Clinical study demonstrates bioavailability and absorption of folate ingredient Optifolin+

According to recently published results from a randomized, double-blind cross-over study, the ingredient Optifolin+ (L-5-methyltetrahydrofolate [L-5-MTHF] folate) from Balchem demonstrates higher bioavailability than folic acid.¹ It also demonstrated superior absorption in adults compared to standard folic acid. As explained in a November 3 press release, Optifolin+ is a choline-enriched folate, delivering seven times the methyl groups that are found in other folate products.² It is also combined with Balchem’s choline brand VitaCholine and intended for supporting cellular health at all life stages. The clinical study, “Pharmacokinetics of (6S)-5-Methyltetrahydrofolate dicholine salt compared to folic acid: a randomized double-blind single dose cross-over study,” was published in Food & Nutrition Research in September 2025.

Study design

The study compares the effects of one oral dose of the test product ((6S)-5-MethylTHF-2Cho, Optifolin+) and standard folic acid in eight healthy adults, both men and women. Blood samples were taken regularly over 24 hours after the dose to measure plasma concentrations.

Results: increased bioavailability and absorption

After taking the dose (in capsules), of (6S)-5-MethylTHF-2Cho, the folate bioavailability of (6S)-5-MethylTHF was 1.64-fold higher in plasma total folate, and 2.56-fold higher for plasma, compared to folic acid.

Additionally, maximum folate concentrations were reached faster (0.8 hours) after the intake of (6S)-5-MethylTHF-2Chol compared to the intake of folic acid (2.8 hours).

It was also noted that a significant increase in unmetabolized folic acid (UMFA) concentration occurred after the intake of folic acid, but not after intake of (6S)-5-MethylTHF-2Chol. High levels of UMFA, the press release explains, is associated with health risks.

“The bioavailability of (6S)-5-MethylTHF-2Chol is higher compared to folic acid,” the researchers concluded. “The crystalline structure of (6S)-5-MethylTHF-2Chol and its water solubility are advantageous in terms of stability in nutraceutical products and absorption in the gut. (6S)-5-MethylTHF-2Chol is the source of folate that may enable the development of new applications.”

No serious adverse events were reported during the study.

Applications for supplementations

The press release from Balchem noted the potential for formulation innovations 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,” stated Eric Ciappio, PhD, RD, senior manager, nutrition science, Balchem HNH, in the press release. “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.”

It also noted the significance of the participants included in the study.

“Another exciting element of this trial is the broad demographics of participants," added Lauren Eisen, senior marketing and 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.”

References

1. Schön, C.; Micka, A.; Menzel, D.;Wilhelm, M.; Obeid, R.Pharmacokinetics of (6S)-5-Methyltetrahydrofolate dicholine salt compared to folic acid: a randomized double-blind single dose cross-over study. Food & Nutrition Research, 2025. 69. DOI: 10.29219/fnr.v69.12633
2. Balchem. New Clinical Study Confirms Optifolin+® Delivers Superior Folate Bioavailability and Rapid Absorption Compared to Folic Acid. November 3, 2025.