Vitamin C

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This article is about the nutrient.

For the musician, see Colleen Fitzpatrick.

For a general discussion on the chemical properties of the molecule, see Ascorbic acid

Vitamin C is a water-soluble nutrient essential for life, 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 humans and a small number of other animals, including, apes, guinea pigs, the red-vented bulbul, a fruit-eating bat and a species of trout. This has led a minority of scientists, most notably Linus Pauling to conclude that failure to produce the chemical by an animal species is a genetic defect and to hypothesise that if it were replaced in humans to the level found in animals better health would result.

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

Vitamin C is a weak acid, called ascorbic acid or ascorbate (an L-enantiomer of ascorbic acid; an l-enantiomer is simply one of two mirror image forms of the same chemical molecular structure, see optical isomers). The active part of the substance is the ascorbate ion, which can express itself as either an acid or a salt of ascorbate that is neutral or slightly basic. Commercial vitamin C is often a mix of ascorbic acid, sodium ascorbate and/or other ascorbates. Some supplements contain in part the d-entantiomer, which is harmless but useless. See the ascorbic acid article for a full description of the molecule's chemical properties.

Contents 1 Discovery and history 2 Sources 2.1 Plant sources 2.2 Animal sources 2.3 Artificial chemical synthesis 3 Functions in the body 4 Vitamin C deficiency 5 Daily requirement 5.1 The Recommended daily allowance 5.2 Advocacy amounts 6 Food preparation 7 Therapeutic uses 8 Advocacy arguments 9 Reported potential harmful effects 10 References 11 External links 12 Footnotes

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. 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.

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. 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 or sea water, along with their normal rations. 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 citrus fruits prevented the disease. Lind wrote up his work and published it in 1753, in Treatise on the Scurvy.

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. There was also the fact that fresh fruit was very expensive to keep on board, whereas boiling it down to juice allowed easy storage but destroyed the vitamin. Ships' captains assumed wrongly that it didn't work, because the juice failed to cure scurvy. Most juices sold at present are prepared by squeezing, rather than boiling, which while it does not allow lengthy storage at room temperature (which we do not need in the home) preserves the vitamin.

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 beyond without losing any of his men to scurvy. For this otherwise unheard of feat, he was awarded a medal by the British Admiralty. So the Navy was certainly well aware of the principle. The cost of providing fresh fruit on board was probably a factor in this long delay. Luxuries or non-standard 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 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 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 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. The synthetic form of the vitamin is identical to the natural form.

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.

American biochemist Irwin Stone was the first to exploit Vitamin C for its food preservative properties and held patents on this. He developed the theory that vitamin C was a vitamin in humans as a result of a genetic defect that afflicted the whole human race.

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 or vegetable:

Animal sources

Image:Goat.jpg

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 4 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 last enzyme in the process, l-gulonolactone oxidase, cannot be made by man because of a defective gene that he carries. The loss of an enzyme concerned with ascorbic acid synthesis has occurred quite frequently in evolution and has affected most fish, many birds; some bats, guinea pigs and most but not all primates, including Man. The mutations have not been lethal because ascorbic acid is so prevalent in the surrounding food sources (it may be noted that many of these species feed, or fed, largely on fruit).

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. Trauma or injury has been demonstrated to use up large quantities of vitamin C in animals and man.

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. China is slowly becoming the major world supplier as its prices undercut those of the US and European manufacturers. [1].

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 through 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 anemia

It is eventually fatal, and was a common condition among sailors and during winter. Scurvy is now very rare in industrialized countries. It should not be confused with "subclinical scurvy" or "chronic scurvy", both high-dose advocate terms for the normal human condition of blood levels lower than those typical among mammals.

Daily requirement

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

The Recommended daily allowance

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 without supplementation. 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.

Advocacy amounts

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 or more during illness or pregnancy (up to 300g for some illnesses) – Vitamin C Foundation's recommendation. [2]

6000-12000 mg per day – Thomas Levy, Colorado Integrative Medical Centre recommendation.

6000-18000 mg per day – Linus Pauling's daily recommendation

from 3000 mg to 200,000 mg based on bowel tolerance levels (see Cathcart below)

High doses (thousands of mg) may result in diarrhea, which is harmless if the dose is reduced immediately. Some researchers (Cathcart) claim the onset of diarrhea 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 diarrhea 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. The fact that animals like rats pass ascorbate into their urinary tract, after expending valuable energy manufacturing it, implies that there is a benefit to having vitamin C passing through, and this does not represent waste.

