Vitamin

Vitamins are organic molecules (or a set of closely related molecules called vitamers) that are essential to an organism in small quantities for proper metabolic function. These essential nutrients cannot be synthesized in the organism in sufficient quantities for survival, and therefore must be obtained through consumption. For example, vitamin C can be synthesized by some species but not by others; it is not considered a vitamin in the first instance but is in the second. Most vitamins are not single molecules, but groups of related molecules called vitamers. For example, there are eight vitamers of vitamin E: four tocopherols and four tocotrienols.

The other essential nutrients are minerals, essential fatty acids, essential amino acids, and choline.

Major health organizations list thirteen vitamins:

• Vitamin A (all-trans-retinols, all-trans-retinyl-esters, as well as all-trans-β-carotene and other provitamin A carotenoids)
• Vitamin B₁ (thiamine)
• Vitamin B₂ (riboflavin)
• Vitamin B₃ (niacin)
• Vitamin B₅ (pantothenic acid)
• Vitamin B₆ (pyridoxine)
• Vitamin B₇ (biotin)
• Vitamin B₉ (folic acid and folates)
• Vitamin B₁₂ (cobalamins)
• Vitamin C (ascorbic acid and ascorbates)
• Vitamin D (calciferols)
• Vitamin E (tocopherols and tocotrienols)
• Vitamin K (phylloquinones, menaquinones, and menadiones)

Some writers include choline as a vitamin.

Vitamins have diverse biochemical functions. Vitamin A acts as a regulator of cell and tissue growth and differentiation. Vitamin D provides a hormone-like function, regulating mineral metabolism for bones and other organs. The B complex vitamins function as enzyme cofactors (coenzymes) or the precursors for them. Vitamins C and E function as antioxidants. Both deficient and excess intake of a vitamin can potentially cause clinically significant illness, although excess intake of water-soluble vitamins is less likely to do so.

All the vitamins were discovered between 1910 and 1948. Historically, when intake of vitamins from the diet was lacking, the results were vitamin deficiency diseases. Then, starting in 1935, commercially produced tablets of yeast-extract vitamin B complex and semi-synthetic vitamin C became available. Recommendations for folic acid supplementation during pregnancy reduced the risk of infant neural tube defects.

List of vitamins

{| class="wikitable sortable col3center"

|-

! colspan="2" scope="col" | Vitamin

! class="unsortable" scope="col" | Vitamers

! scope="col" | Solubility

! class="unsortable" scope="col" | U.S. recommended dietary allowances<br /> per day<br /> (ages 19–70)

