The Full Wiki

Vitamin c: Wikis


Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.


(Redirected to Vitamin C article)

From Wikipedia, the free encyclopedia

Vitamin C
Systematic (IUPAC) name
2-oxo-L-threo-hexono-1,4- lactone-2,3-enediol
(R)-3,4-dihydroxy-5-((S)- 1,2-dihydroxyethyl)furan-2(5H)-one
CAS number 50-81-7
ATC code A11G
PubChem 5785
Chemical data
Formula C6H8O6 
Mol. mass 176.14 grams per mole
Synonyms L-ascorbic acid
Physical data
Density 1.694 g/cm³
Melt. point 190–192 °C (374–378 °F) decomposes
Boiling point 553 °C (1027 °F)
Pharmacokinetic data
Bioavailability rapid & complete
Protein binding negligible
Half life 30 minutes
Excretion renal
Therapeutic considerations
Pregnancy cat. A
Legal status general public availability
Routes oral
 Yes check.svgY(what is this?)  (verify)

Vitamin C or L-ascorbic acid is an essential nutrient for humans and certain other animal species, in which it functions as a vitamin. Ascorbate (an ion 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; notable mammalian group exceptions are most or all of the order chiroptera (bats), and one of the two major primate suborders, the Anthropoidea (Haplorrhini) (tarsiers, monkeys and apes, including mankind). Ascorbic acid is also not synthesized by guinea pigs and 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.[1][2][3] It is also widely used as a food additive.[4]

The pharmacophore of vitamin C is the ascorbate ion. In living organisms, ascorbate is an anti-oxidant, since it protects the body against oxidative stress,[5] and is a cofactor in at least eight enzymatic reactions, including several collagen synthesis reactions that cause the most severe symptoms of scurvy when they are dysfunctional.[6]

Scurvy has been known since ancient times. People in many parts of the world assumed it was caused by a lack of fresh plant foods. The British Navy started giving sailors lime juice to prevent scurvy in 1795.[7] Ascorbic acid was finally isolated in 1932 and commercially synthesized in 1934. The uses and recommended daily intake of vitamin C are matters of on-going debate, with RDI ranging from 45 to 95 mg/day. Proponents of megadosage propose from 200 mg to more than 2000 mg/day. The fraction of vitamin C in the diet that is absorbed and the rate at which the excess is eliminated from the body vary strongly with the dose.

A recent meta-analysis of 68 reliable antioxidant supplementation experiments, involving a total of 232,606 individuals, concluded that consuming additional ascorbate from supplements may not be as beneficial as thought,[8] though most of these studies so far generally do not evaluate the effects of megadosages at the levels recommended by megadosage activists.


Biological significance

Vitamin C is purely the L-enantiomer of ascorbate; the opposite D-enantiomer has no physiological significance. Both forms are mirror images of the same molecular structure. When L-ascorbate, which is a strong reducing agent, carries out its reducing function, it is converted to its oxidized form, L-dehydroascorbate.[6] L-dehydroascorbate can then be reduced back to the active L-ascorbate form in the body by enzymes and glutathione.[9] During this process semidehydroascorbic acid radical is formed. Ascorbate free radical reacts poorly with oxygen, and thus, will not create a superoxide. Instead two semidehydroascorbate radicals will react and form one ascorbate and one dehydroascorbate. With the help of glutathione, dehydroxyascorbate is converted back to ascorbate.[10] The presence of glutathione is crucial since it spares ascorbate and improves antioxidant capacity of blood.[11] Without it dehydroxyascorbate could not convert back to ascorbate.

L-Ascorbate is a weak sugar acid structurally related to glucose that naturally occurs attached either to a hydrogen ion, forming ascorbic acid, or to a metal ion, forming a mineral ascorbate.



Model of a vitamin C molecule. Black is carbon, red is oxygen, and white is hydrogen

The vast majority of animals and plants are able to synthesize their own vitamin C, through a sequence of four enzyme-driven steps, which convert glucose to vitamin C.[6] The glucose needed to produce ascorbate in the liver (in mammals and perching birds) is extracted from glycogen; ascorbate synthesis is a glycogenolysis-dependent process.[12] 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 (to be specific, one of two major primate suborders, the anthropoidea, also called haplorrhini, which includes humans), guinea pigs, a number of species of passerine birds (but not all of them—there is some suggestion that the ability was lost separately a number of times in birds), and many (probably all) major families of bats, including major insect and fruit-eating bat families. These animals all lack the L-gulonolactone oxidase (GULO) enzyme, which is required in the last step of vitamin C synthesis, because they have a defective form of the gene for the enzyme (Pseudogene ΨGULO).[13] Some of these species (including humans) are able to make do with the lower levels available from their diets by recycling oxidised vitamin C.[14]

Most simians consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans.[15] 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.

An adult goat, a typical example of a vitamin C-producing animal, will manufacture more than 13 g of vitamin C per day in normal health and the biosynthesis will increase "manyfold under stress".[16] Trauma or injury has also been demonstrated to use up large quantities of vitamin C in humans.[17] Some microorganisms such as the yeast Saccharomyces cerevisiae have been shown to be able to synthesize vitamin C from simple sugars.[18][19]

Vitamin C in evolution

Venturi and Venturi [20][21] suggested that the antioxidant action of ascorbic acid developed first in the plant kingdom when, about 500 million years ago (Mya), plants began to adapt to antioxidant-mineral deficient fresh-waters of estuaries. Some biologists suggested that many vertebrates had developed their metabolic adaptive strategies in estuary environment.[22] In this theory, some 400-300 Mya, when living plants and animals first began the move from the sea to rivers and land, environmental iodine deficiency was a challenge to the evolution of terrestrial life.[23] In plants, animals and fishes, the terrestrial diet became deficient in many essential antioxidant marine micronutrients, including iodine, selenium, zinc, copper, manganese, iron, etc. Freshwater algae and terrestrial plants, in replacement of marine antioxidants, slowly optimized the production of other endogenous antioxidants such as ascorbic acid, polyphenols, carotenoids, tocopherols etc., some of which became essential “vitamins” in the diet of terrestrial animals (vitamins C, A, E, etc.).

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 haemorrhage, 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.[24]

Some scientists have suggested that the loss of human ability to make vitamin C may have caused a rapid simian evolution into modern man.[25][26][27] However, the loss of ability to make vitamin C in simians must have occurred much farther back in evolutionary history than the emergence of humans or even apes, since it evidently occurred rather soon after the appearance of the first primates, yet sometime after the split of early primates into its 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.[28] According to molecular clock dating, these two suborder primate branches parted ways about 63 to 60 Mya [29] 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.[30][31] 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 evolutionary loss of the ability 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.[32]

Absorption, transport, and disposal

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 imported the reduced form of ascorbate across plasma membrane.[33] GLUT1 and GLUT3 are the two glucose transporters and only transfer dehydroascorbic acid form of Vitamin C.[34] 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.[35][36] 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,[33] the notable exception being red blood cells, which lose SVCT proteins during maturation.[37] "SVCT2 knockout" animals genetically engineered to lack this functional gene, die shortly after birth,[38] 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 (12g), fractional human absorption of ascorbic acid may be as low as 16%; at low intake (<20 mg) the absorption rate can reach up to 98%.[39] 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 half-life for the remainder of the vitamin C store in the body increases greatly, with the half-life lengthening as the body stores are depleted.[40]

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.[41] 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 liver 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,[42] and so the body soon depletes itself if fresh supplies are not consumed.

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.[43]

Nobel prize winner Linus Pauling and Dr. G. C. Willis have asserted that chronic long term low blood levels of vitamin C (chronic scurvy) is a cause of atherosclerosis.[44]

Western societies generally consume 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,[45] that is higher than the RDA recommendation.

Notable human dietary studies of experimentally-induced scury have been conducted on concientious objectors during WW II in Britain, and on Iowa state prisoner "volunteers" 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 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.[46] 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.[47]

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 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%.[48] However, because this was not an intervention study, causation could not be proven, and vitamin C blood levels acting as a proxy market for other differences between the groups could not be ruled out. However, the prospective nature of the study did rule out vitamin-C lowering effects of terminal illness or end-of-life poor health.

Studies with much higher doses of vitamin C, usually between 200 and 6000 mg, for the treatment of infections and wounds have shown inconsistent results.[49] While combinations of antioxidants seem to improve wound healing,[50] this effect cannot be achieved with vitamin C alone.[51]

History of human understanding

James Lind, a British Royal Navy surgeon who, in 1747, identified that a quality in fruit prevented the disease of scurvy in what was the first recorded controlled experiment.

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 explorer Jacques Cartier, 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.[52][53]

Throughout history, the benefit of plant food to survive long sea voyages has been occasionally recommended by authorities. 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."[54]

While the earliest documented case of scurvy was described by Hippocrates around the year 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 comparing results on two populations of a factor applied to one group only with all other factors the same. The results conclusively showed that citrus fruits prevented the disease. Lind published his work in 1753 in his Treatise on the Scurvy.[55]

Citrus fruits were one of the first sources of vitamin C available to ship's surgeons.

