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These results suggest that high levels of vitamin D3 intake are safe and worthy of trial, even though it didn't have any impact on disease progression. I can't help wondering what a huge song and dance the big pharma would have made if this was their product, seeing as how the number of gadolinium enhancing lesions is significantly reduced:

Safety of vitamin D3 in adults with multiple sclerosis.

Am J Clin Nutr. 2007 Sep;86(3):645-51

Authors: Kimball SM, Ursell MR, O'connor P, Vieth R

BACKGROUND: Vitamin D(3) may have therapeutic potential in several diseases, including multiple sclerosis. High doses of vitamin D(3) may be required for therapeutic efficacy, and yet tolerability-in the present context, defined as the serum concentration of 25-hydroxyvitamin D [25(OH)D] that does not cause hypercalcemia-remains poorly characterized. OBJECTIVE: The objective of the study was to characterize the calcemic response to specific serum 25(OH)D concentrations. DESIGN: In a 28-wk protocol, 12 patients in an active phase of multiple sclerosis were given 1200 mg elemental Ca/d along with progressively increasing doses of vitamin D(3): from 700 to 7000 mug/wk (from 28 000 to 280 000 IU/wk). RESULTS: Mean (+/- SD) serum concentrations of 25(OH)D initially were 78 +/- 35 nmol/L and rose to 386 +/- 157 nmol/L (P < 0.001). Serum calcium concentrations and the urinary ratio of calcium to creatinine neither increased in mean values nor exceeded reference values for any participant (2.1-2.6 mmol/L and <1.0, respectively). Liver enzymes, serum creatinine, electrolytes, serum protein, and parathyroid hormone did not change according to Bonferroni repeated-measures statistics, although parathyroid hormone did decline significantly according to the paired t test. Disease progression and activity were not affected, but the number of gadolinium-enhancing lesions per patient (assessed with a nuclear magnetic brain scan) decreased from the initial mean of 1.75 to the end-of-study mean of 0.83 (P = 0.03). CONCLUSIONS: Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D(3) for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.

PMID: 17823429 [PubMed - in process]

Wow, you're not kidding: p=0.03, greater than 50% reduction in enhancing lesions...sounds like copaxone. I hope they keep pushing these vit D trials along fast.

yea given the positive results of this study, hopefully at some point it would be feasible to do with more than 12 people, and for longer than 28 weeks re: disease progression.

After taking large doses of Vitamin D daily for over a year with no changes in MS symptoms, I have to think there is something else at play in the north-south gradient factor. It seems more likely that annual temperature, which allows for fewer colds and viruses to be passed between people, is responsible for the well-recognized difference in geographical prevalence.

Just another of my thoughts.

heyas, i don't know if it's supposed to change symptoms, just reduce rate of relapses? don't have time to fish thru the research at the moment, does anyone else remember reading about anything involving D and reduction in EDSS? i don't think i've seen that anywhere.

I believe there is something to the Vitamin D/Sunshine theory. Have any of you read the papers by Dr. Hector DeLuca, Harvard Medical School, and many many others?

My husband's levels were checked and they were very low. The appropriate test is "25(OH)D" not "1,25(OH)D". He is on 2000 to 4000 IU's daily and his levels have barely risen. He has been taking for two years and has his levels checked every six months.

There is research that recommends that higher levels of Vitmain D in expectant mothers can prevent autoimmune diseases in their children.

Also, it is thought that the recommended levels are too low.

Too much to write here about the research.

heya maggie, probably have read deluca but don't recall specifically right now. so what was "very low"? my personal thoughts are that 2000 to 4000 are about maintenance, or perhaps gradual accumulation, and getting your baseline up over 100 nmol/L requires much larger doses. the best number i was able to achieve was 150 nmol/L 25(OH)D3, but i didn't keep up the 4000 per day and at last test was back down to 80 nmol/L, a lot closer to where i was at when i started out! i have not been organized enough to get tests every 6 months but that sounds like a wise step for me to take, i'm too sporadic for sure.

Jimmylegs,

The test is for "serum 25 hydroxyvitamin D". We always go to Quest Labs and the report lists his total vitamin D and then gives a breakdown of D3 and D2. Is the test that you are taking only for D3?

Dr. DeLuca is a renowned research in the field of Vitamin D. An abstract of one of his papers: http://www.fasebj.org/cgi/content/full/15/14/2579

I did read about reduction in EDSS score; that info came from a Dr. Prendergast. He recommends to his patients 50,000iu of D3 daily for a short period of time. Check out this blog: http://d3ms.blogspot.com/

Anothre interesting paper: http://www.direct-ms.org/pdf/VitDImmuno ... ntorna.pdf

I don't think that it will reduce my husband's EDSS score, but it may help to keep him from getting worse.

hi again, yep i only test for D3. will check out the deluca and prendergast links. interesting, the only time i got my serum level up to 149 was after i talked to the drug info centre at the hospital and they said 50,000 iu per day for 10 days, which i did, and it worked great (at getting the level up i mean, i don't know if it did anything for me in terms of edss). but i didn't keep taking the 4000IU per day and it drops right back down so i'm considering doing it again, what the heck. i've been taking 4000IU per day for quite some time now and i'm going to ask for more bloodwork at my annual appt coming up in october so that'll be good to find out.

i never went through my journals to try to correlate what i took with how i felt, except when cause and effect links are really startling. once i graduate i am going to go through it all properly and see what trends emerge.

will check out the direct-ms thing too but unless they're pretty new i think i'll find everything familiar. thanks!

