Vitamin C

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Vitamin C
Systematic (IUPAC) name
2-oxo-L-threo-hexono-1,4- lactone-2,3-enediol or (R)-3,4-dihydroxy-5-((S)- 1,2-dihydroxyethyl)furan-2(5H)-one
Identifiers
CAS number	50-81-7
ATC code	A11G
PubChem	644104
Chemical data
Formula	C6H8O6
Mol. mass	176.13 grams per mol
Synonyms	L-ascorbate
Physical data
Melt. point	190–192 °C (374–378 °F) decomposes
Pharmacokinetic data
Bioavailability	rapid & complete
Protein binding	negligible
Metabolism	?
Half life	30 minutes
Excretion	renal
Therapeutic considerations
Pregnancy cat.	A
Legal status	general public availability
Routes	oral

Top: ascorbic acid
(reduced form)
Bottom: dehydroascorbic acid
(oxidized form)

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 in plants and is made internally by almost all organisms. It is widely known as the vitamin that prevents scurvy in humans.^[1][2][3]

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 a cofactor in several vital enzymatic reactions.^[5]

As a nutrient, its uses and the daily requirement are matters of on-going debate. As a food additive, vitamin C is used as an antioxidant preservative and an acidity regulator. Several E numbers account for the vitamin, depending on its chemical structure: E300 as ascorbic acid, E301 as sodium ascorbate, E302 as calcium ascorbate, and E303 as potassium ascorbate.

[edit] 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 oxidised form, L-dehydroascorbate.^[5] L-dehydroscorbate 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.

[edit] 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] Of the eight enzymes, three participate in collagen hydroxylation.^[8][9][10] These reactions add hydroxyl groups to the amino acids proline or lysine in the collagen molecule, thereby allowing the collagen molecule to assume its triple helix structure. Two other vitamin C dependent enzymes are necessary for synthesis of carnitine.^[11][12] Carnitine is essential for the transport of fatty acids into mitochondria for ATP generation. The remaining three vitamin C dependent enzymes have the following functions: one participates in the biosynthesis of norepinephrine from dopamine,^[13][14] one adds amide groups to peptide hormones, greatly increasing their stability,^[15][16] and one modulates tyrosine metabolism.^[17][18]

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.^[19] 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.

[edit] 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.^[20] 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, along with the rest of the ape family in which we reside, 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.^[21] The mutation has not been lethal because vitamin C is prevalent in their food sources, with many of these species' natural diets consisting largely of fruit.

Some physicians and researchers, including chemist Linus Pauling have hypothesised that if the diets of the species who lost the ability to produce their own vitamin C were supplemented with an amount of the nutrient proportional to the amount produced in animal species that do synthesize their own vitamin C, better health would result. Most simians consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans.^[22] 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.^[23] 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 as much as 100,000 mg daily when faced with life-threatening disease, trauma or stress. ^{[24] [25]} Trauma or injury has also been demonstrated to 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]

[edit] 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 cannot store vitamin C,^[29] and so the body soon depletes itself if fresh supplies are not consumed through the digestive system.

[edit] 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.^[30][31]

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^[32]). 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 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.

[edit] 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.^[33]

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 1959 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.^[34][35] 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.

[edit] 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).^[36] Other related species sharing the same inability to produce vitamin C and requiring exogenous vitamin C consume 20 to 80 times this reference intake.^[37][38] 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.^[39] It is generally agreed that a balanced diet without supplementation contains enough vitamin C to prevent acute scurvy in an average healthy adult, while those who are pregnant, smoke tobacco, or are under stress require slightly more.^[36]

Vitamin C is recognized to be one of the least toxic substances known to medicine,^[36] with the LD50 being 11,900 milligrams per kilogram.^[32][40] High doses (thousands of milligrams) may result in diarrhoea, which is harmless if the dose is reduced immediately. Some researchers^[41] claim the onset of diarrhoea to be an indication of where the body’s true vitamin C requirement lies. Both Cathcart^[41] and Cameron have demonstrated that very sick patients with cancer or influenza do not display any evidence of diarrhoea at all until ascorbate intake reaches levels as high as 200 grams (half a pound).

[edit] Government recommended intakes

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

• 40 milligrams per day — the United Kingdom's Food Standards Agency^[1]
• 45 milligrams per day — the World Health Organization^[42]
• 60-95 milligrams per day — United States' National Academy of Sciences^[36]

The United States defined Tolerable Upper Intake Level for a 25-year old male is 2000 milligrams per day.

