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Vitamin D Deficiency In MS: What The Genetic Link Means

For nearly a decade researchers worldwide have been investigating a link between vitamin D deficiency and autoimmune diseases, particularly multiple sclerosis (MS). In patients with the autoimmune hyperthyroid disorder Graves' disease the link has been explored even further with evidence suggesting that genetic polymorphism of the vitamin D receptor sometimes seen in patients with Graves' disease prevents adequate absorption of the vitamin D hormone. Whether the problem in autoimmune diseases is one of poor vitamin D absorption or the fact that labs have difficulty measuring vitamin D effectively in general, a number of studies have shown that vitamin D levels are often deficient or inadequate in patients with multiple sclerosis and other autoimmune disorders. In 2008, after finding low levels of vitamin D in children with MS, the American Academy of Pediatrics raised the minimum amount of vitamin D recommended for children.

In the latest study reporting vitamin D deficiency in multiple sclerosis published in PLoS Genetics in February 2009, researchers from the University of Oxford and the University of British Columbia demonstrated a genetic link for this observed hormone deficiency. Previous studies have shown that the immune system gene HLA-DRB1 on chromosome 6 is commonly seen in patients with MS. Among Northern Europeans who have this gene, the most common variant, out of 400 possible variations, is HLA-DRB1*1501. Individuals with this allele have been reported to have a three-fold greater risk of developing MS.
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Vitamin and Supplements

University of Oxford researchers George Ebers and Julian Knight report in this study that HLA-DRB1*1501 contains a receptor or switch that is activated by one form of vitamin D. This switch or vitamin D response element is not seen in other variants or alleles of the HLA-DRB1 gene that are not associated with MS. The researchers hope that testing for this gene variant can help in showing risk for vitamin D deficiency associated with MS.

Like other immune system genes, HLA-DRB1 determines which protein antigens the immune system will react with, and it determines the severity of the immune system's response to a particular antigen. To further complicate matters, other HLA antigens can offer protection and prevent certain immune system reactions, particularly to the body's own proteins (the situation in autoimmune diseases), from occurring. If vitamin D deficiency in MS isn't a lab anomaly related to measuring the inactive hormone and it is truly related to disease development, the question still remains whether the problem is one of inadequate absorption of vitamin D or poor hormone conversion.

As a result of this study's release, sales of vitamin D supplements in Scotland, where the incidence of MS is the highest in the world, have skyrocketed. However, there's no data to show that supplements are the answer for vitamin D deficiency. In fact, in high doses supplements could make matters worse. In a study published in Science Daily in January 2008, Trevor Marshall, Ph.D. a professor at Australia's Murdoch School of Biological Medicine and Biotechnology reported that supplements of vitamin D3, the recommended form for supplements, can interfere with vitamin D's ability to react with the vitamin D receptor, altering the genetic expression of vitamin D. The Vitamin D receptor, a protein on cells that reacts with vitamin D molecules is involved in the repression or transcription of hundreds of genes associated with diseases ranging from cancers to multiple sclerosis. The Vitamin D receptor also regulates innate immunity particularly the body's natural antimicrobial peptides. By persistently activating the Vitamin D receptor with vitamin D3 supplements, other natural proteins are prevented from reacting with the vitamin D receptor. This ultimately suppresses the immune system. Marshall as well as other experts in the field suggest that a minimum daily exposure of 15 minutes to natural sunlight without the use of sunblock offers adequate protection against vitamin D deficiency.

The debate in clinical laboratories still continues over which form of vitamin D should be measured. Research suggests that tests for 25-OH Vitamin D3 may provide a better picture of vitamin D status. Roche introduced the first tests for 25-OH Vitamin D3 in the fall of 2008 and as this test becomes more popular, a different picture of vitamin D deficiency may emerge.

By: Elaine A. Moore - Mon, 02/09/2009 - 21:55

What is the blood test to check your blood level of vit D? Do I ask for 25(OH)D? I have a doctor’s appointment Tuesday morning and I want to ask for the right test. Also, can I still take vit D3 the day before or on the day I have the blood test or could that give me results that are very high even if my real levels are low?

yes you have the right test. if you want to "wash out" d3 before a test i'd skip the supplements for a week. it won't fall off very far in one week and then you can get back on your regimen
HTH,
JL

Thanks jimmylegs!

