Who Found Vitamin B12, and the Liver Cure That Started It All

A 1926 diet for pernicious anemia led to the 1934 Nobel Prize for liver therapy, and the vitamin itself was isolated in 1948. This history covers where B12 comes from, what Eastern texts say about liver, how intakes and studies differ across countries, and what the evidence shows now.

Vitamin B12 was found in a clinic before it was found in a laboratory. In 1926, George Minot and William Murphy treated people with pernicious anemia with a special diet of large amounts of lightly cooked liver and muscle meat. The vitamin itself was not isolated as crystals until 1948. The 22 years between those two dates are the core of this story. Here is a detail most readers do not expect. The NIH Office of Dietary Supplements says vitamin B12 occurs in foods of animal origin and is not naturally present in plant foods. Fortified breakfast cereals and nutritional yeasts are the plant-based sources it names ([NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/)). This article covers where the vitamin comes from, who found it and when, how the science changed, how health agencies set intakes, and how several countries have studied it. It ends with the evidence and one product, placed last. ## Where vitamin B12 comes from Start with food. The NIH food table lists 70.7 micrograms of B12 in three ounces of cooked, pan-fried beef liver, nearly 30 times the adult Daily Value of 2.4 micrograms ([NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/)). A serving that supplies 25 percent of the Daily Value gives 0.6 micrograms. The NIH also says the bioavailability of B12 from dietary supplements is about 50 percent higher than from food, and that foods fortified with B12, such as nutritional yeasts, can substantially reduce the risk of deficiency. The body keeps a reserve. The NIH says the body stores about 1 to 5 milligrams of vitamin B12, roughly 1,000 to 2,000 times the amount typically consumed in a day, and it links that store to the slow onset of deficiency symptoms. The supplement supply runs through a factory rather than a field. The 2022 review by Álvaro Calvillo and colleagues in Bioengineering says the vitamin can only be produced by fermentation, because its chemical synthesis is so complex ([DOI](https://doi.org/10.3390/bioengineering9080365)). ## The earliest records: Eastern texts first Eastern texts come first, and Ayurveda comes first among them. The Pandu chapter of the Charaka Samhita, chapter 16 of the Chikitsa Sthana, is titled "Management of Pandu (Anemia and diseases due to blood deficiency)" in the online translation cited here ([Charaka Samhita, Pandu chapter](https://www.carakasamhitaonline.com/index.php/Pandu_Chikitsa)). That translation does not date the text, so no date is given for it. The chapter's blood remedies include foods and iron preparations. It recommends a vegetable soup made from the pulses mudga, adhaki and masura, and the meat soup of animals. Several formulas use lauha bhasma, an iron preparation, which the text says should be impregnated for seven nights with cow's urine. A formula called navayasa churna, built on lauha bhasma, is attributed to Krishnatreya. The chapter also lists several mandura formulas, including Mandura vataka and Tapayadi lauha. These are what the text recommends, not advice. Neither the word liver nor its Sanskrit form, yakrit, appears in this chapter. That is a finding about one chapter, not about all of Ayurveda. China has a dated text. Li Shizhen's Bencao Gangmu, completed in 1578, is a large Chinese materia medica. Its volume 50 lower opens its animal entries with cattle, and the cattle entry includes a liver section. The text says liver nourishes the liver and brightens the eyes, citing the earlier Bielu compendium. It also records liver boiled in vinegar and eaten for fevers with chills (瘧) and for dysentery, a use the text credits to Meng Shen ([Li Shizhen, Bencao Gangmu, Siku Quanshu edition, volume 50 lower, Chinese Wikisource](https://zh.wikisource.org/wiki/%E6%9C%AC%E8%8D%89%E7%B6%B1%E7%9B%AE_%28%E5%9B%9B%E5%BA%AB%E5%85%A8%E6%9B%B8%E6%9C%AC%29/%E5%8D%B750%E4%B8%8B)). The cattle liver entry lists no blood condition. The same volume's cattle brain entry includes an added formula for vomiting blood, coughing blood and the "five debilities and seven injuries" (吐血咯血五勞七傷). It uses a water buffalo brain, dried on paper and cooked with skinned almonds, walnut kernels, honey and sesame oil until dry. The