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Vitamin C

2007 Schools Wikipedia Selection. Related subjects: Food and agriculture;
General Chemistry

   Chemical structure of vitamin C
   Chemical structure of vitamin C

   Vitamin C is a water- soluble nutrient and human vitamin essential for
   life and for maintaining optimal health, used by the body for many
   purposes. It is also known by the chemical name of its principal form,
   L-ascorbic acid. The article on ascorbic acid contains information on
   its chemical properties. This article describes its biological
   functions, discovery and the debate on how it is used by society.
   Moreover, vitamin C can cure many diseases, such as skin diseases

General description

   Vitamin C is a weak acid, called ascorbic acid or a salt ascorbate. It
   is the L-enantiomer of ascorbic acid. The D-enantiomer shows no
   biological activity. Both are 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-enantiomer, which is useless and harmless. See
   the ascorbic acid article for a full description of the molecule's
   chemical properties.

Synthesis in organisms

   Almost all animals and plants synthesize their own vitamin C. There are
   some exceptions, such as 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 some scientists, including chemist
   Linus Pauling to hypothesize that these species either lost (or never
   had) the ability to produce their own Vitamin C, and that if their
   diets 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. The species-specific 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 (electron-donors). This has led to the
   suggestion that in higher primates, uric acid has taken over some of
   the functions of ascorbate. Ascorbic acid can be broken down by
   ascorbic acid oxdase an enzyme which catalyes the oxidation of ascorbic
   acid.

   Some microorganisms such as the yeast Saccharomyces cerevisiae have
   been shown to be able to synthesize ascorbic acid.

Discovery

   Vitamin C was first isolated in 1928, and in 1932 it was proved to be
   the agent which prevents scurvy. Both Charles Glen King at the
   University of Pittsburgh and Albert Szent-Györgyi (working with ex-
   Pittsburgh researcher Joseph Svirbely) came to discover what is now
   known as Vitamin C around April of 1932. Although Szent-Györgyi was
   awarded the 1937 Nobel Prize in Medicine, many feel King is as
   responsible for its development if not more so. A detailed history of
   Vitamin C is provided below.

Vitamin C deficiency

   No bodily organ stores ascorbate as a primary function, and so the body
   soon depletes itself of ascorbate if fresh supplies are not consumed
   through the digestive system, eventually leading to the deficiency
   disease known as scurvy (a form of avitaminosis), which results in
   illness and death if consumption of vitamin C is not resumed in time.

Daily requirements and dose dependent effects

   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.

Government agency recommended intake levels

   A balanced diet without supplementation contains enough Vitamin C to
   prevent acute scurvy in an average healthy adult. For people who smoke,
   those under stress, and pregnant women it takes slightly more.

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

   40 mg per day: Food Standards Agency (UK)

   60–95 mg per day, Dietary Reference Intake (DRI), Recommended Daily
   Allowance (RDA), U.S. Food and Nutrition Board 2004.

   The U.S. Dietary Reference Intake Tolerable Upper Intake Level (UL) for
   a 25-year old male is 2,000 mg/day. Vitamin C is recognized to be one
   of the least toxic substances known to medicine. Its LD50 for rats is
   11,900 mg kg^-1 , , .

Independent dose recommendations

   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.
          500 mg twice per day – Professor Roc Ordman's recommendation in
          free radical research.
          3000 mg per day or more during illness or pregnancy (up to 300g
          for some illnesses) – 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 own daily recommendation
          from 3000 mg to 200,000 mg per day based on a protocol described
          by Robert Cathcart known as a vitamin C flush wherin escalating
          doses of Vitamin C are given until diarrhea develops, then
          choosing the highest dose that does not cause diarrhea (bowel
          tolerance threshold). High doses (thousands of mg) may result in
          diarrhea, which is harmless if the dose is reduced immediately.
          Some researchers 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 (½ pound).

   There is a strong advocacy movement for large doses of Vitamin C (see
   Advocacy arguments below), although not all purported benefits are
   supported by the medical establishment. Many pro-Vitamin C
   organizations promote usage levels well beyond the current Dietary
   Reference Intake (DRI).

