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Cholecalciferol (D<sub>3</sub>) is produced photochemically in the [[skin]] from [[7-dehydrocholesterol]]; 7-dehydrocholesterol is produced in relatively large quantities{{Clarify|date=January 2012}} in the skin of most vertebrate animals, including humans.<ref>{{cite journal |pmid=12514284 |year=2003 |last1=Crissey |first1=SD |last2=Ange |first2=KD |last3=Jacobsen |first3=KL |last4=Slifka |first4=KA |last5=Bowen |first5=PE |last6=Stacewicz-Sapuntzakis |first6=M |last7=Langman |first7=CB |last8=Sadler |first8=W |last9=Kahn |first9=S |title=Serum concentrations of lipids, vitamin D metabolites, retinol, retinyl esters, tocopherols and selected carotenoids in twelve captive wild felid species at four zoos |volume=133 |issue=1 |pages=160–6 |journal=The Journal of nutrition}}</ref> The [[naked mole rat]] appears to be naturally cholecalciferol deficient, as serum 25-OH vitamin D levels are undetectable.<ref>{{cite journal |pmid=8384476 |year=1993 |last1=Yahav |first1=S |last2=Buffenstein |first2=R |title=Cholecalciferol supplementation alters gut function and improves digestibility in an underground inhabitant, the naked mole rat (Heterocephalus glaber), when fed on a carrot diet |volume=69 |issue=1 |pages=233–41 |journal=The British journal of nutrition |doi=10.1079/BJN19930025}}</ref>
Cholecalciferol (D<sub>3</sub>) is produced photochemically in the [[skin]] from [[7-dehydrocholesterol]]; 7-dehydrocholesterol is produced in relatively large quantities{{Clarify|date=January 2012}} in the skin of most vertebrate animals, including humans.<ref>{{cite journal |pmid=12514284 |year=2003 |last1=Crissey |first1=SD |last2=Ange |first2=KD |last3=Jacobsen |first3=KL |last4=Slifka |first4=KA |last5=Bowen |first5=PE |last6=Stacewicz-Sapuntzakis |first6=M |last7=Langman |first7=CB |last8=Sadler |first8=W |last9=Kahn |first9=S |title=Serum concentrations of lipids, vitamin D metabolites, retinol, retinyl esters, tocopherols and selected carotenoids in twelve captive wild felid species at four zoos |volume=133 |issue=1 |pages=160–6 |journal=The Journal of nutrition}}</ref> The [[naked mole rat]] appears to be naturally cholecalciferol deficient, as serum 25-OH vitamin D levels are undetectable.<ref>{{cite journal |pmid=8384476 |year=1993 |last1=Yahav |first1=S |last2=Buffenstein |first2=R |title=Cholecalciferol supplementation alters gut function and improves digestibility in an underground inhabitant, the naked mole rat (Heterocephalus glaber), when fed on a carrot diet |volume=69 |issue=1 |pages=233–41 |journal=The British journal of nutrition |doi=10.1079/BJN19930025}}</ref>
In some animals, the presence of fur or feathers blocks the UV rays from reaching the skin. In birds and fur-bearing mammals, vitamin D is generated from the oily secretions of the skin deposited onto the feathers or fur and is obtained orally during grooming.<ref>{{cite book |first1=Sam D. |last1=Stout |first2=Sabrina C. |last2=Agarwal |last3=Stout |first3=Samuel D. |title=Bone loss and osteoporosis: an anthropological perspective |publisher=Kluwer Academic/Plenum Publishers |location=New York |year=2003 |isbn=0-306-47767-X}}</ref>
In some animals, the presence of fur or feathers blocks the UV rays from reaching the skin. In birds and fur-bearing mammals, vitamin D is generated from the oily secretions of the skin deposited onto the feathers or fur and is obtained orally during grooming.<ref>{{cite book |first1=Sam D. |last1=Stout |first2=Sabrina C. |last2=Agarwal |last3=Stout |first3=Samuel D. |title=Bone loss and osteoporosis: an anthropological perspective |publisher=Kluwer Academic/Plenum Publishers |location=New York |year=2003 |isbn=0-306-47767-X}}</ref>

====Interactive pathway map====
{{Template:VitaminDSynthesis_WP1531}}


==Mechanism of action==
==Mechanism of action==

Revision as of 19:40, 24 January 2012

For other uses, see Vitamin D (disambiguation).
Vitamin D
Drug class
Cholecalciferol (D3)
Class identifiers
UseRickets, osteoporosis, vitamin D deficiency
ATC codeA11CC
Biological targetvitamin D receptor
Clinical data
Drugs.comMedFacts Natural Products
External links
MeSHD014807
Legal status
In Wikidata

Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it (as vitamin D3) when sun exposure is adequate (hence its nickname, the "sunshine vitamin").

Measures of serum levels (from a vitamin D3 blood test) reflect endogenous synthesis from exposure to sunlight as well as intake from the diet, and it is believed that synthesis may contribute generally to the maintenance of adequate serum concentrations. The evidence indicates that the synthesis of vitamin D from sun exposure works in a feedback loop that prevents toxicity but, because of uncertainty about the cancer risk from sunlight, no recommendations are issued by the Institute of Medicine, USA, for the amount of sun exposure required to meet vitamin D requirements. Accordingly, the Dietary Reference Intakes for vitamin D assume that no synthesis occurs and that all of a person's vitamin D is from their diet.

When synthesized in the kidneys, calcitriol circulates as a hormone, regulating the concentration of calcium and phosphate in the bloodstream and promoting the healthy growth and remodeling of bone. Vitamin D prevents rickets in children and osteomalacia in adults, and, together with calcium, helps to protect older adults from osteoporosis. Vitamin D also affects neuromuscular function, inflammation, and influences the action of many genes that regulate the proliferation, differentiation and apoptosis of cells.[1]

The evidence for the health effects of vitamin D supplementation in the general population is inconsistent.[2][3] The best evidence of benefit is for bone health[4] and a decrease in mortality in elderly women.[5]

Health effects

The effects of vitamin D supplementation on health are uncertain.[3] A United States Institute of Medicine, (IOM) report states: "Outcomes related to cancer, cardiovascular disease and hypertension, diabetes and metabolic syndrome, falls and physical performance, immune functioning and autoimmune disorders, infections, neuropsychological functioning, and preeclampsia could not be linked reliably with calcium or vitamin D intake and were often conflicting."[4] Some researchers claim the IOM was too definitive in its recommendations and made a mathematical mistake when calculating the blood level of vitamin D associated with bone health.[6] Members of the IOM panel maintain that they used a "standard procedure for dietary recommendations" and that the report is solidly based on the data. Research on vitamin D supplements, including large scale clinical trials, is continuing.[6]

Mortality

Low blood levels of vitamin D are associated with increased mortality.[7] Supplemental vitamin D3 appears to decrease all cause mortality, with the best evidence of a benefit in elderly women.[5] Vitamin D2, alfacalcidol, and calcitriol do not appear to be effective.[5] Excess or deficiency levels of vitamin D appear to cause abnormal functioning and premature aging[8][9][10] with a U-shaped risk curve between serum 25OHD level and all-cause mortality.[11] The detrimental effects appear at a lower level in people with black skin.[11]

Bone health

Low serum vitamin D levels are associated with rickets, falls, and low bone mineral density.[12] Supplementation with vitamin D and calcium improves bone mineral density slightly, as well as decreases the risk of falls and fractures in certain groups of people.[12] This appears to apply more to people in institutions than those living independently.[13] The quality of the evidence is, however, poor.[14]

