Although the details of early development are different for parazoans and coelenterates, most share a stage in which external flagellated cells invaginate to form the inner layer, which lines the cavity, of these diploblastic two-layered animals. The horse Equus ferus caballus   is one of two extant subspecies of Equus ferus. Insects are more cooperative and show a greater degree of altruism than is true of vertebrate societies. Opinion Case ". Thus, before your teeth and gums start giving you any trouble, be sure to maintain a calcium-rich diet.
Symptoms of Calcium Deficiency
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If you have any questions, please Contact Us. Even eating nuts every day does not appear to result in expected weight gain Nuts and Obesity: The Weight of Evidence , so enjoy! Alhava EM, et al. Bone fluoride in proximal femur fractures. Effects of fluoride on bone in Finland. Histomorphometry of cadaver bone from low and high fluoride areas. Acta Orthopaedica Scandinavica 56 2: Fluoride content in human iliac bone: Journal of Bone and Mineral Research 3 5: Call RA, et al.
Histological and chemical studies in man on effects of fluoride. Public Health Reports Charen J, et al. Bone fluoride concentrations associated with fluoridated drinking water. Calcified Tissue International 27 2: Cohen-Solal ME, et al. Fluoride and strontium accumulation in bone does not correlate with osteoid tissue in dialysis patients. Nephrology Dialysis Transplantation Eble DM, et al. Fluoride concentrations in human and rat bone. Journal of Public Health Dentistry Glock GE, et al.
The retention and elimination of fluoride in bones. Hefti A, Marthaler TM. Bone fluoride concentrations after 16 years of drinking water fluoridation. Caries Research 15 1: Jackson D, Weidman SM. Fluorine in human bone related to age and the water supply of different regions. Journal of Pathological Bacteriology Fluoride levels in human rib bone: Canadian Journal of Public Health 65 5: Ng AHM, et al.
Association between fluoride, magnesium, aluminum and bone quality in renal osteodystrophy. Parkins FM, et al. Relationships of human plasma fluoride and bone fluoride to age.
Richards A, et al. Normal age-related changes in fluoride content of vertebral trabecular bone - Relation to bone quality. Smith FA, et al. Age increase and fluoride content in human bone. Stein ID, Granik G. Relation of strength, porosity, and mineralization to fluoride content. Wix P, Mohamedally SM. The significance of age-dependent fluoride accumulation in bone in relation to daily intake of fluoride.
Zipkin L, et al. Fluoride deposition in human bones after prolonged ingestion of fluoride in drinking water. US Public Health Reports F actors which Increase Accumulation of Fluoride in Bone: Annals of Internal Medicine 63 6: Kono K, et al. Urinary fluoride excretion in fluoride exposed workers with diminished renal function. Industrial Health 22 1: Noel C, et al. Spak CJ, et al. Renal clearance of fluoride in children and adolescents. Welsch M, et al.
Factors which Increase Accumulation of Fluoride in Bone: Nutritional Deficiencies back to top. The effects of fluoride and low calcium on the physical properties of the rat femur.
The Anatomical Record Li G, Ren L. Likimani S, et al. The effects of protein deficiency and fluoride on bone mineral content of rat tibia. Calcified Tissue International 50 2: Marier JR, et al. Accumulation of skeletal fluoride and its implications.
The effects of sodium fluoride on bone breaking strength. Indian Journal of Pediatrics 65 3: Bucher JR, et al. Results and conclusions of the National Toxicology Program's rodent carcinogenicity studies with sodium fluoride.
International Journal of Cancer 48 5: Technical report Series No. See executive summary See study See news articles. For commentary on NTP Study, see: A Statement of Concern.
Video-taped interview with Dr. Fluoridation and Bone Cancer. Liteplo RG, et al. Evaluation of risks to health from environmental exposure in Canada.
Journal of Environmental Science and Health. William Marcus,to Alan B. World Health Organ ization. Environmental Health Criteria World Health Organization, Geneva. Dose determination and carcinogenicity studies of sodium fluoride in Crl: CD-1 Mice and Crl: US Public Health Service. Maurer JK, et al. Confounded carcinogenicity study of sodium fluoride in CD-1 mice. Regulatory Toxicology and Pharmacology Two-year carcinogenicity study of sodium fluoride in rats.
