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Ácido fólico


¿Qué es?

El ácido fólico es una vitamina B hidrosoluble. Desde 1998, a requerimiento del gobierno federal, se ha agregado a los cereales fríos, a la harina, al pan, a los fideos, a los productos de panadería, a las galletas dulces y a las galletas saladas. Los alimentos ricos en ácido fólico incluyen las hortalizas de hojas verdes (como la espinaca, el brócoli y la lechuga), la ocra, los espárragos, las frutas (como los plátanos, los melones, y los limones), los frijoles o porotos, la levadura, las callampas, la carne (como el hígado de vacuno y los riñones), el jugo de naranja y el jugo de tomates.

El ácido fólico se utiliza tanto para la prevención y el tratamiento de los bajos niveles de ácido fólico (deficiencia de ácido fólico) como para las complicaciones que resultan, incluyendo la “sangre cansada” (anemia) y la inhabilidad del intestino de absorber los nutrientes de manera apropiada. El ácido fólico también se usa para otras afecciones comúnmente asociadas con la deficiencia de ácido fólico, incluyendo la colitis ulcerosa, la enfermedad del hígado, el alcoholismo y la diálisis renal.

Las mujeres que están embarazadas o podrían quedar embarazadas toman ácido fólico para prevenir un aborto involuntario y los “defectos del tubo neural,” defectos de nacimiento tal como la espina bífida que ocurre cuando algunos arcos vertebrales del feto no se han fusionado correctamente durante la gestación.

Algunas personas usan el ácido fólico para prevenir el cáncer de colon o el cáncer cervical. Se utiliza también para prevenir las enfermedades del corazón y los derrames cerebrales, y para reducir los niveles de una sustancia química llamada homocisteína. Altos niveles de homocisteína pueden ser un factor de riesgo para las enfermedades del corazón.

El ácido fólico se usa para la pérdida de la memoria, la enfermedad de Alzheimer, la pérdida de audición relacionada con la edad, para prevenir la enfermedad ocular llamada degeneración macular relacionada con la edad (AMD), para reducir los signos de envejecimiento, para la debilidad de los huesos (osteoporosis), para el movimiento incontrolable de las piernas (el síndrome de las piernas inquietas), para los problemas para dormir, para la depresión, los dolores de los nervios, los dolores musculares, el SIDA, para una enfermedad de la piel llamada vitiligo y para una enfermedad hereditaria llamada el síndrome X Frágil. También se utiliza para disminuir los efectos dañinos del tratamiento con los medicamentos lometrexol y metotrexato.

Algunas personas aplican el ácido fólico directamente sobre las encías para tratar las infecciones de las encías.

El ácido fólico se usa en combinación con otras vitaminas B.

¿Qué tan efectivo es?

Natural Medicines Comprehensive Database (La Base Exhaustiva de Datos de Medicamentos Naturales) clasifica la eficacia, basada en evidencia científica, de acuerdo a la siguiente escala: Eficaz, Probablemente Eficaz, Posiblemente Eficaz, Posiblemente Ineficaz, Probablemente Ineficaz, Ineficaz, e Insuficiente Evidencia para Hacer una Determinación.

La clasificación de la eficacia para este producto es la siguiente:

Eficaz para...

  • El tratamiento y la prevención de la deficiencia de ácido fólico.

Probablemente eficaz para...

  • Bajar los niveles de homocisteina en las personas con enfermedad renal. Alrededor de un 85% de las personas con enfermedad renal grave tienen altos niveles de homocisteína. Altos niveles de homocisteína han sido vinculados con enfermedades cardíacas y derrames cerebrales. El tomar ácido fólico baja los niveles de homocisteína en las personas con enfermedad renal grave.
  • Bajar los niveles de homocisteína en las personas con grandes cantidades de homocisteína en la sangre (“hiperhomocisteinemia”). Altos niveles de homocisteína han sido vinculados con enfermedades cardíacas y derrames cerebrales.
  • Disminuir los efectos dañinos de un medicamento llamado metotrexato, el que se usa a veces en el tratamiento de la artritis reumática y la psoriasis. El tomar ácido fólico parece reducir la nausea y los vómitos que son los posibles efectos secundarios del tratamiento con el metotrexato.
  • Disminuir el riesgo de algunos defectos de nacimiento (defectos del tubo neural) cuando se toma por las mujeres embarazadas.

Posiblemente eficaz para...

  • Reducir el riesgo de contraer cáncer del colon y recto. El obtener más ácido fólico de la dieta y suplementos parece disminuir las probabilidades de desarrollar cáncer del colon, pero no parece ayudar a aquellos que ya tienen cáncer.
  • Reducir el riesgo de cáncer de mamas. El beneficio es mayor si las mujeres, además del ácido fólico, consumen extra vitamina B12 y vitamina B6 en la dieta.
  • La depresión, cuando se usa con los medicamentos antidepresivos convencionales. Algunas investigaciones sugieren que el ácido fólico por si solo no ayuda para la depresión.
  • El tratamiento de una enfermedad de la piel llamada vitiligo.
  • Los problemas a las encías debidos al uso de un medicamento llamado fenitoina, cuando se aplica a las encías.
  • El tratamiento de enfermedades de las encías durante el embarazo, cuando se usa como un enjuague bucal.
  • Reducir el riesgo de cáncer pancreático.
  • La degeneración macular. Algunas investigaciones muestran que el tomar ácido fólico con otras vitaminas, incluyendo vitamina B6 y vitamina B12 podría ayudar a prevenir la enfermedad de los ojos llamada degeneración macular relacionada con la edad.

Posiblemente ineficaz para...

  • Reducir el riesgo de ataque al corazón, derrame cerebral y otras condiciones relacionadas en aquellas personas con enfermedad coronaria.
  • Reducir la posibilidad de otro derrame cerebral.
  • Reducir los efectos dañinos de un medicamento llamado lometrexol.
  • El síndrome de fatiga crónica.

Probablemente ineficaz para...

  • El tratamiento de una enfermedad hereditaria llamada síndrome X Frágil.

Insuficiente evidencia para hacer una determinación para...

  • Prevenir que se vuelvan a obstruir los vasos sanguíneos después de una angioplastia, un procedimiento que se usa para abrir un vaso sanguíneo que está cerrado. El tomar ácido fólico más vitamina B6 y vitamina B12 podría de hecho interferir con la curación en los casos en que un dispositivo (stent) se inserta en el vaso sanguíneo para mantenerlo abierto.
  • La enfermedad de Alzheimer. Cierta evidencia sugiere que la gente anciana que ingiere más ácido fólico que la ingesta diaria recomendada (RDA) parece tener un menor riesgo de desarrollar la enfermedad de Alzheimer que las personas que consumen menos ácido fólico.
  • La memoria y la agilidad mental en las personas de más edad. Hay evidencia conflictiva sobre el rol del ácido fólico en la disminución de la memoria con la edad y la agilidad mental.
  • Prevenir el cáncer cervical. Hay cierta evidencia que indica que aumentando la ingesta de ácido fólico ya sea en la dieta o en forma de suplementos y tomando además tiamina, riboflavina y vitamina B12 podría ayudar a prevenir el cáncer cervical.
  • La infertilidad masculina. Algunas investigaciones sugieren que el tomar diariamente ácido fólico y sulfato de zinc puede aumentar el recuento de espermas en los hombres que tienen una cantidad baja de espermas.
  • El cáncer del pulmón. No parece haber una relación entre los niveles bajos de ácido fólico y el cáncer del pulmón.
  • El síndrome de las piernas inquietas. El tomar ácido fólico parece reducir los síntomas. Los investigadores están estudiando si es posible que una deficiencia de ácido fólico produce el síndrome de las piernas inquietas.
  • El cáncer debido a una enfermedad llamada colitis ulcerosa. El tomar ácido fólico podría ayudar a evitar que las personas con colitis ulcerosa contraigan cáncer.
  • La enfermedad hepática.
  • El alcoholismo.
  • La pérdida de audición con el avance de la edad.
  • La enfermedad de células falciformes.
  • La debilidad de los huesos (osteoporosis).
  • Otras afecciones.
Se necesita más evidencia para aprobar al ácido fólico para estos usos.

¿Cómo funciona?

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El ácido fólico ese necesario para el desarrollo normal del cuerpo humano. Está involucrado en la producción del material genético llamado ADN y participa en numerosas funciones corporales.

¿Hay preocupación por la seguridad de su uso?

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El ácido fólico es PROBABLEMENTE SEGURO para la mayoría de las personas. La mayoría de los adultos no sufren efectos secundarios si consumen 400 mcg al dia, la cantidad recomendada. No tome más de 400 mcg por día a menos que se lo recomiende su proveedor de atención médica.

Altas dosis de ácido fólico podrían producir calambres abdominales, diarrea, erupciones, trastornos del sueño, irritabilidad, confusión, nausea, molestias estomacales, cambios en el comportamiento, reacciones en la piel, convulsiones, gas, excitabilidad y otros efectos secundarios.

Investigaciones preliminares sugieren que el ácido fólico podría aumentar el riesgo de un ataque al corazón en las personas que tienen problemas cardiacos. Otras investigaciones preliminares sugieren que dosis altas de ácido fólico podrían aumentar el riesgo de cáncer. Hay también la preocupación de que el tomar grandes cantidades de una multivitamina además de un suplemento de ácido fólico podría aumentar las posibilidades de desarrollar cáncer de la próstata en los hombres.

Advertencias y precauciones especiales:

Cuando se usa en las cantidades recomendadas el ácido fólico es PROBABLEMENTE SEGURO para las mujeres embarazadas o amamantando. Para las mujeres embarazadas, se recomiendan de 300-400 mcg por día para prevenir los defectos del tubo neural en los bebés.

