Folates: supplemental forms and therapeutic applications.

Folates function as a single carbon donor in the synthesis of serine from glycine, in the synthesis of nucleotides form purine precursors, indirectly in the synthesis of transfer RNA, and as a methyl donor to create methylcobalamin, which is used in the re-methylation of homocysteine to methionine. Oral folates are generally available in two supplemental forms, folic and folinic acid. Administration of folinic acid bypasses the deconjugation and reduction steps required for folic acid. Folinic acid also appears to be a more metabolically active form of folate, capable of boosting levels of the coenzyme forms of the vitamin in circumstances where folic acid has little to no effect. Therapeutically, folic acid can reduce homocysteine levels and the occurrence of neural tube defects, might play a role in preventing cervical dysplasia and protecting against neoplasia in ulcerative colitis, appears to be a rational aspect of a nutritional protocol to treat vitiligo, and can increase the resistance of the gingiva to local irritants, leading to a reduction in inflammation. Reports also indicate that neuropsychiatric diseases secondary to folate deficiency might include dementia, schizophrenia-like syndromes, insomnia, irritability, forgetfulness, endogenous depression, organic psychosis, peripheral neuropathy, myelopathy, and restless legs syndrome.

[1]  M. Fava,et al.  Nutrition and depression: the role of folate. , 2009, Nutrition reviews.

[2]  L. Juhlin,et al.  Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure. , 1997, Acta dermato-venereologica.

[3]  S. M. Razali,et al.  Reduced red-cell folate in mania. , 1997, Journal of affective disorders.

[4]  M. Fava,et al.  Folate, vitamin B12, and homocysteine in major depressive disorder. , 1997, The American journal of psychiatry.

[5]  L. Bailey,et al.  Bioavailability for humans of deuterium-labeled monoglutamyl and polyglutamyl folates is affected by selected foods. , 1996, The Journal of nutrition.

[6]  H. Savoia,et al.  The Significance of Subnormal Serum Vitamin B12 Concentration in Older People: A Case Control Study , 1996, Journal of the American Geriatrics Society.

[7]  F. Raucci,et al.  [Folic acid and cervix dysplasia]. , 1996, Minerva ginecologica.

[8]  J. Selhub,et al.  Plasma total homocysteine in healthy subjects: sex-specific relation with biological traits. , 1996, The American journal of clinical nutrition.

[9]  N R Campbell,et al.  How safe are folic acid supplements? , 1996, Archives of internal medicine.

[10]  H. Morrison,et al.  Serum folate and risk of fatal coronary heart disease. , 1996, JAMA.

[11]  W. Haefeli,et al.  Low whole-blood S-adenosylmethionine and correlation between 5-methyltetrahydrofolate and homocysteine in coronary artery disease. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[12]  C. Khoo,et al.  Dietary and serum folate: their influence on the outcome of pregnancy. , 1996, The American journal of clinical nutrition.

[13]  W. Willett,et al.  A prospective study of folate and vitamin B6 and risk of myocardial infarction in US physicians. , 1996, Journal of the American College of Nutrition.

[14]  B. Christensen [Folate deficiency, cancer and congenital abnormalities. Is there a connection?]. , 1996, Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke.

[15]  T. Basu,et al.  Folate and vitamin B12 status of the elderly. , 1996, European journal of clinical nutrition.

[16]  David P Miller,et al.  Hyperhomocysteinemia and low pyridoxal phosphate. Common and independent reversible risk factors for coronary artery disease. , 1995, Circulation.

[17]  D C Shields,et al.  A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects. , 1995, QJM : monthly journal of the Association of Physicians.

[18]  G. Omenn,et al.  A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. , 1995, JAMA.

[19]  S. Hunt,et al.  Higher plasma homocyst(e)ine and increased susceptibility to adverse effects of low folate in early familial coronary artery disease. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[20]  G. Shaw,et al.  PERICONCEPTIONAL VITAMIN USE, DIETARY FOLATE, AND THE OCCURRENCE OF NEURAL TUBE DEFECTS , 1995, Epidemiology.

