Vitamin B9 (Folic Acid): Benefits, Dosage, Contraindications
Other name(s)
Folic acid, folate
Scientific name(s)
5'-methyltetrahydrofolate
Family or group:
Vitamins
Indications
Rating methodology
EFSA approval.
Vitamin B9 Deficiency ✪✪✪✪✪
The imbalance between dietary intake and needs is the leading cause of deficiency worldwide, particularly when needs increase (pregnancy, breastfeeding, chronic hemolysis) or when digestive absorption is impaired in chronic diarrhea and inflammatory bowel diseases (Crohn's disease, tropical sprue, celiac disease). Chronic alcoholism also induces deficiencies due to lack of intake, malabsorption, liver uptake impairment, and increased renal excretion. Renal insufficiency in dialysis is also associated with folate deficiency, as are certain "anti-metabolite" treatments that impair folate use, such as antiepileptics. The most common consequence of deficiencies is hematopoietic, a direct reflection of decreased DNA synthesis. This explains mucosal disorders associated with these deficiencies, such as glossitis, and especially the classic megaloblastic anemia. Vitamin B9 deficiency is also accompanied by various neurological disorders, due to lack of ATP, GTP (phosphate group transfer coenzymes), and phospholipids forming myelin sheaths. In cases of anemia, doses of about 5 to 15 mg per day are usually prescribed.
Posologie
Orally
0.33 - 15 mg
Pregnancy ✪✪✪✪✪
Epidemiological studies have shown an association between maternal folic acid status and the frequency of miscarriages, prematurity rates, and neural tube closure anomalies. The need for folates in women increases by 50% during pregnancy, during which, in the first trimester, a diet enriched with at least 600 micrograms per day (600 mcg/day) of folates is recommended. Before conception, a 400 mcg folate supplementation is recommended for 1 to 3 months. Women with a history of congenital neural tube defects generally take a higher dose of folic acid, corresponding to 4 mg per day, starting one month before and continuing until three months after conception.
Posologie
Orally
0.4 - 4 mg
Synergies
Folic acid supplementation for the prevention of neural tube defects: US preventive services task force recommendation statement
Folic acid supplementation for the prevention of neural tube defects: US preventive services task force recommendation statement.
The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths.
Folic acid, methylation and neural tube closure in humans.
Folate status during pregnancy in women is improved by long-term high vegetable intake compared with the average western diet.
Scientific Opinion on the substantiation of health claims related to folate and blood formation (ID 79), homocysteine metabolism (ID 80), energy-yielding metabolism (ID 90), function of the immune system (ID 91), function of blood vessels (ID 94, 175, 192), cell division (ID 193), and maternal tissue growth during pregnancy (ID 2882)
Guidelines for Perinatal Care. 7th ed. Washington, DC: The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists;
Letter regarding dietary supplement health claim for folic acid with respect to neural tube defects.
Effect of folic acid supplementation during pregnancy on gestational hypertension/preeclampsia: A systematic review and meta-analysis.
Maternal folic acid supplementation for the prevention of preeclampsia: A systematic review and meta-analysis.
Folic acid to reduce neonatal mortality from neural tube disorders.
Fatigue ✪✪✪✪✪
Vitamin B9 (folate) plays a role in reducing fatigue by supporting cellular energy production and regulating oxygen in the body. Folate is involved in several carbon transfer reactions essential for amino acid metabolism and nucleic acid synthesis. A folate deficiency can lead to megaloblastic anemia, reducing the blood's oxygen transport capacity and increasing fatigue. Folate and B vitamins supplementation can be an effective strategy to support cognitive function and reduce fatigue. European health authorities (EFSA, European Food Safety Authority, and the European Commission) have considered that dietary supplements containing vitamin B9 may claim to contribute to the reduction of fatigue and normal cognitive functions.
