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Colegio de Medicina Interna de México.

2022, Número 3

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Med Int Mex 2022; 38 (3)


Beneficios del ácido folínico como terapia coadyuvante

Pérez-Arenas LU, Torres-Ortega H, Escamilla-Zúñiga M, Cota-Peimbert C, Mares-Martínez MJ

Idioma: Español
Referencias bibliográficas: 45
Paginas: 571-585
Archivo PDF: 261.90 Kb.


RESUMEN

El ácido folínico participa en la síntesis y reparación del ADN, por lo que es esencial para el metabolismo celular normal. Por consiguiente, la alteración de los folatos se relaciona con diversas enfermedades en distintos aparatos y sistemas. Se realizó la búsqueda de artículos originales y reportes de casos en el idioma inglés, publicados desde 2010 a 2020 en distintas bases de datos científicas. Se recopilaron 125 artículos, de los que se seleccionaron 45 con el objetivo de reunir y destacar los efectos benéficos del ácido folínico como terapia coadyuvante. Se describieron beneficios en áreas como neurología, psiquiatría, oncología, toxicología, infectología, dermatología, gastroenterología y genética. Tras la administración del ácido folínico se obtuvieron los siguientes beneficios: en pacientes autistas mejoraron las funciones cognitivo-conductuales, en sujetos con esquizofrenia se atenuaron los síntomas positivos y negativos y en pacientes epilépticos se controlaron las convulsiones. En pacientes con VIH aumentaron las concentraciones de folatos y se redujo la homocisteína sérica. Además, se estimuló la síntesis de metaloproteinasas y colágeno, promoviendo la cicatrización. En malabsorción de folatos hereditaria, se eliminaron los síntomas sistémicos y neurológicos; además, mejoró el desarrollo psicomotor y el cociente de desarrollo en pacientes con síndrome de Down. Por otra parte, se incrementó la tolerancia y eficacia de fármacos oncológicos. Disminuyeron la toxicidad neurológica, intestinal y ósea del metotrexato, así como la teratogénesis por lamotrigina. Por tanto, se concluyó que los beneficios de la administración del ácido folínico son amplios y evidentes en las enfermedades mencionadas.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Duman N, Duman R, Tosun M, Akıcı M, Göksel E, et al.Topical folinic acid enhances wound healing in rat model.Adv Med Sci 2018; 63 (2): 347-352. doi: 10.1016/j.advms.2018.04.011.

  2. Masingue M, Benoist JF, Roze E, Moussa F, Sedel F, LubetzkiC, Nadjar Y. Cerebral folate deficiency in adults: A heterogeneouspotentially treatable condition. J Neurol Sci 2019; 396: 112-118. doi: 10.1016/j.jns.2018.11.014.

  3. Banka S, Blom HJ, Walter J, Aziz M, Urquhart J, Clouthier, etal. Identification and characterization of an inborn error ofmetabolism caused by dihydrofolate reductase deficiency.Am J Hum Genet 2011; 88 (2): 216-225. doi: 10.1016/j.ajhg.2011.01.004.

  4. Wang S, Wang L, Zhou Z, Deng Q, Li L, Zhang M, et al.Leucovorin enhances the anti-cancer effect of bortezomibin colorectal cancer cells. Sci Rep 2017; 7 (1): 682. doi:10.1038/s41598-017-00839-9.

  5. Khalid BM, Munawar HM, Nauman SHM, Sye RNR, AkramA, Nasim F, et al. UV and visible spectrophotometricmethod for the determination of leucovorin. J Chem SocPak 2012; 34 (6): 1601-1604.

  6. Odin E, Sondén A, Carlsson G, Gustavsson B, Wettergren Y.Folate pathway genes linked to mitochondrial biogenesisand respiration are associated with outcome of patientswith stage III colorectal cancer. Tumour Biol 2019; 41 (6):1-10. doi: 10.1177/1010428319846231.

  7. Taflin H, Odin E, Derwinger K, Carlsson G, Gustavsson B,Wettergren Y. Relationship between folate concentrationand expression of folate-associated genes in tissue andplasma after intraoperative administration of leucovorin inpatients with colorectal cancer. Cancer Chemother Pharmacol2018; 82: 987-997. doi: 10.1007/s00280-018-3690-9.

