Thefolic acid is probably the vitamin whose benefit is best demonstrated across all nutrition: 400 µg per day before conception reduces the risk of neural tube defects in babies by approximately two-thirds. It is also one of the most misunderstood. Folic acid, folates, and vitamin B9 are confused, the word "MTHFR" is discovered on a forum, people wonder if methylfolate is worth the extra cost, and many women learn they should have started before pregnancy the moment they discover they are pregnant.
This guide sets the record straight, backed by evidence: what vitamin B9 really is, what it does, how much you need based on your situation, which foods contain it, when and how to take it before and during pregnancy, what signs of deficiency look like, what the MTHFR gene changes (or doesn't change), what folic acid and methylfolate are worth, and what you need to know about safety. It extends our B vitamins overview and complements our vitamin B12 guide, its inseparable partner.
All eight B vitamins in one daily vegetable capsule, including B9 in the form of Quatrefolic® (400 µg of 5-MTHF, 200% of RDA), B12 as methylcobalamin, and B6 as pyridoxal-5-phosphate. Allergen-free, manufactured in France.
Vitamin B9 exists in three forms: natural folates from food, synthetic folic acid from supplements, and methylfolate (5-MTHF), an active form already usable by the body. It is essential for DNA synthesis, so for every cell that divides: red blood cells, mucous membranes, and especially the embryo in the first few weeks. Requirements are 330 µg per day for an adult and 600 µg during pregnancy. When planning pregnancy, 400 µg per day started at least four weeks before conception and continued until 12 weeks reduces the risk of neural tube defects by approximately two-thirds (Cochrane, 2015). Legumes, green vegetables, liver, and citrus fruits are the best sources. Methylfolate bypasses the MTHFR polymorphism and masks a B12 deficiency less, but folic acid remains the form used in major studies. The safety limit is 1,000 µg of synthetic folic acid per day.
- Folic acid, folates, vitamin B9, methylfolate: who is who?
- What is vitamin B9 for? The claims recognized by the EFSA
- How much vitamin B9 per day? Requirements based on your profile
- Foods rich in folates
- Folic acid and pregnancy: why before, how much, until when
- Vitamin B9 deficiency: symptoms, diagnosis, and at-risk individuals
- MTHFR: what this gene really changes
- Folic acid, folinic acid or methylfolate: which form to choose?
- The hidden vitamin B12 trap
- Homocysteine, heart and brain: what the trials say
- Folic acid in men: useful for what?
- Safety, maximum dose and interactions
- Choosing wisely: B9 alone, B complex or preconception formula?
- Frequently asked questions
1. Folic acid, folates, vitamin B9, methylfolate: who is who?
The word "folate" comes from the Latin folium, the leaf: the vitamin was isolated from spinach in the 1940s. Hidden under this name is a family of molecules built around the same skeleton (pterine, para-aminobenzoic acid and one or more glutamate units), which differ by their oxidation state and by the small chemical group they carry. This detail changes everything in practice, because it determines how many steps separate what you swallow from what your cells use.
| Form | Where to find it | What you need to know |
|---|---|---|
| Dietary folates | Legumes, green vegetables, liver, citrus fruits, eggs, nuts and seeds | Reduced forms, mostly already methylated, but fragile (heat, light, cooking water) and absorbed at approximately 50% |
| Folic acid | Supplements, medications (0.4 mg and 5 mg), fortified foods | Oxidized synthetic form, very stable, absorbed at approximately 85%; must be reduced by the liver then transformed by the MTHFR enzyme before becoming active; form used in virtually all major studies |
| Folinic acid (folinate) | Hospital medication (leucovorin) | Reduced form used in medicine to protect healthy cells during certain treatments (methotrexate); not a common supplement |
| 5-MTHF (methylfolate) | Premium supplements (Quatrefolic®, Metafolin®), some prenatal formulas | Active circulating form, directly usable, which bypasses the MTHFR step; more expensive and more sensitive to oxidation, stabilized as a salt form (glucosamine for Quatrefolic®) |
Because these forms are not absorbed in the same way, nutritionists think in terms of dietary folate equivalents (DFE): 1 µg of folic acid taken on an empty stomach is worth approximately 1.7 µg of dietary folates, and 1 µg taken with a meal approximately 1.2 µg. This is why official recommendations are expressed in DFE, and why "400 µg of folic acid" represents a greater intake than it appears.
2. What is vitamin B9 for? The health claims recognized by EFSA
At the biochemical level, folates act as shuttles: they carry fragments of a carbon atom and deliver them where the cell needs them. Two destinations are particularly important. The first is DNA base synthesis (thymidylate and purines): a cell lacking folates can no longer duplicate its genome and remains blocked, grows without dividing, which explains the giant red blood cells of folate deficiency anemia. The second is the recycling of homocysteine into methionine, which requires both a methylated folate and vitamin B12, and which fuels all methylation reactions in the body, from gene regulation to neurotransmitter synthesis.