Anemia: El ácido fólico puede enmascarar los síntomas de una condición llamada anemia perniciosa (deficiencia de vitamina B12). Esto puede impedir que reciba el tratamiento adecuado con vitamina B12 y resultar en daño de los nervios. Si piensa que tiene algún tipo de anemia, no tome ácido fólico. Es necesario identificar el tipo de anemia que tiene.

Convulsiones: El ácido fólico, especialmente en cantidades altas (sobre 1000 mcg) podría desencadenar convulsiones en las personas que tienden a tener convulsiones. No use más ácido fólico que las cantidades recomendadas.

Enfermedades del corazón: En las personas que tienen enfermedades del corazón el tomar ácido fólico junto con vitamina B6 podría aumentar las posibilidades de sufrir un ataque al corazón. Hasta que no se tenga más información y tiene problemas cardiacos, evite tomar ácido fólico en dosis mayores que la cantidad diaria recomendada. Si además tiene deficiencia de ácido fólico, el consumo de suplementos de ácido fólico debe ser supervisado por su proveedor de atención médica.

Cáncer: Grandes dosis de ácido fólico podría aumentar el riesgo de tener cáncer. Si alguna vez ha tenido cáncer, evite tomar dosis diarias de ácido fólico más altas que las recomendadas hasta que no se tenga más información al respecto.

¿Existen interacciones con medicamentos?

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Moderadas

Tenga cuidado con esta combinación

5-Fluorouracil
Hay preocupación de que el tomar grandes cantidades de ácido fólico con 5-fluorouracil podría aumentar los efectos secundarios del 5-fluorouracil, especialmente los problemas estomacales. Antes de tomar ácido fólico, converse con su proveedor de atención médica.

Capecitabine (Xeloda)
Hay preocupación de que el tomar grandes cantidades de ácido fólico podría aumentar los efectos secundarios de capecitabine, especialmente los problemas estomacales como la diarrea y los vómitos. Antes de tomar ácido fólico, converse con su proveedor de atención médica.

Fenitoina (Dilantin)
El cuerpo descompone la fenitoina (Dilantin) para eliminarla. El ácido fólico puede aumentar la rapidez con que el cuerpo descompone la fenitoina (Dilantin). El tomar ácido fólico y fenitoina (Dilantin) podría disminuir la eficacia de la fenitoina (Dilantin) y aumentar las posibilidades de tener convulsiones.

Fenobarbital (Luminal)
El fenobarbital (Luminal) se usa para prevenir las convulsiones. El tomar ácido fólico puede disminuir lo bien que funciona el fenobarbital (Luminal) para prevenir las convulsiones.

Fosfenitoina (Cerebyx)
La fosfenitoina (Cerebyx) se usa para prevenir las convulsiones. El cuerpo descompone la fosfenitoina (Cerebyx) para eliminarla. El ácido fólico puede aumentar la rapidez con que el cuerpo descompone la fosfenitoina (Cerebyx). El tomar ácido fólico junto con fosfenitoina (Cerebyx) podría disminuir la eficacia de la fosfenitoina (Cerebyx) para prevenir las convulsiones.

Metotrexato (MTX, Rheumatrex)
El metotrexato (MTX, Rheumatrex) funciona disminuyendo los efectos del ácido fólico en las células del cuerpo. El tomar tabletas de ácido fólico junto con metotrexato podría disminuir la eficacia del metotrexato (MTX, Rheumatrex).

Pirimetamina (Daraprim)
La pirimetamina (Daraprim) se usa para el tratamiento de las infecciones con parásitos. El ácido fólico podría disminuir la eficacia de pirimetamina (Daraprim) para el tratamiento de las infecciones con parásitos.

Primidona (Mysoline)
La primidona (Mysoline) se usa para prevenir las convulsiones. El ácido fólico podría producir convulsiones en algunas personas. El tomar ácido fólico junto con primidona (Mysoline) podría disminuir lo bien que funciona la primidona para prevenir las convulsiones.

¿Existen interacciones con hierbas y suplementos?

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Té verde
Hay un poco de preocupación de que el té verde podría interferir con el funcionamiento del ácido fólico en el cuerpo. Esto podría llevar a una condición que es similar a la deficiencia de ácido fólico.

¿Existen interacciones con alimentos?

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Alimentos
El tomar ácido fólico junto con alimentos reduce en forma leve su absorción, pero probablemente no lo suficiente para que sea importante.

Zinc
Los investigadores no están de acuerdo si el ácido fólico interfiere o no con la absorción de zinc. Pero para las personas que obtienen suficiente zinc en la dieta, el efecto del ácido fólico probablemente no es importante.

¿Qué dosis se utiliza?

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Las siguientes dosis han sido estudiadas en investigaciones científicas:

POR VIA ORAL:
  • Para la deficiencia de ácido fólico: la dosis típica es de 250-1000 mcg (microgramos) por día.
  • Para la prevención de defectos del tubo neural: las mujeres que pueden quedar embarazadas deben tomar por lo menos 400 mcg de ácido fólico por día, ya sea de suplementos o alimentos fortificados, y continuar por el primer mes de embarazo. Las mujeres con un historial de embarazos previos con complicaciones por defectos del tubo neural generalmente toman 4 mg por día empezando un mes antes de quedar embarazadas y continuando por 3 meses.
  • Para disminuir el riesgo de cáncer del colon: 400 mcg por día.
  • Para el tratamiento de niveles elevados de homocisteína en la sangre:
    • Se ha usado 0.5-5 mg (miligramos) por día, pero parece que 0.8-1 mg por día es más efectivo.
    • En las personas con enfermedad renal terminal, los niveles altos de homocisteína son más difíciles de tratar, y se han usado dosis de 0.8-15 mg por día. También se han usado dosis de 2.5-5 mg tres veces a la semana. Las dosis mayores de 15 mg no parecen ser más eficaces.
  • Para mejorar la respuesta a los medicamentos para la depresión: se ha usado 200-500 mcg diarios.
  • Para el vitiligo: típicamente se toma 5 mg dos veces al día.
  • Para la reducción de la toxicidad asociada con la terapia con metotrexato para la artritis reumática o para la psoriasis: 1 mg al día es probablemente suficiente, pero se puede usar hasta 5 mg por día.
  • Para prevenir la degeneración macular: se toma 2.5 mg de ácido fólico, 1000 mcg de vitamina B12 (cianocobalamina) y 50 mg de vitamina B6 (piridoxina) una vez al día.
La ingesta adecuada (AI) para los infantes son 65 mcg para los infantes de 0-6 meses y 80 mcg para los infantes de 7-12 meses de edad. La ingesta diaria recomendada (RDA) para el folato en DFE ( equivalente dietético de folato), incluyendo tanto el folato como el ácido fólico de los alimentos enriquecidos y de los suplementos es: Para los niños de 1-3 años, 150 mg; Para los niños de 4-8 años, 200 mcg; Para los niños de 9-13 años 300 mcg. Para los adultos mayores de 13 años, 400 mcg; Para las mujeres embarazada 600 mcg; Para las mujeres amamantando, 500 mcg. El nivel máximo tolerable (UL) de folato es de 300 mcg para los niños de 1-3 años, 400 mcg para los niños de 4-8 años, 600 mcg para los niños de 9-13 años, 800 mcg para los adolescentes de 14-18 años, y 1000 mcg para todos los mayores de 18 años.

Otros nombres

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5'-methyltetrahydrofolate, 5'-MTHF, Acide Folique, Acide Ptéroylglutamique, Acide Ptéroylmonoglutamique, B Complex Vitamin, Complexe de Vitamines B, Complexe Vitaminique B, Dihydrofolate, Folacin, Folacine, Folate, Folinic Acid, L-methylfolate, Methylfolate, Méthylfolate, Pteroylglutamic Acid, Pteroylmonoglutamic Acid, Pteroylpolyglutamate, Tetrahydrofolate, Tétrahydrofolate, Vitamin B9, Vitamine B9.

Metodología

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Para saber más sobre cómo este artículo fue escrito, refiérase a la metodología metodología (http://www.nlm.nih.gov/medlineplus/spanish/druginfo/natural/methodology-sp.html) de la Base exhaustiva de datos de medicamentos naturales.

