Folic Acid
OVERVIEW
Folate and folic acid are forms of a water-soluble B vitamin. Folate occurs naturally in food, and folic acid is the synthetic form of this vitamin. Since 1998, folic acid has been added to cold cereals, flour, breads, pasta, bakery items, cookies, and crackers, as required by federal law. Foods that are naturally high in folate include leafy vegetables (such as spinach, broccoli, and lettuce), okra, asparagus, fruits (such as bananas, melons, and lemons) beans, yeast, mushrooms, meat (such as beef liver and kidney), orange juice, and tomato juice.
Folic acid is used for preventing and treating low blood levels of folate (folate deficiency) and high blood levels of homocysteine (hyperhomocysteinemia). Women who are pregnant or might become pregnant take folic acid to prevent miscarriage and "neural tube defects." These are serious birth defects such as spina bifida, when the fetal spine and back do not close in the womb. Folic acid is also used for many other conditions including depression, stroke, decline in memory and thinking skills in older people that is more than what is normal for their age, and many others.
Folic acid is often used in combination with other B vitamins.
CLASSIFICATION
Is a form of:
Water-soluble B vitamin
Primary Functions:
Preventing and treating Low Blood Levels of folate
Also Known As:
AcidoFolico, B Complex Vitamin, Complexe de Vitamines B, ComplexeVitaminique B
HOW DOES IT WORK?
Folic acid is needed for the proper development of the human body. It is involved in producing the genetic material called DNA and in numerous other bodily functions.
USES
- Folate deficiency. Taking folic acid improves folate deficiency.
- An eye disease that leads to vision loss in older adults (age-related macular degeneration or AMD). Research shows that taking folic acid with other vitamins including vitamin B6 and vitamin B12 reduces the risk of developing age-related vision loss.
- Decline in memory and thinking skills in older people that is more than what is normal for their age. Research shows that taking folic acid with or without other B vitamins may improve memory and thinking skills in older people with larger than normal declines in these skills. Folic acid seems to work best in people who have low levels of folate or high levels of homocysteine in the blood.
- Limited research shows that taking folic acid along with antidepressants seems to improve symptoms in people with depression.
- High blood pressure. Research shows that taking folic acid daily for at least 6 weeks reduces blood pressure in people with high blood pressure. But Taking folic acid with blood pressure medication does not seem to lower blood pressure more than taking only blood pressure medicine
- Gum enlargement caused by the drug phenytoin. Applying folic acid to the gums seems to prevent gum problems caused by phenytoin. However, taking folic acid by mouth does not seem to improve symptoms of this condition.
- Gum disease in women who are pregnant. Applying folic acid to the gums seems to improve gum disease during pregnancy.
- Taking folic acid can reduce the risk of stroke by 10% to 25% in people who live in countries that don't fortify grain products with folic acid. But folic acid doesn't seem to prevent strokes in most people who live in countries that do fortify grain products with folic acid.
- A skin disorder that causes white patches to develop on the skin (vitiligo). Taking folic acid by mouth seems to improve symptoms of vitiligo.
RECOMMENDED DOSING
The following doses have been studied in scientific research:
ADULTS
BY MOUTH:
- For folic acid deficiency: the typical dose is 250 mcg (micrograms) to 1 mg (milligrams) per day.
- For preventing birth defects of the brain and spine (neural tube birth defects): Women capable of becoming pregnant should take 400 mcg of folic acid per day from fortified foods or supplements. Women who are pregnant are advised to take 600 mcg of folic acid per day from fortified foods or supplements. Women with a history of previous pregnancy complicated by neural tube defects usually take 4 mg per day beginning one month before and continuing for up to 3 months after conception.
- For reducing colon cancer risk: 400 mcg per day.
-
For treating high amounts of homocysteine in the blood (hyperhomocysteinemia):
- 200 mcg to 15 mg per day has been used, although daily doses of 800 mcg to 1 mg appear to be most effective.
- In people with end-stage renal disease, high homocysteine levels may be more difficult to treat, and doses of 800 mcg to 40 mg per day have been used. Other dosage plans such as 2.5-5 mg three times weekly have also been used. Doses higher than 15 mg daily do not seem to be more effective than lower doses.
- For improving the response to medications for depression: 200-500 mcg daily has been used.
- For a skin disorder that causes white patches to develop on the skin (vitiligo): 5 mg is typically taken twice daily.
- For reduction of toxicity caused by the drug methotrexate: 1 mg per day is probably enough, but up to 5 mg per day may be used.
