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Vitamin

 Fruit and vegetables on display at a market.
Fruits and vegetables are often a good source of many vitamins.

A vitamin is an organic compound required as a nutrient in tiny amounts by an organism.[1] In other words, an organic chemical compound (or related set of compounds) 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 (vitamin C) is a vitamin for humans, but not for most other animals, and biotin and vitamin D are required in the human diet only in certain circumstances. By convention, the term vitamin does not include other essential nutrients such as dietary minerals , essential fatty acids or essential amino acids (which are needed in larger amounts than vitamins), nor does it encompass the large number of other nutrients that promote health, but are otherwise required less often.[2] Thirteen vitamins are presently universally recognized.

Vitamins are classified by their biological and chemical activity, not their structure. Thus, each "vitamin" refers to a number of 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 four known carotenoids. Vitamers by definition are convertible to the active form of the vitamin in the body, and are sometimes inter-convertible to one another, as well.

Vitamins have diverse biochemical functions. Some have hormone-like functions as regulators of mineral metabolism (e.g. vitamin D), or regulators of cell and tissue growth and differentiation (e.g. some forms of vitamin A). Others function as antioxidants (e.g. vitamin E and sometimes vitamin C).[3] The largest number of vitamins (e.g. B complex vitamins) function as precursors for enzyme cofactors, that help enzymes in their work as catalysts in metabolism. In this role, vitamins may be tightly bound to enzymes as part of prosthetic groups: for example, biotin is part of enzymes involved in making fatty acids. Alternately, vitamins may also be less tightly bound to enzyme catalysts as coenzymes, detachable molecules which function to carry chemical groups or electrons between molecules. For example, folic acid carries various forms of carbon group ' methyl, formyl and methylene - in the cell. Although these roles in assisting enzyme-substrate reactions are vitamins' best-known function, the other vitamin functions are equally important.[4]

Until the mid-1930s, when the first commercial yeast-extract and semi-synthetic vitamin C supplement tablets were sold, 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 semisynthetic and synthetic-source multivitamin dietary supplements, since the middle of the 20th century.

The term vitamin was historically derived from "vitamine," a combination word from vita and amine, meaning amine of life, because it was suggested in 1912 that the organic micronutrient food factors which prevented beriberi and perhaps other similar dietary-deficiency diseases, might be chemical amines. This proved incorrect for the micronutrient class, and the word was shortened to vitamin.

Contents

[edit] History

The discovery dates of the vitamins and their sources (year is approximate, depending on definition of "discovery.")
Year of discovery Vitamin Food source
1913 Vitamin A (Retinol) Cod liver oil, carrots
1910 Vitamin B1 (Thiamine) Rice bran
1920 Vitamin C (Ascorbic acid) Citrus, most fresh foods
1920 Vitamin D (Calciferol) Cod liver oil
1920 Vitamin B2 (Riboflavin) Meat, eggs
1922 Vitamin E (Tocopherol) Wheat germ oil, unrefined vegetable oils
1926 Vitamin B12 (Cobalamins) Liver, eggs, animal products
1929 Vitamin K (Phylloquinone/phytol naphthoquinone) Leafy green vegetables
1931 Vitamin B5 (Pantothenic acid) Meats, whole grains,
in many foods
1931 Vitamin B7 (Biotin) Meats, dairy products, eggs
1934 Vitamin B6 (Pyridoxine) Meat, dairy products.
1936 Vitamin B3 (Niacin) Meat, eggs, grains
1941 Vitamin B9 (Folic acid) Leafy green vegetables

The value of eating a certain food to maintain health was recognized long before vitamins were identified. The ancient Egyptians knew that feeding liver to a patient would help cure night blindness, an illness now known to be caused by a vitamin A deficiency.[5] 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 ships' crews.[6]

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.[5] 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.[5] 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.[5]

During the late 18th and early 19th centuries, 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.[7] In 1881, Russian surgeon Nikolai Lunin studied the effects of scurvy while at the University of Tartu in present-day Estonia.[8] 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."[8] 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.[citation needed]

 Image illustrating rich and good nutritional sources of copper including: oysters, beef or lamb liver, Brazil nuts, blackstrap molasses, cocoa, and black pepper, lobster, nuts and sunflower seeds, green olives, and wheat bran.
The Ancient Egyptians knew that feeding a patient liver (back, right) would help cure night blindness.

