Vitamins areorganic molecules (or a set of closely related molecules calledvitamers) that are essential to anorganism in small quantities for propermetabolic function. Theseessential nutrients cannot besynthesized in the organism in sufficient quantities for survival, and therefore must be obtained through thediet. 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 ofvitamin E: fourtocopherols and fourtocotrienols.
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. TheB complex vitamins function as enzymecofactors (coenzymes) or theprecursors for them. Vitamins C and E function asantioxidants.[7] 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 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.[8] This was followed in the 1950s by the mass production and marketing ofvitamin supplements, includingmultivitamins, to prevent vitamin deficiencies in the general population.[8] Governments have mandated the addition of some vitamins tostaple foods such as flour or milk, referred to asfood fortification, to prevent deficiencies.[9] Recommendations for folic acid supplementation duringpregnancy reduced risk of infantneural tube defects.[10]
The value of eating certain foods to maintain health was recognized long before vitamins were identified. Theancient Egyptians knew that feedingliver to a person may help withnight blindness, an illness now known to be caused by avitamin A deficiency.[24] The advance of ocean voyages during theAge of Discovery resulted in prolonged periods without access to fresh fruits and vegetables, and made illnesses from vitamin deficiency common among ships' crews.[25]
The discovery dates of the vitamins and their sources
In 1747, theScottishsurgeonJames Lind discovered thatcitrus foods helped prevent scurvy, a particularly deadly disease in whichcollagen is not properly formed, causing poor wound healing, bleeding of thegums, severe pain, and death.[24] In 1753, Lind published hisTreatise on the Scurvy, which recommended usinglemons andlimes to avoidscurvy, which was adopted by the BritishRoyal Navy. This led to the nicknamelimey for British sailors. However, during the 19th century, limes grown in the West Indies were substituted for lemons; these were subsequently found to be much lower in vitamin C.[27] As a result, Arctic expeditions continued to be plagued by scurvy and otherdeficiency diseases. In the early 20th century, whenRobert Falcon Scott made his two expeditions to theAntarctic, the prevailing medical theory was that scurvy was caused by "tainted"canned food.[28]
In 1881,Russian medical doctorNikolai Lunin studied the effects of scurvy at theUniversity of Tartu. He fed mice an artificial mixture of all the separate constituents of milk known at that time, namely theproteins,fats,carbohydrates, andsalts. 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.[29] A similar result byCornelis Adrianus Pekelharing appeared in Dutch medical journalNederlands Tijdschrift voor Geneeskunde in 1905,[a] but it was not widely reported.[29]
InEast Asia, where polishedwhite rice was the common staple food of the middle class,beriberi resulting from lack of vitamin B1 wasendemic. In 1884,Takaki Kanehiro, a British-trained medical doctor of theImperial Japanese Navy, observed that beriberi was endemic among low-ranking crew who often ate nothing but rice, but not among officers who consumed a Western-style diet. With the support of the Japanese navy, he experimented using crews of twobattleships; 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 Takaki and the Japanese Navy that diet was the cause of beriberi, but they mistakenly believed that sufficient amounts of protein prevented it.[31] That diseases could result from some dietary deficiencies was further investigated byChristiaan Eijkman, who in 1897 discovered that feeding unpolishedrice instead of the polished variety to chickens helped to prevent a kind ofpolyneuritis that was the equivalent of beriberi.[32] The following year,Frederick Hopkins postulated that some foods contained "accessory factors" – in addition to proteins, carbohydrates, fatsetc. – that are necessary for the functions of the human body.[24]
Jack Drummond's single-paragraph article in 1920 which provided structure and nomenclature used today for vitamins
"Vitamine" to vitamin
In 1910, the first vitamin complex was isolated by Japanese scientistUmetaro Suzuki, who succeeded in extracting a water-soluble complex of micronutrients from rice bran and named itaberic acid (laterOrizanin). He published this discovery in a Japanese scientific journal.[33] 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 biochemistCasimir Funk, working in London, isolated the same complex of micronutrients and proposed the complex be named "vitamine".[34] It was later to be known as vitamin B3 (niacin), though he described it as "anti-beri-beri-factor" (which would today be called thiamine or vitamin B1). Funk proposed the hypothesis that other diseases, such as rickets, pellagra, coeliac disease, and scurvy could also be cured by vitamins.Max Nierenstein a friend and Reader of Biochemistry at Bristol University reportedly suggested the "vitamine" name (from "vital amine").[35][36] The name soon became synonymous with Hopkins' "accessory factors", and, by the time it was shown that not all vitamins areamines, the word was already ubiquitous. In 1920,Jack Cecil Drummond proposed that the final "e" be dropped to deemphasize the "amine" reference, hence "vitamin", after researchers began to suspect that not all "vitamines" (in particular, vitamin A) have an amine component.[31]
Nobel Prizes for vitamin research
The Nobel Prize for Chemistry for 1928 was awarded toAdolf Windaus "for his studies on the constitution of the sterols and their connection with vitamins", the first person to receive an award mentioning vitamins, even though it was not specifically about vitamin D.[37]
TheNobel Prize in Physiology or Medicine for 1929 was awarded to Christiaan Eijkman andFrederick 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.[38]
