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Vitamin C , also known as ascorbic acid and L -sorborbic acid , is a vitamin found in foods and is used as a dietary supplement. The scabies are prevented and treated with foods containing vitamin C or dietary supplements. The evidence does not support the use of the general population for the prevention of the common cold. However, some evidence that regular use may shorten the duration of colds. It is unclear whether supplementation affects the risk of cancer, cardiovascular disease, or dementia. It can be taken or by injection.

Vitamin C is generally well tolerated. Large doses can cause gastrointestinal discomfort, headache, sleeping difficulties, and redness of the skin. The normal dose is safe during pregnancy. The American Institute of Medicine recommends not to use large doses.

Vitamin C is an essential nutrient involved in tissue repair and enzymatic production of certain neurotransmitters. Necessary for the proper functioning of several enzymes and essential for immune system function. It also acts as an antioxidant. Foods that contain vitamin C include citrus fruits, broccoli, Brussels sprouts, raw peppers, and strawberries. Old storage or cooking can reduce the vitamin C content in the diet.

Vitamin C was invented in 1912, isolated in 1928, and in 1933 was the first vitamin to be produced chemically. This is a List of Essential Medicines Models of the World Health Organization, the most effective and safe medicines needed in the health system. Vitamin C is available as a generic and drug-free medication. By 2015, wholesale costs in developing countries are less than US $ 0.01 per tablet. Partly for his discovery, Albert Szent-GyÃÆ'¶rgyi and Walter Norman Haworth awarded the 1937 Nobel Prize in Physiology and Medicine and Chemistry, respectively.

Video Vitamin C



Biology

Significance

Vitamin C is an essential nutrient for certain animals including humans. The term vitamin C includes some vitamers that have vitamin C activity in animals. Ascorbic salts such as sodium ascorbate and calcium ascorbate are used in some dietary supplements. This release improves digestion. Ascorbate and ascorbic acid are naturally present in the body, due to interconvert forms according to pH. The oxidized forms of molecules such as dehydroascorbic acid are converted back to ascorbic acid by reducing agents.

Vitamin C is a cofactor at least in eight enzymatic reactions in animals (and humans) is important in many important functions, including wound healing. In humans, vitamin C deficiency impairs collagen synthesis, contributing to the more severe symptoms of scurvy. More generally, the biochemical role of vitamin C is to act as an antioxidant (reducing agents) by donating electrons to various enzymatic and non-enzymatic reactions. Doing so turns vitamin C into an oxidized state - either as a semidehydroascorbic acid or a dehydroascorbic acid. These compounds can be restored to a reduced state by the enzymatic mechanism of glutathione and NADPH-dependent.

In plants, vitamin C is the substrate for ascorbate peroxidase. This enzyme uses ascorbate to neutralize toxic hydrogen peroxide (H 2 O 2 ) by converting it to water (H 2 O).

Disadvantages

Scurvy is a disease resulting from vitamin C deficiency, because without this vitamin, the collagen made by the body is too unstable to perform its function.

Scurvy leads to the formation of brown spots on the skin, sponge gums, and bleeding from all mucous membranes. The most abundant spots on the thighs and legs, and someone with the disease appear pale, feeling depressed, and some can not move. In advanced scab disease there are open wounds, festering and loss of teeth, and finally death. The human body can only store some vitamin C, and therefore the body supply will run out if fresh supplies are not consumed. The time frame for the onset of scurvy symptoms in adults without stress on a completely vitamin C-free diet, however, can range from one month to over six months, depending on prior loading of vitamin C.

An important human dietary study of experimental-induced scurvy has been done on the opponents of conscience during World War II in Britain and in Iowa country prisoners in the late 1960s to the 1980s. These studies both found that all the obvious symptoms of scurvy previously induced by an experimental scorptic diet with very low vitamin C content could be completely reversed with supplemental vitamin C supplements of only 10 mg daily. In this experiment, no clinical differences were noted between men who were given 70 mg of vitamin C per day (which resulted in vitamin C blood levels of about 0.55 mg/dl, about 1/3 tissue saturation level) and those given 10 mg per day. Men in prison studies developed the first signs of scurvy about four weeks after starting a vitamin C-free diet, while in the UK study, six to eight months were needed, possibly because of pre-loading this group with 70 mg/day of supplementation for six weeks before diet scorbutic is fed.

Men in both studies on a diet that were altogether, or almost nonexistent, vitamin C had too low levels of vitamin C in the blood to be accurately measured when they developed signs of scurvy, and in the Iowa study, presently estimated (by labeled vitamin C dilution) has a body pool of less than 300 mg, with a daily turnover of only 2.5 mg/day, implying an instant part of the current 83 days at this time (constant elimination of 4 months).

Maps Vitamin C



Usage

Vitamin C has a definitive role in treating scurvy, which is a disease caused by vitamin C deficiency. Beyond that, the role of vitamin C as prevention or treatment for various diseases is debated, with reviews reporting conflicting results. A review of Cochrane 2012 reported no effect of vitamin C supplementation on overall mortality. It is listed in the World Health Organization's Essential Medicines List as one of the most effective and safe drugs needed in the health system.

