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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. In 1937 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. Discovery and historyThe 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." 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. SourcesPlant sourcesCitrus 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 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 sourcesThe 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 humans because the gene for this enzyme is defective. 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, including humans. 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 synthesisVitamin 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
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 deficiencyLack of ascorbic acid in the daily diet leads to a disease called scurvy, a form of avitaminosis that is characterized by:
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 requirementThere is a continuing debate within the scientific community over the optimum amount of vitamin C for humans.2 The recommended daily allowanceA healthy person on a balanced diet should be able to get the vitamin C needed to prevent the symptoms of scurvy from their daily diet without supplementation. People who smoke, those under stress, and pregnant women 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:
Advocacy amountsSome researchers have calculated the amount needed for an adult human to achieve similar blood serum levels as Vitamin C synthesising mammals as follows:
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 preparationIt 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:
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 usesFrom 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 general, 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 an initial usage of up to 8 grams of vitamin C every 20-30 minutes [4] 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 claimed that evidence exists for its therapeutic role in a wide range of viral infections and for the treatment of 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 argumentsThe 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 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 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 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. [5] Known harmful effectsVitamin C is recognized to be one of the least toxic substances known to medicine. Its LD50 for rats is 11900 mg kg-1 [6], [7], [8].
Unproven reports of harmful effectsReports 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.
References
External links
Footnotes1 Combs GF. The Vitamins, Fundamental Aspects in Nutrition and Health. 2nd ed. San Diego, CA: Academic Press, 2001:245-272. Data originally published on Wikipedia |