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AbstractVitamin 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.
CitationProg. Biophys. Mol. Biol. 2006, 92 (1):4-8
DescriptionKEYWORDS CLASSIFICATION: Animals;biomarkers of exposure & effect: validation;Bone Diseases;Calcium;deficiency;Europe;genetics;Genetic Predisposition to Disease;Humans;metabolism;methods;nursing;Netherlands;physiology;physiopathology;prevention & control;radiation effects;Risk;Skin;Ultraviolet Therapy;Vitamin D;Vitamin D Deficiency.
- Role of vitamin D, its metabolites, and analogs in the management of osteoporosis.
- Authors: Bikle DD
- Issue date: 1994 Aug
- [Changes in mineral metabolism in stage 3, 4, and 5 chronic kidney disease (not on dialysis)].
- Authors: Lorenzo Sellares V, Torregrosa V
- Issue date: 2008
- Prevention of hip fractures by correcting calcium and vitamin D insufficiencies in elderly people.
- Authors: Meunier P
- Issue date: 1996
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Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk.Kirsh, Victoria A.; Hayes, Richard B.; Mayne, Susan T.; Chatterjee, Nilanjan; Subar, Amy F.; Dixon, L. Beth; Albanes, Demetrius; Andriole, Gerald L.; Urban, Donald A.; Peters, Ulrike (2006-02-15)BACKGROUND: Vitamin E, beta-carotene, and vitamin C are micronutrient antioxidants that protect cells from oxidative damage involved in prostate carcinogenesis. In separate trials, supplemental vitamin E was associated with a decreased risk of prostate cancer among smokers and supplemental beta-carotene was associated with a decreased risk of prostate cancer among men with low baseline plasma beta-carotene levels. METHODS: We evaluated the association between intake of these micronutrient antioxidants from foods and supplements and the risk of prostate cancer among men in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. At baseline, trial participants completed a 137-item food frequency questionnaire that included detailed questions on 12 individual supplements. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: We identified 1338 cases of prostate cancer among 29 361 men during up to 8 years of follow-up. Overall, there was no association between prostate cancer risk and dietary or supplemental intake of vitamin E, beta-carotene, or vitamin C. However, among current and recent (i.e., within the previous 10 years) smokers, decreasing risks of advanced prostate cancer (i.e., Gleason score > or = 7 or stage III or IV) were associated with increasing dose (RR for > 400 IU/day versus none = 0.29, 95% CI = 0.12 to 0.68; Ptrend = .01) and duration (RR for > or = 10 years of use versus none = 0.30, 95% CI = 0.09 to 0.96; Ptrend = .01) of supplemental vitamin E use. Supplemental beta-carotene intake at a dose level of at least 2000 microg/day was associated with decreased prostate cancer risk in men with low (below the median of 4129 microg/day) dietary beta-carotene intake (RR = 0.52, 95% CI = 0.33 to 0.81). Among smokers, the age-adjusted rate of advanced prostate cancer was 492 per 100,000 person-years in those who did not take supplemental vitamin E, 153 per 100,000 person-years in those who took more than 400 IU/day of supplemental vitamin E, and 157 per 100,000 person-years in those who took supplemental vitamin E for 10 or more years. Among men with low dietary beta-carotene intake, the age-adjusted rate of prostate cancer was 1122 per 100,000 person-years in those who did not take supplemental beta-carotene, and 623 per 100,000 person-years in those who took at least 2000 microg/day of supplemental beta-carotene. CONCLUSIONS: Our results do not provide strong support for population-wide implementation of high-dose antioxidant supplementation for the prevention of prostate cancer. However, vitamin E supplementation in male smokers and beta-carotene supplementation in men with low dietary beta-carotene intakes were associated with reduced risk of this disease.
Vitamins A and E during Pregnancy and Allergy Symptoms in an Early Childhood-Lack of Association with Tobacco Smoke Exposure.Gromadzinska, Jolanta; Polanska, Kinga; Kozlowska, Lucyna; Mikolajewska, Karolina; Stelmach, Iwona; Jerzyńska, Joanna; Stelmach, Włodzimierz; Grzesiak, Mariusz; Hanke, Wojciech; Wasowicz, Wojciech; et al. (2018)Epidemiological studies have suggested an association between maternal antioxidant levels during pregnancy and development of allergic diseases in their offspring. The aim of the study was to determine plasma vitamins A and E concentration in the 1st trimester of pregnancy, at delivery and in cord blood and to search for a relationship with allergy in up to 2-year-old children who were prenatally exposed or not exposed to tobacco smoke. The study participants included 252 mother-child pairs from Polish Mother and Child Cohort. Vitamin concentrations were measured using the HPLC-UV method, smoking status—as saliva cotinine level using the HPLC-MS/MS technique. Children’s health status was assessed using a questionnaire and pediatricians/allergists examination. Cord plasma vitamin concentrations were significantly lower than their levels in maternal plasma in the 1sttrimester and at delivery (p < 0.001). Significantly higher concentrations of vitamin E have been shown to occur during the 1st trimester of pregnancy in plasma of the women who have actively/passively smoked cigarettes compared to the non-smokers (p < 0.02). Multivariate analysis with inclusion of a variety of confounding factors have not indicated any statistically significant associations between β-carotene, vitamins A and E and the risk of food allergy, atopic dermatitis and wheezing in their children up to 2 years of age. The interaction between smoking during pregnancy and vitamins levels on the risk of allergy was not statistically significant (p < 0.4). The relationship between plasma concentration of vitamins A and E, and the risk of allergy in their young children has not been demonstrated.
Vitamins and selenium.Dragsted, Lars O.; Loft, Steffen; Moller, Peter; Cook, Marcus S.; Rozalski, Rafal; Olinski, Ryszard; Linseisen, Jakob; Abbas, Sascha; Akesson, Bjorn; Bruzelius, Katharina; et al. (The Nofer Institute of Occupational Medicine, 2007-04)