Cardiovascular disease

Evidence for health effects from vitamin D supplementation for cardiovascular health is poor.[2][15] Moderate to high doses may reduce cardiovascular disease risk but are of questionable clinical significance.[2][16]

Cancer

Low vitamin D levels are associated with some cancers. When supplementation is used to treat people with prostate cancer, however, there does not appear to be a benefit.[17] Results for a protective or harmful effect of vitamin D supplementation in other types of cancer are inconclusive.[3]

Multiple sclerosis

Vitamin D appears to have a protective effect against multiple sclerosis.[18][19][20] While the initial hypothesis was based on that fact that MS occurred at high rates in the region of the world with long periods with little sunlight, further supportive evidence is now available.[18] The relationship between latitude and UVB penetration is, however, complicated by factors such as atmosphere height (50% higher at the equator), cloud cover (denser at the equator) and ozone layer density, and latitude does not consistently predict the average serum vitamin D level of a population. UVB penetrating to the earth's surface over 24 hours during the summer months in northern Canada (where summer days are longer) equals or exceeds UVB penetration at the equator, allowing sufficient opportunity during the spring, summer, and fall at high latitude to form and store vitamin D3. This, combined with recent computer modeling may call into question the assumption that vitamin D levels in the population follow a latitude gradient.[1] Research has found direct connections between vitamin D and the genes known to be involved in MS, but exact pathology and whether vitamin D supplements during pregnancy or childhood can lessen the likelihood of the child developing MS later in life is not known.[21][22]

Infections

Vitamin D appears to have effects on immune function.[23] It has been postulated to play a role in influenza with lack of vitamin D synthesis during the winter as one explanation for high rates of influenza infection during the winter.[24] For viral infections, other implicated factors include low relative humidities produced by indoor heating and cold temperatures that favor virus spread.[25] Low levels of vitamin D appear to be a risk factor for tuberculosis[26] and historically, it was used as a treatment.[27] As of 2011 it is being investigated in controlled clinical trials.[27] Vitamin D may also play a role in HIV.[28]

Deficiency

Main article: Hypovitaminosis D

Low blood calcidiol (25-hydroxy-vitamin D) can result from avoiding the sun.[29] Deficiency results in impaired bone mineralization, and leads to bone softening diseases[30] including:

  • Rickets, a childhood disease characterized by impeded growth and deformity of the long bones, can be caused by calcium or phosphorus deficiency as well as a lack of vitamin D; today it is largely found in low income countries in Africa, Asia or the Middle East [31] and in those with genetic disorders such as pseudovitamin D deficiency rickets.[32] Rickets was first described in 1650, by Francis Glisson who said it had first appeared about 30 years previously in the counties of Dorset and Somerset.[33] In 1857, John Snow suggested that rickets, then widespread in Britain, was being caused by the adulteration of bakers bread with alum.[34] The role of diet in the development of rickets[35][36] was determined by Edward Mellanby between 1918–1920.[37] Nutritional rickets exists in countries with intense year-round sunlight such as Nigeria and can occur without vitamin D deficiency.[38][39] Although rickets and osteomalacia are now rare in Britain there have been outbreaks in some immigrant communities in which osteomalacia sufferers included women with seemingly adequate daylight outdoor exposure wearing Western clothing.[40] Having darker skin and reduced exposure to sunshine did not produce rickets unless the diet deviated from a Western omnivore pattern characterized by high intakes of meat, fish and eggs, and low intakes of high-extraction cereals.[41][42][43] The dietary risk factors for rickets include abstaining from animal foods.[40][44] Vitamin D deficiency remains the main cause of rickets among young infants in most countries, because breast milk is low in vitamin D and social customs and climatic conditions can prevent adequate UVB exposure. In sunny countries such as Nigeria, South Africa, and Bangladesh, where the disease occurs among older toddlers and children, it has been attributed to low dietary calcium intakes, which are characteristic of cereal-based diets with limited access to dairy products.[43] Rickets was formerly a major public health problem among the US population; in Denver where ultraviolet rays are approximately 20% stronger than at sea level on the same latitude [45] almost two thirds of 500 children had mild rickets in the late 1920s.[46] An increase in the proportion of animal protein [44][47] in the 20th century American diet coupled with increased consumption of milk [48][49] fortified with relatively small quantities of vitamin D coincided with a dramatic decline in the number of rickets cases.[50]
  • Osteomalacia, a bone-thinning disorder that occurs exclusively in adults, is characterized by proximal muscle weakness and bone fragility. The effects of osteomalacia are thought to contribute to chronic musculoskeletal pain,[51][52] there is no persuasive evidence of lower vitamin D status in chronic pain sufferers.[53]

Adequate vitamin D may also be associated with healthy hair follicle growth cycles.[54] There are also associations between low 25(OH)D levels and peripheral vascular disease,[55] certain cancers, multiple sclerosis, rheumatoid arthritis, juvenile diabetes,[50] Parkinson's and Alzheimer's disease.[56] However these associations were found in observational studies and vitamin D vitamin supplements have not been demonstrated to reduce the risks of these diseases.[57]

Research shows that dark-skinned people living in temperate climates have lower vitamin D levels.[58][59][59] It has been suggested that dark-skinned people are less efficient at making vitamin D because melanin in the skin hinders vitamin D synthesis; however, a recent study has found novel evidence that low vitamin D levels among Africans may be due to other reasons.[60] Recent evidence implicates parathyroid hormone in adverse cardiovascular outcomes, black women have an increase in serum PTH at a lower 25(OH)D level than white women.[61] A large scale association study of the genetic determinants of vitamin D insufficiency in Caucasians found no links to pigmentation.[62][63]

The Director General of Research and Development and Chief Scientific Adviser for the UK Department of Health and NHS said that children aged six months to five years should be given vitamin D supplements—particularly during the winter. However, people who get enough vitamin D from their diets and from sunlight are not recommended for vitamin D supplements.[64]

With an emphasis on recommending treatment and intake levels for patients at risk of deficiency listed below, a panel of experts issued a clinical guideline in 2011, stating that vitamin D2 and D3 sources are equivalent.[65]

Toxicity

Further information: hypervitaminosis D

In healthy adults, sustained intake of more than 1250 micrograms/day (50,000 IU) can produce overt toxicity after several months;[66] those with certain medical conditions such as primary hyperparathyroidism[67] are far more sensitive to vitamin D and develop hypercalcemia in response to any increase in vitamin D nutrition, while maternal hypercalcemia during pregnancy may increase fetal sensitivity to effects of vitamin D and lead to a syndrome of mental retardation and facial deformities.[67][68] Pregnant or breastfeeding women should consult a doctor before taking a vitamin D supplement. For infants (birth to 12 months), the tolerable upper limit (maximum amount that can be tolerated without harm) is set at 25 micrograms/day (1000 IU). One thousand micrograms (40,000 IU) per day in infants has produced toxicity within one month.[66] After being commissioned by the Canadian and American governments, the Institute of Medicine (IOM) as of 30 November 2010, has increased the tolerable upper limit (UL) to 2500 IU per day for ages 1–3 years, 3000 IU per day for ages 4–8 years and 4000 IU per day for ages 9–71+ years (including pregnant or lactating women).[69] Vitamin D overdose causes hypercalcemia, and the main symptoms of vitamin D overdose are those of hypercalcemia:anorexia, nausea, and vomiting can occur, frequently followed by polyuria, polydipsia, weakness, nervousness, pruritus, and, ultimately, renal failure.Proteinuria, urinary casts, azotemia, and metastatic calcification(especially in the kidneys) may develop.[66] 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.[67] Within about 20 minutes of ultraviolet exposure in light-skinned individuals (3–6 times longer for pigmented skin), the concentrations of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D that is produced is degraded.[70] According to some sources, endogenous production with full body exposure to sunlight is approximately 250 µg (10,000 IU) per day.[67] According to Holick, "the skin has a large capacity to produce cholecalciferol" his experiments indicate: "[W]hole-body exposure to one minimal erythemal dose [a dose that would just begin to produce sunburn in a given individual] of simulated solar ultraviolet radiation is comparable with taking an oral dose of between 250 and 625 micrograms (10,000 and 25,000 IU) vitamin D."[70]