European regulation No. 432/2012 authorizes eight claims for folates, provided the product supplies at least 15% of the NRV per serving. Folates contribute to:
- to growth of maternal tissues during pregnancy ;
- to normal synthesis of amino acids ;
- to normal blood formation ;
- to normal metabolism of homocysteine ;
- to normal psychological functions ;
- to normal functioning of the immune system ;
- à reduce fatigue ;
- to normal cell division process.
A ninth claim, referred to as "reduced disease risk," is permitted under strict conditions: "taking a folic acid supplement increases folate status in the mother; low maternal folate status is a risk factor for the development of neural tube defects in the developing fetus." It may only appear on products providing at least 400 µg per day, intended for women of childbearing age, with a mention of use at least one month before conception and up to three months after.
It does not make you pregnant. Its proven role is to protect the embryo from the first days, not to increase the chances of conception. It does not cause weight gain : it provides no calories and does not affect fat storage. It does not provide energy to those who don't lack it: fatigue reduction concerns people whose intake is insufficient. And it does not replace vitamin B12: the two work together, and one does not correct the deficiency of the other (we return to this in section 9).
3. How much vitamin B9 per day? Requirements by profile
| Profile | Reference (micrograms EFA per day) | Source |
|---|---|---|
| Children 1 to 3 years | 120 | EFSA |
| Children 4 to 6 years | 140 | EFSA |
| Children 7 to 10 years | 200 | EFSA |
| Adolescents aged 11 to 14 years | 270 | EFSA |
| Adults (15 years and older) | 330 | ANSES (RNP) and EFSA (PRI) |
| Women planning pregnancy | 330 + 400 µg of folic acid as a supplement | HAS, WHO |
| Pregnant women | 600 | EFSA |
| Breastfeeding women | 500 | EFSA |
| Labeling NRV (all adults) | 200 | EU Regulation No. 1169/2011 |
Two clarifications. The difference between the 330 µg of the reference and the 200 µg of the labeling NRV explains why a supplement at "100% of NRV" does not cover needs on its own; it is a supplement that is added to normally adequate food intake. And the 400 µg dose for women planning pregnancy does not replace dietary folates: it is added to them, because diet alone rarely reaches the blood folate level that protects the neural tube. The section 5 details the timeline and situations that warrant additional supplementation.
4. Folate-rich foods
| Food | Content (micrograms per 100 g) | Reference |
|---|---|---|
| Nutritional yeast flakes | 1,000 to 2,500 | One tablespoon (10 g) covers one-third to two-thirds of daily needs |
| Liver (poultry, veal, lamb) | 250 to 700 | Poultry liver is the richest source; should be limited during pregnancy (vitamin A) |
| Lentils, chickpeas, dried beans (cooked) | 100 to 180 | A serving of 200 g of cooked lentils provides approximately 350 µg |
| Spinach, watercress, arugula, mâche lettuce | 100 to 200 | Raw or steamed to preserve folates |
| Asparagus | 100 to 150 | Five to six green asparagus spears cover one third of daily needs |
| Broccoli, Brussels sprouts (cooked) | 60 to 110 | Short steam cooking recommended |
| Avocado | 60 to 90 | Half an avocado provides approximately 60 µg |
| Nuts, hazelnuts, peanuts, sunflower seeds | 70 to 240 | A handful of 30 g provides 20 to 70 µg |
| Eggs | 40 to 60 | One egg provides approximately 25 µg, mainly in the yolk |
| Oranges, kiwis, strawberries | 25 to 45 | One orange provides 40 to 60 µg, and vitamin C protects folates |
Approximate values based on composition tables (Ciqual, USDA); contents vary depending on variety, freshness, and cooking method.
Natural folates have two weaknesses. They are fragile : sensitive to heat, light, and oxygen, and soluble in water, they leach into cooking water. Spinach boiled for a long time can lose half its folates, hence the benefit of short cooking times, steam cooking, and raw or lightly seared vegetables. They are also less well absorbed than folic acid: approximately 50%, compared to 85% for the synthetic form, because they must first be stripped of their glutamate chain in the intestine.
Unlike around sixty countries (United States, Canada, Chile, Australia), France does not fortify its flours with folic acid. Intake therefore relies entirely on diet and supplements, which makes dietary advice and preconceptional supplementation all the more important. For legumes, which combine folates, fiber, and plant protein, find our recipe ideas in the vitamins and minerals section and our meal plans.
5. Folic acid and pregnancy: why before, how much, until when
The neural tube is the rudiment of the brain and spinal cord. It forms as a groove that closes on itself between the third and fourth week after conception. If closure is incomplete, a neural tube defect results: spina bifida when the defect affects the spine, anencephaly when it affects the skull. These malformations affect approximately one in a thousand pregnancies in France. The cells that close the tube divide at high speed and consume enormous amounts of folates; insufficient status at the precise moment of closure increases the risk.
