Folate and Folic Acid: From 1930s Bombay to Fortified Bread

Folate is the B vitamin in food. Folic acid is the synthetic form in supplements and fortified flour. This history starts with Ayurvedic and Unani texts, follows Lucy Wills's 1930s anemia papers in Bombay, and ends with the neural tube trials, the 1996 US grain rule and the national positions of the EU, the UK and China.

Folate is the B vitamin that occurs in food. Folic acid is the synthetic form that goes into supplements and fortified flour. People use the two words as if they mean the same thing, and the history of how they came apart is longer and stranger than most accounts admit. This article follows that history from three directions. It starts with medical texts from South and East Asia, which are older than any folate chemistry. It moves to 1930s Bombay, where a British physician named Lucy Wills treated anemia in pregnant women and described the use of a yeast extract, Marmite, against it. It ends with the trials and rules that tied folic acid to neural tube defects, and with the national positions that still differ. One surprise comes early. According to the NIH Office of Dietary Supplements, bacteria in the colon also make some folate, although how much of it the body can use is unclear. ## What the names mean Folate is the umbrella term. The [NIH Office of Dietary Supplements](https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/) (ODS) says folate was formerly known as folacin and is sometimes called vitamin B9. It covers the naturally occurring folates in food, the folates in supplements, and the folates in fortified foods, including folic acid. Folic acid is the fully oxidized form used in most supplements and in fortified foods. Some supplements contain 5-methyltetrahydrofolate (5-MTHF) instead. ODS notes that no formal conversion factor has been set for supplemental 5-MTHF on the dietary folate equivalent scale. Labels use dietary folate equivalents (DFE) because the body absorbs folic acid better than the folate already in food. ODS gives the conversion this way: 1 mcg DFE equals 1 mcg of food folate, 0.6 mcg of folic acid from fortified food or a supplement taken with food, or 0.5 mcg of folic acid from a supplement taken on an empty stomach. ODS estimates that at least 85 percent of folic acid is bioavailable when taken with food, compared with about 50 percent of the folate that occurs naturally in food. ## Where folate comes from According to ODS, folate occurs in dark green leafy vegetables, fruits and fruit juices, nuts, beans, peas, seafood, eggs, dairy, meat, poultry and grains. Spinach, liver, asparagus and Brussels sprouts rank among the richest sources. ODS's table lists braised beef liver at 215 mcg DFE per three-ounce serving, which is 54 percent of the Daily Value. ## Eastern medical texts: what they describe Ayurveda is the first thread. Britannica's entry on the Sushruta Samhita describes the Caraka Samhita and the Sushruta Samhita as texts attributed to Caraka, a physician, and Sushruta, a surgeon. It estimates that the Caraka Samhita reached its present form around the 1st century CE, after earlier versions, and that the Sushruta Samhita probably originated in the last centuries BCE. Ayurvedic literature has also been sorted into historical periods. According to PubMed, a 2022 review in the Chinese journal Zhonghua Yi Shi Za Zhi, by Li and colleagues, divides it into Vedic, Samhita, Sangraha and modern periods ([DOI](https://doi.org/10.3760/cma.j.cn112155-20210423-00059)). The modern transmission matters as well. According to PubMed, a 2024 article by Sunil K. Pandya in the Journal of Medical Biography describes Pranjivandas Manekchand Mehta (1889 to 1981), a physician in Bombay who oversaw a detailed translation of an ancient Sanskrit medical text into English, Hindi and Gujarati, published in six volumes in 1949. The article's keywords name the Caraka Samhita ([DOI](https://doi.org/10.1177/09677720241304740)). Both texts are dated. As far as we have found, neither the Caraka Samhita nor the Sushruta Samhita contains a passage recommending leafy greens or legumes for anemia. Unani and Persian medicine comes next. A Bodleian Libraries document dates Ibn Sina's Canon of Medicine to 1025, describes it as a five-volume work, and says its authority lasted into the late 1600s in both the Islamic world and Europe. The same document