What foods are bad to eat when you're on a come down from ecstasy?


Tips? Let your body rest, eat some food and get plenty of water, juice should be good because it has plenty of needed vitamin c after a night of nothing but water.

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Vitamin A
Key:FPIPGXGPPPQFEQ-OVSJKPMPSA-NYes  Vitamin A is a group of nutritionally unsaturated hydrocarbons, which include retinol, retinal, retinoic acid, and several provitamin A carotenoids, among which beta-carotene is the most important. Vitamin A has multiple functions, it is important for growth and development, for the maintenance of the immune system and good vision. Vitamin A is needed by the retina of the eye in the form of retinal, which combines with protein opsin to form rhodopsin the light-absorbing molecule , that is necessary for both low-light (scotopic vision) and color vision. Vitamin A also functions in a very different role as an irreversibly oxidized form of retinol known as retinoic acid, which is an important hormone-like growth factor for epithelial and other cells. In foods of animal origin, the major form of vitamin A is an ester, primarily retinyl palmitate, which is converted to retinol (chemically an alcohol) in the small intestine. The retinol form functions as a storage form of the vitamin, and can be converted to and from its visually active aldehyde form, retinal. The associated acid (retinoic acid), a metabolite that can be irreversibly synthesized from vitamin A, has only partial vitamin A activity, and does not function in the retina for the visual cycle. Retinoic acid is used for growth and cellular differentiation. All forms of vitamin A have a beta-ionone ring to which an isoprenoid chain is attached, called a retinyl group. Both structural features are essential for vitamin activity. The orange pigment of carrots – beta-carotene – can be represented as two connected retinyl groups, which are used in the body to contribute to vitamin A levels. Alpha-carotene and gamma-carotene also have a single retinyl group, which give them some vitamin activity. None of the other carotenes have vitamin activity. The carotenoid beta-cryptoxanthin possesses an ionone group and has vitamin activity in humans. Vitamin A can be found in two principal forms in foods: The discovery of vitamin A may have stemmed from research dating back to 1816, when physiologist Magendie, observed that dogs deprived of nutrition developed corneal ulcers and had high mortality rate. In 1912, Frederick Gowland Hopkins demonstrated that unknown "accessory factors" found in milk, other than carbohydrates, proteins, and fats were necessary for growth in rats. Hopkins received a Nobel Prize for this discovery in 1929. By 1917 one of these substances was independently discovered by Elmer McCollum at the University of Wisconsin–Madison, and Lafayette Mendel and Thomas Burr Osborne at Yale University who studied the role of fats in the diet. The "accessory factors" were termed "fat soluble" in 1918 and later "vitamin A" in 1920. In 1919, Steenbock (University of Wisconsin) proposed a relationship between yellow plant pigments (beta-carotene) and vitamin A. In 1931, a Swiss Chemist Paul Karrer described the chemical structure of vitamin A. Vitamin A was first synthesized in 1947 by two Dutch chemists, David Adriaan van Dorp and Jozef Ferdinand Arens. As some carotenoids can be converted into vitamin A, attempts have been made to determine how much of them in the diet is equivalent to a particular amount of retinol, so that comparisons can be made of the benefit of different foods. The situation can be confusing because the accepted equivalences have changed. For many years, a system of equivalencies in which an international unit (IU) was equal to 0.3 μg of retinol, 0.6 μg of β-carotene, or 1.2 μg of other provitamin-A carotenoids was used. Later, a unit called retinol equivalent (RE) was introduced. Prior to 2001, one RE corresponded to 1 μg retinol, 2 μg β-carotene dissolved in oil (it is only partly dissolved in most supplement pills, due to very poor solubility in any medium), 6 μg β-carotene in normal food (because it is not absorbed as well as when in oils), and 12 μg of either α-carotene, γ-carotene, or β-cryptoxanthin in food. Newer research has shown that the absorption of provitamin-A carotenoids is only half as much as previously thought. As a result, in 2001 the US Institute of Medicine recommended a new unit, the retinol activity equivalent (RAE). Each μg RAE corresponds to 1 μg retinol, 2 μg of β-carotene in oil, 12 μg of "dietary" beta-carotene, or 24 μg of the three other dietary provitamin-A carotenoids. Because the conversion of retinol from provitamin carotenoids by the human body is actively regulated by the amount of retinol available to the body, the conversions apply strictly only for vitamin A-deficient humans. The absorption of provitamins depends greatly on the amount of lipids ingested with the provitamin; lipids increase the uptake of the provitamin. The conclusion that can be drawn from the newer research is that fruits and vegetables are not as useful for obtaining vitamin A as was thought; in other words, the IUs that these foods were reported to contain were worth much less than the same number of IUs of fat-dissolved oils and (to some extent) supplements. This is important for vegetarians, as night blindness is prevalent in countries where little meat or vitamin A-fortified foods are available. A sample vegan diet for one day that provides sufficient vitamin A has been published by the Food and Nutrition Board (page 120). On the other hand, reference values for retinol or its equivalents, provided by the National Academy of Sciences, have decreased. The RDA (for men) of 1968 was 5000 IU (1500 μg retinol). In 1974, the RDA was set to 1000 RE (1000 μg retinol), whereas now the Dietary Reference Intake is 900 RAE (900 μg or 3000 IU retinol). This is equivalent to 1800 μg of β-carotene supplement (3000 IU) or 10800 μg of β-carotene in food (18000 IU). Vitamin A
Dietary Reference Intake: Adequate intakes (AI*)
μg/day μg/day 0–6 months
7–12 months 1–3 years
4–8 years 9–13 years
14–18 years
19 – >70 years 9–13 years
14–18 years
19 – >70 years <19 years
19 – >50 years <19 years
19 – >50 years (The limit is for synthetic and natural retinol ester forms of vitamin A. Carotene forms from dietary sources are not toxic.) According to the Institute of Medicine of the National Academies, "RDAs are set to meet the needs of almost all (97 to 98%) individuals in a group. For healthy breastfed infants, the AI is the mean intake. The AI for other life stage and gender groups is believed to cover the needs of all individuals in the group, but lack of data prevents being able to specify with confidence the percentage of individuals covered by this intake." Vitamin A is found naturally in many foods: Note: data taken from USDA database bracketed values are retinol activity equivalences (RAEs) and percentage of the adult male RDA, per 100 grams of the foodstuff (average). Conversion of carotene to retinol varies from person to person and bioavailability of carotene in food varies. Vitamin A plays a role in a variety of functions throughout the body, such as: The role of vitamin A in the visual cycle is specifically related to the retinal form. Within the eye, 11-cis-retinal is bound to protein "opsin" to form rhodospin in rods and iodopsin (cones) at conserved lysine residues. As light enters the eye, the 11-cis-retinal is isomerized to the all-"trans" form. The all-"trans" retinal dissociates from the opsin in a series of steps called photo-bleaching. This isomerization induces a nervous signal along the optic nerve to the visual center of the brain. After separating from opsin, the all-"trans"-retinal is recycled and converted back to the 11-"cis"-retinal form by a series of enzymatic reactions. In addition, some of the all-"trans" retinal may be converted to all-"trans" retinol form and then transported with an interphotoreceptor retinol-binding protein (IRBP) to the pigment epithelial cells. Further esterification into all-"trans" retinyl esters allow for storage of all-trans-retinol within the pigment epithelial cells to be reused when needed. The final stage is conversion of 11-cis-retinal will rebind to opsin to reform rhodopsin (visual purple) in the retina. Rhodopsin is needed to see in low light (contrast) as well as for night vision. Kühne showed that the regeneration of rhodopsin only occurs when retina is attached to retinal pigmented epithelial (RPE). It is for this reason that a deficiency in vitamin A will inhibit the reformation of rhodopsin and lead to one of the first symptoms, night blindness. Vitamin A, in the retinoic acid form, plays an important role in gene transcription. Once retinol has been taken up by a cell, it can be oxidized to retinal (retinaldehyde) by retinol dehydrogenases and then retinaldehyde can be oxidized to retinoic acid by retinaldehyde dehydrogenases. The conversion of retinaldehyde to retinoic acid is an irreversible step, meaning that the production of retinoic acid is tightly regulated, due to its activity as a ligand for nuclear receptors. The physiological form of retinoic acid (all-trans-retinoic acid) regulates gene transcription by binding to nuclear receptors known as retinoic acid receptors (RARs) which are bound to DNA as heterodimers with retinoid "X" receptors (RXRs). RAR and RXR must dimerize before they can bind to the DNA. RAR will form a heterodimer with RXR (RAR-RXR), but it does not readily form a homodimer (RAR-RAR). RXR, on the other hand, may form a homodimer (RXR-RXR) and will form heterodimers with many other nuclear receptors as well, including the thyroid hormone receptor (RXR-TR), the Vitamin D3 receptor (RXR-VDR), the peroxisome proliferator-activated receptor (RXR-PPAR) and the liver "X" receptor (RXR-LXR). The RAR-RXR heterodimer recognizes retinoic acid response elements (RAREs) on the DNA whereas the RXR-RXR homodimer recognizes retinoid "X" response elements (RXREs) on the DNA; although several RAREs near target genes have been shown to control physiological processes, this has not been demonstrated for RXREs. The heterodimers of RXR with nuclear receptors other than RAR (i.e. TR, VDR, PPAR, LXR) bind to various distinct response elements on the DNA to control processes not regulated by vitamin A. Upon binding of retinoic acid to the RAR component of the RAR-RXR heterodimer, the receptors undergo a conformational change that causes co-repressors to dissociate from the receptors. Coactivators can then bind to the receptor complex, which may help to loosen the chromatin structure from the histones or may interact with the transcriptional machinery. This response can upregulate (or downregulate) the expression of target genes, including Hox genes as well as the genes that encode for the receptors themselves (i.e. RAR-beta in mammals). Vitamin A, and more specifically, retinoic acid, appears to maintain normal skin health by switching on genes and differentiating keratinocytes (immature skin cells) into mature epidermal cells. Exact mechanisms behind pharmacological retinoid therapy agents in the treatment of dermatological diseases are being researched. For the treatment of acne, the most prescribed retinoid drug is 13-cis retinoic acid (isotretinoin). It reduces the size and secretion of the sebaceous glands. Although it is known that 40 mg of isotretinoin will break down to an equivalent of 10 mg of ATRA — the mechanism of action of the drug (original brand name Accutane) remains unknown and is a matter of some controversy. Isotretinoin reduces bacterial numbers in both the ducts and skin surface. This is thought to be a result of the reduction in sebum, a nutrient source for the bacteria. Isotretinoin reduces inflammation via inhibition of chemotactic responses of monocytes and neutrophils. Isotretinoin also has been shown to initiate remodeling of the sebaceous glands; triggering changes in gene expression that selectively induce apoptosis. Isotretinoin is a teratogen with a number of potential side-effects. Consequently, its use requires medical supervision. Vitamin A deprived rats can be kept in good general health with supplementation of retinoic acid. This reverses the growth-stunting effects of vitamin A deficiency, as well as early stages of xerophthalmia. However, such rats show infertility (in both male and females) and continued degeneration of the retina, showing that these functions require retinal or retinol, which are intraconvertable but which cannot be recovered from the oxidized retinoic acid. The requirement of retinol to rescue reproduction in vitamin A deficient rats is now known to be due to a requirement for local synthesis of retinoic acid from retinol in testis and embryos. Vitamin A deficiency is estimated to affect approximately one third of children under the age of five around the world. It is estimated to claim the lives of 670,000 children under five annually. Approximately 250,000–500,000 children in developing countries become blind each year owing to vitamin A deficiency, with the highest prevalence in Southeast Asia and Africa. Vitamin A deficiency can occur as either a primary or a secondary deficiency. A primary vitamin A deficiency occurs among children and adults who do not consume an adequate intake of provitamin A carotenoids from fruits and vegetables or preformed vitamin A from animal and dairy products. Early weaning from breastmilk can also increase the risk of vitamin A deficiency. Secondary vitamin A deficiency is associated with chronic malabsorption of lipids, impaired bile production and release, and chronic exposure to oxidants, such as cigarette smoke, and chronic alcoholism. Vitamin A is a fat soluble vitamin and depends on micellar solubilization for dispersion into the small intestine, which results in poor use of vitamin A from low-fat diets. Zinc deficiency can also impair absorption, transport, and metabolism of vitamin A because it is essential for the synthesis of the vitamin A transport proteins and as the cofactor in conversion of retinol to retinal. In malnourished populations, common low intakes of vitamin A and zinc increase the severity of vitamin A deficiency and lead physiological signs and symptoms of deficiency. A study in Burkina Faso showed major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children. Due to the unique function of retinal as a visual chromophore, one of the earliest and specific manifestations of vitamin A deficiency is impaired vision, particularly in reduced light – night blindness. Persistent deficiency gives rise to a series of changes, the most devastating of which occur in the eyes. Some other ocular changes are referred to as xerophthalmia. First there is dryness of the conjunctiva (xerosis) as the normal lacrimal and mucus-secreting epithelium is replaced by a keratinized epithelium. This is followed by the build-up of keratin debris in small opaque plaques (Bitot's spots) and, eventually, erosion of the roughened corneal surface with softening and destruction of the cornea (keratomalacia) and leading to total blindness. Other changes include impaired immunity (increased risk of ear infections, urinary tract infections, Meningococcal disease), hyperkeratosis (white lumps at hair follicles), keratosis pilaris and squamous metaplasia of the epithelium lining the upper respiratory passages and urinary bladder to a keratinized epithelium. With relations to dentistry, a deficiency in Vitamin A leads to enamel hypoplasia. Adequate supply, but not excess vitamin A, is especially important for pregnant and breastfeeding women for normal fetal development and in breastmilk. Deficiencies cannot be compensated by postnatal supplementation. Excess vitamin A, which is most common with high dose vitamin supplements, can cause birth defects and therefore should not exceed recommended daily values. Vitamin A metabolic inhibition as a result of alcohol consumption during pregnancy is the elucidated mechanism for fetal alcohol syndrome and is characterized by teratogenicity closely matching maternal vitamin A deficiency. Global efforts to support national governments in addressing vitamin A deficiency are led by the Global Alliance for Vitamin A (GAVA), which is an informal partnership between A2Z, the Canadian International Development Agency, Helen Keller International, the Micronutrient Initiative, UNICEF, USAID, and the World Bank. Joint GAVA activity is coordinated by the Micronutrient Initiative. While strategies include intake of vitamin A through a combination of breast feeding and dietary intake, delivery of oral high-dose supplements remain the principal strategy for minimizing deficiency. A meta-analysis of 43 studies showed that vitamin A supplementation of children under five who are at risk of deficiency reduces mortality by up to 24%. About 75% of the vitamin A required for supplementation activity by developing countries is supplied by the Micronutrient Initiative with support from the Canadian International Development Agency. Food fortification approaches are becoming increasingly feasible but cannot yet ensure coverage levels. The World Health Organization estimates that Vitamin A supplementation has averted 1.25 million deaths due to vitamin A deficiency in 40 countries since 1998. In 2008 it was estimated that an annual investment of US$60 million in vitamin A and zinc supplementation combined would yield benefits of more than US$1 billion per year, with every dollar spent generating benefits of more than US$17. These combined interventions were ranked by the Copenhagen Consensus 2008 as the world’s best development investment. Since vitamin A is fat-soluble, disposing of any excesses taken in through diet takes much longer than with water-soluble B vitamins and vitamin C. This allows for toxic levels of vitamin A to accumulate. In general, acute toxicity occurs at doses of 25,000 IU/kg of body weight, with chronic toxicity occurring at 4,000 IU/kg of body weight daily for 6–15 months. However, liver toxicities can occur at levels as low as 15,000 IU per day to 1.4 million IU per day, with an average daily toxic dose of 120,000 IU per day, particularly with excessive consumption of alcohol. In people with renal failure, 4000 IU can cause substantial damage. In addition, excessive alcohol intake can increase toxicity. Children can reach toxic levels at 1,500 IU/kg of body weight. Excessive vitamin A consumption can lead to nausea, irritability, anorexia (reduced appetite), vomiting, blurry vision, headaches, hair loss, muscle and abdominal pain and weakness, drowsiness, and altered mental status. In chronic cases, hair loss, dry skin, drying of the mucous membranes, fever, insomnia, fatigue, weight loss, bone fractures, anemia, and diarrhea can all be evident on top of the symptoms associated with less serious toxicity. Some of these symptoms are also common to acne treatment with Isotretinoin. Chronically high doses of vitamin A, and also pharmaceutical retinoids such as 13-cis retinoic acid, can produce the syndrome of pseudotumor cerebri. This syndrome includes headache, blurring of vision and confusion, associated with increased intracerebral pressure. Symptoms begin to resolve when intake of the offending substance is stopped. Chronic intake of 1500 RAE of preformed vitamin A may be associated with osteoporosis and hip fractures because it suppresses bone building while simultaneously stimulating bone breakdown. High vitamin A intake has been associated with spontaneous bone fractures in animals. Cell culture studies have linked increased bone resorption and decreased bone formation with high intakes. This interaction may occur because vitamins A and D may compete for the same receptor and then interact with parathyroid hormone, which regulates calcium. Indeed, a study by Forsmo et al. shows a correlation between low bone mineral density and too high intake of vitamin A. Toxic effects of vitamin A have been shown to significantly affect developing fetuses. Therapeutic doses used for acne treatment have been shown to disrupt cephalic neural cell activity. The fetus is particularly sensitive to vitamin A toxicity during the period of organogenesis. These toxicities only occur with preformed (retinoid) vitamin A (such as from liver). The carotenoid forms (such as beta-carotene as found in carrots), give no such symptoms, except with supplements and chronic alcoholism, but excessive dietary intake of beta-carotene can lead to carotenodermia, which causes orange-yellow discoloration of the skin. Smokers and chronic alcohol consumers have been observed to have increased risk of mortality due to lung cancer, esophageal cancer, gastrointestinal cancer and colon cancer. Hepatic (liver) injury has been found in human and animal studies where consumption of alcohol is paired with high dose vitamin A and beta-carotene supplementation. Researchers have succeeded in creating water-soluble forms of vitamin A, which they believed could reduce the potential for toxicity. However, a 2003 study found water-soluble vitamin A was approximately 10 times as toxic as fat-soluble vitamin. A 2006 study found children given water-soluble vitamin A and D, which are typically fat-soluble, suffer from asthma twice as much as a control group supplemented with the fat-soluble vitamins. In some studies, the use of Vitamin A supplements has been linked to an increased rate mortality, but there is minimal evidence to show this. Retinyl palmitate has been used in skin creams, where it is broken down to retinol and ostensibly metabolised to retinoic acid, which has potent biological activity, as described above. The retinoids (for example, 13-cis-retinoic acid) constitute a class of chemical compounds chemically related to retinoic acid, and are used in medicine to modulate gene functions in place of this compound. Like retinoic acid, the related compounds do not have full vitamin A activity, but do have powerful effects on gene expression and epithelial cell differentiation. Pharmaceutics utilizing mega doses of naturally occurring retinoic acid derivatives are currently in use for cancer, HIV, and dermatological purposes. At high doses, side-effects are similar to vitamin A toxicity. Severe side effects related to vitamin A toxicity, and a small optimal range of use are key obstacles in developing vitamin A-derived pharmaceutics for therapeutic use.][ M: NUT cof, enz, met noco, nuvi, sysi/epon, met drug (A8/11/12)

Vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for enhancing intestinal absorption of calcium and phosphate. In humans, the most important compounds in this group are vitamin D3 (also known as cholecalciferol) and vitamin D2 (ergocalciferol). Cholecalciferol and ergocalciferol can be ingested from the diet and from supplements. The body can also synthesize vitamin D (specifically cholecalciferol) in the skin, from cholesterol, when sun exposure is adequate (hence its nickname, the "sunshine vitamin"). Although vitamin D is commonly called a vitamin, it is not actually an essential dietary vitamin in the strict sense, as it can be synthesized in adequate amounts by most mammals exposed to sunlight. A substance is only classified as an essential vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from its diet. In common with other compounds commonly called vitamins, vitamin D was nevertheless discovered in an effort to find the dietary substance lacking in a disease, namely rickets, the childhood form of osteomalacia. Additionally, like other compounds called vitamins, in the developed world, vitamin D is added to staple foods, such as milk, to avoid disease due to deficiency. Synthesis from exposure to sunlight, as well as intake from the diet, generally contribute to the maintenance of adequate serum concentrations. Evidence indicates the synthesis of vitamin D from sun exposure is regulated by a negative feedback loop that prevents toxicity, but, because of uncertainty about the cancer risk from sunlight, no recommendations are issued by the Institute of Medicine, USA, for the amount of sun exposure required to meet vitamin D requirements. Accordingly, the Dietary Reference Intake for vitamin D assumes no synthesis occurs and all of a person's vitamin D is from food intake, although that will rarely occur in practice. Beyond its use to prevent osteomalacia or rickets, the evidence for other health effects of vitamin D supplementation in the general population is inconsistent. The best evidence of benefit is for bone health and a decrease in mortality in elderly women. In the liver, cholecalciferol (vitamin D3) is converted to calcidiol, which is also known as calcifediol (INN), 25-hydroxycholecalciferol, or 25-hydroxyvitamin D3 — abbreviated 25(OH)D3. Ergocalciferol (vitamin D2) is converted in the liver to 25-hydroxyergocalciferol, also known as 25-hydroxyvitamin D2 — abbreviated 25(OH)D2. These are the two specific vitamin D metabolites that are measured in serum to determine a person's vitamin D status. Part of the calcidiol is converted by the kidneys to 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 the healthy growth and remodeling of bone. Calcitriol also affects neuromuscular and immune function. American researchers Elmer McCollum and Marguerite Davis in 1914 discovered a substance in cod liver oil which later was called "vitamin A". British doctor Edward Mellanby noticed dogs that were fed cod liver oil did not develop rickets and concluded vitamin A, or a closely associated factor, could prevent the disease. In 1922, Elmer McCollum tested modified cod liver oil in which the vitamin A had been destroyed. The modified oil cured the sick dogs, so McCollum concluded the factor in cod liver oil which cured rickets was distinct from vitamin A. He called it vitamin D because it was the fourth vitamin to be named. It was not initially realized that, unlike other vitamins, vitamin D can be synthesised by humans through exposure to UV light. In 1925, it was established that when 7-dehydrocholesterol is irradiated with light, a form of a fat-soluble vitamin is produced (now known as D3). Alfred Fabian Hess showed "light equals vitamin D." Adolf Windaus, at the University of Göttingen in Germany, received the Nobel Prize in Chemistry in 1928, for his work on the constitution of sterols and their connection with vitamins. In 1929 a group at NIMR in Hampstead, London, were working on the structure of vitamin D, which was still unknown, as well as the structure of steroids. A meeting took place with J.B.S. Haldane, J.D. Bernal and Dorothy Crowfoot to discuss possible structures, which contributed to bringing a team together. X-ray crystallography demonstrated that sterol molecules were flat, not as proposed by the German team led by Windaus. In 1932, Otto Rosenheim and Harold King published a paper putting forward structures for sterols and bile acids which found immediate acceptance. The informal academic collaboration between the team members Robert Benedict Bourdillon, Otto Rosenheim, Harold King and Kenneth Callow was very productive and led to the isolation and characterization of vitamin D. At this time the policy of the Medical Research Council was not to patent discoveries, believing that results of medical research should be open to everybody. In the 1930s Windaus clarified further the chemical structure of vitamin D. In 1923, American biochemist Harry Steenbock at the University of Wisconsin demonstrated that irradiation by ultraviolet light increased the vitamin D content of foods and other organic materials. After irradiating rodent food, Steenbock discovered the rodents were cured of rickets. A vitamin D deficiency is a known cause of rickets. Using $300 of his own money, Steenbock patented his invention. His irradiation technique was used for foodstuffs, most memorably for milk. By the expiration of his patent in 1945, rickets had been all but eliminated in the US. In 1971–72, the further metabolism of vitamin D to active forms was discovered. In the liver, vitamin D was found to be converted to calcidiol. Part of the calcidiol is then converted by the kidneys to 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 the healthy growth and remodeling of bone. Both calcidiol and calcitriol were identified by a team led by Michael F. Holick in the laboratory of Hector DeLuca. Vitamin D deficiency causes osteomalacia (called rickets when it occurs in children). Beyond that, low serum vitamin D levels have been associated with falls, and low bone mineral density. In 2012, the US Preventive Services Task Force issued a draft statement stating not enough evidence is available to indicate that healthy postmenopausal women should use supplemental doses of calcium or vitamin D to prevent fractures. Some studies have shown that supplementation with vitamin D and calcium may improve bone mineral density slightly, as well as decreasing the risk of falls and fractures in certain groups of people, specifically those older than 65 years. This appears to apply more to people in institutions than those living independently. The quality of the evidence is, however, poor. And there does not appear to be a benefit to bone health from vitamin D without sufficient calcium. Low blood levels of vitamin D are associated with increased mortality, and giving supplementary vitamin D3 to elderly women in institutional care seems to decrease the risk of death. Vitamin D2, alfacalcidol, and calcitriol do not appear to be effective. However, both an excess and a deficiency in vitamin D appear to cause abnormal functioning and premature aging. The relationship between serum calcidiol level and all-cause mortality is parabolic, Harm from vitamin D appears to occur at a lower vitamin D level in the black population than in the white population.:435 Though low levels of circulating vitamin D may be associated with a higher death rate in some cancers, it is not known whether low vitamin D status increases mortality from cancer or is just a consequence of poorer general health caused by cancer. Studies into the possible effect of vitamin D supplementation on the survival of cancer patients produce contradictory and inconclusive results. The currently available evidence is insufficient to recommend vitamin D supplementation in cancer patients. If there is a causal relationship between serum vitamin D level and prognosis, the relationship may not be a simple linear one. One study found that the relationship may be U-shaped instead, with a higher risk of death at both serum levels less than 32 ng/mL and greater than 44 ng/mL. That is, both hypovitaminosis D and hypervitaminosis D may negatively affect prognosis in cancer patients. That another study found both low and high serum vitamin D levels are associated with a higher prostate cancer risk suggests both conditions may stimulate cancer growth. Evidence for health effects from vitamin D supplementation for cardiovascular health is poor. Moderate to high doses may reduce cardiovascular disease risk but are of questionable clinical significance. In general, vitamin D functions to activate the innate and dampen the adaptive immune systems. Vitamin D deficiency has been linked to increased risk of viral infections. It has been postulated to play a role in influenza with lack of vitamin D synthesis during the winter as one explanation for high rates of influenza infection during the winter. For viral infections, other implicated factors include low relative humidities produced by indoor heating and low temperatures that favor virus spread.][ Low levels of vitamin D appear to be a risk factor for tuberculosis, and historically it was used as a treatment. As of 2011, it is being investigated in controlled clinical trials. Vitamin D may also play a role in HIV. Although there are tentative data linking low levels of vitamin D to asthma, there is inconclusive evidence to support a beneficial effect from supplementation. Accordingly, supplementation is not currently recommended for treatment or prevention of asthma. Low levels of vitamin D are associated with multiple sclerosis. Supplementation with vitamin D may have a protective effect, but there are uncertainties and unanswered questions. "The reasons why vitamin D deficiency is thought to be a risk factor for MS are as follows: (1) MS frequency increases with increasing latitude, which is strongly inversely correlated with duration and intensity of UVB from sunlight and vitamin D concentrations; (2) prevalence of MS is lower than expected at high latitudes in populations with high consumption of vitamin-D-rich fatty fish; and (3) MS risk seems to decrease with migration from high to low latitudes." A clinical trial sponsored by Charite University in Berlin, Germany, was begun in 2011, with the goal of examining the efficacy, safety, and tolerability of vitamin D3 in the treatment of multiple sclerosis. Low levels of vitamin D in pregnancy are associated with gestational diabetes, pre-eclampsia, and small infants. The benefit of supplements, however, is unclear. Pregnant women who take an adequate amount of vitamin D during gestation may experience positive immune effects. Pregnant women often do not take the recommended amount of vitamin D. A trial of supplementation has found 4000 IU of vitamin D3 superior to lesser amount in pregnant women for achieving specific target blood levels. A diet deficient in vitamin D causes osteomalacia (or rickets when it occurs in children), which is a softening of the bones. In the developed world, this is a rare disease. However, vitamin D deficiency has become worldwide issue in the elderly and remains common in children and adults. Low blood calcidiol (25-hydroxy-vitamin D) can result from avoiding the sun. Deficiency results in impaired bone mineralization and bone damage which leads to bone-softening diseases including: Rickets, a childhood disease, is characterized by impeded growth, soft, weak, deformity of the long bones that bend and bow under their weight as children start to walk. This condition is characterized by bow legs, which can be caused by calcium or phosphorus deficiency, as well as a lack of vitamin D; today, it is largely found in low-income countries in Africa, Asia, or the Middle East and in those with genetic disorders such as pseudovitamin D deficiency rickets. Rickets was first described in 1650 by Francis Glisson, who said it had first appeared about 30 years previously in the counties of Dorset and Somerset. In 1857, John Snow suggested that rickets, then widespread in Britain, was being caused by the adulteration of bakers' bread with alum. The role of diet in the development of rickets was determined by Edward Mellanby between 1918–1920. Nutritional rickets exists in countries with intense year-round sunlight such as Nigeria and can occur without vitamin D deficiency. Although rickets and osteomalacia are now rare in Britain, there have been outbreaks in some immigrant communities in which osteomalacia sufferers included women with seemingly adequate daylight outdoor exposure wearing Western clothing. Having darker skin and reduced exposure to sunshine did not produce rickets unless the diet deviated from a Western omnivore pattern characterized by high intakes of meat, fish, and eggs, and low intakes of high-extraction cereals. The dietary risk factors for rickets include abstaining from animal foods. Vitamin D deficiency remains the main cause of rickets among young infants in most countries, because breast milk is low in vitamin D and social customs and climatic conditions can prevent adequate UVB exposure. In sunny countries such as Nigeria, South Africa, and Bangladesh, where the disease occurs among older toddlers and children, it has been attributed to low dietary calcium intakes, which are characteristic of cereal-based diets with limited access to dairy products. Rickets was formerly a major public health problem among the US population; in Denver, where ultraviolet rays are approximately 20% stronger than at sea level on the same latitude, almost two-thirds of 500 children had mild rickets in the late 1920s. An increase in the proportion of animal protein in the 20th century American diet coupled with increased consumption of milk fortified with relatively small quantities of vitamin D coincided with a dramatic decline in the number of rickets cases. Also, in the United States and Canada, vitamin D fortified milk, infant vitamin supplements, and vitamin supplements have helped to eradicate majority of rickets for children with fat malabsorption conditions. Osteomalacia is a disease in adults that results from vitamin D deficiency. Characteristics of this disease are softening of the bones, leading to bending of the spine, bowing of the legs, proximal muscle weakness, bone fragility, and increased risk for fractures. Osteomalacia reduces calcium absorption and increases calcium loss from bone, which increases the risk for bone fractures. Osteomalacia is usually present when 25-hydroxyvitamin D levels are less than about 10 ng/mL. The effects of osteomalacia are thought to contribute to chronic musculoskeletal pain, There is no persuasive evidence of lower vitamin D levels in chronic pain sufferers. Osteoporosis is defined as a bone disease characterized by a decrease in bone mineral density and the appearance of small holes in bones due to loss of minerals. Vitamin D inadequacy is common among patients with osteoporosis. Vitamin D inadequacy is seen with low serum 25-hydroxyvitamin D levels of less than 20 ng/mL, however, this value can vary. Osteoporosis and osteomalacia are closely associated, as both have similar symptoms for higher risk of fractures and bone loss. Supplementing with vitamin D can increase bone density and slow bone turnover in seniors. Also, supplementation for individuals with low vitamin D blood levels can significantly improve the reduction in risk of osteoporotic fractures, especially hip fractures. Some research shows that dark-skinned people living in temperate climates have lower vitamin D levels. It has been suggested that dark-skinned people are less efficient at making vitamin D because melanin in the skin hinders vitamin D synthesis; however, a recent study has found novel evidence that low vitamin D levels among Africans may be due to other reasons. Recent evidence implicates parathyroid hormone in adverse cardiovascular outcomes. Black women have an increase in serum PTH at a lower 25(OH)D level than white women. A large scale association study of the genetic determinants of vitamin D insufficiency in Caucasians found no links to pigmentation. On the other hand, the uniform occurrence of low serum 25(OH)D in Indians living in India and Chinese in China, does not support the hypothesis that the low levels seen in the more pigmented are due to lack of synthesis from the sun at higher latitudes. The leader of the study has urged dark-skinned immigrants to take vitamin D supplements nonetheless, saying, "I see no risk, no downside, there's only a potential benefit. " Vitamin D toxicity is rare. The threshold for vitamin D toxicity has not been established; however, the tolerable upper intake level (UL) is 4000 IU/day for ages 9–71. Vitamin D toxicity is not caused by sunlight exposure, but can be caused by supplementing with high doses of vitamin D. In healthy adults, sustained intake of more than 1250 micrograms/day (50,000 IU) can produce overt toxicity after several months and can increase serum 25-hydroxyvitamin D levels to 150 ng/mL and greater; those with certain medical conditions, such as primary hyperparathyroidism, are far more sensitive to vitamin D and develop hypercalcemia in response to any increase in vitamin D nutrition, while maternal hypercalcemia during pregnancy may increase fetal sensitivity to effects of vitamin D and lead to a syndrome of mental retardation and facial deformities. Since hypercalcemia is a strong indication of vitamin D toxicity, this condition is noted with an increase in urination and thirst. If hypercalcemia is not treated, it results in excess deposits of calcium in soft tissues and organs such as the kidneys, liver, and heart, resulting in pain and organ damage. Pregnant or breastfeeding women should consult a doctor before taking a vitamin D supplement. The FDA advised manufacturers of liquid vitamin D supplements that droppers accompanying these products should be clearly and accurately marked for 400 international units (IU). In addition, for products intended for infants, the FDA recommends that the dropper hold no more than 400 IU. For infants (birth to 12 months), the tolerable upper limit (maximum amount that can be tolerated without harm) is set at 25 micrograms/day (1000 IU). One thousand micrograms (40,000 IU) per day in infants has produced toxicity within one month. After being commissioned by the Canadian and American governments, the Institute of Medicine (IOM) as of 30 November 2010[update], has increased the tolerable upper limit (UL) to 2500 IU per day for ages 1–3 years, 3000 IU per day for ages 4–8 years and 4000 IU per day for ages 9–71+ years (including pregnant or lactating women). Vitamin D overdose causes hypercalcemia, and the main symptoms of vitamin D overdose are those of hypercalcemia: anorexia, nausea, and vomiting can occur, frequently followed by polyuria, polydipsia, weakness, insomnia, nervousness, pruritus, and, ultimately, renal failure. 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 bone growth and formation, diarrhea, irritability, weight loss, and severe depression. Vitamin D toxicity is treated by discontinuing vitamin D supplementation and restricting calcium intake. Kidney damage may be irreversible. Exposure to sunlight for extended periods of time does not normally cause vitamin D toxicity. Within about 20 minutes of ultraviolet exposure in light-skinned individuals (3–6 times longer for pigmented skin), the concentrations of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D that is produced is degraded. Published cases of toxicity involving hypercalcemia in which the vitamin D dose and the 25-hydroxy-vitamin D levels are known all involve an intake of ≥40,000 IU (1000 μg) per day. Recommending supplementation, when those supposedly in need of it are labeled healthy, has proved contentious, and doubt exists concerning long term effects of attaining and maintaining high serum 25(OH)D by supplementation. The effects of vitamin D supplementation on health are uncertain. A United States Institute of Medicine, (IOM) report states: "Outcomes related to cancer, cardiovascular disease and hypertension, diabetes and metabolic syndrome, falls and physical performance, immune functioning and autoimmune disorders, infections, neuropsychological functioning, and preeclampsia could not be linked reliably with calcium or vitamin D intake and were often conflicting.":5 Some researchers claim the IOM was too definitive in its recommendations and made a mathematical mistake when calculating the blood level of vitamin D associated with bone health. Members of the IOM panel maintain that they used a "standard procedure for dietary recommendations" and that the report is solidly based on the data. Research on vitamin D supplements, including large scale clinical trials, is continuing. The Director General of Research and Development and Chief Scientific Adviser for the UK Department of Health and NHS said that children aged six months to five years should be given vitamin D supplements, particularly during the winter. However, vitamin D supplements are not recommended for people who get enough vitamin D from their diets and from sunlight. Several forms (vitamers) of vitamin D exist (see table). The two major forms are vitamin D2 or ergocalciferol, and vitamin D3 or cholecalciferol; vitamin D without a subscript refers to either D2 or D3 or both. These are known collectively as calciferol. Vitamin D2 was chemically characterized in 1931. In 1935, the chemical structure of vitamin D3 was established and proven to result from the ultraviolet irradiation of 7-dehydrocholesterol. Chemically, the various forms of vitamin D are secosteroids; i.e., steroids in which one of the bonds in the steroid rings is broken. The structural difference between vitamin D2 and vitamin D3 is in their side chains. The side chain of D2 contains a double bond between carbons 22 and 23, and a methyl group on carbon 24. Vitamin D3 (cholecalciferol) is produced through the action of ultraviolet irradiation (UV) on its precursor 7-dehydrocholesterol. Our skin makes vitamin D3 and supplies about 90 percent of our vitamin D. This molecule occurs naturally in the skin of animals and in milk. Vitamin D3 can be made by exposure of the skin to UV, or by exposing milk directly to UV (one commercial method). Vitamin D3 is also found in oily fish and cod liver oil. Vitamin D2 is a derivative of ergosterol, a membrane sterol named for the ergot fungus, which is produced by some kinds of phytoplankton, invertebrates, yeasts, and higher fungi such as mushrooms. The vitamin ergocalciferol (D2) is produced in all of these organisms from ergosterol, in response to UV irradiation. Like all forms of vitamin D, it cannot be produced without UV irradiation. D2 is not produced by green land plants or vertebrates, because they lack the precursor ergosterol. The biological fate for producing 25(OH)D from vitamin D2 is expected to be the same as for 25(OH)D3, although some controversy exists over whether or not D2 can fully substitute for vitamin D3 in the human diet.
