Vitamin D is a fat-soluble condensed group responsible for increasing the absorption of calcium, magnesium, and intestinal phosphate, and several other biological effects. In humans, the most important compounds in this group are vitamin D 3 (also known as cholecalciferol) and vitamin D 2 (ergocalciferol). Cholecalciferol and ergocalciferol can be ingested from diet and from supplements. Only some foods contain vitamin D. The main natural source of vitamins is the synthesis of cholecalciferol in the skin from cholesterol through chemical reactions that depend on sun exposure (especially UVB radiation). Dietary recommendations usually assume that all of a person's vitamin D is taken, as sun exposure in the population varies and recommendations about the amount of safe exposure to sunlight are uncertain in view of the risk of skin cancer.
Vitamin D from diet or skin synthesis is biologically inactive; enzymatic (hydroxylation) conversion in the liver and kidney is required for activation. Because vitamin D can be synthesized in sufficient quantities by most mammals exposed to enough sunlight, it is not an important food factor, and therefore is not technically a vitamin. Instead it can be thought of as a hormone, with the activation of pro-hormone vitamin D that produces the active form, calcitriol, which then produces the effect through nuclear receptors in different locations. Cholecalciferol converted in the liver into calcifediol (25-hydroxycholecalciferol); ergocalciferol is converted to 25-hydroxyergocalciferol. Both of these vitamin D metabolites (called 25-hydroxyvitamin D or 25 (OH) D) were measured in serum to determine the vitamin D status of a person. Calcifediol is further dihydroxylated by the kidney to form calcitriol (also known as 1,25-dihydroxececalciferol), the biologically active form of vitamin D. Calcitriol circulates as a hormone in the blood, has a major role governing the concentration of calcium and phosphate, and promotes bone growth and remodeling that is healthy. Calcitriol also has other effects, including some on cell growth, neuromuscular and immune functions, and reduction of inflammation.
Vitamin D has an important role in calcium and metabolic homeostasis. His discovery was due to efforts to find less dietary substances in children with rickets (osteomalacia childhood forms). Vitamin D supplements are given to treat or prevent osteomalacia and rickets, but evidence for other health effects of vitamin D supplements in the general population is inconsistent. The effect of vitamin D supplementation on mortality was unclear, with one meta-analysis finding a small decrease in mortality in elderly people, and other conclusions there was no clear justification for recommending supplementation to prevent many diseases, and that further research of similar designs was not required in this area.
Video Vitamin D
Type
Some forms (vitamers) of vitamin D exist. The two main forms are vitamin D 2 or ergocalciferol, and vitamin D 3 or cholecalciferol; Vitamin D without subscript refers to D 2 or D 3 or both. These are known collectively as calciferol. Vitamin D 2 was chemically marked in 1931. In 1935, the chemical structure of vitamin D 3 was established and proved to be the result of 7-dehydrocholesterol ultraviolet irradiation.
Chemically, various forms of vitamin D are secosteroids, ie, steroids where one of the bonds in the steroid ring is damaged. The structural difference between vitamin D 2 and vitamin D 3 is the side chain D 2 contains a double bond between carbon 22 and 23, 24.
Maps Vitamin D
Biology
The active vitamin D metabolite of calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is primarily located in the nucleus of the target cell. The binding of calcitriol to VDR allows VDR to act as a transcription factor that modulates the expression of transport protein gene (such as TRPV6 and calbindin), which is involved in calcium absorption in the intestine. Vitamin D receptors are included in the steroid/thyroid hormone receptor superfamily receptors, and VDR is expressed by cells in most organs, including the brain, heart, skin, gonad, prostate, and breast.
VDR activation in gland, bone, kidney, and parathyroid cells leads to the maintenance of calcium and phosphorus levels in the blood (with the help of parathyroid hormone and calcitonin) and for the maintenance of bone content.
One of the most important roles of vitamin D is maintaining skeletal calcium balance by increasing calcium absorption in the intestine, promoting bone resorption by increasing the number of osteoclasts, maintaining calcium and phosphate levels for bone formation, and enabling proper functioning of parathyroid hormone to maintain serum. calcium levels. Vitamin D deficiency can result in lower bone mineral density and increased risk of reduced bone density (osteoporosis) or fractures due to vitamin D deficiency alters mineral metabolism in the body. Thus, vitamin D is also important for bone remodeling through its role as a potential stimulator of bone resorption.
VDR can be involved in cell proliferation and differentiation. Vitamin D also affects the immune system, and VDR is expressed in some white blood cells, including monocytes and activated T and B cells. In vitro, vitamin D increases the expression of tyrosine hydroxylase gene in adrenal medulla cells, and affects the synthesis of neurotrophic factors, nitric oxide synthase, and glutathione.
Disadvantages
Dietary vitamin D deficiency in conjunction with inadequate sun exposure causes osteomalacia (or rickets when it occurs in children), which is a bone softening. In developed countries, this is a rare disease. However, vitamin D deficiency has become a world problem in older people and remains common in children and adults. Low blood calcifediol (25-hydroxy-vitamin D) can result from avoiding the sun. Lacking causes damage to bone mineralization and bone damage that causes bone disease, including rickets and osteomalacia.
