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Initial phase

Treating vitamin D deficiency depends on the severity of the deficit.[63] Treatment involves an initial high-dosage treatment phase until the required serum levels are reached, followed by the maintenance of the acquired levels. The lower the 25(OH)D serum concentration is before treatment, the higher the dosage that is needed to quickly reach an acceptable serum level.[63]

The initial high-dosage treatment can be given on a daily or weekly basis or can be given in form of one or several single doses (also known as stoss therapy, from the German word Stoß, meaning "push").[64]

Therapy prescriptions vary, and there is no consensus yet on how best to arrive at an optimum serum level. While there is evidence that vitamin D3 raises 25(OH)D blood levels more effectively than vitamin D2,[65] other evidence indicates that D2 and D3 are equal for maintaining 25(OH)D status.[63]

Supplement

Vitamin D2 supplements
In the United States, the Food and Nutrition Board at the National Academies of Sciences, Engineering, and Medicine has established Recommended Dietary Allowances and Adequate Intakes for vitamin D. These values range from 15 to 20 mcg (600–800 IU) for adults and from 10 to 15 mcg (400–600 IU) for infants, children, and adolescents, depending on age.[61] The Canadian Paediatric Society recommends that pregnant or breastfeeding women consider taking 2000 IU/day, that all babies who are exclusively breastfed receive a supplement of 400 IU/d, and that babies living north of 55°N get 800 IU/d from October to April.[62]

Sun tanning
Further information: Sun tanning
Light therapy
Main article: Light therapy § Vitamin D deficiency
Exposure to photons (light) at specific wavelengths of narrowband UVB enables the body to produce vitamin D to treat vitamin D deficiency.[60]

Screening
The official recommendation from the United States Preventive Services Task Force is that for persons that do not fall within an at-risk population and are asymptomatic, there is not enough evidence to prove that there is any benefit in screening for vitamin D deficiency.[57]

Treatment

This article needs to be updated. Please help update this article to reflect recent events or newly available information. (January 2021)
UVB exposure
Vitamin D overdose is impossible from UV exposure: the skin reaches an equilibrium where the vitamin degrades as fast as it is created.[58][59]

Levels of 25(OH)D that are consistently above 200 nanograms per milliliter (ng/mL) (500 nanomoles per liter, nmol/L) are potentially toxic.[55] Vitamin D toxicity usually results from taking supplements in excess.[56] Hypercalcemia is often the cause of symptoms,[56] and levels of 25(OH)D above 150 ng/mL (375 nmol/L) are usually found, although in some cases 25(OH)D levels may appear to be normal. Periodic measurement of serum calcium in individuals receiving large doses of vitamin D is recommended.[4]

Diagnosis
See also: Reference ranges for blood tests § Vitamins
The serum concentration of calcifediol, also called 25-hydroxyvitamin D (abbreviated 25(OH)D), is typically used to determine vitamin D status. Most vitamin D is converted to 25(OH)D in the serum, giving an accurate picture of vitamin D status.[54] The level of serum 1,25(OH)D (calcitriol) is not usually used to determine vitamin D status because it often is regulated by other hormones in the body such as parathyroid hormone.[54] The levels of 1,25(OH)D can remain normal even when a person may be vitamin D deficient.[54] Serum level of 25(OH)D is the laboratory test ordered to indicate whether or not a person has vitamin D deficiency or insufficiency.[54] It is also considered reasonable to treat at-risk persons with vitamin D supplementation without checking the level of 25(OH)D in the serum, as vitamin D toxicity has only been rarely reported to occur.[54]

Intestinal conditions that result in malabsorption of nutrients may also contribute to vitamin D deficiency by decreasing the amount of vitamin D absorbed via diet.[1] In addition, a vitamin D deficiency may lead to decreased absorption of calcium by the intestines, resulting in increased production of osteoclasts that may break down a person's bone matrix.[53] In states of hypocalcemia, calcium will leave the bones and may give rise to secondary hyperparathyroidism, which is a response by the body to increase serum calcium levels.[53] The body does this by increasing the uptake of calcium by the kidneys and continuing to take calcium away from the bones.[53] If prolonged, this may lead to osteoporosis in adults and rickets in children.[53]