mixture is ground and taken with spirit on an empty stomach. The passage does not name the source of this formula. It records what the text recommends, not evidence that it works. We have found no Japanese text that records liver as a treatment, and none that dates the start of liver therapy in Japan. ## Europe and the Islamic world: what the record shows We have found no Greek, Roman or Islamic record of liver used for a blood condition. The clinical picture was known long before the liver diet. According to PubMed, Marvin Stone's 2020 article says William Osler described the clinical findings and blood picture of pernicious anemia nearly a half century before Minot, but that his observations were largely ignored ([DOI](https://doi.org/10.1080/08998280.2020.1784499)). Stone's article says the therapies it covers were discovered shortly after Osler died on 29 December 1919. Physicians had a name for the disease and a picture of its blood changes. What they lacked was a treatment that worked. The liver diet supplied one before anyone could name the factor in liver that did the work. That question runs through the next sections. ## The 1926 liver diet and the 1934 Nobel Prize Minot and Murphy's work was published in 1926. The 2022 Calvillo review describes their treatment as a special diet with high amounts of lightly cooked liver and muscle meat. Minot and Murphy theorized that an unknown "extrinsic factor" in animal liver was responsible ([DOI](https://doi.org/10.3390/bioengineering9080365)). The same review lists the symptoms of the disease, including headaches and, in severe cases, dementia, memory loss, muscle weakness and peripheral neuropathy, which can become lethal without treatment. According to PubMed, Scott and Molloy's 2012 historical review says the 19th-century clinical reports gave enough clinical definition for Minot and Murphy's study. It also says the liver diet produced consistent improvement in the clinical and blood status of all subjects, most of whom remained in remission indefinitely ([DOI](https://doi.org/10.1159/000343114)). The prize followed. In 1934, the Nobel Committee gave the Prize in Physiology or Medicine jointly to George Hoyt Whipple, George Richards Minot and William Parry Murphy "for their discoveries concerning liver therapy in cases of anaemia" ([NobelPrize.org](https://www.nobelprize.org/prizes/medicine/1934/summary/)). The citation names a treatment, not a vitamin. The prize honored the treatment before anyone had identified the molecule that made it work. The same review describes what untreated deficiency could do. According to PubMed, many early clinical studies recognized that B12 deficiency caused a severe neuropathy leading to paralysis and death, and post-mortem analysis showed spinal cord demyelination. The article notes that vitamin B12 is still the subject of intense research ([DOI](https://doi.org/10.1159/000343114)). ## Intrinsic factor: why the stomach matters Food B12 has to be freed from its protein before the body can use it. According to the NIH, stomach acid and enzymes release it, it binds haptocorrin in saliva, and in the duodenum digestive enzymes free it so it can bind intrinsic factor. Intrinsic factor is a binding protein secreted by the stomach's parietal cells. The complex is absorbed in the distal ileum by receptor-mediated endocytosis ([NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/)). Castle's experiments set out the distinction between extrinsic and intrinsic factors. According to PubMed, a 1999 historical review by K. Okuda of Chiba University describes those experiments as establishing the theory of extrinsic and intrinsic factors as hemopoietic principles ([PubMed](https://pubmed.ncbi.nlm.nih.gov/10207776/)). Pernicious anemia breaks that chain at its first link. The NIH describes atrophic gastritis, an autoimmune condition that affects 2 percent of the general population and 8 to 9 percent of adults aged 65 and older. The NIH describes it as an irreversible autoimmune disease that affects the gastric mucosa and results in gastric atrophy. It also says pernicious anemia is the most common cause of clinically evident B12 deficiency around the world. Without intrinsic factor, food B12 is not absorbed in the usual way. The dose arithmetic is the practical part. The NIH says absorption is about 50 percent at doses under 1 to 2 micrograms, which fall within the binding capacity of intrinsic factor. Above that, absorption is substantially