Glaucoma specialists typically consider treatment in terms of topical medications, laser procedures, and surgery. However, patients often ask whether lifestyle modifications can complement medical therapy. One area of interest is food and dietary supplements. Although dietary modification does not replace established glaucoma treatments, it may enhance standard therapy.
The pathophysiology of glaucoma is multifactorial, with several proposed mechanisms, including mechanical stress on the optic nerve related to elevated intraocular pressure (IOP), impaired ocular blood flow, neurodegeneration associated with mitochondrial dysfunction and oxidative stress, immune and inflammatory pathways, and genetic predisposition. Specific nutrients have been proposed to target neurodegenerative, oxidative stress–related, and inflammatory mechanisms implicated in glaucoma development. This article reviews current data on the potential effects of nutritional supplementation on glaucoma progression.
Antioxidants
Antioxidants neutralize damage caused by reactive oxygen species (ROS) by stabilizing them through electron donation. Glaucoma development may be driven, in part, by ROS-mediated injury to retinal ganglion cells (RGC) and the optic nerve head, leading to neurodegeneration.1 Mechanisms of cellular damage include lipid peroxidation, DNA damage, and protein modification.2 Recent literature has explored whether increasing the bioavailability of antioxidants through supplementation may help mitigate these processes.
Vitamin C
Vitamin C (ascorbic acid) is found in foods such as citrus fruits, green and red peppers, and strawberries and exhibits both nonenzymatic3 and enzymatic antioxidant effects. It can directly neutralize ROS through electron donation and also support endogenous antioxidant enzymes as a cofactor.4 In a cross-sectional study of 1,168 eyes from African American patients older than 65 years, intake of more than 2 servings per week of oranges and peaches was associated with lower odds of glaucoma compared with intake of fewer than 1 serving per week.5 Another study reported lower serum vitamin C levels in patients with normal-tension glaucoma compared with healthy controls.6
Vitamin A
Vitamin A (retinol) consists of retinoids and carotenoids and is present in vegetables such as carrots and spinach.7 Dietary vitamin A intake of at least 1,400 retinol equivalents (RE) has been associated with a lower incidence of glaucoma in women compared with intake of fewer than 800 RE.8 Higher dietary intake of vitamin A and alpha-carotene has also been associated with a protective effect against glaucoma, with a borderline but not statistically significant association observed for beta-carotene.5 The Rotterdam Study reported an increased risk of open-angle glaucoma with lower retinol intake8 and a decreased risk with higher consumption of vitamin A–rich foods.9
Retinoic acid functions as a transcription factor that upregulates myocilin.10 Myocilin is a glycoprotein expressed in trabecular meshwork (TM) cells and is involved in regulation of aqueous humor outflow. Misfolded myocilin has been shown to cause intracellular aggregation and apoptosis of TM cells, impaired aqueous outflow, and the development of primary open-angle glaucoma (POAG).11-13
Vitamin E
Vitamin E (tocopherol) and its related compounds are well recognized for their antioxidant properties and are found in foods such as almonds, hazelnuts, and plant oils.14 In glaucoma, vitamin E has been proposed to improve vasoregulation. In a study of patients with glaucoma of various etiologies, oral vitamin E supplementation (300 to 600 mg/day) was associated with improved ocular blood flow and prevention of visual field progression compared with controls.15
Carotenoids
Lutein and zeaxanthin are non–vitamin A carotenoids concentrated in the macular lutea.16 In a prospective guinea pig study, supplementation with lutein and zeaxanthin produced an intraocular antioxidant effect and reduced RGC loss.17 In a human study, higher intake of foods containing these carotenoids was associated with a lower incidence of glaucoma.5
Saffron is composed of the carotenoid derivatives crocin and crocetin, both of which act as radical scavengers and exhibit proangiogenic and antiapoptotic properties.18 In a pilot study of patients with POAG, 4 weeks of oral saffron extract supplementation was associated with a mean IOP reduction of 3.2 mmHg compared with placebo; this effect was not sustained after discontinuation.19 A controlled animal study demonstrated protection of rat photoreceptors from photo-oxidative damage, with preservation of photoreceptor morphology and function in saffron-treated animals.20 In vivo studies have shown that crocin improves retinal and choroidal perfusion and may protect against RGC apoptosis through activation of the PI3K/AKT signaling pathway and scavenging of reactive oxygen species.21,22
Flavonoids and Phenols
Flavonoids are naturally occurring polyphenols with neuroprotective and antioxidant properties.23 They are found in high concentrations in citrus fruits and tea.24,25 Clinical data suggest slowed glaucomatous visual field progression in patients receiving oral flavonoids.26 Multiple experimental studies have demonstrated neuroprotective effects of flavonoids in cultured human and rat RGCs, with prolonged cell survival despite exposure to oxidative and hypoxic stress.27,28 In a crossover randomized controlled trial, patients with ocular hypertension and open-angle glaucoma who received the flavonoid epigallocatechin gallate showed improvement in pattern electroretinogram measures compared with placebo.29
One flavonoid-rich compound of particular interest is Ginkgo biloba extract (GBE), which has demonstrated vasoregulatory, antioxidant, and neuroprotective effects.30-32 Preclinical data suggest that GBE supplementation reduces vasospasm, increases central and peripheral blood flow, and inhibits apoptosis, potentially mitigating vascular dysregulation implicated in glaucoma.33,34 In a study of 45 patients with POAG, a month of antioxidant and GBE supplementation was associated with increased blood flow in the retinal and retrobulbar circulation.35 GBE may be particularly beneficial in glaucoma subtypes that progress despite adequate IOP control, such as normal-tension glaucoma (NTG) or high-tension glaucoma with normalized IOP.36 Three studies in patients with NTG have reported associations between GBE supplementation and improved visual field function.37-39
Anthocyanins, another class of flavonoid polyphenols found in berries, also exhibit antioxidant, neuroprotective, and vasoprotective properties.40,41 In vitro studies suggest that the strong free radical–scavenging activity of anthocyanins protects retinal pigment epithelial cells.42 In a randomized controlled trial, patients with POAG who received black currant anthocyanins for 24 months demonstrated improvements in ocular blood flow and visual field parameters compared with controls.43 In addition, a retrospective chart review reported improved visual function in patients with NTG who received bilberry anthocyanins compared with controls.38
B Vitamins
B vitamins obtained from dietary sources or supplements represent the nutritional class with the most robust evidence for neuroprotective and antioxidative effects, particularly vitamins B3 (nicotinamide), B12 (cobalamin), B6 (pyridoxine), B1 (thiamine), and B2 (riboflavin). Meats and legume seeds are rich sources of B vitamins.44-46 Among these, nicotinamide has been the most extensively studied.
