Methylation is a cellular process in which carbon units (or methyl groups) are added to molecules such as DNA, influencing its function and expression. Disruptions in DNA methylation patterns are associated with genomic instability, and insufficient availability of methyl donor nutrients such as folate can contribute to genomic disruptions over time.
Writing in the Journal of Dietary Supplements, scientists from the University of Arkansas for Medical Sciences report that Optifolin+ may increase the primary methyl donor in cellular metabolism, S-adenosylmethionine (SAM), by 71% and enhance cellular DNA methylation inside the cell by up to 14x over a 96-hour period.
“Folate plays a foundational role in cellular function, yet, modern lifestyle factors from stress or suboptimal diets can affect methylation efficiency. For brands looking to innovate beyond traditional folate products, understanding biological performance matters,” said Lauren Eisen, sr. marketing and business development manager, Minerals and Nutrients, Balchem Corporation – Human Nutrition & Health.
“This latest research demonstrates how Optifolin+’s unique choline-enriched structure translates into meaningful cellular activity. These findings provide a stronger scientific foundation for next-generation healthy aging and epigenetic health solutions.”
Optifolin+
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.
Well established for its benefits in prenatal nutrition, 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, cardiovascular health and epigenetic health.
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.
Balchem launched Optifolin+, which is a combination of folate (L-5-MTHF) and choline (VitaCholine), in 2024.
Data from 2025 randomized, double-blind, controlled crossover study, published in Food & Nutrition Research, reported that the ingredient is 2.6 times more bioavailable and absorbed 3.5 times faster than standard folic acid.
Researchers in Germany found that not only were plasma concentrations of L-5-MTHF, the bioactive form of folate that is used by the body to support vital cellular functions, significantly higher following Optifolin+ intake compared to those after folic acid, but folate status (as 5-MTHF) was also increased by more than 240%, compared to folic acid.
Study details
For the new study, the Arkansas-based researchers used HepaRG cells and treated them with different doses of Optifolin+ ranging from 0 to 40 nM for 96 hours.
While SAM increased by 71% at 40 nM, the researchers reported a modest decrease in S-adenosylhomocysteine (SAH), a biomarker of impaired cellular methylation capacity, at the 1 nM dose. Methionine, the essential amino acid precursor for S-adenosylmethionine (SAM), did not change across doses.
The ingredient was also associated with selected increases in DNA methylation at different repetitive elements, stretches of DNA that occur over and over again throughout the genome.
“These findings support 5-MTHF-DCh as a modulator of methyl-donor status with measurable epigenetic endpoints in a human hepatic cell model, and provide mechanistic evidence relevant to further evaluation of this folate-choline ingredient,” wrote the researchers.
Source: Journal of Dietary Supplements, 2026;23(4):461-474. doi: 10.1080/19390211.2026.2680313. “(6S)-5-Methyltetrahydrofolate Dicholine Salt Modulates Methyl-Donor Metabolites and Repetitive-Element DNA Methylation in HepaRG Cells”. Authors: K. Clement, et al.
