Vitamin B9 and fertility: what is the role of folic acid before and during pregnancy?

Nearly three-quarters of women of childbearing age will not reach the recommended intake of vitamin B9. Yet, this nutrient plays an essential role as soon as you start trying to conceive. It participates in DNA synthesis, cell division, and the growth of maternal tissues during pregnancy, mechanisms that are indispensable in the early stages of embryonic development.

This is why health authorities recommend vitamin B9 supplementation as soon as you wish to conceive and throughout the first trimester of pregnancy. Role, dosage, different forms of vitamin B9, and selection criteria: discover the essentials you need to know to prepare for your baby project with peace of mind.

Vitamin B9 holds a special place in preparing for pregnancy. Its role, the forms it can take, and the right time to start taking it follow a precise biological logic.

Behind the term vitamin B9, there are actually several very distinct forms.

• Folates refer to vitamin B9 as it is found naturally in foods (leafy vegetables, liver). This form is unstable and fragile.
• Folic acid is the synthetic version, used in medicines and food supplements: stable and inexpensive.

Regardless of the origin of the vitamin B9, the body must convert it into its active form, methylfolate, also called 5-MTHF, which is the only form directly usable by cells.

However, about one in two people in Europe carries a genetic variation (on the MTHFR gene) that results in a defect in converting vitamin B9 into the active 5-MTHF form. For these individuals, standard folic acid supplementation may prove insufficient, even when taken according to recommendations. The 5-MTHF form, marketed under the patented brand Quatrefolic®, has the advantage of being directly usable by the body without requiring a prior conversion step. This is why the most advanced formulas now favor this form.

Vitamin B9 is recommended when planning a pregnancy because certain essential stages of embryonic development occur very early after conception. The neural tube, which forms the brain and spinal cord, forms and closes between the 21st and 28th day of pregnancy, often before the pregnancy is even diagnosed.

For this reason, French and international health authorities recommend starting vitamin B9 supplementation before conception, ideally at least one month before the start of pregnancy. This supplementation is then continued throughout the first trimester to ensure intake is adapted to the needs related to embryonic development.

Even before conception, vitamin B9 plays a recognized role in fertility and reproduction, making it a key nutrient to monitor when planning a pregnancy.

Several scientific studies have explored the link between folate concentrations in the follicular environment and certain parameters of oocyte maturation. A study published in Human Reproduction observed that a higher level of folates in the follicular fluid was associated with better oocyte maturation and better in-vitro fertilization results. Although these observations do not establish a direct causal link, they underscore the value of sufficient vitamin B9 intake when planning a pregnancy.

Vitamin B9 is involved in the metabolism of homocysteine, an amino acid naturally present in the body. When folate intake is insufficient, homocysteine levels can rise. However, high concentrations of homocysteine have been associated, in several studies, with impaired parameters of female reproductive health.

Vitamin B9, along with vitamins B6 and B12, contributes to normal homocysteine metabolism. This is why these three vitamins are frequently combined in food supplements for women who are planning a pregnancy or wish to optimize their nutritional intake during the preconception period.

Vitamin B9 plays a central role throughout pregnancy: its role is particularly important during the first weeks of embryonic development, but its functions continue as it participates in cell division mechanisms and the growth of maternal tissues.

The link between folic acid supplementation and the prevention of neural tube defects is one of the best documented. These defects, which involve the brain and spinal cord of the future baby, occur very early during pregnancy, often before the pregnancy is even known.

Historical studies from the 1990s, notably the work of Czeizel and Dudas published in the New England Journal of Medicine (1992), demonstrated a 72% reduction in these malformations in the supplemented group versus placebo. These data led to official recommendations in more than 80 countries.

Reference works published in the early 1990s, including the Czeizel and Dudas study in the New England Journal of Medicine, showed that folic acid supplementation before conception and in early pregnancy significantly reduced the risk of these malformations. These results led to the adoption of official recommendations in many countries.

In France, the recommendation is clear: 400 µg of folic acid per day starting at least one month before conception and continuing until the end of the first trimester. For women with a history of this type of malformation, the doctor may prescribe a higher dose.

Vitamin B9 plays an essential role throughout pregnancy. By participating in DNA synthesis and cell renewal, it supports the growth of maternal tissues and the development of the future baby. From the very first weeks of pregnancy, it is involved in numerous indispensable biological processes, including placenta formation, the establishment of organs and tissues, and the production of blood cells.

