MS Nutrition-summary pts 1st post, p.1

Tell us what you are using to treat your MS-- and how you are doing.

insulin/D update

Postby jimmylegs » Wed Jun 07, 2006 10:55 am

oo ooo i just got a search result that said excess insulin may lead to alzheimer's. i have already seen that vitamin d status and incidence of alzheimer's are linked. so now i really have to figure out if vitamin D can bring insulin down as well as boost it.
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insulin and Alzheimer's

Postby lyndacarol » Wed Jun 07, 2006 11:55 am

Hi Legs! I know I posted this here before, but can't recall just where.

A Harvard researcher, Dennis J. Selkoe, believes that an Insulin Degrading Enzyme (IDE) breaks down amyloid-beta (causing plaques in the brain in AD) as well as insulin, but is preferentially drawn to the insulin (thereby leaving the amyloid-beta to accumulate).

I still wonder if vitamin D lowers the insulin level somehow....
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kasuku, this is for you!!!

Postby jimmylegs » Thu Jun 08, 2006 12:21 pm

hi k, found some more interesting stuff. i LOVE finding these things out, it's so fun.

It is UV-B which is primarily responsible for the production of vitamin D in the skin. The vitamin so produced requires time to show up maximally in the blood. Cholesterol-containing body oils are critical for the absorption process, and the body needs about 30 to 60 minutes for these vitamin-containing oils to be fully absorbed. Thus it is advisable to delay showering or bathing for at least one hour after exposure. Skin oils with vitamin D can also be removed by chlorine in swimming pools.11

Normally, between 90% and 95% of most human requirement for vitamin D comes from exposure to the sun,1 and the intensity of UV-B light reaching the skin has a dramatic effect on the production of vitamin D. Furthermore, greater skin pigmentation can cause up to a 50-fold reduction, while application of a sunscreen with sun protection factor (SPF) of only 8 reduces the UV-B penetration into the epidermis by as much as 97%.12 While UV-A is present throughout the day, UV-B is available in adequate quantities only between about 10 am and 3 pm during summer in both northern and southern hemispheres, the hours that we are told to avoid exposure to the sun.13 With progression of winter and an increase in the zenith angle of the sun, more and more of the UV-B photons are absorbed by the ozone layer in the stratosphere. At the height of winter in the temperate regions of the world very few of the UV-B rays reach the earth's surface. That is the reason why during winter very little vitamin D is produced in the skin at latitudes above 35°N and below 35°S. At higher altitudes, UV-B intensity is also greater than at lower altitudes. Thus, time of day, season of the year, weather conditions, latitude, and altitude all significantly affect the cutaneous production of the vitamin. A simple meter is now available to determine UV-B levels at different locations.11

Currently, it is suggested that exposure of hands, arms, and face to the sun should occur for 10 to 20 minutes, three times a week. However, this will provide only 200 to 400 IU of vitamin D each time or an average of 100 to 200 IU per day during the summer and much less during the winter. To achieve maximum levels of vitamin D, 80% to 90% of the body needs exposure to the midday sun. About 100 to 200 IU are produced for each 5% of body surface exposed, and we need a minimum of about 4,000 IU.14 Light skinned people need at least 10 to 20 minutes of exposure, while dark skinned people need 90 to 120 minutes to produce the same amount of the vitamin.7 Cultural traditions and practices may also have a significant impact. For instance, even in sunny countries, such as those in the Middle East, traditional attire, especially for most women and girls, covers well over 95% of the body, leading to drastically insufficient UV-B irradiation of the skin. Generally, vitamin D status is more troublesome in elderly persons in comparison with young adults.15,16 This is due mainly to the elderly's often modest outdoor activities and the marked decrease in the aging human skin's capacity to produce vitamin D, probably because of a decline in cutaneous levels of the vitamin D precursor, 7-dehydrocholesterol. A very low vitamin D status has also been observed in institutionalized patients.

http://www.uspharmacist.com/index.asp?s ... 8_1352.htm

isn't that great detail? whee!
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Postby LisaBee » Thu Jun 08, 2006 5:20 pm

jimmylegs,

Do keep us posted on the vitamin D results. I am very curious as my own levels were very low two months post MS diagnosis, although not below the lab reference range. I was under 20 ng/ml (I think those are the units), which is probably about 40 nmol/L (I think, units may be off). I used to have the conversions written down, so that might not be accurate.

