Could Saffron, Curcumin, and Other Natural Compounds Protect Astronauts’ Eyes in Deep Space?

Long-duration spaceflight changes more than an astronaut’s muscles and bones. It can quietly reshape the eye itself. Spaceflight-Associated Neuro-Ocular Syndrome, or SANS, is a constellation of findings that includes optic disc edema, swelling of the retinal nerve fiber layer, flattening of the back of the eyeball, chorioretinal folds, and shifts in refraction toward farsightedness of roughly 0.50 to 1.75 diopters. First systematically described in 2011, the syndrome typically emerges on missions lasting 30 days or longer, and about 48 percent of astronauts report hyperopic shifts after long-duration flight compared with only 23 percent after short missions. Although many changes improve once crews return to Earth, some astronauts have shown persistent globe flattening, chorioretinal folds, and refractive shifts documented up to a year after landing. With NASA’s Artemis program and eventual Mars expeditions on the horizon, SANS has been designated a high-priority risk, and a new review in Frontiers in Ophthalmology argues that the countermeasure toolkit may need to include something unexpected: natural compounds borrowed from terrestrial ophthalmology.

The review, authored by R. Mikal Lange and Tasneem P. Sharma of Indiana University School of Medicine, takes stock of why SANS has proven so stubborn. On Earth, hydrostatic pressure gradients push one to two liters of fluid toward the legs when a person stands upright, keeping intracranial pressure relatively low. In microgravity that gradient disappears, and fluid redistributes toward the head. Contrary to early expectations, lumbar puncture data and ground-based analogues suggest intracranial pressure in orbit is only mildly elevated, but it stays elevated chronically because astronauts cannot assume an upright posture. This persistent mild elevation narrows the translaminar pressure gradient across the lamina cribrosa, the meshwork where the optic nerve exits the eye, which may help drive posterior globe flattening, optic disc edema, and remodeling of the optic nerve head. Optic disc edema is detected in roughly 70 percent of crew members on long missions, appearing as early as flight day 30 and progressing throughout flight.

Mechanical forces are only part of the story. Microgravity also impairs cranial venous outflow: astronauts have shown stagnant retrograde flow in the internal jugular veins, one documented case of in-flight jugular vein thrombosis, and greater increases in dural venous sinus volumes among those who developed SANS. Emerging magnetic resonance imaging evidence points to glymphatic dysfunction as well, with perivascular spaces in white matter and basal ganglia enlarging from preflight to postflight in proportion to SANS severity. Meanwhile, galactic cosmic radiation and microgravity generate a robust oxidative stress response, producing reactive oxygen species that damage DNA, proteins, and lipids, alongside endothelial dysfunction, disrupted nitric oxide signaling, and chronic low-grade inflammation. A recent analysis even suggested that SANS may involve retinal vascular rarefaction rather than the pathological neovascularization seen in wet macular degeneration and diabetic retinopathy. Crucially, the pattern of Bruch’s membrane deformations in SANS differs from idiopathic intracranial hypertension, and one modeling study proposed that anteriorly directed force from orbital fat swelling in microgravity may press on the globe more powerfully than pressure changes alone.

Because no single unifying mechanism has been proven, Lange and Sharma hypothesize that mitigating SANS will require a multimodal approach hitting oxidative, inflammatory, microvascular, and metabolic pathways simultaneously. That is where natural compounds enter the picture. The authors argue that in space, where medical resources are limited and even mild side effects can be consequential, agents with high therapeutic indices are especially attractive. They frame these compounds primarily as prophylactic countermeasures, administered before and during flight to blunt the injury cascades that drive SANS, rather than as cures for established pathology. Their evidence base is drawn from terrestrial eye diseases, chiefly glaucoma, age-related macular degeneration, and diabetic retinopathy, which converge with SANS on the same downstream pathways of oxidative stress, endothelial dysfunction, and inflammation even though the diseases themselves are distinct.

The first candidate, Mirtogenol, combines bilberry anthocyanins with French maritime pine bark extract. Its constituents scavenge reactive oxygen species, upregulate antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, boost nitric oxide production to relax blood vessels, and stabilize leaky retinal capillaries. In a prospective controlled trial of 38 people with elevated intraocular pressure, Mirtogenol lowered pressure from about 25.2 to 22.0 millimeters of mercury over two to three months while improving blood flow in the central retinal, ophthalmic, and posterior ciliary arteries, and a Wistar rat glaucoma model showed reduced retinal ganglion cell apoptosis. The authors stress that the rationale in space is not pressure lowering, since in-flight intraocular pressure rises only about 1.3 millimeters of mercury on average, but rather antioxidant, anti-inflammatory, and vasoprotective effects that could counter venous congestion. Safety data across six months showed no observed adverse effects.