Based on the non-observation of toxicity at daily intakes of up to 50,000 IU per day, leading to calcidiol levels of more than 600 nmol/L, and the similar effect of supplementation and whole body exposure to one erythemal dose, it is believed that 250 micrograms/day (10,000 IU) in healthy adults are safe and can thus be adopted as the tolerable upper limit.[71]

Published cases of toxicity involving hypercalcemia in which the vitamin D dose and the 25-hydroxy-vitamin D levels are known all involve an intake of ≥40,000 IU (1000 mcg) per day.[67] Recommending supplementation, when those supposedly in need of it are labeled healthy, has proved contentious, and doubt exists concerning long term effects of attaining and maintaining serum 25(OH)D of at least 80 nmol/L by supplementation.[72] A Toronto study concluded, "skin pigmentation, assessed by measuring skin melanin content, showed an inverse relationship with serum 25(OH)D."

The uniform occurrence of low serum 25(OH)D in Indians living in India[73] and Chinese in China,[74] does not support the hypothesis that the low levels seen in the more pigmented are due to lack of synthesis from the sun at higher latitudes; the leader of the study has urged dark-skinned immigrants to take vitamin D supplements nonetheless, saying, "I see no risk, no downside, there's only a potential benefit.[75][76]"

Forms

Name Chemical composition Structure
Vitamin D1 molecular compound of ergocalciferol with lumisterol, 1:1
Vitamin D2 ergocalciferol (made from ergosterol) Note double bond at top center.
Vitamin D3 cholecalciferol (made from 7-dehydrocholesterol in the skin).
Vitamin D4 22-dihydroergocalciferol
Vitamin D5 sitocalciferol (made from 7-dehydrositosterol) File:VitaminD5 structure.png

Several forms (vitamers) of vitamin D exist (see table). The two major forms are vitamin D2 or ergocalciferol, and vitamin D3 or cholecalciferol, vitamin D without a subscript refers to either D2 or D3 or both. These are known collectively as calciferol.[77] Vitamin D2 was chemically characterized in 1932. In 1936, the chemical structure of vitamin D3 was established and resulted from the ultraviolet irradiation of 7-dehydrocholesterol.[78]

Chemically, the various forms of vitamin D are secosteroids; i.e., steroids in which one of the bonds in the steroid rings is broken.[79] The structural difference between vitamin D2 and vitamin D3 is in their side chains. The side chain of D2 contains a double bond between carbons 22 and 23, and a methyl group on carbon 24.

Vitamin D3 (cholecalciferol) is produced by ultraviolet irradiation (UV) of its precursor 7-dehydrocholesterol. This molecule occurs naturally in the skin of animals and in milk. Vitamin D3 can be made by exposure of the skin to UV, or by exposing milk directly to UV (one commercial method).

Vitamin D2 is a derivative of ergosterol, a membrane sterol named for the ergot fungus, which is produced by some organisms of phytoplankton, invertebrates, and fungi. The vitamin ergocalciferol (D2) is produced in these organisms from ergosterol in response to UV irradiation. D2 is not produced by land plants or vertebrates, because they lack the precursor ergosterol.[80] The biological fate for producing 25(OH)D from vitamin D2 is expected to be the same as for D3,[65] although some controversy exists over whether or not D2 can fully substitute for vitamin D3 in the human diet.[81] [82]

Evolution

The photosynthesis of vitamin D evolved over an estimated 750 million years ago; the phytoplankton coccolithophore Emiliania huxleyi is an early example. Vitamin D played a critical role in the maintenance of a calcified skeleton in vertebrates as they left their calcium-rich ocean environment for land over an estimated 350 million years ago.[citation needed]

Vitamin D can be synthesized only via a photochemical process, so early vertebrates that ventured onto land either had to ingest foods that contained vitamin D or had to be exposed to sunlight to photosynthesize vitamin D in their skin to satisfy their body's vitamin D requirement.[83]

Production in the skin

In the epidermal strata of the skin, production is greatest in the stratum basale (colored red in the illustration) and stratum spinosum (colored light brown).

Vitamin D3 is made in the skin when 7-dehydrocholesterol reacts with ultraviolet light (UVB) at wavelengths between 270 and 300 nm, with peak synthesis occurring between 295 and 297 nm.[84] These wavelengths are present in sunlight when the UV index is greater than three, as well as in the light emitted by the UV lamps in tanning beds (which produce ultraviolet primarily in the UVA spectrum, but typically produce 4% to 10% of the total UV emissions as UVB). At a UV index greater than three, which occurs daily within the tropics, daily during the spring and summer seasons in temperate regions, and almost never within the arctic circles, vitamin D3 can be made in the skin. Latitude does not consistently predict the average serum 25OHD level of a population. The assumption that vitamin D levels in the population follow a latitude gradient is especially questionable in view of surveys which have shown that UVB penetrating to the earth's surface over 24 hours during the summer months in northern Canada equals or exceeds UVB penetration at the equator. Accordingly, there is sufficient opportunity during the spring, summer, and fall months at high latitude for humans to form and store vitamin D3.[85] Depending on the intensity of UVB rays and the minutes of exposure, an equilibrium can develop in the skin, and vitamin D degrades as fast as it is generated.[70]

The skin consists of two primary layers: the inner layer called the dermis, composed largely of connective tissue, and the outer, thinner epidermis. Thick epidermis in the soles and palms consists of five strata; from outer to inner they are: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Vitamin D is produced in the two innermost strata, the stratum basale and stratum spinosum.

Cholecalciferol (D3) is produced photochemically in the skin from 7-dehydrocholesterol; 7-dehydrocholesterol is produced in relatively large quantities[clarification needed] in the skin of most vertebrate animals, including humans.[86] The naked mole rat appears to be naturally cholecalciferol deficient, as serum 25-OH vitamin D levels are undetectable.[87] In some animals, the presence of fur or feathers blocks the UV rays from reaching the skin. In birds and fur-bearing mammals, vitamin D is generated from the oily secretions of the skin deposited onto the feathers or fur and is obtained orally during grooming.[88]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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|alt=Vitamin D Synthesis Pathway (view / edit)]]
Vitamin D Synthesis Pathway (view / edit)
  1. ^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

Mechanism of action

Calcium regulation in the human body.[89] The role of vitamin D is shown in orange.