Food preparation

It is important to choose a suitable method of food preparation that conserves vitamin c content. When cooking vegetables, one should seek to minimize temperature and duration of cooking and not discard water used in preparation. e.g. by steam cooking or by making soup. Food source vitamin C is identical to that in supplements. The structure of vitamin C is well understood ,see ascorbic acid, and there is no difference in benefit between natural and synthetic forms.

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. Copper pots will destroy the vitamin.

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.

Therapeutic uses

From its ready availability in pure form in the 1930s some practitioners experimented in using vitamin C as a treatment for diseases other than scurvy. Most notable was Fred R. Klenner, a doctor in general practise in Reidsville, North Carolina. He utilised both oral and intravenous vitamin C to treat a wide range of infections and poisons. He published a paper in 1949 that described how he had seen poliomyelitis yield to vitamin C in sufficiently large doses.

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 owing to its recommendation by prominent biochemist Linus Pauling. In genereal, twenty years of studies have not supported the view that medium doses of vitamin C reduce the incidence of the common cold. Large doses have been associated with decreased cold duration and severity, possibly as a result of an antihistamine effect. [3]

There is a strong advocacy movement for large doses of Vitamin C. The Vitamin C Foundation 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. Most of the studies showing little or no effect employ doses of ascorbate such as 100 mg to 500 mg per day, considered "small" by the vitamin C advocates. It should be noted that the not for profit foundation is involved in selling vitamin C, which some might see as a potential conflict of interest. However, others have suggested daily doses into the 200+ g/day range, so the foundation is not alone in this.

There is also evidence that Vitamin C is useful in preventing lead poisoning, possibly helping to chelate the toxic heavy metal from the body.

In 2002 a meta-study into all the published research on effectiveness of ascorbic acid in the treatment of infectious disease and toxins was conducted, by Thomas Levy, Medical Director of the Colorado Integrative Medical Centre in Denver. He found that overwhelming scientific evidence exists for its therapeutic role in a wide range of viral infections and to treat snake bites.

Orthomolecular medicine) and a minority of scientific opinion sees vitamin C as being a low cost and safe way to treat viral disease and to deal with a wide range of poisons. If this is the case, the large doses, in the tens of grams per day, put ascorbic acid in a different class to almost all other therapeutic agents.

Advocacy arguments

The fact that man possesses three of the four enzymes that animals employ to manufacture the substance in relatively large amounts, has led researchers such as Irwin Stone and Linus Pauling to hypothesize that man's ancestors once manufactured this substance in the 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 vital macronutrient like fat or carbohydrate.

Dr. Hickey, of Manchester Metropolitan University, believes that man carries a mutated and ineffective form of the genetic machinery for manufacturing the fourth of the four enzymes used by all mammals to make ascorbic acid. Cosmic rays or a retro virus could have caused this mutation, millions of years ago. In humans the three surviving enzymes continue to produce the precurors to ascorbic acid but the process is incomplete and the body then disassembes them

In the 1960s Nobel Prize winning chemist Linus Pauling, after contact with Irwin Stone, began actively promoting vitamin C as a means to greatly improve human health and resistance to disease. His book How to Live Longer and Feel Better was a best seller and advocated taking more than 10,000 milligrams per day. It sold widely and many advocates today see its influence as the reason there was a marked downward trend in US heart disease from the early 1980s onwards.

Stone's work also informed the practise of Dr. Robert F. Cathcart III, in the 1970s and 1980s. He applied large doses of ascorbate to a wide range of viral diseases with successful results. Cathcart developed the concept of Bowel tolerance , the use of the onset of diarrhea as an indication of when the body's true requirement of ascorbic acid had been reached. He found that seriously ill people could often tolerate levels of tens of grams per day before their tolerance limit is reached.