   There exist an extensive and growing literature critical of
   governmental agency dose recommendations. Key arguments include:
     * The biological halflife for vitamin C is quite short, about 30
       minutes in blood plasma, a fact which NIH and IM researchers have
       failed to recognize. NIH researchers established the current RDA
       based upon tests conducted 12 hours (24 half lives) after
       consumption. "To be blunt," says Hickey, "the NIH gave a dose of
       vitamin C, waited until it had been excreted, and then measured
       blood levels."
     * NIH don't take into account individual differences such as age,
       weight, etc. For example, heavier individuals generally need more
       vitamin C.
     * The figures represent the amount needed to prevent the acute form
       of deficiency disease, while subclinical levels of the disease are
       not even acknowledged.
     * The amount needed to prevent other diseases is not considered.
     * Optimal health is not a consideration, as the level of health
       targeted is that which is marginally better than that which is
       considered malnourished.

Testing for ascorbate levels in the body

   Simple tests exist which measure levels of ascorbate ion in the urine
   and in serum or blood plasma. However these do not accurately reflect
   actual tissue ascorbate levels. Reverse phase high performance liquid
   chromatography (HPLC) 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.

Therapeutic applications and doses

   Vitamin C is needed in the diet to prevent scurvy, however, from the
   time it became available in pure form in the 1930s, some practitioners
   experimented with vitamin C as a treatment for diseases other than
   scurvy.

Colds

   At least 29 controlled clinical trials (many double-blind and
   placebo-controlled) involving a total of over 11,000 participants have
   been conducted into vitamin C and the Common cold. These trials were
   reviewed in the 1990s and again recently. The trials show that vitamin
   C reduces the duration and severity of colds but not the frequency. The
   data indicate that there is a normal dose-response relationship.
   Vitamin C is more effective the higher the dose. The vast majority of
   the trials were limited to doses below 1 g/day. As doses rise, it
   becomes increasingly difficult to keep the trials double blind because
   of the obvious gastro-intestinal side effects. So, the most effective
   trials at doses between 2 and 10 g/day are met with skepticism. Reports
   from physicians have provided ample clinical confirmation.

   The controlled trials and clinical experience prove that vitamin C in
   doses ranging from 0.1 to 2.0 g/day have a relatively small effect. The
   duration of colds was reduced by 7% for adults and 15% for children.
   The studies provide ample justification for businesses to encourage
   their employees to take 1 to 2 g/day during the cold season to improve
   workplace productivity and reduce sick days. The clinical reports
   provide the strongest possible evidence that vitamin C at higher doses
   is significantly more effective. However, the effectiveness typically
   comes at the price of gastro-intestinal side effects. It is easy for
   physicians to minimize these side effects since they cause no lasting
   harm. Adult patients, however, have proven reluctant to subject
   themselves to gas and cramping to deliver an unknown benefit (the
   duration and severity of colds is highly variable so the patient never
   knows what he/she is warding off). It is well worth the effort of
   identifying the small subset of individuals who can benefit from high
   daily doses (>10 g/day) of vitamin C without side effects and training
   them to regularly take 5 g/day during cold season and to increase the
   dose at the onset of a cold.

   The trials proved that vitamin C is more effective for children.
   Reports from the field confirm the observations in the trials and
   suggest that children are less prone to vitamin C side effects. Colds
   and flu are a serious problem for children. Every time a cold infects a
   child, its growing mind and body must divert energy from its usual
   business of growth and development. If the cold is followed by an
   opportunistic infection, such as bronchitis or ear infection, more
   energy must be diverted. Colds are the number one trigger for asthma.
   Pre-school children in daycare are nearly constantly fighting
   infections (5-10 per year). Chronic disease in childhood is believed to
   sometimes have permanent developmental consequences which can
   contribute to decreased life expectancy.

Polio

   Most notable was Fred R. Klenner, a doctor in general practice in
   Reidsville, North Carolina. He utilized 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. No controlled clinical trials
   have been conducted to confirm effectiveness.

Heart disease

   Vitamin C is the main component of the three ingredients in Linus
   Pauling's patented preventive cure for Lp(a) related heart disease, the
   other two being the amino acid lysine and nicotinic acid (a form of
   Vitamin B3). Lp(a) as an atherosclerotic, evolutionary substitute for
   ascorbate is still discussed as a hypothesis by mainstream medical
   science and the Rath-Pauling related protocols have not been rigorously
   tested and evaluated as conventional medical treatment by the FDA.