Vitamin D is carried in the bloodstream to the liver, where it is converted into the prohormone calcidiol. Circulating calcidiol may then be converted into calcitriol, the biologically active form of vitamin D, either in the kidneys or by monocyte-macrophages in the immune system. When synthesized by monocyte-macrophages, calcitriol acts locally as a cytokine, defending the body against microbial invaders.[90] Following the final converting step in the kidney, calcitriol (the physiologically active form of vitamin D) is released into the circulation. By binding to vitamin D-binding protein (VDBP), a carrier protein in the plasma, calcitriol is transported to various target organs.[79]

Calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is principally located in the nuclei of target cells.[79] The binding of calcitriol to the VDR allows the VDR to act as a transcription factor that modulates the gene expression of transport proteins (such as TRPV6 and calbindin), which are involved in calcium absorption in the intestine.[91]

The vitamin D receptor belongs to the nuclear receptor superfamily of steroid/thyroid hormone receptors, and VDRs are expressed by cells in most organs, including the brain, heart, skin, gonads, prostate, and breast. VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the maintenance of calcium and phosphorus levels in the blood (with the assistance of parathyroid hormone and calcitonin) and to the maintenance of bone content.[50]

Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells. It also is involved in the biosynthesis of neurotrophic factors, synthesis of nitric oxide synthase, and increased glutathione levels.[92]

The VDR is known to be involved in cell proliferation and differentiation. Vitamin D also affects the immune system, and VDRs are expressed in several white blood cells, including monocytes and activated T and B cells.[93]

Apart from VDR activation, various alternative mechanisms of action are known. An important one of these is its role as a natural inhibitor of signal transduction by hedgehog (a hormone involved in morphogenesis).[94][95]

One of the most important roles of vitamin D is to maintain skeletal calcium balance by promoting calcium absorption in the intestines, promoting bone resorption by increasing osteoclast number, maintaining calcium and phosphate levels for bone formation, and allowing proper functioning of parathyroid hormone to maintain serum calcium levels. Vitamin D deficiency can result in lower bone mineral density and an increased risk of bone loss (osteoporosis) or bone fracture because a lack of vitamin D alters mineral metabolism in the body.[96]

Recommendations

Dietary reference intakes

Different institutions propose different recommendations concerning daily amounts of the vitamin :

(Conversion : 1 µg = 40 IU and 0.025 µg = 1 IU.[97])

Australia and New Zealand

Australia and New Zealand have established average intakes for vitamin D, as follows:[98] Children 5.0 μg /day Adults 19–50 yr 5.0 μg/day, 51–70 yr 10.0 μg/day, >70 yr 15.0 μg/day

Canada

According to Health Canada[99] the recommended dietary allowances (RDA) for vitamin D are:

  • 0–12 months: 400 IU/day (10 μg/day)
  • 1–70 years of age: 600 IU/day (15 μg/day)
  • 71+ years of age: 800 IU/day (20 μg/day)
  • Pregnant/lactating: 600 IU/day (15 μg/day)

European Union

The recommended daily amount for vitamin D in the European Union is 5 µg.[100]

The European Menopause and Andropause Society (EMAS) recommended 15 µg (600 IU) until age 70, and 20 µg (800 IU) in older than 71 years, in postmenopausal women. This dose should be increased up to 4,000 IU/day in some patients with very low vitamin D status or in case of co-morbid conditions.[101]

United States

According to the United States Institute of Medicine,[4] the recommended dietary allowances of vitamin D are:

  • 1–70 years of age: 600 IU/day (15 μg/day)
  • 71+ years of age: 800 IU/day (20 μg/day)
  • Pregnant/lactating: 600 IU/day (15 μg/day)
Upper intake levels

The Tolerable Upper Intake Level 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 .[102]" Although tolerable upper intake levels are believed to be safe, information on the long term effects is incomplete and these levels of intake are not recommended [103]:

  • 0–6 months of age: 1,000 IU
  • 6–12 months of age: 1,500 IU
  • 1–3 years of age: 2,500 IU
  • 4–8 years of age: 3,000 IU
  • 9-71+ years of age: 4,000 IU
  • Pregnant/lactating: 4,000 IU [4]
Comment

The Dietary Reference Intake for vitamin D issued by the American (U.S.) Institute of Medicine (IOM) in 2010 superseded a previous recommendation which had Adequate Intake status. 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, is intended for the North American population, and assumes that calcium requirements are being met.[4]

One school of thought contends that human physiology is fine tuned to an intake of 4000–12,000 IU/day from sun exposure with concomitant serum 25-hydroxyvitamin D levels of 40 to 80 ng/mL[104] and that this is required for optimal health. Proponents of this view, who include some members of the panel that drafted a now superseded 1997 report on vitamin D from the Institute of Medicine, contend that the IOM's warning about serum concentrations above 50 ng/mL lacks biological plausibility. They suggest that for some people reducing the risk of preventable disease requires a higher level of vitamin D than that recommended by the IOM.[105][104]

Serum 25-hydroxyvitamin D

An (U.S.) Institute of Medicine committee concluded that a serum 25-hydroxyvitamin D level of 20 ng/mL is desirable for bone and overall health. The Dietary Reference Intakes for vitamin D are chosen with a margin of safety and 'overshoot' the targeted serum value to ensure that the specified levels of intake achieve the desired serum 25-hydroxyvitamin D levels in almost all persons. It is assumed there are no contributions to serum 25-hydroxyvitamin D level from sun exposure and the recommendations are fully applicable to people with dark skin or negligible exposure to sunlight.[106]

The Institute found that serum 25-hydroxyvitamin D concentrations above 30 ng/mL are "not consistently associated with increased benefit". Serum 25-hydroxyvitamin D levels above 50 ng/mL may be cause for concern.[106]

Dietary sources

In some countries, staple foods are artificially fortified with vitamin D.[107] Dietary sources of vitamin D include:[1]

  • Fatty fish species, such as:
    • Catfish, 85 g (3 oz) provides 425 IU (5 IU/g)
    • Salmon, cooked, 100 g (3.5 oz) provides 360 IU (3.6 IU/g)
    • Mackerel, cooked, 100 g (3.5 oz), 345 IU (3.45 IU/g)
    • Sardines, canned in oil, drained, 50 g (1.75 oz), 250 IU (5 IU/g)
    • Tuna, canned in oil, 100 g (3.5 oz), 235 IU (2.35 IU/g)
    • Eel, cooked, 100 g (3.5 oz), 200 IU (2.00 IU/g)
  • A whole egg provides 20 IU if egg weighs 60 g (0.333 IU/g)
  • Beef liver, cooked, 100 g (3.5 oz), provides 15 IU (0.15 IU/g)
  • Fish liver oils, such as cod liver oil, 1 Tbs. (15 ml) provides 1360 IU (90.6 IU/ml)
  • UV-irradiated mushrooms and yeast are the only known vegan significant sources of vitamin D from food sources.[108][109] Exposure of portabella mushrooms to UV provides an increase of vitamin D content in an 100-g portion (grilled) from about 14 IU (0.14 IU/g non-exposed) to about 500 IU (5 IU/g exposed to UV light).[110]

History

American researchers Elmer McCollum and Marguerite Davis in 1913 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 1921, Elmer McCollum tested modified cod liver oil in which the vitamin A had been destroyed. The modified oil cured the sick dogs, so McCollum concluded the factor in cod liver oil which cured rickets was distinct from vitamin A. He called it vitamin D because it was the fourth vitamin to be named.[111][112][113] It was not initially realized that, unlike other vitamins, vitamin D can be synthesised by humans through exposure to UV light.