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 Imperial 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 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 Takaki and the Japanese Navy that diet was the cause of beriberi, but mistakenly believed that sufficient amounts of protein prevented it.[9] 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 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.[5] Hopkins and Eijkman were awarded the Nobel Prize for Physiology or Medicine in 1929 for their discovery of several vitamins.[10]

In 1910, the first vitamin complex was isolated by Japanese scientist Umetaro Suzuki who succeeded in extracting a water-soluble complex of micronutrients from rice bran and named it aberic acid (later Orizanin). He published this discovery in a Japanese scientific journal.[11] 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 biochemist Kazimierz Funk isolated the same complex of micronutrients and proposed the complex be named "Vitamine" (a portmanteau of "vital amine").[12] 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 researchers began to suspect that not all "vitamines" (particularly vitamin A) had an amine component.[9]

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 anti-scorbutic activity 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 1967, George Wald was awarded the Nobel Prize (along with Ragnar Granit and Haldan Keffer Hartline) for his discovery that vitamin A could participate directly in a physiological process.[10]

[edit] 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 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.[13] Because they are not readily stored, consistent daily intake is important.[14] Many types of water-soluble vitamins are synthesized by bacteria.[15] 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.[16]

[edit] List of vitamins

Each vitamin is typically used in multiple reactions and, therefore, most have multiple functions.[17]

Vitamin generic
descriptor name
Vitamer chemical name(s) (list not complete) Solubility Recommended dietary allowances
(male, age 19'70)[18]
Deficiency disease Upper Intake Level
(UL/day)[18]
Overdose disease
Vitamin A Retinol, retinal, and
four carotenoids
including beta carotene
Fat 900 –g Night-blindness and
Keratomalacia[19]
3,000 –g Hypervitaminosis A
Vitamin B1 Thiamine Water 1.2 mg Beriberi, Wernicke-Korsakoff syndrome N/D[20] Drowsiness or muscle relaxation with large doses.[21]
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)[22] and other problems
Vitamin B5 Pantothenic acid Water 5.0 mg[23] Paresthesia N/D Diarrhea; possibly nausea and heartburn.[24]
Vitamin B6 Pyridoxine, pyridoxamine, pyridoxal Water 1.3'1.7 mg Anemia[25] peripheral neuropathy. 100 mg Impairment of proprioception, nerve damage (doses > 100 mg/day)
Vitamin B7 Biotin Water 30.0 –g Dermatitis, enteritis N/D
Vitamin B9 Folic acid, folinic acid Water 400 –g Deficiency during pregnancy is associated with birth defects, such as neural tube defects 1,000 –g May mask symptoms of vitamin B12 deficiency; other effects.
Vitamin B12 Cyanocobalamin, hydroxycobalamin, methylcobalamin Water 2.4 –g Megaloblastic anemia[26] N/D No known toxicity[26]
Vitamin C Ascorbic acid Water 90.0 mg Scurvy 2,000 mg Vitamin C megadosage
Vitamin D Ergocalciferol, cholecalciferol Fat 5.0 –g'10 –g[27] Rickets and Osteomalacia 50 –g Hypervitaminosis D
Vitamin E Tocopherols, tocotrienols Fat 15.0 mg Deficiency is very rare; mild hemolytic anemia in newborn infants.[28] 1,000 mg Increased congestive heart failure seen in one large randomized study.[29]
Vitamin K phylloquinone, menaquinones Fat 120 –g Bleeding diathesis N/D Increases coagulation in patients taking warfarin.[30]

[edit] In nutrition and diseases

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.[31]

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.[18]

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.[3]

[edit] Deficiencies

Venturi and Venturi[32][33] suggested that when about 500 million years ago plants and animals began to transfer from the sea to rivers and land, environmental deficiency of marine mineral antioxidants, was a challenge to the evolution of terrestrial life. Terrestrial plants slowly optimized the production of 'new' endogenous antioxidants such as ascorbic acid ( Vitamin C), polyphenols, flavonoids, tocopherols etc. Since this age dietary vitamin deficiencies appeared in terrestrial animals. Humans must consume vitamins periodically but with differing schedules, 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,[28] and an adult human's diet may be deficient in vitamins A 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 the human body in significant amounts, so stores may only last a couple of weeks.[19][28] 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 which determined body stores.[34]

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.[28] 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.