Scurvy

Scurvy is caused by vitamin C deficiency and can be prevented and treated with foods containing vitamin C or dietary supplements. It takes at least a little month until there is no vitamin C before symptoms appear. Early symptoms are malaise and lethargy, developing into shortness of breath, bone pain, bleeding gums, prone to bruising, poor wound healing, and finally fever, seizures and eventually death. Until fairly late in the disease, the damage can be reversed, as with vitamin C, healthy collagen replaces damaged collagen. Treatment can be done orally or by intramuscular or intravenous injection. Scurvy is known to Hippocrates in the classical era. The disease was proven to be prevented by citrus fruits in early controlled trials by Royal Navy surgeon James Lind in 1747, and from 1796 lemon juice was released to all Royal Navy crew.

Infection

The effects of vitamin C on common cold have been widely investigated. The earliest publication of controlled clinical trials appears to have originated from 1945. Researchers continue to work on this question, but research interests and public interest have soared after Linus Pauling, the recipient of two Nobel prizes (Chemistry Prize, 1954, Peace Prize 1962). ), began publishing research on the topic and also published the book "Vitamin C and Common Cold" in 1970. The revised and expanded edition of "Vitamin C, Common Cold and the Flu" was published in 1976.

A Cochrane Review published in 2013 with inclusion criteria limited to trials that call for at least 200 mg/day concluded that regularly taken vitamin C is not effective in preventing the common cold. Limiting inclusions to trials that call for at least 1000 mg/day is no different. However, taking vitamin C regularly does reduce the average duration of 8% in adults and 14% in children, and also reduce the severity of colds. The test subset reports that supplementation reduces the incidence of colds by half in marathon runners, skiers, or soldiers in subarctic conditions. Other parts of the trial look at therapeutic uses, which means that vitamin C does not start unless people begin to feel the onset of a cold. In this case, vitamin C does not affect the duration or severity. Previous reviews have stated that vitamin C does not prevent colds, reduces duration, does not reduce severity. The Cochrane review authors concluded that "... given the consistent effects of vitamin C on the duration and severity of colds in regular supplementation studies, and low cost and safety, it may be beneficial for ordinary flu patients to test on individually whether therapeutic vitamin C is beneficial to them. "

Vitamin C is easily distributed in high concentrations into immune cells, has antimicrobial cell activity and natural killer cells, promotes lymphocyte proliferation, and is consumed rapidly during infection, the effect indicating a prominent role in the regulation of the immune system. The European Food Safety Authority finds a cause and effect relationship between dietary intake of vitamin C and normal immune system function in adults and children under the age of three.

Cancer

There are two approaches to the question of whether vitamin C has an impact on cancer. First, within the normal range of dietary intake without supplemental dietary supplements, do people who consume more vitamin C are at lower risk for developing cancer, and if so, are oral supplements having the same benefits? Secondly, for people diagnosed with cancer, will a large number of ascorbic acid be given intravenously to treat cancer, reduce the adverse effects of other treatments, and prolong survival and improve quality of life? The 2013 Cochrane Review found no evidence that vitamin C supplementation reduces the risk of lung cancer in healthy or high-risk people (smokers and asbestos). Meta-analysis of 2014 found that vitamin C intake may protect against lung cancer risk. A second meta-analysis found no effect on the risk of prostate cancer. Two meta-analyzes evaluated the effect of vitamin C supplementation on the risk of colorectal cancer. One found a weak association between vitamin C consumption and reduced risk, and the other did not find a supplemental effect. A 2011 meta-analysis failed to find support for breast cancer prevention with vitamin C supplements, but a second study concluded that vitamin C could be associated with increased survival in those already diagnosed.

Under the rubric of orthomolecular medicine, "Vitamin C intravenous is a controversial additional cancer therapy, widely used in naturopathic and integrative oncology settings." With the efficiency of absorption oral administration decreases with increasing number. Intravenous giving goes through this. Doing so makes it possible to achieve plasma concentrations of 5 to 10 millimoles/liter (mmol/L), which far exceeds about 0.2 mmol/L limit of oral consumption. Theories of the mechanism are contradictory. At high tissue concentrations, ascorbic acid is described as acting as a pro-oxidant, producing hydrogen peroxide (H 2 O 2 ) to kill tumor cells. The same literature claims that ascorbic acid acts as an antioxidant, thereby reducing the adverse effects of chemotherapy and radiation therapy. Research continues in this area, but the 2014 review concludes: "Today, high doses of vitamin C (as an anticancer agent) can not be recommended beyond clinical trials." The 2015 review adds: "There is no high-quality evidence to suggest that ascorbic supplementation in cancer patients increases the antitumor effect of chemotherapy or reduces its toxicity." The evidence for ascorbate anti-tumor effects is limited to case reports and observational and uncontrolled research. "

Cardiovascular Disease

A meta-analysis 2013 found no evidence that vitamin C supplementation reduces the risk of myocardial infarction, stroke, cardiovascular mortality, or all-cause mortality. However, a second analysis found an inverse relationship between circulating vitamin C levels or dietary vitamin C and stroke risk.