Being deficient in vitamin D can cause absorption of calcium in the intestine to 15%. When not inferior, an individual usually absorbs between 60-80%.
Rickets
Raft, a childhood illness, is characterized by stunted growth and soft, weak, long bone defects that bend and bend under their weight when the children start walking. This condition is characterized by swollen feet, which can be caused by a lack of calcium or phosphorus, as well as a lack of vitamin D; today, mostly found in low-income countries in Africa, Asia, or the Middle East and in those with genetic disorders such as D deficiency pseudovitamin rackets.
Vitamin D deficiency in the mother can cause a real bone disease since before birth and decrease bone quality after birth. Nutritional rickets exist in countries with intense year-round sunshine such as Nigeria and can occur without vitamin D deficiency.
Although rickets and osteomalacia are now scarce in the UK, outbreaks have occurred in some immigrant communities where osteomalacia patients include women with adequate daytime exposure in Western attire. Having darker skin and reducing exposure to sunlight does not produce rheumatic unless the diet deviates from a Western omnivorous pattern characterized by a high intake of meat, fish, and eggs, and a low intake of high-extraction cereals. Food risk factors for rickets include abstinence from animal foods.
Vitamin D deficiency remains a major cause of rickets among young infants in most countries, as low vitamin D milk and social habits and climatic conditions can prevent exposure to sufficient sunlight. In bright countries such as Nigeria, South Africa, and Bangladesh, where rickets occur between toddlers and older children, it has been linked to low dietary calcium intake, which is characteristic of a cereal-based diet with limited access to the product milk.
Ricket was once a major public health problem among US residents; in Denver, where ultraviolet light is about 20% stronger than at sea level at the same latitude, nearly two-thirds of 500 children have mild rickets in the late 1920s. An increase in the proportion of animal protein in American food in the 20th century coupled with an increase in milk consumption enriched with relatively small amounts of vitamin D coincided with a dramatic decline in the number of rickets. Also, in the United States and Canada, vitamin D fortified milk, baby vitamin supplements, and vitamin supplements have helped to eradicate the majority of cases of rickets for children with fat malabsorption conditions.
Osteomalacia
Osteomalacia is an adult disease resulting from vitamin D deficiency. Characteristics of this disease are softening of the bones, causing bending of the spine, bending in the legs, proximal muscle weakness, bone fragility, and increased risk of fractures. Osteomalacia reduces calcium absorption and increases calcium-bone loss, which increases the risk of fractures. Osteomalacia is usually present when the level of 25-hydroxyvitamin D is less than about 10 ng/mL. Although the effects of osteomalacia are thought to contribute to chronic musculoskeletal pain, there is no persuasive evidence of lower vitamin D levels in patients with chronic pain or supplementation that relieve non-specific musculoskeletal pain.
Skin pigmentation
Dark-skinned people living in temperate climates have been shown to have low vitamin D levels but this significance is uncertain. Dark-skinned people may be less efficient at making vitamin D because melanin in the skin inhibits vitamin D synthesis.
Use of supplements
The effect of vitamin D supplementation on health is uncertain. Overview 2013 found no effect of supplementation on disease level, other than a temporary decrease in mortality in the elderly. Vitamin D supplements do not change outcomes for myocardial infarction, stroke or cerebrovascular disease, cancer, fractures or knee osteoarthritis. Low vitamin D levels can occur due to illness rather than causing illness.
A report from the Institute of Medicine in the United States states: "Outcomes related to cancer, cardiovascular disease and hypertension, and diabetes and metabolic syndrome, fall and physical performance, immune function and autoimmune disorders, infections, neuropsychological function, and preeclampsia can not be attributed to intake calcium or vitamin D and often contradictory. "Some researchers claim that IOM is too definitive in its recommendations and make a math error when calculating levels of vitamin D in the blood associated with bone health. Members of the IOM panel argue that they use "standard procedures for diet recommendations" and that the reports are solidly based on data. Research on vitamin D supplements, including large-scale clinical trials, continues.
Mortality, all causes
Vitamin D supplements 3 have been found tentatively to reduce the risk of death in the elderly, but the effect has not been considered sufficient or sufficient to make the recommended supplement. Other forms (Vitamin D 2 , alfacalcidol, and calcitriol) appear to have no beneficial effects with respect to the risk of death. High blood levels seem to be associated with a lower risk of death, but it is not clear whether supplementation can produce these benefits. Both excess and vitamin D deficiency seem to cause abnormal function and premature aging. The association between serum calcifediol and all-cause mortality was parabola. The dangers of vitamin D appear to occur at lower vitamin D levels in the black population than in the white population.
