InteractionsGuide Index Page

 
Case Analysis Toolclose
Enter Each Substance:


Analysis Search Terms:

Folic Acid

Nutrient Name: Folic acid; folate, folinic acid.
Synonyms: Folacin; folate triglutamate, folicin, pteroyltriglutamate, pteroylglutamic acid, vitamin B9, vitamin Bc, vitamin M; 5-formyltetrahydrofolate (5-FTHF), 5-methyltetrahydrofolate (5-MTHF), 6(S) 5-MTHF,L-methylfolate; calcium folinate, calcium levofolinate, citrovorum factor, sodium folinate.

Summary Table
nutrient description

Chemistry and Forms

The Latin word for leaf, folium , was chosen to designate the nutrient present in green leafy vegetables and originally isolated from four tons of spinach leaves in 1946. The terms “folic acid” and “folate” are often used interchangeably for this water-soluble B-complex vitamin. However, folate is the preferred term for the mixture of related compounds occurring naturally in foods, whereas folic acid is the more stable form and is used in supplements and added to fortified foods, but rarely occurs in foods or the human body. Thus, forms are preferentially referred to on this basis in most usages within this monograph, with deference to nomenclature of original sources.

Folic acid may be more specifically identified as pteroylmonoglutamate or pteroylglutamic acid (PGA). Described chemically as N-[4-[[(2-amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-glutamic acid, it is comprised of para-aminobenzoic acid (PABA) linked at one end to a pteridine ring and at the other end to glutamic acid. Its molecular formula is C19H19N7O6, and its molecular weight is 441.40 daltons. Folic acid forms yellowish orange crystals. The color is imparted by the pteridine ring of folic acid. Pteridine also imparts color to the wings of certain butterflies.

Pteroylmonoglutamate (PGA) is the parent compound for many structurally related, derivative compounds that exhibit the biological activity of folic acid and are collectively referred to by the generic term folate . Most naturally occurring folates are pteroylpolyglutamate derivatives, containing two to seven glutamates joined in amide (peptide) linkages to the gamma-carboxyl of glutamate, with folylpoly-γ-glutamates being the predominant, naturally occurring form of dietary folates. Naturally occurring folates include 5-methyltetrahydrofolate (5-MTHF), 5-formyltetrahydrofolate (5-formyl-THF), 10-formyltetrahydrofolate (10-formyl-THF), 5,10-methylenetetrahydrofolate (5,10-methylene-THF), 5,10-methenyltetrahy-drofolate (5,10-methenyl-THF), 5-formiminotetrahydrofolate (5-formimino-THF), 5,6,7,8-tetrahydrofolate (THF), and dihydrofolate (DHF). The term folate is also used specifically to designate the anionic form of folic acid.

Physiology and Function

Folate, usually present as pteroylpolyglutamate derivatives in food, is hydrolyzed to pteroylmonoglutamate forms by folyl conjugase (also known as folate conjugase or γ-glutamylhydrolase) from the pancreas and mucosal conjugase from the intestinal wall before absorption from the small intestine. The monoglutamate forms of folate, including folic acid, are transported across the proximal small intestine, primarily the jejunum, by both active transport and diffusion. This is a saturable pH-dependent process, so absorption is decreased in an alkali medium and in the presence of added zinc. When ingested on an empty stomach, folic acid is generally twice as available as dietary sources of folate; folic acid consumed with food is 1.7 times as available as folate in food.

Following absorption of physiological amounts of folic acid into the enterocytes, a certain percentage undergoes reduction. Folic acid (PGA) is the inactive precursor of tetrahydrofolic acid (THFA) and methyltetrahydrofolate; it is converted to THFA, its biologically active form, with the participation of niacin and vitamin C, as well as several coenzymes and other nutrients. However, a functional methionine synthase deficiency can develop within the context of vitamin B12deficiency so that essentially all the folate becomes trapped as the N5-methyl THF derivative, thus preventing the synthesis of other THF derivatives required for the purine and thymidine nucleotide biosynthesis pathways. Reduced folate is transported to the liver via the portal circulation, where it is metabolized to polyglutamate derivatives by the action of folylpolyglutamate synthase. These pteroylpolyglutamate forms are the active cellular cofactor forms of folate.

The total body store of folate is about 12 to 28 mg. All tissue forms of folate are polyglutamates, with pteroylpentaglutamates being the principal type of intracellular folates. Approximately two thirds of folate in plasma is protein bound. Circulating forms of folate are monoglutamates, with pteroylmonoglutamates as the principal extracellular folates and 5-MTHF in its monoglutamate form being the principal folate in the plasma. The liver contains approximately 50% of the body stores of folate, or about 6 to 14 mg. Folate is excreted in the bile, and much of it is reabsorbed through the enterohepatic circulation. This enterohepatic recycling is important for modulating serum levels. Folate is also synthesized by the gut microflora, and as a result, some folates may be eliminated in the feces. However, the kidneys provide the predominant route for folate excretion. Folate enters the glomerulus intact and is reabsorbed into the proximal renal tubule. It is excreted in the urine primarily as folate cleavage products, with only a small amount of intact folate. The excretion of folates found through the breast milk represents a critical pathway for folate activity by providing availability for infant development.

The functions of folate in human physiology are relatively simple, but the implications of their activity (and dysfunction) can be profound and far-reaching. Through its coenzymes, folate plays an essential role in synthesis of nucleic acids, interconversion of amino acids, and single-carbon metabolism. Mediation of single-carbon transfer reactions is considered the primary and possibly exclusive function of folate coenzymes involved in a variety of reactions critical to the metabolism of nucleic acids and amino acids, especially the synthesis of purines and pyrimidines, glycine, and methionine. Thus, through its role in the synthesis of nucleotides from guanine, adenine/pyrimidine, and thymine, folate is required for the synthesis, methylation, and repair of deoxyribonucleic acid (DNA) and is involved in the synthesis of transfer ribonucleic acid (tRNA). This role in cell division is critical in cellular development and maturation, including tissue regeneration, but especially fetal growth and development in general and healthy formation of the nervous system in particular.

Folate plays a fundamental role in synthesis and interconversion of amino acids and the formation and utilization of formate. Folate is involved in the synthesis of glutamic acid, norepinephrine, and serotonin and the detoxification of homocysteine (Hcy) to methionine. Notably, several genetic mutations, including the 677CT polymorphism, influence Hcy metabolism by their effect on the activity of 5,10-methylenetetrahydrofolate reductase, the gene that provides instructions for making methylenetetrahydrofolate reductase (MTHFR), a critical enzyme (requiring flavin adenine dinucleotide [FAD] as a cofactor) that converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is required for the conversion of Hcy to methionine. Consequently, individuals who are homozygous (TT) for the abnormal gene have lower levels of the MTHFR enzyme and a marked tendency to hyperhomocysteinemia. Improved folate nutriture appears to stabilize the MTHFR enzyme, as does adequate riboflavin nutriture (the source of FAD), resulting in improved enzyme levels and lower Hcy levels. Methionine synthase (another enzyme requiring folate and B12as cofactors) combines Hcy with the 5-MTHF produced in the reaction catalyzed by MTHFR so that the Hcy becomes methionine and the 5-MTHF becomes MTHF. Thus, this folate coenzyme plays a critical role in the synthesis of methionine, which is required for the synthesis of S-adenosylmethionine (SAMe), the universal methyl donor essential to many biological methylation reactions.

Folate is also essential for the formation and maturation of red blood cells (RBCs) and white blood cells (WBCs). Folic acid is required for nucleoprotein synthesis and maintenance in erythropoiesis and is the single carbon carrier in the formation of heme; it also stimulates WBC and platelet production. Folate deficiency anemia is one of the megaloblastic anemias and is clinically and pathologically indistinguishable from vitamin B12deficiency anemia (pernicious anemia).

Impairment of any of these activities of folate, whether caused by genetic mutations, dietary deficiency, or drug-induced depletion, can produce a cascade of adverse effects directly influencing fetal development, DNA replication, healthy cellular and system function, and development of atherosclerosis, heart disease, and cancer.

nutrient in clinical practice

Known or Potential Therapeutic Uses

Within conventional practice, supplemental folic acid and dietary folate are used exclusively for the prevention of neural tube defects (NTDs; e.g., spina bifida, anencephaly) during in utero development and the treatment of demonstrated folate deficiency, primarily manifesting as megaloblastic and macrocytic anemias. However, epidemiological and clinical evidence continues to emerge regarding the preventive and therapeutic efficacy of enhanced folate intake in reducing atherogenic Hcy levels and improving endothelial function to modify cardiovascular risks, supporting neurotransmitter levels in relation to mood disorders and neurodegenerative processes, and preventing cancers, particularly breast, pancreatic, and colon cancers.

Broad efforts at preventing NTDs through dietary fortification have produced mixed benefits. Thus, although largely successful, these programs have exhibited varied penetration of key susceptible populations, and controversy as to their adequacy continues regarding both NTDs and other epidemiological patterns. 1-9For example, a 2006 survey showed that, even after mandatory fortification of U.S. cereals and grains with folic acid in 1998, women in racial and ethnic minority groups had lower serum folate levels than non-Hispanic white women. 10 Thus, pregnant women who do not regularly take folic acid–containing supplements are eight times more likely to have low serum folate values, despite eating folate-fortified foods. 11 Additionally, expanding knowledge of the multiple polymorphisms affecting folate metabolism is providing a working understanding of susceptibilities to folate-related pathologies and is highlighting the influence of individual genomic variability in the effectiveness of preventive measures and therapeutic applications.

Historical/Ethnomedicine Precedent

The long-standing adages declaring the value of leafy green vegetables in health maintenance and disease prevention may be a result, at least in part, of their being rich in folates.

Possible Uses

Acquired immunodeficiency syndrome and human immunodeficiency virus (AIDS/HIV) support, age-related hearing loss (reduction), Alzheimer's disease, anemia (thalassemia, if deficient), anger (hyperhomocysteinemia associated with MTHFR mutations), atherosclerosis, bipolar disorder, breast cancer prevention (risk reduction in women who consume alcohol), canker sores (with deficiency), cardiac events and death (risk reduction after first stroke), celiac disease (deficiency only), cervical cancer prevention, cervical dysplasia (abnormal Pap test), Crohn's disease, colon cancer prevention, depression, dermatitis herpetiformis (deficiency), diarrhea, Down syndrome, epilepsy, folate metabolism polymorphisms, gingivitis (as rinse), gout, hemorrhagic stroke (risk reduction), hypercholesterolemia, hyperhomocysteinemia, hypertension (risk reduction), laryngeal leukoplakia (risk reduction), lung cancer (risk reduction), malabsorption and gastrointestinal inflammation, megaloblastic anemia, migraine headaches, myocardial infarction, neural tube defect (prevention), osteoarthritis (with vitamin B12), osteoporosis, periodontal disease, peripheral vascular disease, postpartum support, preeclampsia, pregnancy (potential or known), psoriasis, restless legs syndrome, rheumatoid arthritis, schizophrenia (deficiency or hyperhomocysteinemia associated with MTHFR mutations), seborrheic dermatitis, second stroke (risk reduction), seizure disorders, sickle cell anemia (hyperhomocysteinemia), skin ulcers, ulcerative colitis, vitiligo.

Deficiency Symptoms

Folate deficiency results in reduction of DNA synthesis and thus in reduction of cell division. Because the main metabolic consequences of folic acid deficiency are changes in cellular nuclear morphology, rapidly multiplying cells are most affected, such as fetal tissue, erythrocytes, and the epithelial cells of the stomach, intestines, vagina, and cervix. Thus, folate deficiencies result in neural tube and other birth defects, impaired infant development, poor growth, megaloblastic (macrocytic) anemia and other blood disorders, fatigue, weakness, frequent infections, insomnia, irritability, paranoid behavior, mental confusion, hostility, forgetfulness, depression, syncope, headache, palpitations, elevated Hcy level, atherosclerosis, dyspnea, anorexia, glossitis, nausea, dyspepsia, constipation, diarrhea, cervical dysplasia, and hair loss. Gastrointestinal (GI) disturbances are common, resulting from atrophy of digestive tract epithelium. Reduced production of platelets can increase risk of abnormal bleeding. Likewise, impairments in WBC development reduce immune response and increase susceptibility to infections.

Folate deficiency is common, and folate activity is subject to many stressors. Intake of dietary folate and supplemental folic acid is inadequate for a significant proportion of the population, and mild folic acid deficiencies are often undetected. Populations particularly at risk for compromised folate nutriture include alcoholics, the elderly, impoverished people, women using birth control pills, and individuals with malabsorption disorders. Some conditions, such as chronic alcohol consumption and celiac disease, are associated with both low dietary intake and diminished absorption. Tobacco decreases the absorption of folic acid. Certain conditions, such as pregnancy, lactation, hemolytic anemia, leukemia, and other cancers, result in increased rates of cell division and metabolism, leading to an increase in the body's demand for folate. In 1975, folate deficiency during pregnancy was estimated as high as 60%; programs of folate fortification of grains have not been consistently effective in eliminating this significant risk factor. Finally, numerous medications can interfere with folate metabolism, deplete folate (especially with long-term use), or exacerbate folate deficiency in those with other factors adversely influencing folate status.

Several genetic mutations may directly impair folate activity, with profound implications only beginning to be understood. Most prominently, the C677T MTHFR polymorphism, a common variation involving the gene for methylenetetrahydrofolate reductase (MTHFR), can adversely affect folate metabolism and function, particularly the conversion of 5,10-methylene-THF to 5-methyl-THF. Elevated Hcy levels and increased risk for vascular disease are strongly associated with these MTHFR mutations because methyl-THF is the predominant circulatory form of folate and the main carbon donor for the remethylation of homocysteine to methionine. A mutation in the MTHFR gene leading to mild to moderate hyperhomocysteinemia has been found in 15% of patients with premature cerebrovascular disease. Individuals with severe MTHFR deficiency (0%-20% residual activity) present in infancy or adolescence with developmental delay, motor and gait dysfunction, seizures, schizophrenic disturbances, and other neurological abnormalities; they are also at risk of vascular complications.

Homocysteic acid, the oxidation product of Hcy, exerts potent excitatory effects and may be associated with anger, hostility, schizophrenia-like psychosis, depression, and bipolar disorder, particularly in individuals with the homozygous TT genotype of the thermolabile C677T MTHFR polymorphism. The risk of elevated serum levels of total homocysteine (tHcy) is increased in individuals with the combination of the MTHFR 677TT and RFC1 80GG genotypes. Devlin et al. 12 conducted a study of interactions among polymorphisms in folate-metabolizing genes and serum tHcy concentrations in a healthy elderly population. They found that folate and tHcy concentrations were not affected individually by the MTHFR 1298AC, RFC1 80GA, or GCPII 1561CT polymorphisms or by combinations of the MTHFR 677CT and MTHFR 1298AC genotypes. However, individuals with the combination of MTHFR 677TT and RFC1 80GG genotypes exhibited higher serum tHcy.

Inherited defects in methionine synthase, dihydrofolate reductase, and glutamate formiminotransferase, as well as congenital conditions affecting folate absorption and membrane transport, can also influence vascular and mental health through their impact on folate metabolism.

Administration of folic acid will produce marked alleviation of pernicious anemia (the megaloblastic anemia related to vitamin B12deficiency), but the GI signs and symptoms and the neurological lesions continue to progress. For this reason, supplements of 1000 µg (1 mg) or greater of folic acid require a prescription in the United States and some other Western countries. Combining 1 mg or more of oral vitamin B12with 1 mg or more of folic acid would obviate this problem; 1 mg or more of vitamin B12will reliably correct B12deficiency, even in the presence of pernicious anemia, atrophic gastritis, chronic proton pump inhibitor therapy, or other B12malabsorption syndromes.

Dietary Sources

Foods rich in folates include dark-green leafy vegetables (spinach, kale, mustard greens, turnip greens, escarole, chard, arugula, beet greens, bok choy, dandelion green, mache, radicchio, rapini or broccoli de rabe, Swiss chard), liver (beef or chicken) and other organ meats, egg yolk, and brewer's yeast. Folylpoly-γ-glutamates are the predominant form of folates occurring naturally in foods. Other good sources are beets, broccoli, brussel sprouts, cabbage, cauliflower, asparagus, orange juice, cantaloupe, kidney and lima beans, pinto beans, garbanzo beans, black-eyed peas, lentils, soybeans, soy flour, potato, wheat germ, and whole-grain cereals and breads. Fortified cereals made from processed grains can also serve as sources of folic acid. The symbiotic flora comprising the intestinal microbiota, if intact, also synthesize a significant amount of folate.

Folic acid is water soluble, with some forms stable to heat and others heat sensitive. Some forms are stable to acid and others destroyed. Vegetables stored at room temperature undergo considerable loss of folic acid. Virtually all the folate in dried milk has been destroyed.

The absorption efficiency of natural folates is approximately 50% that of folic acid in supplements or fortified foods. The model of dietary folate equivalents (DFEs) has been introduced to account for the difference in absorption efficiency between natural food folate and folic acid. Thus, DFEs can be calculated as follows: 1 microgram (µg) of DFEs = 1µg food folate = 0 .5 µg folic acid taken on empty stomach = 0 .6 µg folic acid taken with meals

Nutrient Preparations Available

The principal form of supplemental folate is folic acid, as a single ingredient or in combination products such as B-complex formulations. Folate triglutamate (pteroyltriglutamate) is also used. 5-Methyl folate and 5-formyl folate are commercially available reduced folates.

5-formyltetrahydrofolate (5-FTHF) and 5-methyltetrahydrofolate (5-MTHF) are the reduced and metabolically active forms of folic acid. Folinic acid, the free acid of calcium folinate, is the more frequently used form and is also known as calcium folinate (Leucovorin Calcium, Leukovorin, Wellcovorin), calcium levofolinate (Isovorin), citrovorum factor (Citrovorum), and sodium folinate (Sodiofolin). Folinic acid is a racemic mixture of levorotatory and dextrorotatory isomers. The levo-isomer is the metabolically active moiety. These calcium or sodium salts are used for parenteral or oral administration.

Metafolin, Merck's patented synthetic form of 6(S) 5-MTHF, orL-methylfolate, is the only form available (for the duration of Merck's patent) of the levorotatory (L) chiral isomer of 5-MTHF, which is the chiral isomer made by human metabolism from folic acid, and also the chiral form found in foods which contain 5-MTHF. It is derived from commercially available B-complex vitamin folic acid, which is reduced to tetrahydrofolate in a process that leads to the formation of a new chiral center and two diastereoisomers in an equimolar ratio. TheLisomer (6S-isomer) of methylfolate is then isolated by selective crystallization. Metafolin is promoted as a form of folate that requires no reduction steps once absorbed and that is immediately bioavailable and thus unaffected by the MTHFR C→T polymorphism. 14L-Methylfolate also bypasses most folate-interfering compounds, such as those that inhibit dihydrofolate reductase (e.g., methotrexate, pemetrexed, EGCG).

Dosage Forms Available

  • Oral:   Capsule, liposomal spray, liquid, tablet, tablet (effervescent).
  • Injection:   Deep intramuscular, subcutaneous, or intravenous; sodium folate solution (0.1 mg folic acid per 1 mL), usually 5 mg/mL (10 mL), contains benzyl alcohol.

Source of Materials for Nutrient Preparations

Folic acid used in supplements, prescriptions, and food fortification (e.g., wheat flour) is synthesized from guanidine and glutamic acid as starting materials. The chemical synthesis ofL-5-MTHF (Metafolin) starts from the commercially available vitamin folic acid, which is chemically reduced to tetrahydrofolate (THF). This reduction step leads to the formation of a new chiral center and two diastereoisomers in an equimolar ratio. In nature, reduced folates consist only of the pure levo (L) isomer (corresponding to the 6S isomer for methylfolate); thus, processes were developed allowing the isolation of the naturalLform by selective crystallization. 13

Dosage Range

Adult

Dietary: 300 µg folic acid daily for adults. In United Kingdom, average adult daily diet for women provides 224 µg, and for men, 322 µg.

  • Supplemental/Maintenance:   400 µg daily for adults.

The U.S. Food and Drug Administration (FDA) recommends 600 µg folic acid for pregnant women and 500 µg for nursing women. Based on survey data published in 1996, Lawrence et al. 10 recommend, “Until the optimal folate level is identified that confers maximum protection against neural tube defects, health care providers and women's health advocates should continue to encourage women who can become pregnant to take a vitamin containing 400 micrograms of folic acid every day.” Women who could become pregnant are advised to take 400 to 800 µg of folic acid per day in anticipation of the possibility of conceiving because folic acid deficiency is most critical during the initial stages of pregnancy, when many women are not yet aware of their being pregnant.

The folic acid dose in over-the-counter (OTC) nutritional supplements is limited to 900 µg. Doses of 1 mg or greater require a prescription. Folic acid is best taken between or with meals, preferably with the dose divided throughout the day.

Pharmacological/Therapeutic:

  • 500 to 800 µg/day is common.
  • Pregnant and lactating women: 0.8 mg/day
  • Pharmacological dosages in scientific literature: 400 to 4000 µg

Administration of 5 to 10 mg daily may occur in research or other specialized settings, including treatment of severe deficiency. Men show a smaller increase in folate and decrease in Hcy to a given dose of folic acid than women. 15

  • Toxic:   Folic acid is essentially nontoxic, even at very high doses. The tolerable upper intake level (UL) established by the U.S. Institute of Medicine's Food and Nutrition Board is 1000 µg/day (based on synthetic folic acid). This UL is based on folic acid doses of 1 mg or more masking an undiagnosed vitamin B12deficiency (by correcting the anemia that occurs with B12deficiency, which is often the sole sign that alerts health care providers to the presence of an underlying B12deficiency).

Pediatric (<18 Years)

Dietary:

  • Infants, birth to 6 months: 25 µg/day
  • Infants, 7 to 12 months: 35 µg/day
  • Children, 1 to 3 years: 150 µg/day
  • Children, 4 to 8 years: 200 µg/day
  • Children, 9 to 13 years: 300 µg/day
  • Adolescents, 14 to 18 years: 300 µg/day

Supplemental/Maintenance:

  • Infants, birth to 12 months: 0.1 mg/day
  • Children, 1 to 3 years: up to 0.3 mg/day
  • Children, 4 years and older: 0.4 mg/day

  • Pharmacological/Therapeutic:   None specifically established at this time.

  • Toxic:   None specifically established at this time.

Laboratory Values

Serum Folate

Serum folate reflects recent dietary intake and is most useful when combined with assays of vitamin B12and red blood cell (RBC) folic acid. However, serum folate and serum vitamin B12can be normal in mild folate and vitamin B12deficiencies. Homocysteine (folate and B12) and methylmalonic acid (B12only) are more sensitive indicators of mild folate and vitamin B12deficiencies.

  • Normal levels: 4.5 to 30 nmol/L or 5.4 to 24 µg/mL.

Red Blood Cell Folate (Erythrocyte Folate)

The RBC folate levels reflect body folate stores. RBCs are generally macrocytic when folate and/or B12deficiency states are present except in combined deficiencies of both folate and iron, common in malnourished individuals.

  • Normal levels: 280 to 790 ng/mL RBCs.
  • Levels < 312 nmol/L can indicate deficiency.
  • Note:   Different laboratories use different reference ranges for serum folate and RBC folate because their analytical assays vary. Many antibiotics may interfere with the microbiological assay for serum and erythrocyte folic acid and can produce falsely low results.

Neutrophilic Hypersegmentation Index (NHI)

The neutrophilic hypersegmentation index (NHI) can identify the earliest stages of folate insufficiency. Deficiency indicated when the ratio of neutrophils with five or more lobes to those with four or fewer lobes is greater than 30%. Hypersegmentation can also result from vitamin B12deficiency and is not reliable during pregnancy.

Serum Methylmalonic Acid

Methylmalonic acid (MMA) is useful in differentiating folate and cobalamin deficiency.L-Methylmalonyl coenzyme A (CoA mutase is a vitamin B12–dependent enzyme; therefore a B12deficiency, but not a folate deficiency, will lead to an increase in MMA.

Total Homocysteine

Total homocysteine (tHcy) concentration indicates folate and/or cobalamin deficiency and serves as predictor of risk for arterial stiffness, ischemic stroke, and myocardial infarction. Homocysteine levels can also be elevated by genetic polymorphisms that result in greater requirements of pyridoxine (vitamin B6), as well as deficiencies of pyridoxine and methyl donor nutrients in general.

A plasma tHcy concentration exceeding 15 µmol/L indicates hyperhomocysteinemia, although many investigators propose that achieving much lower levels (7-10 µmol/L) is necessary for decreasing vascular disease risk.

If anticoagulated blood tubes are allowed to sit longer than 10 minutes before spinning, the tHcy level can be falsely elevated. Pharmacological doses of niacin also falsely elevate tHcy levels and should be held for 24 hours before drawing blood to determine tHcy levels.

Serum Homocysteine

Serum Hcy indicates folate or cobalamin deficiency and serves as predictor of risk for ischemic stroke and myocardial infarction. It is used to assess homocystinuria.

  • Normal levels: Male: 4.3-11.4 micromol/L
  • Female: 3.3-10.4 micromol/L

Emerging and Related Tests

  • Tetrahydrofolate (THF) concentrations.
  • Whole-blood folate may also be valuable in some settings, but standards have only recently been established.
  • Fluorescence polarization immunoassay (FPIA) can be performed for the quantitation of total human L-homocysteine in serum or plasma.
  • Methylene-THFR identifies normal, heterozygous, and homozygous genotypes.
  • 5,10-Methylene-THFR C677T polymorphism identifies the mutation and provides preliminary evaluation of associated increased thrombotic risk and obstetrical risk.

Emerging research indicates the need to test for MTHFR 1298AC, RFC1 80GA, and GCPII 1561CT polymorphisms in establishing cardiovascular risk. 12

Analysis of both the C677T mutation and the A1298C mutation is recommended for evaluation of obstetrical risk in patients with recurrent fetal loss. Patients who are heterozygous for the C677T mutation are reflex-tested for the A1298C mutation. Only C677T homozygotes and C677T/A1298C compound heterozygotes are at increased risk for thrombotic events.

  • Note:   S-adenosylmethionine (SAMe) has a similar molecular form to S-adenosylhomocysteine, and exogenous intake, at therapeutic levels, may interfere with this assay.

safety profile

Overview

Supplemental folic acid is essentially nontoxic, even at high doses, and extremely safe at nutritional doses. Folic acid doses up to 1 mg daily are well tolerated. Substantive and consistent evidence of adverse effects attributable to folic acid supplementation is lacking. Adverse effects attributed to folic acid primarily derive from issues of diagnosis and clinical management.

Health care professionals are advised to counsel patients to avoid supplementing with 800 µg or more of folic acid daily unless they have been evaluated for vitamin B12deficiency or they coadminister 1 mg or more of B12. Inappropriate use of folic acid in large doses could precipitate neuropathy in individuals with undiagnosed B12deficiency (usually from pernicious anemia). More than 100 cases have been reported in which vitamin B12–deficient subjects receiving oral folic acid at 5 mg or more daily experienced progression of neurological symptoms and signs. Reports are rare of such complications in individuals receiving doses of folic acid less than 5 mg daily. Consequently, the U.S. Food and Nutrition Board advises that all adults limit their intake of folic acid to 1000 µg daily. The concerns regarding safety underlying dose restrictions are limited to synthetic folic acid intake through supplements and fortification. Folate from food sources is generally considered highly unlikely to mask vitamin B12deficiency.

Aggravations of seizure disorders have been reported in patients who initiated folic acid supplementation while undergoing anticonvulsant therapy. Such reactions may result from folic acid interfering with the activity of antiepileptic drugs.

Nutrient Adverse Effects

General Adverse Effects

Sleep disturbances, mental changes, and GI effects have been associated with high-dose folic acid intake, greater than 10 mg daily. Doses greater than 5 mg (5000 µg) daily may cause digestive upset in some individuals. Wheezing, dyspnea, fever, erythema, skin rash, itching, and other symptoms of allergic reactions have been reported on rare occasions.

Some secondary sources suggest that extended intake of high doses may cause uricosuria or produce folacin crystals in the kidney. Dialysis patients have increased requirements for folic acid and vitamin B6, needing at least 800 µg to 1 mg or more of folic acid and 10 mg or more of B6each day.

Adverse Effects Among Specific Populations

Folic acid supplementation, without vitamin B12, is contraindicated in patients with B12deficiency, especially pernicious anemia.

The effects of folate on cognitive function have generally been considered salubrious, particularly in elderly persons. However, a single study in 2005 produced the unexpected finding that high folate intake was associated with more rapid cognitive decline in older adults, particularly men and women taking supplemental folic acid at levels greater than 400 µg/day. Subjects in the top quintile of folate intake (> 700 µg/day) exhibited twice the rate of mental decline over 6 years as those who with the lowest folate intake. Although suggesting caution in routine use of folic acid supplements (without vitamin B12), the authors emphasized that evidence was lacking to confirm that folate itself caused the cognitive deterioration seen in some study participants and noted that high folate intake might be masking a vitamin B12deficiency in some individuals. 16 No other research has pointed to similar patterns. An intervention trial administering folate supplements, B12supplements (in equivalent doses to the folate), and both folate and B12together, with single and double placebo control groups, to elderly subjects over 5 years would be required to address the issues conclusively. Notably, in the subsequent Veterans Affairs Normative Aging Study, Tucker et al. 17 found that high Hcy and low B-vitamin plasma levels predicted cognitive decline in aging men. Moreover, folate (plasma and dietary) “remained independently protective against a decline in spatial copying score after adjustment for other vitamins and for plasma homocysteine.”

Preschool children administered folic acid (and iron) may be at higher risk of severe illness and death in a high-malaria-transmission setting. Routine prophylactic supplementation should be avoided pending further research. However, within the context of an active program “to detect and treat malaria and other infections, iron-deficient and [anemic] children can benefit from supplementation.” 18

Haggarty et al. 19 reported that high levels of serum folate appear to increase the risk of a dizygotic twin birth after women are impregnated through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). In particular, the rate of twins was associated with elevated levels of plasma and RBC folate (odds ratio [OR] 1.27 for each 100-g change in folate intake). However, the authors noted that “there was no significant association between folate and vitamin B12intake, or blood levels, and pregnancy or rate of live births or pregnancy loss after IVF.”

Pregnancy and Nursing

Enhancement of dietary folates and supplemental folic acid is recommended for any woman of childbearing age who might become pregnant, and this is specifically required during pregnancy. Folate enters breast milk and is beneficial. Folic acid and folate are specifically recommended to prevent developmental birth defects, particularly neural tube defects. Specific maximum safe dosages have not been established for pregnant or nursing women. (See, however, previous discussion on possible effects of high folate levels in relation to assisted reproduction.)

Infants and Children

No adverse effects have been reported in children or would be predicted.

Contraindications

Folic acid at doses greater than 800 µg/day is contraindicated when vitamin B12status is uncertain. Doses greater than 1 mg/day may obscure pernicious anemia, with irreversible progression of neuropathy, unless the B12deficiency is corrected with high-dose (1-2 mg/day) oral or parenteral B12.

Prophylactic folic acid (and iron) may be contraindicated for children in malarial environments. 18

Some clinicians have suggested that individuals with elevated blood levels of histamine (i.e., histadelia) should avoid supplemental folic acid because it can produce further histamine excess and aggravate a tendency to depression, schizophrenia, or other adverse effects purported to be associated with elevated histamine levels.