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".[56] 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).[57] 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.[58] 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.[59]

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 striking European Arctic explorers living on similar high-meat cooked 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 were eaten.[60]


Albert Szent-Györgyi, pictured here in 1948, was awarded the 1937 Nobel Prize in Medicine "for his discoveries in connection with the biological combustion processes, with special reference to vitamin C and the catalysis of fumaric acid".

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 contracted aboard ship's crews 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.[61]

In 1912, the Polish-American biochemist Casimir Funk, while researching beriberi in pigeons, developed the concept of vitamins to refer to the non-mineral micro-nutrients that are essential to health. The name is a blend of "vital", due to the vital role they play biochemically, 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. [62]

From 1928 to 1933, the Hungarian research team of Joseph L. Svirbely and Albert Szent-Györgyi and the American worker Charles Glen King, first identified the anti-scorbutic factor, calling it "ascorbic acid" for its vitamin activity. Szent-Györgyi had isolated the chemical 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 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, a former worker in King's lab who had recently joined Szent-Györgyi's lab, the last of this 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 teamwork effort by both groups, since Szent-Györgyi was unwilling to do the difficult and messy animal studies). By 1932, Szent-Györgyi's group had discovered that paprika peppers, a common spice in the Hungarian diet, was a rich source of hexuronic acid, the antiscorbutic factor, by then named ascorbic acid, in honor of its activity against scurvy.[63] Ascorbic acid turned out not to be an amine, nor even to contain any nitrogen.

For his accomplishment, Szent-Györgyi was alone awarded the 1937 Nobel Prize in Medicine "for his discoveries in connection with the biological combustion processes, with special reference to vitamin C and the catalysis of fumaric acid".[64]

Between 1933 and 1934, the British chemists Sir Walter Norman Haworth and Sir Edmund Hirst and, independently, the Polish chemist Tadeus Reichstein, succeeded in synthesizing the vitamin, making it the first to be artificially produced. This made possible the cheap mass-production of what was by then known as vitamin C. Only Haworth was awarded the 1937 Nobel Prize in Chemistry 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.[65][66] 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.[67]

In 1957 the American J.J. Burns showed that the reason some mammals were susceptible to scurvy was the inability of their liver to produce the active enzyme L-gulonolactone oxidase, which is the last of the chain of four enzymes that synthesize vitamin C.[68][69] 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.[70]

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.[71]

Physiological function

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;[3] and an enzyme cofactor for the biosynthesis of many important biochemicals. Vitamin C acts as an electron donor for important enzymes:[72]

Collagen, carnitine, and tyrosine synthesis, and microsomal metabolism

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.[73] Ascorbate acts as a reducing agent (i.e. electron donor, anti-oxidant) in the above-described syntheses, maintaining iron and copper atoms in their reduced states.

Vitamin C acts as an electron donor for eight different enzymes:[72]


Ascorbic acid is well known for its antioxidant activity. Ascorbate acts as a reducing agent to reverse oxidation in aqueous solution. When there are more free radicals (reactive oxygen species) in the human body than antioxidants, the condition is called oxidative stress.[85] Oxidative stress induced diseases encompass cardiovascular diseases, hypertension, chronic inflammatory diseases and diabetes.[86][87][88][89] The plasma ascorbate concentration in a patient with oxidative stress (measured as less than 45 µmol/L) is lower than that of a healthy individual (61.4-80 µmol/L).[90] According to McGregor and Biesalski (2006),[85] increasing the individual's plasma ascorbate level may have therapeutic effects in cases of oxidative stress. Individuals with oxidative stress and healthy individuals have different pharmacokinetics of ascorbate.

Although initial studies suggested that some antioxidant supplements might promote health, later large clinical trials did not detect any benefit on overall mortality rates with vitamin C supplementation.[91]


Ascorbic acid behaves not only as an antioxidant but also as a pro-oxidant.[85] 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 dehydroxyascorbate in vitro.[92] 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.[85] Recent studies show that intravenous injection of 7.5g of ascorbate daily for six days did not increase pro-oxidant markers;[93] thus, ascorbate as a pro-oxidant is unlikely to convert metals to create ROS in vivo.

Immune system

Some advertisements claim that Vitamin C "supports" or is "important" for immune system function. These claims are partially supported by the scientific evidence.[94]

Daily requirements

The North American Dietary Reference Intake recommends 90 milligrams per day and no more than 2 grams (2,000 milligrams) per day.[95] Other related species sharing the same inability to produce vitamin C and requiring exogenous vitamin C consume 20 to 80 times this reference intake.[96][97] 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.[98] It is generally agreed that a balanced diet without supplementation 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.[95]

High doses (thousands of milligrams) may result in diarrhea in healthy adults. Proponents of alternative medicine (specifically orthomolecular medicine)[99] claim the onset of diarrhea to be an indication of where the body’s true vitamin C requirement lies, because this is the point where the body uses vitamin's water solubility to simply flush out the unusable portion, as the diarrhea length/intensity is directly correlated to the quantity of the overdose, though this has yet to be clinically verified.

United States vitamin C recommendations[95]
Recommended Dietary Allowance (adult male) 90 mg per day
Recommended Dietary Allowance (adult female) 75 mg per day
Tolerable Upper Intake Level (adult male) 2,000 mg per day
Tolerable Upper Intake Level (adult female) 2,000 mg per day

Government recommended intakes

Recommendations for vitamin C intake have been set by various national agencies:

The United States defined Tolerable Upper Intake Level for a 25-year-old male is 2,000 milligrams per day.

Alternative recommendations on intakes

Some independent researchers have calculated the amount needed for an adult human to achieve similar blood serum levels as vitamin C synthesising mammals as follows:

Therapeutic uses

Vitamin C is necessary for the treatment and prevention of scurvy. Scurvy is commonly comorbid with other diseases of malnutrition; sufficient vitamin C to prevent scurvy occurs in most diets in industrialized nations.[107][108][109]

Vitamin C functions as an antioxidant. Adequate intake is necessary for health, but supplementation is probably not necessary in most cases.[110][111][112][113]

Based on animal and epidemiological models, high doses of vitamin C may have "protective effects" on lead-induced nerve and muscle abnormalities,[114] especially in smokers.[115][116]

Dehydroascorbic acid, the main form of oxidized vitamin C in the body, may reduce neurological deficits and mortality following stroke due to its ability to cross the blood-brain barrier, while "the antioxidant ascorbic acid (AA) or vitamin C does not penetrate the blood-brain barrier".[117]

Vitamin C's effect on the common cold has been extensively researched and shown to have no effect.[118]

Vitamin C megadosage

Several individuals and organizations advocate large doses of vitamin C based on in vitro and retrospective studies,[119] although large, randomized clinical trials on the effects of high doses on the general population have never taken place. Individuals who have recommended intake well in excess of the current Dietary Reference Intake (DRI) include Robert Cathcart, Ewan Cameron, Steve Hickey, Irwin Stone, Matthias Rath and Linus Pauling. Arguments for megadosage are based on the diets of closely related apes and the likely diet of pre-historical humans, and that most mammals synthesize vitamin C rather than relying on dietary intake.

Stone[120] and Pauling[97] calculated, based on the diet of primates[96] (similar to what our common ancestors are likely to have consumed when the gene mutated), that the optimum daily requirement of vitamin C is around 2,300 milligrams for a human requiring 2,500 kcal a day. Pauling also criticized the established RDA as sufficient to prevent scurvy, but not necessarily the dosage for optimal health.[106]

Higher vitamin C intake reduces serum uric acid levels, and is associated with lower incidence of gout.[121]

Vitamin C has also been promoted as efficacious against a vast array of diseases and syndromes. Research has been done on the effects of Vitamin C on a variety of disorders and diseases including the following:[122] pneumonia,[123] heart disease,[122][124] AIDS,[125][126] autism,[127] low sperm count,[128] age-related macular degeneration,[129][130] altitude sickness,[131] pre-eclampsia,[132] amyotrophic lateral sclerosis,[133] heroin addiction,[134] asthma,[135] tetanus,[136] and cancer.[137][138][139][140] These uses are poorly supported by the evidence, and sometimes contraindicated.[141][142][143][144][145]

Testing for ascorbate levels in the body

Simple tests use dichlorphenolindophenol, 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.[6] 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.[146][147]

Adverse effects

Common side-effects

Relatively large doses of vitamin C may cause indigestion, particularly when taken on an empty stomach. When taken in large doses, vitamin C 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, vomitting, diarrhea, flushing of the face, headache, fatigue and disturbed sleep. The main toxic reactions in the infants were skin rashes.[148]

Possible side-effects

As vitamin C enhances iron absorption,[149] 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.[150]

There is a longstanding belief among the mainstream medical community that vitamin C causes kidney stones, which is based on little science.[151] Although recent studies have found a relationship,[152] a clear link between excess ascorbic acid intake and kidney stone formation has not been generally established.[153] Some case reports exist for a link between patients with oxalate deposits and a history of high dose vitamin C usage.[154]

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.[155] 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.'[156] 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.[157]

Recent rat and human studies suggest that adding Vitamin C supplements to an exercise training program can cause a decrease in mitochondria production, hampering endurance capacity.[158] A cancer-causing mechanism of hexavalent chromium may be triggered by vitamin C.[159]

Chance of overdose

Vitamin C exhibits remarkably low toxicity. The LD50 (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 taken orally.[57] The LD50 in humans remains unknown, owing to medical ethics that preclude experiments that would put patients at risk of harm. However, as with all substances tested in this way, the LD50 is taken as a guide to its toxicity in humans and no data to contradict this has been found.

