The following vitamin D abstracts support the use of supplemental Vitamin D3. Integratedhealth.com has designed Vitamin D3 Plus with this vitamin D research in mind.
(REFERENCE 1 OF 20)
Endocrinol Metab Clin North Am. 2010 Jun;39(2):287-301, table of contents.
Low vitamin D status: definition, prevalence, consequences, and correction.
Binkley N, Ramamurthy R, Krueger D.
University of Wisconsin-Madison Osteoporosis Clinical Center and Research Program, Madison, WI 53705, USA. firstname.lastname@example.org
Vitamin D is obtained from cutaneous production when 7-dehydrocholesterol is converted to vitamin D(3) (cholecalciferol) by ultraviolet B radiation or by oral intake of vitamin D(2) (ergocalciferol) and D(3). An individual’s vitamin D status is best evaluated by measuring the circulating 25-hydroxyvitamin D (25(OH)D) concentration. Although controversy surrounds the definition of low vitamin D status, there is increasing agreement that the optimal circulating 25(OH)D level should be approximately 30 to 32 ng/mL or above. Using this definition, it has been estimated that approximately three-quarters of all adults in the United States have low levels. Low vitamin D status classically has skeletal consequences such as osteomalacia/rickets. More recently, associations between low vitamin D status and increased risk for various nonskeletal morbidities have been recognized; whether all of these associations are causally related to low vitamin D status remains to be determined. To achieve optimal vitamin D status, daily intakes of at least 1000 IU or more of vitamin D are required. The risk of toxicity with “high” amounts of vitamin D intake is low. Substantial between-individual variability exists in response to the same administered vitamin D dose. When to monitor 25(OH)D levels has received little attention. Supplementation with vitamin D(3) may be preferable to vitamin D(2).
(REFERENCE 2 OF 20)
Aliment Pharmacol Ther. 2010 Aug;32(3):377-83. Epub 2010 May 11.
Clinical trial: vitamin D3 treatment in Crohn’s disease – a randomized double-blind placebo-controlled study.
Jørgensen SP, Agnholt J, Glerup H, Lyhne S, Villadsen GE, Hvas CL, Bartels LE, Kelsen J, Christensen LA, Dahlerup JF.
Department of Medicine V, Aarhus University Hospital, Denmark. email@example.com
BACKGROUND: Vitamin D has immune-regulatory functions in experimental colitis, and low vitamin D levels are present in Crohn’s disease.
AIM: To assess the effectiveness of vitamin D3 treatment in Crohn’s disease with regard to improved disease course.
METHODS: We performed a randomized double-blind placebo-controlled trial to assess the benefits of oral vitamin D3 treatment in Crohn’s disease. We included 108 patients with Crohn’s disease in remission, of which fourteen were excluded later. Patients were randomized to receive either 1200 IU vitamin D3 (n = 46) or placebo (n = 48) once daily during 12 months. The primary endpoint was clinical relapse.
RESULTS: Oral vitamin D3 treatment with 1200 IU daily increased serum 25OHD from mean 69 nmol/L [standard deviation (s.d.) 31 nmol/L] to mean 96 nmol/L (s.d. 27 nmol/L) after 3 months (P < 0.001). The relapse rate was lower among patients treated with vitamin D3 (6/46 or 13%) than among patients treated with placebo (14/48 or 29%), (P = 0.06).
CONCLUSIONS: Oral supplementation with 1200 IE vitamin D3 significantly increased serum vitamin D levels and insignificantly reduced the risk of relapse from 29% to 13%, (P = 0.06). Given that vitamin D3 treatment might be effective in Crohn’s disease, we suggest larger studies to elucidate this matter further.
(REFERENCE 3 OF 20)
Pediatr Endocrinol Rev. 2010 Dec;8(2):103-7.
Non-classic unexpected functions of vitamin D.
