Skip to main content
SpringerLink
Log in

Folic and Folinic Acids

  • Reference work entry
  • First Online:
Critical Care Toxicology

  • 420 Accesses

Abstract

Folic acid is a water-soluble B-complex vitamin essential for nucleoprotein synthesis, which is necessary for normal growth and development. It traditionally is administered for the treatment of megaloblastic anemias, as for a vitamin supplement or as food fortification due its ability to reduce fetal neural tube defects. Medical toxicologists use folic and folinic acid in the treatment of drug-induced toxicity due to folic acid antagonists and methanol. The focus of this chapter is the use of folic and folinic acids as antidotes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 338.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kothari BV, Bhende YM. Crude liver extract, refined liver extract and folic acid in the treatment of pernicious anaemia of pregnancy. Indian J Med Res. 1950;38(4):385–92.

    CAS  PubMed  Google Scholar 

  2. van der Weyden MB, Cooper M, Firkin BG. Altered erythrocyte pyrimidine activity in vitamin B12 or folate deficiency. Br J Haematol. 1979;42(1):85–91.

    Article  PubMed  Google Scholar 

  3. Butterworth Jr CE, Baugh CM, Krumdieck C. A study of folate absorption and metabolism in man utilizing carbon-14 – labeled polyglutamates synthesized by the solid phase method. J Clin Invest. 1969;48(6):1131–42. doi:10.1172/JCI106070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Berry RJ, Li Z, Erickson JD, et al. Prevention of neural-tube defects with folic acid in china. China-U.S. Collaborative Project for neural tube defect prevention. N Engl J Med. 1999;341(20):1485–90. doi:10.1056/NEJM199911113412001.

    Article  CAS  PubMed  Google Scholar 

  5. Smithells RW, Sheppard S. Possible prevention of neural-tube defects by periconceptional vitamin supplementation. Lancet. 1980;1(8169):647.

    Article  CAS  PubMed  Google Scholar 

  6. Honein MA, Paulozzi LJ, Mathews TJ, Erickson JD, Wong LY. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA. 2001;285(23):2981–6. doi:joc10010 [pii].

    Article  CAS  PubMed  Google Scholar 

  7. Williams J, Mai CT, Mulinare J, et al. Updated estimates of neural tube defects prevented by mandatory folic acid fortification – United States, 1995–2011. MMWR Morb Mortal Wkly Rep. 2015;64(1):1–5. doi:mm6401a2 [pii].

    PubMed  Google Scholar 

  8. Gamble MV, Liu X, Ahsan H, et al. Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh. Environ Health Perspect. 2005;113(12):1683–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chen Y, Factor-Litvak P, Howe GR, et al. Arsenic exposure from drinking water, dietary intakes of B vitamins and folate, and risk of high blood pressure in Bangladesh: a population-based, cross-sectional study. Am J Epidemiol. 2007;165(5):541–52. doi:kwk037 [pii].

    Article  PubMed  Google Scholar 

  10. Heck JE, Gamble MV, Chen Y, et al. Consumption of folate-related nutrients and metabolism of arsenic in Bangladesh. Am J Clin Nutr. 2007;85(5):1367–74. doi:85/5/1367 [pii].

    CAS  PubMed  Google Scholar 

  11. Fan CM, Foster BK, Hui SK, Xian CJ. Prevention of bone growth defects, increased bone resorption and marrow adiposity with folinic acid in rats receiving long-term methotrexate. PLoS One. 2012;7(10):e46915. doi:10.1371/journal.pone.0046915.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xian CJ, Cool JC, Scherer MA, Fan C, Foster BK. Folinic acid attenuates methotrexate chemotherapy-induced damages on bone growth mechanisms and pools of bone marrow stromal cells. J Cell Physiol. 2008;214(3):777–85. doi:10.1002/jcp.21274.

    Article  CAS  PubMed  Google Scholar 

  13. Treon SP, Chabner BA. Concepts in use of high-dose methotrexate therapy. Clin Chem. 1996;42(8 Pt 2):1322–9.

    CAS  PubMed  Google Scholar 

  14. Bleyer WA. New vistas for leucovorin in cancer chemotherapy. Cancer. 1989;63(6 Suppl):995–1007.

    Article  CAS  PubMed  Google Scholar 

  15. Bozzette SA, Forthal D, Sattler FR, et al. The tolerance for zidovudine plus thrice weekly or daily trimethoprim-sulfamethoxazole with and without leucovorin for primary prophylaxis in advanced HIV disease. California Collaborative Treatment Group. Am J Med. 1995;98(2):177–82. doi:S000293439980401X [pii].