Posologie
Oral
0.4 - 15 mg
Synergies
Scientific Opinion on the substantiation of health claims related to folate and contribution to normal psychological functions (ID 81, 85, 86, 88), maintenance of normal vision (ID 83, 87), reduction of tiredness and fatigue (ID 84), cell division (ID 195, 2881) and contribution to normal amino acid synthesis (ID 195, 2881)
Fetal Development ✪✪✪✪✪
Folic acid, essential before and during pregnancy, plays a key role in fetal development. A low level of folic acid increases the risk of congenital malformations such as neural tube defects. Folic acid supplementation before conception and during the first months of pregnancy is associated with a significant reduction in these risks. A Cochrane review showed that folic acid supplementation improves average birth weight and reduces the incidence of megaloblastic anemia, without a significant impact on pregnancy outcomes such as preterm births or preeclampsia. Clinical guidelines recommend that anyone who might become pregnant take 400 mcg of folic acid per day through fortified foods or supplements to prevent neural tube defects in infants. During pregnancy, 600 mcg of folic acid per day is advised.
Posologie
Oral
0.33 - 15 mg
Synergies
Folic Acid Supplementation for the Prevention of Neural Tube Defects: US Preventive Services Task Force Recommendation Statement
Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes
Depression ✪✪✪✪✪
Studies suggest that depression is linked to a low folate level, particularly in women. Oral folic acid taken in conjunction with conventional antidepressants seems to improve treatment response in patients suffering from major depressive disorder. However, taking folic acid alone does not appear to be effective. Folic acid has been used at a dose of 200 mcg to 15 mg per day for 6 months, in conjunction with antidepressants.
Posologie
Oral
0.2 - 15 mg
6 months
Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study.
Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial.
Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity.
Folate for depressive disorders.
Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample.
Plasma folate concentrations are associated with depressive symptoms in elderly Latina women despite folic acid fortification.
Hyperhomocysteinemia ✪✪✪✪✪
Oral folic acid intake lowers fasting homocysteine levels by 20% to 30% in individuals with normal to moderately elevated homocysteine levels. The higher the homocysteine level and the lower the folate level before treatment, the greater the effect of folic acid supplementation. Further evidence suggests that the higher the initial homocysteine levels, the less folic acid dose required to achieve the maximum reduction in homocysteine levels. The effects of folic acid supplementation on homocysteine concentrations appear to be more significant in women than in men. Additionally, the combination of 50 to 250 mg of pyridoxine and folic acid seems to further decrease post-prandial hyperhomocysteinemia. This combination is generally recommended. Moreover, the daily addition of 500 mcg of vitamin B12 to folic acid results in an additional reduction of homocysteine levels by about 7% on average, but this effect is likely present only in individuals with a vitamin B12 deficiency. A dose of 200 mcg to 15 mg per day of folic acid for 4 weeks to 3.5 years has been used, with or without vitamin B12 and/or pyridoxine.
Posologie
Oral
0.2 - 15 mg
Potential clinical and economic effects of homocyst(e)ine lowering.
Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers.
Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials.
Folate status of elderly women following moderate folate depletion responds only to a higher folate intake.
Secondary prevention with folic acid: effects on clinical outcomes.
Diagnosis and treatment of hyperhomocysteinemia.
The effect of different treatment regimens in reducing fasting and postmethionine-load homocysteine concentrations.
Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study.
Multivitamin supplements are effective and inexpensive agents to lower homocysteine levels.
Combination of low-dose folic acid and pyridoxine for treatment of hyperhomocysteinaemia in patients with premature arterial disease and their relatives.
Randomized trial of folic acid supplementation and serum homocysteine levels.
Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration.
Renal Insufficiency ✪✪✪✪✪
More than 85% of individuals with end-stage renal disease (ESRD) present with hyperhomocysteinemia, due to reduced renal absorption and metabolism of homocysteine in severe renal insufficiency, and hemodialysis may contribute to vitamin deficiencies. Oral folic acid intake reduces homocysteine levels in patients with ESRD. Daily doses of 800 mcg to 15 mg are generally used. In many studies, folic acid was combined with vitamin B12 and pyridoxine.