The liver is required to transform vitamin D into 25-hydroxyvitamin D. This is an inactive metabolite of vitamin D but is a necessary precursor (building block) to create the active form of vitamin D.[1]

The kidneys are responsible for converting 25-hydroxyvitamin D to 1,25-hydroxyvitamin D. This is the active form of vitamin D in the body. Kidney disease reduces 1,25-hydroxyvitamin D formation, leading to a deficiency of the effects of vitamin D.[1]

Pathophysiology
Decreased exposure of the skin to sunlight is a common cause of vitamin D deficiency.[1] People with a darker skin pigment with increased amounts of melanin may have decreased production of vitamin D.[3] Melanin absorbs ultraviolet B radiation from the sun and reduces vitamin D production.[3] Sunscreen can also reduce vitamin D production.[3] Medications may speed up the metabolism of vitamin D, causing a deficiency.[3]

Breastfeeding
Infants who exclusively breastfeed need a vitamin D supplement, especially if they have dark skin or have minimal sun exposure.[52] The American Academy of Pediatrics recommends that all breastfed infants receive 400 international units (IU) per day of oral vitamin D.[52]

Critical illness
Vitamin D deficiency is associated with increased mortality in critical illness.[50] People who take vitamin D supplements before being admitted for intensive care are less likely to die than those who do not take vitamin D supplements.[50] Additionally, vitamin D levels decline during stays in intensive care.[51] Vitamin D3 (cholecalciferol) or calcitriol given orally may reduce the mortality rate without significant adverse effects.[51]

Malabsorption
Rates of vitamin D deficiency are higher among people with untreated celiac disease,[47][48] inflammatory bowel disease, exocrine pancreatic insufficiency from cystic fibrosis, and short bowel syndrome,[48] which can all produce problems of malabsorption. Vitamin D deficiency is also more common after surgical procedures that reduce absorption from the intestine, including weight loss procedures.[49]

Darker skin color
Because of melanin which enables natural sun protection, dark-skinned people are susceptible to vitamin D deficiency.[6][46] Three to five times greater sun exposure is necessary for naturally darker skinned people to produce the same amount of vitamin D as those with light skin.[46]

Regions far from the equator have a high seasonal variation of the amount and intensity of sunlight. In the UK, the prevalence of low vitamin D status in children and adolescents is found to be higher in winter than in summer.[44] Lifestyle factors such as indoor versus outdoor work and time spent in outdoor recreation play an important role.

Additionally, vitamin D deficiency has been associated with urbanisation in terms of both air pollution, which blocks UV light, and an increase in the number of people working indoors. The elderly are generally exposed to less UV light due to hospitalisation, immobility, institutionalisation, and being housebound, leading to decreased levels of vitamin D.[45]

Sun exposure
The use of sunscreen with a sun protection factor of 8 can theoretically inhibit more than 95% of vitamin D production in the skin.[35] In practice, however, sunscreen is applied so as to have a negligible effect on vitamin D status.[41] Vitamin D sufficiency of those in Australia and New Zealand is unlikely to have been affected by campaigns advocating sunscreen.[42] Instead, wearing clothing is more effective at reducing the amount of skin exposed to UVB and reducing natural vitamin D synthesis. Clothing that covers a large portion of the skin, when worn on a consistent and regular basis, such as the burqa, is correlated with lower vitamin D levels and an increased prevalence of vitamin D deficiency.[43]

Obesity
There is an increased risk of vitamin D deficiency in people who are considered overweight or obese based on their body mass index (BMI) measurement.[39] The relationship between these conditions is not well understood. Different factors could contribute to this relationship, particularly diet, and sunlight exposure.[39] Alternatively, vitamin D is fat-soluble, so excess amounts can be stored in fat tissue and used during winter when sun exposure is limited.[40]

