Biological, dietetic and pharmacological properties of vitamin B9
Status PubMed-not-MEDLINE Jazyk angličtina Země Velká Británie, Anglie Médium electronic
Typ dokumentu časopisecké články, přehledy
PubMed
40075081
PubMed Central
PMC11904035
DOI
10.1038/s41538-025-00396-w
PII: 10.1038/s41538-025-00396-w
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Humans must obtain vitamin B9 (folate) from plant-based diet. The sources as well as the effect of food processing are discussed in detail. Industrial production, fortification and biofortification, kinetics, and physiological role in humans are described. As folate deficiency leads to several pathological states, current opinions toward prevention through fortification are discussed. Claimed risks of increased folate intake are mentioned as well as analytical ways for measurement of folate.
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Rossi, M., Raimondi, S., Costantino, L. & Amaretti, A. Folate: Relevance of chemical and microbial production. In Industrial Biotechnology of Vitamins, Biopigments, and Antioxidants (eds Vandamme, E. J. & Revuelta, J. L.) 5, 103–128 (Wiley-VCH Verlag GmbH & Co. KGaA, 2016).
Gorelova, V. et al. Folates in plants: research advances and progress in crop biofortification. Front. Chem.5, 21 (2017). PubMed PMC
Gorelova, V. et al. Evolution of folate biosynthesis and metabolism across algae and land plant lineages. Sci. Rep.9, 5731 (2019). PubMed PMC
Basset, G. et al. Folate synthesis in plants: the first step of the pterin branch is mediated by a unique bimodular GTP cyclohydrolase I. Proc. Natl. Acad. Sci.99, 12489–12494 (2002). PubMed PMC
Basset, G. J. et al. Folate synthesis in plants: the p-aminobenzoate branch is initiated by a bifunctional PabA-PabB protein that is targeted to plastids. Proc. Natl. Acad. Sci.101, 1496–1501 (2004). PubMed PMC
Basset, G. J. C. et al. Folate synthesis in plants: the last step of the p‐aminobenzoate branch is catalyzed by a plastidial aminodeoxychorismate lyase. Plant J.40, 453–461 (2004). PubMed
Noiriel, A., Naponelli, V., Gregory, J. F. III & Hanson, A. D. Pterin and folate salvage. Plants and Escherichia coli lack capacity to reduce oxidized pterins. Plant Physiol.143, 1101–1109 (2007). PubMed PMC
Orsomando, G. et al. Evidence for folate‐salvage reactions in plants. Plant J.46, 426–435 (2006). PubMed
Hanson, A. D. & Gregory, J. F. III Synthesis and turnover of folates in plants. Curr. Opin. Plant Biol.5, 244–249 (2002). PubMed
Hanson, A. D. & Gregory, J. F. III Folate biosynthesis, turnover, and transport in plants. Annu. Rev. Plant Biol.62, 105–125 (2011). PubMed
Swarbrick, J., Iliades, P., Simpson, J. S. & Macreadie, I. Folate biosynthesis–reappraisal of old and novel targets in the search for new antimicrobials. Open Enzym Inhib. J.1, 12–33 (2008).
Vickers, T. J. & Beverley, S. M. Folate metabolic pathways in Leishmania. Essays Biochem.51, 63–80 (2011). PubMed PMC
Ravanel, S., Douce, R. & Rébeillé, F. Metabolism of folates in plants. In Advances in Botanical Research 59 (eds Rébeillé, F. & Douce, R.) Ch. 3, 67–106 (Academic Press, 2011).
Liu, Z. et al. B vitamin supply in plants and humans: the importance of vitamer homeostasis. Plant J.111, 662–682 (2022). PubMed PMC
Levin, I. et al. An alternative pathway for reduced folate biosynthesis in bacteria and halophilic archaea. Mol. Microbiol.54, 1307–1318 (2004). PubMed
Cantwell-Jones, A. et al. Global plant diversity as a reservoir of micronutrients for humanity. Nat. Plants8, 225–232 (2022). PubMed
Molina-Venegas, R., Morales-Castilla, I. & Rodríguez, M. Á. Unreliable prediction of B-vitamin source species. Nat. Plants9, 31–33 (2023). PubMed
Verhoef, H., Veenemans, J., Mwangi, M. N. & Prentice, A. M. Safety and benefits of interventions to increase folate status in malaria‐endemic areas. Br. J. Haematol.177, 905–918 (2017). PubMed PMC
Maynard, C., Cummins, I., Green, J. & Weinkove, D. A bacterial route for folic acid supplementation. BMC Biol.16, 1–10 (2018). PubMed PMC
Kordus, S. L. & Baughn, A. D. Revitalizing antifolates through understanding mechanisms that govern susceptibility and resistance. Med. Chem. Commun.10, 880–895 (2019). PubMed PMC
Braakman, R. & Smith, E. The emergence and early evolution of biological carbon-fixation. PLoS Comput. Biol.8, e1002455 (2012). PubMed PMC
de Crécy-Lagard, V. et al. Comparative genomics of bacterial and plant folate synthesis and salvage: predictions and validations. BMC Genom.8, 1–15 (2007). PubMed PMC
Falb, M. et al. Metabolism of halophilic archaea. Extremophiles12, 177–196 (2008). PubMed PMC
Sousa, F. L. & Martin, W. F. Biochemical fossils of the ancient transition from geoenergetics to bioenergetics in prokaryotic one carbon compound metabolism. Biochim. Biophys. Acta Bioenerg.1837, 964–981 (2014). PubMed
Blancquaert, D. et al. Folates and folic acid: from fundamental research toward sustainable health. Crit. Rev. Plant Sci.29, 14–35 (2010).
Krishnan, A., Kloehn, J., Lunghi, M. & Soldati-Favre, D. Vitamin and cofactor acquisition in apicomplexans: Synthesis versus salvage. J. Biol. Chem.295, 701–714 (2020). PubMed PMC
Perli, T. et al. Vitamin requirements and biosynthesis in Saccharomyces cerevisiae. Yeast37, 283–304 (2020). PubMed PMC
Akhtar, T. A. et al. A central role for gamma‐glutamyl hydrolases in plant folate homeostasis. Plant J64, 256–266 (2010). PubMed
Gambonnet, B. et al. Folate distribution during higher plant development. J. Sci. Food Agric.81, 835–841 (2001).
Meir, Z. & Osherov, N. Vitamin biosynthesis as an antifungal target. J. Fungus4, 72 (2018). PubMed PMC
Goyer, A. et al. 5-Formyltetrahydrofolate is an inhibitory but well tolerated metabolite in Arabidopsis leaves. J. Biol. Chem.280, 26137–26142 (2005). PubMed
de Crécy-Lagard, V. R. et al. Comparative genomics guided discovery of two missing archaeal enzyme families involved in the biosynthesis of the pterin moiety of tetrahydromethanopterin and tetrahydrofolate. ACS Chem. Biol7, 1807–1816 (2012). PubMed PMC
Jakobsen, J., Melse-Boonstra, A. & Rychlik, M. Challenges to quantify total vitamin activity: how to combine the contribution of diverse vitamers? Curr. Dev. Nutr.3, nzz086 (2019). PubMed PMC
Saini, R. K., Nile, S. H. & Keum, Y.-S. Folates: Chemistry, analysis, occurrence, biofortification and bioavailability. Food Res. Int.89, 1–13 (2016). PubMed
Striegel, L. et al. Durian fruits discovered as superior folate sources. Front. Nutr.5, 114 (2018). PubMed PMC
Striegel, L. et al. Promising tropical fruits high in folates. Foods8, 363 (2019). PubMed PMC
Zou, Y. et al. Quantification of polyglutamyl 5-methyltetrahydrofolate, monoglutamyl folate vitamers, and total folates in different berries and berry juice by UHPLC–MS/MS. Food Chem.276, 1–8 (2019). PubMed
Ramos-Parra, P. A., García-Salinas, C. & Hernández-Brenes, C. & Díaz de la Garza, R. o. I. Folate levels and polyglutamylation profiles of papaya (Carica papaya cv. Maradol) during fruit development and ripening. J. Agric. Food Chem.61, 3949–3956 (2013). PubMed
Thomas, P. M., Flanagan, V. P. & Pawlosky, R. J. Determination of 5-methyltetrahydrofolic acid and folic acid in citrus juices using stable isotope dilution− mass spectrometry. J. Agric. Food Chem.51, 1293–1296 (2003). PubMed
Ringling, C. & Rychlik, M. Analysis of seven folates in food by LC–MS/MS to improve accuracy of total folate data. Eur. Food Res. Technol.236, 17–28 (2013).
Ringling, C. & Rychlik, M. Origins of the difference between food folate analysis results obtained by LC–MS/MS and microbiological assays. Anal. Bioanal. Chem.409, 1815–1825 (2017). PubMed
Zhang, H. et al. Improved folate monoglutamate extraction and application to folate quantification from wild lentil seeds by ultra-performance liquid chromatography-selective reaction monitoring mass spectrometry. J. Chromatogr. B1121, 39–47 (2019). PubMed
Zhang, H. et al. Folate stability and method optimization for folate extraction from seeds of pulse crops using LC-SRM MS. J. Food Compos. Anal.71, 44–55 (2018).
Shohag, M. et al. Folate content and composition of vegetables commonly consumed in China. J. Food Sci.77, H239–H245 (2012). PubMed
Shohag, M. et al. Natural variation of folate content and composition in spinach (Spinacia oleracea) germplasm. J. Agric. Food Chem.59, 12520–12526 (2011). PubMed
Shohag, M. et al. A rapid method for sensitive profiling of folates from plant leaf by ultra-performance liquid chromatography coupled to tandem quadrupole mass spectrometer. J. Chromatogr. B1040, 169–179 (2017). PubMed
Wang, C., Riedl, K. M. & Schwartz, S. J. A liquid chromatography–tandem mass spectrometric method for quantitative determination of native 5-methyltetrahydrofolate and its polyglutamyl derivatives in raw vegetables. J. Chromatogr. B878, 2949–2958 (2010). PubMed PMC
Strålsjö, L., Åhlin, H., Witthöft, C. M. & Jastrebova, J. Folate determination in Swedish berries by radioprotein-binding assay (RPBA) and high performance liquid chromatography (HPLC). Eur. Food Res. Technol.216, 264–269 (2003).
Strålsjö, L. M., Witthöft, C. M., Sjöholm, I. M. & Jägerstad, M. I. Folate content in strawberries (Fragaria× ananassa): effects of cultivar, ripeness, year of harvest, storage, and commercial processing. J. Agric. Food Chem.51, 128–133 (2003). PubMed
Islam, M. S., Mehmood, S., Zhang, C. & Liang, Q. Identification of the prepared foods promising for dietary folate intake in Beijing, China. Food Sci. Nutr.8, 6557–6567 (2020). PubMed PMC
Hall, C., Hillen, C. & Garden Robinson, J. Composition, nutritional value, and health benefits of pulses. Cereal Chem.94, 11–31 (2017).
Vishnumohan, S., Arcot, J. & Pickford, R. Naturally-occurring folates in foods: method development and analysis using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Food Chem.125, 736–742 (2011).
Vishnumohan, S. et al. Determination of folate contents in selected Indian foods using the tri-enzyme extraction and estimated folate intakes of the population based on 24-h recall. Int. J. Food Sci. Nutr.60, 170–180 (2009). PubMed
Vishnumohan, S., Pickford, R. & Arcot, J. Naturally occurring folates in selected traditionally prepared foods in Southern India. J. Food Sci. Technol.54, 4173–4180 (2017). PubMed PMC
Meng, Z. et al. Optimized extraction and characterization of folates from date palm fruits and their tracking during fruits wine fermentation. Front. Nutr.8, 699555 (2021). PubMed PMC
Fajardo, V., Alonso-Aperte, E. & Varela-Moreiras, G. Lack of data on folate in convenience foods: should ready-to-eat products be considered relevant for folate intake? The European challenge. J. Food Compos. Anal.28, 155–163 (2012).
Fajardo, V., Alonso-Aperte, E. & Varela-Moreiras, G. Total folate content in ready-to-eat vegetable meals from the Spanish market. J. Food Compos. Anal.64, 223–231 (2017).
López, A. et al. Chemical composition and antioxidant capacity of lettuce: Comparative study of regular-sized (Romaine) and baby-sized (Little Gem and Mini Romaine) types. J. Food Compos. Anal.33, 39–48 (2014).
Yang, X., Gil, M. I., Yang, Q. & Tomás‐Barberán, F. A. Bioactive compounds in lettuce: Highlighting the benefits to human health and impacts of preharvest and postharvest practices. Compr. Rev. Food Sci. Food Saf.21, 4–45 (2022). PubMed
Devi, R., Arcot, J., Sotheeswaran, S. & Ali, S. Folate contents of some selected Fijian foods using tri-enzyme extraction method. Food Chem.106, 1100–1104 (2008).
Chew, S., Loh, S. & Khor, G. Determination of folate content in commonly consumed Malaysian foods. Int. Food Res. J.19, 189–197 (2012).
Tornero, E. M., Espinosa-Mansilla, A. & Merás, I. D. High-performance liquid chromatography with fast-scanning fluorescence detection and post-column on-line photoderivatization for the analysis of folic acid and its metabolites in vegetables. Microchem. J.133, 333–345 (2017).
Sen Gupta, D. et al. Lentils (Lens culinaris L.), a rich source of folates. J. Agric. Food Chem.61, 7794–7799 (2013). PubMed
Kim, D.-E. et al. Metabolite profiling of green, green/red, and red lettuce cultivars: Variation in health beneficial compounds and antioxidant potential. Food Res. Int.105, 361–370 (2018). PubMed
Kim, M. J. et al. Nutritional value, bioactive compounds and health benefits of lettuce (Lactuca sativa L.). J. Food Compos. Anal.49, 19–34 (2016).
Strandler, H. S., Patring, J., Jägerstad, M. & Jastrebova, J. Challenges in the determination of unsubstituted food folates: impact of stabilities and conversions on analytical results. J. Agric. Food Chem.63, 2367–2377 (2015). PubMed
Alfthan, G. et al. Folate intake, plasma folate and homocysteine status in a random Finnish population. Eur. J. Clin. Nutr.57, 81–88 (2003). PubMed
Bogers, R. P. et al. Effect of increased vegetable and fruit consumption on plasma folate and homocysteine concentrations. Nutr23, 97–102 (2007). PubMed
Johansson, M., Jägerstad, M. & Frølich, W. Folates in lettuce: a pilot study. Scand. J. Food Nutr.51, 22–30 (2007).
Bennett, L. E., Singh, D. P. & Clingeleffer, P. R. Micronutrient mineral and folate content of Australian and imported dried fruit products. Crit. Rev. Food Sci. Nutr.51, 38–49 (2011). PubMed
Rychlik, M. Revised folate content of foods determined by stable isotope dilution assays. J. Food Compos. Anal.17, 475–483 (2004).
Paucean, A. et al. Folic acid, minerals, amino-acids, fatty acids and volatile compounds of green and red lentils. Folic acid content optimization in wheat-lentils composite flours. Chem. Cent. J.12, 1–9 (2018). PubMed PMC
Jamieson, J. A., Viana, L. & English, M. M. Folate content and chemical composition of commercially available gluten-free flour alternatives. Plant Foods Hum. Nutr.75, 337–343 (2020). PubMed
Tulipani, S. et al. Folate content in different strawberry genotypes and folate status in healthy subjects after strawberry consumption. BioFactors34, 47–55 (2008). PubMed
Witthöft, C. M., Forssén, K., Johannesson, L. & Jägerstad, M. Folates-food sources, analyses, retention and bioavailability. Food Nutr. Res.43, 138–146 (1999).
Öhrvik, V. E., Olsson, J. C., Sundberg, B. E. & Witthöft, C. M. Effect of 2 pieces of nutritional advice on folate status in Swedish women: a randomized controlled trial. Am. J. Clin. Nutr.89, 1053–1058 (2009). PubMed
Rampersaud, G. C., Kauwell, G. P. & Bailey, L. B. Folate: a key to optimizing health and reducing disease risk in the elderly. J. Am. Coll. Nutr.22, 1–8 (2003). PubMed
Angeles-Agdeppa, I. et al. Food sources, energy and nutrient intakes of adults: 2013 Philippines National Nutrition Survey. Nutr. J.18, 59 (2019). PubMed PMC
Jägerstad, M. & Jastrebova, J. Occurrence, stability, and determination of formyl folates in foods. J. Agric. Food Chem.61, 9758–9768 (2013). PubMed
Hefni, M., Ӧhrvik, V., Tabekha, M. & Witthöft, C. Folate content in foods commonly consumed in Egypt. Food Chem.121, 540–545 (2010).
Allen, L. H. Causes of vitamin B12 and folate deficiency. Food Nutr. Bull.29, S20–S34 (2008). PubMed
Han, J.-Y. & Tyler, R. T. Determination of folate concentrations in pulses by a microbiological method employing trienzyme extraction. J. Agric. Food Chem.51, 5315–5318 (2003). PubMed
Iwatani, Y., Arcot, J. & Shrestha, A. K. Determination of folate contents in some Australian vegetables. J. Food Compos. Anal.16, 37–48 (2003).
Martin, H. et al. Quantification of folate in fruits and vegetables: a fluorescence-based homogeneous assay. Anal. Biochem.402, 137–145 (2010). PubMed
Bationo, F., Savadogo, B. & Goubgou, M. Folates in various African foods: contents, food processing and matrix effects. Int. J. Vitam. Nutr. Res.93, 459–470 (2022). PubMed
Rawalpally, T. R. Folic acid. Kirk-Othmer Encycl. Chem. Technol., 1–18, 10.1002/0471238961.0615120918012301.a01.pub2 (2014).
Pajari, A. M. et al. Bioactive compounds in whole grains and their implications for health. In Whole Grains and Health (ed. Rikard Landberg, N. S.) Ch. 16, 301–336 (John Wiley & Sons Ltd., 2021).
Hager, A.-S. et al. Nutritional properties and ultra-structure of commercial gluten free flours from different botanical sources compared to wheat flours. J. Cereal Sci.56, 239–247 (2012).
Mudryj, A. N., Yu, N. & Aukema, H. M. Nutritional and health benefits of pulses. Appl. Physiol. Nutr. Metab.39, 1197–1204 (2014). PubMed
Naderi, N. & House, J. D. Recent Developments in Folate Nutrition. In Advances in Food and Nutrition Research 83 (ed. Eskin, M.) Ch. 5, 195–213 (Academic Press, 2018). PubMed
Yazynina, E., Johansson, M., Jägerstad, M. & Jastrebova, J. Low folate content in gluten-free cereal products and their main ingredients. Food Chem.111, 236–242 (2008).
Czarnowska-Kujawska, M. et al. Folate content and yolk color of hen eggs from different farming systems. Molecules26, 1034 (2021). PubMed PMC
Czarnowska-Kujawska, M., Gujska, E. & Michalak, J. Folate determination in livers of different animal species. Czech J. Food Sci.38, 43–48 (2020).
Gmelch, L. et al. Comprehensive vitamer profiling of folate mono-and polyglutamates in baker’s yeast (Saccharomyces cerevisiae) as a function of different sample preparation procedures. Metabolites10, 301 (2020). PubMed PMC
Patring, J. D. et al. Development of a simplified method for the determination of folates in baker’s yeast by HPLC with ultraviolet and fluorescence detection. J. Agric. Food Chem.53, 2406–2411 (2005). PubMed
Jastrebova, J., Strandler, H. S., Patring, J. & Wiklund, T. Comparison of UPLC and HPLC for analysis of dietary folates. Chromatographia73, 219–225 (2011).
Nojavan, Y. et al. Ion pair-based dispersive liquid–liquid microextraction followed by high performance liquid chromatography as a new method for determining five folate derivatives in foodstuffs. Talanta137, 31–37 (2015). PubMed
EFSA Panel on Dietetic Products Nutrition and Allergies Scientific opinion on dietary reference values for folate. EFSA J.12, 3893 (2014).
Réhault-Godbert, S., Guyot, N. & Nys, Y. The golden egg: nutritional value, bioactivities, and emerging benefits for human health. Nutrients11, 684 (2019). PubMed PMC
Roe, M., Church, S., Pinchen, H. & Finglas, P. Nutrient analysis of eggs: analytical report, 1–44 (Institute of Food Research, 2013).
Williams, P. Nutritional composition of red meat. Nutr. Diet.64, S113–S119 (2007).
Bassett, M. & Sammán, N. Folate content and retention in selected raw and processed foods. Arch. Latinoam. Nutr.60, 298–305 (2010). PubMed
Hjortmo, S., Patring, J., Jastrebova, J. & Andlid, T. Inherent biodiversity of folate content and composition in yeasts. Trends Food Sci. Technol.16, 311–316 (2005).
Strandler, H. S., Jastrebova, J. & Mattisson, I. Folate content in Swedish eggs: influence of breed, feed and processing. Eur. Food Res. Technol.233, 923–930 (2011).
Ložnjak, P. et al. Quantification of folate in food using deconjugase of plant origin combined with LC-MS/MS: A method comparison of a large and diverse sample set. Food Chem.305, 125450 (2020). PubMed
Delchier, N., Herbig, A. L., Rychlik, M. & Renard, C. M. Folates in fruits and vegetables: contents, processing, and stability. Compr. Rev. Food Sci. Food Saf.15, 506–528 (2016). PubMed
Partearroyo, T. et al. Dietary sources and intakes of folates and vitamin B12 in the Spanish population: Findings from the ANIBES study. PLoS One12, e0189230 (2017). PubMed PMC
Park, J. Y. et al. Comparison of standardised dietary folate intake across ten countries participating in the European Prospective Investigation into Cancer and Nutrition. Br. J. Nutr.108, 552–569 (2012). PubMed
Imaeda, N. et al. Folate intake and food sources in Japanese female dietitians. Environ. Health Prev. Med.7, 156–161 (2002). PubMed PMC
Yoshino, K. et al. Trends in dietary intake of folate, vitamins B6, and B12 among Japanese adults in two rural communities from 1974 through 2001. J. Epidemiol.15, 29–37 (2005). PubMed PMC
Iglesia, I. et al. Foods contributing to vitamin B 6, folate, and vitamin B 12 intakes and biomarkers status in European adolescents: the HELENA study. Eur. J. Nutr.56, 1767–1782 (2017). PubMed
Steluti, J., Martini, L. A., Peters, B. S. & Marchioni, D. M. Folate, vitamin B6 and vitamin B12 in adolescence: serum concentrations, prevalence of inadequate intakes and sources in food. J. Pediatr.87, 43–49 (2011). PubMed
Krishnaswamy, K. & Nair, K. M. Importance of folate in human nutrition. Br. J. Nutr.85, S115–S124 (2001). PubMed
Pravst, I. et al. Dietary intake of folate and assessment of the folate deficiency prevalence in Slovenia using serum biomarkers. Nutrients13, 3860 (2021). PubMed PMC
Brevik, A. et al. Plasma concentration of folate as a biomarker for the intake of fruit and vegetables: the Hordaland Homocysteine Study. Am. J. Clin. Nutr.81, 434–439 (2005). PubMed
Zekovic, M. et al. Validity of the food frequency questionnaire assessing the folate intake in women of reproductive age living in a country without food fortification: application of the method of triads. Nutrients9, 128 (2017). PubMed PMC
Konings, E. J. et al. Folate intake of the Dutch population according to newly established liquid chromatography data for foods. Am. J. Clin. Nutr.73, 765–776 (2001). PubMed
Planells, E. et al. Vitamins B6 and B12 and folate status in an adult Mediterranean population. Eur. J. Clin. Nutr.57, 777–785 (2003). PubMed
Kim, Y.-N. & Cho, Y.-O. Folate food source, usual intake, and folate status in Korean adults. Nutr. Res. Pract.12, 47–51 (2018). PubMed PMC
Finglas, P. M. & Wright, A. J. Folate bioavailability and health. Phytochem. Rev.1, 189–198 (2002).
Palchetti, C. Z. et al. Prevalence of inadequate intake of folate in the post-fortification era: data from the Brazilian National Dietary Surveys 2008–2009 and 2017–2018. Br. J. Nutr.128, 1638–1646 (2022). PubMed
Evans, S. E. et al. Effect of increasing voluntary folic acid food fortification on dietary folate intakes and adequacy of reproductive-age women in New Zealand. Public Health Nutr.17, 1447–1453 (2014). PubMed PMC
Saubade, F., Hemery, Y. M., Guyot, J.-P. & Humblot, C. Lactic acid fermentation as a tool for increasing the folate content of foods. Crit. Rev. Food Sci. Nutr.57, 3894–3910 (2017). PubMed
Shewry, P. R. & Hey, S. J. The contribution of wheat to human diet and health. Food Energy Secur.4, 178–202 (2015). PubMed PMC
Lockyer, S. & Spiro, A. The role of bread in the UK diet: An update. Nutr. Bull.45, 133–164 (2020).
Patring, J., Wandel, M., Jägerstad, M. & Frølich, W. Folate content of Norwegian and Swedish flours and bread analysed by use of liquid chromatography–mass spectrometry. J. Food Compos. Anal.22, 649–656 (2009).
Öhrvik, V., Öhrvik, H., Tallkvist, J. & Witthöft, C. Folates in bread: retention during bread-making and in vitro bioaccessibility. Eur. J. Nutr.49, 365–372 (2010). PubMed
McNulty, H., Ward, M., Caffrey, A. & Pentieva, K. Contribution of folic acid to human health and challenges of translating the science into effective policy: a call to action for the implementation of food fortification in Ireland. Proc. Nutr. Soc.82, 91–103 (2023). PubMed
Laskowski, W. et al. How important are cereals and cereal products in the average polish diet? Nutrients11, 679 (2019). PubMed PMC
Schoenlechner, R., Wendner, M., Siebenhandl-Ehn, S. & Berghofer, E. Pseudocereals as alternative sources for high folate content in staple foods. J. Cereal Sci.52, 475–479 (2010).
Gujska, E. & Kuncewicz, A. Determination of folate in some cereals and commercial cereal-grain products consumed in Poland using trienzyme extraction and high-performance liquid chromatography methods. Eur. Food Res. Technol.221, 208–213 (2005).
Caselato‐Sousa, V. M. & Amaya‐Farfán, J. State of knowledge on amaranth grain: a comprehensive review. J. Food Sci.77, R93–R104 (2012). PubMed
Martínez-Villaluenga, C., Peñas, E. & Hernández-Ledesma, B. Pseudocereal grains: Nutritional value, health benefits and current applications for the development of gluten-free foods. Food Chem. Toxicol.137, 111178 (2020). PubMed
Motta, C. et al. Folates in quinoa (Chenopodium quinoa), amaranth (Amaranthus sp.) and buckwheat (Fagopyrum esculentum): Influence of cooking and malting. J. Food Compos. Anal.64, 181–187 (2017).
Ahmad, R. S., Imran, A. & Hussain, M. B. Nutritional composition of meat. In Meat Science and Nutrition (ed. Arshad, M. S.) Ch. 4, 61–75 (IntechOpen Limited, 2018).
Neufingerl, N. & Eilander, A. Nutrient intake and status in adults consuming plant-based diets compared to meat-eaters: a systematic review. Nutrients14, 29 (2022). PubMed PMC
Gilsing, A. M. et al. Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study. Eur. J. Clin. Nutr.64, 933–939 (2010). PubMed PMC
Koebnick, C. et al. Folate status during pregnancy in women is improved by long-term high vegetable intake compared with the average western diet. J. Nutr.131, 733–739 (2001). PubMed
Öhrvik, V. et al. Dietary intake and biomarker status of folate in Swedish adults. Eur. J. Nutr.57, 451–462 (2018). PubMed PMC
Brouwer, I. A. et al. Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial. J. Nutr.129, 1135–1139 (1999). PubMed
Hatzis, C. M. et al. Dietary and other lifestyle correlates of serum folate concentrations in a healthy adult population in Crete, Greece: a cross-sectional study. Nutr. J.5, 1–10 (2006). PubMed PMC
Davey, G. K. et al. EPIC–Oxford:lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK. Public Health Nutr.6, 259–268 (2003). PubMed
Larsson, C. L. & Johansson, G. K. Dietary intake and nutritional status of young vegans and omnivores in Sweden. Am. J. Clin. Nutr.76, 100–106 (2002). PubMed
Cade, J. E., Burley, V. J., Greenwood, D. C. & Group, U. Ws. C. S. S. The UK Women’s Cohort Study: comparison of vegetarians, fish-eaters and meat-eaters. Public Health Nutr.7, 871–878 (2004). PubMed
Cosgrove, M., Flynn, A. & Kiely, M. Consumption of red meat, white meat and processed meat in Irish adults in relation to dietary quality. Br. J. Nutr.93, 933–942 (2005). PubMed
Iyer, R. & Tomar, S. Folate: a functional food constituent. J. Food Sci.74, R114–R122 (2009). PubMed
Verwei, M. et al. The binding of folic acid and 5-methyltetrahydrofolate to folate-binding proteins during gastric passage differs in a dynamic in vitro gastrointestinal model. J. Nutr.134, 31–37 (2004). PubMed
Buttriss, J. L. Folate status in the UK. Nutr. Bull.40, 153–157 (2015).
Forssén, K. M., Jagerstad, M. I., Wigertz, K. & Witthöft, C. M. Folates and dairy products: a critical update. J. Am. Coll. Nutr.19, 100S–110S (2000). PubMed
Ezekiel, R., Singh, N., Sharma, S. & Kaur, A. Beneficial phytochemicals in potato-a review. Food Res. Int.50, 487–496 (2013).
Goyer, A. & Navarre, D. A. Determination of folate concentrations in diverse potato germplasm using a trienzyme extraction and a microbiological assay. J. Agric. Food Chem.55, 3523–3528 (2007). PubMed
Goyer, A. Maximizing the nutritional potential of potato: the case of folate. Potato Res.60, 319–325 (2017).
Goyer, A. & Navarre, D. A. Folate is higher in developmentally younger potato tubers. J. Sci. Food Agric.89, 579–583 (2009).
Morales, P. et al. Optimization and application of FL-HPLC for folates analysis in 20 species of Mediterranean wild vegetables. Food Anal. Methods8, 302–311 (2015).
Ogle, B. M., Johansson, M., Tuyet, H. T. & Johannesson, L. Evaluation of the significance of dietary folate from wild vegetables in Vietnam. Asia Pac. J. Clin. Nutr.10, 216–221 (2001). PubMed
Fyfe, S. et al. Future flavours from the past: sensory and nutritional profiles of green plum (Buchanania obovata), red bush apple (Syzygium suborbiculare) and wild peach (Terminalia carpentariae) from East Arnhem Land, Australia. Future Foods5, 100136 (2022).
