Vitamin

Fruits and vegetables are often a good source of vitamins.

A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. A compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on the circumstances and the particular organism. For example, ascorbic acid functions as vitamin C for some animals but not others, and vitamins D and K are required in the human diet only in certain circumstances. The term vitamin does not include other essential nutrients such as dietary minerals, essential fatty acids, or essential amino acids, nor does it encompass the large number of other nutrients that promote health but are otherwise required less often.

Vitamins are classified by their biological and chemical activity, not their structure. Thus, each "vitamin" may refer to several vitamer compounds that all show the biological activity associated with a particular vitamin. Such a set of chemicals are grouped under an alphabetized vitamin "generic descriptor" title, such as "vitamin A," which includes the compounds retinal, retinol, and many carotenoids. Vitamers are often inter-converted in the body.

Vitamins have diverse biochemical functions, including function as hormones (e.g. vitamin D), antioxidants (e.g. vitamin E), and mediators of cell signaling and regulators of cell and tissue growth and differentiation (e.g. vitamin A). The largest number of vitamins (e.g. B complex vitamins) function as precursors for enzyme cofactor bio-molecules (coenzymes), that help act as catalysts and substrates in metabolism. When acting as part of a catalyst, vitamins are bound to enzymes and are called prosthetic groups. For example, biotin is part of enzymes involved in making fatty acids. Vitamins also act as coenzymes to carry chemical groups between enzymes. For example, folic acid carries various forms of carbon group – methyl, formyl and methylene - in the cell. Although these roles in assisting enzyme reactions are vitamins' best-known function, the other vitamin functions are equally important.

Until the 1900s, vitamins were obtained solely through food intake, and changes in diet (which, for example, could occur during a particular growing season) can alter the types and amounts of vitamins ingested. Vitamins have been produced as commodity chemicals and made widely available as inexpensive pills for several decades, allowing supplementation of the dietary intake.

Retinol (one vitamer of Vitamin A)

History

The Ancient Egyptians knew that feeding a patient liver (back, right) would help cure night blindness.

The value of eating a certain food to maintain health was recognized long before vitamins were identified. The ancient Egyptians knew that feeding a patient liver would help cure night blindness, an illness now known to be caused by a vitamin A deficiency. The advancement of ocean voyage during the Renaissance resulted in prolonged periods without access to fresh fruits and vegetables, and made illnesses from vitamin deficiency common among ship's crew.

In 1749, the Scottish surgeon James Lind discovered that citrus foods helped prevent scurvy, a particularly deadly disease in which collagen is not properly formed, causing poor wound healing, bleeding of the gums, severe pain, and death. In 1753, Lind published his Treatise on the Scurvy, which recommended using lemons and limes to avoid scurvy, which was adopted by the British Royal Navy. This led to the nickname Limey for sailors of that organization. Lind's discovery, however, was not widely accepted by individuals in the Royal Navy's Arctic expeditions in the 19th century, where it was widely believed that scurvy could be prevented by practicing good hygiene, regular exercise, and by maintaining the morale of the crew while on board, rather than by a diet of fresh food. As a result, Arctic expeditions continued to be plagued by scurvy and other deficiency diseases. In the early 20th century, when Robert Falcon Scott made his two expeditions to the Antarctic, the prevailing medical theory was that scurvy was caused by "tainted" canned food.

In 1881, Russian surgeon Nikolai Lunin studied the effects of scurvy while at the University of Tartu in present-day Estonia. He fed mice an artificial mixture of all the separate constituents of milk known at that time, namely the proteins, fats, carbohydrates, and salts. The mice that received only the individual constituents died, while the mice fed by milk itself developed normally. He made a conclusion that "a natural food such as milk must therefore contain, besides these known principal ingredients, small quantities of unknown substances essential to life." However, his conclusions were rejected by other researchers when they were unable to reproduce his results. One difference was that he had used table sugar (sucrose), while other researchers had used milk sugar (lactose) that still contained small amounts of vitamin B.

