   #copyright

Vitamin D

2007 Schools Wikipedia Selection. Related subjects: Food and agriculture;
General Chemistry

   Cholecalciferol (D3)
   Enlarge
   Cholecalciferol (D[3])
   Ergocalciferol (D2)
   Enlarge
   Ergocalciferol (D[2])

   Vitamin D refers to a group of fat-soluble alcohols that contribute to
   the maintenance of normal levels of calcium and phosphorus in the
   blood. The two major forms of vitamin D are D[2] (or ergocalciferol)
   and D[3] or cholecalciferol. Vitamin D is required for the formation of
   strong bones and teeth. It is manufactured in the skin by the
   activation of a sterol (7-dehydrocholesterol) by ultraviolet radiation
   (sunlight). Vitamin D is classified as a vitamin because it is required
   for metabolism and deficiency can result in disease, including rickets
   and osteoporosis.

Overview

   Vitamin D plays an important role in the maintenance of an intact and
   strong skeleton. The role traditionally attributed to the vitamin D
   system is to regulate the amount of calcium and phosphorus in the blood
   by ensuring correct intake from intestines and secretion. Vitamin D has
   also been implicated in a growing list of functions related to human
   biology.

   Vitamin D is produced in skin exposed to ultraviolet B radiation. The
   cholesterol precursor, 7-dehydrocholesterol, is unstable in UVB light,
   and the B-ring of the steroid structure breaks open to produce the
   seco-steroid, vitamin D3, more formally known as cholecalciferol. Diet
   is usually a minor secondary source of vitamin D, and even foods such
   as oily fish and eggs contain only very small amounts. It actualys
   plays the important role of acidic acid in the maintenance of
   preventing osteoperosis

Forms

     * Vitamin D[1]: molecular compound of ergocalciferol with lumisterol,
       1:1
     * Vitamin D[2]: ergocalciferol or calciferol (made from ergosterol)
     * Vitamin D[3]: cholecalciferol (made from 7-dehydrocholesterol).
       Cholecalciferol is the precursor of calcidiol, which in turn is the
       precursor of calcitriol
     * Vitamin D[4]: 22,23-dihydroergocalciferol
     * Vitamin D[5]: sitocalciferol (made from 7-dehydrositosterol)

   Vitamin D[2] is derived by irradiating fungi to produce ergocalciferol.
   Ergocalciferol does not naturally occur in the human body unless added
   by supplementation. In most mammals including humans, D[3] is more
   effective than D[2] at increasing 25-hydroxyvitamin D, the circulating
   reservoir of the vitamin D hormone. In the rat, D[2] is more effective
   as a vitamin than D[3], and in the squirrel monkey and the chick, D[3]
   is more effective.

   Vitamin D[3], also known as cholecalciferol, is the form of vitamin D
   that is natural to all animal life, including human. It is made in the
   skin when 7-dehydrocholesterol reacts with UVB ultraviolet light with
   wavelengths 290 to 315 nm. This light is present in sunlight when the
   sun at sea level is more than 45 degrees above the horizon (when your
   shadow is no longer than you are tall, or when the UV index is more
   than 3). Typically, 10,000   IU (250 micrograms) can be made in the
   skin only after one minimal erythemal dose of exposure, or until the
   skin just begins to turn pink. An equilibrium is achieved in the skin
   when longer exposure to UVB simply degrades the product as fast as it
   is generated.

Biochemistry

   Cholecalciferol is transported to the liver where it is hydroxylated to
   calcidiol or 25-hydroxy-vitamin D, the form of the vitamin that the
   body stores. A blood calcidiol level is the accepted way to determine
   vitamin D nutritional status. The optimal level of serum
   25-hydroxyvitamin D remains a contentious point for debate among
   medical scientists. One recent consensus concludes that for optimal
   prevention of osteoporotic fracture the concentration should be higher
   than 30 ng/mL (US units), which is equal to 75 nmol/L (System
   International units).