In 1923, it was established that when 7-dehydrocholesterol is irradiated with light, a form of a fat-soluble vitamin is produced (now known as D3). Alfred Fabian Hess showed "light equals vitamin D."[114] Adolf Windaus, at the University of Göttingen in Germany, received the Nobel Prize in Chemistry in 1928, for his work on the constitution of sterols and their connection with vitamins.[115] In the 1930s he clarified further the chemical structure of vitamin D.[116]

In 1923, 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.[117] After irradiating rodent food, Steenbock discovered the rodents were cured of rickets. A vitamin D deficiency is a known cause of rickets. Using $300 of his own money, Steenbock patented his invention. His irradiation technique was used for foodstuffs, most memorably for milk. By the expiration of his patent in 1945, rickets had been all but eliminated in the US.[118]

Industrial production

Vitamin D3 (cholecalciferol) is produced industrially by exposing 7-dehydrocholesterol to UVB light, followed by purification.[119] The 7-dehydrocholesterol is a natural substance in wool grease (lanolin) from sheep or other woolly animals. Vitamin D 2 (ergocalciferol) is produced in a similar way using ergosterol from yeast or mushrooms as a starting material.[119]

Synthesis

In the skin, 7-dehydrocholesterol, a derivative of cholesterol, is photolyzed by ultraviolet light in a 6-electronconrotatory electrocyclic reaction. The product is previtamin D3.
Previtamin D3 spontaneously isomerizes to vitamin D 3 (cholecalciferol) in a antarafacial sigmatropic [1,7] hydride shift. At room temperature, the transformation of previtamin D3 to vitamin D3 takes about 12 days to complete.[83]
Whether it is made in the skin or ingested, cholecalciferol is hydroxylated in the liver at position 25 (upper right of the molecule) to form 25-hydroxycholecalciferol (calcidiol or 25(OH)D). This reaction is catalyzed by the microsomal enzyme vitamin D 25-hydroxylase,[120] which is produced by hepatocytes. Once made, the product is released into the plasma, where it is bound to an α-globulin, vitamin D binding protein.[121]
Calcidiol is transported to the proximal tubules of the kidneys, where it is hydroxylated at the 1-α position (lower right of the molecule) to formcalcitriol (aka 1,25-dihydroxycholecalciferol and abbreviated to 1,25(OH)2D). This product is a potent ligand of the vitamin D receptor (VDR), which mediates most of the physiological actions of the vitamin. The conversion of calcidiol to calcitriol is catalyzed by the enzyme25-hydroxyvitamin D3 1-alpha-hydroxylase, the levels of which are increased by parathyroid hormone (and additionally by low calcium or phosphate).

