Vitamín B9 – kyselina listová

492879651
Obrázok: Freepik

Kyselina listová, syntetická forma folátu, je esenciálny vitamín B, ktorý je najznámejší pre svoju úlohu pri prevencii defektov neurálnej trubice u dojčiat. Zohráva tiež úlohu pri podpore celkového zdravia, ale vo veľkých množstvách môže byť škodlivý.

AKA
Folát, kyselina pteroyl L-glutamová

Zhrnutie

Folát je esenciálny vitamín, niekedy označovaný ako vitamín B9, ale bežnejšie známy ako syntetická doplnková forma „kyselina listová“. Kyselina listová sa v malých množstvách nachádza vo väčšine potravinových produktov rastlinného pôvodu a v niektorých krajinách sa pridáva do pšeničných zŕn čím dochádza k obohateniu pšeničných produktov. Kyselina listová zohráva dôležitú úlohu pri vývine plodu a novorodenca, ako aj u dospelých pri podpore procesu metylácie DNA.

Kyselina listová je známa predovšetkým ako „tehotenský doplnok“. Ženy, ktoré plánujú otehotnieť, užívajú 400 μg kyseliny listovej denne. To je rozhodujúce pri prevencii defektov neurálnej trubice (NTD), ktoré sú spôsobené nedostatočným prísunom folátu do plodu, v období keď sa formuje jeho nervová trubica. Kombináciou obohacovania potravy a suplementácie sa tieto vývinové defekty výrazne obmedzili.

Okrem toho sa folát a kyselina listová používajú na podporu metylácie v tele. Tieto dva doplnky sa v dôsledku eventuálneho vytvorenia molekuly známej ako 5-metyltetrahydrofolát (5-MTHF alebo L-metylfolát) podieľajú na nepriamej podpore a tvorbe S-adenosylmetionínu (SAMe) v tele. Z tohto dôvodu vykazujú do značnú podobnosť s doplnkami SAMe a niektoré paralely s doplnkami, ktoré tiež podporujú hladiny SAMe (napr. doplnky ako kreatín a trimetylglycín (TMG). Tieto paralely sú najlepšie demonštrované v ich účinkoch na depresiu, kde všetky podporujú antidepresíva na báze serotonínu (zvyčajne SSRI), pričom zvyčajne  prospievajú ženám viac ako mužom.

Napriek týmto výhodám sa ukazuje, že kyselina listová (na rozdiel od iných vitamínov B) má potenciálne vedľajšie účinky, keď sa užíva vo vysokých dávkach. Aj keď užívanie veľmi veľkej dávky kyseliny listovej niekoľko tisíc násobku odporúčanej dennej dávky (RDA) nespôsobí okamžité poškodenie, dlhodobé vystavenie hladinám až 250 % RDA môže byť spojené s relatívnym zvýšením výskytu rakoviny, najmä rakoviny hrubého čreva medzi staršími ľuďmi; dobre to bolo demonštrované akútnym zvýšením miery rakoviny hrubého čreva, keď Kanada aj USA zaviedli obohacovanie potravín týmto vitamínom (pričom obe ochorenia dovtedy klesali). Zdá sa, že spomedzi vitamínov B je práve folát tým, pri ktorom by ste sa mali snažiť o rovnováhu vo svojom každodennom živote a mali by ste sa vyhnúť doplnkovým zdrojom s vysokým obsahom folátu, ak vám ich neodporučil lekár.

Doplnky bývajú v jednej z troch foriem: folát, kyselina listová a L-metylfolát. Z týchto doplnkov je kyselina listová najbežnejšia, ale pri nadmernej konzumácii sa považuje za rizikovú. L-metylfolát sa javí ako najsľubnejší, pretože sa zdá, že mnoho ľudí má genetické mutácie v enzýme, ktorý produkuje L-metylfolát z folátu a kyseliny listovej, takže suplementáciou posledných dvoch si pomôžu iba čiastočne, zatiaľ čo dopĺňanie L-metylfolátu to môže obísť túto mutáciu obmedzujúcu rýchlosť produkcie L-metylfolátu. Okrem toho sa zdá, že L-metylfolát je najsľubnejším prostriedkom na podporu hladín SAMe, pretože SAMe ako doplnok je dosť drahý a táto cesta sa javí ako účinnejšia ako tá, pri ktorej sa užíva kreatín a TMG.