   The most active form of the vitamin is calcitriol (1,25 dihydroxy
   vitamin D[3]). This is both a potent hormone produced by the kidney and
   released into the circulation, and it is a paracrine/autocrine
   signalling molecule produced by many tissues for local regulation of
   cellular biology, but not released into the circulation. Calcitriol is
   synthesized from calcidiol in the kidneys to perform its endocrine
   function of maintaining the calcium economy. Calcitriol binds to a
   transcription factor which then regulates gene expression of transport
   proteins like TRPV6 and calbindin that are involved in calcium
   absorption in the intestine. The general result is the maintenance of
   calcium and phosphorus levels in the bone and blood with the assistance
   of parathyroid hormone and calcitonin.

   Biochemically, the various forms of vitamin D, including calcidiol
   (25D) and calcitriol (1,25(OH)2D) are secosteroids; i.e. broken-open
   steroids. Secosteroids are very similar in structure to steroids except
   that two of the B-ring carbon atoms (C9 and 10) of the typical four
   steroid rings are not fused, whereas in steroids they are fused.
   Molecular modeling calculations suggest that at least in theory,
   vitamin D might have an affinity for several steroid receptors,
   including glucocorticoid and thyroid receptors.

Synthesis mechanism (form 3)

   1. Vitamin D[3] is synthesized from 7-dehydrocholesterol, a derivative
   of cholesterol, which is then photolyzed by ultraviolet light in
   6-electron conrotatory electrocyclic reaction. The product is
   pre-vitamin D[3].
   2. Pre-vitamin D[3] then spontaneously isomerizes to Vitamin D[3] in a
   antarafacial hydride [1,7] Sigmatropic shift.
   3. Vitamin D[3] (cholecalciferol) is then hydroxylated in the liver to
   25-hydroxycholecalciferol (calcidiol) and stored until it is needed.
   25-hydroxycholecalciferol is further hydroxylated in the kidneys to the
   main biologically active form 1,25-dihydroxycholecalciferol
   (calcitriol) in a tightly regulated fashion. Calcitriol is represented
   below right (hydroxylated Carbon 1 is on the lower ring at right,
   hydroxylated Carbon 25 is at the upper right end).

Nutrition

   The U.S. Dietary Reference Intake (DRI) for an Adequate Intake (AI) for
   a 25-year old male for vitamin D is 5 micrograms/day (200 units/day).
   This rises to 15 micrograms/day (600 units/day) at age 70.

In food

   At higher latitudes, total vitamin D input from sunlight is usually not
   sufficient, especially in the winter. To minimize risk of low serum
   25-hydroxyvitamin D concentrations (the measure of vitamin D nutrition
   status), foods such as milk are often fortified with vitamin D[2] or
   vitamin D[3], typically giving 100  IU per glass. Fortified foods are
   the major dietary sources of vitamin D. Prior to the fortification of
   milk products with vitamin D in the 1930s, rickets, commonly caused by
   vitamin D deficiency, was a major public health problem. In the United
   States milk is fortified with 10 micrograms (400  IU) of vitamin D per
   quart, and rickets is now uncommon there.

   One cup of vitamin D fortified milk supplies about one-fourth of the
   official estimated adequate intake of vitamin for adults older than age
   50 years. Although milk is often fortified with vitamin D, dairy
   products made from milk (cheese, yogurt, ice cream, and so forth) are
   generally not. Only a few foods naturally contain significant amounts
   of vitamin D, including:
     * Shiitake mushrooms, one of a few natural sources of vegan and
       kosher vitamin D (vitamin D2),
     * Fish liver oils, such as cod liver oil, 1  Tbs. (15 mL), 1,360 IU
       (340% Daily value)
     * Fatty fish, such as:
          + Salmon, cooked, 3.5  oz, 360 IU (90% DV)
          + Mackerel, cooked, 3.5 oz, 345 IU (90% DV)
          + Sardines, canned in oil, drained, 1.75 oz, 250 IU (70% DV)
          + Tuna, canned in oil, 3 oz, 200 IU (50% DV)
          + Eel, cooked, 3.5 oz, 200 IU
     * One whole egg, 20 IU (6% DV)

   The U.S. Dietary Reference Intake Tolerable Upper Intake Level (UL) for
   a 25-year old male for vitamin D is 50 micrograms/day. This is
   equivalent to 2000 IU/day.