Natural and synthetic dietary sources

Rose hips are a particularly rich source of vitamin C

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.[160]

Plant sources

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, the soil condition, the climate in which it grew, the length of time since it was picked, the storage conditions, and the method of preparation.[161]

The following table is approximate and shows the relative abundance in different raw plant sources.[162][163][164] 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:

Plant source Amount
(mg / 100g)
Kakadu plum 3100
Camu Camu 2800
Rose hip 2000
Acerola 1600
Seabuckthorn 695
Jujube 500
Indian gooseberry 445
Baobab 400
Blackcurrant 200
Red pepper 190
Parsley 130
Guava 100
Kiwifruit 90
Broccoli 90
Loganberry 80
Redcurrant 80
Brussels sprouts 80
Wolfberry (Goji) 73 †
Lychee 70
Cloudberry 60
Elderberry 60
Persimmon 60

† average of 3 sources; dried

Plant source Amount
(mg / 100g)
Papaya 60
Strawberry 60
Orange 50
Kale 41
Lemon 40
Melon, cantaloupe 40
Cauliflower 40
Garlic 31
Grapefruit 30
Raspberry 30
Tangerine 30
Mandarin orange 30
Passion fruit 30
Spinach 30
Cabbage raw green 30
Lime 30
Mango 28
Blackberry 21
Potato 20
Melon, honeydew 20
Cranberry 13
Tomato 10
Blueberry 10
Pineapple 10
Pawpaw 10
Plant source Amount
(mg / 100g)
Grape 10
Apricot 10
Plum 10
Watermelon 10
Banana 9
Carrot 9
Avocado 8
Crabapple 8
Persimmon - fresh 7
Cherry 7
Peach 7
Apple 6
Asparagus 6
Beetroot 5
Chokecherry 5
Pear 4
Lettuce 4
Cucumber 3
Eggplant 2
Raisin 2
fig 2
Bilberry 1
Horned melon 0.5
Medlar 0.3

Animal sources

Goats, like almost all animals, make their own vitamin C. An adult goat, weighting approx. 70 kg, will manufacture more than 13,000 mg of vitamin C per day in normal health, and levels manyfold higher when faced with stress.[165][166]

The overwhelming majority of species of animals and plants synthesise their own vitamin C, making some, but not all, animal products, 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 mother's milk and, in lower amounts, in raw cow's milk, with pasteurized milk containing only trace amounts.[167] 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 milligram of vitamin C per 100 grams of food:

Animal Source Amount
(mg / 100g)
Calf liver (raw) 36
Beef liver (raw) 31
Oysters (raw) 30
Cod roe (fried) 26
Pork liver (raw) 23
Lamb brain (boiled) 17
Chicken liver (fried) 13
Animal Source Amount
(mg / 100g)
Lamb liver (fried) 12
Calf adrenals (raw) 11[168]
Lamb heart (roast) 11
Lamb tongue (stewed) 6
Human milk (fresh) 4
Goat milk (fresh) 2
Camel milk (fresh) 5[169]
Cow milk (fresh) 2

Food preparation

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[170] 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.[171] Longer cooking times also add to this effect, as will copper food vessels, which catalyse the decomposition.[57]

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 doesn't leach in all vegetables at the same rate; research shows broccoli seems to retain more than any other.[172] Research has also shown that fresh-cut fruits don't lose significant nutrients when stored in the refrigerator for a few days.[173]

Vitamin C supplements

Vitamin C is widely available in the form of tablets and powders. The Redoxon brand, launched in 1934 by Hoffmann-La Roche, was the first mass-produced synthetic vitamin C.

Vitamin C is the most widely taken dietary supplement.[174] It is available in many forms including caplets, tablets, capsules, drink mix packets, in multi-vitamin formulations, in multiple antioxidant formulations, and 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 teaspoon of vitamin C crystals equals 5,000 mg).

Industrial synthesis

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.[175]

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.[18]

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. China is slowly becoming the major world supplier as its prices undercut those of the US and European manufacturers.[176] By 2008 only the DSM plant in Scotland remained operational outside the strong price competition from China.[177] 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.[178]

Food Fortification

Health Canada evaluated the effect of fortification of foods with abscorbate in the guidance document, Addition of Vitamins and Minerals to Food, 2005.[179] Health Canada categorized abscorbate as a ‘Risk Category A nutrients’. This means it is either 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. Health Canada recommended a minimum of 3 mg or 5% of RDI in order for the food to claim to be a source of Vitamin C and maximum fortification of 12 mg (20% of RDI) in order to be claimed "Excellent Source".[179]