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.[18][28] In addition to these classical vitamin deficiency diseases, some evidence has also suggested links between vitamin deficiency and a number of different disorders.[35][36]

[edit] 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 (vitamin poisoning) from vitamin supplementation does occur. At high enough dosages some vitamins cause side effects such as nausea, diarrhea, and vomiting.[19][37] When side effects emerge, recovery is often accomplished by reducing the dosage. The doses of vitamins different individual can tolerate varies widely, and appear to be related to age and state of health.[38]

In 2008, overdose exposure to all formulations of vitamins and multivitamin-mineral formulations was reported by 68,911 individuals to the American Association of Poison Control Centers (nearly 80% of these exposures were in children under the age of 6), leading to 8 "major" life-threatening outcomes and 0 deaths.[39]

[edit] 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 vitamin supplements is well established for certain health conditions, but others need further study.[40] 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.[40] Dietary supplements may also contain levels of vitamins many times higher, and in different forms, than one may ingest through food.[41]

There have been mixed studies on the importance and safety of dietary supplementation. One study released in May 2009 found that antioxidants such as vitamins C and E may actually curb some benefits of exercise.[42] A meta-analysis published 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.[43] National Institutes of Health (NIH) suggests that developments in vitamin E research show that the studies are flawed, and that 'evidence for toxicity of a specific form of tocopherol in excess may not be used to conclude that high-dosage "vitamin E" supplementation may increase all-cause mortality.' [44] Moreover, NIH states that 'the diets of most Americans provide less than the RDA levels of vitamin E.' [45] The majority of the medical community appears to agree with popular consensus that dietary supplementation is important. In a peer reviewed study, Council for Responsible Nutrition (which its own webpage calls a "trade organization") found that '72 percent of physicians and 89 percent of nurses used dietary supplements and that 79 percent of physicians and 82 percent of nurses said that they recommend dietary supplements to their patients.' [46]

[edit] 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. Regulation varies depending on the country. In the E.U., the Food Supplements Directive [47] requires that only those supplements that have been proven safe can be sold without a prescription.

In the United States, a dietary supplement is defined under the Dietary Supplement Health and Education Act of 1994[48] (DSHEA). In addition, the Food and Drug Administration (FDA) uses the Adverse Event Reporting System (AERS) [49] to monitor for new adverse events and errors that might occur with these marketed supplements. The Federal Food, Drug, and Cosmetic Act (FD&C Act) also requires that manufacturers and distributors who wish to market dietary supplements that contain "new dietary ingredients" give notification to FDA, which must include information that a dietary supplement containing a new ingredient will 'reasonably be expected to be safe under the conditions of use recommended or suggested in the labeling.' [50]

Many countries have welcomed guidance from International Alliance of Dietary Supplement Associations (IADSA), an expert organization that aims to build an international platform for the development of the food supplement sector worldwide. The climate is constantly changing in the dietary supplement industry, and will most likely continue to evolve. See also the 'Regulation' section of Dietary Supplements.

[edit] Names in current and previous nomenclatures

Nomenclature of reclassified vitamins
Previous name Chemical name Reason for name change[51]
Vitamin B4 Adenine DNA metabolite; synthesized in body
Vitamin B8 Adenylic acid DNA metabolite; synthesized in body
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 Catechol nonessential; flavin reclassified as B2
Vitamin L1[52] Anthranilic acid Non essential
Vitamin L2[52] Adenylthiomethylpentose RNA metabolite; synthesized in body
Vitamin M Folic acid Reclassified as Vitamin B9
Vitamin O Carnitine Synthesized in body
Vitamin P Flavonoids No longer classified as a vitamin
Vitamin PP Niacin Reclassified as Vitamin B3
Vitamin S Salicylic acid Proposed inclusion[53] of salicylate as an essential micronutrient
Vitamin U S-Methylmethionine Protein metabolite; synthesized in body

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.[51][54] The table on the right 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.

