The research funded by NutriScience Innovations and published in Nutraceuticals used a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of ButyraGen on self-reported GI health in 596 participants across the US.
The results “suggest potential applications for managing digestive discomfort and improving overall digestive quality of life,” wrote Edward Dosz and Michael Lelah from NutriScience Innovations and Devin Conley from Conley Labs. The study was designed and executed by Radicle Science.
Butyrate supplement for digestive health
The short-chain fatty acid (SCFA) butyrate plays a key role in gut health by reducing inflammation, strengthening the gut barrier and promoting a balanced microbiome. It is produced in the gut by bacteria during the fermentation of dietary fiber or can be consumed in supplement form.
In the gut, butyrate enhances the mucosal layer by signaling for the production of proteins and mucus that seal and protect intestinal walls, which can help prevent “leaky gut” and digestive issues like IBS.
ButyraGen is a patent-pending supplement that has been designed to generate butyrate without the “off-putting aroma” of some other sources.
As Dosz told NutraIngredients, ButyraGen uses tributyrin, an odorless triglyceride form where butyrate is chemically bound to glycerol.
“This ester bond in tributyrin, along with our fiber complex, significantly reduces odor and ensures stability during handling and storage,” he explained.
“Once ingested, ButyraGen is broken down by digestive enzymes to release butyrate directly where it’s utilized, not relying on fermentation or the state of the microbiome.”
“This ester bond prevents the butyrate from volatilizing and releasing its strong, rancid smell during handling or storage,” he explained.
“Once ingested, digestive enzymes break down tributyrin inside the gut, safely releasing butyrate where it’s needed without causing odor issues.”
As well as tributyrin, it contains Sunfiber - a partially hydrolyzed guar fiber, and in previous research it was found to reduce stool acetate and propionate levels, elevated quantities of which can be associated with IBS.
ButyraGen supplement reduces belly pain and bloating
Participants were recruited online and through Radicle’s email list, and all were adults over age 21 who wanted to improve their digestive health.
The researchers randomly assigned participants to either the ButyraGen or placebo group and instructed them to take the product daily for six weeks.
ButyraGen, supplied by NutriScience Innovations, contained 200 mg of a complex including tributyrin (100 mg) and prebiotic fibers (90 mg). The placebo used maltodextrin, and both products were encapsulated identically to maintain blinding.
Participants completed demographic and diet surveys, along with baseline health questionnaires. Throughout the study, they completed validated weekly assessments via SMS or email, including a DQLQ (Digestion-associated Quality of Life Questionnaire) and self-reported scores on belly pain, gas and bloating, constipation, diarrhea, reflux, and nausea and vomiting.
Results showed that participants in the active group showed an 18% greater reduction in belly pain compared to the placebo, and week-by-week analysis revealed consistently greater improvement in the active group, especially during weeks five and six.
“This evidence confirms that ButyraGen can provide broad-spectrum, practical digestive support, bridging the gap between fiber fermentation and direct butyrate supplementation without the odor or tolerance issues of free butyric acid,” said Dosz.
Additionally, post-menopausal women were found to experience the most significant improvements in belly pain and gas/bloating when taking ButyraGen from week five onwards, whereas men did not show significant changes.
“The sex-specific differences likely relate to the estrobolome, the collection of gut microbes that metabolize and regulate circulating estrogen levels,” said Dosz.
“Butyrate, generated by ButyraGen, helps strengthen the gut barrier and modulate inflammation, which may help normalize reabsorption of estrogen and support more balanced hormone levels. Additionally, ButyraGen may help maintain tight junction integrity and microbial diversity, key factors influencing how the estrobolome functions.
He noted that those combined actions could explain why post-menopausal women, who often have shifts in estrogen balance and gut microbiome composition, saw pronounced benefits.
The research was conducted virtually with no in-clinic visits, using a series of validated questionnaires, which the researchers note represents real-world conditions and a diverse U.S. population. This meant they couldn’t collect blood or stool samples, preventing the correlation of perceived digestive health with measurable digestive biomarkers.
They add that the delayed onset of some benefits suggests that further research could extend a trial period to uncover additional health benefits. Furthermore, the sex-specific differences invite an investigation into the biological mechanisms driving variations.
Source: Nutraceuticals 2025, 5(2), 14; doi: 10.3390/nutraceuticals5020014 “A Novel Direct Butyrate Generator Reduces Belly Pain in a Randomized, Double-Blind, Placebo-Controlled Clinical Study.” Authors: E. Dosz, et al.