The problem is one of timing: on day 28 after conception, a woman is approximately two weeks late for her period, and many do not yet know they are pregnant. Starting folic acid upon discovering pregnancy therefore, most often, comes after the neural tube has closed. This is why all authorities recommend starting before conception. In France, according to the National Perinatal Survey, only a minority of women take folic acid from the preconceptional period onward, when that is when it is useful.
In five randomized trials totaling 7,391 women, daily folic acid supplementation started before conception, alone or combined with other vitamins and minerals, reduced the risk of neural tube defect by 69% (relative risk 0.31), and reduced the risk of recurrence by 66% in women who had previously had an affected pregnancy. The effect did not depend on either the dose (400 µg or more) or association with other micronutrients.
De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, Rayco-Solon P. Cochrane Database Syst Rev 2015;12:CD007950. DOI : 10.1002/14651858.CD007950.pub3
These results have since been confirmed by population studies covering more than one million pregnancies: the 2023 update for the American prevention authority found approximately a 50% reduction in risk among women supplemented before and during pregnancy, with no adverse effects reported, whether involving twin pregnancies, autism spectrum disorder, or maternal cancer (Viswanathan, JAMA, 2023).
This is one of the most frequent concerns, and it deserves a clear answer: in the vast majority of cases, everything is fine. The baseline risk is low (approximately one pregnancy in a thousand), and most women who did not take folic acid before conception have a perfectly healthy baby; supplementation reduces an already small risk, it does not create one in its absence. What you should do: start 400 µg per day right now if you are less than 12 weeks along, discuss it with your doctor or midwife, and know that first trimester ultrasounds and especially the second trimester scan allow you to verify your baby's proper development. Guilt serves no purpose; information does: for a future pregnancy, you will know to start beforehand.
When should you stop? Prevention of neural tube defects ends at 12 weeks, but nothing requires you to stop: continuing a nutritional dose of folates throughout pregnancy is safe and meets needs that remain high. Do you need a prescription? Folic acid at 0.4 mg is available in pharmacies without a prescription, but it is reimbursed on prescription; the 5 mg formulation requires one. What about prenatal supplements? Check that they provide 400 µg of B9 (folic acid or methylfolate), and avoid combining multiple products that contain it. Our formula Female Fertility provides 300 µg of folic acid with myo-inositol, iron, zinc and vitamin D3 in a comprehensive preconception approach; our B Complex Vitamins provides 400 µg of methylfolate with the other seven B vitamins. In both cases, your doctor's advice remains the reference.
The B Complex Vitamins provides 400 µg of Quatrefolic® daily (200% of NRV), the active form of folate, with B12 as methylcobalamine, B6 as P-5-P, and B2 which serves as a cofactor for the MTHFR enzyme. One vegetable capsule in the morning, allergen-free, made in France.
Discover B Complex Vitamins →Planning a pregnancy? Talk to your doctor or midwife, who will adapt the dose to your situation. Also discover our preconception formula Female Fertility.
6. Vitamin B9 deficiency: symptoms, diagnosis and at-risk populations
A serum folate below 7 nmol/L (approximately 3 ng/mL) indicates deficiency; it reflects intake from the last few days. Red blood cell folate, more stable, reflects reserves from the last three months: below 305 nmol/L, it indicates deficiency. For prevention of neural tube defects, the WHO considers that a red blood cell folate above 906 nmol/L is the protective level, a threshold rarely achieved by diet alone, which justifies supplementation. A homocysteine level above 15 µmol/L suggests a B9, B12, or B6 deficiency. The interpretation is up to the physician, in light of the complete blood count and treatments.
Who lacks folates? The causes fall into three categories. Insufficient intake : diet poor in vegetables and legumes, very restrictive diets, poverty, and especially excessive alcohol consumption, which combines low intake, malabsorption, and accelerated folate degradation. Malabsorption : celiac disease, Crohn's disease, bariatric surgery, and certain medications. And increased needs : pregnancy, especially multiple or closely spaced pregnancies, breastfeeding, hemolytic anemias, extensive psoriasis, dialysis. <<<33>>> Regarding medications, several classes directly interfere with folates:
Côté médicaments, plusieurs classes interfèrent directement avec les folates : le methotrexate (rheumatoid arthritis, psoriasis, cancers), which blocks the enzyme that activates folic acid and whose prescription is systematically accompanied by supplementation decided by the physician; anticonvulsants <<<37>>> such as valproate, carbamazepine, or phenytoin, which lower folate levels and require a 5 mg dose in case of pregnancy; comme le valproate, la carbamazépine ou la phénytoïne, qui abaissent les folates et imposent la dose de 5 mg en cas de grossesse ; la sulfasalazine (inflammatory bowel diseases); and trimethoprim ; and, more modestly, metformin and oral contraception. In all these cases, it is the prescriber who adjusts supplementation, never the patient alone.
