What is the story of vitamin D.

Structural formula
Common name Vitamin D3
other names
  • Cholecalciferol
  • Calciol
  • (3β, 5Z, 7E) -9,10-secocholesta- 5,7,10 (19) -trien-3-ol
  • 3- [2- [7a-methyl-1- (6-methylheptan-2-yl) -2,3,3a, 5,6,7-hexahydro-1H-inden-4-ylidene] ethylidene] -4-methylidene - cyclohexan-1-ol
Molecular formula C.27H44O
CAS number 67-97-0
Brief description colorless solid
Occurrence especially oily fish
function Precursor of calcitriol, as such: regulation of the calcium balance, maturation of immune cells
Daily need 5-12.5 µg
Consequences in case of deficiency Rickets, osteomalacia
Overdose 50 µg / day (> 10 years old), 25 µg / day (0-10 years old)[1]
Molar mass 384.64 g mol−1
Physical state firmly
Melting point 84.5-87 ° C
boiling point decomposition
solubility fat-soluble, 50-80% protein-bound in the blood (to VDBP)
safety instructions
Hazardous substance labeling from RL 67/548 / EEC, appendix 1
R and S phrases R: 24 / 25-26-48 / 25
S: (1/2) 28-36 / 37-45
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions.

  Cholecalciferol (short Calciol), Vitamin D3 (short D.3) is the physiologically occurring vitamin D. Since it can be formed in the body with the help of UV-B light in the skin, the historical term vitamin is incorrect. It is mainly found in food in fatty fish or is added to food as a dietary supplement. It has the function of a prohormone in the body and is converted to the hormone calcitriol via an intermediate stage.

The endocrine vitamin D system plays an essential role in regulating the calcium level in the blood and in building a physiological bone architecture. A vitamin D deficiency leads to a number of changes in metabolism, which in the medium term lead to rickets in children and osteomalacia in adults.

Research since the 1990s has shown that the vitamin D system also has essentially autocrine functions in a wide variety of other tissues, including cell differentiation, inhibition of cell proliferation, apoptosis, immunomodulation and the control of other hormonal systems. As a result, subclinical vitamin D deficiency is an independent risk factor for:

  • Autoimmune diseases (such as multiple sclerosis, Crohn's disease, type 1 diabetes mellitus, systemic lupus erythematosus),
  • Skin diseases such as B. psoriasis,
  • Infectious diseases such as tuberculosis as well
  • high blood pressure
  • Vitamin D and calcium are protective against colon cancer[2]

The vitamin D system is also important for the development and function of the nervous and muscular systems.

All of these non-infectious diseases are civilization diseases, the connection between which to vitamin D and sunlight is not immediately obvious, and which for the most part have a multifactorial cause; a vitamin D deficiency or lack of light seems to be a factor.

Other forms of vitamin D

In addition to vitamin D, which is effective in the body3 a distinction is made between the following substances from the vitamin D class:

  • Vitamin D1: Compound of ergocalciferol (D2) and Lumisterol, 1: 1
  • Vitamin D2: Calciferol, more precisely: Ergocalciferol (synthesized from Ergosterol)
  • Vitamin D4: 22,23-dihydroergocalciferol (saturated form of vitamin D.2)
  • Vitamin D5: Sitocalciferol (synthesized from 7-dehydrositosterol)


The discovery of vitamin D is linked to the search for a cure for rickets.[3] In 1919 it was shown that rickets can be cured by irradiation with artificially generated UV light[4], two years later this was also demonstrated by exposure to normal sunlight.[5] Regardless of these findings, the British doctor Sir Edward Mellanby was at about the same time convinced that rickets was caused by a nutritional deficit and was also able to show in experiments with dogs in 1919 that rickets could be cured with butter, milk and, in particular, cod liver oil. He then considered vitamin A, which had only recently been discovered in cod liver oil, to be the triggering factor. It was known that vitamin A is destroyed by oxidation. Cod liver oil therefore loses its ability to cure night blindness after oxidative treatment. Cod liver oil treated in this way was still able to cure rickets. The chemist McCollum in collaboration with the pediatrician John Howland concluded that another substance independent of the known vitamin A was responsible for this effect.[6] As the fourth vitamin found (after vitamins A, B and C) it was named "vitamin D".