- For preventing an eye disease that leads to vision loss in older adults (age-related macular degeneration or AMD): 2.5 mg of folic acid, 1 mg of vitamin B12 (cyanocobalamin), and 50 mg of vitamin B6 (pyridoxine) per day have been used.
- For a decline in memory and thinking skills in older people that is more than what is normal for their age. 400 mcg of folic acid per day or 800 mcg of folic acid with 20 mg of vitamin B6 and 500 mcg of vitamin B12 per day have been used for up to 2 years. A higher folic acid dose of 15 mg has also been used, but only for up to 60 days.
- For preventing stroke. 500 mcg to 40 mg of folic acid per day have been used. The greatest benefit seems to occur with folic acid doses of 800 mcg per day or lower.
APPLIED TO THE SKIN:
- For gum disease in women who are pregnant: a mouthwash containing folic acid has been used twice daily for one minute.
GIVEN BY NEEDLE:
- For homocysteine lowering in people with end-stage renal disease (ESRD): 10 mg post-hemodialysis three times per week has been given in the vein.
CHILDREN
BY MOUTH:
- For gum enlargement caused by the drug phenytoin (6-15 years): folic acid 500 mcg daily has been used.
The adequate intakes (AI) for infants are 65 mcg for infants 0-6 months and 80 mcg for infants 7-12 months of age. The recommended dietary allowances (RDAs) for folate in DFE, including both food folate and folic acid from fortified foods and supplements are: Children 1-3 years, 150 mcg; Children 4-8 years, 200 mcg; Children 9-13 years, 300 mcg; Adults over 13 years, 400 mcg; Pregnant women 600 mcg; and breast-feeding women, 500 mcg. The tolerable upper intake levels (UL) of folate are 300 mcg for children 1-3 years of age, 400 mcg for children 4-8 years, 600 mcg for children 9-13 years, 800 mcg for adolescents 14-18 years, and 1 mg for everyone over 18 years of age.
FREQUENTLY ASKED QUESTIONS:
What are the benefits of taking folic acid?
Folic acid helps your body produce and maintain new cells, and also helps prevent changes to DNA that may lead to cancer. As a medication, folic acid is used to treat folic acid deficiency and certain types of anemia (lack of red blood cells) caused by folic acid deficiency.
Is it OK to take folic acid when not pregnant?
Doctors usually recommend that non-pregnant women and men get 400 mcg daily, whereas pregnant women should get 600 mcg and breastfeeding women should get 500 mcg. Providers may advise some patients to take higher doses, including: Those with a family history of neural tube defects.
Who should take folic acid supplements?
Folic Acid. CDC urges all women of reproductive age to take 400 micrograms (mcg) of folic acid each day, in addition to consuming food with folate from a varied diet, to help prevent some major birth defects of the baby's brain (anencephaly) and spine (spina bifida).
Does folic acid have side effects?
Although doses up to 5 mg daily have been safely used in some research, doses of folic acid greater than 1 mg daily might cause abdominal cramps, diarrhea, rash, sleep disorders, irritability, confusion, nausea, stomach upset, behavior changes, skin reactions, seizures, gas, excitability, and other side effects.
Is it good to take folic acid everyday?
Folic acid is a B vitamin. ... Women need to take folic acid every day, starting before they are pregnant to help prevent NTDs. CDC and the US Public Health Service urge every woman who could become pregnant to get 400 micrograms (400 mcg) of synthetic folic acid every day.
Does folic acid cause weight gain?
Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. ... Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.
Does folic acid grow hair?
Folic acid is primarily responsible for healthy cell growth. These cells include those found inside your skin tissues as well as in your hair and nails. Such effects on your hair has spurred interest in folic acid as a possible hair-growth treatment measure. Additionally, folic acid helps keep red blood cells healthy.
Why folic acid is bad?
Folate deficiency, of course, is harmful. But excess in the form of folic acid has its own dangers. Just to be clear: folic acid is not the same as natural folate. ... But it has the potential to disrupt normal folate metabolism and there is substantial evidence that it can even promote cancer growth.
Does folic acid make you more fertile?
'Folic acid helps fertility in women' Women who take folic acid supplements every day have a better chance of getting pregnant, say researchers. Long known to safeguard the health of the unborn baby, this is the first timefolic acid, a form of vitamin B, has been shown to aid conception too.
When should you stop taking folic acid?
Once you reach 12 weeks pregnant your baby's spine will have developed, so you can stop taking folic acid if you wish. Howeveryou can continue to take supplements after 12 weeks if you choose to and it.