In 1930,Paul Karrer elucidated the correct structure forbeta-carotene, the main precursor of vitamin A, and identified othercarotenoids. Karrer andNorman Haworth confirmed Albert Szent-Györgyi's discovery ofascorbic acid and made significant contributions to the chemistry offlavins, which led to the identification oflactoflavin. For their investigations on carotenoids, flavins and vitamins A and B2, they both received theNobel Prize in Chemistry in 1937.[39]
In 1931,Albert Szent-Györgyi and a fellow researcherJoseph Svirbely suspected that "hexuronic acid" was actuallyvitamin C, and gave a sample toCharles Glen King, who proved its ability to counter scurvy in his long-establishedguinea pig scorbutic assay. In 1937, Szent-Györgyi was awarded the Nobel Prize in Physiology or Medicine for his discovery. In 1943,Edward Adelbert Doisy andHenrik Dam were awarded the Nobel Prize in Physiology or Medicine for their discovery ofvitamin 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.[40]
In 1967,George Wald,Ragnar Granit andHaldan 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.[38][42]
History of promotional marketing
Once discovered, vitamins were actively promoted in articles and advertisements inMcCall's,Good Housekeeping, and other media outlets.[32] Marketers enthusiastically promotedcod-liver oil, a source of vitamin D, as "bottled sunshine", and bananas as a "natural vitality food".[43] They promoted foods such asyeast cakes, a source of B vitamins, on the basis of scientifically determined nutritional value, rather than taste or appearance.[43] In 1942, when flourenrichment with nicotinic acid began, a headline in the popular press said "Tobacco in Your Bread." In response, the Council on Foods and Nutrition of theAmerican Medical Association approved of theFood and Nutrition Board's new namesniacin andniacin amide for use primarily by non-scientists. It was thought appropriate to choose a name to dissociate nicotinic acid fromnicotine, to avoid the perception that vitamins or niacin-rich food contains nicotine, or that cigarettes contain vitamins. The resulting nameniacin was derived fromnicotinicacid +vitamin.[44][45] Researchers also focused on the need to ensure adequate nutrition, especially to compensate for what was lost in the manufacture ofprocessed foods.[32]
Robert W. Yoder is credited with first using the termvitamania, in 1942, to describe the appeal of relying on nutritional supplements rather than on obtaining vitamins from a varied diet of foods. The continuing preoccupation with a healthy lifestyle led to an obsessive consumption of vitamins and multi-vitamins, the beneficial effects of which are questionable.[8] As one example, in the 1950s, theWonder Bread company sponsored theHowdy Doody television show, with hostBuffalo Bob Smith telling the audience, "Wonder Bread builds strong bodies 8 ways", referring to the number ofadded nutrients.[46]
Etymology
The term "vitamin" was derived from "vitamine", aportmanteau coined in 1912 by thebiochemist Casimir Funk while working at theLister Institute of Preventive Medicine.[34] Funk created the name fromvital andamine, because it appeared that these organic micronutrient food factors that prevent beriberi and perhaps other similar dietary-deficiency diseases were required for life, hence "vital", and were chemical amines, hence "amine". This was true ofthiamine, but after it was found that vitamin C and other such micronutrients were not amines, the word was shortened to "vitamin" in English.[35]
Classification
Vitamins are classified as eitherwater-soluble orfat-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.[47] Because they are not as readily stored, more consistent intake is important.[48] Fat-soluble vitamins are absorbed through thegastrointestinal tract with the help oflipids (fats). Vitamins A and D can accumulate in the body, which can result in dangeroushypervitaminosis. Fat-soluble vitamin deficiency due to malabsorption is of particular significance incystic fibrosis.[49]
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 ofbiotin; it is deactivated by cooking.[50] Pyrithiamine, a synthetic compound, has a molecular structure similar to thiamine,vitamin B1, and inhibits theenzymes that use thiamine.[51]
Biochemical functions
Each vitamin is typically used in multiple reactions, and therefore most have multiple functions.[52]
Vitamins are essential for the normal growth and development of a multicellular organism. Using the genetic blueprint inherited from its parents, afetusdevelops from the nutrients it absorbs. It requires certain vitamins and minerals to be present at certain times.[10] These nutrients facilitate the chemical reactions that produce among other things,skin,bone, andmuscle. 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.[53]
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 forcellular respiration.[7]
Intake
Sources
For the most part, vitamins are obtained from the diet, but some are acquired by other means: for example, microorganisms in thegut flora produce vitamin K and biotin; and one form of vitamin D is synthesized in skin cells when they are exposed to a certain wavelength of ultraviolet light present insunlight. Humans can produce some vitamins from precursors they consume: for example, vitamin A is synthesized frombeta carotene; andniacin is synthesized from theamino acidtryptophan.[54] 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.[9]
Thebody's stores for different vitamins vary widely; vitamins A, D, and B12 are stored in significant amounts, mainly in theliver,[20] 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.[12][20] For vitamin C, the first symptoms of scurvy in experimental studies of complete vitamin C deprivation in humans have varied widely, from a month to more than six months, depending on previous dietary history that determined body stores.[55]