Viral diseases, and poisons

   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.

   Vitamin C has a growing reputation for being useful in the treatment of
   colds and flu, owing to its recommendation by prominent biochemist
   Linus Pauling. In the years since Pauling's popular books about vitamin
   C, general agreement by medical authorities about larger than RDA
   amounts of vitamin C in health and medicine has remained elusive.
   Ascorbate usage in studies of up to several grams per day, however,
   have been associated with decreased cold duration and severity of
   symptoms, possibly as a result of an antihistamine effect . The highest
   dose treatments, published clinical results of specific orthomolecular
   therapy regimes pioneered by Drs. Klenner (repeated IV treatments,
   400-700+ mg/kg/day ) and Cathcart (oral use to bowel tolerance, up to
   ~150 grams ascorbate per day for flu), have remained experimentally
   unaddressed by conventional medical authorities for decades.

   The Vitamin C Foundation recommends an initial usage of up to 8 grams
   of vitamin C every 20-30 minutes 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 vitamin C advocates. Equally
   importantly, the plasma half life of high dose ascorbate is
   approximately 30 minutes, which implies that most high dose studies
   have been methodologically defective and would be expected to show a
   minimum benefit. Clinical studies of divided dose supplementation,
   predicted on pharmacological grounds to be effective, have only rarely
   been reported in the literature. Essentially all the claims for high
   dose vitamin C remain to be scientifically refuted. The clinical
   effectiveness of large and frequent doses of vitamin C is an open
   scientific question.

   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 claimed that evidence exists for its
   therapeutic role in a wide range of viral infections and for the
   treatment of snake bites.

Lead poisoning

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

Cancer

   In 2005 in vitro research by the National Institutes of Health
   indicated that Vitamin C administered in pharmacological concentrations
   (i.e. intravenous) was preferentially toxic to several strains of
   cancer cells. The authors noted: "These findings give plausibility to
   intravenous ascorbic acid in cancer treatment, and have unexpected
   implications for treatment of infections where H[2]O[2] may be
   beneficial." This research appeared to support Linus Pauling's claims
   that Vitamin C can be used to fight cancer.

   In 2006 the Canadian Medical Association Journal published in vivo
   research that demonstrated that intravenous vitamin C can subdue
   advanced-stage cancer.

Cataracts

   It has been also suggested that Vitamin C might prevent the formation
   of cataracts.

Other effects

Contraindications

   A Contraindication is a condition which makes an individual more likely
   to be harmed by a dose of Vitamin C than an average person.
     * A primary concern is people with unusual or unaddressed iron
       overload conditions, including hemochromatosis. Vitamin C enhances
       iron absorption. If sufferers of iron overload conditions take gram
       sized doses of Vitamin C, they may worsen the iron overload due to
       enhanced iron absorption.

     * Inadequate Glucose-6-phosphate dehydrogenase enzyme (G6PD) levels,
       a genetic condition, may predispose some individuals to hemolytic
       anaemia after intake of specific oxidizing substances present in
       some food and drugs. This includes repeated, very large intravenous
       or oral dosages of vitamin C. There is a test available for G6PD
       deficiency . High dose Vitamin E has been proposed as a potential
       protective factor.

Side-effects

     * Vitamin C causes diarrhea in everyone if taken in quantities beyond
       a certain limit, which is variable to the individual. Cathcart has
       called this limit the Bowel Tolerance Limit and observed that it is
       higher in people with serious illness than those in good health. It
       ranges from 5 to 25 grams per day in healthy individuals to 300
       grams per day in the seriously ill persons, such as those with AIDS
       and cancer. The diarrhea side-effect is harmless, though it can be
       inconvenient. The diarrhea will cease as soon as the dose is
       reduced.