Why would a doctor prescribe folic acid?
Folic acid helps your body produce and maintain new cells, and also helps prevent changes to DNA that may lead to cancer. As a medication, folic acid is used to treat folic acid deficiency and certain types of anemia (lack of red blood cells) caused by folic acid deficiency.
Is it OK to take 1mg of folic acid?
Most over-the-counter supplements of folic acid are 400 mcg tablets. Prescription folic acid for pregnant women is usually for 1 mg (i.e., 1,000 mcg) tablets. Adults over 18, including pregnant women, should not take more than 1,000 mcg of folic acid a day.
Can folic acid help you lose weight?
Taking a folic acid supplement will ensure that protein is metabolized properly, which will help your body maintain a stable insulin level. ... Along with good nutrition and enough exercise, supplements and vitamins like Omega Oils, B Complex, and folic acid will help your body maximize your weight loss efforts.
How long does it take for folic acid to work?
Folic acid usually starts to work in a few hours. But if you're taking it for folate deficiency anaemia, it may be a few weeks before you start to feel better.
Can too much folic acid be harmful?
You can't get too much from foods that naturally contain folate. You should not get more than 1,000 micrograms of folic acid a day, unless your doctor prescribes a higher amount. Too much folic acid can hide signs that you lack vitamin B12, which can cause nerve damage.
What does folic acid do for a woman?
Folic acid is a B vitamin that is used by the body to manufacture DNA. DNA is required for rapid cell division and organ/tissue formation in the developing baby. Folic acid can only help prevent NTDs during the first weeks of pregnancy, usually before a woman even knows she's pregnant.
Does folic acid make you tired?
Folic acid is one of the B vitamins, and it helps your body make new cells, including new red blood cells. ... If you don't have enough red blood cells, you have anemia, which can make you feel weak and tired. So it's important that you get enough folic acid every day.
Does folic acid help you get pregnant faster?
Folic acid is an important vitamin for both men and women. Getting enough folic acid can help decrease the risk of birth defects, and it may improve sperm count in men. They do make fertility supplements for men and women who are trying to conceive, but they are not all equal.
Does folic acid make you hungry?
Folic acid is a powerful appetite stimulant, especially in higher doses (>400-600 mcg/day). If an individual is deficient in folic acid, the first thing that goes is their appetite.
Does folic acid stay in your system?
Why do I have to take it every day? Your body does not store folic acid so you need to take it every day to maintain enough quantities in your body. This is because folic acid is water-soluble (dissolves in water) and leftover amounts leave the body through the urine.
Can I take vitamin D and folic acid together?
No interactions were found between folic acid and Vitamin D3. This does not necessarily mean no interactions exist. Always consult your healthcare provider.
Â
What causes high folic acid levels?
There are several other medical conditions that may increase folic acid needs including anyone taking medications for epilepsy, Rheumatoid arthritis, lupus, psoriasis, asthma, and inflammatory bowel disease; anyone with kidney disease who is on dialysis; anyone with liver, sickle cell, or celiac diseases.
CLINICAL STUDIES
- ^ ab Kawashima A, et al. Four week supplementation with mixed fruit and vegetable juice concentrates increased protective serum antioxidants and folate and decreased plasma homocysteine in Japanese subjects. Asia Pac J Clin Nutr. (2007)
- ^ abCzeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. (1992)
- ^ Almeida OP, et al. B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial. Ann Neurol. (2010)
- ^ Ford AH, et al. Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: results from a 2-year placebo-controlled randomized trial. J Clin Psychiatry. (2008)
- ^ abc Christensen H, et al. No clear potentiation of antidepressant medication effects by folic acid+vitamin B12 in a large community sample. J Affect Disord. (2011)
