Optimizing Brain Biology Through Near-Infrared-Induced Mitochondrial Melatonin Synthesis: A Hypothesis Paper

The human brain consumes approximately 20% of total energy production despite comprising only 2% of body mass, rendering neurons particularly vulnerable to oxidative damage. Modern indoor lifestyles have dramatically reduced exposure to near-infrared (NIR) radiation, a component of sunlight that penetrates biological tissues. Concurrently, age-related declines in both pineal melatonin production and mitochondrial function have been implicated in the pathogenesis of neurodegenerative diseases. Additionally, aging is associated with declining availability of glutathione precursors, particularly glycine and cysteine, which may limit endogenous antioxidant responses even when enzymatic capacity is preserved. This hypothesis paper synthesizes evidence from photobiomodulation (PBM) research, mitochondrial biology, and melatonin biochemistry to propose a mechanistic framework whereby NIR radiation activates mitochondrial melatonin synthesis, potentially triggering an antioxidant cascade that may confer neuroprotection. The framework explicitly incorporates the requirement for adequate glutathione precursor substrate availability as a potential rate-limiting factor. A targeted narrative synthesis informed the development of the proposed mechanistic framework. Peer-reviewed publications were identified through searches of PubMed, Web of Science, and Google Scholar (1990-2025) using terms related to PBM, mitochondrial melatonin, glutathione metabolism, and neuroprotection. Studies were selected based on relevance to the proposed framework, with emphasis on mechanistic studies, randomized controlled trials, and systematic reviews. Priority was given to publications from 2020 to 2025, while seminal foundational studies were retained regardless of publication date. Evidence supporting each component of the proposed cascade was categorized by strength to maintain transparency regarding the distinction between established findings and untested hypotheses. The proposed NIR-mitochondrial melatonin-glutathione cascade represents a biologically plausible mechanism for endogenous neuroprotection, contingent upon adequate substrate availability. While substantial evidence supports individual components, the integrated hypothesis requires rigorous experimental validation. Concurrent attention to glutathione precursor status through glycine and N-acetylcysteine (NAC) supplementation may be necessary to realize the full therapeutic potential of this approach.