A meta-analysis of 44 clinical trials has demonstrated a significant positive effect of vitamin C on endothelial function when taken at doses greater than 500 mg per day. The endothelium is a layer of cells that line the inner surface of a blood vessel. Endothelial dysfunction is involved in many aspects of vascular disease. The researchers note that the effect of vitamin C supplementation appears to depend on health status, with a stronger effect on those who have a higher risk of cardiovascular disease.

Other diseases

Studies that examine the effect of vitamin C intake on the risk of Alzheimer's disease have reached conflicting conclusions. Maintaining a healthy food intake may be more important than supplementation to achieve potential benefits. The 2010 review found no role for vitamin C supplementation in the treatment of rheumatoid arthritis. Vitamin C supplementation does not prevent or slow the development of age-related cataracts.

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Side effects

More than two to three grams can cause indigestion, especially when taken on an empty stomach. However, taking vitamin C in the form of sodium ascorbate and calcium ascorbate can minimize this effect. Other symptoms reported for large doses include nausea, abdominal cramps and diarrhea. This effect is associated with the osmotic effects of vitamin C that are not absorbed through the intestines. In theory, high intake of vitamin C can lead to excessive iron absorption. A summary of supplementation reviews on healthy subjects did not report the problem, but left as untested the possibility that individuals with hereditary hemochromatosis may be affected. There is a longstanding belief among mainstream medical community that vitamin C increases the risk of kidney stones. "Reports of kidney stone formation associated with excessive ascorbic acid intake are limited to individuals with kidney disease". Review states that "data from epidemiological studies do not support the association between excessive ascorbic acid intake and kidney stone formation in apparently healthy individuals", although one large multi-year trial reported a nearly doubled increase in kidney stones in men who regularly took supplements vitamin C. Vitamin C is a water soluble vitamin, with excess diet not absorbed, and excess in the blood is quickly excreted in the urine, thus showing very low acute toxicity.

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Diet

Suggested levels

Recommendations for vitamin C intake by adults have been established by various national institutions:

  • 40 milligrams per day: India National Institute of Nutrition, Hyderabad
  • 45 milligrams per day or 300 milligrams per week: World Health Organization
  • 80 milligrams per day: Council of the European Commission on nutrition labeling
  • 90 mg/day (men) and 75 mg/day (women): Health Canada 2007
  • 90 mg/day (male) and 75 mg/day (female): United States National Academy of Sciences.
  • 100 milligrams per day: Japan National Institute of Health and Nutrition.
  • 110Ã, mg/day (men) and 95Ã, mg/day (women): European Food Safety Authority

In 2000 North American Dietary Reference Intake chapter on vitamin C updated Recommended Dietary Allowance (RDA) to 90 milligrams per day for adult men and 75A mg/day for adult women, and set a tolerable level of intake (UL) for adults of 2,000 mg/day. The table shows the RDA for the United States and Canada for children, and for pregnant and lactating women. For EU, EFSA set higher recommendation for adults, and also for children: 20a mg/day for age 1-3, temperature 30 mg/day for age 4-6, temperature 45 mg/day for age 7 -10, 70 mg/day for age 11-14, 100mg/day for men ages 15-17, 90mg/day for women aged 15-17 years. For pregnancy 100 mg/day; for lactation 155 mg/day. Indian recommendations, on the other hand, have set much lower: 40A mg/day for age 1 to adult, 60 mg/day for pregnancy, and 80A mg/day for breastfeeding. Clearly, there is no consensus among countries.

Smoker smokers and people exposed to someone else's cigarette smoke have lower plasma vitamin C levels than nonsmokers. The thought is that inhaling smoke causes oxidative damage, depleting this antioxidant vitamin. The US Institute of Medicine estimates that smokers need 35 mg more vitamin C per day than nonsmokers, but do not formally assign a higher RDA to smokers. One meta-analysis showed an inverse association between vitamin C intake and lung cancer, although it was concluded that more research is needed to confirm these observations.

The US National Center for Health Statistics conducts a two-year National Health and Nutrition Assessment (NHANES) survey to assess the health and nutrition status of adults and children in the United States. Some results are reported as What We Eat In America. The 2013-2014 Survey reported that for adults over 20 years old, men consume an average of 83.3 mg/day and women 75.1 mg/day. This means that half the women and more than half of men do not consume RDA for vitamin C. The same survey states that about 30% of adults report they are taking vitamin C dietary supplements or multi-vitamin/mineral supplements that include vitamin C, and that for people these total consumption is between 300 and 400 mg/day.

In 2000, the Institute of Medicine of the US National Academy of Sciences established a tolerable upper intake (UL) level for adults 2,000 mg/day. The amount was chosen because human trials have reported diarrhea and other indigestion at an intake of more than 3,000 mg/day. This is the Lowest Observed Rate (LOAEL), which means that other detrimental effects are observed at higher consumption. The European Food Safety Authority (EFSA) reviewed security inquiries in 2006 and reached the conclusion that there was not enough evidence to establish UL for vitamin C. Japan's National Institute of Health and Nutrition reviewed the same question in 2010 and also reached the conclusion that there is no evidence enough to set the UL.