Diseases caused by deficiency

   Vitamin D deficiency is known to cause several bone diseases including:
     * Rickets: a childhood disease characterized by failure of growth and
       deformity of long bones.
     * Osteoporosis: a condition characterized by fragile bones.
     * Osteomalacia: a bone-thinning disorder in adults that is
       characterised by proximal muscle weakness and bone fragility.
       Osteomalacia can only occur in a mature skeleton.

   The isolation of vitamin D and its functional role in rickets was
   determined by Edward Mellanby between 1918– 1920. The 1928 Nobel Prize
   was awarded to Adolf Windaus, who discovered the steroid,
   7-dehydrocholesterol, the precursor of vitamin D.

   Vitamin D malnutrition may be linked to chronic diseases such as cancer
   ( breast, ovarian, colon, prostate, lung and skin cancer), chronic
   pain, several autoimmune diseases, high blood pressure, depression, and
   seasonal affective disorder.

   However, recent research indicates that in many chronic diseases where
   vitamin D levels (25 hydroxyvitamin D) appear to be low, vitamin D
   supplementation can actually cause long term harm. For example,
   supplementation with vitamin D is potentially hazardous for those with
   sarcoidosis and other diseases involving vitamin D hypersensitivity and
   dysregulation. There is increasing evidence for similar vitamin D
   hypersensitivity and dysregulation in a wide variety of autoimmune
   diseases, including rheumatoid arthritis and inflammatory bowel
   disease. Waterhouse et al reports vitamin D may appear to be low in
   these conditions, but only because it is being energetically converted
   to its active hormonal form (1,25 dihydroxyvitamin D) by disease
   processes.

Groups at greater risk

   Older people (age 50 and over) have a higher risk of developing vitamin
   D deficiency. The ability of skin to convert 7-dehydrocholesterol to
   pre-vitamin D[3] is decreased in older individuals. The kidneys, which
   help convert calcidiol to its active form, sometimes do not work as
   well when people age. Therefore, many older people may need vitamin D
   supplementation.

   Newborn infants who are exclusively breastfed require vitamin D
   supplements. Breast milk does not contain significant levels of the
   vitamin, and although infants could receive this vitamin from sunlight,
   parents are usually advised to avoid exposing babies to open sunshine.
   The Canadian and American Pediatric Associations advise vitamin D
   supplementation from birth onwards, with 200 IU/day (5 mcg/d) in the
   south up to 800 IU/day in the north. Infant formula is generally
   fortified with vitamin D, so this requirement only applies to breastfed
   infants. Liquid "drops" of vitamin D for infants usually include
   vitamin A or other vitamins, and are available in pharmacies. These
   products are either detergent-solublized water based preparations
   (given at 0.5-1 mL/day) or oil-based preparations. Vitamin D as a
   single infant nutrient is also available in an oil that is given as one
   drop/day ("Baby Drops" in North America, or "Vigantol oil" in Europe).

   Those who avoid or are not exposed to summer midday sunshine may also
   require vitamin D supplements. In particular, recent studies have shown
   Australians and New Zealanders are vitamin D deficient, particularly
   after the successful " Slip-Slop-Slap" health campaign encouraging
   Australians to cover up when exposed to sunlight to prevent skin
   cancer. Ironically, a vitamin D deficiency may also lead to skin
   cancer, although few minutes of exposure for light-skinned individuals
   may be all that is required; as the production of vitamin D is very
   rapid. However, the dermatology community contends that even a few
   minutes of unprotected ultraviolet exposure a day increases the risk of
   skin cancer and causes photoaging of the skin. Therefore,
   dermatologists are now recommending supplementation of vitamin D along
   with sunscreen use.

   Dark-skinned individuals may require extra vitamin D because melanin
   acts like a sun-block, prolonging the time required to generate vitamin
   D. This does not pose a problem at latitudes below about 30 degrees,
   where the sunshine is so high in the sky all year that enough vitamin D
   is produced despite the dark skin colour. At higher latitudes, however,
   the decreased angle of the sun's rays, reduced daylight hours in
   winter, and protective clothing worn to guard against cold weather
   diminish absorption of sunlight and the production of vitamin D.
   Light-skinned people at higher latitudes also face these problems, but
   the lower amount of pigmentation in their skin allows more sunlight to
   be absorbed, thereby reducing the risk of vitamin D deficiency.