7. MTHFR: what this gene really changes
Few genes have fueled health forums as much as MTHFR. It codes for methylenetetrahydrofolate reductase, the enzyme that performs the final step in converting folates to 5-MTHF, the form that circulates in the blood and allows homocysteine recycling. The most studied variant, C677T, replaces an amino acid in the enzyme and makes it thermolabile: it functions less effectively at body temperature. In people carrying two copies of the variant (TT genotype), residual activity is only around 30%; in those carrying one copy (CT), it is moderately reduced (Liew, Eur J Med Genet, 2015).
The frequency of TT genotype varies greatly by population: approximately 10% in the United Kingdom and Ireland, higher in southern Europe and Latin America, where it can exceed 20%. TT carriers have higher homocysteine and lower blood folates than others, and a 14 to 21% increased risk of coronary artery disease in meta-analyses (McNulty, Proc Nutr Soc, 2008). The variant has also been associated, less firmly, with increased risk of neural tube defects, recurrent miscarriages, or migraine.
The difference in homocysteine and folates between TT genotype carriers and others disappears when folic acid intakes are sufficient: the variant is a vulnerability factor in cases of low intake, not an irreversible deficiency. Riboflavin (vitamin B2), a cofactor of the enzyme, also strongly lowers homocysteine specifically in TT carriers, by stabilizing the defective enzyme.
Hiraoka M, Kagawa Y. Congenit Anom 2017;57(5):142-149. DOI: 10.1111/cga.12232 ; McNulty H et al. Proc Nutr Soc 2008;67(2):232-237. DOI: 10.1017/S0029665108007076
Two practical consequences. First, MTHFR genetic testing is not recommended as routine screening by genetics professional societies: regardless of the result, the course of action is the same—ensure good intakes of folates, B12, B6, and B2, and test homocysteine if any doubt exists. Next, methylfolate takes on full meaning here: being already in the form that the MTHFR enzyme is supposed to produce, it bypasses the defective step. This is one of the reasons we chose Quatrefolic® in our complex, combined with 10 mg of riboflavin. This does not make the complex a treatment for "MTHFR syndrome," which does not exist as a disease: it makes it an intake adapted to a common genetic variation.
8. Folic acid, folinic acid, or methylfolate: which form to choose?
| Form | Nature | Strengths | Limitations | Common use |
|---|---|---|---|---|
| Folic acid | Synthetic, oxidized, very stable | Form used in nearly all neural tube prevention trials; 85% absorption; minimal cost; reimbursable on prescription | Must be reduced by the liver (limited capacity) then activated by MTHFR; beyond approximately 200 µg per dose, some circulates in unmetabolized form; can mask B12 deficiency at high doses | Medications 0.4 mg and 5 mg, standard supplements, fortified foods |
| Folinic acid (calcium folinate) | Reduced form, intermediate | Does not depend on the enzyme blocked by methotrexate; well-codified medical use | Medication, not a supplement; still depends on MTHFR to become 5-MTHF | Protection during methotrexate treatments, certain chemotherapies |
| 5-MTHF (methylfolate, Quatrefolic®) | Active circulating form, glucosamine or calcium salt | Directly usable; bypasses MTHFR; no unmetabolized folic acid; masks B12 deficiency less; good absorption even if gastric acidity is reduced | More expensive; no direct trial on neural tube defects (evidence relies on elevated blood folate levels, at least equivalent); sensitivity to oxidation, hence stabilized forms | Premium supplements, B complexes, recent prenatal formulas |
Natural 5-MTHF has advantages over synthetic folic acid: it is well absorbed even when gastric pH is altered, its bioavailability is not affected by metabolic defects, it reduces the risk of masking hematological signs of B12 deficiency, limits interactions with drugs that inhibit dihydrofolate reductase, bypasses MTHFR polymorphism and avoids potential effects of unconverted folic acid in circulation.
Scaglione F, Panzavolta G. Xenobiotica 2014;44(5):480-488. DOI: 10.3109/00498254.2013.845705
The question ofunmetabolized folic acidremains. The human liver reduces folic acid slowly; beyond a certain dose, a fraction passes into the blood as-is, and it is detected in most people taking supplements or eating fortified foods. Is this a problem? The most balanced review on the subject concludes that the phenomenon is real and dose-proportional, but that evidence of a harmful health effect is inconsistent and that free folic acid has no cofactor function that would make a causal role in disease plausible (Obeid, Curr Drug Metab, 2012). In other words: a signal to monitor, not a reason to fear folic acid, and a reasonable additional argument in favor of methylfolate for long-term use.
Our position is therefore simple. For prevention of neural tube defects, folic acid at 400 µg remains the official standard and no one needs to change a prescribed treatment. For long-term daily intake, particularly in carriers of an MTHFR variant, people who absorb poorly or those who want to avoid unmetabolized folic acid, methylfolate at 400 µg is at least as effective at raising blood folate levels and offers real physiological advantages. This is the form we selected in our Vitamin B Complex, without claiming it performs better than folic acid where the latter has proven itself.