Food label

For the labeling of food and US dietary supplements, the amount in the presentation is expressed as a percent of Daily Value (% DV). For the purpose of giving vitamin C 100% of Daily Value is 60 mg, but on May 27, 2016 it was revised to 90 mg to make it agree with the RDA. The old and new daily Adult Value table is given in Daily Intake References. Food and supplement companies have until January 1, 2020 to comply with changes. EU regulations require that labels express energy, protein, fat, saturated fat, carbohydrates, sugar, and salt. Voluntary nutrition can be shown if present in significant amounts. Instead of Daily Value, the number is displayed as percent of Reference Intakes (RIs). For vitamin C, 100% RI is set at 80 mg in 2011.

Source

The richest natural sources are fruits and vegetables. Vitamin C is the most widely consumed nutritional supplement available in various forms, including tablets, beverage mixtures, and in capsules.

Plant source

While the plant is generally a good source of vitamin C, the amount in the plant's diet depends on the crop varieties, soil conditions, the climate in which it grows, the length of time since picking, storage conditions, and preparation methods. The following table is approximate and shows relative abundance in various sources of raw crops. Because some plants are freshly analyzed while others are dried (thereby, increasing the concentration of individual constituents such as vitamin C) artificially, the data is subject to potential variations and difficulties for comparison. The amount is given in milligrams per 100 gram servings of edible fruits or vegetables:

Animal sources

Foods derived from animals do not provide much vitamin C, and what exists, is destroyed by the heat of cooking. For example, raw chicken livers contain 17.9 mg/100 g, but are fried, the contents are reduced to 2.7 mg/100 g. Chicken eggs do not contain vitamin C, raw or cooked. Vitamin C is present in breast milk at 5.0, mg/100 g and 6.1 mg/100 g in a single sample of infants tested, but cow's milk contains only 1.0 mg, mg/100 g.

Food preparation

Vitamin C chemically decomposes under certain conditions, many of which may occur during cooking meals. The concentration of vitamin C in various nutrients decreases with time proportional to the temperature at which they are stored and cooking can reduce the vitamin C content of vegetables by about 60% probably in part due to an increase in enzymatic damage because it may be more significant in the boiling sub- Longer cooking times also add to this effect, as do the copper food vessels, which catalyze decomposition.

Another cause of vitamin C lost from food is washing, where water soluble vitamins dissolve into boiled water, which is then poured and not consumed. However, vitamin C does not seep in all vegetables at the same level; research shows that broccoli seems to retain more than others. Research also shows that freshly cut fruit does not lose essential nutrients when stored in the refrigerator for several days.

Supplements

Vitamin C food supplements are available as tablets, capsules, beverage mix packages, in multi-vitamin/mineral formulations, in antioxidant formulations, and as crystalline powders. Vitamin C is also added to some fruit juices and juice drinks. Capsules and capsules range from 25 mg to 1500 mg per serving. The most commonly used supplemental compounds are ascorbic acid, sodium ascorbate and calcium ascorbate. Vitamin C molecules can also be bound to palmitic fatty acids, creating ascorbyl palmitate, or incorporated into liposomes.

Food fortification

In 2014, the Canadian Food Inspection Agency evaluates the fortification effect of food with ascorbate in the guidance document, Foods Vitamins, Nutritional and Amino Acids May or Be Added . The castle is voluntary and must be described for various food classes. Among the foods classified for compulsory fortification with vitamin C are flavored fruit, mixed, and concentrated drinks, low-energy diet foods, food substitutes, and evaporated milk.

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Action mechanism

Absorption, transport, and excretion

From the US National Institute of Health: [In humans] "Approximately 70% -90% of vitamin C is absorbed at a moderate intake of 30-180 mg/day, but at doses above 1,000 mg/day, absorption decreases to less than 50%. "It is transported through the gut through glucose-sensitive and glucose-insensitive mechanisms, so the presence of large amounts of sugar in the intestine can slow down absorption.

Ascorbic acid is absorbed in the body by active transport and simple diffusion. Sodium-Dependent Active Transport - Sodium-Ascorbate Co-Transporter (SVCT) and Hexose transporters (GLUTs) - are the two transporter proteins required for active absorption. SVCT1 and SVCT2 import reduced ascorbate forms across the plasma membrane. GLUT1 and GLUT3 are glucose carriers, and only transfer dehydroascorbic acid (DHA) form of vitamin C. Although dehydroascorbic acid is absorbed in a higher rate than ascorbate, the amount of dehydroascorbic acid found in plasma and tissue under normal conditions is low, as cells quickly reduce dehydroascorbic acid becomes ascorbate.

