Vitamin B9 — 5-methylhydrofolate (5-MTHF) — is the preferred form of active folate.
Folate is a water-soluble vitamin found naturally in dark green leafy vegetables, nuts and legumes.
It is required for DNA replication and as a substrate for the enzymatic reactions involved in amino acid synthesis and vitamin metabolism.
Unlike folic acid, all women can safely and effectively absorb and utilise folate.
Up to 40% of women worldwide (as well as men) have a genetic polymorphism (MTHFR) that inhibits a significant amount of ingested folic acid (usually in supplement form) from working in the body.
The MTHFR gene impedes the body’s ability to convert folic acid into the biologically active 5-MTHF form.
For this large and unknowing portion of the population, this means that precious money is being wasted as the folic acid supplement, if consumed as directed, will not provide the health support benefits claimed on its label.
Quatrefolic® active folate bypasses this conversion step as it is ready for the body to use.
Folate supports women of all life stages
Vitamin B9 is recognised as a mandatory vitamin supplement during pregnancy for its essential role in cell division and DNA synthesis.
Yet, it is recommended that humans maintain adequate dietary intakes of folate throughout their lives, not just in times of reproduction.
Owing to its impact on homocysteine levels, folate is vital for many other aspects of health and wellness, such as cardiovascular function, fertility, stable moods, cognition and bone health.1
Fertility: Folate supports improved fertility in both women and men. Low circulating folate has been implicated in female and male infertility, often the result of the MTHFR polymorphism.
In men, folate is essential for healthy sperm creation; low levels in semen have been related to poor sperm DNA stability and damage.2
In women, high homocysteine and low folate levels can impede pregnancy and increase the risk of early miscarriage.2
Pregnancy: As a critical nutrient facilitating healthy cell growth, folate reduces the risk of congenital disabilities.
Folate is a vital nutrient that’s needed during periods of rapid cell growth and proliferation, which occur during the early stages of pregnancy and embryo development.2
Folate is involved in rapid growth and development periods, such as pregnancy and childhood, as it contributes to the proper development of the baby’s skull and spinal cord.
Low levels of this vitamin before and during pregnancy can lead to neural tube defects.1
Menopause: Studies have shown that folate supplementation significantly reduces hot flushes in postmenopausal women by interacting with key monoamine neurotransmitters (such as dopamine and serotonin) in the brain.
Women who supplemented with 1 mg of folate daily experienced significant improvements in the severity, duration and frequency of hot flushes.3
Mood and mental health: During menopause, many women experience mood fluctuations … and folate can help.
Folate crosses the blood-brain barrier where it helps to produce key neurotransmitters that govern cognitive function and overall mental well-being.
Folate is involved in the creation of “feel-good” monoamine neurotransmitters such as dopamine and serotonin.
Folate insufficiency contributes to sparse neurotransmitter levels and elevated amounts of homocysteine, which can negatively impact moods.
In people with depression, folate concentrations were highly correlated with homocysteine levels and, in one study, nearly one-third of severely depressed individuals had a folate deficiency.4
Indeed, folate is a powerful vitamin. Now, research has revealed its ability to support skin’s structural components when faced with environmental hazards such as sun/UVB exposure.
Of course, this is of interest to women, but market research shows it’s now of interest to the growing men’s health market.
Men are becoming more conscious of their skin health; in a 2022 survey of 800 men aged 18 and older, 56% reported spending $26–100 monthly on personal care items, and 57% are using more supplements than they did in the previous 5 years.5
New evidence, new market opportunity: skin health
Skin health is more than simply reducing wrinkles and preventing a dry, dull texture.
Minimising the free radicals and inflammation generated by direct sun exposure protects the structure of the skin and its normalised regeneration (healthy skin renews itself every 27–30 days).
One-carbon metabolism needs folate as this vitamin is essential for skin cell growth, repair and regeneration.
However, solar radiation reduces skin folate levels, impairing these processes. Unlike folic acid, bioavailable 5-MTHF as Quatrefolic has shown improved stability, penetration and antioxidant properties, making it a promising skincare ingredient.
Previous studies demonstrate Quatrefolic’s ability to protect dermal fibroblasts against UVA-induced oxidative stress, enhance their proliferation, reduce DNA damage and support collagen synthesis.
These findings highlight Quatrefolic’s potential as a science-backed solution for antiageing and photoprotection.
Folate as Quatrefolic has been shown to boost DNA repair and synthesis, which is necessary for healthy skin cell production and turnover, antioxidant activity and enhanced collagen production.
Thus, it contributes to skin health and protection against sun-induced damage. New research substantiates Quatrefolic 5-MTHF as a nutrient that supports healthy skin by protecting against damage to specific components in the skin’s structure.6
In a recent study, dermal fibroblasts were exposed to UVA irradiation to mimic sun exposure. Cells were supplemented with 5-MTHF (as Quatrefolic) before (pre) or after (post) UVA irradiation.
In post-treatment, the cells were first exposed to UVA and then treated with 5-MTHF. The researchers evaluated 5-MTHF bioavailability and uptake, protection against UVA-induced mitochondrial ROS (by cytometry) and DNA damage (by comet assay), as well as fibroblast proliferation efficacy.6
The researchers found that 5-MTHF showed dose-dependent uptake by dermal fibroblasts, remaining stable for up to 48 hours. This prolonged intracellular presence is critical when it comes to promoting proper cellular repair.
Additionally, 5-MTHF provided significant protection against UVA-induced oxidative stress by reducing cytosolic and mitochondrial ROS production, especially at higher concentrations.
Furthermore, 5-MTHF supplementation improved fibroblast viability and DNA integrity.6 Another point to consider is the importance of bioavailability for active ingredients; Quatrefolic has clinical evidence to support its superiority here as well.
Earlier this year, Gnosis shared results from a clinical study in Indonesia that confirmed that Quatrefolic (as HY-FOLIC) is twice as bioavailable as folic acid, with significantly higher Cmax and AUCt values.
These findings reinforce Quatrefolic’s superiority in both efficacy and versatility, expanding its relevance from foundational nutrition to skin regeneration and beauty-from-within applications.7
Conclusion
Folate as Quatrefolic is tailor-made for women. Its ability to combat skin ageing is an attractive reason to add it to nutricosmetics or products that target youthful skin support.
References
- J.A. Greenberg, et al., Rev. Obstet. Gynecol. 4(2), 52–59 (2011).
- T. Forges, et al., Hum. Reprod. Update 13(3), 225–238 (2007).
- S. Bani, et al., J. Caring Sci. 2(2), 131–40 (2013).
- T. Bottiglieri, Am. J. Clin. Nutr. 76(5), 1151S–1157S (2002).
- https://gcimagazine.texterity.com/gcimagazine/october_2022/MobilePagedArticle.action?articleId=1823533#articleId1823533.
- D.C. Birradale and M.G. Kimlin, Nutr. Rev. 70(7), 414–22 (2012).
- N. Nafrialdi and F.D. Suyatna, Int. J. Applied Pharmaceutics 16(6), 64–68 (2024).