Bone health
In general, there is no evidence to support the general belief that vitamin D supplements can help prevent osteoporosis. Their general use for the prevention of this disease in those with vitamin D deficiency is unlikely to be necessary. For elderly people with osteoporosis, taking vitamin D with calcium may help prevent hip fractures, but also slightly increase the risk of stomach and kidney problems. Supplementation with higher doses of vitamin D, in those older than 65, may reduce the risk of fractures. The effect is small or absent for people who live independently. Low serum vitamin D levels have been associated with falls, and low bone mineral density. However, taking extra vitamin D does not seem to change the risks. Athletes with vitamin D deficiency are at increased risk of stress fractures and/or major breaks, especially those involved in contact sports. The greatest benefit with supplementation is seen in a deficient athlete (25 (OH) D serum & lt; 30 ng/ml), or very deficient (25 (OH) D serum & lt; 25 ng/ml). The gradual decrease in risk was observed with increased serum 25 (OH) D concentrations at 50 ng/ml without additional benefit seen at levels beyond this point.
Given the mounting evidence for the benefits to bone health, despite not finding good evidence about other benefits, the US Food and Drug Administration has required manufacturers to declare the amount of vitamin D on the nutritional facts label, as "public health nutrition". significance ", since May 2016. With the extension of the proposed deadline, small producers with less than $ 10 million in annual food sales must comply with 1 Jan 2021, while larger ones must comply with 1 Jan 2020.
Cancer
Vitamin D supplements have been widely marketed for the anticancer properties claimed. The association has been shown in observational studies between low vitamin D levels and the risk of developing certain cancers including colon cancer. It is unclear, if taking extra vitamin D in the diet or as a supplement affects the risk of cancer. Reviews have described the evidence as "inconsistent, inconclusive for causality, and insufficient to inform nutritional requirements" and "not strong enough to draw conclusions". One review of 2014 found that supplements did not have a significant effect on cancer risk. Another 2014 review concluded that vitamin D 3 could reduce the risk of dying from cancer (one less death in 150 treated people over 5 years), but concerns about data quality were noted. Evidence is not sufficient to recommend vitamin D supplements for people with cancer, although some evidence suggests that low vitamin D may be associated with poor outcomes for some cancers, and that higher levels of vitamin D 25-hydroxy at the time of diagnosis are associated with more good. results.
Cardiovascular Disease
Taking vitamin D supplements does not mean reducing the risk of stroke, cerebrovascular disease, cardinal infarction, or ischemic heart disease. Supplementation has no effect on blood pressure.
Immune system
Infectious diseases
In general, vitamin D serves to activate the innate and reduce the adaptive immune system. Deficiency is associated with an increased risk or severity of viral infections, including HIV. Low levels of vitamin D appear to be a risk factor for tuberculosis, and historically used as a treatment. Supplementation slightly lowers the risk of respiratory infections and asthma exacerbations. Evidence is less on whether it occurs in children under the age of five. No clinical trials were conducted to assess its effect on the prevention of other infections, such as malaria.
Autoimmune Disease
Although the data while linking low levels of vitamin D with asthma, evidence to support beneficial effects in asthmatics from supplementation can not be concluded. Thus, supplementation is currently not recommended for the treatment or prevention of asthma. Vitamin D and multiple sclerosis events have been linked, but it is unclear what the nature of any causal relationship might be. There is no evidence that vitamin D supplementation is beneficial for treating people with multiple sclerosis.
Inflammatory bowel disease
Low vitamin D levels associated with the two major forms of human intestinal inflammation disease (IBD): Crohn's disease and ulcerative colitis. However, further research is needed to determine the significance and potential role of vitamin D axis in IBD.
Other conditions
Diabetes - A systematic review of 2014 concluded that the available studies did not show evidence of vitamin D3 supplementation that had an effect on glucose homeostasis or diabetes prevention. A 2016 review article reported that while there is growing evidence that vitamin D deficiency may be a risk factor for diabetes, evidence of vitamin D levels and diabetes mellitus is contradictory, requiring further investigation.
Depression - Clinical trials of vitamin D supplementation for depressive symptoms are generally of low quality and do not show overall effect, although subgroup analysis suggests supplementation for participants with clinically significant depression or depressive disorder has moderate effects..
Cognition and dementia - A systematic review of clinical studies found an association between low vitamin D levels with cognitive impairment and a higher risk of developing Alzheimer's disease. However, lower vitamin D concentrations are also associated with poor nutrition and spend less time outdoors. Therefore, an alternative explanation for an increase in cognitive impairment exists and hence a direct causal relationship between vitamin D levels and cognition can not be determined.
Pregnancy - Low vitamin D levels in pregnancy are associated with gestational diabetes, pre-eclampsia, and small infants (for gestational age). Although taking vitamin D supplements during pregnancy increases vitamin D levels in the mother's blood, too many benefits for the mother or baby are unclear. Pregnant women who take adequate amounts of vitamin D during pregnancy may be at risk for pre-eclampsia and a lower positive immune effect. A review of 2018 found that supplements can reduce the risk of infants too small and their growth rates are poor. Pregnant women often do not take the recommended amount of vitamin D.
