*2.1. Participants Study 1*

Sixty-five participants in Study 1 were randomly assigned to the three blinded treatment groups. This assignment resulted in 21 participants being assigned to the placebo group, 21 participants to the 2 g dose of extract group, and 23 participants to the 4 g dose of extract group. One participant who was assigned to the 4 g dose of extract group withdrew consent due to reasons unrelated to the study (Figure S1 during the trial and so 64 participants completed the trial. Study participants had a median age of 55 years and a median BMI of 29 kg/m2. There were more female (*n* = 40) than male (*n* = 24) participants recruited, but the distribution of gender was not significantly different between the treatment groups (*p =* 0.26) so the population was analyzed as one. There were no significant differences at baseline between the three treatment gro ups for any of the outcome measures (Table 1).

**Table 1.** Baseline demographics across treatment groups in Study 1.


Data presented as median, 25th, and 75th percentile. SXRG84—sulfated xylorhamnogalactouronan, BMI body mass index, HDL—high-density lipoprotein, LDL—low-density lipoprotein, TG—triglyceride, CRP—Creactive protein, HOMA IR—Homeostatic model assessment for insulin resistance. <sup>1</sup> Log-transformed variable, \* Nonparametric Kruskal–Wallis test; § *n* = 19 for 2-h insulin due to missing data (Placebo = 6, 2 g = 6 and 4 g = 7).

There were no significant changes post intervention between the three treatment groups. However, given the differences in metabolic flexibility between overweight and obese participants, a secondary data analysis was conducted comparing overweight and obese participants. The baseline characteristics of overweight and obese participants only are shown in Table 2. As expected, there were significant differences between overweight and obese participants; notably an 18% increase in BMI, a 67% increase in CRP, a 47% increase in HOMA, a 36% increase in C-peptide, a 49% increase in fasting insulin, and a trend towards a 47% increase (*p =* 0.07) in insulin following a two-hour OGTT in the obese participants compared to the overweight participants.


**Table 2.** Comparison of overweight and obese participants at baseline in Study 1.

Median (25th and 75th percentile). <sup>1</sup> *t*-test on log10-transformed data. <sup>2</sup> *t*-test on square root-transformed data. \* nonparametric Wilcoxon signed-rank test used for nonparametric data. § *n* = 10 overweight and 7 obese for 2-h insulin levels due to missing data.

However, the baseline parameters between the three treatment groups (placebo, 2 g, and 4 g) did not differ in either the overweight participants or the obese participants (Table 3).