This is characteristic of cereal-based diets with limited access to dairy products.[33] Rickets was formerly a major public health problem among the US population; in Denver, almost two-thirds of 500 children had mild rickets in the late 1920s.[34] An increase in the proportion of animal protein in the 20th-century American diet coupled with increased consumption of milk fortified with relatively small quantities of vitamin D coincided with a dramatic decline in the number of rickets cases.[35][36][37] One study of children in a hospital in Uganda, however, showed no significant difference in vitamin D levels of malnourished children compared to non-malnourished children. Because both groups were at risk due to darker skin pigmentation, both groups had vitamin D deficiency. Nutritional status did not appear to play a role in this study.[38]

Malnutrition
Although rickets and osteomalacia are now rare in Britain, osteomalacia outbreaks in some immigrant communities included women with seemingly adequate daylight outdoor exposure wearing typical Western clothing.[30] 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.[31][32][33] In sunny countries where rickets occurs among older toddlers and children, rickets has been attributed to low dietary calcium intakes.

Age
Elderly people have a higher risk of having a vitamin D deficiency due to a combination of several risk factors, including decreased sunlight exposure, decreased intake of vitamin D in the diet, and decreased skin thickness, which leads to further decreased absorption of vitamin D from sunlight.[28]

Fat percentage
Since vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) are fat-soluble, humans and other animals with a skeleton need to store some fat. Without fat, the animal will have a hard time absorbing vitamin D2 and vitamin D3, and the lower the fat percentage, the greater the risk of vitamin deficiency, which is the case in some athletes who strive to get as lean as possible.[29]

Risk factors
Those most likely to be affected by vitamin D deficiency are people with little exposure to sunlight.[27] Certain climates, dress habits, the avoidance of sun exposure, and the use of too much sunscreen protection can all limit the production of vitamin D.[27]

Parkinson's disease: Many studies have confirmed the association between Parkinson's disease and low levels of vitamin D. Because vitamin D has neuroprotective functions, it is possible that vitamin D deficiency can cause Parkinson's disease, but firm conclusions remains uncertain.[26]

Schizophrenia: Vitamin D deficiency is associated with the development of schizophrenia.[5] People with schizophrenia generally have lower levels of vitamin D.[24] The environmental risk factors of seasonality of birth, latitude, and migration linked to schizophrenia all implicate vitamin D deficiency, as do other health conditions such as maternal obesity.[5][25] Vitamin D is essential for the normal development of the nervous system.[5][24] Maternal vitamin D deficiency can cause prenatal neurodevelopmental defects, which influence neurotransmission, altering brain rhythms and the metabolism of dopamine.[24] Vitamin D receptors, CYP27B1, and CYP24A1 are found in various regions of the brain, showing that vitamin D is a neuroactive, neurosteroid hormone essential for the development of the brain and normal function.[5] Inflammation as a causative factor in schizophrenia is normally suppressed by vitamin D.[24]

Respiratory infections and COVID-19: Vitamin D deficiency may increase the risk of severe acute respiratory infections and COPD.[19][20] Emerging studies have suggested a link between vitamin D deficiency and COVID-19 symptoms.[21][22] A review has shown that vitamin D deficiency is not associated with a higher chance of having COVID-19 but is associated with a greater severity of the disease, including 80% increases in the rates of hospitalization and mortality.[23]

Myopathy: Muscle aches, weakness, and twitching (fasciculations) due to reduced blood calcium (hypocalcemia);[3][14] impaired muscle glycogen metabolism (abnormal glycogen accumulation), atrophy of type II (fast-twitch/glycolytic) muscle fibres, and diminished calcium uptake by the sarcoplasmic reticulum (needed for muscle contraction).[15]
Periodontitis, local inflammatory bone loss that can result in tooth loss.[16]
Pre-eclampsia: There has been an association between vitamin D deficiency and women who develop pre-eclampsia in pregnancy. The exact relationship of these conditions is not well understood.[17] Maternal vitamin D deficiency may affect the baby, causing overt bone disease from before birth and impairment of bone quality after birth.[9][18]