Folate requirements naturally increase during pregnancy to meet this intense biological activity. Diet alone does not always provide the recommended intake. This is why adapted supplementation is generally recommended as soon as you plan a pregnancy and throughout the first trimester. Vitamin B9 thus contributes to the growth of maternal tissues during pregnancy and plays a role in the process of cell division, two functions essential to healthy embryonic and fetal development.

Vitamin B9 is also involved in several biological mechanisms involved in male fertility, particularly those related to cell division and DNA synthesis.

The production of sperm, known as spermatogenesis, is a continuous process that relies on numerous cell divisions. Vitamin B9 plays an essential role in DNA synthesis and cell renewal, two mechanisms indispensable for the formation of sperm.

Several studies have shown a correlation between insufficient vitamin B9 and zinc status in men and a higher frequency of sperm abnormalities. These data fully justify integrating vitamin B9 into a preconception preparation plan for men.

When planning a pregnancy, vitamin B9 is thus frequently combined with other micronutrients involved in male reproductive health, notably zinc, which contributes to the maintenance of normal fertility and reproduction.

Vitamin B9 contributes to biological mechanisms essential to sperm production, notably DNA synthesis and cell division. Several studies have explored the link between folate status and sperm quality.

A study published in Fertility and Sterility suggests that adequate intake of vitamin B9 and zinc could be associated with better sperm parameters, notably sperm concentration and morphology. However, the effect of vitamin B9 supplementation on male fertility has not been formally established. Nevertheless, ensuring sufficient vitamin B9 intake is part of an overall approach to preparing for conception.

Sperm are renewed continuously during spermatogenesis. It takes about 74 days to produce a new sperm cell, plus several days of maturation. This is why health professionals generally recommend optimizing lifestyle and nutritional intake at least three months before starting attempts at conception.

A vitamin B9 deficiency can go unnoticed for several months or even years, as it does not cause specific symptoms. However, folates are involved in many biological processes involved in reproduction and embryonic development.

When vitamin B9 intake is insufficient, homocysteine metabolism can be disrupted, leading to an increase in blood levels. Several studies have associated insufficient folate status or high homocysteine concentrations with certain impairments in reproductive health, in both women and men.

In women, insufficient folate intake could be associated with an environment less favorable to the smooth progression of the early stages of pregnancy. In men, several studies have observed a link between poor folate status and certain alterations in sperm parameters or the integrity of sperm DNA.

Beyond fertility, the importance of vitamin B9 during pregnancy is well established. Adequate intake helps reduce the risk of neural tube defects and contributes to the growth and cell division mechanisms essential for embryonic and fetal development.

Several profiles present a higher risk of vitamin B9 deficiency:

• Women and men carrying a MTHFR gene variation, who convert folic acid into its active 5-MTHF form less efficiently;
• Women who have taken oral contraception over a long period, which can lower blood vitamin B9 levels;
• Women and men whose diet is low in green vegetables and legumes, the main natural sources of folates;
• Smokers, for whom folate absorption is less effective;
• Women who have had a recent pregnancy, whose stores have not yet been replenished.

Health authority recommendations define precise vitamin B9 intakes for women planning a pregnancy. They specify both the recommended dose and the time at which supplementation should begin in order to cover the needs of the early stages of embryonic development.

For adult women, the recommended vitamin B9 intake is 330 µg per day. For those planning a pregnancy, health authorities recommend a daily supplement of 400 µg of vitamin B9, ideally starting at least one month before conception and continuing throughout the first trimester. This recommendation is primarily aimed at reducing the risk of neural tube defects.

Since then, EFSA and ANSES have re-evaluated (in 2017 and 2021) satisfactory intake levels at 600 µg of folates per day for pregnant women or those likely to become pregnant, a level more consistent with all the needs related to conception and fetal development.

Current recommendations suggest starting vitamin B9 supplementation at least one month before conception. Ideally, this can be implemented as soon as contraception is stopped or from the beginning of the pregnancy plan in order to optimize folate status before the first stages of embryonic development.

A varied and balanced diet, rich in green leafy vegetables, legumes, and nuts, naturally contributes to vitamin B9 intake. However, folate needs increase with pregnancy, and it can be difficult to meet them through diet alone. Furthermore, the bioavailability of folates naturally present in food is generally lower than that of the folic acid forms used in dietary supplements.

