Vitamin C

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Vitamin C
Clinical data
SynonymsL-ascorbate
Pregnancy
category
  • A
Routes of
administration		oral
ATC code
Legal status
Legal status
  • general public availability
Pharmacokinetic data
Bioavailabilityrapid & complete
Protein bindingnegligible
Elimination half-life16 days (3.4 hours in people who have excess levels of vitamin C)
Excretionrenal
Identifiers
CAS Number
PubChem CID
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC6H8O6
Molar mass176.14 grams per mol
Melting point190 to 192 °C (Expression error: Unrecognized word "to". °F) decomposes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]



Overview

Vitamin C or L-ascorbate is an essential nutrient for higher primates, and a small number of other species. The presence of ascorbate is required for a range of essential metabolic reactions in all animals and plants. It is made internally by almost all organisms, humans being one notable exception. It is widely known as the vitamin whose deficiency causes scurvy in humans.[1][2][3] It is also widely used as a food additive.

The pharmacophore of vitamin C is the ascorbate ion. In living organisms, ascorbate is an antioxidant, as it protects the body against oxidative stress,[4] and is a cofactor in several vital enzymatic reactions.[5]

The uses and the daily requirement of vitamin C are matters of on-going debate.

Biological significance

Further information: [[:ascorbic acid]]

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.[5] L-dehydroascorbate can then be reduced back to the active L-ascorbate form in the body by enzymes and glutathione.[6]

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

Function

In humans, vitamin C is a highly effective antioxidant, acting to lessen oxidative stress, a substrate for ascorbate peroxidase,[3] as well as an enzyme cofactor for the biosynthesis of many important biochemicals. Vitamin C acts as an electron donor for eight different enzymes:[7]

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.[20] 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.

Biosynthesis

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.[5] 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.[21] 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, guinea pigs, the red-vented bulbul,and fruit-eating bats.[5] Most notably, humans have no capability to manufacture vitamin C. The cause of this phenomenon is that the last enzyme in the synthesis process, L-gulonolactone oxidase, cannot be made by the listed animals because the gene for this enzyme, Pseudogene ΨGULO, is defective.[22] The mutation has not been lethal because vitamin C is abundant in their food sources, with many of these species' natural diets consisting largely of fruit.

Most simians consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans.[23] This discrepancy constitutes the basis of the controversy on current recommended dietary allowances (see Vitamin C as a macronutrient - Evolutionary rationales).

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. 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.[24] Ascorbic acid can be oxidised (broken down) in the human body by the enzyme ascorbic acid oxidase.

An adult goat, a typical example of a vitamin C-producing animal, will manufacture more than 13,000 mg of vitamin C per day in normal health and the biosynthesis will increase "many fold under stress".[25] Trauma or injury has also been demonstrated to also use up large quantities of vitamin C in humans.[26] Some microorganisms such as the yeast Saccharomyces cerevisiae have been shown to be able to synthesize vitamin C from simple sugars.[27][28]

Deficiency

Scurvy is an avitaminosis resulting from lack of vitamin C, as without this vitamin, the synthesised collagen is too unstable to meet 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.,[29] and so the body soon depletes itself if fresh supplies are not consumed.

Smoking cigarettes has a negative correlation to the amount of vitamin c in the blood stream. The relative amounts of vitamin c drop with the increased amount of cigarettes smoked. [30]

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 peoples 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.[31][32]

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."

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.

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 he gave conflicting evidence within the book, and partly because the British admiralty saw care for the well-being of crews as a sign of weakness. In addition, 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[33]). Ship captains assumed wrongly that Lind's suggestions didn't work because those juices failed to 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 weren't 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 fresh and preserved foods, such as sauerkraut, by taking his crews to the Hawaiian Islands and beyond without losing any of his men to scurvy. For this otherwise unheard of feat, the British Admiralty awarded him a medal.

The name "antiscorbutic" was used in the eighteenth and nineteenth centuries as general term for those foods known to prevent scurvy, even though there was no understanding of the reason for this. These foods included but were not limited to: lemons, limes, and oranges; sauerkraut, cabbage, malt, and portable soup.

In 1907, Axel Holst and Theodor Frølich, two Norwegian physicians studying beriberi contracted aboard ship's crews in the Norwegian Fishing Fleet, wanted a small test mammal to substitute for the pigeons they used. They fed guinea pigs their test diet, which had earlier produced beriberi in their pigeons, and were surprised when scurvy resulted instead. Until that time scurvy had not been observed in any organism apart from humans, and had been considered an exclusively human disease.

