This Is MS Multiple Sclerosis Knowledge & Support Community

Thanks for the reasurance Sarah.

J.

Here is something that might be helpful, an abstract by Vieth et al. 2004. This paper also supports the 4000 IU dose as safe.

Abstract copied below, link to full-text here:

http://www.pubmedcentral.gov/articleren ... d=15260882


^^^^^^^^
Nutr J. 2004 Jul 19;3:8.
Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients.

Vieth R, Kimball S, Hu A, Walfish PG.

Department of Laboratory Medicine and Pathology, University of Toronto, Canada. rvieth@mtsinai.on.ca

BACKGROUND: For adults, vitamin D intake of 100 mcg (4000 IU)/day is physiologic and safe. The adequate intake (AI) for older adults is 15 mcg (600 IU)/day, but there has been no report focusing on use of this dose. METHODS: We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded, randomized trial. In Study 1, 64 outpatients (recruited if summer 2001 25(OH)D <61 nmol/L) were given 15 or 100 mcg/day vitamin D in December 2001. Biochemical responses were followed at subsequent visits that were part of clinical care; 37 patients completed a wellbeing questionnaire in December 2001 and February 2002. Subjects for Study 2 were recruited if their 25(OH)D was <51 nmol/L in summer 2001. 66 outpatients were given vitamin D; 51 completed a wellbeing questionnaire in both December 2002 and February 2003. RESULTS: In Study 1, basal summer 25-hydroxyvitamin D [25(OH)D] averaged 48 +/- 9 (SD) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 +/- 30 nmol/L for the 15 mcg/day group, and 112 +/- 41 nmol/L for the 100 mcg/day group. Both doses lowered plasma parathyroid hormone with no effect on plasma calcium. Between December and February, wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group (1-tail Mann-Whitney p = 0.036). In Study 2, 25(OH)D averaged 39 +/- 9 nmol/L, and winter wellbeing scores improved with both doses of vitamin D (two-tail p < 0.001). CONCLUSION: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin D.

PMID: 15260882 [PubMed]
^^^^^^^^^^^

Dr. Vieth is a major researcher into Vitamin D and has published a lot on VItamin D, and has painstakingly gone back to the roots of the doses associated with toxicity and found that much of the concern about potential toxicity of vitamin D at lower doses are unfounded. It IS toxic at high doses as mentioned already by Jaded, but as can be seen in this study, 4000 IU for six months did not cause any problems in the adult subjects.

Now that it is winter, I would personally go up to 4000 IU, but not higher, and I plan on increasing gradually to let my PTH adjust down if it needs to.

I'm not an endocrine expert, but I suspect that in people whose Vitamin D levels are so low they actually have secondary hyperparathyroidism, a sudden big jolt in Vitamin D intake might cause a transient jump in plasma calcium until PTH adjusts down in response to improved Vitamin D levels. An endocrinologist would know the answer to that! If someone knows one, please ask for me!

Lisa

Another article about sunshine / Vit D and possible protection againt MS.

http://c.moreover.com/click/here.pl?j444965538&w=464753


Think of me tomorrow as I hit the beaches of southern Spain (no suntan cream)! I'll spare a thought for all you Canadians stuck in front of you fires as the blizzards rage outside.

Ian

Ian,

Have a safe journey and a super time. Get that Vitamin D topped up and see you back on this board soon!


J.

I mentioned my vitamin D supplementation to my GP and he didn't seem to think 4000 IU would be a problem at all. However, he did add that since Vit D is stored in fat, many people have trouble losing weight when taking the supplement. I find this very puzzling, as many vitamins are stored in fat, but don't necessarily affect the body's ability to burn fat. I have also never read anything about Vitamin D and it's hinderance of fat burning.


Has anyone ever heard this or is this doc just misinformed?

I'd be interested to see what he has based a weight gain on Vitamin D on. It doesn't make sense and I can't find anything on it. Sorry but I think he got confused. My opinion only

Again, vitamin D seems to be very important but we don’t know yet what the mechanism is or how it relates to environment and individual biochemistry — but there may be a correlation between rising rates of obesity and vitamin D deficiency. If you are having difficulty with weight gain — or can’t keep the pounds off once you lose them — you may want to have your vitamin D levels checked by your healthcare practitioner.

