This article is about the nutrient. For the musician, see Colleen Fitzpatrick.

Vitamin C is a water-soluble nutrient essential for life and used by the human body for many purposes. To the best of scientific knowledge, all animals and plants synthesize their own vitamin C, except for a small number of animals, including guinea pigs, humans, apes, the red vented bulbil, a fruit eating bat and a species of trout, that cannot. This fact, and the related fact that man possesses three of the four enzymes that animals employ to manufacture the substance in relatively large amounts, has lead researchers such as Irwin Stone and Linus Pauling to hypopthesize that man once manufactured this substance in his body millions of years ago in quantities roughly estimated at 3,000-4,000 mg daily, but later lost the ability to do this through evolution. If true, this would of course mean that vitamin C was misnamed as a vitamin and is in fact a macronutrient, like fat or carbohydrate.

Vitamin C was first isolated in 1928, and in 1932 it was proved to be the agent which prevents scurvy. Szent-Gyorgyi was awarded the Nobel prize for this feat.

Vitamin C is the L-enantiomer of ascorbic acid (in one of its well known forms). The defining part of the substance is the ascorbate ion, which can be associated either with acids or bases. Commercial vitamin C is often a mix of ascorbic acid, sodium ascorbate and/or other ascorbates. See the ascorbic acid article for a description of the molecule's chemical properties.

Discovery and history

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, infusions of spruce needles were used in the temperate zones, or the leaves from species of drought-resistant trees in desert areas.

Through history the benefit of plant food for the survival of sieges and long sea voyages was recommended by enlightened authorities. In the seventeenth century Richard Woodall, a ship's surgeon to the British East India Company, recommended the use of lemon juice as a preventive and cure in his book "Surgeon's Mate". The early eighteenth century Dutch writer, Johannes Bachstrom 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."

The first attempt to give scientific basis for the cause of scurvy was by a ship's surgeon in the British Royal Navy, James Lind, who at sea in May 1747 provided some crew members with lemon juice in addition to normal rations while others continued on normal rations alone. In the history of science this is considered to be the first example 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 lemons prevented the disease. Lind wrote up his work and published it in 1753.

Lind's work was slow to be noticed, partly because he gave conflicting evidence within the book and partly because of social inertia in some elements at the British admiralty who saw care for the well-being of ships' crew as a sign of weakness. It was 1795 before the British navy adopted lemons or lime as standard issue at sea. (This practice led to the nickname limey for British people, especially British sailors.) 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 back without losing any of his men to scurvy. For this otherwise unheard of and stupendous feat, he was awarded a medal by the British Admiralty. So the Navy was certainly well aware of the priciple. The cost of providing fresh fruit on board was probably a factor in this long delay. Non standard or extra supplies not provided by the Admiralty were usually provided by the Captains.

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 include lemons, limes, and oranges; sauerkraut, salted cabbage, malt, and portable broth were employed with variable effect.

In 1907, Alex Holst and Theodore Frohlich, two Norwegian biochemists studying beriberi contracted aboard ship's crews in the Norwegian Fishing Fleet, wanted a small test mammal to substitute for the pigeons then used. They fed guinea pigs the 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 it was considered an exclusively human disease.

In 1928 the arctic anthropologist and adventurer Vilhjalmur Stefansson attempted to prove his theory of how Eskimo (Inuit) people are able to avoid scurvy with almost no plant food in their diet. This had long been a puzzle because the disease had struck European Arctic explorers living on similar high-meat diets. Stefansson theorised that the native peoples of the Arctic got their vitamin C from fresh meat that was raw or minimally cooked. Starting in February 1928, for one year he and a colleague lived on an animal-flesh-only diet under medical supervision at New York's Bellevue Hospital; they remained healthy.

In the early twentieth century, the Polish-American scientist Casimir Funk conducted research into deficiency diseases, and in 1912 Funk developed the concept of vitamins, for the elements in food 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.

In 1933-1934, the British chemists Sir Walter Norman Haworth and Sir Edmund Hirst and, independently, the Polish Tadeus Reichstein, succeeded in synthesizing the vitamin, the first to be artificially produced. This made possible the cheap mass production of vitamin C. Haworth was awarded the 1937 Nobel Prize for Chemistry largely for this work.

