Vitamin D deficiency
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] 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 fall and bone fractures in adults.[1] Vitamin D deficiency is associated with the development of schizophrenia.[5]
Vitamin D deficiency
Hypovitaminosis D
Usually asymptomatic
Rickets, osteomalacia, other associated disorders
Age, people with dark skin, obesity, malabsorption, bariatric surgery, breastfed infants[1]
Measuring the concentration of calcifediol in the blood
Sufficient sunlight exposure, dietary intake
Supplements
Severe deficiency (<30 nmol/L): Europe 13%, US 5.9%, Canada 7.4%. Deficiency (<50 nmol/L): Europe 40%, US 24%, Canada 37%[2]
Vitamin D can be synthesized in the skin under the exposure of 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]
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).
Vitamin D levels falling within this normal range prevent clinical manifestations of vitamin D insufficiency as well as vitamin D toxicity.[1][7][2]
Pathophysiology[edit]
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]
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]
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.[52] 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.[52] The body does this by increasing uptake of calcium by the kidneys and continuing to take calcium away from the bones.[52] If prolonged, this may lead to osteoporosis in adults and rickets in children.[52]
Screening[edit]
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.[56]
Bioavailability[edit]
Not all D3 deficiencies can be effectively supplemented or treated with vitamin D3 on its own. Older people or those who have fatty liver or metabolic syndrome have a reduced ability to absorb vitamin D3.[82] In addition, in overweight or obese persons, excessive adipose tissue can sequester D3 from the circulation and reduce its access to other tissues.[82] With age or in obesity, metabolic activation of D3 may be reduced by liver steatosis or by microbiome imbalance.[82][83] Since Vitamin D is fat-soluble, it's advised to be taken with a meal high in fat since it significantly increase its uptake in healthy individuals.[84]
For vitamin D3 to perform its hormonal roles, it is converted into its biologically active metabolite, calcifediol, also known as 25-hydroxyvitamin D3, an activation occurring by a hydroxylation reaction in the liver via the cytochrome P450 system, and in the gut microbiome.[85]
History[edit]
The role of diet in the development of rickets was determined by Edward Mellanby between 1918 and 1920.[92] 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.[92] The 1928 Nobel Prize in Chemistry was awarded to Adolf Windaus, who discovered the steroid 7-dehydrocholesterol, the precursor of vitamin D.
Prior to 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.[34]
Research[edit]
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.[93] Taking vitamin D supplements has no significant effect on cancer risk.[94] Vitamin D3, however, appears to decrease the risk of death from cancer but concerns with the quality of the data exist.[95] Nevertheless, studies suggest that Vitamin D deficiency is associated with increased risk of development melanoma.[96] 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.[96]
Vitamin D deficiency is thought to play a role in the pathogenesis of non-alcoholic fatty liver disease.[97][98]
Evidence suggests that vitamin D deficiency may be associated with impaired immune function.[99][100] 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.[7]
Review studies have also seen associations between vitamin D deficiency and pre-eclampsia.[101]