Referencias

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Para ver todas las referencias de la página de Ácido fólico, por favor diríjase a http://www.nlm.nih.gov/medlineplus/spanish/druginfo/natural/1017.html.
  1. Marti-Carvajal, A. J., Sola, I., Lathyris, D., Karakitsiou, D. E., and Simancas-Racines, D. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane.Database.Syst.Rev. 2013;1:CD006612. View abstract.
  2. Thomson, M. E. and Pack, A. R. Effects of extended systemic and topical folate supplementation on gingivitis of pregnancy. J Clin Periodontol. 1982;9:275-280. View abstract.
  3. Froster-Iskenius, U., Bodeker, K., Oepen, T., Matthes, R., Piper, U., and Schwinger, E. Folic acid treatment in males and females with fragile-(X)-syndrome. Am J Med Genet. 1986;23(1-2):273-289. View abstract.
  4. Coppen, A., Chaudhry, S., and Swade, C. Folic acid enhances lithium prophylaxis. J.Affect.Disord. 1986;10:9-13. View abstract.
  5. Yang, H. T., Lee, M., Hong, K. S., Ovbiagele, B., and Saver, J. L. Efficacy of folic acid supplementation in cardiovascular disease prevention: an updated meta-analysis of randomized controlled trials. Eur.J.Intern.Med. 2012;23:745-754. View abstract.
  6. Castillo, L., Tur, J. A., and Uauy, R. [Folate and breast cancer risk: a systematic review]. Rev.Med.Chil. 2012;140:251-260. View abstract.
  7. Sudchada, P., Saokaew, S., Sridetch, S., Incampa, S., Jaiyen, S., and Khaithong, W. Effect of folic acid supplementation on plasma total homocysteine levels and glycemic control in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2012;98:151-158. View abstract.
  8. Jardine, M. J., Kang, A., Zoungas, S., Navaneethan, S. D., Ninomiya, T., Nigwekar, S. U., Gallagher, M. P., Cass, A., Strippoli, G., and Perkovic, V. The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: systematic review and meta-analysis. BMJ 2012;344:e3533. View abstract.
  9. Huo, Y., Qin, X., Wang, J., Sun, N., Zeng, Q., Xu, X., Liu, L., Xu, X., and Wang, X. Efficacy of folic acid supplementation in stroke prevention: new insight from a meta-analysis. Int.J.Clin Pract. 2012;66:544-551. View abstract.
  10. Castillo, Lancellotti C., Tur Mari, J. A., and Uauy, Dagach R. [Effect of folate and related nutrients on cognitive function in older people; systematic review]. Nutr.Hosp. 2012;27:90-102. View abstract.
  1. Castillo-Lancellotti, C., Tur Mari, J. A., and Uauy, Dagach R. [Folic acid supplementation and colorrectal adenoma recurrence: systematic review]. Nutr.Hosp. 2012;27:13-21. View abstract.
  2. Pan, Y., Guo, L. L., Cai, L. L., Zhu, X. J., Shu, J. L., Liu, X. L., and Jin, H. M. Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials. Br.J.Nutr. 2012;108:400-407. View abstract.
  3. Ford, A. H. and Almeida, O. P. Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. J.Alzheimers.Dis. 2012;29:133-149. View abstract.
  4. Qin, X., Xu, M., Zhang, Y., Li, J., Xu, X., Wang, X., Xu, X., and Huo, Y. Effect of folic acid supplementation on the progression of carotid intima-media thickness: a meta-analysis of randomized controlled trials. Atherosclerosis 2012;222:307-313. View abstract.
  5. Bao, Y., Michaud, D. S., Spiegelman, D., Albanes, D., Anderson, K. E., Bernstein, L., van den Brandt, P. A., English, D. R., Freudenheim, J. L., Fuchs, C. S., Giles, G. G., Giovannucci, E., Goldbohm, R. A., Hakansson, N., Horn-Ross, P. L., Jacobs, E. J., Kitahara, C. M., Marshall, J. R., Miller, A. B., Robien, K., Rohan, T. E., Schatzkin, A., Stevens, V. L., Stolzenberg-Solomon, R. Z., Virtamo, J., Wolk, A., Ziegler, R. G., and Smith-Warner, S. A. Folate intake and risk of pancreatic cancer: pooled analysis of prospective cohort studies. J.Natl.Cancer Inst. 12-21-2011;103:1840-1850. View abstract.
  6. Zhou, Y. H., Tang, J. Y., Wu, M. J., Lu, J., Wei, X., Qin, Y. Y., Wang, C., Xu, J. F., and He, J. Effect of folic acid supplementation on cardiovascular outcomes: a systematic review and meta-analysis. PLoS.One. 2011;6:e25142. View abstract.
  7. Holmes, M. V., Newcombe, P., Hubacek, J. A., Sofat, R., Ricketts, S. L., Cooper, J., Breteler, M. M., Bautista, L. E., Sharma, P., Whittaker, J. C., Smeeth, L., Fowkes, F. G., Algra, A., Shmeleva, V., Szolnoki, Z., Roest, M., Linnebank, M., Zacho, J., Nalls, M. A., Singleton, A. B., Ferrucci, L., Hardy, J., Worrall, B. B., Rich, S. S., Matarin, M., Norman, P. E., Flicker, L., Almeida, O. P., van Bockxmeer, F. M., Shimokata, H., Khaw, K. T., Wareham, N. J., Bobak, M., Sterne, J. A., Smith, G. D., Talmud, P. J., van, Duijn C., Humphries, S. E., Price, J. F., Ebrahim, S., Lawlor, D. A., Hankey, G. J., Meschia, J. F., Sandhu, M. S., Hingorani, A. D., and Casas, J. P. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet 8-13-2011;378:584-594. View abstract.
  8. Imdad, A., Yakoob, M. Y., and Bhutta, Z. A. The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths. BMC.Public Health 2011;11 Suppl 3:S4. View abstract.
  9. Arya, R., Gulati, S., Kabra, M., Sahu, J. K., and Kalra, V. Folic acid supplementation prevents phenytoin-induced gingival overgrowth in children. Neurology 4-12-2011;76:1338-1343. View abstract.
  10. Wald, D. S., Morris, J. K., and Wald, N. J. Reconciling the evidence on serum homocysteine and ischaemic heart disease: a meta-analysis. PLoS.One. 2011;6:e16473. View abstract.
  11. Singh, J. A., Reddy, S. G., and Kundukulam, J. Risk factors for gout and prevention: a systematic review of the literature. Curr Opin.Rheumatol. 2011;23:192-202. View abstract.
  12. Kennedy, D. A., Stern, S. J., Moretti, M., Matok, I., Sarkar, M., Nickel, C., and Koren, G. Folate intake and the risk of colorectal cancer: a systematic review and meta-analysis. Cancer Epidemiol. 2011;35:2-10. View abstract.
  13. Figueiredo, J. C., Mott, L. A., Giovannucci, E., Wu, K., Cole, B., Grainge, M. J., Logan, R. F., and Baron, J. A. Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials. Int J Cancer 7-1-2011;129:192-203. View abstract.
  14. Qin, X., Huo, Y., Langman, C. B., Hou, F., Chen, Y., Matossian, D., Xu, X., and Wang, X. Folic acid therapy and cardiovascular disease in ESRD or advanced chronic kidney disease: a meta-analysis. Clin J Am Soc Nephrol. 2011;6:482-488. View abstract.
  15. DiFabio, J. M., Gori, T., Thomas, G., Jedrzkiewicz, S., and Parker, J. D. Daily low-dose folic acid supplementation does not prevent nitroglycerin-induced nitric oxide synthase dysfunction and tolerance: a human in vivo study. Can.J Cardiol 2010;26:461-465. View abstract.
  16. Clarke, R., Halsey, J., Lewington, S., Lonn, E., Armitage, J., Manson, J. E., Bonaa, K. H., Spence, J. D., Nygard, O., Jamison, R., Gaziano, J. M., Guarino, P., Bennett, D., Mir, F., Peto, R., and Collins, R. Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals. Arch.Intern.Med 10-11-2010;170:1622-1631. View abstract.
  17. Kim, D. H., Smith-Warner, S. A., Spiegelman, D., Yaun, S. S., Colditz, G. A., Freudenheim, J. L., Giovannucci, E., Goldbohm, R. A., Graham, S., Harnack, L., Jacobs, E. J., Leitzmann, M., Mannisto, S., Miller, A. B., Potter, J. D., Rohan, T. E., Schatzkin, A., Speizer, F. E., Stevens, V. L., Stolzenberg-Solomon, R., Terry, P., Toniolo, P., Weijenberg, M. P., Willett, W. C., Wolk, A., Zeleniuch-Jacquotte, A., and Hunter, D. J. Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer. Cancer Causes Control 2010;21:1919-1930. View abstract.
  18. Ebbing, M., Bonaa, K. H., Arnesen, E., Ueland, P. M., Nordrehaug, J. E., Rasmussen, K., Njolstad, I., Nilsen, D. W., Refsum, H., Tverdal, A., Vollset, S. E., Schirmer, H., Bleie, O., Steigen, T., Midttun, O., Fredriksen, A., Pedersen, E. R., and Nygard, O. Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials. J Intern.Med 2010;268:367-382. View abstract.
  19. Miller, E. R., III, Juraschek, S., Pastor-Barriuso, R., Bazzano, L. A., Appel, L. J., and Guallar, E. Meta-analysis of folic acid supplementation trials on risk of cardiovascular disease and risk interaction with baseline homocysteine levels. Am J Cardiol 8-15-2010;106:517-527. View abstract.
  20. Wald, D. S., Kasturiratne, A., and Simmonds, M. Effect of folic acid, with or without other B vitamins, on cognitive decline: meta-analysis of randomized trials. Am J Med 2010;123:522-527. View abstract.
  21. Lee, M., Hong, K. S., Chang, S. C., and Saver, J. L. Efficacy of homocysteine-lowering therapy with folic Acid in stroke prevention: a meta-analysis. Stroke 2010;41:1205-1212. View abstract.
  22. Blencowe, H., Cousens, S., Modell, B., and Lawn, J. Folic acid to reduce neonatal mortality from neural tube disorders. Int J Epidemiol. 2010;39 Suppl 1:i110-i121. View abstract.
  23. Carroll, C., Cooper, K., Papaioannou, D., Hind, D., Tappenden, P., Pilgrim, H., and Booth, A. Meta-analysis: folic acid in the chemoprevention of colorectal adenomas and colorectal cancer. Aliment.Pharmacol.Ther 2010;31:708-718. View abstract.
  24. Oaks, B. M., Dodd, K. W., Meinhold, C. L., Jiao, L., Church, T. R., and Stolzenberg-Solomon, R. Z. Folate intake, post-folic acid grain fortification, and pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr 2010;91:449-455. View abstract.
  25. Mei, W., Rong, Y., Jinming, L., Yongjun, L., and Hui, Z. Effect of homocysteine interventions on the risk of cardiocerebrovascular events: a meta-analysis of randomised controlled trials. Int J Clin Pract. 2010;64:208-215. View abstract.