The discovery of vitamins and their sources

Year of discovery	Vitamin	Source
1909	Vitamin A (Retinol)	Cod liver oil
1912	Vitamin B1 (Thiamine)	Rice bran
1912	Vitamin C (Ascorbic acid)	Lemons
1918	Vitamin D (Calciferol)	Cod liver oil
1920	Vitamin B2 (Riboflavin)	Eggs
1922	Vitamin E (Tocopherol)	Wheat germ oil, Cosmetic and Liver
1926	Vitamin B12 (Cyanocobalamin)	Liver
1929	Vitamin K (Phylloquinone)	Alfalfa
1931	Vitamin B5 (Pantothenic acid)	Liver
1931	Vitamin B7 (Biotin)	Liver
1934	Vitamin B6 (Pyridoxine)	Rice bran
1936	Vitamin B3 (Niacin)	Liver
1941	Vitamin B9 (Folic acid)	Liver

In east Asia, where polished white rice was the common staple food of the middle class, beriberi resulting from lack of vitamin B1 was endemic. In 1884, Takaki Kanehiro, a British trained medical doctor of the Japanese Navy, observed that beriberi was endemic among low-ranking crew who often ate nothing but rice, but not among crews of Western navies and officers who consumed a Western-style diet. Kanehiro initially believed that lack of protein was the chief cause of beriberi. With the support of the Japanese navy, he experimented using crews of two battleships; one crew was fed only white rice, while the other was fed a diet of meat, fish, barley, rice, and beans. The group that ate only white rice documented 161 crew members with beriberi and 25 deaths, while the latter group had only 14 cases of beriberi and no deaths. This convinced Kanehiro and the Japanese Navy that diet was the cause of beriberi. This was confirmed in 1897, when Christiaan Eijkman discovered that feeding unpolished rice instead of the polished variety to chickens helped to prevent beriberi in the chickens. The following year, Frederick Hopkins postulated that some foods contained "accessory factors"—in addition to proteins, carbohydrates, fats, et cetera—that were necessary for the functions of the human body. Hopkins was awarded the 1929 Nobel Prize for Physiology or Medicine with Christiaan Eijkman for their discovery of several vitamins.

In 1910, Japanese scientist Umetaro Suzuki succeeded in extracting a water-soluble complex of micronutrients from rice bran and named it aberic acid. He published this discovery in a Japanese scientific journal.

When the article was translated into German, the translation failed to state that it was a newly discovered nutrient, a claim made in the original Japanese article, and hence his discovery failed to gain publicity. Polish biochemist Kazimierz Funk isolated the same complex of micronutrients and proposed the complex be named "Vitamine" (a portmanteau of "vital amine") in 1912. The name soon became synonymous with Hopkins' "accessory factors", and by the time it was shown that not all vitamins were amines, the word was already ubiquitous. In 1920, Jack Cecil Drummond proposed that the final "e" be dropped to deemphasize the "amine" reference after the discovery that vitamin C had no amine component.

Throughout the early 1900s, the use of deprivation studies allowed scientists to isolate and identify a number of vitamins. Initially, lipid from fish oil was used to cure rickets in rats, and the fat-soluble nutrient was called "antirachitic A". Thus, the first "vitamin" bioactivity ever isolated, which cured rickets, was initially called "vitamin A", although confusingly the bioactivity of this compound is now called vitamin D. What we now call "vitamin A" was identified in fish oil as a separate factor that was inactivated by ultraviolet light. In 1931, Albert Szent-Györgyi and a fellow researcher Joseph Svirbely determined that "hexuronic acid" was actually vitamin C and noted its anti-scorbutic activity. In 1937, Szent-Györgyi was awarded the Nobel Prize for his discovery. In 1943 Edward Adelbert Doisy and Henrik Dam were awarded the Nobel Prize for their discovery of vitamin K and its chemical structure.

In humans

Vitamins are classified as either water-soluble or fat soluble. In humans there are 13 vitamins: 4 fat-soluble (A, D, E and K) and 9 water-soluble (8 B vitamins and vitamin C).

Water-soluble

Water-soluble vitamins dissolve easily in water, and in general, are readily excreted from the body, to the degree that urinary output is a strong predictor of vitamin consumption. Because they are not readily stored, consistent daily intake is important. Many types of water-soluble vitamins are synthesized by bacteria.

Fat-soluble

Fat-soluble vitamins are absorbed through the intestinal tract with the help of lipids (fats). Because they are more likely to accumulate in the body, they are more likely to lead to hypervitaminosis than are water-soluble vitamins. Fat-soluble vitamin regulation is of particular significance in cystic fibrosis.

List of vitamins

Each vitamin is typically used in multiple reactions and, therefore, most have multiple functions.