- ^ ab Ji HF, Tang GY, Zhang HY. A theoretical study on the structure-activity relationships of metabolites of folates as antioxidants and its implications for rational design of antioxidants. Bioorg Med Chem. (2005)
- ^ Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. (2008)
- ^ Florio R, et al. Serine hydroxymethyltransferase: a model enzyme for mechanistic, structural, and evolutionary studies. BiochimBiophys Acta. (2011)
- ^ Bhargava S, Tyagi SC. Nutriepigenetic regulation by folate-homocysteine-methionine axis: a review. Mol Cell Biochem. (2014)
- ^ Mato JM, et al. S-adenosylmethionine synthesis: molecular mechanisms and clinical implications. PharmacolTHer. (1997)
- ^ Turner MA, et al. Structure and function of S-adenosylhomocysteine hydrolase. Cell BiochemBiophys. (2000)
- ^ abcde Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Institute of Medicine. (1998)
- ^ Crider KS, Bailey LB, Berry RJ. Folic acid food fortification-its history, effect, concerns, and future directions. Nutrients. (2011)
- ^ Craig GM, Elliot C, Hughes KR. Masked vitamin B12 and folate deficiency in the elderly. Br J Nutr. (1985)
- ^ Ellison AB. Pernicious anemia masked by multivitamins containing folic acid. J Am Med Assoc. (1960)
- ^ Allen RH, et al. Diagnosis of cobalamin deficiency I: usefulness of serum methylmalonic acid and total homocysteine concentrations. Am J Hematol. (1990)
- ^ Crosby WH. The danger of folic acid in multivitamin preparations. Mil Med. (1960)
- ^ abAgamanolis DP, et al. Neuropathology of experimental vitamin B12 deficiency in monkeys. Neurology. (1976)
- ^ abc Morris MS, et al. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr. (2007)
- ^ ab Hunter R, et al. Toxicity of folic acid given in pharmacological doses to healthy volunteers. Lancet. (1970)
- ^ ab Gibberd FB, et al. Toxicity of folic acid. Lancet. (1970)
- ^ ab Hellström L. Lack of toxicity of folic acid given in pharmacological doses to healthy volunteers. Lancet. (1971)
- ^ ab Richens A. Toxicity of folic acid. Lancet. (1971)
- ^ ab Sheehy TW. Folic acid: lack of toxicity. Lancet. (1973)
- ^ ab Suarez RM, Spies TD, Suarez RM Jr.. The use of folic acid in sprue. Ann Intern Med. (1947)
- ^ abcdef Kelly P, et al. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr. (1997)
- ^ abcd Sweeney MR, McPartlin J, Scott J. Folic acid fortification and public health: report on threshold doses above which unmetabolised folic acid appear in serum. BMC Public Health. (2007)
- ^ abcde Troen AM et al.. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr. (2006)
- ^ Morris MS, et al. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors. Am J Clin Nutr. (2010)
- ^ abcd Christensen KE et al.. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice. Am J Clin Nutr. (2015)
- ^ Lok A et al.. The one-carbon-cycle and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in recurrent major depressive disorder; influence of antidepressant use and depressive state?. J Affect Disord. (2014)
- ^ abcd Wright AJ, Dainty JR, Finglas PM. Folic acid metabolism in human subjects revisited: potential implications for proposed mandatory folic acid fortification in the UK. Br J Nutr. (2007)
- ^ Obeid R. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients. (2013)
- ^ Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. (2015)
- ^ ab Yan J et al.. MTHFR C677T genotype influences the isotopic enrichment of one-carbon metabolites in folate-compromised men consuming d9-choline. Am J Clin Nutr. (2011)
- ^ abcdef Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidemiol. (2007)
- ^ Rozen R. Molecular genetics of methylenetetrahydrofolate reductase deficiency. J Inherit Metab Dis. (1996)
- ^ Lievers KJ et al.. A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk. J Mol Med (Berl). (2001)
- ^ Goyette P, et al. Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. Am J Hum Genet. (1995)
- ^ Goyette P, et al. Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR. Am J Hum Genet. (1996)
- ^ Trembath D et al.. Analysis of select folate pathway genes, PAX3, and human T in a Midwestern neural tube defect population. Teratology. (1999)
- ^ ab Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol. (2000)