References

  1. ^ a b "Dietary Supplement Fact Sheet: Vitamin D". Office of Dietary Supplements (ODS). National Institutes of Health (NIH). Retrieved 2010-04-11.
  2. ^ a b c Pittas, AG (2010 Mar 2). "Vitamin D and Cardiometabolic Outcomes: A Systematic Review". Annals of internal medicine. 152 (5): 307–14. doi:10.1059/0003-4819-152-5-201003020-00009. PMC 3211092. PMID 20194237. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  3. ^ a b c Chung, M (2009 Aug). "Vitamin D and calcium: a systematic review of health outcomes". Evidence report/technology assessment (183): 1–420. PMID 20629479. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  4. ^ a b c d e Reference Intakes for Calcium and Vitamin D (2011) Page 5
  5. ^ a b c Bjelakovic, G (2011 Jul 6). Bjelakovic, Goran (ed.). "Vitamin D supplementation for prevention of mortality in adults". Cochrane database of systematic reviews (Online) (7): CD007470. doi:10.1002/14651858.CD007470.pub2. PMID 21735411. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  6. ^ a b Maxmen A. (2011). "Nutrition advice: the vitamin D-lemma" (PDF). Nature. 475 (7354): 23–5. doi:10.1038/475023a. PMID 21734684.
  7. ^ Zittermann, A (2009 Nov). "Vitamin D deficiency and mortality". Current opinion in clinical nutrition and metabolic care. 12 (6): 634–9. doi:10.1097/MCO.0b013e3283310767. PMID 19710612. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  8. ^ Tuohimaa, P (2009). "Vitamin D and aging". The Journal of Steroid Biochemistry and Molecular Biology. 114 (1–2): 78–84. doi:10.1016/j.jsbmb.2008.12.020. PMID 19444937. {{cite journal}}: Unknown parameter |month= ignored (help)
  9. ^ Tuohimaa, P.; Keisala, T.; Minasyan, A.; Cachat, J.; Kalueff, A. (2009). "Vitamin D, nervous system and aging". Psychoneuroendocrinology. 34: S278–86. doi:10.1016/j.psyneuen.2009.07.003. PMID 19660871.
  10. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 20590845, please use {{cite journal}} with |pmid=20590845 instead.
  11. ^ a b Dietary Reference Intakes for Calcium and Vitamin D (2011)Page 435
  12. ^ a b Cranney, A (2007 Aug). "Effectiveness and safety of vitamin D in relation to bone health". Evidence report/technology assessment (158): 1–235. PMID 18088161. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  13. ^ Chung, M; Lee, J; Terasawa, T; Lau, J; Trikalinos, TA (2011). "Vitamin D with or Without Calcium Supplementation for Prevention of Cancer and Fractures: An Updated Meta-analysis for the U.S. Preventive Services Task Force". Annals of internal medicine. 155 (12): 827–38. doi:10.1059/0003-4819-155-12-201112200-00005. PMID 22184690.
  14. ^ Cranney, A (2008 Aug). "Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health". The American journal of clinical nutrition. 88 (2): 513S–519S. PMID 18689393. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  15. ^ McGreevy, C; Williams, D (2011). "New insights about vitamin d and cardiovascular disease: A narrative review". Annals of internal medicine. 155 (12): 820–6. doi:10.1059/0003-4819-155-12-201112200-00004. PMID 22184689.
  16. ^ Wang, L (2010 Mar 2). "Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events". Annals of internal medicine. 152 (5): 315–23. doi:10.1059/0003-4819-152-5-201003020-00010. PMID 20194238. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  17. ^ Buttigliero, C (2011). "Prognostic role of vitamin d status and efficacy of vitamin d supplementation in cancer patients: a systematic review". The oncologist. 16 (9): 1215–27. doi:10.1634/theoncologist.2011-0098. PMID 21835895. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  18. ^ a b Ascherio, A (2010 Jun). "Vitamin D and multiple sclerosis". Lancet neurology. 9 (6): 599–612. doi:10.1016/S1474-4422(10)70086-7. PMID 20494325. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  19. ^ Pierrot-Deseilligny, C (2010 Jul). "Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis?". Brain : a journal of neurology. 133 (Pt 7): 1869–88. doi:10.1093/brain/awq147. PMID 20584945. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  20. ^ Pierrot-Deseilligny, C (2011 Apr). "Widespread vitamin D insufficiency: A new challenge for primary prevention, with particular reference to multiple sclerosis". Presse medicale (Paris, France : 1983). 40 (4 Pt 1): 349–56. doi:10.1016/j.lpm.2011.01.003. PMID 21333483. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  21. ^ "Vitamin D helps control MS gene". BBC News. 5 February 2009. Retrieved 2010-03-25.
  22. ^ "Genetic Study Supports Vitamin D Deficiency as an Environmental Factor in MS Susceptibility. Multiple Sclerosis Society of Canada. 5 February 2009". Mssociety.ca. Retrieved 2010-03-25.
  23. ^ Beard, JA (2011 Mar). "Vitamin D and the anti-viral state". Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 50 (3): 194–200. doi:10.1016/j.jcv.2010.12.006. PMID 21242105. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  24. ^ Cannell, J. J.; Vieth, R.; Umhau, J. C.; Holick, M. F.; Grant, W. B.; Madronich, S.; Garland, C. F.; Giovannucci, E. (2006). "Epidemic influenza and vitamin D". Epidemiology and Infection. 134 (6): 1129–40. doi:10.1017/S0950268806007175. PMC 2870528. PMID 16959053.
  25. ^ Bruce, D; Ooi, JH; Yu, S; Cantorna, MT (2010). "Vitamin D and host resistance to infection? Putting the cart in front of the horse". Experimental biology and medicine (Maywood, N.J.). 235 (8): 921–7. doi:10.1258/ebm.2010.010061. PMC 3138330. PMID 20660091.
  26. ^ Nnoaham, KE (2008 Feb). "Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis". International journal of epidemiology. 37 (1): 113–9. doi:10.1093/ije/dym247. PMID 18245055. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  27. ^ a b Luong, K (2011 Jun). "Impact of vitamin D in the treatment of tuberculosis". The American journal of the medical sciences. 341 (6): 493–8. doi:10.1097/MAJ.0b013e3182070f47. PMID 21289501. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  28. ^ Spector, SA (2011 Feb-Mar). "Vitamin D and HIV: letting the sun shine in". Topics in antiviral medicine. 19 (1): 6–10. PMID 21852710. {{cite journal}}: Check date values in: |date= (help)
  29. ^ Schoenmakers, I; Goldberg, GR; Prentice, A (2008). "Abundant sunshine and vitamin D deficiency". British journal of nutrition. 99 (6): 1171–3. doi:10.1017/S0007114508898662. PMC 2758994. PMID 18234141.
  30. ^ Grant, WB; Holick, MF (2005). "Benefits and requirements of vitamin D for optimal health: a review". Alternative medicine review. 10 (2): 94–111. PMID 15989379.
  31. ^ Lerch, C; Meissner, T; Lerch, Christian (2007). Lerch, Christian (ed.). "Interventions for the prevention of nutritional rickets in term born children". Cochrane database of systematic reviews (Online) (4): CD006164. doi:10.1002/14651858.CD006164.pub2. PMID 17943890.
  32. ^ Zargar, A. H.; Mithal, A; Wani, AI; Laway, BA; Masoodi, SR; Bashir, MI; Ganie, MA (2000). "Pseudovitamin D deficiency rickets—a report from the Indian subcontinent". Postgraduate Medical Journal. 76 (896): 369–72. doi:10.1136/pmj.76.896.369. PMC 1741602. PMID 10824056. {{cite journal}}: Unknown parameter |month= ignored (help)
  33. ^ Gibbs, D (1994). "Rickets and the crippled child: an historical perspective". Journal of the Royal Society of Medicine. 87 (12): 729–32. PMC 1294978. PMID 7503834.
  34. ^ Dunnigan, M (2003). "Commentary: John Snow and alum-induced rickets from adulterated London bread: an overlooked contribution to metabolic bone disease". International journal of epidemiology. 32 (3): 340–1. doi:10.1093/ije/dyg160. PMID 12777415.
  35. ^ Pileggi, V; De Luca, HF; Steenbock, H (1955). "The role of vitamin D and intestinal phytase in the prevention of rickets in rats on cereal diets". Archives of Biochemistry and Biophysics. 58 (1): 194–204. doi:10.1016/0003-9861(55)90106-5. PMID 13259690. {{cite journal}}: Unknown parameter |month= ignored (help)
  36. ^ Ford, JA; Colhoun, EM; McIntosh, WB; Dunnigan, MG (1972). "Biochemical Response of Late Rickets and Osteomalacia to a Chupatty-free Diet". British medical journal. 3 (5824): 446–7. doi:10.1136/bmj.3.5824.446. PMC 1786011. PMID 5069221.
