Among diabetic patients, the most common complications leading to vision loss are diabetic macular edema (DME) and diabetic retinopathy (DR).1,2 In recent years, numerous in vitro and in vivo studies have highlighted the potential benefits of various dietary nutrients in managing DR, citing their neuroprotective, vasoprotective, anti-inflammatory, and antioxidant properties.³ This article reviews the current evidence on the role of dietary nutrients in the prevention and management of diabetic retinopathy.
Carotenoids
Lutein and zeaxanthin are yellow-orange pigments known as carotenoids that are abundant in green leafy vegetables and accumulate in the macula. Both serum and retinal levels of lutein and zeaxanthin have been associated with reducing the risk and severity of DR.3,4 Studies using human retinal pigment epithelial (RPE) cells have shown that lutein can block the increase in intracellular reactive oxygen species (ROS) caused by high glucose levels, reduce oxidative stress markers, and protect against oxidative damage.5,6 Similar protective effects have been observed in animal models, where lutein and zeaxanthin supplementation reduced oxidative stress and inflammation while enhancing antioxidant enzyme activity.7,8 These carotenoids also help maintain mitochondrial function and protect against mitochondrial dysfunction, which is significant in the context of DR.8 Furthermore, lutein and zeaxanthin have been shown to reduce inflammation by decreasing proinflammatory cytokines such as nuclear factor (NF-κB) and interleukin-1β (IL-1β), thereby mitigating changes associated with DR progression, including increased cell permeability and apoptosis.8-10
In a retrospective study involving 120 eyes of 60 patients with type 2 diabetes mellitus (T2DM), with or without DR or DME, supplementation with lutein, zeaxanthin, and meso-zeaxanthin resulted in an increase in central foveal thickness and improved retinal function.11 These results emphasize the importance of carotenoids, particularly lutein and zeaxanthin, as valuable adjuncts in the prevention and management of diabetic retinopathy and its associated complications.
Curcumin
Curcumin, a yellow lipophilic polyphenol, is the major bioactive component of Curcuma longa (turmeric). It belongs to the group of phytochemicals and is considered a pleiotropic molecule, offering a wide range of effects, including antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties.12 Increasing evidence suggests that curcumin may offer protection against DR, primarily through its anti-inflammatory and antioxidant properties.13,14
Curcumin has been shown to reduce retinal thinning and prevent cell death in the retinal ganglion cell and inner retinal layers.15 It also helps reduce capillary basement membrane thickening and protects the photoreceptor membranes from damage. In 1 study, curcumin treatment at a dose of 1 g/kg body weight for 16 weeks in diabetic rats reduced hyperglycemia, decreased levels of proinflammatory cytokines, increased antioxidant enzyme activity, and prevented retinal damage.16 Another study demonstrated that curcumin effectively repaired and regenerated the choroidal microvasculature in diabetic rats by improving and restoring the health of choroidal blood vessels affected by diabetes.17
Further research by Mrudula and colleagues, using a streptozotocin-induced diabetic rat model, showed that an 8-week curcumin treatment significantly reduced VEGF expression in the retina compared to the control group.18 In a human clinical study, the effects of a fixed combination of curcumin, artemisia, bromelain, and black pepper were evaluated in patients with DR. Notably, this supplementation improved central retinal thickness, visual acuity, and retinal sensitivity in people with and without DME.19,20
Another clinical study showed a synergistic effect of curcumin together with Boswellia serrata to improve baseline central macular thickness and best-corrected visual acuity over time.21,22
However, curcumin is poorly bioavailable, so further studies are necessary to enhance bioavailability and its associated effects in humans.21,22
Coenzyme Q10
Coenzyme Q10 (CoQ10), also referred to as ubiquinone, is a fat-soluble molecule that is synthesized de novo by animal cells. It is found in all cell membranes and primarily functions as a cofactor for mitochondrial enzymes that are essential for ATP production. In its reduced form, CoQ10 provides both direct and indirect antioxidant effects.23 Two randomized, double-blind, phase 2a, placebo-controlled studies confirmed the antioxidant effects of CoQ10.24,25 In these studies, 60 patients with nonproliferative diabetic retinopathy (NPDR) without DME were randomized into 3 groups: 1 received 400 mg of CoQ10, another received a combination of antioxidants (including lutein, astaxanthin, zeaxanthin, vitamin C, vitamin E, zinc, and copper), and the third received placebo. After 8 months, both the CoQ10 and combined antioxidant groups showed a significant reduction in lipid peroxidation products, nitrites/nitrates, and an increase in total antioxidant capacity compared to placebo.24,25 Further research is necessary to establish the efficacy of CoQ10 in protecting patients with DR and related ocular complications.24,26
Zinc
Zinc is the second most prevalent trace element in the human body and plays a vital role as an essential micronutrient and cofactor for numerous enzymes and transcription factors.27 Zinc levels are often lower in individuals with diabetes, and supplementation may offer protective effects against oxidative damage during the early stages of the disease.28,29 In a randomized trial, Kheirouri et al studied 50 patients with DR who received either 30 mg of zinc daily or a placebo for 3 months.30 The study evaluated the impact on VEGF, brain-derived neurotrophic factor, and nerve growth factor. Notably, there was a negative correlation between VEGF levels and zinc levels, suggesting a possible association between zinc status and the progression of DR.30 Ultimately, zinc appears to reduce lipid peroxidation and retinal damage in diabetes, potentially offering protection against retinal degeneration and DR by helping regulate glucose levels and reduce oxidative stress.30,31
Polyunsaturated Fatty Acid Omega-3.