Posologie
Oral
0.8 - 15 mg
Hyperhomocysteinemia in hemodialysis patients: effects of 12-month supplementation with hydrosoluble vitamins.
Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients.
Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?
Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients.
Treatment of mild hyperhomocysteinemia in renal transplant recipients versus hemodialysis patients.
Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna multicenter study.
Oral vitamin B(12) and high-dose folic acid in hemodialysis patients with hyper-homocyst(e)inemia.
Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease.
Controlled comparison of L-5-methyltetrahydrofolate versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients.
Hypertension artérielle ✪✪✪✪✪
La recherche clinique montre que la prise quotidienne de 5 à 10 mg d'acide folique pendant au moins 6 semaines réduit la pression artérielle systolique de 2,03 mmHg et améliore la dilatation vasculaire chez les personnes hypertendues. Par ailleurs, certaines recherches ont montré que la prise d'acide folique en association avec l'énalapril (un médicament antihypertenseur) n'améliore pas la tension artérielle par rapport à l'énalapril seul.
Posologie
Par voie orale
5 - 10 mg
6 - semaines
Folic acid therapy reduces the risk of mortality associated with heavy proteinuria among hypertensive patients.
High-dose folic acid supplementation effects on endothelial function and blood pressure in hypertensive patients: a meta-analysis of randomized controlled clinical trials.
Accident vasculaire cérébral ✪✪✪✪✪
Des études épidémiologiques ont montré que les personnes ayant un apport plus élevé en acide folique d'origine alimentaire ont un risque réduit d'accident vasculaire cérébral (AVC) hémorragique mais non ischémique. Plusieurs études faites dans des régions dépourvues des politiques d'enrichissement de l'alimentation en acide folique, ont constaté que la supplémentation en acide folique, avec ou sans autres vitamines B, réduit le risque d'AVC de 10% à 25%. L'effet semble être plus important lorsque l'acide folique est pris à faibles doses (généralement 0,8 mg par jour ou moins), chez les patients présentant un taux de cholestérol initial élevé, chez les patients ayant un taux d'homocystéine diminué d'au moins 20% et chez les patients ayant le taux de folate initial le plus faible.
Posologie
Par voie orale
0.8 mg
Folic Acid Supplementation for Stroke Prevention in Patients With Cardiovascular Disease.
Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials.
Meta-analysis of folic acid efficacy trials in stroke prevention: Insight into effect modifiers.
Efficacy of folic acid supplementation in cardiovascular disease prevention: an updated meta-analysis of randomized controlled trials.
Efficacy of folic acid supplementation in stroke prevention: new insight from a meta-analysis.
Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial.
Efficacy of folic acid supplementation in stroke prevention: a meta-analysis.
Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: a prospective, nested case-referent study of plasma concentrations and dietary intake.
DMLA ✪✪✪✪✪
Une étude clinique menée à grande échelle, montre que la prise de 50 mg de pyridoxine par jour en association avec 1 mg de cyanocobalamine et 2,5 mg d'acide folique, pendant en moyenne 7,3 ans, réduit considérablement le risque de développement de DMLA (dégénérescence maculaire liée à l'âge) chez les femmes de 40 ans ayant des antécédents de maladie cardiovasculaire ou présentant des facteurs de risque de maladie cardiovasculaire, par rapport au placebo.
Posologie
Par voie orale
2.5 mg
Déclin cognitif ✪✪✪✪✪
Des recherches montrent que l'acide folique peut jouer un rôle dans la prévention du déclin cognitif, particulièrement chez les personnes âgées avec des niveaux élevés d'homocystéine, un facteur lié à des risques accrus de maladies neurodégénératives. Une étude a administré 800 mcg/jour d'acide folique pendant 3 ans à des participants ayant un taux élevé d'homocystéine, observant une amélioration notable dans plusieurs domaines cognitifs. D'autres études ont exploré l'impact de l'acide folique sur le déclin cognitif, montrant des résultats positifs. Une essai clinique chez des patients de plus de 65 ans avec un trouble cognitif léger a révélé qu'une supplémentation quotidienne de 400 mcg d'acide folique pendant deux ans améliorait les scores de QI. D'autres recherches ont trouvé des améliorations de la fonction cognitive avec des doses plus élevées. L'association de l'acide folique avec d'autres vitamines B ou le DHA a également montré des bénéfices.