Faculty of Medicine, Tel Aviv University, and Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel. firstname.lastname@example.org
In the past three decades, our understanding of the physiologic functions of vitamin D1 has extended and includes many unexpected non-classic biological actions. Vitamin D receptors (VDR) and 25-hydroxyvitamin D-1 α-hydroxylase, the enzyme responsible for the production of 1,25(OH)2D3, the active form of vitamin D, are present in many tissues which are not associated with calcium or bone metabolism. Indeed, 1,25(OH)2D regulates cell proliferation, differentiation and apoptosis in many normal and cancer cells. Epidemiologic studies have shown that vitamin D deficiency increases the risk of cancer, cardiovascular disease and autoimmune disease. However, large scale randomized controlled intervention trials are needed to prove the effects of vitamin D on the prevention and treatment of these diseases. Expression of vitamin D or its metabolites without a subscript refer to both vitamin D2 and vitamin D3 or their metabolites.
(REFERENCE 4 OF 20)
Prog Biophys Mol Biol. 2006 Sep;92(1):4-8. Epub 2006 Feb 28.
Vitamin D physiology.
Department of Endocrinology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands. email@example.com
Vitamin D3 is synthesized in the skin during summer under the influence of ultraviolet light of the sun, or it is obtained from food, especially fatty fish. After hydroxylation in the liver into 25-hydroxyvitamin D (25(OH)D) and kidney into 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite can enter the cell, bind to the vitamin D-receptor and subsequently to a responsive gene such as that of calcium binding protein. After transcription and translation the protein is formed, e.g. osteocalcin or calcium binding protein. The calcium binding protein mediates calcium absorption from the gut. The production of 1,25(OH)2D is stimulated by parathyroid hormone (PTH) and decreased by calcium. Risk factors for vitamin D deficiency are premature birth, skin pigmentation, low sunshine exposure, obesity, malabsorption and advanced age. Risk groups are immigrants and the elderly. Vitamin D status is dependent upon sunshine exposure but within Europe, serum 25(OH)D levels are higher in Northern than in Southern European countries. Severe vitamin D deficiency causes rickets or osteomalacia, where the new bone, the osteoid, is not mineralized. Less severe vitamin D deficiency causes an increase of serum PTH leading to bone resorption, osteoporosis and fractures. A negative relationship exists between serum 25(OH)D and serum PTH. The threshold of serum 25(OH)D, where serum PTH starts to rise is about 75nmol/l according to most surveys. Vitamin D supplementation to vitamin D-deficient elderly suppresses serum PTH, increases bone mineral density and may decrease fracture incidence especially in nursing home residents. The effects of 1,25(OH)2D and the vitamin D receptor have been investigated in patients with genetic defects of vitamin D metabolism and in knock-out mouse models. These experiments have demonstrated that for active calcium absorption, longitudinal bone growth and the activity of osteoblasts and osteoclasts both 1,25(OH)2D and the vitamin D receptor are essential. On the other side, bone mineralization can occur by high ambient calcium concentration, so by high doses of oral calcium or calcium infusion. The active metabolite 1,25(OH)2D has its effects through the vitamin D receptor leading to gene expression, e.g. the calcium binding protein or osteocalcin or through a plasma membrane receptor and second messengers such as cyclic AMP. The latter responses are very rapid and include the effects on the pancreas, vascular smooth muscle and monocytes. Muscle cells contain vitamin D receptor and several studies have demonstrated that serum 25(OH)D is related to physical performance. The active metabolite 1,25(OH)2D has an antiproliferative effect and downregulates inflammatory markers. Extrarenal synthesis of 1,25(OH)2D occurs under the influence of cytokines and is important for the paracrine regulation of cell differentiation and function. This may explain that vitamin D deficiency can play a role in the pathogenesis of auto-immune diseases such as multiple sclerosis and diabetes type 1, and cancer. In conclusion, the active metabolite 1,25(OH)2D has pleiotropic effects through the vitamin D receptor and vitamin D responsive elements of many genes and on the other side rapid non-genomic effects through a membrane receptor and second messengers. Active calcium absorption from the gut depends on adequate formation of 1,25(OH)2D and an intact vitamin D receptor. Bone mineralization mainly depends on ambient calcium concentration. Vitamin D metabolites may play a role in the prevention of auto-immune disease and cancer.