  26. Fife, J., Raniga, S., Hider, P. N., and Frizelle, F. A. Folic acid supplementation and colorectal cancer risk: a meta-analysis. Colorectal Dis. 2011;13:132-137. View abstract.
  27. Ibrahim, E. M. and Zekri, J. M. Folic acid supplementation for the prevention of recurrence of colorectal adenomas: metaanalysis of interventional trials. Med Oncol. 2010;27:915-918. View abstract.
  28. McRae, M. P. High-dose folic acid supplementation effects on endothelial function and blood pressure in hypertensive patients: a meta-analysis of randomized controlled clinical trials. J Chiropr.Med 2009;8:15-24. View abstract.
  29. Behzadi, A. H., Omrani, Z., Chalian, M., Asadi, S., and Ghadiri, M. Folic acid efficacy as an alternative drug added to sodium valproate in the treatment of acute phase of mania in bipolar disorder: a double-blind randomized controlled trial. Acta Psychiatr.Scand. 2009;120:441-445. View abstract.
  30. Blom, H. J. Folic acid, methylation and neural tube closure in humans. Birth Defects Res A Clin Mol.Teratol. 2009;85:295-302. View abstract.
  31. Prey, S. and Paul, C. Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review. Br J Dermatol. 2009;160:622-628. View abstract.
  32. Malouf, R. and Grimley, Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane.Database.Syst.Rev 2008;:CD004514. View abstract.
  33. Potter, K., Hankey, G. J., Green, D. J., Eikelboom, J., Jamrozik, K., and Arnolda, L. F. The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis. BMC.Cardiovasc.Disord. 2008;8:24. View abstract.
  34. Mao, G., Hong, X., Xing, H., Liu, P., Liu, H., Yu, Y., Zhang, S., Jiang, S., Wang, X., and Xu, X. Efficacy of folic acid and enalapril combined therapy on reduction of blood pressure and plasma glucose: a multicenter, randomized, double-blind, parallel-controlled, clinical trial. Nutrition 2008;24(11-12):1088-1096. View abstract.
  35. Johnson, C. Y. and Little, J. Folate intake, markers of folate status and oral clefts: is the evidence converging? Int J Epidemiol. 2008;37:1041-1058. View abstract.
  36. Logan, R. F., Grainge, M. J., Shepherd, V. C., Armitage, N. C., and Muir, K. R. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 2008;134:29-38. View abstract.
  37. Grosse, S. D. and Collins, J. S. Folic acid supplementation and neural tube defect recurrence prevention. Birth Defects Res A Clin Mol.Teratol. 2007;79:737-742. View abstract.
  38. Dockerty, J. D., Herbison, P., Skegg, D. C., and Elwood, M. Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study. BMC.Public Health 2007;7:136. View abstract.
  39. Gilbody, S., Lightfoot, T., and Sheldon, T. Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity. J Epidemiol.Community Health 2007;61:631-637. View abstract.
  40. Cole, B. F., Baron, J. A., Sandler, R. S., Haile, R. W., Ahnen, D. J., Bresalier, R. S., McKeown-Eyssen, G., Summers, R. W., Rothstein, R. I., Burke, C. A., Snover, D. C., Church, T. R., Allen, J. I., Robertson, D. J., Beck, G. J., Bond, J. H., Byers, T., Mandel, J. S., Mott, L. A., Pearson, L. H., Barry, E. L., Rees, J. R., Marcon, N., Saibil, F., Ueland, P. M., and Greenberg, E. R. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 6-6-2007;297:2351-2359. View abstract.
  41. Wang, X., Qin, X., Demirtas, H., Li, J., Mao, G., Huo, Y., Sun, N., Liu, L., and Xu, X. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 6-2-2007;369:1876-1882. View abstract.
  42. Balk, E. M., Raman, G., Tatsioni, A., Chung, M., Lau, J., and Rosenberg, I. H. Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials. Arch.Intern.Med 1-8-2007;167:21-30. View abstract.
  43. Larsson, S. C., Giovannucci, E., and Wolk, A. Folate and risk of breast cancer: a meta-analysis. J Natl Cancer Inst. 1-3-2007;99:64-76. View abstract.
  44. Bazzano, L. A., Reynolds, K., Holder, K. N., and He, J. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA 12-13-2006;296:2720-2726. View abstract.
  45. Badovinac, R. L., Werler, M. M., Williams, P. L., Kelsey, K. T., and Hayes, C. Folic acid-containing supplement consumption during pregnancy and risk for oral clefts: a meta-analysis. Birth Defects Res A Clin Mol.Teratol. 2007;79:8-15. View abstract.
  46. Lewis, S. J., Harbord, R. M., Harris, R., and Smith, G. D. Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. J Natl Cancer Inst. 11-15-2006;98:1607-1622. View abstract.
  47. Larsson, S. C., Giovannucci, E., and Wolk, A. Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 2006;131:1271-1283. View abstract.
  48. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am.J Clin.Nutr 2005;82:806-812. View abstract.
  49. Sachdev, P. S., Parslow, R. A., Lux, O., Salonikas, C., Wen, W., Naidoo, D., Christensen, H., and Jorm, A. F. Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Psychol.Med 2005;35:529-538. View abstract.
  50. Ranganathan, L. N. and Ramaratnam, S. Vitamins for epilepsy. Cochrane.Database.Syst.Rev 2005;:CD004304. View abstract.
  51. Sanjoaquin, M. A., Allen, N., Couto, E., Roddam, A. W., and Key, T. J. Folate intake and colorectal cancer risk: a meta-analytical approach. Int J Cancer 2-20-2005;113:825-828. View abstract.
  52. Ramos, M. I., Allen, L. H., Haan, M. N., Green, R., and Miller, J. W. Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification. Am J Clin Nutr 2004;80:1024-1028. View abstract.
  53. Ellinson, M., Thomas, J., and Patterson, A. A critical evaluation of the relationship between serum vitamin B, folate and total homocysteine with cognitive impairment in the elderly. J Hum Nutr Diet 2004;17:371-383. View abstract.
  54. Shen, H., Wei, Q., Pillow, P. C., Amos, C. I., Hong, W. K., and Spitz, M. R. Dietary folate intake and lung cancer risk in former smokers: a case-control analysis. Cancer Epidemiol.Biomarkers Prev. 2003;12:980-986. View abstract.
  55. Halsted, C. H., Villanueva, J. A., Devlin, A. M., and Chandler, C. J. Metabolic interactions of alcohol and folate. J Nutr 2002;132(8 Suppl):2367S-2372S. View abstract.
  56. Thorand, B., Kohlmeier, L., Simonsen, N., Croghan, C., and Thamm, M. Intake of fruits, vegetables, folic acid and related nutrients and risk of breast cancer in postmenopausal women. Public Health Nutr 1998;1:147-156. View abstract.
  57. Cooper, K., Squires, H., Carroll, C., Papaioannou, D., Booth, A., Logan, R. F., Maguire, C., Hind, D., and Tappenden, P. Chemoprevention of colorectal cancer: systematic review and economic evaluation. Health Technol.Assess. 2010;14:1-206. View abstract.
  58. Roswall N, Olsen A, Christensen J, et al. Micronutrient intake and risk of colon and rectal cancer in a Danish cohort. Cancer Epidemiol. 2010;34:40-6. View abstract.
  59. Schernhammer ES, Ogino S, Fuchs CS. Folate and vitamin B6 intake and risk of colon cancer in relation to p53 expression. Gastroenterology. 2008;135:770-80. View abstract
  60. Lin RJ, Krall R, Westerberg BD, et al. Systematic review and meta-analysis of the risk factors for sudden sensorineural hearing loss in adults. Laryngoscope. 2012;122:624-35. View abstract.
  61. De-Regil LM, Fernández-Gaxiola AC, Dowswell T, et al. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2010;:CD007950. View abstract.
  62. Willems FF, Boers GH, Blom HJ, et al. Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. Br J Pharmacol 2004;141:825-30. View abstract.
  63. Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to calcium L-methylfolate. EFSA J 2004;135:1-20. Available at: http://www.efsa.europa.eu/en/scdocs/doc/135.pdf. (Accessed 18 March 10).
  64. L-methylfolate. Pharmacist's Letter / Prescriber's Letter 2010;26:260311.
  65. Ebbing M, Bonaa KH, Nygard O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA 2009;302:2119-26. View abstract.
  66. Bedford Laboratories. Leucovorin calcium [package insert]. Bedford, OH. September 2008. Available at: http://www.bedfordlabs.com/BedfordLabsWeb/products/inserts/LCV-P02.pdf.
  67. Clippe C, Freyer G, Milano G, Trillet-Lenoir V. Lethal toxicity of capecitabine due to abusive folic acid prescription. Clin Oncol (R Coll Radiol) 2003;15:299-300. View abstract.
  68. Figueiredo JC, Grau MV, Haile RW, et al. Folic acid and risk of prostate cancer: Results from a randomized clinical trial. J Natl Cancer Inst 2009;101:432-5. View abstract.
  69. Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 2007;99:754-64. View abstract.
  70. Durga J, van Boxtel MP, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 2007;369:208-16. View abstract.
  71. Luchsinger JA, Tang MX, Miller J, et al. Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol 2007;64:86-92. View abstract.
  72. Durga J, Verhoef P, Anteunis LJC, et al. Effects of folic acid supplementation on hearing in older adults. Ann Intern Med 2007;146:1-9. View abstract.
  73. Navarro-Peran E, Cabezas-Herrera J, Garcia-Canovas F, et al. The antifolate activity of tea catechins. Cancer Res 2005;65:2059-64. View abstract.
  74. Christen WG, Glynn RJ, Chew EY, et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women. Arch Intern Med 2009;169:335-41. View abstract.
  75. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 2006;354:2764-72. View abstract.
  76. Van Guelpen B, Hultdin J, Johansson I, et al. Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: a prospective, nested case-referent study of plasma concentrations and dietary intake. Stroke 2005;36:1426-31. View abstract.
  77. Bonaa KH, Njolstad I, Ueland PM, et al. NORVIT: Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Enlg J Med 2006;354:1578-88. View abstract.
