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MS research update – High doses of vitamin D may modify the immune system in MS – 4 January 2016

Summary

Vitamin D has several important roles in the body including regulating immune responses. However, the possible role of vitamin D in multiple sclerosis is the focus of much debate and research. This pilot study sought to investigate the effect of vitamin D on the immune system and also determine if high doses were safe to take.

40 people with relapsing remitting MS in the USA took part in the study. Each participant received either 800 IU or 10,400 IU of vitamin D3 (cholecalciferol) every day for six months. The researchers found that for the participants taking the higher dose, levels of vitamin D in the blood increased and proportion of specific immune system T-cells which are related to MS activity decreased. The higher the levels of vitamin D in the blood, the greater the reduction in the numbers of these cells.

These results are encouraging however the study was only a pilot study in a small number of people. The researchers conclude that further studies would be needed to determine the mechanism of the effect of vitamin D on the immune system and randomised controlled clinical trials could establish if vitamin D could be used as a therapy for MS.

Background

Vitamin D has several important roles in the body including regulating immune responses. However, the possible role of vitamin D in multiple sclerosis is the focus of much debate and research. Studies have shown that low levels of vitamin D appear to be associated with an increased risk of developing MS. Furthermore in people diagnosed with MS there is some evidence that lower levels of vitamin D are associated with higher relapse rates and greater disability.

Some neurologists now recommend people with MS and their families take high doses of vitamin D supplements. The immune system effects of taking a high dose of vitamin D compared to lower doses are not yet understood. This pilot study sought to investigate the effect of vitamin D on the immune system and also determine if high doses were safe to take.

How this study was carried out

40 people with relapsing remitting MS in the USA took part in the study. To be included in the study participants had to be aged between 18 and 55 years old, have a blood vitamin D level of 20–50 ng/mL (i.e. not deficient in vitamin D, which would be a level below 20).

People were not allowed to take part in the study if they had changed their disease modifying drug (DMD) in the last three months, were pregnant or had a relapse or used steroids within the last 30 days.

Participants were randomised to receive either 400 IU or 10,000 IU of vitamin D3 (cholecalciferol) every day for six months. All study participants also received a daily multivitamin that included 400 IU vitamin D3 and 1,000 mg calcium. So the final doses were 800 IU (low vitamin D group) or 10,400 IU (high vitamin D group) of vitamin D3 a day. There were no significant differences between the two groups, they each had a similar average age, gender split, EDSS score, DMD treatments and had lived with MS for a similar amount of time.

Blood tests were performed before the study started, after 3 months and 6 months to determine vitamin D levels and numbers of immune cells. Patients were interviewed by telephone every month to assess if they were still taking the supplements as instructed, if they had consumed any additional vitamin D (such as in their diet) and if they had experienced any adverse events or reactions.

What was found

The researchers found that taking high doses of vitamin D appeared to be safe. During the study there were a few adverse events but they were all minor and the numbers did not differ between the groups. The most common adverse events were nausea and high levels of calcium in the urine, which could indicate kidney problems.

The study found that for the participants taking the higher dose of supplement, levels of vitamin D in the blood increased and the proportion of specific immune system T-cells which are related to MS activity decreased. The higher the levels of vitamin D in the blood, the greater the reduction in the numbers of these cells.

What does it mean?

These results are encouraging as it shows that vitamin D may be effective against immune system activity that is associated with MS. However the study was only a pilot study in a small number of people and the numbers of people involved were too small to detect differences in MS disease activity and it had several limitations. Firstly the participants were taking a variety of DMDs, and previous research has shown that beta interferon and vitamin D may interact to complement each other and vitamin D may also have an impact on how effective a DMD is (one such study was covered in a recent research update). The researchers also found that there were a subgroup of participants where a more profound effect on the immune system was observed in those taking high dose vitamin D, however due to small numbers of participants involved, they could not do a full analysis to investigate this further, to determine what was going on and why.

The researchers conclude that further studies would be needed to determine the mechanism of the effect of vitamin D on the immune system and randomised controlled clinical trials could establish if vitamin D could be used as a therapy for MS.

Comment

This study has encouraging results, but the trial was in a small number of people and further larger trials are needed. The results appear to show that how much vitamin D you have in your blood is more important, rather than how much you take, as the higher the levels the stronger the effect on the immune system was. Before taking high doses of vitamin D you should talk with your MS team. They can check your vitamin D levels, ensure any supplements get you into a beneficial blood vitamin D level range (around 50-nmol/L has been shown in studies to be beneficial for people with MS) and also monitor you for any side effects.

