for prospective studies to further establish this relationship. Given the current evidence of the potential benefits of vitamin D, it appears to be reasonable and safe to consider vitamin D supplementation at dosing adequate to achieve normal levels in patients with MS and clinically isolated syndrome.

——————

B12 and MS

4) http://www.ncbi.nlm.nih.gov/pubmed/15896807
J Neurol Sci. 2005 Jun 15;233(1-2):93-7.
Vitamin B12, demyelination, remyelination and repair in multiple sclerosis.
Miller A, Korem M, Almog R, Galboiz Y.
Division of Neuroimmunology and Multiple Sclerosis Center, Carmel Medical Center, Haifa 34362, Israel.

Multiple Sclerosis (MS) and vitamin B12 deficiency share common inflammatory and neurodegenerative pathophysiological characteristics. Due to similarities in the clinical presentations and MRI findings, the differential diagnosis between vitamin B12 deficiency and MS may be difficult. Additionally, low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent studies suggest that vitamin B12, in addition to its known role as a co-factor in myelin formation, has important immunomodulatory and neurotrophic effects. These observations raise the questions of possible causal relationship between the two disorders, and suggest further studies of the need to close monitoring of vitamin B12 levels as well as the potential requirement for supplementation of vitamin B12 alone or in combination with the immunotherapies for MS patients.

5) http://www.ncbi.nlm.nih.gov/pubmed/8407160
Int J Neurosci. 1993 Jul-Aug;71(1-4):93-9.
Vitamin B12 and its relationship to age of onset of multiple sclerosis.
Sandyk R, Awerbuch GI.  NeuroCommunication Research Laboratories, Danbury, CT 06811.

Attention has been focused recently on the association between vitamin B12 metabolism and the pathogenesis of multiple sclerosis (MS). Several recent reports have documented vitamin B12 deficiency in patients with MS. The etiology of this deficiency in MS is unknown. The majority of these patients do not have pernicious anemia and serum levels of the vitamin are unrelated to the course or chronicity of the disease. Moreover, vitamin B12 does not reverse the associated macrocytic anemia nor are the neurological deficits of MS improved following supplementation with vitamin B12.

It has been suggested that vitamin B12 deficiency may render the patient more vulnerable to the putative viral and/or immunologic mechanisms widely suspected in MS. In the present communication, we report that serum vitamin B12 levels in MS patients are related to the age of onset of the disease.

Specifically, we found in 45 MS patients that vitamin B12 levels were significantly lower in those who experienced the onset of first neurological symptoms prior to age 18 years (N = 10) compared to patients in whom the disease first manifested after age 18 (N = 35).

In contrast, serum folate levels were unrelated to age of onset of the disease. As vitamin B12 levels were statistically unrelated to chronicity of illness, these findings suggest a specific association between the timing of onset of first neurological symptoms of MS and vitamin B12 metabolism. In addition, since vitamin B12 is required for the formation of myelin and for immune mechanisms, we propose that its deficiency in MS is of critical pathogenetic significance.

6) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386885/?tool=pubmed
BMC Med. 2012 Jun 7;10:57.

Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis.  Biswas S, Benedict SH, Lynch SG, Levine SM.  Source  Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA.

Corticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump inhibitor or antacid to prevent or ameliorate this disturbance. Additionally, patients with multiple sclerosis may be taking these medications independent of corticosteroid treatment. Interventions for gastric disturbances can influence the activation state of the immune system, a principal mediator of pathology in multiple sclerosis. Although histamine release promotes inflammation, activation of the histamine receptor-2 can suppress a proinflammatory immune response, and blocking histamine receptor-2 with an antagonist could shift the balance more towards immune stimulation.

Studies utilizing an animal model of multiple sclerosis indicate that histamine receptor-2 antagonists potentially augment disease activity in patients with multiple sclerosis. In contrast, proton pump inhibitors appear to favor immune suppression, but have not been studied in models of multiple sclerosis. Antacids, histamine receptor-2 antagonists and proton pump inhibitors also could alter the intestinal microflora, which may indirectly lead to immune stimulation. Additionally, elevated gastric pH can promote the vitamin B12 deficiency that patients with multiple sclerosis are at risk of developing. Here, we review possible roles of gastric acid inhibitors on immunopathogenic mechanisms associated with multiple sclerosis.

Vitamin D and MS

7) http://www.ncbi.nlm.nih.gov/pubmed/22926855
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.
Multiple Sclerosis Center, Department of Neurology, University of California at San Francisco, San Francisco, CA.

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.

The measured 25(OH)D levels were assessed for an association with T2 lesions on brain MRI, clinical relapses, and disability. T2 images from an MRI show both old and new inflammation on the brain since onset of MS.

The authors collected a total of 2,362 brain MRI scans from 469 patients. The researchers found that with each 10 ng/ml increase in 25(OH)D level, the risk of new T2 lesions in the brain decreased by 15%. Also, the 10 ng/ml increase was associated with a 32% lower risk of gadolinium-enhancing lesions, representing “active” lesions. They also found that higher vitamin D levels were associated with lower relapse risk, although this finding was not statistically significant (p=.037).

8) http://www.ncbi.nlm.nih.gov/pubmed/22362918
J Neurol Neurosurg Psychiatry. 2012 May;83(5):565-71. Epub 2012 Feb 22.

A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon ß-1b in patients with multiple sclerosis.
Soilu-Hänninen M, Aivo J, Lindström BM, Elovaara I, Sumelahti ML, Färkkilä M, Tienari P, Atula S, Sarasoja T, Herrala L, Keskinarkaus I, Kruger J, Kallio T, Rocca MA, Filippi M.

Department of Neurology, University of Turku, Turku, Finland.
To study the safety and efficacy of vitamin D3 as an add on therapy to interferon ß-1b (IFN in patients with multiple sclerosis (MS).
METHODS:1 year, double blind, placebo controlled, randomised study in 66 MS patients. The primary outcomes were T2 burden of disease (BOD) on MRI scans, proportion of patients with serum levels of 25-hydroxyvitamin D (25(OH)D) =85 nmol/l or intact parathyroid hormone (PTH) =20 ng/l, and number of adverse events. Secondary outcomes were number of MRI enhancing T1 lesions and new T2 lesions, annual relapse rate, changes in the Expanded Disability Status Scale score, timed 25 foot walk test and timed 10 foot tandem walk tests.

RESULTS:Median change in BOD was 287 mm(3) in the placebo group and 83 mm(3) in the vitamin D group (p=0.105).

Serum levels of 25(OH)D increased from a mean of 54 (range 19-82) nmol/l to 110 (range 67-163) nmol/l in the vitamin D group. 84% of patients reached a serum 25(OH)D level >85 nmol/l in the vitamin D group and 3% in the placebo group (p<0.0001).

Patients in the vitamin D group showed fewer new T2 lesions (p=0.286) and a significantly lower number of T1 enhancing lesions (p=0.004), as well as a tendency to reduced disability accumulation (p=0.071) and to improved timed tandem walk (p=0.076). There were no significant differences in adverse events or in the annual relapse rate.

CONCLUSION:Vitamin D3 add on treatment to IFNB reduces MRI disease activity in MS.

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