Register      Login
Animal Production Science Animal Production Science Society
Food, fibre and pharmaceuticals from animals
REVIEW

Folate metabolism and application of folic acid in ruminant production

Bo Wang https://orcid.org/0000-0001-9507-0199 A B * and Mengjiao Sun A B
+ Author Affiliations
- Author Affiliations

A Qingdao Key Laboratory of Specialty Plant Germplasm Innovation and Utilization in Saline Soils of Coastal Beach, College of Grassland Science, Qingdao Agricultural University, Qingdao 266109, China.

B Key Laboratory of National Forestry and Grassland Administration on Grassland Resources and Ecology in the Yellow River Delta, Qingdao Agricultural University, Qingdao 266109, China.

* Correspondence to: wangbo@qau.edu.cn

Handling Editor: Surinder Chauhan

Animal Production Science 65, AN24127 https://doi.org/10.1071/AN24127
Submitted: 16 April 2024  Accepted: 6 December 2024  Published: 2 January 2025

© 2025 The Author(s) (or their employer(s)). Published by CSIRO Publishing

Abstract

Folic acid, also known as vitamin B9, is a water-soluble vitamin from the B group that plays a pivotal role (as the carrier of one-carbon units) in the regulation of early development and nutrient metabolism in animals. Traditional animal nutrition posits that rumen microorganisms can synthesize folate, thereby meeting the growth, development, and production needs of ruminants. However, the quantity of synthesized folate is subject to variations in dietary composition, genetic enhancements, increased production performance, and changes in feeding systems. These factors may result in the folate synthesized by rumen microorganisms not reaching the optimal production potential of the animals. Despite a significant proportion of dietary folic acid/folate being degraded in the rumen, studies have shown that supplementing folic acid (or combined with vitamin B12, methionine, etc.) in the diet can enhance rumen fermentation, increase the folate level in ruminant tissues (such as the liver and blood), regulate nutrient metabolism, and improve milk yield and quality to a certain extent. Further research is required to assess the impact of dietary folic acid levels on rumen microbial metabolism, folate distribution among different tissues and organs, and the demand for folate at various developmental stages, as well as the interaction between folic acid and other nutrients which are involved in one-carbon metabolism process. This will help to optimize the nutritional supply for ruminants and fully exploit their production performance potential.

Keywords: blood, folate, folic acid, liver, milk, production performance, rumen, ruminants.

References

Abbasi IHR, Abbasi F, Soomro RN, Abd El-Hack ME, Abdel-Latif MA, Li W, Hao R, Sun F, Bodinga BM, Hayat K, Yao J, Cao Y (2017) Considering choline as methionine precursor, lipoproteins transporter, hepatic promoter and antioxidant agent in dairy cows. AMB Express 7, 214.
| Crossref | Google Scholar |

Angier RB, Boothe JH, Hutchings BL, Mowat JH, Semb J, Stokstad ELR, Subbarow Y, Waller CW, Cosulich DB, Fahrenbach MJ, Hultquist ME, Kuh E, Northey EH, Seeger DR, Sickels JP, Smith JM, Jr. (1945) Synthesis of a compound identical with the L. Casei factor isolated from liver. Science 102, 227-228.
| Crossref | Google Scholar |

Antony AC (2007) In utero physiology: role of folic acid in nutrient delivery and fetal development. The American Journal of Clinical Nutrition 85, 598S-603S.
| Crossref | Google Scholar |

Ashokkumar B, Mohammed ZM, Vaziri ND, Said HM (2007) Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells. The American Journal of Clinical Nutrition 86, 159-166.
| Crossref | Google Scholar |

Bender DA (1992) Folic acid and other pterins and vitamin B12. In ‘Nutritional Biochemistry of the Vitamins’. (Ed. DA Bender) pp. 269–317. (Cambridge University Press: Cambridge)

Cawley S, McCartney D, Woodside JV, Sweeney MR, Mcdonnell R, Molloy AM, Turner MJ (2018) Optimization of folic acid supplementation in the prevention of neural tube defects. Journal of Public Health 40, 827-834.
| Crossref | Google Scholar |