Ako užívať

Existuje niekoľko možností dopĺňania kyseliny listovej  v závislosti od toho, akú formu sa rozhodnete užívať:

  • Pri suplementácii folátu užite do 400 DFE (400 mcg folátu)
  • Pri suplementácii kyseliny listovej použite do 400 DFE (200 mcg sa užíva na lačno, 240 mcg, ak sa užíva s jedlom)
  • Pri suplementácii L-metylfolátu použite 400 mcg. Väčšina doplnkov obsahuje L-metylfolát v dávke 7,5 – 15 mg/deň, ale nie je jasné, či je to potrebné.

Pri pestrej vyváženej zdravej strave je dávka folátu alebo kyseliny listovej viac než dostatočná na udržanie dostatočných hladín všetkých metabolitov folátov. L-metylfolát je pre mnohých pravdepodobne nepotrebný, ale pre tých, ktorí majú podozrenie alebo vedia, že majú genetickú mutáciu v enzýme MTHFR, môže byť rozumné užívať L-metylfolát namiesto ostatných dvoch foriem, pretože sú menej účinné.

Literatúra

  1. Kawashima A, et al. Four week supplementation with mixed fruit and vegetable juice concentrates increased protective serum antioxidants and folate and decreased plasma homocysteine in Japanese subjects. Asia Pac J Clin Nutr. (2007)
  2. Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. (1992)
  3. Almeida OP, et al. B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial. Ann Neurol. (2010)
  4. Ford AH, et al. Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: results from a 2-year placebo-controlled randomized trial. J Clin Psychiatry. (2008)
  5. Christensen H, et al. No clear potentiation of antidepressant medication effects by folic acid+vitamin B12 in a large community sample. J Affect Disord. (2011)
  6. Ji HF, Tang GY, Zhang HY. A theoretical study on the structure-activity relationships of metabolites of folates as antioxidants and its implications for rational design of antioxidants. Bioorg Med Chem. (2005)
  7. Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. (2008)
  8. Florio R, et al. Serine hydroxymethyltransferase: a model enzyme for mechanistic, structural, and evolutionary studies. Biochim Biophys Acta. (2011)
  9. Bhargava S, Tyagi SC. Nutriepigenetic regulation by folate-homocysteine-methionine axis: a review. Mol Cell Biochem. (2014)
  10. Mato JM, et al. S-adenosylmethionine synthesis: molecular mechanisms and clinical implications. Pharmacol THer. (1997)
  11. Turner MA, et al. Structure and function of S-adenosylhomocysteine hydrolase. Cell Biochem Biophys. (2000)
  12. Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Institute of Medicine. (1998)
  13. Crider KS, Bailey LB, Berry RJ. Folic acid food fortification-its history, effect, concerns, and future directions. Nutrients. (2011)
  14. Craig GM, Elliot C, Hughes KR. Masked vitamin B12 and folate deficiency in the elderly. Br J Nutr. (1985)
  15. Ellison AB. Pernicious anemia masked by multivitamins containing folic acid. J Am Med Assoc. (1960)
  16. Allen RH, et al. Diagnosis of cobalamin deficiency I: usefulness of serum methylmalonic acid and total homocysteine concentrations. Am J Hematol. (1990)
  17. Crosby WH. The danger of folic acid in multivitamin preparations. Mil Med. (1960)
  18. Agamanolis DP, et al. Neuropathology of experimental vitamin B12 deficiency in monkeys. Neurology. (1976)
  19. Morris MS, et al. 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. (2007)
  20. Hunter R, et al. Toxicity of folic acid given in pharmacological doses to healthy volunteers. Lancet. (1970)
  21. Gibberd FB, et al. Toxicity of folic acid. Lancet. (1970)
  22. Hellström L. Lack of toxicity of folic acid given in pharmacological doses to healthy volunteers. Lancet. (1971)
  23. Richens A. Toxicity of folic acid. Lancet. (1971)
  24. Sheehy TW. Folic acid: lack of toxicity. Lancet. (1973)
  25. Suarez RM, Spies TD, Suarez RM Jr.. The use of folic acid in sprue. Ann Intern Med. (1947)
  26. Kelly P, et al. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr. (1997)
  27. Sweeney MR, McPartlin J, Scott J. Folic acid fortification and public health: report on threshold doses above which unmetabolised folic acid appear in serum. BMC Public Health. (2007)
  28. Troen AM et al.. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr. (2006)