says the Canon incorporated Persian, Chinese and Indian practice. We have found no passage in the Canon on greens or legumes. Korean practice offers another text. According to PubMed, a 2017 study of herbal prescriptions at a Korean hospital, by Lee and colleagues, used the Dongui-Bogam to classify the medicines it recorded ([DOI](https://doi.org/10.1007/s11655-017-2903-0)). We have found no folate-related use in that text. The Chinese materia medica is the other classical thread. According to PubMed, a 2022 paper in the Journal of Ethnopharmacology notes that ginkgo fruit was used for cough, asthma and as a disinfectant, and that the Compendium of Materia Medica (Ben Cao Gang Mu) and Shen Nong's herbal classic (Shen Nong Ben Cao Jing) contain similar records ([DOI](https://doi.org/10.1016/j.jep.2022.115602)). No Traditional Chinese Medicine or Kampo text we have found documents a folate-related use. We have found no Greek, Roman, Islamic or European record of greens or legumes used for anemia, so none is described here. ## Bombay in the 1930s: Lucy Wills and the anemia of pregnancy Lucy Wills's published record starts before Bombay. According to PubMed, her note "Production of pernicious anaemia (Bartonella anaemia) in rats by deficient feeding" appeared in the British Medical Journal on 28 June 1930 ([DOI](https://doi.org/10.1136/bmj.1.3625.1167)). The title shows that her early work used feeding experiments in animals, a year before her paper on treating patients. On 20 June 1931 the same journal published her paper "Treatment of 'pernicious anaemia of pregnancy' and 'tropical anaemia'" ([DOI](https://doi.org/10.1136/bmj.1.3676.1059)). PubMed lists no abstract for it. The Bombay link is documented. According to PubMed, her 1933 note in the Indian Medical Gazette, "A Note on the Use of Marmite in Tropical Macrocytic Anaemia, Including Pernicious Anaemia of Pregnancy," lists her affiliation as the Haffkine Institute in Parel, Bombay ([PubMed record](https://pubmed.ncbi.nlm.nih.gov/29009274/)). Marmite is a yeast extract, and the note's title says it concerns the use of that extract in tropical macrocytic anemia. The record does not give the results. Four years later, Wills worked with two colleagues in London. According to PubMed, the 1937 Biochemical Journal paper by Wills, Clutterbuck and Evans is titled "A new factor in the production and cure of macrocytic anaemias and its relation to other haemopoietic principles curative in pernicious anaemia." Its affiliations are the London School of Hygiene and Tropical Medicine and the Royal Free Hospital ([DOI](https://doi.org/10.1042/bj0312136)). The title describes a new factor curative in these anemias. The record does not name that factor in chemical terms. The NIH Office of Dietary Supplements says megaloblastic anemia is the primary clinical sign of folate or vitamin B12 deficiency. Its symptoms include weakness, fatigue, difficulty concentrating, irritability, headache, heart palpitations and shortness of breath. ## Neural tube defects and the trials that changed the advice The shift from anemia to birth defects happened in trials. According to PubMed, the Medical Research Council Vitamin Study randomized 1,817 women who had previously had a pregnancy affected by a neural tube defect (NTD) to folic acid, other vitamins, both, or neither. Among 1,195 women whose pregnancy outcome was known, 27 had an NTD: 6 in the folic acid groups and 21 in the other groups. The authors reported a 72 percent protective effect of folic acid (relative risk 0.28; 95% CI 0.12 to 0.71). The other vitamins showed no significant effect ([PubMed record](https://pubmed.ncbi.nlm.nih.gov/1677062/)). In 1992 Czeizel and Dudás reported a randomized trial in Hungary. Women planning a pregnancy took either a multivitamin tablet containing 0.8 mg of folic acid or a trace-element supplement. Congenital malformations were less common in the vitamin group, at 13.3 per 1,000 against 22.9 per 1,000 in the trace-element group. There were six NTDs in the trace-element group and none in the vitamin group. The authors concluded that periconceptional vitamin use decreased the first occurrence of NTDs ([DOI](https://doi.org/10.1056/NEJM199212243272602)). China provided the next large test. According to PubMed, a public health campaign in 1993 to 1995 asked women in northern and southern China to take 400 mcg of folic acid