[21]  A. Lindgren,et al.  Plasma homocysteine in acute myocardial infarction: homocysteine‐lowering effect of folic acid , 1995, Journal of internal medicine.

[22]  H. Blom,et al.  Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease , 1995, European journal of clinical investigation.

[23]  R. D'Agostino,et al.  Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. , 1995, The New England journal of medicine.

[24]  W. Vermaak,et al.  Vitamin requirements for the treatment of hyperhomocysteinemia in humans. , 1994, The Journal of nutrition.

[25]  R. Joffe,et al.  Change in folate status with antidepressant treatment , 1994, Psychiatry Research.

[26]  M. Levene,et al.  The methylfolate axis in neural tube defects: in vitro characterisation and clinical investigation. , 1994, Biochemical medicine and metabolic biology.

[27]  M. Shimoda,et al.  Pharmacokinetics and bioavailability of folic acid and plasma levels of bioactive folates after folic acid administration to pigs. , 1994, The Veterinary quarterly.

[28]  P. Bernardi,et al.  [Correlations between folic acid, human papilloma virus (HPV) and cervix neoplasms]. , 1994, Minerva ginecologica.

[29]  M. Seller,et al.  Investigation of folate intake and metabolism in women who have had two pregnancies complicated by neural tube defects , 1994, British journal of obstetrics and gynaecology.

[30]  H. Blom,et al.  Treatment of mild hyperhomocysteinemia in vascular disease patients. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[31]  R. Grio,et al.  Antineoblastic activity of antioxidant vitamins: the role of folic acid in the prevention of cervical dysplasia. , 1993, Panminerva medica.

[32]  M Macaluso,et al.  A case control study of nutritional factors and cervical dysplasia. , 1993, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[33]  P. Lundberg,et al.  Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[34]  G. Menke,et al.  [Pharmacokinetics and relative bioavailability of iron and folic acid in healthy volunteers]. , 1993, Arzneimittel-Forschung.

[35]  T. Sheldon,et al.  Investigation of factors influencing folate status in women who have had a neural tube defect‐affected infant , 1993, British journal of obstetrics and gynaecology.

[36]  S. Shapiro,et al.  Periconceptional folic acid exposure and risk of occurrent neural tube defects. , 1993, JAMA.

[37]  J. Cruysberg,et al.  Hyperhomocysteinemia in retinal artery and retinal vein occlusion. , 1993, American journal of ophthalmology.

[38]  D. Cucinotta,et al.  Oral 5′-methyltetrahydrofolic acid in senile organic mental disorders with depression: Results of a double-blind multicenter study , 1993, Aging.

[39]  A. Czeizel,et al.  Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. , 1992, The New England journal of medicine.

[40]  H. Hoffman,et al.  Maternal serum folate and zinc concentrations and their relationships to pregnancy outcome. , 1992, The American journal of clinical nutrition.

[41]  L. Montes,et al.  Folic acid and vitamin B12 in vitiligo: a nutritional approach. , 1992, Cutis.

[42]  L. Bailey,et al.  Relative bioavailability of deuterium-labeled monoglutamyl tetrahydrofolates and folic acid in human subjects. , 1992, The American journal of clinical nutrition.

[43]  H. Hoffman,et al.  Serum Folate and Fetal Growth Retardation: A Matter of Compliance? , 1992, Obstetrics and gynecology.

[44]  K. Hatch,et al.  Oral folic acid supplementation for cervical dysplasia: a clinical intervention trial. , 1992, American journal of obstetrics and gynecology.

[45]  K. Hatch,et al.  Folate deficiency and cervical dysplasia. , 1992, JAMA.

[46]  E. Fine,et al.  Myths about vitamin B12 deficiency. , 1991, Southern medical journal.

[47]  A. Clifford,et al.  Biological activity of racemic folate mixtures fed to folate-depleted rats. , 1991, The Journal of nutrition.

[48]  P. Revell,et al.  Folic acid absorption in patients infected with the human immunodeficiency virus , 1991, Journal of internal medicine.

