Vitamin D deficiency

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. One nanogram per millilitre () is equivalent to 2.5 nanomoles per litre (). • Severe deficiency: < = < • Deficiency: < = < • Insufficient:  = • Normal: = Vitamin D levels falling within this normal range prevent clinical manifestations of vitamin D insufficiency as well as vitamin D toxicity. ==Signs and symptoms==

In most cases, vitamin D deficiency is almost asymptomatic. It may only be detected on blood tests but is the cause of some bone diseases and is associated with other conditions: The earliest sign of vitamin D deficiency is craniotabes, abnormal softening or thinning of the skull. • 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. • Osteoporosis, a condition characterized by reduced bone mineral density and increased bone fragility • Increased risk of fracture • Myopathy: Muscle aches, weakness, and twitching (fasciculations) due to reduced blood calcium (hypocalcemia); 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). • Periodontitis, local inflammatory bone loss that can result in tooth loss. • 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. Maternal vitamin D deficiency may affect the baby, causing overt bone disease from before birth and impairment of bone quality after birth. • Respiratory infections and COVID-19: Vitamin D deficiency may increase the risk of severe acute respiratory infections and COPD. Emerging studies have suggested a link between vitamin D deficiency and COVID-19 symptoms. 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. • Schizophrenia: Vitamin D deficiency is associated with the development of schizophrenia. People with schizophrenia generally have lower levels of vitamin D. 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. Vitamin D is essential for the normal development of the nervous system. == Risk factors ==

Those most likely to be affected by vitamin D deficiency are people with little exposure to sunlight. 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. 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. 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. 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. In sunny countries where rickets occurs among older toddlers and children, rickets has been attributed to low dietary calcium intakes. This is characteristic of cereal-based diets with limited access to dairy products. 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. 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. 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. The relationship between these conditions is not well understood. Different factors could contribute to this relationship, particularly diet, and sunlight exposure. 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. Vitamin D sufficiency of those in Australia and New Zealand is unlikely to have been affected by campaigns advocating sunscreen. 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. 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. 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. Darker skin color Because of melanin which enables natural sun protection, dark-skinned people are susceptible to vitamin D deficiency. 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. inflammatory bowel disease, exocrine pancreatic insufficiency from cystic fibrosis, and short bowel syndrome, Critical illness Vitamin D deficiency is associated with increased mortality in critical illness. 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. Vitamin D3 (cholecalciferol) or calcitriol given orally may reduce the mortality rate without significant adverse effects. The American Academy of Pediatrics recommends that all breastfed infants receive (IU) per day of oral vitamin D. == Pathophysiology ==

Decreased exposure of the skin to sunlight is a common cause of vitamin D deficiency. == Diagnosis ==

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. 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. Vitamin D toxicity usually results from taking supplements in excess. Hypercalcemia is often the cause of symptoms, 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. == 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. == Treatment ==

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. Sun tanning Light therapy Exposure to photons (light) at specific wavelengths of narrowband UVB enables the body to produce vitamin D to treat vitamin D deficiency. Supplement 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. 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 , and that babies living north of 55°N get from October to April. Treating vitamin D deficiency depends on the severity of the deficit. 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. 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, other evidence indicates that D2 and D3 are equal for maintaining 25(OH)D status. In another proposed cholecalciferol loading dose guideline for vitamin D-deficient adults, a weekly dosage is given, up to a total amount that is proportional to the required serum increase (up to the level of ) and within certain bodyweight limits, to body weight. According to new data and practices relevant to vitamin D levels in the general population in France, to establish optimal vitamin D status and frequency of intermittent supplement dosing, patients with or at high risk for osteoporosis and vitamin D deficiency should start supplementation with a loading phase consisting of weekly of vitamin D for eight weeks in patients with levels 37.5° latitude), obese patients, and those on certain medications. Patients with chronic liver disease or intestinal malabsorption disorders may also require larger doses of vitamin D (up to , or , daily). Co-supplementation with vitamin K The combination of vitamin D and vitamin K supplements has been shown in trials to improve bone quality. As high intake of vitamin D is a cause of raised calcium levels (hypercalcemia), the addition of vitamin K may be beneficial in helping to prevent vascular calcification, particularly in people with chronic kidney disease. == Epidemiology ==

The estimated percentage of the population with a vitamin D deficiency varies based on the threshold used to define a deficiency. Recommendations for 25(OH)D serum levels vary across authorities, and probably vary based on factors like age; calculations for the epidemiology of vitamin D deficiency depend on the recommended level used. A 2011 Institute of Medicine (IOM) report set the sufficiency level at (), while in the same year The Endocrine Society defined sufficient serum levels at and others have set the level as high as . Applying the IOM standard to NHANES data on serum levels, for the period from 1988 to 1994 22% of the US population was deficient, and 36% were deficient for the period between 2001 and 2004; applying the Endocrine Society standard, 55% of the US population was deficient between 1988 and 1994, and 77% were deficient for the period between 2001 and 2004. == History ==

The role of diet in the development of rickets was determined by Edward Mellanby between 1918 and 1920. In 1921, Elmer McCollum identified an antirachitic substance found in certain fats that could prevent rickets. Because the newly discovered substance was the fourth vitamin identified, it was called vitamin D. which were later observed clinically by Michael F. Holick and Raphael E. Cuomo. Before the fortification of milk products with vitamin D, rickets was a major public health problem. In the United States, milk has been fortified with 10 micrograms (400 IU) of vitamin D per quart since the 1930s, leading to a dramatic decline in the number of rickets cases. ==Research==

Some evidence suggests vitamin D deficiency may be associated with a worse outcome for some cancers, but evidence is insufficient to recommend that vitamin D be prescribed for people with cancer. Taking vitamin D supplements has no significant effect on cancer risk. Vitamin D3, however, appears to decrease the risk of death from cancer but concerns with the quality of the data exist. Nevertheless, studies suggest that Vitamin D deficiency is associated with increased risk of development melanoma. Low levels of 25-hydroxyvitamin D, a routinely used marker for vitamin D, have been suggested as a contributing factor in increasing the risk the development and progression of various types of cancer. Vitamin D requires activation by cytochrome P450 (CYP) enzymes to become active and bind to the VDR. Specifically, CYP27A1, CYP27B1, and CYP2R1 are involved in the activation of vitamin D, while CYP24A1 and CYP3A4 are responsible for the degradation of the active vitamin D. CYP24A1, the primary catabolic enzyme of calcitriol, is overexpressed in melanoma tissues and cells. This overexpression could lead to lower levels of active vitamin D in tissues, potentially promoting the development and progression of melanoma. Several drug classes and natural health products can modulate vitamin D-related CYP enzymes, potentially causing lower levels of vitamin D and its active metabolites in tissues, suggesting that maintaining adequate vitamin D levels, that is, avoiding vitamin D deficiency, either through dietary supplements or by modulating CYP metabolism, could be beneficial in decreasing the risk of melanoma development. Evidence suggests that vitamin D deficiency may be associated with impaired immune function. Those with vitamin D deficiency may have trouble fighting off certain types of infections. It has also been thought to correlate with cardiovascular disease, type 1 diabetes, type 2 diabetes, and some cancers. Vitamin D deficiency has also been found to possibly play a role in the development of certain Mental Health Conditions, such as OCD and Depression. == See also ==