<shortened url>



Maybe it is I that is misinformed not the Doctor. Did some more digging

What's the connection?
Just how does calcium help in weight reduction? A possible rationale for the relationship between body weight and calcium is the effect calcium has on the body's energy metabolism.

When your calcium levels are low, a hormone called parathyroid hormone (PTH) and vitamin D increase in response to the low level of calcium. High levels of PTH and vitamin D are also seen during food shortage. In this starvation mode, your body will absorb and store more energy for later use.

Therefore, if your calcium levels are consistently low, the elevated levels of PTH and vitamin D may trick your body into thinking you are starving. As a result, you may store more energy in the form of fat and gain more weight.
<shortened url>

An interesting paper on sunshine, Vit D and autoimmune disease.

Highlight:

A small study of vitamin D, calcium
and magnesium supplementation in MS patients showed that, after
a period of 1–2 years, less than half the number of exacerbations
were observed than the expected number based on case histories
(64). More recently, a small (n 5 39) randomized control trial
comparing 6 months of 1000 international units of vitamin D and
800 mg calcium compared with 800 mg calcium alone reported
a significant increase in transforming growth factor beta (TGF b)
levels (65), an important anti-inflammatory cytokine (66).

But as always it seems

Randomized controlled trials to evaluate the effect of longer term
vitamin D supplementation on clinical and MRI indicators of
multiple sclerosis disease activity are required.

Link : http://phot.allenpress.com/pdfserv/10.1 ... -15-IR-441

I remember that Dignan reported somewhere in the drug pipeline that vitamin D is undergoing a trial in MS patients in Toronto. I wonder if there are any updates on that.

Lisa

i take approx 4000IU of D per day. have not had my levels tested yet - it's in the works. my doc at the ms clinic looked at my vitamin list and he agreed with the D. don't think he cared much about the rest of it tho!

hi turns out that my serum 25-hydroxy-vitamin d was 72 nmol/l. after what turned out to be just over 3400 IU per day from supplements for over 90 days, plus some dietary from fish (approx 2x per week) and recent addition of egg 2x per week for the last two weeks.

the docs say my target serum d should be 125-150 nmol/l. so, a long way to go. liver and renal function are fine therefore i am able to hydroxylate to calcitriol properly. it's just a matter of getting more in i suppose!

Clin Lab Med. 2000 Sep;20(3):569-90.
Calcium and vitamin D. Diagnostics and therapeutics.
Holick MF.
Department of Medicine, Boston University School of Medicine, Massachusetts, USA.

Vitamin D is neither a vitamin nor a nutrient if adequate exposure to sunlight is available to produce adequate quantities of vitamin D3 in the skin. It is well known that an adequate supply of vitamin D, either from the diet or from the skin, is important for maximum bone health throughout life. The new revelation that 25(OH)D can be metabolized to 1,25(OH)2D in the colon, prostate, and skin opens a new chapter in the vitamin D story. It is quite possible that there are two levels of vitamin D sufficiency. One level requires that the serum 25(OH)D levels be at least 20 ng/mL to satisfy the body's requirement for the renal production of 1,25(OH)2D that regulates calcium absorption, and bone calcium mobilization and bone mineralization. The second level may need higher circulating levels of 25(OH)D for maximum cellular health because of the conversion of 25(OH)D to 1,25(OH)2D in extrarenal tissues, such as the prostate, colon, and skin.

American Journal of Clinical Nutrition, Vol. 69, No. 5, 842-856, May 1999
© 1999 American Society for Clinical Nutrition
Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety1,2
Reinhold Vieth

For adults, the 5-µg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension.

Total-body sun exposure easily provides the equivalent of 250 µg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20–50 µg (800–2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D
[25(OH)D] response that is surprisingly flat up to 250 µg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 µg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 µg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of 1000 µg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 µg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 µg (2000 IU)/d is too low by at least 5-fold.

American Journal of Clinical Nutrition, Vol. 80, No. 6, 1706S-1709S, December 2004
© 2004 American Society for Clinical Nutrition
VITAMIN D AND HEALTH IN THE 21ST CENTURY: BONE AND BEYOND
Functional indices of vitamin D status and ramifications of vitamin D deficiency1,2,3,4
Robert P Heaney
1 From Creighton University Medical Center, Omaha

Serum 25-hydroxyvitamin D3 [25(OH)D3] concentrations are currently recognized as the functional status indicator for vitamin D. Evidence is reviewed that shows that serum 25(OH)D3 concentrations of < 80 nmol/L are associated with reduced calcium absorption, osteoporosis, and increased fracture risk. For typical older individuals, supplemental oral intakes of 1300 IU/d are required to reach the lower end of the optimal range. Evidence of substantial problems in routine clinical measurement of serum 25(OH)D3 concentrations among patients is cited. There is great need for standardization and improved reproducibility and sensitivity of measurements of serum 25(OH)D3 concentrations.