Precautions and Warnings

Self-administration of folic acid at levels greater than 400 µg/day is inadvisable in individuals being treated with anticonvulsants, antifolates, and other medications with a mechanism of action based on interfering with folate activity.

interactions review

Strategic Considerations

Folate is a vital nutrient for everyone, as evidenced by universal recommendation to eat bountiful amounts of dark-green leafy vegetables and other folate-rich foods. Overwhelming evidence indicates that folate deficiency is widespread, even among those presumed to have adequate diets, but particularly among the elderly population, malnourished individuals, tobacco smokers, and those who excessively consume alcohol or processed foods. Furthermore, the folate that is consumed in the diet, produced endogenously, and ingested as a supplement is fragile, or at least vulnerable to a wide range of stressors, most notably pharmacological agents.

Healthy levels of folate in the blood and target tissues enable many key physiological functions, such as normal DNA synthesis and healthy cell division, homocysteine regulation, and endothelial function, and thus play a key role in preventing many pathological processes, including carcinogenesis and atherogenesis. However, polymorphisms in the genes coding for key folate metabolism enzymes, such as MTHFR, thiopurine methyltransferase (TPMT), and inosine triphosphate pyrophosphatase (ITPase), play a key role in folate status, susceptibility to folate-related pathologies, response to folate administration, and tolerance of and therapeutic response to medications affecting folate.

Conventional medicine does not generally employ laboratory tests adequately sensitive for detecting compromised folate status, particularly depletion patterns and deficiency states at the tissue and mitochondrial level, before they reach pathological proportions at a system-wide level. Unless specifically contraindicated, folic acid supplementation could reasonably be recommended for everyone as basic nutritional support for health maintenance and prevention of many pathological and degenerative processes, especially if the person is taking one of the medications discussed later. The supervising caregiver then focuses on carefully monitoring the patient in specific situations requiring closer clinical management. The implications of folate deficiency can be profound and severe, from teratogenesis during pregnancy to stroke later in life, and constitute the primary clinically significant influence of drug interactions involving folate and folic acid for both short-term medical management and long-term strategies of wellness and prevention.

The main caution against folic acid administration is that vitamin B12deficiency, especially severe deficiencies such as those associated with pernicious anemia, might be masked. This warning, however, seems misplaced or at least uninformed because almost every folic acid product on the market is formulated with vitamin B12, at a minimum, or a comprehensive range of synergistic nutrients, as in a multivitamin or B-complex formulation. All health care providers experienced in nutritional therapeutics routinely coadminister folic acid and vitamin B12as a matter of safety, synergy, and efficacy. The more significant (and sometimes controversial) question centers on appropriate dosage levels, and emerging evidence is clarifying this clinical picture. Generous quantities of B12may be critical to effectiveness much more often than previously thought, especially in older people. Generally, conventional nutritional education has framed folate dosing in hundreds of micrograms and B12in single-digit micrograms because of the difference in quantity that prevents serious deficiency states. However, a pivotal clinical trial by Eussen et al. 20 showed that once deficient (by MMA levels), at least 500 to 600 µg of oral vitamin B12is required to correct an established pattern of “mild” depletion. Thus it is advisable always to give equivalent amounts of B12with folate.

Folic acid interacts with and is depleted by a wide range of medications. Some agents incidentally impair folate absorption and transport, but others rely on competitive inhibition and other means of directly interfering with folate activation and folate-dependent enzymes as central to their mechanism of action. In most cases, coadministration of folic acid offers a safe, easy, and inexpensive means of preventing, reducing, or reversing drug-induced adverse reactions, particularly folate deficiency at blood, tissue, and cellular levels, and interference with physiological activities of folate and related enzymes. Folate coadministration is contraindicated only in patients being treated with antifolate medications for tumors, and then primarily in doses greater than 1000 µg/day. Moreover, when the toxic effects of these medications exceed tolerance or safety limits, folic acid, or more often folinic acid, the activated form, is applied “to pull the situation back from the brink” (so-called rescue). Such contraindications are generally not applicable when the same medications, particularly methotrexate, are used for reasons other than antineoplastic activity.

Research and clinical experience increasingly indicate significant clinical benefits from use of 5-FTHF (folinic acid) and 5-MTHF as sources of activated folate in light of impaired enzyme activity, especially MTHFR, as a result of drug interference and genetic polymorphisms. For many years the use of folinic acid (5-FTHF) has largely been restricted to rescue use with methotrexate and other antifolate medications. The therapeutic significance of this and other forms of folate administration that bypass enzymatic inhibition (e.g., 5-MTHF) becomes more apparent, with growing awareness of the potential adverse implications of unintended decreases in functional folate levels.

Along with the major risk of neural tube defects from folate deficiency during early gestation, homocysteine (Hcy) regulation appears as the most recurrent theme in reviewing the strategic significance of drug interactions with dietary folate and supplemental folic acid. The pervasive and destructive effects of elevated Hcy levels are well documented and widely known. Methionine synthase, the enzyme that metabolizes Hcy to methionine, uses 5-MTHF and vitamin B12as cofactors. Folic acid may have antiatherogenic mechanisms independent of lowering Hcy levels. Besides effects on the vascular system, plasma tHcy level and low serum folate concentrations are independent risk factors for dementia as well as low bone mineral density, particularly among women. 17,21-26In a randomized, placebo-controlled trial involving 46 Taiwanese subjects (42 men, average age 73), Lin et al. 27 demonstrated that low-dose folic acid (400 µg daily) supplementation reduces Hcy concentration in hyperhomocysteinemic coronary artery disease (CAD) patients and could also reduce CAD risk. Compliance was assessed over 8 weeks by 24-hour diet recalls at week 0 and week 8. Notably, although the low-dose folic acid supplements had no significant effect on Hcy concentrations in the general study population, levels did significantly decrease in hyperhomocysteinemic subjects, by 1.8 µmol/L, especially for carriers of the T-allele.

The evolving debate as to whether Hcy represents a causal or coincident factor in heart disease, cerebrovascular accident (stroke), and related conditions shifted to a new level with publication of the Vitamin Intervention for Stroke Prevention (VISP) trial. When the VISP intention-to-treat analysis failed to show efficacy of combined vitamin therapy for recurrent vascular events in patients with nondisabling stroke, Spence et al. 27a conducted an “efficacy analysis limited to patients most likely to benefit from the treatment, based on hypotheses arising from evidence developed since VISP was initiated.” After excluding “patients with low and very high B12levels at baseline,” they found “a 21% reduction in the risk of events in the high-dose group compared with the low-dose group.” Also, “patients with a baseline B12level at the median or higher randomized to high-dose vitamin had the best overall outcome, and those with B12less than the median assigned to low-dose vitamin had the worst.” They concluded: “In the era of folate fortification, B12plays a key role in vitamin therapy for total homocysteine. Higher doses of B12, and other treatments to lower total homocysteine, may be needed for some patients.”

Subsequently, the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), NORVIT, and HOPE-2 trials supported research demonstrating that these nutrients help lower Hcy levels. However, these trials failed to support the hypothesis that lowering Hcy levels alone will provide protection against a future cardiovascular event in high-risk patients with established cardiovascular disease. For example, in the Norwegian study of post–myocardial infarction (MI) patients randomized to a folate-B12-B6formulation or placebo, Bønaa et al. 28,29observed a pattern of increased risk of a second MI in the intervention group, despite a lowering of Hcy. Although relevant to certain patient populations, the findings from these trials suggest that such a study of secondary prevention (patients with previous MI) have limited applicability to primary prevention (individuals without previous vascular events) in healthy individuals and in those with elevated risk. Notably, the HOPE-2 study demonstrated a statistically significant 25% reduction in nonfatal strokes. 30

Nevertheless, the current data are incomplete because all patients were taking standard post-MI medications (e.g., beta blockers, ACE inhibitors, aspirin). Also, investigators did not monitor drug levels to see if the B vitamins were depleted by the medications or, conversely, if the medications were impaired or levels lowered by the nutrients, as may occur if the nutrients (e.g., vitamin E) induce the pregnane X receptor (PXR). Such potentially significant variables, which were not assessed or factored in, might explain the unexpected “increased risk” associated with the B vitamins, which would actually be analogous to poor compliance with medication. Research into PXR is in preliminary stages, and a focus on its relevance to B vitamins may be warranted and could clarify these and other findings. More broadly, such findings do not detract from other potential benefits derived from lowering Hcy levels, or at least reversing processes associated with elevated Hcy.

An ongoing dialectic between reviews and meta-analyses continues and is unlikely to produce definitive conclusions and more precise recommendations until large-scale, long-term, and well-designed prospective interventional clinical trials are conducted. In reviewing the data from numerous cohort studies, Wald et al. 31 (2006) determined that despite controversy and apparently conflicting evidence in reports of the benefits of folate consumption on cardiovascular disease risk, the weight of evidence supports recommending folic acid for cardiovascular health. Their meta-analysis showed that a 3-µmol/L decrease in serum Hcy levels, considered achievable with a daily folic acid intake with 0.8 mg, lowers the risk of heart attack and stroke by 15% and 24%, respectively. Furthermore, in studies focusing on MTHFR genotypes, the investigators reported that high Hcy levels were associated as “causal” for the risk of stroke and that the “dose-response relation in the genetic studies is particularly relevant in suggesting a causal effect.” Overall, the estimate from the trials was consistent with a short-term protective effect of 12% on ischemic heart disease episodes and 22% on stroke, or a greater long-term effect. The degree that folic acid reduces Hcy concentration depends on background folate levels, so increasing folic acid consumption should reduce the risk of heart attack and stroke to a degree related to the Hcy reduction. The authors concluded “that the evidence is now sufficient to justify action on lowering homocysteine concentrations, although the position should be reviewed as evidence from ongoing trials emerges.” 31

Conversely, in a meta-analysis, Bazzano et al. 32 evaluated the effects of folic acid supplementation on risk of cardiovascular diseases and mortality in randomized controlled trials among persons with preexisting cardiovascular or renal disease. They concluded that folic acid supplementation “has not been shown to reduce risk of cardiovascular diseases or all-cause mortality among participants with prior history of vascular disease,” but noted that “ongoing trials with large sample sizes might provide a definitive answer to this important clinical and public health question.”

The issue of whether the potential benefits of folic acid and related nutrients that affect Hcy derive from other functions and effects, beyond lowering Hcy, appears increasingly important given the controversial findings and disappointed expectations of Hcy-centered interventional trials and meta-analyses. The role of folic acid in reversing endothelial dysfunction may be central to these protective effects. In a small but potentially pivotal study involving 128 patients with CAD, Moat et al. 33 found that high-dose folic acid (5 mg/day) for 6 weeks significantly improved endothelial function, independent of its effect on lowering plasma Hcy levels. Notably, these investigators observed that subjects administered folate at either 400 µg/day or 5 mg/day had significant increases in plasma folate and significant decreases in plasma Hcy, whereas only subjects who received 5 mg/day exhibited significant improvements in flow-mediated dilation. Another subgroup of subjects, administered betaine (3 g twice daily), showed significant impairment in flow-mediated dilation, despite a reduction in plasma Hcy. The authors’ conclusion that their findings suggest that folic acid “dose-dependently improves endothelial function in CAD via a mechanism independently of Hcy lowering” may portend a significant evolution in this body of research.

In a related experiment focused on the mechanism(s) underlying such observed phenomena, Moat et al. 34 demonstrated that folic acid can reverse “both the endothelial dysfunction and increased production of superoxide following depletion of rabbit aortic ring tetrahydrobiopterin (BH4) levels with 2,4-diamino-6-hydroxy-pyrimidine (DAHP) and N-acetyl-5-hydroxy-tryptamine (NAS).” Thus, they concluded that “folic acid reverses the endothelial dysfunction induced by BH4 depletion independently of either the regeneration or stabilization of BH4 or an antioxidant effect.”

Emerging evidence indicates that the influence of elevated Hcy levels extends beyond risk of stroke and heart disease, and that folate and other B vitamins have an important role in preventing or reducing other degenerative processes, especially those associated with aging. The literature associating hyperhomocysteinemia with dementia is well known and suggests a broader focus for future research and preventive nutritional support. For example, in a 3-year, randomized, placebo-controlled trial involving 728 subjects age 50 to 72, Durga et al. 35 found that folate (800 µg/day) may reduce age-associated hearing loss, particularly in individuals with elevated Hcy levels. The interconnections between Hcy, folate nutriture, and degenerative processes will undoubtedly be the subject of continued investigation.

The causes of hyperhomocysteinemia are broadly categorized as “inherited” and “acquired.” Many causes involve folate nutriture, metabolism, and function. The inherited causes include MTHFR deficiency or defect, methionine synthase defect, vitamin B12transport defect, vitamin B12coenzyme synthesis defect, and cystathionine-β-synthase deficiency. The acquired causes can be grouped as vitamin deficiencies, chronic diseases, and medication effects. Nutritional deficits of folic acid, vitamin B12, and vitamin B6can usually be remedied by ensuring adequate dietary sources and administering supplements that provide these synergistic nutrients. Enhanced folate intake may be of direct and indirect benefit for patients with chronic renal failure, hypothyroidism, psoriasis, and malignancies (including acute lymphoblastic leukemia). Notably, conventional treatment of these conditions often involves drug therapies that deplete or interfere with folate. Also, medications that adversely affect folate status and function constitute one of the primary risk factors for hyperhomocysteinemia. Fortunately, this last factor may be the most amenable to clinician intervention, with this monograph being a tool in providing safe and effective medical management by employing an evidence-based, integrative approach to health care delivery.

nutrient-drug interactions
Acetylsalicylic Acid (Aspirin) and Salsalate
Antacids
Cimetidine and Related Histamine (H 2 ) Receptor Antagonists
Proton Pump Inhibitors
Anticonvulsant Medications, Including Phenobarbital, Phenytoin, and Valproic Acid
Antifolates and Related Antimetabolites, Including Lometrexol, Methotrexate, Pemetrexed
Bile Acid Sequestrants
  • Evidence: Cholestyramine (Locholest, Prevalite, Questran), colestipol (Colestid).
Extrapolated, based on similar properties: Colesevelam (Welchol).
Drug-Induced Nutrient Depletion, Supplementation Therapeutic, Not Requiring Professional Management
Adverse Drug Effect on Nutritional Therapeutics, Strategic Concern
Beneficial or Supportive Interaction, with Professional Management

Probability: 2. Probable
Evidence Base: Consensus

Effect and Mechanism of Action

Through their intended effect of limiting absorption and assimilation of dietary lipids, bile acid sequestrants may prevent absorption and reduce bioavailability of folic acid as well as other nutrients, such as the fat-soluble vitamins, A, D, E, and K. 57,171-174

Through complementary mechanisms, folinic acid and cholestyramine can be used together to counter methotrexate toxicity.

Research

In 1979, Leonard et al. 175 demonstrated that cholestyramine and colestipol bound, to a great extent, vitamin B 12 –intrinsic factor complex, folic acid, and iron citrate in vitro. Likewise, in studying the mechanisms of intestinal folate transport, Strum 176 found that cholestyramine (20 mg) adsorbs 95% of pteroylglutamate (folate) in vitro.

Using a rodent model, Hoppner and Lampi 177 observed that cholestyramine significantly reduced the intestinal deconjugation, absorption, and bioavailability of folic acid compared with brewer's yeast folate.

Several human studies have specifically documented the effects of bile acid sequestrants on folate absorption and bioavailability. In a trial involving 20 children and young adults with familial hypercholesterolemia, Farah et al. 178 investigated the effects of cholestyramine in the context of a diet low in cholesterol and high in polyunsaturated fats. Cholestyramine administration was associated with a significant decrease in mean serum folate levels in female patients. Tonstad et al. 179 conducted a study involving 37 boys and 29 girls age 10 to 16 years with familial hypercholesterolemia, first in an 8-week, double blind, placebo-controlled protocol, then in open treatment for 44 to 52 weeks. Levels of serum folate, vitamin E, and carotenoids were reduced in the colestipol group. Only a minority of adolescents adhered to the new formulation of orange-flavored “colestipol granules” for the full year. Nevertheless, the authors concluded that “folate and possibly vitamin D supplementation is recommended.” Subsequently, in a randomized controlled trial involving children with familial hypercholesterolemia, Tonstad et al. 180 and another Norwegian team of investigators found that heterozygosity and homozygosity for the C677T mutation in the MTHFR gene was associated with low serum folate and increased susceptibility to elevation of plasma tHcy during cholestyramine treatment. These authors recommended folic acid coadministration as “prudent in these children” because of the independent relationship between elevated plasma tHcy and cardiovascular disease.

The ability of hypocholesterolemic resins to adsorb and reduce bioavailability of both folic acid and methotrexate (MTX) may be relevant in countering the toxicity of this potent antimetabolite, well-known for a range of adverse effects influencing tolerance and compliance. Interestingly, cholestyramine may be used to enhance the biliary excretion of MTX, which acts as an antifolate through competitive inhibition. 181 Based on multiple experiments examining the relative adsorption of MTX and calcium leucovorin (folinic acid) onto cholestyramine in vitro, Merino-Sanjuan et al. 182 suggested that “cholestyramine may be a potentially useful adjunctive therapy in the treatment of an overdose of MTX.” Fernandez et al. 183 described severe MTX-induced toxicity secondary to renal failure in a patient with non-Hodgkin's lymphoma. “Corrective measures included folinic acid rescue therapy, cholestyramine resin administration, hydration and urine alkalinization, urine pH monitoring, and extracorporeal clearance techniques.”

Nutritional Therapeutics, Clinical Concerns, and Adaptations

Physicians prescribing bile acid sequestrants are advised to coadminister folic acid, vitamins B 12 and B 6 , mixed tocopherols and tocotrienols, vitamin D, coenzyme Q10, and other synergistic nutrients within a comprehensive and individualized strategy of integrative therapeutics for the prevention and treatment of cardiovascular disease. The relationship between folate status and homocysteine would be adequate by itself to justify increased intake of dietary folate and supplemental folic acid, of at least 800 µg/day, in such a patient population. The probable interference with absorption and bioavailability of folate and other relevant nutrients by these hypocholesteremic resins further heightens the imperative for enhanced nutriture. Daily administration of a high-potency multivitamin/mineral combination will replace the nutrients impeded by the drug. Folic acid (as well as other nutrients and medications) should be taken 1 hour before or 4 to 6 hours after bile acid sequestrants to reduce impairment of absorption and obtain optimal bioavailability.