Discovery of ascorbic acid

Albert Szent-Györgyi, pictured here in 1948, was awarded the 1937 Nobel Prize in Medicine for the discovery of vitamin C

In 1912, the Polish-American biochemist Casimir Funk, while researching deficiency diseases, developed the concept of vitamins to refer to the nutrients which are essential to health. Then, from 1928 to 1933, the Hungarian research team of Joseph L Svirbely and Albert Szent-Györgyi and, independently, the American Charles Glen King, first isolated vitamin C and showed it to be ascorbic acid. For this, Szent-Györgyi was awarded the 1937 Nobel Prize in Medicine.[34]

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 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.

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, the first to be artificially produced. This made possible the cheap mass-production of vitamin C. Only Haworth was awarded the 1937 Nobel Prize in Chemistry for this work, but the process for vitamin C retained Reichstein's name.

In 1934 Hoffmann–La Roche became the first pharmaceutical company to mass-produce synthetic vitamin C, under the brand name of Redoxon.

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 which synthesize vitamin C.[35][36] 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.

Daily requirements

The North American Dietary Reference Intake recommends 90 milligrams per day and no more than 2 grams per day (2000 milligrams per day).[37] Other related species sharing the same inability to produce vitamin C and requiring exogenous vitamin C consume 20 to 80 times this reference intake.[38][39] 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.[40] 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.[37]

High doses (thousands of milligrams) may result in diarrhea. Proponents of alternative medicine (specifically orthomolecular medicine)[41] claim the onset of diarrhea to be an indication of where the body’s true vitamin C requirement lies. Both Cathcart[41] and Cameron have hypothesized that very sick patients with cancer or influenza do not display any evidence of diarrhea at all until ascorbate intake reaches levels as high as 200 grams (nearly half a pound).

United States vitamin C recommendations[37]
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:

Vitamin C as a macronutrient

Main articles: Vitamin C megadosage, Megavitamin therapy, and Orthomolecular medicine

There is a strong advocacy movement for large doses of vitamin C, promoting a great deal of added benefits. Drawing on a wide, [48] but still inconclusive, body of evidence as to the benefits beyond those dosages recommended in the Dietary Reference Intakes, many pro-vitamin C organizations promote usage levels well beyond the current Dietary Reference Intake. The movement is led by scientists and doctors such as Robert Cathcart, Ewan Cameron, Steve Hickey, Irwin Stone and the twice Nobel Prize laureate Linus Pauling and the more controversial Matthias Rath. There is some scientific literature critical of governmental agency dose recommendations.[40][49] The biological halflife for vitamin C is fairly short, about 30 minutes in blood plasma, a fact which high dose advocates say that mainstream researchers have failed to take into account. Researchers at the National Institutes of Health decided upon the current RDA based upon tests conducted 12 hours (24 half lives) after consumption.

Evolutionary rationales

Humans carry a mutated and ineffective form of the gene required by all mammals for manufacturing the fourth of the four enzymes that manufacture vitamin C.[50] The inability to produce vitamin C, hypoascorbemia, is, according to the Online Mendeleian Inheritance in Man database, a "public" inborn error of metabolism.

The gene, Pseudogene ΨGULO, lost its function millions of years ago, when the anthropoids branched out.[51] In humans, the three functional enzymes continue to produce the precursors to vitamin C, but the process is incomplete; these enzymes ultimately undergo proteolytic degradation. Stone[52] and Pauling[39] calculated, based on the diet of our primate cousins[38] (similar to what our common descendants 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.

