The possible role of vitamin D in multiple sclerosis is the focus of much debate.
There is evidence that low levels of vitamin D are associated with an increased risk of getting MS. In established MS, low levels of vitamin D have been associated with relapses and increased disability.
So far, initial studies have failed to show that taking supplements to increase vitamin D levels will reduce the risk of getting MS or reduce the severity of MS. Larger studies are underway to further evaluate vitamin D supplementation.
While results from these larger studies are awaited, some MS neurologists are recommending that people with MS and family members supplement with 4000-5000 IU/day vitamin D but opinions vary widely as to whether this is appropriate.
Since the 1920s, vitamin D has been known to have an important role in maintaining healthy bones.
In recent years, studies of vitamin D have expanded and it has been shown to have important effects throughout the body, including the regulation of immune system responses. These additional effects appear to require vitamin D blood levels which are considerably higher than those found in the general population. Low vitamin D levels have been associated with a wide range of conditions including heart disease, diabetes, cancer and multiple sclerosis. This finding has led some clinicians to conclude that significantly increasing vitamin D intake may reduce the incidence or course of these conditions. Others have urged caution, pointing out that, beyond a role in bone health, there is little direct evidence for a beneficial effect of vitamin D supplementation.
The possible role of vitamin D in multiple sclerosis is the focus of much debate and research has focused on two areas:
- does vitamin D affect the risk of getting MS?
- does vitamin D affect the course of MS?
As well as finding answers to these two questions, research is needed to establish appropriate doses of vitamin D, who is most likely to benefit, and when treatment will be most effective.
The term 'vitamin D' generally refers to two very similar molecules. Vitamin D3, also known as cholecalciferol, is created by skin cells in response to ultraviolet B light. Vitamin D2, or ergocalciferol, occurs naturally in some mushrooms and yeast.
The body converts both forms of vitamin D to 25-hydroxyvitamin D (25D). Tests to assess vitamin D status measure levels of 25D in the blood.
25D is itself converted to the biologically active form 1,25-dihydroxyvitamin D, also known as calcitriol.
Sources of vitamin D
For most people the most important source of vitamin D is through exposure of the skin to sunlight. In a fair skinned person, 20 to 30 minutes of sunlight on the face and forearms at midday repeated two or three times a week are estimated to generate sufficient vitamin D in the summer in the UK. This should be less than the amount of time needed for skin to redden and burn; excessive sun exposure carries a risk of skin cancer.
For six months of the year (October to April) the sunlight in the UK is not strong enough for the skin to make sufficient vitamin D. The amount of vitamin D generated by sunlight exposure is reduced for people with darker skin, in older or obese people and those who use sunscreen.
Only a relatively small number of foods contain substantial amounts of vitamin D. Oily fish, including salmon, mackerel and trout contain the largest amounts of vitamin D3. Cod liver oil is a rich source of vitamin D3. Smaller amounts are found in eggs.
Vitamin D2 occurs naturally in some mushrooms (for example shiitake and chanterelle) and yeast. The amount in most vegetables is negligible.
Some foods, such as breakfast cereals and margarine, have vitamin D added during manufacture.
Vitamin D supplements are measured in both micrograms (µg or mcg) and International Units (IU).
1 microgram (µg or mcg) is equivalent to 40 IU of vitamin D2 or D3.
There are two types of vitamin D supplements: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D3 produces higher and more sustained blood levels of 25D and is generally recommended over vitamin D2.
How much vitamin D should I take?
Vitamin D status is determined by measuring the amount of 25D in the blood. The following categories for blood levels of 25D have been proposed:
greater than 75 nmol/l
less than 25 nmol/l
Using these levels, a UK study reported that more than half of the adult population have insufficient levels of vitamin D and that 16% have deficient levels during winter and spring. While there is general agreement that levels below 25 nmol/l qualify as deficient, there is no standard definition of optimal 25D levels.
If you are concerned about your vitamin D levels, speak to your doctor.
In the UK, a recommended dietary intake has not been set for the general population. The Department of Health advises that most people should be able to get all the vitamin D they need from their diet and by getting a little sun.
A daily 400 IU (10 micrograms) vitamin D supplement is recommended for:
- pregnant and breastfeeding women
- people aged 65 and over
- people with low sun exposure such as those who stay indoors a lot, or cover up when outside.
A daily vitamin D supplement of 280 IU (7 micrograms) is recommended for:
- children aged 6 months to 5 years.
Pregnant women and children who qualify for the Healthy Start program can get free supplements containing vitamin D.
There is concern that the recommended daily amounts of vitamin D, which are based on maintaining healthy bones, may be too low to achieve blood levels now considered necessary for the broader health benefits of vitamin D. Consequently, there have been calls for national and international agencies to increase dietary recommendations.
In July 2012, the European Food Safety Authority (EFSA) proposed a Tolerable Upper Intake Level of 4000 IU (100 micrograms) per day for vitamin D in adults and children over 11. This is the amount that can be taken daily without causing harm.
A comprehensive review carried out by the Institute of Medicine, part of the US National Academy of Sciences, concluded that adequate levels of vitamin D could be achieved with 600 IU/day (800 for those older than 70), which most people would be able to get from sunlight and diet without the need for vitamin D supplements.
A working group of the Scientific Advisory Committee on Nutrition (a committee of independent experts which advises the Department of Health and other government agencies) has published draft guidelines that people in the UK should have a dietary intake of 10 micrograms (400IU) of vitamin D per day. This level is based on protecting musculoskeletal health in the general population rather than any effect on MS. After a consultation period, this guidance is due to be published in 2016.
Some MS neurologists are now recommending that people with MS and their family members take 4000-5000 IU vitamin D per day, some propose lower doses of between 800-3000 IU/day, while others advise waiting for more evidence of effectiveness from clinical trials before taking supplements.