Compendial status


  1. ^ a b "Vitamin C". Food Standards Agency (UK). Retrieved 2007-02-19. 
  2. ^ "Vitamin C". University of Maryland Medical Center. January 2007. Retrieved 2008-03-31. 
  3. ^ a b Higdon, Jane, Ph.D. (2006-01-31). "Vitamin C". Oregon State University, Micronutrient Information Center. Retrieved 2007-03-07. 
  4. ^ McCluskey, Elwood S. (1985). "Which Vertebrates Make Vitamin C?" (PDF). Origins 12 (2): 96–100. 
  5. ^ Padayatty S, Katz A, Wang Y, Eck P, Kwon O, Lee J, Chen S, Corpe C, Dutta A, Dutta S, Levine M (2003). "Vitamin C as an Antioxidant: evaluation of its role in disease prevention" (PDF). J Am Coll Nutr 22 (1): 18–35. PMID 12569111. 
  6. ^ a b c d "Vitamin C – Risk Assessment" (PDF). UK Food Standards Agency. Retrieved 2007-02-19. 
  7. ^ , Wilson LG. The Clinical Definition of Scurvy and the Discovery of Vitamin C J Hist of Med1975;40-60.
  8. ^ Bjelakovic G, et al. (2007). "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". JAMA 297 (8): 842–57. doi:10.1001/jama.297.8.842. PMID 17327526. 
  9. ^ Meister A (1994). "Glutathione-ascorbic acid antioxidant system in animals" (PDF). J Biol Chem 269 (13): 9397–400. PMID 8144521. 
  10. ^ , Nualart FJ, Rivas CI, Montecinos VP, et al. Recycling of vitamin C by a bystander effect. J Biol Chem 2003; 278:10128–10133.
  11. ^ Gropper SS, Smith JL, Grodd JL. 2004. Advanced Nutrition and Human Metabolism. Fourth Edition. Thomson Wadsworth, Belmont, CA. USA. pp. 260-275.
  12. ^ Bánhegyi G, Mándl J (2001). "The hepatic glycogenoreticular system". Pathol Oncol Res 7 (2): 107–10. doi:10.1007/BF03032575. PMID 11458272. 
  13. ^ Harris, J. Robin (1996). Ascorbic Acid: Subcellular Biochemistry. Springer. p. 35. ISBN 0306451484. OCLC 46753025 34307319 46753025. 
  14. ^ How Humans Make Up For An 'Inborn' Vitamin C Deficiency. 
  15. ^ Milton K (June 1999). "Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us?". Nutrition 15 (6): 488–98. doi:10.1016/S0899-9007(99)00078-7. PMID 10378206. 
  16. ^ Stone, Irwin (July 16, 1978). "Eight Decades of Scurvy. The Case History of a Misleading Dietary Hypothesis". Retrieved 2007-04-06. "Biochemical research in the 1950s showed that the lesion in scurvy is the absence of the enzyme, L-Gulonolactone oxidase (GLO) in the human liver (Burns, 1959). This enzyme is the last enzyme in a series of four that convert blood sugar, glucose, into ascorbate in the mammalian liver. This liver metabolite, ascorbate, is produced in an unstressed goat, for instance, at the rate of about 13,000 mg per day per 150 pounds body weight (Chatterjee, 1973). A mammalian feedback mechanism increases this daily ascorbate production many fold under stress (Subramanian et al., 1973)" 
  17. ^ C. Long, et al. (2003). "Ascorbic acid dynamics in the seriously ill and injured". Journal of Surgical Research 109 (2): 144–148. doi:10.1016/S0022-4804(02)00083-5. PMID 12643856. 
  18. ^ a b R.D. Hancock & R. Viola. "Ascorbic acid biosynthesis in higher plants and micro-organisms" (PDF). Scottish Crop Research Institute. Retrieved 2007-02-20. 
  19. ^ Hancock RD, Galpin JR, Viola R. (2000). "Biosynthesis of L-ascorbic acid (vitamin C) by Saccharomyces cerevisiae" (PDF). FEMS Microbiol Lett. 186 (2): 245–50. doi:10.1111/j.1574-6968.2000.tb09112.x. PMID 10802179. Retrieved 2007-02-19. 
  20. ^ Venturi S, Venturi M. Evolution of Dietary Antioxidant Defences. European EPI-Marker. 2007, 11, 3 :1-7.
  21. ^ Venturi S, Donati FM, Venturi A, Venturi M. 2000. Environmental iodine deficiency: A challenge to the evolution of terrestrial life? Thyroid. 10 (8):727-9.
  22. ^ Purves WK, Sadava D, Orians GH, Heller HC. 1998. Life.The Science of Biology. Part 4: The Evolution of Diversity. Chapter 30
  23. ^ Venturi S, Venturi M. 1999. Iodide, thyroid and stomach carcinogenesis: Evolutionary story of a primitive antioxidant? Eur J Endocrinol . 140:371-372.
  24. ^ Hardie LJ, Fletcher TC, Secombes C.J.1991. The effect of dietary vitamin C on the immune response of the Atlantic salmon (Salmo salar). Aquaculture 95:201–214
  25. ^ Challem, JJ, Taylor, EW. 1998. Retroviruses, ascorbate, and mutations, in the evolution of Homo sapiens. Free Radical Biology and Medicine. 25(1):130-132.
  26. ^ Benhegyi, G. 1997. Ascorbate metabolism and its regulation in animals. Free Radical Biology and Medicine. 23(5):793-803.
  27. ^ Stone I. 1979. Homo sapiens ascorbicus, a biochemically corrected robust human mutant. Medical Hypotheses. 5(6):711-721
  28. ^ Vitamin C biosynthesis in prosimians: Evidence for the anthropoid affinity of Tarsius. J. I. Pollock 1, R. J. Mullin. American Journal of Physical Anthropology. 1986. Volume 73 Issue 1, Pages 65 - 70. Published Online: 3 May 2005: Digital Object Identifier (DOI) 10.1002/ajpa.1330730106, see [1] Accessed March 15, 2010
  29. ^ Poux, C. and Douzery, E.J.P., 2004. Primate phylogeny, evolutionary rate variations,and divergence times: a contribution from the nuclear gene IRBP. American Journal of Physical Anthropology, 124: 1-16.
  30. ^ Goodman, M., Porter, C.A., Czelusniak, J., Page, S.L., Schneider, H., Shoshani, J., Gunnell, G. and Groves, C.P., 1998. Toward a phylogenetic classification of primates based on DNA evidence complemented by fossil evidence. Molecular Phylogenetics and Evolution, 9: 585-598
  31. ^ Porter, C.A., Page, S.L., Czelusniak, J., Schneider, H., Schneider, M.P.C., Sampaio, I. and Goodman, M., 1997. Phylogeny and evolution of selected primates as determined by sequences of the ?-globin locus and 5’flanking regions. International Journal of Primatology, 18: 261-295. Refs Poux, Porter and Goodman preceeding, as quoted in [2]
  32. ^ Proctor P (1970). "Similar functions of uric acid and ascorbate in man?". Nature 228 (5274): 868. doi:10.1038/228868a0. PMID 5477017. 
  33. ^ a b Savini, I., Rossi, A., Pierro, C., et al. SVCT1 and SVCT2: key proteins for vitamin C uptake. Amino Acids 2008; 34: 347–355
  34. ^ Rumsey SC, Kwon O, Xu GW, et al. Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J Biol Chem 1997; 272:18982–18989.
  35. ^ May, J. M., Qu, Z. C., Neel, D. R., and Li, X. Recycling of vitamin C from its oxidized forms by human endothelial cells. Biochim Biophys Acta 2003; 1640(2-3):153-161
  36. ^ Packer, L. (1997) Vitamin C and redox cycling antioxidants. In: Packer L, F. J. (ed). Vitamin C in health and disease, Marcel Dekker Inc, New York
  37. ^ James M. May, Zhi-chao Qua, Huan Qiaoa and Mark J. Kourya. Maturational Loss of the Vitamin C Transporter in Erythrocytes. Biochem Biophys Res Commun. 2007; 360:295-298.
  38. ^ Sotiriou, S., Gispert, S., Cheng, J., Wang, Y., Chen, A., Hoogstraten-Miller, S., Miller, G. F., Kwon, O., Levine, M., Guttentag, S. H., and Nussbaum, R. L. (2002) Nat Med, 8:514-517
  39. ^ Levine M, et al. Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proc Natl Acad Sci USA. 1996; 93:3704–3709.
  40. ^ Renal excretion of ascorbic acid: effect of age and sex. D. G. Oreopoulos, R. D. Lindeman, D. J. VanderJagt, A. H. Tzamaloukas, H. N. Bhagavan and P. J. Garry. Journal of the American College of Nutrition, Vol 12, Issue 5 537-542.
  41. ^ Hediger MA (May 2002). "New view at C". Nat. Med. 8 (5): 445–6. doi:10.1038/nm0502-445. PMID 11984580. 
  42. ^ a b MedlinePlus Encyclopedia Ascorbic acid
  43. ^ "The influence of smoking on Vitamin C status in adults". BBC news and Cambridge University. 2000-09-31. Retrieved 2007-12-12. 
  44. ^ Rath, M; Pauling, L. (1990). "Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig". Proceedings of the National Academy of Sciences 87 (23): 9388–9390. doi:10.1073/pnas.87.23.9388. 
  45. ^ Statistics Canada, Canadian Community Health Survey, Cycle 2.2, Nutrition (2004)