The established RDA has been criticized by Pauling to be one that will prevent acute scurvy, and is not necessarily the dosage for optimal health.[47]

Therapeutic uses

Main articles: Vitamin C megadosage, Megavitamin therapy, and Orthomolecular medicine

Since its discovery vitamin C has been considered by some enthusiastic proponents a "universal panacea", although this led to suspicions by others of it being over-hyped.[53] Other proponents of high dose vitamin C consider that if it is given "in the right form, with the proper technique, in frequent enough doses, in high enough doses, along with certain additional agents and for a long enough period of time,"[54] it can prevent and, in many cases, cure, a wide range of common and/or lethal diseases, notably the common cold and heart disease,[55] although the NIH considers there to be "fair scientific evidence against this use."[56] Some proponents issued controversial statements involving it being a cure for AIDS,[57] bird flu, and SARS.[58][59][60]

Probably the most controversial issue, the putative role of ascorbate in the management of AIDS, is still unresolved, more than 16 years after the landmark study published in the Proceedings of National Academy of Sciences (USA) showing that non toxic doses of ascorbate suppress HIV replication in vitro.[61] Other studies expanded on those results, but still, no large scale trials have yet been conducted.[62][63][64]

In an animal model of lead intoxication, vitamin C demonstrated "protective effects" on lead-induced nerve and muscle abnormalities[65] In smokers, blood lead levels declined by an average of 81% when supplemented with 1000 mg of vitamin C, while 200 mg were ineffective, suggesting that vitamin C supplements may be an "economical and convenient" approach to reduce lead levels in the blood.[66] The Journal of the American Medical Association published a study which concluded, based on an analysis of blood lead levels in the subjects of the Third National Health and Nutrition Examination Survey, that the independent, inverse relationship between lead levels and vitamin C in the blood, if causal, would "have public health implications for control of lead toxicity".[67]

Vitamin C has limited popularity as a treatment for autism spectrum symptoms. A 1993 study of 18 children with ASD found some symptoms reduced after treatment with vitamin C,[68] but these results have not been replicated.[69] Small clinical trials have found that vitamin C might improve the sperm count, sperm motility, and sperm morphology in infertile men[70], or improve immune function related to the prevention and treatment of age-associated diseases.[71] However, to date, no large clinical trials have verified these findings.

A preliminary study published in the Annals of Surgery found that the early administration of antioxidant supplementation using α-tocopherol and ascorbic acid reduces the incidence of organ failure and shortens ICU length of stay in this cohort of critically ill surgical patients.[72] More research on this topic is pending.

Dehydroascorbic acid, the main form of oxidized Vitamin C in the body, was shown to 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".[73] In this study published by the Proceedings of the National Academy of Sciences in 2001, the authors concluded that such "a pharmacological strategy to increase cerebral levels of ascorbate in stroke has tremendous potential to represent the timely translation of basic research into a relevant therapy for thromboembolic stroke in humans". No such "relevant therapies" are available yet and no clinical trials have been planned.

In January 2007 the US Food and Drug Administration approved a Phase I toxicity trial to determine the safe dosage of intravenous vitamin C as a possible cancer treatment for "patients who have exhausted all other conventional treatment options."[74] Additional studies over several years would be needed to demonstrate whether it is effective.[75]

In February 2007, an uncontrolled study of 39 terminal cancer patients showed that, on subjective questionnaires, patients reported an improvement in health, cancer symptoms, and daily function after administration of high-dose intravenous vitamin C.[76] The authors concluded that "Although there is still controversy regarding anticancer effects of vitamin C, the use of vitamin C is considered a safe and effective therapy to improve the quality of life of terminal cancer patients".

Testing for ascorbate levels in the body

Simple tests use DCPIP 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.[5] 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.[77][78]

Adverse effects

While being harmless in most typical quantities, as with all substances to which the human body is exposed, vitamin C can still cause harm under certain conditions.

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 one trial, doses up to 6 grams of ascorbic acid were given to 29 infants, 93 children of preschool and school age, and 20 adults for more than 1400 days. With the higher doses, toxic manifestations were observed in five adults and four infants. The signs and symptoms in adults were nausea, vomiting, diarrhea, flushing of the face, headache, fatigue and disturbed sleep. The main toxic reactions in the infants were skin rashes.[79]

Possible side-effects

As vitamin C enhances iron absorption[80], 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.[81]

For decades, large doses of vitamin C have been speculated to trigger oxalate formation and increase absorption of dietary oxalate, possibly causing kidney stones.[82] However, this speculation may not be justified since there is no clear relationship between excess ascorbic acid intake and kidney stone formation. [83]

During the first month of pregnancy, high doses of vitamin C may suppress the production of progesterone from the corpus luteum.[84] 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) is 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 point out that this relationship may not necessarily be a causal one.[85]

Chance of overdose

As discussed previously, 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 when taken orally.[33] The LD50 in humans remains unknown, owing to medical ethics that preclude experiments which 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 artificial dietary sources