Fyfe, S. A. et al. Buchanania obovata: an Australian indigenous food for diet diversification. Nutr. Diet.75, 527–532 (2018). PubMed
Woortman, D. V. et al. Microalgae a superior source of folates: quantification of folates in halophile microalgae by stable isotope dilution assay. Front. Bioeng. Biotechnol.7, 481 (2020). PubMed PMC
Fujii, K., Nakashima, H. & Hashidzume, Y. Isolation of folate‐producing microalgae, from oligotrophic ponds in Yamaguchi, Japan. J. Appl. Microbiol.108, 1421–1429 (2010). PubMed
Edelmann, M. et al. Riboflavin, niacin, folate and vitamin B12 in commercial microalgae powders. J. Food Compos. Anal.82, 103226 (2019).
Bito, T., Okumura, E., Fujishima, M. & Watanabe, F. Potential of Chlorella as a dietary supplement to promote human health. Nutrients12, 2524 (2020). PubMed PMC
Han, Y., Yon, M. & Hyun, T. Folate intake estimated with an updated database and its association to blood folate and homocysteine in Korean college students. Eur. J. Clin. Nutr.59, 246–254 (2005). PubMed
Yon, M. & Hyun, T. H. Folate content of foods commonly consumed in Korea measured after trienzyme extraction. Nutr. Res.23, 735–746 (2003).
De Quirós, A. R.-B., De Ron, C. C., López-Hernández, J. & Lage-Yusty, M. Determination of folates in seaweeds by high-performance liquid chromatography. J. Chromatogr. A1032, 135–139 (2004). PubMed
Jach, M. E. & Malm, A. Yarrowia lipolytica as an alternative and valuable source of nutritional and bioactive compounds for humans. Molecules27, 2300 (2022). PubMed PMC
Jach, M. E. et al. Production of enriched in B vitamins biomass of Yarrowia lipolytica grown in biofuel waste. Saudi J. Biol. Sci.28, 2925–2932 (2021). PubMed PMC
Phillips, K. M., Ruggio, D. M. & Haytowitz, D. B. Folate composition of 10 types of mushrooms determined by liquid chromatography–mass spectrometry. Food Chem.129, 630–636 (2011). PubMed
Nakalembe, I., Kabasa, J. D. & Olila, D. Comparative nutrient composition of selected wild edible mushrooms from two agro-ecological zones, Uganda. Springerplus4, 1–15 (2015). PubMed PMC
Raman, J. et al. Cultivation and nutritional value of prominent Pleurotus spp.: an overview. Mycobiology49, 1–14 (2021). PubMed PMC
Mattila, P. et al. Contents of vitamins, mineral elements, and some phenolic compounds in cultivated mushrooms. J. Agric. Food Chem.49, 2343–2348 (2001). PubMed
Weber, N. et al. Folate contents in insects as promising food components quantified by stable isotope dilution. Front. Nutr.9, 970255 (2022). PubMed PMC
Nowak, V., Persijn, D., Rittenschober, D. & Charrondiere, U. R. Review of food composition data for edible insects. Food Chem.193, 39–46 (2016). PubMed
Alagappan, S. et al. Nutritional analysis, volatile composition, antimicrobial and antioxidant properties of Australian green ants (Oecophylla smaragdina). Future Foods3, 100007 (2021).
Bouckaert, K. P. et al. Critical evaluation of folate data in European and international databases: recommendations for standardization in international nutritional studies. Mol. Nutr. Food Res.55, 166–180 (2011). PubMed
Arcot, J. & Shrestha, A. Folate: methods of analysis. Trends Food Sci. Technol.16, 253–266 (2005).
Nicolas, G. et al. Compilation of a standardised international folate database for EPIC. Food Chem.193, 134–140 (2016). PubMed
Westenbrink, S., Jansen-van der Vliet, M. & van Rossum, C. Updated folate data in the Dutch Food Composition Database and implications for intake estimates. Food Nutr. Res.56, 5449 (2012). PubMed PMC
Octavia, L. & Choo, W. S. Folate, ascorbic acid, anthocyanin and colour changes in strawberry (Fragaria× annanasa) during refrigerated storage. LWT86, 652–659 (2017).
Pinela, J. et al. Stability of total folates/vitamin B9 in irradiated watercress and buckler sorrel during refrigerated storage. Food Chem.274, 686–690 (2019). PubMed
Munyaka, A. W. et al. Influence of Thermal Processing on Hydrolysis and Stability of Folate Poly-γ-glutamates in Broccoli (Brassica oleracea var. italica), Carrot (Daucus carota) and Tomato (Lycopersicon esculentum). J. Agric. Food Chem.58, 4230–4240 (2010). PubMed
Upadhyaya, P. et al. Natural variation in folate levels among tomato (Solanum lycopersicum) accessions. Food Chem.217, 610–619 (2017). PubMed
Houlihan, A. et al. Folate content of Asian vegetables (Rural Industries Research and Development Corporation, 2011).
Puwastien, P., Pinprapai, N., Judprasong, K. & Tamura, T. International inter-laboratory analyses of food folate. J. Food Compos. Anal.18, 387–397 (2005).
EFSA Panel on Nutrition Novel Foods and Food Allergens Conversion of calcium‐l‐methylfolate and (6S)‐5‐methyltetrahydrofolic acid glucosamine salt into dietary folate equivalents. EFSA J.20, e07452 (2022). PubMed PMC
Witthöft, C. M., Straålsjoö, L., Berglund, G. & Lundin, E. G. A human model to determine folate bioavailability from food: a pilot study for evaluation. Food Nutr. Res.47, 6–18 (2003).
Seyoum, E. & Selhub, J. Properties of food folates determined by stability and susceptibility to intestinal pteroylpolyglutamate hydrolase action. J. Nutr.128, 1956–1960 (1998). PubMed
Bailey, L. B. Dietary reference intakes for folate: the debut of dietary folate equivalents. Nutr. Rev.56, 294–299 (1998). PubMed
Nygren-Babol, L. & Jägerstad, M. Folate-binding protein in milk: a review of biochemistry, physiology, and analytical methods. Crit. Rev. Food Sci. Nutr.52, 410–425 (2012). PubMed
Nygren-Babol, L., Sternesjö, Å., Jägerstad, M. & Björck, L. Affinity and rate constants for interactions of bovine folate-binding protein and folate derivatives determined by optical biosensor technology. Effect of stereoselectivity. J. Agric. Food Chem.53, 5473–5478 (2005). PubMed
Cochrane, K. M. et al. Is natural (6 S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study. Trials21, 1–12 (2020). PubMed PMC
Buffière, C. et al. Food matrix structure (from biscuit to custard) has an impact on folate bioavailability in healthy volunteers. Eur. J. Nutr.60, 411–423 (2021). PubMed
Scaglione, F. & Panzavolta, G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica44, 480–488 (2014). PubMed
Ringling, C. & Rychlik, M. Simulation of food folate digestion and bioavailability of an oxidation product of 5-methyltetrahydrofolate. Nutrients9, 969 (2017). PubMed PMC
Marchetta, C. M. et al. Assessing the association between natural food folate intake and blood folate concentrations: a systematic review and Bayesian meta-analysis of trials and observational studies. Nutrients7, 2663–2686 (2015). PubMed PMC
Liu, F., Edelmann, M., Piironen, V. & Kariluoto, S. 5-Methyltetrahydrofolate is a crucial factor in determining the bioaccessibility of folate in bread. J. Agric. Food Chem.70, 13379–13390 (2022). PubMed PMC
Liu, F., Edelmann, M., Piironen, V. & Kariluoto, S. The bioaccessibility of folate in breads and the stability of folate vitamers during in vitro digestion. Food Funct.13, 3220–3233 (2022). PubMed
Henderson, A. M. et al. L-5-methyltetrahydrofolate supplementation increases blood folate concentrations to a greater extent than folic acid supplementation in Malaysian women. J. Nutr.148, 885–890 (2018). PubMed
Rychlik, M. et al. Application of stable isotope dilution assays based on liquid chromatography–tandem mass spectrometry for the assessment of folate bioavailability. J. Chromatogr. B792, 167–176 (2003). PubMed
Hannon-Fletcher, M. P. et al. Determining bioavailability of food folates in a controlled intervention study. Am. J. Clin. Nutr.80, 911–918 (2004). PubMed
Mönch, S. et al. Folate bioavailability from foods rich in folates assessed in a short term human study using stable isotope dilution assays. Food Funct.6, 241–247 (2015). PubMed
Mönch, S. et al. Pilot study on folate bioavailability from a Camembert cheese reveals contradictory findings to recent results from a human short-term study. Front. Nutr.3, 9 (2016). PubMed PMC
Konings, E. J. et al. Intestinal absorption of different types of folate in healthy subjects with an ileostomy. Br. J. Nutr.88, 235–242 (2002). PubMed
Hiolle, M. et al. In vitro digestion of complex foods: how microstructure influences food disintegration and micronutrient bioaccessibility. Food Res. Int.128, 108817 (2020). PubMed
Winkels, R. M. et al. Bioavailability of food folates is 80% of that of folic acid. Am. J. Clin. Nutr.85, 465–473 (2007). PubMed
Brouwer, I. A., van Dusseldorp, M., West, C. E. & Steegers-Theunissen, R. P. Bioavailability and bioefficacy of folate and folic acid in man. Nutr. Res. Rev.14, 267–294 (2001). PubMed
Wright, A. et al. Single oral doses of 13C forms of pteroylmonoglutamic acid and 5-formyltetrahydrofolic acid elicit differences in short-term kinetics of labelled and unlabelled folates in plasma: potential problems in interpretation of folate bioavailability studies. Br. J. Nutr.90, 363–371 (2003). PubMed
Wright, A. J., Dainty, J. R. & Finglas, P. M. Folic acid metabolism in human subjects revisited: potential implications for proposed mandatory folic acid fortification in the UK. Br. J. Nutr.98, 667–675 (2007). PubMed
Gregory, J. III, Quinlivan, E. & Davis, S. Integrating the issues of folate bioavailability, intake and metabolism in the era of fortification. Trends Food Sci. Technol.16, 229–240 (2005).
Gregory, J. III Case study: folate bioavailability. J. Nutr131, 1376s–1382s (2001). PubMed
Öhrvik, V. E. et al. Folate bioavailability from breads and a meal assessed with a human stable-isotope area under the curve and ileostomy model. Am. J. Clin. Nutr.92, 532–538 (2010). PubMed
Öhrvik, V. E. & Witthöft, C. M. Human folate bioavailability. Nutrients3, 475–490 (2011). PubMed PMC
Bhandari, S. & Gregory, J. III Inhibition by selected food components of human and porcine intestinal pteroylpolyglutamate hydrolase activity. Am. J. Clin. Nutr.51, 87–94 (1990). PubMed
Wei, M.-M., Bailey, L. B., Toth, J. P. & Gregory, J. F. III Bioavailability for humans of deuterium-labeled monoglutamyl and polyglutamyl folates is affected by selected foods. J. Nutr.126, 3100–3108 (1996). PubMed
Wei, M.-M. & Gregory, J. F. III Organic acids in selected foods inhibit intestinal brush border pteroylpolyglutamate hydrolase in vitro: potential mechanism affecting the bioavailability of dietary polyglutamyl folate. J. Agric. Food Chem.46, 211–219 (1998). PubMed
Picciano, M. F. et al. Effect of cow milk on food folate bioavailability in young women. Am. J. Clin. Nutr.80, 1565–1569 (2004). PubMed
Caudill, M. A. Folate bioavailability: implications for establishing dietary recommendations and optimizing status. Am. J. Clin. Nutr.91, 1455S–1460S (2010). PubMed PMC
Sanderson, P. et al. Folate bioavailability: UK food standards agency workshop report. Br. J. Nutr.90, 473–479 (2003). PubMed
McNulty, H. & Pentieva, K. Folate bioavailability. Proc. Nutr. Soc.63, 529–536 (2004). PubMed
McKillop, D. J. et al. The rate of intestinal absorption of natural food folates is not related to the extent of folate conjugation. Am. J. Clin. Nutr.84, 167–173 (2006). PubMed
Pietrzik, K., Bailey, L. & Shane, B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin. Pharmacokinet.49, 535–548 (2010). PubMed
Chan, Y.-M., Bailey, R. & O’Connor, D. L. Folate. Adv. Nutr.4, 123–125 (2013). PubMed PMC
Brandon, E. et al. Bioaccessibility of vitamin A, vitamin C and folic acid from dietary supplements, fortified food and infant formula. Int. J. Food Sci. Nutr.65, 426–435 (2014). PubMed
Yaman, M. et al. The bioaccessibility of water-soluble vitamins: a review. Trends Food Sci. Technol.109, 552–563 (2021).
Yaman, M., Mızrak, Ö. F., Catak, J. & Sargın, H. S. In vitro bioaccessibility of added folic acid in commercially available baby foods formulated with milk and milk products. Food Sci. Biotechnol.28, 1837–1844 (2019). PubMed PMC
Etcheverry, P., Grusak, M. A. & Fleige, L. E. Application of in vitro bioaccessibility and bioavailability methods for calcium, carotenoids, folate, iron, magnesium, polyphenols, zinc, and vitamins B6, B12, D, and. E. Front. Physiol.3, 317 (2012). PubMed PMC
Hughes, J. & Buttriss, J. An update on folates and folic acid: contribution of MAFF‐funded research. Nutr. Bull.25, 113–124 (2000).
Verwei, M. et al. Folic acid and 5-methyltetrahydrofolate in fortified milk are bioaccessible as determined in a dynamic in vitro gastrointestinal model. J. Nutr.133, 2377–2383 (2003). PubMed
Arkbåge, K. Vitamin B12, Folate and Folate Binding Proteins in Dairy Products: Analysis, Process, Retention and Bioavailability (Swedish University of Agricultural Sciences, 2003).
Melse-Boonstra, A. Bioavailability of micronutrients from nutrient-dense whole foods: zooming in on dairy, vegetables, and fruits. Front. Nutr.7, 101 (2020). PubMed PMC
Melse-Boonstra, A., Verhoef, P. & West, C. Quantifying folate bioavailability: a critical appraisal of methods. Curr. Opin. Clin. Nutr. Metab. Care7, 539–545 (2004). PubMed
Melse-Boonstra, A. et al. A dual-isotope-labeling method of studying the bioavailability of hexaglutamyl folic acid relative to that of monoglutamyl folic acid in humans by using multiple orally administered low doses. Am. J. Clin. Nutr.84, 1128–1133 (2006). PubMed
Prinz‐Langenohl, R. et al. [6S]‐5‐methyltetrahydrofolate increases plasma folate more effectively than folic acid in women with the homozygous or wild‐type 677C→ T polymorphism of methylenetetrahydrofolate reductase. Br. J. Pharmacol.158, 2014–2021 (2009). PubMed PMC
West, A. A. et al. Folate. In Present Knowledge in Nutrition (eds Marriott, B. P., Birt, D. F., Stallings, V. A. & Yates, A. A.) Ch. 14, 239–255 (Academic Press, 2020). https://www.sciencedirect.com/science/article/abs/pii/B9780323661621000147, https://www.sciencedirect.com/book/9780323661621/present-knowledge-in-nutrition#book-info.
Munyaka, A. W. et al. Acidification, crushing and thermal treatments can influence the profile and stability of folate poly-γ-glutamates in broccoli (Brassica oleracea L. var. italica). Food Chem117, 568–575 (2009).
Pentieva, K. et al. The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men. J. Nutr.134, 580–585 (2004). PubMed
Green, T. J. et al. Wheat rolls fortified with microencapsulated L-5-methyltetrahydrofolic acid or equimolar folic acid increase blood folate concentrations to a similar extent in healthy men and women. J. Nutr.143, 867–871 (2013). PubMed
Jia, X. et al. Association between tea drinking and plasma folate concentration among women aged 18–30 years in China. Public Health Nutr.24, 4929–4936 (2021). PubMed PMC
Alemdaroglu, N. C. et al. Influence of green and black tea on folic acid pharmacokinetics in healthy volunteers: potential risk of diminished folic acid bioavailability. Biopharm. Drug Dispos.29, 335–348 (2008). PubMed
Liu, J. et al. Tea consumption is not associated with reduced plasma folate concentration among Chinese pregnant women. Birth Defects Res. A Clin. Mol. Teratol.103, 747–753 (2015). PubMed
Umegaki, K. et al. Effect of tea catechins on folate analysis in green tea by microbiological assay. J. Nutr. Sci. Vitaminol.62, 134–138 (2016). PubMed
Shiraishi, M. et al. Association between the serum folate levels and tea consumption during pregnancy. BioSci. Trends4, 225–230 (2010). PubMed
Otake, M., Sakurai, K., Watanabe, M. & Mori, C. Association between serum folate levels and caffeinated beverage consumption in pregnant women in Chiba: the Japan environment and children’s study. J. Epidemiol.28, 414–419 (2018). PubMed PMC
Moretti, D. et al. Bioavailability of iron, zinc, folic acid, and vitamin A from fortified maize. Ann. N. Y. Acad. Sci.1312, 54–65 (2014). PubMed
Chandra-Hioe, M. V. et al. Transport of folic acid across Caco-2 cells is more effective than 5-methyltetrahydrofolate following the in vitro digestion of fortified bread. Food Res. Int.53, 104–109 (2013).
Bailey, S. W. & Ayling, J. E. The pharmacokinetic advantage of 5-methyltetrahydrofolate for minimization of the risk for birth defects. Sci. Rep.8, 4096 (2018). PubMed PMC
Åkesson, A. et al. Preparatory work for the update of the tolerable upper intake levels for folic acid/folate. EFSA Support. Publ.20, 7940E (2023).
Gregory, J. III Accounting for differences in the bioactivity and bioavailability of vitamers. Food Nutr. Res.56, 5809 (2012). PubMed PMC
Strozzi, G. P. & Mogna, L. Quantification of folic acid in human feces after administration of Bifidobacterium probiotic strains. J. Clin. Gastroenterol.42, S179–S184 (2008). PubMed
Chan, Y.-M., Aufreiter, S., O’Keefe, S. J. & O’Connor, D. L. Switching to a fibre-rich and low-fat diet increases colonic folate contents among African Americans. Appl. Physiol. Nutr. Metab.44, 127–132 (2019). PubMed PMC
Kim, T. H., Yang, J., Darling, P. B. & O’Connor, D. L. A large pool of available folate exists in the large intestine of human infants and piglets. J. Nutr.134, 1389–1394 (2004). PubMed
Biesalski, H. K. Nutrition meets the microbiome: micronutrients and the microbiota. Ann. N. Y. Acad. Sci.1372, 53–64 (2016). PubMed
Engevik, M. A. et al. Microbial metabolic capacity for intestinal folate production and modulation of host folate receptors. Front. Microbiol.10, 2305 (2019). PubMed PMC
Rowland, I. et al. Gut microbiota functions: metabolism of nutrients and other food components. Eur. J. Nutr.57, 1–24 (2018). PubMed PMC
Magnusdottir, S., Ravcheev, D., de Crecy-Lagard, V. & Thiele, I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Front. Genet.6, 148 (2015). PubMed PMC
Rodionov, D. A. et al. Micronutrient requirements and sharing capabilities of the human gut microbiome. Front. Microbiol.10, 1326 (2019). PubMed PMC
Soto-Martin, E. C. et al. Vitamin biosynthesis by human gut butyrate-producing bacteria and cross-feeding in synthetic microbial communities. mBio11, e0088620 (2020). PubMed PMC
Das, P., Babaei, P. & Nielsen, J. Metagenomic analysis of microbe-mediated vitamin metabolism in the human gut microbiome. BMC Genom.20, 1–11 (2019). PubMed PMC
D’Aimmo, M. R. et al. The potential of bifidobacteria as a source of natural folate. J. Appl. Microbiol.112, 975–984 (2012). PubMed
Rosario, D. et al. Systematic analysis of gut microbiome reveals the role of bacterial folate and homocysteine metabolism in Parkinson’s disease. Cell Rep.34, 108807 (2021). PubMed
Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature473, 174–180 (2011). PubMed PMC
Costea, P. I. et al. Enterotypes in the landscape of gut microbial community composition. Nat. Microbiol.3, 8–16 (2018). PubMed PMC
Kurokawa, K. et al. Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes. DNA Res.14, 169–181 (2007). PubMed PMC
Bäckhed, F. et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe17, 690–703 (2015). PubMed
Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature486, 222–227 (2012). PubMed PMC
Christian, T., R, F. L. & TJ, G. Citrus pectin and oligofructose improve folate status and lower serum total homocysteine in rats. Int. J. Vitam. Nutr. Res.73, 403–409 (2003). PubMed
Houghton, L. A. et al. Association between dietary fiber intake and the folate status of a group of female adolescents. Am. J. Clin. Nutr.66, 1414–1421 (1997). PubMed
Aufreiter, S., Kim, J. H. & O’Connor, D. L. Dietary oligosaccharides increase colonic weight and the amount but not concentration of bacterially synthesized folate in the colon of piglets. J. Nutr.141, 366–372 (2011). PubMed
Pompei, A. et al. Administration of folate-producing bifidobacteria enhances folate status in Wistar rats. J. Nutr.137, 2742–2746 (2007). PubMed
Valentini, L. et al. Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota–The “RISTOMED project”: Randomized controlled trial in healthy older people. Clin. Nutr.34, 593–602 (2015). PubMed
Sugahara, H. et al. Differences in folate production by bifidobacteria of different origins. Biosci. Microbiota Food Health34, 87–93 (2015). PubMed PMC
Sepehr, E. et al. Folate derived from cecal bacterial fermentation does not increase liver folate stores in 28-d folate-depleted male Sprague-Dawley rats. J. Nutr.133, 1347–1354 (2003). PubMed
Asrar, F. M. & O’Connor, D. L. Bacterially synthesized folate and supplemental folic acid are absorbed across the large intestine of piglets. J. Nutr. Biochem.16, 587–593 (2005). PubMed
Aufreiter, S. et al. Folate is absorbed across the colon of adults: evidence from cecal infusion of 13C-labeled [6S]-5-formyltetrahydrofolic acid. Am. J. Clin. Nutr.90, 116–123 (2009). PubMed PMC
Lakoff, A. et al. Folate is absorbed across the human colon: evidence by using enteric-coated caplets containing 13C-labeled [6S]-5-formyltetrahydrofolate. Am. J. Clin. Nutr.100, 1278–1286 (2014). PubMed PMC
Visentin, M., Diop-Bove, N., Zhao, R. & Goldman, I. D. The intestinal absorption of folates. Annu. Rev. Physiol.76, 251–274 (2014). PubMed PMC
Dudeja, P. et al. Mechanism of folate transport across the human colonic basolateral membrane. Am. J. Physiol. Gastrointest. Liver Physiol.281, G54–G60 (2001). PubMed
Zhan, Q. et al. Unveiling of dietary and gut-microbiota derived B vitamins: metabolism patterns and their synergistic functions in gut-brain homeostasis. Crit. Rev. Food Sci. Nutr. 64, 4046–4058 (2024). PubMed
Klaassen, M. A. et al. Anti-inflammatory gut microbial pathways are decreased during Crohn’s disease exacerbations. J. Crohns Colitis13, 1439–1449 (2019). PubMed PMC
Liu, M. et al. Probiotic potential of a folate-producing strain Latilactobacillus sakei LZ217 and its modulation effects on human gut microbiota. Foods11, 234 (2022). PubMed PMC
Gholami, H., Chmiel, J. A., Burton, J. P. & Maleki Vareki, S. The role of microbiota-derived vitamins in immune homeostasis and enhancing cancer immunotherapy. Cancers15, 1300 (2023). PubMed PMC
O’Keefe, S. J. et al. Products of the colonic microbiota mediate the effects of diet on colon cancer risk. J. Nutr.139, 2044–2048 (2009). PubMed PMC
Hossain, K. S., Amarasena, S. & Mayengbam, S. B vitamins and their roles in gut health. Microorganisms10, 1168 (2022). PubMed PMC
Crott, J. W. et al. Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling and folate uptake in human colonic epithelial cell lines. J. Nutr. Biochem.19, 328–335 (2008). PubMed PMC
Thomas, C. M. et al. FolC2‐mediated folate metabolism contributes to suppression of inflammation by probiotic Lactobacillus reuteri. Microbiologyopen5, 802–818 (2016). PubMed PMC
Said, H. M. Intestinal absorption of water-soluble vitamins in health and disease. Biochem. J.437, 357–372 (2011). PubMed PMC
Said, H. M. Recent advances in transport of water-soluble vitamins in organs of the digestive system: a focus on the colon and the pancreas. Am. J. Physiol. Gastrointest. Liver Physiol.305, G601–G610 (2013). PubMed PMC
Kok, D. E. et al. Bacterial folate biosynthesis and colorectal cancer risk: more than just a gut feeling. Crit. Rev. Food Sci. Nutr.60, 244–256 (2020). PubMed
Williams, E. A. et al. Systemic folate status, rectal mucosal folate concentration and dietary intake in patients at differential risk of bowel cancer (The FAB2 Study). Eur. J. Nutr.52, 1801–1810 (2013). PubMed
McGlynn, A. P. et al. Low colonocyte folate is associated with uracil misincorporation and global DNA hypomethylation in human colorectum. J. Nutr.143, 27–33 (2013). PubMed
Flood, A. et al. Concentration of folate in colorectal tissue biopsies predicts prevalence of adenomatous polyps. Gut60, 66–72 (2011). PubMed PMC
Barkhidarian, B. et al. Probiotic supplementation and micronutrient status in healthy subjects: a systematic review of clinical trials. Nutrients13, 3001 (2021). PubMed PMC
Berry Ottaway, P. Stability of vitamins during food processing and storage. In Chemical Deterioration and Physical Instability of Food and Beverages (eds Skibsted, H. L., Risbo, J. & Andersen, L. M.) Ch. 19, 539–560 (Woodhead Publishing, 2010).
Godoy, H. T., Amaya-Farfan, J. & Rodriguez-Amaya, D. B. Degradation of vitamins. In Chemical Changes During Processing and Storage of Foods (eds Rodriguez-Amaya, D. B. & Amaya-Farfan, J.) Ch. 8, 329–383 (Academic Press, 2021).
Bationo, F. et al. Total folate in West African cereal-based fermented foods: bioaccessibility and influence of processing. J. Food Compos. Anal.85, 103309 (2020).
Wusigale & Liang, L. Folates: stability and interaction with biological molecules. J. Agric. Food Res.2, 100039 (2020).
Delchier, N. et al. Mechanisms of folate losses during processing: diffusion vs. heat degradation. Food Chem.157, 439–447 (2014). PubMed
Saubade, F. et al. Influence of fermentation and other processing steps on the folate content of a traditional African cereal-based fermented food. Int. J. Food Microbiol.266, 79–86 (2018). PubMed
Wahengbam, E. D. et al. Effect of iron and folic acid fortification on in vitro bioavailability and starch hydrolysis in ready-to-eat parboiled rice. Food Chem.292, 39–46 (2019). PubMed
Jastrebova, J. et al. HPLC determination of folates in raw and processed beetroots. Food Chem.80, 579–588 (2003).
Witthöft, C. M. & Hefni, M. Folic acid and folates: Physiology and health effects. In Encyclopedia of Food and Health (eds Caballero, B., Finglas, P. M. & Toldrá, F.) 724-730 (Academic Press, 2016).
Lešková, E. et al. Vitamin losses: Retention during heat treatment and continual changes expressed by mathematical models. J. Food Compost. Anal.19, 252–276 (2006).
Jägerstad, M. et al. Increasing natural food folates through bioprocessing and biotechnology. Trends Food Sci. Technol.16, 298–306 (2005).
Scott, J., Rébeillé, F. & Fletcher, J. Folic acid and folates: the feasibility for nutritional enhancement in plant foods. J. Sci. Food Agric.80, 795–824 (2000).
Giordano, D., Reyneri, A. & Blandino, M. Folate distribution in barley (Hordeum vulgare L.), common wheat (Triticum aestivum L.) and durum wheat (Triticum turgidum durum Desf.) pearled fractions. J. Sci. Food Agric.96, 1709–1715 (2016). PubMed
Boz, H. Effect of processing on cereal folates. J. Cereal Sci.99, 103202 (2021).
Henry, C. & Heppell, N. Nutritional losses and gains during processing: future problems and issues. Proc. Nutr. Soc.61, 145–148 (2002). PubMed
Buri, R. C., von Reding, W. & Gavin, M. H. Description and characterization of wheat aleurone. Cereal Foods World49, 274 (2004).
Hemery, Y. et al. Potential of dry fractionation of wheat bran for the development of food ingredients, part II: electrostatic separation of particles. J. Cereal Sci.53, 9–18 (2011).
Blandino, M. et al. Distribution of bioactive compounds in maize fractions obtained in two different types of large scale milling processes. J. Cereal Sci.77, 251–258 (2017).
McIntosh, S. R., Brushett, D. & Henry, R. J. GTP cyclohydrolase 1 expression and folate accumulation in the developing wheat seed. J. Cereal Sci.48, 503–512 (2008).
Suri, D. J. & Tanumihardjo, S. A. Effects of different processing methods on the micronutrient and phytochemical contents of maize: from A to Z. Compr. Rev. Food Sci. Food Saf.15, 912–926 (2016). PubMed
Slavin, J. L., Jacobs, D. & Marquart, L. Grain processing and nutrition. Crit. Rev. Food Sci. Nutr.40, 309–326 (2000). PubMed
Thielecke, F., Lecerf, J.-M. & Nugent, A. P. Processing in the food chain: do cereals have to be processed to add value to the human diet? Nutr. Res. Rev.34, 159–173 (2021). PubMed
Lebert, L., Buche, F., Sorin, A. & Aussenac, T. The wheat aleurone layer: optimisation of its benefits and application to bakery products. Foods11, 3552 (2022). PubMed PMC
Meziani, S. et al. Wheat aleurone layer: A site enriched with nutrients and bioactive molecules with potential nutritional opportunities for breeding. J. Cereal Sci.100, 103225 (2021).