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 ascorbic acid.

Sources

Plant sources

Citrus fruits (lime, lemon, orange, grapefruit), tomatoes, and potatoes are good common sources of vitamin C. Other foods that are good sources of vitamin C include papaya, broccoli, brussels sprouts, black currants, strawberries, cauliflower, spinach, cantaloupe, and kiwifruit. Also, cranberries and red peppers are good sources of the vitamin.

The amount of vitamin C 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,
• the method of preparation. Cooking in particular is often said to destroy vitamin C - but see the section on Food preparation.

The following table is approximate and shows the relative abundance in different raw plant sources. The amount is given in mg per 100 grams of fruit:

Animal sources

The overwhelming majority of species of animals and plants 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.

For example 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.

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 which make up the modern western diet are however poor sources. As with fruit and vegetables cooking destroys the vitamin C content.

The following table shows the relative abundance of vitamin C in various foods of animal origin, given in mg of vitamin C per 100 grams of food:

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 in the body

• As a participant in hydroxylation, vitamin C is needed for the production of collagen in the connective tissue. These fibres are ubiquitous throughout the body; providing firm but flexible structure. Some tissues have a greater percentage of collagen, especially: skin, mucous membranes, teeth and bones.
• Vitamin C is required for synthesis of dopamine, noradrenaline and adrenaline in the nervous system or in the adrenal glands.
• Vitamin C is also needed to synthesise carnitine, important in the transfer of energy to the cell mitochondria.
• It is a strong antioxidant.
• The tissues with greatest percentage of vitamin C — over 100 times the level in blood plasma — are the adrenal glands, pituitary, thymus, corpus luteum, and retina.
• The brain, spleen, lung, testicle, lymph nodes, liver, thyroid, small intestinal mucosa, leukocytes, pancreas, kidney and salivary glands usually have 10 to 50 times the concentration present in plasma.

No bodily organ stores ascorbate as a primary function, and so the body soon depletes itself of ascorbate if fresh supplies do not continue to arrive though the digestive system, eventually leading to death if unresolved.

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:

• loose teeth
• superficial bleeding
• fragility of blood vessels
• poor healing
• compromised immunity
• mild anaemia.

Daily requirement

There is a continuing debate within the scientific community over the optimum amount of vitamin C for humans.²

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. However, a person who is just freed from a scorbutic condition with only a small amount of ascorbate (RDA quantities) is arguably a very unhealthy individual, and certainly not one in optimum health. 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 of scurvy 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:

400 mg per day – Linus Pauling Institute & 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. Both Cathcart 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 (1/2 pound)

The small size of the ascorbic acid molecule means the kidneys cannot retain it in the body. Some other explanation is required to explain why very sick persons retain such huge quantities of vitamin C without any discharge. 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.

Food preparation

It is important to choose a suitable method of food preparation. When cooking vegetables, one should seek to minimize or not discard the water used in their preparation, e.g. by frying the food – which unfortunately increases fat content, steam cooking or by making soup.

Recent observations suggest that the impact of temperature and cooking on vitamin C may have been overestimated:

1. Since it is water soluble, vitamin C will strongly leach into the cooking water while cooking most vegetables — but this doesn't necessarily mean the vitamin is destroyed — it's still there, but it's in the cooking water. (This may also suggest how the apparent misconception about the extent to which boiling temperatures destroy vitamin C might have been the result of flawed research: If the vitamin C content of vegetables (and not of the water) was measured subsequent to cooking them, then that content would have been much lower, though the vitamin has not actually been destroyed.)
2. Not only the temperature, but also the exposure time is significant. Contrary to what was previously and is still commonly assumed, it can take much longer than two or three minutes to destroy vitamin C at boiling point.

It also appears that cooking doesn't necessarily leach vitamin C in all vegetables at the same rate; it has been suggested that the vitamin is not destroyed when boiling broccoli.¹, this may however just be a result of vitamin C leaching into the cooking water at a slower rate from this vegetable.