[49]  A. Procter,et al.  Enhancement of Recovery from Psychiatric Illness by Methylfolate , 1991, British Journal of Psychiatry.

[50]  M. Gnant,et al.  Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study , 1991, The Lancet.

[51]  J. Culebras,et al.  [Folates in human nutrition, Different clinical situations in which folate deficiencies exist]. , 1991, Nutricion hospitalaria.

[52]  G. Gomez Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. , 1991, Gastroenterology.

[53]  W. Bottomley,et al.  The administration of folic acid to institutionalized epileptic adults with phenytoin-induced gingival hyperplasia. A double-blind, randomized, placebo-controlled, parallel study. , 1991, Oral surgery, oral medicine, and oral pathology.

[54]  F. Rabbia,et al.  [The calcium salt of folinic acid for the treatment of deficiency anemia]. , 1991, Minerva medica.

[55]  J. Collins,et al.  Effect of folic acid on recurrence of phenytoin-induced gingival overgrowth following gingivectomy. , 1991, Journal of clinical periodontology.

[56]  R. Schilsky,et al.  Clinical pharmacokinetics of high-dose leucovorin calcium after intravenous and oral administration. , 1990, Journal of the National Cancer Institute.

[57]  E. H. Reynolds,et al.  Enhancement of recovery from psychiatric illness by methylfolate , 1990, The Lancet.

[58]  M. Ferrari,et al.  [Folinic acid in the treatment of elderly patients with macrocytic anemia]. , 1990, La Clinica terapeutica.

[59]  R. G. Vergel,et al.  Primary prevention of neural tube defects with folic acid supplementation: Cuban experience , 1990, Prenatal diagnosis.

[60]  S. Young,et al.  Folic acid and psychopathology , 1989, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[61]  C. Halsted The intestinal absorption of dietary folates in health and disease. , 1989, Journal of the American College of Nutrition.

[62]  K J Rothman,et al.  Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects. , 1989, JAMA.

[63]  J. Zittoun,et al.  Pharmacokinetics of (-)-folinic acid after oral and intravenous administration of the racemate. , 1989, British journal of clinical pharmacology.

[64]  G. Su,et al.  Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. A case-control study. , 1989, Gastroenterology.

[65]  C. Butterworth,et al.  Folic acid safety and toxicity: a brief review. , 1989, The American journal of clinical nutrition.

[66]  A. Coppen,et al.  Serum and red blood cell folate in depression , 1989, Acta psychiatrica Scandinavica.

[67]  J. Heijbel,et al.  Folate treatment of diphenylhydantoin-induced gingival hyperplasia. , 1989, Scandinavian journal of dental research.

[68]  F. Stanley,et al.  Dietary folate as a risk factor for neural‐tube defects: evidence from a case‐control study in Western Australia , 1989, The Medical journal of Australia.

[69]  R. Russell,et al.  Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. , 1988, The Journal of laboratory and clinical medicine.

[70]  W. Molofsky,et al.  Effect of folate on phenytoin hyperplasia. , 1987, Journal of clinical periodontology.

[71]  M. Ferguson-Smith,et al.  Is disordered folate metabolism the basis for the genetic predisposition to neural tube defects? , 1987, Clinical genetics.

[72]  R. D. Steele,et al.  Modification of hepatic folate metabolism in rats fed excess retinol. , 1986, Life sciences.

[73]  D. Wilcken,et al.  Homocystinuria due to cystathionine beta-synthase deficiency--the effects of betaine treatment in pyridoxine-responsive patients. , 1985, Metabolism: clinical and experimental.

[74]  A. Pack Folate mouthwash: effects on established gingivitis in periodontal patients. , 1984, Journal of clinical periodontology.

[75]  R. Ferone,et al.  Folic acid does not inactivate xanthine oxidase. , 1984, The Journal of biological chemistry.

[76]  S. Purcell,et al.  Inhibition of mammalian xanthine oxidase by folate compounds and amethopterin. , 1984, The Journal of biological chemistry.

[77]  D. Wilcken,et al.  Homocystinuria--the effects of betaine in the treatment of patients not responsive to pyridoxine. , 1983, The New England journal of medicine.