  46. ^ J Pemberton. Medical experiments carried out in Sheffield on conscientious objectors to military service during the 1939–45 war. International Journal of Epidemiology 2006 35(3):556-558; doi:10.1093/ije/dyl020 full text.
  47. ^ Hodges, R. E.; Baker, E. M.; Hood, J.; Sauberlich, H. E.; March, S. C. (1969). "Experimental Scurvy in Man". American Journal of Clinical Nutrition 22 (5): 535–548. PMID 4977512. 
  48. ^ Khaw, KT; Bingham S, Welch A et al. (March 2001). "Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition". Lancet 357 (9257): 657–63. doi:10.1016/S0140-6736(00)04128-3. PMID 11247548. 
  49. ^ Hemil, Harri (15 October 2007). "The Role of Vitamin C in the Treatment of the Common Cold". Americal Family Physician. 
  50. ^ Barbosa, E; Faintuch J, Machado Moreira EA et al. (2009). "Supplementation of vitamin E, vitamin C, and zinc attenuates oxidative stress in burned children: a randomized, double-blind, placebo-controlled pilot study". J Burn Care Res 30 (5): 859–66. doi:10.1097/BCR.0b013e3181b487a8. PMID 19692922. 
  51. ^ ter Riet, Gerben; Alphons G. H. Kessels; Paul G. Knipschild (December 1995). "Randomized clinical trial of ascorbic acid in the treatment of pressure ulcers". Journal of Clinical Epidemiology 48 (12): 1453–60. doi:10.1016/0895-4356(95)00053-4. PMID 8543959. 
  52. ^ "Jacques Cartier's Second Voyage - 1535 - Winter & Scurvy". Retrieved 2007-02-25. 
  53. ^ Martini E. (June 2002). "Jacques Cartier witnesses a treatment for scurvy". Vesalius 8 (1): 2–6. PMID 12422875. 
  54. ^ Armstrong, Alexander (1858). "Observation on Navel Hygiene and Scarvy, more particularly as the later appeared during the Polar Voyaje". British and foreign medico-chirurgical review: or, Quarterly journal of practial medicine and surgery 22: 295–305. 
  55. ^ Lind, James (1753). A Treatise of the Scurvy. London: A. Millar. 
  56. ^ Singh, Simon; Edzard Ernst (2008). Trick of Treatment: The Undeniable Facts about Alternative Medicine. WW Norton & Company. pp. 15–18. ISBN 9780393066616. 
  57. ^ a b c "Safety (MSDS) data for ascorbic acid". Oxford University. 2005-10-09. Retrieved 2007-02-21. 
  58. ^ Cook, James; Philip Edwards (1999). The Journals of Captain Cook. Penguin Books. p. 38. ISBN 0140436472. OCLC 42445907. 
  59. ^ Stevens, David; Reeve, John (2006). Navy and the nation: the influence of the navy on modern Australia. Allen & Unwin. p. 74. ISBN 9781741142006. 
  60. ^ Kuhnlein HV, Receveur O, Soueida R, Egeland GM (1 June 2004). "Arctic indigenous peoples experience the nutrition transition with changing dietary patterns and obesity". J Nutr. 134 (6): 1447–53. PMID 15173410. 
  61. ^ PMID 12555613 Tidsskr Nor Laegeforen. 2002 Jun 30;122(17):1686-7. [Axel Holst and Theodor Frolich--pioneers in the combat of scurvy][Article in Norwegian] Norum KR, Grav HJ.
  62. ^ PMID 9105273 L Rosenfeld. Vitamine--vitamin. The early years of discovery. Clin Chem. 1997 Apr;43(4):680-5.
  63. ^ Story of Vitamin C's chemical discovery. Accessed Jan 21, 2010
  64. ^ "Pitt History - 1932: Charles Glen King". University of Pittsburgh. Retrieved 2007-02-21. "In recognition of this medical breakthrough, some scientists believe that King also deserved Nobel Prize recognition." 
  65. ^ Boudrant, J. (1990): Microbial processes for ascorbic acid biosynthesis: a review. In: Enzyme Microb Technol. 12(5); 322–9; PMID 1366548; doi:10.1016/0141-0229(90)90159-N
  66. ^ Bremus, C. et al. (2006): The use of microorganisms in L-ascorbic acid production. In: J Biotechnol. 124(1); 196–205; PMID 16516325; doi:10.1016/j.jbiotec.2006.01.010
  67. ^ Bächi, Beat (2008). "Natürliches oder künstliches Vitamin C?". NTM Zeitschrift für Geschichte der Wissenschaften, Technik und Medizin 16 (4): 445–470. doi:10.1007/s00048-008-0309-y. 
  68. ^ BURNS JJ, EVANS C (1 December 1956). "The synthesis of L-ascorbic acid in the rat from D-glucuronolactone and L-gulonolactone". J Biol Chem. 223 (2): 897–905. PMID 13385237. 
  69. ^ Burns JJ, Moltz A, Peyser P (December 1956). "Missing step in guinea pigs required for the biosynthesis of L-ascorbic acid". Science 124 (3232): 1148–9. doi:10.1126/science.124.3232.1148-a. PMID 13380431. 
  70. ^ Henson,, Donald Earl; Block, Gladys; Levine, Mark (1991). "Ascorbic Acid: Biologic Functions and Relation to Cancer". Journal of the National Cancer Institute 83 (8): 547–550. doi:10.1093/jnci/83.8.547. PMID 1672383. 
  71. ^ "How Humans Make Up For An 'Inborn' Vitamin C Deficiency". ScienceDaily. Cell Press. March 21, 2008. Retrieved 2009-02-24. 
  72. ^ a b Levine M, Rumsey SC, Wang Y, Park JB, Daruwala R (2000). "Vitamin C". in Stipanuk MH. Biochemical and physiological aspects of human nutrition. Philadelphia: W.B. Saunders. pp. 541–67. ISBN 0-7216-4452-X. 
  73. ^ (Gropper, et al., 2005)
  74. ^ Prockop DJ, Kivirikko KI (1995). "Collagens: molecular biology, diseases, and potentials for therapy". Annu Rev Biochem. 64: 403–34. doi:10.1146/ PMID 7574488. 
  75. ^ Peterkofsky B (1 December 1991). "Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy". Am J Clin Nutr. 54 (6 Suppl): 1135S–1140S. PMID 1720597. 
  76. ^ Kivirikko KI, Myllylä R (1985). "Post-translational processing of procollagens". Ann. N. Y. Acad. Sci. 460: 187–201. doi:10.1111/j.1749-6632.1985.tb51167.x. PMID 3008623. 
  77. ^ Rebouche CJ (1991). "Ascorbic acid and carnitine biosynthesis" (PDF). Am J Clin Nutr 54 (6 Suppl): 1147S–1152S. PMID 1962562. 
  78. ^ Dunn WA, Rettura G, Seifter E, Englard S (1984). "Carnitine biosynthesis from gamma-butyrobetaine and from exogenous protein-bound 6-N-trimethyl-L-lysine by the perfused guinea pig liver. Effect of ascorbate deficiency on the in situ activity of gamma-butyrobetaine hydroxylase" (PDF). J Biol Chem 259 (17): 10764–70. PMID 6432788. 
  79. ^ Levine M, Dhariwal KR, Washko P, et al. (1992). "Ascorbic acid and reaction kinetics in situ: a new approach to vitamin requirements". J Nutr Sci Vitaminol. Spec No: 169–72. PMID 1297733. 
  80. ^ Kaufman S (1974). "Dopamine-beta-hydroxylase". J Psychiatr Res 11: 303–16. doi:10.1016/0022-3956(74)90112-5. PMID 4461800. 
  81. ^ Eipper BA, Milgram SL, Husten EJ, Yun HY, Mains RE (April 1993). "Peptidylglycine alpha-amidating monooxygenase: a multifunctional protein with catalytic, processing, and routing domains". Protein Sci. 2 (4): 489–97. doi:10.1002/pro.5560020401 (inactive 2009-11-29). PMID 8518727. 
  82. ^ Eipper BA, Stoffers DA, Mains RE (1992). "The biosynthesis of neuropeptides: peptide alpha-amidation". Annu Rev Neurosci. 15: 57–85. doi:10.1146/ PMID 1575450. 
  83. ^ Englard S, Seifter S (1986). "The biochemical functions of ascorbic acid". Annu. Rev. Nutr. 6: 365–406. doi:10.1146/ PMID 3015170. 
  84. ^ Lindblad B, Lindstedt G, Lindstedt S (December 1970). "The mechanism of enzymic formation of homogentisate from p-hydroxyphenylpyruvate". J Am Chem Soc. 92 (25): 7446–9. doi:10.1021/ja00728a032. PMID 5487549. 
  85. ^ a b c d McGregor GP, Biesalski HK. Rationale and impact of vitamin C in clinical nutrition. Curr Opin Clin Nutr Metab Care 2006; 9:697–703
  86. ^ Kelly FJ. Use of antioxidants in the prevention and treatment of disease. J Int Fed Clin Chem 1998; 10:21–23
  87. ^ Mayne ST. Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research. J Nutr 2003; 133 (Suppl 3):933S–940S
  88. ^ Tak PP, Zvaifler NJ, Green DR, Firestein GS. Rheumatoid arthritis and p53: how oxidative stress might alter the course of inflammatory diseases. Immunol Today 2000; 21:78–82.
  89. ^ Goodyear-Bruch C, Pierce JD. Oxidative stress in critically ill patients. Am J Crit Care 2002; 11:543–551; quiz 552–543.