[edit] Anti-Vitamins

Anti-vitamins are chemical compounds that inhibit the absorption or actions of vitamins. For example, avidin is a protein in egg whites that inhibits the absorption of biotin.[55] Pyrithiamine is similar to thiamine vitamin B1 and inhibits the enzymes that use thiamine.[56]

[edit] See also


[edit] References

  1. ^ Lieberman, S, Bruning, N (1990). The Real Vitamin & Mineral Book. NY: Avery Group, 3.
  2. ^ Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. ISBN 0-13-981176-1. OCLC 32308337. 
  3. ^ a b Bender, David A. (2003). Nutritional biochemistry of the vitamins. Cambridge, U.K.: Cambridge University Press. ISBN 978-0-521-80388-5. 
  4. ^ Bolander FF (2006). "Vitamins: not just for enzymes". Curr Opin Investig Drugs 7 (10): 912'5. PMID 17086936. 
  5. ^ a b c d e Jack Challem (1997). "The Past, Present and Future of Vitamins"
  6. ^ Jacob, RA. (1996). "Three eras of vitamin C discovery.". Subcell Biochem 25: 1'16. PMID 8821966. 
  7. ^ Bellis, Mary. Vitamins - Production Methods The History of the Vitamins. Retrieved 1 February 2005.
  8. ^ a b 1929 Nobel lecture
  9. ^ a b Rosenfeld, L. (Apr 1997). "Vitamine'vitamin. The early years of discovery.". Clin Chem 43 (4): 680'5. PMID 9105273. 
  10. ^ a b Carpenter, Kenneth (22 June 2004). "The Nobel Prize and the Discovery of Vitamins". http://nobelprize.org/nobel_prizes/medicine/articles/carpenter/index.html. Retrieved 5 October 2009. 
  11. ^ Tokyo Kagaku Kaishi: (1911)
  12. ^ Funk, C. and H. E. Dubin. The Vitamines. Baltimore: Williams and Wilkins Company, 1922.
  13. ^ Fukuwatari T, Shibata K (June 2008). "Urinary water-soluble vitamins and their metabolite contents as nutritional markers for evaluating vitamin intakes in young Japanese women" ([dead link] ' Scholar search). J. Nutr. Sci. Vitaminol. 54 (3): 223'9. doi:10.3177/jnsv.54.223. PMID 18635909. http://joi.jlc.jst.go.jp/JST.JSTAGE/jnsv/54.223?from=PubMed. 
  14. ^ "Water-Soluble Vitamins". http://www.ext.colostate.edu/PUBS/FOODNUT/09312.html. Retrieved 2008-12-07. 
  15. ^ Said HM, Mohammed ZM (March 2006). "Intestinal absorption of water-soluble vitamins: an update". Curr. Opin. Gastroenterol. 22 (2): 140'6. doi:10.1097/01.mog.0000203870.22706.52. PMID 16462170. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00001574-200603000-00011. 
  16. ^ Maqbool A, Stallings VA (November 2008). "Update on fat-soluble vitamins in cystic fibrosis". Curr Opin Pulm Med 14 (6): 574'81. doi:10.1097/MCP.0b013e3283136787. PMID 18812835. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00063198-200811000-00012. 
  17. ^ Kutsky, R.J. (1973). Handbook of Vitamins and Hormones. New York: Van Nostrand Reinhold.
  18. ^ a b c d Dietary Reference Intakes: Vitamins The National Academies, 2001.
  19. ^ a b c Vitamin and Mineral Supplement Fact Sheets Vitamin A
  20. ^ N/D= "Amount not determinable due to lack of data of adverse effects. Source of intake should be from food only to prevent high levels of intake"(see Dietary Reference Intakes: Vitamins).
  21. ^ "Thiamin, vitamin B1: MedlinePlus Supplements". http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-thiamin.html. Retrieved 5 October 2009. 
  22. ^ J.G. Hardman et al., eds., Goodman and Gilman's Pharmacological Basis of Therapeutics, 10th ed., p.992.
  23. ^ Plain type indicates Adequate Intakes (A/I). "The AI is believed to cover the needs of all individuals, but a lack of data prevent being able to specify with confidence the percentage of individuals covered by this intake" (see Dietary Reference Intakes: Vitamins).
  24. ^ "Pantothenic acid, dexpanthenol: MedlinePlus Supplements". http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-vitaminb5.html. Retrieved 5 October 2009. 
  25. ^ Vitamin and Mineral Supplement Fact Sheets Vitamin B6
  26. ^ a b Vitamin and Mineral Supplement Fact Sheets Vitamin B12