Weight - Although hypothesized that vitamin D supplementation may be an effective treatment for obesity other than caloric restriction, a systematic review found no association of supplementation with weight or fat mass. A 2016 meta-analysis found that circulating vitamin D status was enhanced by weight loss, suggesting that fat mass may be inversely related to levels of vitamin D in the blood.
Permitted health claims
Government regulatory agencies are assigned to certain food and food supplement food security industries that are permitted as statements on the packaging.
European Food Safety Authority
- normal function of the immune system
- normal inflammatory response
- normal muscle function
- reduces the risk of falling in people over the age of 60
US Food and Drug Administration
- "Enough calcium and vitamin D, as part of a balanced diet, along with physical activity, can reduce the risk of osteoporosis."
Health Canada
- Simply calcium and regular exercise can help to achieve strong bones in children and adolescents and can reduce the risk of osteoporosis in older adults. Adequate vitamin D intake is also required
Another possible agency with a claim guide: Japan FOSHU and Australia-New Zealand.
Food intake
Suggested levels
Conversion: 1 Âμg = 40 IU.
Various agencies have proposed different recommendations for the amount of daily intake of vitamin D. It varies according to the exact definition, age, pregnancy or breast-feeding, and assumptions so far made about vitamin D skin synthesis.
United States
The food reference intake for vitamin D released in 2010 by the Institute of Medicine (IOM) for North America replaces previous recommendations that provide adequate intake values. Recommendations are formed with the assumption that individuals do not have vitamin D skin synthesis due to inadequate exposure to sunlight. The reference intake for vitamin D refers to the total intake of foods, beverages and supplements, and assumes that calcium requirements are met.
The tolerable upper intake (UL) level is defined as "the highest average daily intake of a nutrient that tends not to pose a risk of adverse health effects for almost everyone in the general population." Although a reliable upper level of intake is believed to be safe, information on long-term effects is incomplete and this level of intake is not recommended.
For purposes of labeling US food and dietary supplements, the amount in one presentation is expressed as a percent of Daily Value (% DV). For vitamin D labeling purposes, 100% of Daily Value is 400 IU (10 G), but on May 27, 2016 it was revised to 800 IU (20 Âμg) to make it agree with the RDA. The deadline for compliance is extended by the FDA until January 1, 2020 for large companies and 1 January 2021 for small companies.
Canada
Health Canada issues recommended diet allowance (RDA) recommendations and a tolerable upper intake level for vitamin D by 2012 based on the Institute of Medicine report.
Australia and New Zealand
Australia and New Zealand published nutritional reference values ​​including guidelines for dietary vitamin D intake in 2005. About one-third of Australians suffer from vitamin D deficiency.
European Union
The European Food Safety Authority (EFSA) in 2016 reviewed current evidence, finding the relationship between serum 25 (OH) D concentrations and musculoskeletal health outcomes widely varied. They assume that the average need and value of the population reference intake for vitamin D can not be decreased, and that the concentration of 25 (OH) D serum 50 nmol/L is the appropriate target value. For all people over the age of 1, including women who are pregnant or breastfeeding, they set a sufficient intake of 15 g/day (600 IU).
EFSA review the safe level of intake in 2012, setting a tolerable upper limit for adults at 100? G/day (4000 IU), the same conclusion as IOM.
The UK National Health Service recommends infants and young children aged six months to five years, pregnant or lactating women, and sun-deficient parents should take vitamin supplements daily to ensure adequate vitamin D intake. In July 2016, Public Health England recommended that everyone consider taking daily supplements containing 10 Âμg vitamin D during autumn and winter due to inadequate sunlight for vitamin D synthesis.
Non-governmental organizations in Europe have made their own recommendations. The German Society for Nutrition recommends 20 Ã,Âμg. The European Menopause and Andropause Society recommends that postmenopausal women take 15Ã,Âμg (600 IU) to 70, and 20 Âμg (800 IU) from age 71. This dose should be increased to 100 Âμg (4,000 IU) in some patients with vitamin D very low. status or in the case of co-morbid conditions.
Source
Although vitamin D is not present naturally in most foods, it is usually added as fortification in the food it produces. In some countries, staple foods are artificially enriched with vitamin D.
Natural resources
In general, vitamin D 2 is found in fungi and vitamin D 3 is found in animals. Vitamin D 2 is produced by ultraviolet ergosterol irradiation found in many fungi. The contents of vitamin D 2 in mushrooms and Cladina arbuscula , lichens, increases with exposure to ultraviolet light. This process is replicated by industrial ultraviolet light, concentration of vitamin D 2 level to a higher level.
The US Department of Agriculture reports content D 2 and D 3 are combined in a single value.
- Mushroom sources
- C. arbuscula (lichen), thalli, dry: vitamin D 3 0.67 to 2.04? g/g (27 to 82 IU/g); vitamin D 2 0.22-0.55Ã, g/g (8.8 to 22 IU/g).