Hey everyone,

So i got a call from my neuro today saying that my latest blood test says i'm vitamin D deficient and i have to start taking 2000 IU of vitamin D for the time being.

Has anyone else had this happen? Could this have cause my latest relapse? so many questions....

I don't have time to get you all the links, but yes. My wife is taking 8,000iu/daily. I'll try to get back here and link you to some excellent Vit D links. Also, Jimmylegs will have something to say, I bet. Welcome to TIMS!!! Note, look for D3 not D2. Ken

heya meegs napay was right lol!
how deficient are you? what's the test result? you want to aim for at least 100nmol/L. i try for 150.

I agree with jimmylegs, you should ask for your test results so you will know your starting level. From my experience I doubt 2,000 IUs a day will be enough to get you levels up to (100nmol/L. i try for 150) very quickly. I needed to take 6,500 IUs a day for six months, now on 4,500 IUs a day to keep my levels up. But, everyone is different when it comes to how much vitamin d they need, so that's why you will need to get tested every six months or so for the first year or two. Good Luck Lots of information on the site about Vitamin d.

i share your doubts dave! i referred meegs to the mega d thread probably a good starting point, then there are the other threads full of abstracts too..

Hi Meegs,
I believe a supplementation of D is on everyone's intake list these days, especially in the winter. Let's not forget it is now recommended that the average person take 1000 in the darker months.

But for a person with ms, the intake is higher. I'm now up to 4000 or higher when needed. I suspect some meds deplete vitamins after a while and jimmylegs provided some specifics for that issue (there is a post of it's own).

To answer the question of whether a deficiency causes a relapse, yes and no. In most cases the symptoms that present themselves because of the lack of D can feel like an exacerbation. But on the other hand, if the body's levels are low in D and other vitamins and nutrients there is a greater chance of a weaker system overall. Thus, a relapse.

Maintaining a healthy level for your body is important. For me, when levels are low I can feel it, I just know when it's off because I feel a certain way. It is comparable to being anemic, the symptoms of anemia are similar to some ms symptoms, so it is like a double whammy when iron levels are down. Again, it is more of an exacerbation of existing symptoms.

Maintaining optimal health in all areas will help to avoid many relapses.
Happy D3 Dosing!

Hi,
as I got my Vitamin D results today, I thought it would be a good idea to start ONE thread where all people can put up their Vit D results. For anyone interested this would supply good data on how MS patients Vit D levels are at start and how they change with what kind of supplements.

--Frank

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Sorry, I didnt do a test prior supplementation.

Regime:
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- 1x daily 2.000 iu Vit D (from september to april)
- 1x daily 400mg Calcium + 1x daily 200mg Magnesium
- lots of dairy products

Results dated 20.02.2009:
---------------------------------
Vitamin D (25-OH): 48.6 ng/ml - equals - 121,5 nmols/L
Calcium : 2.45nmol/l

good for you frank! i'll check back in in a month with mine. i've been dosing my roomie too and her last test came back 119nmol/L. not an ms patient.

Researchers explore the benefits of supersized doses of Vitamin D for Multiple Sclerosis and other diseases

Researchers are taking a fresh look at vitamin D - the over-the-counter supplement much-ballyhooed as a way to prevent diseases - to determine whether it could be effective as a medical treatment for those who already have chronic illnesses such as cancer.

Although the investigations are in their early stages, any successful outcomes could be a major health breakthrough, giving patients an inexpensive treatment option that's as close as the nearest pharmacy.

Already the so-called sunshine vitamin is glowing brightly in medical circles, with recent studies showing its efficacy in preventing everything from cancer to the flu. Typical of the recent investigations was one conducted at St. Michael's Hospital in Toronto, where multiple sclerosis patients received one of the largest vitamin D doses ever dispensed in a clinical setting.

It yielded some tantalizing evidence that supersizing the nutrient helps calm symptoms of the neurological disease.

The MS patients took up to 40,000 IU daily, or the amount in 50 multivitamins or 400 cups of fortified milk.