daily, from their premarital examination until the end of the first trimester. In the north, where NTD rates were high, the rate among pregnancies of at least 20 weeks without folic acid was 4.8 per 1,000. With periconceptional use it was 1.0 per 1,000. The largest reduction, 85 percent (95% CI 62 to 94), was among women who took more than 80 percent of their pills. In the south the reduction was 41 percent (95% CI 3 to 64) ([DOI](https://doi.org/10.1056/NEJM199911113412001)). The NIH fact sheet summarizes the mechanism question carefully. ODS says the mechanism has not been fully established, but clinical trial evidence shows that adequate periconceptional folic acid intake by women prevents a substantial proportion of NTDs. For that reason the US Preventive Services Task Force recommends that women planning or able to become pregnant take a daily supplement with 400 to 800 mcg of folic acid, as ODS reports. ## How the science changed, step by step A 2001 review by Hoffbrand and Weir, "The history of folic acid," covers this subject ([DOI](https://doi.org/10.1046/j.1365-2141.2001.02822.x)). The science moved in steps, and the dates matter. The oldest dated anchors come from the Eastern texts. Britannica places the present form of the Caraka Samhita around the 1st century CE and the Sushruta Samhita in the last centuries BCE, and the Bodleian dates Ibn Sina's Canon of Medicine to 1025. Those texts describe medicine in general, and we have found no folate-rich foods named in them. The modern thread begins in 1930. Wills's rat-feeding note appeared that June, her Marmite note in 1933, and the London paper with two colleagues in 1937. The neural tube question came next. The MRC trial was reported in 1991, the Hungarian trial in 1992 and the Chinese campaign results in 1999. The fortification decisions followed. The US published its grain rule in 1996, with compliance mandatory from 1998, and Canada's requirement took effect in 1998. Then came the evaluation phase. Honein and colleagues reported the US decline in 2001. De Wals and colleagues reported Canada's full-fortification decline in 2007, and the Crider review summarized the global picture in 2011. Vollset and colleagues pooled the cancer trials in 2013, and the US Preventive Services Task Force recommendation that ODS cites dates to 2017. The most recent steps are regional and policy-driven. Yila and colleagues published their Hokkaido analysis in 2016, Yamamoto and Wada their Osaka survey in 2017, and the PRAYAS database in 2025. The UK's non-wholemeal flour requirement is set to begin in December 2026. Each step narrowed the question. The first asked whether folic acid could prevent a defect. The later ones ask who takes it, what high doses do, and where it belongs in food. ## Fortification: the US, Canada and the rules that followed Food fortification turned the trial results into a population policy. The US rule is a Food and Drug Administration final rule published on March 5, 1996 (61 FR 8781). It set the level for enriched cereal-grain products at 140 micrograms of folic acid per 100 grams, which is 0.635 mg per pound. The effective date was January 1, 1998 ([Federal Register](https://www.federalregister.gov/documents/1996/03/05/96-5014/food-standards-amendment-of-standards-of-identity-for-enriched-grain-products-to-require-addition-of)). According to PubMed, Honein and colleagues compared birth certificate data from before and after mandatory fortification. The birth prevalence of NTDs fell from 37.8 to 30.5 per 100,000 live births, a 19 percent decline (prevalence ratio 0.81; 95% CI 0.75 to 0.87). The authors noted that factors other than fortification may have contributed ([DOI](https://doi.org/10.1001/jama.285.23.2981)). ODS estimates that the program raised mean US folic acid intake by about 190 mcg per day. Canada moved in the same direction. ODS reports that Canada has required 150 mcg of folic acid per 100 g in many grains since 1 November 1998. According to PubMed, De Wals and colleagues compared seven provinces from 1993 to 2002. NTD prevalence fell from 1.58 to 0.86 per 1,000 births after full fortification, a 46 percent reduction (95% CI 40 to 51). Spina bifida fell by 53 percent, anencephaly by 38 percent and encephalocele by 31 percent ([DOI](https://doi.org/10.1056/NEJMoa067103)). Not every defect responded. In a companion analysis, De Wals and colleagues