    Article  CAS  PubMed  Google Scholar 

  16. Safrin S, Lee BL, Sande MA. Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death. J Infect Dis. 1994;170(4):912–7.

    Article  CAS  PubMed  Google Scholar 

  17. Grush OC, Morgan SK. Folinic acid rescue for vincristine toxicity. Clin Toxicol. 1979;14(1):71–8. doi:10.3109/15563657909030115.

    Article  CAS  PubMed  Google Scholar 

  18. Kosmidis HV, Bouhoutsou DO, Varvoutsi MC, et al. Vincristine overdose: experience with 3 patients. Pediatr Hematol Oncol. 1991;8(2):171–8.

    Article  CAS  PubMed  Google Scholar 

  19. Beer M, Cavalli F, Martz G. Vincristine overdose: treatment with and without leucovorin rescue. Cancer Treat Rep. 1983;67(7–8):746–7.

    CAS  PubMed  Google Scholar 

  20. Jackson Jr DV, McMahan RA, Pope EK, et al. Clinical trial of folinic acid to reduce vincristine neurotoxicity. Cancer Chemother Pharmacol. 1986;17(3):281–4.

    Article  PubMed  Google Scholar 

  21. Thomas LL, Braat PC, Somers R, Goudsmit R. Massive vincristine overdose: failure of leucovorin to reduce toxicity. Cancer Treat Rep. 1982;66(11):1967–9.

    CAS  PubMed  Google Scholar 

  22. McMartin KE, Makar AB, Martin G, Palese M, Tephly TR. Methanol poisoning. I. The role of formic acid in the development of metabolic acidosis in the monkey and the reversal by 4-methylpyrazole. Biochem Med. 1975;13(4):319–33.

    Article  CAS  PubMed  Google Scholar 

  23. Clay KL, Murphy RC, Watkins WD. Experimental methanol toxicity in the primate: analysis of metabolic acidosis. Toxicol Appl Pharmacol. 1975;34(1):49–61.

    Article  CAS  PubMed  Google Scholar 

  24. McMartin KE, Ambre JJ, Tephly TR. Methanol poisoning in human subjects. Role for formic acid accumulation in the metabolic acidosis. Am J Med. 1980;68(3):414–8.

    Article  CAS  PubMed  Google Scholar 

  25. McMartin KE, Martin-Amat G, Makar AB, Tephly TR. Methanol poisoning. V. Role of formate metabolism in the monkey. J Pharmacol Exp Ther. 1977;201(3):564–72.

    CAS  PubMed  Google Scholar 

  26. Sejersted OM, Jacobsen D, Ovrebo S, Jansen H. Formate concentrations in plasma from patients poisoned with methanol. Acta Med Scand. 1983;213(2):105–10.

    Article  CAS  PubMed  Google Scholar 

  27. Palese M, Tephly TR. Metabolism of formate in the rat. J Toxicol Environ Health. 1975;1(1):13–24. doi:10.1080/15287397509529305.

    Article  CAS  PubMed  Google Scholar 

  28. Noker PE, Eells JT, Tephly TR. Methanol toxicity: treatment with folic acid and 5-formyl tetrahydrofolic acid. Alcohol Clin Exp Res. 1980;4(4):378–83.

    Article  CAS  PubMed  Google Scholar 

  29. Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA, American Academy of Clinical Toxicology Ad Hoc Committee on the Treatment Guidelines for Methanol Poisoning. American academy of clinical toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol. 2002;40(4):415–46.

    Article  CAS  PubMed  Google Scholar 

  30. Flombaum CD, Meyers PA. High-dose leucovorin as sole therapy for methotrexate toxicity. J Clin Oncol. 1999;17(5):1589–94.

    Article  CAS  PubMed  Google Scholar 

  31. Grimes DJ, Bowles MR, Buttsworth JA, et al. Survival after unexpected high serum methotrexate concentrations in a patient with osteogenic sarcoma. Drug Saf. 1990;5(6):447–54.

    Article  CAS  PubMed  Google Scholar 

  32. Cudmore J, Seftel M, Sisler J, Zarychanski R. Methotrexate and trimethoprim-sulfamethoxazole: toxicity from this combination continues to occur. Can Fam Physician. 2014;60(1):53–6. doi:60/1/53 [pii].

    PubMed  PubMed Central  Google Scholar 

  33. Smith SW, Nelson LS. Case files of the New York city poison control center: antidotal strategies for the management of methotrexate toxicity. J Med Toxicol. 2008;4(2):132–40.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Folic acid. Package insert. 2006.

    Google Scholar 

  35. McGuire BW, Sia LL, Leese PT, Gutierrez ML, Stokstad EL. Pharmacokinetics of leucovorin calcium after intravenous, intramuscular, and oral administration. Clin Pharm. 1988;7(1):52–8.