  29. Morris MS, et al. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors. Am J Clin Nutr. (2010)
  30. Christensen KE et al.. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice. Am J Clin Nutr. (2015)
  31. Lok A et al.. The one-carbon-cycle and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in recurrent major depressive disorder; influence of antidepressant use and depressive state?. J Affect Disord. (2014)
  32. Wright AJ, Dainty JR, Finglas PM. Folic acid metabolism in human subjects revisited: potential implications for proposed mandatory folic acid fortification in the UK. Br J Nutr. (2007)
  33. Obeid R. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients. (2013)
  34. Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. (2015)
  35. Yan J et al.. MTHFR C677T genotype influences the isotopic enrichment of one-carbon metabolites in folate-compromised men consuming d9-choline. Am J Clin Nutr. (2011)
  36. Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidemiol. (2007)
  37. Rozen R. Molecular genetics of methylenetetrahydrofolate reductase deficiency. J Inherit Metab Dis. (1996)
  38. Lievers KJ et al.. A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk. J Mol Med (Berl). (2001)
  39. Goyette P, et al. Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. Am J Hum Genet. (1995)
  40. Goyette P, et al. Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR. Am J Hum Genet. (1996)
  41. Trembath D et al.. Analysis of select folate pathway genes, PAX3, and human T in a Midwestern neural tube defect population. Teratology. (1999)
  42. Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol. (2000)
  43. Vandana Rai, et al. Maternal Methylenetetrahydrofolate Reductase C677T Polymorphism and Down Syndrome Risk: A Meta-Analysis from 34 Studies. PLoS One. (2014)
  44. Sharp L, Little J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol. (2004)
  45. Bjelland I, et al. Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry. (2003)
  46. Lewis SJ, Ebrahim S, Davey Smith G. Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?. BMJ. (2005)
  47. David S Wald, Malcolm Law, and Joan K Morris. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. (2002)
  48. Robien K, Ulrich CM. 5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Leukemia Risk: A HuGE Minireview. Am J Epidemiol. (2003)
  49. Chandler CJ, Wang TT, Halsted CH. Pteroylpolyglutamate hydrolase from human jejunal brush borders. Purification and characterization. J Biol Chem. (1986)
  50. Strum WB. Enzymatic reduction and methylation of folate following pH-dependent, carrier-mediated transport in rat jejunum. Biochim Biophys Acta. (1979)
  51. Bhandari SD, Gregory JF 3rd. Folic acid, 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate exhibit equivalent intestinal absorption, metabolism and in vivo kinetics in rats. J Nutr. (1992)
  52. Clifford AJ, et al. The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid. Adv Exp Med Biol. (1998)
  53. Krumdieck CL, et al. A long-term study of the excretion of folate and pterins in a human subject after ingestion of 14C folic acid, with observations on the effect of diphenylhydantoin administration. Am J Clin Nutr. (1978)
  54. Rogers LM, et al. A dual-label stable-isotopic protocol is suitable for determination of folate bioavailability in humans: evaluation of urinary excretion and plasma folate kinetics of intravenous and oral doses of {13C5} and {2H2}folic acid. J Nutr. (1997)
  55. Steinberg SE, Campbell CL, Hillman RS. Kinetics of the normal folate enterohepatic cycle. J Clin Invest. (1979)
  56. Steinberg SE. Mechanisms of folate homeostasis. Am J Physiol. (1984)
  57. V. Michael Whitehead, et al. Intestinal Conversion of Folinic Acid to 5-Methyltetrahydrofolate in Man. Br J Haematol. (1972)
  58. Smith ME, Matty AJ, Blair JA. The transport of pteroylglutamic acid across the small intestine of the rat. Biochim Biophys Acta. (1970)
  59. Tani M, Iwai K. High-performance liquid chromatographic separation of physiological folate monoglutamate compounds. Investigation of absorption and conversion of pteroylglutamic acid in the small intestine of the rat in situ. J CHromatogr. (1983)