Liukkonen, K.-H. et al. Process-induced changes on bioactive compounds in whole grain rye. Proc. Nutr. Soc.62, 117–122 (2003). PubMed
Kamal-Eldin, A. et al. Physical, microscopic and chemical characterisation of industrial rye and wheat brans from the Nordic countries. Food Nutr. Res.53, 1912 (2009). PubMed PMC
MacDonald, R. & Reitmeier, C. Food processing. In Understanding Food Systems: Agriculture, Food Science, and Nutrition in the United States (eds MacDonald, R. & Reitmeier, C.) Ch. 6, 179–225 (Academic Press, 2017).
Hegedüs, M., Pedersen, B. & Eggum, B. F. O. The influence of milling on the nutritive value of flour from cereal grains. 7. Vitamins and tryptophan. Plant Foods Hum. Nutr.35, 175–180 (1985).
Călinoiu, L. F. & Vodnar, D. C. Whole grains and phenolic acids: a review on bioactivity, functionality, health benefits and bioavailability. Nutrients10, 1615 (2018). PubMed PMC
Liang, Q. et al. Folate content and retention in wheat grains and wheat-based foods: Effects of storage, processing, and cooking methods. Food Chem.333, 127459 (2020). PubMed
Jiang, Z. et al. Effect of milling on nutritional components in common and zinc-biofortified wheat. Nutrients15, 833 (2023). PubMed PMC
Dunn, M. L., Jain, V. & Klein, B. P. Stability of key micronutrients added to fortified maize flours and corn meal. Ann. N. Y. Acad. Sci.1312, 15–25 (2014). PubMed
Edelmann, M., Kariluoto, S., Nyström, L. & Piironen, V. Folate in barley grain and fractions. J. Cereal Sci.58, 37–44 (2013).
Garg, M. et al. Vitamins in cereals: a critical review of content, health effects, processing losses, bioaccessibility, fortification, and biofortification strategies for their improvement. Front. Nutr.8, 586815 (2021). PubMed PMC
Gwirtz, J. A. & Garcia‐Casal, M. N. Processing maize flour and corn meal food products. Ann. N. Y. Acad. Sci.1312, 66–75 (2014). PubMed PMC
Edelmann, M., Kariluoto, S., Nyström, L. & Piironen, V. Folate in oats and its milling fractions. Food Chem.135, 1938–1947 (2012). PubMed
Tiozon, R. J. N., Fernie, A. R. & Sreenivasulu, N. Meeting human dietary vitamin requirements in the staple rice via strategies of biofortification and post-harvest fortification. Trends Food Sci. Technol.109, 65–82 (2021).
DGExpert. DGE Deutsche Gesellschaft für Ernährung, http://www.nutrisurvey.de/info/interaktives/search.htm (2018).
Dong, W. et al. Determination of folate content in rice germplasm (Oryza sativa L.) using tri-enzyme extraction and microbiological assays. Int. J. Food Sci. Nutr.62, 537–543 (2011). PubMed
de Pee, S. Proposing nutrients and nutrient levels for rice fortification. Ann. N. Y. Acad. Sci.1324, 55–66 (2014). PubMed
Monks, J. L. F. et al. Effects of milling on proximate composition, folic acid, fatty acids and technological properties of rice. J. Food Compos. Anal.30, 73–79 (2013).
WHO. Guideline: Fortification of rice with vitamins and minerals as a public health strategy (World Health Organization, 2018). PubMed
Sumczynski, D. et al. Preparation of non-traditional Dickkopf and Richard wheat flakes: Phenolic and vitamin profiles and antioxidant activity. LWT90, 31–37 (2018).
Akhtar, M. J., Khan, M. A. & Ahmad, I. Photodegradation of folic acid in aqueous solution. J. Pharm. Biomed. Anal.19, 269–275 (1999). PubMed
Bergström, L. Nutrient Losses and Gains in the Preparation of Foods (National Food Administration, 1994).
Schnellbaecher, A., Binder, D., Bellmaine, S. & Zimmer, A. Vitamins in cell culture media: Stability and stabilization strategies. Biotechnol. Bioeng.116, 1537–1555 (2019). PubMed PMC
Riaz, M. N., Asif, M. & Ali, R. Stability of vitamins during extrusion. Crit. Rev. Food Sci. Nutr.49, 361–368 (2009). PubMed
Yessaad, M. et al. Development of a stability indicating method for simultaneous analysis of five water-soluble vitamins by liquid chromatography. Pharm. Technol. Hosp. Pharm.3, 207–218 (2018).
Lorente, C. & Thomas, A. H. Photophysics and photochemistry of pterins in aqueous solution. Acc. Chem. Res.39, 395–402 (2006). PubMed
Patro, B. S., Adhikari, S., Mukherjee, T. & Chattopadhyay, S. Possible role of hydroxyl radicals in the oxidative degradation of folic acid. Bioorg. Med. Chem. Lett.15, 67–71 (2005). PubMed
Steindal, A. H., Juzeniene, A., Johnsson, A. & Moan, J. Photodegradation of 5‐methyltetrahydrofolate: biophysical aspects. Photochem. Photobiol.82, 1651–1655 (2006). PubMed
Off, M. K. et al. Ultraviolet photodegradation of folic acid. J. Photochem. Photobiol. B Biol.80, 47–55 (2005). PubMed
Martin, C. B., Walker, D. & Soniat, M. Density functional theory study of possible mechanisms of folic acid photodecomposition. J. Photochem. Photobiol. A Chem.208, 1–6 (2009).
Gazzali, A. M. et al. Stability of folic acid under several parameters. Eur. J. Pharm. Sci.93, 419–430 (2016). PubMed
Liang, X. S., Zhao, F. Q. & Hao, L. X. Research on stability of synthetic folic acid. Adv. Mater. Res.781, 1215–1218 (2013).
Yang, Y. et al. Degradation of 5-methyltetrahydrofolate in model and egg yolk systems and strategies for its stabilization. J. Food Sci. Technol.58, 3473–3481 (2021). PubMed PMC
Araújo, M. et al. LC/MS/MS identification of some folic acid degradation products after E-beam irradiation. Radiat. Phys. Chem.81, 1166–1169 (2012).
Araújo, M. M. et al. Irradiation stability of folic acid in powder and aqueous solution. J. Agric. Food Chem.59, 1244–1248 (2011). PubMed
Araújo, M. M. et al. Mechanism of folic acid radiolysis in aqueous solution. LWT63, 599–603 (2015).
Vora, A., Riga, A., Dollimore, D. & Alexander, K. Thermal stability of folic acid in the solid-state. J. Therm. Anal. Calorim.75, 709–717 (2004).
Neves, D. A. et al. Thermal and in vitro digestion stability of folic acid in bread. J. Food Compos. Anal.84, 103311 (2019).
Mair, P. et al. Vitamins, 12. Vitamin B9. In Ullmann’s Encyclopedia of Industrial Chemistry, 1–15 (Wiley‐VCH Verlag GmbH & Co. KGaA, 2019).
Fitzpatrick, T. B. et al. Vitamin deficiencies in humans: can plant science help? Plant Cell24, 395–414 (2012). PubMed PMC
Wu, Z., Li, X., Hou, C. & Qian, Y. Solubility of folic acid in water at pH values between 0 and 7 at temperatures (298.15, 303.15, and 313.15) K. J. Chem. Eng. Data55, 3958–3961 (2010).
Juzeniene, A., Tam, T. T. T., Iani, V. & Moan, J. 5-methyltetrahydrofolate can be photodegraded by endogenous photosensitizers. Free Radic. Biol. Med.47, 1199–1204 (2009). PubMed
Vorobey, P. et al. Influence of human serum albumin on photodegradation of folic acid in solution. Photochem. Photobiol.82, 817–822 (2006). PubMed
Tam, T. T. T. et al. Photodegradation of 5-methyltetrahydrofolate in the presence of uroporphyrin. J. Photochem. Photobiol. B Biol.94, 201–204 (2009). PubMed
Hrubša, M. et al. Biological properties of vitamins of the B-complex, part 1: vitamins B1, B2, B3, and B5. Nutrients14, 484 (2022). PubMed PMC
Steindal, A. H. et al. 5-Methyltetrahydrofolate is photosensitive in the presence of riboflavin. Photochem. Photobiol. Sci.7, 814–818 (2008). PubMed
Scurachio, R. S., Skibsted, L. H., Metzker, G. & Cardoso, D. R. Photodegradation of folate sensitized by riboflavin. Photochem. Photobiol.87, 840–845 (2011). PubMed
Akhtar, M. J., Khan, M. A. & Ahmad, I. Effect of riboflavin on the photolysis of folic acid in aqueous solution. J. Pharm. Biomed. Anal.23, 1039–1044 (2000). PubMed
Delchier, N. et al. Thermal degradation of folates under varying oxygen conditions. Food Chem.165, 85–91 (2014). PubMed
Zheng, Y. & Cantley, L. C. Toward a better understanding of folate metabolism in health and disease. J. Exp. Med.216, 253–266 (2019). PubMed PMC
Indrawati et al. Comparative study on pressure and temperature stability of 5-methyltetrahydrofolic acid in model systems and in food products. J. Agric. Food Chem.52, 485–492 (2004). PubMed
Indrawati et al. Implications of β-mercaptoethanol in relation to folate stability and to determination of folate degradation kinetics during processing: a case study on [6 S]-5-methyltetrahydrofolic acid. J. Agric. Food Chem.52, 8247–8254 (2004). PubMed
Servent, A., Cazals, G., Perfetto, C. & Achir, N. Kinetic modeling of four folates in a model solution at different temperatures and pH to mimic their behavior in foods during processing. J. Food Process Eng.46, e14288 (2023).
De Brouwer, V. et al. pH stability of individual folates during critical sample preparation steps in prevision of the analysis of plant folates. Phytochem. Anal.18, 496–508 (2007). PubMed
Nguyen, M., Oey, I., Hendrickx, M. & Van Loey, A. Kinetics of (6 R, S) 5-formyltetrahydrofolic acid isobaric–isothermal degradation in a model system. Eur. Food Res. Technol.223, 325–331 (2006).
Nguyen, M. T. Study on folate stability during thermal processing. Can Tho University J. Sci. 4, 87–94. https://ctujs.ctu.edu.vn/index.php/ctujs/article/view/208 (2016).
Nguyen, M. T. The kinetics study on 5-formyltetrahydrofolic acid degradation and 5, 10-methenyltetrahydrofolic acid formation during thermal and combined high pressure thermal treatments. Can Tho University J. Sci.5, 132–140 (2017).
Kariluoto, S. et al. Effect of baking method and fermentation on folate content of rye and wheat breads. Cereal Chem.81, 134–139 (2004).
Shrestha, A. K., Arcot, J. & Yuliani, S. Susceptibility of 5-methyltetrahydrofolic acid to heat and microencapsulation to enhance its stability during extrusion processing. Food Chem.130, 291–298 (2012).
Nguyen, M. T., Indrawati & Hendrickx, M. Model studies on the stability of folic acid and 5-methyltetrahydrofolic acid degradation during thermal treatment in combination with high hydrostatic pressure. J. Agric. Food Chem.51, 3352–3357 (2003). PubMed
Ministry of Education Sports Science and Technology-Japan. Standard tables of food composition in Japan, 7th Revised ed., https://www.mext.go.jp/en/policy/science_technology/policy/title01/detail01/1374030.htm (2015).
Public Health England. McCance and Widdowson’s composition of foods integrated dataset, https://assets.publishing.service.gov.uk/media/60538e66d3bf7f03249bac58/McCance_and_Widdowsons_Composition_of_Foods_integrated_dataset_2021.pdf (2021).
Roe, M., Church, S., Pinchen, H. & Finglas, P. Nutrient analysis of fruit and vegetables: analytical report. 17–76 (Institute of Food Research, 2013).
Roe, M., Church, S., Pinchen, H. & Finglas, P. Nutrient analysis of fish and fish products: analytical report. 14–70 (Institute of Food Research, 2013).
Delchier, N., Reich, M. & Renard, C. M. Impact of cooking methods on folates, ascorbic acid and lutein in green beans (Phaseolus vulgaris) and spinach (Spinacea oleracea). LWT49, 197–201 (2012).
Bognár, A. Tables on Weight Yield of Food and Retention Factors of Food Constituents for the Calculation of Nutrient Composition of Cooked Foods (Dishes) (Bundesforschungsanstalt für Ernährung, 2002).
USDA. USDA table of nutrient retention factors, Release 6, https://data.nal.usda.gov/dataset/usda-table-nutrient-retention-factors-release-6-2007 (2007).
Öhrvik, V., Carlsen, M. H., Källman, A. & Martinsen, T. A. Improving Food Composition Data by Standardizing Calculation Methods (Nordic Council of Ministers, 2015).
Bell, S. et al. Report on nutrient losses and gains factors used in European food composition databases (European Food Information Resource Network, 2006).
McKillop, D. J. et al. The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet. Br. J. Nutr.88, 681–688 (2002). PubMed
Stea, T. H., Johansson, M., Jägerstad, M. & Frølich, W. Retention of folates in cooked, stored and reheated peas, broccoli and potatoes for use in modern large-scale service systems. Food Chem101, 1095–1107 (2007).
Holasova, M., Fiedlerova, V. & Vavreinova, S. Determination of folates in vegetables and their retention during boiling. Czech J. Food Sci.26, 31–37 (2008).
Maharaj, P. P., Prasad, S., Devi, R. & Gopalan, R. Folate content and retention in commonly consumed vegetables in the South Pacific. Food Chem.182, 327–332 (2015). PubMed
Hong, J. et al. Folate content of Korean vegetable dishes prepared outside the home: comparison between analyzed and calculated values. J. Food Compos. Anal.103, 104088 (2021).
Renard, C. M. et al. Relative role of leaching and chemical degradation in the loss of water-soluble vitamins C and B9 from frozen vegetables cooked in water. LWT180, 114694 (2023).
Macova, E. & Krkoskova, B. Effect of heat processing on folic acid and biotin content in food of plant origin. Agriculture49, 349–356 (2003).
Czarnowska-Kujawska, M., Draszanowska, A. & Starowicz, M. Effect of different cooking methods on the folate content, organoleptic and functional properties of broccoli and spinach. LWT167, 113825 (2022).
Della Lucia, C. M. et al. Folates retention in brassica vegetables consumed in Brazil after different cooking methods. Arch. Latinoam. Nutr.64, 59–68 (2014). PubMed
Bureau, S. et al. Are folates, carotenoids and vitamin C affected by cooking? Four domestic procedures are compared on a large diversity of frozen vegetables. LWT64, 735–741 (2015).
Melse-Boonstra, A. et al. Influence of processing on total, monoglutamate and polyglutamate folate contents of leeks, cauliflower, and green beans. J. Agric. Food Chem.50, 3473–3478 (2002). PubMed
Puupponen‐Pimiä, R. et al. Blanching and long‐term freezing affect various bioactive compounds of vegetables in different ways. J. Sci. Food Agric.83, 1389–1402 (2003).
Czarnowska, M. & Gujska, E. Effect of freezing technology and storage conditions on folate content in selected vegetables. Plant Foods Hum. Nutr.67, 401–406 (2012). PubMed
Delchier, N. et al. Effects of industrial processing on folate content in green vegetables. Food Chem.139, 815–824 (2013). PubMed
Islam, M. S. et al. Folate content in fresh corn: effects of harvest time, storage and cooking methods. J. Food Compos. Anal.103, 104123 (2021).
Wawire, M. et al. Effect of harvest age and thermal processing on poly-γ-glutamate folates and minerals in African cowpea leaves (Vigna unguiculata). J. Food Compos. Anal.25, 160–165 (2012).
Rumm-Kreuter, D. & Demmel, I. Comparison of vitamin losses in vegetables due to various cooking methods. J. Nutr. Sci. Vitaminol.36, S7–S15 (1990). PubMed
Johansson, M., Furuhagen, C., Frølich, W. & Jägerstad, M. Folate content in frozen vegetarian ready meals and folate retention after different reheating methods. LWT41, 528–536 (2008).
Gutzeit, D. et al. Folate content in sea buckthorn berries and related products (Hippophae rhamnoides L. ssp. rhamnoides): LC-MS/MS determination of folate vitamer stability influenced by processing and storage assessed by stable isotope dilution assay. Anal. Bioanal. Chem.391, 211–219 (2008). PubMed
Wang, C., Riedl, K. M. & Schwartz, S. J. Fate of folates during vegetable juice processing—Deglutamylation and interconversion. Food Res. Int.53, 440–448 (2013).
Strålsjö, L., Alklint, C., Olsson, M. E. & Sjöholm, I. Total folate content and retention in rosehips (Rosa ssp.) after drying. J. Agric. Food Chem.51, 4291–4295 (2003). PubMed
Akissoé, L. et al. Impact of traditional processing on proximate composition, folate, mineral, phytate, and alpha-galacto-oligosaccharide contents of two West African cowpea (Vigna unguiculata L. Walp) based doughnuts. J. Food Compos. Anal.96, 103753 (2021).
Ferawati, F., Hefni, M. & Witthöft, C. Flours from Swedish pulses: effects of treatment on functional properties and nutrient content. Food Sci. Nutr.7, 4116–4126 (2019). PubMed PMC
Coffigniez, F. & Briffaz, A. Modelling of the nutritional behaviour of cowpea seeds during soaking, germination and cooking process. Food Chem.401, 134177 (2023). PubMed
Miftakhussolikhah et al. Folate content of mung bean flour prepared by various heat-treatments. Procedia Food Sci.3, 69–73 (2015).
Dang, J., Arcot, J. & Shrestha, A. Folate retention in selected processed legumes. Food Chem.68, 295–298 (2000).
Xue, S. et al. Degradation kinetics of folate (5-methyltetrahydrofolate) in navy beans under various processing conditions. LWT44, 231–238 (2011).
Liang, Q. et al. Investigation of folate composition and influence of processing on folate stability in pulse accessions developed in China. J. Food Compos. Anal.114, 104785 (2022).
Hefni, M. & Witthöft, C. M. Folate content in processed legume foods commonly consumed in Egypt. LWT57, 337–343 (2014).
Coffigniez, F. et al. Localization and modeling of reaction and diffusion to explain folate behavior during soaking of cowpea. J. Food Eng.253, 49–58 (2019).
Arcot, J., Wong, S. & Shrestha, A. K. Comparison of folate losses in soybean during the preparation of tempeh and soymilk. J. Sci. Food Agric.82, 1365–1368 (2002).
Ginting, E., Arcot, J. & Chox, J. M. Determination of folate retention during tofu preparation using trienzyme treatment and microbiological assay. Indones. J. Agric. Sci.4, 12–17 (2003).
Mo, H. et al. Effect of soybean processing on content and bioaccessibility of folate, vitamin B12 and isoflavones in tofu and tempe. Food Chem.141, 2418–2425 (2013). PubMed
Ginting, E. & Arcot, J. High-performance liquid chromatographic determination of naturally occurring folates during tempe preparation. J. Agric. Food Chem.52, 7752–7758 (2004). PubMed
Ktenioudaki, A., Alvarez-Jubete, L. & Gallagher, E. A review of the process-induced changes in the phytochemical content of cereal grains: The breadmaking process. Crit. Rev. Food Sci. Nutr.55, 611–619 (2015). PubMed
Arcot, J. et al. Folate levels in twelve Australian wheats and changes during processing into bread. Food Aust.54, 18–20 (2002).
Osseyi, E. S., Wehling, R. L. & Albrecht, J. A. HPLC determination of stability and distribution of added folic acid and some endogenous folates during breadmaking. Cereal Chem.78, 375–378 (2001).
Hefni, M. & Witthöft, C. M. Increasing the folate content in Egyptian baladi bread using germinated wheat flour. LWT44, 706–712 (2011).
Kariluoto, S. et al. Effects of yeasts and bacteria on the levels of folates in rye sourdoughs. Int. J. Food Microbiol.106, 137–143 (2006). PubMed
Katina, K. et al. Fermentation-induced changes in the nutritional value of native or germinated rye. J. Cereal Sci.46, 348–355 (2007).
Gujska, E., Michalak, J. & Klepacka, J. Folates stability in two types of rye breads during processing and frozen storage. Plant Foods Hum. Nutr.64, 129–134 (2009). PubMed
Helou, C. et al. The impact of raw materials and baking conditions on Maillard reaction products, thiamine, folate, phytic acid and minerals in white bread. Food Funct.7, 2498–2507 (2016). PubMed
Omar, R. M. et al. Effect of processing on folic acid fortified Baladi bread and its possible effect on the prevention of colon cancer. Food Chem. Toxicol.47, 1626–1635 (2009). PubMed
Gujska, E. & Majewska, K. Effect of baking process on added folic acid and endogenous folates stability in wheat and rye breads. Plant Foods Hum. Nutr.60, 37–42 (2005). PubMed
Anderson, W. A., Slaughter, D., Laffey, C. & Lardner, C. Reduction of folic acid during baking and implications for mandatory fortification of bread. Int. J. Food Sci. Technol.45, 1104–1110 (2010).
Johansson, M., Witthöft, C. M., Bruce, Å. & Jägerstad, M. Study of wheat breakfast rolls fortified with folic acid: the effect on folate status in women during a 3-month intervention. Eur. J. Nutr.41, 279–286 (2002). PubMed
Tomiuk, S. et al. Studies on the retention of microencapsulated L-5-methyltetrahydrofolic acid in baked bread using skim milk powder. Food Chem.133, 249–255 (2012). PubMed
Liu, Y., Green, T. J., Wong, P. & Kitts, D. D. Microencapsulation of L-5-methyltetrahydrofolic acid with ascorbate improves stability in baked bread products. J. Agric. Food Chem.61, 247–254 (2013). PubMed
López-Nicolás, R. et al. Folate fortification of white and whole-grain bread by adding Swiss chard and spinach. Acceptability by consumers. LWT59, 263–269 (2014).
Tamene, A., Kariluoto, S., Baye, K. & Humblot, C. Quantification of folate in the main steps of traditional processing of tef injera, a cereal based fermented staple food. J. Cereal Sci.87, 225–230 (2019).
Ekıncı, R. The effect of fermentation and drying on the water-soluble vitamin content of tarhana, a traditional Turkish cereal food. Food Chem.90, 127–132 (2005).
Chapman, J. et al. Stability of native folate and added folic acid in micronutrient‐fortified corn masa and tortillas. Cereal Chem.87, 434–438 (2010).
Burton, K. et al. Effect of micronutrient fortification on nutritional and other properties of nixtamal tortillas. Cereal Chem.85, 70–75 (2008).
Dunn, M. L., Serna‐Saldivar, S. O., Sanchez‐Hernandez, D. & Griffin, R. W. Commercial evaluation of a continuous micronutrient fortification process for nixtamal tortillas. Cereal Chem.85, 746–752 (2008).
Adolphson, S. J. et al. Evaluation of bacterial effects on folic acid loss in fortified, nixtamalized corn masa flour. Cereal Chem.93, 508–512 (2016).
Phillips, R., Pike, O. A., Eggett, D. L. & Dunn, M. L. Folate stability in folic acid enriched corn masa flour, tortillas, and tortilla chips over the expected shelf life. Cereal Chem.94, 917–921 (2017).
Koren, D., Hegyesné Vecseri, B. & Kun-Farkas, G. Evolution of folate content during barley malt production. Acta Aliment50, 238–246 (2021).
Kariluoto, S. et al. Effect of germination and thermal treatments on folates in rye. J. Agric. Food Chem.54, 9522–9528 (2006). PubMed
Yoo, J. et al. Rice-shaped extruded kernels: physical, sensory, and nutritional properties. Int. J. Food Prop.16, 301–321 (2013).
Soongsongkiat, M. et al. Testing of folate conjugase from chicken pancreas vs. commercial enzyme and studying the effect of cooking on folate retention in Thai foods. J. Food Compos. Anal.23, 681–688 (2010).
Gray, P. J., Conklin, S. D., Todorov, T. I. & Kasko, S. M. Cooking rice in excess water reduces both arsenic and enriched vitamins in the cooked grain. Food Addit. Contam. Part A33, 78–85 (2016). PubMed
Silveira, C. M. M. et al. Effect of cooking methods on the stability of thiamin and folic acid in fortified rice. Int. J. Food Sci. Nutr.68, 179–187 (2017). PubMed
Porasuphatana, S. et al. Production and shelf stability of multiple‐fortified quick‐cooking rice as a complementary food. J. Food Sci.73, S359–S366 (2008). PubMed
Shrestha, A. K., Arcot, J. & Paterson, J. L. Edible coating materials—their properties and use in the fortification of rice with folic acid. Food Res. Int.36, 921–928 (2003).
de Ambrosis, A. et al. Relative bioavailability of 13C5-folic acid in pectin-coated folate fortified rice in humans using stable isotope techniques. Eur. J. Clin. Nutr.71, 103–106 (2017). PubMed
Wieringa, F. T. et al. Stability and retention of micronutrients in fortified rice prepared using different cooking methods. Ann. N. Y. Acad. Sci.1324, 40–47 (2014). PubMed
Thiruselvam, N. et al. Micronutrients fortification of rice by parboiling: lab scale and pilot scale studies. J. Nutr. Food Sci.4, 1–7 (2014).
Kam, K., Arcot, J. & Ward, R. Fortification of rice with folic acid using parboiling technique: Effect of parboiling conditions on nutrient uptake and physical characteristics of milled rice. J. Cereal Sci.56, 587–594 (2012).
Tiozon, R. N. Jr et al. Efficient fortification of folic acid in rice through ultrasonic treatment and absorption. Food Chem.335, 127629 (2021). PubMed
Bui, L. T. & Small, D. M. Folates in Asian noodles: II. a comparison of commercial samples and the impact of cooking. J. Food Sci.72, C283–C287 (2007). PubMed
Bui, L. T. & Small, D. M. Folates in Asian noodles: III. fortification, impact of processing, and enhancement of folate intakes. J. Food Sci.72, C288–C293 (2007). PubMed
Cheung, R. H. F., Hughes, J. G., Marriott, P. J. & Small, D. M. Investigation of folic acid stability in fortified instant Asian noodles by use of capillary electrophoresis. Food Chem.112, 507–514 (2009). PubMed
Cheung, R. H. F., Morrison, P. D., Small, D. M. & Marriott, P. J. Investigation of folic acid stability in fortified instant noodles by use of capillary electrophoresis and reversed-phase high performance liquid chromatography. J. Chromatogr. A1213, 93–99 (2008). PubMed
Liu, Y., Green, T. J. & Kitts, D. D. Stability of microencapsulated L-5-methyltetrahydrofolate in fortified noodles. Food Chem.171, 206–211 (2015). PubMed
Ruggeri, S. et al. Design of cereal products naturally enriched in folate from barley pearling by-products. Nutrients14, 3729 (2022). PubMed PMC
Malahayati, N., Muhammad, K., Bakar, J. & Karim, R. The effect of processing method on fortified rice noodle quality and fortificant retention. Int. J. Food Sci. Nutr.4, 30–37 (2017).
Malahayati, N., Muhammad, K., Bakar, J. & Karim, R. Quality and fortificant retention of rice noodles as affected by flour particle size. Cereal Chem.92, 211–217 (2015).
Muehlhoff, E., Bennett, A. & McMahon, D. Milk and Dairy Products in Human Nutrition 43–64 (Food and Agriculture Organization of the United Nations, 2013).
Shetty, S. A., Young, M. F., Taneja, S. & Rangiah, K. Quantification of B-vitamins from different fresh milk samples using ultra-high performance liquid chromatography mass spectrometry/selected reaction monitoring methods. J. Chromatogr. A1609, 460452 (2020). PubMed
Oamen, E., Hansen, A. & Swartzel, K. Effect of ultra-high temperature steam injection processing and aseptic storage on labile water-soluble vitamins in milk. J. Dairy Sci.72, 614–619 (1989).
Van Heerden, S., Schönfeldt, H., Smith, M. & van Rensburg, D. J. Nutrient content of South African chickens. J. Food Compos. Anal.15, 47–64 (2002).
Czarnowska-Kujawska, M., Draszanowska, A. & Gujska, E. Effect of different cooking methods on folate content in chicken liver. Foods9, 1431 (2020). PubMed PMC
Cáceres, E., García, M. & Selgas, M. Conventional and reduced-fat cooked meat sausages enriched with folic acid. Fleischwirtschaft23, 58–60 (2008).
Jiratanan, T. & Liu, R. H. Antioxidant activity of processed table beets (Beta vulgaris var, conditiva) and green beans (Phaseolus vulgaris L.). J. Agric. Food Chem.52, 2659–2670 (2004). PubMed
Hefni, M. E., Shalaby, M. T. & Witthöft, C. M. Folate content in faba beans (Vicia faba L.)—effects of cultivar, maturity stage, industrial processing, and bioprocessing. Food Sci. Nutr.3, 65–73 (2015). PubMed PMC
Jägerstad, M., Jastrebova, J. & Svensson, U. Folates in fermented vegetables—a pilot study. LWT37, 603–611 (2004).
Lester, G. E., Hallman, G. J. & Pérez, J. A. γ-Irradiation dose: effects on baby-leaf spinach ascorbic acid, carotenoids, folate, α-tocopherol, and phylloquinone concentrations. J. Agric. Food Chem.58, 4901–4906 (2010). PubMed
Galán, I., García, M. & Selgas, M. Irradiation is useful for manufacturing ready-to-eat cooked meat products enriched with folic acid. Meat Sci.87, 330–335 (2011). PubMed
Galán, I., García, M. & Selgas, M. Effects of irradiation on hamburgers enriched with folic acid. Meat Sci.84, 437–443 (2010). PubMed
Luo, S., Duan, H., Zou, Y. & Wang, C. High pressure processing and post-high pressure storage induce the change of polyglutamyl folate and total folate from different legumes. J. Food Sci. Technol.54, 3521–3531 (2017). PubMed PMC
Oey, I., Van der Plancken, I., Van Loey, A. & Hendrickx, M. Does high pressure processing influence nutritional aspects of plant based food systems? Trends Food Sci. Technol.19, 300–308 (2008).
Verlinde, P., Oey, I., Hendrickx, M. & Van Loey, A. High-pressure treatments induce folate polyglutamate profile changes in intact broccoli (Brassica oleraceae L. cv. Italica) tissue. Food Chem.111, 220–229 (2008).
Ravichandran, C. et al. Influence of high pressure pasteurization on nutritional, functional and rheological characteristics of fruit and vegetable juices and purees-an updated review. Food Control146, 109516 (2023).
Ramos-Parra, P. A., Hernández-Brenes, C. & Díaz de la Garza, R. I. High hydrostatic pressure modulates the folate and ascorbic acid accumulation in Papaya (Carica papaya cv. Maradol) fruit. Food Eng. Rev.13, 613–621 (2021).