Chloramphenicol
Colchicine
Fenofibrate, Bezafibrate, and Related Fibrates
Fluoxetine and Related Selective Serotonin Reuptake Inhibitor and Serotonin-Norepinephrine Reuptake Inhibitor (SSRI and SSRI/SNRI) Antidepressants
Isoniazid, Rifampin, and Related Antitubercular Agents
Levodopa and Related Antiparkinsonian Agents
Lithium Carbonate
Mercaptopurine, Azathioprine, and Thioguanine (Thiopurines)
Metformin and Related Biguanides
Neomycin
Nitroglycerin and Related Nitrates
Nitrous Oxide
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Oral Contraceptives: Monophasic, Biphasic, and Triphasic Estrogen Preparations (Synthetic Estrogen and Progesterone Analogs)
Pancreatic Enzymes, Pancreatin, and Related Proteolytic Enzymes
Pyrimethamine
Sulfasalazine and Related Sulfonamide Antibiotics (Systemic)
Tetracycline Antibiotics (Systemic)
Triamterene and Related Potassium-Sparing Diuretics
Trimethoprim-Sulfamethoxazole
Zidovudine/AZT
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Acyclovir
Antibiotics
Beta-Adrenergic Blocking Agents and Calcium Channel Blockers (Systemic)
Corticosteroids, Oral, Including Prednisone
Cycloserine
Fluorouracil
Furosemide and Related Loop Diuretics
Medroxyprogesterone
Raltitrexed
Thiazide Diuretics
nutrient-nutrient interactions
B Vitamins
Pancreatin and Proteolytic Enzymes
Vitamin C
Zinc
herb-nutrient interaction
Coffee
Citations and Reference Literature
  • 1.Pfeiffer CM, Caudill SP, Gunter EW et al. Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999-2000. Am J Clin Nutr 2005;82:442-450.
  • 2.Canfield MA, Collins JS, Botto LD et al. Changes in the birth prevalence of selected birth defects after grain fortification with folic acid in the United States: findings from a multi-state population-based study. Birth Defects Res A Clin Mol Teratol 2005;73:679-689.View Abstract
  • 3.Stark KD, Pawlosky RJ, Beblo S et al. Status of plasma folate after folic acid fortification of the food supply in pregnant African American women and the influences of diet, smoking, and alcohol consumption. Am J Clin Nutr 2005;81:669-677.View Abstract
  • 4.Brent RL, Oakley GP Jr. The Food and Drug Administration must require the addition of more folic acid in “enriched” flour and other grains. Pediatrics 2005;116:753-755.
  • 5.Brent RL, Oakley GP Jr. Triumph and/or tragedy: the present Food and Drug Administration program of enriching grains with folic acid. Pediatrics 2006;117:930-932.View Abstract
  • 6.Martinez ME, Giovannucci E, Jiang R et al. Folate fortification, plasma folate, homocysteine and colorectal adenoma recurrence. Int J Cancer 2006;119:1440-1446.View Abstract
  • 7.Bentley TG, Willett WC, Weinstein MC, Kuntz KM. Population-level changes in folate intake by age, gender, and race/ethnicity after folic acid fortification. Am J Public Health 2006;96:2040-2047.View Abstract
  • 8.Sherwood KL, Houghton LA, Tarasuk V, O’Connor DL. One-third of pregnant and lactating women may not be meeting their folate requirements from diet alone based on mandated levels of folic acid fortification. J Nutr 2006;136:2820-2826.
  • 9.Ricciuto LE, Tarasuk VS. An examination of income-related disparities in the nutritional quality of food selections among Canadian households from 1986-2001. Soc Sci Med 2007;64:186-198.
  • 10.Lawrence JM, Watkins ML, Chiu V et al. Do racial and ethnic differences in serum folate values exist after food fortification with folic acid? Am J Obstet Gynecol 2006;194:520-526.
  • 11.Bol KA, Collins JS, Kirby RS. Survival of infants with neural tube defects in the presence of folic acid fortification. Pediatrics 2006;117:803-813.View Abstract
  • 12.Devlin AM, Clarke R, Birks J et al. Interactions among polymorphisms in folate-metabolizing genes and serum total homocysteine concentrations in a healthy elderly population. Am J Clin Nutr 2006;83:708-713.
  • 13.MetafolinTM scientific review. Darmstadt, Germany: Merck KGaA; 2004.
  • 14.Metafolin®: about the product. Product brochure. Darmstadt, Germany: Merck KGaA; 2004.
  • 15.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;143:177-183.View Abstract
  • 16.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;62:641-645.
  • 17.Tucker KL, Qiao N, Scott T et al. High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affairs Normative Aging Study. Am J Clin Nutr 2005;82:627-635.View Abstract
  • 18.Sazawal S, Black RE, Ramsan M et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet 2006;367:133-152.View Abstract
  • 19.Haggarty P, McCallum H, McBain H et al. Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study. Lancet 2006;367:1513-1519.View Abstract
  • 20.Eussen SJ, de Groot LC, Clarke R et al. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med 2005;165:1167-1172.View Abstract
  • 21.Bottiglieri T, Díaz-Arrastia R. Hyperhomocysteinemia and cognitive function: more than just a casual link? Am J Clin Nutr 2005;82:493-494.
  • 22.Ramos MI, Allen LH, Mungas DM et al. Low folate status is associated with impaired cognitive function and dementia in the Sacramento Area Latino Study on Aging. Am J Clin Nutr 2005;82:1346-1352.View Abstract
  • 23.Ravaglia G, Forti P, Maioli F et al. Homocysteine and folate as risk factors for dementia and Alzheimer disease. Am J Clin Nutr 2005;82:636-643.View Abstract
  • 24.Ravaglia G, Forti P, Maioli F et al. Folate, but not homocysteine, predicts the risk of fracture in elderly persons. J Gerontol A Biol Sci Med Sci 2005;60:1458-1462.View Abstract
  • 25.Gjesdal CG, Vollset SE, Ueland PM et al. Plasma total homocysteine level and bone mineral density: the Hordaland Homocysteine Study. Arch Intern Med 2006;166:88-94.View Abstract
  • 26.Durga J, van Boxtel MP, Schouten EG et al. Folate and the methylenetetrahydrofolate reductase 677C→T mutation correlate with cognitive performance. Neurobiol Aging 2006;27:334-343.View Abstract
  • 27.Lin P-T, Lee B-J, Chang H-H et al. Low-dose folic acid supplementation reduces homocysteine concentration in hyperhomocysteinemic coronary artery disease patients. Nutr Res 2006;26:460-466.
  • 27a.Spence JD, Bang H, Chambless LE, Stampfer MJ. Vitamin Intervention for Stroke Prevention Trial: an efficacy analysis. Stroke 2005;36(11):2404-2409.
  • 28.Bønaa KH. NORVIT: Norwegian Study of Homocysteine Lowering with B Vitamins in Myocardial Infarction. European Society of Cardiology 2005 Congress. Stockholm, 2005.
  • 29.Bønaa KH, Njølstad I, Ueland PM et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006;354:1578-1588.
  • 30.Lonn E, Yusuf S, Arnold JM et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567-1577.
  • 31.Wald DS, Wald NJ, Morris JK, Law M. Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. BMJ 2006;333:1114-1117.View Abstract
  • 32.Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA 2006;296:2720-2726.View Abstract
  • 33.Moat SJ, Madhavan A, Taylor SY et al. High- but not low-dose folic acid improves endothelial function in coronary artery disease. Eur J Clin Invest 2006;36:850-859.View Abstract
  • 34.Moat SJ, Clarke ZL, Madhavan AK et al. Folic acid reverses endothelial dysfunction induced by inhibition of tetrahydrobiopterin biosynthesis. Eur J Pharmacol 2006;530:250-258.View Abstract
  • 35.Durga J, Verhoef P, Anteunis LJC et al. Effects of folic acid supplementation on hearing in older adults: a randomized, controlled trial. Ann Intern Med 2007;146:1-9.
  • 36.Buist RA. Drug-nutrient interactions: an overview. Int Clin Nutr Rev 1984;4:114.
  • 37.Alter HJ, Zvaifler NJ, Rath CE. Interrelationship of rheumatoid arthritis, folic acid, and aspirin. Blood 1971;38:405-416.View Abstract
  • 38.Lawrence VA, Loewenstein JE, Eichner ER. Aspirin and folate binding: in vivo and in vitro studies of serum binding and urinary excretion of endogenous folate. J Lab Clin Med 1984;103:944-948.View Abstract
  • 39.Baggott JE, Morgan SL, Ha T et al. Inhibition of folate-dependent enzymes by non-steroidal anti-inflammatory drugs. Biochem J 1992;282(pt 1):197-202.View Abstract
  • 40.Benn A, Swan CH, Cooke WT et al. Effect of intraluminal pH on the absorption of pteroylmonoglutamic acid. BMJ 1971;1:148-150.View Abstract
  • 41.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;112:458-463.View Abstract
  • 42.Stumm W, Morgan JJ. Aquatic Chemistry: an Introduction Emphasizing Chemical Equilibria in Natural Waters. New York: Wiley; 1981.
  • 42a.Ruscin JM, Page RL 2nd, Valuck RJ. Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother 2002;36:812-816.
  • 43.Berg MJ, Stumbo PJ, Chenard CA et al. Folic acid improves phenytoin pharmacokinetics. J Am Diet Assoc 1995;95:352-356.View Abstract
  • 44.Lewis DP, Van Dyke DC, Willhite LA et al. Phenytoin–folic acid interaction. Ann Pharmacother 1995;29:726-735.View Abstract
  • 45.Kishi T, Fujita N, Eguchi T, Ueda K. Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy. J Neurol Sci 1997;145:109-112.
  • 46.Apeland T, Mansoor MA, Pentieva K et al. Fasting and post-methionine loading concentrations of homocysteine, vitamin B2, and vitamin B6 in patients on antiepileptic drugs. Clin Chem 2003;49:1005-1008.View Abstract
  • 47.Reynolds EH. Mental effects of anticonvulsants, and folic acid metabolism. Brain 1968;91:197-214.View Abstract
  • 48.Hendel J, Dam M, Gram L et al. The effects of carbamazepine and valproate on folate metabolism in man. Acta Neurol Scand 1984;69:226-231.View Abstract
  • 49.Isojarvi JI, Pakarinen AJ, Myllyla VV. Basic haematological parameters, serum gamma-glutamyl-transferase activity, and erythrocyte folate and serum vitamin B12 levels during carbamazepine and oxcarbazepine therapy. Seizure 1997;6:207-211.
  • 50.Chang T, Savory A, Glazko AJ. A new metabolite of 5,5-diphenylhydantoin (Dilantin). Biochem Biophys Res Commun 1970;38:444-449.View Abstract
  • 51.LaJoie J, Moshe SL. Effects of seizures and their treatment on fetal brain. Epilepsia 2004;45 Suppl 8:48-52.View Abstract
  • 52.Morrell MJ. The new antiepileptic drugs and women: efficacy, reproductive health, pregnancy, and fetal outcome. Epilepsia 1996;37 Suppl 6:S34-44.View Abstract
  • 53.Jensen PK, Gram L, Schmutz M. Oxcarbazepine. Epilepsy Res Suppl 1991;3:135-140.View Abstract
  • 54.Hoffbrand AV, Necheles TF. Mechanism of folate deficiency in patients receiving phenytoin. Lancet 1968;2:528-530.View Abstract
  • 55.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;32:802-817.View Abstract
  • 56.Holmes LB, Harvey EA, Coull BA et al. The teratogenicity of anticonvulsant drugs. N Engl J Med 2001;344:1132-1138.View Abstract
  • 57.Wyszynski DF, Nambisan M, Surve T et al. Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology 2005;64:961-965.
  • 58.Vinten J, Adab N, Kini U et al. Neuropsychological effects of exposure to anticonvulsant medication in utero. Neurology 2005;64:949-954.View Abstract
  • 59.Ono H, Sakamoto A, Eguchi T et al. Plasma total homocysteine concentrations in epileptic patients taking anticonvulsants. Metabolism 1997;46:959-962.View Abstract
  • 60.Schwaninger M, Ringleb P, Winter R et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia 1999;40:345-350.View Abstract
  • 61.Apeland T, Mansoor MA, Strandjord RE. Antiepileptic drugs as independent predictors of plasma total homocysteine levels. Epilepsy Res 2001;47:27-35.View Abstract
  • 62.Reynolds EH, Mattson RH, Gallagher BB. Relationships between serum and cerebrospinal fluid anticonvulsant drug and folic acid concentrations in epileptic patients. Neurology 1972;22:841-844.
  • 63.Martinez Figueroa A, Johnson RH, Lambie DG, Shakir RA. The role of folate deficiency in the development of peripheral neuropathy caused by anticonvulsants. J Neurol Sci 1980;48:315-323.View Abstract
  • 64.Dastur DK, Dave UP. Effect of prolonged anticonvulsant medication in epileptic patients: serum lipids, vitamins B6, B12, and folic acid, proteins, and fine structure of liver. Epilepsia 1987;28:147-159.View Abstract
  • 65.Dansky LV, Andermann E, Rosenblatt D et al. Anticonvulsants, folate levels, and pregnancy outcome: a prospective study. Ann Neurol 1987;21:176-182.View Abstract
  • 66.Apeland T, Mansoor MA, Strandjord RE et al. Folate, homocysteine and methionine loading in patients on carbamazepine. Acta Neurol Scand 2001;103:294-299.View Abstract
  • 67.Karabiber H, Sonmezgoz E, Ozerol E et al. Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid. Brain Dev 2003;25:113-115.View Abstract
  • 68.Reynolds EH, Chanarin I, Milner G, Matthews DM. Anticonvulsant therapy, folic acid and vitamin B12 metabolism and mental symptoms. Epilepsia 1966;7:261-270.View Abstract
  • 69.Goggin T, Gough H, Bissessar A et al. A comparative study of the relative effects of anticonvulsant drugs and dietary folate on the red cell folate status of patients with epilepsy. Q J Med 1987;65:911-919.View Abstract
  • 70.James GK, Jones MW, Pudek MR. Homocyst(e)ine levels in patients on phenytoin therapy. Clin Biochem 1997;30:647-649.View Abstract
  • 71.Apeland T, Mansoor MA, Strandjord RE, Kristensen O. Homocysteine concentrations and methionine loading in patients on antiepileptic drugs. Acta Neurol Scand 2000;101:217-223.View Abstract
  • 72.Verrotti A, Pascarella R, Trotta D et al. Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine. Epilepsy Res 2000;41:253-257.View Abstract
  • 73.Yoo JH, Hong SB. A common mutation in the methylenetetrahydrofolate reductase gene is a determinant of hyperhomocysteinemia in epileptic patients receiving anticonvulsants. Metabolism 1999;48:1047-1051.View Abstract
  • 74.Dean JC, Moore SJ, Osborne A et al. Fetal anticonvulsant syndrome and mutation in the maternal MTHFR gene. Clin Genet 1999;56:216-220.View Abstract
  • 75.Samren EB, van Duijn CM, Koch S et al. Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy. Epilepsia 1997;38:981-990.View Abstract
  • 76.Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000;343:1608-1614.
  • 77.Fonager K, Larsen H, Pedersen L, Sorensen HT. Birth outcomes in women exposed to anticonvulsant drugs. Acta Neurol Scand 2000;101:289-294.View Abstract
  • 78.Hvas CL, Henriksen TB, Ostergaard JR, Dam M. Epilepsy and pregnancy: effect of antiepileptic drugs and lifestyle on birthweight. BJOG 2000;107:896-902.View Abstract
  • 79.Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Neural tube defects in relation to use of folic acid antagonists during pregnancy. Am J Epidemiol 2001;153:961-968.
  • 80.Hansen DK. The embryotoxicity of phenytoin: an update on possible mechanisms. Proc Soc Exp Biol Med 1991;197:361-368.View Abstract
  • 81.Elmazar MM, Nau H. Ethanol potentiates valproic acid-induced neural tube defects (NTDs) in mice due to toxicokinetic interactions. Reprod Toxicol 1995;9:427-433.View Abstract
  • 82.Artama M, Auvinen A, Raudaskoski T et al. Antiepileptic drug use of women with epilepsy and congenital malformations in offspring. Neurology 2005;64:1874-1878.View Abstract
  • 83.Kaneko S, Battino D, Andermann E et al. Congenital malformations due to antiepileptic drugs. Epilepsy Res 1999;33:145-158.View Abstract
  • 84.Kaaja E, Kaaja R, Hiilesmaa V. Major malformations in offspring of women with epilepsy. Neurology 2003;60:575-579.View Abstract
  • 85.Back DJ, Orme ML. Pharmacokinetic drug interactions with oral contraceptives. Clin Pharmacokinet 1990;18:472-484.View Abstract
  • 86.Crawford P, Chadwick DJ, Martin C et al. The interaction of phenytoin and carbamazepine with combined oral contraceptive steroids. Br J Clin Pharmacol 1990;30:892-896.View Abstract
  • 87.Shane-McWhorter L, Cerveny JD, MacFarlane LL, Osborn C. Enhanced metabolism of levonorgestrel during phenobarbital treatment and resultant pregnancy. Pharmacotherapy 1998;18:1360-1364.
  • 88.Nulman I, Laslo D, Koren G. Treatment of epilepsy in pregnancy. Drugs 1999;57:535-544.View Abstract
  • 89.Palmieri C, Canger R. Teratogenic potential of the newer antiepileptic drugs: what is known and how should this influence prescribing? CNS Drugs 2002;16:755-764.
  • 90.Reynolds EH. Effects of folic acid on the mental state and fit-frequency of drug-treated epileptic patients. Lancet 1967;1:1086-1088.View Abstract
  • 91.Baylis EM, Crowley JM, Preece JM et al. Influence of folic acid on blood-phenytoin levels. Lancet 1971;1:62-64.View Abstract
  • 92.Gibberd FB, Nicholls A, Wright MG. The influence of folic acid on the frequency of epileptic attacks. Eur J Clin Pharmacol 1981;19:57-60.View Abstract
  • 93.Biale Y, Lewenthal H. Effect of folic acid supplementation on congenital malformations due to anticonvulsive drugs. Eur J Obstet Gynecol Reprod Biol 1984;18:211-216.View Abstract
  • 94.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
  • 95.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 (Clin Res Ed) 1983;287:577-579.
  • 96.Pack AR, Thomson ME. Effects of topical and systemic folic acid supplementation on gingivitis in pregnancy. J Clin Periodontol 1980;7:402-414.View Abstract
  • 97.Thomson ME, Pack AR. Effects of extended systemic and topical folate supplementation on gingivitis of pregnancy. J Clin Periodontol 1982;9:275-280.View Abstract
  • 98.Pack AR. Effects of folate mouthwash on experimental gingivitis in man. J Clin Periodontol 1986;13:671-676.View Abstract
  • 99.Drew HJ, Vogel RI, Molofsky W et al. Effect of folate on phenytoin hyperplasia. J Clin Periodontol 1987;14:350-356.View Abstract
  • 100.Francetti L, Maggiore E, Marchesi A et al. [Oral hygiene in subjects treated with diphenylhydantoin: effects of a professional program]. Prev Assist Dent 1991;17:40-43.View Abstract
  • 101.Brown RS, Di Stanislao PT, Beaver WT, Bottomley WK. 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;71:565-568.View Abstract
  • 102.Bell GS, Nashef L, Kendall S et al. Information recalled by women taking anti-epileptic drugs for epilepsy: a questionnaire study. Epilepsy Res 2002;52:139-146.View Abstract
  • 103.Brent RL, Oakley GP Jr. The folate debate. Pediatrics 2006;117:1418-1419.View Abstract
  • 104.Cuskelly GJ, McNulty H, Scott JM. Fortification with low amounts of folic acid makes a significant difference in folate status in young women: implications for the prevention of neural tube defects. Am J Clin Nutr 1999;70:234-239.View Abstract
  • 105.Botto LD, Lisi A, Robert-Gnansia E et al. International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? BMJ 2005;330:571.
  • 106.Lucock M, Yates Z. Folic acid: vitamin and panacea or genetic time bomb? Nat Rev Genet 2005;6:235-240.
  • 107.Frenkel EP, McCall MS, Sheehan RG. Cerebrospinal fluid folate, and vitamin B12 in anticonvulsant-induced megaloblastosis. J Lab Clin Med 1973;81:105-115.View Abstract
  • 108.Melamed E, Reches A, Hershko C. Reversible central nervous system dysfunction in folate deficiency. J Neurol Sci 1975;25:93-98.View Abstract
  • 109.Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976;5:661-696.View Abstract
  • 110.Girdwood RH. Drug-induced anaemias. Drugs 1976;11:394-404.View Abstract
  • 111.Weber TH, Knuutila S, Tammisto P, Tontti K. Long-term of phenytoin: effects on whole blood and red cell folate and haematological parameters. Scand J Haematol 1977;18:81-85.View Abstract
  • 112.Scott JM, Weir DG. Drug-induced megaloblastic change. Clin Haematol 1980;9:587-606.View Abstract
  • 113.Rivey MP, Schottelius DD, Berg MJ. Phenytoin-folic acid: a review. Drug Intell Clin Pharm 1984;18:292-301.View Abstract
  • 114.Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30:145-155.View Abstract
  • 115.Shalev O, Gilon D, Nubani NH. Masked phenytoin-induced megaloblastic anemia in beta-thalassemia minor. Acta Haematol 1987;77:186-187.View Abstract
  • 116.Taliani U, Camellini A, Bernardi P et al. [A clinical case of severe megaloblastic anemia during treatment with primidone]. Acta Biomed Ateneo Parmense 1989;60:245-248.
  • 117.Ravakhah K, West BC. Case report: subacute combined degeneration of the spinal cord from folate deficiency. Am J Med Sci 1995;310:214-216.View Abstract
  • 118.Guidolin L, Vignoli A, Canger R. Worsening in seizure frequency and severity in relation to folic acid administration. Eur J Neurol 1998;5:301-303.View Abstract
  • 119.Torres OA, Miller VS, Buist NM, Hyland K. Folinic acid–responsive neonatal seizures. J Child Neurol 1999;14:529-532.View Abstract
  • 120.Craig J, Morrison P, Morrow J, Patterson V. Failure of periconceptual folic acid to prevent a neural tube defect in the offspring of a mother taking sodium valproate. Seizure 1999;8:253-254.View Abstract
  • 121.Duncan S, Mercho S, Lopes-Cendes I et al. Repeated neural tube defects and valproate monotherapy suggest a pharmacogenetic abnormality. Epilepsia 2001;42:750-753.View Abstract
  • 122.Beardsley GP, Moroson BA, Taylor EC, Moran RG. A new folate antimetabolite, 5,10-dideaza-5,6,7,8-tetrahydrofolate, is a potent inhibitor of de novo purine synthesis. J Biol Chem 1989;264:328-333.View Abstract
  • 123.Taylor EC, Harrington PJ, Fletcher SR et al. Synthesis of the antileukemic agents 5,10-dideazaaminopterin and 5,10-dideaza-5,6,7,8-tetrahydroaminopterin. J Med Chem 1985;28:914-921.View Abstract
  • 124.Taylor EC. Design and synthesis of inhibitors of folate-dependent enzymes as antitumor agents. Adv Exp Med Biol 1993;338:387-408.View Abstract
  • 125.Smorenburg CH, Sparreboom A, Bontenbal M, Verweij J. Combination chemotherapy of the taxanes and antimetabolites: its use and limitations. Eur J Cancer 2001;37:2310-2323.View Abstract
  • 126.Synold TW, Newman EM, Carroll M et al. Cellular but not plasma pharmacokinetics of lometrexol correlate with the occurrence of cumulative hematological toxicity. Clin Cancer Res 1998;4:2349-2355.View Abstract
  • 127.Jackson RC. Biological effects of folic acid antagonists with antineoplastic activity. Pharmacol Ther 1984;25:61-82.View Abstract
  • 128.Norman P. Pemetrexed disodium (Eli Lilly). Curr Opin Investig Drugs 2001;2:1611-1622.View Abstract
  • 129.O’Shaughnessy JA. Pemetrexed: an active new agent for breast cancer. Semin Oncol 2002;29:57-62.
  • 130.Adjei AA. Pharmacology and mechanism of action of pemetrexed. Clin Lung Cancer 2004;5 Suppl 2:S51-S55.View Abstract
  • 131.Adjei AA. Pemetrexed (Alimta), a novel multitargeted antineoplastic agent. Clin Cancer Res 2004;10:4276s-4280s.View Abstract
  • 132.Calvert AH. Biochemical pharmacology of pemetrexed. Oncology (Huntingt) 2004;18:13-17.View Abstract
  • 133.Tishler M, Caspi D, Fishel B, Yaron M. The effects of leucovorin (folinic acid) on methotrexate therapy in rheumatoid arthritis patients. Arthritis Rheum 1988;31:906-908.View Abstract
  • 134.Hanrahan PS, Russell AS. Concurrent use of folinic acid and methotrexate in rheumatoid arthritis. J Rheumatol 1988;15:1078-1080.View Abstract
  • 135.Buckley LM, Vacek PM, Cooper SM. Administration of folinic acid after low dose methotrexate in patients with rheumatoid arthritis. J Rheumatol 1990;17:1158-1161.View Abstract
  • 136.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
  • 137.Joyce DA, Will RK, Hoffman DM et al. Exacerbation of rheumatoid arthritis in patients treated with methotrexate after administration of folinic acid. Ann Rheum Dis 1991;50:913-914.View Abstract
  • 138.Morgan SL, Baggott JE, Vaughn WH et al. 5 mg or 50 mg/week dose of folic acid supplementation does not alter the efficacy of methotrexate-treated rheumatoid arthritis patients (abstract). Arthritis Rheum 1993;36:S79.
  • 139.Shiroky JB, Neville C, Esdaile JM et al. Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis: results of a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum 1993;36:795-803.View Abstract
  • 140.Weinblatt ME, Maier AL, Coblyn JS. Low-dose leucovorin does not interfere with the efficacy of methotrexate in rheumatoid arthritis: an 8-week randomized placebo-controlled trial. J Rheumatol 1993;20:950-952.
  • 141.Sessa C, de Jong J, D’Incalci M et al. Phase I study of the antipurine antifolate lometrexol (DDATHF) with folinic acid rescue. Clin Cancer Res 1996;2:1123-1127.
  • 142.Tomudex®, raltitrexed disodium. Mississauga, Ontario: AstraZeneca; 1998.
  • 143.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;13:459-463.
  • 144.Shiroky JB. The use of folates concomitantly with low-dose pulse methotrexate. Rheum Dis Clin North Am 1997;23:969-980.View Abstract
  • 145.Hunt PG, Rose CD, McIlvain-Simpson G, Tejani S. The effects of daily intake of folic acid on the efficacy of methotrexate therapy in children with juvenile rheumatoid arthritis: a controlled study. J Rheumatol 1997;24:2230-2232.View Abstract
  • 146.Alarcon GS, Morgan SL. Guidelines for folate supplementation in rheumatoid arthritis patients treated with methotrexate: comment on the guidelines for monitoring drug therapy. Arthritis Rheum 1997;40:391; author reply 391-392.View Abstract
  • 147.Van Ede AE, Laan RF, Blom HJ et al. Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Semin Arthritis Rheum 1998;27:277-292.View Abstract
  • 148.Morgan SL, Baggott JE, Lee JY, Alarcon GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during long-term, low-dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol 1998;25:441-446.
  • 149.Duhra P. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J Am Acad Dermatol 1993;28:466-469.View Abstract
  • 150.Suzuki Y, Uehara R, Tajima C et al. Elevation of serum hepatic aminotransferases during treatment of rheumatoid arthritis with low-dose methotrexate: risk factors and response to folic acid. Scand J Rheumatol 1999;28:273-281.
  • 151.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;39:1102-1109.
  • 152.Van den Berg PB, Reicher A, de Jong-van den Berg LTW. Concomitant use of folic acid prolongs duration of MTX-therapy in the treatment of RA. Pharmacoepidemiol Drug Saf 2000;9 Suppl:S16-S17.
  • 153.Van Ede AE, Laan RF, Rood MJ et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 2001;44:1515-1524.View Abstract
  • 154.Hoekstra M, van Ede AE, Haagsma CJ et al. Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis. Ann Rheum Dis 2003;62:423-426.View Abstract
  • 155.Khanna D, Park GS, Paulus HE et al. Reduction of the efficacy of methotrexate by the use of folic acid: post hoc analysis from two randomized controlled studies. Arthritis Rheum 2005;52:3030-3038.View Abstract
  • 156.Kirby B, Lyon CC, Griffiths CE, Chalmers RJ. The use of folic acid supplementation in psoriasis patients receiving methotrexate: a survey in the United Kingdom. Clin Exp Dermatol 2000;25:265-268.View Abstract
  • 157.Kager L, Cheok M, Yang W et al. Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics. J Clin Invest 2005;115:110-117.View Abstract
  • 158.Toffoli G, Veronesi A, Boiocchi M, Crivellari D. MTHFR gene polymorphism and severe toxicity during adjuvant treatment of early breast cancer with cyclophosphamide, methotrexate, and fluorouracil (CMF). Ann Oncol 2000;11:373-374.
  • 159.Ueland PM, Hustad S, Schneede J et al. Biological and clinical implications of the MTHFR C677T polymorphism. Trends Pharmacol Sci 2001;22:195-201.View Abstract
  • 160.Ulrich CM, Yasui Y, Storb R et al. Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood 2001;98:231-234.
  • 161.Chiusolo P, Reddiconto G, Casorelli I et al. Preponderance of methylenetetrahydrofolate reductase C677T homozygosity among leukemia patients intolerant to methotrexate. Ann Oncol 2002;13:1915-1918.
  • 162.Laverdiere C, Chiasson S, Costea I et al. Polymorphism G80A in the reduced folate carrier gene and its relationship to methotrexate plasma levels and outcome of childhood acute lymphoblastic leukemia. Blood 2002;100:3832-3834.View Abstract
  • 163.Taub JW, Matherly LH, Ravindranath Y et al. Polymorphisms in methylenetetrahydrofolate reductase and methotrexate sensitivity in childhood acute lymphoblastic leukemia. Leukemia 2002;16:764-765.View Abstract
  • 164.Toffoli G, Russo A, Innocenti F et al. Effect of methylenetetrahydrofolate reductase 677C→T polymorphism on toxicity and homocysteine plasma level after chronic methotrexate treatment of ovarian cancer patients. Int J Cancer 2003;103:294-299.View Abstract
  • 165.Dervieux T, Furst D, Lein DO et al. Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis 2005;64:1180-1185.View Abstract
  • 166.Ettinger DS. Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. Clin Lung Cancer 2002;3 Suppl 1:S22-S25.View Abstract
  • 167.Budde LS, Hanna NH. Pemetrexed (Alimta): improving outcomes in malignant pleural mesothelioma. Expert Rev Anticancer Ther 2004;4:361-368.View Abstract
  • 168.Suwanrusme H, Meyer ML, Green MR. Pemetrexed alone and in combination with platinum compounds in the management of malignant mesothelioma. Clin Lung Cancer 2004;5 Suppl 2:S56-S60.View Abstract
  • 169.Bunn P Jr. New investigative regimens and cytotoxic agents in thoracic cancers: gemcitabine and pemetrexed. Oncology (Huntingt) 2004;18:5-11.View Abstract
  • 170.Vogelzang NJ, Rusthoven JJ, Symanowski J et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003;21:2636-2644.View Abstract
  • 171.Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther 1982;4:423-440.View Abstract
  • 172.Werbach MR. Foundations of Nutritional Medicine. Tarzana, Calif: Third Line Press; 1997.
  • 173.Cardiovascular Drugs, antihyperlipidemic agents, bile acid sequestrants. In: Threlkeld DS, ed. Facts and Comparisons Drug Information. St Louis: Facts and Comparisons; February 1999:171L.
  • 174.Desouza C, Keebler M, McNamara DB, Fonseca V. Drugs affecting homocysteine metabolism: impact on cardiovascular risk. Drugs 2002;62:605-616.View Abstract
  • 175.Leonard JP, Desager JP, Beckers C, Harvengt C. In vitro binding of various biological substances by two hypocholesterolaemic resins: cholestyramine and colestipol. Arzneimittelforschung 1979;29:979-981.
  • 176.Strum WB. Characteristics of the transport of pteroylglutamate and amethopterin in rat jejunum. J Pharmacol Exp Ther 1981;216:329-333.View Abstract
  • 177.Hoppner K, Lampi B. Bioavailability of folate following ingestion of cholestyramine in the rat. Int J Vitam Nutr Res 1991;61:130-134.View Abstract
  • 178.Farah JR, Kwiterovich PO Jr, Neill CA. Dose-effect relation of cholestryamine in children and young adults with familial hypercholesterolaemia. Lancet 1977;1:59-63.View Abstract
  • 179.Tonstad S, Sivertsen M, Aksnes L, Ose L. Low dose colestipol in adolescents with familial hypercholesterolaemia. Arch Dis Child 1996;74:157-160.View Abstract
  • 180.Tonstad S, Refsum H, Ose L, Ueland PM. The C677T mutation in the methylenetetrahydrofolate reductase gene predisposes to hyperhomocysteinemia in children with familial hypercholesterolemia treated with cholestyramine. J Pediatr 1998;132:365-368.View Abstract
  • 181.Furst DE. Practical clinical pharmacology and drug interactions of low-dose methotrexate therapy in rheumatoid arthritis. Br J Rheumatol 1995;34 Suppl 2:20-25.View Abstract
  • 182.Merino-Sanjuan M, Carrera A, Monte E, Jimenez-Torres NV. Adsorption of methotrexate and calcium leucovorin onto cholestyramine in vitro. Int J Pharm 2004;278:283-291.View Abstract
  • 183.Fernandez Megia MJ, Alos Alminana M, Terol Castera MJ. [Managing methotrexate toxicity: a case report]. Farm Hosp 2004;28:371-374.View Abstract