In 2003 Steve Hickey and Hilary Roberts of the Manchester Metropolitan University published a fundamental criticism of the approach taken to fix the nutritional requirement of Vitamin C. They argued the in 2004 that the RDA which is based on blood plasma and white blood cell saturation data from the National Institutes of Health (NIH) was based on flawed data. [4]. According to these authors, the doses required to achieve blood, tissue and body “saturation” are much larger than previously believed. They allege that the Institute of Medicine (IoM) and the NIH had ignored an open letter from a number of scientists and medical researchers notabley Drs Steve Hickey, Hilary Roberts, Ian Brighthope, Robert Cathcart, Abram Hoffer, Archie Kalokerinos, Tom Levy, Richard Passwater, Hugh Riordan, Andrew Saul and Patrick Holford, which called for revision of the RDA.

It has been suggested by some advocates that ascorbic acid is really a food group in its own right like carbohydrates or protein and should not be seen as a pharmaceutical or vitamin at all.

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 and that pharmaceutical companies are unwilling to fund research or promotion of a substance in which they stand to make little profit and which advocates claim will compete with the companies' patented medicines in which they have invested large sums.

Some advocates have gone so far as to term the epidemic of heart disease and cancer resulting from low C doses a "genocide", implying that health care providers (and particularly cardiologists and pharmaceutical companies) are aware of its benefits and are deliberately seeking to block its acceptance as a therapeutic agent. [4]

Reported potential harmful effects

Reports of harmful effects of vitamin C tend to receive great prominence in the world's media. Many such reports never go on to be published in peer reviewed journals.

• People with hemochromatosis, who take large doses of Vitamin C run the risk of iron overload through its iron absorption enhancing properties.

Robert Cathcart,MD states: "My clinical experience would indicate that vitamin C increases iron absorbtion when iron is needed. It seems to increase excretion of iron when there is an excessive amount of iron."

• In April 1998 the journal '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. [5]

• 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 later pointed out by vitamin C advocates that this can be explained by vitamin C's collagen synthesising role leading to thicker and stronger artery walls. ([6] para 10)

• 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."

• "Rebound scurvy" is a theoretical, but never observed condition that occurs when the amount of daily intake of Vitamin C is rapidly reduced from a very large amount to a relatively lower amount.

This is an exaggeration of the rebound effect that occurs because ascorbate-dependent enzyme reactions continue for 24-48 hours, and use up vitamin C in the blood that is not being replenished. The effect is to lower one's serum vitamin C blood concentration to less than normal for a short amount of time. During this period of time there is a slight risk of cold or flu infection through reduced resistance. Within a couple of days the enzyme reactions shut down and blood serum returns to the normal level of someone not taking high supplements. This is not scurvy, which takes weeks of zero vitamin c consumption to produce symptoms. It is something people who take large vitamin C supplements need to be aware of in order to manage phased rather than sudden changes to the amount taken. ([7] para 4) This may be a theoretical risk for those taking supplements, who may find themselves severely ill and in a hospital without the supplements at a time when they need normal or better levels of vitamin C to fight the disease. ([8], and search for "the major problem")

• Kidney stones are a much cited harmful side effect of taking vitamin C in larger than normal amounts.

However research has shown this not to be the case ³ , [9], [10]

• Copper deficiency, some writers [11] have identified a theoretical risk of poor copper absorption from high doses of Vitamin C although no experimental evidence supports this.

References

• Pauling, Linus (1986), How to Live Longer and Feel Better, W. H. Freeman and Company, ISBN 0-380-70289-4
• Thomas Levy (September 2002), Vitamin C, Infectious Diseases, and Toxins, Xlibris Corporation (Paperback). ISBN 1401069630 (Note: Xlibris 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 is a print on demand self-publishing house.)

External links

• United Kingdom Foods Standards Agency Official UK view on vitamin C.
• The Vitamin C Foundation 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 among all time most-viewed articles published by BioMed Central (free access)
• AscorbateWeb "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."

• Vitamin C May Not Have Much Effect on Colds health.dailynewscentral.com Finding that 200mg per day has little effect on colds but a single dose of 8 grams does.
• Ascorbate and cancer Discussion of both historical and current uses of Vitamin C in cancer treatment
• Vitamin C Requirements: Optimal Health Benefits vs Overdose A moderately high dose advocacy supporting site .

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) [12]
³ The Linus Pauling Institute at Oregon State University, "What About Vitamin C and Kidney Stones? "[13]
⁴ Hickey, Steve & Roberts, Hilary; (March, 2005), Ridiculous Dietary Allowance, Lulu Press, Inc. ISBN 1411622219.(Note: Lulu is a print on demand publisher.)