  60. Masters JN, Attardi G. The nucleotide sequence of the cDNA coding for the human dihydrofolic acid reductase. Gene. (1983)
  61. Obeid R, et al. Concentrations of unmetabolized folic acid and primary folate forms in plasma after folic acid treatment in older adults. Metabolism. (2011)
  62. Matherly LH, Hou Z, Deng Y. Human reduced folate carrier: translation of basic biology to cancer etiology and therapy. Cancer Metastasis Rev. (2007)
  63. Leamon CP, Jackman AL. Exploitation of the folate receptor in the management of cancer and inflammatory disease. Vitam Horm. (2008)
  64. Zhao R, et al. Mechanisms of membrane transport of folates into cells and across epithelia. Annu Rev Nutr. (2011)
  65. Zhao R, et al. Impact of the reduced folate carrier on the accumulation of active thiamin metabolites in murine leukemia cells. J Biol Chem. (2001)
  66. Zhao R, Matherly LH, Goldman ID. Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues. Expert Rev Mol Med. (2009)
  67. Whetstine JR, Flatley RM, Matherly LH. The human reduced folate carrier gene is ubiquitously and differentially expressed in normal human tissues: identification of seven non-coding exons and characterization of a novel promoter. Biochem J. (2002)
  68. Goldman ID, et al. The antifolates: evolution, new agents in the clinic, and how targeting delivery via specific membrane transporters is driving the development of a next generation of folate analogs. Curr Opin Investig Drugs. (2010)
  69. Said et al.. Adaptive regulation of intestinal folate uptake: effect of dietary folate deficiency. Am J Physiol Cell Physiol. (2000)
  70. Liu M et al.. Structure and regulation of the murine reduced folate carrier gene: identification of four noncoding exons and promoters and regulation by dietary folates. J Biol Chem. (2005)
  71. Kamen BA, Smith AK. A review of folate receptor alpha cycling and 5-methyltetrahydrofolate accumulation with an emphasis on cell models in vitro. Adv Drug Deliv Rev. (2004)
  72. Ross JF, et al. Folate receptor type beta is a neutrophilic lineage marker and is differentially expressed in myeloid leukemia. Cancer. (1999)
  73. Wang H, et al. Differentiation-independent retinoid induction of folate receptor type beta, a potential tumor target in myeloid leukemia. Blood. (2000)
  74. Yamaguchi T et al.. Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity. (20007)
  75. Shen F, et al. Folate receptor type gamma is primarily a secretory protein due to lack of an efficient signal for glycosylphosphatidylinositol modification: protein characterization and cell type specificity. Biochemistry. (1995)
  76. Piedrahita JA et al.. Mice lacking the folic acid-binding protein Folbp1 are defective in early embryonic development. Nat Genet. (1999)
  77. Qiu A et al.. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell. (2006)
  78. Wang Y, Zhao R, Goldman ID. Characterization of a folate transporter in HeLa cells with a low pH optimum and high affinity for pemetrexed distinct from the reduced folate carrier. Clin Cancer Res. (2004)
  79. Zhao R, et al. Selective preservation of pemetrexed pharmacological activity in HeLa cells lacking the reduced folate carrier: association with the presence of a secondary transport pathway. Cancer Res. (2004)
  80. Shayeghi M et al.. Identification of an intestinal heme transporter. Cell. (2005)
  81. Qiu A et al.. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell. (2006)
  82. Ormazabal A et al.. Determination of 5-methyltetrahydrofolate in cerebrospinal fluid of paediatric patients: reference values for a paediatric population. Clin Chim Acta. (2006)
  83. Reynolds EH, Mattson RH, Gallagher BB. Relationships between serum and cerebrospinal fluid anticonvulsant drug and folic acid concentrations in epileptic patients. Neurology. (1972)
  84. Wesson VA, Levitt AJ, Joffe RT. Change in folate status with antidepressant treatment. Psychiatry Res. (1994)
  85. Fava M, et al. Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry. (1997)
  86. Gilbody S, Lightfoot T, Sheldon T. Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity. J Epidemiol Community Health. (2007)