(The Canadian Cancer Society recommends taking 1,000 international units daily.)

"We definitely had fewer episodes in the treated group," said Jodie Burton, the principal investigator.

Because no one knows the dose most helpful for MS, Dr. Burton's group wanted to establish first that it was safe to take a lot of the vitamin. Although overdoses are rare, it is possible to take too much, with symptoms including excess calcium in the urine and blood, cardiac rhythm disturbances and kidney damage.

The researchers didn't find these problems. "We saw absolutely no evidence of any issues," Dr. Burton said. "What evidence there is suggests that you can go quite high with this before people start to report side effects."

Many scientists have been wondering whether a lack of vitamin D causes MS because the disease is far more common in countries, such as Canada, where people have low levels of the nutrient in fall and winter because of the seasonal drop in sunlight.

Although vitamin D is available in supplements and is found naturally in some foods, such as oily coldwater fish, most of what people have in their bodies they make themselves, through a chemical reaction that starts when cholesterol in skin is exposed to intense summertime light.

"There is a lot of evidence that suggests if your vitamin D status is really quite good, the risk of getting MS is low," Dr. Burton said. "The natural question after that is, 'Well, what happens after the fact, if you already have MS? Is there any benefit to vitamin D intervention?' "

The researchers gave the vitamin in escalating doses for a year, starting with amounts under 10,000 IU and gradually increasing intakes to peak at 40,000 IU a day. They then reversed the process and slowly lowered the doses to zero.

Averaged out, the patients received 14,000 IU a day, not far off the estimated 10,000 IU a day that people make in their skin if they live year-round in a sunny climate and spend time outdoors. A separate group of MS patients, known as a control group, was able to take up to 4,000 IU a day, the amount Dr. Burton says is the standard recommendation at her clinic.

Those in the trial took the vitamin as a concentrated liquid. The doses had about the same volume as a teaspoon, saving patients from swallowing hundreds of pills.

The amounts were far above Health Canada's recommendations of 200 IU to 600 IU a day, depending on age. The agency also pegs at 2,000 IU daily the safe upper intake by those not under medical supervision - although the MS research suggests the government's limit may be far too conservative.

MS researchers aren't the only ones speculating on the therapeutic benefits of the vitamin: Some cancer researchers also hypothesize that upping intake of the vitamin might be beneficial.

A number of cancer treatment centres have begun looking at large doses, hoping to give their patients a survival edge. The approach is considered experimental because no research has yet established that an existing tumour will shrink or grow more slowly in response to having more of the vitamin.

The notion of positive effects against cancer rests partly on suggestive recent research. Studies have found that rates of some cancers, particularly colon and breast, are higher where people are unable to make the vitamin year-round in their skin. Other studies have found that those diagnosed with cancer in the summer, when vitamin levels are generally higher, have the best outcomes.

The risk of developing cancer "may be associated with vitamin D deficiency," said Donald Trump, president of the Roswell Park Cancer Institute in Buffalo. "That would suggest that giving vitamin D might slow the growth or reduce the recurrence rate of a cancer."

Dr. Trump said that while routinely having patients take vitamin D is not part of a standard treatment protocol at Roswell, it is "increasingly being adopted" by many of its physicians. The institute is running formal trials to assess the safety of longer-term supplementation with doses up to 10,000 IU a day.

But Dr. Trump has given some prostate cancer patients presenting with very low levels of vitamin D up to 20,000 IU for short periods to make sure they're not suffering from insufficiency. "What I do in my patients with cancer is try to restore their levels to the high normal range," Dr. Trump said of the approach. "I think there is a good prospect that optimizing vitamin D intake might favourably affect the outcome in cancer patients, and it vitally needs to be studied."

Another physician hot on the trail of vitamin D is Ira Cantor, at the Steiner Medical and Therapeutic Centre in Phoenixville, Pa.

Dr. Cantor became interested in the vitamin after seeing the studies on how those diagnosed with cancer seemed to do better if their malignancies were discovered in summer. Medical treatments, such as chemotherapy and surgery, don't vary by season, raising the possibility that the higher summertime levels of vitamin D play a role.