Rose hips are a particularly rich source of vitamin C

The richest natural sources are fruits and vegetables, and of those, the camu camu fruit and the Kakadu plum 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.[86]

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.[87]

The following table is approximate and shows the relative abundance in different raw plant sources.[88][89][90] 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
Amla 720
Seabuckthorn 695
Jujube 500
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
Persimmon 60

^ average of 3 sources; dried

Plant source Amount
(mg / 100g)
Papaya 60
Strawberry 60
Orange 50
Lemon 40
Melon, cantaloupe 40
Cauliflower 40
Grapefruit 30
Raspberry 30
Tangerine 30
Mandarin orange 30
Passion fruit 30
Spinach 30
Cabbage raw green 30
Lime 20
Mango 20
Potato 20
Melon, honeydew 20
Mango 16
Cranberry 13
Tomato 10
Blueberry 10
Pineapple 10
Plant source Amount
(mg / 100g)
Pawpaw 10
Grape 10
Apricot 10
Plum 10
Watermelon 10
Banana 9
Carrot 9
Avocado 8
Crabapple 8
Cherry 7
Peach 7
Apple 6
Blackberry 6
Beetroot 5
Pear 4
Lettuce 4
Cucumber 3
Eggplant 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 will manufacture more than 13,000 mg of vitamin C per day in normal health and levels manyfold higher when faced with stress.

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.[91] 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:

Food 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
Lamb liver (fried) 12
Lamb heart (roast) 11
Food Amount
(mg / 100g)
Lamb tongue (stewed) 6
Human milk (fresh) 4
Goat milk (fresh) 2
Cow milk (fresh) 2
Beef steak (fried) 0
Hen's egg (raw) 0
Pork bacon (fried) 0
Calf veal cutlet (fried) 0
Chicken leg (roast) 0


Food preparation

Vitamin C chemically decomposes under certain conditions, many of which may occur during the cooking of food. Normally, boiling water at 100°C is not hot enough to cause any significant destruction of the nutrient, which only decomposes at 190°C, [33] despite popular opinion. However, pressure cooking, roasting, frying and grilling food is more likely to reach the decomposition temperature of vitamin C. Longer cooking times also add to this effect, as will copper food vessels, which catalyse the decomposition.[33]

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.[92] Research has also shown that fresh-cut fruit don't lose significant nutrients when stored in the refrigerator for a few days.[93]

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.[94] 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).

Artificial modes of 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.[95]

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.[27]

World production of synthesised vitamin C is currently estimated at approximately 110,000 tonnes annually. Main producers today are 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.[96]

See also

References

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  19. ↑ Lindblad B, Lindstedt G, Lindstedt S: The mechanism of enzymic formation of homogentisate from p-hydroxyphenylpyruvate. J Am Chem Soc 92:7446–7449, 1970.
  20. ↑ New view at C Matthias A. Hediger , Nature Medicine 8, 445 - 446 (2002) doi:10.1038/nm0502-445

    "Plasma vitamin C concentrations are maintained between 10 and 160 μM, and any excess of the vitamin is excreted by the kidney. In contrast, the vitamin is concentrated to at least 100 times the plasma level in specific tissues such as the adrenal glands, pituitary gland, thymus, retina, corpus luteum, and a variety of neuronal cell types."
  21. ↑ Bánhegyi G, Mándl J (2001). "The hepatic glycogenoreticular system". Pathol Oncol Res. 7 (2): 107–10. PMID 11458272.
  22. ↑ Harris, J. Robin (1996). Ascorbic Acid: Subcellular Biochemistry. Springer. pp. p. 35. ISBN 0306451484.
  23. ↑ Milton, K. (1999) "Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us?" Nutrition. 1999 Jun;15(6):488-98.
  24. ↑ Proctor P (1970). "Similar functions of uric acid and ascorbate in man?". Nature. 228 (5274): 868. doi:10.1038/228868a0. PMID 5477017.
  25. ↑ 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 1950’s 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 which converts 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)
  26. ↑ C. Long; et al. "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.

    "Our results show that plasma ascorbic acid levels following trauma and during infection are extremely low and are not normalized with 300 or even 1000 mg/day supplemented TPN."
  27. ↑ 27.0 27.1 R.D. Hancock & R. Viola. "Ascorbic acid biosynthesis in higher plants and micro-organisms" (PDF). Scottish Crop Research Institute. Retrieved 2007-02-20.