Vitamin D and MS
Does vitamin D affect the risk of getting MS?
The causes of MS still remain unclear. It is generally agreed that some people have a genetic makeup that predisposes them to MS and that one or more environmental factors act as a trigger which sets off a chain of events leading to them developing MS. Some studies have suggested that these environmental factors may act before birth and/or during the early years.
While the evidence to support an involvement of vitamin D as a trigger for MS is still not conclusive, a number of studies suggest that there may be a connection. This has led to the theory that, for people with a pre-existing genetic predisposition to MS, low sunlight exposure leads to low vitamin D production which in turn leads to an increased risk of developing MS.
Geographical distribution of MS
Many studies have shown that the number of people with MS increases with distance from the equator. In the UK, a higher prevalence of MS is found in Scotland than in England. The reverse is seen for blood levels of vitamin D, with higher levels being found in people living closer to the equator and lower levels found with distance from the equator. A north-south gradient has been reported for vitamin D levels in the UK.
Sun exposure and risk of MS
Low levels of sun exposure, particularly during childhood, have been linked to the risk of developing MS. A study of 79 pairs of identical twins (who therefore have the same genetic makeup), where only one of the twins had MS, found that the twin who developed MS had significantly lower exposure to the sun during childhood, assessed on the basis of nine different activities implying sun exposure. In another study, when a group of people with MS were compared to another group without MS, the risk of MS was found to be lower in those who in their childhood had been exposed to sunlight during their holidays and weekends, a finding that was confirmed by skin changes indicating cumulative sun exposure.
Vitamin D levels and risk of MS
The study, led by researchers from McGill University in Montreal, identified genes associated with lower vitamin D levels. They used information form the International Multiple Sclerosis Genetics Consortium study, which involved almost 15,000 people with MS and 24,000 healthy controls, and found that there was an association between genetically reduced vitamin D levels and susceptibility to MS.
A review of blood samples taken from US military personnel when they enlisted found that levels of vitamin D in those who subsequently developed MS were lower than levels in those without the condition. Another study of nurses found that those who had lower levels of vitamin D from diet or supplements were more likely to develop MS.
A number of studies have drawn a connection between vitamin D levels in mothers and subsequent risk of developing MS in their children. Studies have found that more people with MS than would be expected are born in April and May than in October and November. This mirrors research in Australia where, with the seasons reversed, November was the higher risk month and April the lower. For babies born in spring, later stages of the pregnancy will have coincided with the darkest months of the year. The suggestion is that decreased exposure to the sun during winter pregnancies results in low maternal vitamin D levels which in some way increases the risk of developing MS later in life for children who are genetically susceptible.
Do vitamin D supplements reduce the risk of getting MS?
Some studies suggest that low vitamin D levels before birth and/or the early years may increase the risk of developing MS in later life. To fully investigate the role of vitamin D it would be necessary to design a trial starting in pregnancy or early childhood with a large number of participants monitored for many years. The complexity and cost of carrying out such a study makes it unlikely to happen. Investigating people at higher risk of developing MS, such as first degree relatives of someone with MS, would be a more practical approach but at the present time there are no studies of this type underway or planned.
Another group at greater risk of developing MS is those who have had a first episode of neurological symptoms (clinically isolated syndrome, CIS). One small study investigated the effect of vitamin D3 supplementation on conversion of optic neuritis to clinically definite MS. 30 participants with optic neuritis and low blood levels of vitamin D (30 ng/ml) took part; 15 people received 50,000 IU vitamin D3 per week (equivalent to 7000 IU per day), 15 received placebo for 12 months. During the 12 months of the study, none of the vitamin D group experienced a second episode of symptoms suggestive of MS while five of the placebo group did, leading to a diagnosis of confirmed MS. The researchers concluded that giving vitamin D supplements to people with optic neuritis who also have low blood levels of vitamin D reduces the risk of conversion from CIS to full MS.
A larger study (approximately 300 participants) plans to investigate whether vitamin D supplements (100,000 IU every 2 weeks, equivalent to 7000 IU/day) for up to 2 years will reduce the risk of conversion from CIS to full MS. The study is expected to finish in June 2017.
The PrevANZ study in Australia and New Zealand (160 participants initially) will test whether daily doses of 1000, 5000 and 10000 IU vitamin D or placebo for 48 weeks after a first episode of symptoms can prevent or delay the time to a definite diagnosis of MS. Results of this study are also expected in 2017.
Does vitamin D affect the course of MS?
Levels of vitamin D in people with MS
Studies have reported lower vitamin D levels associated with relapses or increased disability. Although this suggests a link between more active MS and low vitamin D levels there could be a number of explanations for this linkage, including:
- low vitamin D levels cause more active MS
- more active MS causes low vitamin D levels (for example someone with more active MS may be less likely to spend time outdoors in the sun)
- a third unknown factor causes more active MS and also low vitamin D levels (but MS activity and vitamin D levels are not directly related)
Do vitamin D supplements affect the course of MS?
Despite the accumulating evidence to support a role of vitamin D in MS, only a few studies have directly measured the effect of vitamin D supplements on MS activity. The trials have been small (10-62 people), used a wide range of doses (from 1000-40,000 IU/day), different forms of vitamin D (D2 and D3) and generated variable results, making it difficult to draw conclusions.
A number of studies looking at the effect of vitamin D supplements in relapsing remitting MS, are currently underway or planned, with study completion in 2014-15:
- vitamin D as an add-on to injectable disease modifying treatments
- vitamin D as a treatment to reduce relapse rate in relapsing remitting MS
Studies of the role of vitamin D supplements on secondary or primary progressive MS are not currently planned.
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Last updated: 21 July 2016
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