Vitamin D3 - vitamin or prohormone?

Most vertebrates, including humans, get much of their vitamin D needs by exposing their skin to sunlight. Overall, the photosynthesis of vitamin D has been used by organisms in evolution for over 750 million years and already occurs in certain types of plankton (phytoplankton coccolithophore Emeliani huxleii).[7] Thus, vitamin D is actually not a vitamin.

By definition, vitamins are substances that the body cannot produce itself, but which are required for life and must therefore be supplied. The precursors of the so-called vitamin D are produced by the body itself. In a figurative sense, the necessary "vitamin" is sunlight, which must be added to the provitamin 7-dehydrocholesterol (the starting substance for vitamin D synthesis) present in the body. Vitamin D3 is therefore called a vitamin for historical reasons. Due to its endogenous synthesis and the fact that its effect affects other tissues in addition to the site of synthesis, vitamin D should3 called a prohormone. About the substance “Vitamin D3"So actually the" sunlight banned into the test tube "(Meinhard von Pfaundler * 1872, † 1947) is effective.

Photosynthetic formation of vitamin D.3

In the skin, the highest concentrations of 7-dehydrocholesterol are found in the stratum spinosum and stratum basale. In humans and most mammals, 7-dehydrocholesterol is abundantly available for vitamin D production (an exception are domestic cats, for example).

  1. Is 7-dehydrocholesterol with UVB light with wavelengths in the range 290-315 nm and an intensity of at least 18 mJ / cm2[9] irradiated, the B-ring in 7-dehydrocholesterol can be broken up by a photochemically induced 6-electron conrotatory electrocyclic reaction: it is formed Previtamin D3.
  2. The previtamin D3 is thermodynamically unstable and experiences a (1-7) sigmatropic shift of a proton from C-9 to C-10 with subsequent isomerization: It is formed Vitamin D3. The vitamin D.3 gets into the blood and is mainly bound to the vitamin D binding protein (DBP) transported to the liver, where it is further converted into 25 (OH) vitamin D.3 is hydroxylated. 80% of previtamin D is in the test tube3 to vitamin D.3 Isomerized within 3 days, in the skin this happened after 8 hours.[7]

Vitamin D self-regulation3-Education

If a certain amount of 7-dehydrocholesterol is exposed to simulated equatorial sunlight in a test tube experiment, approx. 20% of the initial amount becomes previtamin D after a few minutes3 transformed. This amount of Previtamin D3 remains in a constant equilibrium with further irradiation, because also Previtamin-D3 is photolabile and becomes physiologically inactive during further UVB irradiation during the next 8 hours Lumisterol and to Tachysterol broken down before it becomes vitamin D.3 isomerized. During this time, the 7-dehydrocholesterol drops to approx. 30% of the initial amount. (On the other hand, under unnatural narrow-spectrum UVB irradiation with a wavelength of 290 to 300 nm, 65% of the original 7-dehydrocholesterol in previtamin D3 transformed).[7]

That from previtamin D too3 resulting vitamin D.3 is photolabile: Can the vitamin D.3 are not removed quickly enough in the blood, UVB and UVA radiation (up to 345 nm) result in at least three other ineffective products: Suprasterol-1 and -2 and 5,6-transvitamin D.3.

For example, a short exposure to sunlight (with a sufficiently high proportion of UVB) produces a similar amount of vitamin D for a few minutes3 formed like a comparable irradiation over a longer period of time. In this way, the body protects itself against vitamin D intoxication from too much light for a short time.

In the long term, the body protects itself from vitamin D intoxication by increasing the formation of melanin in the skin, which absorbs UV light with a wavelength of 290-320 nm (tanning, darker skin type in southern countries).

The 7-dehydrocholesterol content of the skin decreases with age. Furthermore, in old age, the skin's ability to produce vitamin D decreases3 to form, about a factor of 3 compared to a 20-year-old person.[7]

For the pale skin of a fair-skinned, young, adult person, the minimum erythema dose (when the skin starts to turn red) is reached after 10 to 12 minutes on a sunny summer afternoon at 42 ° latitude at sea level (according to Boston, Barcelona or Rome), a dark-skinned person needs 120 minutes accordingly. If the skin of these people is completely irradiated, it will give so much vitamin D within the next 24 hours3 to the blood like when taking 10,000 to 20,000 IU of vitamin D3 would be consumed through food (10,000 [IU] corresponds to 250 µg). This is compared to the recommended diet (200–500 IU vitamin D3 daily) a large amount.[9] A strong vitamin D.3Formation in the skin is therefore possible even with short but intense exposure to sunlight with a high UVB content.