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.[20] People who eat a varied diet are unlikely to develop a severe primary vitamin deficiency, but may be consuming less than the recommended amounts; a national food and supplement survey conducted in the US over 2003–2006 reported that over 90% of individuals who did not consume vitamin supplements were found to have inadequate levels of some of the essential vitamins, notably vitamins D and E.[56]
Well-researched human vitamin deficiencies involve thiamine (beriberi), niacin (pellagra),[32] vitamin C (scurvy), folate (neural tube defects) and vitamin D (rickets).[8] 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.[20] In addition to these classical vitamin deficiency diseases, some evidence has also suggested links between vitamin deficiency and a number of different disorders.[57][58]
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 establishedtolerable upper intake levels (ULs) for those vitamins which have documented toxicity (see table).[11][59][60] The likelihood of consuming too much of any vitamin from food is remote, but excessive intake (vitamin poisoning) from dietary supplements does occur. In 2016, overdose exposure to all formulations of vitamins and multi-vitamin/mineral formulations was reported by 63,931 individuals to theAmerican Association of Poison Control Centers with 72% of these exposures in children under the age of five.[61] 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.[56]
Effects of cooking
TheUSDA has conducted extensive studies on the percentage losses of various nutrients from food types and cooking methods.[62] Some vitamins may become more "bio-available" – that is, usable by the body – when foods are cooked.[63] 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.[64]
Vitamin
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 °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 °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.[59][11][60] For example, for vitamin C, recommended intakes range from 40 mg/day in India[65] to 155 mg/day for the European Union.[66] 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.[67]
RDA US Recommended Dietary Allowances; higher for adults than for children, and may be even higher for women who are pregnant or lactating.
AI US and EFSA Adequate Intake; AIs established when there is not sufficient information to set EARs and RDAs.
PRI Population Reference Intake is European Union equivalent of RDA; higher for adults than for children, and may be even higher for women who are pregnant or lactating. For Thiamin and Niacin the PRIs are expressed as amounts per MJ of calories consumed. MJ = megajoule = 239 food calories.
UL or Upper Limit Tolerable upper intake levels.
ND ULs have not been determined.
NE EARs have not been established.
Supplementation
Calcium combined with vitamin D (as calciferol) supplement tablets with fillers.
In those who are otherwise healthy, there is little evidence that supplements have any benefits with respect tocancer orheart disease.[68][69][70] 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 includedsmokers for whom it was already known that beta-carotene supplements can be harmful.[69][71] A 2018 meta-analysis found no evidence that intake of vitamin D or calcium for community-dwelling elderly people reduced bone fractures.[72]
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 thetolerable 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.[11][59][60]
Dietary supplements often contain vitamins, but may also include other ingredients, such as minerals, herbs, and botanicals.Scientific evidence supports the benefits of dietary supplements for persons with certain health conditions.[73] 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.[73] They may also contain levels of vitamins many times higher, and in different forms, than one may ingest through food.
Most countries place dietary supplements in a special category under the general umbrella offoods, not drugs. As a result, the manufacturer, and not the government, has the responsibility of ensuring that its dietary supplement products are safe before they are marketed. Regulation of supplements varies widely by country. In theUnited States, a dietary supplement is defined under theDietary Supplement Health and Education Act of 1994.[74] There is no FDA approval process for dietary supplements, and no requirement that manufacturers prove the safety or efficacy of supplements introduced before 1994.[32][8] TheFood and Drug Administration must rely on its Adverse Event Reporting System to monitor adverse events that occur with supplements.[75]
In 2007, the USCode 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.[76] In the European Union, theFood Supplements Directive requires that only those supplements that have been proven safe can be sold without a prescription.[77] For most vitamins,pharmacopoeial standards have been established. In the United States, theUnited States Pharmacopeia (USP) sets standards for the most commonly used vitamins and preparations thereof. Likewise, monographs of theEuropean Pharmacopoeia (Ph.Eur.) regulate aspects of identity and purity for vitamins on the European market.
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 B, which became a complex of vitamins.
The Danish-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 coagulation of blood following wounding (from theDanish wordKoagulation). 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.[78][81] The tableNomenclature 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 isfolic acid and five of the folates are in the range B11 through B16. Others, such asPABA (formerly B10), are biologically inactive, toxic, or with unclassifiable effects in humans, or not generally recognised as vitamins by science,[82] such as the highest-numbered, which somenaturopath practitioners call B21 and B22. There are also lettered B substances (e.g., Bm) listed atB 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 treatmentlaetrile 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 ofibuprofen as a pain-relieving treatment.[83]
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