Butyrate producer ButyraGen demonstrates mood and brain support in clinical study

The patented butyrate generator ButyraGen from NutriScience demonstrates brain function and mood support through gut modification, according to a recently published clinical study. The short-chain fatty acid (SCFA) butyrate has implications for metabolism, immunity, and inflammation control, the study explains, with the need for more research on its potential effect on the gut-brain axis. Butyrate is produced from the fermentation of dietary fiber and supports the integrity of intestinal barriers, mucus production, and inflammation regulation, also contributing to brain health.

The study, “A Novel Butyrate Generator Helps Modulate the Gut-Brain Axis: A Randomized Double-Blind Placebo-Controlled Clinical Study,” was published in Nutrition and Dietary Supplements in December 2025.

Study design

The randomized, double-blind, placebo-controlled study involved 596 adults (32% males and 68% females, average age of 44 years) consuming either 200 mg per day of ButyraGen or placebo for six weeks. ButyraGen contained 50% tributyrin and about 45% fiber. The participants completed questionnaires on anxiety, depression, and functional outcomes. The study was fully virtual and the study population represented a diverse sample of US adults.

Highlighted results

The supplement demonstrated significant reduction of self-reported feelings of fear and unease, with notable effects in specific groups.

• Men reported higher improvements in anxiety compared with placebo, and the improvements began starting in week 2
• Participants less than 40 years old demonstrated significant reduction of feelings of helplessness, hopelessness, and depression
• Improvements in anxiety rates in the entire supplement group were 9.29% higher than in placebo
• For quality of life, participants who reported being “distracted” at baseline showed a 17.15% lower rate of distraction compared with placebo

Among overall benefits for depression, participants who did not have a gastrointestinal disease experienced a twofold greater likelihood of improvement in depression symptoms compared with placebo.

The results highlighted a potential targeted application for supporting brain function through the gut-brain axis. “These results suggest that ButyraGen may supports both psychological and physiological well-being, particularly in men, younger individuals, and those without gastrointestinal disease,” the researchers concluded. “Benefits began to appear within weeks two and three and were sustained through six weeks, highlighting its potential as a fast-acting intervention for both gut and brain health, indicative of the gut-brain axis connection.”

Impact on butyrate supplementation

The study suggested two possible and connected pathways for ButyraGen to influence brain function. First, an indirect route by improving physiological well-being by supporting gut physiology. Second, the direct route is by influencing brain function without gut function, modulating neuroinflammation and neurotransmitter synthesis.

“This is the first clinical study to show that directly generating butyrate from tributyrin can deliver gut-brain axis benefits that go beyond digestion,” explained study co-author Dr. Edward Dosz, Ph.D., NutriScience vice president of science and innovation, in a press release.² “By engaging the gut–brain axis, the two-way communication network between the gut and brain, ButyraGen® highlights a new, more holistic approach to whole-body and mental well-being.”

ButyraGen directly produces the SCFA in the small intestine, has a neutral aroma, and comes in powdered format.

An earlier study, published in June 2025, examined the effect of ButyraGen on gastrointestinal issues, specifically belly pain and digestive health, as well as quality of life.³ The 595 participants consumed either 200 mg of ButyraGen daily or placebo for six weeks. Starting at weeks 5 and 6, significant improvements in belly pain were seen, especially in women and post-menopausal women. Quality of life also showed improvements, and the ingredient was found to be well tolerated with mild or moderate side effects reported.

References

1. Dosz, E.; Conley, D.; Lelah M. A Novel Butyrate Generator Helps Modulate the Gut-Brain Axis: A Randomized Double-Blind Placebo-Controlled Clinical Study. Nutrition and Dietary Supplements. 2025.17:127-143 DOI: 10.2147/NDS.S565532
2. NutriScience Innovations. ButyraGen® Demonstrates Clinically Significant Gut– Brain Benefits in Groundbreaking New Clinical Study. January 2026. (Accessed 2025-01-14).
3. McEvoy, E. Clinical trial finds prebiotic complex significantly reduces belly pain in adults with GI issues. July 8, 2025. https://www.nutritionaloutlook.com/view/clinical-trial-finds-prebiotic-complex-significantly-reduces-belly-pain-in-adults-with-gi-issues (Accessed 2025-01-14).