Vitamin C enriched teas and infusions have increasingly appeared on supermarket shelves. Such products would be nonsense if boiling temperatures did indeed destroy vitamin C at the rate it had previously been suggested. It should be noted however that as of 2004 most academics not directly involved in vitamin C research still teach that boiling temperatures will destroy vitamin C very rapidly.

Reported potential harmful effects

Reports of harmful effects of vitamin C tend to receive great prominence in the world's media. Many such reports have never been published in peer reviewed journals, which casts some suspicion on their credibility.

• In April 1998 Nature reported alleged carcinogenic and teratogenic effects of excessive doses of vitamin C. 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.

• University of Southern California researchers in April 2000, reported a thickening of the arteries of the neck in persons taking high vitamin C doses. It was pointed out by vitamin C advocates that vitamin C's collagen synthesising role would lead to thicker and stronger artery walls.

• In June 2004, Duke University researchers reported an increased susceptibility to osteo-arthritis in guinea pigs fed a diet high in vitamin C. However, a 2003 study at Umeå University in Sweden, found that "the plasma levels of vitamin C, retinol and uric acid were inversely correlated to variables related to rheumatoid arthritis disease activity."

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, unless the studies are divided by dose size and dosing regime. When that is done, it is remarkable that most of the studies showing little or no effect employ quite small doses of ascorbate such as 100mg to 500mg per day. ("small" according to the vitamin C advocates) The Vitamin C foundation (1 (http://www.vitamincfoundation.org/surefire.htm)) recommends 8 grams of vitamin C every half hour in order to show an effect on the symptoms of a cold infection that is in progress.

Advocacy

Fred R. Klenner, a doctor in Reidsville, North Carolina reported in 1949 that 60 cases poliomyelitis yielded to vitamin C. Dr. Klenner proved that 15 of these cases were indeed poliomyelitis, by using spinal taps. He refused to do any more taps for fear of spreading the polio virus to the spinal cord.

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 diseases, such as influenza and cancer.

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. The dosage claimed to be effective in a therapeutic situation are much larger than those needed to prevent symptoms of scurvy and range from half a gram to tens of grams per day orally. Intravenously hundreds of grams may be used, and have been used on a growing number of patients.

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 hold that the wider adoption of vitamin C for therapeutic use is hindered by the fact that it cannot now be patented, meaning that pharmaceutical companies will be unwilling to fund research or promotion of a substance in which they stand to make little profit and which will compete with some of their own patented medicines.

References

• Thomas Levy (September 2002), Vitamin C, Infectious Diseases, and Toxins, Xlibris Corporation (Paperback). ISBN 1401069630 (Note: Xlibris (http://www.xlibris.com) is a print on demand self-publishing house.)
• Hickey, Steve & Roberts, Hilary; (May, 2004), Ascorbate: The Science of Vitamin C, Lulu Press, Inc. ISBN 1411607244 (Note: Lulu (http://www.lulu.com/ascorbate) is a print on demand self-publishing house.)

External links

• United Kingdom Foods Standards Agency (http://www.eatwell.gov.uk/healthydiet/nutritionessentials/vitaminsandminerals/vitaminc/) Official UK view on vitamin C.
• The Vitamin C Foundation (http://www.vitamincfoundation.org) Vitamin C high dosage advocacy organisation with links to much research supporting their view.
• Vitamin C in human health and disease is still a mystery? An overview (http://www.nutritionj.com/content/2/1/7) among all time most-viewed articles published by BioMed Central (free access)
• AscorbateWeb (http://www.seanet.com/~alexs/ascorbate/) "An historical review of the medical & scientific literature attesting to the efficacy of Ascorbate (Ascorbic Acid, Cevitamic Acid, Sodium Ascorbate etc. a.k.a. “Vitamin C”) in the treatment and prevention of human and animal ills, conditions and diseases."

Footnotes

¹ Combs GF. The Vitamins, Fundamental Aspects in Nutrition and Health. 2nd ed. San Diego, CA: Academic Press, 2001:245-272.
² British pharmacology professors debate with the US National Institutes of Health over the optimum vitamin c dose (from PR Newswire - 6th July 2004) [1] (http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/07-06-2004/0002204911&EDATE=)