Vitamin D formation in winter

The higher the position of the sun, the shorter the path of sunlight through the atmosphere. The shorter-wave UVB light is absorbed much more strongly by the atmosphere. Therefore, the height of the sun is a decisive factor for vitamin D.3Formation in the skin.[7] If it falls below it all day long in otherwise good lighting conditions, that no vitamin D3 more can be formed in the skin, one speaks of that "Vitamin D Winter"[10]which is actually a "vitamin D polar winter". Furthermore, the cloud cover, the ozone, the height above sea level, the nature of the earth's surface etc. play a role for the light intensity. From a certain sum of UVB light absorbing factors, the light intensity is too low to still contain vitamin D3 to be able to form in the skin. There is an internet-based calculator that calculates for a place, time and other conditions to be entered, how long the daily light conditions allow a maximum of vitamin D formation in the skin to be expected.

According to this calculator, a vitamin D polar winter begins safely above the 52nd parallel (London, Ruhr area), so there is no vitamin D here all day north of this limit in winter3 more are formed in the skin. The model on which this calculator is based still has uncertain requirements[10]so that the vitamin D winter could possibly begin further south, as American researchers publish: They write that during the 4 dark months above a latitude of 42 ° (Boston, Rome, Barcelona) no significant vitamin D even at noon3 more can be formed through the skin, above the 52nd parallel (Edmonton, London, Düsseldorf, Berlin) the vitamin D formation in the skin largely ceases during the 6 dark months. Below the 37th parallel (Los Angeles, Sicily), on the other hand, adequate vitamin D biosynthesis is safely possible throughout the year.[7][11]

In the moderate latitudes, the formation of vitamin D in the skin increases exponentially with the height of the sun and is therefore strongly dependent on the season. When the sun is low, with a predominantly UVA component of the sunlight, the line between effective vitamin D formation in the skin and sunburn is narrow or not reachable at all.

Vitamin D, a lifestyle disease3-Defect

About a million years ago, small, probably initially dark-skinned groups of people slowly migrated north from Africa. The farther north they lived, the lighter their skin became over longer periods of time and thus could better use the dwindling UVB light for vitamin D production.[9] The only exception are the Inuit, who have only been living in the Arctic for a relatively short time and meet their vitamin D requirements through food (fatty fish).

We are not evolutionarily adapted to comparatively very modern living conditions: Extensive life in closed rooms, under glass, with artificial light, under a UVB light-filtering smog, consistent use of sun cream (which partially filters UVB light in a targeted manner) or largely complete coverage the skin with clothes in the open air. The deficiency disease rickets had already been described in ancient Rome; it was particularly widespread in the industrial cities of Europe and North America during the times of industrialization in the 18th, 19th and early 20th centuries.[12] In the first half of the 20th century, the connection between rickets, sunlight and vitamin D was recognized3.

A suboptimal vitamin D supply can still be found today in epidemiological studies in broad sections of the population.[11] If people with dark skin now live at higher latitudes, their risk of vitamin D deficiency increases further. Vitamin D deficiency can occur particularly during pregnancy. Vitamin D supplementation during pregnancy can be insufficient. Lisa Bodnar and colleagues found deficits in a study in 80 percent of African American women and almost half of white American women, even though nine out of ten of the total of 400 pregnant women were taking a vitamin supplement.[13]

Vitamin D3 in food

Under optimal conditions that are not always and everywhere optimal (see above), the skin of a young adult person can produce 10,000 to 20,000 IU (i.e. 250 to 500 µg) of vitamin D per day. In contrast, few foods contain vitamin D.3 in comparable quantities. It is found mainly in oily fish.