Journal of the National Cancer Institute Cancer Causes and Control See excerpt of study. New Jersey Department of Health Environ. See Executive Summary See Study. Douglass CW, Joshipura K.
Caution needed in fluoride and osteosarcoma study. International trends in the incidence of bone cancer are not related to drinking water fluoridation. Fluoride exposure and childhood osteosarcoma: Hoover RN, et al. Bone cancer incidence rates in New York State: Osteosarcoma, seasonality, and environmental factors in Wisconsin, Regression analysis of cancer incidence rates and water fluoride in the U.
International Agency for Research on Cancer. Journal of Epidemiology Relationship between fluoride concentration in drinking water and mortality rate from uterine cancer in Okinawa prefecture, Japan. Journal of Epidemiology 6 4: Yang CY, et al.
Fluoride in drinking water and cancer mortality in Taiwan. The biology and epidemiology of bone and oral cancer related to fluoridation.
Grandjean P, Olsen J. Extended follow-up of cancer incidence in fluoride-exposed workers. See commentary on study. Grandjean P, et al. Cancer incidence and mortality in workers exposed to fluoride. Journal of the National Cancer Institute 84 Mortality and cancer morbidity after occupational fluoride exposure. Studies where fluoride is accompanied with other contaminants, particularly PAH - the presumed causative agent. Risk of cancer in the Norwegian aluminum industry. International Journal of Cancer Armstrong B, et al.
Lung cancer mortality and polynuclear aromatic hydrocarbons: A case-cohort study of aluminum production workers in Arvida, Quebec, Canada.
Gibbs GW, Horowitz I. Lung cancer mortality in aluminum reduction plant workers. Mortality in aluminum reduction plant workers. Moulin JJ, et al. A mortality study among potroom workers in a French aluminum reduction plant. International Archives of Occupational and Environmental Health Romundstad P, et al. Cancer incidence among workers in six Norwegian aluminum plants. Scandinavian Jour nal of Worker and Environmental Health Ronneberg A, Andersen A.
Mortality and cancer morbidity in workers from an aluminum smelter with prebaked carbon anodes - part II: Occupational and Environmental Medicine Spinelli JJ, et al. Mortality and cancer incidence in aluminum reduction plant workers. Sodium fluoride-induced chromosome aberrations in different stages of the cell cycle: Sodium fluoride and chromosome damage in vitro human lymphocyte and in vivo micronucleus assays. Analysis of chromosomal abnormalities at anaphase-telophase induced by sodium fluoride in vitro.
Caspary WJ, et al Mutagenic activity of fluorides in mouse lymphoma cells. Mutation Research 3: Cole J, et al. Crespi CL, et al. Sodium fluoride is a less efficient human cell mutagen at low concentrations. Environmental Molecular Mutagenesis 15 2: Department of Health and Human Services Review of fluoride benefits and risks. Edwards SL, et al. The crystal structure of fluoride-inhibited cytochrome c peroxidase.
Journal of Biological Chemistry See article discussing study. Emsley J, et al. The uracil fluoride interaction: Journal of the Chemical Society Chemical Communications Emsley J, et al An unexpectedly strong hydrogen bond: Ab initio calculations and spectroscopic studies of amide-fluoride systems. Journal of the American Chemical Society Gadhia PK, Joseph S.
Sodium fluoride induced chromosome aberrations and sister chromatid exchange in cultured human lymphocytes. Gerdes RA, et al. The effects of atmospheric hydrogen fluoride upon Drosophila melanogaster. Fecundity, hatchability and fertility.
Cytogenetic effects of gaseous fluorides on grain crops. Hayashi N, Tsutsui T. Cell cycle dependence of cytotoxicity and clastogenicity induced by treatment of synchronized human diploid fibroblasts with sodium fluoride.
Jachimczak D, Skotarczak B. The effect of fluori ne and lead ions on the chromosomes of human leucocytes in vitro. Genetica Polonica 19 3: Jagiello G, Lin JS. Sodium fluoride as potential mutagen in mammalian eggs. Joseph S, Gadhia PK. Sister chromatid exchange frequency and chromosome aberrations in residents of fluoride endemic regions of South Gujarat.
