Countering Evolutionary Mismatch: A Targeted Bioenergetic and Circadian Protocol for Prefrontal Cortical Fatigue and Sensory Overload in Modern Environments

The human central nervous system evolved under ancestral selective pressures character-ized by cyclical diurnal solar irradiance, natural spectral filtering, high physical expenditure,and episodic rather than continuous demands on executive cognitive control. In sharpcontrast, modern techno-ecological environments subject the prefrontal cortex (PFC) topersistent high-energy visible (HEV) blue-wavelength radiation (450 –480 nm), unremittingmulti-stream attentional switching, and prolonged cognitive vigilance. This evolutionarymismatch precipitates a dual-axis pathology: localized bioenergetic collapse within Brod-mann Areas 9 and 46 (manifesting as a depletion of the phosphocreatine-to-ATP ratio andintracellular adenosine accumulation), alongside severe circadian dysregulation mediated byintrinsically photosensitive retinal ganglion cells (ipRGCs) and the suppression of pinealmelatonin synthesis via the retinohypothalamic tract.Here, we articulate an exhaustive, mechanistic framework integrating astrocyte-neuronmetabolic coupling, purinergic receptor kinetics (A1 and A2A), suprachiasmatic nucleus (SCN)hypothermic thermoregulation, and macular carotenoid optics. To counter this mismatch,we present a multimodal, translationally validated protocol: (1) high-efficiency cerebralbioenergetic replenishment via creatine monohydrate to saturate brain-type creatine kinase(CKB, EC 2.7.3.2) across the blood-brain barrier through the SLC6A8 transporter; (2) centraladenosinergic attunement via stoichiometric co-administration of L-theanine and caffeine(2 : 1 ratio) targeting glutamatergic-GABAergic balance and α-wave oscillatory coherence(8 –12 Hz ); (3) suprachiasmatic hypothermia and slow-wave sleep consolidation via glycine-induced peripheral vasodilation (mediated by SCN NMDA receptor co-agonist activation)compounded with high-bioavailability chelated magnesium bisglycinate; and (4) intraocularoptical filtration and reactive oxygen species scavenging via macular xanthophyll carotenoids(lutein and zeaxanthin) coupled with dynamic chronological spectral management.We provide precise receptor kinetic profiles, metabolic flux stoichiometry, dosing schedules,clinical biomarker monitoring paradigms, and safety parameters. This protocol establishes aclinically actionable blueprint to rescue prefrontal cognitive capacity and circadian home-ostasis in modern anthropogenic environments.Version 2.0: Expanded with long-chain PUFA membrane dynamics, Vitamin D3/K2 endocrine axis, SAMe transmethylation kinetics, intra-mitochondrial melatonin, and critical deconstruction of BCAA and antioxidant paradigms.