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Low vitamin D levels linked to increased multiple sclerosis risk

Thursday 27 August 2015

"Lack of vitamin D may cause multiple sclerosis, study finds," reports the Guardian. A large study found people genetically programmed to have lower vitamin D levels are at an increased risk of multiple sclerosis (MS).

MS is a condition where the immune system attacks the coating of nerves in the brain and spinal cord, leading to symptoms such as vision loss, fatigue, and difficulties with balance and co-ordination.

Our body makes vitamin D under the skin in reaction to sunlight. We also get small amounts of the vitamin from our diet in foods such as eggs and oily fish.

A link between vitamin D deficiency and an increased risk of MS has long been suspected, as the condition is more common in areas of the world with less sunlight, such as northern Scotland. But it has been difficult to prove cause and effect because other factors may be involved.

This study used a genetic approach believed to be less susceptible to the problem of confounding – where other factors influence the results.

The researchers learned four genetic variants influence vitamin D levels found in the blood. People can have different combinations of these genetic variations. They found people with a combination of the genetic variations giving them lower levels of vitamin D had double the risk of MS.

But what the study does not tell us is whether MS could be prevented in those at higher risk by increasing their vitamin D levels through taking supplements or other methods.

Find out more about the "sunshine vitamin" in our special report on the health claims made about vitamin D.

Where did the story come from?

The study was carried out by researchers from McGill University and the Jewish General Hospital in Canada; the University of Bristol and King's College London in the UK; and Massachusetts General Hospital and Harvard Medical School in the US.

It was funded by the Canadian Institute of Health Research, The Fonds de la Recherche en Santé Québec, the Lady Davis Institute, the Jewish General Hospital, and the Canadian Diabetes Association.

The study was published in the peer-reviewed journal PLOS Medicine on an open-access basis, so it is free to read online.

The UK media reported the story accurately, and many reports included reactions to the research findings from experts such as Professor Danny Altmann, an immunologist at Imperial College London. 

Professor Altmann said: "While it may be too much to expect therapeutic vitamin D to treat or reverse ongoing MS, this paper will add to the weight of argument for routine vitamin D supplementation of foodstuffs as a broad preventative public health measure." 

What kind of research was this?

This genetic study looked at whether there is an association between genetically influenced levels of vitamin D and the risk of MS.

Previous observational studies found an association between lower levels of vitamin D and MS risk. In particular, MS is more common in people living in geographical areas with reduced sunlight – vitamin D levels are increased by exposing the skin to the sun.

But these studies were unable to prove cause and effect. Questions remain, such as whether the low vitamin D caused MS, or whether vitamin D levels go down in people with MS because they have less exposure to the sun as a result of their condition.

Exposure to sunlight is just one way to increase our vitamin D levels. There is also a genetic component that will have a lifetime influence. This study specifically looked for genetic variations linked to vitamin D levels and whether these genetic variations were also associated with MS risk.

This type of study is called a Mendelian randomisation study because these genetic variations are inherited randomly (each parent will have two copies of each, which one we inherit is random). The term is named after Gregor Mendel, a pioneering 19th century scientist, widely regarded as the father of modern genetics.

The study design means confounding by other factors is not a problem.The researchers in the study took additional steps to be sure this was the case. 

What did the research involve?

The researchers identified genetic variations associated with vitamin D levels using data from the SUNLIGHT study. The Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits included blood samples from 33,996 people.

They identified four genetic variations associated with lower vitamin D levels. These were close to four genes that create products that have an effect on the level of vitamin D:

  • a protein that binds to vitamin D and carries it in the blood to target organs
  • an enzyme involved in making vitamin D in the body in response to sunlight
  • an enzyme that activates production of vitamin D
  • an enzyme that inactivates vitamin D

They then used data from the Canadian Multicentre Osteoporosis study (CaMos) of 2,347 people to confirm the effect of these four genetic variants on vitamin D levels.

The researchers used the results to investigate the risk of MS depending on the genetic variations a person carried and their genetically determined lifetime level of vitamin D using data from two studies:

  • the International Multiple Sclerosis Genetics Consortium (IMSGC), which has data from 14,498 people with MS and 24,091 healthy controls, all of European descent
  • the IMSGC/Wellcome Trust Case Control Consortium 2 (IMSGC/WTCCC2) study, which has data from 9,772 people with MS and 6,332 controls

The researchers took the following factors into account when analysing the results:

  • age
  • sex
  • body mass index (BMI)
  • time of year the blood sample was taken
  • ethnicity  

What were the basic results?

The four genetic variants associated with reduced vitamin D levels were also associated with an increased risk of MS, with three showing stronger links than the fourth. Each variant was only associated with a relatively small increase in the odds of MS (odds ratio [OR] of 1.04 to 1.11).

Each genetically determined standard deviation decrease in vitamin D levels doubled the risk of MS (OR 2.0, 95% confidence interval [CI] 1.7 to 2.5).

How did the researchers interpret the results?

The researchers concluded: "Genetically lowered 25OHD [a form of vitamin D in the blood] level is associated with an increase in the risk of MS in people of European descent."

They said that: "These findings provide rationale for further investigating the potential therapeutic benefits of vitamin D supplementation in preventing the onset and progression of MS." 


This study found people with a genetic susceptibility to having lower levels of vitamin D have an increased risk of developing MS.

What the study does not tell us is whether MS could be prevented in those at higher risk by taking steps to increase their vitamin D levels. The results also may not apply to people who are not of European descent.

Studies in healthy children and adults are now underway to explore this area. This study does not show what effect taking supplementary vitamin D would have in people who already have MS.

Previous research into vitamin D being used as a treatment for MS and to prevent relapse has been inconclusive because of small study sizes and poor methodology, so large randomised controlled trials are required.

Nevertheless, this piece of research adds to the growing picture that low levels of vitamin D appear to play some part in the development of MS.

You can usually get enough vitamin D through modest exposure of the skin to sunlight (no suntanning required) and a healthy diet that includes oily fish, eggs and foods fortified with vitamin D.

Some people may require vitamin D supplements, such as people aged 65 and over or those not exposed to much sunlight. The NHS suggests that if you take vitamin D supplements, you should not take more than 25 micrograms (0.025mg) a day as it could be harmful.

Find out more about vitamin D.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Why sunlight could protect against multiple sclerosis

The Daily Telegraph, 25 August 2015

Low vitamin-D genes linked to MS

BBC News, 26 August 2015

Lack of vitamin D may cause multiple sclerosis, study finds

The Guardian, 25 August 2015

Links to the science

Mokry LE, Ross S, Ahmad OS, et al.

Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study

PLOS Medicine. Published online August 25 2015