Medscape (WebMD)
Vitamin D Linked With Neuromuscular Performance in the Elderly
Linda Little

Sept. 28, 2005 (Nashville) — Low serum levels of vitamin D in the body may make elderly persons more susceptible to falls, Netherlands researchers reported here at the American Society of Mineral and Bone Research (ASBMR) 27th annual meeting.

"Low levels of vitamin D were associated with low physical performance," said Ilse Wicherts, a doctorate student at Vu University Medical Center in Amsterdam, the Netherlands. "This study shows that neuromuscular performance in those with lower levels of vitamin D was significantly lower than those with adequate levels.

"These individuals already are fragile," added Ms. Wicherts, the winner of an ASMBR Young Investigator Award. "The lack of mobility places them at high risk of falls and fractures."

In the study 1,238 men and women (mean age, 75 years) by Ms. Wicherts and colleagues, a low serum level of vitamin D was associated with lower neuromuscular performance. The study was undertaken within the framework of the Longitudinal Aging Study Amsterdam (LASA).

Neuromuscular performance was measured by five chair stands for muscle strength, a walking test for balance, and tandem stand testing coordination and mobility where participants must stand with one foot in front of the other. Each performance test was scored in seconds and was classified with scores from 1 to 4 according to quartiles of distribution. The total performance score for muscle strength and balance ranged from 0 to 12. The researchers used a multivariate regression analysis adjusted for age, sex, and body mass index.

Eleven percent of the participants had serum vitamin D levels less than 25 nmol/L, 37% had levels between 25 and 50 nmol/L, 33% had levels between 50 and 75 nmol/L, and 17% had levels of 75 nmol/L or above.

Scores for chair stands, the walking test, and tandem stand each showed significant improvement with increased serum levels of vitamin D.

Participants with vitamin D at 25 nmol/L had a performance score of 4.9 while those with vitamin D levels between 25 and 50 nmol/L had scores of 6.82 and those with levels between 50 and 75 nmol/L had scores of 8.10. Participants with vitamin D levels of 75 nmol/L or higher had performance scores of 8.72.

"There was a linear progression," Ms. Wicherts said. "The change in performance scores with increasing serum 25(OH)D was significant for all steps."

When researchers adjusted for age, sex, body mass index, smoking, and alcohol consumption, the performance score increased significantly with serum vitamin D levels up to 50 nmol/L.

Performance was reduced 18% if the vitamin D levels were lower than 25 nmol/L compared with participants with levels of 75 nmol/L or higher and 5% if vitamin D levels were between 25 and 50 nmol/L after adjusting for other risk factors, Ms. Wicherts said.

"Persons with low serum vitamin D levels had a higher risk for low physical performance," Ms. Wiecherts told Medscape. "The strongest effects were found in persons with a major deficiency."

"This is a very important study because it suggests that vitamin D is not only important for bone health, but is important in neuromuscular stability," said Elizabeth Shane, MD, president-elect of ASBMR. "Bone fracture is due to not only bone issues, but issues contributing to falls.

"There is a two-pronged effect here that can increase the propensity for fractures in the elderly," Dr. Shane said. "Adequate Vitamin D can aid in improving muscle strength and preventing falls in this older age group."