  • 184.Luketic GC, Santini R Jr, Butterworth CE Jr. Depression of whole blood folate activity by colchicine. Proc Soc Exp Biol Med 1965;120:13-16.View Abstract
  • 185.Bissonnette R, Treacy E, Rozen R et al. Fenofibrate raises plasma homocysteine levels in the fasted and fed states. Atherosclerosis 2001;155:455-462.View Abstract
  • 186.Dierkes J, Westphal S, Luley C. Fenofibrate-induced hyperhomocysteinaemia: clinical implications and management. Drug Saf 2003;26:81-91.View Abstract
  • 187.Dierkes J, Westphal S, Luley C. The effect of fibrates and other lipid-lowering drugs on plasma homocysteine levels. Expert Opin Drug Saf 2004;3:101-111.View Abstract
  • 188.Legendre C, Causse E, Chaput E et al. Fenofibrate induces a selective increase of protein-bound homocysteine in rodents: a PPARalpha-mediated effect. Biochem Biophys Res Commun 2002;295:1052-1056.View Abstract
  • 189.Luc G, Jacob N, Bouly M et al. Fenofibrate increases homocystinemia through a PPARalpha-mediated mechanism. J Cardiovasc Pharmacol 2004;43:452-453.View Abstract
  • 190.Melenovsky V, Stulc T, Kozich V et al. Effect of folic acid on fenofibrate-induced elevation of homocysteine and cysteine. Am Heart J 2003;146:110.View Abstract
  • 191.De Lorgeril M, Salen P, Paillard F et al. Lipid-lowering drugs and homocysteine. Lancet 1999;353:209-210.View Abstract
  • 192.Dierkes J, Westphal S, Luley C. Serum homocysteine increases after therapy with fenofibrate or bezafibrate. Lancet 1999;354:219-220.View Abstract
  • 193.Dierkes J, Westphal S, Kunstmann S et al. Vitamin supplementation can markedly reduce the homocysteine elevation induced by fenofibrate. Atherosclerosis 2001;158:161-164.View Abstract
  • 193a.Mayer O Jr, Simon J, Holubec L et al. Fenofibrate-induced hyperhomocysteinemia may be prevented by folate co-administration. Eur J Clin Pharmacol 2003;59(5-6):367-371.
  • 194.Milionis HJ, Papakostas J, Kakafika A et al. Comparative effects of atorvastatin, simvastatin, and fenofibrate on serum homocysteine levels in patients with primary hyperlipidemia. J Clin Pharmacol 2003;43:825-830.View Abstract
  • 195.Papakostas GI, Petersen T, Mischoulon D et al. Serum folate, vitamin B12, and homocysteine in major depressive disorder. Part 1. Predictors of clinical response in fluoxetine-resistant depression. J Clin Psychiatry 2004;65:1090-1095.View Abstract
  • 196.Taylor MJ, Carney SM, Goodwin GM, Geddes JR. Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. J Psychopharmacol 2004;18:251-256.View Abstract
  • 197.Coppen A, Bolander-Gouaille C. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol 2005;19:59-65.View Abstract
  • 198.Bjelland I, Tell GS, Vollset SE et al. Folate, vitamin B12, homocysteine, and the MTHFR 677C→T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry 2003;60:618-626.View Abstract
  • 199.Wilkinson AM, Anderson DN, Abou-Saleh MT et al. 5-Methyltetrahydrofolate level in the serum of depressed subjects and its relationship to the outcome of ECT. J Affect Disord 1994;32:163-168.View Abstract
  • 200.Mischoulon D. The role of folate in major depression: mechanisms and clinical implications. Am Soc Clin Psychopharmacol Prog Notes 1996;7:4-5.
  • 201.Ramos MI, Allen LH, Haan MN et al. 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
  • 202.Mischoulon D, Burger JK, Spillmann MK et al. Anemia and macrocytosis in the prediction of serum folate and vitamin B12 status, and treatment outcome in major depression. J Psychosom Res 2000;49:183-187.View Abstract
  • 203.Fava M, Borus JS, Alpert JE et al. Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry 1997;154:426-428.View Abstract
  • 204.Papakostas GI, Petersen T, Mischoulon D et al. Serum folate, vitamin B12, and homocysteine in major depressive disorder. Part 2. Predictors of relapse during the continuation phase of pharmacotherapy. J Clin Psychiatry 2004;65:1096-1098.View Abstract
  • 205.Papakostas GI, Petersen T, Lebowitz BD et al. The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine. Int J Neuropsychopharmacol 2005:1-6.
  • 206.Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo-controlled trial. J Affect Disord 2000;60:121-130.View Abstract
  • 207.Zanotelli F, Perusi O. [Possibilities and limitations of multiple chemoantibiotics in treatment of chronic pulmonary tuberculosis]. G Ital Mal Torace 1966;20:365-378.View Abstract
  • 208.Zajaczkowska J, Krychniak W, Krakowka P, Buraczewska M. Results of one-year chemotherapy with isoniazid (INH), streptomycin (SM) and ethionamide (ETA) in previously untreated patients with cavernous pulmonary tuberculosis. Pol Med J 1966;5:339-344.View Abstract
  • 209.Roberts PD, Hoffbrand AV, Mollin DL. Iron and folate metabolism in tuberculosis. BMJ 1966;5507:198-202.View Abstract
  • 210.Markkanen T, Levanto A, Sallinen V, Virtanen S. Folic acid and vitamin B12 in tuberculosis. Scand J Haematol 1967;4:283-291.View Abstract
  • 211.Klipstein FA, Berlinger FC, Reed LJ. Folate deficiency associated with drug therapy for tuberculosis. Blood 1967;29:697-712.View Abstract
  • 212.Evans DI, Attock B. Folate deficiency in pulmonary tuberculosis: relationship to treatment and to serum vitamin A and beta-carotene. Tubercle 1971;52:288-294.View Abstract
  • 213.Cameron SJ, Horne NW. The effect of tuberculosis and its treatment on erythropoiesis and folate activity. Tubercle 1971;52:37-48.View Abstract
  • 214.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;40:331-340.View Abstract
  • 215.Chabbou A, Maalej M, Zbiba M et al. [Analytic study of 80 cases of pulmonary tuberculosis treated with the INH-STRE-PAS regimen during 1971-2]. Tunis Med 1974;52:305-311.
  • 216.Wada M. [The adverse reactions of anti-tuberculosis drugs and its management]. Nippon Rinsho 1998;56:3091-3095.View Abstract
  • 217.Bate J, Cole AJ. Rifampicin and the assay of folate and vitamin B12. Med Lab Technol 1974;31:199-203.View Abstract
  • 218.Woitalla D, Kuhn W, Muller T. MTHFR C677T polymorphism, folic acid and hyperhomocysteinemia in levodopa-treated patients with Parkinson’s disease. J Neural Transm Suppl 2004:15-20.
  • 219.Kuhn W, Roebroek R, Blom H et al. Elevated plasma levels of homocysteine in Parkinson’s disease. Eur Neurol 1998;40:225-227.
  • 220.Zoccolella S, Lamberti P, Armenise E et al. Plasma homocysteine levels in Parkinson’s disease: role of antiparkinsonian medications. Parkinsonism Relat Disord 2005;11:131-133.
  • 221.Miller JW, Shukitt-Hale B, Villalobos-Molina R et al. Effect of l-dopa and the catechol-O-methyltransferase inhibitor Ro 41-0960 on sulfur amino acid metabolites in rats. Clin Neuropharmacol 1997;20:55-66.View Abstract
  • 222.Yassin MS, Cheng H, Ekblom J, Oreland L. Inhibitors of catecholamine metabolizing enzymes cause changes in S-adenosylmethionine and S-adenosylhomocysteine in the rat brain. Neurochem Int 1998;32:53-59.View Abstract
  • 223.Daly D, Miller JW, Nadeau MR, Selhub J. The effect of l-dopa administration and folate deficiency on plasma homocysteine concentrations in rats. J Nutr Biochem 1997;8:634-640.
  • 224.Muller T, Werne B, Fowler B, Kuhn W. Nigral endothelial dysfunction, homocysteine, and Parkinson’s disease. Lancet 1999;354:126-127.
  • 225.Yasui K, Nakaso K, Kowa H et al. Levodopa-induced hyperhomocysteinaemia in Parkinson’s disease. Acta Neurol Scand 2003;108:66-67.
  • 226.Muller T, Woitalla D, Hauptmann B et al. Decrease of methionine and S-adenosylmethionine and increase of homocysteine in treated patients with Parkinson’s disease. Neurosci Lett 2001;308:54-56.
  • 227.Muller T, Woitalla D, Fowler B, Kuhn W. 3-OMD and homocysteine plasma levels in parkinsonian patients. J Neural Transm 2002;109:175-179.View Abstract
  • 228.Rogers JD, Sanchez-Saffon A, Frol AB, Díaz-Arrastia R. Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease. Arch Neurol 2003;60:59-64.
  • 229.Miller JW, Selhub J, Nadeau MR et al. Effect of l-dopa on plasma homocysteine in PD patients: relationship to B-vitamin status. Neurology 2003;60:1125-1129.View Abstract
  • 229a.Lokk J. [Treatment with levodopa can affect latent vitamin B12 and folic acid deficiency. Patients with Parkinson disease run the risk of elevated homocysteine levels]. Lakartidningen 2003;100(35):2674-2677. (Review)
  • 230.Yasui K, Kowa H, Nakaso K et al. Plasma homocysteine and MTHFR C677T genotype in levodopa-treated patients with PD. Neurology 2000;55:437-440.View Abstract
  • 231.O’Suilleabhain PE, Sung V, Hernández C et al. Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations. Arch Neurol 2004;61:865-868.
  • 232.Muller T, Renger K, Kuhn W. Levodopa-associated increase of homocysteine levels and sural axonal neurodegeneration. Arch Neurol 2004;61:657-660.View Abstract
  • 233.O’Suilleabhain PE, Bottiglieri T, Dewey RB, Jr. et al. Modest increase in plasma homocysteine follows levodopa initiation in Parkinson’s disease. Mov Disord 2004;19:1403-1408.
  • 234.Lamberti P, Zoccolella S, Iliceto G et al. Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson’s disease patients. Mov Disord 2005;20:69-72.
  • 235.Valkovic P, Benetin J, Blazicek P et al. Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients. Parkinsonism Relat Disord 2005;11:253-256.View Abstract
  • 236.Chen H, Zhang SM, Schwarzschild MA et al. Folate intake and risk of Parkinson’s disease. Am J Epidemiol 2004;160:368-375.
  • 237.Lamberti P, Zoccolella S, Armenise E et al. Hyperhomocysteinemia in l-dopa treated Parkinson’s disease patients: effect of cobalamin and folate administration. Eur J Neurol 2005;12:365-368.
  • 238.Stern SL, Brandt JT, Hurley RS et al. Serum and red cell folate concentrations in outpatients receiving lithium carbonate. Int Clin Psychopharmacol 1988;3:49-52.View Abstract
  • 239.Lee S, Chow CC, Shek CC et al. Folate concentration in Chinese psychiatric outpatients on long-term lithium treatment. J Affect Disord 1992;24:265-270.View Abstract
  • 240.Coppen A, Abou-Saleh MT. Plasma folate and affective morbidity during long-term lithium therapy. Br J Psychiatry 1982;141:87-89.
  • 241.Coppen A, Chaudhry S, Swade C. Folic acid enhances lithium prophylaxis. J Affect Disord 1986;10:9-13.View Abstract
  • 242.Yates CR, Krynetski EY, Loennechen T et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med 1997;126:608-614.View Abstract
  • 243.Black AJ, McLeod HL, Capell HA et al. Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine. Ann Intern Med 1998;129:716-718.View Abstract
  • 244.Relling MV, Hancock ML, Rivera GK et al. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst 1999;91:2001-2008.View Abstract
  • 245.Weinshilboum R. Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase. Drug Metab Dispos 2001;29:601-605.View Abstract
  • 246.Evans WE, Hon YY, Bomgaars L et al. Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine. J Clin Oncol 2001;19:2293-2301.
  • 247.Ma XL, Zhu P, Wu MY et al. [Relationship between single nucleotide polymorphisms in thiopurine methyltransferase gene and tolerance to thiopurines in acute leukemia]. Zhonghua Er Ke Za Zhi 2003;41:929-933.
  • 248.Formea CM, Myers-Huentelman H, Wu R et al. Thiopurine S-methyltransferase genotype predicts azathioprine-induced myelotoxicity in kidney transplant recipients. Am J Transplant 2004;4:1810-1817.View Abstract
  • 249.Stanulla M, Schaeffeler E, Flohr T et al. Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. JAMA 2005;293:1485-1489.View Abstract
  • 250.Achkar JP, Stevens T, Easley K et al. Indicators of clinical response to treatment with six-mercaptopurine or azathioprine in patients with inflammatory bowel disease. Inflamm Bowel Dis 2004;10:339-345.View Abstract
  • 251.Marinaki AM, Ansari A, Duley JA et al. Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). Pharmacogenetics 2004;14:181-187.View Abstract
  • 252.Gearry RB, Roberts RL, Barclay ML, Kennedy MA. Lack of association between the ITPA 94C>A polymorphism and adverse effects from azathioprine. Pharmacogenetics 2004;14:779-781.
  • 253.Breen DP, Marinaki AM, Arenas M, Hayes PC. Pharmacogenetic association with adverse drug reactions to azathioprine immunosuppressive therapy following liver transplantation. Liver Transpl 2005;11:826-833.View Abstract
  • 254.Zazgornik J, Druml W, Balcke P et al. Diminished serum folic acid levels in renal transplant recipients. Clin Nephrol 1982;18:306-310.View Abstract
  • 255.Lennard L, Lilleyman JS, Maddocks JL. The effect of folate supplements on 6-mercaptopurine remission maintenance therapy in childhood leukaemia. Br J Cancer 1986;53:115-119.View Abstract
  • 255a.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. Pediatr Hematol Oncol 1986;3(3):241-247.
  • 256.Bernstein CN, Artinian L, Anton PA, Shanahan F. Low-dose 6-mercaptopurine in inflammatory bowel disease is associated with minimal hematologic toxicity. Dig Dis Sci 1994;39:1638-1641.View Abstract
  • 257.Caspary WF. Biguanides and intestinal absorptive function. Acta Hepatogastroenterol (Stuttg) 1977;24:473-480.View Abstract
  • 258.Bauman WA, Shaw S, Jayatilleke E et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000;23:1227-1231.View Abstract
  • 259.Wolever TMS, Assif L, Basu T et al. Miglitol, an alpha-glucosidase inhibitor, prevents the metformin-induced fall in serum folate and vitamin B12 in subjects with type 2 diabetes. Nutr Res 2000;20:1447-1456.
  • 260.Andres E, Perrin AE, Demangeat C et al. The syndrome of food-cobalamin malabsorption revisited in a department of internal medicine: a monocentric cohort study of 80 patients. Eur J Intern Med 2003;14:221-226.View Abstract
  • 261.Sorensen TK, Malinow MR, Williams MA et al. Elevated second-trimester serum homocyst(e)ine levels and subsequent risk of preeclampsia. Gynecol Obstet Invest 1999;48:98-103.View Abstract
  • 262.Vrbikova J, Bicikova M, Tallova J et al. Homocysteine and steroid levels in metformin-treated women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2002;110:74-76.
  • 263.Fiorina P, Lanfredini M, Montanari A et al. Plasma homocysteine and folate are related to arterial blood pressure in type 2 diabetes mellitus. Am J Hypertens 1998;11:1100-1107.View Abstract
  • 264.Smulders YM, Rakic M, Slaats EH et al. Fasting and post-methionine homocysteine levels in NIDDM: determinants and correlations with retinopathy, albuminuria, and cardiovascular disease. Diabetes Care 1999;22:125-132.View Abstract
  • 265.Fisman EZ, Tenenbaum A, Motro M, Adler Y. Oral antidiabetic therapy in patients with heart disease: a cardiologic standpoint. Herz 2004;29:290-298.View Abstract
  • 266.Forman JP, Rimm EB, Stampfer MJ, Curhan GC. Folate intake and the risk of incident hypertension among US women. JAMA 2005;293:320-329.
  • 267.Carpentier JL, Bury J, Luyckx A, Lefebvre P. Vitamin B12 and folic acid serum levels in diabetics under various therapeutic regimens. Diabete Metab 1976;2:187-190.
  • 268.Callaghan TS, Hadden DR, Tomkin GH. Megaloblastic anaemia due to vitamin B12 malabsorption associated with long-term metformin treatment. Br Med J 1980;280:1214-1215.View Abstract
  • 268a.DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med 1995;333(9):541-549.
  • 269.Hoogeveen EK, Kostense PJ, Jakobs C et al. Does metformin increase the serum total homocysteine level in non-insulin-dependent diabetes mellitus? J Intern Med 1997;242:389-394.
  • 270.Carlsen SM, Folling I, Grill V et al. Metformin increases total serum homocysteine levels in non-diabetic male patients with coronary heart disease. Scand J Clin Lab Invest 1997;57:521-527.View Abstract
  • 271.Hermann LS, Kalen J, Katzman P et al. Long-term glycaemic improvement after addition of metformin to insulin in insulin-treated obese type 2 diabetes patients. Diabetes Obes Metab 2001;3:428-434.View Abstract
  • 272.Hermann LS, Nilsson B, Wettre S. Vitamin B12 status of patients treated with metformin: a cross-sectional cohort study. Br J Diabetes Vasc Dis 2004;4:401-406.
  • 273.Wulffele MG, Kooy A, Lehert P et al. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med 2003;254:455-463.View Abstract
  • 274.Aarsand AK, Carlsen SM. Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment. J Intern Med 1998;244:169-174.View Abstract
  • 275.Child DF, Hudson PR, Jones H et al. The effect of oral folic acid on glutathione, glycaemia and lipids in type 2 diabetes. Diabetes Nutr Metab 2004;17:95-102.View Abstract
  • 276.Knowler WC, Barrett-Connor E, Fowler SE et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.View Abstract
  • 277.Molitch ME, Fujimoto W, Hamman RF, Knowler WC. The Diabetes Prevention Program and its global implications. J Am Soc Nephrol 2003;14:S103-S107.View Abstract
  • 278.Orchard TJ, Temprosa M, Goldberg R et al. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med 2005;142:611-619.View Abstract
  • 279.Robinson C, Weigly E. Basic Nutrition and Diet Therapy. New York: Macmillan; 1984.
  • 280.Roe DA. Drug-Induced Nutritional Deficiencies. 2nd ed. Westport, Conn: Avi Publishing; 1985.
  • 281.Roe DA. Risk factors in drug-induced nutritional deficiencies. In: Roe DA, Campbell T, eds. Drugs and Nutrients: the Interactive Effects. New York: Marcel Dekker; 1984:505-523.
  • 282.Faloon WW, Paes IC, Woolfolk D et al. Effect of neomycin and kanamycin upon intestinal absorption. Ann NY Acad Sci 1966;132:879-887.
  • 283.Hardison WG, Rosenberg IH. The effect of neomycin on bile salt metabolism and fat digestion in man. J Lab Clin Med 1969;74:564-573.View Abstract
  • 284.Sydow K, Daiber A, Oelze M et al. Central role of mitochondrial aldehyde dehydrogenase and reactive oxygen species in nitroglycerin tolerance and cross-tolerance. J Clin Invest 2004;113:482-489.View Abstract
  • 285.Loscalzo J. Folate and nitrate-induced endothelial dysfunction: a simple treatment for a complex pathobiology. Circulation 2001;104:1086-1088.View Abstract
  • 286.Pritchard KA Jr, Groszek L, Smalley DM et al. Native low-density lipoprotein increases endothelial cell nitric oxide synthase generation of superoxide anion. Circ Res 1995;77:510-518.View Abstract
  • 287.Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996;271:C1424-C1437.View Abstract
  • 288.Verhaar MC, Wever RM, Kastelein JJ et al. 5-Methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia. Circulation 1998;97:237-241.View Abstract
  • 289.Stroes ES, van Faassen EE, Yo M et al. Folic acid reverts dysfunction of endothelial nitric oxide synthase. Circ Res 2000;86:1129-1134.View Abstract
  • 290.Kaesemeyer WH, Ogonowski AA, Jin L et al. Endothelial nitric oxide synthase is a site of superoxide synthesis in endothelial cells treated with glyceryl trinitrate. Br J Pharmacol 2000;131:1019-1023.View Abstract
  • 291.Wilmink HW, Stroes ES, Erkelens WD et al. Influence of folic acid on postprandial endothelial dysfunction. Arterioscler Thromb Vasc Biol 2000;20:185-188.View Abstract
  • 292.Leopold JA, Loscalzo J. Organic nitrate tolerance and endothelial dysfunction: role of folate therapy. Minerva Cardioangiol 2003;51:349-359.View Abstract
  • 293.Bec N, Gorren AC, Voelker C et al. Reaction of neuronal nitric-oxide synthase with oxygen at low temperature: evidence for reductive activation of the oxy-ferrous complex by tetrahydrobiopterin. J Biol Chem 1998;273:13502-13508.View Abstract
  • 294.Huang A, Vita JA, Venema RC, Keaney JF Jr. Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. J Biol Chem 2000;275:17399-17406.View Abstract
  • 295.Mayer B, Pitters E, Pfeiffer S et al. A synthetic peptide corresponding to the putative dihydrofolate reductase domain of nitric oxide synthase inhibits uncoupled NADPH oxidation. Nitric Oxide 1997;1:50-55.View Abstract
  • 296.Gruhn N, Aldershvile J, Boesgaard S. Tetrahydrobiopterin improves endothelium-dependent vasodilation in nitroglycerin-tolerant rats. Eur J Pharmacol 2001;416:245-249.View Abstract
  • 297.Gori T, Burstein JM, Ahmed S et al. Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study. Circulation 2001;104:1119-1123.View Abstract
  • 298.Chanarin I. Cobalamins and nitrous oxide: a review. J Clin Pathol 1980;33:909-916.View Abstract
  • 299.Flippo TS, Holder WD Jr. Neurologic degeneration associated with nitrous oxide anesthesia in patients with vitamin B12 deficiency. Arch Surg 1993;128:1391-1395.View Abstract
  • 300.Drummond JT, Matthews RG. Nitrous oxide inactivation of cobalamin-dependent methionine synthase from Escherichia coli: characterization of the damage to the enzyme and prosthetic group. Biochemistry 1994;33:3742-3750.View Abstract
  • 301.Amos RJ, Amess JA, Hinds CJ, Mollin DL. Investigations into the effect of nitrous oxide anaesthesia on folate metabolism in patients receiving intensive care. Chemioterapia 1985;4:393-399.View Abstract
  • 302.Shane B, Stokstad EL. The interrelationships among folate, vitamin B12, and methionine metabolism. Adv Nutr Res 1983;5:133-170.
  • 303.Ermens AA, Schoester M, Lindemans J, Abels J. Effect of nitrous oxide and methotrexate on folate coenzyme pools of blast cells from leukemia patients. Leuk Res 1991;15:165-171.View Abstract
  • 304.Horne DW, Holloway RS. Compartmentation of folate metabolism in rat pancreas: nitrous oxide inactivation of methionine synthase leads to accumulation of 5-methyltetrahydrofolate in cytosol. J Nutr 1997;127:1772-1775.View Abstract
  • 305.Herbert V, Zalusky R. Interrelations of vitamin B12 and folic acid metabolism: folic acid clearance studies. J Clin Invest 1962;41:1263-1276.View Abstract
  • 306.Green JM, Ballou DP, Matthews RG. Examination of the role of methylenetetrahydrofolate reductase in incorporation of methyltetrahydrofolate into cellular metabolism. FASEB J 1988;2:42-47.View Abstract
  • 307.Keeling PA, Rocke DA, Nunn JF et al. Folinic acid protection against nitrous oxide teratogenicity in the rat. Br J Anaesth 1986;58:528-534.View Abstract
  • 308.Koblin DD, Tomerson BW, Waldman FM. Disruption of folate and vitamin B12 metabolism in aged rats following exposure to nitrous oxide. Anesthesiology 1990;73:506-512.View Abstract
  • 309.Koblin DD, Tomerson BW, Waldman FM et al. Effect of nitrous oxide on folate and vitamin B12 metabolism in patients. Anesth Analg 1990;71:610-617.View Abstract
  • 310.Ermens AA, Refsum H, Rupreht J et al. Monitoring cobalamin inactivation during nitrous oxide anesthesia by determination of homocysteine and folate in plasma and urine. Clin Pharmacol Ther 1991;49:385-393.
  • 311.Salo M, Rajamaki A, Nikoskelainen J. Absence of signs of vitamin B12–nitrous oxide interaction in operating theatre personnel. Acta Anaesthesiol Scand 1984;28:106-108.View Abstract
  • 312.Nunn JF, Chanarin I, Tanner AG, Owen ER. Megaloblastic bone marrow changes after repeated nitrous oxide anaesthesia: reversal with folinic acid. Br J Anaesth 1986;58:1469-1470.View Abstract
  • 313.Selhub J, Dhar GJ, Rosenberg IH. Inhibition of folate enzymes by sulfasalazine. J Clin Invest 1978;61:221-224.View Abstract
  • 314.Baum CL, Selhub J, Rosenberg IH. Antifolate actions of sulfasalazine on intact lymphocytes. J Lab Clin Med 1981;97:779-784.View Abstract
  • 315.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;56:421-429.View Abstract
  • 316.Oakley GP Jr, Adams MJ, Dickinson CM. More folic acid for everyone, now. J Nutr 1996;126:751S-755S.View Abstract
  • 317.Wertalik LF, Metz EN, LoBuglio AF, Balcerzak SP. Decreased serum B12 levels with oral contraceptive use. JAMA 1972;221:1371-1374.View Abstract
  • 318.Bielenberg J. [Folic acid and vitamin deficiency caused by oral contraceptives]. Med Monatsschr Pharm 1991;14:244-247.View Abstract
  • 319.Shojania AM, Hornady G, Barnes PH. Oral contraceptives and serum-folate level. Lancet 1968;291:1376-1377.View Abstract
  • 320.Food and Nutrition Board IoM. Folic acid. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998:193-305.
  • 321.Durand P, Prost M, Blache D. Folic acid deficiency enhances oral contraceptive–induced platelet hyperactivity. Arterioscler Thromb Vasc Biol 1997;17:1939-1946.View Abstract
  • 322.Lindenbaum J, Whitehead N, Reyner F. Oral contraceptive hormones, folate metabolism, and the cervical epithelium. Am J Clin Nutr 1975;28:346-353.View Abstract
  • 323.MoojI PN, Thomas CM, Doesburg WH, Eskes TK. Multivitamin supplementation in oral contraceptive users. Contraception 1991;44:277-288.
  • 324.Steegers-Theunissen RP, Van Rossum JM, Steegers EA et al. Sub-50 oral contraceptives affect folate kinetics. Gynecol Obstet Invest 1993;36:230-233.View Abstract
  • 325.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
  • 326.Baillargeon JP, McClish DK, Essah PA, Nestler JE. Association between the current use of low-dose oral contraceptives and cardiovascular arterial disease: a meta-analysis. J Clin Endocrinol Metab 2005;90:3863-3870.
  • 327.Martinez O, Roe DA. Effect of oral contraceptives on blood folate levels in pregnancy. Am J Obstet Gynecol 1977;128:255-261.View Abstract
  • 328.Whitehead N, Reyner F, Lindenbaum J. Megaloblastic changes in the cervical epithelium: association with oral contraceptive therapy and reversal with folic acid. JAMA 1973;226:1421-1424.View Abstract
  • 329.Butterworth CE Jr, 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
  • 330.Zarcone R, Bellini P, Carfora E et al. [Folic acid and cervix dysplasia]. Minerva Ginecol 1996;48:397-400.View Abstract
  • 331.Kwasniewska A, Tukendorf A, Semczuk M. Folate deficiency and cervical intraepithelial neoplasia. Eur J Gynaecol Oncol 1997;18:526-530.View Abstract
  • 332.Sedjo RL, Inserra P, Abrahamsen M et al. Human papillomavirus persistence and nutrients involved in the methylation pathway among a cohort of young women. Cancer Epidemiol Biomarkers Prev 2002;11:353-359.
  • 333.Roe DA. Diet and Drug Interactions. New York: Van Nostrand Reinhold; 1989.
  • 334.Russell RM, Dutta SK, Oaks EV et al. Impairment of folic acid absorption by oral pancreatic extracts. Dig Dis Sci 1980;25:369-373.View Abstract
  • 335.Walzer PD, Kim CK, Foy JM et al. Inhibitors of folic acid synthesis in the treatment of experimental Pneumocystis carinii pneumonia. Antimicrob Agents Chemother 1988;32:96-103.View Abstract
  • 336.Halsted CH, Gandhi G, Tamura T. Sulfasalazine inhibits the absorption of folates in ulcerative colitis. N Engl J Med 1981;305:1513-1517.View Abstract
  • 337.Longstreth GF, Green R. Folate status in patients receiving maintenance doses of sulfasalazine. Arch Intern Med 1983;143:902-904.View Abstract
  • 338.Gregory JF 3rd. Case study: folate bioavailability. J Nutr 2001;131:1376S-1382S.View Abstract
  • 339.Skold O. Sulfonamide resistance: mechanisms and trends. Drug Resist Update 2000;3:155-160.View Abstract
  • 340.Grindulis KA, McConkey B. Does sulphasalazine cause folate deficiency in rheumatoid arthritis? Scand J Rheumatol 1985;14:265-270.
  • 341.Grieco A, Caputo S, Bertoli A et al. Megaloblastic anaemia due to sulphasalazine responding to drug withdrawal alone. Postgrad Med J 1986;62:307-308.View Abstract
  • 342.Longstreth GF, Green R. Folate levels in inflammatory bowel disease. N Engl J Med 1982;306:1488.View Abstract
  • 343.Ma J, Stampfer MJ, Giovannucci E et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 1997;57:1098-1102.View Abstract
  • 344.Ma J, Stampfer MJ, Christensen B et al. A polymorphism of the methionine synthase gene: association with plasma folate, vitamin B12, homocyst(e)ine, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 1999;8:825-829.View Abstract
  • 345.Eichholzer M, Luthy J, Moser U, Fowler B. Folate and the risk of colorectal, breast and cervix cancer: the epidemiological evidence. Swiss Med Wkly 2001;131:539-549.View Abstract
  • 346.Shannon B, Gnanasampanthan S, Beilby J, Iacopetta B. A polymorphism in the methylenetetrahydrofolate reductase gene predisposes to colorectal cancers with microsatellite instability. Gut 2002;50:520-524.View Abstract
  • 347.Terry P, Jain M, Miller AB et al. Dietary intake of folic acid and colorectal cancer risk in a cohort of women. Int J Cancer 2002;97:864-867.View Abstract
  • 348.Pufulete M, Al-Ghnaniem R, Rennie JA et al. Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer. Br J Cancer 2005;92:838-842.
  • 349.Mason JB, Choi SW. The mechanisms by which folate depletion enhances colorectal carcinogenesis: a unified scheme. Nestle Nutr Workshop Ser Clin Perform Programme 2000;4:87-99; discussion 99-101.View Abstract
  • 350.Mason JB, Choi SW. Folate and carcinogenesis: developing a unifying hypothesis. Adv Enzyme Regul 2000;40:127-141.View Abstract
  • 351.Choi SW, Mason JB. Folate and carcinogenesis: an integrated scheme. J Nutr 2000;130:129-132.View Abstract
  • 352.Song J, Medline A, Mason JB et al. Effects of dietary folate on intestinal tumorigenesis in the apcMin mouse. Cancer Res 2000;60:5434-5440.View Abstract
  • 353.Kim YI, Baik HW, Fawaz K et al. Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial. Am J Gastroenterol 2001;96:184-195.View Abstract
  • 354.Khosraviani K, Weir HP, Hamilton P et al. Effect of folate supplementation on mucosal cell proliferation in high risk patients for colon cancer. Gut 2002;51:195-199.View Abstract
  • 355.Swinson CM, Perry J, Lumb M, Levi AJ. Role of sulphasalazine in the aetiology of folate deficiency in ulcerative colitis. Gut 1981;22:456-461.View Abstract
  • 356.Lashner BA, Heidenreich PA, Su GL et al. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis: a case-control study. Gastroenterology 1989;97:255-259.View Abstract
  • 357.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
  • 357a.Norgard B, Czeizel AE, Rockenbauer M, et al. Population-based case control study of the safety of sulfasalazine use during pregnancy. Aliment Pharmacol Ther 2001;15(4):483-486.
  • 358.Logan EC, Williamson LM, Ryrie DR. Sulphasalazine-associated pancytopenia may be caused by acute folate deficiency. Gut 1986;27:868-872.View Abstract
  • 359.Hoshino J, Sugawara K, Ishikawa S et al. [A case of ulcerative colitis with folate-deficient megaloblastic anemia induced by sulfasalazine]. Nippon Shokakibyo Gakkai Zasshi 1999;96:840-845.View Abstract
  • 360.Omray A, Varma KC. Evaluation of pharmacokinetic parameters of tetracycline hydrochloride upon oral administration with vitamin C and vitamin B complex. Hindustan Antibiot Bull 1981;23:33-37.
  • 361.Shojania AM, Hornady G. Effect of antimicrobial agents on serum folate assay. Am J Clin Pathol 1969;52:454-456.View Abstract
  • 362.Banwell JG, Gorbach SL, Chatterjee B, Mitra R. Tropical sprue: a study of small intestinal function and the changes resulting from vitamin B12, folate, and tetracycline therapy. Gut 1968;9:725.View Abstract
  • 363.Klipstein FA, Samloff IM. Folate synthesis by intestinal bacteria. Am J Clin Nutr 1966;19:237-246.View Abstract
  • 364.Klipstein FA, Falaiye JM. Tropical sprue in expatriates from the tropics living in the continental United States. Medicine (Baltimore) 1969;48:475-491.View Abstract
  • 365.Westergaard H. Tropical sprue. Curr Treat Options Gastroenterol 2004;7:7-11.View Abstract
  • 366.Hanson JP. Tropical sprue in Far North Queensland. Med J Aust 2005;182:536-537.View Abstract
  • 367.Zimmerman J, Selhub J, Rosenberg IH. Competitive inhibition of folic acid absorption in rat jejunum by triamterene. J Lab Clin Med 1986;108:272-276.View Abstract