lower, at about 2 percent at 500 micrograms. A small percentage of a large dose can still add up to a meaningful amount. ## From liver to crystal, 1948 The vitamin was isolated in 1948, when the factor was still called the "anti-pernicious anaemia factor." The University of Bristol chemistry page credits Folkers and his co-workers at Merck Laboratories, and Smith and Parker at Glaxo Laboratories, with isolating the crystals, and says small red crystals of vitamin B12 were then grown ([University of Bristol](https://www.chm.bris.ac.uk/motm/vitaminb12/life.html)). Calvillo's review names the same teams and says they isolated a cobalt compound from animal liver at almost the same time ([DOI](https://doi.org/10.3390/bioengineering9080365)). The review describes the compound as a red crystalline octahedral cobalt compound, which it calls vitamin B12. It adds that the same compound could also be isolated from milk, beef and several bacterial cultures. Both the Bristol page and the Calvillo review date the isolation to 1948. According to PubMed, Okuda's 1999 historical review describes studies on purification of the anti-pernicious anaemia principle from liver tissue that ended in the crystallization of vitamin B12 and identification of its coenzyme forms ([PubMed](https://pubmed.ncbi.nlm.nih.gov/10207776/)). ## Dorothy Hodgkin and the structure Dorothy Hodgkin is the name most readers do not connect to a vitamin. The Nobel Prize biography says her research on vitamin B12 began in 1948 ([NobelPrize.org](https://www.nobelprize.org/prizes/chemistry/1964/hodgkin/biographical/)). Her 1964 Nobel Prize in Chemistry was given "for her determinations by X-ray techniques of the structures of important biochemical substances." The citation does not name B12 itself ([NobelPrize.org](https://www.nobelprize.org/prizes/chemistry/1964/summary/)). According to PubMed, Scott and Molloy's review says the vitamin was isolated by two groups simultaneously and was crystallized and characterized in Hodgkin's laboratory ([DOI](https://doi.org/10.1159/000343114)). The Calvillo review says Hodgkin solved the structure of the first cobalamin isoform in 1955 ([DOI](https://doi.org/10.3390/bioengineering9080365)). The next section covers what that molecule is built from. ## Structure, cobalt, and the two active forms Vitamin B12 is a family of compounds, and the family name carries the chemistry. The NIH says the vitamin contains the mineral cobalt, which is why its compounds are called cobalamins ([NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/)). The Calvillo review describes the core as a corrin ring, with a central cobalt atom bonded to four nitrogen atoms, a design it compares with heme in hemoglobin ([DOI](https://doi.org/10.3390/bioengineering9080365)). Two forms are active in the body. The NIH names methylcobalamin and 5-deoxyadenosylcobalamin as the metabolically active forms. Hydroxocobalamin and cyanocobalamin become active after conversion into one of those two. Vitamin B12 is a cofactor for two enzymes. Methionine synthase converts homocysteine into methionine, which is needed to make S-adenosylmethionine, a methyl donor used by almost 100 different substrates. The NIH ties B12 to three functions: development and function of the central nervous system, healthy red blood cell formation, and DNA synthesis. ## How chemists built it, and why the label says cyanocobalamin The full chemical synthesis was a long road. The Calvillo review notes an elaborate biosynthesis, with over 30 biotransformation steps in organisms. It also says Woodward and colleagues described the complete synthesis in 1973, after a study that spanned more than a decade. The route involved more than 60 steps and gave very low yields, under 1 percent ([DOI](https://doi.org/10.3390/bioengineering9080365)). The Bristol page gives a different measure of the same effort. It says the synthesis took 11 more years, with more than 90 separate reactions performed by over 100 co-workers ([University of Bristol](https://www.chm.bris.ac.uk/motm/vitaminb12/life.html)). Calvillo says the adenosyl and methyl forms are light sensitive, while cyanocobalamin is more stable and is readily converted in the body into an active coenzyme form. The review presents that stability as the reason the commercial form is cyanocobalamin ([DOI](https://doi.org/10.3390/bioengineering9080365)). The NIH agrees that cyanocobalamin is the most common form in dietary supplements, with