- Agaricus bisporus (ordinary mushrooms), D 2 D 3 , per 100 grams (3.5 oz):
- raw portobello: 0.3Ã, g (10 IU); exposed to ultraviolet light: 11.2 Âμg (446 IU)
- raw crimini: 0.1Ã,? g (3 IU); exposed to ultraviolet light: 31.9 Âμg (1276 IU)
- Animal sources
- Fish liver oil, such as cod liver oil, 450 IU per teaspoon (4.5 g); (100 IU/g)
- Species of fatty fish, such as:
- Salmon, pink, ripe, dry heat, 100 grams (3.5 oz): 522 IU (5.2 IU/g)
- Mackerel, Pacific and jack, mixed species, cooked, dry heat, 100 grams (3.5 oz): 457 IU (4.6 IU/g)
- Tuna, canned in oil, 100 grams (3.5 oz): 269 IU (2.7 IU/g)
- Sardines, canned in oil, dried, 100 grams (3.5 oz): 193 IU (1.9 IU/g)
- Cooked egg yolks: 44 IU for 61 g eggs (0.7 IU/g)
- Beef liver, cooked, boiled, 100 grams (3.5 oz): 49 IU (0.5 IU/g)
Food fortification
The foods produced are enriched with Vitamin D including some fruit juices and fruit juice drinks, food replacement energy bars, soy protein based beverages, cheese and certain cheese products, flour products, baby formula, plenty of breakfast cereals and milk.
In 2016 in the United States, the Food and Drug Administration (FDA) changed the dietary supplement rules for milk fortification, stating that vitamin D 3 levels did not exceed 42 IU of vitamin D per 100 g (400 IU per US). quart) dairy milk, 84 IU of vitamin D 2 per 100 g (800 IU per liter) of plant milk, and 89 IU per 100 g (800 IU per liter) in plant-based yogurt. Plant milk is defined as a drink made from soy, almond, rice, among other plant sources intended as an alternative to milk milk.
While some studies have found that vitamin D 3 increases 25 (OH) D levels of blood faster and remains active in the body longer, others argue that vitamin D 2 equally available biologically. and effective as D 3 to increase and maintain 25 (OH) D.
Food preparation
The content of vitamin D in typical foods varies considerably with cooking. Boiled, fried, and baked foods have 69-89% of the original vitamin D.
Recommended serum levels
Recommendations at recommended serum 25 (OH) D levels vary across authority, and vary according to factors such as age. US laboratories generally report levels of 25 (OH) D in ng/ml. Other countries often use nmol/L. One ng/ml is roughly equal to 2.5 nmol/L.
A review of 2014 concluded that the most favorable serum levels for 25 (OH) D for all outcomes appear to be close to 30 ng/ml (75 nmol/L). Optimal levels of vitamin D are controversial and other reviews conclude that between 30 to 40 ng/ml (75 to 100 nmol/L) is recommended for athletes. Part of the controversy is that many studies have found differences in serum 25 (OH) D levels between ethnic groups; Studies show the genetic and environmental reasons behind this variation. Supplementation to achieve this level of standard can lead to dangerous calcification of blood vessels.
A 2012 meta-analysis showed that the risk of cardiovascular disease increased when blood vitamin D levels were lowest in the range of 8 to 24 ng/ml (20 to 60 nmol/L), although the results among the analyzed studies were inconsistent.
In 2011, the IOM Committee concluded that serum 25 (OH) D level of 20 ng/ml (50 nmol/L) was required for bone and overall health. The dietary reference intake for vitamin D is selected by the safety margin and 'overshoot' targeted serum values ​​to ensure a certain intake level reaches the desired level of serum 25 (OH) D in almost everyone. No contribution to serum 25 (OH) D levels was assumed from sun exposure and the recommendation is fully applicable to people with dark skin or negligible exposure to sunlight. The Institute found serum 25 (OH) D concentrations above 30 ng/ml (75 nmol/L) "were not consistently associated with increased benefits". Serum 25 (OH) D levels above 50 ng/ml (125 nmol/L) may be of concern. However, some people with serum 25 (OH) D between 30 and 50 ng/ml (75 nmol/L-125 nmol/L) will also have inadequate vitamin D.
Excess
Vitamin D toxicity is rare. This is due to supplementation with high doses of vitamin D than sunlight. Threshold for vitamin D toxicity has not been established; However, according to some studies, the tolerable upper intake rate (UL) is 4,000 IU/day for ages 9-71 (100 Âμg/day), while other studies conclude that, in healthy adults, a sustained intake of more than 1250 μg/day./day (50,000 IU) can produce clear toxicity after several months and can increase serum 25-hydroxyvitamin D levels up to 150 ng/ml and greater. Those with certain medical conditions, such as primary hyperparathyroidism, are much more sensitive to vitamin D and develop hypercalcaemia in response to increased vitamin D supplements, while maternal hypercalcemia during pregnancy may increase the fetal sensitivity to vitamin D effects and cause syndrome. mental retardation and facial deformity.
A review published in 2015 notes that side effects have been reported only at serum 25 (OH) D concentrations above 200 nmol/L.
