Frontiers in Science and Engineering · Apr 22, 2026
Clinical Evaluation of an AKG-PQQ-Agaricus bisporus Composition for Mitochondrial Function and Healthy Aging
By Ziraoui NE, González M, Romano S
Background: A formulation centered on alpha-ketoglutarate (AKG), pyrroloquinoline quinone disodium salt (PQQ), and Agaricus bisporus extract is intended to support mitochondrial resilience through complementary energetic, redox, and cytoprotective mechanisms. Objective: We evaluated the translational and clinical relevance of this combination by integrating our formulation-level comparison data with published human clinical evidence for AKG-related interventions, PQQ, and ergothioneine-rich mushroom or ergothioneine supplementation. Methods: We retained the original composition framework and in vitro comparison of the study formulation and matched them with publicly available human intervention studies identified from primary biomedical literature. Results: In our formulation comparison, the index composition was associated with higher relative mitochondrial membrane potential and lower mitochondrial reactive oxygen species than the comparator that omitted Agaricus bisporus extract. Across human studies, PQQ showed the most mature evidence base, with randomized trials reporting improvements in inflammatory markers, selected cognitive domains, muscle strength, and some indices related to mitochondrial biogenesis. Ergothioneine-containing mushroom and purified ergothioneine trials demonstrated human bioavailability, safety, and signals in cognition, sleep-related outcomes, and skin hydration. Direct completed efficacy trials for AKG in healthy-aging settings remain limited, although active randomized trial programs indicate strong translational interest. Conclusions: The combined evidence supports a credible mitochondria-focused rationale for the AKG-PQQ-Agaricus bisporus composition, but a registered head-to-head randomized trial of the full formulation is still needed before superiority claims can be made.