  78. Corrada M, Kawas C. Reduced risk of Alzheimer's disease with high folate Intake: The Baltimore Longitudinal Study of Aging. Alzheimers Dement 2005;1:11-18. View abstract.
  79. Morris MC, Evans DA, Bienias JL, et al. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Arch Neurol 2005;62:641-5. View abstract.
  80. Oakley GP, Mandel JS. Folic acid fortification remains an urgent health priority. Br Med J 2004;329:1376. View abstract.
  81. Charles D, Ness AR, Campbell D, et al. Taking folate in pregnancy and risk of maternal breast cancer. Br Med J 2004;329:1375-6. View abstract.
  82. Herrmann H. Prevention of cardiovascular events after percutaneous coronary intervention. N Engl J Med 2004;350:2708-10. View abstract.
  83. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004;350:2673-81. View abstract.
  84. Hanley DF. The challenge of stroke prevention. JAMA 2004;291:621-2. View abstract.
  85. Toole JF, Malinow MR, Chambless LE, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-75.. View abstract.
  86. van Oort FV, Melse-Boonstra A, Brouwer IA, et al. Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study. Am J Clin Nutr 2003;77:1318-23. View abstract.
  87. Liem A, Reynierse-Buitenwerf GH, Zwinderman AH, et al. Secondary prevention with folic acid: effects on clinical outcomes. J Am Coll Cardiol 2003;41:2105-13. . View abstract.
  88. Hernandez BY, McDuffie K, Wilkens LR, et al. Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12. Cancer Causes Control 2003;14:859-70. View abstract.
  89. Godfrey PS, Toone BK, Carney MW, et al. Enhancement of recovery from psychiatric illness by methylfolate. Lancet 1990;336:392-5.. View abstract.
  90. Passeri M, Cucinotta D, Abate G, et al. Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study. Aging (Milano) 1993;5:63-71.. View abstract.
  91. Coppen A, Swade C, Jones SA, et al. Depression and tetrahydrobiopterin: the folate connection. J Affect Disord 1989;16:103-7.. View abstract.
  92. Taylor MJ, Carney S, Geddes J, Goodwin G. Folate for depressive disorders. Cochrane Database Syst Rev 2003;:CD003390.. View abstract.
  93. Tolmunen T, Voutilainen S, Hintikka J, et al. Dietary folate and depressive symptoms are associated in middle-aged Finnish men. J Nutr 2003;133:3233-6.. View abstract.
  94. Morris MS, Fava M, Jacques PF, et al. Depression and folate status in the US Population. Psychother Psychosom 2003;72:80-7.. View abstract.
  95. Tiemeier H, van Tuijl HR, Hofman A, et al. Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study. Am J Psychiatry 2002;159:2099-101.. View abstract.
  96. Alpert M, Silva RR, Pouget ER. Prediction of treatment response in geriatric depression from baseline folate level: interaction with an SSRI or a tricyclic antidepressant. J Clin Psychopharmacol 2003;23:309-13.. View abstract.
  97. Bottiglieri T, Laundy M, Crellin R, et al. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 2000;69:228-32.. View abstract.
  98. van der Griend R, Haas FJ, Biesma DH, et al. Combination of low-dose folic acid and pyridoxine for treatment of hyperhomocysteinaemia in patients with premature arterial disease and their relatives. Atherosclerosis 1999;143:177-83.. View abstract.
  99. Eros E, Geher P, Gomor B, Czeizel AE. Epileptogenic activity of folic acid after drug induces SLE (folic acid and epilepsy). Eur J Obstet Gynecol Reprod Biol 1998;80:75-78.. View abstract.
  100. Fishman SM, Christian P, West KP. The role of vitamins in the prevention and control of anaemia. Public Health Nutr 2000;3:125-50.. View abstract.
  101. Badner NH, Freeman D, Spence JD. Preoperative oral B vitamins prevent nitrous oxide-induced postoperative plasma homocysteine increases. Anesth Analg 2001;93:1507-10.. View abstract.
  102. Hartman TJ, Woodson K, Stolzenberg-Solomon R, et al. Association of the B-vitamins pyridoxal 5'-phosphate (B6), B12, and folate with lung cancer risk in older men. Am J Epidemiol 2001;153:688-94.. View abstract.
  103. Keating JN, Wada L, Stokstad ELR, King JC. Folic acid: effect on zinc absorption in humans and in the rat. Am J Clin Nutr 1987;46:835-9. View abstract.
  104. Schroder H, Clausen N, Ostergard E, Pressler T. Folic acid supplements in vitamin tablets: a determinant of hematological drug tolerance in maintenance therapy of childhood acute lymphoblastic leukemia. Ped Hematol Oncol 1986;3:241-7. View abstract.
  105. Endresen GK, Husby G. Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis. An update and proposal for guidelines. Scand J Rheumatol 2001;30:129-34. View abstract.
  106. Griffith SM, Fisher J, Clarke S, et al. Do patients with rheumatoid arthritis established on methotrexate and folic acid 5 mg daily need to continue folic acid supplements long term? Rheumatology (Oxford) 2000;39:1102-9. View abstract.
  107. Dierkes J, Domrose U, Ambrosch A, et al. Response of hyperhomocysteinemia to folic acid supplementation in patients with end-stage renal disease. Clin Nephrol 1999;51:108-15. View abstract.
  108. Bostom AG, Shemin D, Gohh RY, et al. Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients. Kidney Int 2001;59:s246-s252. View abstract.
  109. Dierkes J, Domrose U, Bosselmann P, et al. Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease. J Renal Nutr 2001;11:67-72. View abstract.
  110. Bostom A, Shemin D, Gohh R, et al. Treatment of mild hyperhomocysteinemia in renal transplant recipients versus hemodialysis patients. Transplantation 2000;69:2128-31. View abstract.
  111. Sunder-Plassmann G, Fodinger M, Buchmayer H, et al. Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna Multicenter Study. J Am Soc Nephrol 2000;11:1106-16. View abstract.
  112. Schnyder G, Roffi M, Flammer Y, et al. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention. The Swiss Heart Study: A randomized controlled trial. JAMA 2002;288:973-9. View abstract.
  113. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995;274:1049-57. View abstract.
  114. den Heijer M, Brouwer IA, Bos GMJ, et al. Vitamin supplementation reduces blood homocysteine levels. A controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol 1998;18:356-61. View abstract.
  115. Sunder-Plassmann G, Winkelmayer WC, Fodinger M. Therapeutic potential of total homocysteine-lowering drugs on cardiovascular disease. Expert Opin Investig Drugs 2000;9:2637-51. View abstract.
  116. Keebler ME, De Souza C, Fonesca V. Diagnosis and treatment of hyperhomocysteinemia. Curr Atheroscler Rep 2001;3:54-63. View abstract.
  117. Selhub J, Jacques PF, Bostom AG, et al. Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification. Publ Health Rev 2000;28:117-45. View abstract.
  118. van der Griend R, Biesma DH, Haas FJLM, et al. The effect of different treatment regimens in reducing fasting and postmethionine-load homocysteine concentrations. J Int Med 2000;248:223-9. View abstract.
  119. Clarke R, Armitage J. Vitamin supplements and cardiovascular risk: review of the randomized trials of homocysteine-lowering vitamin supplements. Semin Thromb Hemost 2000;26:341-8. View abstract.
  120. Bostom AG, Selhub J, Jacques PF, Rosenberg IH. Power shortage: clinical trials testing the "homocysteine hypothesis" against a background of folic acid-fortified cereal grain flour. Ann Int Med 2001;135:133-7. View abstract.
  121. Holven KB, Holm T, Aukrust P, et al. Effect of folic acid treatment on endothelium-dependent vasodilation and nitric oxide-derived end products in hyperhomocysteinemic subjects. Am J Med 2001;110:536-42. View abstract.
  122. Ueland PM, Refsum H, Beresford SA, Vollset SE. The controversy over homocysteine and cardiovascular risk. Am J Clin Nutr 2000;72:324-32. View abstract.
  123. Bronstrup A, Hages M, Prinz-Langenohl R, Pietrzik K. Effects of folic acid and combinations of folic acid and vitamin B12 on plasma homocysteine concentrations in healthy young women. Am J Clin Nutr 1998;68:1104-10. View abstract.
  124. Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomized trials. BMJ 1998;316:894-8. View abstract.
  125. Nunn PP, Allistone JC. Resistance to trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonia. Implication of folinic acid. Chest 1984;86:149-50. View abstract.
  126. Bygbjerg IC, Lund JT, Hording M. Effect of folic and folinic acid on cytopenia occurring during cotrimoxazole treatment of Pneumocystis carinii pneumonia. Scand J Infect Dis 1988;20:685-6. View abstract.
  127. Halsted CH, McIntyre PA. Intestinal malabsorption caused by aminosalicylic acid therapy. Arch Int Med 1972;130;935-9. View abstract.
  128. Evans DI, Attock B. Folate deficiency in pulmonary tuberculosis: relationship to treatment and to serum vitamin A and beta carotene. Tubercle 1971;52:288-94. View abstract.
  129. Line DH, Seitanidis B, Morgan JO, Hoffbrand AV. The effects of chemotherapy on iron, folate, and vitamin B12 metabolism in tuberculosis. Q J Med 1971;40:331-40. View abstract.
  130. Koutts J, Van der Weyden MB, Cooper M. Effect of trimethoprim on folate metabolism in human bone marrow. Aust NZ J Med 1973;3:245-50. View abstract.
  131. Kauwell GPA, Baily LB, Gregory JF, et al. Zinc status is not adversely affected by folic acid supplementation and zinc intake does not impair folate utilization in human subjects. J Nutr 1995;125:66-72. View abstract.
  132. Fuller NJ, Bates CJ, Evans PH, Lucas A. High folate intakes related to zinc status in preterm infants. Eur J Pediatr 1992;151:51-3. View abstract.