Just as an aside, there are approximately 35 studies on, or commenting on, vitamin D and its role in reversal or prevention of EAE in lab animals in PubMed. Those are controlled studies. Sadly, the number of actual clinical trials with vitamin D or its analogues in people, as abstracted in PubMed can about be counted on the fingers of one hand. More sadly still, the first human study, although not a randomized or controlled study, was Goldberg et al. 1986, which is twenty years ago, in which calcium, magnesium, and vitamin D supplements cut relapse rates in more than half compared to expected based on patient history, with no side effects. I don't know what the dosages were - they may have been low for Vitamin D compared to what you are taking.. The epidemiology on MS and Vitamin D/sunlight has been hashed on the Canadian/Vit D thread, so I don't need to go there again. I am just flabbergasted that the confluence of epidemiology and animal studies has not triggered more research on VItamin D as a potential treatment for people with MS. I am especially flabbergasted since MS patients, especially those on corticosteroids, are at very high risk for severe osteoporosis, and the medical literature is filling up with studies on administering Vitamin D to people with various conditions that require corticosteroid therapy. I don't see much on MSers, though, in that arena.

There is apparently a Toronto study ongoing to investigate vitamin D as a treatment for MS, which is the burning question everyone with MS already has.

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Postby Kasuku » Thu Jun 08, 2006 6:39 pm

Hi Jimmylegs,

I am impressed; there is a lot of interesting information in your posts. So it appears that we (living at latitude >35N) don't get much vitamin D during the winter months from the sun even if we were exposed all day. That's when the supplements are crucial, but how much? I guess we have to get serum levels especially during the winter.
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Jimmylegs, is this related?

Postby lyndacarol » Thu Jun 08, 2006 7:13 pm

I caught an interesting tidbit on "Jeopardy" the other day. It seems that iguanas must be exposed to ultraviolet light in order to have healthy bones.

Do you suppose it is UVB? Are such lights available at pet stores? Would it help MSers?

You once envisioned naked MSers lying on the beach; I now envision an MS rush to pet stores! I'm sure this disease works on our imaginations, too--warping them!
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reply to lisa and kasu

Postby jimmylegs » Thu Jun 08, 2006 7:13 pm

hey lis, wish i was in that toronto study! or maybe i don't, if they're not supplementing at high enough levels...!

i think i am going to have a little trouble getting my D results. the first baseline test came back as 72 nmol/l. nmol/l is the units for calcidiol, which is what you want to test. and my range to aim for was given as 125-150. then i realized that for the latest test, we only wrote d3 on the lab req, not "25(OH)D3" (calcidiol). so in the lab's computer system, d3 defaults to "1,25(OH)2D3" (calcitriol). which is outlandish to me because you can read anywhere that calcidiol reflects hypo or hypervitaminosis most accurately, whereas calcitriol is a more difficult and expensive test, and levels are affected by too many variables.

anyway, the calcitriol test will come back in pmol/l. i won't be able to compare it to the original 72 number, and if it's high, i won't know whether it's because i'm still calcidiol deficient, or because the calcidiol is high.

i gave the calcidiol/calcitriol/lab-weirdness spiel to my doctor who talked to my other doctor and i got a message on the machine that calcitriol is the right test. sure, it'll be nice to know if my renal hydroxylation is properly converting calcidiol to calcitriol. calcitriol *is* the form used by the immune system, after all. but i still need to know what the calcidiol level is, to determine my actual serum status - hypo, optimal, or hyper. and i don't know if they're going to give me that lab req any more.

FYI, the conversion factor for ng/ml to nmol/l for calcidiol is 2.496.
http://www.unc.edu/~rowlett/units/scale ... _data.html. so you were under 50 nmol/l!!!! not a happy place!! with regards to any lab's current reference range, i take another quote from this article:
http://www.uspharmacist.com/index.asp?show=article&page=8_1352.htm
"In the opinion of many vitamin D and Ca researchers, recent findings provide overwhelming evidence that the guidelines for optimal vitamin D intake as established by the Food and Nutrition Board (FNB) of the American Institute of Medicine7 are grossly inadequate. " (my boldface)

i've read that now they're saying at least 80nmol/l is recommended for bone health, and i don't see how that leaves any left over for use by the immune system. of course i don't imagine that the bones would automatically get all 80nmol but you know what i mean. i don't think 80 is high enough.