adenosylcobalamin, methylcobalamin and hydroxocobalamin also in use ([NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/)). ## Making B12 for the bottle: fermentation and production Because synthesis is so complex, supplemental B12 is made by microbes. The 2022 Calvillo review says the vitamin can only be produced by fermentation ([DOI](https://doi.org/10.3390/bioengineering9080365)). It describes the dominant worldwide producers as based in China, naming North China Pharmaceutical Company, the Henan Luyuan Pharmaceutical Company, the Hebei Yuxing Bio-Engineering Company and the Chinese CSPC Huarong Pharmaceutical Company. It reports combined output of about 31.41 tons in 2020, with an estimated value of USD 339.8 million. The strains have a history. The review says a high-producing Pseudomonas strain, MB-580, was first described and patented in 1962. It says the French company Rhône-Poulenc, now part of Sanofi, developed improved strains from that line, and it describes Sanofi as the main European vitamin B12 manufacturer. The review says the Sanofi strain was originally generated by a combination of random mutagenesis and molecular biology techniques. According to PubMed, a 2026 chapter led by Zhang Dawei of the Tianjin Institute of Industrial Biotechnology calls microbial fermentation the core method for industrial production. It names strains such as Pseudomonas denitrificans and Propionibacterium freudenreichii, and says production remains relatively low ([DOI](https://doi.org/10.1007/10_2026_338)). No record we have found dates the start of vitamin B12 production in Japan or China. ## How health agencies set intakes, and where they differ The figures below rest on different methods and different years, so they are not interchangeable. Side by side, they still disagree on the adult figure. The United States sets an RDA of 2.4 micrograms a day for adults aged 19 and older, 2.6 micrograms in pregnancy and 2.8 micrograms in lactation. The NIH cites a 1998 National Academies report for these values. Across age groups, the NIH lists 0.4 to 2.8 micrograms for infants, children and adolescents, depending on age. It says no tolerable upper intake level was set, because vitamin B12 has a low potential for toxicity ([NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/)). The European Food Safety Authority set a different kind of figure in its 2015 scientific opinion, EFSA Journal opinion 4150. It sets an Adequate Intake of 4 micrograms a day for adults, based on several biomarkers of B12 status. It also notes observed mean intakes of 4.2 to 8.6 micrograms a day in several EU countries ([EFSA](https://www.efsa.europa.eu/en/efsajournal/pub/4150)). The United Kingdom's 1991 Department of Health guide, Dietary Reference Values: A Guide, gives a reference nutrient intake (RNI), the level that meets the needs of nearly all people in a group, of 1.5 micrograms a day for people aged 15 and over. Its estimated average requirement is 1.25 micrograms, and its lower reference nutrient intake is 1.0 microgram ([Department of Health, 1991](https://assets.publishing.service.gov.uk/media/5bab995240f0b607130bd49d/Dietary_Reference_Values_-_A_Guide__1991_.pdf)). The guide says the RNI is enough not only to prevent anaemia but also to create liver stores of the vitamin. The Indian Council of Medical Research (ICMR) and the National Institute of Nutrition published a 2020 brief note on Nutrient Requirements for Indians. It sets a recommended dietary allowance of 2.2 micrograms a day for adult men and women, with an estimated average requirement of 2.0 micrograms. The 2010 RDA was 1.0 microgram. The note recommends the EAR for assessing population adequacy and for diet planning, and it defines the RDA as the 97.5th percentile of the requirement distribution ([ICMR-NIN 2020](https://www.nin.res.in/rdabook/brief_note.pdf)). Japan's Ministry of Health, Labour and Welfare (MHLW) summarized its 2025 Dietary Reference Intakes for Japanese in February 2025. For vitamin B12 it sets an adequate intake (目安量) and no estimated average requirement, recommended dietary allowance or tolerable upper intake level ([MHLW, February 2025](https://www.mhlw.go.jp/content/10904750/001734207.pdf)). The EFSA adult figure of 4 micrograms sits well above the 1.5 microgram UK figure from 1991 and the 2.2 microgram Indian RDA. The EFSA figure is an adequate intake set from several biomarkers of status. The UK and Indian values are built on estimated average requirements. ## What