Chlorella and Arthrospira (Spirulina) as Multi-Pathway Biological Response Modulators: Molecular Mechanisms, Signaling Pathways and Clinical Evidence

Chlorella and Arthrospira (spirulina) are aquatic microalgae of increasing nutraceutical interest due to their dense bioactive composition and multi-target biological activity. This narrative review provides a comparative, mechanistically integrated synthesis of molecular mechanisms and clinical evidence related to their supplementation. Current data indicate that both microalgae converge on three central regulatory axes: activation of Nrf2-dependent antioxidant responses, attenuation of NF-κB-driven inflammatory signaling, and modulation of AMP-activated protein kinase (AMPK)/protein kinase B (AKT)-mediated metabolic pathways. Spirulina demonstrates stronger mechanistic links to intracellular signaling and more consistent clinical evidence for improvements in lipid profile, insulin sensitivity, and systemic inflammation. In contrast, chlorella provides complementary effects, particularly in antioxidant capacity, blood pressure regulation, gut microbiota modulation, and detoxification-related contexts. Their bioactive components—including phycocyanin, carotenoids, polysaccharides, and peptides—act synergistically to influence mitochondrial function, immune homeostasis, and metabolic resilience. While clinical findings are generally consistent, heterogeneity in study design and product standardization limits definitive conclusions. Overall, chlorella and spirulina emerge as complementary multi-pathway biological response modulators with potential applications in preventive and integrative medicine.