Chandler CJ, Wang TT, Halsted CH (1986) Pteroylpolyglutamate hydrolase from human jejunal brush borders. Purification and characterization. The Journal of Biological Chemistry 261, 928-933.
| Crossref | Google Scholar |

Cheng KF, Wang C, Zhang GW, Du HS, Wu ZZ, Liu Q, Guo G, Huo WJ, Zhang J, Chen L, Pei CX (2020) Effects of betaine and rumen-protected folic acid supplementation on lactation performance, nutrient digestion, rumen fermentation and blood metabolites in dairy cows. Animal Feed Science and Technology 262, 114445.
| Crossref | Google Scholar |

Clifford AJ, Heid MK, Müller HG, Bills ND (1990) Tissue distribution and prediction of total body folate of rats. The Journal of Nutrition 120, 1633-1639.
| Crossref | Google Scholar |

Cronje PB (2018) Essential role of methyl donors in animal productivity. Animal Production Science 58, 655-665.
| Crossref | Google Scholar |

Dev S, Ahmad WN, Kaur J (2011) Regulatory mechanisms of intestinal folate uptake in a rat model of folate oversupplementation. British Journal of Nutrition 105, 827-835.
| Crossref | Google Scholar |

Du HS, Wang C, Wu ZZ, Zhang GW, Liu Q, Guo G, Huo WJ, Zhang YL, Pei CX, Zhang SL (2019) Effects of rumen-protected folic acid and rumen-protected sodium selenite supplementation on lactation performance, nutrient digestion, ruminal fermentation and blood metabolites in dairy cows. Journal of the Science of Food and Agriculture 99, 5826-5833.
| Crossref | Google Scholar |

Ebara S (2017) Nutritional role of folate. Congenital Anomalies 57, 138-141.
| Crossref | Google Scholar | PubMed |

Evans E, Fontaine E, AIZahal O, Gwyn C (2023) Assessment of the effects of supplemental rumen protected b vitamins and choline for periparturient cows: a meta-analysis of 28 feeding studies. Open Journal of Animal Sciences 13, 151-165.
| Crossref | Google Scholar |

Giordano D, Reyneri A, Blandino M (2016) Folate distribution in barley (Hordeum vulgare L.), common wheat (Triticum aestivum L.) and durum wheat (Triticum turgidum durum Desf.) pearled fractions. Journal of the Science of Food and Agriculture 96, 1709-1715.
| Crossref | Google Scholar |

Girard CL (1998) B-complex vitamins for dairy cows: a new approach. Canadian Journal of Animal Science 78, 71-90.
| Google Scholar |

Girard CL, Matte JJ (1999) Changes in serum concentrations of folates, pyridoxal, pyridoxal-5-phosphate and vitamin B12 during lactation of dairy cows fed dietary supplements of folic acid. Canadian Journal of Animal Science 79, 107-114.
| Crossref | Google Scholar |

Girard CL, Matte JJ (2005) Folic acid and vitamin B12 requirements of dairy cows: a concept to be revised. Livestock Production Science 98, 123-133.
| Crossref | Google Scholar |

Girard CL, Rémond D (2003) Net flux of folates and vitamin B12 through the gastrointestinal tract of sheep. Canadian Journal of Animal Science 83, 273-278.
| Crossref | Google Scholar |

Girard CL, Matte JJ, Tremblay GF (1989) Serum folates in gestating and lactating dairy cows. Journal of Dairy Science 72, 3240-3246.
| Crossref | Google Scholar |

Girard CL, Chiquette J, Matte JJ (1994) Concentrations of folates in ruminal content of steers: responses to a dietary supplement of folic acid in relation with the nature of the diet. Journal of Animal Science 72, 1023-1028.
| Crossref | Google Scholar |

Girard CL, Castonguay F, Fahmy MH, Matte JJ (1996) Serum and milk folates during the first two gestations and lactations in Romanov, Finnsheep, and Suffolk ewes. Journal of Animal Science 74, 1711-1715.
| Crossref | Google Scholar |