makes this history interesting Four facts make this story worth telling beyond the bottle. The first is where the vitamin comes from. The NIH says plant foods do not naturally contain it, and the supplement is made by microbes, so it is a fermentation product rather than a crop. The second is the timeline. Physicians had a working treatment in 1926 and a purified vitamin in 1948, 22 years apart. The third is the chemistry: a cobalt-centered ring whose full synthesis took more than a decade. The fourth is the reserve. The NIH says adults store about 1 to 5 milligrams, roughly 1,000 to 2,000 times a typical day's intake, which is why the first symptoms are slow to appear. ## How the science has been studied, country by country The UK. Alesia Hunt, Dominic Harrington and Susan Robinson, of the haematology department at Guy's and St Thomas' NHS Foundation Trust in London, wrote a review titled "Vitamin B12 deficiency" for the BMJ in 2014. The NIH fact sheet cites the review ([PubMed](https://pubmed.ncbi.nlm.nih.gov/25189324/)). China. According to PubMed, a 2025 single-center cross-sectional study at China-Japan Friendship Hospital in Beijing examined 303 patients with autoimmune gastritis over eight years. Of them, 116 had gastric neuroendocrine tumors and 187 did not. Vitamin B12 deficiency was more common in the tumor group, at 77.2 percent, than in the group without tumors, at 55.8 percent ([DOI](https://doi.org/10.3748/wjg.v31.i41.111449)). A cross-sectional design shows an association, not a cause. Japan. According to PubMed, a 2025 study in Rinsho Ketsueki, The Japanese Journal of Clinical Hematology, tested a non-invasive way to identify myelodysplastic neoplasms using gradient-boosted models, WT1 levels and vitamin B12 deficiency. Among patients with probable or indeterminate disease and WT1 levels above 150 copies per microgram of RNA, the share correctly diagnosed rose from 87.2 percent to 91.9 percent when patients with vitamin B12 deficiency were excluded from the analysis ([DOI](https://doi.org/10.11406/rinketsu.66.535)). India. According to PubMed, a 2025 retrospective cohort study from HealthWatch Nutrition Clinic in Mumbai examined women with polycystic ovary syndrome. It found that vitamin B12 and vitamin D3 levels had no significant impact on metabolic parameters, while body mass index and waist circumference were stronger predictors of metabolic risk ([DOI](https://doi.org/10.59556/japi.73.1281)). ## What the evidence shows now, and where it is disputed The NIH reviews the evidence for B12 in four areas: cancer, cardiovascular disease, dementia and cognitive function, and energy and endurance. Treatment is the best-studied question. According to PubMed, a 2018 Cochrane review by Wang and colleagues found three randomized trials with 153 participants comparing oral and intramuscular vitamin B12. The oral arms used 1,000 or 2,000 micrograms a day. The authors rated the evidence that the two routes normalize serum levels similarly as low quality, noted that oral treatment costs less, and rated the safety evidence as very low quality ([DOI](https://doi.org/10.1002/14651858.CD004655.pub3)). The NIH says high oral doses "might also be effective" for deficiency. It also says high oral doses of methylcobalamin, 1,000 micrograms a day, appear as effective as hydroxocobalamin injections in normalizing B12 levels. For Crohn's disease, the NIH notes that injections are typical, but high oral cyanocobalamin, such as 1,000 micrograms a day, might be equally effective. Injected B12, in the forms cyanocobalamin and hydroxocobalamin, is a prescription medication usually given intramuscularly. The NIH also says evidence suggests no difference in efficacy between oral and sublingual forms. Cognition is where claims run ahead of data. The NIH reports that randomized controlled trials have shown no improvement in cognitive function among older adults with or without dementia, mild cognitive impairment or Alzheimer's disease, whether B12 was given alone or with folic acid or vitamin B6. A study the NIH cites, of 27,882 participants, most of them 60 or older, found little to no effect on global cognitive function when supplements were given for up to five years. A separate Cochrane review of people with mild cognitive impairment included five trials with 879 participants that studied B vitamin supplements, according to the NIH. Readers looking at brain-health supplements can start with our [brain health