The transformation that converts 7-dehydrocholesterol to Vitamin D3 (cholecalciferol) occurs in two steps. First, 7-dehydrocholesterol, is photolyzed by ultraviolet light in a 6-electron conrotatory electrocyclic reaction. The product is 3previtamin D. Second, previtamin D3 spontaneously isomerizes to vitamin D3 (cholecalciferol) in an antarafacial sigmatropic [1,7] hydride shift. At room temperature, the transformation of previtamin D3 to vitamin D3 takes about 12 days to complete. Photosynthesis of vitamin D in the ocean by phytoplankton (such as coccolithophore and Emiliania huxleyi) has existed for more than 500 million years and continues to the present. Although primitive vertebrates in the ocean could absorb calcium from the ocean into their skeletons and eat plankton rich in vitamin D, land animals required another way to satisfy their vitamin D requirement for a calcified skeleton without relying on plants. Land vertebrates have been making their own vitamin D for more than 350 million years. Vitamin D can be synthesized only via a photochemical process, so land vertebrates had to ingest foods that contained vitamin D or had to be exposed to sunlight to photosynthesize vitamin D in their skin to satisfy their body's vitamin D requirement.
Vitamin D3 (cholecalciferol) is produced photochemically in the skin from 7-dehydrocholesterol. The precursor of vitamin D3, 7-Dehydrocholesterol is produced in relatively large quantities, 10,000 to 20,000 IU of vitamin D are produced in 30 minutes of whole-body exposure, in the skin of most vertebrate animals, including humans. 7-dehydrocholesterol reacts with ultraviolet light of UVB type at wavelengths between 270 and 300 nm, with peak synthesis occurring between 295 and 297 nm. These wavelengths are present in sunlight when the UV index is greater than three, as well as in the light emitted by the UV lamps in tanning beds (which produce ultraviolet primarily in the UVA spectrum, but typically produce 4% to 10% of the total UV emissions as UVB). At a UV index greater than three, which occurs daily within the tropics, daily during the spring and summer seasons in temperate regions, and almost never within the arctic circles, vitamin D3 can be made in the skin. Even if the UV index is high enough, exposure to light through windows is insufficient because glass almost completely blocks UVB light. Depending on the intensity of UVB rays and the minutes of exposure, an equilibrium can develop in the skin, and vitamin D degrades as fast as it is generated. The skin consists of two primary layers: the inner layer called the dermis, composed largely of connective tissue, and the outer, thinner epidermis. Thick epidermis in the soles and palms consists of five strata; from outer to inner they are: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Vitamin D is produced in the two innermost strata, the stratum basale and stratum spinosum. The naked mole rat appears to be naturally cholecalciferol deficient, as serum 25-OH vitamin D levels are undetectable. In some animals, the presence of fur or feathers blocks the UV rays from reaching the skin. In birds and fur-bearing mammals, vitamin D is generated from the oily secretions of the skin deposited onto the feathers or fur and is obtained orally during grooming. Sunscreen absorbs ultraviolet light and prevents it from reaching the skin. It has been reported that sunscreen with a sun protection factor (SPF) of 8 based on the UVB spectrum can decrease vitamin D synthetic capacity by 95 percent, whereas sunscreen with an SPF of 15 can reduce synthetic capacity by 98 percent.
Vitamin D is carried in the bloodstream to the liver, where it is converted into the prohormone calcidiol. Circulating calcidiol may then be converted into calcitriol, the biologically active form of vitamin D, in the kidneys. Following the final converting step in the kidney, calcitriol (the physiologically active form of vitamin D) is released into the circulation. By binding to vitamin D-binding protein (VDBP), a carrier protein in the plasma, calcitriol is transported to various target organs. In addition to the kidneys, calcitriol is also synthesized by monocyte-macrophages in the immune system. When synthesized by monocyte-macrophages, calcitriol acts locally as a cytokine, defending the body against microbial invaders by stimulating the innate immune system. Whether it is made in the skin or ingested, cholecalciferol is hydroxylated in the liver at position 25 (upper right of the molecule) to form 25-hydroxycholecalciferol (calcidiol or 25(OH)D). This reaction is catalyzed by the microsomal enzyme vitamin D 25-hydroxylase, which is produced by hepatocytes. Once made, the product is released into the plasma, where it is bound to an α-globulin, vitamin D binding protein. Calcidiol is transported to the proximal tubules of the kidneys, where it is hydroxylated at the 1-α position (lower right of the molecule) to form calcitriol (aka 1,25-dihydroxycholecalciferol and abbreviated to 1,25(OH)2D). This product is a potent ligand of the vitamin D receptor (VDR), which mediates most of the physiological actions of the vitamin. The conversion of calcidiol to calcitriol is catalyzed by the enzyme 1-alpha-hydroxylase325-hydroxyvitamin D, the levels of which are increased by parathyroid hormone (and additionally by low calcium or phosphate).
The active vitamin D metabolite calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is principally located in the nuclei of target cells. The binding of calcitriol to the VDR allows the VDR to act as a transcription factor that modulates the gene expression of transport proteins (such as TRPV6 and calbindin), which are involved in calcium absorption in the intestine. The vitamin D receptor belongs to the nuclear receptor superfamily of steroid/thyroid hormone receptors, and VDRs are expressed by cells in most organs, including the brain, heart, skin, gonads, prostate, and breast. VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the maintenance of calcium and phosphorus levels in the blood (with the assistance of parathyroid hormone and calcitonin) and to the maintenance of bone content. One of the most important roles of vitamin D is to maintain skeletal calcium balance by promoting calcium absorption in the intestines, promoting bone resorption by increasing osteoclast number, maintaining calcium and phosphate levels for bone formation, and allowing proper functioning of parathyroid hormone to maintain serum calcium levels. Vitamin D deficiency can result in lower bone mineral density and an increased risk of reduced bone density (osteoporosis) or bone fracture because a lack of vitamin D alters mineral metabolism in the body. Thus, although it may initially appear paradoxical, vitamin D is also critical for bone remodeling through its role as a potent stimulator of bone resorption. The VDR is known to be involved in cell proliferation and differentiation. Vitamin D also affects the immune system, and VDRs are expressed in several white blood cells, including monocytes and activated T and B cells. Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells. It also is involved in the biosynthesis of neurotrophic factors, synthesis of nitric oxide synthase, and increased glutathione levels. Apart from VDR activation, various alternative mechanisms of action are known. An important one of these is its role as a natural inhibitor of signal transduction by hedgehog (a hormone involved in morphogenesis). Click on genes, proteins and metabolites below to link to respective articles. Different institutions propose different recommendations concerning daily amounts of the vitamin. Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. (Conversion : 1 µg = 40 IU and 0.025 µg = 1 IU) About a third of Australians have vitamin D deficiency. Australia and New Zealand have established average intakes for vitamin D, as follows: children 5.0 μg /day; adults 19–50 yr 5.0 μg/day, 51–70 yr 10.0 μg/day, >70 yr 15.0 μg/day. According to Health Canada the recommended dietary allowances (RDA) for vitamin D are: Note*: Adequate Intake rather than Recommended Dietary Allowance. The recommended daily amount for vitamin D in the European Union is 5 µg. The European Menopause and Andropause Society (EMAS) recommended 15 µg (600 IU) until age 70, and 20 µg (800 IU) in older than 71 years, in postmenopausal women. This dose should be increased up to 4,000 IU/day in some patients with very low vitamin D status or in case of co-morbid conditions. According to the European Food Safety Authority the Tolerable Upper Intake Levels are: According to the United States Institute of Medicine, the recommended dietary allowances of vitamin D are: The Tolerable Upper Intake Level is defined as "the highest average daily intake of a nutrient that is likely to pose no risk of adverse health effects for nearly all persons in the general population.:403 " Although tolerable upper intake levels are believed to be safe, information on the long-term effects is incomplete and these levels of intake are not recommended::403:433 The Dietary Reference Intake for vitamin D issued by the American (U.S.) Institute of Medicine (IOM) in 2010 superseded a previous recommendation which had Adequate Intake status. The recommendations were formed assuming the individual has no skin synthesis of vitamin D because of inadequate sun exposure. The reference intake for vitamin D refers to total intake from food, beverages and supplements, is intended for the North American population, and assumes that calcium requirements are being met.:5 One school of thought contends that human physiology is fine tuned to an intake of 4000–12,000 IU/day from sun exposure with concomitant serum 25-hydroxyvitamin D levels of 40 to 80 ng/mL and that this is required for optimal health. Proponents of this view, who include some members of the panel that drafted a now superseded 1997 report on vitamin D from the Institute of Medicine, contend that the IOM's warning about serum concentrations above 50 ng/mL lacks biological plausibility. They suggest that for some people reducing the risk of preventable disease requires a higher level of vitamin D than that recommended by the IOM. US labs generally report 25(OH)D levels as ng/mL. Other countries often use nmol/L. A U.S. Institute of Medicine committee concluded that a serum 25-hydroxyvitamin D level of 20 ng/mL (50 nmol/L) is desirable for bone and overall health. The Dietary Reference Intakes for vitamin D are chosen with a margin of safety and 'overshoot' the targeted serum value to ensure that the specified levels of intake achieve the desired serum 25-hydroxyvitamin D levels in almost all persons. It is assumed there are no contributions to serum 25-hydroxyvitamin D level from sun exposure and the recommendations are fully applicable to people with dark skin or negligible exposure to sunlight.:1 The Institute found that serum 25-hydroxyvitamin D concentrations above 30 ng/mL (75 nmol/L) are "not consistently associated with increased benefit". Serum 25-hydroxyvitamin D levels above 50 ng/mL (125 nmol/L) may be cause for concern. However, the desired range of serum 25-hydroxyvitamin D is between 20-50 ng/mL. There is a lower risk of cardiovascular disease when vitamin D ranged from 20 to 60 nmol/L (8 to 24 ng/mL). There appears to be a "threshold effect" once 60 nmol/L (24 ng/mL) have been reached i.e., levels of vitamin D over 60 nmol/L did not show added benefit. Apart from the above discussion on health effects or scientific evidence for lowering disease risk, governmental regulatory agencies stipulate for the food industry health claims allowable as statements on packaging. European Food Safety Authority (EFSA) US Food and Drug Administration (FDA) Health Canada Other possible agencies with claim guidance: Japan FOSHU and Australia-New Zealand. Vitamin D is found in few dietary sources. Sunlight exposure is the primary source of vitamin D for majority of people, other than supplements. Fungus, from USDA nutrient database (per 100 g): Vitamin D2, or ergocalciferol found in fungi, is synthesized from viosterol, which in turn is activated when ultraviolet light stimulates ergosterol. Human bioavailability of vitamin D2 from vitamin D2-enhanced button mushrooms via UV-B irradiation is effective in improving vitamin D status and not different from a vitamin D2 supplement. from UV-irradiated yeast baked into bread is bioavailable. By visual assessment or using a chromometer, no significant discoloration of irradiated mushrooms, as measured by the degree of "whiteness", was observed. Claims have been made that a normal serving (approx. 3 oz or 1/2 cup, or 60 grams) of fresh mushrooms treated with ultraviolet light have increased vitamin D content to levels up to 80 micrograms, or 2700 IU if exposed to just 5 minutes of UV light after being harvested. Plants In some countries, staple foods are artificially fortified with vitamin D. Vitamin D3 (cholecalciferol) is produced industrially by exposing 7-dehydrocholesterol to UVB light, followed by purification. The 7-dehydrocholesterol is a natural substance in wool grease (lanolin) from sheep or other woolly animals. Vitamin D2 (ergocalciferol) is produced in a similar way using ergosterol from yeast or mushrooms as a starting material. M: NUT cof, enz, met noco, nuvi, sysi/epon, met drug (A8/11/12) Testis: testosterone  AMH  inhibin Ovary: estradiol  progesterone  activin and inhibin  relaxin (pregnancy) Thymus: Thymosin (Thymosin α1, Thymosin beta)  Thymopoietin  Thymulin Digestive system: Stomach: gastrin  ghrelin  Duodenum: CCK  Incretins (GIP, GLP-1)   secretin  motilin  VIP  Ileum: enteroglucagon  peptide YY  Liver/other: Insulin-like growth factor (IGF-1, IGF-2) Adipose tissue: leptin  adiponectin  resistin Skeleton: Osteocalcin Kidney: JGA (renin)  peritubular cells (EPO)  calcitriol  prostaglandin M: END anat/phys/devp/horm noco (d)/cong/tumr, sysi/epon proc, drug (A10/H1/H2/H3/H5)

Vegetable juice
Vegetable juice (also referred as: Green Drink) is a drink made primarily of blended vegetables and also available in the form of powders. Vegetable juice is often mixed with fruits such as tomatoes or grapes to improve flavor. It is often touted as a low-sugar alternative to fruit juice, although some commercial brands of vegetable juices use fruit juices as sweeteners, and may contain large amounts of sodium. Making vegetable juice at home is an alternative to buying commercial juices, and may be beneficial for supplementing diets low in vegetables and fruits. Special vegetable juicers are recommended for blending vegetables, as they employ either a slow-geared grinding mechanism or a unit powered by centrifugal force. Compared to a higher speed blender or fruit juicer, the slower speed protects the vegetables from oxidation and heat (from friction), which reduces nutrient breakdown. Commercial vegetable juices are commonly made from varying combinations of carrots, beets, pumpkin, and tomatoes. The latter two, although not technically vegetables, are commonly used to increase palatability. Other popular items in vegetable juices are parsley, dandelion greens, kale, celery, fennel, and cucumbers. Lemon, garlic and ginger may be added by some for medicinal purposes. Other common juices include carrot juice, tomato juice, turnip juice, and V8 Juice. In Asian cultures, primarily Chinese, Dioscorea opposita (Chinese: shān yào, Japanese: nagaimo) is also used for vegetable juices. They are used quite sparingly, however, for many Chinese consider it to be a medicine rather than a vegetable. Kale juice marketed as Aojiru in Japan has become well known for its purported health benefits and bitter taste. Japan also markets several kinds of vegetable juices which, unlike Western juices such as V8, usually depend on carrots and fruits instead of large amounts of tomato juice for their flavor. The Yasai Seikatsu brand by Kagome is a popular variety, and is even an option in McDonald's Happy Meals in Japan. In general, vegetable juices are recommended as supplements to whole vegetables, rather than as a replacement. However, the actual nutritional value of juices versus whole vegetables is still contested. USDA guidelines for Americans states that 3/4 cup of 100% vegetable juice is equivalent to one serving of vegetables. This is upheld by a recent study, which found that juices provide the same health benefits as whole vegetables in terms of reducing risks of cardiovascular disease and cancer. Another study has found that drinking vegetable juice reduces risks of Alzheimer's Disease by 76%. However, the British Nutrition Foundation holds that although vegetable juice counts as a serving, it can only count as one serving, regardless of the amount of juice drunk. It is unclear whether this is referring to commercial juices only, or includes home-made juices. Additionally, A 2007 Japanese study showed that although Japanese commercial juices had nutritional benefits, they were insufficient as a primary mode of vegetable consumption. Many popular vegetable juices, particularly ones with high tomato content, are high in sodium, and therefore consumption of them for health must be carefully considered. Some vegetables such as beets also contain large amounts of sugar, so care must be taken when adding these to juices. Although the actual nutritional benefits of vegetable juice are contested, a recent UC Davis study found that drinking vegetable juice daily significantly increased drinkers' chances of meeting the daily recommended number of vegetable servings. Having an easy source of vegetables encouraged drinkers to incorporate more vegetables into their diets.