Chromosome aberrations in cultured rat bone marrow cells treated with inorganic fluorides. Mutation Research 1: Kishi K, Ishida T. Clastogenic activity of sodium fluoride in great ape cells.
Kishi K, Tonomura A. Cytogenetic effects of sodium fluoride. Kleinsasser NH, et al. Lasne C, et al. Cell Biology and Toxicology 4 3: Lazutka JR, et al. Chromosomal aberrations and sister-chromatid exchanges in Lithuanian populations: Li YM, et al. Genotoxic effects of fluoride: Mutation Research 2: Meng Z, Zhang B. Chromosomal aberrations and micronuclei in lymphocytes of workers at a phosphate fertilizer factory.
Meng Z, et al. Sister-chromatid exchanges in lymphocytes of workers at a phosphate fertilizer factory. Mihashi M, Tsutsui T. Clastogenic activity of sodium fluoride to rat vertebral body-derived cells in culture. Cytological effects of sodium fluoride on mice. Cytogenetic effects of hydrogen fluoride gas on maize. Chromosomal changes in maize induced by hydrogen fluoride gas.
Canadian Journal of Genetics and Cytology Cytogenetic effects of hydrogen fluoride on plants. The effect of sodium fluoride and idoacetamide on mutation induction by X-irradiation in mature spermatozoa of drosophila. Genotoxicity o f Fluoride.
Health effects of ingested fluoride. Genotoxic effect of an environmental pollutant, sodium fluoride, in mammalian in vivo test system. Ramesh N, et al. Low levels of p53 mutations in Indian patients with osteosarcoma and the correlation with fluoride levels in bone.
Journal of Environmental Pathology, Toxicology, and Oncology 20 3: Rao MV, Tiwari H. Ribeiro DA, et al. Lack of DNA damage induced by fluoride on mouse lymphoma and human fibroblast cells by single cell gel comet assay. Brazilian Dental Journal Rivedal E, et al. Morphological transformation and effect on gap junction intercellular communication in Syrian hamster embryo cells as screening tests for carcinogens devoid of mutageni c activity.
Toxicology In Vitro 14 2: Scott D, Roberts SA. Extrapolation from in vitro tests to human risk: Sheth FJ, et al. A study in fluorotic individuals of North Gujurat. Is fluoride a mutagen? Science of the Total Environment Suzuki N, Tsutsui T.
Taylor A, Taylor NC. Effect of sodium fluoride on tumor growth. Tazhibaev ShS, et al. Cancer Research 44 3: Cytotoxicity, chromosome aberrations and unscheduled DNA synthesis in cultured human diploid fibroblasts induced by sodium fluoride. Mutation Research 4: Induction of unscheduled DNA synthesis in cultured human oral keratinocytes by sodium fluoride.
Voroshilin SI, et al. Mutagenic effect of hydrogen fluoride on animals. Wu DQ, Wu Y. Zeiger E, et al. Genetic toxicity of fluoride. Environmental Molecular Mutagenesis 21 4: Cytogenetic studies of sodium fluoride in mice. Zhang Y, et al. DNA damage induced by fluoride in rat osteoblasts. Fluoride treatment for Hyperthyroidism back to top. Galletti P, Joyet G. Compt Rend Soc Biol Paris Parents of Fluoride Poisoned Children. Stecher P, et al.
The Merck Index of Chemicals and Drugs. Burgi H, et al. Fluorine and thyroid gland function: Klin Wochenschr 15;62 Fluoride, Water Hardness, and Endemic Goitre. Desai VK, et al. Epidemiological study of goitre in endemic fluorosis district of Gujarat. Endemic goitre in the absence of iodine deficiency in schoolchildren of the Northern Cape Province of South Africa. European Journal of Clinical Nutrition 53 1: Progress of the year in the investigation of mottled enamel with special reference to its association with artesian water.
Journal of the National Dental Association 5: Goitre and fluorosis in Kenya. East African Medical Journal Steyn DG, et al. Union of South Africa. De partment of Nutrition. Besteht ein Antagonismus zwischen Fluor und Jod? Fluo rine in the aetiology of endemic goitre. The Lancet Feb Zhao W, et al.
Long-term effects of various iodine and fluorine doses on the thyroid and fluorosis in mice. Endocrine Regulations 32 2: Synergistic action of iodine-deficiency and fluorine-intoxication on rat thyroid.
