Nutritional and biological insights into natural α-glycerylphosphoryl derivatives (α-NGPs): a comprehensive review of α-GPA, α-GPC, α-GPE, α-GPI, and α-GPS

This is the first comprehensive review to systematically evaluate the entire family of natural alpha-glycerylphosphoryl derivatives (α-NGPs), redefining them as essential bioactive metabolites with critical impacts on neurocognition, membrane homeostasis, and mitochondrial dynamics. While α-glycerylphosphorylcholine (α-GPC) is widely studied for amplifying cholinergic neurotransmission and post-exercise growth hormone secretion, the physiological contributions of its structural analogs (α-GPA, α-GPE, α-GPI, and α-GPS) remain severely overlooked. We elucidate their interconnected biosynthetic pathways, highlighting synergistic benefits like the cooperative action of α-GPC and α-GPS in neuroprotection. Critically, we address an oxidative paradox where supraphysiological α-GPC intake induces localized stress, proposing a hypothetical mechanistic model in which α-GPA potentially neutralizes these adverse effects by inhibiting Drp1-mediated mitochondrial fission. To overcome severe analytical bottlenecks in quantifying trace α-NGPs, we advocate integrating multidimensional NMR, HRMS, FTIR, and HPLC. Furthermore, we highlight a commercial paradigm shift toward zero-waste, sustainable α-GPC production by valorizing fermentation by-products within a circular bioeconomy. Ultimately, exploiting the synergistic interplay among these metabolites necessitates a transition from single-molecule supplementation to multi-lipid strategies. Standardizing nomenclature and expanding rigorous analytical profiling are critical to fully harness the therapeutic potential of α-NGPs against neurodegeneration, metabolic dysfunction, and aging-related decline.