- ^ Vandana Rai, et al. Maternal Methylenetetrahydrofolate Reductase C677T Polymorphism and Down Syndrome Risk: A Meta-Analysis from 34 Studies. PLoS One. (2014)
- ^ abc Sharp L, Little J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol. (2004)
- ^ Bjelland I, et al. Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry. (2003)
- ^ Lewis SJ, Ebrahim S, Davey Smith G. Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?. BMJ. (2005)
- ^ David S Wald, Malcolm Law, and Joan K Morris. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. (2002)
- ^ Robien K, Ulrich CM. 5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Leukemia Risk: A HuGE Minireview. Am J Epidemiol. (2003)
- ^ Chandler CJ, Wang TT, Halsted CH. Pteroylpolyglutamate hydrolase from human jejunal brush borders. Purification and characterization. J Biol Chem. (1986)
- ^ ab Strum WB. Enzymatic reduction and methylation of folate following pH-dependent, carrier-mediated transport in rat jejunum. Biochim Biophys Acta. (1979)
- ^ Bhandari SD, Gregory JF 3rd. Folic acid, 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate exhibit equivalent intestinal absorption, metabolism and in vivo kinetics in rats. J Nutr. (1992)
- ^ Clifford AJ, et al. The dynamics of folic acid metabolism in an adult given a small tracer dose of 14C-folic acid. Adv Exp Med Biol. (1998)
- ^ Krumdieck CL, et al. A long-term study of the excretion of folate and pterins in a human subject after ingestion of 14C folic acid, with observations on the effect of diphenylhydantoin administration. Am J Clin Nutr. (1978)
- ^ Rogers LM, et al. A dual-label stable-isotopic protocol is suitable for determination of folate bioavailability in humans: evaluation of urinary excretion and plasma folate kinetics of intravenous and oral doses of {13C5} and {2H2}folic acid. J Nutr. (1997)
- ^ ab Steinberg SE, Campbell CL, Hillman RS. Kinetics of the normal folate enterohepatic cycle. J Clin Invest. (1979)
- ^ Steinberg SE. Mechanisms of folate homeostasis. Am J Physiol. (1984)
- ^ Michael Whitehead, et al. Intestinal Conversion of Folinic Acid to 5-Methyltetrahydrofolate in Man. Br J Haematol. (1972)
- ^ Smith ME, Matty AJ, Blair JA. The transport of pteroylglutamic acid across the small intestine of the rat. Biochim Biophys Acta. (1970)
- ^ Tani M, Iwai K. High-performance liquid chromatographic separation of physiological folate monoglutamate compounds. Investigation of absorption and conversion of pteroylglutamic acid in the small intestine of the rat in situ. J CHromatogr. (1983)
- ^ Masters JN, Attardi G. The nucleotide sequence of the cDNA coding for the human dihydrofolic acid reductase. Gene. (1983)
- ^ Obeid R, et al. Concentrations of unmetabolized folic acid and primary folate forms in plasma after folic acid treatment in older adults. Metabolism. (2011)
- ^ Matherly LH, Hou Z, Deng Y. Human reduced folate carrier: translation of basic biology to cancer etiology and therapy. Cancer Metastasis Rev. (2007)
- ^ Leamon CP, Jackman AL. Exploitation of the folate receptor in the management of cancer and inflammatory disease. Vitam Horm. (2008)
- ^ abcde Zhao R, et al. Mechanisms of membrane transport of folates into cells and across epithelia. Annu Rev Nutr. (2011)
- ^ Zhao R, et al. Impact of the reduced folate carrier on the accumulation of active thiamin metabolites in murine leukemia cells. J Biol Chem. (2001)
- ^ Zhao R, Matherly LH, Goldman ID. Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues. Expert Rev Mol Med. (2009)
- ^ Whetstine JR, Flatley RM, Matherly LH. The human reduced folate carrier gene is ubiquitously and differentially expressed in normal human tissues: identification of seven non-coding exons and characterization of a novel promoter. Biochem J. (2002)
- ^ Goldman ID, et al. The antifolates: evolution, new agents in the clinic, and how targeting delivery via specific membrane transporters is driving the development of a next generation of folate analogs. Curr Opin Investig Drugs. (2010)
- ^ Said et al.. Adaptive regulation of intestinal folate uptake: effect of dietary folate deficiency. Am J Physiol Cell Physiol. (2000)
- ^ ab Liu M et al.. Structure and regulation of the murine reduced folate carrier gene: identification of four noncoding exons and promoters and regulation by dietary folates. J Biol Chem. (2005)
