What is Quatrefolic?
Folic acid, the synthetic form of folate used in many supplements and fortified foods, is not biologically active. Before the body can use it, folic acid must be converted into the active form, 5-methyltetrahydrofolate (5-MTHF). This conversion relies on several steps in which the MTHFR enzyme (methylenetetrahydrofolate reductase) plays a central role.
Folate status during pregnancy is critical for healthy foetal development. Humans cannot produce folate, and many pregnant women do not consume sufficient amounts through diet alone. Supplementation is important for supporting healthy foetal formation, including the neural tube.
Some people have genetic variations—MTHFR polymorphisms—that reduce the activity or effectiveness of the MTHFR enzyme. When this occurs, the body struggles to convert folic acid into its active form. Quatrefolic®, a biologically active and structurally identical form of reduced folate, bypasses this impaired step entirely. It delivers folate in its “finished”, usable state without requiring any conversion.
Women with MTHFR polymorphisms have an increased risk of several complications during pregnancy. These may include cleft palate, attention-related behavioural concerns, low birth weight, pregnancy loss, preeclampsia and other developmental challenges.
Because Quatrefolic® provides the active form of folate directly, it may be particularly useful during preconception, pregnancy and breastfeeding, supplying folate the body can utilise immediately.
Hyper-homocysteinemia in recurrent pregnancy loss (RPL)
Elevated homocysteine levels in pregnancy, known as hyper-homocysteinaemia, have been linked to a range of complications. These may include deep venous thrombosis, recurrent miscarriage, placental abruption, preeclampsia, neural tube defects, foetal growth restriction and other abnormalities.
Around one in three women experiencing recurrent pregnancy loss have elevated homocysteine. Supporting the reduction of homocysteine levels can help improve pregnancy outcomes, and Quatrefolic® has been shown to assist in lowering plasma homocysteine.
Fertility & Reproduction
MTHFR polymorphisms can impact fertility and have been associated with reduced reproductive capacity in women. By bypassing the disrupted folate metabolism pathway, Quatrefolic® may support reproductive health and improve outcomes in fertility treatment.
A case series by Servy et al. (2018) explored the benefits of Quatrefolic® in couples with long-standing fertility challenges, including repeated miscarriage, premature ovarian insufficiency and abnormal sperm parameters. Many of the women had previously taken 5 mg of folic acid daily without improvement.
In the study, both partners took 800 mcg of Quatrefolic®, resulting in an overall pregnancy rate of 86.7%.
Research on Quatrefolic® and homocysteine reduction
Another study evaluated whether Quatrefolic® could reduce homocysteine in individuals with the MTHFR C677T polymorphism. Hyper-homocysteinaemia is one of the most common risk factors for thrombophilia, a condition associated with increased blood clotting. In pregnancy, this tendency can heighten miscarriage risk.
According to the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), around:
- 1.5% of the population is homozygous for the C677T variant (inherited from both parents)
- 25% is heterozygous (inherited from one parent)
RANZCOG notes that this “thrombophilic tendency is minimised by adequate folate, riboflavin (vitamin B2), vitamin B6 and vitamin B12”.
In the study, 89 couples with fertility challenges for at least three years were assessed. As expected, homocysteine levels were higher in the homozygous group. Participants were then given 600 mcg of Quatrefolic® for three months.
Both groups experienced a significant reduction in homocysteine, with the greatest improvement seen in those who were homozygous. These findings support results from another Quatrefolic® study conducted the year prior, in which couples experiencing recurrent miscarriage due to MTHFR C677T polymorphisms were treated with 800 mcg of Quatrefolic®.
Final thoughts
Quatrefolic® offers a direct, active form of folate that bypasses genetic limitations and supports healthy folate metabolism when it matters most. By helping to reduce homocysteine levels and supplying bioactive folate without relying on MTHFR conversion, it provides meaningful support during preconception, pregnancy and breastfeeding. For individuals with MTHFR polymorphisms or a history of recurrent miscarriage, this form of folate may offer an important advantage in maintaining optimal folate status and supporting reproductive health.
References
- Clément A, Menezo Y, Cohen M, Cornet D, Clément P. 5-Methyltetrahydrofolate reduces blood homocysteine level significantly in C677T methyltetrahydrofolate reductase single-nucleotide polymorphism carriers consulting for infertility. J Gynecol Obstet Hum Reprod. 2020.
- RANZCOG. Vitamin and Mineral Supplementation and Pregnancy. Published November 2019.