  • 368.Schalhorn A, Siegert W, Sauer HJ. Antifolate effect of triamterene on human leucocytes and on a human lymphoma cell line. Eur J Clin Pharmacol 1981;20:219-224.View Abstract
  • 369.Tuckerman M, Turco S. Human Nutrition. Philadelphia: Lea & Febiger; 1983.
  • 370.Jackson EK. Diuretics. Goodman and Gilman’s the Pharmacological Basis of Therapeutics. New York: McGraw-Hill; 1996:706.
  • 371.Maass AR, Wiebelhaus VD, Sosnowski G et al. Effect of triamterene on folic reductase activity and reproduction in the rat. Toxicol Appl Pharmacol 1967;10:413-423.View Abstract
  • 372.Mason JB, Zimmerman J, Otradovec CL et al. Chronic diuretic therapy with moderate doses of triamterene is not associated with folate deficiency. J Lab Clin Med 1991;117:365-369.View Abstract
  • 373.Amitai Y, Leventhal A. Folic acid antagonists during pregnancy and risk of birth defects. N Engl J Med 2001;344:933; author reply 934-935.
  • 374.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;92:866-870.View Abstract
  • 375.Lieberman FL, Bateman JR. Megaloblastic anemia possibly induced by triamterene in patients with alcoholic cirrhosis: two case reports. Ann Intern Med 1968;68:168-173.View Abstract
  • 376.Evers S, Di Padova K, Meyer M et al. Strategies towards a better understanding of antibiotic action: folate pathway inhibition in Haemophilus influenzae as an example. Electrophoresis 1998;19:1980-1988.View Abstract
  • 377.Kahn SB, Fein SA, Brodsky I. Effects of trimethoprim on folate metabolism in man. Clin Pharmacol Ther 1968;9:550-560.View Abstract
  • 378.Fleischman SH, Brooks CL 3rd. Protein-drug interactions: characterization of inhibitor binding in complexes of DHFR with trimethoprim and related derivatives. Proteins 1990;7:52-61.View Abstract
  • 379.Vinnicombe HG, Derrick JP. Dihydropteroate synthase from Streptococcus pneumoniae: characterization of substrate binding order and sulfonamide inhibition. Biochem Biophys Res Commun 1999;258:752-757.View Abstract
  • 380.Bjornson BH, McIntyre AP, Harvey JM, Tauber AI. Studies of the effects of trimethoprim and sulfamethoxazole on human granulopoiesis. Am J Hematol 1986;23:1-7.View Abstract
  • 381.Bygbjerg IC, Lund JT, Hording M. Effect of folic and folinic acid on cytopenia occurring during co-trimoxazole treatment of Pneumocystis carinii pneumonia. Scand J Infect Dis 1988;20:685-686.
  • 382.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;170:912-917.View Abstract
  • 383.Systemic anti-infectives, miscellaneous anti-infectives, trimethoprim. In: Threlkeld DS, ed. Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons; August 1992:408-408a.
  • 384.Sahai J. Urinary tract infections. In: Young LY, Koda-Kimble MA, eds. Applied Therapeutics: the Clinical Use of Drugs. 6th ed. Vancouver, Wash: Applied Therapeutics; 1995:63-66.
  • 385.Cronkite E, Bullis J, Honikel L. Partial amelioration of AZT-induced macrocytic anemia in the mouse by folic acid. Stem Cells 1993;11:393-397.View Abstract
  • 386.Tefferi A. Anemia in adults: a contemporary approach to diagnosis. Mayo Clin Proc 2003;78:1274-1280.View Abstract
  • 387.Romanelli F, Empey K, Pomeroy C. Macrocytosis as an indicator of medication (zidovudine) adherence in patients with HIV infection. AIDS Patient Care STDS 2002;16:405-411.View Abstract
  • 388.Manfredi R, Ricchi E, Costigliola P et al. [Monitoring of several hematological parameters of the erythroid series in patients with HIV infection treated with zidovudine]. Recenti Prog Med 1992;83:361-366.View Abstract
  • 389.Snower DP, Weil SC. Changing etiology of macrocytosis. Zidovudine as a frequent causative factor. Am J Clin Pathol 1993;99:57-60.View Abstract
  • 390.Falguera M, Perez-Mur J, Puig T, Cao G. Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine. Eur J Haematol 1995;55:97-102.View Abstract
  • 391.Gorbach SL. Bengt E. Gustafsson Memorial Lecture. Function of the normal human microflora. Scand J Infect Dis Suppl 1986;49:17-30.View Abstract
  • 392.Simon GL, Gorbach SL. The human intestinal microflora. Dig Dis Sci 1986;31:147S-162S.View Abstract
  • 393.De Simone C, Vesely R, Bianchi SB et al. The role of probiotics in modulation of the immune system in man and in animals. Int J Immunother 1993;9:23-28.
  • 394.Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997;6 Suppl 1:S43-S45.View Abstract
  • 395.Cummings JH, Macfarlane GT. Role of intestinal bacteria in nutrient metabolism. JPEN J Parenter Enteral Nutr 1997;21:357-365.View Abstract
  • 396.Macfarlane GT, Macfarlane S. Human colonic microbiota: ecology, physiology and metabolic potential of intestinal bacteria. Scand J Gastroenterol Suppl 1997;222:3-9.View Abstract
  • 397.Mombelli B, Gismondo MR. The use of probiotics in medical practice. Int J Antimicrob Agents 2000;16:531-536.View Abstract
  • 398.Kopp-Hoolihan L. Prophylactic and therapeutic uses of probiotics: a review. J Am Diet Assoc 2001;101:229-238; quiz 239-241.View Abstract
  • 399.Montalto M, Arancio F, Izzi D et al. [Probiotics: history, definition, requirements and possible therapeutic applications]. Ann Ital Med Int 2002;17:157-165.View Abstract
  • 400.Drisko JA, Giles CK, Bischoff BJ. Probiotics in health maintenance and disease prevention. Altern Med Rev 2003;8:143-155.View Abstract
  • 401.Reid G, Sanders ME, Gaskins HR et al. New scientific paradigms for probiotics and prebiotics. J Clin Gastroenterol 2003;37:105-118.View Abstract
  • 402.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;274:1049-1057.View Abstract
  • 403.Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996;27:517-527.View Abstract
  • 404.Ballal RS, Jacobsen DW, Robinson K. Homocysteine: update on a new risk factor. Cleve Clin J Med 1997;64:543-549.View Abstract
  • 405.Bronstrup A, Hages M, Prinz-Langenohl R, Pietrzik K. Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women. Am J Clin Nutr 1998;68:1104-1110.View Abstract
  • 406.Malinow MR, Duell PB, Hess DL et al. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med 1998;338:1009-1015.View Abstract
  • 407.Giles WH, Kittner SJ, Croft JB et al. Serum folate and risk for coronary heart disease: results from a cohort of US adults. Ann Epidemiol 1998;8:490-496.View Abstract
  • 408.Rimm EB, Willett WC, Hu FB et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 1998;279:359-364.
  • 409.Prasad K. Homocysteine, a risk factor for cardiovascular disease. Int J Angiol 1999;8:76-86.View Abstract
  • 410.Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet 1999;354:407-413.View Abstract
  • 411.Eikelboom JW, Lonn E, Genest J Jr et al. Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med 1999;131:363-375.View Abstract
  • 412.Booth GL, Wang EE. Preventive health care, 2000 update: screening and management of hyperhomocysteinemia for the prevention of coronary artery disease events. The Canadian Task Force on Preventive Health Care. CMAJ 2000;163:21-29.View Abstract
  • 413.Temple ME, Luzier AB, Kazierad DJ. Homocysteine as a risk factor for atherosclerosis. Ann Pharmacother 2000;34:57-65.View Abstract
  • 414.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;36:758-765.View Abstract
  • 415.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
  • 416.Aguilar B, Rojas JC, Collados MT. Metabolism of homocysteine and its relationship with cardiovascular disease. J Thromb Thrombolysis 2004;18:75-87.View Abstract
  • 417.Strain JJ, Dowey L, Ward M et al. B-vitamins, homocysteine metabolism and CVD. Proc Nutr Soc 2004;63:597-603.View Abstract
  • 418.Landgren F, Israelsson B, Lindgren A et al. Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid. J Intern Med 1995;237:381-388.View Abstract
  • 419.Dongari A, McDonnell HT, Langlais RP. Drug-induced gingival overgrowth. Oral Surg Oral Med Oral Pathol 1993;76:543-548.View Abstract
  • 420.Chowers Y, Sela BA, Holland R et al. Increased levels of homocysteine in patients with Crohn’s disease are related to folate levels. Am J Gastroenterol 2000;95:3498-3502.
  • 421.Refai TM, Al-Salem IH, Nkansa-Dwamena D, Al-Salem MH. Hyperhomocysteinaemia and risk of thrombosis in systemic lupus erythematosus patients. Clin Rheumatol 2002;21:457-461.View Abstract
  • 422.Roe D, Campbell T. Drugs and Nutrients: the Interactive Effects. New York: Marcel Dekker; 1984:288-289, 505-523.
  • 423.Pullarkat ST, Stoehlmacher J, Ghaderi V et al. Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenom J 2001;1:65-70.View Abstract
  • 424.Zhu AX, Puchalski TA, Stanton VP Jr et al. Dihydropyrimidine dehydrogenase and thymidylate synthase polymorphisms and their association with 5-fluorouracil/leucovorin chemotherapy in colorectal cancer. Clin Colorectal Cancer 2004;3:225-234.View Abstract
  • 425.Mainwaring P, Grygiel JJ. Interaction of 5-fluorouracil with folates. Aust NZ J Med 1995;25:60.View Abstract
  • 426.Den Heijer M, Koster T, Blom HJ et al. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 1996;334:759-762.View Abstract
  • 427.Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med 1998;49:31-62.View Abstract
  • 428.Robinson K, Arheart K, Refsum H et al. Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. European COMAC Group. Circulation 1998;97:437-443.View Abstract
  • 429.Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 1999;99:178-182.View Abstract
  • 430.Christensen B, Landaas S, Stensvold I et al. Whole blood folate, homocysteine in serum, and risk of first acute myocardial infarction. Atherosclerosis 1999;147:317-326.View Abstract
  • 431.Joshi UM, Virkar KD, Amatayakul K et al. Impact of hormonal contraceptives vis-a-vis non-hormonal factors on the vitamin status of malnourished women in India and Thailand. World Health Organization: Special Programme of Research, Development and Research Training in Human Reproduction. Task Force on Oral Contraceptives. Hum Nutr Clin Nutr 1986;40:205-220.View Abstract
  • 432.Clarke SJ, Hanwell J, de Boer M et al. Phase I trial of ZD1694, a new folate-based thymidylate synthase inhibitor, in patients with solid tumors. J Clin Oncol 1996;14:1495-1503.
  • 433.Kohne CH, Thuss-Patience P, Friedrich M et al. Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity. Br J Cancer 1998;77:973-977.View Abstract
  • 434.AstraZeneca. Product Information: Tomudex®, raltitrexed disodium. Mississauga, Ontario; 2000.
  • 435.McKinley MC, McNulty H, McPartlin J et al. Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete. Am J Clin Nutr 2001;73:759-764.View Abstract
  • 436.Tucker KL, Olson B, Bakun P et al. Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial. Am J Clin Nutr 2004;79:805-811.View Abstract
  • 437.Moat SJ, Ashfield-Watt PA, Powers HJ et al. Effect of riboflavin status on the homocysteine-lowering effect of folate in relation to the MTHFR (C677T) genotype. Clin Chem 2003;49:295-302.View Abstract
  • 438.McNulty H, Dowey LC, Scott JM. Riboflavin supplementation lowers plasma homocysteine in individuals homozygous for the MTHFR C677T polymorphism. J Inherit Metab Dis 2003;26 Suppl 1:12.
  • 439.Schnyder G, Roffi M, Pin R et al. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med 2001;345:1593-1600.View Abstract
  • 440.Sato Y, Honda Y, Iwamoto J et al. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA 2005;293:1082-1088.View Abstract
  • 441.Sato Y, Honda Y, Iwamoto J et al. Homocysteine as a predictive factor for hip fracture in stroke patients. Bone 2005;36:721-726.View Abstract
  • 442.Mukherjee MD, Sandstead HH, Ratnaparkhi MV et al. Maternal zinc, iron, folic acid, and protein nutriture and outcome of human pregnancy. Am J Clin Nutr 1984;40:496-507.View Abstract
  • 443.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;39:535-539.View Abstract
  • 444.Simmer K, Pearson TC, Wheeler MJ, Thompson RP. Zinc status in polycythaemia. Eur J Haematol 1987;38:433-436.View Abstract
  • 445.Butterworth CE Jr, Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr 1989;50:353-358.View Abstract
  • 446.Kauwell GP, Bailey LB, Gregory JF 3rd 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.
  • 447.Strandhagen E, Landaas S, Thelle DS. Folic acid supplement decreases the homocysteine increasing effect of filtered coffee: a randomised placebo-controlled study. Eur J Clin Nutr 2003;57:1411-1417.View Abstract
  • .[No author given.] Folate-responsive homocystinuria and “schizophrenia.” Nutr Rev 1982;40:242-245.
  • .[No authors listed.] Guidelines for monitoring drug therapy in rheumatoid arthritis: American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum 1996;39(5):723-731.
  • .[No author given.] How folate fights disease. Nature Struct Biol 1999;6:293-294.
  • .[No author given.] Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Morb Mortal Wkly Rep 1992;42(RR-14):1-7.
  • .[No author given.] Sulfasalazine inhibits folate absorption. Nutr Rev 1988;46(9):320-323.
  • .Adams JF, Clark JS, Ireland JT, et al. Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy. Diabetologia 1983;24:16-18.
  • .Adank C, Green TJ, Skeaff CM, et al. Weekly high-dose folic Acid supplementation is effective in lowering serum homocysteine concentrations in women. Ann Nutr Metab 2003;47(2):55-59.
  • .Adinolfi LE, Ingrosso D, Cesaro G, et al. Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients. Hepatology 2005;41(5):995-1003.
  • .Aguilar B, Rojas JC, Collados MT. Metabolism of homocysteine and its relationship with cardiovascular disease. J Thromb Thrombolysis 2004;18(2):75-87.
  • .Ahn E, Kapur B, Koren G. Study on circadian variation in folate pharmacokinetics. Can J Clin Pharmacol 2005;12(1):e4-9.
  • .Alati T, Worzalla JF, Shih C, et al. Augmentation of the therapeutic activity of lometrexol -(6-R)5,10-dideazatetrahydrofolate- by oral folic acid. Cancer Res 1996;56(10):2331-2335.
  • .Al-Delaimy WK, Rexrode KM, Hu FB, et al. Folate intake and risk of stroke among women. Stroke 2004;35(6):1259-1263.
  • .Allegra CJ, Chabner BA, Drake JC, et al. Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates. J Biol Chem 1985;260(17):9720-9726.
  • .Alpert JE, Fava M. Nutrition and depression: the role of folate. Nutr Rev 1997;55(5):145-149.
  • .Alfthan G, Laurinen MS, Valsta LM, et al. Folate intake, plasma folate and homocysteine status in a random Finnish population. Eur J Clin Nutr 2003;57(1):81-88.
  • .Alfthan G, Aro A, Gey KF. Plasma homocysteine and cardiovascular disease mortality. Lancet 1997;349:397.
  • .Almadori G, Bussu F, Galli J, et al. Serum levels of folate, homocysteine, and vitamin B12 in head and neck squamous cell carcinoma and in laryngeal leukoplakia. Cancer 2005;103(2):284-292.
  • .Almadori G, Bussu F, Navarra P, et al. Pilot phase IIA study for evaluation of the efficacy of folic acid in the treatment of laryngeal leucoplakia. Cancer 2006;107(2):328-336.
  • .Also-Rallo E, Lopez-Quesada E, Urreizti R, et al. Polymorphisms of genes involved in homocysteine metabolism in preeclampsia and in uncomplicated pregnancies. Eur J Obstet Gynecol Reprod Biol 2005;120(1):45-52.
  • .Ames BN. A role for supplements in optimizing health: the metabolic tune-up. Arch Biochem Biophys 2004;423(1):227-234. (Review)
  • .Ames BN. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res 2001;475(1-2):7-20. (Review)
  • .Ames BN. Increasing longevity by tuning up metabolism: to maximize human health and lifespan, scientists must abandon outdated models of micronutrients. EMBO Rep 2005;6(Suppl 1):S20-24. (Review)
  • .Ames BN. Micronutrient deficiencies: a major cause of DNA damage. Ann N Y Acad Sci 1999;889:87-106. (Review)
  • .Ames BN. The metabolic tune-up: metabolic harmony and disease prevention. J Nutr 2003;133(5):1544S-1548S.
  • .Ames BN, Atamna H, Killilea DW. Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging. Mol Aspects Med 2005;26(4-5):363-378. (Review)
  • .Ames BN, Elson-Schwab I, Silver EA. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms. Am J Clin Nutr 2002;75(4):616-658. (Review)
  • .Amitai Y, Fisher N, Haringman M, et al. Increased awareness, knowledge and utilization of preconceptional folic acid in Israel following a national campaign. Prev Med 2004;39(4):731-737.
  • .Amos RJ, Amess JA, Hinds CJ, et al. Incidence and pathogenesis of acute megaloblastic bone-marrow change in patients receiving intensive care. Lancet 1982;2:835-838.
  • .Andrès E, Noel E, Goichot B. Metformin-associated vitamin B12 deficiency. Arch Intern Med 2002;162:2251-2252.
  • .Andrès E, Perrin A-E, Demangeat C, et al. The syndrome of food-cobalamin malabsorption revisited in a department of internal medicine: a monocentric cohort study of 80 patients. Eur J Intern Med 2003;14:221-226.
  • .Ansari A, Hassan C, Duley J, et al. Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease. Aliment Pharmacol Ther 2002;16(10):1743-1750.
  • .Apeland T, Mansoor MA, Pentieva K, et al. Fasting and post-methionine loading concentrations of homocysteine, vitamin B2, and vitamin B6 in patients on antiepileptic drugs. Clin Chem 2003;49(6 Pt 1):1005-1008.
  • .Arakawa T, Narisawa K, Tanno K, et al. Megaloblastic anemia and mental retardation associated with hyperfolic-acidemia: probably due to N5 methyltetrahydrofolate transferase deficiency. Tohoku J Exp Med 1967;93:1-22.
  • .Arakawa T. Congenital defects in folate utilization. Am J Med 1970;48:594-598.
  • .Arinami T, Yamada N, Yamakawa-Kobayashi K, et al. Methylenetetrahydrofolate reductase variant and schizophrenia/depression. Am J Med Genet 1997;74:526-528.
  • .Ashfield-Watt PA, Pullin CH, Whiting JM, et al. Methylenetetrahydrofolate reductase 677C→T genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: a randomized controlled trial. Am J Clin Nutr 2002;76(1):180-186.
  • .Ashfield-Watt PA, Whiting JM, Clark ZE, et al. A comparison of the effect of advice to eat either ‘5-a-day’ fruit and vegetables or folic acid-fortified foods on plasma folate and homocysteine. Eur J Clin Nutr 2003;57(2):316-323.
  • .Auer J, Berent R, Weber T, et al. [Homocysteine and cardiovascular risk] Wien Med Wochenschr 2001;151(1-2):25-28. (Review) [German]
  • .Bach Kristensen M, Tetens I, Alstrup Jorgensen AB, et al. A decrease in iron status in young healthy women after long-term daily consumption of the recommended intake of fibre-rich wheat bread. Eur J Nutr 2005;44(6):334-340.
  • .Baggott JE, Morgan SL, Ha TS, et al. Antifolates in rheumatoid arthritis: a hypothetical mechanism of action. Clin Exp Rheumatol 1993;11(Suppl 8):S101-105. (Review)
  • .Bagree R, Gibby OM, Penney MD, et al. Prevalence of vitamin B12 deficiency with metformin treatment. Diabetic Med 1999;16(suppl 1):P61.
  • .Bailey LB. Dietary reference intakes for folate: the debut of dietary folate equivalents. Nutr Rev 1998;56(10):294-299.
  • .Bailey LB. Folate and vitamin B12 recommended intakes and status in the United States. Nutr Rev 2004;62(6 Pt 2):S14-21. (Review)
  • .Bailey LB. Folate, methyl-related nutrients, alcohol, and the MTHFR 677C→T polymorphism affect cancer risk: intake recommendations. J Nutr 2003;133(11 Suppl 1):3748S-3753S. (Review)
  • .Bailey LB. New standard for dietary folate intake in pregnant women. Am J Clin Nutr 2000;71(5 Suppl):1304S-1307S. (Review)
  • .Bailey LB, Duhaney RL, Maneval DR, et al. Vitamin B-12 status is inversely associated with plasma homocysteine in young women with C677T and/or A1298C methylenetetrahydrofolate reductase polymorphisms. J Nutr 2002;132(7):1872-1878.
  • .Bailey LB, Gregory JF III. Folate metabolism and requirements. J Nutr 1999;129(4):779-782.
  • .Bailey LB, Berry RJ. Folic acid supplementation and the occurrence of congenital heart defects, orofacial clefts, multiple births, and miscarriage. Am J Clin Nutr 2005;81:1213-1217.
  • .Bailey LB, Gregory JF III. Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr 1999;129(5):919-922.
  • .Bailey LB, Gregory JF, Caudill M, et al. The relationship between increased folate stetabolism and the increased requirement for folate in pregnancy. Br J Obstet Gynaecol 2001;108(7):772-773.
  • .Baillargeon JP, McClish DK, Essah PA, et al. Association between the current use of low-dose oral contraceptives and cardiovascular arterial disease: a meta-analysis. J Clin Endocrinol Metab 2005;90(7):3863-3870.
  • .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.
  • .Bates CJ, Fuller NJ. The effect of riboflavin deficiency on methylene tetrahydrofolate reductase (NADPH) (EC 1.5.1.20) and folate metabolism in the rat. Br J Nutr 1985;55:455-464.
  • .Bayly AM, Berglez JM, Patel O, et al. Folic acid utilisation related to sulfa drug resistance in Saccharomyces cerevisiae. FEMS Microbiol Lett 2001;204(2):387-390.
  • .Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Safety 1998;19(5):355-371. (Review)
  • .Bazzano LA, He J, Ogden LG, et al. Dietary intake of folate and risk of stroke in US men and women: NHANES I Epidemiologic Follow-up Study: National Health and Nutrition Examination Survey. Stroke 2002;33:1183-1188.
  • .Bazzano LA, Reynolds K, Holder KN, et al. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA 2006;296:2720-2726. (Meta-analysis)
  • .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;19:2918-2921.
  • .Beck WS. Drugs and the intestinal absorption of folate. J Lab Clin Med 1986;108(4):263-264.
  • .Becker A, Henry RM, Kostense PJ, et al. Plasma homocysteine and S-adenosylmethionine in erythrocytes as determinants of carotid intima-media thickness: different effects in diabetic and non-diabetic individuals: the Hoorn Study. Atherosclerosis 2003;169(2):323-330. Erratum in Atherosclerosis 2004;173(1):153.
  • .Becker A, Smulders YM, Teerlink T, et al. S-adenosylhomocysteine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine are not related to folate, cobalamin and vitamin B6 concentrations. Eur J Clin Invest 2003;33(1):17-25.
  • .Bellamy MF, McDowell IF, Ramsey MW, et al. Oral folate enhances endothelial function in hyperhomocysteinaemic subjects. Eur J Clin Invest 1999;29(8):659-662.
  • .Benito E, Stigglebout A, Bosch FX, et al. Nutritional factors in colorectal cancer risk: a case-control study in Majorca. Int J Cancer 1991;49:161-167.
  • .Benn A, Swan CH, Cooke WT, et al. Effect of intraluminal pH on the absorption of pteroylmonoglutamic acid. Br Med J 1971;1(741):148-150.
  • .Bentley TG, Willett WC, Weinstein MC, et al. Population-level changes in folate intake by age, gender, and race/ethnicity after folic acid fortification. Am J Public Health 2006;96(11):2040-2047.
  • .Benzinger P, Alscher DM. [Untreated homocystinuria in adulthood] Dtsch Med Wochenschr 2005;130(43):2439-2443. [German]
  • .Berg MJ, Fincham RW, Ebert BE, et al. Decrease of serum folates in healthy male volunteers taking phenytoin. Epilepsia 1988;29(1):67-73.
  • .Berg MJ, Rivey MP, Vern BA, et al. Phenytoin and folic acid: individualized drug-drug interaction. Ther Drug Monit 1983;5:395-399.
  • .Berry RJ, Li Z, Erickson JD, et al. Prevention of neural-tube defects with folic acid in China. N Engl J Med 1999;341:1485-1490.
  • .Bilsborough W, Green DJ, Mamotte CD, et al. Endothelial nitric oxide synthase gene polymorphism, homocysteine, cholesterol and vascular endothelial function. Atherosclerosis 2003;169(1):131-138.
  • .Björnsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology 2005;42(2):481-489.
  • .Bleie O, Refsum H, Ueland PM, et al. Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention. Am J Clin Nutr 2004;80(3):641-648.
  • .Blount BC, Mack MM, Wehr CM, et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci U S A 1997;94(7):3290-3295.
  • .Blount BC, Ames BN. DNA damage in folate deficiency. Baillieres Clin Haematol 1995;8(3):461-78. (Review)
  • .Blouvier B, Duvulder B. Folic acid, xanthine oxidase, and uric acid. Ann Intern Med 1978;88(2):269. (Letter)
  • .Bocci G, Danesi R, Di Paolo AD, et al. Comparative pharmacokinetic analysis of 5-fluorouracil and its major metabolite 5-fluoro-5,6-dihydrouracil after conventional and reduced test dose in cancer patients. Clin Cancer Res 2000;6:3032-3728.
  • .Bol KA, Collins JS, Kirby RS. Survival of infants with neural tube defects in the presence of folic acid fortification. Pediatrics 2006;117:803-813.
  • .Bønaa KH, Njølstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006;354(15):1578-1588.
  • .Boss GR, Ragsdale RA, Zettner A, et al. Failure of folic acid (pteroylglutamic acid) to affect hyperuricemia. J Lab Clin Med 1980;96:783-789.
  • .Bostom AG, Gohh RY, Beaulieu AJ, et al. Treatment of hyperhomocysteinemia in renal transplant recipients: a randomized, placebo-controlled trial. Ann Intern Med 1997;127:1089-1092.
  • .Bostom AG, Jacques PF, Liaugaudas G, et al. Total homocysteine lowering treatment among coronary artery disease patients in the era of folic acid-fortified cereal grain flour. Arterioscler Thromb Vasc Biol 2002;22(3):488-491.
  • .Bostom AG, Rosenberg IH, Silbershatz H, et al. Nonfasting plasma total homocysteine levels and stroke incidence in elderly persons: the Framingham Study. Ann Intern Med 1999;131(5):352-355.
  • .Bostom AG, Silbershatz H, Rosenberg IH, et al. Non-fasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med 1999;159:1077-1080.
  • .Botez MI. Folate deficiency and neurological disorders in adults. Med Hypothesis 1976;2:135-140.
  • .Botez MI, Cadotte M, Beaulieu R, et al. Neurologic disorders responsive to folic acid therapy. Can Med Assoc J 1976;115(3):217-223.
  • .Botez MI, Botez T, Ross-Chouinard A, et al. Thiamine and folate treatment of chronic epileptic patients: a controlled study with the Wechsler IQ scale. Epilepsy Res 1993;16(2):157-163.
  • .Bottiglieri ET, Crellin RF, Reynolds EH. Folates and neuropsychiatry. In: Bailey LB, ed. Folates in health and disease. New York: Marcel Dekker; 1995:435-462.
  • .Bottiglieri T, Diaz-Arrastia R. Hyperhomocysteinemia and cognitive function: more than just a casual link? Am J Clin Nutr 2005;82(3):493-494.
  • .Bottiglieri T, Laundy M, Crellin R, et al. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 2000;69(2):228-232.
  • .Bottiglieri T, Parnetti L, Arning E, et al. Plasma total homocysteine levels and the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene: a study in an Italian population with dementia. Mech Ageing Dev 2001;122(16):2013-2023.
  • .Botto LD, Lisi A, Robert-Gnansia E, et al. International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? BMJ 2005;330(7491):571.
  • .Boushey CJ, Beresford SAA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intake. JAMA 1995;274:1049-1057.
  • .Branda RF, Moldow CF, MacArthur JR, et al. Folate-induced remission in aplastic anemia with familial defect of cellular folate uptake. N Engl J Med 1978;298:469-475.
  • .Branda RF, Nelson NL. Inhibition of 5-methyltetrahydrofolic acid transport by amphipathic drugs. Drug Nutr Interact 1981;1(1):45-53.
  • .Brattstrom LE, Hultberg BL, Hardebo JE. Folic acid responsive postmenopausal homocysteinemia. Metabolism 1985;34(11):1073-1077.
  • .Brattstrom L, Israelsson B, Olsson A. Plasma homocysteine in women on oral oestrogen-containing contraceptives and in men with oestrogen-treated prostatic carcinoma. Scand J Clin Lab Invest 1992;52(4):283-287.
  • .Brent RL, Oakley GP Jr. The folate debate. Pediatrics 2006;117(4):1418-1419. (Editorial)
  • .Brent RL, Oakley GP Jr. The Food and Drug Administration must require the addition of more folic acid in "enriched" flour and other grains. Pediatrics 2005;116(3):753-755.
  • .Brent RL, Godfrey P. Oakley GP Jr. Triumph and/or tragedy: the present Food and Drug Administration program of enriching grains with folic acid. Pediatrics 2006;117:930-932. (Editorial)
  • .Brevik A, Vollset SE, Tell GS, et al. Plasma concentration of folate as a biomarker for the intake of fruit and vegetables: the Hordaland Homocysteine Study. Am J Clin Nutr 2005;81(2):434-439.
  • .Brigden ML. A systematic approach to macrocytosis: sorting out the causes. Postgrad Med 1995;97(5):171-172, 175-177, 181-184 passim.
  • .Bronstrup A, Hages M, Prinz-Langenohl R, et al. Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy young women. Am J Clin Nutr 1998;68:1104-1110.
  • .Brosnan JT. Homocysteine and cardiovascular disease: interactions between nutrition, genetics and lifestyle. Can J Appl Physiol 2004;29(6):773-780.
  • .Brouwer IA, van Dusseldorp M, Thomas CMG, et al. Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial. Am J Clin Nutr 1999;69:99-104.
  • .Brouwer IA, van Dusseldorp M, West CE, et al. Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial. J Nutr 1999;129(6):1135-1139.
  • .Buccianti G, Bamonti Catena F, Patrosso C, et al. Reduction of the homocysteine plasma concentration by intravenously administered folinic acid and vitamin B(12) in uraemic patients on maintenance haemodialysis. Am J Nephrol 2001;21(4):294-299.
  • .Buckley DI, McPherson RS, North CQ, et al. Dietary micronutrients and cervical dysplasia in Southwestern American Indian women. Nutr Cancer 1992;17(2):179-185.
  • .Budd GT, Herzog P, Bukowski RM. Phase I/II trial of dipyridamole, 5-fluorouracil, leukovorin, and mitoxantrone in metastatic breast cancer. Invest New Drugs 1994;12(4):283-287.
  • .Bugge JF. Severe hyperkalaemia induced by trimethoprim in combination with an angiotensin-converting enzyme inhibitor in a patient with transplanted lungs. J Intern Med 1996;240(4):249-251.
  • .Buist RA. Drug-nutrient interactions: an overview. Int Clin Nutr Rev 1984;4(3):114. (Review)
  • .Bunout D, Petermann M, Hirsch S, et al. Low serum folate but normal homocysteine levels in patients with atherosclerotic vascular disease and matched healthy controls. Nutrition 2000;16(6):434-438.
  • .Busby A, Abramsky L, Dolk H, et al. Preventing neural tube defects in Europe: population based study. BMJ 2005;330(7491):574-575.
  • .Butterworth CE Jr. Effect of folate on cervical cancer: synergism among risk factors. Ann N Y Acad Sci 1992;669:293-299.
  • .Butterworth CE Jr, Bendich A. Folic acid and the prevention of birth defects. Annu Rev Nutr 1996;16:73-97.
  • .Butterworth CE Jr, 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(1):73-82.
  • .Butterworth CE Jr, Hatch KD, Macaluso M, et al. Folate deficiency and cervical dysplasia. JAMA 1992;267(4):528-533.
  • .Butterworth CE, Hatch KD, Mueller H, et al. Folate-induced regression of cervical intraepithelial neoplasia (CIN) in users of oral contraceptive agents (OCA). Am J Clin Nutr 1980;33:926.
  • .Butterworth CE Jr, Hatch KD, Soong SJ, et al. Oral folic acid supplementation for cervical dysplasia: a clinical intervention trial. Am J Obstet Gynecol 1992;166:803-809.
  • .Butterworth CE Jr, Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr 1989;50:353-358.
  • .Callaghan TJ. The effect of folic acid on seborrheic dermatitis. Cutis 1967;3:583-588.
  • .Campbell NRC. How safe are folic acid supplements? Arch Intern Med 1996;156:1638-1644.
  • .Camilo E, Zimmerman J, Mason JB, et al. Folate synthesized by bacteria in the human upper small intestine is assimilated by the host. Gastroenterology 1996;110(4):991-998.
  • .Campbell AK, Jagust WJ, Mungas DM, et al. Low erythrocyte folate, but not plasma vitamin B-12 or homocysteine, is associated with dementia in elderly Latinos. J Nutr Health Aging 2005;9(1):39-43.