  133. Butterworth CE, Hatch K, Cole P, et al. Zinc concentration in plasma and erythrocytes of subjects receiving folic acid supplementation. Am J Clin Nutr 1988;47:484-6. View abstract.
  134. Kakar F, Henderson MM. Potential toxic side effects of folic acid (letter). J Natl Cancer Inst 1985;74:263. View abstract.
  135. Milne DB, Canfield WK, Mahalko JR, Sandstead HH. Effect of oral folic acid supplements on zinc, copper, and iron absorption and excretion. Am J Clin Nutr 1984;39:535-9. View abstract.
  136. Thompson JB, Hess DR, Poley JR, et al. Intestinal malabsorption induced by paraminosalicylic acid (abstract). Gastroenterology 1970;58:1001.
  137. 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;170:912-7. View abstract.
  138. Stock C. Trimethoprim-sulfamethoxazole and folinic acid (letter). Ann Intern Med 1985;102:277. View abstract.
  139. Hollander H. Leukopenia, trimethoprim-sulfamethoxazole, and folinic acid (letter). Ann Intern Med 1985;102:138. View abstract.
  140. Kinzie BJ, Taylor JW. Trimethoprim and folic acid (letter). Ann Int Med 1984;101:565. View abstract.
  141. Naderer O, Nafziger AN, Bertino JS. Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions. Antimicrob Agents Chemother 1997;41:2466-70. View abstract.
  142. Kobrinsky NL, Ramsay NKC. Acute megaloblastic anemia induced by high-dose trimethoprim-sulfamethoxazole. Ann Int Med 1981;94:780-1. View abstract.
  143. Pelliniemi TT, Kasanen A, Sundquist H. Lack of haematological side effects during prophylactic use of trimethoprim over four years. Curr Ther Res 1983;34:436-40.
  144. Van Delden C, Hirschel B. Folinic acid supplements to pyrimethamine-sulfadiazine for Toxoplasma encephalitis are associated with better outcome (letter). J Infect Dis 1996;173:1294-5. View abstract.
  145. Lashner BA, Heidenreich PA, Su GL, et al. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. Gastroenterology 1989;97:255-9. View abstract.
  146. Drake S, Lampasona V, Nicks HL, Schwarzmann SW. Pentamidine isethionate in the treatment of Pneumocystis carinii pneumonia. Clin Pharm 1985;4:507-16. View abstract.
  147. Longstreth GF, Green R. Folate status in patients receiving maintenance doses of sulfasalazine. Arch Int Med 1983;143:902-4. View abstract.
  148. Prouse PJ, Shawe D, Gumpel JM. Macrocytic anemia in patients treated with sulfasalazine for rheumatoid arthritis. BMJ 1986;293:1407. View abstract.
  149. Corcino J, Waxman S, Herbert V. Mechanism of triamterene-induced megaloblastosis. Ann Intern Med 1970;73:419-24. View abstract.
  150. Russell RM, Dutta SK, Oaks EV, et al. Impairment of folic acid absorption by oral pancreatic extracts. Dig Dis Sci 1980;25:369-73. View abstract.
  151. Mooij PN, Thomas CM, Doesburg WH, Eskes TK. Multivitamin supplementation in oral contraceptive users. Contraception 1991;44:277-88. View abstract.
  152. Barone C, Bartoloni C, Ghirlanda G, Gentiloni N. Megaloblastic anemia due to folic acid deficiency after oral contraceptives. Haematologica 1979;64:190-5. View abstract.
  153. Shojania AM. Oral contraceptives: effect on folate and vitamin B12 metabolism. Can Med Assoc J 1982;126:244-7. View abstract.
  154. Check WA. Folate for oral contraceptive users may reduce cervical cancer risk. J Am Med Assoc 1980;244:633-4. View abstract.
  155. Ortiz Z, Shea B, Suarez Almazor M, et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis (Cochrane Review). Cochrane Database Syst Rev 2000;2:CD000951. View abstract.
  156. Berchtold P, Dahlqvist A, Gustafson A, Asp NG. Effects of a biguanide (metformin) on vitamin B12 and folic acid absorption and intestinal enzyme activities. Scand J Gastroenterol 1971;6:751-4. View abstract.
  157. Aarsand AK, Carlsen SM. Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment. J Int Med 1998;244:169-74. View abstract.
  158. Buysschaert M, Wallemacq PE, Dramais AS, Hermans MP. Hyperhomocysteinemia in type 2 diabetes. Diabetes Care 2000;23:1816-22. View abstract.
  159. Russell RM, Krasinski SD, Samloff IM, et al. Folic acid malabsorption in atrophic gastritis: possible compensation by bacterial folate synthesis. Gastroenterology 1986;91:1476-82. View abstract.
  160. Klipstein FA, Berlinger FG, Reed LJ. Folate deficiency associated with drug therapy for tuberculosis. Blood 1967;29:697-712. View abstract.
  161. Frequin ST, Wevers RA, Braam M, et al. Decreased vitamin B12 and folate levels in cerebrospinal fluid and serum of multiple sclerosis patients after high-dose intravenous methylprednisolone. J Neurol 1993;240:305-8. View abstract.
  162. Baggott JE, Morgan SL, Ha T, et al. Inhibition of folate-dependent enzymes by non-steroidal anti-inflammatory drugs. Biochem J 1992;282:197-202. View abstract.
  163. Alter HJ, Zvaifler NJ, Rath CE. Interrelationship of rheumatoid arthritis, folic acid and aspirin. Blood 1971;38:405-16. View abstract.
  164. Reynolds EH, Trimble MR. Adverse neuropsychiatric effects of anticonvulsant drugs. Drugs 1985;29:570-81. View abstract.
  165. Reynolds EH. Folate metabolism and anticonvulsant therapy. Proc R Soc Med 1974;67:68. View abstract.
  166. Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976;5:661-96. View abstract.
  167. Lewis DP, Van Dyke DC, Stumbo PJ, Berg MJ. Drug and environmental factors associated with adverse pregnancy outcomes. Part I: antiepileptic drugs, contraceptives, smoking, and folate. Ann Pharmacother 1998;32:802-17. View abstract.
  168. Dansky LV, Rosenblatt DS, Andermann E. Mechanisms of teratogenesis: folic acid and antiepileptic therapy. Neurology 1992;42:32-42. View abstract.
  169. Hiilesmaa VK, Teramo K, Granstrom ML, Bardy AH. Serum folate concentrations during pregnancy in women with epilepsy: relation to antiepileptic drug concentrations, number of seizures, and fetal outcome. Br Med J 1983;287:577-9. View abstract.
  170. Halsted CH, Gandhi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative colitis. New Engl J Med 1981;305:1513-7. View abstract.
  171. Butterworth CE, Hatch KD, Gore H, et al. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr 1982;35:73-82. View abstract.
  172. Lawrence VA, Loewenstein JE, Eichner ER. Aspirin and folate binding: in vivo and in vitro studies of serum binding and urine excretion of endogenous folate. J Lab Clin Med 1984;103:944-8. View abstract.
  173. Wong WY, Merkus HM, Thomas CM, et al. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril 2002;77:491-8.. View abstract.
  174. Botez MI, Peyronnard J, Berube L, Labrecque R. Relapsing neuropathy, cerebral atrophy and folate deficiency. Appl Neurophysiol 1979;42:171-83.. View abstract.
  175. Botez MI, Cadotte M, Beaulieu R, et al. Neurologic disorders responsive to folic acid therapy. Can Med Assoc J 1976;115:217-23.. View abstract.
  176. Smith AD. Homocysteine, B vitamins, and cognitive deficit in the elderly. Am J Clin Nutr 2002;75:785-6. View abstract.
  177. Duthie SJ, Whalley LJ, Collins AR, et al. Homocysteine, B vitamin status, and cognitive function in the elderly. Am J Clin Nutr 2002;75:908-13.. View abstract.
  178. Huang RF, Ho Y, Lin H, et al. Folate deficiency induces a cell cycle-specific apoptosis in HepG2 cells. J Nutr 1999;129:25-31.. View abstract.
  179. Shrubsole MJ, Jin F, Dai Q, et al. Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Res 2001;61:7136-41.. View abstract.
  180. Stolzenberg-Solomon RZ, Pietinen P, Barrett MJ, et al. Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am J Epidemiol 2001;153:680-7.. View abstract.
  181. Fuchs CS, Willett WC, Colditz GA, et al. The influence of folate and multivitamin use on the familial risk of colon cancer in women. Cancer Epidemiol Biomarkers Prev 2002;11:227-34.. View abstract.
  182. Su LJ, Arab L. Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study. Ann Epidemiol 2001;11:65-72.. View abstract.
  183. van der Dijs FP, Fokkema MR, Dijck-Brouwer DA, et al. Optimization of folic acid, vitamin B12, and vitamin B6 supplements in pediatric patients with sickle cell disease. Am J Hematol 2002;69:239-46.. View abstract.
  184. Thambyrajah J, Landray MJ, McGlynn FJ, et al. Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure? Circulation 2000;102:871-5.. View abstract.
  185. Stulc T, Melenovsky V, Grauova B, et al. Folate supplementation prevents plasma homocysteine increase after fenofibrate therapy. Nutrition 2001;17:721-3.. View abstract.
  186. Stehouwer CD. Clinical relevance of hyperhomocysteinaemia in atherothrombotic disease. Drugs and Aging 2000;16:251-60.. View abstract.
  187. Mayer O, Simon J, Rosolova H, et al. The effects of folate supplementation on some coagulation parameter and oxidative status surrogates. Eur J Clin Pharmacol 2002;58:1-5.. View abstract.
  188. Bazzano LA, He J, Ogden LG, et al. Dietary intake of folate and risk of stroke in US men and women: NHANES I epidemiolgic follow-up study. Stroke 2002;33:1183-8.. View abstract.
  189. Loscalzo J. Folate and nitrate-induced endothelial dysfunction. A simple treatment for a complex pathobiology. Circulation 2001;104:1086-8. View abstract.
  190. Gori T, Burstein JM, Ahmed S, et al. Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance. Circulation 2001:104;1119-23.. View abstract.
  191. Pullin CH, Ashfield-Watt PA, Burr ML, et al. Optimization of dietary folate or low-dose folic acid supplements lower homocysteine but do not enhance endothelial function in healthy adults, irrespective of the methylenetetrahydrofolate reductase (C677T) genotype. J Am Coll Cardiol 2001;38:1799-805.. View abstract.