  8. Cario H, Smith DEC, Blom H, Blau N, Bode H, Holzmann K, etal. Dihydrofolate reductase deficiency due to a homozygousDHFR mutation causes megaloblastic anemia and cerebralfolate deficiency leading to severe neurologic disease.Am J Hum Genet 2011; 88 (2): 226-231. doi: 10.1016/j.ajhg.2011.01.007.

  9. Tso W, Kwong AK, Fung CW, Wong VCN. Folinic acid responsiveepilepsy in ohtahara syndrome caused by STXBP1mutation. Pediatr Neurol 2014; 50 (2): 177-180. doi:

  10. 10.1016/j.pediatrneurol.2013.10.006.10. Dill P, Schneider J, Weber P, Trachsel D, Tekin M, Jakobs C,et al. Pyridoxal phosphate-responsive seizures in a patientwith cerebral folate deficiency (CFD) and congenital deafnesswith labyrinthine aplasia, microtia and microdontia(LAMM). Mol Genet Metab 2011; 104 (3): 362-368. doi:10.1016/j.ymgme.2011.05.019.

  11. Ramaekers VT, Thöny B, Sequeira JM, Ansseau M, PhilippeP, Boemer F, et al. Folinic acid treatment for schizophreniaassociated with folate receptor autoantibodies. MolGenet Metab 2014; 113 (4): 307-314. doi: 10.1016/j.ymgme.2014.10.002.

  12. Frye RE, Sequeira JM, Quadros EV, James SJ, RossignolDA. Cerebral folate receptor autoantibodies in autismspectrum disorder. Mol Psychiatry 2012; 18 (3): 369-381.doi: 10.1038/mp.2011.175.

  13. Ramaekers VT, Sequeira JM, DiDuca M, Vrancken G, ThomasA, Philippe C, et al. Improving outcome in infantile autismwith folate receptor autoimmunity and nutritional derangements:A self-controlled trial. Autism Res Treat 2019;2019: 1-12. doi: 10.1155/2019/7486431.

  14. Frye RE, Slattery J, Delhey L, Furgerson B, Strickland T, TippettM, et al. Folinic acid improves verbal communicationin children with autism and language impairment: a randomizeddouble-blind placebo-controlled trial. Mol Psychiatry2016; 23 (2): 247-256. doi: 10.1038/mp.2016.168.

  15. Batebi N, Moghaddam HS, Hasanzadeh A, Fakour Y, MohammadiMR, Akhondzadeh S. Folinic acid as adjunctivetherapy in treatment of inappropriate speech in childrenwith autism: a double-blind and placebo-controlled randomizedtrial. Child Psychiatry Hum Dev 2020. doi: 10.1007/s10578-020-01072-8.

  16. Adams JB, Audhya T, McDonough-Means S, Rubin RA, QuigD, Geis E, et al. Effect of a vitamin/mineral supplement onchildren and adults with autism. BMC Pediatr 2011; 11 (1):111. doi: 10.1186/1471-2431-11-111.

  17. Frye RE, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O,et al. Effectiveness of methylcobalamin and folinic acidtreatment on adaptive behavior in children with autisticdisorder is related to glutathione redox status. Autism ResTreat 2013; 2013: 1-9. doi: 10.1155/2013/609705.

  18. Adams JB, Audhya T, McDonough-Means S, Rubin RA, QuigD, Geis E, et al. Nutritional and metabolic status of childrenwith autism vs. neurotypical children, and the associationwith autism severity. Nutr Metab 2011; 8 (1): 34. doi:10.1186/1743-7075-8-34.

  19. Al-Baradie RS, Chudary MW. Diagnosis and management ofcerebral folate deficiency. A form of folinic acid-responsiveseizures. Neurosciences 2014; 19 (4): 312-316.

  20. Delmelle F, Thöny B, Clapuyt P, Blau N, Nassogne MC.Neurological improvement following intravenous highdosefolinic acid for cerebral folate transporter deficiencycaused by FOLR-1 mutation. Eur J Paediatr Neurol 2016; 20(5): 709-713. doi: 10.1016/j.ejpn.2016.05.021.