    CAS  PubMed  Google Scholar 

  36. Folate dietary supplement fact sheet. Updated 2012. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/. Accessed 11 Aug 2015.

  37. Rossouw JE, Labadarios D, Davis M, Williams R. Water-soluble vitamins in severe liver disease. S Afr Med J. 1978;54(5):183–6.

    CAS  PubMed  Google Scholar 

  38. Folinic acid. Package insert. 2011.

    Google Scholar 

  39. Gershanik J, Boecler B, Ensley H, McCloskey S, George W. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982;307(22):1384–8. doi:10.1056/NEJM198211253072206.

    Article  CAS  PubMed  Google Scholar 

  40. Tamura T, Aiso K, Johnston KE, Black L, Faught E. Homocysteine, folate, vitamin B-12 and vitamin B-6 in patients receiving antiepileptic drug monotherapy. Epilepsy Res. 2000;40(1):7–15. doi:S0920-1211(00)00101-7 [pii].

    Article  CAS  PubMed  Google Scholar 

  41. Lewis DP, Van Dyke DC, Willhite LA, Stumbo PJ, Berg MJ. Phenytoin-folic acid interaction. Ann Pharmacother. 1995;29(7–8):726–35.

    Article  CAS  PubMed  Google Scholar 

  42. Seligmann H, Potasman I, Weller B, Schwartz M, Prokocimer M. Phenytoin-folic acid interaction: a lesson to be learned. Clin Neuropharmacol. 1999;22(5):268–72.

    CAS  PubMed  Google Scholar 

  43. Finkelstein Y, Zevin S, Heyd J, Bentur Y, Zigelman Y, Hersch M. Emergency treatment of life-threatening intrathecal methotrexate overdose. Neurotoxicology. 2004;25(3):407–10. doi:10.1016/j.neuro.2003.10.004.

    Article  PubMed  Google Scholar 

  44. Pruitt AW, Kinkade Jr JM, Patterson JH. Accidental ingestion of methotrexate. J Pediatr. 1974;85(5):686–8.

    Article  CAS  PubMed  Google Scholar 

  45. Gibbon BN, Manthey DE. Pediatric case of accidental oral overdose of methotrexate. Ann Emerg Med. 1999;34(1):98–100. doi:S0196064499001997 [pii].

    Article  CAS  PubMed  Google Scholar 

  46. Badurdeen S, Kang SL, Saravanan M. Accidental methotrexate ingestion in a 19-month-old child. BMJ Case Rep. 2011. doi:10.1136/bcr.11.2010.3477.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. VCU Health System, Richmond, VA, USA

    Michelle A. Hieger

  2. Division of Clinical Toxicology, Department of Emergency Medicine, Virginia Commonwealth University Health, Richmond, VA, USA

    S. Rutherfoord Rose

Authors
  1. Michelle A. Hieger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Rutherfoord Rose
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michelle A. Hieger .

Editor information

Editors and Affiliations

  1. Department of Medicine, Division of Clinical Pharmacology and Toxicology, University of Colorado, School of Medicine, Aurora, Colorado, USA

    Jeffrey Brent

  2. FDA, Office of New Drugs/Immediate Office, Center for Drug Evaluation and Research, Silver Spring, Maryland, USA

    Keith Burkhart

  3. Clinical Toxicology, St Thomas’ Hospital, Silver Spring, Maryland, USA

    Paul Dargan

  4. Toxicology Associates, University of Colorado, School of Medicine, Denver, Colorado, USA

    Benjamin Hatten

  5. Medical Toxicological Intensive Care Unit, Lariboisiere Hospital, Paris-Diderot University, Paris, France

    Bruno Megarbane

  6. Toxicology Associates, University of Colorado, School of Medicine, Denver, Colorado, USA

    Robert Palmer

  7. Toxinology Department, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia

    Julian White

Grading System for Levels of Evidence Supporting Recommendations in Critical Care Toxicology, 2nd Edition

  1. I

    Evidence obtained from at least one properly randomized controlled trial.

  2. II-1

    Evidence obtained from well-designed controlled trials without randomization.

  3. II-2

    Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group.

  4. II-3

    Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.

  5. III

    Opinions of respected authorities, based on clinical experience, descriptive studies and case reports, or reports of expert committees.

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this entry

Cite this entry

Hieger, M.A., Rose, S.R. (2017). Folic and Folinic Acids. In: Brent, J., et al. Critical Care Toxicology. Springer, Cham. https://doi.org/10.1007/978-3-319-17900-1_163

Download citation

Publish with us

Policies and ethics

Search

Navigation