The vitamin D3-Content of some selected foods shows the mostly minor role of food for the vitamin D supply: (1 µg corresponds to 40 IU)

food µg / 100greference
Cod liver oil 330 ?
Cod liver oil 210 ?
herring 31 ?
salmon 16 ?
sardine 7,05 ?
veal 3,8 ?
Chicken egg 3,5 ?
Liver (beef) 1,7 ?
Liver (poultry) 1,3 ?
cod 1,3 ?
cream 1,1 ?
Cow's milk 0,08 ?
industrially produced baby milk in Germany 1-2 µg / 100kcal [1]
Breast milk 0,01–0,12 [1]

In the USA, industrially produced baby milk must be supplemented with 1 to 2.5 µg / 100 kcal. Infants who are breastfed or who drink less than 500 ml of this formula should receive 200 IU (5 µg) of vitamin D daily3 to get.[14]

Mushrooms (e.g. yeasts) contain the mycosterol ergosterol, which, when exposed to sufficient UV light, turns into biologically active ergocalciferol (vitamin D2) can convert. Other plants also contain traces of this.

Vitamin D ingested with food is quickly absorbed in the small intestine and enters the bloodstream together with the fats via the lymph. There it has a half-life of 19 to 25 hours.[15] During this time it is either deposited in adipose tissue or in the liver to form 25 (OH) vitamin D.3 hydroxlated.

In the USA and Canada, drinking milk is regularly supplied with 10 µg of vitamin D.3 substituted per liter. In the UK, Ireland and Australia breakfast cereals and margarine containing vitamin D are allowed3 be substituted. In Norway and Japan, fatty fish consumption contributes to the supply of vitamin D through the diet. In most other countries there is little vitamin D in the diet3 recorded. The daily intake of vitamin D with food is roughly as follows (1 µg corresponds to 40 IU of vitamin D.3):

Population group daily vitamin D3-Admission Vitamin D supplemented with it3reference
young, white, American men 8.1 µg 5.1 µg [16]
young white American women 7.3 µg 3.1 µg [16]
black American adults 6.2 µg 4.3 µg [16]
british men 4.2 µg 1.4 µg [16]
british women 3.7 µg 1.1 µg [16]
japanese women 7.1 µg 0 µg [16]
Norwegian men 6.8 µg 2.9 µg [16]
Norwegian women 5.9 µg 2.9 µg [16]
spanish men approx. 4 µg [16]
spanish women approx. 3 µg [16]
German men 4 µg [1]
German women 3.1 µg [1]
Italian households 3.0 µg [1]

However, these average figures vary considerably within these population groups and between the studies evaluated.[16]

Vitamin D biochemistry3 after education

Vitamin D3 is mainly bound to the vitamin D-binding protein and transported to the liver via the blood. There it becomes calcidiol (25 (OH) vitamin D) from the cytochromes P450CYP27A1 in mitochondrial membranes and CYP2R1 in the microsomes3) hydroxylated.[17] This is again bound to vitamin D-binding protein and released into the blood, where it has a half-life of approx. 19 days.[15] This enzymatic reaction is probably not subject to any regulation worth mentioning, since the 25 (OH) vitamin D3- Blood levels pretty much the longer-term vitamin D3-Supply of the last 3-4 months reflects while the vitamin D.3-Mirror shows the supply of the last hours to days.

25 (OH) vitamin D.3 is something like a storage form of vitamin D.3. There has to be one in order to be able to intercept the large peaks and pauses in the main vitamin D supply caused by the light. The medium to long-term vitamin D supply of an organism can best be determined via the blood level of 25 (OH) vitamin D.3 determine (for details see below).

The 25 (OH) D thus formed3 now, mainly bound to the vitamin D-binding protein, reaches its target tissues such as the kidneys, where it then becomes calcitriol (1α, 25 (OH)2Vitamin D3) is activated (see below). This is the main activating ligand for the vitamin D receptor. This last activation step is redundant on many levels and regulated differently from tissue to tissue in order to always be adapted to the current need of the body and the target tissue for the vitamin D effect.

25 (OH) vitamin D.3 can probably also activate the vitamin D receptor itself, but about 100 times less than calcitriol. This probably occurs, among other things, in the event of vitamin D poisoning3 to wear when the last regulation of the activation of vitamin D.3 from excessive 25 (OH) vitamin D.3-Mirror is ignored.[18]

The determination of vitamin D.3-The level in the blood serum only reflects the vitamin D uptake with food or the self-synthesis in the skin during the last hours or days; it is therefore only of interest for research purposes. Determining the 25 (OH) vitamin D is practically more useful for an investigation of the long-term vitamin D status3-Level in the blood, which contains vitamin D.3 is rapidly converted in the liver (see above). The half-life of 25 (OH) vitamin D.3 in the blood circulation is about 1–2 months, depending on the overall vitamin D status. It can take up to four months until a new steady state with a stable serum value is established after a change in the daily vitamin D intake[1].