|-

! rowspan="8" | B

! scope="row" | B₁

| thiamine, thiamine monophosphate, thiamine pyrophosphate

|

| 1.2&nbsp;mg/1.1&nbsp;mg

| beriberi, Wernicke–Korsakoff syndrome

|

|pork, wholemeal grains, brown rice, vegetables, potatoes

|

|-

! scope="row" | B₂

| riboflavin, flavin mononucleotide, flavin adenine dinucleotide

|

| 1.3&nbsp;mg/1.1&nbsp;mg

| ariboflavinosis

|

|dairy products, meat, liver, refined grains

|

|-

! scope="row" | B₅

| pantothenic acid, panthenol, pantethine

|

| 5&nbsp;mg/5&nbsp;mg

| paresthesia

| diarrhea

|meat, vegetables, seeds, yeast

|

|-

! B₆

| pyridoxine, pyridoxamine, pyridoxal

|

| 1.3–1.7&nbsp;mg/1.2–1.5&nbsp;mg

| anemia, neurological symptoms, dermatitis, cheilosis, glossitis

| neuropathy

|meat, vegetables, tree nuts, bananas

|

|-

! B₉

| folates, folic acid

|

| 400&nbsp;μg/400&nbsp;μg

| style="text-align:left;"| folate deficiency

| may mask symptoms of vitamin B₁₂ deficiency

|leafy vegetables, legumes, lentils, cereal, liver

|

|-

! B₁₂

| cyanocobalamin, hydroxocobalamin, methylcobalamin, adenosylcobalamin

|

| 2.4&nbsp;μg/2.4&nbsp;μg

| vitamin B₁₂ deficiency anemia

|

|fish, eggs, milk products

|

|-

! rowspan="5" |D

! style="whitespace:nowrap;" |D₁

| mixture of molecular compounds of ergocalciferol with lumisterol, 1:1

|

| rowspan="5" | 15&nbsp;μg/15&nbsp;μg

| rowspan="5" | vitamin D deficiency

| rowspan="5" | hypervitaminosis D

|

| rowspan="5" |

|-

!D₂

|ergocalciferol

|

|Finger millet, mushrooms, seeds, soya bean, Colocasia leaves, yeast

|-

!D₃

|cholecalciferol

|

|fatty fish, fish liver oils, eggs, milk products

|-

!D₄

|22-dihydroergocalciferol

|

|

|-

!D₅

|sitocalciferol

|

|

|-

! colspan="2" |E

| tocopherols, tocotrienols

|

| 15&nbsp;mg/15&nbsp;mg

| align="left" | vitamin E deficiency

| bleeding

|many fruits and vegetables, nuts, seeds, seed oils

|

|-

! rowspan="2" |K

! K₁

| phylloquinone

|

| rowspan="2" | AI: 110&nbsp;μg/120&nbsp;μg

| rowspan="2" | vitamin K deficiency

| rowspan="2" | skin rash, gastrointestinal symptoms

| leafy green vegetables

| rowspan="2" |

|-

!K₂

|menaquinone

|

|poultry and eggs, nattō, beef, pork, or fish

|}

History

Etymology

The term "vitamin" was derived from "vitamine", a portmanteau coined from "vital amine" in 1912 by the biochemist Casimir Funk and his friend Max Nierenstein, Reader of Biochemistry at Bristol University, while Funk was working at the Lister Institute of Preventive Medicine. Funk created the name from vital and amine as suggested by Nierenstein,

{| class="wikitable sortable" style = "float:right; font-size:90%; margin-left:15px"

|+ The discovery dates of the vitamins

|- class="hintergrundfarbe6"

! Year of discovery !! Vitamin

|-

| 1913 || Vitamin A (Retinol)

|-

| 1910 || Vitamin B₁ (Thiamine)

|-

| 1920 || Vitamin C (Ascorbic acid)

|-

| 1920 || Vitamin D (Calciferol)

|-

| 1920 || Vitamin B₂ (Riboflavin)

|-

| 1922 || Vitamin E (Tocopherol)

|-

| 1929 || Vitamin K₁ (Phylloquinone)

|-

| 1931 || Vitamin B₅ (Pantothenic acid)

|-

| 1934 || Vitamin B₆ (Pyridoxine)

|-

| 1936 || Vitamin B₇ (Biotin)

|-

| 1936 || Vitamin B₃ (Niacin)

|-

| 1941 || Vitamin B₉ (Folic acid)

|-

| 1948 || Vitamin B₁₂ (Cobalamins)

|-

|}

In 1747, 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; Portuguese and Spanish sailors had independently known about the disease they acquired and how it was reduced after eating oranges and vegetables such as yams and turnips. 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 medical doctor Nikolai Lunin studied the effects of scurvy at the University of Tartu. 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 his advisor, Gustav von Bunge. A similar result by Cornelis Adrianus Pekelharing appeared in Dutch medical journal Nederlands Tijdschrift voor Geneeskunde in 1905, but it was not widely reported. That diseases could result from some dietary deficiencies was further investigated by Christiaan Eijkman, who in 1897 discovered that feeding unpolished rice instead of the polished variety to chickens helped to prevent a kind of polyneuritis that was the equivalent of beriberi. The following year, Frederick Hopkins postulated that some foods contained "accessory factors"&nbsp;– in addition to proteins, carbohydrates, fats etc.&nbsp;– that are necessary for the functions of the human body. 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. In 1912 Polish-born biochemist Casimir Funk, working in London, isolated the same complex of micronutrients and proposed the complex be named "vitamine",