Nicotinamide is a nontoxic precursor of nicotinamide adenine dinucleotide (NAD+), a critical substrate in complex I of the mitochondrial electron transport chain responsible for adenosine triphosphate production.47 Nicotinamide has been associated with reduced oxidative damage from protein oxidation and lipid peroxidation, as well as axonal neuroprotection and prevention of neurodegenerative disease.48,49 Age-related declines in NAD+ contribute to mitochondrial dysfunction and have been linked to RGC loss.50 Animal studies have shown that nicotinamide prevents optic nerve excavation and axonal loss in mice51 and reduces ischemic and phototoxic injury in rat RGCs.52 In both animals and humans, nicotinamide has been shown to stabilize blood flow in the retina and optic nerve head.53
Independent of IOP, nicotinamide demonstrates strong neuroprotective effects in glaucoma. In a mouse study, the lowest administered dose (equivalent to approximately 2.7 g/day for a 60-kg human) protected 70% of eyes from glaucomatous neurodegeneration, whereas the highest dose (equivalent to approximately 9.8 g/day) protected 93%.54,55 Human studies have also demonstrated potential antiglaucoma effects. In a randomized controlled trial of 57 patients with early to moderate glaucoma, nicotinamide supplementation was associated with improvements in inner retinal function and visual field measures compared with placebo.56 Additional reviews and randomized controlled trials have reported short-term improvements in visual field sensitivity with nicotinamide supplementation, although long-term effects remain uncertain.57,58 Even niacin, another form of vitamin B3, has shown potential benefit; in a cross-sectional population-based study, higher niacin intake was associated with lower glaucoma risk, whereas lower intake was associated with glaucoma development.59
Vitamins B12 and B6 serve as cofactors in homocysteine metabolism. Elevated homocysteine levels are associated with vascular dysfunction, oxidative stress, and RGC apoptosis, mechanisms that may contribute to glaucomatous optic neuropathy. In addition, both vitamins exhibit direct neuroprotective properties. Vitamin B12 acts as a superoxide scavenger in neuronal cells, including RGCs,60 and vitamin B6 has antioxidant effects.61 In a cross-sectional case-control study, patients with pseudoexfoliation glaucoma had lower serum levels of vitamins B12 and B6 compared with controls.62 In another large cross-sectional study of participants with self-reported glaucoma, higher vitamin B6 intake, and to a lesser extent vitamin B12 intake, was associated with a lower incidence of glaucoma.63
Vitamins B1 and B2 may also confer protective effects. In a prospective cohort study of 7,983 participants, lower vitamin B1 intake was associated with an increased risk of open-angle glaucoma.8 In a cross-sectional cohort study of 1,115 women older than 65 years, dietary vitamin B2 intake of 2 mg/day or greater was associated with a lower likelihood of a glaucoma diagnosis compared with intake of less than 1 mg/day.64 Another cross-sectional study similarly found that higher vitamin B2 consumption was associated with a reduced risk of glaucoma.59
Conclusion
Although numerous supplements are commercially available and present in specific foods, glaucoma specialists must critically appraise the evidence to provide data-driven guidance to patients. Among the supplements discussed, nicotinamide currently has the most robust scientific support for potential protection against glaucoma. Other B vitamins and antioxidants demonstrate promising preclinical findings, but clinical data supporting their use as glaucoma treatments remain limited. Available evidence is heterogeneous, and some studies have reported no association between glaucoma and supplementation with vitamins B1, B2, B6, B12, or antioxidants.65-69 Confounding factors may also have influenced the results of certain studies. Additional long-term randomized controlled trials are needed to better define the efficacy of dietary modification and supplementation. Nonetheless, current research suggests a potential role for nutrient-rich foods and dietary supplements as preventive and adjunctive approaches in glaucoma management.70 GP
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