Vitamin C
Key:CIWBSHSKHKDKBQ-JLAZNSOCSA-NYes  Vitamin C or L-ascorbic acid, or simply ascorbate (the anion of ascorbic acid), is an essential nutrient for humans and certain other animal species. Vitamin C refers to a number of vitamers that have vitamin C activity in animals, including ascorbic acid and its salts, and some oxidized forms of the molecule like dehydroascorbic acid. Ascorbate and ascorbic acid are both naturally present in the body when either of these is introduced into cells, since the forms interconvert according to pH. Vitamin C is a cofactor in at least eight enzymatic reactions, including several collagen synthesis reactions that, when dysfunctional, cause the most severe symptoms of scurvy. In animals, these reactions are especially important in wound-healing and in preventing bleeding from capillaries. Ascorbate may also act as an antioxidant against oxidative stress. However, the fact that the enantiomer D-ascorbate (not found in nature) has identical antioxidant activity to L-ascorbate, yet far less vitamin activity, underscores the fact that most of the function of L-ascorbate as a vitamin relies not on its antioxidant properties, but upon enzymic reactions that are stereospecific. "Ascorbate" without the letter for the enantiomeric form is always presumed to be the chemical L-ascorbate. Ascorbate (the anion of ascorbic acid) is required for a range of essential metabolic reactions in all animals and plants. It is made internally by almost all organisms; the main exceptions are bats, guinea pigs, capybaras, and the Anthropoidea (i.e., Haplorrhini, one of the two major primate suborders, consisting of tarsiers, monkeys, and humans and other apes). Ascorbate is also not synthesized by some species of birds and fish. All species that do not synthesize ascorbate require it in the diet. Deficiency in this vitamin causes the disease scurvy in humans. Ascorbic acid is also widely used as a food additive, to prevent oxidation. The name vitamin C always refers to the -enantiomerL of ascorbic acid and its oxidized forms. The opposite -enantiomerD called D-ascorbate has equal antioxidant power, but is not found in nature, and has no physiological significance. When D-ascorbate is synthesized and given to animals that require vitamin C in the diet, it has been found to have far less vitamin activity than the -enantiomerL. Therefore, unless written otherwise, "ascorbate" and "ascorbic acid" refer in the nutritional literature to L-ascorbate and L-ascorbic acid respectively. This notation will be followed in this article. Similarly, their oxidized derivatives (dehydroascorbate, etc., see below) are all -enantiomersL, and also need not be written with full sterochemical notation here. Ascorbic acid is a weak sugar acid structurally related to glucose. In biological systems, ascorbic acid can be found only at low pH, but in neutral solutions above pH 5 is predominantly found in the ionized form, ascorbate. All of these molecules have vitamin C activity, therefore, and are used synonymously with vitamin C, unless otherwise specified. The biological role of ascorbate is to act as a reducing agent, donating electrons to various enzymatic and a few non-enzymatic reactions. The one- and two-electron oxidized forms of vitamin C, semidehydroascorbic acid and dehydroascorbic acid, respectively, can be reduced in the body by glutathione and NADPH-dependent enzymatic mechanisms. The presence of glutathione in cells and extracellular fluids helps maintain ascorbate in a reduced state. The vast majority of animals and plants are able to synthesize vitamin C, through a sequence of enzyme-driven steps, which convert monosaccharides to vitamin C. In plants, this is accomplished through the conversion of mannose or galactose to ascorbic acid. In some animals, glucose needed to produce ascorbate in the liver (in mammals and perching birds) is extracted from glycogen; ascorbate synthesis is a glycogenolysis-dependent process. In reptiles and birds the biosynthesis is carried out in the kidneys. Among the animals that have lost the ability to synthesise vitamin C are simians and tarsiers, which together make up one of two major primate suborders, Haplorrhini. This group includes humans. The other more primitive primates (Strepsirrhini) have the ability to make vitamin C. Synthesis does not occur in a number of species (perhaps all species) in the small rodent family Caviidae that includes guinea pigs and capybaras, but occurs in other rodents (rats and mice do not need vitamin C in their diet, for example). A number of species of passerine birds also do not synthesise, but not all of them, and those that don't are not clearly related; there is a theory that the ability was lost separately a number of times in birds. All tested families of bats, including major insect and fruit-eating bat families, cannot synthesise vitamin C. A trace of gulonolactone oxidase (GULO) was detected in only 1 of 34 bat species tested, across the range of 6 families of bats tested. However, recent results show that there are at least two species of bats, frugivorous bat (Rousettus leschenaultii) and insectivorous bat (Hipposideros armiger), that retain their ability of vitamin C production. The ability to synthesize vitamin C has also been lost in teleost fish. These animals all lack the -gulonolactone oxidaseL (GULO) enzyme, which is required in the last step of vitamin C synthesis, because they have a differing non-synthesizing gene for the enzyme (Pseudogene ΨGULO). A similar non-functional gene is present in the genome of the guinea pigs and in primates, including humans. Some of these species (including humans) are able to make do with the lower levels available from their diets by recycling oxidised vitamin C. Most simians consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans. This discrepancy constitutes much of the basis of the controversy on current recommended dietary allowances. It is countered by arguments that humans are very good at conserving dietary vitamin C, and are able to maintain blood levels of vitamin C comparable with other simians, on a far smaller dietary intake. Like plants and animals, some microorganisms such as the yeast Saccharomyces cerevisiae have been shown to be able to synthesize vitamin C from simple sugars. Ascorbic acid or vitamin C is a common enzymatic cofactor in mammals used in the synthesis of collagen. Ascorbate is a powerful reducing agent capable of rapidly scavenging a number of reactive oxygen species (ROS). Freshwater teleost fishes also require dietary vitamin C in their diet or they will get scurvy. The most widely recognized symptoms of vitamin C deficiency in fishes are scoliosis, lordosis and dark skin coloration. Freshwater salmonids also show impaired collagen formation, internal/fin hemorrhage, spinal curvature and increased mortality. If these fishes are housed in seawater with algae and phytoplankton, then vitamin supplementation seems to be less important, it is presumed because of the availability of other, more ancient, antioxidants in natural marine environment. Some scientists have suggested that loss of the vitamin C biosynthesis pathway may have played a role in rapid evolutionary changes, leading to hominids and the emergence of human beings. However, another theory is that the loss of ability to make vitamin C in simians may have occurred much farther back in evolutionary history than the emergence of humans or even apes, since it evidently occurred soon after the appearance of the first primates, yet sometime after the split of early primates into the two major suborders Haplorrhini (which cannot make vitamin C) and its sister suborder of non-tarsier prosimians, the Strepsirrhini ("wet-nosed" primates), which retained the ability to make vitamin C. According to molecular clock dating, these two suborder primate branches parted ways about 63 to 60 Mya. Approximately three to five million years later (58 Mya), only a short time afterward from an evolutionary perspective, the infraorder Tarsiiformes, whose only remaining family is that of the tarsier (Tarsiidae), branched off from the other haplorrhines. Since tarsiers also cannot make vitamin C, this implies the mutation had already occurred, and thus must have occurred between these two marker points (63 to 58 Mya). It has been noted that the loss of the ability to synthesize ascorbate strikingly parallels the inability to break down uric acid, also a characteristic of primates. Uric acid and ascorbate are both strong reducing agents. This has led to the suggestion that, in higher primates, uric acid has taken over some of the functions of ascorbate. Ascorbic acid is absorbed in the body by both active transport and simple diffusion. Sodium-Dependent Active Transport—Sodium-Ascorbate Co-Transporters (SVCTs) and Hexose transporters (GLUTs)—are the two transporters required for absorption. SVCT1 and SVCT2 import the reduced form of ascorbate across plasma membrane. GLUT1 and GLUT3 are the two glucose transporters, and transfer only the dehydroascorbic acid form of Vitamin C. Although dehydroascorbic acid is absorbed in higher rate than ascorbate, the amount of dehydroascorbic acid found in plasma and tissues under normal conditions is low, as cells rapidly reduce dehydroascorbic acid to ascorbate. Thus, SVCTs appear to be the predominant system for vitamin C transport in the body. SVCT2 is involved in vitamin C transport in almost every tissue, the notable exception being red blood cells, which lose SVCT proteins during maturation. "SVCT2 knockout" animals genetically engineered to lack this functional gene, die shortly after birth, suggesting that SVCT2-mediated vitamin C transport is necessary for life. With regular intake the absorption rate varies between 70 to 95%. However, the degree of absorption decreases as intake increases. At high intake (1.25 g), fractional human absorption of ascorbic acid may be as low as 33%; at low intake (<200 mg) the absorption rate can reach up to 98%. Ascorbate concentrations over renal re-absorption threshold pass freely into the urine and are excreted. At high dietary doses (corresponding to several hundred mg/day in humans) ascorbate is accumulated in the body until the plasma levels reach the renal resorption threshold, which is about 1.5 mg/dL in men and 1.3 mg/dL in women. Concentrations in the plasma larger than this value (thought to represent body saturation) are rapidly excreted in the urine with a half-life of about 30 minutes. Concentrations less than this threshold amount are actively retained by the kidneys, and the excretion half-life for the remainder of the vitamin C store in the body thus increases greatly, with the half-life lengthening as the body stores are depleted. This half-life rises until it is as long as 83 days by the onset of the first symptoms of scurvy. Although the body's maximal store of vitamin C is largely determined by the renal threshold for blood, there are many tissues that maintain vitamin C concentrations far higher than in blood. Biological tissues that accumulate over 100 times the level in blood plasma of vitamin C are the adrenal glands, pituitary, thymus, corpus luteum, and retina. Those with 10 to 50 times the concentration present in blood plasma include the brain, spleen, lung, testicle, lymph nodes, liver, thyroid, small intestinal mucosa, leukocytes, pancreas, kidney and salivary glands. Ascorbic acid can be oxidized (broken down) in the human body by the enzyme L-ascorbate oxidase. Ascorbate that is not directly excreted in the urine as a result of body saturation or destroyed in other body metabolism is oxidized by this enzyme and removed. Scurvy is an avitaminosis resulting from lack of vitamin C, since without this vitamin, the synthesised collagen is too unstable to perform its function. Scurvy leads to the formation of brown spots on the skin, spongy gums, and bleeding from all mucous membranes. The spots are most abundant on the thighs and legs, and a person with the ailment looks pale, feels depressed, and is partially immobilized. In advanced scurvy there are open, suppurating wounds and loss of teeth and, eventually, death. The human body can store only a certain amount of vitamin C, and so the body stores are depleted if fresh supplies are not consumed. The time frame for onset of symptoms of scurvy in unstressed adults on a completely vitamin C free diet, however, may range from one month to more than six months, depending on previous loading of vitamin C (see below). It has been shown that smokers who have diets poor in vitamin C are at a higher risk of lung-borne diseases than those smokers who have higher concentrations of vitamin C in the blood. Nobel prize winners Linus Pauling and G. C. Willis have asserted that chronic long term low blood levels of vitamin C ("chronic scurvy") is a cause of atherosclerosis. Western societies generally consume far more than sufficient Vitamin C to prevent scurvy. In 2004, a Canadian Community health survey reported that Canadians of 19 years and above have intakes of vitamin C from food of 133 mg/d for males and 120 mg/d for females; these are higher than the RDA recommendations. Notable human dietary studies of experimentally induced scurvy have been conducted on conscientious objectors during WW II in Britain, and on Iowa state prisoners in the late 1960s. These studies both found that all obvious symptoms of scurvy previously induced by an experimental scorbutic diet with extremely low vitamin C content could be completely reversed by additional vitamin C supplementation of only 10 mg a day. In these experiments, there was no clinical difference noted between men given 70 mg vitamin C per day (which produced blood level of vitamin C of about 0.55 mg/dl, about 1/3 of tissue saturation levels), and those given 10 mg per day. Men in the prison study developed the first signs of scurvy about 4 weeks after starting the vitamin C free diet, whereas in the British study, six to eight months were required, possibly due to the pre-loading of this group with a 70 mg/day supplement for six weeks before the scorbutic diet was fed. Men in both studies on a diet devoid, or nearly devoid, of vitamin C had blood levels of vitamin C too low to be accurately measured when they developed signs of scurvy, and in the Iowa study, at this time were estimated (by labeled vitamin C dilution) to have a body pool of less than 300 mg, with daily turnover of only 2.5 mg/day, implying an instantaneous half-life of 83 days by this time (elimination constant of 4 months). Moderately higher blood levels of vitamin C measured in healthy persons have been found to be prospectively correlated with decreased risk of cardiovascular disease and ischaemic heart disease, and an increase life expectancy. The same study found an inverse relationship between blood vitamin C levels and cancer risk in men, but not in women. An increase in blood level of 20 micromol/L of vitamin C (about 0.35 mg/dL, and representing a theoretical additional 50 grams of fruit and vegetables per day) was found epidemiologically to reduce the all-cause risk of mortality, four years after measuring it, by about 20%. However, because this was not an intervention study, causation could not be proven, and vitamin C blood levels acting as a proxy marker for other differences between the groups could not be ruled out. However, the four-year long and prospective nature of the study did rule out proxy effect from any vitamin C lowering effects of immediately terminal illness, or near-end-of-life poor health. Studies with much higher doses of vitamin C, usually between 200 and 6000 mg/day, for the treatment of infections and wounds have shown inconsistent results. Combinations of antioxidants seem to improve wound healing. In humans, vitamin C is essential to a healthy diet as well as being a highly effective antioxidant, acting to lessen oxidative stress; a substrate for ascorbate peroxidase in plants (APX is plant specific enzyme); and an enzyme cofactor for the biosynthesis of many important biochemicals. Vitamin C acts as an electron donor for important enzymes: Ascorbic acid performs numerous physiological functions in the human body. These functions include the synthesis of collagen, carnitine, and neurotransmitters; the synthesis and catabolism of tyrosine; and the metabolism of microsome. During biosynthesis ascorbate acts as a reducing agent, donating electrons and preventing oxidation to keep iron and copper atoms in their reduced states. Vitamin C acts as an electron donor for eight different enzymes: Ascorbic acid is well known for its antioxidant activity, acting as a reducing agent to reverse oxidation in liquids. When there are more free radicals (reactive oxygen species, ROS) in the human body than antioxidants, the condition is called oxidative stress, and has an impact on cardiovascular disease, hypertension, chronic inflammatory diseases, diabetes as well as on critically ill patients and individuals with severe burns. Individuals experiencing oxidative stress have ascorbate blood levels lower than 45 µmol/L, compared to healthy individual who range between 61.4-80 µmol/L. It is not yet certain whether vitamin C and antioxidants in general prevent oxidative stress-related diseases and promote health. Clinical studies regarding the effects of vitamin C supplementation on lipoproteins and cholesterol have found that vitamin C supplementation does not improve certain disease markers in the blood. Vitamin C may contribute to decreased risk of cardiovascular disease and strokes through a small reduction in systolic blood pressure, and was also found to both increase ascorbic acid levels and reduce levels of resistin serum, another likely determinant of oxidative stress and cardiovascular risk. However, so far there is no consensus that vitamin C intake has an impact on cardiovascular risks in general, and an array of studies found negative results. Meta-analysis of a large number of studies on antioxidants, including vitamin