New clinical research funded by the women’s health supplement brand Ritual has found that prenatal multivitamins containing 5-methyltetrahydrofolate (5-MTHF) — the active form of folate — instead of folic acid may help minimize levels of unmetabolized folic acid (UMFA) in pregnant women.
Additionally, it was found to maintain adequate folate levels in both mothers and babies.
The study involved Ritual’s Essential Prenatal supplement. The specialized multivitamin is formulated to support foundational health before and during pregnancy by filling common nutrient gaps.
The formula comprises twelve ingredients — including methylated folate, algae-based omega-3 docosahexaenoic acid, choline, and chelated iron — to support neural tube development and fetal brain health. These nutrients are delivered in a vegan, non-GMO, delayed-release capsule designed for optimal absorption and digestive comfort.
“This study allows us to directly compare how different supplemental forms of folate are processed during pregnancy,” says the study’s principal investigator, Dr. Xinyin Jiang, a professor of health and nutrition sciences at the City University of New York (CUNY).
“We found that 5-MTHF can maintain folate status just as effectively as folic acid, but with significantly less unmetabolized folic acid circulating in the body.”
Dangers of high supplement use
While folic acid is a commonly used synthetic form of folate in supplements and fortified in foods, the body must convert this into an active form (5-MTHF) before it can be used by cells.
When intake is too high, the body cannot process all of it. This leads to a buildup of unmetabolized folic acid (UMFA) in the bloodstream, which is becoming more commonly seen among consumers with high supplement use, according to Ritual.
Excessive UMFA is generally safe at low levels but is linked to potential health concerns. These include impaired immune function, accelerated cognitive decline, potential cancer progression, and masking vitamin B12 deficiencies, according to Allergy Research Group.
Published in Frontiers in Nutrition, the randomized, double-blind, controlled clinical trial spanned 24 weeks and involved 62 pregnant women in the second and third trimesters.
The study cohort included a broad range of participants, with an average age of 32 years, and varied educational and marital backgrounds. They were also racially and ethnically diverse: 33.9% identified as White, 29% as Black, 22.6% as Asian, and 14.5% as another race (of which 34% identified as Hispanic or Latino).
Participants in their second trimester were assigned to receive a prenatal multivitamin containing either 5-MTHF or synthetic folic acid and continued taking the supplements as directed until delivery.
The researchers found that 5-MTHF is effective at maintaining folate status, as there was no difference in total folate levels between groups.
There were significantly fewer individuals with detectable blood UMFA in the 5-MTHF group (7%) compared with the folic acid group (31%). Additionally, among those taking the supplement, the team recorded lower UMFA concentrations in maternal blood and in the placenta.
Dr. Mastaneh Sharafi, Ph.D., RD, and SVP of Science & Innovation at Ritual, notes there are still major gaps in prenatal nutrition research, underscoring the responsibility to help build that evidence base, particularly in diverse study populations.
Existing research has highlighted other nutrient gaps among pregnant women, including choline and omega-3s.
Ritual has committed US$5 million dollars to complete clinical trials for its entire product portfolio by 2030.
The brand has completed five clinical studies, having published the results of three in peer-reviewed journals.
“As a founder and a mother, I am deeply aware that women’s health, and specifically pregnancy, has long been underrepresented in clinical research,” says Katerina Schneider, founder and CEO of Ritual.
“By intentionally funding research in these often-excluded populations, we aim to not only evaluate our own products but also to proactively raise the bar for the entire industry and contribute to a deeper understanding of maternal and fetal nutrition.”