found no clear decline in lipomyelomeningocele, with 86 cases among about 1.9 million births. They described the condition as pathogenically distinct from myelomeningocele ([DOI](https://doi.org/10.1002/bdra.20418)). A 2011 review by Crider, Bailey and Berry lists the fortification rules that other countries had adopted. Its table gives 180 mcg per 100 g in Costa Rica from 1998, 220 mcg per 100 g in Chile from 2000 and 150 mcg per 100 g in South Africa from 2003. The review reports that mandatory wheat flour fortification was in place in 53 countries, although many of those rules had not been implemented. It also notes that WHO and FAO published guidelines in 2006 to help countries set fortification levels, and it reports NTD declines of 19 to 55 percent in several of these countries ([DOI](https://doi.org/10.3390/nu3030370)). ## Australia, New Zealand, the UK and the EU Australia and New Zealand chose bread. According to Food Standards Australia New Zealand (FSANZ), millers in both countries must add folic acid to wheat flour for bread making. Plain, fancy and sweet breads, rolls and buns, bagels, focaccia, English muffins, yeast flatbreads and flour sold for domestic bread making must contain it. Organic bread is not required to contain folic acid. FSANZ also states that two thirds of the world's population has access to folic acid fortified flour. The UK tells a similar story with a later start. The gov.uk folic acid page says that more than 60 countries have adopted wheat flour fortification, mandatory or voluntary, including Australia, Canada and the USA. It says the UK's Scientific Advisory Committee on Nutrition (SACN) first recommended fortification in 2006 after reviewing the evidence. It estimates that fortifying non-wholemeal wheat flour will reduce NTD rates by around 20 percent. The page, updated on 10 July 2026, sets the requirement for non-wholemeal flour to begin in December 2026 at 0.25 mg per 100 g. The European position comes from the European Food Safety Authority (EFSA). Its 2014 opinion on folate dietary reference values sets an average requirement of 250 mcg DFE per day for adults and a population reference intake (PRI) of 330 mcg DFE per day ([EFSA opinion](https://efsa.europa.eu/en/efsajournal/pub/3893)). The average requirement rests on the intake needed to keep serum folate at or above 10 nmol/L and red blood cell folate at or above 340 nmol/L. The PRI assumes a coefficient of variation of 15 percent, to allow for the higher requirement of people with the MTHFR 677TT genotype. The same opinion sets an adequate intake of 600 mcg DFE per day for pregnant women and a PRI of 500 mcg DFE per day for women who are breastfeeding. A PRI covers the needs of nearly all people in a group, which is a different target from an adequate intake. ## China, Japan and India: national programmes and regional studies China's national programme began in 2009. According to PubMed, China launched a national folic acid supplementation programme that year, and Guangxi added a free premarital medical check-up policy in 2010 ([DOI](https://doi.org/10.7189/jogh.16.04129)). In Guangxi, the NTD incidence rate fell from 2009 to 2023 as folic acid supplementation rose, with a Spearman correlation of r = -0.932 between the supplementation rate and the NTD rate. Awareness of folic acid rose over the same period, with a Spearman correlation of r = -0.976 between awareness and the NTD rate. The study is descriptive, so it shows a correlation over time rather than a trial result. Japan has two regional studies in this history. Yamamoto and Wada surveyed 1,862 pregnant women at a perinatal centre in Osaka between September 2014 and December 2015. Only 20.5 percent took folic acid supplements before conception, although 70.4 percent knew about its protective effect. Age of 35 or older and knowledge of the benefits were both associated with supplement use. The authors' conclusion is aimed at countries where foods are not fortified with folic acid ([DOI](https://doi.org/10.1017/S1368980017003172)). A larger Japanese study came from Hokkaido. According to PubMed, Yila and colleagues analyzed 15,266 pregnant women in the Hokkaido Study on Environment and Children's Health, with data from 2002 to 2012. Folate status was measured from first-trimester biochemical assays, and predictors came from self-reported questionnaires. Supplement use was the most