yes kasuku, winter supplementation is pretty critical. also, since your maximum serum D is offset in time from your maximum D exposure/supplementation, i think it may be important to take at least quarterly tests of serum d3 (calcidiol) for the first year - a baseline measurement, later tests to gauge impact of starting supplementation, and seasonal variation and lag times for max supp/exp to max serum values. then you could get a sense of your timing for annual "worst case scenario" and have your yearly test at the right time.
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Postby LisaBee » Fri Jun 09, 2006 10:28 am

jimmylegs,

Yep, my 25-OHD was very low - I think it was about 17 ng/ml. I think the 1,25 OHD was about 30 or 32, in whatever unit that came in - it was also in the "normal" lab range. Unfortunately, the lower end of the lab reference range for the 25 OHD was 9 ng/ml, so I didn't show up as "abnormal" and got no recomendations for treatment, followup, repeat tests, etc. However, like you, I have read in many studies that below 20 ng/ml is considered, at best, insufficient by some and frankly deficient by others. So I am charting my own course. Right now I am trying to get some sun as I can and am taking 1000 IU per day.

lyndacarol,

I had a weird random thought driving home as it was getting dark, that your comment about iguanas re-ignited today. The current animal models for MS (the EAE models) are all in rodents, to my knowledge. The mice and rats used are all nocturnal animals. If one has ever worked with these lab animals, they definitely sleep during the day and are active in the dark. All activities, most eating, and breeding, occur in darkness. That got me thinking about Vitamn D and how vitamin D synthesis occurs in nocturnal animals. Then I thought about furry animals in general - how do they get their vitamin D? For some, it is probably all dietary. This will be a fun one to explore! Maybe this is all a side effect of MS. Am I getting weird or what!? :D

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Postby Kasuku » Fri Jun 09, 2006 11:21 am

Yes Lisa you are right that most rodents and many other animal species are nocturnals and get little if at all sun exposure. Moreover, they are covered with fur so the skin except for the nose, tail, feet and part of the eyelids isn't in contact with sunlight or UVB. Research animals (at least rodents) as opposed to wild ones are kept indoors for their lifetime and never see the sun. They get 12 hours of fluorescent lighting per day but that's it. These animals do not seem to develop any neurologic pathologies that resemble what we see in people with MS, unless it is induced in the EAE model. Hypervitaminose D in laboratory animals (mice and rats) is easy to induce and causes severe hypercalcemia of most organs and vessels. I suspect it is one of the reasons why most doctors are shy to recommend high dose of vit. D in people. They remember the toxicity described in animal models during their years in medical school. Again people and mice are very different.
I also would like to attract your attention to the paper on vit. D in the latest posts. The paper described that people with depression did better if they were located in the side of the hospital with sun exposure as well as people recovering from surgery. I assume that the exposure is mostly sunlight filtered by windows so in theory no UVB exposure. Light itself stimulates the pituitary gland resulting in hormone secretions and that could explain quicker recovery from depression as opposed to people kept in darker rooms. Perhaps light itself plays a role in addition to vit D. from UVB exposure. I guess my understanding is that UVB are filtered by glass. Am I right on this? What do you think Jimmylegs?
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rats and rays

Postby jimmylegs » Fri Jun 09, 2006 11:40 am

hiyas :D

lis, my brand new understanding is that vitamin d is toxic to mice and rats BECAUSE they evolved underground. i read the other day about a dog who had to be treated for hypervitaminosis d after consuming rat poison (which was vitamin d). i didn't make the connection until i read today's developments on this string.

so i gather things that evolve with their skin covered, or underground, do not have the same vitamin d biochemistry as bare-skinned light-condition-evolved humans.

also lisa i imagine you've heard this from me before, but i have read research that suggests 4000 IU of D is required daily for maintenance - forget about building up a low level.

your comments on light stimulating the pituitary should be very interesting to lyndacarol, kasuku. we were wondering a short while back what else sunlight did for people besides trigger the production of D. and yes i too have read that glass screws up the transmission of UVB.
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Postby LisaBee » Fri Jun 09, 2006 3:41 pm

I also had poked around a little bit over lunch and couldn't find the vitamin D requirements for rats and mice. I did find that rabbits don't need much vitamin D either, and lab rabbits are easily overdosed with vitamin D in diet. There was a fair bit about monkeys - monkeys, particularly New World monkeys, need a lot of vitamin D, like a minimum of 3000 IU per day. lyndcarol's iguanas likely need a lot and I read without an artificial source of UVB illumination, it is hard to get them enough via diet. I guess in nature, iguanas spend a lot of time soaking up sun.

