Vitamin C

The need to include fresh plant food or raw animal flesh in the diet to prevent disease was known from ancient times. Native people living in marginal areas incorporated this into their medicinal lore. For Example, spruce needles were used in temperate zones in infusions, or the leaves from species of drought-resistant trees in desert areas. In 1536, the French explorers Jacques Cartier and Daniel Knezevic, 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.

Authorities occasionally recommended plant food to prevent scurvy during long sea voyages. John Woodall, the first surgeon to the British East India Company, recommended the preventive and curative use of lemon juice in his 1617 book, The Surgeon's Mate. In 1734, the Dutch Writer Johann Bachstrom gave the firm opinion that "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens."

The first attempt to give scientific basis for the cause of this disease was by a ship's surgeon in the 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, sulfuric acid or seawater, along with their normal rations, in one of the world's first controlled experiments. The results showed that citrus fruits prevented the disease. Lind published his work in 1753 in his Treatise on the Scurvy.

Fresh fruit was expensive to keep on board, whereas boiling it down to juice allowed easy storage but destroyed the vitamin (especially if boiled in copper kettles). It was 1796 before the British navy adopted lemon juice as standard issue at sea. In 1845, ships in the West Indies were provided with lime juice instead, and in 1860 lime juice was used throughout the Royal Navy, giving rise to the American use of the nickname "limey" for the British. Captain James Cook had previously demonstrated the advantages of carrying "Sour krout" on board, by taking his crews to the Hawaiian Islands without losing any of his men to scurvy. For this, the British Admiralty awarded him a medal.

In 1907 a laboratory animal model which would help to identify the antiscorbutic factor was discovered by the Norwegian Physicians Axel Holst and Theodor Frølich, who when studying shipboard beriberi, fed guinea pigs their test diet of grains and flour and were surprised when scurvy resulted instead of beriberi. By luck, this species did not make its own vitamin C, whereas mice and rats do. In 1912, the Polish biochemist Casimir Funk developed the concept of vitamins. One of these was thought to be the anti-scorbutic factor. In 1928, this was referred to as "water-soluble C," although its chemical structure had not been determined.

Vitamin C was discovered in 1912, isolated in 1928 and synthesized in 1933, making it the first vitamin to be synthesized. Shortly thereafter Tadeus Reichstein succeeded in synthesizing the vitamin in bulk by what is now called the Reichstein process. This made possible the inexpensive mass-production of vitamin C. In 1934 Hoffmann–La Roche trademarked synthetic vitamin C under the brand name Redoxon and began to market it as a dietary supplement.

From 1928 to 1932, Albert Szent-Györgyi and Joseph L. Svirbely's Hungarian team, and Charles Glen King's American team, identified the anti-scorbutic factor. Szent-Györgyi isolated hexuronic acid from animal adrenal glands, and suspected it to be the antiscorbutic factor. In late 1931, Szent-Györgyi gave Svirbely the last of his adrenal-derived hexuronic acid with the suggestion that it might be the anti-scorbutic factor. By the spring of 1932, King's laboratory had proven this, but published the result without giving Szent-Györgyi credit for it. This led to a bitter dispute over priority. In 1933, Walter Norman Haworth chemically identified the vitamin as L-hexuronic acid, proving this by synthesis in 1933. Haworth and Szent-Györgyi proposed that L-hexuronic acid be named a-scorbic acid, and chemically L-ascorbic acid, in honor of its activity against scurvy. The term's etymology is from Latin, "a-" meaning away, or off from, while -scorbic is from Medieval Latin scorbuticus (pertaining to scurvy), cognate with Old Norse skyrbjugr, French scorbut, Dutch scheurbuik and Low German scharbock. Partly for this discovery, Szent-Györgyi was awarded the 1937 Nobel Prize in Medicine, and Haworth shared that year's Nobel Prize in Chemistry.

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 modern two-step fermentation process, 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.

The effect of vitamin C on the Common cold has been extensively researched. The earliest publication of a controlled clinical trial appears to be from 1945. Researchers continued to work on this question, but research interest and public interest spiked after Linus Pauling, two-time awardee of the Nobel Prize (Chemistry Prize, 1954, Peace Prize 1962), started publishing research on the topic and also published a book "Vitamin C and the Common Cold" in 1970. A revised and expanded edition "Vitamin C, the Common Cold and the Flu" was published in 1976.

In 1957, J.J. Burns showed that some mammals are susceptible to scurvy as their liver does not produce the enzyme L-gulonolactone oxidase, the last of the chain of four enzymes that synthesize vitamin C. American biochemist Irwin Stone was the first to exploit vitamin C for its food preservative properties. He later developed the theory that humans possess a mutated form of the L-gulonolactone oxidase coding gene.