favorable predictor of folate status, with an adjusted odds ratio of 0.19 for low folate status. Younger age, lower education, lower income and tobacco smoke exposure were linked to low folate status ([DOI](https://doi.org/10.1017/S0007114516001628)). The paper's introduction cites an International Clearinghouse report of a rise in spina bifida prevalence in Japan. India's modern evidence is organized around anemia. According to PubMed, the PRAYAS database, published in Frontiers in Public Health in 2025, pools 88 datasets from 1994 to 2023 with 319,721 participants for anemia prevalence, most of them pregnant women. Its interventions include intravenous iron and combined intravenous iron with vitamin B12, folic acid and niacinamide. The database is meant to support India's test, treat and track approach under the Anemia Mukt Bharat program. It also aims to measure how far iron and other micronutrient deficiencies contribute to anemia ([DOI](https://doi.org/10.3389/fpubh.2025.1696787)). ## National and regional numbers at a glance These are the figures each body set, or each study found, listed in no particular order. - **US Food and Drug Administration, 1996 rule, effective 1998:** 140 mcg of folic acid per 100 g of enriched cereal-grain product (0.635 mg per pound). - **EFSA, 2014:** average requirement 250 mcg DFE per day and PRI 330 mcg DFE per day for adults; adequate intake 600 mcg DFE per day in pregnancy; PRI 500 mcg DFE per day in lactation. - **UK SACN and government, 2006 and 2026:** SACN recommended fortification in 2006; non-wholemeal wheat flour is set to carry 0.25 mg per 100 g from December 2026. - **China, 2009 and 1993 to 1995:** a national folic acid supplementation programme from 2009; the 1993 to 1995 campaign asked for 400 mcg a day. - **Japan, regional studies, 2014 to 2015 and 2002 to 2012:** 20.5 percent of 1,862 pregnant women in Osaka took folic acid before conception; in Hokkaido, supplement use was the most favorable predictor of folate status (odds ratio 0.19 for low status). ## What the evidence shows now, and where it is disputed The strongest evidence is about NTD prevention. The MRC trial, the Hungarian trial and the Chinese campaign all found reductions in NTDs with folic acid before conception, and the US and Canadian fortification data show population declines after food rules took effect. The evidence is not equally strong for every outcome people have asked about, and the open questions are worth separating from the settled one. Cancer is one of the open questions. According to PubMed, Vollset and colleagues pooled 13 randomized trials with 49,621 participants, most of them in cardiovascular trials. Allocation to folic acid quadrupled plasma folic acid concentrations over an average treatment of 5.2 years, yet overall cancer incidence was not significantly changed (rate ratio 1.06; 95% CI 0.99 to 1.13), and there was no significant effect on any specific cancer site. The authors noted that fortification delivers doses roughly an order of magnitude smaller than the trial doses ([DOI](https://doi.org/10.1016/S0140-6736(12)62001-7)). ODS also reports a combined analysis of two Norwegian trials, in a setting without food fortification, in which 800 mcg of folic acid plus 400 mcg of vitamin B12 daily increased cancer incidence by 21 percent in people with ischemic heart disease. The disagreement is real, and it is about dose and population as much as about folate itself. Cardiovascular outcomes are similarly split. ODS summarizes the trial evidence by saying that folic acid, alone or with vitamins B6 and B12, does not affect the risk of heart attack or death from any cause, but does reduce the risk of stroke. A second open question is vitamin B12. ODS says some experts have been concerned that high folate intake might mask a B12 deficiency until its neurological effects become irreversible, and that those questions remain unresolved. ODS gives the tolerable upper intake for folic acid from supplements or fortified foods as 1,000 mcg a day for adults 19 and older. Some defects did not respond to fortification in the Canadian data, as noted above, so the rule is not a universal fix. The summary is narrower than the slogans: folic acid before conception is well supported for NTD prevention, fortification lowered NTD rates where it was applied, and the cancer and cardiovascular questions are still argued