Vitamin C



Vitamin C is a water-soluble vitamin used by the body for several purposes. Most animals can synthesize their own vitamin C, but some animals, including guinea pigs, humans, and other primates, cannot. Vitamin C was first isolated in 1928, and in 1932 it was proved to be the agent which prevents scurvy.

Vitamin C is the L-enantiomer of ascorbic acid. Commercial vitamin C is often a mix of ascorbic acid, sodium ascorbate and/or other ascorbates. See the ascorbic acid article for a description of the molecule's chemical properties.

Discovery and history

The need to include fresh plant food 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 pine needles are used in the arctic zone, or the leaves from species of drought-resistant trees in desert areas.

Through history the benefit of plant food for the survival of sieges and long sea voyages was recommended by enlightened authorities. In the seventeenth century Richard Woodall, a ship's surgeon to the British East India Company, recommended the use of lemon juice as a preventive and cure in his book "Surgeon's Mate". The early eighteenth century Dutch writer, Johannes Bachstrom gave the firm opinion that "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens; which is alone the primary cause of the disease."

The first attempt to give scientific basis for the cause of scurvy was by a ship's surgeon in the British Royal Navy, James Lind, who at sea in May 1747 provided some crew members with lemon juice in addition to normal rations while others continued on normal rations alone. In the history of science this is considered to be the first example of a controlled experiment comparing results on two populations of a factor applied to one group only with all other factors the same. The results conclusively showed that lemons prevented the disease. Lind wrote up his work and published it in 1753.

Lind's work was slow to be noticed, partly because he gave conflicting evidence within the book and partly because of social inertia in some elements at the British admiralty who saw care for the well-being of ships' crew as a sign of weakness. It was 1795 before the British navy adopted lemon or lime juice as standard issue at sea. (This practice is probably what led to the nickname limey for British people, especially British sailors.)

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. James Cook relied on sauerkraut to prevent the disease on his voyages of exploration.

In 1907, Alex Holst and Theodore Frohlich, two Norwegian biochemists studying beriberi contracted aboard ship's crews in the Norwegian Fishing Fleet, wanted a small test mammal to substitute for the pigeons then used. They fed guinea pigs the test diet, which had earlier produced beriberi in their pigeons, and were surprised when scurvy resulted instead. Until that time scurvy had not been observed in any organism apart from humans, and it was considered an exclusively human disease.

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

In the early twentieth century, the Polish-American scientist Casimir Funk conducted research into deficiency diseases, and in 1912 Funk developed the concept of vitamins, for the elements in food which are essential to health. Then, from 1928 to 1933, the Hungarian research team of Joseph L Svirbely and Albert Szent-Györgyi and, independently, the American Charles Glen King, first isolated vitamin C and showed it to be ascorbic acid.

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

In 1959 the American J.J. Burns showed that the reason some mammals were susceptible to scurvy was the inability of their liver to produce the active enzyme L-gulonolactone oxidase, which is the last of the chain of four enzymes which synthesize ascorbic acid.

Most species of animals synthesise their own vitamin C. It is therefore not a vitamin for them. Synthesis is achieved through a sequence of enzyme driven steps, which convert glucose to ascorbic acid. It is carried out either in the kidneys, in reptiles and birds, or the liver, in mammals and perching birds. The loss of an enzyme concerned with ascorbic acid synthesis has occurred quite frequently in evolution and has affected most fish, many birds; some bats, guinea pigs and most but not all primates, including Man. The mutations have not been lethal because ascorbic acid is so prevalent in the surrounding food sources.

For example an adult goat can internally 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.

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.

Advocacy

Fred R. Klenner, a doctor in Reidsville, North Carolina reported in 1949 that poliomyelitis yielded to vitamin C.

Nobel Prize winning chemist Linus Pauling began actively promoting vitamin C in the 1960s as a means to greatly improve human health and resistance to disease.

A minority of medical and scientific opinion continues to see vitamin C as being a low cost and safe way to treat infectious disease and to deal with a wide range of poisons. The dosage claimed to be effective in a therapeutic situation are much larger than those needed to prevent symptoms of scurvy and range from half a gram to tens of grams per day orally. Intravenously hundreds of grams may be used.

A meta-study into the published research on effectiveness of ascorbic acid in the treatment of infectious disease and toxins was conducted, in 2002, by Thomas Levy, Medical Director of the Colorado Integrative Medical Center in Denver. It claimed that overwhelming scientific evidence exists for its therapeutic role.

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