PMID: 16563471 [PubMed – indexed for MEDLINE]
(REFERENCE 5 OF 20)
Altern Med Rev. 2010 Sep;15(3):199-222.
Vitamins D and K as pleiotropic nutrients: clinical importance to the skeletal and cardiovascular systems and preliminary evidence for synergy.
University of California, Berkeley, USA. firstname.lastname@example.org
Vitamins D and K are lipid-phase nutrients that are pleiotropic – endowed with versatile homeostatic capacities at the organ, tissue, and cellular levels. Their metabolic and physiologic roles overlap considerably, as evidenced in the bone and cardiovascular systems. Vitamin D₃ (cholecalciferol, D₃) is the prehormone for the vitamin D endocrine system. Vitamin D₃ undergoes initial enzymatic conversion to 25-hydroxyvitamin D (25D, calcidiol), then to the seco-steroid hormone 1alpha, 25-dihydroxyvitamin D (1,25D, calcitriol). Beyond its endocrine roles in calcium homeostasis, 1,25D likely has autocrine, paracrine, and intracrine effects. At least 17 tissues likely synthesize 1,25D, and 35 carry the vitamin D receptor (VDR). Vitamin D functional deficiency is widespread in human populations. Vitamin K₁ (phylloquinone) is more abundant in foods but less bioactive than the vitamin K₂ menaquinones (especially MK-4, menatetrenone). Menadione (vitamin K₃) has minimal K activity. Vitamin K compounds undergo oxidation-reduction cycling within the endoplasmic reticulum membrane, donating electrons to activate specific proteins via enzymatic gamma-carboxylation of glutamate groups before being enzymatically re-reduced. Warfarin inhibits this vitamin K reduction, necessitating K supplementation during anticoagulation therapy. Along with coagulation factors (II, VII, IX, X, and prothrombin), protein C and protein S, osteocalcin (OC), matrix Gla protein (MGP), periostin, Gas6, and other vitamin K-dependent (VKD) proteins support calcium homeostasis, facilitate bone mineralization, inhibit vessel wall calcification, support endothelial integrity, are involved in cell growth control and tissue renewal, and have numerous other effects. This review updates vitamin D and K skeletal and cardiovascular benefits and evidence for their synergy of action.
PMID: 21155624 [PubMed – in process]
(REFERENCE 6 OF 20)
Nutr J. 2010 Dec 8;9(1):65. [Epub ahead of print]
Vitamin D in health and disease: Current perspectives.
ABSTRACT: Despite the numerous reports of the association of vitamin D with a spectrum of development, disease treatment and health maintenance, vitamin D deficiency is common. Originating in part from the diet but with a key source resulting from transformation by exposure to sunshine, a great deal of the population suffers from vitamin D deficiency especially during winter months. It is linked to the treatment and pathogenesis and/or progression of several disorders including cancer, hypertension, multiple sclerosis, rheumatoid arthritis, osteoporosis, muscle weakness and diabetes. This widespread deficiency of Vitamin D merits consideration of widespread policies including increasing awareness among the public and healthcare professionals.
(REFERENCE 7 OF 20)
Expert Rev Anti Infect Ther. 2010 Dec;8(12):1359-69.
Vitamin D: emerging roles in infection and immunity.
Department of Otolaryngology-Head and Neck Surgery, Counties-Manukau District Health Board, Auckland, New Zealand. email@example.com
In the preantibiotic era, TB of the skin was treated successfully with UV light. By the 1920s, pulmonary TB was being treated with regular sun exposure. During the last decade, basic laboratory research into the antimicrobial actions of vitamin D has provided new insights into these historical observations. Vitamin D has a critical role in the innate immune system through the production of antimicrobial peptides – particularly cathelicidin. Vitamin D would appear to have an important role in respiratory tract, skin and potentially gut health. A number of autoimmune diseases, including multiple sclerosis, Type I diabetes, systemic lupus erythematosus and rheumatoid arthritis, are associated with vitamin D deficiency. Vitamin D could have an important role in the prevention and possible treatment of these conditions; however, much of the current evidence relates to basic science and epidemiological research. In many situations, appropriate double-blind, randomized controlled trial data to guide clinicians treating infectious and autoimmune disease is still lacking.