The 25 (OH) D3 can be determined since the beginning of the 80s of the last century and enabled a further understanding of the physiology of vitamin D.3.

Low 25 (OH) Vitamin D.3-Mirror

People from southern countries who are exposed to a lot of the sun and do not completely cover their skin often have serum concentrations of 50 to 90 ng / dl[11]. However, one could determine increased calcium excretion in the urine of Israeli lifeguards with such values.[1]

From a serum concentration of less than 30 ng / ml, the body compensates for insufficient vitamin D effects on the calcium balance with an increased parathyroid hormone (see below). Furthermore, the calcium absorption in the intestine is from a 25 (OH) vitamin D.3-Level below 30 ng / dl braked.

So today we assume the following evaluation of the serum concentration for 25 (OH) D3 out:

  • values below 11 ng / ml pose a serious risk of rickets for young children and infants.
  • values below 20 ng / ml mean a long-term relevant vitamin D deficiency (even if manifest rickets or osteomalacia only possibly occurs later).
  • values ​​between 30-60 ng / ml mean a physiologically safe adequate supply.
  • values over 88 ng / ml mean a vitamin D oversupply
  • values over 150 ng / ml mean vitamin D intoxication.[9][11]
  • values over 280 ng / ml lead to serious disturbances in calcium homeostasis.[19]

The literature data differ with regard to these standard values.

It is interesting that the blood level is kept in a fairly constant range of 30 to 88 ng / ml over a fairly wide dose range of daily vitamin D intake from 20 µg to 250–500 µg in adults and only rises rapidly with even higher supplements. This upper limit corresponds to the maximum daily production of vitamin D.3 in the skin.[1]

Frequency lower 25 (OH) vitamin D.3-Mirror

Depending on the season, geographical latitude, food habits, population group and lifestyle, the 25 (OH) vitamin D falls3- Levels in areas in which one must assume a vitamin D deficiency. Low vitamin D levels are an independent and long-term risk factor for a number of diseases (cancer, autoimmune diseases, susceptibility to infections, more fragile bones). Since (as explained above) a low vitamin D level is due to civilization, it is often normal, but not yet healthy. The following values ​​were found in various studies:

place geogr. width Group, dude Summer autumn
(ng / ml ± SD)
Winter / spring
(ng / ml ± SD)
Miami (Florida) 26° over 18 years 26.8 ± 10.3 (men)
25.0 ± 9.4 (women)
23,3 ± 8,4 [11]
Boston, Massachusetts 43° white women 20–40 Lj. 34,2 ± 13,2 24,0 ± 8,6 [11]
Boston, Massachusetts 43° black women 20–40 Lj. 16,4 ± 6,6 12,1 ± 7,9 [11]
Paris 49° male adolescents 23,4 ± 8,0 8,2 ± 2,8[11]
Calgary, Alberta 51° 27.-89. Lj. 28,6 ± 9,4 22,9 ± 8,5 [11]

Paris was included in the table as a representative of Central European conditions with regard to geographical latitude, dietary habits and supplementation. The extremely low value in winter is particularly noticeable here. One thing to consider, however, is the reduction in UV radiation caused by smog.
The effect of different skin pigmentation becomes clear from the example from Boston.

Vitamin D intake3 from food

Vitamin D3 is not an ordinary food component, because the natural supply would correspond to the irradiation with UVB light, which our African ancestors had generously available all year round for thousands of years. Only in the last 10 years has it been increasingly recognized which diseases of civilization (apart from rickets and osteomalacia) are associated with the endemic lack of light in modern societies (see under Calcitriol). Therefore, the publicly recommended daily requirement (RDA) of vitamin D becomes3 lively debated among scholars and health care leaders. Current recommendations are viewed by researchers in the field as either irrelevant (for those adequately exposed to UVB light) or inadequate (for the majority of the population in higher latitude civilized societies).