  87. Ginsberg LD, Oubre AY, Daoud YA. L-methylfolate Plus SSRI or SNRI from Treatment Initiation Compared to SSRI or SNRI Monotherapy in a Major Depressive Episode. Innov Clin Neurosci. (2011)
  88. Wollack JB et al.. Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model. J Neurochem. (2008)
  89. Serot JM, et al. CSF-folate levels are decreased in late-onset AD patients. J Neural Transm (Vienna). (2001)
  90. Moretti P et al.. Cerebral folate deficiency with developmental delay, autism, and response to folinic acid. Neurology. (2005)
  91. Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidemiol. (2007)
  92. Wu D, Pardridge WM. Blood-brain barrier transport of reduced folic acid. Pharm Res. (1999)
  93. Zhao et al.. The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption. Blood. (2007)
  94. Baxter MG, Miller AA, Webster RA. Some studies on the convulsant action of folic acid. Br J Pharmacol. (1973)
  95. Kehl SJ, McLennan H, Collingridge GL. Effects of folic and kainic acids on synaptic responses of hippocampal neurones. Neuroscience. (1984)
  96. Weller M, et al. The reduced unsubstituted pteroate moiety is required for folate toxicity of cultured cerebellar granule neurons. J Pharmacol Exp Ther. (1994)
  97. Olney JW, et al. Intrastriatal folic acid mimics the distant but not local brain damaging properties of kainic acid. Neurosci Lett. (1981)
  98. Selhub J, et al. Folate-vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency. Am J Clin Nutr. (2009)
  99. Quan FS, et al. Protective effects of folic acid against central nervous system neurotoxicity induced by lead exposure in rat pups. Genet Mol Res. (2015)
  100. Solon O, et al. Associations between cognitive function, blood lead concentration, and nutrition among children in the central Philippines.
  101. Lee MG, Chun OK, Song WO. Determinants of the blood lead level of US women of reproductive age. J Am Coll Nutr. (2005)
  102. Budni J et al.. Neurotoxicity induced by dexamethasone in the human neuroblastoma SH-SY5Y cell line can be prevented by folic acid. Neuroscience. (2011)
  103. Lin Y, et al. Group B vitamins protect murine cerebellar granule cells from glutamate/NMDA toxicity. Neuroreport. (2004)
  104. Yu HL, et al. Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by beta-amyloid 31-35. Br J Nutr. (2009)
  105. Tagliari B, et al. Hyperhomocysteinemia increases damage on brain slices exposed to in vitro model of oxygen and glucose deprivation: prevention by folic acid. Int J Dev Neurosci. (2006)
  106. Bjelland I, et al. Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry. (2003)
  107. Kelly CB et al.. The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland. J Psychopharmacol. (2004)
  108. Almeida OP, et al. Contribution of the MTHFR gene to the causal pathway for depression, anxiety and cognitive impairment in later life. Neurobiol Aging. (2005)
  109. Carney MW, Sheffield BF. Serum folic acid and B12 in 272 psychiatric in-patients. Psychol Med. (1978)
  110. Ramos MI, et al. Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification. Am J Clin Nutr. (2004)
  111. Sachdev PS, et al. Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Psychol Med. (2005)
  112. Tolmunen T et al.. Dietary folate and the risk of depression in Finnish middle-aged men. A prospective follow-up study. Psychother Psychosom. (2004)
  113. Papakostas GI et al.. The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine. Int J Neuropsychopharmacol. (2005)
  114. Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affect Disord. (2000)
  115. Passeri M et al.. Oral 5′-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study. Aging (Milano). (1993)
  116. Godfrey PS et al.. Enhancement of recovery from psychiatric illness by methylfolate. Lancet. (1990)
  117. Taylor MJ, et al. Folate for depressive disorders. Cochrane Database Syst Rev. (2003)
  118. Loria-Kohen V, et al. A pilot study of folic acid supplementation for improving homocysteine levels, cognitive and depressive status in eating disorders. Nutr Hosp. (2013)