It is interesting that humans are considered to need so little vitamin D as compared to monkeys, although this attitude is apparently changing. I will look more to find out requirements for great apes - they are closest to us. A key difference is their fur, although their faces are bare. Maybe we should start a separate thread on the comparative vitamin D needs of humans versus other animals! I feel like I am starting to hijack this regimen thread with animal tales. But wow, I learned something today.

more on point -

jimmylegs, I am aiming to take up to 4000 IU per day, because ironically, the hotter and more summery it gets here in Florida, my time outdoors stops dropping. It gets too hot to work outdoors here for all but the most heat-acclimated people - most of my yardwork has to be at dawn or dusk. I am reluctant to take more as a bolus dose for a short period because I am not getting any monitoring for vitamin D levels or calcium levels. I was taking less oral vitamin D earlier, because I was getting a lot more sun. I forgot to mention, that when my vitamin D levels were measured, I had actually been taking some daily multi-vitamins for a little while, about 400-800 IU per day. The actual levels prior to the event leading to my diagnosis was probably even lower. I have no idea what my levels are now - I bet (hope) they are higher, but probably are still not close to optimum.


Here's an interesting abstract. I may have posted this before. elsewehre, if so I'm sorry. This was an experiment, probably by some dairy food processors, looking at the effect of vitamin D fortification of cheese and blood levels in elderly people. They are comparing D2 and D3 supplementation as well. The key point is at the end, that during periods of limited sunlight, ingesting 600 IU daily of vitamin D3 in cheese for two months did not change the blood levels in the subjects during a period of limited sunlight. - Lisa

**********
J Dairy Sci. 2005 Jul;88(7):2295-301. Related Articles, Links


Bioavailability of vitamin D from fortified process cheese and effects on vitamin D status in the elderly.

Johnson JL, Mistry VV, Vukovich MD, Hogie-Lorenzen T, Hollis BW, Specker BL.

Dairy Science Department, South Dakota State University, Brookings, 57007, USA.

We conducted 2 studies to determine the effect of vitamin D-fortified cheese on vitamin D status and the bioavailability of vitamin D in cheese. The first study was designed to determine the effect of 2 mo of daily consumption of vitamin D3-fortified (600 IU/d) process cheese on serum 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), and osteocalcin (OC) concentrations among 100 older (> or =60 yr) men and women. Participants were randomized to receive vitamin D-fortified cheese, nonfortified cheese, or no cheese. Serum levels of 25-OHD, PTH, and OC were measured at the beginning and end of the study. There were no differences in 25-OHD, PTH, or OC after 2 mo of fortified cheese intake. The vitamin D-fortified cheese group had a greater decrease in 25-OHD than other groups, due to higher baseline 25-OHD. A second study was conducted to determine whether the bioavailability of vitamin D2 in cheese (delivering 5880 IU of vitamin D2/56.7-g serving) and water (delivering 32,750 IU/250 mL) is similar and whether absorption differs between younger and older adults. The second study was a crossover trial involving 2 groups of 4 participants each (younger and older group) that received single acute feedings of either vitamin D2-fortified cheese or water. Serial blood measurements were taken over 24 h following the acute feeding. Peak serum vitamin D and area under the curve were similar between younger (23 to 50 yr) and older (72 to 84 yr) adults, and vitamin D2 was absorbed more efficiently from cheese than from water. These studies demonstrated that vitamin D in fortified process cheese is bioavailable, and that young and older adults have similar absorption. Among older individuals, consuming 600 IU of vitamin D3 daily from cheese for 2 mo was insufficient to increase serum 25-OHD during limited sunlight exposure.

Publication Types:
Randomized Controlled Trial

PMID: 15956292 [PubMed - indexed for MEDLINE]
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Postby LisaBee » Fri Jun 09, 2006 3:51 pm

Kasuku,

Your point about the ease of inducing vitamin D toxicity in lab rodents, and the resulting concern about vitamin D toxicity in humans was really interesting! Thank you for pointing that out.

I will never again look at vitamin D research in lab animals without thinking about these points.