Girard CL, Castonguay F, Matte JJ (1999) Response of serum concentrations of folates to dietary supplements of folic acid given to ewes during gestation. Canadian Journal of Animal Science 79, 387-389.
| Crossref | Google Scholar |

Girard CL, Lapierre H, Desrochers A, Benchaar C, Jacques Matte J, Rémond D (2001) Net flux of folates and vitamin B12 through the gastrointestinal tract and the liver of lactating dairy cows. British Journal of Nutrition 86, 707-715.
| Crossref | Google Scholar |

Girard CL, Lapierre H, Matte JJ, Lobley GE (2005) Effects of dietary supplements of folic acid and rumen-protected methionine on lactational performance and folate metabolism of dairy cows. Journal of Dairy Science 88, 660-670.
| Crossref | Google Scholar |

Girard CL, Benchaar C, Chiquette J, Desrochers A (2009) Net flux of nutrients across the rumen wall of lactating dairy cows as influenced by dietary supplements of folic acid. Journal of Dairy Science 92, 6116-6122.
| Crossref | Google Scholar |

Graulet B, Matte JJ, Desrochers A, Doepel L, Palin M-F, Girard CL (2007) Effects of dietary supplements of folic acid and vitamin B12 on metabolism of dairy cows in early lactation. Journal of Dairy Science 90, 3442-3455.
| Crossref | Google Scholar |

Guay F, Jacques Matte J, Girard CL, Palin M-F, Giguère A, Laforest J-P (2002) Effects of folic acid and vitamin B12 supplements on folate and homocysteine metabolism in pigs during early pregnancy. British Journal of Nutrition 88, 253-263.
| Crossref | Google Scholar |

Hall G, Cheng EW, Burroughs W (1955) B-vitamins stimulatory to cellulose digestion by washed suspensions of rumen microorganisms. Proceedings of the Iowa Academy of Science 62, 273-278.
| Google Scholar |

Hoyo C, Murtha AP, Schildkraut JM, Forman MR, Calingaert B, Demark-Wahnefried W, Kurtzberg J, Jirtle RL, Murphy SK (2011) Folic acid supplementation before and during pregnancy in the newborn epigenetics study (NEST). BMC Public Health 11, 46.
| Crossref | Google Scholar |

Islam MS, Liu J, Jiang L, Zhang C, Liang Q (2021) Folate content in fresh corn: effects of harvest time, storage and cooking methods. Journal of Food Composition and Analysis 103, 104123.
| Crossref | Google Scholar |

Kalli KR, Oberg AL, Keeney GL, Christianson TJH, Low PS, Knutson KL, Hartmann LC (2008) Folate receptor alpha as a tumor target in epithelial ovarian cancer. Gynecologic Oncology 108, 619-626.
| Crossref | Google Scholar |

Kirksey A (1986) Effects of vitamin supplementation on vitamin levels in human milk: vitamin B-6, vitamin C and folacin. In ‘Human lactation 2’. (Eds M Hamosh, AS Goldman) pp. 339–348. (Springer)

La S, Li H, Wang C, Liu Q, Guo G, Huo W, Zhang Y, Pei C, Zhang S (2019) Effects of rumen-protected folic acid and dietary protein level on growth performance, ruminal fermentation, nutrient digestibility and hepatic gene expression of dairy calves. Journal of Animal Physiology and Animal Nutrition 103, 1006-1014.
| Crossref | Google Scholar |

Lan X, Field MS, Stover PJ (2018) Cell cycle regulation of folate-mediated one-carbon metabolism. WIREs Systems Biology and Medicine 10, e1426.
| Crossref | Google Scholar |

Li HQ, Liu Q, Wang C, Yang ZM, Guo G, Huo WJ, Pei CX, Zhang YL, Zhang SL, Wang H, Liu JX, Huang YX (2016) Effects of dietary supplements of rumen-protected folic acid on lactation performance, energy balance, blood parameters and reproductive performance in dairy cows. Animal Feed Science and Technology 213, 55-63.
| Crossref | Google Scholar |

