Ditch the sun screen ?

JFH · Posted: Mon Apr 03, 2006 7:34 am Post subject: Ditch the sun screen ?

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

Highlight:

LisaBee · Posted: Thu Apr 06, 2006 4:01 pm Post subject:

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

jimmylegs · Family Elder Joined: Mar 12, 2006 Posts: 2089

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!

jimmylegs · Family Elder Joined: Mar 12, 2006 Posts: 2089

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!

jimmylegs · Family Elder Joined: Mar 12, 2006 Posts: 2089

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

jimmylegs · Family Elder Joined: Mar 12, 2006 Posts: 2089

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.

jimmylegs · Family Elder Joined: Mar 12, 2006 Posts: 2089

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.

jimmylegs · Family Elder Joined: Mar 12, 2006 Posts: 2089

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.

jimmylegs · Family Elder Joined: Mar 12, 2006 Posts: 2089

Tidsskr Nor Laegeforen. 2006 Apr 6;126( Cool

: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.

jimmylegs · Family Elder Joined: Mar 12, 2006 Posts: 2089

J Neurogenet. 2005 Jan-Mar;19(1):25-38.
Variation in the vitamin D receptor gene is associated with multiple sclerosis in an Australian population.
Tajouri L, Ovcaric M, Curtain R, Johnson MP, Griffiths LR, Csurhes P, Pender MP, Lea RA.
Genomics Research Centre, School of Health Science, Griffith University Gold Coast, Southport, Queensland, Australia.

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) resulting in accumulating neurological disability. The disorder is more prevalent at higher latitudes. To investigate VDR gene variation using three intragenic restriction fragment length polymorphisms (Apa I, Taq I and Fok I) in an Australian MS case-control population. One hundred and four Australian MS patients were studied with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 104 age-, sex-, and ethnicity-matched controls were investigated as a comparative group. Our results show a significant difference of genotype distribution frequency between the case and control groups for the functional exon 9 VDR marker Taq I (p(Gen) = 0.016) and interestingly, a stronger difference for the allelic frequency (p(All) = 0.0072). The Apa I alleles were also found to be associated with MS (p(All) = 0.04) but genotype frequencies were not significantly different from controls (p(Gen) = 0.1). The Taq and Apa variants are in very strong and significant linkage disequilibrium (D' = 0.96, P < 0.0001). The genotypic associations are strongest for the progressive forms of MS (SP-MS and PP-MS). Our results support a role for the VDR gene increasing the risk of developing multiple sclerosis, particularly the progressive clinical subtypes of MS.

Postepy Hig Med Dosw (Online). 2005 Apr 6;59:129-39.
[Biological activity of calcitriol and its new analogues -- potential therapeutic applications]
[Article in Polish]
Pelczynska K, Jaroszewicz I, Switalska M, Opolski A.
Laboratorium Doswiadczalnej Terapii Przeciwnowotworowej, Zaklad Onkologii Doswiadczalnej Instytutu Immunologii i Terapii Doswiadczalnej PAN, Wroclaw.

Calcitriol is effective not only in the regulation of calcium-phosphate homeostasis, but also in promoting the differentiation and inhibition of proliferation of various cells. Calcitriol seems to be a potent drug with various therapeutic applications, such as regulation of calcium-phosphate homeostasis and treatment of psoriasis, autoimmune diseases, and cancer. Since clinical use of calcitriol is largely limited, due to its undesirable side effect of hypercalcemia, numerous calcitriol analogues have been synthesized to obtain compounds with better therapeutic profiles. This paper summarizes the current state of knowledge concerning the cellular mechanisms of calcitriol's biological activity and their clinical implications. Such medical application includes treatment (as a single-drug or in combination) of osteoporosis, renal osteodystrophy, psoriasis (calcipotriol or tacalcitol ointment), autoimmunological diseases (including multiple sclerosis), and some cancers. The efforts to obtain new vitamin D3 analogues are also briefly reviewed. The structures and roles of vitamin D receptors in the biological effects of calcitriol and its analogues are discussed.

Endocr Rev. 2005 Aug;26(5):662-87. Epub 2005 Mar 29.
Noncalcemic actions of vitamin D receptor ligands.
Nagpal S, Na S, Rathnachalam R.
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. nagpal_sunil@lilly.com

1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the active metabolite of vitamin D(3), is known for the maintenance of mineral homeostasis and normal skeletal architecture. However, apart from these traditional calcium-related actions, 1,25-(OH)(2)D(3) and its synthetic analogs are being increasingly recognized for their potent antiproliferative, prodifferentiative, and immunomodulatory activities. These actions of 1,25-(OH)(2)D(3) are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25-(OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential therapeutic applications of VDR ligands in inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, actinic keratosis, seborrheic dermatitis, photoaging), osteoporosis (postmenopausal and steroid-induced osteoporosis), cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), secondary hyperparathyroidism, and autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis, and organ transplantation). As a result, VDR ligands have been developed for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. Furthermore, encouraging results have been obtained with VDR ligands in clinical trials of prostate cancer and hepatocellular carcinoma. This review deals with the molecular aspects of noncalcemic actions of vitamin D analogs that account for the efficacy of VDR ligands in the above-mentioned indications.

Mutat Res. 2005 Apr 1;571(1-2):207-19. Epub 2005 Jan 28.
Ultraviolet radiation: effects on risks of prostate cancer and other internal cancers.
Moon SJ, Fryer AA, Strange RC.
Human Genomics Research Group, Institute of Science and Technology in Medicine and Department of Urology, Keele University School of Medicine, University Hospital of North Staffordshire, UK.