This prompted Dr. Cantor to devise a way of jolting patients up to high, summertime readings of vitamin D in a matter of weeks. To this end, he gives one-time doses ranging from 50,000 IU to 300,000 IU, depending on how low a person's levels are initially, followed by 4,000 IU a day.

Dr. Cantor has been trying this regimen for a year, treating about 100 patients. He said it is too early to say if the step is helping, but he is encouraged. "You have a certain anecdotal impression if your patients are doing better than you would expect," he said. "I have that impression individually, but I wouldn't scientifically state that."

As a safety precaution, Dr. Cantor monitors patients for calcium and parathyroid hormone levels, another marker of excessive vitamin D intake, but has found nothing abnormal. "There was absolutely no toxicity," he said.

Further evidence on the safety of high doses is coming from two recently conducted clinical trials in the United States on perhaps the most sensitive people of all, pregnant and lactating women. The latter were given high doses - 6,000 IU a day - to find what amount of vitamin D ensured that mother's milk had adequate levels of the nutrient.

"We never saw one single adverse event that would have been related to anything remotely due to vitamin D," said Bruce Hollis, one of the researchers and professor of pediatrics at the Medical University of South Carolina.

One of the problems with conventional drugs is that they often have nasty side effects and compliance can be an issue. But Dr. Burton at St. Michael's says taking vitamin D is a big hit among her patients.

"People are looking for something natural, so it's very helpful," she said. "It's inexpensive. It's got multiple health benefits. Unless there is a contraindication there is really no downside."

A role in other illnesses

Scientists have long known that rickets, a debilitating childhood bone disease, and osteoporosis among the elderly are caused by low levels of vitamin D. But there is evidence the vitamin plays a role in many other conditions, among them:

Multiple sclerosis

The neurological disease has a marked global distribution, with the odds of having it increasing the farther further people live away from the equator. This implicates vitamin D because we make most of the nutrient circulating in our bodies ourselves, when skin is exposed to ultraviolet summer light. A study in the Journal of the American Medical Association in 2006 found that Caucasian U.S. military personnel had a 41-per-cent decrease in MS risk for every 50 nanomole/litre increase in vitamin D levels in their blood.

Prostate cancer

The season in which a man is diagnosed affects the outcome of the disease, raising the possibility of a vitamin D connection. A study of Norwegian men published in 2007 found that those diagnosed in summer and autumn had the best prognosis. The authors speculated the seasonal increase in vitamin D was the cause.

Colorectal cancer There is a growing body of research linking low vitamin D to this often deadly cancer. An analysis of blood levels of vitamin D found a 50-per-cent reduction in risk for those with the highest amounts, according to a study published in 2007 in the American Journal of Preventative Medicine.

Breast cancer

A review from 2007 found a 50-per-cent decrease in breast-cancer risk for those with the highest level of the vitamin in their blood. The authors of the study, published in the Journal of Steroid Biochemistry and Molecular Biology, said women could attain the blood levels associated with low breast-cancer risk by taking 2,000 IU a day and, when weather permits, 10 to 15 minutes in the sun.

Vitamin D in the body

Vitamin D may have drug-like qualities because our bodies convert it into a powerful steroid hormone.

1. Sunlight We make vitamin D in our bodies when cholesterol in skin is exposed to strong, summertime ultraviolet light. This produces a substance scientists have dubbed D3, the same compound found in vitamin pills. The more sun exposure people receive, or the more supplements they take, the higher the levels of vitamin D they will have.

2. In the Liver After it's made in skin or taken as a pill, D3 is converted in the liver into another form, called 25 D, which is what is measured when people have tests for blood levels of the vitamin.

3. In the Kidneys 25D is convertedby enzymes into a steroid hormone known as 1,25 D.

Hormones are some of the most powerful compounds in our bodies. Scientists believe that the production of this hormone is why vitamin D may have drug-like qualities in the prevention and treatment of cancer and many other conditions.

Source: The Globe and Mail © Copyright 2009 CTVglobemedia Publishing Inc.(16/03/09)

sounds promising!

Inadequate Vitamin D Levels Linked To High Use Of Narcotic Medication By Patients In Chronic Pain.

http://www.sciencedaily.com/releases/20 ... 112114.htm

--Frank