The Nobel Prize in Physiology or Medicine for 1929 was awarded to Christiaan Eijkman and Frederick Gowland Hopkins for their contributions to the discovery of vitamins. Thirty-five years earlier, Eijkman had observed that chickens fed polished white rice developed neurological symptoms similar to those observed in military sailors and soldiers fed a rice-based diet, and that the symptoms were reversed when the chickens were switched to whole-grain rice. He called this "the anti-beriberi factor", which was later identified as vitamin B₁, thiamine.

In 1930, Paul Karrer elucidated the correct structure for beta-carotene, the main precursor of vitamin A, and identified other carotenoids. Karrer and Norman Haworth confirmed Albert Szent-Györgyi's discovery of ascorbic acid and made significant contributions to the chemistry of flavins, which led to the identification of lactoflavin. For their investigations on carotenoids, flavins and vitamins A and B₂, they both received the Nobel Prize in Chemistry in 1937.

In 1931, Albert Szent-Györgyi and a fellow researcher Joseph Svirbely suspected that "hexuronic acid" was actually vitamin C, and gave a sample to Charles Glen King, who proved its ability to counter scurvy in his long-established guinea pig scorbutic assay. In 1937, Szent-Györgyi was awarded the Nobel Prize in Physiology or Medicine for his discovery. In 1943, Edward Adelbert Doisy and Henrik Dam were awarded the Nobel Prize in Physiology or Medicine for their discovery of vitamin K and its chemical structure.

In 1938, Richard Kuhn was awarded the Nobel Prize in Chemistry for his work on carotenoids and vitamins, specifically B₂ and B₆.

Five people have been awarded Nobel Prizes for direct and indirect studies of vitamin B₁₂: George Whipple, George Minot and William P. Murphy (1934), Alexander R. Todd (1957), and Dorothy Hodgkin (1964).

In 1967, George Wald, Ragnar Granit and Haldan Keffer Hartline were awarded the Nobel Prize in Physiology and Medicine "...for their discoveries concerning the primary physiological and chemical visual processes in the eye." Wald's contribution was discovering the role vitamin A had in the process.

History of promotional marketing

Once discovered, vitamins were actively promoted in articles and advertisements in McCall's, Good Housekeeping, and other media outlets. In 1942, when flour enrichment with nicotinic acid began, a headline in the popular press said "Tobacco in Your Bread." In response, the Council on Foods and Nutrition of the American Medical Association approved of the Food and Nutrition Board's new names niacin and niacin amide for use primarily by non-scientists. It was thought appropriate to choose a name to dissociate nicotinic acid from nicotine, to avoid the perception that vitamins or niacin-rich food contains nicotine, or that cigarettes contain vitamins. The resulting name niacin was derived from cotinic id + vitam. Researchers also focused on the need to ensure adequate nutrition, especially to compensate for what was lost in the manufacture of processed foods.

Classification

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 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 as readily stored, more consistent intake is important. Fat-soluble vitamins are absorbed through the gastrointestinal tract with the help of lipids (fats). Vitamins A and D can accumulate in the body, which can result in dangerous hypervitaminosis. Fat-soluble vitamin deficiency due to malabsorption is of particular significance in cystic fibrosis.

Anti-vitamins

Anti-vitamins are chemical compounds that inhibit the absorption or actions of vitamins. For example, avidin is a protein in raw egg whites that inhibits the absorption of biotin; it is deactivated by cooking. Pyrithiamine, a synthetic compound, has a molecular structure similar to thiamine, vitamin B₁, and inhibits the enzymes that use thiamine.

Biochemical functions

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

On fetal growth and childhood development

Vitamins are essential for the normal growth and development of a multicellular organism. Using the genetic blueprint inherited from its parents, a fetus develops from the nutrients it absorbs. It requires certain vitamins and minerals to be present at certain times.