9. The B12 masking trap
Folate and vitamin B12 are locked together by a single reaction, methionine synthase, which needs both to recycle homocysteine. When B12 is lacking, folates remain trapped in their methylated form, unusable for making DNA: this is the "folate trap," and the resulting anemia is identical to that from B9 deficiency. Yet massive folic acid intake can manage to bypass this blockade for bone marrow: red blood cells become normal, fatigue fades, and everyone is reassured.
The problem is that B12 has a second function, independent of folates: maintaining the myelin sheath of nerves. This damage is not corrected by folic acid and progresses silently, until tingling, balance problems, and in advanced cases, permanent nerve damage. This risk of masking led EFSA to set the safety limit for synthetic folic acid at 1,000 µg per day, and explains why countries that fortify their flour monitor B12 status in older people.
In practice: if you take folic acid long-term at nutritional dose (up to 400 µg), the risk is theoretical; if you are over 50, vegetarian or vegan, or take metformin or an antacid, have your B12 levels checked before any high-dose folate supplementation, and prioritize a complex that provides both. Methylfolate, which does not bypass the blockade in the same way, masks this deficiency less, though blood testing is still recommended. To understand this B12 mechanism, read our complete vitamin B12 guide.
10. Homocysteine, heart and brain: what the trials show
<<<33>>> Homocysteinehomocystéine is an amino acid that the body constantly recycles through vitamins B9, B12, and B6. When one is lacking, it accumulates, and elevated homocysteine has been associated for thirty years with increased risk of atherosclerosis, thrombosis, fractures, and cognitive decline. Folic acid is by far the most effective way to lower it: 400 to 800 µg per day reduces it by 20 to 25% in a few weeks. The question that occupied cardiologists for twenty years is whether lowering homocysteine truly provides protection.
In eleven randomized trials in patients with cardiovascular disease, folic acid supplementation reduced stroke risk by 10%. The effect was more pronounced in participants whose homocysteine dropped by at least 25%, with doses below 2 mg per day (-22%) and in regions without mandatory flour fortification (-13%).
Tian T, Yang KQ, Cui JG, Zhou LL, Zhou XL. Am J Med Sci 2017;354(4):379-387. DOI: 10.1016/j.amjms.2017.05.020
The overall picture is therefore as follows: major trials have not shown a reduction in heart attacks or cardiovascular mortality with B vitamins, but they repeatedly find a reduction in stroke, more marked in people whose initial intakes are low. France, which does not fortify its flours, is among the contexts where this effect is most plausible. This does not make folic acid a heart medication: it makes it a nutrient that must not be lacking, particularly after age 50, when homocysteine tends to rise.
On the brain side, two lines of evidence are documented. The first concerns cognitive aging : elevated homocysteine predicts faster decline, and folate supplementation in elderly people with elevated homocysteine has yielded encouraging results on certain cognitive functions, without being able to speak of dementia prevention. The second concernsmood : a meta-analysis of nine studies found that L-methylfolate, added to antidepressant treatment in adults with depression, modestly increased response rate (relative risk 1.25), particularly in patients with inflammatory markers or overweight (Maruf, Pharmacopsychiatry, 2021). This is an adjuvant on prescription, at doses of 7.5 to 15 mg, in no way comparable to a dietary supplement, and never an alternative to treatment.
11. Folic acid in men: useful for what?
The search "folic acid men" hides two questions. The first is simple: does a man need folates? Yes, as much as a woman outside pregnancy, for the same reasons (red blood cell production, homocysteine, cell division), and with the same risk factors for deficiency, alcohol chief among them. A man who eats few vegetables and legumes, drinks regularly, or takes a medication that interferes with folates has as much reason to monitor his intakes as a woman.
The second question concerns fertility. Sperm renew constantly, and their production consumes folates; older studies, small in size, had suggested that the combination of folic acid and zinc improved sperm concentration in infertile men. More recent and much larger randomized trials, conducted in couples undergoing fertility treatment, found no improvement in live births or sperm parameters with this combination. The honest message is therefore: meet your needs, correct a deficiency if it exists, but do not expect folic acid to improve normal male fertility. For a comprehensive couple approach, read how to increase your chances naturally, and find our formula Male Fertility in the collection libido and fertility.
Finally, a point of physiology that closes the debate on preventing birth defects: the embryo's neural tube closes in an entirely maternal environment. The father's intakes play no direct role in this, and no recommendation asks men to take folic acid in preconception.
12. Safety, maximum dose and interactions
Vitamin B9 is water-soluble: excess is eliminated in urine and no direct toxic effect has been described, even at doses far exceeding requirements. The upper safety limit set by EFSA, 1,000 µg of synthetic folic acid per day in adults (less in children, proportional to weight), is not based on toxicity but on the risk of masking B12 deficiency described above. It does not apply to food folates, which can be consumed without limit.
