**Improved Plasma Lipids, Anti-Inflammatory Activity, and Microbiome Shifts in Overweight Participants: Two Clinical Studies on Oral Supplementation with Algal Sulfated Polysaccharide**

**Lauren A. Roach 1,\*, Barbara J. Meyer 1,\*, J. Helen Fitton <sup>2</sup> and Pia Winberg 3,\***


**Abstract:** Seaweed polysaccharides in the diet may influence both inflammation and the gut microbiome. Here we describe two clinical studies with an *Ulva* sp. 84-derived sulfated polysaccharide— "xylorhamnoglucuronan" (SXRG84)—on metabolic markers, inflammation, and gut flora composition. The first study was a double-blind, randomized placebo-controlled trial with placebo, and either 2 g/day or 4 g/day of SXRG84 daily for six weeks in 64 overweight or obese participants (median age 55 years, median body mass index (BMI) 29 kg/m2). The second study was a randomized double-blind placebo-controlled crossover trial with 64 participants (median BMI 29 kg/m2, average age 52) on placebo for six weeks and then 2 g/day of SXRG84 treatment for six weeks, or vice versa. In Study 1, the 2 g/day dose exhibited a significant reduction in non-HDL (high-density lipoprotein) cholesterol (−10% or −0.37 mmol/L, *p =* 0.02) and in the atherogenic index (−50%, *p =* 0.05), and two-hour insulin (−12% or −4.83 mU/L) showed trends for reduction in overweight participants. CRP (C-reactive protein) was significantly reduced (−27% or −0.78 mg/L, *p =* 0.03) with the 4 g/day dose in overweight participants. Significant gut flora shifts included increases in *Bifidobacteria*, *Akkermansia*, *Pseudobutyrivibrio*, and *Clostridium* and a decrease in *Bilophila*. In Study 2, no significant differences in lipid measures were observed, but inflammatory cytokines were improved. At twelve weeks after the SXRG84 treatment, plasma cytokine concentrations were significantly lower than at six weeks post placebo for IFN-γ (3.4 vs. 7.3 pg/mL), IL-1β (16.2 vs. 23.2 pg/mL), TNF-α (9.3 vs. 12.6 pg/mL), and IL-10 (1.6 vs. 2.1 pg/mL) (*p* < 0.05). Gut microbiota abundance and composition did not significantly differ between groups (*p* > 0.05). Together, the studies illustrate improvements in plasma lipids and an anti-inflammatory effect of dietary SXRG84 that is participant specific.

**Keywords:** seaweed; metabolic syndrome; prediabetes; sulfated polysaccharide; anti-inflammation; cholesterol; Ulva; microbiome
