Synergistic Effects of Omega-3 Fatty Acids and Coenzyme Q10 on Gut Microbiota-Mediated Lipid Metabolism in Borderline Dyslipidemia: A Single-center Randomized Open Labeled Controlled Clinical Trial

Background: Borderline dyslipidemia is a prevalent cardiovascular risk factor for which pharmacological intervention is not always indicated. Omega-3 polyunsaturated fatty acids and coenzyme Q10 (CoQ10)  have been reported to influence lipid metabolism and oxidative status; however, their combined effects in individuals with borderline dyslipidemia remain unclear. Objective: This study aimed to explore the associations of combined supplementation with α-linolenic acid (ALA) and CoQ10 with lipid metabolism, gut microbiota, and serum metabolites in patients with borderline dyslipidemia. Methods: In a 12-week, single-center randomized, open-label controlled trial, 90 participants with borderline dyslipidemia were assigned to receive either ALA (1.6 g/d) plus CoQ10 (136 mg/d) or standard dietary and exercise guidance alone. Primary outcomes included changes in serum lipids, lipoprotein subfractions (by NMR spectroscopy), gut microbiota (16S rRNA sequencing), and serum metabolomic profiles. Results:  Eighty-two participants completed the trial. Compared with the control group, the Omega-3_Q10 group showed significantly different change-from-baseline values in multiple lipid parameters, with mixed directions of change. Exploratory analyses identified concurrent changes in selected lipoprotein subfractions, gut microbiota composition, bile acid-related metabolites, and antioxidant markers. Conclusions:  Combined supplementation with ALA and CoQ10 was associated with short-term changes in lipid-related and metabolic markers in individuals with borderline dyslipidemia. Given the exploratory nature of the analyses, short intervention duration, and absence of clinical cardiovascular endpoints, the long-term clinical implications of these findings remain uncertain and warrant confirmation in larger, prospective studies with defined clinical outcomes.