   There is also evidence that obese people have lower levels of the
   circulating form of vitamin D, probably because it is deposited in body
   fat compartments and is less bioavailable, so obese people whose
   vitamin D production and intake is marginal or inadequate are at higher
   risk of deficiency. Patients with chronic liver disease or intestinal
   malabsorption may require larger doses of vitamin D (up to 40,000 IU or
   1 mg (1000 micrograms) daily). To maintain blood levels of calcium,
   therapeutic vitamin D doses are sometimes administered (up to
   100,000 IU or 2.5 mg daily) to patients who have had their parathyroid
   glands removed (most commonly renal dialysis patients who have had
   tertiary hyperparathyroidism, but also patients with primary
   hyperparathyroidism) or who suffer with hypoparathyroidism.

Overdose

   Vitamin D in the human body has a large volume of distribution and a
   long half-life. In any case all common foods and correctly-formulated
   vitamin pills contain such small amounts of viatmin D that overdose
   could never occur under normal circumstances. Indeed, Stoss therapy
   involves taking a dose over a thousand times the daily RDA once every
   few months, and even then often fails to normalise vitamin D[3] levels
   in the body. However, oral overdose has been recorded due to
   manufacturing and industrial accidents and leads to hypercalcaemia and
   atherosclerosis.

   The exact long-term safe dose is not entirely known, but intakes of up
   to 2000 IU (10x the RDA) are believed to be safe, and some researchers
   believe that 10,000 IU does not lead to long term overdose. It seems
   that there are chemical processes that destroy excess vitamin D, even
   when taken orally, although these processes have not been identified
   (in experiments blood levels of vitamin D do not continue to increase
   over many months at these doses as presumably would be needed for
   toxicity to occur.) Although normal food and pill vitamin D
   concentration levels are too low to be toxic, because of the high
   vitamin A content in cod-liver oil (if taken in multiples of the normal
   dose) it is possible to reach poisonous levels .

   Other research disputes the view that high vitamin D intake is benign.
   In one study, hypercalciuria and bone loss occurred at serum
   concentrations of 25D above approximately 50 ng/mL in patients
   supplementing with up to 3600 IU/day of D3. Another study showed
   elevated risk of ischaemic heart disease when 25D was above 89 ng/mL.
   In many chronic diseases, research indicates that vitamin D
   supplementation is inadvisable. There is increasing recognition that
   Th1 immune inflammation, occurring in rheumatic diseases can result in
   excessive numbers of activated macrophages converting 25-hydroxyvitamin
   D (25D) to its active 1,25 dihydroxyvitamin D (1,25D) hormonal form.
   This can lead to vitamin D dysregulation/hypersensitivity, which can
   lead to hypervitaminosis D, hypercalcemia and other symptoms. This is
   recognized as occurring in sarcoidosis and other diseases.

In cancer prevention and recovery

   Research suggests that cancer patients who have their surgery or
   treatment in the summer — and therefore get more vitamin D — have a
   better chance of surviving than those who undergo treatment in the
   winter when they are exposed to less sunlight.

   In 2005, U.S. scientists released a study, published in the American
   Journal of Public Health, which seems to demonstrate a beneficial
   correlation between vitamin D intake and prevention of cancer. Drawing
   from their meta-analysis of 63 published reports, the scientists
   claimed that an additional intake of 1,000 international units (IU) —
   or 25 micrograms — of the vitamin daily could lower an individual's
   cancer risk by 50% in colon cancer, and by 30% in breast and ovarian
   cancer. These are cross-sectional data, and thus the evidence is
   circumstantial. Longitudinal trials would be able to provide more
   conclusive proof of vitamin D's ability to prevent cancer.
   Retrieved from " http://en.wikipedia.org/wiki/Vitamin_D"
   This reference article is mainly selected from the English Wikipedia
   with only minor checks and changes (see www.wikipedia.org for details
   of authors and sources) and is available under the GNU Free
   Documentation License. See also our Disclaimer.