Indrawati, Van Loey, A. & Hendrickx, M. Pressure and temperature stability of 5-methyltetrahydrofolic acid: a kinetic study. J. Agric. Food Chem.53, 3081–3087 (2005). PubMed
Butz, P. et al. Influence of high‐pressure treatment at 25°C and 80 °C on folates in orange juice and model media. J. Food Sci.69, SNQ117–SNQ121 (2004).
Wang, C. et al. Influence of high-pressure processing on the profile of polyglutamyl 5-methyltetrahydrofolate in selected vegetables. J. Agric. Food Chem.59, 8709–8717 (2011). PubMed PMC
Verlinde, P. H. et al. Mechanism and related kinetics of 5-methyltetrahydrofolic acid degradation during combined high hydrostatic pressure− thermal treatments. J. Agric. Food Chem.57, 6803–6814 (2009). PubMed
Pandrangi, S. & LaBorde, L. Retention of folate, carotenoids, and other quality characteristics in commercially packaged fresh spinach. J. Food Sci.69, C702–C707 (2004).
O’Hare, T. et al. Impact of low temperature storage on active and storage forms of folate in choy sum (Brassica rapa subsp. parachinensis). Postharvest Biol. Technol.74, 85–90 (2012).
Striegel, L., Chebib, S., Netzel, M. E. & Rychlik, M. Improved stable isotope dilution assay for dietary folates using LC-MS/MS and its application to strawberries. Front. Chem.6, 11 (2018). PubMed PMC
Phillips, K. M. et al. Stability of 5-methyltetrahydrofolate in frozen fresh fruits and vegetables. Food Chem.92, 587–595 (2005).
Iniesta, M. D. et al. Folate content in tomato (Lycopersicon esculentum). Influence of cultivar, ripeness, year of harvest, and pasteurization and storage temperatures. J. Agric. Food Chem.57, 4739–4745 (2009). PubMed
Frommherz, L. et al. Degradation of folic acid in fortified vitamin juices during long term storage. Food Chem.159, 122–127 (2014). PubMed
Öhrvik, V. & Witthöft, C. Orange juice is a good folate source in respect to folate content and stability during storage and simulated digestion. Eur. J. Nutr.47, 92–98 (2008). PubMed
Hemery, Y. M. et al. Influence of storage conditions and packaging of fortified wheat flour on microbial load and stability of folate and vitamin B12. Food Chem. X5, 100076 (2020). PubMed PMC
Li, Y. O., Diosady, L. L. & Jankowski, S. Folic acid stability in the presence of various formulation components including iron compounds in fortified extruded Ultra Rice® over prolonged storage at 40 °C and 60% relative humidity (RH). Int. J. Food Sci. Technol.46, 379–385 (2011).
Zwart, S. et al. Assessment of nutrient stability in foods from the space food system after long‐duration spaceflight on the ISS. J. Food Sci.74, H209–H217 (2009). PubMed
House, J. et al. The enrichment of eggs with folic acid through supplementation of the laying hen diet. Poult. Sci.81, 1332–1337 (2002). PubMed
Altic, L. et al. Validation of folate-enriched eggs as a functional food for improving folate intake in consumers. Nutrients8, 777 (2016). PubMed PMC
Ford, J. E., Hurrell, R. F. & Finot, P. A. Storage of milk powders under adverse conditions. 2. Influence on the content of water-soluble vitamins. Br. J. Nutr.49, 355–364 (1983). PubMed
Chitisankul, W. T., Murakami, M., Tsukamoto, C. & Shimada, K. Effects of long-term soaking on nutraceutical and taste characteristic components in Thai soybeans. LWT115, 108432 (2019).
Coffigniez, F. et al. Modelling folates reaction kinetics during cowpea seed germination in comparison with soaking. Food Chem.340, 127960 (2021). PubMed
Koehler, P., Hartmann, G., Wieser, H. & Rychlik, M. Changes of folates, dietary fiber, and proteins in wheat as affected by germination. J. Agric. Food Chem.55, 4678–4683 (2007). PubMed
Hübner, F. & Arendt, E. K. Germination of cereal grains as a way to improve the nutritional value: a review. Crit. Rev. Food Sci. Nutr.53, 853–861 (2013). PubMed
Sallam, S. M., Shawky, E. & El Sohafy, S. M. Determination of the effect of germination on the folate content of the seeds of some legumes using HPTLC-mass spectrometry-multivariate image analysis. Food Chem.362, 130206 (2021). PubMed
Shohag, M., Wei, Y. & Yang, X. Changes of folate and other potential health-promoting phytochemicals in legume seeds as affected by germination. J. Agric. Food Chem.60, 9137–9143 (2012). PubMed
Zhang, H. et al. Validated B vitamin quantification from lentils by selected reaction monitoring mass spectrometry. Food Chem.359, 129810 (2021). PubMed
Ma, M. et al. Response of nutritional and functional composition, anti-nutritional factors and antioxidant activity in germinated soybean under UV-B radiation. LWT118, 108709 (2020).
Hefni, M. & Witthöft, C. M. Effect of germination and subsequent oven-drying on folate content in different wheat and rye cultivars. J. Cereal Sci.56, 374–378 (2012).
Chang, J. et al. Red light enhances folate accumulation in wheat seedlings. J. Zhejiang Univ. Sci. B22, 906–916 (2021). PubMed PMC
Liu, F. et al. The manipulation of gene expression and the biosynthesis of Vitamin C, E and folate in light-and dark-germination of sweet corn seeds. Sci. Rep.7, 7484 (2017). PubMed PMC
Wan, X. et al. Simultaneous extraction and determination of mono-/polyglutamyl folates using high-performance liquid chromatography-tandem mass spectrometry and its applications in starchy crops. Anal. Bioanal. Chem.411, 2891–2904 (2019). PubMed
Romanini, E. et al. Pyridoxine and folates during small and large scale brewing. J. Inst. Brew.127, 135–139 (2021).
Bertuzzi, T. et al. Targeted healthy compounds in small and large-scale brewed beers. Food Chem.310, 125935 (2020). PubMed
Koren, D. et al. Folic acid content and antioxidant activity of different types of beers available in Hungarian retail. Int. J. Food Sci. Technol.54, 1158–1167 (2017). PubMed PMC
Koren, D., Vecseri, B. H. & Kun-Farkas, G. Evolution of folate content during wort production. Acta Aliment49, 433–440 (2020).
Owens, J. E., Clifford, A. J. & Bamforth, C. W. Folate in beer. J. Inst. Brew.113, 243–248 (2007).
Póo‐Prieto, R., Alonso‐Aperte, E. & Varela‐Moreiras, G. Analysis of folate form distribution in Spanish beers using combined affinity and Ion‐pair chromatography. J. Inst. Brew.117, 188–194 (2011).
Mayer, O. Jr, Šimon, J. & Rosolova, H. A population study of the influence of beer consumption on folate and homocysteine concentrations. Eur. J. Clin. Nutr.55, 605–609 (2001). PubMed
Walker, C., Amblar, S. & Patel, D. Die Auswirkungen des Brauprozesses auf den Folsaure-(Vitamin B9)-Gehalt im Bier. Brauwelt142, 350–355 (2002).
Pietercelie, A., Allardin, D. & Van Nedervelde, L. Effect of fermentation conditions of brewing yeasts on folate production. Cerevisia36, 41–45 (2011).
Walkey, C. J., Kitts, D. D., Liu, Y. & van Vuuren, H. J. Bioengineering yeast to enhance folate levels in wine. Process Biochem.50, 205–210 (2015).
Crittenden, R., Martinez, N. & Playne, M. Synthesis and utilisation of folate by yoghurt starter cultures and probiotic bacteria. Int. J. Food Microbiol.80, 217–222 (2003). PubMed
LeBlanc, J. G. et al. Folate production by lactic acid bacteria and other food-grade microorganisms. In: Communicating Current Research and Educational Topics and Trends in Applied Microbiology1 (ed. Méndez Vilas, A.) 329–339 (2007).
de Giori, G. S. & LeBlanc, J. G. Folate production by lactic acid bacteria. In: Polyphenols: Prevention and Treatment of Human Disease (eds Watson, R. R., Preedy, V. R. & Zibadi, S.) Ch. 2, 15–29 (Academic Press, 2018).
Wouters, J. T., Ayad, E. H., Hugenholtz, J. & Smit, G. Microbes from raw milk for fermented dairy products. Int. Dairy J.12, 91–109 (2002).
Xie, C. et al. Effect of amino acids on folates accumulation in wheat seedlings during germination under red light radiation. Molecules27, 6868 (2022). PubMed PMC
Długosz-Grochowska, O., Kołton, A. & Wojciechowska, R. Modifying folate and polyphenol concentrations in Lamb’s lettuce by the use of LED supplemental lighting during cultivation in greenhouses. J. Funct. Foods26, 228–237 (2016).
Puthusseri, B., Divya, P., Lokesh, V. & Neelwarne, B. Enhancement of folate content and its stability using food grade elicitors in coriander (Coriandrum sativum L.). Plant Foods Hum. Nutr.67, 162–170 (2012). PubMed
Puthusseri, B., Divya, P., Lokesh, V. & Neelwarne, B. Salicylic acid-induced elicitation of folates in coriander (Coriandrum sativum L.) improves bioaccessibility and reduces pro-oxidant status. Food Chem.136, 569–575 (2013). PubMed
Watanabe, S. et al. Folate biofortification in hydroponically cultivated spinach by the addition of phenylalanine. J. Agric. Food Chem.65, 4605–4610 (2017). PubMed
Hou, S. et al. Role of miRNAs in regulation of SA-mediated upregulation of genes involved in folate and methionine metabolism in foxtail millet. Front. Plant Sci.13, 1023764 (2022). PubMed PMC
Hu, X. et al. Biosynthesis and accumulation of multi‐vitamins in black sweet corn (Zea mays L.) during kernel development. J. Sci. Food Agric.100, 5230–5238 (2020). PubMed
Shan, Q.-J. et al. Comprehensive evaluation of biosynthesis, accumulation, regulation of folate and vitamin C in waxy maize (Zea mays L. var. ceratina) with kernel development. J. Cereal Sci.87, 215–224 (2019).
Luo, S. et al. Quantification of total folate, folate species and polyglutamyl folate distribution in winged beans (Psophocarus tetragonolobus (L) DC) from different cultivars and growth stages by ultra-high performance liquid chromatography tandem mass spectrometry. J. Nutr. Sci. Vitaminol.63, 69–80 (2017). PubMed
Van Daele, J. et al. Folate profiling in potato (Solanum tuberosum) tubers by ultrahigh-performance liquid chromatography–tandem mass spectrometry. J. Agric. Food Chem.62, 3092–3100 (2014). PubMed
García-Salinas, C., Ramos-Parra, P. A. & de la Garza, R. I. D. Ethylene treatment induces changes in folate profiles in climacteric fruit during postharvest ripening. Postharvest Biol. Technol.118, 43–50 (2016).
Waller, J. C. et al. Developmental and feedforward control of the expression of folate biosynthesis genes in tomato fruit. Mol. Plant3, 66–77 (2010). PubMed
Tyagi, K. et al. Reduced γ-glutamyl hydrolase activity likely contributes to high folate levels in Periyakulam-1 tomato. Hortic. Res.10, uhac235 (2023). PubMed PMC
Tyagi, K. et al. High performance liquid chromatography coupled to mass spectrometry for profiling and quantitative analysis of folate monoglutamates in tomato. Food Chem.179, 76–84 (2015). PubMed
Fyfe, S. et al. Folate vitamers in the Australian green plum: through growth and ripening and across locations. Front. Nutr.9, 1006393 (2022). PubMed PMC
Hoey, L. et al. Laying hens can convert high doses of folic acid added to the feed into natural folates in eggs providing a novel source of food folate. Br. J. Nutr.101, 206–212 (2008). PubMed
Dickson, T. et al. Optimization of folate deposition in eggs through dietary supplementation of folic acid over the entire production cycle of Hy-Line W36, Hy-Line W98, and CV20 laying hens. J. Appl. Poult. Res.19, 80–91 (2010).
Bagheri, S. et al. Laying hen performance, egg quality improved and yolk 5-methyltetrahydrofolate content increased by dietary supplementation of folic acid. Anim. Nutr.5, 130–133 (2019). PubMed PMC
Hebert, K., House, J. & Guenter, W. Effect of dietary folic acid supplementation on egg folate content and the performance and folate status of two strains of laying hens. Poult. Sci.84, 1533–1538 (2005). PubMed
Hebert, K. et al. The effect of cereal type and exogenous enzyme use on total folate content of eggs from laying hens consuming diets supplemented with folic acid. J. Appl. Poult. Res.20, 303–312 (2011).
Tactacan, G. et al. Characterization of folate-dependent enzymes and indices of folate status in laying hens supplemented with folic acid or 5-methyltetrahydrofolate. Poult. Sci.89, 688–696 (2010). PubMed
Sun, D. et al. Modified EMR-lipid method combined with HPLC-MS/MS to determine folates in egg yolks from laying hens supplemented with different amounts of folic acid. Food Chem.337, 127767 (2021). PubMed
Sheehy, T. & Sharma, S. Use of FAO food balance sheets to estimate the potential ability of novel folate-enriched eggs to increase the folate supply in European Union countries. Public Health Nutr.14, 551–556 (2011). PubMed
Liu, F., Kariluoto, S., Edelmann, M. & Piironen, V. Bioaccessibility of folate in faba bean, oat, rye and wheat matrices. Food Chem350, 129259 (2021). PubMed
Liu, Y. et al. Thermal oxidation studies on reduced folate, L‐5‐methyltetrahydrofolic acid (L‐5‐MTHF) and strategies for stabilization using food matrices. J. Food Sci.77, C236–C243 (2012). PubMed
Ruiz-Rico, M. et al. Protection of folic acid through encapsulation in mesoporous silica particles included in fruit juices. Food Chem.218, 471–478 (2017). PubMed
Oey, I., Verlinde, P., Hendrickx, M. & Van Loey, A. Temperature and pressure stability of L-ascorbic acid and/or [6s] 5-methyltetrahydrofolic acid: a kinetic study. Eur. Food Res. Technol.223, 71–77 (2006).
Rozoy, E. et al. The use of cyclic voltammetry to study the oxidation of L-5-methyltetrahydrofolate and its preservation by ascorbic acid. Food Chem.132, 1429–1435 (2012). PubMed
Ng, X., Lucock, M. & Veysey, M. Physicochemical effect of pH and antioxidants on mono-and triglutamate forms of 5-methyltetrahydrofolate, and evaluation of vitamin stability in human gastric juice: implications for folate bioavailability. Food Chem.106, 200–210 (2008).
Wang, Y., Yan, B., Abbaspourrad, A. & Cheng, Y. Improved photostability of folic acid by the radical-scavenging effect of tannic acid. LWT142, 111050 (2021).
Wusigale et al. Protection of resveratrol against the photodecomposition of folic acid and photodecomposition-induced structural change of beta-lactoglobulin. Food Res. Int.102, 435–444 (2017). PubMed
Kadota, K. et al. Inhibition of photodegradation of highly dispersed folic acid nanoparticles by the antioxidant effect of transglycosylated rutin. J. Agric. Food Chem.64, 3062–3069 (2016). PubMed
Wusigale et al. Mechanism for inhibition of folic acid photodecomposition by various antioxidants. J. Agric. Food Chem.68, 340–350 (2020). PubMed
Rozoy, E. et al. Redox properties of catechins and enriched green tea extracts effectively preserve l-5-methyltetrahydrofolate: Assessment using cyclic voltammetry analysis. Food Chem.138, 1982–1991 (2013). PubMed
Schneider, M. et al. Reaction of folic acid with reducing sugars and sugar degradation products. J. Agric. Food Chem. 50, 1647–1651 (2002). PubMed
Rychlik, M. & Mayr, A. Quantitation of N 2-[1-(1-carboxy) ethyl] folic acid, a nonenzymatic glycation product of folic acid, in fortified foods and model cookies by a stable isotope dilution assay. J. Agric. Food Chem.53, 5116–5124 (2005). PubMed
Verlinde, P. H. et al. Influence of reducing carbohydrates on (6 S)-5-methyltetrahydrofolic acid degradation during thermal treatments. J. Agric. Food Chem.58, 6190–6199 (2010). PubMed
Jones, M. L. & Nixon, P. F. Tetrahydrofolates are greatly stabilized by binding to bovine milk folate-binding protein. J. Nutr.132, 2690–2694 (2002). PubMed
de Jong, R. J. et al. Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans. Eur. J. Clin. Nutr.59, 906–913 (2005). PubMed
Puthusseri, B. et al. Evaluation of folate-binding proteins and stability of folates in plant foliages. Food Chem.242, 555–559 (2018). PubMed
Madziva, H., Kailasapathy, K. & Phillips, M. Alginate–pectin microcapsules as a potential for folic acid delivery in foods. J. Microencapsul.22, 343–351 (2005). PubMed
Alborzi, S., Lim, L.-T. & Kakuda, Y. Encapsulation of folic acid and its stability in sodium alginate-pectin-poly (ethylene oxide) electrospun fibres. J. Microencapsul.30, 64–71 (2013). PubMed
Pérez-Esteve, É. et al. Encapsulation of folic acid in different silica porous supports: a comparative study. Food Chem.196, 66–75 (2016). PubMed
Perez-Esteve, E. et al. Enrichment of stirred yogurts with folic acid encapsulated in pH-responsive mesoporous silica particles: Bioaccessibility modulation and physico-chemical characterization. LWT72, 351–360 (2016).
Aceituno-Medina, M., Mendoza, S., Lagaron, J. M. & López-Rubio, A. Photoprotection of folic acid upon encapsulation in food-grade amaranth (Amaranthus hypochondriacus L.) protein isolate – Pullulan electrospun fibers. LWT62, 970–975 (2015).
Ariyarathna, I. R. & Karunaratne, D. N. Use of chickpea protein for encapsulation of folate to enhance nutritional potency and stability. Food Bioprod. Process.95, 76–82 (2015).
do Evangelho, J. A. et al. Thermal and irradiation resistance of folic acid encapsulated in zein ultrafine fibers or nanocapsules produced by electrospinning and electrospraying. Food Res. Int.124, 137–146 (2019). PubMed
Acevedo-Fani, A., Soliva-Fortuny, R. & Martín-Belloso, O. Photo-protection and controlled release of folic acid using edible alginate/chitosan nanolaminates. J. Food Eng.229, 72–82 (2018).
Pérez-Masiá, R. et al. Encapsulation of folic acid in food hydrocolloids through nanospray drying and electrospraying for nutraceutical applications. Food Chem.168, 124–133 (2015). PubMed
Chapeau, A.-L. et al. Scale-up production of vitamin loaded heteroprotein coacervates and their protective property. J. Food Eng.206, 67–76 (2017).
Chapeau, A.-L. et al. Spontaneous co-assembly of lactoferrin and β-lactoglobulin as a promising biocarrier for vitamin B9. Food Hydrocoll57, 280–290 (2016).
Zhang, J. et al. The folic acid/β-casein complex: characteristics and physicochemical implications. Food Res. Int.57, 162–167 (2014).
Liang, L. & Subirade, M. β-Lactoglobulin/folic acid complexes: formation, characterization, and biological implication. J. Phys. Chem. B114, 6707–6712 (2010). PubMed
Tavares, G. M. et al. Binding of folic acid induces specific self-aggregation of lactoferrin: thermodynamic characterization. Langmuir31, 12481–12488 (2015). PubMed
Bourassa, P., Hasni, I. & Tajmir-Riahi, H. Folic acid complexes with human and bovine serum albumins. Food Chem.129, 1148–1155 (2011). PubMed
Fu, X., Cheng, H., Fang, Z. & Liang, L. Mechanism for improved protection of whey protein isolate against the photodecomposition of folic acid. Food Hydrocoll79, 439–449 (2018).
Liang, L., Zhang, J., Zhou, P. & Subirade, M. Protective effect of ligand-binding proteins against folic acid loss due to photodecomposition. Food Chem.141, 754–761 (2013). PubMed
Tofzikovskaya, Z., O’Connor, C. & McNamara, M. Synthesis, characterisation and photo-stability of a folate-modified β-cyclodextrin as a functional food additive. J. Incl. Phenom. Macrocycl. Chem.74, 437–445 (2012).
Cho, S., Johnson, G. & Song, W. O. Folate content of foods: comparison between databases compiled before and after new FDA fortification requirements. J. Food Compos. Anal.15, 293–307 (2002).
Zappacosta, B. et al. Homocysteine lowering by folate-rich diet or pharmacological supplementations in subjects with moderate hyperhomocysteinemia. Nutrients5, 1531–1543 (2013). PubMed PMC
Noam, A. et al. Folate and neural tube defects: the role of supplements and food fortification. Paediatr. Child Health21, 145–149 (2016). PubMed PMC
Shakur, Y. A., Garriguet, D., Corey, P. & O’Connor, D. L. Folic acid fortification above mandated levels results in a low prevalence of folate inadequacy among Canadians. Am. J. Clin. Nutr.92, 818–825 (2010). PubMed
Shakur, Y. A. et al. How much folate is in Canadian fortified products 10 years after mandated fortification? Can. J. Public Health100, 281–284 (2009). PubMed PMC
Ha, A. V. V. et al. Low prevalence of folic acid supplementation during pregnancy: a multicenter study in Vietnam. Nutrients11, 2347 (2019). PubMed PMC
Crider, K. S. et al. Modeling the impact of folic acid fortification and supplementation on red blood cell folate concentrations and predicted neural tube defect risk in the United States: have we reached optimal prevention? Am. J. Clin. Nutr.107, 1027–1034 (2018). PubMed PMC
Fischer, M., Stronati, M. & Lanari, M. Mediterranean diet, folic acid, and neural tube defects. Ital. J. Pediatr.43, 1–8 (2017). PubMed PMC
Flynn, A. et al. Intake of selected nutrients from foods, from fortification and from supplements in various European countries. Food Nutr. Res.53, 2038 (2009). PubMed PMC
Czarnowska-Kujawska, M., Klepacka, J., Zielińska, O. & Samaniego-Vaesken, Md. L. Characteristics of dietary supplements with folic acid available on the Polish market. Nutrients14, 3500 (2022). PubMed PMC
Bailey, R. L. et al. Total folate and folic acid intake from foods and dietary supplements in the United States: 2003–2006. Am. J. Clin. Nutr.91, 231–237 (2010). PubMed PMC
Bailey, R. L. et al. Total folate and folic acid intakes from foods and dietary supplements of US children aged 1–13 y. Am. J. Clin. Nutr.92, 353–358 (2010). PubMed PMC
Kondo, A. et al. Dietary folate intakes and effects of folic acid supplementation on folate concentrations among Japanese pregnant women. J. Obstet. Gynaecol. Re.37, 331–336 (2011). PubMed
Anderson, C. A. et al. Effects of folic acid supplementation on serum folate and plasma homocysteine concentrations in older adults: a dose-response trial. Am. J. Epidemiol.172, 932–941 (2010). PubMed PMC
French, M. R., Barr, S. I. & Levy-Milne, R. Folate intakes and awareness of folate to prevent neural tube defects: a survey of women living in Vancouver, Canada. J. Am. Diet. Assoc.103, 181–185 (2003). PubMed
Johnston, K. E., Lofgren, P. A. & Tamura, T. Folate concentrations of fast foods measured by trienzyme extraction method. Food Res. Int.35, 565–569 (2002).
Johnston, K. E. & Tamura, T. Folate content in commercial white and whole wheat sandwich breads. J. Agric. Food Chem.52, 6338–6340 (2004). PubMed
Czeizel, A. E., Dudás, I., Vereczkey, A. & Bánhidy, F. Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects. Nutrients5, 4760–4775 (2013). PubMed PMC
Donovan, S. et al. Folic acid from fortified foods and/or supplements during pregnancy and lactation and health outcomes: a systematic review (USDA Nutrition Evidence Systematic Review, 2020). PubMed
Bibbins-Domingo, K. et al. Folic acid supplementation for the prevention of neural tube defects: US preventive services task force recommendation statement. JAMA317, 183–189 (2017). PubMed
Eichholzer, M., Tönz, O. & Zimmermann, R. Folic acid: a public-health challenge. Lancet367, 1352–1361 (2006). PubMed
Ledowsky, C., Mahimbo, A., Scarf, V. & Steel, A. Women taking a folic acid supplement in countries with mandatory food fortification programs may be exceeding the upper tolerable limit of folic acid: A systematic review. Nutrients14, 2715 (2022). PubMed PMC
Liu, J. et al. Periconceptional folic acid supplementation and sex difference in prevention of neural tube defects and their subtypes in China: results from a large prospective cohort study. Nutr. J.17, 1–7 (2018). PubMed PMC
Toivonen, K. et al. Folic acid supplementation during the preconception period: a systematic review and meta-analysis. Prev. Med.114, 1–17 (2018). PubMed
Viswanathan, M. et al. Folic Acid Supplementation: An Evidence Review for the U.S. Preventive Services Task Force (Agency for Healthcare Research and Quality, 2017). PubMed
Viswanathan, M. et al. Folic acid supplementation for the prevention of neural tube defects: an updated evidence report and systematic review for the US Preventive Services Task Force. JAMA317, 190–203 (2017). PubMed
De‐Regil, L. M., Peña‐Rosas, J. P., Fernández‐Gaxiola, A. C. & Rayco‐Solon, P. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst. Rev.12, CD007950 (2015). PubMed PMC
Valentin, M. et al. Acid folic and pregnancy: A mandatory supplementation. Ann. Endocrinol.79, 91–94 (2018). PubMed
Krawinkel, M. B. et al. Revised DA-CH intake recommendations for folate: how much is needed? Eur. J. Clin. Nutr.68, 719–723 (2014). PubMed PMC
Wolff, T., Witkop, C. T., Miller, T. & Syed, S. B. Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the US Preventive Services Task Force. Ann. Intern. Med.150, 632–639 (2009). PubMed
Wilson, R. & O’Connor, D. Maternal folic acid and multivitamin supplementation: International clinical evidence with considerations for the prevention of folate-sensitive birth defects. Prev. Med. Rep.24, 101617 (2021). PubMed PMC
WHO. Guideline: Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects (World Health Organization, 2015). PubMed
EFSA Panel on Dietetic Products Nutrition and Allergies. Scientific Opinion on the substantiation of a health claim related to increasing maternal folate status by supplemental folate intake and reduced risk of neural tube defects pursuant to article 14 of regulation (EC) No 1924/2006. EFSA J.11, 3328 (2013).
Hopkins, S. M. et al. Impact of voluntary fortification and supplement use on dietary intakes and biomarker status of folate and vitamin B-12 in Irish adults. Am. J. Clin. Nutr.101, 1163–1172 (2015). PubMed
Kupka, R. The role of folate in malaria–implications for home fortification programmes among children aged 6–59 months. Matern. Child Nutr.11, 1–15 (2015). PubMed PMC
EFSA. ESCO report on analysis of risks and benefits of fortification of food with folic acid. EFSA Support. Publ.6, 3E (2009).
Shea, B. et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst. Rev.5, CD000951 (2013). PubMed
Visser, K. et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann. Rheum. Dis.68, 1086–1093 (2009). PubMed PMC
Bomba-Opoń, D., Hirnle, L., Kalinka, J. & Seremak-Mrozikiewicz, A. Folate supplementation during the preconception period, pregnancy and puerperium. Polish Society of Gynecologists and Obstetricians Guidelines. Ginekol. Polska88, 633–636 (2017). PubMed
Wolak, N. et al. Vitamins B1, B2, B3 and B9–occurrence, biosynthesis pathways and functions in human nutrition. Mini Rev. Med. Chem.17, 1075–1111 (2017). PubMed
Wehrli, C. Method for the production of folic acid United States patent, US5410056A (1995).
Wehrli, C. Verfahren zur Herstellung von Folsäure, EP0608693A2 (1994).
Zhang, G. et al. A kind of environment-friendly type preparation method of synthesis folic acid, China patent, CN106496231A (2016).
Qui, Y., Wang, Q., Ju, L. & Li, X. Simple and convenient folic acid environment-friendly production method, China patent, CN103896945B (2014).
Wang, G., Zhang, J. & Wang, S. Folic acid synthesis method, China patent, CN106046005A (2016).
Zhang, J., Yang, K. & Wang, X. A kind of synthetic method that folic acid is new, China patent, CN108558884A (2018).
EFSA Opinion of the scientific panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to Calcium L‐Methylfolate. EFSA J.2, 135 (2004).
EFSA Panel on Food Additives and Nutrient Sources added to Food Scientific Opinion on (6S)‐5‐methyltetrahydrofolic acid, glucosamine salt as a source of folate added for nutritional purposes to food supplements. EFSA J.11, 3358 (2013).
EFSA Panel on Nutrition Novel Foods and Food Allergens. Calcium l‐methylfolate as a source of folate added for nutritional purposes to infant and follow‐on formula, baby food and processed cereal‐based food. EFSA J.18, e05947 (2020). PubMed PMC
El-Sheekh, M. M., Abd-Elsalam, I. S., Shabana, S. & Zaki, A. Production of vitamin B12 and folic acid from agricultural wastes using new bacterial isolates. Afr. J. Microbiol. Res.7, 966–973 (2013).
Mastella, L., Senatore, V., Beltrani, T. & Branduardi, P. Scheffersomyces stipitis ability to valorize different residual biomasses for vitamin B9 production. Microb. Biotechnol.16, 392–403 (2023). PubMed PMC
Mastella, L. et al. First report on vitamin B9 production including quantitative analysis of its vitamers in the yeast Scheffersomyces stipitis. Biotechnol. Biofuels Bioprod.15, 98 (2022). PubMed PMC
Revuelta, J. L., Serrano-Amatriain, C., Ledesma-Amaro, R. & Jiménez, A. Formation of folates by microorganisms: towards the biotechnological production of this vitamin. Appl. Microbiol. Biotechnol.102, 8613–8620 (2018). PubMed PMC
Serrano-Amatriain, C. et al. Folic acid production by engineered Ashbya gossypii. Metab. Eng.38, 473–482 (2016). PubMed
Zhu, T., Koepsel, R., Domach, M. & Ataai, M. Metabolic engineering of folic acid production. In Fermentation Biotechnology (ed. Saha, B. C.) Ch. 13, 207-219 (American Chemical Society, 2003).