[edit] Independent recommended 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:

• 400 milligrams per day — the Linus Pauling Institute and the US National Institutes of Health
• 500 milligrams per 12 hours — Professor Roc Ordman, from research into biological free radicals^[43]
• 3,000 milligrams per day (or up to 300,000 mg during illness or pregnancy) — the Vitamin C Foundation^[44]
• 6,000–12,000 milligrams per day — Thomas E. Levy, Colorado Integrative Medical Centre
• 6,000–18,000 milligrams per day — Linus Pauling's personal use^[45]
• 3,000–200,000 milligrams per day — Robert Cathcart's protocol known as a "vitamin C flush" wherein escalating doses of vitamin C are given until diarrhoea develops, then choosing the highest dose that does not cause diarrhoea (the bowel tolerance threshold)^[41]

[edit] Vitamin C as a macronutrient

Linus Pauling's popular and influential book How to Live Longer and Feel Better, first published in 1986, advocated very high doses of vitamin C.

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. Many pro-vitamin C organizations promote usage levels well beyond the current Dietary Reference Intake. The movement is fronted 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 an extensive and growing literature critical of governmental agency dose recommendations.^[39][46] 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. Hickey, on this matter, says "To be blunt, the NIH gave a dose of vitamin C, waited until it had been excreted, and then measured blood levels."^[47]

[edit] 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.^[48] 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.^[49] 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^[50] and Pauling^[38] calculated, based on the diet of our primate cousins^[37] (similar to what our common descents are likely to have consumed when the gene mutated), that the optimum daily requirement of vitamin C is around 2300 milligrams for a human requiring 2500 kcal a day. The implication of those calculations, if correct, is that vitamin C was misnamed as a vitamin and is in fact a vital macronutrient like protein or carbohydrate.

The established RDA has been criticised by Pauling to be one that will prevent acute scurvy, and is not necessarily the dosage for optimal health.^[45]

Atherosclerosis has been hypothesised to be a vitamin C deficiency disease

The controversial Matthias Rath hypothesised that during the ice age, when vitamin C was scarce, natural selection favoured human individuals who could repair arteries with a layer of cholesterol. He suggests that although eventually harmful, cholesterol lining of artery walls would be beneficial in that it would keep the individual alive until access to vitamin C allowed arterial damage to be repaired. If this is true, atherosclerosis is in fact a vitamin C deficiency disease. As atherosclerosis is the main cause of ischaemic heart disease, which in turn is the leading cause of death in developed countries,^[51] this would have a profound effect on western medicine.

[edit] Therapeutic uses

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.^[52] As opposed to enthusiastic proponents of the universal panacea hypothesis, the majority of 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,"^[53] it can prevent and, in many cases, cure, a wide range of common and/or lethal diseases, notably the common cold and heart disease.^[54] Some proponents issued controversial statements involving it being a cure for AIDS,^[55] bird flu, and SARS.^[56][57][58]

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 prestigious Proceedings of National Academy of Sciences (USA) showing that non toxic doses of ascorbate suppress HIV replication.^[59] Other studies expanded on those results, but still, no large scale trials have yet been conducted.^[60][61][62]

A 1986 study indicates that vitamin C may be important in regulation of endogenous cholesterol synthesis.^[63]

There have been studies suggesting that vitamin C detoxifies lead,^[64][65] reduces the severity of symptoms in children with autism,^[66] reduces neurological deficits and mortality following stroke,^[67] reduces multiple organ failure and length of stay in the intensive care unit in trauma victims,^[68] improves sperm count, sperm motility, and sperm morphology in infertile men,^[69] and improves immune function in aged persons and could contribute to the prevention and treatment of age-associated diseases.^[70]

[edit] 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.^[71][72]

[edit] 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.

[edit] Common side-effects

Relatively large doses of vitamin C may cause indigestion, particularly when taken on an empty stomach. This unpleasant but harmless side-effect can be avoided by taking the vitamin along with meals or by offsetting its acidity by taking an antacid such as baking soda or calcium carbonate.

When taken in huge doses, vitamin C causes diarrhea. The minimum dose that brings about this effect varies with the individual. Robert Cathcart has called this limit the "bowel tolerance threshold" and observed that it is higher in people with serious illness than those in good health.^[41] It ranges from 5 to 25 grams per day in healthy individuals to 300 grams per day in those that are severely ill. Diarrhea is not harmful, as long as the dose is reduced quickly.

[edit] Rare side-effects

As vitamin C enhances iron absorption, iron poisoning can become an issue to people with rare iron overload disorders, such as haemochromatosis. A genetic condition that results in inadequate levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD), can cause sufferers to develop hemolytic anemia after ingesting specific oxidizing substances, such as very large dosages of vitamin C. However, there is a test available for G6PD deficiency,^[73] and it has been proposed that high doses of vitamin E may protect against this problem.