  119. Venkatasubramanian R, Kumar CN, Pandey RS. A randomized double-blind comparison of fluoxetine augmentation by high and low dosage folic acid in patients with depressive episodes. J Affect Disord. (2013)
  120. Papakostas GI et al.. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry. (2012)
  121. Bedson E et al.. Folate Augmentation of Treatment–Evaluation for Depression (FolATED): randomised trial and economic evaluation. Health Technol Assess. (2014)
  122. Sharpley AL, et al. Folic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial. J Affect Disord. (2014)
  123. Moens AL, Kass DA. Tetrahydrobiopterin and cardiovascular disease. Arterioscler Thromb Vasc Biol. (2006)
  124. Naseem KM. The role of nitric oxide in cardiovascular diseases. Mol Aspects Med. (2005)
  125. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. (2015)
  126. Zhang M, et al. High‑dose folic acid improves endothelial function by increasing tetrahydrobiopterin and decreasing homocysteine levels. Mol Med Rep. (2014)
  127. Moat SJ et al.. High- but not low-dose folic acid improves endothelial function in coronary artery disease. Eur J Clin Invest. (2006)
  128. Low PS, Kularatne SA. Folate-targeted therapeutic and imaging agents for cancer. Curr Opin Chem Biol. (2009)
  129. Iyer SS et al.. Identification of novel markers for mouse CD4(+) T follicular helper cells. Eur J Immunol. (2013)
  130. Jia at el.. A novel splice variant of FR4 predominantly expressed in CD4+CD25+ regulatory T cells. Immunol Invest. (2009)
  131. Tian Y et al.. A novel splice variant of folate receptor 4 predominantly expressed in regulatory T cells.. BMC Immunol. (2012)
  132. Rogers EJ, Chen S, Chan A. Folate deficiency and plasma homocysteine during increased oxidative stress. N Engl J Med. (2007)
  133. Kruman II, et al. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci. (2000)
  134. Kruman II et al.. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer’s disease. J Neurosci. (2002)
  135. Guo X et al.. Protective Effect of Folic Acid on Oxidative DNA Damage: A Randomized, Double-Blind, and Placebo Controlled Clinical Trial. Medicine (Baltimore). (2015)
  136. Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2′ -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. (2009)
  137. Sutton M, Daly LE, Kirke PN. Survival and disability in a cohort of neural tube defect births in Dublin, Ireland. Birth Defects Res A Clin Mol Teratol. (2008)
  138. Hibbard BM, Hibbard ED, Jeffcoate TN. Folic acid and reproduction. Acta Obstet Gynecol Scand. (1965)
  139. NA. Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Recomm Rep. (1992)
  140. U.S. Preventive Services Task Force. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. (2009)
  141. Lewis AS. Rabbit brain purine nucleoside phosphorylase. Physical and chemical properties. Inhibition studies with aminopterin, folic acid and structurally related compounds. Arch Biochem Biophys. (1978)
  142. Hollinger JL, et al. In vitro studies of 5, 10-methylenetetrahydrofolate reductase: inhibition by folate derivatives, folate antagonists, and monoamine derivatives. J Neurochem. (1982)
  143. Baggott JE, Vaughn WH, Hudson BB. Inhibition of 5-aminoimidazole-4-carboxamide ribotide transformylase, adenosine deaminase and 5′-adenylate deaminase by polyglutamates of methotrexate and oxidized folates and by 5-aminoimidazole-4-carboxamide riboside and ribotide. Biochem J. (1986)
  144. Allegra CJ, et al. Inhibition of phosphoribosylaminoimidazolecarboxamide transformylase by methotrexate and dihydrofolic acid polyglutamates. Proc Natl Acad Sci U S A. (1985)
  145. Reeves PG. Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr. (1997)
  146. Hollinger JL, et al. In vitro studies of 5, 10-methylenetetrahydrofolate reductase: inhibition by folate derivatives, folate antagonists, and monoamine derivatives. J Neurochem. (1982)
  147. Farias N, et al. The effects of folic acid on global DNA methylation and colonosphere formation in colon cancer cell lines. J Nutr Biochem. (2015)
  148. Kim Yi. Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res. (2007)
  149. Giovannucci E. Epidemiologic studies of folate and colorectal neoplasia: a review. J Nutr. (2002)
