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Study Strengthens Link Between Low Vitamin D Levels and Risk of MS

SUMMARY

  • A study based on stored blood samples of 800,000 pregnant Finnish women found that vitamin D levels might predict who is at risk for later developing MS.
  • Vitamin D blood levels of 1,092 women later diagnosed with MS were compared to those of 2,123 women around the same age and region who did not develop the disease.
  • Women who developed MS later had average D levels lower than the women who didn’t.
  • More research is needed on how to best supplement vitamin D and to know whether and who it might help. Read more more about Vitamin D and MS.
  • The study was published on September 13, 2017 in Neurology.

DETAILS
Background: Researchers believe that several genetic and environmental factors influence whether a person will get MS. These factors may also impact the severity of the disease. Scientists are eager to find risk factors for MS that can be modified to possibly prevent MS and reduce disease activity. Research is increasingly pointing to reduced levels of vitamin D in the blood as a risk factor for developing MS, and studies are underway to determine if vitamin D levels influence MS disease activity.

This Study: This study — the largest such study to date – took advantage of a unique resource: stored blood samples from 800,000 Finnish women who had undergone routine prenatal testing during pregnancy. The study was designed to determine whether and to what extent vitamin D deficiency is associated with future risk of developing MS. The team identified 1,092 of the women who were later diagnosed with MS. The researchers compared their vitamin D levels to those of 2,123 women who were about the same age and lived in the same area but did not develop MS. Of those women whose medical records were available for examination, an average of 9.5 years had lapsed between the time of the first blood sample and the date of an MS diagnosis. For this study, classifications of blood levels of vitamin D (25-hydroxyvitamin D) included “deficient” (less than 30 nmol/L) and “adequate” (greater than or equal to 50 nmol/L).

Results: The team found that overall as vitamin D levels increased, the risk of later developing MS decreased. Women with the greatest deficiency in vitamin D had a twofold increase in the risk of developing MS, and those with the highest vitamin D levels had the lowest risk of a later MS diagnosis. Most of the women in the study were considered to have deficient or insufficient levels of vitamin D. Of the women who developed MS, 58 percent had deficient levels of vitamin D, compared to 52 percent of the women who did not develop the disease.

The researchers conclude that the results directly support vitamin D deficiency as a risk factor for MS and that correcting this among reproductive age women may reduce their future risk of developing MS. In addition, a previous study of this same group of women found that maternal vitamin D deficiency during pregnancy doubled the risk of MS in their offspring, and a Danish study found that low vitamin D levels in infants was associated with an increased MS risk in adulthood, suggesting that improving a woman’s vitamin D levels during pregnancy may also reduce the risk of MS in her children.

The study, by a team including Drs. Kassandra Munger and Alberto Ascherio (Harvard T. H. Chan School of Public Health in Boston), was published on September 13, 2017 in Neurology.

Comment: This largest study of its kind to date adds to growing evidence that low levels of vitamin D increase the likelihood of developing MS. Since this study included only women, who were mostly white, the results may not apply to men or to other racial groups. It also did not account for other potential risk factors that may have played a role.

An editorial in the same issue of Neurology by Drs. Ruth Ann Marrie Christopher Beck addresses the question of whether there is enough evidence now to make sweeping recommendations on vitamin D supplementation. They note, “Vitamin D supplementation is a simple intervention that would be highly cost-effective even if it prevents only a proportion of MS cases…,” concluding, “It is time to take an active approach to preventing MS, at a minimum targeting those individuals with an elevated risk of MS, including smokers, the obese, and those with a family history of MS.”  Read more more about Vitamin D and MS

 

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Studies Uncover Possible New Factors That Alter a Person’s Risk for Developing MS

Two recent studies have uncovered new lifestyle factors that may influence whether a person develops multiple sclerosis or not:

Harvard researchers — including National MS Society-funded Dr. Cassandra Munger — reported that children whose mothers were deficient in vitamin D during pregnancy may have nearly twice the risk of developing MS. Additional research is needed to confirm and understand this finding.

On the flip side, researchers at the Karolinska Institute in Sweden and Johns Hopkins University reported that people who drank about four cups of coffee daily had a lower risk of developing MS compared to those who did not drink coffee. Further research is needed to understand this link.

MORE: Research on risk factors is complicated, and cause and effect are difficult to establish. It’s important to note that not every mother with low levels of vitamin D will have a child who develops MS, and not everyone who drinks large amounts of coffee will avoid developing MS.

Read more about risk factors for MS

Small Pilot Trial Suggests High-Dose Vitamin D is Safe and Regulates Immune Responses in People with MS

Summary
• High-dose vitamin D supplementation increased vitamin D levels in the blood, was safe and tolerable, and reduced the proportion of immune cells that are thought to drive disease, in a small study of 40 people with relapsing-remitting MS.
• The trial was too small to detect differences in disease activity, but a larger Society sponsored trial of vitamin D supplementation is currently recruiting participants.
• The team (Elias S. Sotirchos, MD, Pavan Bhargava, MD, Peter A. Calabresi, MD, and colleagues, Johns Hopkins University School of Medicine, Baltimore) has published results in Neurology. Dr. Bhargava was funded by a Sylvia Lawry Physician Fellowship from the National MS Society.

Background: Multiple sclerosis involves immune attacks on the brain and spinal cord. A number of genetic and environmental factors influence whether a person will develop MS. These factors may also impact the severity of the disease. There is growing scientific evidence that low levels of vitamin D in the blood are a risk factor for developing MS. In lab mice, vitamin D can reduce the effects of EAE, an MS-like disease, and some evidence suggests it may impact ongoing disease activity in people who have MS.