SVCT appears to be the main system for transport of vitamin C in the body, the exception being red blood cells, which lose SVCT protein during maturation. In both vitamin C synthesizers (eg: mice) and non-synthesizers (eg: human) cells with few exceptions maintaining ascorbic acid concentrations much higher than about 50 micromoles/liter (Ã,Âμmol/L) found in plasma. For example, the ascorbic acid content of the pituitary and adrenal glands may exceed 2,000 Ã,Âμmol/L, and the muscles are at 200-300 μmol/L. The known coenzymic function of ascorbic acid does not require such high concentrations, so there may be other functions that have not yet is known. The consequence of all these organ constituents is that plasma vitamin C is not a good indicator of the whole body status, and people can vary in the amount of time it takes to show symptoms of deficiency when consuming very low vitamin C.

Excretion, can be like ascorbic acid, through urine. In humans, during low dietary intake, vitamin C is reabsorbed by the kidneys rather than excreted. Only when the plasma concentration is 1.4 mg/dL or higher, decreased reabsorption decreases and the excess amount flows freely to the urine. This rescue process delays the onset of deficiency. Ascorbic acid also converts (reversibly) into dehydroascorbate (DHA) and from the compound non-reversibly to 2,3-diketogluonate and then oxalate. These three compounds are also excreted through the urine. Humans are better than guinea pigs to turn DHA back into ascorbate, and thus take longer to become deficient in vitamin C.

Enzymatic cofactors

Ascorbic acid performs many physiological functions in the human body. These functions include the synthesis of collagen, carnitine, and neurotransmitters; synthesis and catabolism of tyrosine; and microsomal metabolism. During biosynthesis ascorbate acts as a reducing agent, donating electrons and preventing oxidation to keep the iron and copper atoms in a reduced state.

Vitamin C acts as an electron donor for eight enzymes:

  • Three enzymes (prolyl-3-hydroxylase, prolyl-4-hydroxylase, and lysyl hydroxylase) are required for proline and lysine hydroxylation in collagen synthesis. These reactions add hydroxyl groups to the proline of amino acids or lysine in collagen molecules through prolyl hydroxylase and lysyl hydroxylase, both of which require vitamin C as a cofactor. Hydroxylation allows collagen molecules to take a triple helix structure, and thus vitamin C is essential for the development and maintenance of scar tissue, blood vessels, and cartilage.
  • Two enzymes (? -N-trimethyl-L-lysine hydroxylase and? -butyrobetaine hydroxylase) are required for the synthesis of carnitine. Carnitine is essential for the transport of fatty acids to mitochondria for the formation of ATP.
  • The three remaining enzymes have the following functions in common, in addition to other functions:
    • dopamine beta hydroxylase participates in the norepinephrine biosynthesis of dopamine.
    • Peptidylglycine alpha-amidating monooxygenase in the middle of the peptide hormone by removing the glyoxylate residue from their c-terminal glycine residue. This improves the stability and activity of the peptide hormone.
    • 4-hydroxyphenylpyruvate dioxygenase modulates tyrosine metabolism.

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Chemistry

The name "vitamin C" always refers to L -enorinated ascorbic acid and oxidized forms, such as dehydroascorbate (DHA). Therefore, unless otherwise noted, "ascorbate" and "ascorbic acid" refer to the nutritional literature to L -ascorbate and L -cascorbic acid. Ascorbic acid is a weak sugar acid structurally related to glucose. In biological systems, ascorbic acid can only be found at low pH, but in solutions above pH 5 is mainly found in ionized form, ascorbate. All of these molecules have vitamin C activity and are thus used synonymously with vitamin C, unless otherwise specified.

Many analytical methods have been developed for detection of ascorbic acid. For example, the vitamin C content of food samples such as fruit juice can be calculated by measuring the volume of samples needed to decolorize dichlorophenolindophenol (DCPIP) solutions and then calibrating the results by comparison with vitamin C.

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Test the level

Simple tests are available to measure vitamin C levels in urine and serum or blood plasma. However this reflects a new dietary intake rather than total body content. It has been observed that while serum or blood plasma concentrations follow a circadian rhythm or reflect short-term dietary effects, the content in the tissues is more stable and can provide a better view of the availability of ascorbate in all organisms. However, very few hospital laboratories are adequately equipped and trained to perform such detailed analysis.

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Synthesis

Biosynthesis

Most animals and plants are able to synthesize vitamin C, in the order of enzyme-driven steps, which convert the monosaccharide to vitamin C. In plants, this is achieved by conversion of mannose or galactose to ascorbic acid. In some animals, the glucose required to produce ascorbate in the liver (in mammals and birds perched) is extracted from glycogen; ascorbate synthesis is a process that relies on glycogenolysis.

Among the mammals who lost the ability to synthesize vitamin C were simian and tarsius, which together form one of the two main suborder primates, Haplorrhini. This group includes humans. More primitive primates (Strepsirrhini) have the ability to make vitamin C. Synthesis does not occur in a number of species (probably all species) in a small family of Caviidae rats that includes guinea pigs and capybaras, but occurs in other rodents (rats and mice do not require vitamin C in their diet, for example).

In reptiles and birds biosynthesis is done in the kidney. A number of species of passerine birds also do not synthesize, but not all, and those without a clear relationship; there is a theory that the ability is lost separately several times in birds. In particular, the ability to synthesize vitamin C is thought to have been lost and then recovered in at least two cases. The ability to synthesize vitamin C has also been lost in about 96% of fish (teleosts).

