Who Found Vitamin B6, and How Rat Skin Studies Led to P5P

Vitamin B6 began with rats that developed skin lesions on a purified diet. Its active coenzyme, P5P, works in more than 100 enzyme reactions, and pyridoxine is the most common form in supplements. The ODS upper limit for adults is 100 mg a day.

The history of vitamin B6 starts with rats that developed skin lesions on a purified diet. Paul Gyorgy showed in 1934 that the factor curing that condition was vitamin B6. Today the name covers six related compounds, and the coenzyme they become works in more than 100 enzyme reactions. ## Rat skin lesions pointed to a missing factor In the 1930s, Rudolf Peters showed that young rats fed a semi-synthetic diet with added thiamin and riboflavin, and nothing else, developed "rat acrodynia," a condition with severe skin lesions. According to PubMed, Irwin Rosenberg's 2012 history of the work says Gyorgy showed in 1934 that the cure was vitamin B6 ([DOI](https://doi.org/10.1159/000343113)). Gyorgy's 1934 Nature letter, "Vitamin B2 and the Pellagra-like Dermatitis in Rats," is one record of that research ([DOI](https://doi.org/10.1038/133498a0)). The [National Medal of Science citation](https://nationalmedals.org/laureate/paul-gyorgy/) for Gyorgy describes the same condition and cure. For another B vitamin with a cure-first history, see [the vitamin B12 origin story](/blog/history/history-of-vitamin-b12-from-liver-cure-to-cobalamin). ## Six compounds, one active coenzyme The [NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/) (ODS) says vitamin B6 is the generic name for six compounds: pyridoxine, pyridoxal and pyridoxamine, plus their 5'-phosphate esters. According to PubMed, Samuel Lepkovsky isolated and crystallized the vitamin in 1938. In 1939, Leslie Harris and Karl Folkers, and Richard Kuhn's group, independently showed it was a pyridine derivative, and Gyorgy proposed the term pyridoxine for that derivative ([DOI](https://doi.org/10.1159/000343113)). According to the [NAS memoir of Roger Williams](https://www.nasonline.org/wp-content/uploads/2024/06/williams-roger.pdf), people in his institute in Austin created the names pyridoxal and pyridoxamine. ## Enzymes that depend on B6 Once converted to the coenzyme, B6 works in more than 100 enzyme reactions, mostly in protein metabolism, per the ODS. For the energy side of those reactions, see our [mitochondrial health guide](/health/mitochondrial-health-complete-guide). According to PubMed, Rosenberg's history notes that pyridoxal, pyridoxamine and pyridoxine have largely equal activity in animals, because the body converts each to PLP. A riboflavin-linked step controls that conversion. McCormick's 2000 review describes a flavin mononucleotide-dependent oxidase that turns the phosphates of pyridoxine and pyridoxamine into PLP, and calls it the primary control point ([DOI](https://doi.org/10.1093/jn/130.2.323S)). Transamination, the transfer of an amino group between molecules, is one of the reactions that mapped this role. According to PubMed, Alexander Braunstein's group discovered enzymatic transamination in the mid-1930s, and by the mid-1950s its wide scope and biological importance were clear ([DOI](https://doi.org/10.1016/0300-9084(89)90169-7)). ## What the ODS says about too much B6 Food has not been reported to cause adverse effects, the ODS says. Chronic pyridoxine doses of 1 to 6 grams a day for 12 to 40 months can cause severe, progressive sensory neuropathy. The FNB set the adult upper limit at 100 mg a day after halving the 200 mg average dose used in studies of up to five years that found no such effect. Frank deficiency is relatively rare in the United States. ## Where P5P fits on the label The most common form in supplements is pyridoxine hydrochloride, and some products use PLP, according to the ODS. [P5P 50 mg](https://mtangelvitamins.com/products/p5p-50mg-vitamin-b6-supplement?utm_source=learn_hub&utm_medium=content&utm_campaign=blog_post&utm_content=history-of-vitamin-b6-from-pyridoxine-to-p5p) from Mt. Angel Vitamins lists 34 mg of vitamin B6 from 50 mg of P5P in each capsule, with 60 capsules to a bottle at one a day. P5P is the coenzyme form that the enzymes above use, so the label names the form directly. For another B vitamin history, see [the folate origin story](/blog/history/history-of-folate-from-lucy-wills-to-fortified-bread). ## Bottom line Vitamin B6 has a well-documented history and a clear high-dose warning. The ODS sets a recommended intake of 1.3 mg a day for adults aged 19 to 50 and a 100 mg upper limit. If you take a B6 product, add up every source, including multivitamins and B-complex blends, before you choose a dose. ## Frequently asked questions ### Which animal studies first pointed to vitamin B6? Rudolf Peters's 1930s work described "rat acrodynia" in young rats fed a purified diet with thiamin and riboflavin. Paul Gyorgy showed in 1934 that the factor curing it was vitamin B6, according to Rosenberg's 2012 history on PubMed. Later studies found convulsions in rats, pigs and dogs, and a microcytic anemia in some animals. The ODS describes frank deficiency in people as relatively rare in the United States. ### Who named vitamin B6, and when? The sources used here do not credit one person with coining "vitamin B6." Gyorgy showed in 1934 that the rat cure was vitamin B6, and in 1939 he proposed the term pyridoxine for the pyridine derivative, according to Rosenberg's history on PubMed. Lepkovsky had isolated and crystallized the vitamin in 1938. The names pyridoxal and pyridoxamine came from people in Roger Williams's institute, according to the NAS memoir. ### What is the difference between pyridoxine and P5P? Pyridoxine is the alcohol form of the vitamin. Pyridoxal 5'-phosphate, written P5P or PLP, is the active coenzyme, according to the ODS. Pyridoxine hydrochloride is the most common form in supplements, and some products contain PLP. Rosenberg's review says the main forms have largely equal activity in animals, because the body converts them to PLP. Both routes end at the same coenzyme. ### Which enzymes depend on vitamin B6? The ODS says the coenzyme forms take part in more than 100 enzyme reactions, mostly in protein metabolism. Transamination, the transfer of amino groups between molecules, is one reaction that Alexander Braunstein's group mapped in the mid-1930s, according to a 1989 PubMed review by Cooper and Meister. McCormick's 2000 review calls the oxidase that makes PLP the primary control point for that conversion. ### How much vitamin B6 is too much? Food sources have not been reported to cause adverse effects, the ODS says. Chronic doses of 1 to 6 grams of pyridoxine a day for 12 to 40 months can cause severe, progressive sensory neuropathy. The FNB set the adult upper limit at 100 mg a day, after halving the 200 mg average dose from studies of up to five years that found no such effect. Upper limits for children are lower, based on body size. ### Why does B6 appear in the neurotransmitter story? The ODS says vitamin B6 plays a role in the biosynthesis of neurotransmitters, and in keeping homocysteine, an amino acid in the blood, at normal levels. The sources used here describe the neurotransmitter role in general terms and do not spell out a melatonin step, so this page does not claim one. Our [melatonin monograph](/ingredients/melatonin) covers that hormone on its own page. ## Next reads - [Our mitochondrial health guide](/health/mitochondrial-health-complete-guide) covers the energy side of enzyme chemistry in more detail. - [The folate origin story](/blog/history/history-of-folate-from-lucy-wills-to-fortified-bread) is another B vitamin history, this one ending in fortified bread. ### Related reading - [the B-complex origin story, from one factor to eight](/blog/history/history-of-the-b-complex-from-one-factor-to-eight) - [the biotin origin story, from egg white injury to vitamin H](/blog/history/history-of-biotin-from-egg-white-injury-to-vitamin-h)