ASBMR 27th Annual Meeting: Abstract 1134. Presented September 26, 2005.
Reviewed by Gary D. Vogin, MD

Vitamin D: a natural inhibitor of multiple sclerosis
Author: Hayes C.E.
Source: Proceedings of the Nutrition Society, Volume 59, Number 4, November 2000, pp.
531-535(5)
Publisher: CABI Publishing

Abstract
Inheriting genetic risk factors for multiple sclerosis (MS) is not sufficient to cause this demyelinating disease of the central nervous system; exposure to environmental risk factors is also required. MS may be preventable if these unidentified environmental factors can be avoided. MS prevalence increases with decreasing solar radiation, suggesting that sunlight may be protective in MS. Since the vitamin D endocrine system is exquisitely responsive to sunlight, and MS prevalence is highest where environmental supplies of vitamin D are lowest, we have proposed that the hormone, 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), may protect genetically-susceptible individuals from developing MS. Evidence consistent with this hypothesis comes not only from geographic studies, but also genetic and biological studies. Over-representation of the vitamin D receptor gene b allele was found in Japanese MS patients, suggesting it may confer MS susceptibility. Fish oil is an excellent vitamin D source, and diets rich in fish may lower MS prevalence or severity. Vitamin D deficiency afflicts most MS patients, as demonstrated by their low bone mass and high fracture rates. However, the clearest evidence that vitamin D may be a natural inhibitor of MS comes from experiments with experimental autoimmune encephalomyelitis (EAE), a model of MS. Treatment of mice with 1,25-(OH)2D3 completely inhibited EAE induction and progression. The hormone stimulated the synthesis of two anti-encephalitogenic cytokines, interleukin 4 and transforming growth factor -1, and influenced inflammatory cell trafficking or apoptosis. If vitamin D is a natural inhibitor of MS, providing supplemental vitamin D to individuals who are at risk for MS would be advisable.

Vitamin D nutrition and multiple sclerosis
If vitamin D is a natural inhibitor of MS, it would be reasonable to provide supplemental vitamin D to individuals who are at risk for MS. It is noteworthy that vitamin D supplementation during childhood significantly decreased the risk of type I diabetes mellitus, an autoimmune disease (EURODIAB Substudy 2 Study Group, 1999). A reassessment of vitamin D nutrition is underway, and there is good evidence that the currently recommended adequate intakes are too low (Vieth, 1999). The adequate intake for adults is currently 5 mg/d, but this does not prevent osteoporosis and secondary hyperparathyroidism (Holick, 1998; Malabanan et al. 1998). To prevent secondary hyperparathyroidism a serum 25-hydroxycholecalciferol concentration › 50 nmol/l is required (Malabanan et al. 1998). Adults living or working in sunny environments, where MS prevalence is lowest, have circulating 25-hydroxycholecalciferol levels between 105 and 163 nmol/l (Vieth, 1999).

Thus, a serum 25-hydroxycholecalciferol concentration >= 100 nmol/l may be optimal to prevent MS. To maintain serum 25-hydroxycholecalciferol at approximately 100 nmol/l an adult who is not exposed to sunlight would need to ingest 100 mg/d (Vieth, 1999). This estimate is between the 95 mg/d that Goldberg (1974b) calculated might prevent MS, and the 125mg/d that was given in the small clinical trial of fish oil (Goldberg et al. 1986).

J Nutr. 2005 Nov;135(11):2739S-48S.
The vitamin D epidemic and its health consequences.
Holick MF.
Boston University School of Medicine, Department of Medicine, Section of Endocrinology, Vitamin D Laboratory, Boston, MA 02118, USA. mfholick@bu.edu

Vitamin D deficiency is now recognized as an epidemic in the United States. The major source of vitamin D for both children and adults is from sensible sun exposure. In the absence of sun exposure 1000 IU of cholecalciferol is required daily for both children and adults. Vitamin D deficiency causes poor mineralization of the collagen matrix in young children's bones leading to growth retardation and bone deformities known as rickets. In adults, vitamin D deficiency induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures. In addition, the poor mineralization of newly laid down bone matrix in adult bone results in the painful bone disease of osteomalacia. Vitamin D deficiency causes muscle weakness, increasing the risk of falling and fractures. Vitamin D deficiency also has other serious consequences on overall health and well-being. There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one's vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination.