Further studies are already underway to determine the effect on the immune system, to use vitamin D as an add on therapy to DMD treatment and also to see if using vitamin D as a treatment can reduce relapse rate in relapsing remitting MS. The MS Trust will report the results when they are available.

Sotirchos ES, Bhargava P, Eckstein C, et al.
Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis.
Neurology. 2015 Dec 30. [Epub ahead of print]
Abstract

More about vitamin D

Vitamin D has several important roles in the body including keeping bones and teeth strong and healthy and regulating immune responses. It can be obtained in several ways. Vitamin D3 is manufactured by the skin when it is exposed to sunlight, it can be obtained in the diet by eating food such as oily fish (including salmon and sardines) or fortified foods such as fat spreads and breakfast cereals or by taking supplements.

Its possible role in multiple sclerosis is the focus of much debate and research. It is known that multiple sclerosis is more common in countries further from the equator. As vitamin D is made in the skin, this has led to the hypothesis that low sunlight exposure and consequent low vitamin D production triggers the development of MS. There is some evidence that lower levels of vitamin D are associated with higher relapse rates and greater disability. Studies are underway to investigate both the role of vitamin D as a protective agent against the development of MS and as a treatment for people with the condition.

You can also read more about Vitamin D in the A to Z of MS.

Research by topic areas...

Disease modifying drugs

Thomas NP, Curkendall S, Farr AM, et al.
The impact of persistence with therapy on inpatient admissions and emergency room visits in the US among patients with multiple sclerosis.
J Med Econ. 2015 Dec 25:1-24. [Epub ahead of print]
Abstract

Economics

Kavaliunas A, Wiberg M, Tinghög P, et al.
Earnings and financial compensation from social security systems correlate strongly with disability for multiple sclerosis patients.
PLoS One. 2015;10(12):e0145435.
Abstract
Read the full text of this paper

Other treatments

Savin Z, Lejbkowicz I, Glass-Marmor L, et al.
Effect of fampridine-PR (prolonged released 4-aminopyridine) on the manual functions of patients with multiple sclerosis.
J Neurol Sci. 2016 Jan 15;360:102-9.
Abstract

Pathophysiology

Yaldizli Ö, Penner IK, Yonekawa T, et al.
The association between olfactory bulb volume, cognitive dysfunction, physical disability and depression in multiple sclerosis.
Eur J Neurol. 2015 Nov 19. [Epub ahead of print]
Abstract

Stone LA, Cutter GR, Fisher E, et al.
Relapse may serve as a mediator variable in longitudinal outcomes in multiple sclerosis.
J Neuroimaging. 2015 Dec 21. [Epub ahead of print]
Abstract

Psychological aspects

Król J, Szcześniak M, Koziarska D, et al.
Time perception and illness acceptance among remitting-relapsing multiple sclerosis patients under treatment.
Psychiatr Pol. 2015;49(5):911-920.
Abstract
Read the full text of this paper (PDF)

Rehabilitation

Gera G, Fling BW, Van Ooteghem K, et al.
Postural motor learning deficits in people with MS in spatial but not temporal control of center of mass.
Neurorehabil Neural Repair. 2015 Dec 23. [Epub ahead of print]
Abstract

Self-management

Jongen PJ, Sinnige LG, van Geel BM, et al.
The interactive web-based program MSmonitor for self-management and multidisciplinary care in multiple sclerosis: concept, content, and pilot results.
Patient Prefer Adherence. 2015;9:1741-50.
Abstract
Read the full text of this paper

Symptoms and symptom management

Amarenco G, Sutory M, Zachoval R, et al.
Solifenacin is effective and well tolerated in patients with neurogenic detrusor overactivity: Results from the double-blind, randomized, active- and placebo-controlled SONIC urodynamic study.
Neurourol Urodyn. 2015 Dec 29. [Epub ahead of print]
Abstract

Milinis K, Young CA; Trajectories of Outcome in Neurological Conditions (TONiC) study.
Systematic review of the influence of spasticity on quality of life in adults with chronic neurological conditions.
Disabil Rehabil. 2015 Dec 29:1-11. [Epub ahead of print]
Abstract

Zhang GQ, Meng Y.
Oral and craniofacial manifestations of multiple sclerosis: implications for the oral health care provider.
Eur Rev Med Pharmacol Sci. 2015 Dec;19(23):4610-20.
Abstract

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