  90. ^ Schorah CJ, Downing C, Piripitsi A, et al. Total vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients. Am J Clin Nutr 1996; 63:760–765.
  91. ^ Bjelakovic G; Nikolova, D; Gluud, LL; Simonetti, RG; Gluud, C (2007). "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". JAMA 297 (8): 842–57. doi:10.1001/jama.297.8.842. PMID 17327526. 
  92. ^ Satoh K, Sakagami H. Effect of metal ions on radical intensity and cytotoxic activity of ascorbate. Anticancer Res 1997; 17:1125–1129.
  93. ^ Muhlhofer A, Mrosek S, Schlegel B, et al. High-dose intravenous vitamin C is not associated with an increase of pro-oxidative biomarkers. Eur J Clin Nutr 2004; 58:1151–1158.
  94. ^ see Chandra RK, 1997, "Nutrition and the immune system: an introduction". The American Journal of Clinical Nutrition 66 (2): 460S–463S. PMID 9250133.
  95. ^ a b c d "US Recommended Dietary Allowance (RDA)" (PDF). Archived from the original on 2008-05-29. Retrieved 2007-02-19. 
  96. ^ a b Milton K (2003). "Micronutrient intakes of wild primates: are humans different?". Comp Biochem Physiol a Mol Integr Physiol 136 (1): 47–59. doi:10.1016/S1095-6433(03)00084-9. PMID 14527629. 
  97. ^ a b Pauling, Linus (1970). "Evolution and the need for ascorbic acid". Proc Natl Acad Sci U S a 67 (4): 1643–8. doi:10.1073/pnas.67.4.1643. PMID 5275366. 
  98. ^ "Linus Pauling Vindicated; Researchers Claim RDA For Vitamin C is Flawed". PR Newswire. 6 July 2004. Retrieved 2007-02-20. 
  99. ^ Cathcart, Robert (1994). "Vitamin C, Titrating To Bowel Tolerance, Anascorbemia, and Acute Induced Scurvy". Orthomed. Retrieved 2007-02-22. 
  100. ^ "Vitamin and mineral requirements in human nutrition, 2nd edition" (PDF). World Health Organization. 2004. Retrieved 2007-02-20. 
  101. ^
  102. ^ Higdon, Jane. "Linus Pauling Institute Recommendations". Oregon State University. Retrieved 2007-04-11. 
  103. ^ Roc Ordman. "The Scientific Basis Of The Vitamin C Dosage Of Nutrition Investigator". Beloit College. Archived from the original on 2008-03-07. Retrieved 2007-02-22. 
  104. ^ "Vitamin C Foundation's RDA". Retrieved 2007-02-12. 
  105. ^ Levy, Thomas E. (2002). Vitamin C Infectious Diseases, & Toxins. Xlibris. ISBN 1401069630. OCLC 123353969.  Chapter 5 - Vitamin C optidosing.
  106. ^ a b Pauling, Linus (1986). How to Live Longer and Feel Better. W. H. Freeman and Company. ISBN 0-380-70289-4. OCLC 15690499 154663991 15690499. 
  107. ^ WHO (June 4, 2001) (PDF). Area of work: nutrition. Progress report 2000. Archived from the original on 2007-07-03. 
  108. ^ Olmedo JM, Yiannias JA, Windgassen EB, Gornet MK (August 2006). "Scurvy: a disease almost forgotten". Int. J. Dermatol. 45 (8): 909–13. doi:10.1111/j.1365-4632.2006.02844.x. PMID 16911372. 
  109. ^ Velandia B, Centor RM, McConnell V, Shah M (August 2008). "Scurvy is still present in developed countries". J Gen Intern Med 23 (8): 1281–4. doi:10.1007/s11606-008-0577-1. PMID 18459013. 
  110. ^ Shenkin A (2006). "The key role of micronutrients". Clin Nutr 25 (1): 1–13. doi:10.1016/j.clnu.2005.11.006. PMID 16376462. 
  111. ^ Woodside J, McCall D, McGartland C, Young I (2005). "Micronutrients: dietary intake v. supplement use". Proc Nutr Soc 64 (4): 543–53. doi:10.1079/PNS2005464. PMID 16313697. 
  112. ^ Stanner SA, Hughes J, Kelly CN, Buttriss J (2004). "A review of the epidemiological evidence for the 'antioxidant hypothesis'". Public Health Nutr 7 (3): 407–22. doi:10.1079/PHN2003543. PMID 15153272. 
  113. ^ Rivers, Jerry M (1987). "Safety of High-level Vitamin C Ingestion". Annals of the New York Academy of Sciences 498: 445. doi:10.1111/j.1749-6632.1987.tb23780.x. PMID 3304071. 
  114. ^ Hasan MY, Alshuaib WB, Singh S, Fahim MA (2003). "Effects of ascorbic acid on lead induced alterations of synaptic transmission and contractile features in murine dorsiflexor muscle". Life Sci. 73 (8): 1017–25. doi:10.1016/S0024-3205(03)00374-6. PMID 12818354. 
  115. ^ Dawson E, Evans D, Harris W, Teter M, McGanity W (1999). "The effect of ascorbic acid supplementation on the blood lead levels of smokers". J Am Coll Nutr 18 (2): 166–70. PMID 10204833. 
  116. ^ Simon JA, Hudes ES (1999). "Relationship of ascorbic acid to blood lead levels". JAMA 281 (24): 2289–93. doi:10.1001/jama.281.24.2289. PMID 10386552. 
  117. ^ Huang J, Agus DB, Winfree CJ, Kiss S, Mack WJ, McTaggart RA, Choudhri TF, Kim LJ, Mocco J, Pinsky DJ, Fox WD, Israel RJ, Boyd TA, Golde DW, Connolly ES Jr. (2001). "Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke". Proceedings of the National Academy of Sciences 98 (20): 11720–4. doi:10.1073/pnas.171325998. PMID 11573006. 
  118. ^ Audera (2001). "Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial". Medical Journal of Australia 389: 175. 
  119. ^ Douglas, RM; Hemilä, H (2005). "Vitamin C for Preventing and Treating the Common Cold". PLoS Medicine 2 (6): e168. doi:10.1371/journal.pmed.0020168. PMID 15971944. 
  120. ^ Stone, Irwin (1972). The Healing Factor: Vitamin C Against Disease. Grosset and Dunlap. ISBN 0-448-11693-6. OCLC 3967737. 
  121. ^ Choi, MD, DrPH, HK; Gao, X; Curhan, G (March 9, 2009). "Vitamin C Intake and the Risk of Gout in Men". Archives of Internal Medicine. 169 (5): 502–507. doi:10.1001/archinternmed.2008.606. PMID 19273781. PMC 2767211. 
  122. ^ a b Rath MW, Pauling LC. U.S. Patent 5,278,189 Prevention and treatment of occlusive cardiovascular disease with ascorbate and substances that inhibit the binding of lipoprotein(a). USPTO. 11 Jan 1994.
  123. ^ Hemilä H, Louhiala P (2007). "Vitamin C for preventing and treating pneumonia". Cochrane Database Syst Rev (1): CD005532. doi:10.1002/14651858.CD005532.pub2. PMID 17253561. 
  124. ^ Vitamin and Mineral Supplements from the American Heart Association
  125. ^ "Nigeria: Vitamin C Can Suppress HIV/Aids Virus". 2006-05-22. Retrieved 2006-06-16. 
  126. ^ Boseley, Sarah (2005-05-14). "Discredited doctor's 'cure' for Aids ignites life-and-death struggle in South Africa". The Guardian.,7369,1483821,00.html. Retrieved 2007-02-21. 
  127. ^ Levy SE, Hyman SL (2005). "Novel treatments for autistic spectrum disorders". Ment Retard Dev Disabil Res Rev 11 (2): 131–42. doi:10.1002/mrdd.20062. PMID 15977319. 
  128. ^ Akmal M, Qadri J, Al-Waili N, Thangal S, Haq A, Saloom K (2006). "Improvement in human semen quality after oral supplementation of vitamin C". J Med Food 9 (3): 440–2. doi:10.1089/jmf.2006.9.440. PMID 17004914. 
  129. ^ Evans JR; Evans, Jennifer R (2006). "Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration". Cochrane Database Syst Rev (2): CD000254. doi:10.1002/14651858.CD000254.pub2. PMID 16625532. 
  130. ^ Evans J (June 2008). "Antioxidant supplements to prevent or slow down the progression of AMD: a systematic review and meta-analysis". Eye 22 (6): 751–60. doi:10.1038/eye.2008.100. PMID 18425071. 
  131. ^ Baillie JK, Thompson AA, Irving JB, et al. (March 2009). "Oral antioxidant supplementation does not prevent acute mountain sickness: double blind, randomized placebo-controlled trial". QJM 102 (5): 341–8. doi:10.1093/qjmed/hcp026. PMID 19273551. 
  132. ^ Rumbold A, Duley L, Crowther CA, Haslam RR (2008). "Antioxidants for preventing pre-eclampsia". Cochrane Database Syst Rev (1): CD004227. doi:10.1002/14651858.CD004227.pub3. PMID 18254042. 
  133. ^ Orrell RW, Lane RJ, Ross M (2007). "Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease". Cochrane Database Syst Rev (1): CD002829. doi:10.1002/14651858.CD002829.pub4. PMID 17253482. 
  134. ^ Libby, Alfred F. & Stone, Irwin (1977-07-16), The Hypoascorbemia-Kwashiorkor Approach to Drug Addiction Therapy: A Pilot Study, 