Mult Scler. 2005 Jun;11(3):266-71.
25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis.
Soilu-Hanninen M, Airas L, Mononen I, Heikkila A, Viljanen M, Hanninen A.
Medicity Research Laboratory, University of Turku, Tykistokatu 6, FIN-20520 Turku, Finland.
mersoi@utu.fi

Past sun exposure and vitamin D supplementation have been associated with a reduction in the risk of MS. We measured the serum concentration of 25-hydroxyvitamin D (25[OH]D) at the time of MS diagnosis in 40 MS patients and 40 controls. We found no difference in the serum levels of 25(OH)D between MS patients and controls when all samples or samples obtained during winter months were compared, but MS patients had significantly lower serum 25(OH)D concentrations in June to September than the controls. The vitamin D stores were adequate for bone metabolism (> 37 nmol/L) in 70% of MS patients throughout the year and within the hypovitaminosis level (< 37 nmol/L) in 30% of MS patients at some time of the year. During MS-relapses, 25(OH)D levels were lower than in remission, but mostly within the reference range observed in relation with normal bone metabolism. We conclude that the vitamin D stores in most MS patients are adequate for their normal bone metabolism. However, lower vitamin D levels during MS relapses than in remission suggest that vitamin D could be involved in the regulation of the clinical disease activity of MS. The optimal serum levels of vitamin D for the regulation of immune responses remain to be determined.

J Am Diet Assoc. 2006 Mar;106(3):418-24.
Vitamin D and autoimmune disease--implications for practice from the multiple sclerosis literature.
Mark BL, Carson JA.
Department of Clinical Nutrition, University of Texas Southwestern Medical Center at Dallas 75390-8877, USA. barbara.mark@utsouthwestern.edu

Recent studies and commentaries link vitamin D with several autoimmune diseases, including multiple sclerosis (MS). Adequate vitamin D intake reduces inflammatory cytokines through control of gene expression, thus inadequate vitamin D intake is suggested as a mechanism that could contribute to inflammation and, consequently, development of MS. Poor vitamin D status has been associated with increased risk for development of MS, and patients with MS may suffer consequences of vitamin D deficiency, such as bone loss. Animal studies and very limited human data suggest possible benefit from vitamin D supplementation in patients with MS. Based on the current state of research, a key principle for practicing dietetics professionals is to include vitamin D status in nutritional assessment. For those at risk for poor vitamin D status, intake can be enhanced by food-based advice and, when indicated, vitamin D supplementation.

Ann Pharmacother. 2006 May 9; [Epub ahead of print]
The Role of Vitamin D in Multiple Sclerosis (June).
Brown SJ.
Drug Information Service, Skaggs School of Pharmacy, College of Health Professions and Biomedical Sciences, The University of Montana, 32 Campus Dr. Skaggs, Bldg 217, Missoula, MT
59812-1522, fax 406/243-4353, sherrill.brown@umontana.edu.

OBJECTIVE: To evaluate the literature about the role of vitamin D in the prevention and treatment of multiple sclerosis (MS). DATA SOURCES: MEDLINE (1966-April 2006) and International Pharmaceutical Abstracts (1970-April 2006) searches were performed. In addition, pertinent references from identified articles were obtained. Key search terms included vitamin D, 25-hydroxyvitamin D, vitamin D deficiency, and multiple sclerosis. DATA SYNTHESIS: Vitamin D supplementation prevented the development and progression of experimental autoimmune encephalitis, an animal model of MS, in mice. A large, prospective, cohort study found that vitamin D supplementation was associated with a 40% reduction in the risk of developing MS. Four small, noncontrolled studies suggested that vitamin D supplementation may decrease exacerbation of MS symptoms. CONCLUSIONS: Vitamin D supplementation may help prevent the development of MS and may be a useful addition to therapy. However, current studies are in small populations and are confounded by other variables, such as additional vitamin and mineral supplementation.

Prog Biophys Mol Biol. 2006 Feb 28; [Epub ahead of print]
Epidemiology of disease risks in relation to vitamin D insufficiency.
Grant WB.
Sunlight, Nutrition and Health Research Center (SUNARC), 2107 Van Ness Avenue, Suite 403B, San Francisco, CA 94109-2529, USA.

Vitamin D from ultraviolet-B (UVB) irradiance, food, and supplements is receiving increased attention lately for its role in maintaining optimal health. Although the calcemic effects of vitamin D
have been known for about a century, the non-calcemic effects have been studied intently only during the past two-three decades. The strongest links to the beneficial roles of UVB and vitamin D to date are for bone and muscle conditions and diseases. There is also a preponderance of evidence from a variety of studies that vitamin D reduces the risk of colon cancer, with 1000 IU/day of vitamin D or serum 25-hydroxyvitamin D levels >33ng/mL (82nmol/L) associated with a 50% lower incidence of colorectal cancer. There is also reasonable evidence that vitamin D reduces the risk of breast, lung, ovarian, and prostate cancer and non-Hodgkin's lymphoma. There is weaker, primarily ecologic, evidence for the role of vitamin D in reducing the risk of an additional dozen types of cancer. There is reasonably strong ecologic and case-control evidence that vitamin D reduces the risk of autoimmune diseases including such as multiple sclerosis and type 1 diabetes mellitus, and weaker evidence for rheumatoid arthritis, osteoarthritis, type 2 diabetes mellitus, hypertension and stroke. It is noted that mechanisms whereby vitamin D exerts its effect are generally well understood for the various conditions and diseases discussed here.