C supplementation, found no relationship between vitamin C and mortality. Ascorbic acid behaves not only as an antioxidant but also as a pro-oxidant. Ascorbic acid has been shown to reduce transition metals, such as cupric ions (Cu2+), to cuprous (Cu1+), and ferric ions (Fe3+) to ferrous (Fe2+) during conversion from ascorbate to dehydroascorbate in vitro. This reaction can generate superoxide and other ROS. However, in the body, free transition elements are unlikely to be present while iron and copper are bound to diverse proteins and the intravenous use of vitamin C does not appear to increase pro-oxidant activity. Thus, ascorbate as a pro-oxidant is unlikely to convert metals to create ROS in vivo. However, vitamin C supplementation has been associated with increased DNA damage in the lymphocytes of healthy volunteers in one study, a study which has been criticized on methodological grounds. Vitamin C is found in high concentrations in immune cells, and is consumed quickly during infections. It is not certain how vitamin C interacts with the immune system; it has been hypothesized to modulate the activities of phagocytes, the production of cytokines and lymphocytes, and the number of cell adhesion molecules in monocytes. Vitamin C is a natural antihistamine. It both prevents histamine release and increases the detoxification of histamine. A 1992 study found that taking 2 grams vitamin C daily lowered blood histamine levels 38 percent in healthy adults in just one week. It has also been noted that low concentrations of serum vitamin C has been correlated with increased serum histamine levels. Ascorbic acid is associated with chloroplasts and apparently plays a role in ameliorating the oxidative stress of photosynthesis. In addition, it has a number of other roles in cell division and protein modification. Plants appear to be able to make ascorbate by at least one other biochemical route that is different from the major route in animals, although precise details remain unknown. The North American Dietary Reference Intake recommends 90 milligrams per day and no more than 2 grams (2,000 milligrams) per day. Other related species sharing the same inability to produce vitamin C require exogenous vitamin C consumption 20 to 80 times this reference intake. There is continuing debate within the scientific community over the best dose schedule (the amount and frequency of intake) of vitamin C for maintaining optimal health in humans. A balanced diet without supplementation usually contains enough vitamin C to prevent scurvy in an average healthy adult, while those who are pregnant, smoke tobacco, or are under stress require slightly more. However, the amount of vitamin C necessary to prevent scurvy is less than the amount required for optimal health, as there are a number of other chronic diseases whose risk are increased by a low vitamin C intake, including cancer, heart disease, and cataracts. A 1999 review suggested a dose of 90–100 mg Vitamin C daily is required to optimally protect against these diseases, in contrast to the lower 45 mg daily required to prevent scurvy. High doses (thousands of milligrams) may result in diarrhea in healthy adults, as a result of the osmotic water-retaining effect of the unabsorbed portion in the gastrointestinal tract (similar to cathartic osmotic laxatives). Proponents of orthomolecular medicine claim the onset of diarrhea to be an indication of where the body's true vitamin C requirement lies, though this has not been clinically verified. Recommendations for vitamin C intake have been set by various national agencies: Vitamin C functions as an antioxidant and is necessary for the treatment and prevention of scurvy, though in nearly all cases dietary intake is adequate to prevent deficiency and supplementation is not necessary. Though vitamin C has been promoted as useful in the treatment of a variety of conditions, most of these uses are poorly supported by the evidence and sometimes contraindicated. Vitamin C may be useful in lowering serum uric acid levels, resulting in a correspondingly lower incidence of gout, although a more recent study revealed that Vitamin C given in doses of 500 mg/day does not reduce uric acid (urate) levels to a clinically significant degree in patients with established gout. Neither prophylactic nor therapeutic use is supported in the prevention or treatment of pneumonia. People with the highest levels of ascorbic acid in their blood stream seem to be at a significantly reduced risk of having a stroke and low ascorbic acid has been suggested as a way of identifying those at high risk of stroke. Vitamin C's effect on the common cold has been extensively researched. It has not been shown effective in prevention or treatment of the common cold, except in limited circumstances (specifically, individuals exercising vigorously in cold environments). Routine vitamin C supplementation does not reduce the incidence or severity of the common cold in the general population, though it may reduce the duration of illness. Several individuals and organizations advocate large doses of vitamin C in excess of 10–100 times RDI in the form of oral or intravenous therapy. Megadoses of vitamin C are employed not as a nutritional supplement but as a therapeutic agent, and have been used to treat a number of health conditions. Clinical trials of vitamin C megadoses have provided contradictory results, dismissing or confirming (International Journal of Oncology, No. 1/2013) these claims. Simple tests use dichlorophenolindophenol, a redox indicator, to measure the levels of vitamin C in the urine and in serum or blood plasma. However these reflect recent dietary intake rather than the level of vitamin C in body stores. Reverse phase high performance liquid chromatography is used for determining the storage levels of vitamin C within lymphocytes and tissue. It has been observed that while serum or blood plasma levels follow the circadian rhythm or short term dietary changes, those within tissues themselves are more stable and give a better view of the availability of ascorbate within the organism. However, very few hospital laboratories are adequately equipped and trained to carry out such detailed analyses, and require samples to be analyzed in specialized laboratories. Relatively large doses of ascorbic acid may cause indigestion, particularly when taken on an empty stomach. However, taking vitamin C in the form of sodium ascorbate and calcium ascorbate may minimize this effect. When taken in large doses, ascorbic acid causes diarrhea in healthy subjects. In one trial in 1936, doses up to 6 grams of ascorbic acid were given to 29 infants, 93 children of preschool and school age, and 20 adults for more than 1400 days. With the higher doses, toxic manifestations were observed in five adults and four infants. The signs and symptoms in adults were nausea, vomiting, diarrhea, flushing of the face, headache, fatigue and disturbed sleep. The main toxic reactions in the infants were skin rashes. As vitamin C enhances iron absorption, iron poisoning can become an issue to people with rare iron overload disorders, such as haemochromatosis. A genetic condition that results in inadequate levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD) can cause sufferers to develop hemolytic anemia after ingesting specific oxidizing substances, such as very large dosages of vitamin C. There is a longstanding belief among the mainstream medical community that vitamin C causes kidney stones, which is based on little science. Although recent studies have found a relationship, a clear link between excess ascorbic acid intake and kidney stone formation has not been generally established. Some case reports exist for a link between patients with oxalate deposits and a history of high-dose vitamin C usage. In a study conducted on rats, during the first month of pregnancy, high doses of vitamin C may suppress the production of progesterone from the corpus luteum. Progesterone, necessary for the maintenance of a pregnancy, is produced by the corpus luteum for the first few weeks, until the placenta is developed enough to produce its own source. By blocking this function of the corpus luteum, high doses of vitamin C (1000+ mg) are theorized to induce an early miscarriage. In a group of spontaneously aborting women at the end of the first trimester, the mean values of vitamin C were significantly higher in the aborting group. However, the authors do state: 'This could not be interpreted as an evidence of causal association.' However, in a previous study of 79 women with threatened, previous spontaneous, or habitual abortion, Javert and Stander (1943) had 91% success with 33 patients who received vitamin C together with bioflavonoids and vitamin K (only three abortions), whereas all of the 46 patients who did not receive the vitamins aborted. A study in rats and humans suggested that adding Vitamin C supplements to an exercise training program lowered the expected effect of training on VO2 Max. Although the results in humans were not statistically significant, this study is often cited as evidence that high doses of Vitamin C have an adverse effect on exercise performance. In rats, it was shown that the additional Vitamin C resulted in lowered mitochondria production. Since rats are able to produce all of their needed Vitamin C, however, it is questionable whether they offer a relevant model of human physiological processes in this regard. A cancer-causing mechanism of hexavalent chromium may be triggered by vitamin C. Vitamin C is water soluble, with dietary excesses not absorbed, and excesses in the blood rapidly excreted in the urine. It exhibits remarkably low toxicity. The 50LD (the dose that will kill 50% of a population) in rats is generally accepted to be 11.9 grams per kilogram of body weight when given by forced gavage (orally). The mechanism of death from such doses (1.2% of body weight, or 0.84 kg for a 70 kg human) is unknown, but may be more mechanical than chemical. The LD50 in humans remains unknown, given lack of any accidental or intentional poisoning death data. However, as with all substances tested in this way, the rat LD50 is taken as a guide to its toxicity in humans. The richest natural sources are fruits and vegetables, and of those, the Kakadu plum and the camu camu fruit contain the highest concentration of the vitamin. It is also present in some cuts of meat, especially liver. Vitamin C is the most widely taken nutritional supplement and is available in a variety of forms, including tablets, drink mixes, crystals in capsules or naked crystals. Vitamin C is absorbed by the intestines using a sodium-ion dependent channel. It is transported through the intestine via both glucose-sensitive and glucose-insensitive mechanisms. The presence of large quantities of sugar either in the intestines or in the blood can slow absorption. While plants are generally a good source of vitamin C, the amount in foods of plant origin depends on the precise variety of the plant, soil condition, climate where it grew, length of time since it was picked, storage conditions, and method of preparation. The following table is approximate and shows the relative abundance in different raw plant sources. As some plants were analyzed fresh while others were dried (thus, artifactually increasing concentration of individual constituents like vitamin C), the data are subject to potential variation and difficulties for comparison. The amount is given in milligrams per 100 grams of fruit or vegetable and is a rounded average from multiple authoritative sources: † average of 3 sources; dried
Source: The overwhelming majority of species of animals (but not humans or guinea pigs) and plants synthesise their own vitamin C. Therefore, some animal products can be used as sources of dietary vitamin C. Vitamin C is most present in the liver and least present in the muscle. Since muscle provides the majority of meat consumed in the western human diet, animal products are not a reliable source of the vitamin. Vitamin C is present in human breast milk, but not present in raw cow's milk. All excess vitamin C is disposed of through the urinary system. The following table shows the relative abundance of vitamin C in various foods of animal origin, given in milligrams of vitamin C per 100 grams of food:
Vitamin C chemically decomposes under certain conditions, many of which may occur during the cooking of food. Vitamin C concentrations in various food substances decrease with time in proportion to the temperature they are stored at and cooking can reduce the Vitamin C content of vegetables by around 60% possibly partly due to increased enzymatic destruction as it may be more significant at sub-boiling temperatures. Longer cooking times also add to this effect, as will copper food vessels, which catalyse the decomposition. Another cause of vitamin C being lost from food is leaching, where the water-soluble vitamin dissolves into the cooking water, which is later poured away and not consumed. However, vitamin C does not leach in all vegetables at the same rate; research shows broccoli seems to retain more than any other. Research has also shown that fresh-cut fruits do not lose significant nutrients when stored in the refrigerator for a few days. Vitamin C is available in caplets, tablets, capsules, drink mix packets, in multi-vitamin formulations, in multiple antioxidant formulations, and as crystalline powder. Timed release versions are available, as are formulations containing bioflavonoids such as quercetin, hesperidin, and rutin. Tablet and capsule sizes range from 25 mg to 1500 mg. Vitamin C (as ascorbic acid) crystals are typically available in bottles containing 300 g to 1 kg of powder (a 5 ml teaspoon of vitamin C crystals equals 5,000 mg). The bottles are usually airtight and brown or opaque in order to prevent oxidation, in which case the vitamin C would become useless, if not damaging. Vitamin C is produced from glucose by two main routes. The Reichstein process, developed in the 1930s, uses a single pre-fermentation followed by a purely chemical route. The modern two-step fermentation process, originally developed in China in the 1960s, uses additional fermentation to replace part of the later chemical stages. Both processes yield approximately 60% vitamin C from the glucose feed. Research is underway at the Scottish Crop Research Institute in the interest of creating a strain of yeast that can synthesise vitamin C in a single fermentation step from galactose, a technology expected to reduce manufacturing costs considerably. World production of synthesised vitamin C is currently estimated at approximately 110,000 tonnes annually. Main producers have been BASF/Takeda, DSM, Merck and the China Pharmaceutical Group Ltd. of the People's Republic of China. By 2008 only the DSM plant in Scotland remained operational outside the strong price competition from China. The world price of vitamin C rose sharply in 2008 partly as a result of rises in basic food prices but also in anticipation of a stoppage of the two Chinese plants, situated at Shijiazhuang near Beijing, as part of a general shutdown of polluting industry in China over the period of the Olympic games. Five Chinese manufacturers met in 2010, among them Northeast Pharmaceutical Group and North China Pharmaceutical Group, and agreed to temporarily stop production in order to maintain prices. In 2011 a case was filed in a US court against 4 Chinese companies that they colluded to limit production and fix prices of vitamin C in the United States. According to the plaintiffs, after the agreement was made, spot prices for vitamin C shot to as high as $7 per kilogram in December 2002 from $2.50 per kilogram in December 2001.The companies do not deny the accusation but say in their defense that the Chinese government compelled them to act in this way. In January 2012 a US judge ruled that the Chinese companies can be sued in the U.S. for the alleged price fixing by buyers acting as a group. In 2005, Health Canada evaluated the effect of fortification of foods with ascorbate in the guidance document, Addition of Vitamins and Minerals to Food. Ascorbate was categorized as a 'Risk Category A nutrients', meaning it is a nutrient for which an upper limit for intake is set but allows a wide margin of intake that has a narrow margin of safety but non-serious critical adverse effects. The need to include fresh plant food or raw animal flesh in the diet to prevent disease was known from ancient times. Native people living in marginal areas incorporated this into their medicinal lore. For example, spruce needles were used in temperate zones in infusions, or the leaves from species of drought-resistant trees in desert areas. In 1536, the French explorers Jacques Cartier and Daniel Knezevic, exploring the St. Lawrence River, used the local natives' knowledge to save his men who were dying of scurvy. He boiled the needles of the arbor vitae tree to make a tea that was later shown to contain 50 mg of vitamin C per 100 grams. Authorities have occasionally recommended the benefit of plant food to promote health and prevent scurvy during long sea voyages. John Woodall, the first appointed surgeon to the British East India Company, recommended the preventive and curative use of lemon juice in his book, The Surgeon's Mate, in 1617. The Dutch writer, Johann Bachstrom, in 1734, gave the firm opinion that "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens, which is alone the primary cause of the disease." Scurvy had long been a principal killer of sailors during the long sea voyages. According to Jonathan Lamb, "In 1499, Vasco da Gama lost 116 of his crew of 170; In 1520, Magellan lost 208 out of 230;...all mainly to scurvy." While the earliest documented case of scurvy was described by Hippocrates around 400 BC, the first attempt to give scientific basis for the cause of this disease was by a ship's surgeon in the British Royal Navy, James Lind. Scurvy was common