Zhu, T. et al. Engineering of Bacillus subtilis for enhanced total synthesis of folic acid. Appl. Environ. Microbiol.71, 7122–7129 (2005). PubMed PMC
Acevedo-Rocha, C. G. et al. Microbial cell factories for the sustainable manufacturing of B vitamins. Curr. Opin. Biotechnol.56, 18–29 (2019). PubMed
WHO. Recommendations on wheat and maize flour fortification meeting report: Interim consensus statement (World Health Organization, 2009). PubMed
WHO. Guideline: Fortification of wheat flour with vitamins and minerals as a public health strategy (World Health Organization, 2022). PubMed
Madhari, R. S. et al. High dietary micronutrient inadequacy in peri‐urban school children from a district in South India: Potential for staple food fortification and nutrient supplementation. Matern. Child Nutr.16, e13065 (2020). PubMed PMC
de Benoist, B. Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food Nutr. Bull.29, S238–S244 (2008). PubMed
Winkels, R. M. et al. Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial. Am. J. Clin. Nutr.88, 348–355 (2008). PubMed
Tucker, K. L. et al. Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial. Am. J. Clin. Nutr.79, 805–811 (2004). PubMed
Bird, J. K., Barron, R., Pigat, S. & Bruins, M. J. Contribution of base diet, voluntary fortified foods and supplements to micronutrient intakes in the UK. J. Nutr. Sci.11, e51 (2022). PubMed PMC
Hannon, E. M., Kiely, M. & Flynn, A. The impact of voluntary fortification of foods on micronutrient intakes in Irish adults. Br. J. Nutr.97, 1177–1186 (2007). PubMed
Hennessy, A., Walsh, E., Walton, J. & Flynn, A. The contribution of fortified foods to micronutrient intake in Irish adults aged 18–64 years. Proc. Nutr. Soc.70, E112 (2011).
Swanepoel, E. et al. Contribution of commercial infant products and fortified staple foods to nutrient intake at ages 6, 12, and 18 months in a cohort of children from a low socio‐economic community in South Africa. Matern. Child Nutr.15, e12674 (2019). PubMed PMC
Fulgoni, V. L. III, Keast, D. R., Bailey, R. L. & Dwyer, J. Foods, fortificants, and supplements: where do Americans get their nutrients? J. Nutr.141, 1847–1854 (2011). PubMed PMC
WHO/FAO. Guidelines on Food Fortification with Micronutrients (World Health Organization, 2006).
Newman, J. C., Malek, A. M., Hunt, K. J. & Marriott, B. P. Nutrients in the US diet: naturally occurring or enriched/fortified food and beverage sources, plus dietary supplements: NHANES 2009–2012. J. Nutr.149, 1404–1412 (2019). PubMed PMC
Berner, L. A., Keast, D. R., Bailey, R. L. & Dwyer, J. T. Fortified foods are major contributors to nutrient intakes in diets of US children and adolescents. J. Acad. Nutr. Diet.114, 1009–1022.e1008 (2014). PubMed
Dietrich, M., Brown, C. J. & Block, G. The effect of folate fortification of cereal-grain products on blood folate status, dietary folate intake, and dietary folate sources among adult non-supplement users in the United States. J. Am. Coll. Nutr.24, 266–274 (2005). PubMed
Hussain, N. M. & Sharma, S. C. Flour fortification with folate to reduce risk of Spina Bifida. Br. Student Doctor J.4, 45–49 (2020).
Chandra-Hioe, M. V., Bucknall, M. P. & Arcot, J. Folate analysis in foods by UPLC-MS/MS: development and validation of a novel, high throughput quantitative assay; folate levels determined in Australian fortified breads. Anal. Bioanal. Chem.401, 1035–1042 (2011). PubMed
Dwyer, J. T. et al. Fortification: new findings and implications. Nutr. Rev.72, 127–141 (2014). PubMed
Serra-Majem, L. Vitamin and mineral intakes in European children. Is food fortification needed? Public Health Nutr.4, 101–107 (2001). PubMed
Palchetti, C. Z. et al. Prevalence of inadequate intake of folate after mandatory fortification: results from the first National Dietary Survey in Brazil. Eur. J. Nutr.59, 2793–2803 (2020). PubMed
Palchetti, C. Z. et al. Folate and vitamin B12 status: temporal evaluation after mandatory fortification in Brazil. Eur. J. Clin. Nutr.76, 1266–1272 (2022). PubMed
Keats, E. C. et al. Improved micronutrient status and health outcomes in low-and middle-income countries following large-scale fortification: evidence from a systematic review and meta-analysis. Am. J. Clin. Nutr.109, 1696–1708 (2019). PubMed PMC
Noor, R. A. et al. Large–scale wheat flour folic acid fortification program increases plasma folate levels among women of reproductive age in urban Tanzania. PLoS One12, e0182099 (2017). PubMed PMC
Chan, Y.-M., MacFarlane, A. J. & O’Connor, D. L. Modeling demonstrates that folic acid fortification of whole-wheat flour could reduce the prevalence of folate inadequacy in Canadian whole-wheat consumers. J. Nutr.145, 2622–2629 (2015). PubMed
Martiniak, Y., Heuer, T. & Hoffmann, I. Intake of dietary folate and folic acid in Germany based on different scenarios for food fortification with folic acid. Eur. J. Nutr.54, 1045–1054 (2015). PubMed PMC
Tablante, E. C., Pachón, H., Guetterman, H. M. & Finkelstein, J. L. Fortification of wheat and maize flour with folic acid for population health outcomes. Cochrane Database Syst. Rev.7, CD012150 (2019). PubMed PMC
Black, A. P. et al. High folate levels in Aboriginal children after subsidised fruit and vegetables and mandatory folic acid fortification. Aust. N. Z. J. Public Health38, 241–246 (2014). PubMed
Cordero, J. F., Do, A. & Berry, R. Review of interventions for the prevention and control of folate and vitamin B12 deficiencies. Food Nutr. Bull.29, S188–S195 (2008). PubMed
Dwyer, J. T. et al. Fortification and health: challenges and opportunities. Adv. Nutr.6, 124–131 (2015). PubMed PMC
Crider, K. S. et al. Systematic review and Bayesian meta-analysis of the dose-response relationship between folic acid intake and changes in blood folate concentrations. Nutrients11, 71 (2019). PubMed PMC
Powers, H. J., Stephens, M., Russell, J. & Hill, M. H. Fortified breakfast cereal consumed daily for 12 wk leads to a significant improvement in micronutrient intake and micronutrient status in adolescent girls: a randomised controlled trial. Nutr. J.15, 1–13 (2016). PubMed PMC
Dhonukshe-Rutten, R. et al. Dietary intake and status of folate and vitamin B12 and their association with homocysteine and cardiovascular disease in European populations. Eur. J. Clin. Nutr.63, 18–30 (2009). PubMed
Della Lucia, C. M. et al. Impact of rice fortified with iron, zinc, thiamine and folic acid on laboratory measurements of nutritional status of preschool children. Cien. Saude Colet.22, 583–592 (2017).
Choumenkovitch, S. F. et al. Folic acid intake from fortification in United States exceeds predictions. J. Nutr.132, 2792–2798 (2002). PubMed
Bailey, L. B. et al. Biomarkers of nutrition for development—folate review. J. Nutr.145, 1636S–1680S (2015). PubMed PMC
Food Safety Authority of Ireland. Report of the scientific committee of the food safety authority of Ireland, update report on folic acid and the prevention of birth defects in Ireland (FSAI Dublin, 2016).
Mudryj, A. N., de Groh, M., Aukema, H. M. & Yu, N. Folate intakes from diet and supplements may place certain Canadians at risk for folic acid toxicity. Br. J. Nutr.116, 1236–1245 (2016). PubMed
Chakraborty, H. et al. Folic acid fortification and women’s folate levels in selected communities in Brazil—a first look. Int. J. Vitam. Nutr. Res.84, 286–294 (2014). PubMed PMC
Saldanha, L. G. et al. Perspective: time to resolve confusion on folate amounts, units, and forms in prenatal supplements. Adv. Nutr.11, 753–759 (2020). PubMed PMC
Pfeiffer, C. M. et al. Folate status in the US population 20 y after the introduction of folic acid fortification. Am. J. Clin. Nutr.110, 1088–1097 (2019). PubMed PMC
Slagman, A. et al. Folic acid deficiency declined substantially after introduction of the mandatory fortification programme in Queensland, Australia: a secondary health data analysis. Public Health Nutr.22, 3426–3434 (2019). PubMed PMC
Obeid, R. & Herrmann, W. The emerging role of unmetabolized folic acid in human diseases: myth or reality? Curr. Drug Metab.13, 1184–1195 (2012). PubMed
Mills, J. L., Molloy, A. M. & Reynolds, E. H. Do the benefits of folic acid fortification outweigh the risk of masking vitamin B12 deficiency? BMJ360, k724 (2018). PubMed PMC
Caffrey, A. et al. Maternal folate nutrition and offspring health: evidence and current controversies. Proc. Nutr. Soc.78, 208–220 (2019). PubMed
Crider, K. S. et al. Folic acid and the prevention of birth defects: 30 years of opportunity and controversies. Annu. Rev. Nutr.42, 423–452 (2022). PubMed PMC
Leyvraz, M. et al. An assessment of the potential impact of fortification of staples and condiments on micronutrient intake of young children and women of reproductive age in Bangladesh. Nutrients8, 541 (2016). PubMed PMC
Luo, H. et al. Review of existing models to predict reductions in neural tube defects due to folic acid fortification and model results using data from Cameroon. Adv. Nutr.12, 2401–2414 (2021). PubMed PMC
Cuskelly, G. J., Mooney, K. M. & Young, I. S. Folate and vitamin B12: friendly or enemy nutrients for the elderly: symposium on ‘Micronutrients through the life cycle’. Proc. Nutr. Soc.66, 548–558 (2007). PubMed
Garrett, G. S. & Bailey, L. B. A public health approach for preventing neural tube defects: folic acid fortification and beyond. Ann. N. Y. Acad. Sci.1414, 47–58 (2018). PubMed
Haywood, P. et al. The effectiveness and cost-effectiveness of mandatory folic acid and iodine fortification (Australian Health Ministers’ Advisory Council, 2017).
Engle-Stone, R. et al. Iron, zinc, folate, and vitamin B-12 status increased among women and children in Yaounde and Douala, Cameroon, 1 year after introducing fortified wheat flour. J. Nutr.147, 1426–1436 (2017). PubMed PMC
New Zealand Food Safety. NZFS2019-08 Folic acid fortification: Increasing folic acid availability in food; Discussion Paper No: 2019/08 (Ministry for Primary Industries, 2019).
Patel, K. R. & Sobczyńska-Malefora, A. The adverse effects of an excessive folic acid intake. Eur. J. Clin. Nutr.71, 159–163 (2017). PubMed
New Zealand Food Dafety. Folic acid fortification, Technical supporting document, technical paper No: 2019/04 (Ministry for Primary Industries, 2019).
Wald, N. J., Morris, J. K. & Blakemore, C. Public health failure in the prevention of neural tube defects: time to abandon the tolerable upper intake level of folate. Public Health Rev.39, 1–11 (2018). PubMed PMC
Low, F., Beaglehole, R. & Gluckman, P. The health benefits and risks of folic acid fortification of food (The Office of the Prime Minister’s Chief Science Advisor and the Royal Society Te Apārangi, 2018).
Sirohi, A., Pundhir, A. & Ghosh, S. Food fortification: a nutritional management strategy in India. Innov. J. Food Sci.6, 1–8 (2018).
Haggarty, P. UK introduces folic acid fortification of flour to prevent neural tube defects. Lancet398, 1199–1201 (2021). PubMed
Samaniego-Vaesken, Md. L., Alonso-Aperte, E. & Varela-Moreiras, G. Vitamin food fortification today. Food Nutr. Res.56, 5459 (2012). PubMed PMC
Samaniego-Vaesken, Md. L., Alonso-Aperte, E. & Varela-Moreiras, G. Voluntary fortification with folic acid in Spain: an updated food composition database. Food Chem.193, 148–153 (2016). PubMed
Verkaik-Kloosterman, J. et al. Evaluation of the Dutch general exemption level for voluntary fortification with folic acid. Food Nutr. Res.56, 5443 (2012). PubMed PMC
Egan, E., Kelly, F. & Sweeney, M. R. Voluntary folic acid fortification levels of food staples in Ireland continue to decline: further implications for passive folic acid intakes? J. Public Health43, 281–286 (2021). PubMed
Kelly, F. et al. Folic acid levels in some food staples in Ireland are on the decline: implications for passive folic acid intakes? J. Public Health38, 265–269 (2016). PubMed
Laird, E. J. et al. Voluntary fortification is ineffective to maintain the vitamin B12 and folate status of older Irish adults: evidence from the Irish Longitudinal Study on Ageing (TILDA). Br. J. Nutr.120, 111–120 (2018). PubMed
Wang, A. et al. Impact of voluntary folic acid fortification of corn masa flour on RBC folate concentrations in the US (NHANES 2011–2018). Nutrients13, 1325 (2021). PubMed PMC
Hennessy, Á., Walton, J. & Flynn, A. The impact of voluntary food fortification on micronutrient intakes and status in European countries: a review. Proc. Nutr. Soc.72, 433–440 (2013). PubMed
Bundesinstitut für Risikobewertung. Nutzen-Risiko-Abwägung einer flächendeckenden Anreicherung von Mehl mit Folsäure: Stellungnahme Nr. 027/2017 des BfR vom 13. September 2017 10.17590/20170913-100236 (2017).
Bundesinstitut für Risikobewertung. Updated recommended maximum levels for the addition of vitamins and miner als to food supplements and conventional foods, https://www.bfr.bund.de/en/press_information/2021/11/maximum_levels_for_vitamins_and_minerals_in_food_supplements_and_fortified_foods-270796.html (2021).
Czeizel, A. E. & Kökény, M. Bread is fortified with folic acid in Hungary. BMJ325, 391 (2002). PubMed PMC
Hamner, H. C. & Tinker, S. C. Fortification of corn masa flour with folic acid in the United States: an overview of the evidence. Ann. N. Y. Acad. Sci.1312, 8–14 (2014). PubMed PMC
Fleischman, A. R. & Oinuma, M. Fortification of corn masa flour with folic acid in the United States. Am. J. Public Health101, 1360–1364 (2011). PubMed PMC
Flores, A. L. et al. Adding folic acid to corn Masa flour: partnering to improve pregnancy outcomes and reduce health disparities. Prev. Med.106, 26–30 (2018). PubMed PMC
Redpath, B., Kancherla, V. & Oakley, G. P. Availability of corn masa flour and tortillas fortified with folic acid in Atlanta after national regulations allowing voluntary fortification. JAMA320, 1600–1601 (2018). PubMed PMC
Khalid, S. I. et al. The impact of voluntary folate fortification of corn masa flour on US pregnancies complicated by neural tube defects. Childs Nerv. Syst. 39, 1813–1819 (2023). PubMed PMC
Jentink, J., van de Vrie-Hoekstra, N. W., de Jong-van den Berg, L. T. & Postma, M. J. Economic evaluation of folic acid food fortification in the Netherlands. Eur. J. Public Health18, 270–274 (2008). PubMed
WHO. Guideline: Fortification of maize flour and corn meal with vitamins and minerals (World Health Organization, 2016). PubMed
FSSAI. Food Safety and Standards (Fortification of Foods) Regulations, https://www.fssai.gov.in/upload/uploadfiles/files/Compendium_Food_Fortification_Regulations_30_09_2021.pdf (2018).
Alavi, S. et al. Rice fortification in developing countries: a critical review of the technical and economic feasibility, https://www.semanticscholar.org/paper/Rice-Fortification-in-Developing-Countries-%3A-A-of/e63515126eeda28d442f25615fb6cbf9aeecfcac (2008).
Kam, K., Arcot, J. & Adesina, A. A. Folic acid fortification of parboiled rice: Multifactorial analysis and kinetic investigation. J. Food Eng.108, 238–243 (2012).
Kam, K., Murray, J. M., Arcot, J. & Ward, R. Fortification of parboiled rice with folic acid: Consumer acceptance and sensory evaluation. Food Res. Int.49, 354–363 (2012).
Waller, A. W. et al. Stakeholder’s perceptions of Mexico’s federal corn flour fortification program: a qualitative study. Nutrients12, 433 (2020). PubMed PMC
Orjuela, M. A. et al. Fortification of bakery and corn masa–based foods in Mexico and dietary intake of folic acid and folate in Mexican national survey data. Am. J. Clin. Nutr.110, 1434–1448 (2019). PubMed PMC
Barkley, J. S., Wheeler, K. S. & Pachón, H. Anaemia prevalence may be reduced among countries that fortify flour. Br. J. Nutr.114, 265–273 (2015). PubMed
Murphy, M. E. & Westmark, C. J. Folic acid fortification and neural tube defect risk: analysis of the food fortification initiative dataset. Nutrients12, 247 (2020). PubMed PMC
Biemi, F. D. & Ganji, V. Temporal relation between double fortification of wheat flour with iron and folic acid, and markers and prevalence of anemia in children. Nutrients13, 2013 (2021). PubMed PMC
Southern African Development Community (SADC). English SADC Fortification Minimum Standards, https://www.sadc.int/document/english-sadc-fortification-minimum-standards (2020).
Muthayya, S. et al. Rice fortification: an emerging opportunity to contribute to the elimination of vitamin and mineral deficiency worldwide. Food Nutr. Bull.33, 296–307 (2012). PubMed
Saha, S. & Roy, A. Whole grain rice fortification as a solution to micronutrient deficiency: Technologies and need for more viable alternatives. Food Chem.326, 127049 (2020). PubMed
Cardoso, R. V. et al. Flour fortification for nutritional and health improvement: a review. Food Res. Int.125, 108576 (2019). PubMed
Thurston, L., Borman, B. & Bower, C. Mandatory fortification with folic acid for the prevention of neural tube defects: a case study of Australia and New Zealand. Childs Nerv. Syst., 39, 1737–1741 (2023). PubMed PMC
Barboza-Argüello, M. D. L. P. et al. Neural tube defects in Costa Rica, 1987–2012: origins and development of birth defect surveillance and folic acid fortification. Matern. Child Health J.19, 583–590 (2015). PubMed PMC
Lu, B. et al. Simultaneous determination of four water-soluble vitamins in fortified infant foods by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. J. Chromatogr. Sci.46, 225–232 (2008). PubMed
Liberato, S. C. & Pinheiro-Sant’Ana, H. M. Fortification of industrialized foods with vitamins. Rev. Nutr.19, 215–231 (2006).
European Commission. Commission directive 2006/125/EC on processed cereal-based foods and baby foods for infants and young children. OJEU, 16–35 (European Commission, 2006).
European Commission. Commission directive 2006/141/EC of 22 December 2006 on infant formulae and follow-on formulae and amending Directive 1999/21/EC. OJEU49, 1–33 (2006).
Samaniego-Vaesken, M. D. L., Alonso-Aperte, E. & Varela-Moreiras, G. Analysis and evaluation of voluntary folic acid fortification of breakfast cereals in the Spanish market. J. Food Compos. Anal.23, 419–423 (2010).
Samaniego-Vaesken, M. D. L., Alonso-Aperte, E. & Varela-Moreiras, G. Voluntary folic acid fortification levels and nutrient composition of food products from the Spanish market: A 2011–2015 update. Nutrients9, 234 (2017). PubMed PMC
Kuriyan, R. et al. The effects of regular consumption of a multiple micronutrient fortified milk beverage on the micronutrient status of school children and on their mental and physical performance. Clin. Nutr.35, 190–198 (2016). PubMed
Pentieva, K. et al. Acute absorption of folic acid from a fortified low-fat spread. Eur. J. Clin. Nutr.57, 1235–1241 (2003). PubMed
van den Boom, A. et al. The contribution of ready-to-eat cereals to daily nutrient intake and breakfast quality in a Mediterranean setting. J. Am. Coll. Nutr.25, 135–143 (2006). PubMed
Parliament, E. U. Regulation (EC) No 1925/2006 of the European Parliament and of the Council of 20 December 2006 on the addition of vitamins and minerals and of certain other substances to foods. OJEU50, 26–38 (2006).
McGee, E. J. T., Sangakkara, A. R. & Diosady, L. L. Double fortification of salt with folic acid and iodine. J. Food Eng.198, 72–80 (2017).
Li, Y. O., Diosady, L. L. & Wesley, A. S. Folic acid fortification through existing fortified foods: iodized salt and vitamin A—fortified sugar. Food Nutr. Bull.32, 35–41 (2011). PubMed
Vinodkumar, M. & Rajagopalan, S. Multiple micronutrient fortification of salt. Eur. J. Clin. Nutr.63, 437–445 (2009). PubMed
Modupe, O. & Diosady, L. L. Quadruple fortification of salt for the delivery of iron, iodine, folic acid, and vitamin B12 to vulnerable populations. J. Food Eng.300, 110525 (2021). PubMed PMC
Modupe, O., Krishnaswamy, K. & Diosady, L. L. Technology for triple fortification of salt with folic acid, iron, and iodine. J. Food Sci.84, 2499–2506 (2019). PubMed PMC
Modupe, O., Siddiqui, J., Jonnalagadda, A. & Diosady, L. L. Folic acid fortification of double fortified salt. Sci. Rep.11, 14561 (2021). PubMed PMC
Kancherla, V. et al. Modeling shows high potential of folic acid‐fortified salt to accelerate global prevention of major neural tube defects. Birth Defects Res.112, 1461–1474 (2020). PubMed
Vora, R. M. et al. Potential for elimination of folate and vitamin B12 deficiency in India using vitamin-fortified tea: a preliminary study. BMJ Nutr. Prev. Health.4, 293–306 (2021). PubMed PMC
Vora, R. M. & Antony, A. C. The unresolved tragedy of neural-tube defects in India: The case for folate-and vitamin-B12-fortified tea for prevention. J. Indian Assoc. Pediatr. Surg.27, 1–8 (2022). PubMed PMC
Tapola, N., Karvonen, H., Niskanen, L. & Sarkkinen, E. Mineral water fortified with folic acid, vitamins B6, B12, D and calcium improves folate status and decreases plasma homocysteine concentration in men and women. Eur. J. Clin. Nutr.58, 376–385 (2004). PubMed
Järvenpää, J. et al. Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women. J. Perinat. Med.35, 108–114 (2007). PubMed
Engle-Stone, R. et al. Analyses using national survey data from Cameroon, Haiti, and Ghana indicate the potential for bouillon fortification to help fill dietary gaps for 5 nutrients. Curr. Dev. Nutr.5, 640 (2021). PubMed PMC
Engle‐Stone, R. et al. Weighing the risks of high intakes of selected micronutrients compared with the risks of deficiencies. Ann. N. Y. Acad. Sci.1446, 81–101 (2019). PubMed PMC
De Steur, H., Feng, S., Xiaoping, S. & Gellynck, X. Consumer preferences for micronutrient strategies in China. A comparison between folic acid supplementation and folate biofortification. Public Health Nutr.17, 1410–1420 (2014). PubMed PMC
De Steur, H. et al. Potential impact and cost-effectiveness of multi-biofortified rice in China. N. Biotechnol.29, 432–442 (2012). PubMed
Strobbe, S. & Van Der Straeten, D. Folate biofortification in food crops. Curr. Opin. Biotechnol.44, 202–211 (2017). PubMed
De Steur, H. et al. Health impact in China of folate-biofortified rice. Nat. Biotechnol.28, 554–556 (2010). PubMed
De Lepeleire, J. et al. Folate biofortification of potato by tuber-specific expression of four folate biosynthesis genes. Mol. Plant11, 175–188 (2018). PubMed
McLean, E., de Benoist, B. & Allen, L. H. Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Food Nutr. Bull.29, S38–S51 (2008). PubMed
Strobbe, S. & Van Der Straeten, D. Toward eradication of B-vitamin deficiencies: considerations for crop biofortification. Front. Plant Sci.9, 443 (2018). PubMed PMC
Yu, S. & Tian, L. Breeding major cereal grains through the lens of nutrition sensitivity. Mol. Plant11, 23–30 (2018). PubMed
Kumar, J. et al. Current knowledge on genetic biofortification in lentil. J. Agric. Food Chem.64, 6383–6396 (2016). PubMed
Piironen, V., Edelmann, M., Kariluoto, S. & Bedo, Z. Folate in wheat genotypes in the HEALTHGRAIN diversity screen. J. Agric. Food Chem.56, 9726–9731 (2008). PubMed
Riaz, B. et al. Folate content analysis of wheat cultivars developed in the North China Plain. Food Chem.289, 377–383 (2019). PubMed
Shewry, P. R. et al. Natural variation in grain composition of wheat and related cereals. J. Agric. Food Chem.61, 8295–8303 (2013). PubMed
Hefni, M. E., Schaller, F. & Witthöft, C. M. Betaine, choline and folate content in different cereal genotypes. J. Cereal Sci.80, 72–79 (2018).
Kariluoto, S., Edelmann, M. & Piironen, V. Effects of environment and genotype on folate contents in wheat in the HEALTHGRAIN diversity screen. J. Agric. Food Chem.58, 9324–9331 (2010). PubMed
Zheng, J. et al. Folate (vitamin B9) content analysis in bread wheat (Triticum aestivum L.). Front. Nutr.9, 933358 (2022). PubMed PMC
Ashokkumar, K. et al. Genomics-integrated breeding for carotenoids and folates in staple cereal grains to reduce malnutrition. Front. Genet.11, 414 (2020). PubMed PMC
Shahid, M. et al. Folate monoglutamate in cereal grains: Evaluation of extraction techniques and determination by LC-MS/MS. J. Food Compos. Anal.91, 103510 (2020).
Andersson, A. A. et al. Phytochemical and dietary fiber components in barley varieties in the HEALTHGRAIN diversity screen. J. Agric. Food Chem.56, 9767–9776 (2008). PubMed
Kariluoto, M. S., Vahteristo, L. T. & Piironen, V. I. Applicability of microbiological assay and affinity chromatography purification followed by high‐performance liquid chromatography (HPLC) in studying folate contents in rye. J. Sci. Food Agric.81, 938–942 (2001).
Shewry, P. R. et al. Effects of genotype and environment on the content and composition of phytochemicals and dietary fiber components in rye in the HEALTHGRAIN diversity screen. J. Agric. Food Chem.58, 9372–9383 (2010). PubMed
Shewry, P. R. et al. Phytochemical and fiber components in oat varieties in the HEALTHGRAIN diversity screen. J. Agric. Food Chem.56, 9777–9784 (2008). PubMed
De Brouwer, V. et al. Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) for the sensitive determination of folates in rice. J. Chromatogr. B878, 509–513 (2010). PubMed
Ashokkumar, K., Sivakumar, P. & Saradhadevi, M. Identification and determination of naturally occurring folates in grains of rice (Oryza sativa L.) by UPLC-MS/MS analysis. Nat. Prod. Res.32, 1733–1737 (2018). PubMed
Dong, W. et al. Identification of QTLs underlying folate content in milled rice. J. Integr. Agric.13, 1827–1834 (2014).
Xiao, Y. et al. A genome-wide association study of folates in sweet corn kernels. Front. Plant Sci.13, 1004455 (2022). PubMed PMC
Lian, T. et al. Comparative transcriptome analysis reveals mechanisms of folate accumulation in maize grains. Int. J. Mol. Sci.23, 1708 (2022). PubMed PMC
Hou, S. et al. Folate metabolic profiling and expression of folate metabolism‐related genes during panicle development in foxtail millet (Setaria italica (L.) P. Beauv). J. Sci. Food Agric.102, 268–279 (2022). PubMed
Wang, Y. et al. Foxtail millet [Setaria italica (L.) P. Beauv.] grown under nitrogen deficiency exhibits a lower folate contents. Front. Nutr.10, 1035739 (2023). PubMed PMC
Goyer, A. & Sweek, K. Genetic diversity of thiamin and folate in primitive cultivated and wild potato (Solanum) species. J. Agric. Food Chem.59, 13072–13080 (2011). PubMed
Robinson, B. R., Sathuvalli, V., Bamberg, J. & Goyer, A. Exploring folate diversity in wild and primitive potatoes for modern crop improvement. Genes6, 1300–1314 (2015). PubMed PMC
Singh, J. et al. Genetic variability for vitamin B9 and total dietary fiber in lentil (Lens culinaris L.) cultivars. Int. J. Food Prop.19, 936–943 (2016).
Jha, A. B. et al. Genetic diversity of folate profiles in seeds of common bean, lentil, chickpea and pea. J. Food Compos. Anal.42, 134–140 (2015).
Agyenim-Boateng, K. G. et al. Profiling of naturally occurring folates in a diverse soybean germplasm by HPLC-MS/MS. Food Chem.384, 132520 (2022). PubMed
Agyenim-Boateng, K. G. et al. Identification of quantitative trait loci and candidate genes for seed folate content in soybean. Theor. Appl. Genet.136, 149 (2023). PubMed
Agyenim-Boateng, K. G. et al. Folate biofortification in soybean: challenges and prospects. Agron13, 241 (2023).
Marshall, J. et al. Targeted quantification of B vitamins using ultra-performance liquid chromatography-selected reaction monitoring mass spectrometry in faba bean seeds. J. Food Compos. Anal.95, 103687 (2021).
Goyer, A., Navarre, D. A. & Miklas, P. N. Folate content in select dry bean genotoypes. 132–133 (Annual Report-Bean Improvement Cooperative, 2008).
Martin, C. J., Torkamaneh, D., Arif, M. & Pauls, K. P. Genome-wide association study of seed folate content in common bean. Front. Plant Sci.12, 696423 (2021). PubMed PMC
Khanal, S. et al. Quantitative trait loci analysis of folate content in dry beans, Phaseolus vulgaris L. Int. J. Agron2013, 983641 (2013).
Jha, A. B. et al. Folate profile diversity and associated SNPs using genome wide association study in pea. Euphytica216, 1–16 (2020).