Srp Arh Celok Lek. 2005 Dec;133 Suppl 2:124-8.
[Effects of alfacalcidol therapy on serum cytokine levels in patients with multiple sclerosis]
[Article in Serbian]
[No authors listed]

Multiple sclerosis (MS) is a consequence of genetic and environmental factors. Geographic, genetic, and biological evidence suggests that an important immunopathogenic factor might be the insufficiency of vitamin D. The aim of our study was to investigate the immunomodulatory effect of alfacalcidol, a vitamin D analogue, on cytokine levels in RRMS patients in relapse. We investigated 15 patients suffering from RRMS relapse (an RRMS group) and two control groups: one control group of healthy subjects (n=10) and a NIND group, consisting of patients with non-inflammatory neurological diseases (n=10). All of the MS patients were treated with 5 microgr/day of oral alfacalcidol for a period of five days. The serum cytokine levels of TNF-alpha, IL-10, IL-4, and IL-12 were measured in all the MS patients one day prior to and one day after therapy, and in all the control subjects (ELISA, Quantikine human immunoassay, R&D Systems, UK). Our results showed significantly lower IL-4 and IL-12 levels in the RRMS patients group compared to the N group and the NIND group (p<0.001 Mann-Whitney U-test). No significant differences in TNF-alpha and IL-10 levels were found between the groups, and there was no influence of alfacalcidol on these cytokines in RRMS patients. High doses of oral alfacalcidol induced significant increases in IL-4 and IL-12 levels in RRMS patients (p<0.001, Wilcoxon rank signed test). Therefore, there were no differences in IL-4 and IL-12 levels compared to the N group and the NIND group. Alfacalcidol therapy in RRMS patients did not provoke any side effects. Vitamin D and its analogues, such as alfacalcidol, act as immunomodulatory agents, with potential therapeutic effects for patients with multiple sclerosis.

Prog Biophys Mol Biol. 2006 Feb 28; [Epub ahead of print]
Vitamin D and its role in immunology: Multiple sclerosis, and inflammatory bowel disease.
Cantorna MT.
Department of Veterinary and Biomedical Sciences, Center for Molecular Immunology and Infectious Diseases, The Pennsylvania State University, 115 Henning Bldg., University Park, PA 16802, USA.

Autoimmune diseases like multiple sclerosis (MS) and inflammatory bowel disease (IBD) occur because of an inappropriate immune-mediated attack against self-tissue. Analyses of genetically identical twins shows that besides genetics there are important environmental factors that contribute to MS and IBD development. Vitamin D availability due to sunshine exposure or diet may play a role in the development of MS and IBD. Compelling data in mice show that vitamin D and signaling through the vitamin D receptor dictate the outcome of experimental MS and IBD.

Furthermore, the evidence points to the direct and indirect regulation of T cell development and function by vitamin D. In the absence of vitamin D and signals delivered through the vitamin D receptor, auto reactive T cells develop and in the presence of active vitamin D (1,25(OH)(2)D(3) ) and a functional vitamin D receptor the balance in the T cell response is restored and autoimmunity avoided.

Tidsskr Nor Laegeforen. 2006 Apr 6;126(8):1048-52.
[The photobiology of vitamin D--a topic of renewed focus]
[Article in Norwegian]
Moan J, Porojnicu AC.
Avdeling for stralingsbiologi, Rikshospitalet-Radiumhospitalet, 0310 Oslo.
johan.moan@labmed.uio.no