  37. ^ Rajakumar, K (2003). "Vitamin D, cod-liver oil, sunlight, and rickets: a historical perspective". Pediatrics. 112 (2): e132–5. doi:10.1542/peds.112.2.e132. PMID 12897318.
  38. ^ Oramasionwu, GE; Thacher, TD; Pam, SD; Pettifor, JM; Abrams, SA (2008). "Adaptation of calcium absorption during treatment of nutritional rickets in Nigerian children". The British journal of nutrition. 100 (2): 387–92. doi:10.1017/S0007114507901233. PMID 18197991.
  39. ^ Fischer, PR; Rahman, A; Cimma, JP; Kyaw-Myint, TO; Kabir, AR; Talukder, K; Hassan, N; Manaster, BJ; Staab, DB (1999). "Nutritional rickets without vitamin D deficiency in Bangladesh". Journal of tropical pediatrics. 45 (5): 291–3. doi:10.1093/tropej/45.5.291. PMID 10584471.
  40. ^ a b Dunnigan, MG; Henderson, JB (1997). "An epidemiological model of privational rickets and osteomalacia". The Proceedings of the Nutrition Society. 56 (3): 939–56. doi:10.1079/PNS19970100. PMID 9483661.
  41. ^ Robertson, I; Ford, JA; McIntosh, WB; Dunnigan, MG (1981). "The role of cereals in the aetiology of nutritional rickets: the lesson of the Irish National Nutrition Survey 1943-8". The British journal of nutrition. 45 (1): 17–22. doi:10.1079/BJN19810073. PMID 6970590.
  42. ^ Clements, M. R. (1989). "The problem of rickets in UK Asians". Journal of Human Nutrition and Dietetics. 2 (2): 105. doi:10.1111/j.1365-277X.1989.tb00015.x.
  43. ^ a b Pettifor, JM (2004). "Nutritional rickets: deficiency of vitamin D, calcium, or both?". The American Journal of Clinical Nutrition. 80 (6 Suppl): 1725S–9S. PMID 15585795.
  44. ^ a b Dunnigan, Matthew G.; Henderson, Janet B.; Hole, David J.; Mawer, E. Barbara; Berry, Jacqueline L. (2007). "Meat consumption reduces the risk of nutritional rickets and osteomalacia". British Journal of Nutrition. 94 (6): 983–91. doi:10.1079/BJN20051558. PMID 16351777.
  45. ^ "US National Institutes Of Health, National cancer Institute". Science.education.nih.gov. Retrieved 2010-08-24.
  46. ^ Weick, MT (1967). "A history of rickets in the United States". The American Journal of Clinical Nutrition. 20 (11): 1234–41. PMID 4862158.
  47. ^ Garrison, R., Jr., Somer, E., The nutrition desk reference(1997)
  48. ^ E. Melanie DuPuis., Nature's Perfect Food: How Milk Became America's Drink(2002) ISBN 978-0814719381
  49. ^ Teegarden, D; Lyle, RM; Proulx, WR; Johnston, CC; Weaver, CM (1999). "Previous milk consumption is associated with greater bone density in young women". The American Journal of Clinical Nutrition. 69 (5): 1014–7. PMID 10232644.
  50. ^ a b c Holick, MF (2004). "Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease". The American Journal of Clinical Nutrition. 80 (6 Suppl): 1678S–88S. PMID 15585788.
  51. ^ Holick, MF (2003). "Vitamin D: A millenium perspective". Journal of cellular biochemistry. 88 (2): 296–307. doi:10.1002/jcb.10338. PMID 12520530.
  52. ^ Stewart B. Leavitt. "Vitamin D – A Neglected 'Analgesic' for Chronic Musculoskeletal Pain" (PDF). Pain-Topics.org. Retrieved 2009-03-25.
  53. ^ Straube, S; Andrew Moore, R; Derry, S; McQuay, HJ (2009). "Vitamin D and chronic pain". Pain. 141 (1–2): 10–3. doi:10.1016/j.pain.2008.11.010. PMID 19084336.
  54. ^ Amor, KT; Rashid, RM; Mirmirani, P (2010). "Does D matter? The role of vitamin D in hair disorders and hair follicle cycling". Dermatology online journal. 16 (2): 3. PMID 20178699.
  55. ^ Melamed, ML; Muntner, P; Michos, ED; Uribarri, J; Weber, C; Sharma, J; Raggi, P (2008). "Serum 25-hydroxyvitamin D Levels and the Prevalence of Peripheral Arterial Disease: Results from NHANES 2001–2004". Arteriosclerosis, thrombosis, and vascular biology. 28 (6): 1179–85. doi:10.1161/ATVBAHA.108.165886. PMC 2705139. PMID 18417640.
  56. ^ Evatt, ML; Delong, MR; Khazai, N; Rosen, A; Triche, S; Tangpricha, V (2008). "Prevalence of Vitamin D Insufficiency in Patients With Parkinson Disease and Alzheimer Disease". Archives of neurology. 65 (10): 1348–52. doi:10.1001/archneur.65.10.1348. PMC 2746037. PMID 18852350.
  57. ^ Pittas, AG; Chung, M; Trikalinos, T; Mitri, J; Brendel, M; Patel, K; Lichtenstein, AH; Lau, J; Balk, EM (2010). "Vitamin D and Cardiometabolic Outcomes: A Systematic Review". Annals of Internal Medicine. 152 (5): 307–14. doi:10.1059/0003-4819-152-5-201003020-00009. PMC 3211092. PMID 20194237. {{cite journal}}: Unknown parameter |month= ignored (help)
  58. ^ Azmina Govindji RD (1 July 2010). "When it's sunny, top up your vitamin D". TheIsmaili.org. Retrieved 2010-07-01.
  59. ^ a b Ford, L; Graham, V; Wall, A; Berg, J (2006). "Vitamin D concentrations in an UK inner-city multicultural outpatient population". Annals of Clinical Biochemistry. 43 (6): 468–73. doi:10.1258/000456306778904614. PMID 17132277. {{cite journal}}: Unknown parameter |month= ignored (help)
  60. ^ Signorello, LB; Williams, SM; Zheng, W; Smith, JR; Long, J; Cai, Q; Hargreaves, MK; Hollis, BW; Blot, WJ (2010). "Blood vitamin D levels in relation to genetic estimation of African ancestry". Cancer Epidemiology, Biomarkers & Prevention. 19 (9): 2325–31. doi:10.1158/1055-9965.EPI-10-0482. PMC 2938736. PMID 20647395.
  61. ^ Aloia, JF; Chen, DG; Chen, H (2010). "The 25(OH)D/PTH Threshold in Black Women". The Journal of clinical endocrinology and metabolism. 95 (11): 5069–73. doi:10.1210/jc.2010-0610. PMC 2968726. PMID 20685862.
  62. ^ Wang, TJ; Zhang, F; Richards, JB; Kestenbaum, B; Van Meurs, JB; Berry, D; Kiel, DP; Streeten, EA; Ohlsson, C (2010). "Common genetic determinants of vitamin D insufficiency: a genome-wide association study". Lancet. 376 (9736): 180–8. doi:10.1016/S0140-6736(10)60588-0. PMC 3086761. PMID 20541252.
  63. ^ Bouillon, R (2010). "Genetic and environmental determinants of vitamin D status". Lancet. 376 (9736): 148–9. doi:10.1016/S0140-6736(10)60635-6. PMID 20541253.
  64. ^ "All under-fives should take vitamin D pills to avoid rickets, says Government's health chief". 27 January 2011.
  65. ^ a b Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM (2011-06-06). "Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline". J Clin Endocrinol Metab. 96 (7): 1911–30. doi:10.1210/jc.2011-0385. PMID 21646368.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  66. ^ a b c Vitamin D at Merck Manual of Diagnosis and Therapy Professional Edition
  67. ^ a b c d e Vieth R (1999). "Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety" (PDF). The American Journal of Clinical Nutrition. 69 (5): 842–56. PMID 10232622. {{cite journal}}: Unknown parameter |month= ignored (help)
  68. ^ Tolerable Upper Intake Limits for Vitamins And Minerals. European Food Safety Authority. December 2006. ISBN 92-9199-014-0.
  69. ^ Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA (2011). "The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know". Journal of Clinical Endocrinology & Metabolism. 96 (1): 53–8. doi:10.1210/jc.2010-2704. PMC 3046611. PMID 21118827. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  70. ^ a b c Holick MF (1995). "Environmental factors that influence the cutaneous production of vitamin D" (PDF). The American Journal of Clinical Nutrition. 61 (3 Suppl): 638S–645S. PMID 7879731. {{cite journal}}: Unknown parameter |month= ignored (help)
  71. ^ Hathcock JN, Shao A, Vieth R, Heaney R (2007). "Risk assessment for vitamin D" (PDF). The American Journal of Clinical Nutrition. 85 (1): 6–18. PMID 17209171. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  72. ^ Tseng, Lisa (2003). "Controversies in Vitamin D Supplementation". Nutrition Bytes. 9 (1).
  73. ^ Harinarayan, CV; Joshi, SR (2009). "Vitamin D status in India—its implications and remedial measures". The Journal of the Association of Physicians of India. 57: 40–8. PMID 19753759.
  74. ^ Lips, P (2010). "Worldwide status of vitamin D nutrition". The Journal of steroid biochemistry and molecular biology. 121 (1–2): 297–300. doi:10.1016/j.jsbmb.2010.02.021. PMID 20197091.
  75. ^ CBC "Dark-skinned immigrants urged to take vitamin D". February 16, 2010. CBC News.[unreliable medical source?]
  76. ^ Stephen Strauss."The vitamin D debate"[dead link]. February 13, 2008.CBC News.[unreliable medical source?]