among those with poor access to fresh fruit and vegetables, such as remote, isolated sailors and soldiers. While at sea in May 1747, Lind provided some crew members with two oranges and one lemon per day, in addition to normal rations, while others continued on cider, vinegar, sulfuric acid or seawater, along with their normal rations. In the history of science, this is considered to be the first occurrence of a controlled experiment. The results conclusively showed that citrus fruits prevented the disease. Lind published his work in 1753 in his Treatise on the Scurvy. Lind's work was slow to be noticed, partly because his Treatise was not published until six years after his study, and also because he recommended a lemon juice extract known as rob. Fresh fruit was very expensive to keep on board, whereas boiling it down to juice allowed easy storage but destroyed the vitamin (especially if boiled in copper kettles). Ship captains concluded wrongly that Lind's other suggestions were ineffective because those juices failed to prevent or cure scurvy. It was 1795 before the British navy adopted lemons or lime as standard issue at sea. Limes were more popular, as they could be found in British West Indian Colonies, unlike lemons, which were not found in British Dominions, and were therefore more expensive. This practice led to the American use of the nickname "limey" to refer to the British. Captain James Cook had previously demonstrated and proven the principle of the advantages of carrying "Sour krout" on board, by taking his crews to the Hawaiian Islands and beyond without losing any of his men to scurvy. For this otherwise unheard of feat, the British Admiralty awarded him a medal. The name antiscorbutic was used in the eighteenth and nineteenth centuries as general term for those foods known to prevent scurvy, even though there was no understanding of the reason for this. These foods included but were not limited to: lemons, limes, and oranges; sauerkraut, cabbage, malt, and portable soup. Even before the antiscorbutic substance was identified, there were indications that it was present in amounts sufficient to prevent scurvy, in nearly all fresh (uncooked and uncured) foods, including raw animal-derived foods. In 1928, the Arctic anthropologist Vilhjalmur Stefansson attempted to prove his theory of how the Eskimos are able to avoid scurvy with almost no plant food in their diet, despite the disease's striking European Arctic explorers living on similar high cooked-meat diets. Stefansson theorised that the natives get their vitamin C from fresh meat that is minimally cooked. Starting in February 1928, for one year he and a colleague lived on an exclusively minimally cooked meat diet while under medical supervision; they remained healthy. Later studies done after vitamin C could be quantified in mostly raw traditional food diets of the Yukon, Inuit, and Métís of the Northern Canada, showed that their daily intake of vitamin C averaged between 52 and 62 mg/day, an amount approximately the dietary reference intake (DRI), even at times of the year when little plant-based food was eaten. In 1907, the needed biological-assay model to isolate and identify the antiscorbutic factor was discovered. Axel Holst and Theodor Frølich, two Norwegian physicians studying shipboard beriberi in the Norwegian fishing fleet, wanted a small test mammal to substitute for the pigeons then used in beriberi research. They fed guinea pigs their test diet of grains and flour, which had earlier produced beriberi in their pigeons, and were surprised when classic scurvy resulted instead. This was a serendipitous choice of model. Until that time, scurvy had not been observed in any organism apart from humans, and had been considered an exclusively human disease. (Pigeons, as seed-eating birds, were also later found to make their own vitamin C.) Holst and Frølich found they could cure the disease in guinea pigs with the addition of various fresh foods and extracts. This discovery of a clean animal experimental model for scurvy, made even before the essential idea of vitamins in foods had even been put forward, has been called the single most important piece of vitamin C research. In 1912, the Polish American biochemist Casimir Funk, while researching beriberi in pigeons, developed the concept of vitamins to refer to the non-mineral micronutrients that are essential to health. The name is a blend of "vital", due to the vital biochemical role they play, and "amines" because Funk thought that all these materials were chemical amines. Although the "e" was dropped after skepticism that all these compounds were amines, the word vitamin remained as a generic name for them. One of the vitamins was thought to be the anti-scorbutic factor in foods discovered by Holst and Frølich. In 1928, this vitamin was referred to as "water-soluble C," although its chemical structure had still not been determined. From 1928 to 1932, the Hungarian research team of Albert Szent-Györgyi and Joseph L. Svirbely, as well as the American team led by Charles Glen King in Pittsburgh, first identified the anti-scorbutic factor. Szent-Györgyi had isolated the chemical hexuronic acid (actually, L-hexuronic acid) from animal adrenal glands at the Mayo clinic, and suspected it to be the antiscorbutic factor, but could not prove it, without a biological assay. At the same time, for five years, King's laboratory at the University of Pittsburgh had been trying to isolate the antiscorbutic factor in lemon juice, using the original 1907 model of scorbutic guinea pigs, which developed scurvy when not fed fresh foods, but were cured by lemon juice. They had also considered hexuronic acid, but had been put off the trail when a coworker made the explicit (and mistaken) experimental claim that this substance was not the antiscorbutic substance. Finally, in late 1931, Szent-Györgyi gave Svirbely, formerly of King's lab, the last of his hexuronic acid, with the suggestion that it might be the anti-scorbutic factor. By the spring of 1932, King's laboratory had proven this, but published the result without giving Szent-Györgyi credit for it, leading to a bitter dispute over priority claims (in reality it had taken a team effort by both groups, since Szent-Györgyi was unwilling to do the difficult and messy animal studies). Meanwhile, by 1932, Szent-Györgyi had moved to Hungary and his group had discovered that paprika peppers, a common spice in the Hungarian diet, was a rich source of hexuronic acid, the antiscorbutic factor. With a new and plentiful source of the vitamin, Szent-Györgyi sent a sample to noted British sugar chemist Walter Norman Haworth, who chemically identified it and proved the identification by synthesis in 1933. Haworth and Szent-Györgyi now proposed that the substance L-hexuronic acid be called a-scorbic acid, and chemically L-ascorbic acid, in honor of its activity against scurvy. Ascorbic acid turned out not to be an amine, nor even to contain any nitrogen. In part, in recognition of his accomplishment with vitamin C, Szent-Györgyi was awarded the unshared 1937 Nobel Prize in Medicine. Haworth also shared that year's Nobel Prize in Chemistry, in part for his vitamin C synthetic work. Between 1933 and 1934, not only Haworth and fellow British chemist (later Sir) Edmund Hirst had synthesized vitamin C, but also, independently, the Polish chemist Tadeus Reichstein, succeeded in synthesizing the vitamin in bulk, making it the first vitamin to be artificially produced. The latter process made possible the cheap mass-production of semi-synthetic vitamin C, which was quickly marketed. Only Haworth was awarded the 1937 Nobel Prize in Chemistry in part for this work, but the Reichstein process, a combined chemical and bacterial fermentation sequence still used today to produce vitamin C, retained Reichstein's name. In 1934 Hoffmann–La Roche, which bought the Reichstein process patent, became the first pharmaceutical company to mass-produce and market synthetic vitamin C, under the brand name of Redoxon. In 1957, the American J.J. Burns showed that the reason some mammals are susceptible to scurvy is the inability of their liver to produce the active enzyme -gulonolactone oxidaseL, which is the last of the chain of four enzymes that synthesize vitamin C. American biochemist Irwin Stone was the first to exploit vitamin C for its food preservative properties. He later developed the theory that humans possess a mutated form of the L-gulonolactone oxidase coding gene. In 2008, researchers at the University of Montpellier discovered that, in humans and other primates, the red blood cells have evolved a mechanism to more efficiently utilize the vitamin C present in the body by recycling oxidized L-dehydroascorbic acid (DHA) back into ascorbic acid, which can be reused by the body. The mechanism was not found to be present in mammals that synthesize their own vitamin C. M: NUT cof, enz, met noco, nuvi, sysi/epon, met drug (A8/11/12)

A vitamin ( or ) is an organic compound required by an organism as a vital nutrient in limited amounts. An organic chemical compound (or related set of compounds) is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on the circumstances and on the particular organism. For example, ascorbic acid (vitamin C) is a vitamin for humans, but not for most other animals, and biotin (vitamin H) and vitamin D are required in the human diet only in certain circumstances. By convention, the term vitamin includes neither other essential nutrients, such as dietary minerals, essential fatty acids, or essential amino acids (which are needed in larger amounts than vitamins) nor the large number of other nutrients that promote health but are otherwise required less often. Thirteen vitamins are universally recognized at present. Vitamins are classified by their biological and chemical activity, not their structure. Thus, each "vitamin" refers to a number of vitamer compounds that all show the biological activity associated with a particular vitamin. Such a set of chemicals is grouped under an alphabetized vitamin "generic descriptor" title, such as "vitamin A", which includes the compounds retinal, retinol, and four known carotenoids. Vitamers by definition are convertible to the active form of the vitamin in the body, and are sometimes inter-convertible to one another, as well. Vitamins have diverse biochemical functions. Some have hormone-like functions as regulators of mineral metabolism (such as vitamin D), or regulators of cell and tissue growth and differentiation (such as some forms of vitamin A). Others function as antioxidants (e.g., vitamin E and sometimes vitamin C). The largest number of vitamins (such as B complex vitamins) function as precursors for enzyme cofactors, that help enzymes in their work as catalysts in metabolism. In this role, vitamins may be tightly bound to enzymes as part of prosthetic groups: For example, biotin is part of enzymes involved in making fatty acids. Vitamins may also be less tightly bound to enzyme catalysts as coenzymes, detachable molecules that function to carry chemical groups or electrons between molecules. For example, folic acid may carry methyl, formyl, and methylene groups in the cell. Although these roles in assisting enzyme-substrate reactions are vitamins' best-known function, the other vitamin functions are equally important. Until the mid-1930s, when the first commercial yeast-extract vitamin B complex and semi-synthetic vitamin C supplement tablets were sold, vitamins were obtained solely through food intake, and changes in diet (which, for example, could occur during a particular growing season) usually greatly altered the types and amounts of vitamins ingested. However, vitamins have been produced as commodity chemicals and made widely available as inexpensive semisynthetic and synthetic-source multivitamin dietary and food supplements and additives, since the middle of the 20th century. The term vitamin was derived from "vitamine," a compound word coined in 1912 by the Polish biochemist Kazimierz Funk when working at the Lister Institute of Preventive Medicine. The name is from vital and amine, meaning amine of life, because it was suggested in 1912 that the organic micronutrient food factors that prevent beriberi and perhaps other similar dietary-deficiency diseases might be chemical amines. This proved incorrect for the micronutrient class, and the word was shortened to vitamin. The value of eating a certain food to maintain health was recognized long before vitamins were identified. The ancient Egyptians knew that feeding liver to a person would help cure night blindness, an illness now known to be caused by a vitamin A deficiency. The advancement of ocean voyages during the Renaissance resulted in prolonged periods without access to fresh fruits and vegetables, and made illnesses from vitamin deficiency common among ships' crews. In 1747, the Scottish surgeon James Lind discovered that citrus foods helped prevent scurvy, a particularly deadly disease in which collagen is not properly formed, causing poor wound healing, bleeding of the gums, severe pain, and death. In 1753, Lind published his Treatise on the Scurvy, which recommended using lemons and limes to avoid scurvy, which was adopted by the British Royal Navy. This led to the nickname Limey for sailors of that organization. Lind's discovery, however, was not widely accepted by individuals in the Royal Navy's Arctic expeditions in the 19th century, where it was widely believed that scurvy could be prevented by practicing good hygiene, regular exercise, and maintaining the morale of the crew while on board, rather than by a diet of fresh food. As a result, Arctic expeditions continued to be plagued by scurvy and other deficiency diseases. In the early 20th century, when Robert Falcon Scott made his two expeditions to the Antarctic, the prevailing medical theory was that scurvy was caused by "tainted" canned food. During the late 18th and early 19th centuries, the use of deprivation studies allowed scientists to isolate and identify a number of vitamins. Lipid from fish oil was used to cure rickets in rats, and the fat-soluble nutrient was called "antirachitic A". Thus, the first "vitamin" bioactivity ever isolated, which cured rickets, was initially called "vitamin A"; however, the bioactivity of this compound is now called vitamin D. In 1881, Russian surgeon Nikolai Lunin studied the effects of scurvy while at the University of Tartu in present-day Estonia. He fed mice an artificial mixture of all the separate constituents of milk known at that time, namely the proteins, fats, carbohydrates, and salts. The mice that received only the individual constituents died, while the mice fed by milk itself developed normally. He made a conclusion that "a natural food such as milk must therefore contain, besides these known principal ingredients, small quantities of unknown substances essential to life." However, his conclusions were rejected by other researchers when they were unable to reproduce his results. One difference was that he had used table sugar (sucrose), while other researchers had used milk sugar (lactose) that still contained small amounts of vitamin B.][ In east Asia, where polished white rice was the common staple food of the middle class, beriberi resulting from lack of vitamin B1 was endemic. In 1884, Takaki Kanehiro, a British trained medical doctor of the Imperial Japanese Navy, observed that beriberi was endemic among low-ranking crew who often ate nothing but rice, but not among officers who consumed a Western-style diet. With the support of the Japanese navy, he experimented using crews of two battleships; one crew was fed only white rice, while the other was fed a diet of meat, fish, barley, rice, and beans. The group that ate only white rice documented 161 crew members with beriberi and 25 deaths, while the latter group had only 14 cases of beriberi and no deaths. This convinced Takaki and the Japanese Navy that diet was the cause of beriberi, but mistakenly believed that sufficient amounts of protein prevented it. That diseases could result from some dietary deficiencies was further investigated by Christiaan Eijkman, who in 1897 discovered that feeding unpolished rice instead of the polished variety to chickens helped to prevent beriberi in the chickens. The following year, Frederick Hopkins postulated that some foods contained "accessory factors" — in addition to proteins, carbohydrates, fats etc. — that are necessary for the functions of the human body. Hopkins and Eijkman were awarded the Nobel Prize for Physiology or Medicine in 1929 for their discovery of several vitamins. In 1910, the first vitamin complex was isolated by Japanese scientist Umetaro Suzuki, who succeeded in extracting a water-soluble complex of micronutrients from rice bran and named it aberic acid (later Orizanin). He published this discovery in a Japanese scientific journal. When the article was translated into German, the translation failed to state that it was a newly discovered nutrient, a claim made in the original Japanese article, and hence his discovery failed to gain publicity. In 1912 Polish biochemist Casimir Funk isolated the same complex of micronutrients and proposed the complex be named "vitamine" (from "vital amine", reportedly suggested by Max Nierenstein a friend and reader of Biochemistry at Bristol University). The name soon became synonymous with Hopkins' "accessory factors", and, by the time it was shown that not all vitamins are amines, the word was already ubiquitous. In 1920, Jack Cecil Drummond proposed that the final "e" be dropped to deemphasize the "amine" reference, after researchers began to suspect that not all "vitamines" (in particular, vitamin A) have an amine component. In 1931, Albert Szent-Györgyi and a fellow researcher Joseph Svirbely suspected that "hexuronic acid" was actually vitamin C, and gave a sample to Charles Glen King, who proved its anti-scorbutic activity in his long-established guinea pig scorbutic