Most of the bat families tested (the Chiroptera order), including families of insectivorous bats and large berries, were unable to synthesize vitamin C. A series of gulonolactone oxidase (GULO) was detected in only 1 of 34 bat species tested, in the 6 family range. bat tested. There are at least two species of bats, eating bats (Rousettus leschenaultii ) and insectivorous bats ( Hipposideros armiger ), which retain (or restore) their vitamin C production capability.

These animals all lack the L -gulonolactone oxidase (GULO) enzyme, which is needed in the last stage of vitamin C synthesis. The genome of this species contains GULO as a pseudogen, which serves as an insight into the evolution of the species past.

Some of these species (including humans) can perform with the lower levels available from their diet by recycling the oxidized vitamin C.

Most humans consume vitamins in amounts of 10 to 20 times higher than those recommended by governments for humans. This difference is the basis of the controversy about the recommended dietary allowance today. This is counteracted by the argument that humans are very good at preserving vitamin C diets, and being able to maintain vitamin C levels in the blood is proportional to simian on a much smaller dietary intake, perhaps by recycling oxidized vitamin C.

Route

In vertebrates that can synthesize ascorbic acid, the biosynthetic pathway begins with glucose, either in the liver for mammals and some birds, or kidneys for amphibians, reptiles and some birds. The line is the same. Some enzymes catalyze the steps of D-glucose to D-glucuronate. Furthermore, the enzyme glucuronate reductase converts D-glucuronate to L-gluconate. Then the gulonolactonase enzyme converts L-gluconate to L-gulonolactone. The last enzymatic conversion is by the enzyme L-gulonolactone oxidase (GLO), into 2-keto-gulonolactone. Of these compounds, the final step is spontaneous, ie, non-enzymatic conversion to ascorbic acid (vitamin C). GLO is an enzyme that does not exist in animals that can not synthesize vitamin C.

All plants synthesize ascorbic acid. Ascorbic acid functions as a cofactor for enzymes involved in photosynthesis, the synthesis of plant hormones, as antioxidants as well as other antioxidant regenerators. Plants use multiple pathways to synthesize vitamin C. The main path begins with glucose, fructose or mannose (all simple sugars) and results into L-galactose, L-galaconolactone and ascorbic acid. There is a feedback setting, in which the presence of ascorbic acid suppresses the enzyme in the synthesis pathway. This process follows a diurnal rhythm, so the peak expression of the enzyme in the morning to support later biosynthesis when the daylight intensity of sunlight demands high concentrations of ascorbic acid. Small lanes may be specific to a particular part of the plant; this may be identical to the vertebrate pathway (including the GLO enzyme), or start with inositol and up to ascorbic acid via L-galactonic acid to L-galactonolactone.

Evolution

Ascorbic acid is a common enzymatic cyst in mammals used in collagen synthesis, as well as a powerful reducing agent capable of rapidly searching for a number of reactive oxygen species (ROS). Given that ascorbate has these important functions, it is surprising that the ability to synthesize these molecules is not always preserved. In fact, anthropoid primates, Cavia porcellus (guinea pigs), teleost fish, mostly bats, and some Passeriform birds all independently lose the ability to internally synthesize Vitamin C in either the kidneys or the liver. In all cases where genome analysis was performed on the ascorbic ascorbic auxotroph, the origin of the change was found to be the result of loss-function mutations in the gene encoding L-Gulono -? - lactone oxidase, an enzyme that catalyzes the final step of the ascorbic acid path described above.

In the simian case, it is thought that the loss of the ability to make vitamin C may have occurred further in the history of evolution rather than the appearance of humans or even apes, since that clearly occurred soon after the appearance of the first primates. , but shortly after the initial primate separation into the two main subordo Haplorrhini (which can not make vitamin C) and its subordo sister from non-tarsier prosimians, Strepsirrhini (wet nose primifer), which retains the ability to make vitamins. C. According to the dating of molecular clocks, these two primord subordo branches split up about 63 to 60 million years ago. About three to five million years later (58 million years ago), just moments after that from an evolutionary perspective, the Tarraiformes infraorder, the only family left is Tarsiidae, branched off from other haplorrhines. Since tarsiers also can not make vitamin C, this means mutations have occurred, and thus must occur between these two point markers (63 to 58 million years ago).

One explanation for the loss of recurrent ability to synthesize vitamin C is that it is the result of a genetic shift; assuming that the diet is rich in vitamin C, natural selection will not act to preserve it.

Some scientists claim that the loss of biosynthetic pathways of vitamin C may play a role in rapid evolutionary change, leading to hominids and the emergence of humans. According to this theory, loss of ascorbic acid anti-oxidation properties will lead to increased free radicals in the body. Free radicals are known to increase the frequency of genetic mutations, which will then increase the speed of evolution.

It has also been noted that the loss of ability to synthesize ascorbate is prominently parallel to the inability to break down uric acid, as well as the characteristics of primates. Uric Acid and Ascorbate are both powerful reducing agents. This leads to the suggestion that, in higher primates, uric acid has taken over some ascorbic functions.