  150. Bailey LB, Rampersaud GC, Kauwell GP. Folic acid supplements and fortification affect the risk for neural tube defects, vascular disease and cancer: evolving science. J Nutr. (2003)
  151. Choi JH, et al. Contemporary issues surrounding folic Acid fortification initiatives. Prev Nutr Food Sci. (2014)
  152. Giovannucci E, et al. Multivitamin use, folate, and colon cancer in women in the Nurses‘ Health Study. Ann Intern Med. (1998)
  153. Cole et al.. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. (2007)
  154. Hirsch S, et al. Colon cancer in Chile before and after the start of the flour fortification program with folic acid. Eur J Gastroenterol Hepatol. (2009)
  155. Mattson MP. Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev. (1997)
  156. Triantafyllou NI et al.. Folate and vitamin B12 levels in levodopa-treated Parkinson’s disease patients: their relationship to clinical manifestations, mood and cognition. Parkinsonism Relat Disord. (2008)
  157. Triantafyllou NI et al.. The influence of levodopa and the COMT inhibitor on serum vitamin B12 and folate levels in Parkinson’s disease patients. Eur Neurol. (2007)
  158. Zoccolella S et al.. Plasma homocysteine levels in Parkinson’s disease: role of antiparkinsonian medications. Parkinsonism Relat Disord. (2005)
  159. Lamberti P, et al. Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson’s disease patients. Mov Disord. (2005)
  160. Heikkinen H, et al. Entacapone improves the availability of L-dopa in plasma by decreasing its peripheral metabolism independent of L-dopa/carbidopa dose. Br J Clin Pharmacol. (2002)
  161. Naughton CA, et al. Folate absorption in alcoholic pigs: in vitro hydrolysis and transport at the intestinal brush border membrane. Am J Clin Nutr. (1989)
  162. Halsted CH, Robles EA, Mezey E. Intestinal malabsorption in folate-deficient alcoholics. Gastroenterology. (1973)
  163. Herbet V, Zalusky R, and Davidson CS. Correlation of folate deficiency with alcoholism and associated macrocytosis, anemia, and liver disease. Ann Intern Med. (1963)
  164. Halsted CH, et al. Metabolic interactions of alcohol and folate. J Nutr. (2002)
  165. Halsted C et al.. Decreased Jejunal Uptake of Labeled Folic Acid (3H-PGA) in Alcoholic Patients: Roles of Alcohol and Nutrition. NEJM. (1971)
  166. McMartin KE, et al. Study of dose-dependence and urinary folate excretion produced by ethanol in humans and rats. Alcohol Clin Exp Res. (1986)
  167. Russell RM et al.. Increased urinary excretion and prolonged turnover time of folic acid during ethanol ingestion. Am J Clin Nutr. (1983)
  168. Tamura T, Halsted CH. Folate turnover in chronically alcoholic monkeys. J Lab Clin Med. (1983)
  169. Lieber CS et al.. S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon. Hepatology. (1990)
  170. Lu SC, et al. Changes in methionine adenosyltransferase and S-adenosylmethionine homeostasis in alcoholic rat liver. Am J Physiol Gastrointest Liver Physiol. (2000)
  171. Mato JM et al.. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. (1999)
  172. Amilburu A, et al. Inhibition of intestinal absorption of 5-methyltetrahydrofolate by fluoxetine. J Phys Biochem. (2001)
  173. Butterworth CE Jr, Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr. (1989)
  174. van der Westhuyzen J, Metz J. Tissue S-adenosylmethionine levels in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced neuropathy. Br J Nutr. (1983)
  175. van der Westhuyzen J, Fernandes-Costa F, Metz J. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats : protection by methionine and aggravation by folates. Life Sci. (1982)

Medicínske upozornenie!

alergia antioxidanty ashwagandha autoimunita bacopa bezlepková diéta bolesť bylinky celiakia COVID-19 Crohnova choroba cvičenie deti dezinfekcia fajčenie flavonoidy ginko IBD infekčné choroby karnitín karotenoidy ketogénna diéta koenzým Q10 kofeín kosti kurkumín kĺby meta-analýza mozog mužské zdravie obezita omega-3 pamäť poznávacie funkcie probiotiká psoriáza selén stredomorská diéta terpény vitamín A vitamín C vitamín D vitamín E zelený čaj ženské zdravie