Shohag, M. et al. Genetic and physiological regulation of folate in pak choi (Brassica rapa subsp. Chinensis) germplasm. J. Exp. Bot.71, 4914–4929 (2020). PubMed PMC
Blancquaert, D., De Steur, H., Gellynck, X. & Van Der Straeten, D. Present and future of folate biofortification of crop plants. J. Exp. Bot.65, 895–906 (2014). PubMed
Blancquaert, D. et al. Enhancing pterin and para-aminobenzoate content is not sufficient to successfully biofortify potato tubers and Arabidopsis thaliana plants with folate. J. Exp. Bot.64, 3899–3909 (2013). PubMed
Blancquaert, D. et al. Rice folate enhancement through metabolic engineering has an impact on rice seed metabolism, but does not affect the expression of the endogenous folate biosynthesis genes. Plant Mol. Biol.83, 329–349 (2013). PubMed
De Steur, H. et al. Genetically modified rice with health benefits as a means to reduce micronutrient malnutrition: global status, consumer preferences, and potential health impacts of rice biofortification. In Wheat and Rice in Disease Prevention and Health (eds Watson, R. R., Preedy, R. V. & Zibadi, S.) Ch. 21, 283–299 (Academic Press, 2014).
Sanahuja, G. et al. A question of balance: achieving appropriate nutrient levels in biofortified staple crops. Nutr. Res. Rev.26, 235–245 (2013). PubMed
Bekaert, S. et al. Folate biofortification in food plants. Trends Plant Sci.13, 28–35 (2008). PubMed
Díaz de la Garza, R. et al. Folate biofortification in tomatoes by engineering the pteridine branch of folate synthesis. Proc. Natl. Acad. Sci.101, 13720–13725 (2004). PubMed PMC
Storozhenko, S. et al. Folate enhancement in staple crops by metabolic engineering. Trends Food Sci. Technol.16, 271–281 (2005).
Rébeillé, F. et al. Roles of vitamins B5, B8, B9, B12 and molybdenum cofactor at cellular and organismal levels. Nat. Prod. Rep.24, 949–962 (2007). PubMed
Tyagi, K. et al. Seeing the unseen: a trifoliate (MYB117) mutant allele fortifies folate and carotenoids in tomato fruits. Plant J.112, 38–54 (2022). PubMed
Song, L. et al. Weighted gene co-expression network analysis unveils gene networks regulating folate biosynthesis in maize endosperm. 3 Biotech11, 1–16 (2021). PubMed PMC
Basset, G. J., Quinlivan, E. P., Gregory, J. F. III & Hanson, A. D. Folate synthesis and metabolism in plants and prospects for biofortification. Crop. Sci.45, 449–453 (2005).
Blancquaert, D. et al. Improving folate (vitamin B9) stability in biofortified rice through metabolic engineering. Nat. Biotechnol.33, 1076–1078 (2015). PubMed
Hossain, T. et al. Enhancement of folates in plants through metabolic engineering. Proc. Natl. Acad. Sci.101, 5158–5163 (2004). PubMed PMC
Nunes, A. C., Kalkmann, D. C. & Aragao, F. J. Folate biofortification of lettuce by expression of a codon optimized chicken GTP cyclohydrolase I gene. Transgenic Res.18, 661–667 (2009). PubMed
Díaz de la Garza, R. I., Gregory, J. F. III & Hanson, A. D. Folate biofortification of tomato fruit. Proc. Natl. Acad. Sci.104, 4218–4222 (2007). PubMed PMC
Zanga, D. et al. Freedom‐to‐operate analysis of a transgenic multivitamin corn variety. Plant Biotechnol. J.14, 1225–1240 (2016). PubMed PMC
Liang, Q. et al. Improved folate accumulation in genetically modified maize and wheat. J. Exp. Bot.70, 1539–1551 (2019). PubMed PMC
Ramírez Rivera, N. G., García‐Salinas, C., Aragão, F. J. & Díaz de la Garza, R. I. Metabolic engineering of folate and its precursors in Mexican common bean (Phaseolus vulgaris L.). Plant Biotechnol. J.14, 2021–2032 (2016). PubMed PMC
Dong, W. et al. Overexpression of folate biosynthesis genes in rice (Oryza sativa L.) and evaluation of their impact on seed folate content. Plant Foods Hum. Nutr.69, 379–385 (2014). PubMed
Naqvi, S. et al. Transgenic multivitamin corn through biofortification of endosperm with three vitamins representing three distinct metabolic pathways. Proc. Natl. Acad. Sci.106, 7762–7767 (2009). PubMed PMC
Storozhenko, S. et al. Folate fortification of rice by metabolic engineering. Nat. Biotechnol.25, 1277–1279 (2007). PubMed
Capozzi, V. et al. Lactic acid bacteria producing B-group vitamins: a great potential for functional cereals products. Appl. Microbiol. Biotechnol.96, 1383–1394 (2012). PubMed
LeBlanc, J. et al. B‐Group vitamin production by lactic acid bacteria–current knowledge and potential applications. J. Appl. Microbiol.111, 1297–1309 (2011). PubMed
Rossi, M., Amaretti, A. & Raimondi, S. Folate production by probiotic bacteria. Nutrients3, 118–134 (2011). PubMed PMC
Levit, R., Savoy de Giori, G., De Moreno De Leblanc, A. & LeBlanc, J. G. Recent update on lactic acid bacteria producing riboflavin and folates: application for food fortification and treatment of intestinal inflammation. J. Appl. Microbiol.130, 1412–1424 (2021). PubMed
Mahara, F. A., Nuraida, L. & Lioe, H. N. Fermentation of milk using folate-producing lactic acid bacteria to increase natural folate content: a review. Appl. Biotechnol. Rep.6, 129–136 (2019).
Mahara, F. A., Nuraida, L. & Lioe, H. N. Folate in milk fermented by lactic acid bacteria from different food sources. Prev. Nutr. Food Sci.26, 230–240 (2021). PubMed PMC
Meucci, A. et al. Folates biosynthesis by Streptococcus thermophilus during growth in milk. Food Microbiol.69, 116–122 (2018). PubMed
Laiño, J. E. et al. Folate production and fol genes expression by the dairy starter culture Streptococcus thermophilus CRL803 in free and controlled pH batch fermentations. LWT85, 146–150 (2017).
Tomar, S., Srivatsa, N., Ramya, I. & Rameshwar, S. Estimation of folate production by Streptococcus thermophilus using modified microbiological assay. Milchwissenschaft64, 260–263 (2009).
Sybesma, W. et al. Effects of cultivation conditions on folate production by lactic acid bacteria. Appl. Environ. Microbiol.69, 4542–4548 (2003). PubMed PMC
Ayad, E. H. Starter culture development for improving safety and quality of Domiati cheese. Food Microbiol.26, 533–541 (2009). PubMed
Padalino, M. et al. Effect of fructooligosaccharides and galactooligosaccharides on the folate production of some folate-producing bacteria in media cultures or milk. Int. Dairy J.27, 27–33 (2012).
Albano, C., Silvetti, T. & Brasca, M. Screening of lactic acid bacteria producing folate and their potential use as adjunct cultures for cheese bio-enrichment. FEMS Microbiol. Lett.367, fnaa059 (2020). PubMed
Laiño, J. E., del Valle, M. J., de Giori, G. S. & LeBlanc, J. G. J. Development of a high folate concentration yogurt naturally bio-enriched using selected lactic acid bacteria. LWT54, 1–5 (2013).
Laiño, J. E., del Valle, M. J., de Giori, G. S. & LeBlanc, J. G. J. Applicability of a Lactobacillus amylovorus strain as co-culture for natural folate bio-enrichment of fermented milk. Int. J. Food Microbiol.191, 10–16 (2014). PubMed
Rad, A. H., Khosroushahi, A. Y., Khalili, M. & Jafarzadeh, S. Folate bio-fortification of yoghurt and fermented milk: a review. Dairy Sci. Technol.96, 427–441 (2016).
Olanbiwoninu, A. et al. Microbial-based biofortification to mitigate African micronutrients deficiency: A focus on plant-based fermentation as source of B-group vitamins. Food Biosci55, 102996 (2023).
Mahara, F. A., Nuraida, L., Lioe, H. N. & Nurjanah, S. The occurrence of folate biosynthesis genes in lactic acid bacteria from different sources. Food Technol. Biotechnol.61, 226–237 (2023). PubMed PMC
Patel, A., Shah, N. & Prajapati, J. Biosynthesis of vitamins and enzymes in fermented foods by lactic acid bacteria and related genera-A promising approach. Croat. J. Food Sci. Technol.5, 85–91 (2013).
Mosso, A. L. et al. Increasing the folate content of tuber based foods using potentially probiotic lactic acid bacteria. Food Res. Int.109, 168–174 (2018). PubMed
Mosso, A. L. et al. Effect of fermentation in nutritional, textural and sensorial parameters of vegan-spread products using a probiotic folate-producing Lactobacillus sakei strain. LWT127, 109339 (2020).
Carrizo, S. L. et al. Ancestral Andean grain quinoa as source of lactic acid bacteria capable to degrade phytate and produce B-group vitamins. Food Res. Int.89, 488–494 (2016). PubMed
Kariluoto, S. et al. In situ enrichment of folate by microorganisms in beta-glucan rich oat and barley matrices. Int. J. Food Microbiol.176, 38–48 (2014). PubMed
Thompson, H. O. et al. Fermentation of cauliflower and white beans with Lactobacillus plantarum–impact on levels of riboflavin, folate, vitamin B 12, and amino acid composition. Plant Foods Hum. Nutr.75, 236–242 (2020). PubMed PMC
Da Silva, F. F. P., Biscola, V., LeBlanc, J. G. & de Melo Franco, B. D. G. Effect of indigenous lactic acid bacteria isolated from goat milk and cheeses on folate and riboflavin content of fermented goat milk. LWT71, 155–161 (2016).
Tamene, A., Baye, K. & Humblot, C. Folate content of a staple food increased by fermentation of a cereal using selected folate-producing microorganisms. Heliyon8, e09526 (2022). PubMed PMC
Divya, J. B. & Nampoothiri, K. M. Folate fortification of skim milk by a probiotic Lactococcus lactis CM28 and evaluation of its stability in fermented milk on cold storage. Int. J. Food Sci. Technol.52, 3513–3519 (2015). PubMed PMC
Panda, S. et al. Characterization of novel folate producing Lactobacillus rhamnosus and its appliance in fortification of ragi (Eleusine coracana) gruel. Food Biosci.21, 100–106 (2018).
Okoroafor, I., Banwo, K., Olanbiwoninu, A. A. & Odunfa, S. A. Folate enrichment of Ogi (a fermented cereal gruel) using folate producing starter cultures. Adv. Microbiol.9, 177 (2019).
Tamene, A., Mekuriyaw, T. & Baye, K. Effectiveness of Lactiplantibacillus plantarum in enhancing the folate content of injera made with different cereals. Food Sci. Nutr.11, 6213–6222 (2023). PubMed PMC
Greppi, A. et al. Ability of lactobacilli isolated from traditional cereal-based fermented food to produce folate in culture media under different growth conditions. LWT86, 277–284 (2017).
Pompei, A. et al. Folate production by bifidobacteria as a potential probiotic property. Appl. Environ. Microbiol.73, 179–185 (2007). PubMed PMC
Celik, O. F. & O’Sullivan, D. J. Correlation of gene content in selected bifidobacteria with folate supplier or scavenger status during growth in laboratory media. Food Biosci.51, 102324 (2023).
Czarnowska-Kujawska, M. & Paszczyk, B. Changes in the folate content and fatty acid profile in fermented milk produced with different starter cultures during storage. Molecules26, 6063 (2021). PubMed PMC
Hugenschmidt, S., Schwenninger, S. M., Gnehm, N. & Lacroix, C. Screening of a natural biodiversity of lactic and propionic acid bacteria for folate and vitamin B12 production in supplemented whey permeate. Int. Dairy J.20, 852–857 (2010).
Hugenschmidt, S., Schwenninger, S. M. & Lacroix, C. Concurrent high production of natural folate and vitamin B12 using a co-culture process with Lactobacillus plantarum SM39 and Propionibacterium freudenreichii DF13. Process Biochem.46, 1063–1070 (2011).
Hugenholtz, J., Hunik, J., Santos, H. & Smid, E. Nutraceutical production by propionibacteria. Le Lait82, 103–112 (2002).
Poonam et al. Multifaceted attributes of dairy propionibacteria: a review. World J. Microbiol. Biotechnol.28, 3081–3095 (2012). PubMed
Van Wyk, J. & Britz, T. J. A rapid high-performance liquid chromatography (HPLC) method for the extraction and quantification of folates in dairy products and cultures of Propionibacterium freudenreichii. Afr. J. Biotechnol.11, 2087–2098 (2012).
Van Wyk, J., Witthuhn, R. C. & Britz, T. J. Optimisation of vitamin B12 and folate production by Propionibacterium freudenreichii strains in kefir. Int. Dairy J.21, 69–74 (2011).
Korhola, M. et al. Production of folate in oat bran fermentation by yeasts isolated from barley and diverse foods. J. Appl. Microbiol.117, 679–689 (2014). PubMed
Hjortmo, S., Patring, J. & Andlid, T. Growth rate and medium composition strongly affect folate content in Saccharomyces cerevisiae. Int. J. Food Microbiol.123, 93–100 (2008). PubMed
Hjortmo, S. B., Hellström, A. M. & Andlid, T. A. Production of folates by yeasts in Tanzanian fermented togwa. FEMS Yeast Res.8, 781–787 (2008). PubMed
Greppi, A. et al. Potential probiotic Pichia kudriavzevii strains and their ability to enhance folate content of traditional cereal-based African fermented food. Food Microbiol.62, 169–177 (2017). PubMed
Chandrasekar Rajendran, S. et al. Biofortification of riboflavin and folate in idli batter, based on fermented cereal and pulse, by Lactococcus lactis N8 and Saccharomyces boulardii SAA655. J. Appl. Microbiol.122, 1663–1671 (2017). PubMed
Herranen, M. et al. Isolation and characterization of folate-producing bacteria from oat bran and rye flakes. Int. J. Food Microbiol.142, 277–285 (2010). PubMed
Deatraksa, J. et al. Isolation of folate-producing Weissella spp. from Thai fermented fish (Plaa Som Fug). LWT89, 388–391 (2018).
Kariluoto, S. et al. Production of folate by bacteria isolated from oat bran. Int. J. Food Microbiol.143, 41–47 (2010). PubMed
Laiño, J. E., LeBlanc, J. G. & Savoy de Giori, G. Production of natural folates by lactic acid bacteria starter cultures isolated from artisanal Argentinean yogurts. Can. J. Microbiol.58, 581–588 (2012). PubMed
Saubade, F., Humblot, C., Hemery, Y. M. & Guyot, J.-P. PCR screening of an African fermented pearl-millet porridge metagenome to investigate the nutritional potential of its microbiota. Int. J. Food Microbiol.244, 103–110 (2017). PubMed
D’Aimmo, M. R. et al. Biosynthesis and cellular content of folate in bifidobacteria across host species with different diets. Anaerobe30, 169–177 (2014). PubMed
Masuda, M. et al. Production potency of folate, vitamin B12, and thiamine by lactic acid bacteria isolated from Japanese pickles. Biosci. Biotechnol. Biochem.76, 2061–2067 (2012). PubMed
Misci, C. et al. Fermentation as a tool for increasing food security and nutritional quality of indigenous African leafy vegetables: the case of Cucurbita sp. Food Microbiol.99, 103820 (2021). PubMed
Hjortmo, S., Patring, J., Jastrebova, J. & Andlid, T. Biofortification of folates in white wheat bread by selection of yeast strain and process. Int. J. Food Microbiol.127, 32–36 (2008). PubMed
Sybesma, W. et al. Multivitamin production in Lactococcus lactis using metabolic engineering. Metab. Eng.6, 109–115 (2004). PubMed
Sybesma, W. et al. Increased production of folate by metabolic engineering of Lactococcus lactis. Appl. Environ. Microbiol.69, 3069–3076 (2003). PubMed PMC
Sybesma, W. et al. Controlled modulation of folate polyglutamyl tail length by metabolic engineering of Lactococcus lactis. Appl. Environ. Microbiol.69, 7101–7107 (2003). PubMed PMC
Wegkamp, A., van Oorschot, W., de Vos, W. M. & Smid, E. J. Characterization of the role of para-aminobenzoic acid biosynthesis in folate production by Lactococcus lactis. Appl. Environ. Microbiol.73, 2673–2681 (2007). PubMed PMC
Santos, F. et al. High-level folate production in fermented foods by the B12 producer Lactobacillus reuteri JCM1112. Appl. Environ. Microbiol.74, 3291–3294 (2008). PubMed PMC
Wegkamp, A. et al. Transformation of folate-consuming Lactobacillus gasseri into a folate producer. Appl. Environ. Microbiol.70, 3146–3148 (2004). PubMed PMC
Liu, Y. et al. Enhancing the natural folate level in wine using bioengineering and stabilization strategies. Food Chem.194, 26–31 (2016). PubMed
LeBlanc, J. G. et al. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr. Opin. Biotechnol.24, 160–168 (2013). PubMed
Shin, Y. S. et al. Subcellular localization of gamma-glutamyl carboxypeptidase and of folates. Biochim. Biophys. Acta444, 794–801 (1976). PubMed
Hou, Z. & Matherly, L. H. Biology of the major facilitative folate transporters SLC19A1 and SLC46A1. Curr. Top. Membr.73, 175–204 (2014). PubMed PMC
Ducker, G. S. & Rabinowitz, J. D. One-carbon metabolism in health and disease. Cell Metab.25, 27–42 (2017). PubMed PMC
Watkins, D. & Rosenblatt, D. S. Inherited Disorders of Folate and Cobalamin Transport and Metabolism. In The Online Metabolic and Molecular Bases ofInherited Disease (eds Valle, D. L. et al.) (McGraw-Hill Education, 2019). 10.1036/ommbid.420.
Froese, D. S., Fowler, B. & Baumgartner, M. R. Vitamin B(12), folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation. J. Inherit. Metab. Dis.42, 673–685 (2019). PubMed
Tibbetts, A. S. & Appling, D. R. Compartmentalization of Mammalian folate-mediated one-carbon metabolism. Annu. Rev. Nutr.30, 57–81 (2010). PubMed
Zhao, R., Matherly, L. H. & Goldman, I. D. Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues. Expert Rev. Mol. Med.11, e4 (2009). PubMed PMC
Bosson, G. Reduced folate carrier: biochemistry and molecular biology of the normal and methotrexate-resistant cell. Br. J. Biomed. Sci.60, 117–129 (2003). PubMed
Salazar, M. D. & Ratnam, M. The folate receptor: what does it promise in tissue-targeted therapeutics? Cancer Metastasis Rev.26, 141–152 (2007). PubMed
Low, P. S. & Kularatne, S. A. Folate-targeted therapeutic and imaging agents for cancer. Curr. Opin. Chem. Biol.13, 256–262 (2009). PubMed
Gao, W. et al. Chemotherapeutic drug delivery to cancer cells using a combination of folate targeting and tumor microenvironment-sensitive polypeptides. Biomaterials34, 4137–4149 (2013). PubMed
Zhao, R. & Goldman, I. D. Folate and thiamine transporters mediated by facilitative carriers (SLC19A1-3 and SLC46A1) and folate receptors. Mol. Asp. Med.34, 373–385 (2013). PubMed PMC
Alpers, D., Taylor, B., Bier, D. & Klein, S. Manual of Nutritional Therapeutics 6th edn. (Lippincott Williams & Wilkins, 2015).
Reisenauer, A. M., Krumdieck, C. L. & Halsted, C. H. Folate conjugase: two separate activities in human jejunum. Science198, 196–197 (1977). PubMed
Wang, T. T., Reisenauer, A. M. & Halsted, C. H. Comparison of folate conjugase activities in human, pig, rat and monkey intestine. J. Nutr.115, 814–819 (1985). PubMed
Inoue, K. et al. Functional characterization of PCFT/HCP1 as the molecular entity of the carrier-mediated intestinal folate transport system in the rat model. Am. J. Physiol. Gastrointest. Liver Physiol.294, G660–G668 (2008). PubMed
Subramanian, V. S., Marchant, J. S. & Said, H. M. Apical membrane targeting and trafficking of the human proton-coupled transporter in polarized epithelia. Am. J. Physiol. Cell Physiol.294, C233–C240 (2008). PubMed
Greiner, P. O., Zittoun, J., Marquet, J. & Cheron, J. M. Pharmacokinetics of (-)-folinic acid after oral and intravenous administration of the racemate. Br. J. Clin. Pharmacol.28, 289–295 (1989). PubMed PMC
Garza-Aguilar, S. M. et al. The complexity of folate polyglutamylation in plants: postharvest ripening and ethylene modulate polyglutamylated profiles in climacteric fruits plus systematic analysis of the glutamyl tail-editing enzymes. Sci. Hortic.273, 109588 (2020).
Habeck, L. L. et al. Substrate specificity of mammalian folylpolyglutamate synthetase for 5,10-dideazatetrahydrofolate analogs. Mol. Pharmacol.48, 326–333 (1995). PubMed
Herbert, V. & Zalusky, R. Interrelations of vitamin B12 and folic acid metabolism: folic acid clearance studies. J. Clin. Invest.41, 1263–1276 (1962). PubMed PMC
Gregory, J. III et al. Kinetic model of folate metabolism in nonpregnant women consuming [2H2]folic acid: isotopic labeling of urinary folate and the catabolite para-acetamidobenzoylglutamate indicates slow, intake-dependent, turnover of folate pools. J. Nutr.128, 1896–1906 (1998). PubMed
Steinberg, S. E., Campbell, C. L. & Hillman, R. S. Kinetics of the normal folate enterohepatic cycle. J. Clin. Invest.64, 83–88 (1979). PubMed PMC
Gregory, J. III Bioavailability of folate. Eur. J. Clin. Nutr.51, S54–S59 (1997). PubMed
Gregory, J. III, Williamson, J., Bailey, L. & Toth, J. Urinary excretion of [2H4]folate by nonpregnant women following a single oral dose of [2H4]folic acid is a functional index of folate nutritional status. J. Nutr.128, 1907–1912 (1998). PubMed
McPartlin, J. et al. The quantitative analysis of endogenous folate catabolites in human urine. Anal. Biochem.206, 256–261 (1992). PubMed
Galivan, J. et al. Glutamyl hydrolase: pharmacological role and enzymatic characterization. Pharmacol. Ther.85, 207–215 (2000). PubMed
Suh, J. R., Herbig, A. K. & Stover, P. J. New perspectives on folate catabolism. Annu. Rev. Nutr.21, 255–282 (2001). PubMed
Garrow, T. A. et al. Cloning of human cDNAs encoding mitochondrial and cytosolic serine hydroxymethyltransferases and chromosomal localization. J. Biol. Chem.268, 11910–11916 (1993). PubMed
Gregory, J. III et al. Primed, constant infusion with [2H3]serine allows in vivo kinetic measurement of serine turnover, homocysteine remethylation, and transsulfuration processes in human one-carbon metabolism. Am. J. Clin. Nutr.72, 1535–1541 (2000). PubMed
Herbig, K. et al. Cytoplasmic serine hydroxymethyltransferase mediates competition between folate-dependent deoxyribonucleotide and S-adenosylmethionine biosyntheses. J. Biol. Chem.277, 38381–38389 (2002). PubMed
Ducker, G. S. et al. Reversal of cytosolic one-carbon flux compensates for loss of the mitochondrial folate pathway. Cell Metab.23, 1140–1153 (2016). PubMed PMC
Labuschagne, C. F. et al. Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. Cell Rep.7, 1248–1258 (2014). PubMed
Yamaoka, T. et al. Amidophosphoribosyltransferase limits the rate of cell growth-linked de novo purine biosynthesis in the presence of constant capacity of salvage purine biosynthesis. J. Biol. Chem.272, 17719–17725 (1997). PubMed
Shane, B. Folate and vitamin B12 metabolism: overview and interaction with riboflavin, vitamin B6, and polymorphisms. Food Nutr. Bull.29, S5–S16 (2008). PubMed
Lan, X., Field, M. S. & Stover, P. J. Cell cycle regulation of folate-mediated one-carbon metabolism. Wiley Interdiscip. Rev. Syst. Biol. Med.10, e1426 (2018). PubMed PMC
Prem Veer Reddy, G. Catalytic function of thymidylate synthase is confined to S phase due to its association with replitase. Biochem. Biophys. Res. Commun.109, 908–915 (1982). PubMed
Benkovic, S. J. & Wagner, C. R. Dihydrofolate reductase. In Protein Design and the Development of New Therapeutics and Vaccines (eds Hook, J. B., Poste, G. & Schatz, J.) Ch. 5, 237–249 (Springer US, 1990).
Santi, D. & Danenberg, P. Folates in pyrimidine nucleotide biosynthesis. Folates Pterins1, 345–398 (1984).
Shane, B. Folate, vitamin B12 and vitamin B6. In Biochemical, Physiological, Molecular Aspects of Human Nutrition 2nd edn (ed. Stipanuk, M. H.) 693–732 (W.B. Saunders, 2006).
Shane, B. & Stokstad, E. L. Vitamin B12-folate interrelationships. Annu. Rev. Nutr.5, 115–141 (1985). PubMed
Fenech, M. The role of folic acid and vitamin B12 in genomic stability of human cells. Mutat. Res. Fundam. Mol. Mech. Mutagen.475, 57–67 (2001). PubMed
Jacques, P. F. et al. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N. Engl. J. Med.340, 1449–1454 (1999). PubMed
Refsum, H., Ueland, P. M., Nygård, O. & Vollset, S. E. Homocysteine and cardiovascular disease. Annu. Rev. Med.49, 31–62 (1998). PubMed
Kim, J., Kim, H., Roh, H. & Kwon, Y. Causes of hyperhomocysteinemia and its pathological significance. Arch. Pharm. Res.41, 372–383 (2018). PubMed
Meiser, J. & Vazquez, A. Give it or take it: the flux of one-carbon in cancer cells. FEBS J.283, 3695–3704 (2016). PubMed
Field, M. S. et al. Human mutations in methylenetetrahydrofolate dehydrogenase 1 impair nuclear de novo thymidylate biosynthesis. Proc. Natl. Acad. Sci.112, 400–405 (2015). PubMed PMC
Stead, L. M. et al. Is it time to reevaluate methyl balance in humans? Am. J. Clin. Nutr.83, 5–10 (2006). PubMed
Prem veer Reddy, G. & Pardee, A. B. Multienzyme complex for metabolic channeling in mammalian DNA replication. Proc. Natl. Acad. Sci.77, 3312–3316 (1980). PubMed PMC
Anderson, D. D. et al. Serine hydroxymethyltransferase anchors de novo thymidylate synthesis pathway to nuclear lamina for DNA synthesis. J. Biol. Chem.287, 7051–7062 (2012). PubMed PMC
Blount, B. C. et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc. Natl. Acad. Sci.94, 3290–3295 (1997). PubMed PMC
Field, M. S., Kamynina, E., Chon, J. & Stover, P. J. Nuclear folate metabolism. Annu. Rev. Nutr.38, 219–243 (2018). PubMed PMC
Kapiszewska, M., Kalemba, M., Wojciech, U. & Milewicz, T. Uracil misincorporation into DNA of leukocytes of young women with positive folate balance depends on plasma vitamin B12 concentrations and methylenetetrahydrofolate reductase polymorphisms. A pilot study. J. Nutr. Biochem.16, 467–478 (2005). PubMed
An, S., Kumar, R., Sheets, E. D. & Benkovic, S. J. Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science320, 103–106 (2008). PubMed
Field, M. S., Anderson, D. D. & Stover, P. J. Mthfs is an essential gene in mice and a component of the purinosome. Front. Genet.2, 36 (2011). PubMed PMC
Froese, D. S. et al. Restricted role for methionine synthase reductase defined by subcellular localization. Mol. Genet. Metab.94, 68–77 (2008). PubMed PMC
Mellman, I., Willard, H. F. & Rosenberg, L. E. Cobalamin binding and cobalamin-dependent enzyme activity in normal and mutant human fibroblasts. J. Clin. Invest.62, 952–960 (1978). PubMed PMC
Rassin, D. K. & Gaull, G. E. Subcellular distribution of enzymes of transmethylation and transsulphuration in rat brain. J. Neurochem.24, 969–978 (1975). PubMed
Khan, K. M. & Jialal, I. Folic Acid Deficiency (StatPearls Publishing, 2021). PubMed
Duthie, S. J. Epigenetic modifications and human pathologies: cancer and CVD. Proc. Nutr. Soc.70, 47–56 (2011). PubMed
Grindulis, K. A. & McConkey, B. Does sulphasalazine cause folate deficiency in rheumatoid arthritis? Scand. J. Rheumatol.14, 265–270 (1985). PubMed
Stover, P. J. Folate biochemical pathways and their regulation. In Folate in Health and Disease 2nd edn (ed. Bailey, L. B.) 49–74 (CRC Press Boca Raton, 2009).
Chen, J., Xu, X., Liu, A. & Ulrich, C. M. Folate and cancer: epidemiological perspective. In Folate in Health and Disease 2nd edn (ed. Bailey, L. B.) 205–233 (CRC Press Boca Raton, 2009).
Berger, S. H., Pittman, D. L. & Wyatt, M. D. Uracil in DNA: consequences for carcinogenesis and chemotherapy. Biochem. Pharmacol.76, 697–706 (2008). PubMed PMC
Blencowe, H. et al. Estimates of global and regional prevalence of neural tube defects for 2015: a systematic analysis. Ann. N. Y. Acad. Sci.1414, 31–46 (2018). PubMed
Khoshnood, B. et al. Long term trends in prevalence of neural tube defects in Europe: population based study. BMJ351, h5949 (2015). PubMed PMC
Liu, J. et al. Prevalence and trend of neural tube defects in five counties in Shanxi province of Northern China, 2000 to 2014. Birth Defects Res. A Clin. Mol. Teratol.106, 267–274 (2016). PubMed
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet338, 131–137 (1991). PubMed
Czeizel, A. E. & Dudás, I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N. Engl. J. Med.327, 1832–1835 (1992). PubMed
McNulty, H. et al. Addressing optimal folate and related B-vitamin status through the lifecycle: health impacts and challenges. Proc. Nutr. Soc.78, 449–462 (2019). PubMed
Martinez, H. et al. Global strategies for the prevention of neural tube defects through the improvement of folate status in women of reproductive age. Childs Nerv. Syst., 39, 1719–1736 (2023). PubMed
Martinez, H., Pachón, H., Kancherla, V. & Oakley, G. P. Jr Food fortification with folic acid for prevention of spina bifida and anencephaly: the need for a paradigm shift in evidence evaluation for policy-making. Am. J. Epidemiol.190, 1972–1976 (2021). PubMed PMC
Benavides-Lara, A. et al. Integrated surveillance strategy to support the prevention of neural tube defects through food fortification with folic acid: the experience of Costa Rica. Childs Nerv. Syst.39, 1743–1754 (2023). PubMed PMC
Saing, S. et al. Real-world cost effectiveness of mandatory folic acid fortification of bread-making flour in Australia. Appl. Health Econ. Health Policy17, 243–254 (2019). PubMed
Hertrampf, E. & Cortés, F. Folic acid fortification of wheat flour: Chile. Nutr. Rev.62, S44–S48 (2004). PubMed
Williams, L. J. et al. Prevalence of spina bifida and anencephaly during the transition to mandatory folic acid fortification in the United States. Teratology66, 33–39 (2002). PubMed
De Wals, P. et al. Reduction in neural-tube defects after folic acid fortification in Canada. N. Engl. J. Med.357, 135–142 (2007). PubMed
García-Fragoso, L., García-García, I. & Rivera, C. E. The use of folic acid for the prevention of birth defects in Puerto Rico. Ethn. Dis.18, S2–168-171 (2008). PubMed PMC
Ray, J. G. Folic acid food fortification in Canada. Nutr. Rev.62, S35–S39 (2004). PubMed
Oakley, G. P. & Tulchinsky, T. H. Folic acid and vitamin B12 fortification of flour: a global basic food security requirement. Public Health Rev.32, 284–295 (2010).