Li Z, Wang B, Li H, Jian L, Luo H, Wang B, Zhang C, Zhao X, Xue Y, Peng S, Zuo S (2020) Maternal folic acid supplementation differently affects the small intestinal phenotype and gene expression of newborn lambs from differing litter sizes. Animals 10, 2183.
| Crossref | Google Scholar |

Liang Q, Wang K, Shariful I, Ye X, Zhang C (2020) Folate content and retention in wheat grains and wheat-based foods: effects of storage, processing, and cooking methods. Food Chemistry 333, 127459.
| Crossref | Google Scholar |

Liu J, Yao Y, Yu B, Mao X, Huang Z, Chen D (2012) Effect of folic acid supplementation on hepatic antioxidant function and mitochondrial-related gene expression in weanling intrauterine growth retarded piglets. Livestock Science 146, 123-132.
| Crossref | Google Scholar |

Liu YQ, Wang C, Liu C, Zhang J, Liu Q (2023) Effects of coated folic acid and coated methionine on growth performance, nutrient digestibility and rumen fermentation in Simmental bulls. Animal Feed Science and Technology 298, 115596.
| Crossref | Google Scholar |

Loría A, Vaz-Pinto A, Arroyo P, Ramírez-Mateos C, Sánchez-Medal L (1977) Nutritional anemia. VI. Fetal hepatic storage of metabolites in the second half of pregnancy. The Journal of Pediatrics 91, 569-573.
| Crossref | Google Scholar |

Lucock M (2000) Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Molecular Genetics and Metabolism 71, 121-138.
| Crossref | Google Scholar |

Mabasa L, Samodien E, Sangweni NF, Pheiffer C, Louw J, Johnson R (2020) In utero one-carbon metabolism interplay and metabolic syndrome in cardiovascular disease risk reduction. Molecular Nutrition & Food Research 64, 1900377.
| Crossref | Google Scholar |

Matte JJ, Girard CL, Tremblay GF (1993) Effect of long-term addition of folic acid on folate status, growth performance, puberty attainment, and reproductive capacity of gilts. Journal of Animal Science 71, 151-157.
| Crossref | Google Scholar |

McFadden JW, Girard CL, Tao S, Zhou Z, Bernard JK, Duplessis M, White HM (2020) Symposium review: One-carbon metabolism and methyl donor nutrition in the dairy cow. Journal of Dairy Science 103, 5668-5683.
| Crossref | Google Scholar |

Mercier J, Cinq-Mars D, Berthiaume R, Faucitano L, Girard CL (2015) Effects of dietary total non-structural carbohydrates and folic acid and vitamin B12 supplement on growth and meat quality of yearling steers in a forage-based beef production system. Canadian Journal of Animal Science 95, 281-291.
| Crossref | Google Scholar |

NRC (1998) ‘Nutrient requirements of swine,’ 10th revised edn. pp. 130–131. (National Academy Press: Washington, DC)

NRC (2001) ‘Nutrient requirements of dairy cattle,’ 7th revised edn. pp. 169–172. (National Academy Press: Washington, DC)

Penailillo R, Eckert J, Burdge G, Fleming T, Lillycrop K (2019) The effect of folic acid supplementation in the ovary and upon embryo development. Placenta 83, e49.
| Crossref | Google Scholar |

Preynat A, Lapierre H, Thivierge MC, Palin MF, Matte JJ, Desrochers A, Girard CL (2009) Effects of supplements of folic acid, vitamin B12, and rumen-protected methionine on whole body metabolism of methionine and glucose in lactating dairy cows. Journal of Dairy Science 92, 677-689.
| Crossref | Google Scholar |

Preynat A, Lapierre H, Thivierge MC, Palin MF, Cardinault N, Matte JJ, Desrochers A, Girard CL (2010) Effects of supplementary folic acid and vitamin B12 on hepatic metabolism of dairy cows according to methionine supply. Journal of Dairy Science 93, 2130-2142.
| Crossref | Google Scholar |