     * Large doses of vitamin C may cause acid indigestion (stomach
       upset), 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 (Tums)

Effects of Overdose

   Vitamin C exhibits remarkably low toxicity. For example, in the rat,
   the LD50 (the dose that will kill 50% of a population ) has been
   reported as 11900 mg kg-1. For a 70 kg human, this means that 833,000
   mg of vitamin C would need to be ingested to stand a 50% chance of
   killing the person. However, vitamin C could not result in death when
   administered orally as large amounts of the vitamin cause diarrhea and
   are not absorbed. An extremely large amount of vitamin C would need to
   be rapidly injected by IV to stand any chance of killing a person.
   Robert Cathcart, MD, has used intravenous doses of vitamin C of 250
   grams and reports that he has had no problems. The Council for
   Responsible Nutrition has set an Upper Level (UL) of 2 grams, based on
   transient diarrhea. Their publication on vitamin C safety notes that


   Vitamin C

    ..very large doses of vitamin C have been taken daily over the course
   of many years, and only minor undesirable effects have been attributed
   with any certainty to the vitamin’s use[...] Clearly, vitamin C has a
                           low order of toxicity.


   Vitamin C

Alleged harmful effects

   Reports of harmful effects of vitamin C tend to receive great
   prominence in the world's media. As such, these reports tend to
   generate much debate and more research into Vitamin C. Some of the
   harmful effects described below have been proven to be unfounded in
   later studies, while other effects are still undergoing further
   analysis.
     * In April 1998 the journal Nature reported alleged carcinogenic and
       teratogenic effects of excessive doses of Vitamin C /
       ascorbic-acid. 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.

     * The authors of the study featured in Nature later clarified their
       position in correspondence to the journal, stating that their
       results "show a definite increase in 8-oxoadenine after
       supplementation with Vitamin C. This lesion is at least ten times
       less mutagenic than 8-oxoguanine, and hence our study shows an
       overall profound protective effect of this vitamin".

     * In April 2000, University of Southern California researchers
       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.
       (ref. 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."

     * A speculated increased risk of kidney stones may be a side effect
       of taking Vitamin C in larger than normal amounts (>1g). The
       potential mechanism of action is through the metabolism of Vitamin
       C ( ascorbic acid) to dehydroascorbic acid, which is then
       metabolized to oxalic acid, a known constituent of kidney stones.
       However, this oxalate issue is still controversial, with evidence
       being presented for and against the possibility of this side
       effect. Vitamin C has long been advocated, and used, by some less
       conventional physicians to prevent or alleviate some kinds of
       non-oxalate kidney stone formation. after addressing the oxalate
       issue. Vitamin B6 may mitigate the general risk of oxalate stones
       by decreasing oxalate production. Additionally, thiamine may
       inhibit oxalate formation. Furthermore, correcting any magnesium
       deficiency may decrease the risk of kidney stones by decreasing
       oxalate crystallization. Increasing one's fluid intake also helps
       to prevent oxalate crystallization in the kidney. There is evidence
       that certain intestinal flora influence how much oxalate is
       destroyed and that their absence is a significant causal risk
       factor in oxalate stone formers. Patients with a predispostion to
       form oxalate stones or those on hemodialysis should avoid excess
       use of vitamin C.

     * "Rebound scurvy" is a theoretical, never observed, condition that
       could occur when daily intake of Vitamin C is rapidly reduced from
       a very large amount to a relatively low amount. Advocates suggest
       this is an exaggeration of the rebound effect which occurs because
       ascorbate-dependent enzyme reactions continue for 24-48 hours after
       intake is lowered, and use up vitamin C which 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 large 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 gradually reduce dosage
       rather than quit taking Vitamin C suddenly. (ref. para 4) This is a
       theoretical risk for those taking supplements - e.g. if they 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 (ref. and search for "The major problem"). At
       this time, many doctors and hospital staff do not know much about
       nor administer megadosing of supplements, so that patients may have
       to rely on friends or relatives to bring them their supplements.

     * Some writers have identified a theoretical risk of poor Copper
       absorption from high doses of Vitamin C, although little
       experimental evidence supports this. However, ceruloplasmin levels
       seem specifically lowered by high vitamin C intake. In one study,
       600 milligrams of Vitamin C daily did not decrease copper
       absorption or overall body copper status in young men, but led to
       lower ceruloplasmin levels similar to those caused by copper
       deficiency. In another, ceruloplasmin levels were significantly
       reduced.