Current guidelines in the US recommend 5 µg (200 IU) daily for children and younger adults, 10 µg for 50–70 year olds, and 15 µg for over 70 year olds. The German Nutrition Society recommends 10 µg daily for infants in the first year of life and for seniors from 65 years of age and 5 µg for other children and adults3.[20]

In Germany, most infants in the first year of life and possibly in the second winter are given one tablet with 12.5 µg vitamin D every day3 (500 IU) given for rickets prophylaxis.

How much vitamin D3 you need a 25 (OH) vitamin D, which is regarded as sufficient, in the absence of UVB light3Bringing serum levels over a winter with little UVB radiation? It has been estimated that a daily intake of 1 IU of vitamin D3 in adults the 25 (OH) vitamin D.3-The blood level increases by 0.06 ng / ml (but this varies depending on the vitamin D status). Adults weighing approx. 80 kg require approx. 12.5–25 µg (500–1000 IU) of vitamin D per day3to get an existing low in vitamin D in the medium term3-Maintain levels of 20–30 ng / ml in the blood, provided that no vitamin D formation occurs through light.[21]

If a nursing mother takes 100 µg vitamin D daily (if she is not exposed to UVB light), enough vitamin D activity appears in her breast milk to safely protect the infant from vitamin D deficiency without further intake. At 50 µg this is not yet definitely the case (the number of women examined was small, however).[22]

Vitamin D in breast milk

The amount of vitamin D-effective components in breast milk is remarkably low. It is very dependent on the mother's vitamin D status. Already hydroxylated 25 (OH) vitamin D.3 accounts for most of the antirachitic activity of breast milk. The vitamin D content in the higher-fat hind milk (which the infant drinks last) is greater than in the fore milk. If the mothers living at higher latitudes receive 50 µg (2000 IU) of vitamin D3 take daily in winter, their breast milk reaches the antirachitic activity of unsupplemented mothers in summer, but the answer varies greatly from person to person.[1]

If mothers have a subclinical vitamin D deficiency for them (like most women in civilized societies far away from the equator in winter and especially in Islamic societies), the infants have a significantly higher risk of rapidly developing a relevant vitamin D deficiency to develop. Overall, however, the formation of vitamin D also appears to be beneficial for babies3 to represent the main natural protection against rickets in the skin.

The vitamin D currently in the mother's blood may be lost3 Much better (30–80%) in breast milk than the already hydroxylated 25 (OH) vitamin D.3 (0.5%); Whether this is true is still being researched.

Overdose and toxicity

Acute or chronic vitamin D overdose can lead to vitamin D hypervitaminosis. In 2002, the Scientific Committee on Food of the European Commission issued the following information on the safety of vitamin D.3 Opinion: A maximum daily dose of 50 µg (2000 IU) for adolescents and adults (including pregnant women and nursing mothers) and 25 µg (1000 IU) for children in the first 10 years of life are from healthy people without the risk of side effects, even without medical supervision can be taken in the long term. This information is cautious, at least for adults, and has a safety factor of 2, which means that side effects were actually only observed at doses more than twice as high. Measured against the usual vitamin D doses, this opinion appears to leave sufficient leeway for adults. This safety area is lower for small children[1].

Most authors suggest an intake of up to 100 µg vitamin D for adults3 Regarded as safe for over 6 months, i.e. without verifiable side effects, such as B. an increased excretion of calcium in the urine.[11][19]

Vitamin D metabolism in diseases

Vitamin Patients with tuberculosis, sarcoid and other granulomatous diseases and occasionally cancer also activate the 25 (OH) vitamin D.3 z. B. in macrophages stronger to 1.25 (OH)2Vitamin D3 and can functionally lead to vitamin D hypervitaminosis with hypercalcaemia.[23] This is based on an originally mostly sensible immunological mechanism (for more details see under Calcitriol).

15% of patients with Williams-Beuren syndrome have hypercalcemia. There have been many suspicions of a link to vitamin D metabolism, but the results of such observations have been contradicting.[24]

In patients with Smith-Lemli-Opitz syndrome, the breakdown of the vitamin D precursor 7-dehydrocholesterol into cholesterol is disturbed by mutations in 7-dehydrocholesterol reductase. 7-Dehydrocholesterol builds up in their metabolism; their skin is sometimes photosensitive, but their vitamin D status is still comparable to that of the general population.[25]

Activation of 25 (OH) vitamin to 1.25 (OH)2

The vitamin D metabolites are primarily filtered in the glomerula of the kidneys together with the VDBP, then reabsorbed in the proximal tubular cells with the help of the megalin and released there.