Industrial

Vitamin C is produced from glucose by two major routes. The Reichstein process, developed in the 1930s, used a single pre-fermentation followed by a pure chemical route. The modern two-step fermentation process, originally developed in China in 1960, uses an additional fermentation to replace parts of later chemical stages. Both processes produce about 60% of vitamin C from the glucose feed.

The world production of synthesized vitamin C is estimated at about 110,000 tons per year by the year 2000. Traditionally, major producers are BASF/Takeda, DSM, Merck and China Pharmaceutical Group Ltd. of the People's Republic of China. In 2008 only DSM factories in Scotland remained operating outside of China due to strong price competition from China.

The world price of vitamin C rose sharply in 2008 in part as a result of the rise in basic food prices but also in anticipation of the suspension of two Chinese factories, located in Shijiazhuang near Beijing, as part of the general cessation of the pollution industry in China. during the Olympic games period. Production returned after the Olympics, but then five Chinese manufacturers met in 2010, among them the Northeast Pharmaceutical Group and North China Pharmaceutical Group, and agreed to temporarily halt production to maintain prices. In 2011 an American lawsuit was filed against four Chinese companies allegedly colluding to limit production and fix the price of vitamin C in the United States. The companies did not deny the allegations but said in their defense that the Chinese government forced them to act in this way. In January 2012, a US judge ruled that a Chinese company could be sued in the US by a buyer acting as a group. The verdict reached in March 2013 set a fine of $ 147.8 million. This ruling was reversed by the 2nd US Circuit Court of Appeals in New York, arguing that China formally advised the Court that its law requires the makers of vitamin C to violate the Sherman Act, US antitrust law. In June 2017, the US Supreme Court announced that it would consider an appeal submitted to cancel a lower court decision.

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History

Traditional medicine

The need to include fresh plant foods or raw animal flesh in the diet to prevent disease is known from ancient times. Indigenous people living in marginal areas incorporate this into their drug knowledge. For example, pine needles are used in temperate zones within the infusion, or leaves of drought-resistant tree species in the desert area. In 1536, the French explorer Jacques Cartier and Daniel Knezevic, exploring the St. Lawrence, using local native knowledge to save his dying people from scurvy. He boiled the needle of the arbor vitae tree to make a tea which later proved to contain 50 mg of vitamin C per 100 grams.

Scurvy at sea

In 1497 the Vasco de Gama expedition, the curative effect of citrus fruit is known. The Portuguese planted fruit and vegetable trees in Saint Helena, a halt for shipping from Asia, and left the sick to take home by the next ship.

Authorities sometimes recommend plant-based foods to prevent scurvy during long sea voyages. John Woodall, the first surgeon from the British East India Company, recommended the use of lemon juice in his book in 1617, The Surgeon's Mate . In 1734, the Dutch author Johann Bachstrom gave a strict opinion that "scabies is solely due to the total taboo of fresh plant foods, and vegetables."

Scurvy has long been a major killer of sailors during a long sea cruise. According to Jonathan Lamb, "In 1499, Vasco da Gama lost 116 of his crew which amounted to 170; In 1520, Magellan lost 208 of 230;... mainly because of scabies."

The first attempt to provide a scientific basis for the cause of the disease was by a ship's surgeon at Royal Navy, James Lind. While at sea in May 1747, Lind provided several crew members with two oranges and one lemon per day, in addition to normal rations, while others went on cider, vinegar, sulfuric acid or seawater, along with their normal rations, in one the world's first controlled experiment. The results show that citrus fruits prevent disease. Lind published her work in 1753 in his book Treatise on the Scurvy .

Fresh fruit is expensive to store on the board, while boiling it into juice allows easy storage but destroys vitamins (especially if boiled in copper kettles). It was 1796 before the British navy adopted lemon juice as a standard issue at sea. In 1845, ships in the West Indies were given lime juice instead, and in 1860 lime juice was used throughout the Royal Navy, resulting in the use of the British "limey" nickname by the Americans. Captain James Cook had previously shown the advantage of carrying "Sour krout" on board, carrying his crew to the Hawaiian Islands without losing his men to scabies. For this, the British Admiralty gave it a medal.

The name antiscorbutic was used in the eighteenth and nineteenth centuries for foods known to prevent scurvy. These foods include lemon, lime, orange, sauerkraut, cabbage, malt, and portable soup. In 1928, Canadian Arctic anthropologist Vilhjalmur Stefansson pointed out that Inuit avoids scurvy on most raw meat diets. Subsequent research on the traditional diet diet of Yukon First Nations, Dene, Inuit, and MÃÆ'Â © tis from Northern Canada showed that their daily intake of vitamin C averaged between 52 and 62 mg/day, comparable to the Estimated Average Needs.

Discovery

Vitamin C was invented in 1912, isolated in 1928 and synthesized in 1933, making it the first synthesized vitamin. Soon Tadeus Reichstein succeeded in synthesizing large amounts of vitamins with what is now called the Reichstein process. This enables mass production of vitamin C. In 1934, Hoffmann-La Roche trademarked synthetic vitamin C under the Redoxon brand name and began to market it as a dietary supplement.