Vitamin generic descriptor name	Vitamer chemical name(s) (list not complete)	Solubility	Recommended dietary allowances (male, age 19–70)	Deficiency disease	Upper Intake Level (UL/day)	Overdose disease
Vitamin A	Retinoids (retinol, retinoids and carotenoids)	Fat	900 µg	Night-blindness and Keratomalacia	3,000 µg	Hypervitaminosis A
Vitamin B1	Thiamine	Water	1.2 mg	Beriberi, Wernicke-Korsakoff syndrome	N/D	Rare hypersensitive reactions resembling anaphylactic shock-- injection only; Drowsiness
Vitamin B2	Riboflavin	Water	1.3 mg	Ariboflavinosis	N/D	?
Vitamin B3	Niacin, niacinamide	Water	16.0 mg	Pellagra	35.0 mg	Liver damage (doses > 2g/day) and other problems
Vitamin B5	Pantothenic acid	Water	5.0 mg	Paresthesia	N/D	?
Vitamin B6	Pyridoxine, pyridoxamine, pyridoxal	Water	1.3-1.7 mg	Anemia	100 mg	Impairment of proprioception, nerve damage (doses > 100 mg/day)
Vitamin B7	Biotin	Water	30.0 µg	Dermatitis, enteritis	N/D	?
Vitamin B9	Folic acid, folinic acid	Water	400 µg	Deficiency during pregnancy is associated with birth defects, such as neural tube defects	1,000 µg	Possible decrease in seizure threshold
Vitamin B12	Cyanocobalamin, hydroxycobalamin, methylcobalamin	Water	2.4 µg	Megaloblastic anemia	N/D	No known toxicity
Vitamin C	Ascorbic acid	Water	90.0 mg	Scurvy	2,000 mg	Vitamin C megadosage
Vitamin D	Ergocalciferol, cholecalciferol	Fat	5.0 µg-10 µg	Rickets and Osteomalacia	50 µg	Hypervitaminosis D
Vitamin E	Tocopherols, tocotrienols	Fat	15.0 mg	Deficiency is very rare; mild hemolytic anemia in newborn infants.	1,000 mg	Increased congestive heart failure seen in one large randomized study.
Vitamin K	phylloquinone, menaquinones	Fat	120 µg	Bleeding diathesis	N/D	Increases coagulation in patients taking warfarin.

In nutrition and diseases

Riboflavin (Vitamin B2)

Vitamins are essential for the normal growth and development of a multicellular organism. Using the genetic blueprint inherited from its parents, a fetus begins to develop, at the moment of conception, from the nutrients it absorbs. It requires certain vitamins and minerals to be present at certain times. These nutrients facilitate the chemical reactions that produce among other things, skin, bone, and muscle. If there is serious deficiency in one or more of these nutrients, a child may develop a deficiency disease. Even minor deficiencies may cause permanent damage.

For the most part, vitamins are obtained with food, but a few are obtained by other means. For example, microorganisms in the intestine—commonly known as "gut flora"—produce vitamin K and biotin, while one form of vitamin D is synthesized in the skin with the help of the natural ultraviolet wavelength of sunlight. Humans can produce some vitamins from precursors they consume. Examples include vitamin A, produced from beta carotene, and niacin, from the amino acid tryptophan.

Once growth and development are completed, vitamins remain essential nutrients for the healthy maintenance of the cells, tissues, and organs that make up a multicellular organism; they also enable a multicellular life form to efficiently use chemical energy provided by food it eats, and to help process the proteins, carbohydrates, and fats required for respiration.

Deficiencies

Deficiencies of vitamins are classified as either primary or secondary. A primary deficiency occurs when an organism does not get enough of the vitamin in its food. A secondary deficiency may be due to an underlying disorder that prevents or limits the absorption or use of the vitamin, due to a “lifestyle factor”, such as smoking, excessive alcohol consumption, or the use of medications that interfere with the absorption or use of the vitamin. People who eat a varied diet are unlikely to develop a severe primary vitamin deficiency. In contrast, restrictive diets have the potential to cause prolonged vitamin deficits, which may result in often painful and potentially deadly diseases.

Because human bodies do not store most vitamins, humans must consume them regularly to avoid deficiency. Human bodily stores for different vitamins vary widely; vitamins A, D, and B12 are stored in significant amounts in the human body, mainly in the liver, and an adult human's diet may be deficient in vitamins A and B12 for many months before developing a deficiency condition. Vitamin B3 is not stored in the human body in significant amounts, so stores may only last a couple of weeks.

Well-known human vitamin deficiencies involve thiamine (beriberi), niacin (pellagra), vitamin C (scurvy) and vitamin D (rickets). In much of the developed world, such deficiencies are rare; this is due to (1) an adequate supply of food; and (2) the addition of vitamins and minerals to common foods, often called fortification.

Some evidence also suggests that there is a link between vitamin deficiency and mental disorders.