in the literature. ## Why the story is worth knowing The arc is unusual. A condition that a physician reported treating in Bombay in the 1930s led, by 1998, to a grain rule in the US. The route ran through a London laboratory, a Hungarian trial, a Chinese public health campaign and a Canadian fortification study. Each step answered a narrower question than the last. The names changed along the way. ODS says folate was once called folacin. The word folic acid now stands for one synthetic form, and folate stands for the family. Labels use DFE to bridge them. Much of the confusion people bring to this subject starts with those names, and the history explains why the labels look the way they do. The record also stops in places. The record does not date the first synthesis of folic acid, and it shows no folate-related use in the Eastern or classical texts. ## Next reads If the brain and nutrient links interest you, start with our [brain health guide](/health/brain-health-focus-complete-guide). Readers comparing methyl-group nutrients can look at the [trimethylglycine ingredient page](/ingredients/trimethylglycine). For the other vitamin in this story, our [vitamin B12 article](/blog/immune-support/b12-essential-trio-the-liquid-vitamin-your-body-needs) covers its role in energy and mental function. ## Bottom line If you are planning a pregnancy, the trial evidence favors folic acid before conception, and ODS reports that the US Preventive Services Task Force recommends a daily supplement with 400 to 800 mcg of folic acid. If your diet already includes fortified bread or cereal, add up the folic acid from all sources before you choose a supplement, because the adult upper limit is 1,000 mcg a day. Discuss the amount with the clinician who knows your history. ## Frequently asked questions ### What was the anemia Lucy Wills treated in the 1930s? Her 1931 British Medical Journal paper is titled "Treatment of 'pernicious anaemia of pregnancy' and 'tropical anaemia.'" Her 1933 note refers to tropical macrocytic anemia, including pernicious anemia of pregnancy. Macrocytic means the red blood cells were abnormally large. ### How did a yeast extract cure it? Her 1933 note concerns the use of Marmite, a yeast extract, and her 1937 paper describes a new factor curative in macrocytic anemias. Neither record names that factor chemically, so the mechanism is not described here. ### What was folate called before it had its current name? According to ODS, folate was formerly known as folacin and is sometimes called vitamin B9. ### Is folic acid the same as folate? No. Folate is the umbrella term for naturally occurring food folates, the folates in supplements and the folates in fortified foods. Folic acid is the fully oxidized form used in most supplements and fortified foods. ODS gives the conversion that makes labels comparable: 0.6 mcg of folic acid from fortified food or a supplement taken with food equals 1 mcg DFE. ### When did the US start fortifying grain with folic acid, and why? The FDA rule was published on March 5, 1996, and compliance became mandatory from January 1, 1998. The aim was to lower neural tube defects. Honein and colleagues noted that before fortification only an estimated 29 percent of US women of reproductive age took a supplement with 400 mcg of folic acid daily ([DOI](https://doi.org/10.1001/jama.285.23.2981)). ### What is the difference between food folate and folic acid? Food folate occurs naturally, while folic acid is the synthetic form used in supplements and fortified foods. ODS says at least 85 percent of folic acid is bioavailable when taken with food, compared with about 50 percent of the folate naturally present in food. That difference is why labels use dietary folate equivalents. ### Related reading - [Who found vitamin B12, and the liver cure that started it all](/blog/history/history-of-vitamin-b12-from-liver-cure-to-cobalamin) - [The history of iron supplements and the ferritin test](/blog/history/history-of-iron-supplements-and-the-ferritin-test) - [Who found vitamin C, and how scurvy became a supplement story](/blog/history/history-of-vitamin-c-from-scurvy-to-ascorbic-acid) - [How choline became essential in 1998](/blog/history/history-of-choline-from-ox-bile-to-essential-nutrient) - [Water fluoridation as a 1945 public health program](/blog/history/history-of-fluoride-from-brown-teeth-to-community-water)