(REFERENCE 8 OF 20)
Curr Opin Gastroenterol. 2010 Nov;26(6):591-5.
Vitamin D and mucosal immune function.
Department of Medicine, University of Rochester, Rochester, New York 14642, USA. firstname.lastname@example.org
PURPOSE OF REVIEW: Significant advances have been made in the characterization of Vitamin D and the Vitamin D receptor (VDR) in immune function. The studies of signaling pathways involved in the response to infection and inflammation have led to a more detailed understanding of the cellular response to Vitamin D through VDR. This review summarizes recent progress in understanding how Vitamin D contributes to mucosal immune function, particularly in relation to the molecular mechanisms by which Vitamin D and VDR influence mucosal immunity, bacterial infection, and inflammation.
RECENT FINDINGS: Recently, it was shown that Vitamin D modulates the T cell antigen receptor, further demonstrating that Vitamin D has a nonclassical role in immunoregulation. The anti-inflammation and anti-infection functions for Vitamin D are newly identified and highly significant activities. Vitamin D/VDR have multiple critical functions in regulating the response to intestinal homeostasis, tight junctions, pathogen invasion, commensal bacterial colonization, antimicrobe peptide secretion, and mucosal defense. Interestingly, microorganisms modulate the VDR signaling pathway.
SUMMARY: Vitamin D is known as a key player in calcium homeostasis and electrolyte and blood pressure regulation. Recently, important progress has been made in understanding how the noncanonical activities of Vitamin D influence the pathogenesis and prevention of human disease. Vitamin D and VDR are directly involved in T cell antigen receptor signaling. The involvement of Vitamin D/VDR in anti-inflammation and anti-infection represents a newly identified and highly significant activity for VDR. Studies have indicated that the dysregulation of VDR may lead to exaggerated inflammatory responses, raising the possibility that defects in Vitamin D and VDR signaling transduction may be linked to bacterial infection and chronic inflammation. Further characterization of Vitamin D/VDR will help elucidate the pathogenesis of various human diseases and in the design of new approaches for prevention and treatment.
(REFERENCE 9 OF 20)
Nat Clin Pract Rheumatol. 2008 Aug;4(8):404-12. Epub 2008 Jul 1.
Control of autoimmune diseases by the vitamin D endocrine system.
Intercept Pharmaceuticals, Corciano (Perugia), Italy. email@example.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.
(REFERENCE 10 OF 20)
J Clin Endocrinol Metab. 2009 Oct;94(10):4023-30. Epub 2009 Jul 7.
Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects.
Tarcin O, Yavuz DG, Ozben B, Telli A, Ogunc AV, Yuksel M, Toprak A, Yazici D, Sancak S, Deyneli O, Akalin S.
Section of Endocrinology and Metabolism, Marmara University School of Medicine, 34060 Istanbul, Turkey. firstname.lastname@example.org
CONTEXT: Vitamin D receptors are present in many tissues. Hypovitaminosis D is considered to be a risk factor for atherosclerosis.
OBJECTIVE: This study explores the effects of vitamin D replacement on insulin sensitivity, endothelial function, inflammation, oxidative stress, and leptin in vitamin D-deficient subjects.
DESIGN, SETTING, AND PATIENTS: Twenty-three asymptomatic vitamin D-deficient subjects with 25-hydroxyvitamin D [25(OH)D] levels below 25 nmol/liter were compared with a control group that had a mean 25(OH)D level of 75 nmol/liter. The vitamin D-deficient group received 300,000 IU im monthly for 3 months. The following parameters were evaluated before and after treatment: vitamin D metabolites, leptin, endothelial function by brachial artery flow mediated dilatation (FMD), insulin sensitivity index based on oral glucose tolerance test, and lipid peroxidation as measures of thiobarbituric acid reactive substances (TBARS).