- ^ ab Kamen BA, Smith AK. A review of folate receptor alpha cycling and 5-methyltetrahydrofolate accumulation with an emphasis on cell models in vitro. Adv Drug Deliv Rev. (2004)
- ^ Ross JF, et al. Folate receptor type beta is a neutrophilic lineage marker and is differentially expressed in myeloid leukemia. Cancer. (1999)
- ^ Wang H, et al. Differentiation-independent retinoid induction of folate receptor type beta, a potential tumor target in myeloid leukemia. Blood. (2000)
- ^ abc Yamaguchi T et al.. Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity. (20007)
- ^ Shen F, et al. Folate receptor type gamma is primarily a secretory protein due to lack of an efficient signal for glycosylphosphatidylinositol modification: protein characterization and cell type specificity. Biochemistry. (1995)
- ^ Piedrahita JA et al.. Mice lacking the folic acid-binding protein Folbp1 are defective in early embryonic development. Nat Genet. (1999)
- ^ Qiu A et al.. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell. (2006)
- ^ ab Wang Y, Zhao R, Goldman ID. Characterization of a folate transporter in HeLa cells with a low pH optimum and high affinity for pemetrexed distinct from the reduced folate carrier. Clin Cancer Res. (2004)
- ^ ab Zhao R, et al. Selective preservation of pemetrexed pharmacological activity in HeLa cells lacking the reduced folate carrier: association with the presence of a secondary transport pathway. Cancer Res. (2004)
- ^ Shayeghi M et al.. Identification of an intestinal heme transporter. Cell. (2005)
- ^ Qiu A et al.. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell. (2006)
- ^ ab Ormazabal A et al.. Determination of 5-methyltetrahydrofolate in cerebrospinal fluid of paediatric patients: reference values for a paediatric population. Clin Chim Acta. (2006)
- ^ Reynolds EH, Mattson RH, Gallagher BB. Relationships between serum and cerebrospinal fluid anticonvulsant drug and folic acid concentrations in epileptic patients. Neurology. (1972)
- ^ ab Wesson VA, Levitt AJ, Joffe RT. Change in folate status with antidepressant treatment. Psychiatry Res. (1994)
- ^ ab Fava M, et al. Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry. (1997)
- ^ abc Gilbody S, Lightfoot T, Sheldon T. Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity. J Epidemiol Community Health. (2007)
- ^ abc Ginsberg LD, Oubre AY, Daoud YA. L-methylfolate Plus SSRI or SNRI from Treatment Initiation Compared to SSRI or SNRI Monotherapy in a Major Depressive Episode. Innov Clin Neurosci. (2011)
- ^ abcdefg Wollack JB et al.. Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model. J Neurochem. (2008)
- ^ Serot JM, et al. CSF-folate levels are decreased in late-onset AD patients. J Neural Transm (Vienna). (2001)
- ^ Moretti P et al.. Cerebral folate deficiency with developmental delay, autism, and response to folinic acid. Neurology. (2005)
- ^ Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidemiol. (2007)
- ^ Wu D, Pardridge WM. Blood-brain barrier transport of reduced folic acid. Pharm Res. (1999)
- ^ Zhao et al.. The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption. Blood. (2007)
- ^ ab Baxter MG, Miller AA, Webster RA. Some studies on the convulsant action of folic acid. Br J Pharmacol. (1973)
- ^ ab Kehl SJ, McLennan H, Collingridge GL. Effects of folic and kainic acids on synaptic responses of hippocampal neurones. Neuroscience. (1984)
- ^ ab Weller M, et al. The reduced unsubstituted pteroate moiety is required for folate toxicity of cultured cerebellar granule neurons. J Pharmacol Exp Ther. (1994)
- ^ ab Olney JW, et al. Intrastriatal folic acid mimics the distant but not local brain damaging properties of kainic acid. Neurosci Lett. (1981)
- ^ ab Selhub J, et al. Folate-vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency. Am J Clin Nutr. (2009)
- ^ Quan FS, et al. Protective effects of folic acid against central nervous system neurotoxicity induced by lead exposure in rat pups. Genet Mol Res. (2015)
- ^ Solon O, et al. Associations between cognitive function, blood lead concentration, and nutrition among children in the central Philippines.