The most commonly cited concern is that of an effect on cancer, based on the fact that tumor cells consume many folates and certain chemotherapies work by blocking them. The question has been settled by the largest available analysis.
Over an average treatment duration of 5.2 years, high-dose folic acid (0.5 to 5 mg per day, or four times the plasma concentrations of the placebo group) had no significant effect on overall cancer incidence (1,904 cancers versus 1,809, relative risk 1.06, not significant), nor on any particular site: colon, prostate, lung, breast. The doses of flour fortification are ten times lower still.
Vollset SE, Clarke R, Lewington S, et al. Lancet 2013;381(9871):1029-1036. DOI: 10.1016/S0140-6736(12)62001-7
Methotrexate : folic acid can reduce its adverse effects but may also interfere with its action; supplementation (often with folinic acid) is decided and dosed by the prescriber, never through self-medication.
Antiepileptic drugs (valproate, carbamazepine, phenytoin, phenobarbital): they lower folates, and conversely high doses of folates can modify the concentrations of some of these medications. Medical adjustment essential, particularly in case of pregnancy planning (5 mg prescribed).
Sulfasalazine, trimethoprim, pyrimethamine : they impair the absorption or activation of folates; report any supplement to your doctor.
Vitamin B12 : do not take high doses of folates without verifying your B12 if you are over 50 years old, follow a vegetarian or vegan diet, or take metformin or long-term antacids.
Adverse effects : rare and mild (light digestive disorders, bitter taste, rare allergic reactions). The 5 mg dose is a medication reserved for prescribed indications. Respect the indicated daily dose, keep supplements out of children's reach and do not use them as substitutes for a varied and balanced diet.
13. Choosing wisely: B9 alone, B complex or preconception formula?
B9 never works alone. Its action on homocysteine depends on B12 and B6; its activation by the MTHFR enzyme depends on B2; its role in energy production is part of the cycle of eight B-group vitamins. An isolated intake of folates without B12 is actually the exact configuration of the masking described in section 9. This is why, for daily long-term intake, the B vitamin complex is the most coherent form: it covers the entire group at nutritional doses in a single capsule.
Preconception is a special case. The 400 µg dose is mandatory, but other needs increase at the same time: iron, iodine, vitamin D, and for some women active compounds such as myo-inositol. A preconceptional formula brings them together; verify that it provides 400 µg of B9 or supplement with your doctor. A few selection criteria, valid for all products:
- The B9 dose per serving, in µg, and the percentage of NRV (100% NRV = 200 µg; 400 µg = 200%).
- The named form : folic acid, or methylfolate under its precise name ((6S)-5-methyltetrahydrofolate acid, Quatrefolic®, Metafolin®), rather than a vague "vitamin B9".
- The presence of B12 in the same product if you take folates long-term, and its form (methylcobalamine or cyanocobalamine, see our B12 guide).
- A clean capsule : vegetable capsule (HPMC), without titanium dioxide, without colorant, without major allergen, traceable manufacturing.
- No unintentional accumulation : add up the folates from all your supplements (multivitamins, prenatal, B complex) to stay under 1,000 µg of synthetic folic acid per day.
Quatrefolic® (400 µg), methylcobalamine, pyridoxal-5-phosphate, riboflavin: the B Vitamin Complex provides each day all eight B-group vitamins in active forms, without allergen or titanium dioxide. Thirty capsules, one per day at breakfast.
Discover the B Vitamin Complex →Also find our pregnancy and maternity formulas and all our vitamins and minerals.
Choose the situation that best matches yours: the answer will appear just below.
Start 400 µg of B9 per day at least four weeks before stopping your contraception, and continue until 12 weeks of amenorrhea. Report to your doctor any history of neural tube defect, antiepileptic treatment, diabetes or obesity: they may prescribe 5 mg. The B Vitamin Complex provides 400 µg of methylfolate with B12; our Female Fertility combines 300 µg of folic acid with iron, zinc and vitamin D3. Use only one source of folates at a time, and consult your doctor to decide.
In the vast majority of cases, everything will be fine: the baseline risk is about one pregnancy in a thousand, and supplementation reduces an already low risk. Start 400 µg per day today if you're less than 12 weeks along, make an appointment with your doctor or midwife, who will organize your follow-up and ultrasounds. Read the box in section 5 for details, and keep this information for any future pregnancy: the right window is before conception.
Your need is daily coverage, not a correction dose. A complex that brings together all eight B vitamins, with 400 µg of methylfolate to bypass the MTHFR step, 10 mg of B2 that stabilizes the enzyme and B12 to prevent any masking, is the most coherent answer: this is the formula of the B Vitamin Complex. Add legumes and leafy greens to your plate, and if fatigue persists, a blood test (complete blood count, ferritin, B12, vitamin D, thyroid) will clarify things, as we explain in chronic fatigue: 11 validated plants and nutrients.