  21. Ferreira P, Luco SM, Sawyer SL, Davila J, Boycott KM, DymentDA. Late diagnosis of cerebral folate deficiency: Fewerseizures with folinic acid in adult siblings. Neurol Genet2015; 2 (1): e38. doi: 10.1212/NXG.0000000000000038.

  22. Liu Y, luan L, Xingli W. A randomized Phase ii clinical studyof combining panitumumab and bevacizumab, plus irinotecan,5-fluorouracil, and leucovorin (FOLFIRI) compared withFOlFiri alone as second-line treatment for patients withmetastatic colorectal cancer and Kras mutation. Onco TargetsTher 2015; (8): 1061-1068. doi: 10.2147/OTT.S81442.

  23. Tsujimoto H, Tsukioka S, Ono S, Sakamoto E, Sakamoto K,Tsuta K, et al. Effect of leucovorin on the antitumor efficacyof the 5-FU prodrug, tegafur-uracil, in human colorectalcancer xenografts with various expression levels of thymidylatesynthase. Oncol Lett 2010; 1 (6): 973-980. doi:10.3892/ol.2010.172.

  24. Liu W, Wang F, Zhu Y, Li X, Liu X, Pang J, Pan W. Galactosylatedchitosan-functionalized mesoporous silica nanoparticleloading by calcium leucovorin for colon cancer cell-targeteddrug delivery. Molecules 2018; 23 (12): 3082. doi: 10.3390/molecules23123082.

  25. Hong YS, Nam BH, Kim K, Kim JE, Park SJ, Park YS, et al.Oxaliplatin, fluorouracil, and leucovorin versus fluorouraciland leucovorin as adjuvant chemotherapy for locally advancedrectal cancer after preoperative chemoradiotherapy(ADORE): an open-label, multicentre, phase 2, randomisedcontrolled trial. Lancet Oncol 2014; 15 (11): 1245-53. doi:10.1016/S1470-2045(14)70377-8.

  26. Bano N, Najam R, Mateen A, Qazi F. High and low dosefolinic acid, 5-fluorouracil bolus and continuous infusionfor poor-prognosis patients with advanced colorectal carcinoma.Asian Pac J Cancer Prev 2012; 13 (8): 3589-3593.doi: 10.7314/apjcp.2012.13.8.3589.

  27. Fischer von Weikersthal L, Schalhorn A, Stauch M,Quietzsch D, Maubach PA, Lambertz H, et al. Phase III trialof irinotecan plus infusional 5-fluorouracil/folinic acidversus irinotecan plus oxaliplatin as first-line treatmentof advanced colorectal cancer. Eur J Cancer 2011; 47 (2):206-214. doi: 10.1016/j.ejca.2010.09.022.

  28. Oosterom N, Jonge R, Smith DEC, Pieters R, Tissing WJE,Fiocco M, et al. Changes in intracellular folate metabolismduring high-dose methotrexate and Leucovorin rescuetherapy in children with acute lymphoblastic leukemia.PloS One 2019; 14 (9): e0221591. doi: 10.1371/journal.pone.0221591.

  29. Reiss S, Buie L, Adel N, Goldman DA, Devlin SM, Douer D.Hypoalbuminemia is significantly associated with increasedclearance time of high dose methotrexate in patients beingtreated for lymphoma or leukemia. Ann Hematol 2016; 95(12): 2009-2015. doi: 10.1007/s00277-016-2795-7.

  30. Oosterom N, Fiocco M, Kloos RQH, van der Sluis IM, PietersR, van Zelst BD, et al. The evaluation of red blood cell folateand methotrexate levels during protocol M in childhoodacute lymphoblastic leukemia. BMC Cancer 2020; 20 (1):940. doi: 10.1186/s12885-020-07422-y.

  31. Ramamoorthy SK, Hephziba R. Acute renal failure posthigh dose methotrexate infusion successfully managedwith high dose folinic acid and high flux dialysis. Indian JHematol Blood Transfus 2013; 29 (2): 90-92. doi: 10.1007/s12288-011-0143-6.