- ^ Lee MG, Chun OK, Song WO. Determinants of the blood lead level of US women of reproductive age. J Am Coll Nutr. (2005)
- ^ Budni J et al.. Neurotoxicity induced by dexamethasone in the human neuroblastoma SH-SY5Y cell line can be prevented by folic acid. Neuroscience. (2011)
- ^ Lin Y, et al. Group B vitamins protect murine cerebellar granule cells from glutamate/NMDA toxicity. Neuroreport. (2004)
- ^ Yu HL, et al. Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by beta-amyloid 31-35. Br J Nutr. (2009)
- ^ Tagliari B, et al. Hyperhomocysteinemia increases damage on brain slices exposed to in vitro model of oxygen and glucose deprivation: prevention by folic acid. Int J Dev Neurosci. (2006)
- ^ Bjelland I, et al. Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry. (2003)
- ^ Kelly CB et al.. The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland. J Psychopharmacol. (2004)
- ^ Almeida OP, et al. Contribution of the MTHFR gene to the causal pathway for depression, anxiety and cognitive impairment in later life. Neurobiol Aging. (2005)
- ^ Carney MW, Sheffield BF. Serum folic acid and B12 in 272 psychiatric in-patients. Psychol Med. (1978)
- ^ Ramos MI, et al. Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification. Am J Clin Nutr. (2004)
- ^ Sachdev PS, et al. Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Psychol Med. (2005)
- ^ Tolmunen T et al.. Dietary folate and the risk of depression in Finnish middle-aged men. A prospective follow-up study. Psychother Psychosom. (2004)
- ^ Papakostas GI et al.. The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine. Int J Neuropsychopharmacol. (2005)
- ^ Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affect Disord. (2000)
- ^ Passeri M et al.. Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study. Aging (Milano). (1993)
- ^ Godfrey PS et al.. Enhancement of recovery from psychiatric illness by methylfolate. Lancet. (1990)
- ^ Taylor MJ, et al. Folate for depressive disorders. Cochrane Database Syst Rev. (2003)
- ^ Loria-Kohen V, et al. A pilot study of folic acid supplementation for improving homocysteine levels, cognitive and depressive status in eating disorders. Nutr Hosp. (2013)
- ^ ab Venkatasubramanian R, Kumar CN, Pandey RS. A randomized double-blind comparison of fluoxetine augmentation by high and low dosage folic acid in patients with depressive episodes. J Affect Disord. (2013)
- ^ ab Papakostas GI et al.. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry. (2012)
- ^ ab Bedson E et al.. Folate Augmentation of Treatment--Evaluation for Depression (FolATED): randomised trial and economic evaluation. Health Technol Assess. (2014)
- ^ Sharpley AL, et al. Folic acid supplementation for prevention of mood disorders in young people at familial risk: a randomised, double blind, placebo controlled trial. J Affect Disord. (2014)
- ^ Moens AL, Kass DA. Tetrahydrobiopterin and cardiovascular disease. Arterioscler Thromb Vasc Biol. (2006)
- ^ Naseem KM. The role of nitric oxide in cardiovascular diseases. Mol Aspects Med. (2005)
- ^ Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. (2015)
- ^ Zhang M, et al. High‑dose folic acid improves endothelial function by increasing tetrahydrobiopterin and decreasing homocysteine levels. Mol Med Rep. (2014)
- ^ Moat SJ et al.. High- but not low-dose folic acid improves endothelial function in coronary artery disease. Eur J Clin Invest. (2006)
- ^ Low PS, Kularatne SA. Folate-targeted therapeutic and imaging agents for cancer. Curr Opin Chem Biol. (2009)
- ^ Iyer SS et al.. Identification of novel markers for mouse CD4(+) T follicular helper cells. Eur J Immunol. (2013)
- ^ Jia at el.. A novel splice variant of FR4 predominantly expressed in CD4+CD25+ regulatory T cells. Immunol Invest. (2009)
- ^ ab Tian Y et al.. A novel splice variant of folate receptor 4 predominantly expressed in regulatory T cells.. BMC Immunol. (2012)
- ^ Rogers EJ, Chen S, Chan A. Folate deficiency and plasma homocysteine during increased oxidative stress. N Engl J Med. (2007)
- ^ Kruman II, et al. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci. (2000)
- ^ ab Kruman II et al.. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. J Neurosci. (2002)
- ^ ab Guo X et al.. Protective Effect of Folic Acid on Oxidative DNA Damage: A Randomized, Double-Blind, and Placebo Controlled Clinical Trial. Medicine (Baltimore). (2015)
- ^ Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. (2009)
- ^ Sutton M, Daly LE, Kirke PN. Survival and disability in a cohort of neural tube defect births in Dublin, Ireland. Birth Defects Res A Clin Mol Teratol. (2008)
- ^ Hibbard BM, Hibbard ED, Jeffcoate TN. Folic acid and reproduction. Acta Obstet Gynecol Scand. (1965)
- ^ Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Recomm Rep. (1992)
- ^S. Preventive Services Task Force. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. (2009)
