Obesity is associated with altered physiology and changes in the gut microbial community. This randomized, double-blind, placebo-controlled trial evaluated whether daily chitosan supplementation combined with structured lifestyle changes affects health factors and gut microbiota composition in females with obesity. The trial is registered as NCT04551365.
The study was conducted as a randomized, double-blind, placebo-controlled clinical trial reported in Molecular Nutrition & Food Research (2026). A total of 33 Icelandic females with obesity (BMI range 30.0–54.1 kg/m2) were randomized to receive either LipoSan Ultra chitosan (3 g/day; TRG, n = 18) or placebo (PLG, n = 15) for 12 weeks while participating in a structured lifestyle intervention. Data collection occurred at four time points: baseline (T1), two weeks (T2), post-intervention (T3), and two weeks after the intervention end (T4).
Enrolled participants were Icelandic females meeting the BMI criteria for obesity. Randomization allocated participants to chitosan or placebo arms; both participants and investigators were blinded. The supplement dose was 3 g/day of LipoSan Ultra chitosan for 12 weeks. All participants received an interdisciplinary, structured lifestyle program administered alongside supplementation. The study included secondary subgroup analyses stratified by BMI (< 40 vs ≥ 40 kg/m2).
Clinical evaluations included vital signs and blood markers. Anthropometric measures used DXA to quantify body composition (fat mass and lean mass). Functional assessments included grip strength, endurance testing, and self-rated health questionnaires. Mean arterial pressure and other physiologic measures were recorded. Assessments took place at T1 (baseline) and T3 (post-intervention); some measures were repeatedly sampled across additional time points described above.
Fecal samples were collected at T1, T2 (2 weeks), T3, and T4 (2 weeks post-intervention). Gut microbiota profiling used 16S rRNA sequencing, with analysis performed at the amplicon sequence variant (ASV) level and rarefied data. Community-level differences were assessed using Bray–Curtis distance matrices, visualized by Principal Coordinates Analysis (PCoA), and tested with PERMANOVA. Differential abundance testing used ANCOM-BC2. The study reported trace values for PCoA analyses (TRG and PLG values provided) and considered P ≤ 0.05 statistically significant for reported comparisons.
Across BMI groups, the structured lifestyle intervention produced measurable improvements in health and function. Participants experienced reduced body fat mass and increased lean mass as quantified by DXA. Functional gains included increased grip strength and improved endurance. Mean arterial pressure decreased, and self-rated health improved. These benefits were observed independently of weight loss, indicating that the structured lifestyle changes improved body composition and physical function even without large changes in total body weight.
Overall, chitosan supplementation was associated with a reduction in the Firmicutes/Bacteroidota ratio, suggesting an effect on gut microbial community composition. However, ANCOM-BC2 did not identify any differentially abundant taxa between groups. Participants with BMI ≥ 40 kg/m2 showed a decrease in microbiota diversity over time. Principal Coordinates Analysis illustrated community distances across time points in the chitosan and placebo groups, and PERMANOVA was used to assess statistical differences. The authors caution that subgroup and microbiota findings are constrained by the study's sample size.
Safety parameters were monitored during the trial; details of specific adverse event rates are not reported in the abstract. The authors declared no conflicts of interest. Full text and figures, including flowcharts of recruitment and analysis, are available in the journal publication and associated PMC entry.
The trial shows that an interdisciplinary, structured lifestyle program improved body composition and physical function in females with obesity, independent of weight loss. Supplementation with 3 g/day chitosan for 12 weeks modulated gut microbiota composition as reflected by a lower Firmicutes/Bacteroidota ratio, but no specific taxa reached differential abundance using ANCOM-BC2. The study's interpretation is limited by its small sample size and the exploratory nature of subgroup microbiota analyses. The authors recommend larger, longer-term studies that stratify outcomes by BMI to better evaluate chitosan's therapeutic potential and to clarify clinical relevance of microbiota changes.