“The Need for Vitamin D3 as a Supplement.”

9 August 2008

Reference:  http://www.ajcn.org/cgi/content/abstract/84/4/694

Further reference material is abstracts from PubMed database
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Am J Clin Nutr. 2008 Apr;87(4):1080S-6S.

Vitamin D deficiency: a worldwide problem with health consequences.
Holick MF, Chen TC.
Department of Medicine, Boston University School of Medicine, 715 Albany Street, M-1013, Boston, MA 02118, USA. mfholick@bu.edu

Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800-1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations.
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The case against ergocalciferol (vitamin D2) as a vitamin supplement
Lisa A Houghton and Reinhold Vieth

From the School of Nutrition and Dietetics, Acadia University, Wolfville, Canada (LAH); the Department of Nutritional Sciences, University of Toronto, Toronto, Canada (RV); and the Mount Sinai Hospital, Toronto, Canada (RV)

Supplemental vitamin D is available in 2 distinct forms: ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Pharmacopoeias have officially regarded these 2 forms as equivalent and interchangeable, yet this presumption of equivalence is based on studies of rickets prevention in infants conducted 70 y ago. The emergence of 25-hydroxyvitamin D as a measure of vitamin D status provides an objective, quantitative measure of the biological response to vitamin D administration. As a result, vitamin D3 has proven to be the more potent form of vitamin D in all primate species, including humans. Despite an emerging body of evidence suggesting several plausible explanations for the greater bioefficacy of vitamin D3, the form of vitamin D used in major preparations of prescriptions in North America is vitamin D2. The case that vitamin D2 should no longer be considered equivalent to vitamin D3 is based on differences in their efficacy at raising serum 25-hydroxyvitamin D, diminished binding of vitamin D2 metabolites to vitamin D binding protein in plasma, and a nonphysiologic metabolism and shorter shelf life of vitamin D2. Vitamin D2, or ergocalciferol, should not be regarded as a nutrient suitable for supplementation or fortification.
 
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Nat Clin Pract Rheumatol. 2008 Aug;4(8):404-12. Epub 2008 Jul 1.
Control of autoimmune diseases by the vitamin D endocrine system.

Adorini L, Penna G.
Intercept Pharmaceuticals, Corciano (Perugia), Italy. ladorini@interceptpharma.com

1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], the biologically active form of vitamin D(3), is a secosteroid hormone essential for bone and mineral homeostasis. It regulates the growth and differentiation of multiple cell types, and displays immunoregulatory and anti-inflammatory properties. Cells involved in innate and adaptive immune responses--including macrophages, dendritic cells, T cells and B cells--express the vitamin D receptor (VDR), and can both produce and respond to 1,25(OH)(2)D(3). The net effect of the vitamin D system on the immune response is an enhancement of innate immunity coupled with multifaceted regulation of adaptive immunity. Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of several autoimmune diseases, and clarification of the physiological role of endogenous VDR agonists in the regulation of autoimmune responses will guide the development of pharmacological VDR agonists for use in the clinic. The antiproliferative, prodifferentiative, antibacterial, immunomodulatory and anti-inflammatory properties of synthetic VDR agonists could be exploited to treat a variety of autoimmune diseases, from rheumatoid arthritis to systemic lupus erythematosus, and possibly also multiple sclerosis, type 1 diabetes, inflammatory bowel diseases, and autoimmune prostatitis.
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Curr Rheumatol Rep. 2008 Aug;10(4):273-80.
The link between vitamin D deficiency and systemic lupus erythematosus.

Kamen DL, Aranow C.
Division of Rheumatology, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 912, Charleston, SC 29425, USA. kamend@musc.edu
Vitamin D deficiency is highly prevalent and is increasingly thought to be an important risk factor in many diseases that have high morbidity and mortality, including lupus. Vitamin D is an immunomodulatory hormone with effects on T cells, B cells, and dendritic cells. Animal models of autoimmune disease and epidemiologic studies suggest a role for vitamin D as a modifiable environmental factor in autoimmune disease. Recommendations are available regarding screening for and repletion of vitamin D deficiency. More research is needed to understand the role of vitamin D as an immunomodulator and to determine the optimal range of serum 25-hydroxyvitamin D for musculoskeletal, cardiovascular, and immune health.
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Curr Opin Nephrol Hypertens. 2008 Jul;17(4):408-15.
The noncalciotropic actions of vitamin D: recent clinical developments.

Maalouf NM.
Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8885, USA. naim.maalouf@utsouthwestern.edu
PURPOSE OF REVIEW: This review summarizes recently described actions of 1,25-dihydroxyvitamin D beyond its function in calcium homeostasis and bone metabolism. RECENT FINDINGS: 1,25-Dihydroxyvitamin D stimulates the innate immune system, facilitating the clearance of infections such as tuberculosis. Hypovitaminosis D has been associated with several autoimmune disorders, various malignancies, and cardiovascular risk factors in a number of recent epidemiologic reports. Based on these observational reports, vitamin D and its analogues are being evaluated for the prevention and treatment of a variety of conditions, with early findings showing mixed results. SUMMARY: The broad tissue distribution of the 25-hydroxyvitamin D 1alpha-hydroxylase enzyme and the vitamin D receptor establish a role for 1,25-dihydroxyvitamin D in the pathophysiology of various disease states and provide new therapeutic targets for vitamin D and its analogues
 
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Scand J Immunol. 2008 May 29. [Epub ahead of print] Links
The Complex Role of Vitamin D in Autoimmune Diseases.

Szodoray P, Nakken B, Gaal J, Jonsson R, Szegedi A, Zold E, Szegedi G, Brun JG, Gesztelyi R, Zeher M, Bodolay E.
Division of Clinical Immunology, 3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Vitamin D, besides having well-known control functions of calcium and phosphorus metabolism, bone formation and mineralization, also has a role in the maintenance of immune-homeostasis. The immune-regulatory role of vitamin D affects both the innate and adaptive immune system contributing to the immune-tolerance of self-structures. Impaired vitamin D supply/regulation, amongst other factors, leads to the development of autoimmune processes in animal models of various autoimmune diseases. The administration of vitamin D in these animals leads to improvement of immune-mediated symptoms. Moreover, in human autoimmune diseases, such as multiple sclerosis, or rheumatoid arthritis the pathogenic role of vitamin D has been described. The review aims at describing the complex immune-regulatory role of vitamin D from the cellular level through autoimmune animal models and depicting the known contribution of vitamin D in the pathogenesis of human autoimmune diseases..