https://www.grc.com/health/pdf/Sunlight_and_Vitamin_D.pdf

Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease

Overview of general physiologic features and functions of vitamin D

During the past decade, major advances have been made in vitamin D research that transcend the simple concept that vitamin D is Important for the prevention of rickets in children and has little physiologic relevance for adults. Inadequate vitamin D, in addition to causing rickets, prevents children from attaining their genetically programmed peak bone mass, contributes to and exacerbates osteoporosis in adults, and causes the often painful bone disease osteomalacia. Adequate vitamin D is also important for proper muscle functioning, and controversial evidence suggests it may help prevent type 1 diabetes mellitus, hypertension, and many common cancers. Vitamin D inadequacy has been reported in approximately 36% of otherwise healthy young adults and up to 57% of general medicine inpatients in the United States and in even higher percentages in Europe. Recent epidemiological data document the high prevalence of vitamin D inadequacy among elderly patients and especially among patients with osteoporosis. Factors such as low sunlight exposure, age-related decreases in cutaneous synthesis, and diets low in vitamin D contribute to the high prevalence of vitamin D inadequacy. Vitamin D production from cutaneous synthesis or intake from the few vitamin D-rich or enriched foods typically occurs only intermittently. Supplemental doses of vitamin D and sensible sun exposure could prevent deficiency in most of the general population. The purposes of this article are to examine the prevalence of vitamin D inadequacy and to review the potential implications for skeletal and extraskeletal health.

https://www.grc.com/health/pdf/High_Prevalence_of_Vitamin_D_Inadequacy_and_Implications_for_Health.pdf

High prevalence of vitamin D inadequacy and implications for health.

The vitamin D endocrine system is essential for calcium and bone homeostasis. The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxyvitamin D [1,25-(OH)2D], can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). Absence of a functional VDR or the key activating enzyme, 25-OHD-1α-hydroxylase (CYP27B1), in mice creates a bone and growth plate phenotype that mimics humans with the same congenital disease or severe vitamin D deficiency. The intestine is the key target for the VDR because high calcium intake, or selective VDR rescue in the intestine, restores a normal bone and growth plate phenotype.

The VDR is nearly ubiquitously expressed, and almost all cells respond to 1,25-(OH)2D exposure; about 3% of the mouse or human genome is regulated, directly and/or indirectly, by the vitamin D endocrine system, suggesting a more widespread function. VDR-deficient mice, but not vitamin D- or 1α-hydroxylase-deficient mice, and man develop total alopecia, indicating that the function of the VDR and its ligand is not fully overlapping. The immune system of VDR- or vitamin D-deficient mice is grossly normal but shows increased sensitivity to autoimmune diseases such as inflammatory bowel disease or type 1 diabetes after exposure to predisposing factors. VDR-deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status.

Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice

Vitamins are essential constituents of our diet that have long been known to influence the immune system. Vitamins A and D have received particular attention in recent years as these vitamins have been shown to have an unexpected and crucial effect on the immune response. We present and discuss our current understanding of the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation and proliferation, T-helper-cell differentiation, tissue-specific lymphocyte homing, the production of specific antibody isotypes and regulation of the immune response. Finally, we discuss the clinical potential of vitamin A and D metabolites for modulating tissue-specific immune responses and for preventing and/or treating inflammation and autoimmunity.

/pdf/vitamin-effects-on-the-immune-system-vitamins-a-and-d-take-2cygdunlqf.pdf

Vitamin effects on the immune system: vitamins A and D take centre stage

Anecdotal data suggest that the amount of vitamin D available in the environment either from sunshine exposure or diet may be an important factor affecting the development of inflammatory bowel disease (IBD) in humans. We tested the vitamin D hypothesis in an experimental animal model of IBD. Interleukin (IL)-10 knockout (KO) mice, which spontaneously develop symptoms resembling human IBD, were made vitamin D deficient, vitamin D sufficient or supplemented with active vitamin D (1,25-dihydroxycholecalciferol). Vitamin D-deficient IL-10 KO mice rapidly developed diarrhea and a wasting disease, which induced mortality. In contrast, vitamin D-sufficient IL-10 KO mice did not develop diarrhea, waste or die. Supplementation with 50 IU of cholecalciferol (5.0 microgram/d) or 1, 25-dihydroxycholecalciferol (0.005 microgram/d) significantly (P < 0. 05) ameliorated symptoms of IBD in IL-10 KO mice. 1, 25-Dihydroxycholecalciferol treatment (0.2 microgram/d) for as little as 2 wk blocked the progression and ameliorated (P < 0.05) symptoms in IL-10 KO mice with already established IBD.

/pdf/1-25-dihydroxycholecalciferol-prevents-and-ameliorates-18yzbl4uy3.pdf

1,25-Dihydroxycholecalciferol Prevents and Ameliorates Symptoms of Experimental Murine Inflammatory Bowel Disease

Mucosal insulin delivery systems based on complexation polymer hydrogels: effect of particle size on insulin enteral absorption.

Effects of isoflurane on gastrointestinal motility after brief exposure in rats.

INTRODUCTION The methodology for in vitro testing of insulin delivery systems for long-term infusion of lispro insulin requires insulin flow studies over time, with the measurement of lispro concentrations in wells or other laboratory fluid collection systems. We postulated that the efficiency of the insulin assay could be improved if the insulin collected in the wells could be measured without having to perform dilutions of insulin samples. The manufacturer's method for the identification of Humalog(R) insulin by high-performance liquid chromatography (HPLC) does not provide a detailed method for the quantitation of the clinical formulation. No reports could be found in the literature describing a method to quantitate lispro insulin's entire concentration range, nor could we find detailed information on pH effects. The purpose of this study was to investigate the use of a reversed-phase HPLC method to quantitate Humalog insulin at three levels of pH. METHODS Serial dilutions of Humalog insulin stock solution were prepared at pH levels of 2.6 and 7.4 (concentrations 0.20-100 IU/ml) to construct calibration curves. Samples were also prepared at lower concentrations (0.23-15.0 IU/ml) at pH levels of 4.0 and 7.4. Areas under curve data were plotted against known concentrations, and the limit of quantitation and precision of the assay were determined. RESULTS Calibration curves for the 0.20-100 IU/ml concentration (pH 7.4 and 2.6) revealed no significant differences (p < 0.01) between those curves. pH and concentration did not have an effect on the overall precision of the method. Linearity was not conserved past the 15-IU/ml concentration. Coefficient of variation (CV) values were generally <15% except at the lower concentrations where the largest CVs were observed. Mean known concentrations plotted on a logarithmic scale demonstrated linearity from 12.5 to 100 IU/ml. CONCLUSIONS Humalog insulin clinical formulation can be quantitated over the entire concentration range by a reversed-phase HPLC method using nonlinear regression analysis. The method is reproducible at lower (<15 IU/ml) and higher insulin concentrations. Linear regression analysis may be used when the concentrations of interest are in the 0- to 15-IU range. Preparation of insulin solutions at pH 2.6, 4.0, and 7.4 did not significantly affect the reproducibility of the assay.

Carey Munsick

Papers

1,25-Dihydroxycholecalciferol Prevents and Ameliorates Symptoms of Experimental Murine Inflammatory Bowel Disease

Mucosal insulin delivery systems based on complexation polymer hydrogels: effect of particle size on insulin enteral absorption.

Effects of isoflurane on gastrointestinal motility after brief exposure in rats.

Quantitation of Humalog Insulin by Reversed-Phase High-Performance Liquid Chromatography