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Best source of Vitamin D info

Postby Jimk » Sat Jun 10, 2006 9:13 am

One of the best sources I've found for Vitamin D info is on a CFS website. It is replete with detailed information and references on D, including the misnomers about toxicity and the kinds of test which are actually useful to measure D levels:
http://lassesen.com/cfids/recommended_levels.htm
On Wheldon/Stratton protocal since December '04 for non-MS Cpn: CFS/FMS
Ohio, USA
www.CPn Help.org
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Postby LisaBee » Thu Jun 15, 2006 4:02 pm

Here's the latest abstract from Vieth, one of the advocates for revising the nutritional recommendations for vitamin D:

^^^^^^^^^^^^^

Prog Biophys Mol Biol. 2006 Feb 28; [Epub ahead of print] Related Articles, Links


What is the optimal vitamin D status for health?

Vieth R.

Departments of Nutritional Sciences, and Laboratory Medicine and Pathobiology, University of Toronto, and Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, Canada M5G 1X5.

The most objectively substantiated health-related reason for tanning is that it improves vitamin D status. The serum 25-hydroxyvitamin D concentration (25(OH)D) is the measure of vitamin D nutrition status. Human biology was probably optimized through natural selection for a sun-rich environment that maintained serum 25(OH)D higher than 100nmol/L. These levels are now only prevalent in people who spend an above-average amount of time outdoors, with the sun high in the sky. The best-characterized criteria for vitamin D adequacy are based on randomized clinical trials that show fracture prevention and preservation of bone mineral density. Based upon these studies, 25(OH)D concentrations should exceed 75nmol/L. This concentration is near the upper end of the 25(OH)D reference ("normal") range for populations living in temperate climates, or for people who practice sun-avoidance, or who wear head coverings. Officially mandated nutrition guidelines restrict vitamin D intake from fortified food and supplements to less than 25mcg/day, a dose objectively shown to raise serum 25(OH)D in adults by about 25nmol/L. The combined effect of current nutrition guidelines and current sun-avoidance advice is to ensure that adults who follow these recommendations will have 25(OH)D concentrations lower than 75nmol/L. Therefore, advice to avoid UVB light should be accompanied by encouragement to supplement with vitamin D in an amount that will correct for the nutrient deficit that sun-avoidance will cause.

PMID: 16766239 [PubMed - as supplied by publisher]
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Postby Nick » Fri Jun 16, 2006 1:17 pm

Hi K

DIRECT-MS has compiled a lot of research found here regarding vitamin D and MS. This paperby Embry entitled Vitamin D Supplementation in the Fight Against Multiple Sclerosis, specifically provides insight into how vitamin D serves to regulate the immune system. The vitamin D Council has a fair bit on vitamin D too.

The excerpt below also substantiates the properties that vitamin D possesses and how animal physiology uses it.

Jlegs & LB

Bear in mind it takes about one month for the human body to convert a source of vitamin D, be it from UVR exposure or pills, into the active, measurable form of serum vitamin D.

If the Toronto study you refer to is the one by O’Connor, Vieth et al, the abstract is at the bottom of this post. This was phase I with phase II to follow soon. The trial was more for determining levels of toxicity and appropriate amounts for PwMS than the efficacy of vitamin D in immunoregulation. The trial only involved 12 subjects. DIRECT-MS will be participating in phase II.

Cheers
Nick

----------------
For many years, it has been known that cells of the immune system, including T helper lymphocytes (the primary immune cell orchestrating MS immune dysfunction), possess receptors for vitamin D3 32. More recently, vitamin D3 has been shown to profoundly affect immune responses in cell culture, and in animal disease models mimicking multiple sclerosis32-35.

In vitro, vitamin D3 metabolites have been shown to be potent antiproliferative and immunosuppressive agents. Vitamin D3 metabolites can inhibit T lymphocyte proliferation, and significantly decrease the production of pro-inflammatory cytokines, including interleukin two (IL-2), interferon gamma (IFN-g) and tumour necrosis factor alpha (TNF-µ), all of which are prominently involved in disease immunopathogenesis33.

Vitamin D3 has been demonstrated to function as a physiologic regulator of T lymphocyte differentiation and development in vitro, suggesting important roles in immune regulation36. It has been hypothesized that vitamin D3 may act as a transcriptional regulator of T lymphocyte cytokine synthesis, and indeed, receptors for vitamin D3 can be found in the nuclei of immunocompetent cells, including T helper lymphocytes37-40. Vitamin D3 insufficiency has also been correlated to increasing levels of circulating matrix metalloproteinase 9 (MMP9)41, a molecule involved in the break down of the blood brain barrier, allowing for the transmigration of lymphocytes into the central nervous system, and the initiation of central nervous system inflammation.


