Abstract
BACKGROUND: Butyrate is a health promoting short-chain fatty acid (SCFA) metabolite of fiber fermentation in the gut. Supplementing directly with a butyrate generator may be a dietary alternative with health benefits. OBJECTIVE: To evaluate the effect of tributyrin, a butyrate generator, on tolerability, gut microbiome composition, gut permeability, inflammation and metabolic markers in healthy adults at two dose levels. METHODS: Healthy adults (n = 29) were randomized to this single-blinded, two-arm, 28-day parallel design pilot study. Participants ingested one or two placebo capsules for 7 days followed by one or two (200 or 400 mg, respectively) ButyraGen® capsules, a novel tributyrin complex, daily for 21 days. Tolerability was assessed weekly by questionnaire. Blood and stool were collected at baseline and weekly for metabolic and inflammation markers, gut microbiome composition and SCFA concentrations, respectively. Urine was collected at baseline and end of the study for permeability assays. RESULTS: Twenty-four participants (n = 24, 25±8 years; 24.0±2.8 kg/m2; 66% male) completed the study. ButyraGen® was well-tolerated, with less than 10% (n = 2) reporting gastrointestinal-related discomfort. Fecal acetic (p = 0.03) and propionic (p = 0.03) acids decreased after supplementation (p = 0.03 and p = 0.03, respectively, n = 24) compared to baseline, and triglycerides increased (p = 0.02, 400 mg only, n = 11). Trends in decreased hs-CRP after 200 mg (p = 0.08) and 400 mg (p = 0.07) supplementation and decreased glucose (p = 0.10) after 200 mg supplementation was observed. No other changes in endpoints were observed. CONCLUSIONS: Tributyrin supplementation using ButyraGen® was safe and tolerable at the doses provided. Biological effects were observed suggesting butyrate generation and absorption in the small intestine followed by activity in the liver, though further investigation on mechanism of action is needed for confirmation.
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