Natural compounds as potential countermeasures for spaceflight-associated neuro-ocular syndrome

Spaceflight-Associated Neuro-Ocular Syndrome (SANS) is a complex and multifactorial condition most commonly observed following long-duration spaceflight. Clinical findings of SANS include optic disc edema, retinal nerve fiber layer swelling, globe flattening, chorioretinal folds, and hyperopic refractive shifts. As human space exploration extends toward prolonged missions such as Artemis and Mars expeditions, SANS represents a significant risk to astronaut health and mission success. Although headward fluid shifts, elevated intracranial pressure, venous outflow congestion, and lymphatic dysfunction have been implicated in SANS pathophysiology, no single unifying mechanism or universally effective countermeasure has been identified. Emerging evidence suggests that oxidative stress from galactic cosmic radiation, endothelial dysfunction, inflammation, mitochondrial injury, altered angiogenesis, and disruptions in one-carbon metabolism contribute meaningfully to SANS development. This review summarizes the clinical manifestations and proposed mechanisms underlying SANS and examines naturally occurring compounds with high therapeutic indices that target these pathways. Specifically, we review bilberry anthocyanins with French maritime pine bark extract, Ginkgo biloba extract, saffron/crocin, curcumin, coenzyme Q10, resveratrol, vitamin E, and B vitamins as potential supplemental approaches, highlighting their mechanisms of action and therapeutic efficacy when targeting terrestrial ocular diseases. While direct studies in spaceflight environments remain limited, these compounds demonstrate antioxidant, anti-inflammatory, neuroprotective, vasoregulatory, and metabolic effects relevant to SANS. Collectively, they represent promising adjunctive candidates within a multimodal preventative strategy aimed at mitigating SANS risk during long-duration spaceflight.