- ^ Lewis AS. Rabbit brain purine nucleoside phosphorylase. Physical and chemical properties. Inhibition studies with aminopterin, folic acid and structurally related compounds. Arch Biochem Biophys. (1978)
- ^ Hollinger JL, et al. In vitro studies of 5, 10-methylenetetrahydrofolate reductase: inhibition by folate derivatives, folate antagonists, and monoamine derivatives. J Neurochem. (1982)
- ^ Baggott JE, Vaughn WH, Hudson BB. Inhibition of 5-aminoimidazole-4-carboxamide ribotide transformylase, adenosine deaminase and 5'-adenylate deaminase by polyglutamates of methotrexate and oxidized folates and by 5-aminoimidazole-4-carboxamide riboside and ribotide. Biochem J. (1986)
- ^ Allegra CJ, et al. Inhibition of phosphoribosylaminoimidazolecarboxamide transformylase by methotrexate and dihydrofolic acid polyglutamates. Proc Natl Acad Sci U S A. (1985)
- ^ Reeves PG. Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr. (1997)
- ^ Hollinger JL, et al. In vitro studies of 5, 10-methylenetetrahydrofolate reductase: inhibition by folate derivatives, folate antagonists, and monoamine derivatives. J Neurochem. (1982)
- ^ Farias N, et al. The effects of folic acid on global DNA methylation and colonosphere formation in colon cancer cell lines. J Nutr Biochem. (2015)
- ^ Kim Yi. Folate and colorectal cancer: an evidence-based critical review. Mol Nutr Food Res. (2007)
- ^ Giovannucci E. Epidemiologic studies of folate and colorectal neoplasia: a review. J Nutr. (2002)
- ^ Bailey LB, Rampersaud GC, Kauwell GP. Folic acid supplements and fortification affect the risk for neural tube defects, vascular disease and cancer: evolving science. J Nutr. (2003)
- ^ Choi JH, et al. Contemporary issues surrounding folic Acid fortification initiatives. Prev Nutr Food Sci. (2014)
- ^ Giovannucci E, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med. (1998)
- ^ Cole et al.. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. (2007)
- ^ Hirsch S, et al. Colon cancer in Chile before and after the start of the flour fortification program with folic acid. Eur J Gastroenterol Hepatol. (2009)
- ^ Mattson MP. Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev. (1997)
- ^ Triantafyllou NI et al.. Folate and vitamin B12 levels in levodopa-treated Parkinson's disease patients: their relationship to clinical manifestations, mood and cognition. Parkinsonism Relat Disord. (2008)
- ^ Triantafyllou NI et al.. The influence of levodopa and the COMT inhibitor on serum vitamin B12 and folate levels in Parkinson's disease patients. Eur Neurol. (2007)
- ^ Zoccolella S et al.. Plasma homocysteine levels in Parkinson's disease: role of antiparkinsonian medications. Parkinsonism Relat Disord. (2005)
- ^ Lamberti P, et al. Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients. Mov Disord. (2005)
- ^ Heikkinen H, et al. Entacapone improves the availability of L-dopa in plasma by decreasing its peripheral metabolism independent of L-dopa/carbidopa dose. Br J Clin Pharmacol. (2002)
- ^ Naughton CA, et al. Folate absorption in alcoholic pigs: in vitro hydrolysis and transport at the intestinal brush border membrane. Am J Clin Nutr. (1989)
- ^ Halsted CH, Robles EA, Mezey E. Intestinal malabsorption in folate-deficient alcoholics. Gastroenterology. (1973)
- ^ Herbet V, Zalusky R, and Davidson CS. Correlation of folate deficiency with alcoholism and associated macrocytosis, anemia, and liver disease. Ann Intern Med. (1963)
- ^ ab Halsted CH, et al. Metabolic interactions of alcohol and folate. J Nutr. (2002)
- ^ Halsted C et al.. Decreased Jejunal Uptake of Labeled Folic Acid (3H-PGA) in Alcoholic Patients: Roles of Alcohol and Nutrition. NEJM. (1971)
- ^ McMartin KE, et al. Study of dose-dependence and urinary folate excretion produced by ethanol in humans and rats. Alcohol Clin Exp Res. (1986)
- ^ ab Russell RM et al.. Increased urinary excretion and prolonged turnover time of folic acid during ethanol ingestion. Am J Clin Nutr. (1983)
- ^ Tamura T, Halsted CH. Folate turnover in chronically alcoholic monkeys. J Lab Clin Med. (1983)
- ^ ab Lieber CS et al.. S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon. Hepatology. (1990)
- ^ ab Lu SC, et al. Changes in methionine adenosyltransferase and S-adenosylmethionine homeostasis in alcoholic rat liver. Am J Physiol Gastrointest Liver Physiol. (2000)
- ^ Mato JM et al.. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. (1999)
- ^ ab Amilburu A, et al. Inhibition of intestinal absorption of 5-methyltetrahydrofolate by fluoxetine. J Phys Biochem. (2001)
- ^ ab Butterworth CE Jr, Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr. (1989)
- ^ van der Westhuyzen J, Metz J. Tissue S-adenosylmethionine levels in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced neuropathy. Br J Nutr. (1983)
- ^ van der Westhuyzen J, Fernandes-Costa F, Metz J. Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats : protection by methionine and aggravation by folates. Life Sci. (1982)