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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. There is considerable research activity looking at effects of vitamin D and its metabolites in animal models, cell systems, gene expression studies, epidemiology and clinical therapeutics.
These different types of studies can produce conflicting evidence as to the benefits of interventions with vitamin D. They suggest, for some people, reducing the risk of preventable disease requires a higher level of vitamin D than that recommended by the IOM.
Until such trials are conducted, the implications of the available evidence for public health and patient care will be debated".
Some preliminary studies link low vitamin D levels with disease later in life. Vitamin D deficiency is widespread in the European population.
Apart from VDR activation, various alternative mechanisms of action are under study, such as inhibition of signal transduction by hedgehog , a hormone involved in morphogenesis.
From Wikipedia, the free encyclopedia. For other uses, see Vitamin D disambiguation. The American Journal of Clinical Nutrition.
The Journal of Nutrition. Retrieved 6 June American Association for Clinical Chemistry. Retrieved June 23, A metabolite of vitamin D active in intestine".
Vitamin D and cardiometabolic outcomes". Annals of Internal Medicine. University of California, Riverside.
Retrieved January 24, Molecular vitamin D mediated mechanisms". Journal of Cellular Biochemistry. Canadian Journal of Physiology and Pharmacology.
Retrieved July 9, The New England Journal of Medicine. The British Journal of Nutrition. Nutrition Through the Life Cycle.
The Cochrane Database of Systematic Reviews 4: Calcified Tissue International Review. Journal of Tropical Pediatrics. The Proceedings of the Nutrition Society.
Journal of Human Nutrition and Dietetics. Archived from the original on June 8, Retrieved August 24, The Nutrition Desk Reference. Melanie 1 February A systematic review and meta-analysis".
Therapeutic Advances in Musculoskeletal Disease. Progress in Cardiovascular Diseases. The Cochrane Database of Systematic Reviews.
Preventive Services Task Force". A Systematic Review and Meta-analysis". American Journal of Epidemiology Review. The Journal of Clinical Endocrinology and Metabolism.
Vitamin D and innate and adaptive immunity. Journal of Clinical Virology. Topics in Antiviral Medicine. International Journal of Epidemiology.
The American Journal of the Medical Sciences. Current Topics in Behavioral Neurosciences. The evidence for vitamin D as a treatment for MS is inconclusive.
The available evidence substantiates neither clinically significant benefit nor harm from vitamin D in the treatment of patients with MS. Multiple Sclerosis Journal Systematic Review.
Several preliminary studies have reported results which have shown some promise, but none has yet provided significant evidence of a clinically meaningful improvement.
Role, Current Uses and Future Perspectives". International Journal of Molecular Sciences. Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: World Journal of Diabetes Review.
Updated meta-analysis on maternal outcomes". A Food Labeling Guide Health Claims Food Labeling". Health Claim Regarding Calcium and Osteoporosis".
Archived from the original PDF on March 6, Retrieved January 29, Australian Ministry of Health. Archived from the original on February 27, Updated Dietary Reference Intakes".
Nutrition and Healthy Eating. Retrieved April 28, National Health and Medical Research Council. Revision of the Nutrition and Supplement Facts Labels.
FR page " PDF. Retrieved July 21, Retrieved 21 July Vitamin D and postmenopausal health". Journal of Photochemistry and Photobiology. Unsourced material may be challenged and removed.
University of Hawaii Press. Illustrated Introduction to Latin Epigraphy. University of California Press. Retrieved 3 October History Spread Romanization Roman numerals.
Letters of the ISO basic Latin alphabet. Letter D with diacritics. Retrieved from " https: Graphemes ISO basic Latin letters. Wikipedia indefinitely move-protected pages Wikipedia indefinitely semi-protected pages Articles needing additional references from December All articles needing additional references.
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