[78]  A. Pack,et al.  Effects of extended systemic and topical folate supplementation on gingivitis of pregnancy. , 1982, Journal of clinical periodontology.

[79]  G. Boss,et al.  Failure of folic acid (pteroylglutamic acid) to affect hyperuricemia. , 1980, The Journal of laboratory and clinical medicine.

[80]  A. Pack,et al.  Effects of topical and systemic folic acid supplementation on gingivitis in pregnancy. , 1980, Journal of clinical periodontology.

[81]  M. Botez,et al.  Folic Acid in Neurology, Psychiatry and Internal Medicine , 1979, Psychological Medicine.

[82]  J. Gendre,et al.  [Folate and the nervous system (author's transl)]. , 1979, La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris.

[83]  L. Schneider,et al.  The effect of folic acid on gingival health. , 1976, Journal of periodontology.

[84]  R. Beaulieu,et al.  Neurologic disorders responsive to folic acid therapy. , 1976, Canadian Medical Association journal.

[85]  M. Botez Folate deficiency and neurological disorders in adults. , 1976, Medical hypotheses.

[86]  B. Cooper,et al.  Intestinal Conversion of Folinic Acid to 5‐Methyltetrahydrofolate in Man , 1972, British journal of haematology.

[87]  J. Pincus,et al.  Transport characteristics of folates in cerebrospinal fluid; a study utilizing doubly labeled 5-methyltetrahydrofolate and 5-formyltetrahydrofolate. , 1971, The Journal of clinical investigation.

[88]  A. Kwaśniewska,et al.  Folate deficiency and cervical intraepithelial neoplasia. , 1997, European journal of gynaecological oncology.

[89]  D. Seidner,et al.  The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. , 1997, Gastroenterology.

[90]  C. Stehouwer,et al.  Plasma homocysteine and severity of atherosclerosis in young patients with lower-limb atherosclerotic disease. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[91]  P. Frosst,et al.  Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. , 1996, American journal of human genetics.

[92]  P. Blot,et al.  Relationship between maternal folate status and foetal hypotrophy in a population with a good socio-economical level. , 1995, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[93]  L. Barbara,et al.  Evaluation of oral administration of folic and folinic acid to prevent folate deficiency in patients with inflammatory bowel disease treated with salicylazosulfapyridine. , 1988, International journal of clinical pharmacology research.

[94]  Lee Pt,et al.  Pharmacokinetics of leucovorin calcium after intravenous, intramuscular, and oral administration. , 1988 .

[95]  E. Stokstad,et al.  Pharmacokinetics of leucovorin calcium after intravenous, intramuscular, and oral administration. , 1988, Clinical pharmacy.

[96]  N. Geller,et al.  Systemic absorption of a leucovorin mouth wash: a pharmacologic study. , 1987, Cancer investigation.

[97]  Stokstad El,et al.  Absorption kinetics of orally administered leucovorin calcium. , 1987, NCI monographs : a publication of the National Cancer Institute.

[98]  A. Coppen,et al.  Folic acid enhances lithium prophylaxis. , 1986, Journal of affective disorders.

[99]  K. Hatch,et al.  Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. , 1982, The American journal of clinical nutrition.

[100]  G. Potier de Courcy,et al.  Effects of diets with or without folic acid, with or without methionine, on fetus development, folate stores and folic acid-dependent enzyme activities in the rat. , 1981, Biology of the neonate.

[101]  M. Botez,et al.  Relapsing Neuropathy, Cerebral Atrophy and Folate Deficiency , 1979 .

[102]  M. Botez,et al.  Relapsing neuropathy, cerebral atrophy and folate deficiency. A close association. , 1979, Applied neurophysiology.

[103]  J. Bachevalier,et al.  Folate-responsive neurological and mental disorders: report of 16 cases. Neuropsychological correlates of computerized transaxial tomography and radionuclide cisternography in folic acid deficiencies. , 1977, European neurology.

[104]  L. Sullivan Chapter 8 – Folates in Human Nutrition , 1967 .