On adult health maintenance

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 cellular respiration. Vitamin C can be synthesized by some species but not by others. Vitamin B₁₂ is the only vitamin or nutrient not available from plant sources. The Food Fortification Initiative lists countries which have mandatory fortification programs for vitamins folic acid, niacin, vitamin A and vitamins B₁, B₂ and B₁₂. and an adult's diet may be deficient in vitamins A and D for many months and B₁₂ in some cases for years, before developing a deficiency condition. However, vitamin B₃ (niacin and niacinamide) is not stored in significant amounts, so stores may last only a couple of weeks.

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.

Well-researched human vitamin deficiencies involve thiamine (beriberi), niacin (pellagra), In much of the developed world these deficiencies are rare due to an adequate supply of food and the addition of vitamins to common foods.

Excess intake

Some vitamins have documented acute or chronic toxicity at larger intakes, which is referred to as hypertoxicity. The European Union and the governments of several countries have established tolerable upper intake levels (ULs) for those vitamins which have documented toxicity (see table). In the US, analysis of a national diet and supplement survey reported that about 7% of adult supplement users exceeded the UL for folate and 5% of those older than age 50 years exceeded the UL for vitamin A. Some vitamins may become more "bio-available" – that is, usable by the body – when foods are cooked. The table below shows whether various vitamins are susceptible to loss from heat—such as heat from boiling, steaming, frying, etc. The effect of cutting vegetables can be seen from exposure to air and light. Water-soluble vitamins such as B and C dissolve into the water when a vegetable is boiled, and are then lost when the water is discarded.

{| class="wikitable sortable" border="1" |-

! rowspan="2" |Vitamin

! colspan="4" |Is substance susceptible to losses under given condition?

|-

!Soluble in Water

!Air Exposure

!Light Exposure

!Heat Exposure

|-

|Vitamin A

| no

| partially

| partially

| relatively stable

|-

|Vitamin C

| very unstable

| yes

| no

| no

|-

| Vitamin D

| no

| no

| no

| no

|-

| Vitamin E

| no

| yes

| yes

| no

|-

|Vitamin K

| no

| no

| yes

| no

|-

|Thiamine (B₁)

| highly

| no

| ?

| > 100&nbsp;°C

|-

|Riboflavin (B₂)

| slightly

| no

| in solution

| no

|-

|Niacin (B₃)

| yes

| no

| no

| no

|-

|Pantothenic Acid (B₅)

| quite stable

| no

| no

| yes

|-

|Vitamin B₆

| yes

| ?

| yes

| < 160&nbsp;°C

|-

|Biotin (B₇)

| somewhat

| ?

| ?

| no

|-

|Folic Acid (B₉)

| yes

| ?

| when dry

| at high temp

|-

|Cobalamin (B₁₂)

| yes

| ?

| yes

| no

|}

Recommended levels

In setting human nutrient guidelines, government organizations do not necessarily agree on amounts needed to avoid deficiency or maximum amounts to avoid the risk of toxicity. For example, for vitamin C, recommended intakes range from 40&nbsp;mg/day in India to 155&nbsp;mg/day for the European Union. The table below shows U.S. Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for vitamins, PRIs for the European Union (same concept as RDAs), followed by what three government organizations deem to be the safe upper intake. RDAs are set higher than EARs to cover people with higher than average needs. Adequate Intakes (AIs) are set when there is not sufficient information to establish EARs and RDAs. Governments are slow to revise information of this nature. For the U.S. values, with the exception of calcium and vitamin D, all of the data date to 1997–2004.

All values are consumption per day:

{| class="wikitable"

|-

! rowspan="2" |Nutrient !! rowspan="2" |U.S. EAR Vitamin A and E supplements not only provide no health benefits for generally healthy individuals, but they may increase mortality, though the two large studies that support this conclusion included smokers for whom it was already known that beta-carotene supplements can be harmful. A 2018 meta-analysis found no evidence that intake of vitamin D or calcium for community-dwelling elderly people reduced bone fractures.