Ginkgo biloba extract, particularly the standardized EGb 761 formulation, offers a complementary profile. Its flavonoids scavenge reactive oxygen and nitrogen species, its terpenoids upregulate reducing enzymes including catalase and heme-oxygenase 1, and the extract improves blood rheology by promoting erythrocyte deformability, raising nitric oxide, and lowering fibrinogen, thereby inhibiting microthrombus formation. Studies in normal-tension glaucoma have yielded mixed results on visual field preservation, with one four-year observational study reporting significant improvement while a four-week randomized crossover trial in 28 patients found no benefit. However, human studies consistently show increased ophthalmic artery and retrobulbar blood flow velocities, and rodent work demonstrates increased choroidal blood flow. Systematic reviews found no significant difference in adverse events versus placebo across 80 to 600 milligrams daily, though one review flagged a possible association with bleeding risk that a 50-volunteer coagulation study failed to confirm.

Saffron and its constituents crocin and crocetin bring a different mechanism: activation of the NRF2 transcription factor, which switches on endogenous antioxidant genes, plus suppression of the pro-inflammatory NF-κB pathway and demonstrated enhancement of oxygen diffusion and ocular blood flow in animal studies. In clinical trials, saffron preserved visual acuity and retinal flicker sensitivity in age-related macular degeneration, lowered intraocular pressure as an adjunct to timolol and dorzolamide in a pilot glaucoma study, and improved central macular thickness, visual acuity, and HbA1c in diabetic maculopathy at 15 milligrams daily. Doses under 1.5 grams per day show no excess adverse events, and therapeutic ocular doses run 15 to 50 milligrams daily, giving the spice a high therapeutic index. Curcumin, the turmeric-derived polyphenol, scavenges free radicals, blocks NF-κB, induces heme oxygenase-1, and restored mitochondrial function in a rodent ischemia-reperfusion glaucoma model. Yet the authors caution a critical caveat: curcumin and resveratrol are both anti-angiogenic, and since SANS may involve retinal vascular rarefaction, dampening new vessel growth could theoretically backfire.

The remaining candidates round out four overlapping mechanistic domains. Coenzyme Q10 sits at the heart of the mitochondrial electron transport chain and acts as a potent antioxidant; in a 106-patient trial, a regimen including 30 milligrams daily improved visual field mean defect and foveal sensitivity in macular degeneration, and glaucomatous mice given CoQ10 showed greater retinal ganglion cell survival. Resveratrol upregulates NRF2 and HO-1 antioxidant pathways and suppresses NF-κB, reducing TNF-α, IL-1β, and IL-6, with observational data in wet macular degeneration showing fewer anti-VEGF injections over 24 months. Vitamin E isoforms have demonstrated radioprotective properties, shielding mouse bone marrow and human CD34+ cells from radiation damage, which is directly relevant to cosmic ray exposure, though the NIH tolerable upper limit of 1,000 milligrams daily must be respected to avoid bleeding complications. B vitamins occupy a uniquely SANS-specific niche: astronauts with detectable SANS showed 25 to 45 percent higher serum homocysteine, cystathionine, and methylmalonic acid, and polymorphisms in the one-carbon metabolism genes MTRR and SHMT1 have been linked to chorioretinal folds and optic disc edema, with B-vitamin status predicting ocular outcomes.

The authors are careful to underline how preliminary all of this remains. No spaceflight or analogue studies of these compounds have been conducted, and a single documented in-flight case, in which an astronaut with two genetic risk factors received B6, methylfolate, B12, and riboflavin from flight day 153, showed improvement but was confounded by natural disease course and a simultaneous reduction in cabin carbon dioxide. Practical hurdles also loom: pharmaceuticals degrade faster in space due to radiation, humidity swings, and vibration, so any countermeasure must survive a multi-year Mars mission without resupply, and altered pharmacokinetics in microgravity could change how supplements are absorbed and cleared. To move forward, the review proposes two testable hypotheses: that pre- and in-flight supplementation with an antioxidant or vasoregulatory compound reduces optic disc edema and choroidal thickening, and that combining metabolic supplementation with mechanical countermeasures such as lower body negative pressure yields additive protection. Head-down tilt bed rest, supine bed rest, and rodent unloading models that reproduce retinal nerve fiber changes now offer tractable platforms to put kitchen-sack pharmacology to the test before the first crew leaves for the Red Planet.

Subject of Research: Natural compounds as potential countermeasures for spaceflight-associated neuro-ocular syndrome

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

Article References: Lange, R. M., & Sharma, T. P. (2026). Natural compounds as potential countermeasures for spaceflight-associated neuro-ocular syndrome. Frontiers in Ophthalmology, 6, Article 1801651. https://doi.org/10.3389/fopht.2026.1801651

Image Credits: AI Generated

DOI: 10.3389/fopht.2026.1801651

Keywords: spaceflight-associated neuro-ocular syndrome, SANS, microgravity, oxidative stress, astronaut vision, natural compounds, Mirtogenol, Ginkgo biloba, saffron, curcumin, coenzyme Q10, B vitamins