Side effects and overdose

In large doses, some vitamins have documented side effects that tend to be more severe with a larger dosage. The likelihood of consuming too much of any vitamin from food is remote, but overdosing from vitamin supplementation does occur. At high enough dosages some vitamins cause side effects such as nausea, diarrhea, and vomiting.

When side effects emerge, recovery is often accomplished by reducing the dosage. The concentrations of vitamins an individual can tolerate vary widely, and appear to be related to age and state of health. In the United States, overdose exposure to all formulations of vitamins was reported by 62,562 individuals in 2004 (nearly 80% of these exposures were in children under the age of 6), leading to 53 "major" life-threatening outcomes and 3 deaths;a small number in comparison to the 19,250 people who died of unintentional poisoning of all kinds in the U.S. in the same year (2004).

Supplements

Dietary supplements, often containing vitamins, are used to ensure that adequate amounts of nutrients are obtained on a daily basis, if optimal amounts of the nutrients cannot be obtained through a varied diet. Scientific evidence supporting the benefits of some dietary supplements is well established for certain health conditions, but others need further study. A meta-analysis in 2006 suggested that Vitamin A and E supplements not only provide no tangible health benefits for generally healthy individuals, but may actually increase mortality, although two large studies included in the analysis involved smokers, for which it was already known that beta-carotene supplements can be harmful.

In the United States, advertising for dietary supplements is required to include a disclaimer that the product is not intended to treat, diagnose, mitigate, prevent, or cure disease, and that any health claims have not been evaluated by the Food and Drug Administration. In some cases, dietary supplements may have unwanted effects, especially if taken before surgery, with other dietary supplements or medicines, or if the person taking them has certain health conditions. Vitamin supplements may also contain levels of vitamins many times higher, and in different forms, than one may ingest through food.

Intake of excessive quantities can cause vitamin poisoning, often due to overdose of Vitamin A and Vitamin D (The most common poisoning with multinutrient supplement pills does not involve a vitamin, but is rather due to the mineral iron). Due to toxicity, most common vitamins have recommended upper daily intake amounts.

Since 2005, suppliers have distinguished their products as either Medical Grade or Pharmaceutical Grade products. Both of these classifications indicate products that are manufactured to be easily absorbed by the body. Normal vitamin manufacturing is not regulated in the United States to the same standards as are medicinal pharmaceuticals, although U.S. vitamins which are manufactured for food consumption by humans or animals must be manufactured to Food Chemicals Codex (FCC), grade, commonly called "food grade".

Governmental regulation of vitamin supplements

Most countries place dietary supplements in a special category under the general umbrella of foods, not drugs. This necessitates that the manufacturer, and not the government, be responsible for ensuring that its dietary supplement products are safe before they are marketed. Unlike drug products, which must explicitly be proven safe and effective for their intended use before marketing, there are often no provisions to "approve" dietary supplements for safety or effectiveness before they reach the consumer. Also unlike drug products, manufacturers and distributors of dietary supplements are not generally required to report any claims of injuries or illnesses that may be related to the use of their products.

Names in current and previous nomenclatures

The reason the set of vitamins seems to skip directly from E to K is that the vitamins corresponding to "letters" F-J were either reclassified over time, discarded as false leads, or renamed because of their relationship to "vitamin B", which became a "complex" of vitamins. The German-speaking scientists who isolated and described vitamin K (in addition to naming it as such) did so because the vitamin is intimately involved in the Koagulation of blood following wounding. At the time, most (but not all) of the letters from F through to J were already designated, so the use of the letter K was considered quite reasonable.

The following table lists chemicals that had previously been classified as vitamins, as well as the earlier names of vitamins that later became part of the B-complex:

Previous name	Chemical name	Reason for name change
Vitamin B4	Adenine	DNA metabolite
Vitamin B8	Adenylic acid	DNA metabolite
Vitamin F	Essential fatty acids	Needed in large quantities (does not fit the definition of a vitamin).
Vitamin G	Riboflavin	Reclassified as Vitamin B2
Vitamin H	Biotin	Reclassified as Vitamin B7
Vitamin J	Catechol, Flavin	Protein metabolite
Vitamin L1	Anthranilic acid	Protein metabolite
Vitamin L2	Adenylthiomethylpentose	RNA metabolite
Vitamin M	Folic acid	Reclassified as Vitamin B9
Vitamin O	Carnitine	Protein metabolite
Vitamin P	Flavonoids	No longer classified as a vitamin
Vitamin PP	Niacin	Reclassified as Vitamin B3
Vitamin U	S-Methylmethionine	Protein metabolite