  135. ^ Kaur B, Rowe BH, Arnold E (2009). "Vitamin C supplementation for asthma". Cochrane Database Syst Rev (1): CD000993. doi:10.1002/14651858.CD000993.pub3. PMID 19160185. 
  136. ^ Hemilä H, Koivula TT (2008). "Vitamin C for preventing and treating tetanus". Cochrane Database Syst Rev (2): CD006665. doi:10.1002/14651858.CD006665.pub2. PMID 18425960. 
  137. ^ High Doses of Vitamin C Are Not Effective as a Cancer Treatment
  138. ^ "FDA OKs vitamin C trial for cancer". January 12, 2007. Retrieved 2007-04-06. "Federal approval of a clinical trial on intravenous vitamin C as a cancer treatment lends credence to alternative cancer care, U.S. researchers said." 
  139. ^ Yeom CH, Jung GC, Song KJ (2007). "Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration". J. Korean Med. Sci. 22 (1): 7–11. doi:10.3346/jkms.2007.22.1.7. PMID 17297243. 
  140. ^ from Science News, Vitamin C Injections Slow Tumor Growth In Mice as reported in ScienceDaily Aug. 5, 2008. Retrieved August 5, 2008.
  141. ^ "Vitamin C (Ascorbic acid)". MedLine Plus. National Institute of Health. 2006-08-01. Retrieved 2007-08-03. 
  142. ^ Vitamin C by the American Cancer Society
  143. ^ Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2008). "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". Cochrane Database Syst Rev (2): CD007176. doi:10.1002/14651858.CD007176. PMID 18425980. 
  144. ^ Huang HY, Caballero B, Chang S, et al. (May 2006). "Multivitamin/mineral supplements and prevention of chronic disease". Evid Rep Technol Assess (Full Rep) (139): 1–117. PMID 17764205. 
  145. ^ Brzozowska A, Kaluza J, Knoops KT, de Groot LC (April 2008). "Supplement use and mortality: the SENECA study". Eur J Nutr 47 (3): 131–7. doi:10.1007/s00394-008-0706-y. PMID 18414768. 
  146. ^ Emadi-Konjin P, Verjee Z, Levin A, Adeli K (2005). "Measurement of intracellular vitamin C levels in human lymphocytes by reverse phase high performance liquid chromatography (HPLC)" (PDF). Clinical Biochemistry 38 (5): 450–6. doi:10.1016/j.clinbiochem.2005.01.018. PMID 15820776. 
  147. ^ Yamada H, Yamada K, Waki M, Umegaki K. (2004). "Lymphocyte and Plasma Vitamin C Levels in Type 2 Diabetic Patients With and Without Diabetes Complications" (PDF). Diabetes Care 27 (10): 2491–2. doi:10.2337/diacare.27.10.2491. PMID 15451922. 
  148. ^ "Toxicological evaluation of some food additives including anticaking agents, antimicrobials, antioxidants, emulsifiers and thickening agents". World Health Organization. 4 July 1973. Retrieved 2007-04-13. 
  149. ^ Fleming DJ, Tucker KL, Jacques PF, Dallal GE, Wilson PW, Wood RJ (2002). "Dietary factors associated with the risk of high iron stores in the elderly Framingham Heart Study cohort" (PDF). Am. J. Clin. Nutr. 76 (6): 1375–84. PMID 12450906. 
  150. ^ Cook JD, Reddy MB (2001). "Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet" (PDF). Am. J. Clin. Nutr. 73 (1): 93–8. PMID 11124756. 
  151. ^ Goodwin JS, Tangum MR (November 1998). "Battling quackery: attitudes about micronutrient supplements in American academic medicine". Arch. Intern. Med. 158 (20): 2187–91. doi:10.1001/archinte.158.20.2187. PMID 9818798. 
  152. ^ Massey LK, Liebman M, Kynast-Gales SA (2005). "Ascorbate increases human oxaluria and kidney stone risk" (PDF). J. Nutr. 135 (7): 1673–7. PMID 15987848. 
  153. ^ Naidu KA (2003). "Vitamin C in human health and disease is still a mystery? An overview" (PDF). J. Nutr. 2 (7): 7. doi:10.1186/1475-2891-2-7. PMID 14498993. PMC 201008. 
  154. ^ S. Mashour, MD, J. F. Turner Jr., MD, FCCP, and R. Merrell, MD (2000). "Acute Renal Failure, Oxalosis, and Vitamin C Supplementation* A Case Report and Review of the Literature". Chest 118: 561. doi:10.1378/chest.118.2.561. 
  155. ^ Ovcharov R, Todorov S (1974). "[The effect of vitamin C on the estrus cycle and embryogenesis of rats]" (in Bulgarian). Akusherstvo i ginekologii͡a 13 (3): 191–5. PMID 4467736. 
  156. ^ Vobecky JS, Vobecky J, Shapcott D, Cloutier D, Lafond R, Blanchard R (1976). "Vitamins C and E in spontaneous abortion". International journal for vitamin and nutrition research. Internationale Zeitschrift für Vitamin- und Ernährungsforschung. Journal international de vitaminologie et de nutrition 46 (3): 291–6. PMID 988001. 
  157. ^ Javert CT, Stander HJ (1943). "Plasma Vitamin C and Prothrombin Concentration in Pregnancy and in Threatened, Spontaneous, and Habitual Abortion". Surgery, Gynecology, and Obstetrics 76: 115–122. 
  158. ^ Mari-Carmen Gomez-Cabrera et al. (2008-01). "Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance". American Journal of Clinical Nutrition 87 (1): 142–9. PMID 18175748. 
  159. ^ "Cancer-Causing Compound Can Be Triggered By Vitamin C". 2007-03-13. Retrieved 2009-12-26. 
  160. ^ Wilson JX (2005). "Regulation of vitamin C transport". Annu. Rev. Nutr. 25: 105–25. doi:10.1146/annurev.nutr.25.050304.092647. PMID 16011461. 
  161. ^ "The vitamin and mineral content is stable". Danish Veterinary and Food Administration. Retrieved 2010-02-26. 
  162. ^ "National Nutrient Database". Nutrient Data Laboratory of the US Agricultural Research Service. Retrieved 2007-03-07. 
  163. ^ "Vitamin C Food Data Chart". Healthy Eating Club. Retrieved 2007-03-07. 
  164. ^ "Natural food-Fruit Vitamin C Content". The Natural Food Hub. Retrieved 2007-03-07. 
  165. ^ Chatterjee, IB (1973). "Evolution and the Biosynthesis of Ascorbic Acid". Science 182 (118): 1271–1272. doi:10.1126/science.182.4118.1271. PMID 4752221. 
  166. ^ Irwin Stone, PC-A (1979). "Eight Decades of Scurvy". Orthomolecular Psychiatry 8, (2): 58–62. 
  167. ^ Clark, Stephanie, Ph. D (8 January 2007). "Comparing Milk: Human, Cow, Goat & Commercial Infant Formula". Washington State University. Retrieved 2007-02-28. 
  168. ^ Toutain, P. L.; D. Béchu, and M. Hidiroglou (November 1997). "Ascorbic acid disposition kinetics in the plasma and tissues of calves". Am J Physiol Regul Integr Comp Physiol 273, (5, R1585-R1597): 1585. PMID 9374798. 
  169. ^ Mal. G. (2000) Indian Veterinary Journal; 77: 695-696
  170. ^ Roig, M. G.; Rivera, Z. S.; Kennedy, J. F. (1995). "A model study on rate of degradation of L-ascorbic acid during processing using home-produced juice concentrates". International Journal of Food Sciences and Nutrition 46 (2): 107–115. doi:10.3109/09637489509012538. PMID 7621082. 
  171. ^ Allen, MA,; Burgess, S. G. (1950). "The Losses of Ascorbic Acid during the Large-scale Cooking of Green Vegetables by Different Methods". British Journal of Nutrition 4 (2-3): 95–100. doi:10.1079/BJN19500024. PMID 14801407. 
  172. ^ G. F., Combs (2001). The Vitamins, Fundamental Aspects in Nutrition and Health (2nd ed.). San Diego, CA: Academic Press. pp. 245–272. ISBN 9780121834920. 
  173. ^ Hitti, Miranda (2 June 2006). "Fresh-Cut Fruit May Keep Its Vitamins". WebMD. Retrieved 2007-02-25. 
  174. ^ The Diet Channel Vitamin C might be the most widely known and most popular vitamin purchased as a supplement.
  175. ^ "The production of vitamin C" (PDF). Competition Commission. 2001. Retrieved 2007-02-20. 
  176. ^ Patton, Dominique (2005-10-20). "DSM makes last stand against Chinese vitamin C". nutraingredients. Retrieved 2007-02-20. 
  177. ^ Starling, Shane (2008-06-26). "DSM vitamin plant gains green thumbs-up". Decision News Media SAS. Retrieved 2010-02-25. 
  178. ^ "Vitamin C: Distruptions to Production in China to Maintain Firm Market". Flexnews. 2008-06-30. Retrieved 2010-02-25. 
  179. ^ a b "Addition of Vitamins and Minerals to Food, 2005". Health Canada. Retrieved 2010-02-25. 
  180. ^ British Pharmacopoeia Commission Secretariat (2009). "Index, BP 2009". Retrieved 4 February 2010. 
  181. ^ "Japanese Pharmacopoeia, Fifteenth Edition". 2006. Retrieved 4 Februally 2010. 