  192. Woo KS, Chook P, Chan LL, et al. Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation. Am J Med 2002;112:535-9.. View abstract.
  193. Thambyrajah J, Landray MJ, Jones HJ, et al. A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease. J Am Coll Cardiol 2001;37:1858-63.. View abstract.
  194. Voutilainen S, Rissanen TH, Virtanen J, et al. Low dietary folate intake is associated with an excess incidence of acute coronary events. Circulation 2001;103:2674-80.. View abstract.
  195. Loria CM, Ingram DD, Feldman JJ, et al. Serum folate and cardiovascular disease mortality among US men and women. Arch Intern Med 2000;160:3258-62.. View abstract.
  196. Mangoni AA, Jackson SH. Homocysteine and cardiovascular disease: current evidence and future prospects. Am J Med 2002;112:556-65.. View abstract.
  197. Koebnick C, Heins UA, Hoffman I, et al. Folate status during pregnancy in women is improved by long-term high vegetable intake compared with the average western diet. J Nutr 2001;131:733-9.. View abstract.
  198. Nallamothu BK, Fendrick M, Rubenfire M, et al. Potential clinical and economic effects of homocyst(e)ine lowering. Arch Intern Med 2000;160:3406-12.. View abstract.
  199. Wald DS, Bishop L, Wald NJ, et al. Randomized trial of folic acid supplementation and serum homocysteine levels. Arch Intern Med 2001;161:695-700.. View abstract.
  200. Vos E. Multivitamin supplements are effective and inexpensive agents to lower homocysteine levels. Arch Intern Med 2001;161:774-5. View abstract.
  201. McKay DL, Perrone G, Rasmussen H, et al. Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet. J Nutr 2000;130:3090-6.. View abstract.
  202. de Bree A, Verschuren WM, Blom HJ, Kromhout D. Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20-65 y. Am J Clin Nutr 2001;73:1027-33.. View abstract.
  203. Murua AL, Quintana I, Janson J, et al. Plasmatic homocysteine response to vitamin supplementation in elderly people. Thromb Res 2000;100:495-500.. View abstract.
  204. Rasmussen LB, Ovesen L, Bulow I, et al. Folate intake, lifestyle factors, and homocysteine concentrations in younger and older women. Am J Clin Nutr 2000;72:1156-63.. View abstract.
  205. Fohr IP, Prinz-Langenohl R, Bronstrup A, et al. 5,10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women. Am J Clin Nutr 2002;75:275-82.. View abstract.
  206. Gregory JF. Case study: folate bioavailability. J Nutr 2001;131:1376S-1382S.. View abstract.
  207. Checkoway H, Powers K, Smith-Weller T, et al. Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 2002;155:732-8.. View abstract.
  208. Sunder-Plassmann G, Fodinger M, Buchmayer H, et al. Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna multicenter study. J Am Soc Nephrol 2000;11:1106-16.. View abstract.
  209. Antony AC. Megaloblastic Anemias. In: Hoffman R, Benz Jr EJ, Shattil SJ, et al. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone 2000: 451-79.
  210. Russell RM, Golner BB, Krasinski SD, et al. Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. J Lab Clin Med 1988;112:458-63. View abstract.
  211. Schnyder G, Roffi M, Pin R, et al. Decreased rate of coronary stenosis after lowering of plasma homocysteine levels. N Engl J Med 2001;345:1593-600. View abstract.
  212. Beaulieu AJ, Gohh RY, Han H, et al. Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients. Arterioscler Thromb Vasc Biol 1999;19:2918-21. View abstract.
  213. Green TJ, Houghton LA, Donovan U, et al. Oral contraceptives did not affect biochemical folate indexes and homocysteine concentrations in adolescent females. J Am Diet Assoc 1998;98:49-55. View abstract.
  214. Grace E, Emans SJ, Drum DE. Hematologic abnormalities in adolescents who take oral contraceptive pills. J Pediatrics 1982;101:771-4. View abstract.
  215. Title LM, Cummings PM, Giddens K, et al. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2000;36:758-65. View abstract.
  216. Kaslow JE, Rucker L, Onishi R. Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome. Arch Intern Med 1989;149:2501-3. View abstract.
  217. Manns B, Hyndman E, Burgess E, et al. Oral vitamin B and high-dose folic acid in hemodialysis patients with hyper-homocyst(e)inemia. Kidney Int 2001;59:1103-9. View abstract.
  218. Sandoval M, Charbonnet RM, Okuhama NN, et al. Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection. Free Radic Biol Med 2000;29:71-78. View abstract.
  219. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002. Available at: www.nap.edu/books/0309072794/html/.
  220. Tremblay R, Bonnardeaux A, Geadah D, et al. Hyperhomocystinemia in hemodialysis patients: effects of 12-month supplementation with hydrosoluble vitamins. Kidney Int 2000;58:851-8. View abstract.
  221. Riddell LJ, Chisholm A, Williams S, Mann JI. Dietary strategies for lowering homocysteine concentrations. Am J Clin Nutr 2000;71:1448-54. View abstract.
  222. Kauwell GP, Lippert BL, Wilsky CE, et al. Folate status of elderly women following moderate folate depletion responds only to a higher folate intake. J Nutr 2000;130:1584-90. View abstract.
  223. Lashner BA. Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis. J Cancer Res Clin Oncol 1993;119:549-54. View abstract.
  224. Kuroki F, Iida M, Tominaga M, et al. Multiple vitamin status in Crohn's disease. Correlation with disease activity. Dig Dis Sci 1993;38:1614-8. View abstract.
  225. Nardini M, De Stefano R, Iannuccelli M, et al. Treatment of depression with L-5-hydroxytryptophan combined with chlorimipramine, a double-blind study. Int J Clin Pharmacol Res 1983;3:239-50. View abstract.
  226. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline . Washington, DC: National Academy Press, 2000. Available at: http://books.nap.edu/books/0309065542/html/.
  227. Suitor CW, Bailey LB. Food folate vs synthetic folic acid: a comparison. J Am Diet Assoc 1999;99:285. View abstract.
  228. Suitor CW, Bailey LB. Dietary folate equivalents: interpretation and application. J Am Diet Assoc 2000;100:88-94. View abstract.
  229. Fava M, Borus JS, Alpert JE, et al. Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry 1997;154:426-8. View abstract.
  230. Ortega RM, Manas LR, Andres P, et al. Functional and psychic deterioration in elderly people may be aggravated by folate deficiency. J Nutr 1996;126:1992-9. View abstract.
  231. Nelen WL, Blom HJ, Steegers EA, et al. Homocysteine and folate levels as risk factors for recurrent early pregnancy loss. Obstet Gynecol 2000;95:519-24. View abstract.
  232. Usui M, Matsuoka H, Miyazaki H, et al. Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid. Clin Sci (Colch) 1999;96:235-9. View abstract.
  233. Snowdon DA, Tully CL, Smith CD, et al. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study. Am J Clin Nutr 2000;71:993-8. View abstract.
  234. Jacobson W, Saich T, Borysiewicz, LK, et al. Serum folate and chronic fatigue syndrome. Neurol 1993;43:2645-7. View abstract.
  235. Werbach MR. Nutritional strategies for treating chronic fatigue syndrome. Altern Med Rev 2000;5:93-108. View abstract.
  236. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137-52. View abstract.
  237. Zimmerman J. Drug interactions in intestinal transport of folic acid and methotrexate. Further evidence for the heterogeneity of folate transport in the human small intestine. Biochem Pharmacol 1992;44:1839-42. View abstract.
  238. Longsreth GF, Newcomer AD, Westbrook PR. Para-aminosalicylic acid-induced malabsorption. Am J Dig Dis 1972;17:731-4. View abstract.
  239. Amer College of Rheumatology ad hoc committee on clinical guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996;39:723-31. View abstract.
  240. Joosten E, Pelemans W. Megaloblastic anaemia in an elderly patient treated with triamterene. Neth J Med 1991;38:209-11. View abstract.
  241. Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-55. View abstract.
  242. Glaxo-Wellcome, Inc. Daraprim package insert. Research Triangle Park, NC; August 1996.
  243. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  244. Taliani U, Camellini A, Bernardi P, et al. A clinical case of severe megaloblastic anemia during treatment with primidone. Acta Biomed Ateneo Parmense 1989;60:245-8. View abstract.
  245. Grieco A, Caputo S, Bertoli A, et al. Megaloblastic anemia due to sulphasalazine responding to drug withdrawal alone. Postgrad Med J 1986;62:307-8. View abstract.
  246. Logan EC, Williamson LM, Ryrie DR. Sulphasalazine associated pancytopenia may be caused by acute folate deficiency. Gut 1986;27:868-72. View abstract.
  247. Krogh-Jensen M, Ekelund S, Svendsen L. Folate and homocysteine status and haemolysis in patients treated with sulphasalazine for arthritis. Scand J Clin Lab Invest 1996;56:421-9. View abstract.
  248. Prasad AS, Lei KY, Moghissi KS, et al. Effect of oral contraceptives on nutrients. III. Vitamins B6, B12 and folic acid. Am J Obstet Gynecol 1976;125:1063-9. View abstract.
  249. Dijkmans BA. Folate supplementation and methotrexate. Br J Rheumatol 1995;34:1172-4. View abstract.
  250. Morgan SL, Baggott JE, Lee JY, Alarcón GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol 1998;25:441-6. View abstract.
  251. Leeb BF, Witzmann G, Ogris E, et al. Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose methotrexate therapy of rheumatoid arthritis and psoriatic arthritis patients. Clin Exp Rheumatol 1995;13:459-63. View abstract.