Santos, L. M. P. et al. Prevention of neural tube defects by the fortification of flour with folic acid: a population-based retrospective study in Brazil. Bull. World Health Organ.94, 22–29 (2016). PubMed PMC
Pardo, R. et al. Neural tube defects prevalence does not increase after modification of the folic acid fortification program in Chile. Birth Defects Res.114, 259–266 (2022). PubMed
Rosenthal, J. et al. Neural tube defects in Latin America and the impact of fortification: a literature review. Public Health Nutr.17, 537–550 (2014). PubMed PMC
Cordero, A. et al. CDC grand rounds: additional opportunities to prevent neural tube defects with folic acid fortification. MMWR Morb. Mortal. Wkly. Rep.59, 980–984 (2010). PubMed
Castillo-Lancellotti, C., Tur, J. A. & Uauy, R. Impact of folic acid fortification of flour on neural tube defects: a systematic review. Public Health Nutr.16, 901–911 (2013). PubMed PMC
Atta, C. A. et al. Global birth prevalence of spina bifida by folic acid fortification status: a systematic review and meta-analysis. Am. J. Public Health106, e24–e34 (2016). PubMed PMC
Ebara, S. Nutritional role of folate. Congenital Anomalies57, 138–141 (2017). PubMed
Grosse, S. D. et al. Retrospective assessment of cost savings from prevention: folic acid fortification and spina bifida in the US. Am. J. Prev. Med.50, S74–S80 (2016). PubMed PMC
Grosse, S. D., Waitzman, N. J., Romano, P. S. & Mulinare, J. Reevaluating the benefits of folic acid fortification in the United States: economic analysis, regulation, and public health. Am. J. Public Health95, 1917–1922 (2005). PubMed PMC
Fajardo, V. & Varela-Moreiras, G. Efficacy of adding folic acid to foods. Int. J. Vitam. Nutr. Res.82, 177 (2012). PubMed
Williams, J. et al. Updated estimates of neural tube defects prevented by mandatory folic acid fortification - United States, 1995-2011. MMWR Morb. Mortal. Wkly. Rep.64, 1–5 (2015). PubMed PMC
Arth, A. et al. A 2015 global update on folic acid‐preventable spina bifida and anencephaly. Birth Defects Res. A Clin. Mol. Teratol.106, 520–529 (2016). PubMed
Liu, S. et al. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects. BMC Pregnancy Childb4, 1–10 (2004). PubMed PMC
Wang, H. et al. Effectiveness of folic acid fortified flour for prevention of neural tube defects in a high risk region. Nutrients8, 152 (2016). PubMed PMC
Rodrigues, V. B., Silva, E. N. D. & Santos, M. L. P. Cost-effectiveness of mandatory folic acid fortification of flours in prevention of neural tube defects: A systematic review. PLoS One16, e0258488 (2021). PubMed PMC
Hoddinott, J. The investment case for folic acid fortification in developing countries. Ann. N. Y. Acad. Sci.1414, 72–81 (2018). PubMed PMC
Običan, S. G. et al. Folic acid in early pregnancy: a public health success story. FASEB J.24, 4167–4174 (2010). PubMed PMC
Osterhues, A., Ali, N. S. & Michels, K. B. The role of folic acid fortification in neural tube defects: a review. Crit. Rev. Food Sci. Nutr.53, 1180–1190 (2013). PubMed
Wald, N. J. Folic acid and neural tube defects: discovery, debate and the need for policy change. J. Med. Screen.29, 138–146 (2022). PubMed PMC
Wald, N. J. & Hoffbrand, A. V. Mandatory UK folic acid fortification. Lancet398, 1961–1962 (2021). PubMed
Shlobin, N. A., LoPresti, M. A., Du, R. Y. & Lam, S. Folate fortification and supplementation in prevention of folate-sensitive neural tube defects: a systematic review of policy. J. Neurosurg. Pediatr.27, 294–310 (2020). PubMed
Moore, D. & Young, M. Folic acid fortification: both society and individuals benefit (Ministry for Primary Industries, 2019).
Ricks, D. J. et al. Peru’s national folic acid fortification program and its effect on neural tube defects in Lima. Pan Am. J. Public Health32, 391–398 (2012). PubMed
Johnston, R. B. Will increasing folic acid in fortified grain products further reduce neural tube defects without causing harm?: consideration of the evidence. Pediatr. Res.63, 2–8 (2008). PubMed
Jägerstad, M. Folic acid fortification prevents neural tube defects and may also reduce cancer risks. Acta Paediatr.101, 1007–1012 (2012). PubMed
Morris, J. K. et al. Prevention of neural tube defects in Europe: a public health failure. Front. Pediatr.9, 647038 (2021). PubMed PMC
Kancherla, V. Countries with an immediate potential for primary prevention of spina bifida and anencephaly: Mandatory fortification of wheat flour with folic acid. Birth Defects Res.110, 956–965 (2018). PubMed
Kancherla, V. et al. Mandatory food fortification with folic acid–Authors’ reply. Lancet Glob. Health10, e1391–e1392 (2022). PubMed
Kancherla, V. et al. Preventing birth defects, saving lives, and promoting health equity: an urgent call to action for universal mandatory food fortification with folic acid. Lancet Glob. Health10, e1053–e1057 (2022). PubMed
Kancherla, V. et al. A global update on the status of prevention of folic acid‐preventable spina bifida and anencephaly in year 2020: 30‐Year anniversary of gaining knowledge about folic acid’s prevention potential for neural tube defects. Birth Defects Res.114, 1392–1403 (2022). PubMed
Oakley, G. P. Jr Failure to fortify staple foods with folic acid—still public health malpractice. Childs Nerv. Syst.39, 1699–1701 (2023). PubMed
Crider, K. S., Bailey, L. B. & Berry, R. J. Folic acid food fortification—its history, effect, concerns, and future directions. Nutrients3, 370–384 (2011). PubMed PMC
Wald, N. J. & Oakley, G. P. Should folic acid fortification be mandatory? Yes. BMJ334, 1252–1252 (2007). PubMed PMC
Scientific Advisory Committee on Nutrition. Update on folic Acid (Scientific Advisory Committee on Nutrition, 2017).
Choi, J.-H. et al. Contemporary issues surrounding folic acid fortification initiatives. Prev. Nutr. Food Sci.19, 247–260 (2014). PubMed PMC
Ghotme, K. A. et al. Barriers and facilitators to the implementation of mandatory folate fortification as an evidence-based policy to prevent neural tube defects. Childs Nerv. Syst. 39, 1805–1812 (2023). PubMed PMC
Berry, R. J. et al. Fortification of flour with folic acid. Food Nutr. Bull.31, S22–S35 (2010). PubMed
Rabovskaja, V., Parkinson, B. & Goodall, S. The cost-effectiveness of mandatory folic acid fortification in Australia. J. Nutr.143, 59–66 (2013). PubMed
Wald, N. J. Postscript to ‘Folic acid and neural tube defects: Discovery, debate and the need for policy change. J. Med. Screen.29, 147–147 (2022). PubMed PMC
McNulty, H. The B-Vitamins. In Sustainable Nutrition in aChanging World (eds Biesalski, H. K. et al) Ch. 29, 371–388 (Springer International Publishing AG, 2017).
Wald, N. J., Morris, J. K. & Blakemore, C. Urgent need for folic acid fortification of flour and grains: response to the 2019 UK Government’s public consultation. Arch. Dis. Child.105, 6–9 (2020). PubMed
McNulty, H. & Scott, J. M. Intake and status of folate and related B-vitamins: considerations and challenges in achieving optimal status. Br. J. Nutr.99, S48–S54 (2008). PubMed
Odewole, O. A. et al. Near-elimination of folate-deficiency anemia by mandatory folic acid fortification in older US adults: reasons for geographic and racial differences in stroke study 2003–2007. Am. J. Clin. Nutr.98, 1042–1047 (2013). PubMed PMC
Aune, D. et al. Dietary folate intake and the risk of 11 types of cancer: a case–control study in Uruguay. Ann. Oncol.22, 444–451 (2011). PubMed
Wang, X. et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet369, 1876–1882 (2007). PubMed
Wang, H. et al. Association of maternal plasma folate and cardiometabolic risk factors in pregnancy with elevated blood pressure of offspring in childhood. Am. J. Hypertens.30, 532–540 (2017). PubMed PMC
Wang, Y. et al. The effect of folic acid in patients with cardiovascular disease: a systematic review and meta-analysis. Medicine98, e17095 (2019). PubMed PMC
Huo, Y. et al. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA313, 1325–1335 (2015). PubMed
Li, Y. et al. Folic acid supplementation and the risk of cardiovascular diseases: a meta‐analysis of randomized controlled trials. J. Am. Heart Assoc.5, e003768 (2016). PubMed PMC
Qin, X. et al. Homocysteine-lowering therapy with folic acid is effective in cardiovascular disease prevention in patients with kidney disease: a meta-analysis of randomized controlled trials. Clin. Nutr.32, 722–727 (2013). PubMed
O’Connor, D. M. et al. Low folate predicts accelerated cognitive decline: 8-year follow-up of 3140 older adults in Ireland. Eur. J. Clin. Nutr.76, 950–957 (2022). PubMed
Mason, J. B. Folate and colon cancer: dietary habits from the distant past coming home to roost. Am. J. Clin. Nutr.114, 1–2 (2021). PubMed
Petch, S. et al. Folic acid fortification of flour to prevent neural tube defects in Europe–A position statement by the European Board and college of obstetrics and gynaecology (EBCOG). Eur. J. Obstet. Gynecol. Reprod. Biol.279, 109–111 (2022). PubMed
Durga, J. et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet369, 208–216 (2007). PubMed
Kawakita, D. et al. Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinoma. Ann. Oncol.23, 186–192 (2012). PubMed
Xu, J. et al. Non-linear associations of serum and red blood cell folate with risk of cardiovascular and all-cause mortality in hypertensive adults. Hypertens. Res.46, 1504–1515 (2023). PubMed
Zhang, K. et al. Association between dietary folate intake and cognitive impairment in older US adults: National Health and Nutrition Examination Survey. Arch. Gerontol. Geriatr.109, 104946 (2023). PubMed
Stewart, C. P. et al. Antenatal micronutrient supplementation reduces metabolic syndrome in 6-to 8-year-old children in rural Nepal. J. Nutr.139, 1575–1581 (2009). PubMed
Otsu, Y., Ae, R. & Kuwabara, M. Folate and cardiovascular disease. Hypertens. Res.46, 1816–1818 (2023). PubMed
Wu, K. et al. A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma. Am. J. Clin. Nutr.90, 1623–1631 (2009). PubMed PMC
Kim, Y.-I. Current status of folic acid supplementation on colorectal cancer prevention. Curr. Pharmacol. Rep.2, 21–33 (2016).
Obeid, R., Koletzko, B. & Pietrzik, K. Critical evaluation of lowering the recommended dietary intake of folate. Clin. Nutr.33, 252–259 (2014). PubMed
Pieroth, R., Paver, S., Day, S. & Lammersfeld, C. Folate and its impact on cancer risk. Curr. Nutr. Rep.7, 70–84 (2018). PubMed PMC
Bo, Y. et al. Association between folate and health outcomes: an umbrella review of meta-analyses. Front. Public Health8, 550753 (2020). PubMed PMC
Naninck, E. F., Stijger, P. C. & Brouwer-Brolsma, E. M. The importance of maternal folate status for brain development and function of offspring. Adv. Nutr.10, 502–519 (2019). PubMed PMC
Shulpekova, Y. et al. The concept of folic acid in health and disease. Molecules26, 3731 (2021). PubMed PMC
Tian, T. et al. Folic acid supplementation for stroke prevention in patients with cardiovascular disease. Am. J. Med. Sci.354, 379–387 (2017). PubMed
Ismail, S., Eljazzar, S. & Ganji, V. Intended and unintended benefits of folic acid fortification—a narrative review. Foods12, 1612 (2023). PubMed PMC
Wondemagegn, A. T. & Afework, M. The association between folic acid supplementation and congenital heart defects: Systematic review and meta-analysis. SAGE Open Med. 10, 10.1177/20503121221081069 (2022). PubMed PMC
Mason, J. B. Folate status and colorectal cancer risk: a 2016 update. Mol. Asp. Med.53, 73–79 (2017). PubMed
Fu, H. et al. Folate intake and risk of pancreatic cancer: a systematic review and updated meta-analysis of epidemiological studies. Dig. Dis. Sci.66, 2368–2379 (2021). PubMed
Jiang, Z., Qu, H., Chen, K. & Gao, Z. Beneficial effects of folic acid on inflammatory markers in the patients with metabolic syndrome: meta-analysis and meta-regression of data from 511 participants in 10 randomized controlled trials. Crit. Rev. Food Sci. Nutr. 64, 5450–5461 (2022). PubMed
Jones, P. et al. Folate and inflammation–links between folate and features of inflammatory conditions. J. Nutr. Intermed. Metab.18, 100104 (2019).
Xu, X. et al. Association of folate intake with cardiovascular-disease mortality and all-cause mortality among people at high risk of cardiovascular-disease. Clin. Nutr.41, 246–254 (2022). PubMed
Smith, A. D., Kim, Y.-I. & Refsum, H. Is folic acid good for everyone? Am. J. Clin. Nutr.87, 517–533 (2008). PubMed
Smith, A. D. et al. Mandatory food fortification with folic acid. Lancet Glob. Health10, e1389 (2022). PubMed
Maruvada, P. et al. Knowledge gaps in understanding the metabolic and clinical effects of excess folates/folic acid: a summary, and perspectives, from an NIH workshop. Am. J. Clin. Nutr.112, 1390–1403 (2020). PubMed PMC
Kim, Y. Folate: a magic bullet or a double edged sword for colorectal cancer prevention? Gut55, 1387–1389 (2006). PubMed PMC
Looi, M.-K. Folic acid: The case to rethink the UK’s food fortification plans. BMJ381, p1158 (2023). PubMed
House, S. H., Nichols, J. A. & Rae, S. Folates, folic acid and preconception care–a review. JRSM Open12, h6198 (2021). PubMed PMC
Field, M. S. & Stover, P. J. Safety of folic acid. Ann. N. Y. Acad. Sci.1414, 59–71 (2018). PubMed PMC
Colapinto, C. K. et al. Systematic review of adverse health outcomes associated with high serum or red blood cell folate concentrations. J. Public Health38, e84–e97 (2016). PubMed PMC
Ulrich, C. M. & Potter, J. D. Folate supplementation: too much of a good thing? Cancer Epidemiol. Biomark. Prev.15, 189–193 (2006). PubMed
Boyles, A. L., Yetley, E. A., Thayer, K. A. & Coates, P. M. Safe use of high intakes of folic acid: research challenges and paths forward. Nutr. Rev.74, 469–474 (2016). PubMed PMC
Scientific Committee on Food. Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Folate, https://ec.europa.eu/food/fs/sc/scf/out80e_en.pdf (2000).
Alnabbat, K. I. et al. High dietary folic acid intake is associated with genomic instability in peripheral lymphocytes of healthy adults. Nutrients14, 3944 (2022). PubMed PMC
Allen, L. H. Pros and cons of increasing folic acid and vitamin B12 intake by fortification. In Nestle Nutrition Institute workshop series70, 175–183 (Karger Publishers, 2012). PubMed
Quinlivan, E. P. In vitamin B12 deficiency, higher serum folate is associated with increased homocysteine and methylmalonic acid concentrations. Proc. Natl. Acad. Sci.105, E7–E7 (2008). PubMed PMC
EFSA Panel on Nutrition Novel Foods and Food Allergens. Scientific opinion on the tolerable upper intake level for folate. EFSA J.21, e08353 (2023). PubMed PMC
Fardous, A. M. & Heydari, A. R. Uncovering the hidden dangers and molecular mechanisms of excess folate: a narrative review. Nutrients15, 4699 (2023). PubMed PMC
Liu, M. et al. Relationship of several serum folate forms with the risk of mortality: a prospective cohort study. Clin. Nutr.40, 4255–4262 (2021). PubMed
Cortés, F. et al. Wheat flour fortification with folic acid: changes in neural tube defects rates in Chile. Am. J. Med. Genet. A158a, 1885–1890 (2012). PubMed
Morris, M. S., Jacques, P. F., Rosenberg, I. H. & Selhub, J. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors. Am. J. Clin. Nutr.91, 1733–1744 (2010). PubMed
Mills, J. L. Fortification of foods with folic acid—how much is enough? N. Engl. J. Med.342, 1442–1445 (2000). PubMed
Mills, J. L. et al. Low vitamin B-12 concentrations in patients without anemia: the effect of folic acid fortification of grain. Am. J. Clin. Nutr.77, 1474–1477 (2003). PubMed
Hirsch, S. et al. The Chilean flour folic acid fortification program reduces serum homocysteine levels and masks vitamin B-12 deficiency in elderly people. J. Nutr.132, 289–291 (2002). PubMed
Wyckoff, K. F. & Ganji, V. Proportion of individuals with low serum vitamin B-12 concentrations without macrocytosis is higher in the post–folic acid fortification period than in the pre–folic acid fortification period. Am. J. Clin. Nutr.86, 1187–1192 (2007). PubMed
Qi, Y. P. et al. The prevalence of low serum vitamin B-12 status in the absence of anemia or macrocytosis did not increase among older US adults after mandatory folic acid fortification. J. Nutr.144, 170–176 (2014). PubMed PMC
Morris, M. S., Selhub, J. & Jacques, P. F. Vitamin B‐12 and folate status in relation to decline in scores on the Mini‐Mental State Examination in the Framingham Heart Study. J. Am. Geriatr. Soc.60, 1457–1464 (2012). PubMed PMC
Molloy, A. M. Adverse effects on cognition caused by combined low vitamin B-12 and high folate status—we must do better than a definite maybe! Am. J. Clin. Nutr.112, 1422–1423 (2020). PubMed
EFSA. Tolerable Upper Intake Levels for Vitamins and Minerals (Publications Office 2006).
Moore, E. M. et al. Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from three cohorts. J. Alzheimer’s Dis.39, 661–668 (2014). PubMed
Doets, E. L. et al. Interactions between plasma concentrations of folate and markers of vitamin B12 status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study. Br. J. Nutr.111, 1085–1095 (2014). PubMed
Carter, B. et al. Plasma methylmalonic acid concentration in folic acid–supplemented depressed patients with low or marginal vitamin B-12: a randomized trial. J. Nutr.151, 3738–3745 (2021). PubMed PMC
Smith, A. D. Folic acid fortification: the good, the bad, and the puzzle of vitamin B-12. Am. J. Clin. Nutr.85, 3–5 (2007). PubMed
Berry, R. J., Carter, H. K. & Yang, Q. Cognitive impairment in older Americans in the age of folic acid fortification. Am. J. Clin. Nutr.86, 265–267 (2007). PubMed
Reynolds, E. What is the safe upper intake level of folic acid for the nervous system? Implications for folic acid fortification policies. Eur. J. Clin. Nutr.70, 537–540 (2016). PubMed
Reynolds, E. H. The risks of folic acid to the nervous system in vitamin B12 deficiency: rediscovered in the era of folic acid fortification policies. J. Neurol. Neurosurg. Psychiatry88, 1097–1098 (2017). PubMed
Selhub, J. et al. Perspective: the high-folate–low-vitamin B-12 interaction is a novel cause of vitamin B-12 depletion with a specific etiology—a hypothesis. Adv. Nutr.13, 16–33 (2022). PubMed PMC
Selhub, J. & Rosenberg, I. H. Excessive folic acid intake and relation to adverse health outcome. Biochimie126, 71–78 (2016). PubMed
Bailey, R. L. et al. High folic acid or folate combined with low vitamin B-12 status: potential but inconsistent association with cognitive function in a nationally representative cross-sectional sample of US older adults participating in the NHANES. Am. J. Clin. Nutr.112, 1547–1557 (2020). PubMed PMC
Clarke, R. et al. Folate and vitamin B12 status in relation to cognitive impairment and anaemia in the setting of voluntary fortification in the UK. Br. J. Nutr.100, 1054–1059 (2008). PubMed
Ding, Z. et al. Non-linear association between folate/vitamin B12 status and cognitive function in older adults. Nutrients14, 2443 (2022). PubMed PMC
Deng, Y., Wang, D., Wang, K. & Kwok, T. High serum folate is associated with brain atrophy in older diabetic people with vitamin B12 deficiency. J. Nutr. Health Aging21, 1065–1071 (2017). PubMed
Morris, M. S., Jacques, P. F., Rosenberg, I. H. & Selhub, J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am. J. Clin. Nutr.85, 193–200 (2007). PubMed PMC
Miller, J. W. et al. Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate. Am. J. Clin. Nutr.90, 1586–1592 (2009). PubMed PMC
Lökk, J. Association of vitamin B12, folate, homocysteine and cognition in the elderly. Food Nutr. Res. 47, 132–138 (2003).
Osterhues, A., Holzgreve, W. & Michels, K. B. Shall we put the world on folate? Lancet374, 959–961 (2009). PubMed
Kim, Y.-I. Folate and cancer: a tale of Dr. Jekyll and Mr. Hyde? Am. J. Clin. Nutr.107, 139–142 (2018). PubMed
Mason, J. B. Folate, cancer risk, and the Greek god, Proteus: a tale of two chameleons. Nutr. Rev.67, 206–212 (2009). PubMed PMC
Tomita, L. Y. Folate and cancer: is there any association? J. Inborn Errors Metab. Screen. 4, 10.1177/2326409816661357 (2016).
Mackerras, D., Tan, J. & Larter, C. Folic acid, selected cancers and all-cause mortality: a meta-analysis. Int. Food Risk Anal. J. 4, 10.5772/58396 (2014).