RESULTS: FMD measurements were significantly lower in 25(OH)D-deficient subjects than controls (P = 0.001) and improved after replacement therapy (P = 0.002). Posttreatment values of TBARS were significantly lower than pretreatment levels (P < 0.001). A positive correlation between FMD and 25(OH)D (r = 0.45; P = 0.001) and a negative correlation between FMD and TBARS (r = -0.28; P < 0.05) were observed. There was a significant increase in leptin levels after therapy, and the leptin levels were positively correlated with 25(OH)D levels (r = 0.45; P < 0.05).
CONCLUSIONS: This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation. Replacement of vitamin D has favorable effects on endothelial function. Vitamin D deficiency can be seen as an independent risk factor of atherosclerosis. Hypovitaminosis D-associated endothelial dysfunction may predispose to higher rates of cardiovascular disease in the winter.
(REFERENCE 11 OF 20)
Autoimmun Rev. 2006 Feb;5(2):114-7. Epub 2005 Jun 21.
Vitamin D deficiency in systemic lupus erythematosus.
Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS.
Medical University of South Carolina, Charleston, SC, USA. email@example.com
Evidence from animal models and prospective studies of RA, multiple sclerosis, and type-1 diabetes suggest an important role for vitamin D as a modifiable environmental factor in autoimmune disease. This role has not been well studied in human SLE. We compared serum 25-hydroxyvitamin D (25(OH)D) levels between recently diagnosed SLE cases and matched controls, and examined disease characteristics in relationship to 25(OH)D among cases. Data from a population-based cohort of 123 recently diagnosed SLE patients and 240 controls were used. We found a trend toward lower 25(OH)D levels in cases compared to controls, which was statistically significant in Caucasians (p=0.04), controlling for age, sex, season, and smoking. Overall, 67% of the subjects were vitamin D deficient, with mean levels significantly lower among African Americans (15.9 ng/ml) compared to Caucasians (31.3 ng/ml). Critically low vitamin D levels (<10 ng/ml) were found in 22 of the SLE cases, with presence of renal disease being the strongest predictor (OR 13.3, p<0.01) followed by photosensitivity (OR 12.9, p<0.01). These results suggest vitamin D deficiency as a possible risk factor for SLE and provide guidance for future studies looking at a potential role of vitamin D in the prevention and/or treatment of SLE.
(REFERENCE 12 OF 20)
Nutrition. 2010 Mar;26(3):255-62. Epub 2009 Dec 8.
Breast cancer survivors and vitamin D: a review.
Hines SL, Jorn HK, Thompson KM, Larson JM.
Division of Consultative and Diagnostic Medicine, Mayo Clinic, Jacksonville, Florida, USA. firstname.lastname@example.org
Recent evidence has suggested a role for vitamin D in breast cancer prevention and survival. Studies have reported an inverse relation between vitamin D intake and the risk of breast cancer, improvements in survival after a diagnosis of breast cancer in women with higher levels of vitamin D, and vitamin D insufficiency in up to 75% of women with breast cancer. Preclinical data have indicated that vitamin D affects up to 200 genes that influence cellular proliferation, apoptosis, angiogenesis, terminal differentiation of normal and cancer cells, and macrophage function. Vitamin D receptors have been found in up to 80% of breast cancers, and vitamin D receptor polymorphisms have been associated with differences in survival. Although ongoing studies have investigated a possible link between adequate levels of vitamin D and improved cancer prognosis, breast cancer survivors may derive additional, non-cancer-related benefits from adequate vitamin D levels, including improvements in bone mineral density, quality of life, and mood. Maintaining adequate vitamin D stores is recommended for breast cancer survivors throughout their lifetime.
(REFERENCE 13 OF 20)
Nutr Clin Pract. 2007 Jun;22(3):297-304.