    "Our results demonstrate that yeast cells are capable of direct fermentation of L-galactose to L-AA. However, given that L-galactose is an extremely rare and expensive sugar a process using L-galactose as a starting material could never be economical. In order to overcome this problem, we are currently developing new yeast strains with extended metabolic competence for the synthesis of L-galactose directly from inexpensive substrates."
  28. ↑ Hancock RD, Galpin JR, Viola R. "Biosynthesis of L-ascorbic acid (vitamin C) by Saccharomyces cerevisiae". FEMS Microbiol Lett. 186 (2): 245–50. PMID 10802179. |access-date= requires |url= (help)
  29. ↑ McGee, William (2007-01-02). "Vitamin C". National Institutes of Health. Retrieved 2007-03-09. Check date values in: |date= (help)
  30. ↑ "The influence of smoking on vitamin C status in adults". BBC news and Cambridge University. 2000-31-09. Retrieved 2007-12-12. Check date values in: |date= (help)
  31. ↑ "Jacques Cartier's Second Voyage - 1535 - Winter & Scurvy". Retrieved 2007-02-25.
  32. ↑ Martini E. (June 2002). "Jacques Cartier witnesses a treatment for scurvy". Vesalius. PMID 12422875.
  33. ↑ 33.0 33.1 33.2 33.3 "Safety (MSDS) data for ascorbic acid". Oxford University. 2005-10-09. Retrieved 2007-02-21. Check date values in: |date= (help)
  34. ↑ "Pitt History - 1932: Charles Glen King". University of Pittsburgh. Retrieved 2007-02-21. In recognition of this medical breakthrough, some scientists believe that King deserved a Nobel Prize.
  35. ↑ Burns, J. J., and Evans, C., J. Biol. Chem., 200, 125 (1953).
  36. ↑ Burns, J. J., Peyser, P., and Maltz, A., Science, 124, 1148 (1956).
  37. ↑ 37.0 37.1 37.2 37.3 "US Recommended Dietary Allowance (RDA)" (PDF). Retrieved 2007-02-19.
  38. ↑ 38.0 38.1 Milton K (2003). "Micronutrient intakes of wild primates: are humans different?" (PDF). Comp Biochem Physiol A Mol Integr Physiol. 136 (1): 47–59. PMID 14527629.
  39. ↑ 39.0 39.1 Pauling, Linus. "Evolution and the need for ascorbic acid". Proc Natl Acad Sci U S A. 67 (4): 1643–8. PMID 5275366. |access-date= requires |url= (help)
  40. ↑ 40.0 40.1 "Linus Pauling Vindicated; Researchers Claim RDA For Vitamin C is Flawed". PR Newswire. 6 July, 2004. Retrieved 2007-02-20. Check date values in: |date= (help)
  41. ↑ 41.0 41.1 Cathcart, Robert (1994). "Vitamin C, Titrating To Bowel Tolerance, [[Anascorbemia]], and Acute Induced Scurvy". Orthomed. Retrieved 2007-02-22. URL–wikilink conflict (help)
  42. ↑ "Vitamin and mineral requirements in human nutrition, 2nd edition" (PDF). World Health Organization. 2004. Retrieved 2007-02-20.
  43. ↑ Higdon, Jane. "Linus Pauling Institute Recommendations". Oregon State University. Retrieved 2007-04-11.
  44. ↑ Roc Ordman. "The Scientific Basis Of The Vitamin C Dosage Of Nutrition Investigator". Beloit College. Retrieved 2007-02-22.
  45. ↑ "Vitamin C Foundation's RDA". Retrieved 2007-02-12.
  46. ↑ Levy, Thomas E. (2002). Vitamin C Infectious Diseases, & Toxins. Xlibris. ISBN 1401069630. Chapter 5 - Vitamin C optidosing.
  47. ↑ 47.0 47.1 Pauling, Linus (1986). How to Live Longer and Feel Better. W. H. Freeman and Company. ISBN 0-380-70289-4.
  48. ↑ Ascorbate web An historical compendium of 20th-Century medical & scientific literature attesting to the efficacy of Ascorbate
  49. ↑ Forman, Robert (1981). "Medical Resistance To Innovation". Medical Hypotheses. 7 (8): 1009–1017. Retrieved 2007-02-23.
  50. ↑ OMIM. Online Mendeleian Inheritance in Man. "HYPOASCORBEMIA". Retrieved 2007-03-06.
  51. ↑ Hickey, Steve (2004). Ascorbate: The Science of Vitamin C. Lulu Press, Inc. ISBN 1-4116-0724-4. Unknown parameter |coauthors= ignored (help)
  52. ↑ Stone, Irwin (1972). The Healing Factor: Vitamin C Against Disease. Grosset and Dunlap. ISBN 0-448-11693-6.
  53. ↑ Hemilä, Harri (January 2006). "Do vitamins C and E affect respiratory infections?" (PDF). University of Helsinki. Retrieved 2007-02-21.