Rosario FJ, Nathanielsz PW, Powell TL, Jansson T (2017) Maternal folate deficiency causes inhibition of mTOR signaling, down-regulation of placental amino acid transporters and fetal growth restriction in mice. Scientific Reports 7, 3982.
| Crossref | Google Scholar |

Sacadura FC, Robinson PH, Evans E, Lordelo M (2008) Erratum to “Effects of a ruminally protected B-vitamin supplement on milk yield and composition of lactating dairy cows” [Anim. Feed Sci. Technol. 144 (2008) 111–124]. Animal Feed Science and Technology 144, 350-351.
| Crossref | Google Scholar |

Santschi DE, Chiquette J, Berthiaume R, Martineau R, Matte JJ, Mustafa AF, Girard CL (2005a) Effects of the forage to concentrate ratio on B-vitamin concentrations in different ruminal fractions of dairy cows. Canadian Journal of Animal Science 85, 389-399.
| Crossref | Google Scholar |

Santschi DE, Berthiaume R, Matte JJ, Mustafa AF, Girard CL (2005b) Fate of supplementary B-vitamins in the gastrointestinal tract of dairy cows. Journal of Dairy Science 88, 2043-2054.
| Crossref | Google Scholar |

Schwab EC, Schwab CG, Shaver RD, Girard CL, Putnam DE, Whitehouse NL (2006) Dietary forage and nonfiber carbohydrate contents influence B-Vitamin intake, duodenal flow, and apparent ruminal synthesis in lactating dairy cows. Journal of Dairy Science 89, 174-187.
| Crossref | Google Scholar |

Selhub J, Jeelani Dhar G, Rosenberg IH (1983) Gastrointestinal absorption of folates and antifolates. Pharmacology & Therapeutics 20, 397-418.
| Crossref | Google Scholar | PubMed |

Shane B (2001) Folate chemistry and metabolism. Clinical Research and Regulatory Affairs 18, 137-159.
| Crossref | Google Scholar |

Shane B (2009) ‘Folate chemistry and metabolism.’ (CRC Press: Boca Raton, FL, USA)

Shia J, Klimstra DS, Nitzkorski JR, Low PS, Gonen M, Landmann R, Weiser MR, Franklin WA, Prendergast FG, Murphy L, Tang LH, Temple L, Guillem JG, Wong WD, Paty PB (2008) Immunohistochemical expression of folate receptor α in colorectal carcinoma: patterns and biological significance. Human Pathology 39, 498-505.
| Crossref | Google Scholar |

Souci SW (2008) ‘Food composition and nutrition tables.’ 7th revised and completed edn. (Medpharm)

Tamura T, Goldenberg RL, Chapman VR, Johnston KE, Ramey SL, Nelson KG (2005) Folate status of mothers during pregnancy and mental and psychomotor development of their children at five years of age. Pediatrics 116, 703-708.
| Crossref | Google Scholar |

Visentin M, Diop-Bove N, Zhao R, Goldman ID (2014) The intestinal absorption of folates. Annual Review of Physiology 76, 251-274.
| Crossref | Google Scholar |

Wallingford JB, Niswander LA, Shaw GM, Finnell RH (2013) The continuing challenge of understanding, preventing, and treating neural tube defects. Science 339, 1222002.
| Crossref | Google Scholar |

Wang C, Liu Q, Guo G, Huo WJ, Ma L, Zhang YL, Pei CX, Zhang SL, Wang H (2016) Effects of rumen-protected folic acid on ruminal fermentation, microbial enzyme activity, cellulolytic bacteria and urinary excretion of purine derivatives in growing beef steers. Animal Feed Science and Technology 221, 185-194.
| Crossref | Google Scholar |

