has compiled a lot of research found here
regarding vitamin D and MS. This paper
by 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.
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.