Notable human dietary studies of experimentally induced scurvy have been conducted on conscientious objectors during World War II in Britain and on Iowa state prisoners in the late 1960s to the 1980s. These studies both found that all obvious symptoms of scurvy previously induced by an experimental scorbutic diet with extremely low vitamin C content could be completely reversed by additional vitamin C supplementation of only 10 mg a day. In these experiments, there was no clinical difference noted between men given 70 mg vitamin C per day (which produced blood level of vitamin C of about 0.55 mg/dl, about 1/3 of tissue saturation levels) and those given 10 mg per day. Men in the prison study developed the first signs of scurvy about four weeks after starting the vitamin C-free diet, whereas in the British study, six to eight months were required, possibly due to the pre-loading of this group with a 70 mg/day supplement for six weeks before the scorbutic diet was fed.

Pauling popularized the concept of high dose vitamin C as prevention and treatment of the Common cold in 1970. A few years later he proposed that vitamin C would prevent cardiovascular disease, and that 10 grams/day, initially (10 days) administered intravenously and thereafter orally, would cure late-stage cancer. Mega-dosing with ascorbic acid has other champions, among them Chemist Irwin Stone and the controversial Matthias Rath and Patrick Holford, who both have been accused of making unsubstantiated treatment claims for treating cancer and HIV infection.

World production of synthesized vitamin C was estimated at approximately 110,000 tonnes annually in 2000. Traditionally, the main producers were BASF/Takeda, DSM, Merck and the China Pharmaceutical Group Ltd. of the People's Republic of China. By 2008 only the DSM plant in Scotland remained operational outside of China because of the strong price competition from China.

In 2008, researchers at the University of Montpellier discovered that in humans and other primates the red blood cells have evolved a mechanism to more efficiently utilize the vitamin C present in the body by recycling oxidized L-dehydroascorbic acid (DHA) back into ascorbic acid for reuse by the body. The mechanism was not found to be present in mammals that synthesize their own vitamin C.

Studies examining the effects of vitamin C intake on the risk of Alzheimer's disease have reached conflicting conclusions. Maintaining a healthy dietary intake is probably more important than supplementation for achieving any potential benefit. A 2010 review found no role for vitamin C supplementation in the treatment of rheumatoid arthritis. Vitamin C supplementation does not prevent or slow the progression of age-related cataract.

In February 2011, the Swiss Post issued a postage stamp bearing a depiction of a model of a molecule of vitamin C to mark the International Year of Chemistry.

Vitamin C has a definitive role in treating scurvy, which is a disease caused by vitamin C deficiency. Beyond that, a role for vitamin C as prevention or treatment for various diseases is disputed, with reviews reporting conflicting results. A 2012 Cochrane review reported no effect of vitamin C supplementation on overall mortality. It is on the World Health Organization's List of Essential Medicines as one of the most effective and safe medicines needed in a health system.

From the U.S. National Institutes of Health: [In humans] "Approximately 70%–90% of vitamin C is absorbed at moderate intakes of 30–180 mg/day. However, at doses above 1,000 mg/day, absorption falls to less than 50%."

Ascorbic acid is absorbed in the body by both active transport and simple diffusion. Sodium-Dependent Active Transport—Sodium-Ascorbate Co-Transporters (SVCTs) and Hexose transporters (GLUTs)—are the two transporter proteins required for active absorption. SVCT1 and SVCT2 import the reduced form of ascorbate across plasma membranes. GLUT1 and GLUT3 are glucose transporters, and transfer only the dehydroascorbic acid (DHA) form of vitamin C. Although dehydroascorbic acid is absorbed in higher rate than ascorbate, the amount of dehydroascorbic acid found in plasma and tissues under normal conditions is low, as cells rapidly reduce dehydroascorbic acid to ascorbate.

For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For vitamin C labeling purposes 100% of the Daily Value was 60 mg, but as of May 27, 2016 it was revised to 90 mg to bring it into agreement with the RDA. A table of the old and new adult Daily Values is provided at Reference Daily Intake. Food and supplement companies have until January 1, 2020 to comply with the change. European Union regulations require that labels declare Energy, protein, fat, saturated fat, carbohydrates, sugars, and salt. Voluntary nutrients may be shown if present in significant amounts. Instead of Daily Values, amounts are shown as percent of Reference Intakes (RIs). For vitamin C, 100% RI was set at 80 mg in 2011.