On methotrexate, supplementation (often with folinic acid) is part of the protocol and should not be changed on your own. With antiepileptic drugs, folates are adjusted with your neurologist, especially if you're planning a pregnancy. In case of confirmed deficiency, your doctor prescribes the correction dose (5 mg most often) after verifying vitamin B12, then a follow-up at three months. Do not add any supplement containing folates without their agreement; once the deficiency is corrected and the cause is treated, a B complex can take over daily.
This test provides guidance; it does not replace a blood test or professional medical advice.
Frequently asked questions about folic acid
What is folic acid for?
Folic acid is the synthetic form of vitamin B9 (folates). According to claims authorized by EFSA, folates contribute to the growth of maternal tissues during pregnancy, to normal amino acid synthesis, to normal blood formation, to normal homocysteine metabolism, to normal psychological functions, to normal immune system functioning, to the reduction of fatigue and to the process of cell division. In practice, vitamin B9 is essential for DNA production, and therefore for all cells that renew quickly: red blood cells, mucous membranes, and especially the embryo in the first weeks.
When to take folic acid: morning or evening, before or after meals?
The time of day has no demonstrated importance for folic acid: it is well absorbed with or without meals, in the morning or evening. What matters is regularity. The simplest approach is to link it to a fixed daily habit, like breakfast. Within the context of planning a pregnancy, the real question is not the time but the timing: start at least four weeks before conception and continue until the end of the third month.
Why take folic acid before pregnancy?
Because the neural tube, the precursor of the brain and spinal cord, closes between the 21st and 28th day after conception, often before pregnancy is even known. A daily supplement of 400 µg starting before conception reduces the risk of neural tube defects such as spina bifida by approximately two-thirds (Cochrane review, 2015). French health authorities recommend starting at least four weeks before stopping contraception and continuing until 12 weeks of amenorrhea.
I didn't take folic acid before pregnancy: is this serious?
No, in the vast majority of cases. Neural tube defects affect approximately one in a thousand pregnancies in France, and most women who did not take folic acid before conception have a perfectly healthy baby. Start 400 µg per day today if you're less than 12 weeks along, talk to your doctor or midwife, and know that first and second trimester ultrasounds allow for verification of your baby's normal development.
How much vitamin B9 per day?
The nutritional reference for an adult is 330 µg of dietary folate equivalents per day (ANSES, EFSA). This increases to 600 µg during pregnancy and 500 µg during breastfeeding. The nutritional reference value used on labels is 200 µg. As a supplement, the recommended preconception dose is 400 µg of folic acid (or methylfolate) per day; 5 mg requires a medical prescription. The safety limit set by EFSA is 1,000 µg of synthetic folic acid per day.
Which foods are richest in folic acid?
The foods richest in folates are liver (particularly poultry), nutritional yeast, legumes (lentils, chickpeas, beans), leafy green vegetables (spinach, watercress, arugula, lamb's lettuce), asparagus, broccoli, avocado, nuts and seeds (walnuts, hazelnuts), eggs, and citrus fruits. Natural folates are fragile: prolonged cooking in water can destroy half of them. Raw vegetables or those steamed retain more.
What are the symptoms of folic acid deficiency?
A vitamin B9 deficiency first manifests as persistent fatigue, paleness, shortness of breath on exertion, and palpitations—signs of macrocytic anemia (megaloblastic). This may be accompanied by a red and painful tongue, mouth ulcers, digestive disorders, irritability or depressed mood, concentration problems, and elevated homocysteine in the blood. Diagnosis is based on a blood test (serum or red blood cell folates, complete blood count).
Folic acid or methylfolate (Quatrefolic®): what's the difference?
Folic acid is a synthetic oxidized form that must be transformed by the liver, then by the MTHFR enzyme, to become active. Methylfolate (5-MTHF, Quatrefolic®) is the already-active form, the one that circulates in the blood: it bypasses MTHFR polymorphism, leaves no unmetabolized folic acid in circulation, and less likely masks a vitamin B12 deficiency (Scaglione, 2014). However, nearly all major studies on preventing neural tube defects were conducted with folic acid, which remains the reference for official recommendations.
What is MTHFR polymorphism and should you be tested?
The MTHFR gene codes for the enzyme that transforms folates into their active form. The C677T variant, present in the homozygous state (TT) in approximately one in ten people in Europe, reduces enzyme activity and moderately elevates homocysteine, especially when folate intake is low. Adequate intake of folates, particularly in methylfolate form, and vitamin B2 largely compensates for this effect. Genetic testing is not routinely recommended: it does not change management, which remains ensuring adequate intake.
Does folic acid help with getting pregnant?