Chinese Medical Journal 9: Lin Fa-Fu, et al Minder W, Gordonoff T. An antagonism between iodine and fluorine. Arch Intern Pharma Codyn Effects on the Endocrine System. Sidora VD, et al. Probl Endokrinol Mosk 29 4: Stolc V, Podoba J. Effect of fluoride on the biogenesis of thyroid hormones. The synergistic action of thyroid on fluoride toxicity. Other back to top. Bachinskii PP, et al. Probl Endokrinol Mosk 31 6: Balabolkin MI, et al. Bobek S, et al.
Effect of long-term fluoride administration on thyroid hormones level blood in rats. Endocrinologia Experimentalis 10 4: Bylgyly A, et al.
The effects of fluoride on thyroid hormones in rabbits. Indian Veterinary Journal Comparison of the effects of various agents on thyroidal adenyl cyclase activity with their effects on thyroid hormone release. Journal of Endocrinology 54 1: Koku Eisei Gakkai Zasshi. Hillman D, et al. Hypothyroidism and anemia related to fluoride in dairy cattle. Journal of Dairy Science 62 3: Liu G, et al. Effects of fluoride on metabolism of thyroid hormone in chicks. Chinese Journal of Veterinary Science Effects of fluoride on ultrastructure of thyroid mitochondria in chicks.
Effect of sodium fluoride upon activity of peroxidase in the thyroid gland of chickens. Chinese Journal of Veterinary Science and Technology Effects of adding selenium to diets on the function of thyroid of fluorositic chicks.
Mikhailets ND, et al. Thyroid function during prolonged exposure to fluorides. Okayasu I, et al. Hyperplastic nodules of thyroid parafollicular cells C cells in rats induced by prolonged low dose ingestion of NaF. Is dental fluorosis caused by thyroid hormone disturbances? Biochemical effects of fluoride on thyroid gland during experimental fluorosis. Excess fluoride ingestion and thyroid hormone derangements in children living in Delhi, India.
Tokar VI, et al. Gig Tr Prof Zabol 9: Zhonghua Yi Xue Za Zhi. Altintas A, et al. Serum proteins electrophoresis and kidney function in sheep with natural and industrial fluorosis. Ankara Universitesi Veteriner Fakultesi Dergisi Ando M, et al.
Health effects of fluoride pollution caused by coal burning. Science of the Total Environ ment Kidney changes and kidney stones in endemic fluorosis. Reggabi M, et al. Renal function in residents of an endemic fluorosis area in southern Algeria. Singla VP, et al. Xiong X, et al. Dose-effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children.
Environmental Research Jul 8; [Epub ahead of print]. Atkinson F, Hard GC. Chronic fluorosis in the guinea-pig. Banu Priya C, et al. Toxicity of fluoride to diabetic rats. Bhatnagar M, Susheela AK. Birkner E, et al. Influence of sodium fluoride and caffeine on the kidney function and free-radical processes in that organ in adult rats. Biological Trace Element Research Kidney function and structure in chronic fluorosis. British Journal of Experimental Pathology Chronic fluoride ingestion decreases 45Ca uptake by rat kidney membranes.
Journal of Nutrition 6: Bouaziz H, et al. Pregnancy -- Low levels of vitamin D in pregnancy are associated with gestational diabetes , pre-eclampsia , and small for gestational age infants. Weight loss -- Though hypothesized that vitamin D supplementation may be an effective treatment for obesity apart from calorie restriction , one systematic review found no association of supplementation with body weight or fat mass. Governmental regulatory agencies stipulate for the food and dietary supplement industries certain health claims as allowable as statements on packaging.
European Food Safety Authority. US Food and Drug Administration. Other possible agencies with claim guidance: Various institutions have proposed different recommendations for the amount of daily intake of vitamin D. These vary according to precise definition, age, pregnancy or lactation, and the extent assumptions are made regarding skin synthesis of vitamin D. The dietary reference intake for vitamin D issued in by the Institute of Medicine IOM for North America superseded previous recommendations which gave adequate intake values.