Vitamin D 25 (OH) can be found in the mitochondria of the cells of the proximal tubule of the kidneys3 by 1α-hydroxylase to the biologically active 1,25 (OH)2Vitamin D3 (Calcitriol) further hydroxylated, or by the oppositely regulated 24-hydroxylase to the 24R, 25 (OH)2Vitamin D3 are inactivated or leave the kidney cells unchanged into the blood (in order to be bound again to DBP there).

The formation of the 1,25 (OH)2Vitamin D3 in the kidney is finely regulated: the most important factors that directly promote its enzymatic formation via activation of 1α-hydroxylase are, independently of one another, an increased parathyroid hormone, a decreased calcium level and a low phosphate level in the blood. 1.25 (OH)2D.3 itself inhibits 1α-hydroxylase and activates 24-hydroxylase. Indirectly, mostly via the parathyroid hormone, calcium, estrogen, glucocorticoids, calcitonin, growth hormone and prolactin influence the formation of calcitriol. All these regulations serve to synthesize just enough of the vitamin that the body can meet its calcium and phosphate requirements in its current situation. The regulation of the 24R, 25 (OH)2D.3Incidentally, formation takes place through the same factors, but in the opposite direction.[18]

In other tissues it activates the 25 (OH) vitamin D.3 to 1α, 25 (OH)2Vitamin D3 regulated by other factors: cytokines, growth factors, etc.[18]

1.25 (OH)2D.3 is in a much lower concentration than 25 (OH) D3 and also mainly bound to DBP in the blood. The concentration in particular of free 1.25 (OH)2D.3 (Calcitriol) is strictly regulated and largely correlated with its activity. It is also largely independent of the concentration of its precursor 25-hydroxy-cholecalciferol (Calcidiol) or the VDBP[18].

Functions of the activated 1.25 (OH)2D.3

1.25 (OH) acts in the cells of the target organs2D.3 (Calcitriol) like a steroid hormone: It is bound to an intracellular receptor protein, the vitamin D receptor (VDR), and transported into the cell nucleus. There the vitamin-receptor complex associates with the DNA and changes the transcription of various hormone-sensitive genes, which ultimately leads to changes in protein synthesis with corresponding biological effects.

For more information, see Calcitriol.

Synthesis of vitamin D.

The photochemical synthesis of vitamin D.2 was first discovered and investigated in 1927 by the Göttingen chemist Adolf Windaus (Nobel Prize 1928). His work enabled the manufacture of the anti-rachitic vitamin D.2 by the pharmaceutical companies E. Merck and Bayer (brand name Vigantol), whereby the vitamin deficiency of many children could be treated. For some years now, nutritional supplements have also been made with vitamin D.3 enriched. The fortification of everyday foods with vitamin D is currently prohibited in Germany due to its toxicity. Since butter has a naturally high content, there is a single exemption for margarine in order to make it equivalent to its role model.

In the technical synthesis of vitamin D2 one starts with ergosterol, which is obtained from yeast, and exposes it to the UV radiation of a mercury vapor lamp, whereby all wavelengths outside the band 270-300 nm are filtered out. The resulting mixture of previtamin and vitamin can have a high concentration of vitamin D depending on the temperature of the approach2 which is separated by chromatography.[26] Also in the production of vitamin D.3 the same precursor is assumed as occurs in the body, 7-dehydrocholesterol[27], which in turn is obtained by bromination of a cholesterol ester with subsequent dehydrobromination and saponification.[28] Both photochemical reactions are expediently carried out in microreactors.[29]