Publish cases of toxicity involving hypercalcemia in which vitamin D dosage and 25-hydroxy-vitamin D levels are known to all involve> 40,000 IU (1,000 Âμg) of intake per day.
Pregnant or breastfeeding women should consult a physician before taking vitamin D supplements. The FDA advises that vitamin D supplements of liquid droppers accompanying these products should be clearly and accurately marked for 400 international units (1 IU is the biological equivalent of 25 ng ng cholecalciferol/ergocalciferol). In addition, for products intended for infants, the FDA recommends pipette retaining no more than 400 IU. For infants (born to 12 months), tolerable upper limits (maximum tolerable amounts without harm) are set at 25 Âμg/day (1,000 IU). A thousand micrograms per day in infants has produced toxicity in one month. After being commissioned by the Canadian and American governments, the Institute of Medicine (IOM) as of November 30, 2010, has increased the tolerable upper limit to 2,500 IU per day for 1-3 years, 3,000 IU per day for ages 4-8 year and 4,000 IU per day for 9-71 years of age (including pregnant or lactating women).
Calcitriol itself is automatically regulated in negative feedback cycles, and is also affected by parathyroid hormone, fibroblast growth factor 23, cytokines, calcium, and phosphates.
Excess effect
Vitamin D overdose causes hypercalcaemia, which is a strong indication of vitamin D toxicity - this may be noted with increased urination and thirst. If hypercalcemia is not treated, it results in excess calcium in soft tissues and organs such as the kidneys, liver, and heart, resulting in pain and organ damage.
The main symptoms of vitamin D overdose are hypercalcaemia including anorexia, nausea, and vomiting. This can be followed by polyuria, polydipsia, weakness, insomnia, anxiety, pruritus and ultimately kidney failure. Furthermore, proteinuria, urinary casts, azotemia, and metastatic calcification (especially in the kidneys) may develop. Other symptoms of vitamin D toxicity include mental retardation in young children, abnormal growth and bone formation, diarrhea, irritability, weight loss, and major depression.
Vitamin D toxicity is treated by stopping vitamin D supplementation and limiting calcium intake. Kidney damage may be irreversible. Exposure to sunlight for long periods of time usually does not cause vitamin D toxicity. The concentration of vitamin D precursors produced in the skin reaches equilibrium, and any vitamin D produced is subsequently degraded.
Biosynthesis
The synthesis of vitamin D in nature depends on the presence of UV radiation and subsequent activation in the liver and in the kidney. Many animals synthesize vitamin D 3 from 7-dehydrocholesterol, and many mushrooms synthesize vitamin D 2 from ergosterol.
Interactive path
Click the icon in the lower right corner to open it. Click on the genes, proteins and metabolites below to link to each article.
Photochemistry
The transformation that converts 7-dehydrocholesterol to vitamin D 3 occurs in two steps. First, 7-dehydrocholesterol is photolyzed by ultraviolet light in the electrotiklik reaction of the 6-electron conrotatory electro-ring; the product is previtaminÃ, D 3 . Second, previtaminÃ, D 3 spontaneously binds to vitamin D 3 (cholecalciferol) in a sigmatropic (1,7) interfacial shifting hydride. At room temperature, the transformation of previtaminÃ, D 3 to vitamin D 3 in organic solvent takes about 12 days to complete. Conversion from previtaminÃ, D 3 to vitamin D 3 on skin about 10 times faster than in organic solvent.
The conversion of ergosterol to vitamin D 2 follows the same procedure, forming previtaminÃ, D 2 by photolysis, which binds to vitamin D 2 . Transformation of previtaminÃ, D 2 to vitamin D 2 in methanol has a level comparable to previtaminÃ, D 3 . The process is faster in white button mushrooms.
Synthesis in skin
Vitamin D 3 is produced photochemically from 7-dehydrocholesterol in the skin of vertebrate animals, including humans. Vitamin D precursor 3 , 7-dehydrocholesterol is produced in relatively large quantities. 7-Dehydrocholesterol reacts with UVB rays at wavelengths between 270 and 300 nm, with synthesis peaks occurring between 295 and 297 nm. These wavelengths are present in the sun, as well as in the light emitted by UV lamps in tanning beds (which produce ultraviolet mainly in the UVA spectrum, but typically produce 4% to 10% of total UV emissions as UVB). Exposure to light through the windows is not enough because the glass is almost completely blocking UVB rays.
Sufficient amounts of vitamin D can be produced with moderate sun exposure on the face, arms and legs, averaging 5-30 minutes twice per week, or about 25% of the time for minimal sunburn. The darker the skin, and the weaker the sunlight, the more minutes of exposure it takes. Vitamin D overdose is not possible from UV exposure; the skin reaches a balance where the vitamin is degraded as soon as it is made.
Sunscreens absorb or reflect ultraviolet light and prevent most from reaching the skin. Sunscreen with sun protection factor (SPF) 8 based on the UVB spectrum decreases the synthetic capacity of vitamin D by 95%, and SPF 15 decreases it by 98%.