Complications
Rickets, a childhood disease characterized by impeded growth and deformity of the long bones.[9] The earliest sign of vitamin D deficiency is craniotabes, abnormal softening or thinning of the skull.[10]
Osteomalacia, a bone-thinning disorder that occurs exclusively in adults and is characterized by proximal muscle weakness and bone fragility. Women with vitamin D deficiency who have been through multiple pregnancies are at elevated risk of osteomalacia.[11]
Osteoporosis, a condition characterized by reduced bone mineral density and increased bone fragility
Increased risk of fracture[12][13]

Signs and symptoms

Child with rickets
In most cases, vitamin D deficiency is almost asymptomatic.[8] It may only be detected on blood tests but is the cause of some bone diseases and is associated with other conditions:[1]

Classifications

Mapping of several bone diseases onto levels of vitamin D (calcidiol) in the blood[6]

Normal bone vs. osteoporosis
Vitamin D deficiency is typically diagnosed by measuring the concentration of the 25-hydroxyvitamin D in the blood, which is the most accurate measure of stores of vitamin D in the body.[1][7][2] One nanogram per millilitre (1 ng/mL) is equivalent to 2.5 nanomoles per litre (2.5 nmol/L).

Severe deficiency: <12 ng/mL = <30 nmol/L[2]
Deficiency: <20 ng/mL = <50 nmol/L
Insufficient: 20–29 ng/mL = 50–75 nmol/L
Normal: 30–50 ng/mL = 75–125 nmol/L
Vitamin D levels falling within this normal range prevent clinical manifestations of vitamin D insufficiency as well as vitamin D toxicity.[1][7][2]

Vitamin D can be synthesized in the skin under exposure to UVB from sunlight. Oily fish, such as salmon, herring, and mackerel, are also sources of vitamin D, as are mushrooms. Milk is often fortified with vitamin D; sometimes bread, juices, and other dairy products are fortified with vitamin D.[1] Many multivitamins contain vitamin D in different amounts.[1]

Deficiency impairs bone mineralization, leading to bone-softening diseases, such as rickets in children. It can also worsen osteomalacia and osteoporosis in adults, increasing the risk of bone fractures.[1][4] Muscle weakness is also a common symptom of vitamin D deficiency, further increasing the risk of falls and bone fractures in adults.[1] Vitamin D deficiency is associated with the development of SCHIZOPHRENIA.[5]

Vitamin D deficiency or hypovitaminosis D is a vitamin D level that is below normal. It most commonly occurs in people when they have inadequate exposure to sunlight, particularly sunlight with adequate ultraviolet B rays (UVB).[1][2][3] Vitamin D deficiency can also be caused by inadequate nutritional intake of vitamin D; disorders that limit vitamin D absorption; and disorders that impair the conversion of vitamin D to active metabolites, including certain liver, kidney, and hereditary disorders.[4]

Vitamin D deficiency

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From Wikipedia, the free encyclopedia

Kaler, S.G.; Liew, C.J.; Donsante, A.; Hicks, J.D.; Sato, S.; Greenfield, J.C. (2010). "Molecular correlates of epilepsy in early diagnosed and treated Menkes disease". Journal of Inherited Metabolic Disease. 33 (5): 583–9. doi:10.1007/s10545-010-9118-2. PMC 3113468. PMID 20652413.
Vest, Katherine E.; Hashemi, Hayaa F.; Cobine, Paul A. (2013). "The Copper Metallome in Eukaryotic Cells". In Banci, Lucia (ed.). Metallomics and the Cell. Metal Ions in Life Sciences. Vol. 12. Springer. pp. 451–78. doi:10.1007/978-94-007-5561-1_13. ISBN 978-94-007-5560-4. PMID 23595680. electronic-book ISBN 978-94-007-5561-1 ISSN 1559-0836 electronic-ISSN 1868-0402
Goodman, JC (December 2015). "Neurological Complications of Bariatric Surgery". Current Neurology and Neuroscience Reports. 15 (12) 79. doi:10.1007/s11910-015-0597-2. PMID 26493558. S2CID 21401030.