The development of an animal model that mimics MS-like disease activity, called Experimental Allergic Encephalomyelitis (EAE), has helped to increase our understanding of the autoimmune processes that may be occurring in MS. In this animal model, T lymphocytes, (and more specifically, type-1 helper (Th1) cells), recognize central nervous system antigens of myelin basic protein and elicit an immune response resulting in the production of pro-inflammatory cytokines40.

Conversely, type-2 helper (Th2) lymphocytes, which have anti-inflammatory functions, appear to be down-regulated. Cantorna et al and Lemire et al have shown that vitamin D3 treatment (i.e. with the hormonal form of vitamin D3, 1,25(OH)2D) in mice with EAE results in the inhibition of pro-inflammatory Th1-driven responses, while increasing the proportion of anti-inflammatory Th-2 cell derived cytokines33, 40. Further, mice which are vitamin D3 deficient develop EAE more rapidly than mice which are vitamin D3 sufficient46.

Treatment of mice with 1,25(OH)2D prior to disease induction with myelin antigen immunization, can entirely prevent the development of EAE34,35. In addition, the injection of 1,25(OH)2D into mice with relapsing-remitting EAE at the first sign of neurological dysfunction results in the inhibition of further disease activity, suggesting that vitamin D3 treatment is also effective after disease onset in symptomatic animals34.

Finally, Cantorna et al have shown that combination treatment with 1,25(OH)2D and sub-therapeutic doses of cyclosporine A can suppress the progression of EAE in mice, while avoiding cyclosporine-induced toxicity, suggesting that vitamin D3 may also serve as an effective adjunct therapy to immunosuppressive treatment used in autoimmune disease46. Overall, the evidence supports the hypothesis that vitamin D3 may be one factor shaping the development of the T cell repertoire, and therefore contributing to the development and progression of T cell mediated diseases such as multiple sclerosis.


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

M.R. Ursell, R. Vieth, P.W. O'Connor, B. Gray, S. Kimball (Toronto, CAN)

Background: There is growing epidemiological and biological evidence to suggest that vitamin D3 status may play a role in the development and/or progression of multiple sclerosis. In support, a recent large observational study showed an inverse relationship between vitamin D3 supplementation and the risk of developing MS. Unfortunately, the recommended adequate intake (AI) of vitamin D3 is targeted towards calcium homeostasis, and doses required for the treatment of non-bone disease remain unknown, although they are hypothesized to be much higher than currently recommended doses used for the prevention of Rickets and osteoporosis. Due to concerns of causing hypercalcemia, no study has been conducted to assess the effect of larger doses of vitamin D3 on implicated diseases such as MS.
Objective: In order to characterize the therapeutic safety of higher doses of vitamin D3 in multiple sclerosis, we conducted a phase I dose-escalation study in 12 patients.

Design: Escalating doses of vitamin D3 (4,000–40,000 IU/d) were given orally over 28 weeks to 12 patients with clinically definite MS. MRI scans with gadolinium were obtained at baseline and trial completion to assess for radiological evidence of disease exacerbation. Expanded Disability Status Scores (EDSS), Ambulation Indices (AI) and relapse rates were assessed for each participant. Vitamin D3 nutritional status and calcium homeostasis were assessed by measuring 25-hydroxyvitamin D3 (25(OH)D) levels, parathyroid hormone (PTH), serum calcium and urine calcium:creatinine ratios.

Results: Mean serum 25(OH)D concentrations increased significantly from 79.4 to 452.6 nmol/L (p<0.02). The highest serum vitamin D3 level attained was 800 nmol/L. PTH levels declined from a basal mean concentration of 2.76 to 1.28 pmol/L (p<0.03). Serum and urine calcium levels remained within normal ranges (2.2-2.6mmol/L) for all participants. MRI and clinical data is being analyzed and will be presented for the 12 participants.

Conclusions: Despite attaining serum levels that well exceeded the traditionally accepted “toxic” level for vitamin D3 nutritional status (>250 nmol/L), no participant developed hypercalcemia or adverse clinical effects on doses of vitamin D3 as high as 40,000 IU/day. This data provides a new perspective on the safety of vitamin D3 supplementation for the treatment and/or prevention of diseases such as MS, and will be used to help determine an optimal dose of vitamin D3 in a phase II efficacy trial.
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