  252. Carpentier JL, Bury J, Luyckx A, et al. Vitamin B12 and folic acid serum levels in diabetics under various therapeutic regimens. Diabete Metab 1976;2:187-90. View abstract.
  253. Termanini B, Gibril F, Sutliff VE, et al. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am J Med 1998;104:422-30. View abstract.
  254. Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking anticonvulsant drugs. J Clin Endocrinol Metab 1975;41:1125-9. View abstract.
  255. Berg MJ, Fincham RW, Ebert BE, et al. Phenytoin pharmacokinetics: Before and after folic acid administration. Epilepsia 1992;33:712-20. View abstract.
  256. Berg MJ, Stumbo PJ, Chenard CA, et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc 1995;95:352-6. View abstract.
  257. Lewis DP, Van Dyke DC, Willhite LA, et al. Phenytoin-folic acid interaction. Ann Pharmacother 1995;29:726-35. View abstract.
  258. Kahn SB, Fein SA, Brodsky I. Effects of trimethoprim on folate metabolism in man. Clin Pharmacol Ther 1968;9:550-60. View abstract.
  259. Tonstad S, Silverstein M, Aksnes L, Ose L. Low dose colestipol in adolescents with familial hypercholesterolemia. Arch Dis Child 1996;74:157-60. View abstract.
  260. Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther 1982;4:423-40. View abstract.
  261. West RJ, Lloyd JK. The effect of cholestyramine on intestinal absorption. Gut 1975;16:93-8. View abstract.
  262. Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997;6:S43-5. View abstract.
  263. Gorbach SL. Bengt E. Gustafsson memorial lecture. Function of the normal human microflora. Scand J Infect Dis Suppl 1986;49:17-30. View abstract.
  264. Traccis S, Monaco F, Sechi GP, et al. Long-term therapy with carbamazepine: Effects on nerve conduction velocity. Eur Neurol 1983;22:410-6. View abstract.
  265. Hendel J, Dam M, Gram L, et al. The effects of carbamazepine and valproate on folate metabolism in man. Acta Neurol Scan 1984;69:226-31. View abstract.
  266. Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-82. View abstract.
  267. Kishi T, Fujita N, Eguchi T, et al. Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy. J Neurol Sci 1997;145:109-12. View abstract.
  268. Garabedian-Ruffalo SM, Ruffalo RL. Drug and nutrient interactions. Am Fam Physician 1986;33:165-74. View abstract.
  269. Bostom AG, Garber C. Endpoints for homocysteine-lowering trials. Lancet 2000;355:511-2. View abstract.
  270. Vermeulen EG, Stehouwer CD, Twisk JW, et al. Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial. Lancet 2000;355:517-22. View abstract.
  271. Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affect Dis 2000;60:121-31. View abstract.
  272. US Food and Drug Administration, Center for Food Safety, and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements. Letter regarding dietary supplement health claim for folic acid with respect to neural tube defects. 2000. Available at: http://www.fda.gov/Food/LabelingNutrition/LabelClaims/ QualifiedHealthClaims/ucm073058.htm.
  273. Bostom AG, Shemin D, Bagley P, et al. Controlled comparison of L-5-Methyltetrahydrofolate versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients. Circulation 2000;101:2829-32. View abstract.
  274. Voutilainen S, Lakka TA, Porkkala-Sarataho E, et al. Low serum folate concentrations are associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. Eur J Clin Nutr 2000;54:424-8. View abstract.
  275. Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996;27:517-27. View abstract.
  276. Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins, 1999.
  277. Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998;129:517-24. View abstract.
  278. Ortiz Z, Shea B, Suarez-Almazor ME, et al. The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis. A metaanalysis of randomized controlled trials. J Rheumatol 1998;25:36-43. View abstract.
  279. Morgan SL, Baggott JE, Vaughn WH, et al. The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 1990;33:9-18. View abstract.
  280. Morgan SL, Baggott JE, Vaughn WH, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 1994;121:833-41. View abstract.
  281. Muggia FM, Synold TW, Newman EM, et al. Failure of pretreatment with intravenous folic acid to alter the cumulative hematologic toxicity of lometrexol. J Natl Cancer Inst 1996;88:1495-6. View abstract.
  282. Brown WT, Cohen IL, Fisch GS, et al. High dose folic acid treatment of fragile (X) males. Am J Med Genet 1986;23:263-71. View abstract.
  283. Hagerman RJ, Jackson AW, Levitas A, et al. Oral folic acid versus placebo in the treatment of males with the fragile X syndrome. Am J Med Genet 1986;23:241-62. View abstract.
  284. Rosenblatt DS, Duschenes EA, Hellstrom FV, et al. Folic acid blinded trial in identical twins with fragile X syndrome. Am J Hum Genet 1985;37:543-52. View abstract.
  285. Gillberg C, Wahlstrom J, Johansson R, et al. Folic acid as an adjunct in the treatment of children with the autism fragile-X syndrome (AFRAX). Dev Med Child Neurol 1986;28:624-7. View abstract.
  286. Fisch GS, Cohen IL, Gross AC, et al. Folic acid treatment of fragile X males: a further study. Am J Med Genet 1988;30:393-9. View abstract.
  287. Strom CM, Brusca RM, Pizzi WJ. Double-blind, placebo-controlled crossover study of folinic acid Leucovorin for the treatment of fragile X syndrome. Am J Med Genet 1992;44:676-82. View abstract.
  288. Montes LF, Diaz ML, Lajous J, et al. Folic acid and vitamin B12 in vitiligo: a nutritional approach. Cutis 1992;50:39-42. View abstract.
  289. Juhlin L, Olsson MJ. Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure. Acta Derm Venereol 1997;77:460-2. View abstract.
  290. Pack AR, Thomson ME. Effects of topical and systemic folic acid supplementation on gingivitis in pregnancy. J Clin Periodontol 1980;7:402-14. View abstract.
  291. Drew HJ, Vogel RI, Molofsky W, et al. Effect of folate on phenytoin hyperplasia. J Clin Periodontol 1987;14:350-6. View abstract.
  292. Brown RS, Di Stanislao PT, Beaver WT, et al. The administration of folic acid to institutionalized epileptic adults with phenytoin-induced gingival hyperplasia. A double-blind, randomized, placebo-controlled, parallel study. Oral Surg Oral Med Oral Pathol 1991;70:565-8. View abstract.
  293. Brattstrom LE, Israelsson B, Jeppsson JO, et al. Folic acid-an innocuous means to reduce plasma homocysteine. Scand J Clin Lab Invest 1988;48:215-21. View abstract.
  294. Woodside JV, Yarnell JW, McMaster D, et al. Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial. Am J Clin Nutr 1998;67:858-66. View abstract.
  295. Landgren F, Israelsson B, Lindgren A, et al. Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid. J Intern Med 1995;237:381-8. View abstract.
  296. Brouwer IA, van Dusseldorp M, Thomas CM, et al. Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. Am J Clin Nutr 1999;69:99-104. View abstract.
  297. Freudenheim JL, Graham S, Marshall JR, et al. Folate intake and carcinogenesis of the colon and rectum. Int J Epidemiol 1991;20:368-74. View abstract.
  298. Slattery ML, Schaffer D, Edwards SL, et al. Are dietary factors involved in DNA methylation associated with colon cancer? Nutr Cancer 1997;28:52-62. View abstract.
  299. Baron JA, Sandler RS, Haile RW, et al. Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas. J Natl Cancer Inst 1998;90:57-62. View abstract.
  300. Tseng M, Murray SC, Kupper LL, Sandler RS. Micronutrients and the risk of colorectal adenomas. Am J Epidemiol 1996;144:1005-14. View abstract.
  301. La Vecchia C, Braga C, Negri E et al. Intake of selected micronutrients and risk of colorectal cancer. Int J Cancer 1997;73:525-30. View abstract.
  302. Lashner BA, Provencher KS, Seidner DL, et al. The effect of folic acid supplementation on the risk for cancer or dysplasia in ulcerative colitis. Gastroenterology 1997;112:29-32. View abstract.
  303. Ma J, Stampfer MJ, Giovannucci E, et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 1997;57:1098-102. View abstract.
  304. Christensen B, Landaas S, Stensvold I, et al. Whole blood folate, homocysteine in serum, and risk of first acute myocardial infarction. Atherosclerosis 1999;147:317-26. View abstract.
  305. Morrow LE, Grimsley EW. Long-term diuretic therapy in hypertensive patients: effects on serum homocysteine, vitamin B6, vitamin B12, and red blood cell folate concentrations. South Med J 1999;92:866-70. View abstract.
  306. Bostom AG, Gohh RY, Beaulieu AJ, et al. Treatment of hyperhomocysteinemia in renal transplant recipients. A randomized, placebo-controlled trial. Ann Intern Med 1997;127:1089-92. View abstract.
  307. Duhra P. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J Am Acad Dermatol 1993;28:466-9. View abstract.
  308. Hardman JG, Limbird LL, Molinoff PB, eds. Goodman and Gillman's The Pharmacological Basis of Therapeutics, 9th ed. New York, NY: McGraw-Hill, 1996.
  309. Woo KS, Chook P, Lolin YI, et al. Folic acid improves arterial endothelial function in adults with hyperhomocysteinemia. J Am Coll Cardiol 1999;34:2002-6. View abstract.
  310. Carlsen SM, Folling I, Grill V, et al. Metformin increases total homocysteine levels in non-diabetic male patients with coronary heart disease. Scand J Clin Lab Invest 1997;57:521-7. View abstract.
  311. McKevoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
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