
An interesting collaboration with PT Simex Pharmaceutical Indonesia confirmed the Superior Bioavailability of Quatrefolic®.
The study evalueted the pharmacokinetic profile of HY-FOLIC®, a finished product from PT Simex Pharmaceutical Indonesia, comparing it to folic acid following single oral administration in healthy volunteers. The results revealed that HY-FOLIC®, which contains (6S)-5-Methyltetrahydrofolic Acid, Glucosamine Salt as Quatrefolic ® active folate, is twice as bioavailable as folic acid.
Why is Folate Important?
Folate, also known as vitamin B9, is crucial for women of reproductive age as it supports DNA synthesis, cell division, and proper fetal neurological development. This is especially important for the approximately 140 million women who give birth each year and their newborns.
Currently, folic acid is the recommended form of folate for women trying to conceive. However, many women have an MTHFR gene variant, which hampers the conversion of folic acid into its active form, 5-MTHF, potentially reducing folate availability. Unlike folic acid, active folate forms like Quatrefolic® do not require conversion in the body, making them more effective, particularly for women with this genetic variation.
“Our study findings suggest that HY-FOLIC® increases 5-MTHF levels in the body more effectively than folic acid,” states Merrylin Saragih, Head of Product Department at PT. Simex Pharmaceutical Indonesia. “This is especially important for individuals requiring enhanced folate bioavailability, such as pregnant women or those with genetic polymorphisms affecting folic acid metabolism.”
“We have espoused the need for the standard of care to change,” says Jean Francois Jeanne, Substantiation and Application Manager at Gnosis by Lesaffre, noting that Quatrefolic® from Gnosis is well-studied active folate, with research substantiating and quantifying its benefits in several health contexts for women’s health, including overall folate metabolism [3,4], cardiovascular health [5], and fertility [6]. “We contend that clinically validated Quatrefolic® offers substantial advantages over folic acid, but also for a wider population. This study provides another strong element to that argument.”
The study confirms that HY-FOLIC®, featuring Quatrefolic® active folate, is two-fold more bioavailable than folic acid.
The randomized, open-label, crossover design[1] demonstrated that a single dose of HY-FOLIC® revealed several key advantages of active folate:
- Superior Absorption and Bioavailability: HY-FOLIC® (Quatrefolic®) is two-fold more bioavailable than folic acid (higher peak plasma concentration Cmax and AUCt), ensuring the body can access and utilise folate twice as effectively.
- Avoidance of Metabolic Limitations: Unlike folic acid, HY-FOLIC® bypasses the metabolic conversion steps requiring the DHFR and MTHFR enzymes, making it particularly beneficial for individuals with genetic polymorphisms (~40% of the worldwide population) that impair folic acid metabolism.
- Reduction in Unmetabolized Folic Acid (UMFA): HY-FOLIC® resulted in significantly lower levels of UMFA, which can accumulate in the bloodstream when folic acid is not fully metabolised, potentially causing adverse effects.[2]
- Clinical Importance in Specific Populations: This study highlights HY-FOLIC® as an ideal supplement for groups with higher folate demands, such as pregnant women, individuals with folate deficiencies/inadequacies, or those undergoing methotrexate therapy, where optimal folate availability is crucial.
1 Nafrialdi N and Suyatna FD. Pharmacokinetic study of HY-FOLIC and folic acid in health volunteers. International Journal of Applied Pharmaceutics, 16(6), 64–68.
2 Fardous AM and Heydari AR. Uncovering the Hidden Dangers of Molecular Mechanisms of Excess Folate: A Narrative Review. Nutrients 2023, 15(21), 4699.
3 Weiss D, et al. Scottsdale Magnesium Study: Absorption, Cellular Uptake, and Clinical Effectiveness of a Timed-Release Magnesium Supplement in a Standard Adult Clinical Population. J Am Coll Nutr. 2018 May-Jun;37(4):316-327.
4 Osburn SC, et al. Effects of 12-Week Multivitamin and Omega-3 Supplementation on Micronutrient Levels and Red Blood Cell Fatty Acids in Pre-menopausal Women. Front Nutr. 2021 Jul 13:8:610382.
5 Mazza A, et al. Nutraceutical approaches to homocysteine lowering in hypertensive subjects at low cardiovascular risk: a multicenter, randomized clinical trial. J Biol Regul Homeost Agents 2016; 30:921–7.
6 Cirillo M et al. 5-Methyltetrahydrofolate and Vitamin B12 Supplementation Is Associated with Clinical Pregnancy and Live Birth in Women Undergoing Assisted Reproductive Technology. Int J Environ Res Public Health. 2021, 18(23), 12280.
Ingredients mentioned

Quatrefolic®
Active ingredients
Folate: An innovative dietary ingredient designed to act as a nutrient in all areas where folic acid and folate supplementation is recommended and allowed.
Reproduction & Women’s
Wellness & Immune
Mobility & Joint
Fertility
Pregnancy
Menopause

Quatrefolic® Fine Powder
Active ingredients
Folate: Quatrefolic® Fine Powder is the new versatile form of folate, a new physical form with a finer and narrower particle size distribution of the raw material.
Reproduction & Women’s
Wellness & Immune
Mobility & Joint
Fertility
Pregnancy
Menopause
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