The recommendations were formed assuming the individual has no skin synthesis of vitamin D because of inadequate sun exposure. The reference intake for vitamin D refers to total intake from food, beverages and supplements, and assumes that calcium requirements are being met. The tolerable upper intake level UL is defined as "the highest average daily intake of a nutrient that is likely to pose no risk of adverse health effects for nearly all persons in the general population. Health Canada published recommended dietary allowances RDA and tolerable upper intake levels for vitamin D in  based on the Institute of Medicine report.
Australia and New Zealand published nutrient reference values including guidelines for dietary vitamin D intake in The European Food Safety Authority EFSA in  reviewed the current evidence, finding the relationship between serum 25 OH D concentration and musculoskeletal health outcomes is widely variable.
The UK National Health Service recommends babies and young children aged six months to five years, pregnant or breastfeeding women, and sun-deprived elderly people should take daily vitamin supplements to ensure sufficient vitamin D intake. Non-government organisations in Europe have made their own recommendations. Although vitamin D is not present naturally in most foods,   it is commonly added as a fortification in manufactured foods.
In some countries, staple foods are artificially fortified with vitamin D. In general, vitamin D 2 is found in fungi and vitamin D 3 is found in animals. The vitamin D 2 content in mushrooms and Cladina arbuscula , a lichen, increase with exposure to ultraviolet light. Manufactured foods fortified with Vitamin D include some fruit juices and fruit juice drinks, meal replacement energy bars , soy protein -based beverages, certain cheese and cheese products, flour products, infant formulas , many breakfast cereals , and milk.
While some studies have found that vitamin D 3 raises 25 OH D blood levels faster and remains active in the body longer,   others contend that vitamin D 2 sources are equally bioavailable and effective as D 3 for raising and sustaining 25 OH D.
Vitamin D content in typical foods is reduced variably by cooking. Recommendations on recommended 25 OH D serum levels vary across authorities, and vary based on factors like age. The dietary reference intakes for vitamin D are chosen with a margin of safety and 'overshoot' the targeted serum value to ensure the specified levels of intake achieve the desired serum 25 OH D levels in almost all persons. No contributions to serum 25 OH D level are assumed from sun exposure and the recommendations are fully applicable to people with dark skin or negligible exposure to sunlight.
Vitamin D toxicity is rare. Pregnant or breastfeeding women should consult a doctor before taking a vitamin D supplement. In addition, for products intended for infants, the FDA recommends the dropper hold no more than IU.
One thousand micrograms per day in infants has produced toxicity within one month. Calcitriol itself is auto-regulated in a negative feedback cycle, and is also affected by parathyroid hormone , fibroblast growth factor 23 , cytokines , calcium, and phosphate.
Vitamin D overdose causes hypercalcemia, which is a strong indication of vitamin D toxicity — this can be noted with an increase in urination and thirst.
If hypercalcemia is not treated, it results in excess deposits of calcium in soft tissues and organs such as the kidneys, liver, and heart, resulting in pain and organ damage. The main symptoms of vitamin D overdose which are those of hypercalcemia including anorexia , nausea, and vomiting. These may be followed by polyuria , polydipsia , weakness, insomnia, nervousness, pruritus and ultimately renal failure.
Furthermore, proteinuria , urinary casts , azotemia , and metastatic calcification especially in the kidneys may develop. Vitamin D toxicity is treated by discontinuing vitamin D supplementation and restricting calcium intake. Kidney damage may be irreversible. Exposure to sunlight for extended periods of time does not normally cause vitamin D toxicity.
The concentrations of vitamin D precursors produced in the skin reach an equilibrium , and any further vitamin D produced is degraded. Synthesis of vitamin D in nature is dependent on the presence of UV radiation and subsequent activation in liver and in kidney. Many animals synthesize vitamin D 3 from 7-dehydrocholesterol , and many fungi synthesize vitamin D 2 from ergosterol. Click on icon in lower right corner to open.
Click on genes, proteins and metabolites below to link to respective articles. The transformation that converts 7-dehydrocholesterol to vitamin D 3 occurs in two steps. The process is faster in white button mushrooms. Vitamin D 3 is produced photochemically from 7-dehydrocholesterol in the skin of most vertebrate animals, including humans.
Exposure to light through windows is insufficient because glass almost completely blocks UVB light. The darker the skin, and the weaker the sunlight, the more minutes of exposure are needed.