  • .Carl GF, Hudson FZ, McGuire BS Jr. Phenytoin-induced depletion of folate in rats originates in liver and involves a mechanism that does not discriminate folate form. J Nutr 1997;127(11):2231-2238.
  • .Carrero JJ, Lopez-Huertas E, Salmeron LM, et al. Daily supplementation with (n-3) PUFAs, oleic acid, folic acid, and vitamins B-6 and E increases pain-free walking distance and improves risk factors in men with peripheral vascular disease. J Nutr 2005;135(6):1393-1399.
  • .Caspary WF. Biguanides and intestinal absorptive function. Acta Hepatogastroenterol 1977;24:473-480.
  • .Caudill MA, Bailey LB, Gregory JF III. Consumption of the folate breakdown product para-aminobenzoylglutamate contributes minimally to urinary folate catabolite excretion in humans: investigation using [(13)C(5)]para-aminobenzoylglutamate. J Nutr 2002;132(9):2613-2616.
  • .Cembrowski GS, Zhang MM, Prosser CI, et al. Folate is not what it is cracked up to be. Arch Intern Med 1999;159:2747-2748.
  • .Chadwick D. Monotherapy clinical trials of new antiepileptic drugs: design, indications, and controversies. Epilepsia 1997;38(Suppl 9):S16-20.
  • .Charlton KE, Kolbe-Alexander TL, Nel JH. Development of a novel nutrition screening tool for use in elderly South Africans. Public Health Nutr 2005;8(5):468-479.
  • .Chen L, Guo XB, Deng FR, et al. [Study on the relationship between methylene tetrahydrofolate reductase gene (677C→T) mutation and skin lesions in endemic arsenic poisoning] Wei Sheng Yan Jiu 2005;34(2):146-148. [Chinese]
  • .Chen M, Xia B, Rodriguez-Gueant RM, et al. Genotypes 677TT and 677CT+1298AC of methylenetetrahydrofolate reductase are associated with the severity of ulcerative colitis in central China. Gut 2005;54(5):733-734.
  • .Child DF, Hudson PR, Jones H, et al. The effect of oral folic acid on glutathione, glycaemia and lipids in type 2 diabetes. Diabetes Nutr Metab 2004;17(2):95-102.
  • .Chiuve SE, Giovannucci EL, Hankinson SE, et al. Alcohol intake and methylenetetrahydrofolate reductase polymorphism modify the relation of folate intake to plasma homocysteine. Am J Clin Nutr 2005;82(1):155-162.
  • .Choi SW, Mason JB. Folate and carcinogenesis: an integrated scheme. J Nutr 2000;130(2):129-132.
  • .Chowers Y, Sela BA, Holland R, et al. Increased levels of homocysteine in patients with Crohn’s disease are related to folate levels. Am J Gastroenterol 2000;95(12):3498-3502.
  • .Chu E, Drake JC, Boarman D, et al. Mechanism of thymidylate synthase inhibition by methotrexate in human neoplastic cell lines and normal human myeloid progenitor cells. J Biol Chem 1999;265:8470-8478.
  • .Chung JS, Haque R, Guha Mazumder DN, et al. Blood concentrations of methionine, selenium, beta-carotene, and other micronutrients in a case-control study of arsenic-induced skin lesions in West Bengal, India. Environ Res 2006;101(2):230-237.
  • .Clark DW, Donnelly E, Coulter DM, et al. Linking pharmacovigilance with pharmacogenetics. Drug Safety 2004;27(15):1171-1184.
  • .Clarke R. Vitamin B12, folic acid, and the prevention of dementia. N Engl J Med 2006;354:2817-2819. (Editorial)
  • .Clarke R, Smith AD, Jobst KA, et al. Folate, vitamin B12 and serum homocysteine levels in confirmed Alzheimer’s disease. Arch Neurol 1998;11:1449-1455.
  • .Collins CS, Bailey LB, Hillier S, et al. Red blood cell uptake of supplemental folate in patients on anticonvulsant drug therapy. Am J Clin Nutr 1988;48(6):1445-1450.
  • .Comella P, Casaretti R, De Vita F, et al. Concurrent irinotecan and 5-fluorouracil plus levo-folinic acid given every other week in the first-line management of advanced colorectal carcinoma: a phase I study of the Southern Italy Cooperative Oncology Group. Ann Oncol 1999;10(8):915-921.
  • .Coppen A, Swade C, Jones SA, et al. Depression and tetrahydrobiopterin: the folate connection. J Affect Disord 1989;16(2-3):103-107.
  • .Coppen A, Bolander-Gouaille C. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol 2005;19(1):59-65. (Review)
  • .Coppen A, Swade C, Jones SA, et al. Depression and tetrahydrobiopterin: the folate connection. J Affect Disord 1989;16:103-107.
  • .Coronato A, Glass GB. Depression of the intestinal uptake of radio-vitamin B 12 by cholestyramine. Proc Soc Exp Biol Med 1973;142(4):1341-1344.
  • .Corrada MM, Kawas CH, Hallfrisch J, et al. Reduced risk of Alzheimer’s disease with high folate intake: the Baltimore Longitudinal Study of Aging. Alzheimer’s Dementia 2005;1(1):11-18.
  • .Coulthard SA, Matheson EC, Hall AG, et al. The clinical impact of thiopurine methyltransferase polymorphisms on thiopurine treatment. Nucleosides Nucleotides Nucleic Acids 2004;23(8-9):1385-1391. (Review)
  • .Cravo M. Alcohol, methylenetetrahydrofolate 677C→T genotype, and low folate intake: concurrent causes for hyperhomocysteinemia. Am J Clin Nutr 2005;82:3-4. (Editorial)
  • .Cravo ML, Albuquerque CM, Salazar de Sousa L, et al. Microsatellite instability in non-neoplastic mucosa of patients with ulcerative colitis: effect of folate supplementation. Am J Gastroenterol 1998;93(11):2060-2064.
  • .Crellin R, Bottiglierei T, Reynolds EH. Folates and psychiatric disorders: clinical potential. Drugs 45(5):623-636, 1993.
  • .Crittenden RG, Martinez NR, Playne MJ. Synthesis and utilisation of folate by yoghurt starter cultures and probiotic bacteria. Int J Food Microbiol 2003;80(3):217-222.
  • .Cronstein BN. Pharmacogenetics in the rheumatic diseases. Ann Rheum Dis 2004;63(Suppl 2):ii25-ii27. (Review)
  • .Czeizel AE, Dudas I. Prevention of the first occurrence of neural tube defects by periconceptual vitamin supplementation. N Engl J Med 1992;327:1832-1835.
  • .Czeizel AE, Timar L, Sarkozi A. Dose-dependent effect of folic acid on the prevention of orofacial clefts. Pediatrics 1999;104:e66.
  • .Czeizel AE, Toth M, Rockenbauer M. Population-based case control study of folic acid supplementation during pregnancy. Teratology 1996;53:345-351.
  • .Cuskelly GJ, McNulty H, Scott JM. Fortification with low amounts of folic acid makes a significant difference in folate status in young women: implications for the prevention of neural tube defects. Am J Clin Nutr 1999;70(2):234-239.
  • .Cutolo M, Sulli A, Pizzorni C, et al. Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis 2001;60(8):729-735. (Review)
  • .Daly LE, Kirke PN, Molloy A, et al. Folate levels and neural tube defects. JAMA 1995;274:1698-1702.
  • .Danese S, Sgambato A, Papa A, et al. Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease. Am J Gastroenterol 2005;100(4):886-895.
  • .Davies JF II, Delcamp TJ, Prendergast NJ, et al. Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate. Biochemistry 1990;29:9467-9479.
  • .Davis RE. Clinical chemistry of folic acid. Adv Clin Chem 1986;25:233-294.
  • .Davis SR, Quinlivan EP, Shelnutt KP, et al. Homocysteine synthesis is elevated but total remethylation is unchanged by the methylenetetrahydrofolate reductase 677C→T polymorphism and by dietary folate restriction in young women. J Nutr 2005;135(5):1045-1050.
  • .Davis SR, Quinlivan EP, Shelnutt KP, et al. The methylenetetrahydrofolate reductase 677C→T polymorphism and dietary folate restriction affect plasma one-carbon metabolites and red blood cell folate concentrations and distribution in women. J Nutr 2005;135(5):1040-1044.
  • .Davis SR, Stacpoole PW, Williamson J, et al. Tracer-derived total and folate-dependent homocysteine remethylation and synthesis rates in humans indicate that serine is the main one-carbon donor. Am J Physiol Endocrinol Metab 2004;286(2):E272-279.
  • .Dawson TA. Aciclovir in herpes simplex gingivostomatitis: folic acid may be beneficial in aphthous stomatitis. BMJ 1997;315(7116):1162. (Letter)
  • .de Bree A, Verschuren WM, Blom HJ, et al. Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20-65 y. Am J Clin Nutr 2001;73(6):1027-1033.
  • .de Luis DA, Fernandez N, Arranz ML, et al. Total homocysteine levels relation with chronic complications of diabetes, body composition, and other cardiovascular risk factors in a population of patients with diabetes mellitus type 2. J Diabetes Complications 2005;19(1):42-46.
  • .Dedoussis GV, Panagiotakos DB, Pitsavos C, et al. An association between the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and inflammation markers related to cardiovascular disease. Int J Cardiol 2005;100(3):409-414.
  • .DeFronzo RA, Goodman A, Metformin Investigator Group. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 1995;333:541-549.
  • .Deleu D, Louon A, Sivagnanam S, et al. Long-term effects of nitrous oxide anaesthesia on laboratory and clinical parameters in elderly Omani patients: a randomized double-blind study. J Clin Pharm Ther 2000;25:271-277.
  • .den Heijer M, Brouwer IA, Bos GM. Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol 1998;18:356-361.
  • .Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost 2005;3(2):292-299.
  • .Dennis VW, Robinson K. Homocysteinemia and vascular disease in end-stage renal disease. Kidney Int Suppl 1996;57:S11-S17.
  • .Desouza C, Keebler M, McNamara DB, et al. Drugs affecting homocysteine metabolism: impact on cardiovascular risk. Drugs 2002;62(4):605-616. (Review)
  • .Devlin AM, Clarke R, Birks J, et al. Interactions among polymorphisms in folate-metabolizing genes and serum total homocysteine concentrations in a healthy elderly population. Am J Clin Nutr 2006;83:708-713.
  • .Devlin AM, Ling EH, Peerson JM, et al. Glutamate carboxypeptidase II: a polymorphism associated with lower levels of serum folate and hyperhomocysteinemia. Hum Mol Genet 2000;9:2837-2844.
  • .Devuyst O, Goffin E, Pirson Y, et al. Creatinine rise after fibrate therapy in renal graft recipients. Lancet 1993;341:840. (Letter)
  • .Dierkes J, Kroesen M, Pietrzik K. Folic acid and vitamin B6 supplementation and plasma homocysteine concentrations in healthy young women. Int J Vitam Nutr Res 1998;68:98-103.
  • .Dijkmans BA. Folate supplementation and methotrexate. Br J Rheumatol 1995;34(12):1172-1174. (Review)
  • .Dingle B. Pharmacogenomics in oncology: emerging insights into the impact of genetic variability on cancer care. Oncology Exchange 2004:3(5):8-11. (Review)
  • .Dodelson de Kremer R, Grosso C. Maternal mutation 677C→T in the methylenetetrahydrofolate reductase gene associated with severe brain injury in offspring. Clin Genet 2005;67(1):69-80.
  • .Doshi S, McDowell I, Moat S, et al. Folate improves endothelial function in patients with coronary heart disease. Clin Chem Lab Med 2003;41(11):1505-1512.
  • .Ducloux D, Aboubakr A, Motte G, et al. Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12. Nephrol Dial Transplant 2002;17(5):865-870.
  • .Duell PB, Malinow MR. Homocyst(e)ine: an important risk factor for atherosclerotic vascular disease. Curr Opin Lipidol 1997;8(1):28-34. (Review)
  • .Duhra P, Hodgson C, Martin JA, et al. Intestinal folate absorption in methotrexate treated psoriatic patients. Br J Dermatol 1988;119(3):327-332.
  • .Durga J, Anteunis LJ, Schouten EG, et al. Association of folate with hearing is dependent on the 5,10-methylenetetrahdyrofolate reductase 677C→T mutation. Neurobiol Aging 2006;27(3):482-489.
  • .Durga J, Bots ML, Schouten EG, et al. Low concentrations of folate, not hyperhomocysteinemia, are associated with carotid intima-media thickness. Atherosclerosis 2005;179(2):285-292.
  • .Durga J, van Boxtel MP, Schouten EG, et al. Folate and the methylenetetrahydrofolate reductase 677C→T mutation correlate with cognitive performance. Neurobiol Aging 2006;27(2):334-343.
  • .Durga J, van Tits LJ, Schouten EG, et al. Effect of lowering of homocysteine levels on inflammatory markers: a randomized controlled trial. Arch Intern Med 2005;165(12):1388-1394.
  • .Durga J, Verhoef P, Anteunis LJC, et al. Effects of folic acid supplementation on hearing in older adults: a randomized, controlled trial. Ann Intern Med 2007;146(1):1-9.
  • .Durga J, Verhoef P, Bots ML, et al. Homocysteine and carotid intima-media thickness: a critical appraisal of the evidence. Atherosclerosis 2004;176(1):1-19. (Review)
  • .Ebbesen LS. Hyperhomocysteinemia, thrombosis and vascular biology. Cell Mol Biol (Noisy-le-grand) 2004;50(8):917-930.
  • .Ebly EM, Schaefer JP, Campbell NR, et al. Folate status, vascular disease and cognition in elderly Canadians. Age Ageing 1998;27(4):485-491.
  • .Egger M, Smith GD, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-634.
  • .Eichholzer M, Luthy J, Moser U, et al. Folate and the risk of colorectal, breast and cervix cancer: the epidemiological evidence. Swiss Med Weekly 2001;131(37-38):539-549. (Review)
  • .Elias MF, Robbins MA, Budge MM, et al. Homocysteine, folate, and vitamins B6 and B12 blood levels in relation to cognitive performance: the Maine-Syracuse study. Psychosom Med 2006;68(4):547-554.
  • .Elias MF, Sullivan LM, D’Agostino RB, et al. Homocysteine and cognitive performance in the Framingham offspring study: age is important. Am J Epidemiol 2005;162(7):644-653.
  • .Elliott P, Stamler J, Dyer AR, et al. Association between protein intake and blood pressure: the INTERMAP Study. Arch Intern Med 2006;166;79-87.
  • .Elmazar MM, Thiel R, Nau H. Effect of supplementation with folinic acid, vitamin B6, and vitamin B12 on valproic acid-induced teratogenesis in mice. Fundam Appl Toxicol 1992;18(3):389-394.
  • .Elsborg L. Vitamin B12 and folic acid in Crohn’s disease. Dan Med Bull 1982;29:362-365.
  • .Endres M, Ahmadi M, Kruman I, et al. Folate deficiency increases postischemic brain injury. Stroke 2005;36(2):321-325.
  • .Endresen GK, Husby G. Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis: an update and proposals for guidelines. Scand J Rheumatol 2001;30(3):129-134. (Review)
  • .Erb N. Kitas GD. Homocysteine modulation as a reason for continuous folic acid supplementation in methotrexate-treated rheumatoid arthritis patients. Rheumatology 2001;40(6):715-716.
  • .Erbe RW. Inborn errors of folate metabolism. In: Blakely R, Whitehead V, eds. Folates and pterins. New York: John Wiley; 1986:413-465.
  • .Erbe RW. Inborn errors of folate metabolism (second of two parts). N Engl J Med 1975;293:807-812.
  • .Eskes TK. Open or closed? A world of difference: a history of homocysteine research. Nutr Rev 1998;56(8):236-244.
  • .Eussen SJPM, de Groot LCPGM, Clarke R, et al. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med 2005;165:1167-1172.
  • .Fang X, Namba H, Akamine S, et al. Methylenetetrahydrofolate reductase gene polymorphisms in patients with cerebral hemorrhage. Neurol Res 2005;27(1):73-76.
  • .Farmer JA, Gotto AM Jr. Antihyperlipidaemic agents: drug interactions of clinical significance. Drug Safety 1994;11(5):301-309.
  • .Farmer JA, Gotto AM Jr. Choosing the right lipid-regulating agent: a guide to selection. Drugs 1996;52(5):649-661.
  • .Fava M, Borus JS, Alpert JE, et al. Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry 1997;154(3):426-428.
  • .Fenech M. The role of folic acid and vitamin B12 in genomic stability of human cells. Mutat Res 2001;475(1-2):57-67. (Review)
  • .Fenech M, Baghurst P, Luderer W, et al. Low intake of calcium, folate, nicotinic acid, vitamin E, retinol, beta-carotene and high intake of pantothenic acid, biotin and riboflavin are significantly associated with increased genome instability: results from a dietary intake and micronucleus index survey in South Australia. Carcinogenesis 2005;26(5):991-999.
  • .Fernandez-Miranda C, Yebra M, Aranda JL, et al. Effect of folic acid treatment on carotid intima-media thickness of patients with coronary disease. Int J Cardiol 2007;118(3):345-349.
  • .Ferraroni M, La Vecchia C, D’Avanzo B, et al. Selected micronutrient intake and the role of colon cancer. Br J Cancer 1994;70:1150-1155.
  • .Filioussi K, Bonovas S, Katsaros T. Should we screen diabetic patients using biguanides for megaloblastic anaemia? Aust Fam Phys 2003;32:383-384.
  • .Fiorina P, Lanfredini M, Montanari A, et al. Plasma homocysteine and folate are related to arterial blood pressure in type 2 diabetes mellitus. Am J Hypertens 1998;11(9):1100-1107.
  • .Fiskerstrand T, Ueland PM, Refsum H. Folate depletion induced by methotrexate affects methionine synthase activity and its susceptibility to inactivation by nitrous oxide. J Pharmacol Exp Ther 1997;282(3):1305-1311.
  • .Fitchie JG, Comer RW, Hanes PJ, Reeves GW. The reduction of phenytoin-induced gingival overgrowth in a severely disabled patient: a case report. Compendium 1989;10(6):314, 317-320.
  • .Flicker L, Ames D. Metabolic and endocrinological causes of dementia. Int Psychogeriatr 2005;17(Suppl 1):S79-S92.
  • .Flouvier B, Devulder B. Folic acid, xanthine oxidase, and uric acid. Ann Intern Med 1978;88:269. (Letter)
  • .Flynn MA, Irvin W, Krause G. The effect of folate and cobalamin on osteoarthritic hands. J Am Coll Nutr 1994;13(4):351-356.
  • .Food and Nutrition Board, Institute of Medicine. Folic acid: dietary reference intakes: thiamin, riboflavin, niacin, vitamin B-6, vitamin B-12, pantothenic acid, biotin, and choline. Washington, DC: National Academy Press; 1998:193-305.
  • .Forman JP, Rimm EB, Stampfer MJ, et al. Folate intake and the risk of incident hypertension among US women. JAMA 2005;293(3):320-329.
  • .Fransen J, Laan RF, Van Der Laar MA, et al. Influence of guideline adherence on outcome in a randomised controlled trial on the efficacy of methotrexate with folate supplementation in rheumatoid arthritis. Ann Rheum Dis 2004;63(10):1222-1226.
  • .Freeman JM, Finkelstein JD, Mudd SH. Folate-responsive homocystinuria and “schizophrenia”: a defect in methylation due to deficient 5,10-methylenetetrahydrofolate reductase activity. N Engl J Med 1975;292:491-496.
  • .Freudenheim JL, Graham S, Marshall JR, et al. Folate intake and carcinogenesis of the colon and rectum. Int J Epidemiol 1991;20(2):368-374.
  • .Friso S, Girelli D, Trabetti E, et al. The MTHFR 1298A>C polymorphism and genomic DNA methylation in human lymphocytes. Cancer Epidemiol Biomarkers Prev 2005;14(4):938-943.
  • .Friso S, Jacques PF, Wilson PW, et al. Low circulating vitamin B(6) is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels. Circulation 2001;103(23):2788-2791.
  • .Froscher W, Maier V, Laage M, et al. Folate deficiency, anticonvulsant drugs, and psychiatric morbidity. Clin Neuropharmacol 1995;18:165-182.
  • .Fry DW, Jackson RC. Biological and biochemical properties of new anticancer folate antagonists. Cancer Metastasis Rev 1987;5(3):251-270. (Review)
  • .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(3):227-234.
  • .Fujii K, Golivan JH, Huennekens FM. Activation of methionine synthetase: further characterisation of the flavoprotein system. Arch Biochem Biophys 1977;178:662-670.
  • .Gamble MV, Ahsan H, Liu X, et al. Folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh. Am J Clin Nutr 2005;81:1372-1377.
  • .Gamble MV, Liu X, Ahsan H, et al. Folate and arsenic metabolism: a double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh. Am J Clin Nutr 2006;84(5):1093-1101.
  • .Gamble MV, Liu X, Ahsan H, et al. Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh. Environ Health Perspect 2005;113(12):1683-1688.
  • .Ganji V, Kafai MR. Frequent consumption of milk, yogurt, cold breakfast cereals, peppers, and cruciferous vegetables and intakes of dietary folate and riboflavin but not vitamins B-12 and B-6 are inversely associated with serum total homocysteine concentrations in the US population. Am J Clin Nutr 2004;80(6):1500-1507.
  • .Gaume V, Mougin F, Figard H, et al. Physical training decreases total plasma homocysteine and cysteine in middle-aged subjects. Ann Nutr Metab 2005;49(2):125-131.
  • .Gerhard GT, Duell PB. Homocysteine and atherosclerosis. Curr Opin Lipidol 1999;10(5):417-428.
  • .Ghadirian AM, Ananth J, Engelsmann F. Folic acid deficiency and depression. Psychosomatics 1980;21(11):926-929.
  • .Gibberd FB, Nicholls A, Wright MG. The influence of folic acid on the frequency of epileptic attacks. Eur J Clin Pharmacol 1981;19:57-60.
  • .Giovannucci E, Rimm EB, Ascherio A, et al. Alcohol, low-methionine: low-folate diets, and risk of colon cancer in men. J Natl Cancer Inst 1995;87(4):265-273.
  • .Giovannucci E, Stampfer MJ, Colditz GA, et al. Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst 1993;85:875-884.
  • .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;129:517-524.
  • .Glade MJ. Workshop on folate, B12, and choline: sponsored by the Panel on Folate and other B Vitamins of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine, Washington, D.C., March 3-4, 1997. Nutrition 1999;15:92-96.
  • .Glynn SA, Albanes D, Pietinen P, et al. Colorectal cancer and folate status: a nested case-control study among male smokers. Cancer Epidemiol Biomarkers Prev 1996;5:487-494.
  • .Godfrey PS, Toone BK, Carney MW, et al. Enhancement of recovery from psychiatric illness by methylfolate. Lancet 1990;336(8712):392-395.
  • .Golbahar J, Fathi Z, Tamadon M. Distribution of 5,10-methylenetetrahydrofolate reductase (C667T) polymorphism and its association with red blood cell 5-methyltetrahydrofolate in the healthy Iranians. Clin Nutr 2005;24(1):83-87.
  • .Gomez G. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. Gastroenterology 1991;100(6):1789-1790.
  • .Gong K, Zhang Z, Sun X, et al. The nonspecific anti-inflammatory therapy with methotrexate for patients with chronic heart failure. Am Heart J 2006;151(1):62-68.
  • .Gonin JM Folic acid supplementation to prevent adverse events in individuals with chronic kidney disease and end stage renal disease. Curr Opin Nephrol Hypertens 2005;14(3):277-281.
  • .Gori AM, Corsi AM, Fedi S, et al. A proinflammatory state is associated with hyperhomocysteinemia in the elderly. Am J Clin Nutr 2005;82:335-341.
  • .Gori T, Parker JD. Nitrate tolerance: a unifying hypothesis. Circulation 2002;106(19):2510-2513. (Review)
  • .Gori T, Parker JD. The puzzle of nitrate tolerance: pieces smaller than we thought? Circulation 2002;106(18):2404-2408. (Review)
  • .Graham IM, Daly LE, Refsum HM, et al. Plasma homocysteine as a risk factor for vascular disease: the European Concerted Action Project. JAMA 1997;277:1775-1781.
  • .Gregory JF III. Case study: folate bioavailability. J Nutr 2001;131:1376S-1382S.
  • .Gueant-Rodriguez R-M, Gueant J-L, Debard R, et al. Prevalence of methylenetetrahydrofolate reductase 677T and 1298C alleles and folate status: a comparative study in Mexican, West African, and European populations. Am J Clin Nutr 2006;83:701-707.
  • .Guenther BD, Sheppard CA, Tran P, et al. The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nature Struct Biol 1999;6:359-365.
  • .Haagsma CJ, Blom HJ, van Riel PL, et al. Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Ann Rheum Dis 1999;58(2):79-84.
  • .Handy DE, Loscalzo J. Homocysteine and atherothrombosis: diagnosis and treatment. Curr Atheroscler Rep 2003;5(4):276-283. (Review)
  • .Handy DE, Zhang Y, Loscalzo J. Homocysteine downregulates cellular glutathione peroxidase (GPx1) by decreasing translation. J Biol Chem 2005;280(16):15518-15525.
  • .Hankey GJ, Eikelboom JW, Loh K, et al. Sustained homocysteine-lowering effect over time of folic acid-based multivitamin therapy in stroke patients despite increasing folate status in the population. Cerebrovasc Dis 2005;19(2):110-116.
  • .Hannon-Fletcher MP, Armstrong NC, Scott JM, et al. Determining bioavailability of food folates in a controlled intervention study. Am J Clin Nutr 2004;80(4):911-918.
  • .Hansen DK, Grafton TF, Dial SL, et al. Effect of supplemental folic acid on valproic acid-induced embryotoxicity and tissue zinc levels in vivo. Teratology 1995;52(5):277-285.
  • .Harper JM, Levine AJ, Rosenthal DL, et al. Erythrocyte folate levels, oral contraceptive use and abnormal cervical cytology. Acta Cytol 1994;38(3):324-330.
  • .Hasegawa Y. [Pharmacogenomic approaches for prevention of drug toxicity in cancer chemotherapy] Gan To Kagaku Ryoho 2003;30(3):325-333. (Review) [Japanese]
  • .Hartman M, van Ede A, Severens JL, et al. Economic evaluation of folate supplementation during methotrexate treatment in rheumatoid arthritis. J Rheumatol 2004;31(5):902-908.
  • .Hathcock JN. Metabolic mechanisms of drug-nutrient interactions. Fed Proc 1985;44(1 Pt 1):124-129. (Review)
  • .Hathcock JN. Vitamin and mineral safety. 2nd ed. Washington, DC: Council for Responsible Nutrition; 2004. (Review)
  • .Hayes C, Werler MM, Willett WC, et al. Case-control study of periconceptional folic acid supplementation and oral clefts. Am J Epidemiol 1996;143:1229-1234.
  • .Haynes WG. Hyperhomocysteinemia, vascular function and atherosclerosis: effects of vitamins. Cardiovasc Drugs Ther 2002;16:391-399.
  • .He FJ, Nowson CA, MacGregor GA. Fruit and vegetable consumption and stroke. Lancet 2006;367:320-326. (Meta-analysis)
  • .Heimberger DC. Localized deficiencies of folic acid in aerodigestive tissues. Ann N Y Acad Sci 1992;669:87-96.
  • .Heimburger DC, Alexander CB, Birch R, et al. Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12: report of a preliminary randomized, double-blind intervention trial. JAMA 1988;259:1525-1530.
  • .Hendler SS, Rorvik DR, eds. PDR for nutritional supplements. Montvale, NJ: Medical Economics Company, Inc; 2001. (Review)
  • .Herbert V. Folic acid. In: Shils M, Olson JA, Shike M, et al, eds. Modern nutrition in health and disease. 9th ed. Baltimore: Williams and Wilkins; 1999:433-446.
  • .Herbert V, Colman N, Spivack M, et al. Am J Obstet Gynecol 1975;123(2):175-179.
  • .Herrmann M, Muller S, Kindermann I, et al. Plasma B vitamins and their relation to the severity of chronic heart failure. Am J Clin Nutr 2007;85(1):117-124.
  • .Hertrampf E, Cortes F, Erickson JD, et al. Consumption of folic acid-fortified bread improves folate status in women of reproductive age in Chile. J Nutr 2003;133(10):3166-3169.
  • .Heseker H, Kubler W, Pudel V, et al. Psychological disorders as early symptoms of a mild-moderate vitamin deficiency. Ann N Y Acad Sci 1992;669:352-357.
  • .Hickling S, Hung J, Knuiman M, et al. Impact of voluntary folate fortification on plasma homocysteine and serum folate in Australia from 1995 to 2001: a population based cohort study. J Epidemiol Community Health 2005;59(5):371-376.
  • .Hirakawa K, Aoshima M, Hiraku Y, et al. Photohydrolysis of methotrexate produces pteridine, which induces poly-G-specific DNA damage through photoinduced electron transfer. Photochem Photobiol 2002;76(5):467-472.
  • .Hirsch S, Ronco AM, Vasquez M, et al. Hyperhomocysteinemia in healthy young men and elderly men with normal serum folate concentration is not associated with poor vascular reactivity or oxidative stress. J Nutr 2004;134(7):1832-1835.
  • .Hodges R. Drug-nutrient interaction. In: Nutrition in medical practice. Philadelphia: Saunders; 1980:323-331.
  • .Hodis HN, Mack WJ, LaBree L, et al. Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. JAMA 1995;273(23):1849-1854.
  • .Holick CN, De Vivo I, Feskanich D, et al. Intake of fruits and vegetables, carotenoids, folate, and vitamins A, C, E and risk of bladder cancer among women (United States). Cancer Causes Control 2005;16(10):1135-1145.
  • .Holmes VA, Wallace JM, Alexander HD, et al. Homocysteine is lower in the third trimester of pregnancy in women with enhanced folate status from continued folic acid supplementation. Clin Chem 2005;51(3):629-634.
  • .Holt GA. Food and drug interactions. Chicago: Precept Press; 1998. (Review)
  • .Homocysteine Lowering Trialists’ Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Br Med J 1998;316:894-898.
  • .Hong SY, Yang DH, Chang SK. Plasma homocysteine, vitamin B6, vitamin B12 and folic acid in end-stage renal disease during low-dose supplementation with folic acid. Am J Nephrol 1998;18(5):367-372.
  • .Hopkins PN, Wu LL, Wu J, et al. Higher plasma homocysteine and increased susceptibility to adverse effects of low folate in early familial coronary artery disease. Arterioscler Thromb Vasc Biol 1995;15:1314-1320.
  • .Hortobagyi GN, Yap HY, Blumenschein GR, et al. Phase II evaluation of vinblastine, methotrexate, and calcium leukovorin rescue in patients with refractory metastatic breast cancer. Cancer 1983;51(5):769-772.
  • .Houghton LA, Green TJ, Donovan UM, et al. Association between dietary fiber intake and the folate status of a group of female adolescents. Am J Clin Nutr 1997;66(6):1414-1421.
  • .Houghton LA, Sherwood KL, Pawlosky R, et al. [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation. Am J Clin Nutr 2006;83: 842-850.
  • .Houston DK, Johnson MA, Nozza RJ, et al. Age-related hearing loss, vitamin B-12, and folate in elderly women. Am J Clin Nutr 1999;69:564-571.
  • .Howe RB, Branda RF, Douglas SD, et al. Hereditary dyserythropoiesis with abnormal membrane folate transport. Blood 1979;54:1080-1090.
  • .Howlett HC, Bailey CJ. A risk-benefit assessment of metformin in type 2-diabetes mellitus. Drug Safety 1999;20:489-503.
  • .Huemer M, Fodinger M, Huemer C, et al. Hyperhomocysteinemia in children with juvenile idiopathic arthritis is not influenced by methotrexate treatment and folic acid supplementation: a pilot study. Clin Exp Rheumatol 2003;21(2):249-255.
  • .Huemer M, Huemer C, Ulmer H, et al. No evidence for hyperhomocysteinemia or increased prevalence of genetic polymorphisms in the homocysteine pathway in patients with moderate juvenile idiopathic arthritis. J Rheumatol 2005;32(1):170-174.
  • .Husemoen LL, Thomsen TF, Fenger M, Jorgensen T. Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype: Inter99 (7). Eur J Clin Nutr 2004;58(8):1142-1150.
  • .Hussien MM, McNulty H, Armstrong N, et al. Investigation of systemic folate status, impact of alcohol intake and levels of DNA damage in mononuclear cells of breast cancer patients. Br J Cancer 2005;92(8):1524-1530.
  • .Hustad S, Ueland PM, Vollset SE. Riboflavin as a determinant of plasma total homocysteine: effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. Clin Chem 2000;46:1065-1071.
  • .Ignarro LJ, Napoli C, Loscalzo J. Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide: an overview. Circ Res 2002;90(1):21-28. (Review)
  • .Iivanainen M, Savolainen H. Side effects of phenobarbital and phenytoin during long-term treatment of epilepsy. Acta Neurol Scand Suppl 1983;97:49-67.
  • .Irizarry MC, Gurol ME, Raju S, et al. Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease. Neurology 2005;65(9):1402-1408.
  • .Isotalo PA, Wells GA, Donnelly JG. Neonatal and fetal methylenetetrahydrofolate reductase genetic polymorphisms: an examination of C677T and A1298C mutations. Am J Hum Genet 2000;67(4):986-990.
  • .Jackman AL, Judson IR. The new generation of thymidylate synthase inhibitors in clinical study. Exp Opin Invest New Drugs 1996;5:719-736.
  • .Jacob RA. Folate, DNA methylation, and gene expression: factors of nature and nurture. Am J Clin Nutr 2000;72:903-904.
  • .Jacques PF, Kalmbach R, Bagley PJ. The relationship between riboflavin and plasma total homocysteine in the Framingham Offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene. J Nutr 2002;132:283-288.
