PCOS and Vitamin B9: Why Is Synthetic Folic Acid Often Not Recommended?

PCOS is a complex hormonal disorder that affects the ovaries and the way they function. It is characterised by an imbalance of female sex hormones, often linked to an excess of androgens, which can disrupt ovulation and the regularity of cycles.

In practice, PCOS most commonly manifests as irregular or absent menstrual cycles, rare or absent ovulation, a tendency towards acne, hirsutism, and sometimes weight gain, generally linked to insulin resistance.

In the long term, this syndrome can affect your fertility as well as your metabolism, which is why it is important to opt for a holistic approach, including dietary adjustments and micronutrient supplementation, such as vitamin B9.

What we call "vitamin B9" actually encompasses several forms, which are often lumped together even though they do not behave in the same way in the body. The main distinction is between natural folates and synthetic folic acid.

• Natural folates correspond to the vitamin B9 found in food, for example in leafy green vegetables, legumes or certain fruits. These folates are close to the form the body can readily use and are involved in essential functions such as DNA synthesis, cell division and healthy foetal development during pregnancy.
• Folic acid is a synthetic form of B9, created in a laboratory, which does not exist as such in nature. It has been widely used in food supplements and food fortification policies, as it is very stable and low-cost. The difference from the natural form? Folic acid requires several conversion steps in the body before becoming truly active, and therefore useful. Supplementation is recommended when trying for a baby and during pregnancy, but it is best to avoid this form and choose a best pregnancy food supplement. 

For vitamin B9 to be used properly, the body must convert folates into their active form, known as 5-MTHF (5-methyltetrahydrofolate). This step relies in particular on an enzyme produced from the MTHFR gene.

Some people carry variations of the MTHFR gene, which tend to reduce the efficiency of this enzyme. When it functions less effectively, the conversion of folic acid into its active form is slower or incomplete. This can lead to an accumulation of unmetabolised folic acid in the blood and a reduced actual availability of active vitamin B9 for cells.

Furthermore, these disruptions can be accompanied by a rise in homocysteine, an amino acid whose excess is associated with an increased risk of cardiovascular problems and an unfavourable impact on fertility and embryo implantation. In women on a conception journey, this parameter is of particular importance, especially if they are also affected by PCOS.

With PCOS, we are not just talking about a hormonal disorder, but also an unfavourable metabolic environment. This environment is most often characterised by a tendency towards insulin resistance, low-grade inflammation, and disruptions to carbohydrate and lipid metabolism. In this fragile environment, the way the body metabolises vitamin B9 can make all the difference!

Synthetic folic acid: far from guaranteed effectiveness

Synthetic folic acid requires several conversion steps before becoming fully active. This conversion depends in part on the proper functioning of the MTHFR enzyme. If enzyme activity is reduced — due to a gene variant, for example — some of the folic acid may remain in an unmetabolised form, circulating in the blood without being truly usable by cells.

According to several studies, unmetabolised folic acid can saturate receptors without delivering the expected benefits [1]. This phenomenon can also mask a vitamin B12 deficiency, as both vitamins interact via the same metabolic pathways.

Concrete consequences for fertility and pregnancy

In women affected by PCOS, who are generally looking to optimise their ovulation, egg quality, and implantation, this gap between theoretical intake and actual availability of active vitamin B9 can have serious consequences: persistently elevated homocysteine levels, and suboptimal support for fertility and early embryonic development.

Although folic acid remains the official recommendation of public health authorities for the prevention of neural tube defects, studies suggest that 5-MTHF may be more effective at improving certain metabolic parameters in women with PCOS [2], particularly by reducing homocysteine and inflammation. This is why many fertility professionals now recommend methylfolate in a women's fertility food supplement for women with PCOS who are trying to conceive.

Given the limitations of folic acid, one of the most effective alternatives is to turn to already-active forms of vitamin B9, such as 5-MTHF, sometimes presented under other names (for example Quatrefolic®). The advantage: these forms are directly usable by the body, including in women with reduced MTHFR enzyme activity. In short, it is a particularly interesting option in cases of PCOS or when planning a pregnancy.

In practice, many professionals recommend an intake of 400 µg (micrograms) of vitamin B9 per day[3], in active forms, ideally starting several months before conception.

In cases of PCOS, this strategy often forms part of a broader approach, including blood sugar balancing, work on insulin resistance, weight management where necessary, and sometimes the use of nutrients such as myo-inositol.

Alongside supplements, it is strongly advisable to boost your intake of natural folates through diet: dark leafy greens (spinach, chard, lamb's lettuce), legumes (lentils, chickpeas), citrus fruits, avocados, eggs, and certain nuts and seeds are all good sources of natural B9. 

As you will have gathered, the key idea is to combine dietary sources rich in natural folates with a vitamin B9 supplement in its active form, rather than opting for standard folic acid.