guide](/health/brain-health-focus-complete-guide). Our monographs on [citicoline](/ingredients/citicoline) and [bacopa monnieri](/ingredients/bacopa-monnieri) cover the evidence for those ingredients. Heart, energy and cancer claims are weaker still. The NIH says there is no association between B12 supplementation and cardiovascular disease, although supplements lower homocysteine. It says supplementation does not appear to improve athletic performance or endurance in people with sufficient B12 status. On cancer, it says the evidence is mixed, with some studies linking higher intake or blood levels to higher risk, some linking lower levels to higher risk, and some finding no link. Form and medicines matter in a different way. The NIH says no evidence indicates that absorption rates of supplemental B12 vary by form. It notes that sublingual preparations come as tablets or lozenges. It lists prolonged use of metformin and proton pump inhibitors among the causes or risk factors for deficiency. It also says no tolerable upper intake level has been set, because vitamin B12 is generally considered safe even at large doses ([NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/)). ## Bottom line According to the NIH, average intake from food and beverages in NHANES data is 5.84 micrograms a day for men aged 20 and older and 3.69 micrograms for women. About 24 percent of men and 29 percent of women reported using a supplement containing B12 in NHANES 2017 to March 2020. Both averages are above the 2.4 microgram adult RDA, but deficiency still happens. The NIH estimates that about 3.6 percent of US adults aged 19 and older were deficient in 2007 to 2018 data, using a serum cutoff below 200 picograms per milliliter. Using a cutoff below 300, about 12.5 percent were in the insufficient range. Cutoffs change the picture: in NHANES data from 1999 to 2004, the rate of low levels was 3 percent at a cutoff below 200 picograms per milliliter and 26 percent at a cutoff below 350. The NIH notes that experts suggest checking serum methylmalonic acid when B12 falls between 150 and 399 picograms per milliliter. It also says low or marginal status without symptoms is much more common than clinical deficiency, at up to 40 percent in Western populations, and lists symptoms that include glossitis of the tongue, fatigue, palpitations, pale skin, weight loss and infertility. If you eat animal foods regularly and have no absorption problem, food may cover your needs. If you take metformin or a proton pump inhibitor, are older, or have a known stomach or absorption problem, ask a clinician about testing before you guess. The form on the label matters less than the dose you take and whether your level has been checked. ## A label check, and our B-12 Essential Trio When you compare B12 labels, check three numbers: micrograms per serving, servings per container and price per serving. Our [B-12 Essential Trio](https://mtangelvitamins.com/products/b12-sublingual-essential-trio?utm_source=learn_hub&utm_medium=content&utm_campaign=blog_post&utm_content=history-of-vitamin-b12-from-liver-cure-to-cobalamin) is a 2 fluid ounce liquid. Its product page lists 2,000 micrograms of vitamin B12 as methylcobalamin per serving, one dropper squeeze of about 0.84 grams, with 680 micrograms DFE of folate as folinate and 4 milligrams of vitamin B6. The bottle lists 80 servings, and the page says to refrigerate after opening. At $25.99, the price works out to about 32 cents a day at one serving daily. The NIH names methylcobalamin as one of the two active forms the body uses. It says B12 is required for healthy red blood cell formation and for the development and function of the central nervous system. It also reports that evidence suggests no difference in efficacy between oral and sublingual forms, so dose, daily cost and the testing behind the lot are the first things to compare. Our [supplement safety and quality testing guide](/health/vitamin-d-complete-guide/supplement-safety-quality-testing-guide) covers the testing side in more detail. ## Frequently asked questions ### What was pernicious anemia before B12 was known? Pernicious anemia was a serious blood disease, and untreated B12 deficiency could be fatal. According to PubMed, Scott and Molloy's 2012 article describes a severe neuropathy leading to paralysis and death, with spinal cord demyelination found on post-mortem analysis ([DOI](https://doi.org/10.1159/000343114)). According to PubMed, Marvin Stone's 2020 article says