Governmental and research agencies worldwide have strongly advocated sun avoidance strategies in an attempt to counter marked increases in skin cancer incidence. Concurrently, there are reports describing widespread Vitamin D3 deficiency. Because 1,25-dihydroxyvitamin D3, through interaction with the Vitamin D receptor, exerts pleiotrophic effects, such deficiency might be expected to have clinical consequences. Indeed, various reports indicate that exposure to ultraviolet radiation (UVR) exerts a protective effect on development of some common diseases including internal cancers and multiple sclerosis. We describe studies indicating that modest exposure reduces risk of prostate cancer. The effect of UVR is mediated by skin type; at lower levels of exposure a relative inability to effect skin pigmentation is protective presumably because it allows more efficient Vitamin D3 synthesis. Polymorphic variants in genes associated with pigmentation including melanocyte stimulating hormone receptor and tyrosinase are also associated with prostate cancer risk. Overall, though preliminary and requiring cautious interpretation, these data indicate that moderate UVR exposure together with characteristics linked with less effective tanning confer reduced prostate cancer risk. Clearly, it is important to define safe levels of UVR that do not result in increased risk of skin cancers such as malignant melanoma.

Curr Drug Targets Inflamm Allergy. 2004 Dec;3(4):377-93.
Immunoregulation through 1,25-dihydroxyvitamin D3 and its analogs.
May E, Asadullah K, Zugel U.
Corporate Research Business Area Dermatology, Schering AG, Mullerstrasse 178, D-13342 Berlin, Germany.

Beyond its effects on bone metabolism, calcium and phosphorus homeostasis, 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3), calcitriol) exerts profound effects on the immune system. We here provide an overview over the metabolism, molecular and cellular action of 1,25(OH)(2)D(3) with particular regard to its immunomodulatory function. Effects of 1,25(OH)(2)D(3) on the immune system are manyfold and include suppression of T cell activation, shaping of cytokine secretion patterns, induction of regulatory T cells, modulation of proliferation, and interference with apoptosis. 1,25(OH)(2)D(3) further influences maturation, differentiation, and migration of antigen presenting cells. Altogether, its immunomodulatory potency is comparable to other established immunosuppressants without sharing their typical adverse effects. This profile makes 1,25(OH)(2)D(3) a potential drug for the treatment of immune-mediated diseases. Yet, the

major obstacle for its clinical use, its potent calcemic activity, is not overcome to date. The identification or generation of novel vitamin D derivatives with dissociated calcemic and immunomodulatory properties is therefore a major task. Its success might eventually lead to promising drugs for future therapeutic exploitation of a wide array of immune diseases, such as psoriasis, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and others.

Exp Biol Med (Maywood). 2004 Dec;229(11):1136-42.
Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence.
Cantorna MT, Mahon BD.
Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA. mxc69@psu.edu

Low vitamin D status has been implicated in the etiology of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory bowel disease. The optimal level of vitamin D intake required to support optimal immune function is not known but is likely to be at least that required for healthy bones. Experimentally, vitamin D deficiency results in the increased incidence of autoimmune disease. Mechanistically, the data point to a role for vitamin D in the development of self-tolerance. The vitamin D hormone (1,25-dihydroxy vitamin D(3)) regulates T helper cell (Th1) and dendritic cell function while inducing regulatory T-cell function. The net result is a decrease in the Th1-driven autoimmune response and decreased severity of symptoms. This review discusses the accumulating evidence pointing to a link between vitamin D and autoimmunity. Increased vitamin D intakes might decrease the incidence and severity of autoimmune diseases and the rate of bone fracture.

Loriyas · Posted: Fri May 12, 2006 2:25 pm Post subject:

Thank you for posting these studies on Vit D. I, too, am a firm believer in the benefits of Vit. D, especially from sunshine. Since we moved to Florida from Ohio I have felt much better and have not have any relapses (hope I don't jinx myself!) I have not researched Vit D studies to determine why I felt better but am glad to see the research behind it. I am just grateful to reap the benefits of it!
Lori

jimmylegs · Family Elder Joined: Mar 12, 2006 Posts: 2089

hi there L, i think sunshine is the best too, because of the calcium issues with high oral d supplementation. with my current supplement levels and intent to increase my dosage for the next 10 days or so, i am going to have to get the serum values of a few things in a couple of weeks.

perhaps i should take a month off during each canadian winter and visit a different spot on the equator each year Wink

lyndacarol · Family Elder Joined: Dec 23, 2005 Posts: 526

After poring and poring over the Vitamin D information, I find I cannot ignore it! If I KNOW my insulin level is high and discover (I will ask my doctor for the blood test this week.) my D is low, couldn't they be connected?

Maybe by binding with or breaking down D, insulin is removed from the body? If so, this could explain the lower prevalence of MS the nearer the equator. And the virtual nonexistence among Eskimos, who eat a lot of fish (dietary D AND reduced carbs which promote insulin production) I wonder if the internationally recognized expert on Vitamin D there in Canada, Reinhold Vieth, knows how insulin interacts with D. Do you have any contact with him, jimmylegs?

Time to find those sun rays!

jimmylegs · Family Elder Joined: Mar 12, 2006 Posts: 2089

i know LC isn't it CRAZY?

i have no contact (as yet) with RV. i'll keep digging around for more info.

ciao!