Europe has regulations that define limits of vitamin (and mineral) dosages for their safe use as dietary supplements. Most vitamins that are sold as dietary supplements are not supposed to exceed a maximum daily dosage referred to as the tolerable upper intake level (UL or Upper Limit). Vitamin products above these regulatory limits are not considered supplements and should be registered as prescription or non-prescription (over-the-counter drugs) due to their potential side effects. The European Union, United States and Japan establish ULs. In some cases, vitamin 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. There is no FDA approval process for dietary supplements, and no requirement that manufacturers prove the safety or efficacy of supplements introduced before 1994.

In 2007, the US Code of Federal Regulations (CFR) Title 21, part III took effect, regulating Good Manufacturing Practices (GMPs) in the manufacturing, packaging, labeling, or holding operations for dietary supplements. Even though product registration is not required, these regulations mandate production and quality control standards (including testing for identity, purity and adulterations) for dietary supplements. In the United States, the United States Pharmacopeia (USP) sets standards for the most commonly used vitamins and preparations thereof. Likewise, monographs of the European Pharmacopoeia (Ph.Eur.) regulate aspects of identity and purity for vitamins on the European market.

In the European Union, the Food Supplements Directive requires that only those supplements that have been proven safe can be sold without a prescription. For most vitamins, pharmacopoeial standards have been established.

In Nigeria, the National Agency for Food and Drug Administration and Control has issued regulations which govern the supply and contents of vitamins and supplements.

In England, the National Health Service makes free vitamins available for babies and children under 4 through its "Healthy Start" programme, adopted due to concerns that young children, even if feeding well, would not receive an adequate intake of vitamins A and D.

Naming

{| class="wikitable sortable" style="float:right; font-size:90%; margin-left:20px"

|+Nomenclature of reclassified vitamins

|- class="hintergrundfarbe6"

! Previous name

! Chemical name

! Reason for name change

|Anthranilic acid

| Nonessential

|-

| Vitamin L₂

|Folate

| Reclassified as Vitamin B₉

|-

| Vitamin P

|Flavonoids

| Many compounds, not proven essential

|-

| Vitamin PP

|Niacin

| Reclassified as Vitamin B₃

|-

| Vitamin S

|Salicylic acid

| Nonessential

|-

| Vitamin U

|S-Methylmethionine

| Protein metabolite; synthesized in body

|}

The reason that the set of vitamins skips 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&nbsp;B, which became a complex of vitamins.

The Danish-speaking scientists who isolated and described vitamin&nbsp;K (in addition to naming it as such) did so because the vitamin is intimately involved in the coagulation of blood following wounding (from the Danish word Koagulation). 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 table Nomenclature of reclassified vitamins 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.

The missing numbered B vitamins were reclassified or determined not to be vitamins. For example, B₉ is folic acid and five of the folates are in the range B₁₁ through B₁₆. Others, such as PABA (formerly B₁₀), are biologically inactive, toxic, or with unclassifiable effects in humans, or not generally recognised as vitamins by science, such as the highest-numbered, which some naturopath practitioners call B₂₁ and B₂₂. There are also lettered B substances (e.g., B_m) listed at B vitamins that are not recognized as vitamins. There are other "D vitamins" now recognised as other substances, which some sources of the same type number up to D₇. The controversial cancer treatment laetrile was at one point lettered as vitamin B₁₇. There appears to be no consensus on the existence of substances that may have at one time been named as vitamins Q, R, T, V, W, X, Y or Z.

"Vitamin N" is a term popularized for the mental health benefits of spending time in nature settings. "Vitamin I" is slang among athletes for frequent/daily consumption of ibuprofen as a pain-relieving treatment.

See also

• Vitamin deficiency
• Hypervitaminosis
• Human nutrition

References

Notes

External links

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• USDA RDA chart in PDF format
• Health Canada Dietary Reference Intakes Reference Chart for Vitamins
• NIH Office of Dietary Supplements: Fact Sheets