Just a couple other points of reference for those that are interested. When I first had my vitamin D level checked it was just about 25nmol/L. That was in April after a long cold winter. I took 6,000 IU's a day for six months and also got some sun, in October I tested at 175nmol/L. Thinking I had over done it a little I switched to 3,000 IU's through the winter and in April tested at 80nmol/L. Decided to stay at 3,000 IU's through the summer, need to get checked in October again. My goal is to be at about 150nmol/L. I think if I stay to 4,000 IUs a day in the Winter and about 3,000 IUs in the Summer with some sun that might work for me, but as you can tell I am not quite there yet. It has been harder than I thought to get the dosage right.

all very interesting, dave. i never knew my baseline because i was taking a few thousand a day for months before i got my first ever test, which was 72nmol/L. i've never been up to 175, to my knowledge, but i completely agree with targeting 150. i have never been so high consistently from test to test, so i haven't bothered testing my calcium levels yet. someday!

sounds like you are narrowing down what you need nicely, but it does take a long time! i'm getting checkin in october too. have been doing over 3000 but not quite 4000 per day over the summer, but have been working indoors most of the time. will report the results.

Experts prescribe massive increase of vitamin D

Nursing, pregnant women need 10 times more than current recommendation,
says Canadian Paediatric Society

SHARON KIRKEY
CANWEST NEWS SERVICE

A move to feed pregnant and nursing women 10 times more vitamin D than they get today may still not be enough to protect their babies from chronic diseases, especially in obese women, a top expert says.

The Canadian Paediatric Society is recommending pregnant and lactating women consider taking 2,000 IU (international units) of vitamin D daily, especially during winter, to protect their babies from a litany of illnesses later in life.

The current Health Canada recommendation is 200 IU a day for adults under 50 — including pregnant and nursing mothers. Dr. Bruce Hollis, professor of pediatrics and director of pediatric and nutritional sciences at the Medical University of South Carolina who has studied vitamin D in humans for 30 years, called the society’s new position statement “a remarkable change.” But he said many women of childbearing age, especially in Canada, are “absolutely deficient” in vitamin D. “To say (2,000 IU) daily will replete everybody probably isn’t totally accurate, and I say with confidence it’s not enough to ensure breastfeeding infants get enough (vitamin D) through human milk.”

Vitamin D deficiencies in early life have been linked with an increased risk of small babies, asthma, diabetes, autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease, dental malformations and the development of certain cancers.
In two U.S. government funded studies, Hollis is studying vitamin D supplementation of up to 6,000 IU daily in nursing women, and 4,000 units per day in pregnant women. So far “not one single adverse event” has been observed in women on the highest doses, he said.

The pediatric society says even experimental doses of up to 10,000 IU per day for five months in pregnancy didn’t lead to levels in the toxic range.
After years of telling people to screen out the sun, doctors are finding a host of reasons to load up on the “sunshine vitamin.”

First came cancer: In June, the Canadian Cancer Society for the first time recommended adult Canadians lower their cancer risk by taking 1,000 IU daily. The vitamin has been linked with a lower risk of cancers of the breast, lung and colon. Now, pregnancy: Vitamin D deficiency in mothers and babies continues to be a problem in Canada, particularly among aboriginal women, the pediatric society says, and infants under one are especially vulnerable if they are breastfed.

Hollis said vitamin D is important for brain development and to build tolerance against autoimmune diseases. It also protects the mother from uterine infections that can lead to pre-eclampsia — a common disorder that causes high blood pressure and can lead to poor fetal growth and fatal complications in moms and babies if not treated. Oily fish such as salmon and sardines contain vitamin D and the vitamin is in fortified milk and margarine. But food alone can’t provide sufficient vitamin D, especially in babies.

A daily vitamin D supplement of 400 IU per day has been recommended for breastfed infants in Canada for decades, largely to prevent rickets, 104 confirmed cases of which were reported in Canada between 2002 and 2004.
But the pediatric society says the emphasis now goes far beyond the debilitating bone disease, which requires just a small dose of vitamin D. Severe asthma in three-year-olds and an increased risk of Type I diabetes have been linked to low vitamin D status during fetal life. Still, Health Canada is refusing to budge, calling the pediatric society’s new recommendation “premature” and warning of health risks with taking too much vitamin D.

“They’re the only ones who seem to be saying it’s premature,” said Dr. John Godel, principle author of the new recommendation and professor emeritus in pediatrics at the University of Alberta. He said Health Canada made it clear at a meeting two weeks ago they were “quite loath” to recommend pregnant and nursing women boost their vitamin D intake 10-fold.