The skin consists of two main layers: the inner layer called the dermis, consisting mostly of connective tissue, and the thinner outer epidermis. The thick epidermis in the palm and the palm of the hand consists of five layers; from the outside to the inside, they are: stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and basal stratum. Vitamin D is produced in keratinocytes from the two deepest strata, stratum basale and stratum spinosum.
Evolution
Vitamin D can be synthesized only by photochemical processes. Phytoplankton in the sea (such as coccolithophore and Emiliania huxleyi ) have been doing photosynthetic vitamin D for more than 500 million years. Primitive vertebrates in the ocean can absorb calcium from the ocean into their skeletons and feed on plankton rich in vitamin D.
Inland vertebrates require a source of vitamin D in addition to plants for their calcification framework. They have to swallow it or be exposed to sunlight to photosynthesize on their skin. Ground vertebrates have been doing photosynthetic vitamin D for more than 350 million years.
In feathered birds and mammals, feathers or feathers block UV rays from reaching the skin. In contrast, vitamin D is made from oily secretions of skin deposited onto fur or feathers, and is obtained orally during treatment. However, some animals, such as naked mole rats, are naturally cholecalciferol, because serum 25-OH serum vitamin D levels are undetectable.
Industrial synthesis
Vitamin D 3 (cholecalciferol) is produced industrially by exposing 7-dehydrocholesterol to UVB light, followed by purification. 7-dehydrocholesterol is a natural substance in fish organ, especially liver, or wool fat (lanolin) from sheep. Vitamin D 2 (ergocalciferol) is produced in the same way using ergosterol from yeast or mushroom as the starting material.
Action mechanism
Metabolic activation
Vitamin D is brought in bloodstream to the liver, where it is converted into prohormone calcifediol. The circulating calciumol can then be converted to calcitriol, a biologically active form of vitamin D, in the kidneys.
Whether it is made on the skin or digested, Vitamin D is hydroxylated in the liver at position 25 (right above molecule) to form 25-hydroxycholecalciferol (calcifediol or 25 (OH) D). This reaction is catalyzed by the microsomal enzyme vitamin D 25-hydroxylase, the product of the human gene CYP2R1 , and expressed by hepatocytes. Once created, the product is released to the plasma, where it is bound to a carrier -globulin protein called vitamin D-binding protein.
Calcifediol is transported to the proximal tubules of the kidney, where it is hydroxylated at 1-? position (bottom right of molecule) to form calcitriol (1,25-dihydroxececalciferol, 1,25 (OH) 2 D). The conversion of calcifediol to calcitriol is catalyzed by the enzyme 25-hydroxyvitamin D 3 1-alpha-hydroxylase, which is the product of the human gene CYP27B1 . CYP27B1 activity is increased by parathyroid hormone, and also by low calcium or phosphate.
After the last conversion step in the kidney, calcitriol is released to the circulation. By binding to the vitamin D binding protein, calcitriol is transported throughout the body, including to the target organ of classic bowel, kidney and bone. Calcitriol is the most powerful natural ligand of the vitamin D receptor, which mediates most of the physiological actions of vitamin D.
In addition to the kidney, calcitriol is also synthesized by certain other cells including monocytes-macrophages in the immune system. When synthesized by monocyte-macrophages, calcitriol acts locally as a cytokine, modulating the body's defenses against microbial invaders by stimulating the innate immune system.
Inactivation
The activity of calcifediol and calcitriol can be reduced by hydroxylation at position 24 with vitamin D3 24-hydroxylase, forming the respective caliberifer and calcitrolin.
Difference between substrate
Vitamin D 2 (ergocalciferol) and Vitamin D 3 (cholecaliferol) share the same mechanism of action as described above. Metabolites produced by vitamin D 2 are sometimes named with a prefix - er/or ergo to distinguish them from D 3 peers based. However, these differences are present in the metabolism of Vitamin D 2 and Vitamin D 3 :
- Metabolites produced from Vitamin D 2 tend to bind less with vitamin D binding proteins.
- Vitamin D 3 may alternately be hydroxylated to calcifediol by a 27-hydroxylase sterol (CYP27A1), but Vitamin D 2 can not. Ergocalciferol can be directly dihydroxylated at position 24. Inactivation also tends to have a more profound effect: while calcitriol activity decreases to 60% of the original after 24-hydroxylation, ercalcitriol has a 10-fold decrease in activity on conversion to ercalcitetrol.
History
American researchers Elmer McCollum and Marguerite Davis discovered in 1914 the substance in cod liver oil which came to be called "vitamin A". British physician Edward Mellanby noticed dogs fed cod liver did not develop rickets and concluded vitamin A, or a closely related factor, could prevent the disease. In 1922, Elmer McCollum tested modified cod liver oil in which vitamin A had been destroyed. The modified oil heals the sick dog, so McCollum concludes a factor in cod liver oil that cures rickets differently from vitamin A. He calls it vitamin D because it is the fourth named vitamin. Initially it was not realized that, unlike other vitamins, vitamin D can be synthesized by humans through UV exposure.
