Effects of a slowly fermentable fiber mixture against the background of a high-protein diet on insulin sensitivity and metabolic health in individuals with overweight: a randomized, placebo-controlled trial.
van Kalkeren C, van Deuren T, et al. • Gut microbes • 2025
Fibers combined with a high-protein diet reduced peripheral insulin sensitivity and decreased metabolic flexibility compared to placebo, and coadministration of fiber and protein may compromise gut barrier function and inflammatory responses.
Key Findings
Results
Peripheral insulin sensitivity tended to decrease after fiber supplementation compared to placebo.
Trend toward decrease in peripheral insulin sensitivity in fiber group versus placebo (p = 0.081)
Whole-body insulin sensitivity significantly decreased in the fiber group compared to placebo (p = 0.034)
Study used a 12-week randomized, placebo-controlled design with fiber group (n = 19) versus maltodextrin placebo group (n = 21)
Both groups followed a high-protein diet (25E% protein, ±45% plant-based)
Results
Fiber supplementation mitigated the increase in insulin-mediated carbohydrate oxidation that occurred in the placebo group.
Fiber mitigated the increase in insulin-mediated carbohydrate oxidation compared to placebo (p = 0.027)
Fiber also mitigated the decrease in fat oxidation that occurred in the placebo group (p = 0.006)
These findings indicate decreased metabolic flexibility in the fiber group relative to placebo
Results
Fiber supplementation prevented an increase in protein oxidation observed in the placebo group.
Fiber prevented an increase in protein oxidation compared to placebo (p = 0.048)
Authors interpreted reduced protein oxidation after fiber as potentially reflecting diminished amino acid bioavailability
Both groups were on a high-protein diet (25E% protein)
Results
Fiber supplementation increased colonic gut permeability compared to placebo.
Colonic gut permeability was significantly increased in the fiber group compared to placebo (p = 0.046)
Authors suggest coadministration of fiber and protein may compromise gut barrier function
The fiber supplement consisted of potato fiber and sugar beet pectin, designed to increase distal SCFA production
Results
Fiber supplementation increased plasma interleukin-6 levels compared to placebo.
Plasma interleukin-6 was significantly increased in the fiber group compared to placebo (p = 0.025)
Authors suggest this may reflect a compromised inflammatory response related to coadministration of fiber and protein
This finding was contrary to the hypothesis that distal SCFA production would improve cardiometabolic health
Results
Body composition, microbial composition, fecal and circulating metabolites remained unchanged between the fiber and placebo groups.
No significant differences were found in body composition between groups after 12 weeks
Microbial composition did not significantly differ between the fiber and placebo groups
Fecal and circulating metabolites were also unchanged between groups
The fiber supplement was designed to increase distal SCFA production based on in vitro evidence, but this was not reflected in the measured metabolite outcomes
Background
The study was designed to improve metabolic health by increasing distal colonic SCFA production while inhibiting proteolytic fermentation using a fiber supplement that had shown increased distal SCFA production in vitro.
The fiber mixture of potato fiber and sugar beet pectin was selected because it increased distal SCFA production in vitro
Most dietary fibers are fermented proximally, resulting in increased protein fermentation distally, producing metabolites putatively harmful to metabolic health
The trial ran for 12 weeks with adults with overweight/obesity
The primary outcome was peripheral insulin sensitivity assessed against a background of a high-protein diet
van Kalkeren C, van Deuren T, Coenjaerds M, Galazzo G, Barnett D, Penders J, et al.. (2025). Effects of a slowly fermentable fiber mixture against the background of a high-protein diet on insulin sensitivity and metabolic health in individuals with overweight: a randomized, placebo-controlled trial.. Gut microbes. https://doi.org/10.1080/19490976.2025.2606473