The sun is our most important source of vitamin D. Exposure to solaria, in sub-erythemogenic doses, also gives large amounts of this vitamin. The ultraviolet radiation in these sources converts 7-dihydrocholesterol to previtamin D3 in the skin. Furthermore, heat isomerization to vitamin D3 takes place, then transport to the liver and hydroxylation to calcidiol, which is transported to the kidneys and hydroxylated to the active hormone calcitriol. The vitamin D3 status of the body is supposed to be reliably imaged by calcidiol measurements. Calcidiol levels above 12.5 nmol/l prevent rickets and osteomalacia, but optimal levels are probably higher, in the range 100-250 nmol/l. A daily food intake of 100-200 microg vitamin D3 (50-100 g cod-liver oil), or a weekly exposure to two minimal erythemal doses of ultraviolet radiation (20 to 40 minutes whole body exposure to midday midsummer sun in Oslo, Norway), will give this level. An adequate supply of vitamin D3 seems to reduce the incidence rates or improve the prognosis of several cancer forms, including prostate, breast and colon cancer, as well as of lymphomas. Several other diseases are related to a low vitamin D3 status: heart diseases, multiple sclerosis, diabetes, and arthritis. The action mechanisms of vitamin D are thought to be mainly related to its known cell-differentiating and immuno-modulating effects. Even though most of the 250 annual death cases from skin cancer in Norway are caused by sun exposure, we should, in view of the health effects of ultraviolet radiation, consider modifying our restrictive attitude towards sun exposure and use of solaria.

J Rheumatol Suppl. 2005 Sep;76:11-20.
D-hormone and the immune system.
Cantorna MT, Mahon BD.
Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA. mxc69@psu.edu

D-hormone [1,25(OH)2 D3] is an important immune system regulator that has been shown to inhibit development of autoimmune diseases including experimental inflammatory bowel disease (IBD), rheumatoid arthritis (RA), multiple sclerosis (MS), and type 1 diabetes. Paradoxically, other immune mediated diseases (experimental asthma) and immunity to infectious organisms were not found to be affected by D-hormone treatment. The effectiveness of D-hormone treatment of autoimmune diseases is due to inhibition of the development and function of Th1 cells and the induction of other Th cells including Th2 cells. We report results of microarray analysis of colons from D-hormone treated mice with experimental IBD. Two hundred thirty-nine genes were inhibited and 298 genes were upregulated in the colon by D-hormone treatment of mice with IBD. Of interest was the D-hormone mediated inhibition of 3 tumor necrosis factor-alpha (TNF-alpha, lipopolysaccharide-induced TNF-alpha factor, and TNF receptor) related genes in the colon. It is likely that the effectiveness of D-hormone treatment of experimental autoimmunity is due in part to the inhibition of the TNF family of genes. D-hormone is a selective regulator of the immune system, and the outcome of D-hormone treatment depends on the nature (infectious disease, asthma, autoimmune disease, etc.) of the immune response.

J Neurol Neurosurg Psychiatry. 2005 Sep;76(9):1294-6.
A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis.
Wingerchuk DM, Lesaux J, Rice GP, Kremenchutzky M, Ebers GC.
Mayo Clinic, Scottsdale, Arizona, USA. wingerchuk.dean@mayo.edu

BACKGROUND: Epidemiological and ecological studies suggest links between vitamin D deficiency and increased multiple sclerosis (MS) prevalence. OBJECTIVE: To evaluate the safety and tolerability of oral calcitriol therapy in an open label pilot study. METHODS: 15 ambulatory patients with relapsing-remitting MS and at least one clinical relapse within the previous 12 months received oral calcitriol (target dose: 2.5 microg/d) for 48 weeks. Dietary calcium was restricted to 800 mg/d. Patients were monitored using frequent clinical and laboratory examinations, the expanded disability status scale (EDSS), and brain magnetic resonance imaging (MRI). RESULTS:
Two patients withdrew because of symptomatic hypercalcaemia (serum calcium >3.35 mmol/l in each case) resulting from persistent dietary indiscretion. Two diet compliant patients required temporary dose adjustments for mild asymptomatic hypercalcaemia. Diet compliant patients experienced mild adverse effects. The on-study exacerbation rate (27%) was less than baseline.
Four patients experienced five clinical relapses but only one patient worsened by >1 EDSS point.
Brain MRI revealed enhancing lesions in five patients at baseline (33%) and in four (29%) at both 24 and 48 weeks. CONCLUSIONS: Oral calcitriol is safe and well tolerated for up to one year by diet compliant relapsing-remitting MS patients. Further study of vitamin D related mechanisms is warranted in MS.