     * There are stories circulating among some folk remedy proponents
       that doses of around 12 grams per day of Vitamin C can induce an
       abortion in women under 4 weeks of pregnancy. This is not supported
       by scientific research however.

     * Recent studies into the use of a combination of Vitamin E
       ("natural" source isomer moeity, d-alpha tocopheryl ester) and
       vitamin C (unspecified ascorbate) in preventing oxidative stress
       leading to pre-eclampsia have failed to show significant (p=0.05)
       positive benefit at the dosage tested, Drs. Padayatty and Levine
       with NIH in a "Letter to the Editor" stated that the studies and
       another "Letter to the Editor" overlooked a key reason for the lack
       of vitamin C on the prevention of preeclampsia. Because plasma
       ascorbate concentrations were not reported, we estimated them from
       known data, the placebo and treatment groups in the study probably
       had similar plasma and tissue ascorbate concentrations. Doses of 1
       g per day have little effect on plasma or intracellular ascorbate
       concentrations. In another study the same dosage did decrease
       average gestational time resulting in a higher incidence of low
       birthweight babies in one study. Several other studies have been
       more favorable but large studies into antioxidants for
       pre-eclampsia are continuing.

Conflicts with prescription drugs

   Pharmaceuticals designed to reduce stomach acid such as the proton pump
   inhibitors (PPIs), are among the most widely-selling drugs in the
   world. One PPI, omeprazole, has been found to lower the bioavailability
   of vitamin C by 12%, independent of dietary intake. This means that one
   would have to consume 12% more vitamin C to counteract the use of 40
   mg/day of omeprazole. The probable mechanism of vitamin C reduction,
   intragastric pH elevated into alkalinity, would apply to all other PPI
   drugs, though not necessarily to doses of PPIs low enough to keep the
   stomach slightly acidic.

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. John
   Woodall, the first appointed surgeon to the British East India Company,
   recommended the use of lemon juice as a preventive and cure in his book
   "The Surgeon's Mate" of 1617. The Dutch writer, Johann Bachstrom of
   Leyden, 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."
   Citrus fruits were one of the first sources of vitamin C available to
   ship's surgeons.
   Enlarge
   Citrus fruits were one of the first sources of vitamin C available to
   ship's surgeons.

   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.

   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
   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 soup were employed with variable effect.

   In 1907, Axel Holst and Theodor Frølich, 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
   they 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 in Chemistry largely for this
   work. The synthetic form of the vitamin is identical to the natural
   form.

   The Swiss pharmaceutical company Hoffmann-La Roche was the first to
   mass produce synthetic vitamin C, under the brand name of Redoxon, in
   1934.

   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 an essential nutrient deficient in humans
   as a result of a genetic defect that afflicted the whole human race.

Vitamin C hypothesis

   Since its discovery Vitamin C has been considered a universal panacea
   by some, although this led to suspicions of it being overhyped by
   others.

   The fact that man possesses three of the four enzymes that animals
   employ to manufacture ascorbates 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 a chance of evolution. If
   true, this would mean that vitamin C was misnamed as a vitamin and is
   in fact a vital macronutrient like fat or carbohydrate. {Irwin Stone:
   "The Healing Factor"}

   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. {Hickey: "Ascorbate"} In humans the
   three surviving enzymes continue to produce the precursors to ascorbic
   acid but the process is incomplete and the body then disassembles 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 bestseller 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 extremely large doses of ascorbate
   (300 grams = 0.66 pounds per day) 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.

   Matthias Rath is a controversial German physician who once worked with
   Pauling. He is an active proponent and publicist for high dose vitamin
   C. He has published a theory that deaths from scurvy in humans during
   the ice age, when vitamin C was scarce, selected for individuals who
   could repair arteries with a layer of cholesterol. He theorises 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. Atherosclerosis is
   thus a vitamin C deficiency disease. Rath has also argued publicly that
   high doses of vitamin C can be effectively used against viral epidemics
   such as HIV, SARS and bird flu.