Folic acid is not a fertility treatment: its proven role is to protect the embryo from the first days, not to increase the chances of conception. A few observational studies associate good folate intake with better ovulation quality or better results with assisted reproductive technology, but this data does not prove a causal link. It is precisely because we do not know when conception will occur that it should be taken from the moment pregnancy is desired.
Can you take too much folic acid? Is it dangerous?
Dietary folates have no known toxicity. For synthetic folic acid, EFSA has set a safety limit of 1,000 µg per day in adults, not because of direct toxicity, but because beyond that it can mask anemia from vitamin B12 deficiency while allowing neurological damage to progress. A meta-analysis of 13 trials on 50,000 people showed no increase in cancer incidence with high-dose folic acid over five years (Vollset, Lancet, 2013). The 5 mg dose is a medication to be reserved for prescribed situations.
Does folic acid cause weight gain?
No. Folic acid provides no calories and has no demonstrated effect on appetite or weight. The impression sometimes reported stems from context: it is often started at the time of a pregnancy plan or early in pregnancy, a period when weight changes for other reasons. In a person with a deficiency, correcting the deficit can improve appetite by eliminating fatigue, which is not an effect of the vitamin on fat storage.
Is folic acid useful in men?
Yes, for their own health: men have the same basic needs (330 µg per day) and the same risk of deficiency in case of alcohol use, digestive disease, or certain medications. For male fertility, data are mixed: older studies suggested an effect of the combination of folates and zinc on sperm, but more recent and larger trials have not found benefits for births. Protection of the neural tube, however, depends on the mother's intake, not the father's.
- Folates / Vitamin B9
- Family of water-soluble molecules built around a pterin-PABA-glutamate skeleton, naturally present in foods. The term "vitamin B9" designates them collectively.
- Folic acid
- Synthetic, oxidized, and stable form of vitamin B9, used in supplements, medications, and fortified foods. It must be reduced and then methylated by the body to become active.
- 5-MTHF (methylfolate)
- 5-methyltetrahydrofolate, the active form of vitamin B9 that circulates in the blood and enters cells. Available as a supplement in stabilized salt form (Quatrefolic®, Metafolin®).
- Dietary Folate Equivalent (DFE)
- Unit that corrects absorption differences between forms: 1 µg of folic acid taken with a meal is worth approximately 1.2 µg of DFE, and 1.7 µg taken on an empty stomach. Official recommendations are expressed in DFE.
- MTHFR
- Methylenetetrahydrofolate reductase, the enzyme that performs the final step of folate activation. Its common C677T variant reduces its activity; vitamin B2 is its cofactor.
- Homocysteine
- An intermediate amino acid recycled into methionine thanks to vitamins B9 and B12, or degraded thanks to B6. Its elevation in the blood signals a deficiency in one of these vitamins and is associated with increased cardiovascular risk.
- Neural tube
- Embryonic structure that closes between day 21 and day 28 after conception to form the brain and spinal cord. Its incomplete closure causes spina bifida or anencephaly.
- Megaloblastic anemia
- Anemia characterized by abnormally large red blood cells (MCV greater than 100 fL), due to slowed DNA synthesis from lack of folates or vitamin B12.
- De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, Rayco-Solon P. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2015;12:CD007950. doi:10.1002/14651858.CD007950.pub3
- Viswanathan M, Urrutia RP, Hudson KN, Middleton JC, Kahwati LC. Folic acid supplementation to prevent neural tube defects: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2023;330(5):460-466. doi:10.1001/jama.2023.9864
- Vollset SE, Clarke R, Lewington S, et al. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Lancet. 2013;381(9871):1029-1036. doi:10.1016/S0140-6736(12)62001-7
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- Obeid R, Herrmann W. The emerging role of unmetabolized folic acid in human diseases: myth or reality? Curr Drug Metab. 2012;13(8):1184-1195. doi:10.2174/138920012802850137
- Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2015;58(1):1-10. doi:10.1016/j.ejmg.2014.10.004
- McNulty H, Pentieva K, Hoey L, Ward M. Homocysteine, B-vitamins and CVD. Proc Nutr Soc. 2008;67(2):232-237. doi:10.1017/S0029665108007076
- Hiraoka M, Kagawa Y. Genetic polymorphisms and folate status. Congenit Anom (Kyoto). 2017;57(5):142-149. doi:10.1111/cga.12232
- Maruf AA, Poweleit EA, Brown LC, Strawn JR, Bousman CA. Systematic review and meta-analysis of L-methylfolate augmentation in depressive disorders. Pharmacopsychiatry. 2022;55(3):139-147. doi:10.1055/a-1681-2047
- Finkelstein JL, Cuthbert A, Weeks J, et al. Daily oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2024;8:CD004736. doi:10.1002/14651858.CD004736.pub6
- ANSES. Nutritional references for vitamins and minerals. anses.fr. HAS and Santé publique France: periconceptional folic acid supplementation recommendations. Health claims: regulations (EU) No. 432/2012 and No. 1169/2011.