Vollset, S. E. et al. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Lancet381, 1029–1036 (2013). PubMed PMC
Kotsopoulos, J., Kim, Y.-I. & Narod, S. A. Folate and breast cancer: what about high-risk women? Cancer Causes Control23, 1405–1420 (2012). PubMed
Drake, B. F. & Colditz, G. A. Assessing cancer prevention studies—a matter of time. JAMA302, 2152–2153 (2009). PubMed PMC
Miller, J. W. & Ulrich, C. M. Folic acid and cancer—where are we today? Lancet381, 974–976 (2013). PubMed
Ferrazzi, E., Tiso, G. & Di Martino, D. Folic acid versus 5-methyl tetrahydrofolate supplementation in pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol.253, 312–319 (2020). PubMed
Datta, M. & Vitolins, M. Z. Food fortification and supplement use-are there health implications? Crit. Rev. Food Sci. Nutr.56, 2149–2159 (2016). PubMed PMC
Mills, J. L. & Dimopoulos, A. Folic acid fortification for Europe? BMJ351, 10.1136/bmj.h6198 (2015). PubMed
Lee, J. E. & Chan, A. T. Fruit, vegetables, and folate: cultivating the evidence for cancer prevention. Gastroenterology141, 16–20 (2011). PubMed PMC
Ebbing, M. et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA302, 2119–2126 (2009). PubMed
Moazzen, S. et al. Staple food fortification with folic acid and iron and gastrointestinal cancers: critical appraisal of long-term national fortification. Nutr. Cancer73, 1534–1538 (2021). PubMed
Asemi, Z. et al. Effects of long-term folate supplementation on metabolic status and regression of cervical intraepithelial neoplasia: a randomized, double-blind, placebo-controlled trial. Nutr32, 681–686 (2016). PubMed
Tu, H. et al. Is folic acid safe for non–muscle-invasive bladder cancer patients? An evidence-based cohort study. Am. J. Clin. Nutr.107, 208–216 (2018). PubMed PMC
Jennings, B. A. & Willis, G. How folate metabolism affects colorectal cancer development and treatment; a story of heterogeneity and pleiotropy. Cancer Lett356, 224–230 (2015). PubMed
Figueiredo, J. C. et al. Folate‐genetics and colorectal neoplasia: what we know and need to know next. Mol. Nutr. Food Res.57, 607–627 (2013). PubMed
Figueiredo, J. C. et al. Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials. Int. J. Cancer129, 192–203 (2011). PubMed PMC
Cole, B. F. et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA297, 2351–2359 (2007). PubMed
Mason, J. B. Folate consumption and cancer risk: a confirmation and some reassurance, but we’re not out of the woods quite yet. Am. J. Clin. Nutr.94, 965–966 (2011). PubMed PMC
Mason, J. B. et al. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol. Biomark. Prev.16, 1325–1329 (2007). PubMed
Luebeck, E. G. et al. Does folic acid supplementation prevent or promote colorectal cancer? Results from model-based predictions. Cancer Epidemiol. Biomark. Prev.17, 1360–1367 (2008). PubMed PMC
Hubner, R. A., Houlston, R. D. & Muir, K. R. Should folic acid fortification be mandatory? No. BMJ334, 1253–1253 (2007). PubMed PMC
Kim, D.-H. et al. Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer. Cancer Causes Control21, 1919–1930 (2010). PubMed PMC
Kim, Y.-I. Role of folate in colon cancer development and progression. J. Nutr.133, 3731S–3739S (2003). PubMed
Kim, Y. I. Folate and colorectal cancer: An evidence‐based critical review. Mol. Nutr. Food Res.51, 267–292 (2007). PubMed
Kherbek, H. et al. The relationship between folic acid and colorectal cancer; a literature review. Ann. Med. Surg.80, 104170 (2022). PubMed PMC
Gylling, B. et al. Low folate levels are associated with reduced risk of colorectal cancer in a population with low folate status. Cancer Epidemiol. Biomark. Prev.23, 2136–2144 (2014). PubMed
Protiva, P. et al. Altered folate availability modifies the molecular environment of the human colorectum: implications for colorectal carcinogenesis. Cancer Prev. Res.4, 530–543 (2011). PubMed PMC
Haas, C. B. et al. Interactions between folate intake and genetic predictors of gene expression levels associated with colorectal cancer risk. Sci. Rep.12, 18852 (2022). PubMed PMC
Fife, J., Raniga, S., Hider, P. & Frizelle, F. Folic acid supplementation and colorectal cancer risk: a meta‐analysis. Colorectal Dis13, 132–137 (2011). PubMed
Geijsen, A. J. et al. Circulating folate and folic acid concentrations: associations with colorectal cancer recurrence and survival. JNCI Cancer Spectr4, pkaa051 (2020). PubMed PMC
Gigic, B. et al. Cohort profile: biomarkers related to folate-dependent one-carbon metabolism in colorectal cancer recurrence and survival–the FOCUS Consortium. BMJ Open12, e062930 (2022). PubMed PMC
Moazzen, S. et al. Folic acid intake and folate status and colorectal cancer risk: a systematic review and meta-analysis. Clin. Nutr.37, 1926–1934 (2018). PubMed
Stevens, V. L. et al. High levels of folate from supplements and fortification are not associated with increased risk of colorectal cancer. Gastroenterology141, 98–105.e101 (2011). PubMed
O’Reilly, S. L. et al. Folic acid supplementation in postpolypectomy patients in a randomized controlled trial increases tissue folate concentrations and reduces aberrant DNA biomarkers in colonic tissues adjacent to the former polyp site. J. Nutr.146, 933–939 (2016). PubMed
Keum, N. & Giovannucci, E. L. Folic acid fortification and colorectal cancer risk. Am. J. Prev. Med.46, S65–S72 (2014). PubMed
Qin, T. et al. Folic acid supplements and colorectal cancer risk: meta-analysis of randomized controlled trials. Sci. Rep.5, 12044 (2015). PubMed PMC
Burr, N. E., Hull, M. A. & Subramanian, V. Folic acid supplementation may reduce colorectal cancer risk in patients with inflammatory bowel disease. J. Clin. Gastroenterol.51, 247–253 (2017). PubMed
Lee, J. E. et al. Folate intake and risk of colorectal cancer and adenoma: modification by time. Am. J. Clin. Nutr.93, 817–825 (2011). PubMed PMC
Sanjoaquin, M. A. et al. Folate intake and colorectal cancer risk: a meta‐analytical approach. Int. J. Cancer113, 825–828 (2005). PubMed
Kennedy, D. A. et al. Folate intake and the risk of colorectal cancer: a systematic review and meta-analysis. Cancer Epidemiol.35, 2–10 (2011). PubMed
Hubner, R. & Houlston, R. Folate and colorectal cancer prevention. Br. J. Cancer100, 233–239 (2009). PubMed PMC
Stolzenberg-Solomon, R. Z. et al. Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am. J. Clin. Nutr.83, 895–904 (2006). PubMed
Chen, P. et al. Higher dietary folate intake reduces the breast cancer risk: a systematic review and meta-analysis. Br. J. Cancer110, 2327–2338 (2014). PubMed PMC
Kim, S. J. et al. Folic acid supplement use and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a case–control study. Breast Cancer Res. Treat.174, 741–748 (2019). PubMed
Ren, X. et al. Association of folate intake and plasma folate level with the risk of breast cancer: A dose-response meta-analysis of observational studies. Aging12, 21355 (2020). PubMed PMC
Zhang, Y.-F. et al. Folate intake and the risk of breast cancer: a dose-response meta-analysis of prospective studies. PLoS One9, e100044 (2014). PubMed PMC
Wien, T. N. et al. Cancer risk with folic acid supplements: a systematic review and meta-analysis. BMJ Open2, e000653 (2012). PubMed PMC
De Vogel, S. et al. Serum folate and vitamin B12 concentrations in relation to prostate cancer risk—a Norwegian population-based nested case–control study of 3000 cases and 3000 controls within the JANUS cohort. Int. J. Epidemiol.42, 201–210 (2013). PubMed
Rycyna, K. J., Bacich, D. J. & O’Keefe, D. S. Opposing roles of folate in prostate cancer. Urology82, 1197–1203 (2013). PubMed PMC
Figueiredo, J. C. et al. Folic acid and risk of prostate cancer: results from a randomized clinical trial. J. Natl. Cancer Inst.101, 432–435 (2009). PubMed PMC
Price, A. J. et al. Circulating folate and vitamin B12 and risk of prostate cancer: a collaborative analysis of individual participant data from six cohorts including 6875 cases and 8104 controls. Eur. Urol.70, 941–951 (2016). PubMed PMC
Downer, M. K., Van Blarigan, E. L., Peisch, S. F. & Stampfer, M. J. Should we fear folate? Eur. Urol.70, 952–953 (2016). PubMed
Håberg, S. E. et al. Folic acid supplements in pregnancy and early childhood respiratory health. Arch. Dis. Child.94, 180–184 (2009). PubMed PMC
Parr, C. L. et al. Maternal folate intake during pregnancy and childhood asthma in a population-based cohort. Am. J. Respir. Crit. Care Med.195, 221–228 (2017). PubMed PMC
Alfonso, V. H., Bandoli, G., von Ehrenstein, O. & Ritz, B. Early folic acid supplement initiation and risk of adverse early childhood respiratory health: a population-based study. Matern. Child Health J.22, 111–119 (2018). PubMed
Yang, L. et al. High dose of maternal folic acid supplementation is associated to infant asthma. Food Chem. Toxicol.75, 88–93 (2015). PubMed
Yang, F. et al. Relationship between maternal folic acid supplementation during pregnancy and risk of childhood asthma: systematic review and dose-response meta-analysis. Front. Pediatr.10, 1000532 (2022). PubMed PMC
Best, K. P. et al. Maternal late-pregnancy serum unmetabolized folic acid concentrations are not associated with infant allergic disease: a prospective cohort study. J. Nutr.151, 1553–1560 (2021). PubMed
Molloy, A. M. & Mills, J. L. Folic acid and infant allergy: Avoiding rash judgments. J. Nutr.151, 1367–1368 (2021). PubMed PMC
Bekkers, M. B. et al. Maternal use of folic acid supplements during pregnancy, and childhood respiratory health and atopy. Eur. Respir. J.39, 1468–1474 (2012). PubMed
Wang, T. et al. Is folate status a risk factor for asthma or other allergic diseases? Allergy Asthma Immunol. Res.7, 538–546 (2015). PubMed PMC
Trivedi, M. K. et al. Folic acid in pregnancy and childhood asthma: a US cohort. Clin. Pediatr.57, 421–427 (2018). PubMed PMC
Whitrow, M. J., Moore, V. M., Rumbold, A. R. & Davies, M. J. Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study. Am. J. Epidemiol.170, 1486–1493 (2009). PubMed
McGowan, E. C. et al. Association between folate metabolites and the development of food allergy in children. J. Allergy Clin. Immunol. Pract.8, 132–140.e135 (2020). PubMed PMC
Liu, J. et al. Periconceptional folic acid supplementation and risk of parent-reported asthma in children at 4–6 years of age. ERJ Open Res. 6; 10.1183/23120541.00250-2019 (2020). PubMed PMC
Adgent, M. A. et al. Periconceptional folic acid supplementation and child asthma: a Right From the Start follow-up study. J. Matern. Fetal Neonatal Med.35, 10232–10238 (2022). PubMed PMC
Moser, S. S. et al. High dose folic acid during pregnancy and the risk of autism; The birth order bias: A nested case-control study. Reprod. Toxicol.89, 173–177 (2019). PubMed
DeVilbiss, E. A., Gardner, R. M., Newschaffer, C. J. & Lee, B. K. Maternal folate status as a risk factor for autism spectrum disorders: a review of existing evidence. Br. J. Nutr.114, 663–672 (2015). PubMed
DeVilbiss, E. A. et al. Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: population based cohort study. BMJ359, j4273 (2017). PubMed PMC
Raghavan, R. et al. A prospective birth cohort study on cord blood folate subtypes and risk of autism spectrum disorder. Am. J. Clin. Nutr.112, 1304–1317 (2020). PubMed PMC
Levine, S. Z. et al. Association of maternal use of folic acid and multivitamin supplements in the periods before and during pregnancy with the risk of autism spectrum disorder in offspring. JAMA Psychiatry75, 176–184 (2018). PubMed PMC
Egorova, O. et al. Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers. Mol. Autism.11, 1–15 (2020). PubMed PMC
McNulty, H. et al. Effect of continued folic acid supplementation beyond the first trimester of pregnancy on cognitive performance in the child: a follow-up study from a randomized controlled trial (FASSTT Offspring Trial). BMC Med.17, 1–11 (2019). PubMed PMC
Caffrey, A. et al. Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial. BMC Med.19, 1–13 (2021). PubMed PMC
Valera-Gran, D. et al. Effect of maternal high dosages of folic acid supplements on neurocognitive development in children at 4–5 y of age: the prospective birth cohort Infancia y Medio Ambiente (INMA) study. Am. J. Clin. Nutr.106, 878–887 (2017). PubMed
Murray, L. K., Smith, M. J. & Jadavji, N. M. Maternal oversupplementation with folic acid and its impact on neurodevelopment of offspring. Nutr. Rev.76, 708–721 (2018). PubMed
Obeid, R., Holzgreve, W. & Pietrzik, K. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects? J. Perinat. Med.41, 469–483 (2013). PubMed
Kelly, D., O’Dowd, T. & Reulbach, U. Use of folic acid supplements and risk of cleft lip and palate in infants: a population-based cohort study. Br. J. Gen. Pract.62, e466–e472 (2012). PubMed PMC
Rozendaal, A. M. et al. Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study. Eur. J. Epidemiol.28, 875–887 (2013). PubMed
Cheng, Z., Gu, R., Lian, Z. & Gu, H. F. Evaluation of the association between maternal folic acid supplementation and the risk of congenital heart disease: a systematic review and meta-analysis. Nutr. J.21, 20 (2022). PubMed PMC
Silva, C., Keating, E. & Pinto, E. The impact of folic acid supplementation on gestational and long term health: Critical temporal windows, benefits and risks. Porto Biomed. J.2, 315–332 (2017). PubMed PMC
Bailey, S. W. & Ayling, J. E. The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. Proc. Natl. Acad. Sci.106, 15424–15429 (2009). PubMed PMC
Plumptre, L. et al. High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. Am. J. Clin. Nutr.102, 848–857 (2015). PubMed
Sweeney, M. R. et al. Persistent circulating unmetabolised folic acid in a setting of liberal voluntary folic acid fortification. Implications for further mandatory fortification? BMC Public Health9, 1–7 (2009). PubMed PMC
Obeid, R. Serum unmetabolized folic acid: the straw that broke dihydrofolate reductase’s back? J. Nutr.145, 387–390 (2015). PubMed
Palchetti, C. Z. et al. Association between serum unmetabolized folic acid concentrations and folic acid from fortified foods. J. Am. Coll. Nutr.36, 572–578 (2017). PubMed PMC
Page, R. et al. Total folate and unmetabolized folic acid in the breast milk of a cross-section of Canadian women. Am. J. Clin. Nutr.105, 1101–1109 (2017). PubMed
Cho, E. et al. Unmetabolized folic acid in prediagnostic plasma and the risk for colorectal cancer. J. Natl. Cancer Inst.107, djv260 (2015). PubMed PMC
Hefni, M. E., Witthöft, C. M. & Moazzami, A. A. Plasma metabolite profiles in healthy women differ after intervention with supplemental folic acid v. folate-rich foods. J. Nutr. Sci.7, e32 (2018). PubMed PMC
Troen, A. M. et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J. Nutr.136, 189–194 (2006). PubMed
Hu, J., Wang, B. & Sahyoun, N. R. Application of the key events dose-response framework to folate metabolism. Crit. Rev. Food Sci. Nutr.56, 1325–1333 (2016). PubMed
Williamson, J. M. et al. High folate, perturbed one-carbon metabolism and gestational diabetes mellitus. Nutrients14, 3930 (2022). PubMed PMC
Page, R., Wong, A., Arbuckle, T. E. & MacFarlane, A. J. The MTHFR 677C> T polymorphism is associated with unmetabolized folic acid in breast milk in a cohort of Canadian women. Am. J. Clin. Nutr110, 401–409 (2019). PubMed PMC
Berry, R. J. Lack of historical evidence to support folic acid exacerbation of the neuropathy caused by vitamin B12 deficiency. Am. J. Clin. Nutr.110, 554–561 (2019). PubMed PMC
Committee on toxicity of chemicals in food consumer products and the environment. Folic acid – statement on the tolerable upper level (TUL) - Lay summary (The Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment, 2019).
Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (National Academies Press, 1998). PubMed
FDA. Food additives permitted for direct addition to food for human consumption; folic acid. Final rule. Fed. Reg.81, 22176–22183 (2016). PubMed
National Toxicology Program. NTP monograph: identifying research needs for assessing safe use of high intakes of folic acid, https://ntp.niehs.nih.gov/sites/default/files/ntp/ohat/folicacid/final_monograph_508.pdf (2015).
Porter, K. et al. Causes, consequences and public health implications of low B-vitamin status in ageing. Nutrients8, 725 (2016). PubMed PMC
Kar, A. et al. Mandatory food fortification with folic acid. Lancet Glob. Health10, e1390 (2022). PubMed
Johnson, M. A. If high folic acid aggravates vitamin B12 deficiency what should be done about it? Nutr. Rev.65, 451–458 (2007). PubMed
Molloy, A. M. et al. Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification. Pediatrics123, 917–923 (2009). PubMed PMC
Wang, Z.-P., Shang, X.-X. & Zhao, Z.-T. Low maternal vitamin B12 is a risk factor for neural tube defects: a meta-analysis. J. Matern. Fetal Neonatal Med.25, 389–394 (2012). PubMed
Gibson, T. M. et al. Pre-and postfortification intake of folate and risk of colorectal cancer in a large prospective cohort study in the United States. Am. J. Clin. Nutr.94, 1053–1062 (2011). PubMed PMC
van der Pols, J. C., Baade, P. & Spencer, L. B. Colorectal cancer incidence in Australia before and after mandatory fortification of bread flour with folic acid. Public Health Nutr.24, 1989–1992 (2021). PubMed PMC
Wang, F. et al. Association of folate intake and colorectal cancer risk in the postfortification era in US women. Am. J. Clin. Nutr.114, 49–58 (2021). PubMed PMC
Fu, H. et al. Folate intake and risk of colorectal cancer: a systematic review and up-to-date meta-analysis of prospective studies. Eur. J. Cancer Prev.32, 103–112 (2023). PubMed
Crider, K. S. et al. Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis. Am. J. Clin. Nutr.98, 1272–1281 (2013). PubMed PMC
Wang, M., Li, K., Zhao, D. & Li, L. The association between maternal use of folic acid supplements during pregnancy and risk of autism spectrum disorders in children: a meta-analysis. Mol. Autism8, 1–4 (2017). PubMed PMC
Liu, X. et al. Prenatal folic acid supplements and offspring’s autism spectrum disorder: a meta-analysis and meta-regression. J. Autism Dev. Disord.52, 522–539 (2022). PubMed PMC
Perera, N., Rudland, V. L., Simmons, D. & Price, S. A. Folate supplementation in women with pre-existing diabetes. Nutrients15, 1879 (2023). PubMed PMC
Sweeney, M. R., McPartlin, J. & Scott, J. Folic acid fortification and public health: report on threshold doses above which unmetabolised folic acid appear in serum. BMC Public Health7, 1–7 (2007). PubMed PMC
Murphy, M. S. et al. Impact of high-dose folic acid supplementation in pregnancy on biomarkers of folate status and 1-carbon metabolism: An ancillary study of the Folic Acid Clinical Trial (FACT). Am. J. Clin. Nutr.113, 1361–1371 (2021). PubMed PMC
Koenig, K. L. et al. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate and risk of breast cancer: A nested case-control study. Eur. J. Clin. Nutr.74, 1306–1315 (2020). PubMed PMC
Food Standards Australia New Zealand. L-methylfolate, calcium as a permitted form of folate (Food Standards Australia New Zealand, 2008).
Patanwala, I. et al. Folic acid handling by the human gut: implications for food fortification and supplementation. Am. J. Clin. Nutr.100, 593–599 (2014). PubMed PMC
EFSA Panel on Nutrition Novel Foods and Food Allergens. Safety of monosodium salt of l-5-methyltetrahydrofolic acid as a novel food pursuant to Regulation (EU) 2015/2283 and the bioavailability of folate from this source in the context of Directive 2002/46/EC, Regulation (EU) No 609/2013 and Regulation (EC) No 1925/2006. EFSA J.21, e8417 (2023). PubMed PMC
Troesch, B. et al. Suitability and safety of L-5-methyltetrahydrofolate as a folate source in infant formula: A randomized-controlled trial. PloS One14, e0216790 (2019). PubMed PMC
Niederberger, K. et al. Safety evaluation of calcium L-methylfolate. Toxicol. Rep.6, 1018–1030 (2019). PubMed PMC
Menezo, Y., Elder, K., Clement, A. & Clement, P. Folic acid, folinic acid, 5 methyl tetrahydrofolate supplementation for mutations that affect epigenesis through the folate and one-carbon cycles. Biomolecules12, 197 (2022). PubMed PMC
Greenberg, J. A., Bell, S. J., Guan, Y. & Yu, Y.-H. Folic acid supplementation and pregnancy: more than just neural tube defect prevention. Rev. Obstet. Gynaecol.4, 52–59 (2011). PubMed PMC
Hoekstra, J. et al. Integrated risk–benefit analyses: method development with folic acid as example. Food Chem. Toxicol.46, 893–909 (2008). PubMed
Striepen, B. et al. Gene transfer in the evolution of parasite nucleotide biosynthesis. Proc. Natl. Acad. Sci.101, 3154–3159 (2004). PubMed PMC
Watkins, W. M., Mberu, E. K., Winstanley, P. A. & Plowe, C. V. The efficacy of antifolate antimalarial combinations in Africa: a predictive model based on pharmacodynamic and pharmacokinetic analyses. Trends Parasitol.13, 459–464 (1997). PubMed
Fernández-Villa, D., Aguilar, M. R. & Rojo, L. Folic acid antagonists: antimicrobial and immunomodulating mechanisms and applications. Int. J. Mol. Sci.20, 4996 (2019). PubMed PMC
Anderson, A. C. Targeting DHFR in parasitic protozoa. Drug Discov. Today10, 121–128 (2005). PubMed
Al-Rashood, S. T. et al. Synthesis, biological evaluation and molecular modeling study of 2-(1, 3, 4-thiadiazolyl-thio and 4-methyl-thiazolyl-thio)-quinazolin-4-ones as a new class of DHFR inhibitors. Bioorg. Med. Chem. Lett.24, 4557–4567 (2014). PubMed
Wang, M. et al. Synthesis and antiproliferative activity of a series of novel 6-substituted pyrido[3,2-d]pyrimidines as potential nonclassical lipophilic antifolates targeting dihydrofolate reductase. Eur. J. Med. Chem.128, 88–97 (2017). PubMed
Matherly, L. H. & Hou, Z. Structure and function of the reduced folate carrier a paradigm of a major facilitator superfamily mammalian nutrient transporter. Vitam. Horm.79, 145–184 (2008). PubMed PMC
Tanyi, J. L. et al. A phase III study of pafolacianine injection (OTL38) for intraoperative imaging of folate receptor–positive ovarian cancer (Study 006). J. Clin. Oncol.41, 276–284 (2023). PubMed
Moore, K. N. et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N. Engl. J. Med.389, 2162–2174 (2023). PubMed
Coleman, R. L. et al. Mirvetuximab soravtansine in folate receptor alpha (FRα)–high platinum-resistant ovarian cancer: final overall survival and post hoc sequence of therapy subgroup results from the SORAYA trial. Int. J. Gynecol. Cancer, ijgc-2024-005401; 10.1136/ijgc-2024-005401 (2024). PubMed PMC
Heo, Y.-A. Mirvetuximab soravtansine: first approval. Drugs83, 265–273 (2023). PubMed
Shimizu, T. et al. First-in-human phase 1 study of morab-202, an antibody–drug conjugate comprising farletuzumab linked to eribulin mesylate, in patients with folate receptor-Α–positive advanced solid tumors. Clin. Cancer Res.27, 3905–3915 (2021). PubMed
Gupta, A. et al. Vaccination with folate receptor-alpha peptides in patients with ovarian cancer following response to platinum-based therapy: A randomized, multicenter clinical trial. Gynecol. Oncol.189, 90–97 (2024). PubMed
Spicer, J. et al. Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial. Nat. Commun.14, 4180 (2023). PubMed PMC
Panda, P. K. et al. Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial. Eur. J. Pediatr.183, 4827–4835 (2024). PubMed
Renard, E. et al. Folinic acid improves the score of Autism in the EFFET placebo-controlled randomized trial. Biochimie173, 57–61 (2020). PubMed
Batebi, N. et al. Folinic acid as adjunctive therapy in treatment of inappropriate speech in children with autism: a double-blind and placebo-controlled randomized trial. Child Psychiatry Hum. Dev.52, 928–938 (2021). PubMed
Bao, H. et al. Combined use of amlodipine and folic acid are significantly more efficacious than amlodipine alone in lowering plasma homocysteine and blood pressure among hypertensive patients with hyperhomocysteinemia and intolerance to ACEI: A multicenter, randomized, double‐blind, parallel‐controlled clinical trial. J. Clin. Hypertens.25, 689–699 (2023). PubMed PMC
Zhang, S. et al. Effects of individualized administration of folic acid on prothrombotic state and vascular endothelial function with H-type hypertension: a double-blinded, randomized clinical cohort study. Med101, e28628 (2022). PubMed PMC
Asadi, M. et al. Effect of folic acid on the sexual function of postmenopausal women: a triple-blind randomized controlled trial. J. Sex. Med.20, 1180–1187 (2023). PubMed
Chen, H. et al. Effects of folic acid and vitamin B12 supplementation on cognitive impairment and inflammation in patients with Alzheimer’s disease: A randomized, single-blinded, placebo-controlled trial. J. Prev. Alzheimers Dis.8, 249–256 (2021). PubMed
Kvestad, I. et al. Vitamin B12, folate, and cognition in 6-to 9-year-olds: a randomized controlled trial. Pediatrics145, e20192316 (2020). PubMed
Van Soest, A. P., Van de Rest, O., Witkamp, R. F. & De Groot, L. C. Positive effects of folic acid supplementation on cognitive aging are dependent on ω-3 fatty acid status: a post hoc analysis of the FACIT trial. Am. J. Clin. Nutr.113, 801–809 (2021). PubMed
Li, M. et al. Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial. Eur. J. Nutr.60, 1795–1808 (2021). PubMed
Araghi, S. O. et al. Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease: Extended follow-up of the B-PROOF trial. Clin. Nutr.40, 1199–1206 (2021). PubMed
Satapathy, S. et al. Folic acid and vitamin B12 supplementation in subjects with type 2 diabetes mellitus: A multi-arm randomized controlled clinical trial. Complement. Ther. Med.53, 102526 (2020). PubMed
Schisterman, E. F. et al. Effect of folic acid and zinc supplementation in men on semen quality and live birth among couples undergoing infertility treatment: a randomized clinical trial. JAMA323, 35–48 (2020). PubMed PMC
Jenkins, T. et al. The impact of zinc and folic acid supplementation on sperm DNA methylation: results from the folic acid and zinc supplementation randomized clinical trial (FAZST). Fertil. Steril.117, 75–85 (2022). PubMed
Huang, W. J., Lu, X. L., Li, J. T. & Zhang, J. M. Effects of folic acid on oligozoospermia with MTHFR polymorphisms in term of seminal parameters, DNA fragmentation, and live birth rate: a double‐blind, randomized, placebo‐controlled trial. Andrology8, 110–116 (2020). PubMed
Türkomp. Turkish food composition database https://turkomp.gov.tr/main (2017).
Zhao, M., Lin, Y. & Chen, H. Improving nutritional quality of rice for human health. Theor. Appl. Genet.133, 1397–1413 (2020). PubMed
Nystrom, L. et al. Phytochemicals and dietary fiber components in rye varieties in the HEALTHGRAIN diversity screen. J. Agric. Food Chem.56, 9758–9766 (2008). PubMed
Satyavathi, C. T., Ambawat, S., Khandelwal, V. & Srivastava, R. K. Pearl millet: a climate-resilient nutricereal for mitigating hidden hunger and provide nutritional security. Front. Plant Sci.12, 659938 (2021). PubMed PMC
Adebo, O. A. African sorghum-based fermented foods: past, current and future prospects. Nutrients12, 1111 (2020). PubMed PMC
Arya, S. S., Salve, A. R. & Chauhan, S. Peanuts as functional food: a review. J. Food Sci. Technol.53, 31–41 (2016). PubMed PMC
King, J. C. et al. Tree nuts and peanuts as components of a healthy diet. J. Nutr.138, 1736S–1740S (2008). PubMed
Bonku, R. & Yu, J. Health aspects of peanuts as an outcome of its chemical composition. Food Sci. Hum. Wellness.9, 21–30 (2020).
Sathe, S. K., Monaghan, E. K., Kshirsagar, H. H. & Venkatachalam, M. Chemical composition of edible nut seeds and its implications in human health. In Tree Nuts: Composition, Phytochemicals, and Health Effects (eds Alasalvar, C. & Shahidi, F.) Ch. 2, 11–35 (CRC Press, 2008).
Barreca, D. et al. Almonds (Prunus dulcis Mill. DA webb): a source of nutrients and health-promoting compounds. Nutrients12, 672 (2020). PubMed PMC
Fajardo, V., Alonso-Aperte, E. & Varela-Moreiras, G. Folate content in fresh-cut vegetable packed products by 96-well microtiter plate microbiological assay. Food Chem.169, 283–288 (2015). PubMed
Food Standards Australia New Zealand. Nutritional impact of phytosanitary irradiation of fruits and vegetables (Food Standards Australia New Zealand, 2014).
Ratajczak, A. E. et al. Does folic acid protect patients with inflammatory bowel disease from complications? Nutrients13, 4036 (2021). PubMed PMC
Pandrangi, S. & LaBorde, L. F. Optimization of microbiological assay of folic acid and determination of folate content in spinach. Int. J. Food Sci. Technol.39, 525–532 (2004).
Dreher, M. L. & Davenport, A. J. Hass avocado composition and potential health effects. Crit. Rev. Food Sci. Nutr.53, 738–750 (2013). PubMed PMC
USDA. FoodData Central, https://fdc.nal.usda.gov/ (2019).
O’Connor, A. An overview of the role of bread in the UK diet. Nutr. Bull.37, 193–212 (2012).
Probst, Y. Nutrient Composition of Chicken Meat (Rural Industries Research and Development Corporation, 2009).
Lister, C. Nutritional analysis of mushrooms-a summary (A Plant & Food Research, 2015). https://meadowmushrooms.co.nz/storage/wysiwyg/files/final-nutritional-analysis-of-meadow-mushrooms-a-summary.pdf.
Gahruie, H. H., Eskandari, M. H., Mesbahi, G. & Hanifpour, M. A. Scientific and technical aspects of yogurt fortification: a review. Food Sci. Hum. Wellness.4, 1–8 (2015).
Johnston, K., DiRienzo, D. & Tamura, T. Folate content of dairy products measured by microbiological assay with trienzyme treatment. J. Food Sci.67, 817–820 (2002).
Redeuil, K. M. et al. Simultaneous quantification of 21 water soluble vitamin circulating forms in human plasma by liquid chromatography-mass spectrometry. J. Chromatogr. A1422, 89–98 (2015). PubMed
Oosterink, J. E. et al. Accurate measurement of the essential micronutrients methionine, homocysteine, vitamins B6, B12, B9 and their metabolites in plasma, brain and maternal milk of mice using LC/MS ion trap analysis. J. Chromatogr. B998-999, 106–113 (2015). PubMed
Redeuil, K. et al. A novel methodology for the quantification of B-vitamers in breast milk. J. Anal. Bioanal. Tech.8, 352 (2017).
Khaksari, M. et al. Detection and quantification of vitamins in microliter volumes of biological samples by LC‐MS for clinical screening. AIChE J.64, 3709–3718 (2018).
Zayed, A., Bustami, R., Alabsi, W. & El-Elimat, T. Development and validation of a rapid high-performance liquid chromatography–tandem mass spectrometric method for determination of folic acid in human plasma. Pharm11, 52 (2018). PubMed PMC
Asante, I. et al. Simultaneous quantitation of folates, flavins and B6 metabolites in human plasma by LC–MS/MS assay: Applications in colorectal cancer. J. Pharm. Biomed. Anal.158, 66–73 (2018). PubMed PMC
Nandania, J., Kokkonen, M., Euro, L. & Velagapudi, V. Simultaneous measurement of folate cycle intermediates in different biological matrices using liquid chromatography–tandem mass spectrometry. J. Chromatogr. B1092, 168–178 (2018). PubMed
Kahoun, D. et al. Development and validation of an LC-MS/MS method for determination of B vitamins and some its derivatives in whole blood. PLoS One17, e0271444 (2022). PubMed PMC
Gu, Y. et al. A novel automated multi-cycle magnetic solid-phase extraction coupled to LC-MS/MS to study the disorders of six functional B vitamins in patients with gastroenterology and hyperhomocysteinemia. J. Pharm. Biomed. Anal.241, 115989 (2024). PubMed
Kang, L. et al. Rapid determination of folic acid and riboflavin in urine by polypyrrole magnetic solid-phase extractant combined ultra-performance liquid chromatography. J. Chromatogr. A1648, 462192 (2021). PubMed
Akbari, A. et al. Determination of B vitamins by double-vortex-ultrasonic assisted dispersive liquid–liquid microextraction and evaluation of their possible roles in susceptibility to COVID− 19 infection: Hybrid Box–Behnken design and genetic algorithm. J. Chromatogr. Sci.60, 897–906 (2022). PubMed
Xu, H. et al. Voltammetric determination of folic acid at physiological pH values by using a glassy carbon electrode modified with a multilayer composite consisting of polyoxometalate (H8P2Mo16V2O62) and reduced graphene oxide and prepared via layer-by-layer self-assembly and in-situ photoreduction. Mikrochim. Acta184, 4295–4303 (2017).
Wang, M. et al. Nitrogen-doped carbon quantum dots as a fluorescence probe combined with magnetic solid-phase extraction purification for analysis of folic acid in human serum. Anal. Bioanal. Chem.409, 7063–7075 (2017). PubMed
Gao, X. et al. Synthesis of graphene/ZnO nanowire arrays/graphene foam and its application for determination of folic acid. J. Electroanal. Chem.808, 189–194 (2018).
Güney, S. Electrochemical synthesis of molecularly imprinted poly (p-aminobenzene sulphonic acid) on carbon nanodots coated pencil graphite electrode for selective determination of folic acid. J. Electroanal. Chem.854, 113518 (2019).
Hussain, S. et al. Facile preparation of molybdenum carbide (Mo2C) nanoparticles and its effective utilization in electrochemical sensing of folic acid via imprinting. Biosens. Bioelectron.140, 111330 (2019). PubMed
Wang, Q. et al. A fast and facile electrochemical method for the simultaneous detection of epinephrine, uric acid and folic acid based on ZrO2/ZnO nanocomposites as sensing material. Anal. Chim. Acta1104, 69–77 (2020). PubMed
Yang, B. et al. A water-stable MOF-AgClO4-abtz as fluorescent sensor for detection of folic acid based on inner filter effect. Talanta217, 121019 (2020). PubMed
Yang, M. et al. Visual detection of folic acid based on silica coated CdTeS quantum dots in serum samples. Mater. Res. Bull.144, 111509 (2021).
Fereja, S. L. et al. Silver-enhanced fluorescence of bimetallic Au/Ag nanoclusters as ultrasensitive sensing probe for the detection of folic acid. Talanta233, 122469 (2021). PubMed
Yadav, D. et al. Nanohybrid comprising gold nanoparticles–MoS2 nanosheets for electrochemical sensing of folic acid in serum samples. Electroanalysis35, e202200286 (2023).
Sun, Y., Wang, X. & Zhang, H. Sensitive and stable electrochemical sensor for folic acid determination using a ZIF-67/AgNWs nanocomposite. Biosens12, 382 (2022). PubMed PMC
Li, K., Quan, X. & Yan, B. Eu (III)-functionalized iCOF hybrids by “tandem post-synthetic modifications” for fluorescent detection of folic acid and trimethoprim: a logical judgement by combination of neural networks and logic gates. Sens. Actuators B Chem. 392, 134078 (2023).
Xu, Y. et al. In situ electrodeposition of bismuth oxide nanowires@ MWNT on the carbon fiber microelectrode for the sensitively electrochemical detection of folic acid. Talanta253, 123944 (2023). PubMed
Vegad, Y. et al. Folic acid detection using β-cyclodextrin-functionalized copper nanoclusters and vitamin B6 cofactor pyridoxal. ACS Appl. Nano Mater. 10.1021/acsanm.3c05697 (2024).
Kıranşan, K. D. & Topçu, E. Free‐standing and flexible MoS2/rGO paper electrode for amperometric detection of folic acid. Electroanalysis30, 810–818 (2018).
Immundiagnostik A. G. ID-Vit® Folic acid, https://alpco-docs.s3.amazonaws.com/30/IFU-30-KIF005.pdf (2019).
Abbexa. Folic Acid/Vitamin B9 ELISA Kit, https://www.abbexa.com/documents/manual/abx150387_ifu.pdf (2023).
Cell Biolabs Inc. Folic Acid ELISA Kit, https://www.cellbiolabs.com/sites/default/files/MET-5068-folic-acid-elisa-kit.pdf (2024).
LSBio. All species Folic Acid ELISA Kit (Competitive EIA), https://www.lsbio.com/elisakits/manualpdf/ls-f4330.pdf (2024).
Raimondi, M. V. et al. DHFR inhibitors: reading the past for discovering novel anticancer agents. Molecules24, 1140 (2019). PubMed PMC