Vitamin D and rehabilitation: improving functional outcomes.
Spaulding Rehabilitation Hospital, Boston, MA, USA.
Erratum in: Nutr Clin Pract. 2007 Aug;22(4):table of contents. Shinchuk, Leonid [corrected to Shinchuk, Leonid M].
Vitamin D inadequacy is pandemic among rehabilitation patients in both inpatient and outpatient settings. Male and female patients of all ages and ethnic backgrounds are affected. Vitamin D deficiency causes osteopenia, precipitates and exacerbates osteoporosis, causes the painful bone disease osteomalacia, and worsens proximal muscle strength and postural sway. Vitamin D inadequacy can be prevented by sensible sun exposure and adequate dietary intake with supplementation. Vitamin D status is determined by measurement of serum 25-hydroxyvitamin D. The recommended healthful serum level is between 30 and 60 ng/mL. 25-Hydroxyvitamin D levels of >30 ng/mL are sufficient to suppress parathyroid hormone production and to maximize the efficiency of dietary calcium absorption from the small intestine. This can be accomplished by ingesting 1000 IU of vitamin D(3) per day, or by taking 50,000 IU of vitamin D(2) every 2 weeks. Vitamin D toxicity is observed when 25-hydroxyvitamin D levels exceed 150 ng/mL. Identification and treatment of vitamin D deficiency reduces the risk of vertebral and nonvertebral fractures by improving bone health and musculoskeletal function. Vitamin D deficiency and osteomalacia should be considered in the differential diagnosis of patients with musculoskeletal pain, fibromyalgia, chronic fatigue syndrome, or myositis. There is a need for better education of health professionals and the general public regarding the optimization of vitamin D status in the care of rehabilitation patients.
(REFERENCE 14 OF 20)
Ishir Bhan*†, Sherri-Ann M. Burnett-Bowie‡, Jun Ye*, Marcello Tonelli§, Ravi Thadhani*
Clinical Measures Identify Vitamin D Deficiency in Dialysis
Background and objectives: Vitamin D deficiency (defined by serum levels of 25-hydroxyvitamin D) is common in patients with ESRD on hemodialysis, but risk factors are unknown. This study was conducted to determine whether routinely measured clinical and demographic parameters could identify dialysis patients who are vitamin D deficient.
Design, setting, participants, & measurements: Nine-hundred eight patients with 25-hydroxyvitamin D levels were identified from the Accelerated Mortality on Renal Replacement (ArMORR) cohort of incident U.S. dialysis patients and were divided into training (60%) and validation (40%) sets. Predictive models were generated from routinely assessed clinical and demographic data in the training set using logistic regression modeling, neural networks, and decision trees with vitamin D deficiency as the dependent variable. Models underwent progressive variable reduction to identify the simplest model that remained predictive.
Results: Seventy-nine percent of the population was vitamin D deficient (25-hydroxyvitamin D <30 ng/ml). Black race, female sex, winter season, and hypoalbuminemia (serum albumin ≤3.1 g/dl) were the strongest predictors of vitamin D deficiency. In the validation set, the presence of hypoalbuminemia and winter season increased the likelihood of vitamin D deficiency in black women (from 90% to 100%), black men (from 85% to 100%), white women (from 82% to 94%), and white men (from 66% to 92%).
Conclusions: Deficiency of 25-hydroxyvitamin D is nearly universal among patients with hypoalbuminemia initiating chronic hemodialysis in winter.
(REFERENCE 15 OF 20)
Nutr Res Rev. 2009 Dec;22(2):118-36.
Vitamin D in health and disease: an insight into traditional functions and new roles for the ‘sunshine vitamin’.