Posologie
Par voie orale
0.4 - 15 mg
Synergies
Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial
Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial
Influences of Folate Supplementation on Homocysteine and Cognition in Patients with Folate Deficiency and Cognitive Impairment
Scientific Opinion on the substantiation of health claims related to folate and contribution to normal psychological functions (ID 81, 85, 86, 88), maintenance of normal vision (ID 83, 87), reduction of tiredness and fatigue (ID 84), cell division (ID 195, 2881) and contribution to normal amino acid synthesis (ID 195, 2881)
Effect of folic acid combined with docosahexaenoic acid intervention on mild cognitive impairment in elderly: a randomized double-blind, placebo-controlled trial
Maladie d'Alzheimer ✪✪✪✪✪
Des preuves cliniques suggèrent que les personnes âgées ayant un apport alimentaire en folates ou une supplémentation en acide folique supérieure à l'apport nutritionnel recommandé, ont un risque réduit de développer la maladie d'Alzheimer par rapport aux personnes ayant un apport plus faible. La recherche clinique suggère que la prise de 1 mg d'acide folique par jour pendant 6 mois semble améliorer la réponse des patients atteints de la maladie d'Alzheimer aux inhibiteurs de cholinestérase par rapport au placebo.
Posologie
Par voie orale
1 - 1 mg
6 - mois
Reduced risk of Alzheimer's disease with high folate intake: the Baltimore Longitudinal Study of Aging.
Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial
Properties
Essential
Vitamin B9 acts as a coenzyme in intracellular metabolism and is essential for proper cell function. Indeed, in the body, folates are involved as cofactors in monocarbon unit transfer reactions essential for cellular metabolism, as they are involved in nucleotide synthesis, certain amino acid synthesis, and indirectly in the transfer of methyl groups. Vitamin B9 also plays a role in maintaining pregnancy and preventing fetal development issues (cleft palate, neural tube closure anomalies). Vitamin B9 deficiency is accompanied by various neurological disorders due to lack of ATP, GTP (coenzymes for phosphate group transfer), and phospholipids forming myelin sheaths. Moreover, in the bone marrow, a vitamin B9 deficiency leads to an anomaly in cellular maturation and division, resulting in abnormal red blood cell precursors, called megaloblasts. Megaloblasts are unable to complete maturation into red blood cells, and many are phagocytized by macrophages in the bone marrow, resulting in a type of anemia called megaloblastic anemia.
Usages associés
Cardiovascular
Folic acid can improve endothelial dysfunction in individuals with atherosclerosis and at high risk of developing coronary artery disease. There is also evidence that folic acid can reduce concentrations of von Willebrand factor (necessary for platelet adhesion and factor VIII transport in blood clotting). Folic acid can also reduce fibrinogen concentrations (a clotting factor). Moreover, the remethylation of homocysteine to methionine requires folate and vitamin B12 as cofactors. Therefore, a folic acid deficiency is associated with increased homocysteinemia, known as a risk factor for cardiovascular diseases. The higher the homocysteine level, the better the response to folic acid treatment. Additionally, folic acid has little effect on normal homocysteine levels.
Usages associés
Cognitive Function
Evidence suggests that low folate concentration may be linked to cerebral cortex atrophy. Moreover, in elderly individuals, functional and mental deterioration is sometimes associated with low folate levels. In Alzheimer's patients, folic acid may improve the response to cholinesterase inhibitors by reducing homocysteine levels.