   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. {Irwin Stone: "The
   Healing Factor"}

Chronic scurvy

   Identified and named by Linus Pauling, "chronic scurvy" or "subclinical
   scurvy" is a condition of Vitamin C deficiency which is not as easily
   noticeable as acute scurvy (because chronic scurvy is mostly internal),
   characterized by micro lesions of tissues (such as that caused by blood
   pulsing through arteries, which stretches the arterial walls causing
   them to tear slightly). It is a major contributing factor to cardio
   vascular disease. The condition is almost entirely preventable with
   supplementation of larger doses of Vitamin C (8 grams or more per day).
   Chronic scurvy is commonplace, even in industrialized countries.

Politics of Vitamin C

Regulation

   There are regulations in most countries which limit the claims on the
   treatment of disease that can be placed on food, drug, and nutrient
   product labels. Regulations include:
     * Claims of therapeutic effect with respect to the treatment of any
       medical condition or disease are prohibited by the Food and Drug
       Administration (in the USA, and by the corresponding regulatory
       agencies in other countries) unless the substance has gone through
       a lengthy (10+ years) and expensive (200 million US dollars+)
       approval process, for which the applicant seeking approval must
       pay.
     * In the United States, the following notice is mandatory on food,
       drug, and nutrient product labels which make health claims: These
       statements have not been evaluated by the Food and Drug
       Administration. This product is not intended to diagnose, treat,
       cure or prevent any disease. This statement must be included even
       if substantial scientific evidence exists showing that the message
       isn't true. This may lead consumers to the false belief that
       Vitamin C has no value in preventing or treating diseases other
       than scurvy (for which treatment claims are allowed).

Advocacy arguments

   Vitamin C advocates argue that there is a large body of scientific
   evidence that the vitamin has a wide range of health and therapeutic
   benefits but which they claim have been ignored. They claim the
   following factors affect the marketing and distribution of Vitamin C,
   and the dissemination of information concerning the nutrient:
     * There is increasing evidence of the applications and efficacy of
       Vitamin C, but governmental agency dose and frequency of intake
       recommendations have remained relatively fixed. This has lead some
       researchers to challenge the recommendations. 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 again argued 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. 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 have failed to respond to an open letter
       from a number of scientists and medical researchers, notably
       Doctors 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 RDI (Reference Daily Intake).

     * Research and the treatment approval process are so expensive,
       pharmaceutical companies rarely apply for approval of an
       unpatentable product. To do so without the protection of a patent
       would allow competitors to manufacture the product too, which would
       drive the price (and profit margin) down to a point much less
       desirable than the price point (and profit margin) of patentable
       products. The lower price would also reduce the likelihood of
       recuperating the company's exorbitant research funding and
       treatment approval costs. Vitamin C is not eligible for patenting
       because it is a natural substance, and because it has already been
       marketed to the public for some time. As of yet, no company has
       applied to the FDA (nor paid) for approval of Vitamin C as a
       treatment for any disease.

     * Companies selling a treatment product are not required to inform
       consumers or patients of other treatments, even if those treatments
       are more effective, less expensive, and have fewer side-effects.
       Medical practitioners are not required to inform their patients of
       treatments for which treatment approval has not been granted. This
       situation, coupled with the label censorship explained above makes
       it more difficult to keep the public informed about the benefits of
       and new discoveries concerning the applications and effective
       dosage levels of Vitamin C.

     * Matthias Rath and others point to low doses of Vitamin C as the
       cause of the current epidemics of heart disease and cancer, and
       have termed the situation "a genocide", implying that health care
       providers (and particularly cardiologists and pharmaceutical
       companies) are aware of Vitamin C's benefits and are deliberately
       seeking to block its acceptance as a therapeutic agent. Meanwhile,
       governments, with their bureaucratic systems of treatment approval
       filtering out natural and inexpensive treatments such as those
       applying vitamin C, have also contributed to this technology
       blockade.

Books

     * Cancer and Vitamin C, Ewan Cameron and Linus Pauling, Pauling
       Institute of Science and Medicine, 1979
     * The Healing Factor: Vitamin C Against Disease, Irwin Stone, Grosset
       and Dunlap
     * How to Live Longer and Feel Better, Linus Pauling, W.H. Freeman and
       Company, 1986, ISBN 0-380-70289-4
     * 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

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