Our study found that patients with glaucoma and cataract who took a daily antioxidant supplement showed an increase in BAP, a biomarker of the antioxidant capacity of the body. This may be an important finding, because the development and progression of cataracts are known to be promoted by oxidative damage to the proteins comprising the lens. Oxidative stress may also play an important role in glaucoma, which is an age-related chronic neurodegenerative disease. Our results are particularly interesting for patients with a low antioxidant level and suggest that antioxidant supplementation may be effective in treating them.
BAP was significantly higher than baseline at weeks 8, 12, and 16, while MDA level was significantly reduced at week 8. MDA is an end product of free radical reactions in membrane fatty acids . A variety of antioxidant molecules can be found in human plasma, with the following compounds being most common: α-tocopherol, β-carotene, albumin, ascorbic acid, bilirubin, catalase, ceruloplasmin, ferritin, glutathione peroxidase, lycopene, reduced glutathione, SOD, and uric acid . All these compounds can catalytically remove reactive species such as free radicals. After taking our novel supplement, the antioxidative level increased in the subjects in this study. The higher the level of antioxidative activity, the lower the level of oxidative stress.
A multiple regression analysis showed that SOD, total bilirubin, and diabetes were independent contributing factors to changes in antioxidative potential after supplementation in both the cataract and glaucoma groups. This means that our supplement was effective in patients with a low antioxidative stress level. This is especially interesting for glaucoma, which can sometimes progress even with successful IOP-lowering treatment. There is extensive clinical evidence that systemic oxidative stress contributes to glaucomatous optic neuropathy. Moreover, antioxidant therapy has shown promising results in animal- and human-based research. Antioxidant treatment can decrease the activation of NF-κβ and decrease the production of cytokines in the optic nerve and retina . In a rat glaucoma model, overexpression of thioredoxins can protect the RGCs . Higher green leafy vegetable intake is associated with a lower primary OAG risk . Lee et al. found that ginkgo biloba extract protected against the effects of glaucoma in some patients . These results suggest that insufficient serum antioxidant proteins underlie the contribution of oxidative stress to glaucoma, suggesting that antioxidants should have a neuroprotective effect. Our past research also showed that visual field damage was strongly correlated with systemic antioxidant levels in young, male patients with OAG . Antioxidant treatments might therefore be a useful therapeutic option to delay or prevent disease progression.
Previously, Maekawa et al. reported that three food-derived compounds, hesperidin, tamarindus indica, and crocetin, had a protective effect in a primary culture of retinal cells under oxidative stress. Hesperidin is effective in reducing apoptosis, oxidative stress and inflammation. Maekawa confirmed that hesperidin was effective in vivo in mice, reducing oxidative stress and preventing RGC death caused by NMDA-induced excitotoxicity . Tamarindus indica is indigenous to tropical Africa. It is high in tartaric acid, B vitamins, and minerals. It has antioxidant [29, 30], anti-inflammatory , anti-diabetic , and anti-atherosclerotic effects . Crocetin is a natural apocartenoid dicarboxylic acid that is found in the crocus flower and in Gardenia jasminoides. Crocetin has various effects, acting as an antioxidant  and anti-inflammatory , and can inhibit the caspase pathway, preventing retinal damage induced by N-methyl-D-aspartate (NMDA) . These results suggest that these three food-derived compounds, used as a dietary supplement, might help reduce RGC degeneration in retinal disease.
Systemic oxidative stress may be a key factor in the development of cataracts [37, 38]. Past findings support the idea that antioxidant therapy is effective for cataract patients. Nuclear opacities have been reported to be associated with nutrients (folate, α-carotene, and dietary fiber) from the intake of foods, particularly vegetables . Chylack et al. found that an oral antioxidant slightly slowed cataract progression . Another study found that subjects who received multivitamin/mineral supplementation had a 36% lower prevalence of nuclear cataracts . Hayashi et al. compared the total amount of hydroperoxides in the aqueous humor before and after supplementation with an antioxidant, Ocuvite Lutein , and found that hydroperoxides decreased in female, but not in male, subjects. That study suggested that it might be possible to inhibit oxidative stress in the aqueous humor and the lens epithelium. Lutein has been investigated by several in vitro studies, and has been reported to lower the intracellular accumulation of H2O2 by scavenging both H2O2 and superoxides . Lutein supplementation of lens epithelial cells has also been reported to decrease protein oxidation, lipid peroxidation and DNA damage induced by H2O2 . Based on these data, we consider that a decreased general oxidative stress level after supplementation may result in a reduced oxidative stress level in the aqueous humor, potentially delaying cataract progression.
Our study has some limitations. First, it lacked a placebo arm, which is needed to prove the efficacy of any supplement. Thus, we plan to conduct further studies with a randomized, doubled-blind, placebo-controlled design. Second, while we observed significant differences in BAP before and after supplementation, we did not make a similar finding for dROMs. Nevertheless, the improvement in BAP after supplementation for eight weeks was significant. This discrepancy might have been due to an increase in oxidative stress after supplementation, causing increased endogenous antioxidant activity. Finally, we could not include a control group, because all potential candidates already had cataracts, due to their advanced age. We were also limited in our ability to detect relatively modest associations, making longer follow-up of the subjects necessary in a future study.
Our study indicates that patients with a low systemic antioxidant level may have increased susceptibility to oxidative stress, thereby accelerating the progression of cataract and glaucoma. This raises the possibility that antioxidant supplementation may be a viable option to delay or prevent age-related cataracts and glaucoma progression.