  27. ^ Value represents suggested intake without adequate sunlight exposure (see Dietary Reference Intakes: Vitamins).
  28. ^ a b c d e The Merck Manual: Nutritional Disorders: Vitamin Introduction Please select specific vitamins from the list at the top of the page.
  29. ^ http://findarticles.com/p/articles/mi_m0ISW/is_262/ai_n13675725,
  30. ^ Rohde LE, de Assis MC, Rabelo ER (January 2007). "Dietary vitamin K intake and anticoagulation in elderly patients". Curr Opin Clin Nutr Metab Care 10 (1): 1'5. doi:10.1097/MCO.0b013e328011c46c. PMID 17143047. 
  31. ^ Dr. Leonid A. Gavrilov, Pieces of the Puzzle: Aging Research Today and Tomorrow
  32. ^ Venturi S, Venturi M. Evolution of Dietary Antioxidant Defences. European EPI-Marker. 2007, 11, 3 :1-7. http://web.tiscali.it/iodio/
  33. ^ Venturi S, Donati FM, Venturi A, Venturi M. 2000. Environmental iodine deficiency: A challenge to the evolution of terrestrial life? Thyroid. 10 (8):727-9.
  34. ^ J Pemberton. Medical experiments carried out in Sheffield on conscientious objectors to military service during the 1939'45 war. International Journal of Epidemiology 2006 35(3):556-558; doi:10.1093/ije/dyl020 full text
  35. ^ Lakhan SE; Vieira KF. Nutritional therapies for mental disorders. Nutrition Journal 2008;7(2).
  36. ^ Boy, E.; Mannar, V.; Pandav, C.; de Benoist, B.; Viteri, F.; Fontaine, O.; Hotz, C. (May 2009). "Achievements, challenges, and promising new approaches in vitamin and mineral deficiency control.". Nutr Rev 67 Suppl 1: S24'30. doi:10.1111/j.1753-4887.2009.00155.x. PMID 19453674. 
  37. ^ Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001.
  38. ^ Healthier Kids Section: What to take and how to take it.
  39. ^ Bronstein, AC; et al. (2009). "2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 26th Annual Report" (pdf). Clinical Toxicology 47 (10): 911'1084. doi:10.3109/15563650903438566. PMID 20028214. http://www.aapcc.org/dnn/Portals/0/2008annualreport.pdf. 
  40. ^ a b Use and Safety of Dietary Supplements NIH office of Dietary Supplements.
  41. ^ Jane Higdon Vitamin E recommendations at Linus Pauling Institute's Micronutrient Information Center
  42. ^ Wade, Nicholas (12 May 2009). "Vitamins Found to Curb Exercise Benefits". The New York Times. http://www.nytimes.com/2009/05/12/health/research/12exer.html?em=&pagewanted=print. Retrieved 9 April 2010. 
  43. ^ Bjelakovic G, et al. (2007). "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". JAMA 297 (8): 842'57. doi:10.1001/jama.297.8.842. PMID 17327526. . See also the letter to JAMA by Philip Taylor and Sanford Dawsey and the reply by the authors of the original paper.
  44. ^ [1], Tocotrienols: Vitamin E beyond tocopherols.
  45. ^ [2], Vitamin E.
  46. ^ [3], Physicians and nurses use and recommend dietary supplements: report of a survey.
  47. ^ [4], Directive 2002/46/EC of the European Parliament and of the Council.
  48. ^ US Dietary Supplement Health and Education Act of 1994
  49. ^ [5], Adverse Event Reporting System (AERS).
  50. ^ [6], New Dietary Ingredients in Dietary Supplements - Background for Industry.
  51. ^ a b Every Vitamin Page All Vitamins and Pseudo-Vitamins. Compiled by David Bennett.
  52. ^ a b Michael W. Davidson (2004) Anthranilic Acid (Vitamin L) Florida State University. Accessed 20-02-07
  53. ^ Kamran Abbasi (2003). "Rapid Responses to: Aspirin protects women at risk of pre-eclampsia without causing bleeding". British Medical Journal 327: 7424. doi:10.1136/bmj.327.7424.0-h. http://www.bmj.com/cgi/eletters/327/7424/0-h. 
  54. ^ Vitamins and minerals - names and facts
  55. ^ Roth KS (September 1981). "Biotin in clinical medicine--a review". Am. J. Clin. Nutr. 34 (9): 1967'74. PMID 6116428. http://www.ajcn.org/cgi/reprint/34/9/1967.pdf. 
  56. ^ RINDI G, PERRI V (July 1961). "Uptake of pyrithiamine by tissue of rats". Biochem. J. 80: 214'6. PMID 13741739. 

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