Optifolin+® delivers superior folate bioavailability

A new clinical study published in Food & Nutrition Research has revealed that Balchem’s choline-enriched L-5-methyltetrahydrofolate (L-5-MTHF) folate ingredient, Optifolin+®, is 2.6 times more bioavailable and absorbed 3.5 times faster than standard folic acid in healthy adults.¹ These findings highlight several key benefits that give manufacturers a clear advantage when developing innovative, bioavailable and effective solutions, optimized to support cellular health at every stage of life.

Superior bioavailability, faster

The randomized, double-blind, controlled crossover study aimed to evaluate the relative bioavailability of Optifolin+® versus standard folic acid, comparing their pharmacokinetic profiles over 24 hours in healthy men and women aged 29-40 years. Researchers found that plasma concentrations of L-5-MTHF, the bioactive form of folate that is used by the body to support vital cellular functions, were significantly higher following Optifolin+® intake compared to those after folic acid.¹ This superior absorption was seen in both healthy men and women.¹ Optifolin+® also increased folate status (as 5-MTHF) by over 240% more than folic acid, and significantly faster, reaching maximum plasma levels of L-5-MTHF in under an hour compared to 2.8 hours with folic acid.¹ Additionally, Optifolin+® did not increase blood levels of unmetabolized folic acid (UMFA), unlike folic acid.¹ This is an important finding, as UMFA has no known biological function² and high levels of UMFA have been linked to health risks.³ 

Delivering bioactive folate the body can use

Also known as vitamin B9, folate is an essential nutrient that supports fundamental cellular functions and the production of key molecules such as DNA and RNA, amino acids, neurotransmitters and hormones.^4,5 Well established for its benefits in prenatal nutrition,^4,6 the vitamin’s role providing methyl (CH3) groups for DNA methylation, homocysteine metabolism and other crucial reactions in the body means that folate as L-5-MTHF also plays a key role in the lifelong support of brain health and cognitive function,⁷ cardiovascular health⁶ and epigenetic health.⁵

Currently, many supplements and fortified food and beverages rely on folic acid as a source of folate. However, folic acid is a synthetic form of vitamin B9, which must undergo several enzymatic conversion steps within the body to become the biologically active form, L-5-MTHF. This process is inefficient for a large proportion of consumers – up to 31% of the European population and 40% of the U.S. population for example – who carry variations in the MTHFR gene that can reduce the activity of the enzymes responsible for the final conversion of folic acid into L-5-MTHF.^8,9,10 For these individuals, traditional folic acid supplementation may not provide optimal folate status. Plus, with excessive intake of folic acid, the enzymatic metabolism also risks becoming overwhelmed, leading to UMFA build-up in the bloodstream.¹¹

Folic acid vs. folate: Debate solved with Optifolin+®

“Optifolin+® is the bioactive, choline-enriched L-5-MTHF form of folate, meaning it bypasses the metabolic bottlenecks and genetic hurdles that folic acid faces entirely,” comments Eric Ciappio, PhD, RD, Senior Manager, Nutrition Science, Balchem HNH. “These new study findings demonstrate how leveraging the bioactive form translates to real bioavailability advantages for consumers. Optifolin+® also goes a step further – providing seven times the methyl groups found in standard folate forms for methylation support, as well as excellent solubility and stability for ease of formulation. We are thrilled to see these benefits in action as part of our ongoing commitment to opening up innovation opportunities with this crucial vitamin.”

“Another exciting element of this trial is the broad demographics of participants," adds Lauren Eisen, Sr. Marketing & Business Development Manager, Minerals and Nutrients at Balchem. “While many studies have previously focused on women – due to the prominence of folate in prenatal nutrition – this new study expanded the scope to include healthy men and women across a wide age range and saw significant benefits. Now, with clinically-backed superior bioavailability in this wider population, as well as a seven-times methyl group advantage, Optifolin+® offers a powerful tool for supplement brands to create next-generation solutions to support health at all stages of life.”

For more information about Balchem and its choline-enriched folate, Optifolin+®, visit: https://balchem.com/hnh/mn/optifolinplus/

References

¹ Schön, C., Micka, A., Menzel, D., Wilhelm, M., & Obeid, R. (2025). Pharmacokinetics of (6S)-5-Methyltetrahydrofolate dicholine salt compared to folic acid: a randomized double-blind single dose cross-over study. Food & Nutrition Research.

² Obeid R, et al. (2013). Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects? J Perinat Med, 41(5): 469-83.

³ Troen, A. M., et al. (2006). Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. The Journal of nutrition, 136(1), 189-194.

⁴ Menezo, Y., et al. (2020). Methylation: an ineluctable biochemical and physiological process essential to the transmission of life. International journal of molecular sciences, 21(23), 9311.

⁵ Office of Dietary Supplements (2022) Folate – Fact sheet for health professionals. Available at: https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

⁶ Code of Federal regulations, Section 101.79: Folate and neural tube defects. (Updated 02 Dec 2024) Available at: https://www.ecfr.gov/current/title-21/chapter-I/subchapter-B/part-101#101.79

⁷ Moretti, R., & Caruso, P. (2019). The controversial role of homocysteine in neurology: from labs to clinical practice. International journal of molecular sciences, 20(1), 231.

⁸ Chita, D. S., et al. (2020). MTHFR gene polymorphisms prevalence and cardiovascular risk factors involved in cardioembolic stroke type and severity. Brain Sciences, 10(8), 476.

⁹ Pietruszyńska-Reszetarska, A., et al. (2024). Coronary Artery Disease Is Related to Methylation Disorders Caused by the c. 1286A> C MTHFR Polymorphism and to Low Serum 5-MTHF and Folic Acid Concentrations—Preliminary Results. Reports, 7(1), 6.

¹⁰ Karczewski, K. J., et al. (2020). The mutational constraint spectrum quantified from variation in 141,456 humans. Nature, 581(7809), 434-443.

¹¹ Sweeney, M. R., McPartlin, J., & Scott, J. (2007). Folic acid fortification and public health: report on threshold doses above which unmetabolised folic acid appear in serum. BMC public health, 7, 1-7.