Spinazzi, M.; De Lazzari, F.; Tavolato, B.; Angelini, C.; Manara, R.; Armani, M. (2007). "Myelo-optico-neuropathy in copper deficiency occurring after partial gastrectomy. Do small bowel bacterial overgrowth syndrome and occult zinc ingestion tip the balance?". Journal of Neurology. 254 (8): 1012–7. doi:10.1007/s00415-006-0479-2. PMID 17415508. S2CID 28373986.
Hedera, P.; Peltier, A.; Fink, J.K.; Wilcock, S.; London, Z.; Brewer, G.J. (2009). "Myelopolyneuropathy and pancytopenia due to copper deficiency and high zinc levels of unknown origin II. The denture cream is a primary source of excessive zinc". Neurotoxicology. 30 (6): 996–9. Bibcode:2009NeuTx..30..996H. doi:10.1016/j.neuro.2009.08.008. PMID 19732792.
Dhawan, S.S.; Ryder, K.M.; Pritchard, E. (2008). "Massive penny ingestion: The loot with local and systemic effects". Journal of Emergency Medicine. 35 (1): 33–37. doi:10.1016/j.jemermed.2007.11.023. PMID 18180130.

Bolamperti, L.; Leone, M. A.; Stecco, A.; Reggiani, M.; Pirisi, M.; Carriero, A.; et al. (2009). "Myeloneuropathy due to copper deficiency: clinical and MRI findings after copper supplementation". Neurological Sciences. 30 (6): 521–4. doi:10.1007/s10072-009-0126-7. PMID 19768378. S2CID 21488713.
Pineles, S.L.; Wilson, C.A.; Balcer, L.J.; Slater, R.; Galetta, S.L. (2010). "Combined optic neuropathy and myelopathy secondary to copper deficiency". Survey of Ophthalmology. 55 (4): 386–392. doi:10.1016/j.survophthal.2010.02.002. PMID 20451943.
Jaiser, S.R.; Duddy, R. (2007). "Copper deficiency masquerading as subacute combined degeneration of the cord and myelodysplastic syndrome" (PDF). Advances in Clinical Neuroscience and Rehabilitation. 7 (3): 20–21. Archived from the original (PDF) on 2020-08-01. Retrieved 2010-11-29.

Schleper, B.; Stuerenburg, H.J. (2001). "Copper deficiency-associated myelopathy in a 46-year-old woman". Journal of Neurology. 248 (8): 705–6. doi:10.1007/s004150170118. PMID 11569901. S2CID 10318175.
Jaiser, S.R.; Winston, G.P. (2008). "Copper deficiency myelopathy and subacute combined degeneration of the cord: why is the phenotype so similar?". Journal of Neurology. 255 (2): 229–236. doi:10.1016/j.mehy.2008.03.027. PMID 18472229.
Ataxic gait demonstration. Online Medical Video Archived 2021-05-05 at the Wayback Machine

PMID 18024379. S2CID 12958829.

Klevay, L.M. (2006). ""Myelodysplasia," myeloneuropathy, and copper deficiency". Mayo Clinic Proceedings. 81 (1): 132. doi:10.4065/81.1.132. PMID 16438490.
Kumar, N. (2006). "Copper deficiency myelopathy (human swayback)". Mayo Clinic Proceedings. 81 (10): 1371–84. doi:10.4065/81.10.1371. PMID 17036563.
Fong, T.; Vij, R.; Vijayan, A.; DiPersio, J.; Blinder, M. (2007). "Copper deficiency: an important consideration in the differential diagnosis of myelodysplastic syndrome". Haematologica. 92 (10): 1429–30. doi:10.3324/haematol.11314.

Jaiser, S.R.; Winston, G.P. (2010). "Copper deficiency myelopathy". Journal of Neurology. 257 (6): 869–881. doi:10.1007/s00415-010-5511-x. PMC 3691478. PMID 20232210.
Kodama, H.; Fujisawa, C. (2009). "Copper metabolism and inherited copper transport disorders: molecular mechanisms, screening, and treatment". Metallomics. 1 (1): 42–52. doi:10.1039/B816011M.
"Copper Information: Benefits, Deficiencies, Food Sources". Archived from the original on 2020-11-09. Retrieved 2010-12-05.