Health Canada has set the upper tolerable limit for adults at 2,000 IU a day from all sources of vitamin D, including milk and supplements.
Godel said “there is a lot of evidence” that even 2,000 IU daily isn’t enough, but that “even at 2,000 we found we were in trouble with Health Canada. “If we went to 4,000 (IU per day) right away we might run into problems and besides that, the evidence wasn’t all in at this time.”

The pediatric society recommends total vitamin D intake from all sources during the first year of life should be 400 IU per day in full-term infants and 200 units for premature babies, with an increase to 800 IU daily between October and April north of the 55th parallel (about the latitude of Edmonton).

They recommend pregnant and nursing women have their blood checked periodically to see whether they’re getting sufficient vitamin D. Hollis said that, for reasons that aren’t clear, obese people need much more vitamin D to maintain their levels.

As well, he said every breastfeeding infant “absolutely needs a vitamin D supplement” even if the mother is supplementing herself with 2,000 IU per day. He recommended vitamin D3, or cholecalciferol, the kind produced in the skin in response to sunlight.

The pediatric society says infants and children should be exposed to sunlight for short periods, probably less than 15 minutes a day.

Cheers
Nick

lol 2000 massive

just diggin in my files and ran across this photocopy from my nutrition appointment last year (sorry, bad table format):

Study IU/d duration D3 (nmol/L)
1995 Byrne et al: 800 4-6 months 60-105
1995 Byrne et al: 1 800 3 months 65, 80
1990 Honkanen et al: 1 800 3 months 57-86
1977 Stamp et al: 10 000 4 weeks 105
1982 Davies et al: 10 000 10 weeks 110
1977 Stamp et al: 20 000 4 weeks 150
1987 Schwartzman & Franck: 50 000 6 weeks 320
1978 Davies & Adams: 50 000 15 years 560

it keeps going after this and the data is not perfect (e.g. extrapolated for 1977, 1982, 1977; also inconsistency of calcium info) but after 50,000, meh. there was one really extreme one - 300,000IU per day for 6 years, serum d3 1692 nmol/L.

don't have the book's details, but i imagine it's not hard to look up the studies themselves to check up on details

An abstract about the Canadian vit D study from ECTRIMS. If these results hold up, will they be enough to at least convince the regulators to increase the recommended daily intake of vit D? Probably not...



A phase I dose-escalation trial of vitamin D3 with calcium supplementation in patients with multiple sclerosis

J.M. Burton, S. Kimball, R. Vieth, A. Bar-Or, H.M. Dosch, L. Thibault, S. Kilborn, C. D'Souza, M. Ursell, P. O'Connor (Toronto, Montreal, CAN)

Background: There is good evidence for a relationship between vitamin D nutritional status and development of multiple sclerosis (MS), which could explain the geographic pattern of MS prevalence. A potential mechanism is Vitamin D3’s regulatory effects on the immune system. The evidence suggests Vitamin D3 may benefit MS patients, but first, a safe and effective dose must be determined.

Objective: To characterize the safety profile of high-dose oral vitamin D3 in MS, we conducted a phase I dose-escalation trial with calcium supplementation in MS patients.

Design: In a prospective controlled 52-week trial, patients with clinically definite MS were matched for age, gender, disease duration, Expanded Disability Status Scale (EDSS) score, Disease Modifying Drugs, and MS subtype, and randomized to treatment or control groups. Treatment group patients received escalating doses of Vitamin D3 starting at 4,000 IU/d and escalating over 28 weeks to 40,000 IU/d, spending approximately 6 weeks at each dose. Patients were then maintained on 10,000 IU/d for 12 weeks, followed by a down-titration to 4,000 IU/d for 8 weeks, and a final 4-week washout period. Calcium (1200mg/d) was given orally throughout the trial. Twenty-five treatment patients and 24 matched controls were enrolled. The primary endpoint is change in serum calcium concentration in the treatment group over the 52-week period. Secondary endpoints are change over the trial in serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, urine calcium:creatinine ratio, liver enzymes and creatinine/urea. Baseline and end-of-trial EDSS, Ambulation Index and relapse rate will be measured in all patients. Serum cytokines, lymphocyte responses and matrix metalloproteinases will be compared over the Vitamin D3 escalation in treatment patients and between treatment and control groups.

Results: At 9 months, 17/25 treatment patients have received 6 weeks of 40,000 IU/d of Vitamin D3 and are now in the 10,000 IU/d maintenance phase. There is no significant difference between groups in age, disease duration, relapse rate, prior Vitamin D3 dose, baseline serum calcium or 25(OH)D. Serum calcium has remained in the reference range (2.2-2.6mmol/L), with no significant differences over escalating doses. Mean 25(OH)D increased from 73.5 +/- 26.4mmo/L at baseline to 402.1 +/- 123.0 mmol/L at 40,000 IU/d (p<0.001).

Conclusions: The results thus far suggest high-dose Vitamin D is safe and tolerable in MS patients.

ECTRIMS link