In 1925, it was determined that when 7-dehydrocholesterol was irradiated with light, a fat-soluble vitamin form was produced (now known as D 3 ). Alfred Fabian Hess stated: "Light is the same as vitamin D." Adolf Windaus, at the University of GÃÆ'¶ttingen in Germany, received the Nobel Prize in Chemistry in 1928 for his work on the sterol constitution and its relationship to vitamins. In 1929, a group at NIMR in Hampstead, London, worked on the structure of vitamin D, which is still unknown, as well as the steroid structure. The meeting took place with J.B.S. Haldane, J.D. Bernal, and Dorothy Crowfoot to discuss possible structures, which contribute to uniting the team. X-ray crystallography shows flat sterol molecules, not as proposed by the German team led by Windaus. In 1932, Otto Rosenheim and Harold King published a paper proposing structures for sterols and bile acids that were immediately accepted. Informal academic collaboration between team members Robert Benedict Bourdillon, Otto Rosenheim, Harold King and Kenneth Callow is very productive and leads to the isolation and characterization of vitamin D. At present, the policy of the Medical Research Council is not to patent. discovery, believes the results of medical research should be open to everyone. In the 1930s, Windaus further explained the chemical structure of vitamin D.
In 1923, American biochemist Harry Steenbock at the University of Wisconsin showed that ultraviolet light radiation increases the vitamin D content of food and other organic matter. After lighting the rodent's food, Steenbock found the rodent was healed of rickets. Vitamin D deficiency is known as a cause of rickets. Using $ 300 of his own money, Steenbock patented his invention. Irradiation techniques are used for foodstuffs, most remembered for milk. With the expiration of his patent in 1945, rickets were removed in the US.
In 1969, after studying the core fragments of intestinal cells, a specific binding protein for Vitamin D called Vitamin D Receptor was identified by Mark Haussler and Tony Norman. In 1971-1972, subsequent metabolism of vitamin D became an active form was found. In the liver, vitamin D is found to be converted to calcifediol. Calcifediol is then converted by the kidney into calcitriol, the biologically active form of vitamin D. Calcitriol circulates as a hormone in the blood, regulating the concentration of calcium and phosphate in the bloodstream and promoting healthy growth and bone remodeling. Vitamin D metabolites, calcifediol and calcitriol, were identified by a competitor team led by Michael F. Holick in Hector DeLuca's laboratory and by Tony Norman and colleagues.
Research
There are many research activities that observe the effects of vitamin D and its metabolites on animal models, cell systems, gene expression studies, epidemiology, and clinical therapy. This different type of research can produce conflicting evidence about the benefits of intervention with vitamin D. One school of thought argues that human physiology is adjusted to the intake of 4,000-12,000 IU/day of sunlight exposure with serum 25-hydroxyvitamin D serum 25 to 80 ng/ml and this is necessary for optimal health. Proponents of this view, including some of the panel members who compiled the 1997 report on vitamin D from IOM, are now being replaced, arguing that IOM warnings about serum concentrations above 50 ng/ml are less biologically reasonable. They suggest, for some, reducing the risk of preventable diseases requiring higher levels of vitamin D than those recommended by IOM.
The National Institutes of Health Office of Diet Supplements in the United States establishes the Vitamin D Initiative by 2014 to track current research and provide education to consumers. In their review in 2016, they acknowledge that more research has shown that vitamin D may play some role in the prevention and treatment of type 1 and 2 diabetes, glucose intolerance, hypertension, multiple sclerosis, and other medical conditions. They further state: "However, the bulk of the evidence for this role comes from in vitro, animal, and epidemiological studies, not randomized clinical trials that are considered more definitive Until such trials are conducted, the implications of the evidence available to public health and care patients will be disputed ".
Some early studies linked low vitamin D levels with later disease. The evidence in 2013 is not enough to determine whether vitamin D affects cancer risk. One meta-analysis found decreased mortality in the elderly. Another meta-analysis involving more than 350,000 people concluded that vitamin D supplementation in unopposed individuals did not reduce skeletal (total fracture) or non-skeletal outcomes (myocardial infarction, ischemic heart disease, stroke, cerebrovascular disease, cancer) by more than 15%, and that further research trials with similar designs are unlikely to change this conclusion.
Vitamin D deficiency is widespread in the European population. European studies assessed levels of vitamin D intake in relation to disease rates and dietary recommendation policy, food fortification, vitamin D supplementation, and small amounts of sun exposure.
Regardless of VDR activation, various alternative mechanisms of action are being investigated, such as inhibition of signal transduction by hedgehogs, hormones involved in morphogenesis.
References
Further reading
- Vitamin D NIH Fact Sheet for Health Professionals from the U.S. National Institute of Health
- Disagreements among experts about the correct dose of vitamin D. (Nature News, 6 July 2011)
External links
- Vitamin D in children of the Royal National Orthopedic Hospital Trust
Source of the article : Wikipedia
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