  • .Jacques PF, Selhub J, Bostom AG, et al. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999;340(19):1449-1454.
  • .Janinis J, Papakostas P, Samelis G, et al. Second-line chemotherapy with weekly oxaliplatin and high-dose 5-fluorouracil with folinic acid in metastatic colorectal carcinoma: a Hellenic Cooperative Oncology Group (HeCOG) phase II feasibility study. Ann Oncol 2000;11(2):163-167.
  • .Jansen G. Receptor- and carrier-mediated transport systems for folates and antifolates: exploitation for folate-based chemotherapy and immunotherapy. In: Jackman AL, ed. Antifolate drugs in cancer therapy. Totowa, NJ: Humana Press; 1999:293-321.
  • .Jiang Q, Chen K, Ma X, et al. Diets, polymorphisms of methylenetetrahydrofolate reductase, and the susceptibility of colon cancer and rectal cancer. Cancer Detect Prev 2005;29(2):146-154.
  • .Johansson M, Witthoft CM, Bruce A, et al. Study of wheat breakfast rolls fortified with folic acid: the effect on folate status in women during a 3-month intervention. Eur J Nutr 2002;41(6):279-286.
  • .Joober R, Benkelfat C, Lal S, et al. Association between the methylenetetrahydrofolate reductase 677CT missense mutation and schizophrenia. Mol Psychiatry 2000;5:323-326.
  • .Joosten E, Lesaffre E, Riezler R, et al. Is metabolic evidence for vitamin B12 and folate deficiency more frequent in elderly patients with Alzheimer’s disease? J Gerontol A Biol Sci Med Sci 1997;52:M76-M79.
  • .Joosten E, Pelemans W. Megaloblastic anaemia in an elderly patient treated with triamterene. Neth J Med 1991;38(5-6):209-211.
  • .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 (Stockh) 1997;77:460-462.
  • .Kado DM, Karlamangla AS, Huang MH, et al. Homocysteine versus the vitamins folate, B6, and B12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging. Am J Med 2005;118(2):161-167.
  • .Kamath AF, Chauhan AK, Kisucka J, et al. Elevated levels of homocysteine compromise blood-brain barrier integrity in mice. Blood 2006;107(2):591-593.
  • .Kamen B. Folate and antifolate pharmacology. Semin Oncol 1997;24(5 Suppl 18):S18-30-S18-39. (Review)
  • .Kashani A, Phillips CO, Foody JM, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation 2006;114(25):2788-2797.
  • .Kaslow JE, Rucker L, Onishi R. Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome. Arch Intern Med 1989;149:2501-2503.
  • .Kato I, Dnistrian AM, Schwartz M, et al. Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study. Br J Cancer 1999;79(11-12):1917-1922.
  • .Kato I, Dnistrian AM, Schwartz M, et al. Epidemiologic correlates of serum folate and homocysteine levels among users and non-users of vitamin supplement. Int J Vitam Nutr Res 1999;69(5):322-329.
  • .Kauwell GP, Wilsky CE, Cerda JJ, et al. Methylenetetrahydrofolate reductase mutation (677C→T) negatively influences plasma homocysteine response to marginal folate intake in elderly women. Metabolism 2000;49(11):1440-1443.
  • .Kavey R-EW, Allada V, Daniels SR, et al. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation 2006;114:2710-2738.
  • .Kaye SB. New antimetabolites in cancer chemotherapy and their clinical impact. Br J Cancer 1998;78(Suppl 3):1-7. (Review)
  • .Kelly CB, McDonnell AP, Johnston TG, et al. The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland. J Psychopharmacol 2004;18(4):567-571.
  • .Kim SM, Kim YK, Hann S-K. Serum levels of folic acid and vitamin B12 in Korean patients with vitiligo. Yonsei Med J 1999;40:195-198.
  • .Kim Y-I. Folate and cancer prevention: a new medical application of folate beyond hyperhomocysteinemia and neural tube defects. Nutr Rev 1999;57:314-321.
  • .Kim Y-I. Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 1999;10:66-88.
  • .Kim Y-I. Methyletetrahydrofolate reductase polymorphisms, folate and cancer risk: a paradigm of gene-nutrient interactions in carcinogenesis. Nutr Rev 2000;58:205-209.
  • .Kim YI, Baik HW, Fawaz K, et al. Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial. Am J Gastroenterol 2001;96(1):184-195.
  • .Kim Y, Mason JB. Folate, epithelial dysplasia and colon cancer. Proc Assoc Am Physicians 1995;107(2):218-227. (Review)
  • .Kim Y-I, Shirwadkar S, Choi S-W, et al. Effects of dietary folate on DNA strand breaks within mutation-prone exons of the p53 gene in the rat colon. Gastroenterol 2000;199(1):151-161.
  • .Kinder AJ, Hassell AB, Brand J, et al. The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions. Rheumatology 2005;44(1):61-66.
  • .Klee GG. Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine versus vitamin B12 and folate. Clin Chem 2000;46;8(B):1277-1283.
  • .Klerk M, Durga J, Schouten EG, et al. No effect of folic acid supplementation in the course of 1 year on haemostasis markers and C-reactive protein in older adults. Thromb Haemost 2005;94(1):96-100.
  • .Klerk M, Verhoef P, Clarke R, et al. MTHFR 677C→T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 2002;288(16):2023-2031.
  • .Klipstein FA, Schenk EA, Samloff IM. Folate repletion associated with oral tetracycline therapy in tropical sprue. Gastroenterology 1966;51(3):317-332.
  • .Klipstein FA, Samloff IM. Folate synthesis by intestinal bacteria. Am J Clin Nutr 1966;19(4):237-246.
  • .Kluijtmans LA, Young IS, Boreham CA, et al. Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults. Blood 2003;101(7):2483-2488.
  • .Kluijtmans LA, Whitehead AS. Methylenetetrahydrofolate reductase genotypes and predisposition to atherothrombotic disease; evidence that all three MTHFR C677T genotypes confer different levels of risk. Eur Heart J 2001;22(4):294-299.
  • .Knock E, Deng L, Qing Wu Q, et al. Low dietary folate initiates intestinal tumors in mice, with altered expression of G2-M checkpoint regulators polo-like kinase 1 and cell division cycle 25c. Cancer Res 2006;66:10349-10356.
  • .Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2(1):10-32.
  • .Koda-Kimble MA, Guglielmo BJ, Young LL, et al, eds. Applied therapeutics: the clinical use of drugs. Philadelphia: Lippincott Williams & Wilkins; 2004.
  • .Kornberg A, Segal R, Theitler J, et al. Folic acid deficiency, megaloblastic anemia and peripheral polyneuropathy due to oral contraceptives. Isr J Med Sci 1989;25(3):142-145.
  • .Kremer JM, Bigaouette J. Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium. J Rheumatol 1996;23(6):990-994.
  • .Kruman II, Kumaravel TS, Lohani A, et al. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer’s disease. J Neurosci 2002;22(5):1752-1762.
  • .Kuhn W, Hummel T, Woitalla D, et al. Plasma homocysteine and MTHFR C677T genotype in levodopa-treated patients with PD. Neurology 2001;56(2):281-282.
  • .Kunugi H, Fukuda R, Hattori M, et al. C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses. Mol Psychiatry 1998;3:435-7.
  • .Kut V, Patel JD, Argiris A. Pemetrexed: a novel antifolate agent enters clinical practice. Expert Rev Anticancer Ther 2004;4(4):511-522. (Review)
  • .Kwasniewska A, Tukendorf A, Semczuk M. Folate deficiency and cervical intraepithelial neoplasia. Eur J Gynaecol Oncol 1997;18(6):526-530.
  • .Lairon D, Arnault N, Bertrais S, et al. Dietary fiber intake and risk factors for cardiovascular disease in French adults. Am J Clin Nutr 2005;82:1185-1194.
  • .Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985;30(2):145-155.
  • .Lamers Y, Prinz-Langenohl R, Bramswig S, et al. Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr 2006;84:156-161.
  • .Lamers Y, Prinz-Langenohl R, Moser R, et al. Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women. Am J Clin Nutr 2004;79(3):473-448.
  • .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(4):381-388.
  • .Laohavinij S, Wedge SR, Lind MJ, et al. A phase I clinical study of the antipurine antifolate lometrexol (DDATHF) given with oral folic acid. Invest New Drugs 1996;14(3):325-335.
  • .Larsson SC, Hakansson N, Giovannucci E, et al. Folate intake and pancreatic cancer incidence: a prospective study of Swedish women and men. J Natl Cancer Inst 2006;98(6):407-413.
  • .Lashner BA. Red blood cell folate is associated with the development of dysplasia and cancer in ulcerative colitis. J Cancer Res Clin Oncol 1993;119:549-554.
  • .Lashner BA, Heidenreich PA, Su GL, et al. Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis: a case-control study. Gastroenterology 1989;97(2):255-259.
  • .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(1):29-32.
  • .Laurence KM, James N, Miller MH, et al. Double-blind randomised controlled trial of folate treatment before conception to prevent recurrence of neural-tube defects. Br Med J (Clin Res Ed) 1981;282(6275):1509-1511.
  • .Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003;326:1423.
  • .Lawrence JM, Watkins ML, Chiu V, et al. Do racial and ethnic differences in serum folate values exist after food fortification with folic acid? Am J Obstet Gynecol 2006;194(2):520-526.
  • .Lerner V, Kanevsky M, Dwolatzky T, et al. Vitamin B12 and folate serum levels in newly admitted psychiatric patients. Clin Nutr 2006;25(1):60-67.
  • .Lewis DP, Van Dyke DC, Stumbo PJ, et al. Drug and environmental factors associated with adverse pregnancy outcomes: part I: antiepileptic drugs, contraceptives, smoking, and folate. Ann Pharmacother 1998;32(7-8):802-817. (Review)
  • .Lewis DP, Van Dyke DC, Stumbo PJ, et al. Drug and environmental factors associated with adverse pregnancy outcomes: part II: improvement with folic acid. Ann Pharmacother 1998;32(9):947-961. (Review)
  • .Lewis SJ, Ebrahim S, Smith GD. Meta-analysis of MTHFR 677C→T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate? BMJ 2005;331(7524):1053. (Meta-analysis)
  • .Li M, Chen J, Li YS, et al. Folic acid reduces adhesion molecules VCAM-1 expression in aortic of rats with hyperhomocysteinemia. Int J Cardiol 2006;106(2):285-288.
  • .Li CL, Werner P, Cohen G. Lipid peroxidation in brain: interactions of L-DOPA/dopamine with ascorbate and iron. Neurodegeneration 1995;4(2):147-153. Erratum in Neurodegeneration 1995;4(3):347.
  • .Liem A, Reynierse-Buitenwerf GH, Zwinderman AH, et al. Secondary prevention with folic acid: results of the Goes extension study. Heart 2005;91(9):1213-1214. (Letter)
  • .Lievers KJ, Boers GH, Verhoef P, et al. A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk. J Mol Med 2001;79(9):522-528.
  • .Lin P-T, Lee B-J, Chang H-H, et al. Low-dose folic acid supplementation reduces homocysteine concentration in hyperhomocysteinemic coronary artery disease patients. Nutr Res 2006;26(9):460-466.
  • .Lindenbaum J. Drugs and vitamin B12 and folate metabolism. Curr Concepts Nutr 1983;12:73-87. (Review)
  • .Lindenbaum J, Roman MJ. Nutritional anemia in alcoholism. Am J Clin Nutr 1980;33(12):2727-2735.
  • .Lipkin GW, Tomson CRV. Severe reversible renal failure with bezafibrate. Lancet 1993;341:371. (Letter)
  • .Liu T, Soong SJ, Wilson NP, et al. A case control study of nutritional factors and cervical dysplasia. Cancer Epidemiol Biomarkers Prev 1993;2(6):525-530.
  • .Lobo A, Naso A, Arheart K, et al. Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12. Am J Cardiol 1999;83(6):821-825.
  • .Lokk J. [Treatment with levodopa can affect latent vitamin B 12 and folic acid deficiency: patients with Parkinson disease run the risk of elevated homocysteine levels] Lakartidningen 2003;100(35):2674-2677. (Review) [Swedish]
  • .Longstreth GF, Green R. Folate levels in inflammatory bowel disease. N Engl J Med 1982;306(24):1488. (Letter)
  • .Lonn E, Held C, Arnold JM, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354(15):1567-1577.
  • .Loscalzo J. Homocysteine trials: clear outcomes for complex reasons. N Engl J Med 2006;354(15):1629-1632. (Editorial)
  • .Loscalzo J. Folate and nitrate-induced endothelial dysfunction: a simple treatment for a complex pathobiology. Circulation 2001;104(10):1086-1088. (Editorial)
  • .Loscalzo J. Homocysteine trials: clear outcomes for complex reasons. N Engl J Med 2006;354(15):1629-1632. (Editorial)
  • .Loscalzo J. The oxidant stress of hyperhomocyst(e)inemia. J Clin Invest 1996;98:5-7.
  • .Loscher W, Schmidt D. Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs. Epilepsia 2006;47(8):1253-1284. (Review)
  • .Lucock M. Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol Genet Metab 2000;71:121-138.
  • .Lucock M, Yates Z. Folic acid: vitamin and panacea or genetic time bomb? Natl Rev Genet 2005;6(3):235-240. (Review)
  • .Luther L, Santini R, Brewster C, et al. Folate binding by insoluble components of American and Puerto Rican diets. Ala J Med Sci 1965;2(4):389-393.
  • .Ma J, Stampfer MJ, Giovannucci E, et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 1997;57(6):1098-1102.
  • .MacKenzie JF, Russell RI. The effect of pH on folic acid absorption in man. Clin Sci Mol Med 1976;51(4):363-368.
  • .MacKenzie KE, Wiltshire EJ, Gent R, et al. Folate and vitamin B6 rapidly normalize endothelial dysfunction in children with type 1 diabetes mellitus. Pediatrics 2006;118(1):242-253.
  • .Makoff R. Vitamin replacement therapy in renal failure patients. Miner Electrolyte Metab 1999;25(4-6):349-351. (Review)
  • .Malet-Martino M, Martino R. Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review. Oncologist 2002;7:288-323. (Review)
  • .Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 1999;99(1):178-182.
  • .Malinow MR, Duell PB, Hess DL, et al. Reduction of plasma homocysteine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med 1998;338:1009-1015.
  • .Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev 2003;(4):CD004514. (Review)
  • .Mangoni AA, Sherwood RA, Swift CG, et al. Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial. J Intern Med 2002;252:497-503.
  • .Maron BA, Loscalzo J. Homocysteine. Clin Lab Med 2006;26(3):591-609, vi.
  • .Marsh S, King CR, Ahluwalia R, et al. Distribution of ITPA P32T alleles in multiple world populations. J Hum Genet 2004;49(10):579-581.
  • .Martinez JJ, Ruiz FA, Candil SD. Baseline serum folate level may be a predictive factor of weight loss in a morbid-obesity-management programme. Br J Nutr 2006;96(5):956-964.
  • .Martinez ME, Giovannucci E, Jiang R, et al. Folate fortification, plasma folate, homocysteine and colorectal adenoma recurrence. Int J Cancer 2006;119(6):1440-1446.
  • .Martinez O, Roe DA. Effect of oral contraceptives on blood folate levels in pregnancy. Am J Obstet Gynecol 1977;128:255-261.
  • .Marz R. Medical nutrition from Marz. 2nd ed. Portland, OR; Omni Press; 1997. (Review)
  • .Mason JB. Folate and colonic carcinogenesis: searching for a mechanistic understanding. J Nutr Biochem 1994;5:170-175.
  • .Mason JB. Folate status: effects on carcinogenesis. In: Bailey LB, ed. Folates in health and disease. New York: Marcel Dekker, 1995:361-378.
  • .Mason P. Dietary supplements. London: Pharmaceutical Press; 2001. (Review)
  • .Mathers JC. Reversal of DNA hypomethylation by folic acid supplements: possible role in colorectal cancer prevention. Gut 2005;54(5):579-581. (Editorial)
  • .Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther 1982;4(6):423-440. (Review)
  • .Mattison LK, Soong R, Diasio RB. Implications of dihydropyrimidine dehydrogenase on 5-fluorouracil pharmacogenetics and pharmacogenomics. Pharmacogenomics 2002;3:485-492.
  • .Mauritz R, Peters GJ, Priest DG, et al. Multiple mechanisms of resistance to methotrexate and novel antifolates in human CCRF-CEM leukemia cells and their implications for folate homeostasis. Biochem Pharmacol 2002;63(2):105-115.
  • .Mayer O Jr, Simon J, Holubec L, et al. Fenofibrate-induced hyperhomocysteinemia may be prevented by folate co-administration. Eur J Clin Pharmacol 2003;59(5-6):367-371.
  • .Mayer O Jr, Simon J, Holubec L, et al. Fibrate treatment and prevalence risk of mild hyperhomocysteinaemia in clinical coronary heart disease patients. Eur J Cardiovasc Prev Rehabil 2004;11(3):244-249.
  • .Mayer O Jr, Simon J, Rosolova H, et al. The effects of folate supplementation on some coagulation parameters and oxidative status surrogates. Eur J Clin Pharmacol 2002;58(1):1-5.
  • .McKillop DJ, McNulty H, Scott JM, et al. The rate of intestinal absorption of natural food folates is not related to the extent of folate conjugation. Am J Clin Nutr 2006;84:167-173.
  • .McLaughlin WS, Ball DE, Seymour RA, et al. The pharmacokinetics of phenytoin in gingival crevicular fluid and plasma in relation to gingival overgrowth. J Clin Periodontol 1995;22(12):942-945.
  • .McLean RR, Karasik D, Selhub J, et al. Association of a common polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene with bone phenotypes depends on plasma folate status. J Bone Miner Res 2004;19(3):410-418.
  • .McLeod HL, Siva C. The thiopurine S-methyltransferase gene locus: implications for clinical pharmacogenomics. Pharmacogenomics 2002;3:89-98.
  • .McMahon JA, Green TJ, Skeaff CM, et al. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 2006;354:2764-2772.
  • .McNulty H, Cuskelly GJ, Ward M. Response of red blood cell folate to intervention: implications for folate recommendations for the prevention of neural tube defects. Am J Clin Nutr 2000;71(5 Suppl):1308S-1311S.
  • .McNulty H, Dowey LC, Scott JM. Riboflavin supplementation lowers plasma homocysteine in individuals homozygous for the MTHFR C677T polymorphism. J Inherited Metab Dis 2003;26(Suppl 1):12.
  • .McNulty H, McKinley MC, Wilson B. Impaired function of thermolabile methylenetetrahydrofolate reductase is dependent on riboflavin status: implications for riboflavin requirements. Am J Clin Nutr 2002;76:436-441.
  • .Medical Research Council Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991;338:131-137.
  • .Melse-Boonstra A, Holm PI, Ueland PM, et al. Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations. Am J Clin Nutr 2005;81:1378-1382.
  • .Mendelsohn LG, Gates SB, Habeck LL, et al. The role of dietary folate in modulation of folate receptor expression, folylpolyglutamate synthetase activity and the efficacy and toxicity of lometrexol. Adv Enzyme Regul 1996;36:365-381.
  • .Meyer F, White E. Alcohol and nutrients in relation to colon cancer in middle-aged adults. Am J Epidemiol 1993;138:225-236.
  • .Meyer RE, Oakley GP Jr. Folic acid fortification. Lancet 1999;354:2168. (Letter)
  • .Milano G, McLeod HL. Can dihydropyrimidine dehydrogenase impact 5-fluorouracil-based treatment? Eur J Cancer 2000;36:37-42.
  • .Miller JW. Assessing the association between vitamin B-12 status and cognitive function in older adults. Am J Clin Nutr 2006;84:1259-1260.
  • .Mills JL. Fortification of foods with folic acid-how much is enough? N Engl J Med 2000;342:1442-1445.
  • .Mills JL, McPartlin P, Kirke PM, et al. Homocysteine metabolism in pregnancies complicated by neural tube defects. Lancet 1995;345:149-151.
  • .Milunsky A, Jick H, Jick SS, et al. Multivitamin/folic acid supplementation in early pregnancy reduces the prevalence of neural tube defects. JAMA 1989;262:2847-2852.
  • .Miriuka SG, Langman LJ, Evrovski J, et al. Genetic polymorphisms predisposing to hyperhomocysteinemia in cardiac transplant patients. Transplant Int 2005;18(1):29-35.
  • .Moat SJ, Ashfield-Watt PA, Powers HJ, et al. Effect of riboflavin status on the homocysteine-lowering effect of folate in relation to the MTHFR (C677T) genotype. Clin Chem 2003;49(2):295-302.
  • .Moat SJ, Clarke ZL, Madhavan AK, et al. Folic acid reverses endothelial dysfunction induced by inhibition of tetrahydrobiopterin biosynthesis. Eur J Pharmacol 2006;530(3):250-258.
  • .Moat SJ, Doshi SN, Lang D, et al. Treatment of coronary heart disease with folic acid: is there a future? Am J Physiol Heart Circ Physiol 2004;287(1):H1-7. (Editorial, Review)
  • .Moat SJ, Hill MH, McDowell IF, et al. Reduction in plasma total homocysteine through increasing folate intake in healthy individuals is not associated with changes in measures of antioxidant activity or oxidant damage. Eur J Clin Nutr 2003;57(3):483-489.
  • .Moat SJ, Madhavan A, Taylor SY, et al. High- but not low-dose folic acid improves endothelial function in coronary artery disease. Eur J Clin Invest 2006;36(12):850-859.
  • .Moghadasian MH, et al. Homocysteine and coronary artery disease. Arch Intern Med 1997;157:2299-2308.
  • .Molloy AM, Daly S, Mills JL, et al. Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red cell folates: implications for folate intake recommendations. Lancet 1997;349:1591-1593.
  • .Monji A, Yanagimoto K, Maekawa T, et al. Plasma folate and homocysteine levels may be related to interictal “schizophrenia-like” psychosis in patients with epilepsy. J Clin Psychopharmacol 2005;25(1):3-5.
  • .Montes LF, Diaz ML, Lajous J, et al. Folic acid and vitamin B12 in vitiligo: a nutritional approach. Cutis 1992;50:39-42.
  • .Morel CF, Duncan AM, Desilets V. A fragile site at 10q23 (FRA10A) in a phenytoin-exposed fetus: a case report and review of the literature. Prenat Diagn 2005;25(4):318-321.
  • .Morgan SL, Baggott JE, Alarcon GS. Methotrexate and sulfasalazine combination therapy: is it worth the risk? Arthritis Rheum 1993;36(2):281-282.
  • .Morgan S, Baggott J, Vaughn W, et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. Ann Intern Med 1994;121:833-841.
  • .Morgan SL, Oster RA, Lee JY, et al. The effect of folic acid and folinic acid supplements on purine metabolism in methotrexate-treated rheumatoid arthritis. Arthritis Rheum 2004;50(10):3104-3111.
  • .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;62:641-645.
  • .Mouzas IA, Papavassiliou E, Koutroubakis I. Chemoprevention of colorectal cancer in inflammatory bowel disease? A potential role for folate. Ital J Gastroenterol Hepatol 1998;30(4):421-425. (Review)
  • .Moyers S, Bailey LB. Fetal malformations and folate metabolism: review of recent evidence. Nutr Rev 2001;59(7):215-224. (Review)
  • .Muller T, Werne B, Fowler B, et al. Nigral endothelial dysfunction, homocysteine, and Parkinson’s disease. Lancet 1999;354(9173):126-7.
  • .Muller T, Woitalla D, Fowler B, et al. 3-OMD and homocysteine plasma levels in Parkinsonian patients. J Neural Transm 2002;109(2):175-179.
  • .Muntjewerff JW, Hoogendoorn ML, Kahn RS, et al. Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: a Dutch population based case-control study. Am J Med Genet B Neuropsychiatr Genet 2005;135(1):69-72.
  • .Murphy JV, Thome LM, Michals K, et al. Folic acid responsive rages, seizures and homocystinuria. J Inherited Metab Dis 1985;8:109-110.
  • .Nagasubramanian R, Innocenti F, Ratain MJ. Pharmacogenetics in cancer treatment. Annu Rev Med 2003;54:437-452. (Review)
  • .Naurath HJ, Joosten E, Riezler R, et al. Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations. Lancet 1995;346:85-89.
  • .Navarro Silvera SA, Jain M, Howe GR, et al. Dietary folate consumption and risk of ovarian cancer: a prospective cohort study. Eur J Cancer Prev 2006;15(6):511-515.
  • .Nelen WL, Blom HJ, Steegers EA, et al. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril 2000;74(6):1196-1199.
  • .Nelen WL, Blom HJ, Steegers EA, et al. Homocysteine and folate levels as risk factors for recurrent early pregnancy loss. Obstet Gynecol 2000;95(4):519-524.
  • .Nelen WLDM, Van der Molen EF, Blom HJ, et al. Recurrent early pregnancy loss and genetic related disturbances in folate and homocysteine metabolism. Br J Hosp Med 1997;58:511-513.
  • .Neuhouser ML, Beresford SA, Hickok DE, et al. Absorption of dietary and supplemental folate in women with prior pregnancies with neural tube defects and controls. J Am Coll Nutr 1998;17(6):625-630.
  • .Nilsson-Ehle H. Age-related changes in cobalamin (vitamin B12) handling: implications for therapy. Drugs Aging 1998;12:277-292.
  • .Nilsson K, Gustafson L, Hultberg B. Plasma homocysteine concentration and its relation to symptoms of vascular disease in psychogeriatric patients. Dementia Geriatr Cogn Disord 2005;20(1):35-41.
  • .Nirmalan N, Sims PF, Hyde JE. Translational up-regulation of antifolate drug targets in the human malaria parasite Plasmodium falciparum upon challenge with inhibitors. Mol Biochem Parasitol 2004;136(1):63-70.
  • .Niyikiza C, Baker SD, Seitz DE, et al. Homocysteine and methylmalonic acid: markers to predict and avoid toxicity from pemetrexed therapy. Mol Cancer Ther 2002;1(7):545-552.
  • .Norlund L, Grubb A, Fex G, et al. The increase of plasma homocysteine concentrations with age is partly due to the deterioration of renal function as determined by plasma cystatin C. Clin Chem Lab Med 1998;36(3):175-178.
  • .Nygard O, Nordrehaug JE, Refsum H, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997;337:230-236.
  • .O’Keeffe ST. Restless legs syndrome: a review. Arch Intern Med 1996;156:243-248.
  • .O’Suilleabhain PE, Sung V, Hernandez C, et al. Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations. Arch Neurol 2004;61(6):865-868.
  • .Oakley GP Jr. Eat right and take a multivitamin. N Engl J Med 1998;338:1060-1061. (Editorial)
  • .Oakley GP Jr, Adams MJ, Dickinson CM. More folic acid for everyone, now. J Nutr 1996;126(3):751S-755S.
  • .Ogawa Y, Kaneko S, Otani K, et al. Serum folic acid levels in epileptic mothers and their relationship to congenital malformations. Epilepsy Res 1991;8(1):75-78.
  • .Olivares AB, Bernal MJ, Ros G, et al. [Quality of data on folic acid content in vegetables included in several Spanish Food Composition Tables and new data on their folate content] Nutr Hosp 2006;21(1):97-108. (Review) [Spanish]
  • .Olszewski AJ, Szostak WB, Bialkowska M, et al. Reduction of plasma lipid and homocysteine levels by pyridoxine, folate, cobalamin, choline, riboflavin, and troxerutin in atherosclerosis. Atherosclerosis 1989;75(1):1-6.
  • .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(1):36-43.
  • .Oster KA. Evaluation of serum cholesterol reduction and xanthine oxidase inhibition in the treatment of atherosclerosis. Recent Adv Stud Cardiac Struct Metab 1973;3:73-80.
  • .O’Shaughnessy JA. Pemetrexed: an active new agent for breast cancer. Semin Oncol 2002;29(6 Suppl 18):57-62. (Review)
  • .O’Suilleabhain PE, Sung V, Hernandez C, et al. Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations. Arch Neurol 2004;61(6):865-868.
  • .Palazzi C, D’Amico E, Pennese E, et al. Normalization of methotrexate-induced high levels of serum transaminases after ursodeoxycholic acid administration in a rheumatoid arthritis patient. Rheumatology 2003;42(10):1266-1267.
  • .Papakostas GI, Petersen T, Mischoulon D, et al. Serum folate, vitamin B12, and homocysteine in major depressive disorder, part 1: predictors of clinical response in fluoxetine-resistant depression. J Clin Psychiatry 2004;65(8):1090-1095.
  • .Papakostas GI, Petersen T, Mischoulon D, et al. Serum folate, vitamin B12, and homocysteine in major depressive disorder, part 2: predictors of relapse during the continuation phase of pharmacotherapy. J Clin Psychiatry 2004;65(8):1096-1098.
  • .Papoutsakis C, Yiannakouris N, Manios Y, et al. Plasma homocysteine concentrations in Greek children are influenced by an interaction between the methylenetetrahydrofolate reductase C677T genotype and folate status. J Nutr 2005;135(3):383-388.
  • .Papoutsakis C, Yiannakouris N, Manios Y, et al. The effect of MTHFR(C677T) genotype on plasma homocysteine concentrations in healthy children is influenced by gender. Eur J Clin Nutr 2006;60(2):155-162.
  • .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(1):63-71.
  • .Paulionis L, Kane SL, Meckling KA. Vitamin status and cognitive function in a long-term care population. BMC Geriatr 2005;5(1):16.
  • .Pearson H. Pervasive vitamin fortification could alter genes. Nature 2005.
  • .Pentieva K, McNulty H, Reichert R, et al. The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men. J Nutr 2004;134(3):580-585.
  • .Perry TL, Applegarth DA, Evans ME, et al. Metabolic studies of a family with massive formiminoglutamic aciduria. Pediatr Res 1975;9:117-122.
  • .Pfeiffer CM, Caudill SP, Gunter EW, et al. Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999-2000. Am J Clin Nutr 2005;82(2):442-450.
  • .Pietarinen GJ, Leichter J, Pratt RF. Dietary folate intake and concentration of folate in serum and erythrocytes in women using oral contraceptives. Am J Clin Nutr 1977;30(3):375-380.
  • .Pironi L, Cornia GL, Ursitti MA, et al. [Prevalence and pathogenesis of folate deficiency in patients with quiescent or clinically mildly active Crohn disease]. Minerva Dietol Gastroenterol 1987;33(4):307-313. [Italian]
  • .Potena L, Grigioni F, Magnani G, et al. Folate supplementation after heart transplantation: effects on homocysteine plasma levels and allograft vascular disease. Clin Nutr 2002;21(3):245-248.
  • .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(8):1063-1069.
  • .Prasad K. Homocysteine, a risk factor for cardiovascular disease. Int J Angiol 1999;8(1):76-86.
  • .Prichard MN, Prichard LE, Shipman C Jr. Inhibitors of thymidylate synthase and dihydrofolate reductase potentiate the antiviral effect of acyclovir. Antiviral Res 1993;20(3):249-259.
  • .Pronsky Z. Powers and Moore’s food-medications interactions. 9th ed. Pottstown, PA: Food-Medication Interactions, 1991. (Review)
  • .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(7):1799-1805.
  • .Pullin CH, Wilson JF, Ashfield-Watt PA, et al. Influence of methylenetetrahydrofolate reductase genotype, exercise and other risk factors on endothelial function in healthy individuals. Clin Sci (Lond) 2002;102(1):45-50.
  • .Puto K, Garey JS. Pemetrexed therapy for malignant pleural mesothelioma. Ann Pharmacother 2005;39(4):678-683.
  • .Quadri P, Fragiacomo C, Pezzati R, et al. Homocysteine and B vitamins in mild cognitive impairment and dementia. Clin Chem Lab Med 2005;43(10):1096-1100.
  • .Quere I, Perneger TV, Zittoun J, et al. Red blood cell methylfolate and plasma homocysteine as risk factors for venous thromboembolism: a matched case-control study. Lancet 2002;359(9308):747-752.
  • .Quinlivan EP, Davis SR, Shelnutt KP, et al. Methylenetetrahydrofolate reductase 677C→T polymorphism and folate status affect one-carbon incorporation into human DNA deoxynucleosides. J Nutr 2005;135(3):389-396.
  • .Racek J, Rusnakova H, Trefil L, et al. The influence of folate and antioxidants on homocysteine levels and oxidative stress in patients with hyperlipidemia and hyperhomocysteinemia. Physiol Res 2005;54(1):87-95.
  • .Ramos MI, Allen LH, Haan MN, et al. Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification. Am J Clin Nutr 2004;80(4):1024-1028.
  • .Ramos MI, Allen LH, Mungas DM, et al. Low folate status is associated with impaired cognitive function and dementia in the Sacramento Area Latino Study on Aging. Am J Clin Nutr 2005;82(6):1346-1352.
  • .Rampersaud GC, Bailey LB, Kauwell GP. Relationship of folate to colorectal and cervical cancer: review and recommendations for practitioners. J Am Diet Assoc 2002;102(9):1273-1282. (Review)
  • .Rampersaud GC, Kauwell GP, Bailey LB. Folate: a key to optimizing health and reducing disease risk in the elderly. J Am Coll Nutr 2003;22(1):1-8. (Review)