[edit] Chance of overdose

As discussed previously, vitamin C exhibits remarkably low toxicity. The LD₅₀ (the dose that will kill 50% of a population) is generally accepted to be 11900 milligrams per kilogram.^[74] This means that for a 60 kilo (132 pound) human, one would need to administer 714,000 mg (714 g or 1.6 pounds) of vitamin C in order to stand a 50% chance of killing the person. However, vitamin C cannot result in death when taken orally as large amounts of the vitamin cause diarrhea and are not absorbed.^[75] An extremely large amount of vitamin C would need to be rapidly injected in order to stand any chance of killing a person. Robert Cathcart declares that he has used intravenous doses of up to 250 grams with no adverse effects.^[76] The United States Council for Responsible Nutrition has set an Upper Level of 2 grams, based on transient diarrhea. Their publication on vitamin C safety notes that:

[edit] 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 billygoat 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.

[edit] 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.^[77]

The following table is approximate and shows the relative abundance in different raw plant sources.^[78][79][80] The amount is given in milligrams per 100 grams of fruit or vegetable and is a rounded average from multiple authoritative sources:

[edit] 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 as much as 100,000 mg daily when faced with life-threatening disease, trauma or 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.^[81]

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:

[edit] 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, 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.^[32]

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.^[82] Research has also shown that fresh-cut fruit don't lose significant nutrients when stored in the refrigerator for a few days.^[83]

[edit] 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-produce synthetic vitamin C.

Vitamin C is the most widely taken dietary supplement.^[84] It is available in many forms including caplets, tablets, capsules, drink mix packets, in multi-vitamin formulations, in multiple antioxidant formulations, as chemically pure crystalline powder, timed release versions, and also including bioflavonoids such as quercetin, hesperidin and rutin. The use of vitamin C supplements with added bioflavonoids and, often, flavours and sweeteners, can be problematic at gram dosages, since those additives are not so well studied as vitamin C. 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). In supplements, vitamin C most often comes in the form of various mineral ascorbates, as they are easier to absorb, more easily tolerated and provide a source of several dietary minerals.

[edit] 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.^[85]

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.^[86]

[edit] See also

Food Portal

Health Portal

• Ascorbyl palmitate & ascorbyl stearate — two fat-soluble esters of vitamin C
• Erythorbic acid & erythorbin acid — two stereoisomers of vitamin C

[edit] References

[edit] Further reading

Journals

• Dolske, M.C., et al. 1993. "A preliminary trial of ascorbic acid as a supplemental therapy for autism." Prog. Neuropsychopharmacol. Biol. Psychiatry, 17(5):765–774.

• Green, V.A., K.A. Pituch, J. Itchon, A. Choi, M. O'Reilly, J. Sigafoos, "Internet survey of treatments used by parents of children with autism," Res Dev Disabil, 2006, 27(1):70–84.

Books

• Cancer and Vitamin C, Ewan Cameron and Linus Pauling, Pauling Institute of Science and Medicine, 1979
• Life Extension: A Practical Scientific Approach (Part IV, Chapter 7: Vitamin C), Durk Pearson and Sandy Shaw, Warner Books, 1982
• Life Extension Revolution, Saul Kent, Morrow, 1980
• Mind Food and Smart Pills: How to Increase Your Intelligence and Prevent Brain Aging (Chapter 3: Vitamin C, The Champion Free Radical Scavenger), Ross Pelton, 1986
• Vitamin C and the Common Cold, Linus Pauling, 1970
• Vitamin C, the Common Cold, and the Flu, Linus Pauling, Freeman, 1976
• Vitamin C, Volumes I, II, III., Monograph by C.A.B Clemetson, 1989 CRC Press, Boca Raton, Florida, ISBN 0-8493-4841-2

[edit] External links

• Jane Higdon, "Vitamin C", Micronutrient Information Center, Linus Pauling Institute
• AscorbateWeb — a collection of twentieth century medical & scientific literature on vitamin C in the treatment and prevention of human disease
• Healing Thresholds — Research on Vitamin C in the treatment of autism.
• U.S. Patent 5,278,189  — "Prevention and treatment of occlusive cardiovascular disease with ascorbate and substances that inhibit the binding of lipoprotein (a)", Inventors: Matthias W. Rath and Linus C. Pauling
• United Kingdom Food Standards Agency on vitamin C
• Vitamin C in human health and disease is still a mystery? An overview — one of BioMed Central most popular pages
• For Doctors: Preparation of Vitamin C IV's — by Andrew W. Saul, PhD.
• Information regarding treatment of the Bird Flu with massive doses of ascorbate. — by Robert Cathcart, M.D.