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

A 12-week randomized, double-blind, placebo-controlled human trial investigated whether adding a slowly fermentable fiber mixture to a high-protein, partially plant-based diet would improve insulin sensitivity and metabolic health in 44 adults with overweight or obesity and impaired glucose regulation. Participants were divided into two groups: one received 15 g/day of a fiber mix made from potato fiber and sugar beet pectin, while the other received an isocaloric placebo (maltodextrin). Both groups followed the same high-protein diet throughout the study.

Researchers measured insulin sensitivity using the hyperinsulinemic–euglycemic clamp (the gold-standard test for how well the body responds to insulin), along with fuel use (carbohydrate, fat, and protein oxidation), gut permeability, inflammatory markers, gut microbiota composition, and short-chain fatty acids, which are beneficial compounds produced when gut bacteria ferment fiber.

The results showed that, contrary to expectations, fiber supplementation did not improve insulin sensitivity. Instead, whole-body insulin sensitivity decreased in the fiber group compared with placebo (p = 0.034), while peripheral insulin sensitivity showed a similar downward trend. The placebo group, consuming the high-protein diet alone, showed improved metabolic flexibility, meaning their bodies were better able to switch between burning carbohydrates and fat. Fiber supplementation blunted this response by reducing insulin-stimulated carbohydrate oxidation and limiting fat oxidation suppression. The fiber group also showed a small but significant increase in distal gut permeability (p = 0.046), suggesting a weakening of the gut barrier in the lower intestine.

Despite being designed to increase beneficial microbial fermentation, the fiber mixture did not meaningfully change gut microbiota composition or fecal fermentation products. Circulating short-chain fatty acids were modestly higher in the fiber group overall, but these changes did not translate into improved metabolic outcomes. Protein oxidation increased in the placebo group but was prevented in the fiber group, which may indicate reduced protein digestion or absorption when fiber and protein were consumed together.

These findings suggest that adding isolated fiber supplements to a high-protein diet may interfere with some of the metabolic benefits of higher protein intake, rather than enhance them. The study highlights the complexity of fiber–protein interactions, especially in individuals with overweight or insulin resistance, and challenges the assumption that more fiber is always metabolically beneficial in every dietary context.

Limitations include the specific population studied, the fixed fiber dose, and the use of isolated fiber supplements rather than whole foods. Future research should examine different fiber types, doses, and delivery within whole-food diets, as well as longer-term interventions and more metabolically flexible populations.

Overall, this study reinforces that dietary context matters: the metabolic effects of fiber depend not only on the fiber itself, but on what it is consumed with, how it is fermented, and the metabolic state of the individual.