  77. ^ Dorland's Illustrated Medical Dictionary, under Vitamin (Table of Vitamins)
  78. ^ History of Vitamin D University of California, Riverside, Vitamin D Workshop.
  79. ^ a b c About Vitamin D Including Sections: History, Nutrition, Chemistry, Biochemistry, and Diseases. University of California Riverside
  80. ^ "Vitamin D". Mayo Clinic
  81. ^ Houghton LA, Vieth R (2006). "The case against ergocalciferol (vitamin D2) as a vitamin supplement" (PDF). The American Journal of Clinical Nutrition. 84 (4): 694–7. PMID 17023693. {{cite journal}}: Unknown parameter |month= ignored (help)
  82. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1210/jc.2007-2308, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1210/jc.2007-2308 instead.
  83. ^ a b Holick, MF (2004). "Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis". The American Journal of Clinical Nutrition. 79 (3): 362–71. PMID 14985208. {{cite journal}}: Unknown parameter |month= ignored (help)
  84. ^ Hume, Eleanor Margaret; Lucas, Nathaniel Sampson; Smith, Hannah Henderson (1927). "On the Absorption of Vitamin D from the Skin". Biochemical Journal. 21 (2): 362–367. PMC 1251921. PMID 16743844.
  85. ^ Dietary Reference Intakes for Calcium and Vitamin D (2011)Page 104
  86. ^ Crissey, SD; Ange, KD; Jacobsen, KL; Slifka, KA; Bowen, PE; Stacewicz-Sapuntzakis, M; Langman, CB; Sadler, W; Kahn, S (2003). "Serum concentrations of lipids, vitamin D metabolites, retinol, retinyl esters, tocopherols and selected carotenoids in twelve captive wild felid species at four zoos". The Journal of nutrition. 133 (1): 160–6. PMID 12514284.
  87. ^ Yahav, S; Buffenstein, R (1993). "Cholecalciferol supplementation alters gut function and improves digestibility in an underground inhabitant, the naked mole rat (Heterocephalus glaber), when fed on a carrot diet". The British journal of nutrition. 69 (1): 233–41. doi:10.1079/BJN19930025. PMID 8384476.
  88. ^ Stout, Sam D.; Agarwal, Sabrina C.; Stout, Samuel D. (2003). Bone loss and osteoporosis: an anthropological perspective. New York: Kluwer Academic/Plenum Publishers. ISBN 0-306-47767-X.
  89. ^ Walter F., PhD. Boron (2003). "The Parathyroid Glands and Vitamin F". Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1094. ISBN 978-1-4160-2328-9.
  90. ^ Adams, J. S.; Hewison, M. (2010). "Update in Vitamin D". Journal of Clinical Endocrinology & Metabolism. 95 (2): 471–8. doi:10.1210/jc.2009-1773. PMC 2840860. PMID 20133466.
  91. ^ Bouillon R, Van Cromphaut S, Carmeliet G. (2003). "Intestinal calcium absorption: Molecular vitamin D mediated mechanisms". Journal of Cellular Biochemistry. 88 (2): 332–9. doi:10.1002/jcb.10360. PMID 12520535.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  92. ^ Puchacz E, Stumpf WE, Stachowiak EK, Stachowiak MK (1996). "Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells". Brain Res Mol Brain Res. 36 (1): 193–6. doi:10.1016/0169-328X(95)00314-I. PMID 9011759. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  93. ^ Vitamin D[dead link] The Physicians Desk Reference. 2006 Thompson Healthcare.
  94. ^ Sarkar FH, Li Y, Wang Z, Kong D. (2010). "The role of nutraceuticals in the regulation of Wnt and Hedgehog signaling in cancer". Cancer Metastasis Reviews. 29 (3): 383–64. doi:10.1007/s10555-010-9233-4. PMC 2974632. PMID 20711635.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  95. ^ "Hedgehog signaling and Vitamin D". Medscape.com. 2009-12-18. Retrieved 2010-03-25.
  96. ^ Bell TD, Demay MB, Burnett-Bowie SAM (2010). "The biology and pathology of vitamin D control in bone". Journal of Cellular Biochemistry. 111 (1): 7–13. doi:10.1002/jcb.22661. PMID 20506379. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  97. ^ "Dietary Reference Intakes Tables [Health Canada, 2005]". Retrieved 21 July 2011.
  98. ^ "Nutrient reference values for Australia and New Zealand" (PDF). National Health and Medical Research Council. 2005-09-09. Retrieved 2010-12-11.
  99. ^ http://www.hc-sc.gc.ca/fn-an/nutrition/vitamin/vita-d-eng.php
  100. ^ "Vitamins: what they do and where to find them (EUFIC)". European Food Information Council. 10-12-2010. Retrieved 2010-12-11. Vitamin D {{cite web}}: Check date values in: |date= (help)
  101. ^ Pérez-López, FR; Brincat, M; Erel, CT; Tremollieres, F; Gambacciani, M; Lambrinoudaki, I; Moen, MH; Schenck-Gustafsson, K; Vujovic, S (2012). "EMAS position statement: Vitamin D and postmenopausal health". Maturitas. 71 (1): 83–8. doi:10.1016/j.maturitas.2011.11.002. PMID 22100145.
  102. ^ Dietary Reference Intakes for Calcium and Vitamin D (2011) page 403
  103. ^ Dietary Reference Intakes for Calcium and Vitamin D (2011) page 403Hazard ratios of risk of death according to baseline serum 25OHD level
  104. ^ a b Heaney RP, Holick MF. (2011). "Perspective: Why the IOM Recommendations for Vitamin D are Deficient". Journal of Bone and Mineral Research. 26 (3): 455–7. doi:10.1002/jbmr.328. PMID 21337617.
  105. ^ Holick MF, Binkley NC, Hike A; et al. (2011). "Evaluation, treatment and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline". Journal of Clinical Endocrinology and Metabolism. 96 (7): 1911–30. doi:10.1210/jc.2011-0385. PMID 21646368. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  106. ^ a b Dietary Reference Intakes for Calcium and Vitamin D Page 1 (Summary)
  107. ^ DRI, Dietary reference intakes: for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, D.C: National Academy Press. 1997. p. 250. ISBN 0-309-06350-7. Nutrition
  108. ^ Bowerman, Susan (2008-03-31). "If mushrooms see the light". Los Angeles Times. Retrieved 2010-03-25.
  109. ^ Koyyalamudi, SR; Jeong, SC; Song, CH; Cho, KY; Pang, G (2009). "Vitamin D2 formation and bioavailability from Agaricus bisporus button mushrooms treated with ultraviolet irradiation". J Agric Food Chem. 57 (8): 3351–5. doi:10.1021/jf803908q. PMID 19281276.
  110. ^ "USDA nutrient database – use the keyword 'portabella' and then click submit".
  111. ^ "Age-old children's disease back in force". Thestar.com. 2007-07-25. Retrieved 2010-08-24.
  112. ^ Elena Conis (2006-07-24). "Fortified foods took out rickets". Los Angeles Times. Retrieved 2010-08-24.
  113. ^ McClean, Franklin C.; Budy, Ann M. "Vitamin A, Vitamin D, Cartilage, Bones, and Teeth" in Harris, Robert S. (1963). Vitamins and Hormones, volume 21, pp. 51–52. London: Academic Press Partial view at Google Books.
  114. ^ "Unraveling The Enigma Of Vitamin D" United States National Academy of Sciences
  115. ^ "Adolf Windaus - Biography". Nobelprize.org. 2010-03-25. Retrieved 2010-03-25.
  116. ^ Hirsch AL. (2011). "Industrial aspects of vitamin D". In Feldman DJ, Pike JW, Adams JS. (eds.) (ed.). Vitamin D. London; Waltham, MA: Academic Press. p. 73. ISBN 9780123870353. {{cite book}}: |editor-last= has generic name (help)CS1 maint: multiple names: editors list (link)
  117. ^ Arvids A. Ziedonis; Mowery, David C.; Nelson, Richard R.; Bhaven N. Sampat (2004). Ivory tower and industrial innovation: university-industry technology transfer before and after the Bayh-Dole Act in the United States. Stanford, Calif: Stanford Business Books. pp. [1]. ISBN 0-8047-4920-5.{{cite book}}: CS1 maint: multiple names: authors list (link)
  118. ^ Marshall, James (2005). Elbridge A. Stuart Founder of the Carnation Company. Kessinger Publishing. p. 235. ISBN 978-1417988839.
  119. ^ a b Holick, Michael F. (2005-11). "The Vitamin D Epidemic and its Health Consequences" (PDF). Journal of Nutrition. 135 (11): 2739S–2748S. PMID 16251641. {{cite journal}}: Check date values in: |date= (help)
  120. ^ Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW (18 May 2004). "Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase". Proc Natl Acad Sci U S A. 101 (20): 7711–7715. Bibcode:2004PNAS..101.7711C. doi:10.1073/pnas.0402490101. PMC 419671. PMID 15128933.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  121. ^ Laing, CJ and Cooke, NE. Vitamin D Binding Protein. In: Vitamin D (Vol. 1) David Feldman, Francis H. Glorieaux, J. Wesley Pike (eds.). Elsevier Press. 2005. pp 117-134.

Further reading

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