assay. In 1937, Szent-Györgyi was awarded the Nobel Prize in Physiology or Medicine for his discovery. In 1943, Edward Adelbert Doisy and Henrik Dam were awarded the Nobel Prize in Physiology or Medicine for their discovery of vitamin K and its chemical structure. In 1967, George Wald was awarded the Nobel Prize (along with Ragnar Granit and Haldan Keffer Hartline) for his discovery that vitamin A could participate directly in a physiological process. Vitamins are classified as either water-soluble or fat-soluble. In humans there are 13 vitamins: 4 fat-soluble (A, D, E, and K) and 9 water-soluble (8 B vitamins and vitamin C). Water-soluble vitamins dissolve easily in water and, in general, are readily excreted from the body, to the degree that urinary output is a strong predictor of vitamin consumption. Because they are not as readily stored, more consistent intake is important. Many types of water-soluble vitamins are synthesized by bacteria. Fat-soluble vitamins are absorbed through the intestinal tract with the help of lipids (fats). Because they are more likely to accumulate in the body, they are more likely to lead to hypervitaminosis than are water-soluble vitamins. Fat-soluble vitamin regulation is of particular significance in cystic fibrosis. Each vitamin is typically used in multiple reactions, and, therefore, most have multiple functions. Vitamins are essential for the normal growth and development of a multicellular organism. Using the genetic blueprint inherited from its parents, a fetus begins to develop, at the moment of conception, from the nutrients it absorbs. It requires certain vitamins and minerals to be present at certain times. These nutrients facilitate the chemical reactions that produce among other things, skin, bone, and muscle. If there is serious deficiency in one or more of these nutrients, a child may develop a deficiency disease. Even minor deficiencies may cause permanent damage. For the most part, vitamins are obtained with food, but a few are obtained by other means. For example, microorganisms in the intestine — commonly known as "gut flora" — produce vitamin K and biotin, while one form of vitamin D is synthesized in the skin with the help of the natural ultraviolet wavelength of sunlight. Humans can produce some vitamins from precursors they consume. Examples include vitamin A, produced from beta carotene, and niacin, from the amino acid tryptophan. Once growth and development are completed, vitamins remain essential nutrients for the healthy maintenance of the cells, tissues, and organs that make up a multicellular organism; they also enable a multicellular life form to efficiently use chemical energy provided by food it eats, and to help process the proteins, carbohydrates, and fats required for respiration. Shown below is percentage loss of vitamins after cooking averaged for common foods such as vegetables, meat or fish. It should be noted however that some vitamins may become more "bio-available" – that is, usable by the body – when steamed or cooked. Table below shows effects of heat such as heat from boiling, steaming, cooking etc. and other agents on various vitamins. Effect of cutting vegetables can be seen from exposure to air and light. Water soluble vitamins such as B and C seep into the water when boiling a vegetable. Humans must consume vitamins periodically but with differing schedules, to avoid deficiency. The human body's stores for different vitamins vary widely; vitamins A, D, and B12 are stored in significant amounts in the human body, mainly in the liver, and an adult human's diet may be deficient in vitamins A and D for many months and B12 in some cases for years, before developing a deficiency condition. However, vitamin B3 (niacin and niacinamide) is not stored in the human body in significant amounts, so stores may last only a couple of weeks. For vitamin C, the first symptoms of scurvy in experimental studies of complete vitamin C deprivation in humans have varied widely, from a month to more than six months, depending on previous dietary history that determined body stores. Deficiencies of vitamins are classified as either primary or secondary. A primary deficiency occurs when an organism does not get enough of the vitamin in its food. A secondary deficiency may be due to an underlying disorder that prevents or limits the absorption or use of the vitamin, due to a "lifestyle factor", such as smoking, excessive alcohol consumption, or the use of medications that interfere with the absorption or use of the vitamin. People who eat a varied diet are unlikely to develop a severe primary vitamin deficiency. In contrast, restrictive diets have the potential to cause prolonged vitamin deficits, which may result in often painful and potentially deadly diseases. Well-known human vitamin deficiencies involve thiamine (beriberi), niacin (pellagra), vitamin C (scurvy), and vitamin D (rickets). In much of the developed world, such deficiencies are rare; this is due to (1) an adequate supply of food and (2) the addition of vitamins and minerals to common foods, often called fortification. In addition to these classical vitamin deficiency diseases, some evidence has also suggested links between vitamin deficiency and a number of different disorders. In large doses, some vitamins have documented side-effects that tend to be more severe with a larger dosage. The likelihood of consuming too much of any vitamin from food is remote, but overdosing (vitamin poisoning) from vitamin supplementation does occur. At high enough dosages, some vitamins cause side-effects such as nausea, diarrhea, and vomiting. When side-effects emerge, recovery is often accomplished by reducing the dosage. The doses of vitamins differ because individual tolerances can vary widely and appear to be related to age and state of health. In 2008, overdose exposure to all formulations of vitamins and multivitamin-mineral formulations was reported by 68,911 individuals to the American Association of Poison Control Centers (nearly 80% of these exposures were in children under the age of 6), leading to 8 "major" life-threatening outcomes, but no deaths. Dietary supplements, often containing vitamins, are used to ensure that adequate amounts of nutrients are obtained on a daily basis, if optimal amounts of the nutrients cannot be obtained through a varied diet. Scientific evidence supporting the benefits of some vitamin supplements is well established for certain health conditions, but others need further study. In some cases, vitamin supplements may have unwanted effects, especially if taken before surgery, with other dietary supplements or medicines, or if the person taking them has certain health conditions. Dietary supplements may also contain levels of vitamins many times higher, and in different forms, than one may ingest through food. There have been mixed studies on the importance and safety of dietary supplementation. A meta-analysis published in 2006 suggested that Vitamin A and E supplements not only provide no tangible health benefits for generally healthy individuals but may actually increase mortality, although two large studies included in the analysis involved smokers, for whom it was already known that beta-carotene supplements can be harmful. Another study published in May 2009 found that antioxidants such as vitamins C and E may actually curb some benefits of exercise. While other findings suggest that evidence of Vitamin E toxicity is limited to specific form taken in excess. A double-blind trial published in 2011 found that vitamin E increases the risk of prostate cancer in healthy men. The conflict of interest section of this study reveals that it has ties to the ambitions of the pharmaceutical companies Merck, Pfizer, Sanofi-Aventis, AstraZeneca, Abbott, GlaxoSmithKline, Janssen, Amgen, Firmagon, and Novartis. Other studies without conflicts of interest reported exactly the opposite - that Vitamin E supplementation reduced the risk of prostate cancer, and increased overall prostate cancer survival. Most countries place dietary supplements in a special category under the general umbrella of foods, not drugs. This necessitates that the manufacturer, and not the government, be responsible for ensuring that its dietary supplement products are safe before they are marketed. Regulation of supplements varies widely by country. In the United States, a dietary supplement is defined under the Dietary Supplement Health and Education Act of 1994. In addition, the Food and Drug Administration uses the Adverse Event Reporting System to monitor adverse events that occur with supplements. In the European Union, the Food Supplements Directive requires that only those supplements that have been proven safe can be sold without a prescription. The reason that the set of vitamins skips directly from E to K is that the vitamins corresponding to letters F-J were either reclassified over time, discarded as false leads, or renamed because of their relationship to vitamin B, which became a complex of vitamins. The German-speaking scientists who isolated and described vitamin K (in addition to naming it as such) did so because the vitamin is intimately involved in the Koagulation of blood following wounding. At the time, most (but not all) of the letters from F through to J were already designated, so the use of the letter K was considered quite reasonable. The table on the right lists chemicals that had previously been classified as vitamins, as well as the earlier names of vitamins that later became part of the B-complex. Anti-vitamins are chemical compounds that inhibit the absorption or actions of vitamins. For example, avidin is a protein in egg whites that inhibits the absorption of biotin. Pyrithiamine is similar to thiamine, 1vitamin B, and inhibits the enzymes that use thiamine.
M: NUT cof, enz, met noco, nuvi, sysi/epon, met drug (A8/11/12) M: NUT cof, enz, met noco, nuvi, sysi/epon, met drug (A8/11/12)

Healthy diet
A healthy diet is one that helps maintain or improve general health. A healthy diet provides the body with essential nutrition: adequate fluid, adequate essential amino acids from protein, essential fatty acids, vitamins, minerals, and adequate calories. The requirements for a healthy diet can be met from a variety of plant-based and animal-based foods. A healthy diet supports energy needs and provides for human nutrition without exposure to toxicity or excessive weight gain from consuming excessive amounts. Where lack of calories is not an issue, a properly balanced diet (in addition to exercise) is also thought to be important for lowering health risks, such as obesity, heart disease, type 2 diabetes, hypertension and cancer. Various nutrition guides are published by medical and governmental institutions to educate the public on what they should be eating to promote health. Nutrition facts labels are also mandatory in some countries to allow consumers to choose between foods based on the components relevant to health. The World Health Organization (WHO) makes the following 5 recommendations with respect to both populations and individuals: Other recommendations include: The American Heart Association, World Cancer Research Fund, and American Institute for Cancer Research recommends a diet that consists mostly of unprocessed plant foods, with emphasis a wide range of whole grains, legumes, and non-starchy vegetables and fruits. This healthy diet is replete with a wide range of various non-starchy vegetables and fruits, that provide different colors including red, green, yellow, white, purple, and orange. They note that tomato cooked with oil, allium vegetables like garlic, and cruciferous vegetables like cauliflower, provide some protection against cancer. This healthy diet is low in energy density, which may protect against weight gain and associated diseases. Finally, limiting consumption of sugary drinks, limiting energy rich foods, including “fast foods” and red meat, and avoiding processed meats improves health and longevity. Overall, researchers and medical policy conclude that this healthy diet can reduce the risk of chronic disease and cancer. The Nutrition Source of Harvard School of Public Health makes the following 10 recommendations for a healthy diet: Other than nutrition, the guide recommends frequent physical activity (exercise) and maintaining a healthy body weight. In addition to dietary recommendations for the general population, there are many specific diets that have primarily been developed to promote better health in specific population groups, such as people with high blood pressure (as in low sodium diets or the more specific DASH diet), or people who are overweight or obese (in weight control diets). However, some of them may have more or less evidence for beneficial effects in normal people as well. A low sodium diet is beneficial for people with high blood pressure. A Cochrane review published in 2008 concluded that a long term (more than 4 weeks) low sodium diet in Caucasians has a useful effect to reduce blood pressure, both in people with hypertension and in people with normal blood pressure. The DASH diet (Dietary Approaches to Stop Hypertension) is a diet promoted by the National Heart, Lung, and Blood Institute (part of the NIH, a United States government organization) to control hypertension. A major feature of the plan is limiting intake of sodium, and it also generally encourages the consumption of nuts, whole grains, fish, poultry, fruits and vegetables while lowering the consumption of red meats, sweets, and sugar. It is also "rich in potassium, magnesium, and calcium, as well as protein". Evidence shows that the Mediterranean diet improves cardiovascular outcomes. Weight control diets aim to maintain a controlled weight. In most cases dieting is used in combination with physical exercise to lose weight in those who are overweight or obese. Diets to promote weight loss are generally divided into four categories: low-fat, low-carbohydrate, low-calorie, and very low calorie. A meta-analysis of six randomized controlled trials found no difference between the main diet types (low calorie, low carbohydrate, and low fat), with a 2–4 kilogram weight loss in all studies. At two years, all calorie-reduced diet types cause equal weight loss irrespective of the macronutrients emphasized. There may be a relationship between lifestyle including food consumption and potentially lowering the risk of cancer or other chronic diseases. A healthy diet may consist mostly of whole plant foods, with limited consumption of energy-dense foods, red meat, alcoholic drinks and salt while reducing consumption of sugary drinks, and processed meat. A healthy diet may contain non-starchy vegetables and fruits, including those with red, green, yellow, white, purple or orange pigments. Tomato cooked with oil, allium vegetables like garlic, and cruciferous vegetables like cauliflower "probably" contain compounds which are under research for their possible anti-cancer activity. A healthy diet is low in energy density, lowering caloric content, thereby possibly inhibiting weight gain and lowering risk against chronic diseases. Chronic Western diseases are associated with pathologically increased IGF-1 levels. Findings in molecular biology and epidemiologic data suggest that milk consumption is a promoter of chronic diseases of Western nations, including atherosclerosis, carcinogenesis and neurodegenerative diseases. An unhealthy diet is a major risk factor for a number of chronic diseases including: high blood pressure, diabetes, abnormal blood lipids, overweight/obesity, cardiovascular diseases, and cancer. The WHO estimates that 2.7 million deaths are attributable to a diet low in fruit and vegetable every year. Globally it is estimated to cause about 19% of gastrointestinal cancer, 31% of ischaemic heart disease, and 11% of strokes, thus making it one of the leading preventable causes of death worldwide. Fad diet usually refers to idiosyncratic diets and eating patterns. They are diets that claim to promote weight loss or treat obesity by various mechanisms, provide little to no scientific reasoning behind their purported health benefits, and have little or no proof to support them. Fears of high cholesterol were frequently voiced up until the mid-1990s. However, more recent research has shown that the distinction between high- and low-density lipoprotein ('good' and 'bad' cholesterol, respectively) must be addressed when speaking of the potential ill effects of cholesterol. Different types of dietary fat have different effects on blood levels of cholesterol. For example, polyunsaturated fats tend to decrease both types of cholesterol; monounsaturated fats tend to lower LDL and raise HDL; saturated fats tend to either raise HDL, or raise both HDL and LDL; and trans fat tend to raise LDL and lower HDL. Dietary cholesterol itself is only found in animal products such as meat, eggs, and dairy, but studies have shown that even large amounts of dietary cholesterol only have negligible effects on blood cholesterol. Vending machines in particular have come under fire as being avenues of entry into schools for junk food promoters. However, there is little in the way of regulation and it is difficult for most people to properly analyze the real merits of a company referring to itself as "healthy." Recently, the United Kingdom removed the rights for McDonald's to advertise its products, as the majority of the foods that were seen have low nutrient values and high fat counts were aimed at children under the guise of the "Happy Meal"][. The British Heart Foundation released its own government-funded advertisements, labeled "Food4Thought", which were targeted at children and adults displaying the gory nature of how fast food is generally constituted. From a psychological and cultural perspective, a healthier diet may be difficult to achieve for people with poor eating habits. This may be due to tastes acquired in childhood and preferences for sugary, salty and/or fatty foods.