In 1907, a laboratory animal model that would help identify the antiscorbutic factor was discovered by Norwegian physicians Axel Holst and Theodor FrÃÆ'¸lich, who when studying beriberi vessels, fed guinea pigs grain and starch test diet and was shocked when scurvy produced instead of beriberi. Fortunately, this species does not make vitamin C itself, while rats and mice. In 1912, the Polish biochemist Casimir Funk developed the concept of vitamins. One of them is considered an anti-scorbutic factor. In 1928, this was referred to as "C soluble in water", although its chemical structure had not yet been determined.

From 1928 to 1932, Albert Szent-GyÃÆ'¶rgyi and the team Joseph L. Svirbely Hungarian, and the American team of Charles Glen King, identified the anti-scorbutic factor. Szent-GyÃÆ'¶rgyi isolates the hexuronic acid from the animal's adrenal glands, and suspect it is an antiscorbutic factor. At the end of 1931, Szent-GyÃÆ'¶rgyi gave Svirbely an adrenal acid-derived adrenal hexuronic with the suggestion that it might be an anti-scorbutic factor. In the spring of 1932, King's lab had proved this, but published the results without giving credit to Szent-GyÃÆ'¶rgyi. This causes a fierce dispute over priorities. In 1933, Walter Norman Haworth chemically identified vitamins as L -exexuronic acid, proving this by synthesis in 1933. Haworth and Szent-GyÃÆ'¶rgyi proposed that L-hexuronic acid was named acid a- scorbic, and chemically L -Asorborbic acid, to honor its activity against scabies. The term etymology is derived from the Latin, "a-" which means distant, or inactive, while -corbor derived from the medieval Latin scorbuticus (associated with scurvy), cognate with Old Norse skyrbjugr , French scorbut , Dutch scheurbuik and German Low scharbock . Partly for this discovery, Szent-GyÃÆ'¶rgyi was awarded the 1937 Nobel Prize in Medicine, and Haworth shared the Nobel Prize that year in Chemistry.

In 1957, J.J. Burns show that some mammals are susceptible to scurvy because their livers do not produce the L -gulonolactone oxidase enzyme, the last of a chain of four enzymes that synthesize vitamin C. American biochemist Irwin Stone is the first to take vitamin C for its preservative properties. He then developed the theory that humans have a mutated form of the oxidase-modifying gene L -gulonolactone.

In 2008, researchers at the University of Montpellier found that in humans and other primates the red blood cells have developed a mechanism to more efficiently utilize the existing vitamin C in the body by recycling small L oxidized oxide (DHA ) returns to ascorbic acid for reuse by the body. The mechanism was not found to be present in mammals that synthesize their own vitamin C.

Large doses

Vitamin C megadosage is a term that describes the consumption or injections of vitamin C in doses that are proportional to or higher than the amount produced by liver mammals that are able to synthesize vitamin C. The theory behind this, though not the actual term, is described in 1970 in a article by Linus Pauling. Briefly, the position is that for optimal health, humans should consume at least 2,300 mg/day to compensate for the inability to synthesize vitamin C. The recommendation also falls into the consumption range for gorillas - a non-synthesizing approaching-relative to humans. A second argument for high intake is that the serum concentration of ascorbic acid increases as intake increases to reach the plate at about 190 to 200 micromoles per liter (Ã,Âμmol/L) after consumption exceeds 1,250 milligrams. As noted, the government recommendation is the range of 40-110 mg/day and the normal plasma is about 50 Ã,Âμmol/L, so 'normal' is about 25% of what can be achieved when oral consumption is within the proposed megadose range.

Pauling popularized the concept of high doses of vitamin C as the prevention and treatment of the common cold in 1970. A few years later he proposed that vitamin C would prevent cardiovascular disease, and that 10 grams/day, initially (10 days) was given intravenously and thereafter, will cure end-stage cancer. Mega doses with ascorbic acid have other champions, including the controversial Irwin Stone and Matthias Rath and Patrick Holford, both of whom are accused of making unproven treatment claims for treating cancer and HIV infection.

The mega-dose theory is to be largely discredited. Simple benefits are shown for the common cold. The benefit is not higher when the supplement intake is more than 1,000 mg/day compared with an intake between 200 and 1,000 mg/day, so it is not limited to the mega dose range. The theory that large amounts of intravenous ascorbic acid can be used to treat end-stage cancer - some forty years after Pauling's paper - is still considered unproven and still requires high-quality research. However, the lack of conclusive evidence has not stopped individual physicians from prescribing intravenous ascorbic acid to thousands of people with cancer.

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Society and culture

In February 2011, the Swiss Post issued a stamp containing a molecular model of vitamin C to mark the International Year of Chemistry.

Vitamin C (Ascorbic Acid) Assessment - Eat For Better Health
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Note


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References


Overloading on Vitamin C? - Dr. Weil
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External links

  • Vitamin C Fact Sheet from U.S. National Institute of Health

Source of the article : Wikipedia

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