Further reading

External links

Simple English

Vitamin C is a vitamin. It is also called ascorbic acid. It dissolves in water. It is found in fresh fruits, berries and green vegetables. Vitamin C helps wounds heal. Lack of vitamin C can cause a sickness called scurvy, where the gums in the mouth bleed easily and wounds do not heal. Lack of Vitamin C was a serious health problem on long ocean trips where supplies of fresh fruit were quickly used up. Many people died from scurvy on such trips.

Most animals make their own vitamin C. Those that can not include guinea pigs, humans, and apes.

Vitamin C was first found in 1928, and in 1932 it was proved to stop the sickness called scurvy.

Through history the need for people to eat fresh plant food to help them get through long sieges or long sea trips was known by some wise people but was often forgotten.

The first attempt to prove this idea was by a ship's doctor in the British Royal Navy called James Lind, who at sea in May 1747 gave some crew members lemon juice as well as their normal ships food, while others continued on normal food alone.

The results showed that lemons prevented the disease. Lind wrote up his work and published it in 1753.

Lind's work was slow to be noticed. It was 1795 before the British navy adopted lemon or lime juice as food for sailors.

As well as lemons, limes and oranges; sauerkraut, salted cabbage, malt, and soup were tried with different effects.

James Cook relied on sauerkraut to prevent the disease on his long voyages of exploration.

It was believed that only humans got scurvy but in 1907, Alex Holst and Theodore Frohlich, two Norwegian chemists found that guinea pigs could also get it if not given fresh food.

In 1928 the Arctic explorer Vilhjalmur Stefansson proved that Eskimo (Inuit) people are able to avoid scurvy with almost no plant food in their diet by eating raw meat.

In 1912 the Polish American scientist Casimir Funk first used the word vitamin for something present in food in small amounts that is essential to health. He named the unknown thing that prevented scurvy Vitamin C.

From 1928 to 1933, the Hungarian research team of Joseph L Svirbely and Albert Szent-Gyorgyi, and separately the American Charles Glen King, first took out vitamin C from food and showed it to be an acid they called ascorbic acid.

In 1933/1934, the British chemists Sir Walter Norman Haworth and Sir Edmund Hirst, and separately the Polish Tadeus Reichstein, successfully synthesized the vitamin. It was the first man-made vitamin. This made it possible to make lots of vitamin C cheaply in factories. Haworth won the 1937 Nobel Prize for Chemistry for this work.

In 1959 the American J.J. Burns showed that the reason why some animals get scurvy is because their liver cannot make just one chemical enzyme that all other animals have.



Plant sources

Citrus fruits (such as lime, lemon, orange, and grapefruit) are good sources of vitamin C.

Other foods that are good sources of vitamin C include papaya, broccoli, brussels sprouts, blackcurrants, strawberries, cauliflower, spinach, cantaloupe, green peppers, and kiwifruit.

The following table is to give an idea of how much vitamin c there is in different plant foods. Each individual fruit will vary.

The amount of vitamin C in foods of plant origin depends on the kind of plant, the kind of soil where it grew, how much rain and sun it got , the length of time since it was picked, and how it was stored since then. Cooking food destroys vitamin C.

Table Showing Relative Abundance of Vitamin C in Principal Fruits and some Raw Vegetables

mg vitamin C per 100 grams of fruit

Fruit Continued

mg vitamin C per 100 grams of fruit

Fruit Continued

mg vitamin C per 100 grams of fruit

CamuCamu 2800 Lemon 40 Grape 10
Rose hip 2000 Melon, cantaloupe 40 Apricot 10
Acerola 1600 Cauliflower 40 Plum 10
Jujube 500 Grapefruit 30 Watermelon 10
Baobab 400 Raspberry 30 Banana 9
Blackcurrant 200 Tangerine/ Mandarin oranges 30 Carrot 9
Guava 100 Passion fruit 30 Avocado 8
Kiwifruit 90 Spinach 30 Crabapple 8
Broccoli 90 Cabbage Raw green 30 Peach 7
Loganberry 80 Lime 20 Apple 6
Redcurrant 80 Mango 20 Blackberry 6
Brussels sprouts 80 Melon, honeydew 20 Beetroot 5
Lychee 70 Raspberry 20 Pear 4
Persimmon 60 Tomato 10 Lettuce 4
Papaya 60 Blueberry 10 Cucumber 3
Strawberry 50 Pineapple 10 Fig 2
Orange 50 Pawpaw 10 Bilberry 1

Animal sources

Most species of animals synthesise their own vitamin C. It is therefore not a vitamin for them. Synthesis is achieved through a sequence of enzyme driven steps, which convert glucose to ascorbic acid. It is carried out either in the kidneys, in reptiles and birds, or the liver, in mammals and perching birds. The loss of an enzyme concerned with ascorbic acid synthesis has occurred quite frequently in evolution and has affected most fish, many birds; some bats, guinea pigs and most but not all primates, including Man. The mutations have not been lethal because ascorbic acid is so prevalent in the surrounding food sources.

It was only realised in the 1920s that some cuts of meat and fish are also a source of vitamin C for humans. The muscle and fat that make up the modern western diet are however poor sources. As with fruit and vegetables cooking destroys the vitamin C content.

Table Showing Relative Abundance of Vitamin C in Foods of Animal Origin
Food of animal origin

mg vitamin C per 100 grams food

Food of animal origin (contd)

mg vitamin C per 100 grams food

Food of animal mg vitamin C per 100 grams food
Calf liver (raw) 36 Chicken liver (fried ) 13 Goats milk (fresh) 2
Beef liver (raw) 31 Lamb liver (Fried) 12 Beef steak (fried) 0
Oysters (raw) 30 Lamb heart (roast) 11 Hens egg (raw ) 0
Cod Roe (fried) 26 Lamb tongue (stewed) 6 Pork Bacon (fried) 0
Pork liver (raw) 23 Human milk (fresh) 4 Calf veal cutlet (fried) 0
Lamb brain (boiled) 17 Cows milk (fresh) 2 Chicken leg (roast) 0

Artificial chemical synthesis

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 more modern Two-Step fermentation process was 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.

In 1934, the Swiss pharmaceutical company Hoffmann-La Roche was the first to mass produce synthetic vitamin C, under the brand name of Redoxon. Main producers today are BASF/ Takeda, Roche, Merck and the China Pharmaceutical Group Ltd of the People's Republic of China.

Functions of vitamin C in the body

Vitamin C deficiency

Lack of ascorbic acid in the daily diet leads to a disease called scurvy, a form of avitaminosis that is characterized by:

Daily requirement

A healthy person on a balanced western diet should be able to get all the vitamin C needed to prevent the symptoms of scurvy from their daily diet. People who smoke, those under stress and women in pregnancy have a slightly higher requirement.

The amount of vitamin C needed to avoid deficiency symptoms and maintain health has been set by variously national agencies as follows:

  • 40 mg per day UK Food Standards Agency
  • 60-95 mg per day US Food and Nutrition Board 2001 revision.

Some researchers have calculated the amount needed for an adult human to achieve similar blood serum levels as Vitamin C synthesising mammals as follows:

  • 200 mg per day - Linus Pauling Institute and US National Institutes of Health (NIH) Recommendation.
  • 3000 mg per day - Vitamin C Foundation's recommendation.
  • 6000-12000 mg per day–Thomas Levy , Colorado Integrative Medical Centre recommendation.
  • 6000-18000 mg per day - Linus Pauling's daily recommendation

High doses (thousands of mg) may result in diarrhoea, which is harmless if the dose is reduced immediately. Some researchers (Cathcart) claim the onset of diarrhoea to be an indication of where the body’s true vitamin C requirement lies.

The small size of the ascorbic acid molecule means the kidneys cannot retain it in the body. Quite a low level in the blood serum will cause traces to be present in the urine. All vitamin C synthesising mammals have traces in the urine at all times.

In April 1998 Nature reported alleged carcinogenic and teratogenic effects of excessive doses of vitamin C. This was given great prominence in the world's media. The effects were noted in test tube experiments and on only two of the 20 markers of free radical damage to DNA. They have not been supported by further evidence from living organisms. Almost all mammals manufacture their own vitamin C in amounts equivalent to human doses of thousands of milligrams per day. Large amounts of the vitamin are used in orthomolecular medicine and no harmful effects have been observed even in doses of 10,000 mg per day or more.

Therapeutic uses

Vitamin C is needed in the diet to prevent scurvy. It also has a reputation for being useful in the treatment of colds and flu. The evidence to support this idea, however, is ambiguous and the effect may depend on the dose size and dosing regime. The Vitamin C foundation (1) recommends 8 grams of vitamin C every half hour to show an effect on cold symptoms.

Vitamin C advocacy

Fred R. Klenner, a doctor in Reidsville, North Carolina reported in 1949 that poliomyelitis yielded to repeated megadoses of intravenous vitamin C.

Nobel Prize winning chemist Linus Pauling began actively promoting vitamin C in the 1960s as a means to greatly improve human health and resistance to disease. A minority of medical and scientific opinion continues to see vitamin C as being a low cost and safe way to treat infectious disease and to deal with a wide range of poisons. A megadose of one-half gram per pound of body weight (one gram per kilogram of body weight) per day of sodium ascorbate salt has been found of theraputic use in both human and veterinary treatments.[needs proof]

A meta-study into the published research on effectiveness of ascorbic acid in the treatment of infectious disease and toxins was conducted, in 2002, by Thomas Levy, Medical Director of the Colorado Integrative Medical Center in Denver. It claimed that overwhelming scientific evidence exists for its therapeutic role.

Some vitamin C advocates say that vitamin C cannot be used therapeutically because it cannot now be patented. Pharmaceutical companies are unwilling to research or promote something that will make them little money.


Got something to say? Make a comment.
Your name
Your email address