Wang C, Liu Q, Guo G, Huo WJ, Liang Y, Pei CX, Zhang SL, Yang WZ, Wang H (2017) Effects of different dietary protein levels and rumen-protected folic acid on ruminal fermentation, degradability, bacterial populations and urinary excretion of purine derivatives in beef steers. The Journal of Agricultural Science 155, 1477-1486.
| Crossref | Google Scholar |

Wang B, Li H, Li Z, Jian L, Gao Y, Qu Y, Liu C, Xu C, Li Y, Diao Z, Lu W, Yu Y, Machaty Z, Luo H (2019a) Maternal folic acid supplementation modulates the growth performance, muscle development and immunity of Hu sheep offspring of different litter size. The Journal of Nutritional Biochemistry 70, 194-201.
| Crossref | Google Scholar |

Wang C, Liu Q, Guo G, Huo WJ, Zhang YL, Pei CX, Zhang SL (2019b) Effects of rumen-protected folic acid and branched-chain volatile fatty acids supplementation on lactation performance, ruminal fermentation, nutrient digestion and blood metabolites in dairy cows. Animal Feed Science and Technology 247, 157-165.
| Crossref | Google Scholar |

Wang C, Wu X, Liu Q, Guo G, Huo W, Zhang Y, Pei C, Zhang S, Wang H (2019c) Effects of folic acid on growth performance, ruminal fermentation, nutrient digestibility and urinary excretion of purine derivatives in post-weaned dairy calves. Archives of Animal Nutrition 73, 18-29.
| Crossref | Google Scholar |

Wang C, Liu C, Zhang GW, Du HS, Wu ZZ, Liu Q, Guo G, Huo WJ, Zhang J, Pei CX, Chen L, Zhang SL (2020a) Effects of rumen-protected folic acid and betaine supplementation on growth performance, nutrient digestion, rumen fermentation and blood metabolites in Angus bulls. British Journal of Nutrition 123, 1109-1116.
| Crossref | Google Scholar |

Wang B, Li Z, Li H, Luo H, Blair HT, Jian L, Diao Z (2020b) Effect of dietary folic acid supplementation during pregnancy on blood characteristics and milk composition of ewes. Animals 10, 433.
| Crossref | Google Scholar |

Wang B, Jian L, Li H, Li Z, Luo H, Gao Y (2022) Folic acid supplementation during pregnancy modulates hepatic methyl metabolism and genes expression profile of neonatal lambs of different litter sizes. British Journal of Nutrition 128, 1-12.
| Crossref | Google Scholar |

Wani NA, Thakur S, Kaur J (2012) Mechanism of intestinal folate transport during folate deficiency in rodent model. The Indian Journal of Medical Research 136, 758-765.
| Google Scholar |

Winkels RM, Brouwer IA, Siebelink E, Katan MB, Verhoef P (2007) Bioavailability of food folates is 80% of that of folic acid. The American Journal of Clinical Nutrition 85, 465-473.
| Crossref | Google Scholar |

Wu S, Zhang J, Li F, Du W, Zhou X, Wan M, Fan Y, Xu X, Zhou X, Zheng L, Zhou Y (2019) One-carbon metabolism links nutrition intake to embryonic development via epigenetic mechanisms. Stem Cells International 2019, 3894101.
| Crossref | Google Scholar |

Yuasa H, Inoue K, Hayashi Y (2009) Molecular and functional characteristics of proton-coupled folate transporter. Journal of Pharmaceutical Sciences 98, 1608-1616.
| Crossref | Google Scholar |

Zhao R, Matherly LH, Goldman ID (2009) Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues. Expert Reviews in Molecular Medicine 11, e4.
| Crossref | Google Scholar |

Zhao R, Diop-Bove N, Visentin M, Goldman ID (2011) Mechanisms of membrane transport of folates into cells and across epithelia. Annual Review of Nutrition 31, 177-201.
| Crossref | Google Scholar |

Zinn RA, Owens FN, Stuart RL, Dunbar JR, Norman BB (1987) B-vitamin supplementation of diets for feedlot calves. Journal of Animal Science 65, 267-277.
| Crossref | Google Scholar |