Dietary fiber
Dietary fiber, dietary fibre, or sometimes roughage and ruffage is the indigestible portion of food derived from plants. There are two main components: Dietary fibers can act by changing the nature of the contents of the gastrointestinal tract and by changing how other nutrients and chemicals are absorbed. Some types of soluble fiber absorb water to become a gelatinous, viscous substance and is fermented by bacteria in the digestive tract. Some types of insoluble fiber have bulking action and are not fermented. Lignin, a major dietary insoluble fiber source, may alter the rate and metabolism of soluble fibers. Other types of insoluble fiber, notably resistant starch, are fully fermented. Chemically, dietary fiber consists of non-starch polysaccharides such as arabinoxylans, cellulose, and many other plant components such as resistant starch, resistant dextrins, inulin, lignin, waxes, chitins, pectins, beta-glucans, and oligosaccharides. A novel position has been adopted by the US Department of Agriculture to include functional fibers as isolated fiber sources that may be included in the diet. The term "fiber" is something of a misnomer, since many types of so-called dietary fiber are not actually fibrous. Food sources of dietary fiber are often divided according to whether they provide (predominantly) soluble or insoluble fiber. Plant foods contain both types of fiber in varying degrees, according to the plant's characteristics. Advantages of consuming fiber are the production of healthful compounds during the fermentation of soluble fiber, and insoluble fiber's ability (via its passive hygroscopic properties) to increase bulk, soften stool, and shorten transit time through the intestinal tract. Disadvantages of a diet high in fiber is the potential for significant intestinal gas production and bloating. Constipation can occur if insufficient fluid is consumed with a high-fiber diet. Originally, fiber was defined to be the components of plants that resist human digestive enzymes, a definition that includes lignin and polysaccharides. The definition was later changed to also include resistant starches, along with inulin and other oligosaccharides. Official definition of dietary fiber differs a little among different institutions:
Dietary fiber is most found in vegetables and fruit. The exact amount of fiber contained in the food can be seen in the following table of expected fiber in USDA food groups/subgroups Dietary fiber is found in plants. While all plants contain some fiber, plants with high fiber concentrations are generally the most practical source. Fiber-rich plants can be eaten directly. Or, alternatively, they can be used to make supplements and fiber-rich processed foods. The Academy of Nutrition and Dietetics (AND), formerly the American Dietetic Association, recommends consuming a variety of fiber-rich foods. Some plants contain significant amounts of soluble and insoluble fiber. For example plums and prunes have a thick skin covering a juicy pulp. The skin is a source of insoluble fiber, whereas soluble fiber is in the pulp. Also, grapes have a fair amount of fiber in them. The root of the konjac plant, or glucomannan, produces results similar to fiber and may also be used to relieve constipation. Glucomannan is sold in various forms, and while safe in some forms, it can be unsafe in others, possibly leading to throat or intestinal blockage. Soluble fiber is found in varying quantities in all plant foods, including: Sources of insoluble fiber include: These are a few example forms of fiber that have been sold as supplements or food additives. These may be marketed to consumers for nutritional purposes, treatment of various gastrointestinal disorders, and for such possible health benefits as lowering cholesterol levels, reducing risk of colon cancer, and losing weight. Soluble fiber supplements may be beneficial for alleviating symptoms of irritable bowel syndrome, such as diarrhea and/or constipation and abdominal discomfort. Prebiotic soluble fiber products, like those containing inulin or oligosaccharides, may contribute to relief from inflammatory bowel disease, as in Crohn's disease, ulcerative colitis, and Clostridium difficile, due in part to the short-chain fatty acids produced with subsequent anti-inflammatory actions upon the bowel. Fiber supplements may be effective in an overall dietary plan for managing irritable bowel syndrome by modification of food choices. The insoluble fiber, resistant starch from high amylose corn, has been used as a supplement and may contribute to improving insulin sensitivity and glycemic management as well as promoting regularity and possibly relief of diarrhea. One preliminary finding indicates that resistant corn starch may reduce symptoms of ulcerative colitis. Chemically defined as oligosaccharides occurring naturally in most plants, inulins have nutritional value as carbohydrates, or more specifically as fructans, a polymer of the natural plant sugar, fructose. Inulin is typically extracted by manufacturers from enriched plant sources such as chicory roots or Jerusalem artichokes for use in prepared foods. Subtly sweet, it can be used to replace sugar, fat, and flour, is often used to improve the flow and mixing qualities of powdered nutritional supplements, and has significant potential health value as a prebiotic fermentable fiber. Inulin is advantageous because it contains 25–30% the food energy of sugar or other carbohydrates and 10–15% the food energy of fat. As a prebiotic fermentable fiber, its metabolism by gut flora yields short-chain fatty acids (see below) which increase absorption of calcium, magnesium, and iron, resulting from upregulation of mineral-transporting genes and their membrane transport proteins within the colon wall. Among other potential beneficial effects noted above, inulin promotes an increase in the mass and health of intestinal Lactobacillus and Bifidobacterium populations. Vegetable gum fiber supplements are relatively new to the market. Often sold as a powder, vegetable gum fibers dissolve easily with no aftertaste. In preliminary clinical trials, they have proven effective for the treatment of irritable bowel syndrome. Examples of vegetable gum fibers are guar gum and acacia Senegal gum. Dietary fibers have three primary mechanisms: bulking, viscosity and fermentation. Dietary fibers can change the nature of the contents of the gastrointestinal tract, and to change how other nutrients and chemicals are absorbed through bulking and viscosity. Some types of soluble fibers bind to bile acids in the small intestine, making them less likely to enter the body; this in turn lowers cholesterol levels in the blood. Viscous soluble fibers may also attenuate the absorption of sugar, reduce sugar response after eating, normalize blood lipid levels and, once fermented in the colon, produce short-chain fatty acids as byproducts with wide-ranging physiological activities (discussion below). Insoluble fiber is associated with reduced diabetes risk, but the mechanism by which this occurs is unknown. One type of insoluble dietary fiber, resistant starch has been shown to directly increase insulin sensitivity in healthy people, in type 2 diabetics, and in individuals with insulin resistance, possibly contributing to reduced risk of type 2 diabetes. Not yet formally proposed as an essential macro-nutrient, dietary fiber is nevertheless regarded as important for the diet, with regulatory authorities in many developed countries recommending increases in fiber intake. Dietary fiber has distinct physicochemical properties. Most semi-solid foods, fiber and fat are a combination of gel matrices which are hydrated or collapsed with microstructural elements, globules, solutions or encapsulating walls. Fresh fruit and vegetables are cellular materials. A slowly eaten meal will enter the absorptive phase of the gastrointestinal tract more slowly than a rapidly eaten meal of similar composition. Many of the differences between low and high glycemic foods would disappear if a meal was eaten slowly. The chemical and physico-chemical nature (lipid, protein, carbohydrate) of the meal will also influence the gastric emptying of the food multiphase system. Fatty foods and hypertonic solutions empty slowly. The movement of food, i.e., chyme, along the gastrointestinal tract is typical of flow in a disperse system. As chyme moves along the gastrointestinal tract, polymer flow and diffusion becomes important. Following a meal, the stomach and upper gastrointestinal contents consist of Micelles are colloid-sized clusters of molecules which form in conditions as those above, similar to the critical micelle concentration of detergents. In the upper gastrointestinal tract, these detergents consist of bile acids and di- and monoacyl glycerols which solubilize triacylglycerols and cholesterol. Two mechanisms bring nutrients into contact with the epithelium: The multiple physical phases in the intestinal tract slow the rate of absorption compared to that of the suspension solvent alone. Adding viscous polysaccharides to carbohydrate meals can reduce post-prandial blood glucose concentrations. Wheat and maize but not oats modify glucose absorption, the rate being dependent upon the particle size. The reduction in absorption rate with guar gum may be due to the increased resistance by viscous solutions to the convective flows created by intestinal contractions. Dietary fiber interacts with pancreatic and enteric enzymes and their substrates. Human pancreatic enzyme activity is reduced when incubated with most fiber sources. Fiber may affect amylase activity and hence the rate of hydrolysis of starch. The more viscous polysaccharides extend the mouth-to-cecum transit time; guar, tragacanth and pectin being slower than wheat bran. The colon may be regarded as two organs, The presence of bacteria in the colon produces an ‘organ’ of intense, mainly reductive, metabolic activity, whereas the liver is oxidative. The substrates utilized by the cecal have either passed along the entire intestine or are biliary excretion products . The effects of dietary fiber in the colon are on Enlargement of the cecum is a common finding when some dietary fibers are fed and this is now believed to be normal physiological adjustment. Such an increase may be due to a number of factors, prolonged cecal residence of the fiber, increased bacterial mass, or increased bacterial end-products. Some non-absorbed carbohydrates, e.g. pectin, gum arabic, oligosaccharides and resistant starch, are fermented to short-chain fatty acids (chiefly acetic, propionic and n-butyric), and carbon dioxide, hydrogen and methane. The cecal fermentation of 40–50 g of complex polysaccharides will yield 400–500 mmol total short-chain fatty acids, 240–300 mmol acetate, and 80–100 mmol of both propionate and butyrate. Almost all of these short-chain fatty acids will be absorbed from the colon. This means that fecal short-chain fatty acid estimations do not reflect cecal and colonic fermentation, only the efficiency of absorption, the ability of the fiber residue to sequestrate short-chain fatty acids, and the continued fermentation of fiber around the colon, which presumably will continue until the substrate is exhausted. The production of short-chain fatty acids has several possible actions on the gut mucosa. All of the short-chain fatty acids are readily absorbed by the colonic mucosa, but only acetic acid reaches the systemic circulation in appreciable amounts. Butyric acid appears to be used as a fuel by the colonic mucosa as the preferred energy source for colonic cells. Dietary fiber may act on each phase of ingestion, digestion, absorption and excretion to affect cholesterol metabolism, such as the following: An important action of some fibers is to reduce the reabsorption of bile acids in the ileum and hence the amount and type of bile acid and fats reaching the colon. A reduction in the reabsorption of bile acid from the ileum has several direct effects. The fibers that are most effective in influencing sterol metabolism (e.g. pectin) are fermented in the colon. It is therefore unlikely that the reduction in body cholesterol is due to adsorption to this fermented fiber in the colon. Feces consist of plasticine-like material, made up of water, bacteria, lipids, sterols, mucus and fiber. Water is distributed in the colon in three ways: Fecal weight is dictated by: Wheat bran is minimally fermented and binds water and when added to the diet increases fecal weight in a predictable linear manner and decreases intestinal transit time. The particle size of the fiber is all-important, coarse wheat bran being more effective than fine wheat bran. The greater the water-holding capacity of the bran, the greater the effect on fecal weight. For most healthy individuals, an increase in wet fecal weight, depending on the particle size of the bran, is generally of the order of 3–5 g/g fiber. The fermentation of some fibers results in an increase in the bacterial content and possibly fecal weight. Other fibers, e.g. pectin, are fermented and have no effect on stool weight. Research has shown that fiber may benefit health in several different ways. Lignin and probably related materials that are resistant to enzymatic degradation, diminish the nutritional value of foods. Color coding of table entries: Fiber does not bind to minerals and vitamins and therefore does not restrict their absorption, but rather evidence exists that fermentable fiber sources improve absorption of minerals, especially calcium. Some plant foods can reduce the absorption of minerals and vitamins like calcium, zinc, vitamin C, and magnesium, but this is caused by the presence of phytate (which is also thought to have important health benefits), not by fiber. An experiment designed with a large sample and conducted by NIH-AARP Diet and Health Study studied the correlation between fiber intake and colorectal cancer. The analytic cohort consisted of 291 988 men and 197 623 women aged 50–71 y. Diet was assessed with a self-administered food-frequency qustionnaire at baseline in 1995-1996; 2974 incident colorectal cancer cases were identified during 5 y of follow-up. The result was that total fiber intake was not associated with colorectal cancer. But on the other hand, the analyses of fiber from different food sources showed that fiber from grains was associated with a lower risk of colorectal cancer. Although many researchers believe that dietary fiber intake reduces risk of colon cancer, one study conducted by researchers at the Harvard School of Medicine of over 88,000 women did not show a statistically significant relationship between higher fiber consumption and lower rates of colorectal cancer or adenomas. Similarly, a 2010 study of 58,279 men found no relationship between dietary fiber and colorectal cancer. Dietary fiber has many functions in diet, one of which may be to aid in energy intake control and reduced risk for development of obesity. The role of dietary fiber in energy intake regulation and obesity development is related to its unique physical and chemical properties that aid in early signals of satiation and enhanced or prolonged signals of satiety. Early signals of satiation may be induced through cephalic- and gastric-phase responses related to the bulking effects of dietary fiber on energy density and palatability, whereas the viscosity-producing effects of certain fibers may enhance satiety through intestinal-phase events related to modified gastrointestinal function and subsequent delay in fat absorption. In general, fiber-rich diets, whether achieved through fiber supplementation or incorporation of high fiber foods into meals, have a reduced energy density compared with high fat diets. This is related to fiber’s ability to add bulk and weight to the diet. However, the subsequent effect of fiber on food intake has been more variable because in some cases, food intake at a test meal was reduced, in other cases, it was not. Although much of the discrepancy in results may be ascribed to differences among studies, different responses related to gender and body weight status (i.e., obese vs. normal weight) may also be responsible. With regard to gender, work in our][ laboratory indicates that women may be more sensitive to dietary manipulation with fiber than men, which is consistent with a previous report by Burley et al. (1993). Moreover, we][ have found that the subjective satiety response to dietary manipulation in men and women is supported by differences in the CCK response, suggesting that signals for satiety differ between genders (Burton-Freeman et al. 1998 and personal communication). The relationship of body weight status and fiber effect on energy intake suggests that obese individuals may be more likely to reduce food intake (Evans and Miller 1975, Porikos and Hagamen 1986) with dietary fiber inclusion. Current recommendations from the United States National Academy of Sciences, Institute of Medicine, suggest that adults should consume 20–35 grams of dietary fiber per day, but the average American's daily intake of dietary fiber is only 12–18 grams. The AND (Academy of Nutrition and Dietetics, previously ADA) recommends a minimum of 20–35 g/day for a healthy adult depending on calorie intake (e.g., a 2000 Cal/8400 kJ diet should include 25 g of fiber per day). The AND's recommendation for children is that intake should equal age in years plus 5 g/day (e.g., a 4 year old should consume 9 g/day). No guidelines have yet been established for the elderly or very ill. Patients with current constipation, vomiting, and abdominal pain should see a physician. Certain bulking agents are not commonly recommended with the prescription of opioids because the slow transit time mixed with larger stools may lead to severe constipation, pain, or obstruction. The British Nutrition Foundation has recommended a minimum fiber intake of 18 g/day for healthy adults. On average, North Americans consume less than 50% of the dietary fiber levels recommended for good health. In the preferred food choices of today's youth, this value may be as low as 20%, a factor considered by experts as contributing to the obesity levels seen in many developed countries. The actual fiber intake gaps of different age groups of Americans are shown in the graph from USDA: Recognizing the growing scientific evidence for physiological benefits of increased fiber intake, regulatory agencies such as the Food and Drug Administration (FDA) of the United States have given approvals to food products making health claims for fiber. In clinical trials to date, these fiber sources were shown to significantly reduce blood cholesterol levels, an important factor for general cardiovascular health, and to lower risk of onset for some types of cancer. Soluble (fermentable) fiber sources gaining FDA approval are: Other examples of fermentable fiber sources (from plant foods or biotechnology) used in functional foods and supplements include inulin, resistant dextrins, fructans, xanthan gum, cellulose, guar gum, fructooligosaccharides (FOS), and oligo- or polysaccharides. Consistent intake of fermentable fiber through foods like berries and other fresh fruit, vegetables, whole grains, seeds, and nuts is now known to reduce risk of some of the world’s most prevalent diseases—obesity, diabetes, high blood cholesterol, cardiovascular disease, and numerous gastrointestinal disorders. In this last category are constipation, inflammatory bowel disease, ulcerative colitis, hemorrhoids, Crohn's disease, diverticulitis, and colon cancer—all disorders of the intestinal tract where fermentable fiber can provide healthful benefits. Insufficient fiber in the diet can complicate defecation. Low-fiber feces are dehydrated and hardened, making them difficult to evacuate—defining constipation and possibly leading to development of hemorrhoids or anal fissures. In June 2007, the British Nutrition Foundation issued a statement to define dietary fiber more concisely and list the potential health benefits established to date: ‘Dietary fibre’ has been used as a collective term for a complex mixture of substances with different chemical and physical properties which exert different types of physiological effects. The use of certain analytical methods to quantify dietary fiber by nature of its indigestibility results in many other indigestible components being isolated along with the carbohydrate components of dietary fiber. These components include resistant starches and oligosaccharides along with other substances that exist within the plant cell structure and contribute to the material that passes through the digestive tract. Such components are likely to have physiological effects. Yet, some differentiation has to be made between these indigestible plant components and other partially digested material, such as protein, that appears in the large bowel. Thus, it is better to classify fiber as a group of compounds with different physiological characteristics, rather than to be constrained by defining it chemically. Diets naturally high in fiber can be considered to bring about several main physiological consequences: Fiber contributes less energy (measured in Calories or kilojoules) than sugars and starches because it cannot be fully absorbed by the body. Sugars and starches provide 4 Calories per gram, and the human body has specific enzymes to break them down into glucose, fructose, and galactose, which can then be absorbed by the body. The human body lacks enzymes to break down fiber. Insoluble fiber does not change inside the body, so the body cannot absorb it and nutritionists say that it contributes 0 Calories per gram. Soluble fiber is partially fermented, with the degree of fermentability varying with the type of fiber, and contributes some energy when broken down and absorbed by the body. Dietitians have not reached a consensus on how much energy is actually absorbed, but some approximate around 2 Calories (8.36 joules) per gram of soluble fiber. Regardless of the type of fiber, the body absorbs fewer than 4 Calories (16.7 kilojoules) per gram of fiber, which can create inconsistencies for actual product nutrition labels. In some countries, fiber is not listed on nutrition labels, and is considered 0 Calories/gram when the food's total Calories are computed. In other countries all fiber must be listed, and is considered 4 Calories per gram when the food's total Calories are computed (because chemically fiber is a type of carbohydrate and other carbohydrates contribute 4 Calories per gram). In the US, soluble fiber must be counted as 4 Calories per gram, but insoluble fiber may be (and usually is) treated as 0 Calories per gram and not mentioned on the label. The American Association of Cereal Chemists has defined soluble fiber this way: "the edible parts of plants or similar carbohydrates resistant to digestion and absorption in the human small intestine with complete or partial fermentation in the large intestine." In this definition: As an example of fermentation, shorter-chain carbohydrates (a type of fiber found in legumes) cannot be digested, but are changed via fermentation in the colon into short-chain fatty acids and gases (which are typically expelled as flatulence). According to a 2002 journal article, fibers compounds with partial or low fermentability include: fiber compounds with high fermentability include: When soluble fiber is fermented, short-chain fatty acids (SCFA) are produced. SCFAs are involved in numerous physiological processes promoting health, including: SCFAs that are absorbed by the colonic mucosa pass through the colonic wall into the portal circulation (supplying the liver), and the liver transports them into the general circulatory system. Overall, SCFAs affect major regulatory systems, such as blood glucose and lipid levels, the colonic environment, and intestinal immune functions. The major SCFAs in humans are butyrate, propionate, and acetate, where butyrate is the major energy source for colonocytes, propionate is destined for uptake by the liver, and acetate enters the peripheral circulation to be metabolized by peripheral tissues. The FDA allows producers of foods containing 1.7g per serving of psyllium husk soluble fiber or 0.75g of oat or barley soluble fiber as beta-glucans to claim that reduced risk of heart disease can result from their regular consumption. The FDA statement template for making this claim is: Soluble fiber from foods such as [name of soluble fiber source, and, if desired, name of food product], as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease. A serving of [name of food product] supplies __ grams of the [necessary daily dietary intake for the benefit] soluble fiber from [name of soluble fiber source] necessary per day to have this effect. Eligible sources of soluble fiber providing beta-glucan include: The allowed label may state that diets low in saturated fat and cholesterol and that include soluble fiber from certain of the above foods "may" or "might" reduce the risk of heart disease. As discussed in FDA regulation 21 CFR 101.81, the daily dietary intake levels of soluble fiber from sources listed above associated with reduced risk of coronary heart disease are: Soluble fiber from consuming grains is included in other allowed health claims for lowering risk of some types of cancer and heart disease by consuming fruit and vegetables (21 CFR 101.76, 101.77, and 101.78). A study of 388,000 adults ages 50 to 71 for nine years found that the highest consumers of fiber were 22% less likely to die over this period. In addition to lower risk of death from heart disease, adequate consumption of fiber-containing foods, especially grains, was also associated with reduced incidence of infectious and respiratory illnesses, and, particularly among males, reduced risk of cancer-related death.
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