Australian Sun and Health Research Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Victoria Point Road, Kelvin Grove, 4059 Brisbane, Australia. email@example.com
Vitamin D is unique among the vitamins in that man can synthesise it via the action of UV radiation upon the skin. This combined with its ability to act on specific target tissues via vitamin D receptors (VDR) make its classification as a steroid hormone more appropriate. While vitamin D deficiency is a recognised problem in some northern latitude countries, recent studies have shown that even in sunny countries, such as Australia, vitamin D deficiency may be more prevalent than first thought. Vitamin D is most well known for its role in bone health; however, the discovery of VDR on a wide variety of tissue types has also opened up roles for vitamin D far beyond traditional bone health. These include possible associations with autoimmune diseases such as multiple sclerosis and inflammatory bowel diseases, cancer, CVD and muscle strength. First, this paper presents an overview of the two sources of vitamin D: exposure to UVB radiation and food sources of vitamin D, with particular focus on both Australian and international studies on dietary vitamin D intake and national fortification strategies. Second, the paper reviews recent epidemiological and experimental evidence linking vitamin D and its role in health and disease for the major conditions linked to suboptimal vitamin D, while identifying significant gaps in the research and possible future directions for research.
(REFERENCE 16 OF 20)
Am J Clin Nutr. 2004 Dec;80(6 Suppl):1678S-88S.
Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease.
Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, Vitamin D, Skin, and Bone Research Laboratory, Boston University Medical Center, Boston, MA 02118, USA. firstname.lastname@example.org
Most humans depend on sun exposure to satisfy their requirements for vitamin D. Solar ultraviolet B photons are absorbed by 7-dehydrocholesterol in the skin, leading to its transformation to previtamin D3, which is rapidly converted to vitamin D3. Season, latitude, time of day, skin pigmentation, aging, sunscreen use, and glass all influence the cutaneous production of vitamin D3. Once formed, vitamin D3 is metabolized in the liver to 25-hydroxyvitamin D3 and then in the kidney to its biologically active form, 1,25-dihydroxyvitamin D3. Vitamin D deficiency is an unrecognized epidemic among both children and adults in the United States. Vitamin D deficiency not only causes rickets among children but also precipitates and exacerbates osteoporosis among adults and causes the painful bone disease osteomalacia. Vitamin D deficiency has been associated with increased risks of deadly cancers, cardiovascular disease, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus. Maintaining blood concentrations of 25-hydroxyvitamin D above 80 nmol/L (approximately 30 ng/mL) not only is important for maximizing intestinal calcium absorption but also may be important for providing the extrarenal 1alpha-hydroxylase that is present in most tissues to produce 1,25-dihydroxyvitamin D3. Although chronic excessive exposure to sunlight increases the risk of nonmelanoma skin cancer, the avoidance of all direct sun exposure increases the risk of vitamin D deficiency, which can have serious consequences. Monitoring serum 25-hydroxyvitamin D concentrations yearly should help reveal vitamin D deficiencies. Sensible sun exposure (usually 5-10 min of exposure of the arms and legs or the hands, arms, and face, 2 or 3 times per week) and increased dietary and supplemental vitamin D intakes are reasonable approaches to guarantee vitamin D sufficiency.
(REFERENCE 17 OF 20)
J Am Board Fam Med. 2009 Nov-Dec;22(6):698-706.
Vitamin D: an evidence-based review.
Kulie T, Groff A, Redmer J, Hounshell J, Schrager S.
Department of Family Medicine, University of Wisconsin, Madison, WI 53715, USA.
Erratum in: J Am Board Fam Med. 2010 Jan-Feb;23(1):138.
Vitamin D is a fat-soluble vitamin that plays an important role in bone metabolism and seems to have some anti-inflammatory and immune-modulating properties. In addition, recent epidemiologic studies have observed relationships between low vitamin D levels and multiple disease states. Low vitamin D levels are associated with increased overall and cardiovascular mortality, cancer incidence and mortality, and autoimmune diseases such as multiple sclerosis. Although it is well known that the combination of vitamin D and calcium is necessary to maintain bone density as people age, vitamin D may also be an independent risk factor for falls among the elderly. New recommendations from the American Academy of Pediatrics [corrected] address the need for supplementation in breastfed newborns and many questions are raised regarding the role of maternal supplementation during lactation. Unfortunately, little evidence guides clinicians on when to screen for vitamin D deficiency or effective treatment options.