  32. Ogushi N, Sasaki K, Shimoda M. Effects of leucovorin (folinicacid) in the methotrexate-treated rat brain. J Vet Med Sci2018; 80 (5): 760-765. doi: 10.1292/jvms.17-0666.

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

  34. Bonda-Shkedi E, Arush MWB, Kaplinsky C, Ash S, GoshenY, Yaniv I, Cohen I. The correlation between dose of folinicacid and neurotoxicity in children and adolescents treatedfor osteosarcoma with high-dose methotrexate (HDMTX). JPediatr Hematol Oncol 2013; 35 (4): 271-275. doi: 10.1097/MPH.0b013e31828c2da1.

  35. Huang X, Fang Q, Rao T, Zeng X, Tan Z, Chen L, et al. Leucovorinameliorated methotrexate induced intestinal toxicityvia modulation of the gut microbiota. Toxicol Appl Pharmacol2020; 391: 114900. doi: 10.1016/j.taap.2020.114900.

  36. Dombrowsky E, Jayaraman B, Narayan M, Barrett JS.Evaluating performance of a decision support system toimprove methotrexate pharmacotherapy in children andyoung adults with cancer. Ther Drug Monit 2011; 33 (1):99-107. doi: 10.1097/FTD.0b013e318203b41e.

  37. Raghu Nadhanan R, Fan CM, Su YW, Howe PRC, Xian CJ.Fish oil in comparison to folinic acid for protection againstadverse effects of methotrexate chemotherapy on bone. JOrthop Res 2013; 32 (4): 587-596. doi: 10.1002/jor.22565.

  38. Abdulrazzaq YM, Shafiullah M, Kochyl J, Padmanabhan R,Bastaki SMA. Ameliorative effects of supplemental folinicacid on lamotrigine-induce fetal malformations in themouse. Mol Cell Biochem 2018; 446 (1-2): 185-197. doi:10.1007/s11010-018-3285-0.

  39. Deopa B, Parakh M, Dara P, Payal V, Chordiya K, Panday A,et al. Effect of folic acid supplementation on seizure controlin epileptic children receiving long term antiepileptic therapy.Indian J Pediatr 2018; 85 (7): 493-497. doi: 10.1007/s12098-018-2608-1.

  40. Grigoletti SS, Guindani G, Moraes RS, Ribeiro JP, SprinzE. Short-term folinic acid supplementation improves vascularreactivity in HIV-infected individuals: A randomizedtrial. Nutrition 2013; 29 (6): 886-891. doi: 10.1016/j.nut.2013.01.015.

  41. Tan J, Li X, Guo Y, Xie K, Wang J, Ma J, Jiang L. Hereditaryfolate malabsorption with a novel mutation onSLC46A1. Medicine 2017; 96 (50): e8712. doi: 10.1097/MD.0000000000008712.

  42. Lubout C, Goorden S, Hurk KVD, Nynke BJ, KoningsbruggenSV, et al. Successful treatment of hereditary folate malabsorptionwith intramuscular folinic acid. Pediatr Neurol2020; 102: 62-66. doi: 10.1016/j.pediatrneurol.2019.06.009.

  43. Manea E, Gissen P, Pope S, Heales S, Batzios S. Role ofintramuscular levofolinate administration in the treatmentof hereditary folate malabsorption: report of three cases.JIMD Rep 2017; 39: 7-12. doi: 10.1007/8904_2017_39.

  44. Blehaut H, Mircher C, Ravel A, Conte M, Portzamparc V,Poret G, et al. Effect of leucovorin (folinic acid) on thedevelopmental quotient of children with Down’s syndrome(trisomy 21) and influence of thyroid status. Plos One 2010;5 (1): e8394. doi: 10.1371/journal.pone.0008394.

  45. Lott T, Doran E, Nguyen V, Tournay A, Head E, Gillen D.Down syndrome and dementia: a randomized, controlledtrial of antioxidant supplementation. Am J Med Genet A2011; 155 (8): 1939-1948. doi: 10.1002/ajmg.a.34114.




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