Individual evidence

  1. abcdefGHijkScientific Committee on Food of the European Commission: Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Vitamin D. 2002
  2. PMID 17215380
  3. Article (engl) website with similar content, German
  4. Huldschinsky, K. Healing of rickets through artificial high altitude sun German med. Weekly, 1919, 45, 712–713
  5. Hess, A. & Unger, L. Cure of infantile rickets by sunlight JAMA, 1921, 77, 39–41
  6. J. Biol. Chem. 1922 53: 293-312. PDF
  7. abcdefG M. F. Holick: Environmental factors that influence the cutaneous production of vitamin D.. On: At J Clin Nutr. Volume 61 (3 Suppl), 1995, pp. 638S-645S.
  8. A. W. Norman: Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D: integral components of the vitamin D endocrine system. In: At J Clin Nutr. Volume 67 (6), 1998, pp. 1108-10.
  9. abcde B. W. Hollis: Circulating 25-Hydroxyvitamin D Levels Indicative of Vitamin D Sufficiency: Implications for Establishing a New Effective Dietary Intake Recommendation for Vitamin D. In: J Nutr. Volume 135 (2), 2005, pp. 317-22.
  10. ab O. Engelsen et al .: UV Radiation, Vitamin D and Human Health: An unfolding Controversy.Daily Duration of Vitamin D Synthesis in Human Skin with Relation to Latitude, Total Ozone, Altitude, Ground Cover, Aerosols and Cloud Thickness. In: Photochemistry and Photobiology. Volume 81, 2005, pp. 1287-1290.
  11. abcdefGHij W. B. Grant and M. F. Holick: Benefits and Requirements of Vitamin D for Optimal Health: A Review. In: Aging Med Rev. Volume 10 (2), 2005, pp. 94-111.
  12. K. Rajakumar: Vitamin D, Cod-Liver-Oil, Sunlight, and Rickets: A Historical Perspective. In: Pediatrics. Volume 112, 2003 pp. 132-135.
  13. Lisa M. Bodnar et al, Journal of Nutrition 137 [2007] 447-52
  14. L. M. Gartner, F. R. Greer: Section on Breastfeeding and Committee on Nutrition: Prevention of Rickets and Vitamin D Deficiency: New Guidelines for Vitamin D Intake. In: Pediatrics. Volume 111, 2003, pp. 908-910.
  15. ab Hazardous Substances Database
  16. abcdefGHijk M. S. Calvo et al .: Vitamin D Intake: A Global Perspective of Current Status. J Nutr 135: 310-316.
  17. J. B. Cheng et al .: De-orphanization of Cytochrome P450 2R1, a microsomal vitamin D 25-hydroxylase. In: J Biol Chem. Volume 278 (39), 2003, pp. 38084-38093.
  18. abcd A. S. Dusso et al .: Vitamin D. In: Am J Physiol Renal Physiol. Volume 289, 2005, pp. F8-F28.
  19. ab R. Vieth: Critique of the Considerations for Establishing the Tolerable Upper Intake Level for Vitamin D: Critical Need for Revision Upwards. In: J Nutr. Volume 136, 2006, pp. 1117-1122.
  20. Reference values ​​for vitamin D3- Supply to the German Society for Nutrition.
  21. R. P. Heaney et al .: Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. In: At J Clin Nutr. Volume 77, 2003, pp. 204-10. Erratum in: At J Clin Nutr. Volume 78, 2003, p. 1047
  22. B. W. Hollis and C. L. Wagner: Vitamin D requirements during lactation: high-dose maternal supplementation as therapy to prevent hypovitaminosis D for both the mother and the nursing infant. In: At J Clin Nutr. Volume 80 (suppl), 2004, pp. 1752S-1758S.
  23. Kang, E.S. et al. Hypercalcemia in granulomatous disorders: a clinical review. Curr Opin Pulm Med. 2000 Sep; 6 (5): 442-7.
  24. Cagle, A.P. et al .: Severe Infantile Hypercalcemia Associated With Williams Syndrome Successfully Treated With Intravenously Administered Pamidronate. PEDIATRICS Vol. 114 No. October 4, 2004, pp. 1091-1095.
  25. Rossi, M. et al .: Vitamin D status in patients affected by Smith-Lemli-Opitz syndrome. J Inherit Metab Dis. 2005; 28 (1): 69-80.
  26. U.S. Patent 3185716
  27. U.S. Patent 3367950
  28. U.S. Patent 3,037,996
  29. U.S. Patent 5543016

Further literature

  • J. Haas: Vigantol - Adolf Windaus and the history of vitamin D. 2007, ISBN 3-8047-2223-7

See also

Categories: Toxic Substance | Chemical compound | Drug | vitamin