Phytomedicine. 2026 Oct 21;162:158870. doi: 10.1016/j.phymed.2026.158870. Online ahead of print.
ABSTRACT
BACKGROUND AND AIM: Standard therapies for diabetic kidney disease (DKD) reduce albuminuria but trigger an acute eGFR decline, limiting clinical initiation. We evaluated whether a standardized marine formula comprising oligo-fucoidan, fucoxanthin, and l-carnitine (FFL) provides potential renoprotective effects with stable renal function.
METHODS: Preclinically, diabetic CKD mice received FFL for 8 weeks. Clinically, a 12-week randomized trial evaluated adjunctive FFL in DKD patients receiving SGLT2 inhibitors (100%) and ACEIs/ARBs (85.5%). Efficacy was analyzed using baseline-adjusted robust ANCOVA (per-protocol, n = 55) and validated under intention-to-treat (ITT, n = 63) sensitivity analysis with Baseline Observation Carried Forward imputation.
RESULTS: Preclinically, FFL significantly attenuated renal dysfunction, tubulointerstitial fibrosis, and inflammation. Clinically, baseline-adjusted robust ANCOVA showed that adjunctive FFL achieved a highly significant, adjusted 39.40% greater reduction in UACR compared to control (Geometric Mean Ratio [GMR] = 0.60; 95% CI: 0.40-0.90; p = 0.01), which was validated under ITT-ANCOVA sensitivity analysis (adjusted 32.18% greater UACR reduction; GMR = 0.67; 95% CI: 0.48-0.93; p = 0.01). Crucially, eGFR remained stable and preserved over 12 weeks (PP adjusted GMR = 1.01, p = 0.74; ITT adjusted GMR = 1.01, p = 0.78). FFL also significantly lowered baseline-adjusted LDL (GMR = 0.85; 95% CI: 0.76-0.95; p < 0.01) with a baseline-dependent response maximizing at a 24.28% reduction in patients with baseline dyslipidemia (p < 0.01), while displaying preliminary, exploratory glycemic signals. No serious adverse events or significant potassium elevations occurred.
CONCLUSION: Standardized marine FFL is a safe, well-tolerated adjunctive therapy that reduces albuminuria and dyslipidemia while preserving stable renal hemodynamics over 12 weeks.
PMID:42966155 | DOI:10.1016/j.phymed.2026.158870