Usages associés
Antidepressant
Folic acid deficiency is common in people with depression. Low folate levels have been linked to poor responses to antidepressant treatment. In the general population, individuals with low folic acid levels or low dietary intake of folates have a higher risk of developing depression. Additionally, low folate levels have been linked to poor responses to antidepressant treatment. The exact role of folic acid in depression is still unknown, but it is necessary for the remethylation of homocysteine to methionine and for the conversion of s-adenosylmethionine (SAMe). Homocysteine remethylation to methionine is important because it prevents homocysteine accumulation, a risk factor for cardiovascular diseases and potentially for depression. Methionine is then converted into S-adenosylmethionine (SAMe), a molecule involved in the production of neurotransmitters like serotonin and dopamine, which are essential for mood. Folic acid also plays a role in the methylation of tetrahydrobiopterin, a key cofactor for hydroxylase enzymes involved in neurotransmitter production such as serotonin.
Usages associés
Anticancer
Certain cancers like hematologic malignancies or colorectal cancers have been statistically associated with reduced folate levels. Potentially deleterious effects of folic acid supplementation on tumor progression have been suggested but remain debated.
Safety dosage
Nourrisson jusqu’à 12 mois : 80 µg
Enfant de 1 jusqu’à 3 an(s) : 120 µg - 200 µg
Adulte à partir de 18 an(s) : 330 µg - 1000 µg
Enfant de 4 jusqu’à 6 an(s) : 140 µg - 300 µg
Enfant de 7 jusqu’à 10 an(s) : 200 µg - 400 µg
Enfant de 11 jusqu’à 14 an(s) : 270 µg - 600 µg
Enfant de 15 jusqu’à 17 an(s) : 330 µg - 800 µg
Femme enceinte à partir de 18 an(s) : 600 µg - 1000 µg
Femme allaitante à partir de 18 an(s) : 500 µg - 1000 µg
Interactions
Médicaments
Anticonvulsifs : interaction modérée
L'acide folique peut être un cofacteur du métabolisme de la phénytoïne. A des doses de 1 mg par jour ou plus, l'acide folique peut réduire les taux sériques de phénytoïne chez certains patients. De plus, la phénytoïne réduit également les niveaux de folate sérique. L'acide folique peut avoir une activité convulsivante directe chez certaines personnes,ce qui peut altérer le contrôle des crises convulsives par le phénobarbital. La phénytoïne peut également réduire les niveaux de folate sérique. D'autre part, la carbamazépine peut réduire les taux sériques d'acide folique. Les mécanismes possibles comprennent une absorption réduite de l'acide folique et un métabolisme accru par les enzymes hépatiques.
5-fluorouracile : interaction modérée
Théoriquement, des doses élevées d'acide folique pourraient augmenter la toxicité du 5-fluorouracile. Une augmentation des effets secondaires gastro-intestinaux avec le 5-fluorouracile tels que la stomatite et la diarrhée a été décrite.
Méthotrexate : interaction modérée
Le méthotrexate exerce des effets cytotoxiques en empêchant la conversion de l'acide folique à la forme active nécessaire aux cellules. Il existe des preuves que les suppléments d'acide folique réduisent l'efficacité du méthotrexate dans le traitement de la leucémie lymphoblastique aiguë et, théoriquement, ils peuvent réduire son efficacité dans le traitement d'autres cancers. De plus, le méthotrexate peut réduire les niveaux de folate sérique.
Oestrogènes : interaction modérée
Des taux réduits de folate sérique peuvent survenir chez certaines femmes prenant des œstrogènes conjugués ou des contraceptifs oraux, mais cet effet est peu probable chez les femmes ayant un apport alimentaire suffisant en folates. Les mécanismes possibles par lesquels les œstrogènes contribuent à la carence en folate comprennent une absorption réduite de folate alimentaire, une excrétion accrue, une induction des enzymes hépatiques et une liaison accrue des folates aux protéines sériques.