  • .Rampersaud GC, Kauwell GP, Hutson AD, et al. Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. Am J Clin Nutr 2000;72(4):998-1003.
  • .Rath HC, Caesar I, Roth M, et al. Nutritional deficiencies and complications in chronic inflammatory bowel diseases. Med Klin 93(1):6-10;1998.
  • .Ravaglia G, Forti P, Maioli F, et al. Folate, but not homocysteine, predicts the risk of fracture in elderly persons. J Gerontol A Biol Sci Med Sci 2005;60(11):1458-1462.
  • .Ravaglia G, Forti P, Maioli F, et al. Homocysteine and folate as risk factors for dementia and Alzheimer disease. Am J Clin Nutr 2005;82(3):636-643.
  • .Ray MS, Muggia FM, Leichman CG, et al. Phase I study of (6R)-5,10-dideazatetrahydrofolate: a folate antimetabolite inhibitory to de novo purine synthesis. J Natl Cancer Inst 1993;85(14):1154-1159.
  • .Refai TM, Al-Salem IH, Nkansa-Dwamena D, et al. Hyperhomocysteinaemia and risk of thrombosis in systemic lupus erythematosus patients. Clin Rheumatol 2002;21(6):457-461.
  • .Regland B, Germgard T, Gottfries CG, et al. Homozygous thermolabile methylenetetrahydrofolate reductase in schizophrenia-like psychosis. J Neural Transm 1997;104:931-941.
  • .Regland B, Johansson BV, Grenfeldt B, et al. Homocysteinemia is a common feature of schizophrenia. J Neural Transm Gen Sect 1995;100:165-169.
  • .Reynolds EH. Effects of folic acid on the mental state and fit frequency of drug treated epileptic patients. Lancet 1967;1:1086.
  • .Reynolds EH, Milner G, Matthews DM, et al. Anticonvulsant therapy, megaloblastic haemopoiesis and folic acid metabolism. QJM 1966;35:521-537.
  • .Riddell LJ, Chisholm A, Williams S, et al. Dietary strategies for lowering homocysteine concentrations. Am J Clin Nutr 2000;71(6):1448-1454.
  • .Rimm EB, Willett WC, Hu FB, et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 1998;279(5):359-364.
  • .Robbins MA, Elias MF, Budge MM, et al. Homocysteine, type 2 diabetes mellitus, and cognitive performance: the Maine-Syracuse Study. Clin Chem Lab Med 2005;43(10):1101-1106.
  • .Robinson C, Weigly E. Basic nutrition and diet therapy. New York: MacMillan; 1984. (Review)
  • .Roe DA. Diet and drug interactions. New York: Van Nostrand Reinhold; 1989. (Review)
  • .Roe DA. Drug-induced nutritional deficiencies. 2nd ed. Westport, CT: Avi Publishing; 1985:158-159. (Review)
  • .Roe DA. Risk factors in drug-induced nutritional deficiencies. In: Roe DA, Campbell T, eds. Drugs and nutrients: the interactive effects. New York: Marcel Decker; 1984:505-523. (Review)
  • .Rohan TE, Jain MG, Howe GR, et al. Dietary folate consumption and breast cancer risk. J Natl Cancer Inst 2000;92:266-269.
  • .Rosenberg IH. Absorption and malabsorption of folates. Clin Haematol 1976;5(3):589-618. (Review)
  • .Rosenberg LE, Fentonk WA. Disorders of propionate and methylmalonate metabolism. In: Scriver C, Beaudet A, Sly W, et al, eds. Metabolic basis of inherited disease. New York: McGraw-Hill; 1989:821-844.
  • .Rosenquist TH, Ratashak SA, Selhub J. Homocysteine induces congenital defects of the heart and neural tube: effect of folic acid. Proc Natl Acad Sci U S A 1996;93:15227-15232.
  • .Rossmann JA, Ingles E, Brown RS. Multimodal treatment of drug-induced gingival hyperplasia in a kidney transplant patient. Compendium 1994;15(10):1266, 1268-1270, 1272-1274.
  • .Russell RM. A minimum of 13,500 deaths annually from coronary artery disease could be prevented by increasing folate intake to reduce homocysteine levels. JAMA 1996;275:1828-1829.
  • .Sakuta H, Suzuki T, Yasuda H, et al. Plasma vitamin B(12), folate and homocysteine levels in gastrectomized men. Clin Nutr 2005;24(2):244-249.
  • .Sanderson P, McNulty H, Mastroiacovo P, et al. Folate bioavailability: UK Food Standards Agency workshop report. Br J Nutr 2003;90(2):473-479. (Review)
  • .Santhosh-Kumar CR, Bisping JS, Kick SD, et al. Folate sufficient subjects do not accumulate additional folates during supplementation. Am J Hematol 2000;64:71-72.
  • .Sato Y, Honda Y, Iwamoto J, et al. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA 2005;293(9):1082-1088.
  • .Sato Y, Honda Y, Iwamoto J, et al. Homocysteine as a predictive factor for hip fracture in stroke patients. Bone 2005;36(4):721-726.
  • .Savage DG, Lindenbaum J. Folate-cobalamin interactions. In: Bailey LB, ed. Folate in health and disease. New York: Marcel Dekker, Inc; 1995:237-285.
  • .Savage DG, Lindenbaum J, Stabler SP, et al. Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. Am J Med 1994;96(3):239-246.
  • .Scagliotti GV, Shin DM, Kindler HL, et al. Phase II study of pemetrexed with and without folic acid and vitamin B12 as front-line therapy in malignant pleural mesothelioma. J Clin Oncol 2003;21(8):1556-1561.
  • .Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 2000;71(5 Suppl):1295S-1303S.
  • .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;288:973-979.
  • .Schnyder G, Roffi M, Pin R, et al. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med 2001;345(22):1593-1600.
  • .Schorah CJ, Devitt H, Lucock M, et al. The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study. Eur J Clin Nutr 1998;52(6):407-411.
  • .Schroder H, Clausen N, Ostergard E, et al. Folic acid supplements in vitamin tablets: a determinant of hematological drug tolerance in maintenance therapy of childhood acute lymphoblastic leukemia. Pediatr Hematol Oncol 1986;3:241-247.
  • .Selhub J, Jacques PF, Wilson PWF, et al. Vitamin status and intake as primary determinants of homocysteinaemia in an elderly population. JAMA 1993;270:2693-2698.
  • .Sellers TA, Kushi LH, Cerhan JR, et al. Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology 2001;12(4):420-428.
  • .Semenza JC, Delfino RJ, Ziogas A, et al. Breast cancer risk and methylenetetrahydrofolate reductase polymorphism. Breast Cancer Res Treat 2003;77(3):217-223.
  • .Senti FR, Pilch SM. Analysis of folate data from the second National Health and Nutrition Examination Survey (NHANES II). J Nutr 1985;115:1398-1402.
  • .Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346(7):476-483.
  • .Seshadri N, Robinson K. Homocysteine, B vitamins, and coronary artery disease. Med Clin North Am 2000;84(1):215-237.
  • .Seymour RA, Thomason JM, Ellis JS. The pathogenesis of drug-induced gingival overgrowth. J Clin Periodontol 1996;23(3 Pt 1):165-175. (Review)
  • .Shafer RB, Nuttall FQ. Calcium and folic acid absorption in patients taking anticonvulsant drugs. J Clin Endocrinol Metab 1975;41(06):1125-1129.
  • .Shane B. Folic acid, vitamin B-12, and vitamin B-6. In: Stipanuk M, ed. Biochemical and physiological aspects of human nutrition. Philadelphia: Saunders; 2000:483-518.
  • .Shaw GM, Lammer EJ, Wasserman CR, et al. Risks of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionially. Lancet 1995;345:393-396.
  • .Shaw GM, O’Malley CD, Wasserman CR, et al. Maternal periconceptional use of multivitamins and reduced risk for conotruncal heart defects and limb deficiencies among offspring. Am J Med Genet 1995;59:536-545.
  • .Shelnutt KP, Kauwell GP, Chapman CM, et al. Folate status response to controlled folate intake is affected by the methylenetetrahydrofolate reductase 677C→T polymorphism in young women. J Nutr 2003;133(12):4107-4111.
  • .Shelnutt KP, Kauwell GP, Gregory JF III, et al. Methylenetetrahydrofolate reductase 677C→T polymorphism affects DNA methylation in response to controlled folate intake in young women. J Nutr Biochem 2004;15(9):554-560.
  • .Sheu WH, Chin HM, Lee WJ, et al. Prospective evaluation of folic acid supplementation on plasma homocysteine concentrations during weight reduction: a randomized, double-blinded, placebo-controlled study in obese women. Life Sci 2005;76(18):2137-2145.
  • .Sherwood KL, Houghton LA, Tarasuk V, et al. One-third of pregnant and lactating women may not be meeting their folate requirements from diet alone based on mandated levels of folic acid fortification. J Nutr 2006;136(11):2820-2826.
  • .Shiroky JB. Folic acid and methotrexate in rheumatoid arthritis. Ann Intern Med 1996;124(1 Pt 1):73-74. (Letter)
  • .Shiroky JB, Neville C, Esdaile JM, et al. Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. Arthritis Rheum 1993;36:795.
  • .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;61:7136-7141.
  • .Shrubsole MJ, Shu XO, Ruan ZX, et al. MTHFR genotypes and breast cancer survival after surgery and chemotherapy: a report from the Shanghai Breast Cancer Study. Breast Cancer Res Treat 2005;91(1):73-79.
  • .Silaste ML, Rantala M, Alfthan G, et al. Plasma homocysteine concentration is decreased by dietary intervention. Br J Nutr 2003;89(3):295-301.
  • .Silaste ML, Rantala M, Sampi M, et al. Polymorphisms of key enzymes in homocysteine metabolism affect diet responsiveness of plasma homocysteine in healthy women. J Nutr 2001;131:2643-2647.
  • .Sim E, Pinter K, Mushtaq A, et al. Arylamine N-acetyltransferases: a pharmacogenomic approach to drug metabolism and endogenous function. Biochem Soc Trans 2003;31(Pt 3):615-619. (Review)
  • .Skibola CF, Forrest MS, Coppede F, et al. Polymorphisms and haplotypes in folate-metabolizing genes and risk of non-Hodgkin lymphoma. Blood 2004;104(7):2155-2162.
  • .Skibola CF, Smith MT, Hubbard A, et al. Polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and risk of adult acute lymphocytic leukemia. Blood 2002;99(10):3786-3791.
  • .Slattery ML, Potter JD, Samowitz W, et al. Methylenetetrahydrofolate reductase, diet, and risk of colon cancer. Cancer Epidemiol Biomarkers Prev 1999;8(6):513-518.
  • .Smith AD. Folic acid fortification: the good, the bad, and the puzzle of vitamin B-12. Am J Clin Nutr 2007;85(1):3-5. (Editorial)
  • .Smith DB, Racusen LC. Folate metabolism and the anticonvulsant efficacy of phenobarbital. Arch Neurol 1973;28(1):18-22.
  • .Smithells RW, Seller MJ, Harris R, et al. Further experience of vitamin supplementation for prevention of neural tube defect recurrences. Lancet 1983;1:1027-1031.
  • .Smithells RW, Sheppard S, Schorah CJ. Vitamin deficiencies and neural tube defects. Arch Dis Child 1976;51(12):944-950.
  • .Smulders YM, Rakic M, Slaats EH, et al. Fasting and post-methionine homocysteine levels in NIDDM: determinants and correlations with retinopathy, albuminuria, and cardiovascular disease. Diabetes Care 1999;22:125-132.
  • .Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med 1999;159:1289-1298. (Review)
  • .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(4):993-998.
  • .Sohn KJ, Smirnakis F, Moskovitz DN, et al. Effects of folylpolyglutamate synthetase modulation on chemosensitivity of colon cancer cells to 5-fluorouracil and methotrexate. Gut 2004;53(12):1825-1831.
  • .Solini A, Santini E, Ferrannini E. Effect of short-term folic acid supplementation on insulin sensitivity and inflammatory markers in overweight subjects. Int J Obes (Lond) 2006;30(8):1197-1202.
  • .Song J, Sohn KJ, Medline A, et al. Chemopreventive effects of dietary folate on intestinal polyps in Apc+/-Msh2-/- mice. Cancer Res 2000;60(12):3191-3199.
  • .Soon SY, Ansari A, Yaneza M, et al. Experience with the use of low-dose methotrexate for inflammatory bowel disease. Eur J Gastroenterol Hepatol 2004;16(9):921-926.
  • .Sosin M, Handa S. Lesson of the week: low dose methotrexate and bone marrow suppression. BMJ 2003;326(7383):266-267.
  • .Spence JD, Bang H, Chambless LE, et al. Vitamin Intervention For Stroke Prevention trial: an efficacy analysis. Stroke 2005;36(11):2404-2409.
  • .Spijkerman AM, Smulders YM, Kostense PJ, et al. S-adenosylmethionine and 5-methyltetrahydrofolate are associated with endothelial function after controlling for confounding by homocysteine: the Hoorn Study. Arterioscler Thromb Vasc Biol 2005;25(4):778-784.
  • .Stabler SP, Allen RH, Fried LP, et al. Racial differences in prevalence of cobalamin and folate deficiencies in disabled elderly women. Am J Clin Nutr 1999;70:911-919.
  • .Stahl Z, Belmaker RH, Friger M, et al. Nutritional and life style determinants of plasma homocysteine in schizophrenia patients. Eur Neuropsychopharmacol 2005;15(3):291-295.
  • .Stam F, van Guldener C, Ter Wee PM, et al. Effect of folic acid on methionine and homocysteine metabolism in end-stage renal disease. Kidney Int 2005;67(1):259-264.
  • .Stanford JL, Molina H, Phillips J, et al. Oral folate reduces plasma homocyst(e)ine levels in hemodialysis patients with cardiovascular disease. Cardiovasc Surg 2000;8(7):567-571.
  • .Stanger O, Semmelrock HJ, Wonisch W, et al. Effects of folate treatment and homocysteine lowering on resistance vessel reactivity in atherosclerotic subjects. J Pharmacol Exp Ther 2002;303(1):158-162.
  • .Stark KD, Pawlosky RJ, Beblo S, et al. Status of plasma folate after folic acid fortification of the food supply in pregnant African American women and the influences of diet, smoking, and alcohol consumption. Am J Clin Nutr 2005;81:669-677.
  • .Steegers-Theunissen RP. Folate metabolism and neural tube defects: a review. Eur J Obstet Gynecol Reprod Biol 1995;61(1):39-48. (Review)
  • .Steffen LM. Eat your fruit and vegetables. Lancet 2006;367:278-279. (Editorial)
  • .Steffen LM, Folsom AR, Cushman M, et al. Greater fish, fruit, and vegetable intakes are related to lower incidence of venous thromboembolism. the Longitudinal Investigation of Thromboembolism Etiology. Circulation 2007;115(2):188-195.
  • .Stein JH, McBride PE. Hyperhomocysteinemia and atherosclerotic vascular disease. Arch Intern Med 1998;158:1301-1306.
  • .Steinberg SC, Steinberg AD. Phenytoin-induced gingival overgrowth control in severely retarded children. J Periodontol 1982;53(7):429-433.
  • .Stevens VL, Rodriguez C, Pavluck AL, et al. Folate nutrition and prostate cancer incidence in a large cohort of US men. Am J Epidemiol 2006;163(11):989-996.
  • .Stolzenberg-Solomon RZ, Chang SC, Leitzmann MF, et al. Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr 2006;83(4):895-904.
  • .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;153:680-687.
  • .Stoney CM, Engebretson TO. Plasma homocysteine concentrations are positively associated with hostility and anger. Life Sci 2000;66:2267-2275.
  • .Stott DJ, Macintosh G, Lowe GD, et al. Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease. Am J Clin Nutr 2005;82(6):1320-1326.
  • .Strain JJ, Dowey L, Ward M, et al. B-vitamins, homocysteine metabolism and CVD. Proc Nutr Soc 2004;63(4):597-603.
  • .Strohle A, Wolters M, Hahn A. Folic acid and colorectal cancer prevention: molecular mechanisms and epidemiological evidence. Int J Oncol 2005;26(6):1449-1464. (Review)
  • .Stumm W, Morgan JJ, eds. Aquatic chemistry: an introduction emphasizing chemical equilibria in natural waters. 2nd ed. New York, NY: Wiley; 1981:240.
  • .Su LJ, Arab L. Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study. Ann Epidemiol 2001;11(1):65-72.
  • .Suitor CW, Bailey LB. Dietary folate equivalents: interpretation and application. J Am Diet Assoc 2000;100(1):88-94.
  • .Sumi S, Marinaki AM, Arenas M, et al. Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency. Hum Genet 2002;111(4-5):360-367.
  • .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;11:1106-1116.
  • .Susser E, Brown AS, Klonowski E, et al. Schizophrenia and impaired homocysteine metabolism: a possible association. Biol Psychiatry 1998;44:141-143.
  • .Swain RA, St Clair L. The role of folic acid in deficiency states and prevention of disease. J Fam Pract 1997;44(2):138-144.
  • .Tamura T, Picciano MF. Folate and human reproduction. Am J Clin Nutr 2006;83:993-1016. (Review)
  • .Tardif JC, Gregoire J, Lavoie MA, et al. Pharmacologic prevention of both restenosis and atherosclerosis progression: AGI-1067, probucol, statins, folic acid and other therapies. Curr Opin Lipidol 2003;14(6):615-620. (Review)
  • .Taylor EC. Design and synthesis of inhibitors of folate-dependent enzymes as antitumor agents. Adv Exp Med Biol 1993;338:387-408. (Review)
  • .Taylor MJ, Carney SM, Goodwin GM, et al. Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. J Psychopharmacol 2004;18(2):251-256. (Review)
  • .Taylor MJ, Geddes J. Folic acid as ultimate in disease prevention: folate also improves mental health. BMJ 2004;328(7442):768-769. (Letter)
  • .Terry P, Jain M, Miller AB, et al. Dietary intake of folic acid and colorectal cancer risk in a cohort of women. Int J Cancer 2002;97(6):864-867.
  • .The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354(15)1567-1577.
  • .Thorpe SJ, Sands D, Heath AB, et al. An international standard for whole blood folate: evaluation of a lyophilised haemolysate in an international collaborative study. Clin Chem Lab Med 2004;42(5):533-539.
  • .Threlkeld DS, ed. Antineoplastics, antimetabolites, methotrexate. In: Facts and Comparisons drug information. St Louis: Facts and Comparisons; 1990:653-654.
  • .Threlkeld DS, ed. Central nervous system drugs, antidepressants, monoamine oxidase inhibitors. In: Facts and Comparisons drug information. St Louis: Facts and Comparisons; 1997. (Review)
  • .Threlkeld DS, ed. Gastrointestinal drugs, sulfasalazine. In: Facts and Comparisons drug information. St Louis: Facts and Comparisons; 1997. (Review)
  • .Threlkeld DS, ed. Hormones, oral contraceptives. In: Facts and Comparisons drug information. St Louis: Facts and Comparisons; 1994. (Review)
  • .Till U, Röhl P, Jentsch A, et al. Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, vitamins B6 and B12. Atherosclerosis 2005;181(1):131-135.
  • .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;36:758-765.
  • .Tjonneland A, Christensen J, Olsen A, et al. Folate intake, alcohol and risk of breast cancer among postmenopausal women in Denmark. Eur J Clin Nutr 2006;60(2):280-286.
  • .Tolarova M. Periconceptional supplementation with vitamins and folic acid to prevent recurrence of cleft lip. Lancet 1982;ii:217. (Letter)
  • .Tolmunen T, Hintikka J, Voutilainen S, et al. Association between depressive symptoms and serum concentrations of homocysteine in men: a population study. Am J Clin Nutr 2004;80(6):1574-1578.
  • .Tomkin GH, Hadden DR, Weaver JA, et al. Vitamin-B12 status of patients on long-term metformin therapy. BMJ 1971;2:685-687.
  • .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;291:565-575.
  • .Torres OA, Miller VS, Buist NM, et al. Folinic acid-responsive neonatal seizures. J Child Neurol 1999;14:529-532.
  • .Trinh BN, Ong CN, Coetzee GA, et al. Thymidylate synthase: a novel genetic determinant of plasma homocysteine and folate levels. Hum Genet 2002;111(3):299-302.
  • .Troen AM. The central nervous system in animal models of hyperhomocysteinemia. Prog Neuropsychopharmacol Biol Psychiatry 2005;29(7):1140-1151. (Review)
  • .Trovato A, Nuhlicek DN, Midtling JE. Drug-nutrient interactions. Am Fam Physician 1991;44(5):1651-1658. (Review)
  • .Truswell AS. ABC of nutrition: nutrition for pregnancy. Br Med J (Clin Res Ed) 1985;291(6490):263-266.
  • .Tse A, Brigle K, Taylor SM, et al. Mutations in the reduced folate carrier gene which confer dominant resistance to 5,10-dideazatetrahydrofolate. J Biol Chem 1998;273(40):25953-25960.
  • .Tucker KL, Olson B, Bakun P, et al. Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial. Am J Clin Nutr 2004;79(5):805-811.
  • .Tucker KL, Qiao N, Scott T, et al. High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affairs Normative Aging Study. Am J Clin Nutr 2005;82(3):627-635.
  • .Tuckerman M, Turco S. Human nutrition. Philadelphia: Lea and Febiger; 1983:215-222.
  • .Ubbink JB, van der Merwe A, Vermaak WJ, et al. Hyperhomocysteinemia and the response to vitamin supplementation. Clin Invest 1993;71(12):993-998.
  • .Ubbink JB, Vermaak WJH, van der Merwe A, et al. Vitamin B12, vitamin B6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 1993;57:47-53.
  • .Ueland PM, Refsum H. [Plasma homocysteine, a risk factor for premature vascular disease: plasma levels in healthy persons; during pathologic conditions and drug therapy] Nord Med 1989;104(11):293-298. [Norwegian]
  • .UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS-34). Lancet 1998;352:854-865.
  • .Ulrich CM, Bigler J, Bostick R, et al. Thymidylate synthase promoter polymorphism, interaction with folate intake, and risk of colorectal adenomas. Cancer Res 2002;62:3361-3364.
  • .Ulrich CM, Bigler J, Velicer CM, et al. Searching expressed sequence tag databases: discovery and confirmation of a common polymorphism in the thymidylate synthase gene. Cancer Epidemiol Biomarkers Prev 2000;9(12):1381-1385.
  • .Ulrich CM, Robien K, McLeod HL. Cancer pharmacogenetics: polymorphisms, pathways and beyond. Nat Rev Cancer 2003;3(12):912-920. (Review)
  • .Ulrich CM, Robien K, Sparks R. Pharmacogenetics and folate metabolism: a promising direction. Pharmacogenomics 2002;3:299-313.
  • .USDA: Composition of foods: USDA handbook #8. Washington, DC: ARS, USDA; 1976-1986.
  • .van Baak MA, Visscher TLS. Public health success in recent decades may be in danger if lifestyles of the elderly are neglected. Am J Clin Nutr 2006;84:1259-1260. (Editorial)
  • .van der Put NM, van Straaten HW, Trijbels FJ, et al. Folate, homocysteine and neural tube defects: an overview. Exp Biol Med 2001;226:243-270.
  • .van Ede AE, Laan RF, Blom HJ, et al. Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. Rheumatology (Oxford) 2002;41(6):658-665.
  • .van Ede AE, Laan RF, Blom HJ, et al. The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients. Arthritis Rheum 2001;44(11):2525-2530.
  • .van Ede AE, Laan RF, De Abreu RA, et al. Purine enzymes in patients with rheumatoid arthritis treated with methotrexate. Ann Rheum Dis 2002;61(12):1060-1064.
  • .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(7):1426-1431.
  • .van Meurs JB, Uitterlinden AG. Homocysteine and fracture prevention. JAMA 2005;293(9):1121-1122.
  • .van Rooij IA, Vermeij-Keers C, Kluijtmans LA, et al. Does the interaction between maternal folate intake and the methylenetetrahydrofolate reductase polymorphisms affect the risk of cleft lip with or without cleft palate? Am J Epidemiol 2003;157(7):583-591.
  • .Varela-Moreiras G. Nutritional regulation of homocysteine: effects of drugs. Biomed Pharmacother 2001;55(8):448-453. (Review)
  • .Vaughn JD, Bailey LB, Shelnutt KP, et al. Methionine synthase reductase 66A→G polymorphism is associated with increased plasma homocysteine concentration when combined with the homozygous methylenetetrahydrofolate reductase 677C→T variant. J Nutr 2004;134(11):2985-2990.
  • .Velzing-Aarts FV, Holm PI, Fokkema MR, et al. Plasma choline and betaine and their relation to plasma homocysteine in normal pregnancy. Am J Clin Nutr 2005;81:1383-1389.
  • .Venn BJ, Green TJ, Moser R, et al. Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placebo-controlled study. Am J Clin Nutr 2003;77(3):658-662.
  • .Venn BJ, Mann JI, Williams SM, et al. Dietary counseling to increase natural folate intake: a randomized, placebo-controlled trial in free-living subjects to assess effects on serum folate and plasma total homocysteine. Am J Clin Nutr 2002;76(4):758-765.
  • .Venn BJ, Mann JI, Williams SM, et al. Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial. Eur J Clin Nutr 2002;56(8):748-754.
  • .Verhaar MC, Stroes E, Rabelink TJ. Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol 2002;22(1):6-13. (Review)
  • .Vehaar MC, Wever RM, Kastelein JJ, et al. Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia: a randomized placebo-controlled trial. Circulation 1999;100:335-338.
  • .Velzing-Aarts FV, Holm PI, Fokkema MR, et al. Plasma choline and betaine and their relation to plasma homocysteine in normal pregnancy. Am J Clin Nutr 2005;81:1383-1389.
  • .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(9203):517-522.
  • .Villareal DT, Miller BV III, Banks M, et al. Effect of lifestyle intervention on metabolic coronary heart disease risk factors in obese older adults. Am J Clin Nutr 2006;84:1317-1323.
  • .Virgos C, Martorell L, Simo JM, et al. Plasma homocysteine and the methylenetetrahydrofolate reductase C677T gene variant: lack of association with schizophrenia. Neuroreport 1999;10:2035-2038.
  • .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;54:424-428.
  • .Voutilainen S, Rissanen TH, Virtanen J, et al. Low dietary folate intake is associated with an excess incidence of acute coronary events: the Kuopio Ischemic Heart Disease Risk Factor Study. Circulation 2001;103(22):2674-2680.
  • .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.
  • .Wald DS, Wald NJ, Morris JK, et al. Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. BMJ 2006;333(7578):1114-1117. (Editorial; Review)
  • .Wald NJ, Bower C. Folic acid, pernicious anaemia, and prevention of neural tube defects. Lancet 1994;343(8893):307.
  • .Wald NJ, Law MR, Morris JK, et al. Quantifying the effect of folic acid. Lancet 2001;358(9298):2069-2073. (Review) Erratum in Lancet 2002;359(9306):630.
  • .Wald NJ, Watt HC, Law MR, et al. Homocysteine and ischaemic heart disease: results of a prospective study with implications on prevention. Arch Intern Med 1998;158:862-867.
  • .Walters T. Congenital megaloblastic anemia responsive to N5-formyl tetrahydrofolic acid administration. J Pediatr 1967;70:686-687.
  • .Wang HX, Wahlin A, Basun H, et al. Vitamin B(12) and folate in relation to the development of Alzheimer’s disease. Neurology 2001;56(9):1188-1194.
  • .Wang TJ, Gona P, Larson MG, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 2006;355(25):2631-2639.
  • .Ward M, McNulty H, McPartlin J. Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid. QJM 1997;90:519-524.
  • .Ware JH. The limitations of risk factors as diagnostic tools. N Engl J Med 2006;355(25):2615-2617. (Editorial)
  • .Watters JW, McLeod HL. Cancer pharmacogenomics: current and future applications. Biochim Biophys Acta 2003;2:99-111.
  • .Wedge SR, Laohavinij S, Taylor GA, et al. Clinical pharmacokinetics of the antipurine antifolate (6R)-5, 10-dideaza-5,6,7,8-tetrahydrofolic acid (Lometrexol) administered with an oral folic acid supplement. Clin Cancer Res 1995;1(12):1479-1486.
  • .Weir DG, Molloy AM. Microvascular disease and dementia in the elderly: are they related to hyperhomocysteinemia? Am J Clin Nutr 2000;71(4):859-860.
  • .Weir DG, Scott JM. Homocysteine as a risk factor for cardiovascular and related disease: nutritional implications. Nutr Res Rev 1998;11:311-338.
  • .Weisberg I, Tran P, Christensen B, et al. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998;64:169-172.
  • .Welch GN, Upchurch GR Jr, Loscalzo J. Homocysteine, oxidative stress, and vascular disease. Hosp Pract (Minneapolis) 1997;32(6):81-82, 85, 88-92. (Review)
  • .Weller MM, Shapiro S, Mitchel AA, et al. Periconceptual folic acid exposure and risk of occurrent neural tube defects. JAMA 1993;269:1257-1261.
  • .Werbach MR. Foundations of nutritional medicine. Tarzana, CA: Third Line Press; 1997:55-57. (Review)
  • .Werler MM, Hayes C, Louik C, et al. Multivitamin supplementation and risk of birth defects. Am J Epidemiol 1999;150:675-682.
  • .Werler MM, Shapiro S, Mitchell AA. Periconceptional folic acid exposure and risk of occurrent neural tube defects. JAMA 1993;269:1257-1261.
  • .West RJ, Lloyd JK. The effect of cholestyramine on intestinal absorption. Gut 1975;16:93-98.
  • .White E, Shannon JS, Patterson RE. Relationship between vitamin and calcium supplement use and colon cancer. Cancer Epidemiol Biomarkers Prev 1997;6:769-774.
  • .Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology 2004;43(3):267-271. (Review)
  • .Wiernsperger N. Metformin: intrinsic vasculoprotective properties. Diabetes Technol Ther 2000;2:259-272.
  • .Wilby J, Kainth A, Hawkins N, et al. Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation. Health Technol Assess 2005;9(15):1-832.
  • .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(5):825-830.
  • .Williams C, Kingwell BA, Burke K, et al. Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype. Am J Clin Nutr 2005;82:26-31.
  • .Wilmink HW, Stroes ESG, Erkelens WD, et al. Influence of folic acid on postprandial endothelial dysfunction. Arterioscler Thromb Vasc Biol 2000;20:185-188.
  • .Winkelmayer WC, Huber A, Wagner OF, et al. Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B in kidney transplant recipients. Kidney Int 2005;67(5):1980-1985.
  • .Wlodarczyk BJ, Cabrera RM, Hill DS, et al. Arsenic-induced gene expression changes in the neural tube of folate transport defective mouse embryos. Neurotoxicology 2006;27(4):547-557.
  • .Wolfe JM, Bailey LB, Herrlinger-Garcia K, et al. Folate catabolite excretion is responsive to changes in dietary folate intake in elderly women. Am J Clin Nutr 2003;77(4):919-923.
  • .Wong A, Mok V, Fan YH, et al. Hyperhomocysteinemia is associated with volumetric white matter change in patients with small vessel disease. J Neurol 2006;253(4):441-447.
  • .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(7):535-539.
  • .Woo KS, Chook P, Lolin YI, et al. Folic acid improves arterial endothelial function in adults with hyperhomocystinemia. J Am Coll Cardiol 1999;34(7):2002-2006.
  • .Wynn V. Vitamins and oral contraceptive use. Lancet 1975;1(7906):561-564.
  • .Xu XY, Zhou WH, Xiao CS, et al. [A clinical study of hyperhomocysteinemia in rheumatological diseases.] Zhonghua Nei Ke Za Zhi 2005;44(2):111-114. [Chinese]
  • .Yang TL, Hung J, Caudill MA, et al. A long-term controlled folate feeding study in young women supports the validity of the 1.7 multiplier in the dietary folate equivalency equation. J Nutr 2005;135(5):1139-1145.
  • .Yerby MS. Problems and management of the pregnant woman with epilepsy. Epilepsia 1987;28(Suppl 3):S29-36. (Review)
  • .Young SN, Ghadirian AM. Folic acid and psychopathology. Prog Neuropsychopharmacol Biol Psychiatry 1989;13(6):841-863. (Review)
  • .Yxfeldt A, Wallberg-Jonsson S, Hultdin J, et al. Homocysteine in patients with rheumatoid arthritis in relation to inflammation and B-vitamin treatment. Scand J Rheumatol 2003;32(4):205-210.
  • .Zarcone R, Bellini P, Carfora E, et al. [Folic acid and cervix dysplasia.] Minerva Ginecol 1996;48(10):397-400. [Italian]
  • .Zeller JL, Burke AE, Glass RM. Folic acid. JAMA 2006;296:2758.
  • .Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA 1999;281(17):1632-1637.
  • .Zhao R, Gao F, Goldman ID. Marked suppression of the activity of some, but not all, antifolate compounds by augmentation of folate cofactor pools within tumor cells. Biochem Pharmacol 2001;61(7):857-865.
  • .Zhu H, Yang W, Lu W, et al. A known functional polymorphism (Ile120Val) of the human PCMT1 gene and risk of spina bifida. Mol Genet Metab 2006;87(1):66-70.
  • .Zittoun J. Congenital errors of folate metabolism. Baillieres Clin Haematol 1995;8:603-616.
  • .Zlotogora J, Amitai Y, Leventhal A. Surveillance of neural tube defects in Israel: the effect of the recommendation for periconceptional folic acid. Isr Med Assoc J 2006;8(9):601-604.
  • .Zoccolella S, Lamberti P, Iliceto G, et al. Plasma homocysteine levels in l-dopa-treated Parkinson’s disease patients with cognitive dysfunctions. Clin Chem Lab Med 2005;43(10):1107-1110.