  54. ↑ Levy, Thomas E. (2002). Curing the Incurable: Vitamin C, Infectious Diseases, and Toxins. Livon Books. pp. p. 36. ISBN 1-4010-6963-0.
  55. ↑ 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.
  56. ↑ "Vitamin C (Ascorbic acid)". MedLine Plus. National Institute of Health. 2006-08-01. Retrieved 2007-08-03. Check date values in: |date= (help)
  57. ↑ "Nigeria: Vitamin C Can Suppress HIV/Aids Virus". allAfrica.com. 2006-05-22. Retrieved 2006-06-16. Check date values in: |date= (help)
  58. ↑ Hemilä H (2003). "Vitamin C and SARS coronavirus". J Antimicrob Chemother. 52 (6): 1049–50. PMID 14613951.
  59. ↑ Boseley, Sarah (2005-05-14). "Discredited doctor's 'cure' for Aids ignites life-and-death struggle in South Africa". The Guardian. Retrieved 2007-02-21. Check date values in: |date= (help)
  60. ↑ Rath, Matthias (2005). "Open letter from Dr. Matthias Rath MD to German Chancellor Merkel". Dr. Rath Health Foundation. Retrieved 2007-02-21.
  61. ↑ Harakeh S, Jariwalla R, Pauling L (1990). "Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells". Proc Natl Acad Sci U S A. 87 (18): 7245–9. PMID 1698293.
  62. ↑ Harakeh S, Jariwalla R (1991). "Comparative study of the anti-HIV activities of ascorbate and thiol-containing reducing agents in chronically HIV-infected cells". Am J Clin Nutr. 54 (6 Suppl): 1231S–1235S. PMID 1720598.
  63. ↑ Harakeh S, Jariwalla R (1997). "NF-kappa B-independent suppression of HIV expression by ascorbic acid". AIDS Res Hum Retroviruses. 13 (3): 235–9. PMID 9115810.
  64. ↑ Harakeh S, Jariwalla R. "Ascorbate effect on cytokine stimulation of HIV production". Nutrition. 11 (5 Suppl): 684–7. PMID 8748252.
  65. ↑ 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. PMID 12818354. |access-date= requires |url= (help)
  66. ↑ 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.
  67. ↑ Simon JA, Hudes ES (1999). "Relationship of ascorbic acid to blood lead levels". JAMA. 281 (24): 2289–93. PMID 10386552. |access-date= requires |url= (help)
  68. ↑ Dolske MC, Spollen J, McKay S, Lancashire E, Tolbert L (1993). "A preliminary trial of ascorbic acid as supplemental therapy for autism". Prog. Neuropsychopharmacol. Biol. Psychiatry. 17 (5): 765–74. PMID 8255984. |access-date= requires |url= (help)
  69. ↑ 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.
  70. ↑ 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. PMID 17004914.
  71. ↑ de la Fuente M, Ferrández M, Burgos M, Soler A, Prieto A, Miquel J (1998). "Immune function in aged women is improved by ingestion of vitamins C and E". Can J Physiol Pharmacol. 76 (4): 373–80. PMID 9795745.
  72. ↑ Nathens A, Neff M, Jurkovich G, Klotz P, Farver K, Ruzinski J, Radella F, Garcia I, Maier R (2002). "Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients". Ann Surg. 236 (6): 814–22. PMID 12454520.
  73. ↑ 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): 11720–11724. PMID 11573006.
  74. ↑ "FDA OKs vitamin C trial for cancer". Physorg.com. 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.
  75. ↑ "Study of High-Dose Intravenous (IV) Vitamin C Treatment in Patients With Solid Tumors". Retrieved August 2, 2007. The primary purpose of this study is to evaluate the safety and tolerability of vitamin C (ascorbic acid) given by injection into the vein. The second and third purpose of conducting this study is to observe any evidence of tumor response to the vitamin C and compare the level of fatigue (weakness), pain control, ability to do things, and quality of life, before and after vitamin C is given. (Phase I) line feed character in |quote= at position 140 (help)
  76. ↑ 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. PMID 17297243. |access-date= requires |url= (help)
  77. ↑ 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)". Clinical Biochemistry. 38 (5): 450–6. PMID 15820776.