This is why health authorities recommend vitamin B9 supplementation for women planning a pregnancy, in addition to a balanced diet. This approach helps ensure adequate intake during the preconception period and the first weeks of embryonic development, when needs are particularly high.

Diet can contribute to daily folate status, even if it is not enough on its own to cover the increased needs during a pregnancy plan.

Liver, leafy green vegetables, and legumes top the list. Here are the most concentrated sources:

Folates are fragile: heat, light, and oxidation degrade them rapidly. Boiling is the most destructive method, as up to 70% of folates can be lost in the cooking water. Prioritizing short steam cooking, braising, or raw consumption helps better preserve the vitamin B9 content of food. This is one of the reasons why, even with a balanced diet regularly including vegetables and legumes, folate intake often remains insufficient.

Not all vitamin B9 supplements are equal: the form, dosage, and active combinations concretely determine their effectiveness.

Not all dietary supplements have the same characteristics. Several criteria can be taken into account when making a choice, including the form of vitamin B9 used, the proposed dosage, and the presence of other complementary nutrients.

The active form, 5-MTHF (sold under the brand Quatrefolic®), is directly assimilable without prior transformation. This is a concrete criterion to look for on a supplement label. The second criterion is the dosage: 400 µg corresponds to the historically recommended dose, but EFSA and ANSES have re-evaluated satisfactory intake at 600 µg per day for pregnant women or those likely to become pregnant. The third is the synergy of active ingredients: vitamin B9 works in concert with vitamins B6 and B12. Combining these 3 active ingredients allows you to benefit from all the advantages of supplementation.

There are different formulas on the market, adapted to different profiles:

The essential formula provides 600 µg of vitamin B9 in the form of 5-MTHF, in line with the satisfactory intake levels re-evaluated by EFSA and ANSES. Combined with vitamins B6 and B12, it is suitable for women without specific risk factors who are newly planning a pregnancy.

The complete formula incorporates a synergy of active ingredients to support 5-MTHF and vitamins B6 and B12: zinc, iodine, vitamin D, myo-inositol, vitamins C and E, selenium. It covers a broader scope of fertility and baby development.

The expert formula adds coenzyme Q10 and probiotics to the complete formula, in order to adapt to all profiles, and particularly in cases of late parenthood and risk of dysbiosis.

Laboratoires DENSMORE offers supplements for couple fertility designed according to this logic of profile adaptation, with special attention paid to the bioavailability of active ingredients and the consistency of the combinations. Regardless of the formula chosen, lifestyle and regularity of intake remain the most determining factors for effectiveness.

For synthetic folic acid, the safety limit set by European authorities is 1 mg per day (or 1,000 µg). Higher doses, notably 5 mg per day, may be prescribed in certain specific medical situations and under the supervision of a healthcare professional.

In the long term, excessive intake of folic acid could mask the signs of a vitamin B12 deficiency, thereby delaying its diagnosis. This safety limit does not apply to folates naturally present in food, for which no adverse effects have been observed at normally consumed levels.

5-MTHF, the biologically active form of vitamin B9, also presents a good safety profile. In the context of supplementation in compliance with current recommendations/re-evaluations, from 400 to 600 µg per day, the intakes usually proposed before and during pregnancy are considered safe for the majority of women.

• Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992;327(26):1832-1835.
• Gaskins AJ, Afeiche MC, Wright DL, et al. Dietary folate and reproductive success among women undergoing assisted reproduction. Obstet Gynecol. 2014;124(4):801-809.
• Wong WY, Merkus HM, Thomas CM, et al. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2002;77(3):491-498.
• EFSA Panel on Dietetic Products, Nutrition and Allergies. Scientific Opinion on the Tolerable Upper Intake Level of folate. EFSA Journal. 2009;7(7):1213.
• Shane B. Folate and vitamin B12 metabolism: overview and interaction with riboflavin, vitamin B6, and polymorphisms. Food Nutr Bull. 2008;29(2 Suppl):S5-16.
• Steegers-Theunissen RP, Twigt J, Pestinger V, Sinclair KD. The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism. Hum Reprod Update. 2013;19(6):640-655.
• Haute Autorité de Santé (HAS). Supplémentation en acide folique pour la prévention du risque d'anomalie de fermeture du tube neural. Recommandation de bonne pratique. 2022.