William Osler described its blood picture nearly half a century before Minot, though his observations were largely ignored ([DOI](https://doi.org/10.1080/08998280.2020.1784499)). ### How did eating liver become a treatment in the 1920s? In 1926, Minot and Murphy put people with pernicious anemia on a special diet of high amounts of lightly cooked liver and muscle meat. The 2022 Calvillo review says the diet freed patients from the condition, and that the authors theorized an unknown "extrinsic factor" in animal liver was responsible ([DOI](https://doi.org/10.3390/bioengineering9080365)). The approach worked before anyone could name the factor in liver that did the work, which is why the 1934 prize honored a treatment rather than a molecule. ### Who won the Nobel Prize for the liver work, and when? In 1934, the Nobel Prize in Physiology or Medicine went jointly to George Hoyt Whipple, George Richards Minot and William Parry Murphy. The citation honors their "discoveries concerning liver therapy in cases of anaemia" ([NobelPrize.org](https://www.nobelprize.org/prizes/medicine/1934/summary/)). It does not name a vitamin. The vitamin itself was isolated in 1948, fourteen years later. ### When was the vitamin itself isolated, and by whom? The vitamin was isolated in 1948, when the factor was still called the "anti-pernicious anaemia factor." The University of Bristol chemistry page credits Folkers and his co-workers at Merck Laboratories, and Smith and Parker at Glaxo Laboratories, with isolating the crystals ([University of Bristol](https://www.chm.bris.ac.uk/motm/vitaminb12/life.html)). The 2022 Calvillo review names the same teams and says they isolated a cobalt compound from animal liver at almost the same time ([DOI](https://doi.org/10.3390/bioengineering9080365)). Dorothy Hodgkin's X-ray work on the structure came after that. ### Why does B12 absorption depend on intrinsic factor? Food B12 must be released from its protein and then bind intrinsic factor, a binding protein secreted by the stomach's parietal cells. The complex is absorbed in the distal ileum ([NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/)). The NIH says absorption falls off once the binding capacity of intrinsic factor is exceeded, at about 1 to 2 micrograms. Pernicious anemia breaks that chain, so food B12 is not absorbed in the usual way. ### How is supplemental B12 made today? Mostly by microbial fermentation. The 2022 Calvillo review says the vitamin can only be produced that way, because its chemical synthesis is so complex ([DOI](https://doi.org/10.3390/bioengineering9080365)). According to PubMed, a 2026 chapter led by Zhang Dawei names strains such as Pseudomonas denitrificans and Propionibacterium freudenreichii as core to industrial production, and says production remains relatively low ([DOI](https://doi.org/10.1007/10_2026_338)). The Calvillo review lists the dominant worldwide producers as based in China. ### Which B12 forms appear on labels, and where do they come from? Cyanocobalamin is the most common form in dietary supplements, according to the NIH. Methylcobalamin, adenosylcobalamin and hydroxocobalamin also appear. The NIH says no evidence indicates that absorption rates vary by form. The Calvillo review explains why cyanocobalamin is the commercial form: it is more stable than the light-sensitive adenosyl and methyl forms, and the body readily converts it into an active form ([DOI](https://doi.org/10.3390/bioengineering9080365)). A label tells you which form is in the bottle, not which form works better. ## Next reads - [Our brain health guide](/health/brain-health-focus-complete-guide) covers the wider evidence on brain-health supplements, including the cognition trials discussed above. - [Who actually owns your vitamins](/blog/new/who-actually-owns-your-vitamins) asks who stands behind a supplement label, which matters as much as the molecule inside it. ### Related reading - [Folate history from Lucy Wills to fortified bread](/blog/history/history-of-folate-from-lucy-wills-to-fortified-bread) - [Iron supplements and the ferritin test](/blog/history/history-of-iron-supplements-and-the-ferritin-test) - [Vitamin C from scurvy to ascorbic acid](/blog/history/history-of-vitamin-c-from-scurvy-to-ascorbic-acid) - [The B12 history post](/blog/history/history-of-the-b-complex-from-one-factor-to-eight) - [The thiamin story: rice, beriberi and the chicken studies](/blog/history/history-of-thiamine-b1-from-beriberi-to-eijkman)