    "Serum and plasma vitamin C measurements do not correlate well with tissue levels while lymphocyte vitamin C levels provide the most accurate assessment of the true status of vitamin C stores and are not affected acutely by circadian rhythm or dietary changes."
  78. ↑ 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: 2491–2.

    "The plasma concentration of vitamin C is considered to be strongly correlated with transient consumption of foods. The measurement of lymphocyte vitamin C might be expected to be a more reliable antioxidant biomarker than plasma vitamin C level. In this report, we demonstrated that the lymphocyte vitamin C level is significantly lower in type 2 diabetic patients, but we could not observe such an association in plasma vitamin C levels. In diabetes, therefore, the measurement of lymphocyte vitamin C might be expected to be a more reliable antioxidant biomarker than plasma vitamin C level."
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  82. ↑ Massey LK, Liebman M, Kynast-Gales SA (2005). "Ascorbate increases human oxaluria and kidney stone risk". J. Nutr. 135 (7): 1673–7. PMID 15987848.
  83. ↑ Naidu KA (2003). "Vitamin C in human health and disease is still a mystery? An overview". J. Nutr. 2. PMID 14498993. Text " issue 7 " ignored (help)
  84. ↑ Ovcharov R, Todorov S (1974). "[The effect of vitamin C on the estrus cycle and embryogenesis of rats]". Akusherstvo i ginekologii͡a (in Bulgarian). 13 (3): 191–5. PMID 4467736.
  85. ↑ 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.
  86. ↑ Wilson JX (2005). "Regulation of vitamin C transport". Annu. Rev. Nutr. 25: 105–25. doi:10.1146/annurev.nutr.25.050304.092647. PMID 16011461.
  87. ↑ "The vitamin and mineral content is stable". Danish Veterinary and Food Administration. Retrieved 2007-03-07.
  88. ↑ "National Nutrient Database". Nutrient Data Laboratory of the US Agricultural Research Service. Retrieved 2007-03-07.
  89. ↑ "Vitamin C Food Data Chart". Healthy Eating Club. Retrieved 2007-03-07.
  90. ↑ "Natural food-Fruit Vitamin C Content". The Natural Food Hub. Retrieved 2007-03-07.
  91. ↑ Clark, Stephanie, Ph. D (8 January 2007). "Comparing Milk: Human, Cow, Goat & Commercial Infant Formula". Washington State University. Retrieved 2007-02-28.
  92. ↑ Combs GF. The Vitamins, Fundamental Aspects in Nutrition and Health. 2nd ed. San Diego, CA: Academic Press, 2001:245–272
  93. ↑ Hitti, Miranda (2 June 2006). "Fresh-Cut Fruit May Keep Its Vitamins". WebMD. Retrieved 2007-02-25.
  94. ↑ The Diet Channel Vitamin C might be the most widely known and most popular vitamin purchased as a supplement.
  95. ↑ "The production of vitamin C" (PDF). Competition Commission. 2001. Retrieved 2007-02-20.
  96. ↑ Patton, Dominique (2005-10-20). "DSM makes last stand against Chinese vitamin C". nutraingredients. Retrieved 2007-02-20. Check date values in: |date= (help)

Further reading

Journals
  • Dolske, M.C.; et al. (1993). "A preliminary trial of ascorbic acid as supplemental therapy for autism". Prog. Neuropsychopharmacol. Biol. Psychiatry. 17 (5): 765–74. PMID 8255984.
  • Green VA, Pituch KA, Itchon J, Choi A, O'Reilly M, Sigafoos J (2006). "Internet survey of treatments used by parents of children with autism". Research in developmental disabilities. 27 (1): 70–84. doi:10.1016/j.ridd.2004.12.002. PMID 15919178.
Books

External links

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