(REFERENCE 18 OF 20)
Ann Epidemiol. 2009 Jul;19(7):468-83.
Vitamin D for cancer prevention: global perspective.
Garland CF, Gorham ED, Mohr SB, Garland FC.
Department of Family and Preventive Medicine, University of California San Diego (UCSD), La Jolla, CA, USA.
PURPOSE: Higher serum levels of the main circulating form of vitamin D, 25-hydroxyvitamin D (25(OH)D), are associated with substantially lower incidence rates of colon, breast, ovarian, renal, pancreatic, aggressive prostate and other cancers.
METHODS: Epidemiological findings combined with newly discovered mechanisms suggest a new model of cancer etiology that accounts for these actions of 25(OH)D and calcium. Its seven phases are disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition (abbreviated DINOMIT). Vitamin D metabolites prevent disjunction of cells and are beneficial in other phases.
RESULTS/CONCLUSIONS: It is projected that raising the minimum year-around serum 25(OH)D level to 40 to 60 ng/mL (100-150 nmol/L) would prevent approximately 58,000 new cases of breast cancer and 49,000 new cases of colorectal cancer each year, and three fourths of deaths from these diseases in the United States and Canada, based on observational studies combined with a randomized trial. Such intakes also are expected to reduce case-fatality rates of patients who have breast, colorectal, or prostate cancer by half. There are no unreasonable risks from intake of 2000 IU per day of vitamin D(3), or from a population serum 25(OH)D level of 40 to 60 ng/mL. The time has arrived for nationally coordinated action to substantially increase intake of vitamin D and calcium.
(REFERENCE 19 OF 20)
J Am Board Fam Med. 2009 Jan-Feb;22(1):69-74.
Improvement of chronic back pain or failed back surgery with vitamin D repletion: a case series.
Department of Family Medicine, University of Alberta, Canada. email@example.com
This article reviews 6 selected cases of improvement/resolution of chronic back pain or failed back surgery after vitamin D repletion in a Canadian family practice setting. Pub Med was searched for articles on chronic back pain, failed back surgery, and vitamin D deficiency. Chronic low back pain and failed back surgery may improve with repletion of vitamin D from a state of deficiency/insufficiency to sufficiency. Vitamin D insufficiency is common; repletion of vitamin D to normal levels in patients who have chronic low back pain or have had failed back surgery may improve quality of life or, in some cases, result in complete resolution of symptoms.
(REFERENCE 20 OF 20)
Arq Bras Endocrinol Metabol. 2008 Jun;52(4):684-91.
[Low levels of 25-hydroxyvitamin D (25OHD) in patients with inflammatory bowel disease and its correlation with bone mineral density]. [Article in Portuguese]
Souza HN, Lora FL, Kulak CA, Mañas NC, Amarante HM, Borba VZ.
Serviço de Endocrinologia e Metabologia, Hospital de Clínicas, Universidade Federal do Paraná, PR, Brasil.
Patients with inflammatory bowel disease (IBD) are at risk of having vitamin D deficiency (25-OHD) and low bone mineral density (BMD).
OBJECTIVES: To measure 25OHD in a young group of IBD patients submitted to a clinical evaluation, routine biochemistry and BMD measurement (lumbar spine and proximal femur).
RESULTS: 39 Crohn disease (CD) and 37 ulcerative colitis (UC) patients had lower serum levels of 25OHD compared to the control group (CD p = 0.003; UC p < 0.001), and 48.5% of the UC patients were 25OHD deficient. Lumbar spine BMD was lower in patients than controls (CD p = 0.001; UC p = 0.008). In CD patients, serum levels of 25OHD were significantly correlated with total femur (r = 0.391; p = 0.027) and femoral neck (r = 0.384; p = 0.03) BMD.
CONCLUSION: It was found lower levels of 25OHD and BMD in young IBD patients compared to normal controls, suggesting an important role of 25OHD deficiency in the pathogenesis of the IBD bone disease.