References
Scheiber, Ivo; Dringen, Ralf; Mercer, Julian F. B. (2013). "Chapter 11. Copper: Effects of Deficiency and Overload". In Astrid Sigel, Helmut Sigel and Roland K. O. Sigel (ed.). Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences. Vol. 13. Springer. pp. 359–387. doi:10.1007/978-94-007-7500-8_11. ISBN 978-94-007-7499-5. PMID 24470097.
Halfdanarson, T.R.; Kumar, N.; Li, C.Y.; Phyliky, R.L.; Hogan, W.J. (2008). "Hematological manifestations of copper deficiency: a retrospective review". European Journal of Haematology. 80 (6): 523–531. doi:10.1111/j.1600-0609.2008.01050.x. PMID 18284630. S2CID 38534852.

See also
Copper in health
Copper deficiency and excess health conditions (non-genetic)

If zinc intoxication is present, discontinuation of zinc may be sufficient to restore copper levels to normal, but this usually is a very slow process.[7] People with zinc intoxication will usually have to take copper supplements in addition to ceasing zinc consumption. Hematological manifestations are often quickly restored to normal.[7] The progression of the neurological symptoms will be stopped and sometimes improved with appropriate treatment, but residual neurological disability is common.[20]

Treatment
Copper deficiency is a very rare disease and is often misdiagnosed several times by physicians before concluding the deficiency of copper through differential diagnosis (copper serum test and bone marrow biopsy are usually conclusive in diagnosing copper deficiency). On average, patients are diagnosed with copper deficiency around 1.1 years after their first symptoms are reported to a physician.[3] Copper deficiency can be treated with either oral copper supplementation or intravenous copper.[7]

Diagnosis
The diagnosis of copper deficiency may be supported by a person's report of compatible signs and symptoms, findings from a thorough physical examination, and supportive laboratory evidence. Low levels of copper and ceruloplasmin in the serum are consistent with the diagnosis as is a low 24-hour urine copper level.[20] Additional supportive bloodwork findings also include neutropenia and anemia.[20] MRI imaging may demonstrate increased T2 signal of the dorsal column–medial lemniscus pathways.[20]

Zinc intoxication
Zinc intoxication may cause anemia by blocking the absorption of copper from the stomach and duodenum.[3] Zinc also upregulates the expression of chelator metallothionein in enterocytes, which are the majority of cells in the intestinal epithelium.[3] Since copper has a higher affinity for metallothionein than zinc, the copper will remain bound inside the enterocyte, which will be later eliminated through the lumen.[3] This mechanism is exploited therapeutically to achieve negative balance in Wilson's disease, which involves an excess of copper.[3] But in copper-deficient individuals, zinc excess may cause this mechanism to further deplete copper levels.

Another speculation for the cause of anaemia involves the mitochondrial enzyme cytochrome c oxidase (complex IV in the electron transport chain). Studies have shown that animal models with impaired cytochrome c oxidase failed to synthesize heme from ferric iron at the normal rate.[6] The lower rate of the enzyme might also cause the excess iron to clump, giving the haeme an unusual pattern.[6] This unusual pattern is also known as ringed sideroblastic anemia cells.

Cell growth halt
The cause of neutropenia is still unclear; however, the arrest of maturing myelocytes, or neutrophil precursors, may cause the neutrophil deficiency.[2][6]

Iron transportation
The anemia caused by copper deficiency is thought to be caused by impaired iron transport. Hephaestin is a copper-containing ferroxidase enzyme located in the duodenal mucosa that oxidizes iron and facilitates its transfer across the basolateral membrane into circulation.[6] Another iron transporting enzyme is ceruloplasmin.[6] This enzyme is required to mobilize iron from the reticuloendothelial cell to plasma.[6] Ceruloplasmin also oxidizes iron from its ferrous state to the ferric form required for iron binding.[4] Impairment in these copper-dependent enzymes that transport iron may cause secondary iron deficiency anemia.[6]

Hematological cause