An important initial step to pursuing this lead was to determine whether taking large doses of vitamin D was safe and provides any hints of impact against the immune activity that is associated with MS. A team at Johns Hopkins University undertook this preliminary step to determine whether a larger-scale clinical trial was warranted.

The Study: Investigators randomly assigned 40 people with MS to receive either 800 IU of vitamin D, or 10,400 IU, daily for six months (nutritional supplementation is typically 600 IU). Participants were maintained on standard disease modifying treatment throughout the course of the study. Blood tests were done at three and six months to determine whether the dose increased the levels of vitamin D in the blood, and immune system effects. Blood and urine were assessed for calcium levels, since an excess of calcium can be a side effect of high-dose vitamin D supplementation. The primary goals of this study were to determine safety and effects on immune activity markers.

The investigators reported a few adverse events that did not differ between the groups, and they were all minor.

Vitamin D levels increased more in the high-dose group, to a level that has been suggested as the optimal target for people with MS. Immune cells known as Th17 cells – which have been suggested to be major players in the immune attack on the brain and spinal cord in MS – were reduced in the high-dose group, but not in the low-dose group. Investigators also found that the higher the levels of vitamin D in the blood, the greater the reduction of Th17 cells.

Results were published in Neurology (published early online, December 30, 2015).

Next Steps: This team is now conducting a larger trial at several centers nationwide, in which they are recruiting 172 people with relapsing-remitting MS to compare the effectiveness of 600 IU of vitamin D supplementation versus 5000 IU vitamin D supplementation at reducing MS disease activity, when added to standard therapy with glatiramer acetate (Copaxone®, Teva Pharmaceutical Industries). The study is funded by a research grant from the National MS Society, with support from the Society’s Greater Delaware Valley Chapter.

Further research in the laboratory also is suggesting that vitamin D’s capabilities go beyond immune regulation. Read more

Read more about the larger, ongoing study
Read more about research on vitamin D and MS

Study Identifies Gene Linked to Vitamin D Deficiency

A recent study at Oxford University in England and published in Annals of Neurology, has identified a gene that causes vitamin D deficiency, a condition suspected of having a role in the development of MS.

The study examined the DNA of a group of people with MS who also have a large number of family members with the disease. All the DNA samples showed a distortion of the CYP27B1 gene which controls vitamin D levels in the body. And in a few rare cases where the DNA showed two copies of the distorted gene, the person was found to have a genetic form of rickets caused by vitamin D deficiency as well as MS.

The cause of myelin damage related to MS is still hotly debated: some believe it to be an autoimmune disease while others cite viruses or the environment as the culprit. There is growing evidence however of a correlation between MS and vitamin D deficiency. Epidemiological studies also show that populations closer to the equator and the sun, have far fewer case of MS than populations closer to the north or south poles. Researchers at Oxford University have now taken this premise a step further by showing that vitamin D deficiency and therefore possibly MS could have a genetic cause.

Despite this pivotal link, not all people with vitamin D deficiency develop MS. More research is needed to fully understand why. However, a distortion of the CYP27B1 gene is increasingly apparent in MS cases and it’s possible that the gene generates other, yet undetected, complications that lead to the disease—such as genetically caused rickets.

“Although vitamin D deficiency doesn’t always cause MS, it unveiled a critical genetic source that could be causing other problems that lead to MS,” says Jeffrey Epstein, whose foundation partially supported the study. “Even if we don’t understand all of the implications of that gene’s distortion, research can focus on gene therapy, and that will accelerate a cure.”

The study was partly funded by the National Multiple Sclerosis Society, The Wellcome Trust and the support of science investor, Jeffrey Epstein and The Jeffrey Epstein VI Foundation.

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Trial of Vitamin D Supplementation Recruiting People with Relapsing-Remitting MS

Summary: Investigators at several centers nationwide are recruiting 172 people with relapsing-remitting MS to compare the effectiveness of the current recommended amount of vitamin D supplementation versus high dose vitamin D supplementation at reducing MS disease activity, when added to standard therapy with glatiramer acetate (Copaxone®, Teva Pharmaceutical Industries). The principal investigator is Ellen Mowry, MD, MCR (Johns Hopkins University, Baltimore) and the study is funded by a research grant from the National MS Society, with partial support from the Society’s Greater Delaware Valley Chapter.

Rationale: A number of genetic and environmental factors influence whether a person will get MS. These factors may also impact the severity of the disease. Research is increasingly pointing to a reduced level of vitamin D in the blood as a risk factor for developing MS. In lab mice, vitamin D can reduce the effects of EAE, an MS-like disease, and growing evidence suggests it is time to test whether vitamin D can provide benefits to people who have MS.

Eligibility and Details: Participants should be between the ages of 18 and 50, and diagnosed with relapsing-remitting MS. Participants must be willing to stop taking additional supplemental vitamin D, except as part of a multivitamin, and must be willing to not take cod liver oil. More details on the enrollment criteria are available from the website and contacts below.

Participants will begin standard Copaxone treatment daily and will be randomly assigned to take either 600 IU (the current recommended daily allowance) or 5000 IU of vitamin D. The primary goal of the study is to determine the effects on reducing the proportion of people who experience a relapse. Other outcomes being studied include relapse rate, quality of life, brain tissue volume, disability progression, and excess calcium levels in the blood (a possible side effect of high doses of vitamin D).

Contact: To learn more about the enrollment criteria for this study, and to find out if you are eligible to participate, please see: http://www.clinicaltrials.gov/ct2/show/NCT01490502, or e-mail vitamindtrialms@jhmi.edu.

Sites are active in the following cities, and more may be added; please refer to the above link to the clinicaltrials.gov listing for the latest information:

San Francisco, California
Baltimore, Maryland
St. Louis, Missouri
Portland, Oregon

Download a brochure that discusses issues to think about when considering enrolling in an MS clinical trial (PDF).

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