Vitamin D overdose is impossible from UV exposure; the skin reaches an equilibrium where the vitamin degrades as fast as it is created. Sunscreen absorbs or reflects ultraviolet light and prevents much of it from reaching the skin. The skin consists of two primary layers: Vitamin D is produced in the keratinocytes  of two innermost strata, the stratum basale and stratum spinosum.
Vitamin D can be synthesized only by a photochemical process. Phytoplankton in the ocean such as coccolithophore and Emiliania huxleyi have been photosynthesizing vitamin D for more than million years.
Primitive vertebrates in the ocean could absorb calcium from the ocean into their skeletons and eat plankton rich in vitamin D. Land vertebrates required another source of vitamin D other than plants for their calcified skeletons. They had to either ingest it or be exposed to sunlight to photosynthesize it in their skin. In birds and fur-bearing mammals, fur or feathers block UV rays from reaching the skin. Instead, vitamin D is created from oily secretions of the skin deposited onto the feathers or fur, and is obtained orally during grooming.
Vitamin D 3 cholecalciferol is produced industrially by exposing 7-dehydrocholesterol to UVB light, followed by purification. Vitamin D 2 ergocalciferol is produced in a similar way using ergosterol from yeast or mushrooms as a starting material. Vitamin D is carried in the bloodstream to the liver, where it is converted into the prohormone calcifediol.
Circulating calcifediol may then be converted into calcitriol , the biologically active form of vitamin D, in the kidneys. Whether it is made in the skin or ingested, Vitamin D is hydroxylated in the liver at position 25 upper right of the molecule to form hydroxycholecalciferol calcifediol or 25 OH D. The conversion of calcifediol to calcitriol is catalyzed by the enzyme hydroxyvitamin D 3 1-alpha-hydroxylase , which is the product of the CYP27B1 human gene.
The activity of CYP27B1 is increased by parathyroid hormone , and also by low calcium or phosphate. Following the final converting step in the kidney, calcitriol is released into the circulation. By binding to vitamin D-binding protein, calcitriol is transported throughout the body, including to the classical target organs of intestine, kidney and bone.
In addition to the kidneys, calcitriol is also synthesized by certain other cells including monocyte - macrophages in the immune system. When synthesized by monocyte-macrophages, calcitriol acts locally as a cytokine , modulating body defenses against microbial invaders by stimulating the innate immune system.
The activity of calcifediol and calcitriol can be reduced by hydroxylation at position 24 by vitamin D3 hydroxylase , forming secalciferol and calcitetrol respecively. American researchers Elmer McCollum and Marguerite Davis in  discovered a substance in cod liver oil which later was called "vitamin A". British doctor Edward Mellanby noticed dogs that were fed cod liver oil did not develop rickets and concluded vitamin A, or a closely associated factor, could prevent the disease.
In , Elmer McCollum tested modified cod liver oil in which the vitamin A had been destroyed. He called it vitamin D because it was the fourth vitamin to be named. In ,  it was established that when 7-dehydrocholesterol is irradiated with light, a form of a fat-soluble vitamin is produced now known as D 3. Alfred Fabian Hess stated: A meeting took place with J. Bernal , and Dorothy Crowfoot to discuss possible structures, which contributed to bringing a team together.
X-ray crystallography demonstrated the sterol molecules were flat, not as proposed by the German team led by Windaus. In , Otto Rosenheim and Harold King published a paper putting forward structures for sterols and bile acids which found immediate acceptance. In the s, Windaus clarified further the chemical structure of vitamin D. In , American biochemist Harry Steenbock at the University of Wisconsin demonstrated that irradiation by ultraviolet light increased the vitamin D content of foods and other organic materials.
A vitamin D deficiency is a known cause of rickets. His irradiation technique was used for foodstuffs, most memorably for milk. By the expiration of his patent in , rickets had been all but eliminated in the US.
In , after studying nuclear fragments of intestinal cells, a specific binding protein for Vitamin D called the Vitamin D Receptor was identified by Mark Haussler and Tony Norman.
In the liver, vitamin D was found to be converted to calcifediol. Calcifediol is then converted by the kidneys to calcitriol, the biologically active form of vitamin D. The vitamin D metabolites, calcifediol and calcitriol, were identified by competing teams led by Michael F.