This randomized, double-blind, placebo-controlled, parallel-group clinical trial evaluated the effects of colon-targeted riboflavin on the gut microbiome in healthy older adults aged 50 to 70 years. A total of 348 participants were randomized to receive riboflavin at doses of 1.4, 10, or 75 mg/day, or placebo. The study duration was 12 weeks. Primary and secondary outcomes included changes in fecal microbial composition, microbiome function, host health biomarkers, and gastrointestinal symptoms.
Regarding microbial composition, no significant changes were observed in overall community-wide diversity metrics between groups. However, the relative abundance of several microbial taxa was significantly altered compared with placebo. Specifically, alpha diversity and total species counts showed within-group increases at week 12 with the 10 mg dose. HACK index values, indicating greater community resilience, were also higher at week 12 with the 10 mg dose. Distinct shifts in KEGG module abundance were observed, including enhanced potential for riboflavin biosynthesis.
Metabolic markers showed dose-specific effects. Fecal butyrate concentrations were higher at week 4 versus placebo with the 75 mg dose. Additionally, the dysbiosis index was significantly reduced within groups receiving the 1.4 mg dose. The study did not report absolute numbers, p-values, or confidence intervals for these specific findings. Safety and tolerability data were not detailed in the provided results. Key limitations include the healthy study population, which may limit generalizability to patients with dysbiosis, and the absence of reported clinical outcomes or quality-of-life improvements. The evidence is observational regarding clinical relevance, as no adverse events or efficacy in disease states were captured.
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Vitamin B2 (riboflavin) is a key redox cofactor that may modulate gut microbial ecology, yet conventional supplements are absorbed proximally and have limited colonic exposure. We evaluated whether colon-targeted riboflavin alters microbiome composition, function and network structure as well as host biomarkers in healthy older adults. In a randomized, double-blind, placebo-controlled, parallel-group clinical trial (N=348; 50-70 years), participants received colon-targeted riboflavin (1.4, 10, or 75 mg/day) or placebo for 12 weeks. The primary endpoint was the change in fecal microbial composition, while secondary endpoints encompassed microbiome function, host health biomarkers, and clinical outcomes. Shotgun metagenomics and fecal/blood biomarkers were assessed at baseline, week 4, and week 12. Although no significant changes were observed between groups in overall community-wide diversity metrics (alpha and beta diversity), colon-delivered riboflavin significantly altered the relative abundance of several microbial taxa compared with placebo. The most pronounced effects on microbiome composition, function, and network structure were observed with the 10 mg dose at week 12, reflected by within-group increases in alpha diversity, the largest rise in total species counts, higher HACK index values indicating greater community resilience, and distinct shifts in KEGG module abundance, including enhanced potential for riboflavin biosynthesis. Supplementation with 75 mg riboflavin led to higher fecal butyrate concentrations at week 4 versus placebo, while the lowest dose (1.4 mg) significantly reduced the dysbiosis index within groups and modestly improved network structure across groups. All three doses (1.4, 10, and 75 mg) influenced keystone species abundance. No between-group differences were observed for gastrointestinal symptoms, quality-of-life measures, fecal pH, high-sensitivity C-reactive protein (hs-CRP), calprotectin, or soluble CD14, except for an increase in plasma riboflavin concentrations at 75 mg after 12 weeks, indicating colonic absorption. The product was safe and well-tolerated across all doses. These findings indicate that colon-targeted riboflavin can act as a functional modulator of the human gut microbiome, with the most consistent effects observed at 10 mg and additional dose-specific effects at 1.4 mg and 75 mg. Future studies are warranted to establish related health benefits, either as a standalone intervention or in combination with classical pre-, pro-, or postbiotics, particularly in target populations such as individuals with IBS, stress, mild cognitive decline, or early metabolic or inflammatory alterations.