Omega-3 fatty acids are essential polyunsaturated fatty acids (PUFAs) that must be obtained through dietary sources such as chia seeds, certain fish species, and fish oil. These fatty acids have strong antioxidant and anti-inflammatory properties, which contribute to their protective role in preventing retinal diseases, including DR.23,24 In addition to omega-3s, the retina also contains omega-6 PUFAs like arachidonic acid, which are important for maintaining membrane structure and facilitating cellular signaling.23
Kowluru et al examined the long-term effects of omega-3 PUFA supplementation in a DR rat model.8 Results demonstrated that the supplementation effectively prevented the development of DR, preserved retinal function, and reduced inflammatory markers compared to the control group.
The large-scale PREDIMED study further supports the beneficial effects of omega-3 PUFAs in patients with T2DM.32 A substudy of PREDIMED revealed a lower incidence of DR among participants who consumed at least 500 mg of omega-3 PUFAs per day, an amount that can be easily achieved with 2 servings of oily fish per week.
Both preclinical and clinical findings indicate that omega-3 PUFAs are promising for preventing and potentially treating DR.32 However, more research is needed to clarify their therapeutic role and to evaluate the long-term effects of supplementation in diabetic populations.8
Vitamin A
Vitamin A, commonly referred to as retinol, is a fat-soluble vitamin that plays a crucial role in the function of rhodopsin and serves as an essential nutrient for retinal photoreceptors.33 A recent study involving 11,727 individuals found that higher blood levels of vitamin A were linked to a reduced risk of DR, particularly among men and adults under the age of 60.34,35 In another study examining 60 patients with T2DM, researchers observed that lower serum levels of both zinc and vitamin A were associated with more severe cases of DR.34 Taken together, these findings suggest that vitamin A may have an important role in DR pathogenesis.35
B Vitamins
The B vitamins, a group of water-soluble vitamins, have been linked to DR in various studies. Satyanarayana et al found that patients with DR had lower levels of vitamin B12, suggesting a potential link to hyperhomocysteinemia.36 Research has also shown that lower blood levels of vitamin B1 in individuals with T2DM were associated with greater severity of DR.37 In the case of vitamin B6, 1 investigation involving Japanese patients with T2DM revealed that higher dietary intake was related to a reduced risk of developing DR.38 Similarly, another study reported that daily vitamin B6 supplementation in doses ranging from 50 mg to 200 mg was associated with a lower long-term incidence of the condition.39 Smolek et al investigated the combined effect of vitamins B6, B9, and B12 in NPDR.40 Notably, patients exhibited improved retinal sensitivity and reduced central retinal thickness.40 Additionally, the Diabetes Visual Function Supplement Study evaluated a vitamin complex that included B1, C, D3, E, omega-3 PUFAs, curcumin, zinc, and other nutrients in type 1 or type 2 DM who had no retinopathy or only mild to moderate NPDR.41 After 6 months, participants demonstrated significantly better visual function compared to those in the placebo group.41
Vitamin E
Vitamin E is a fat-soluble vitamin and potent antioxidant. Several observational studies have reported that individuals with DR exhibit significantly lower serum levels of vitamin E than those without DR.43,45 In a randomized, double-masked, placebo-controlled crossover trial, vitamin E supplementation significantly improved retinal blood flow in patients with type 1 diabetes.46 Additional studies have shown significant reduction in DME and decreased microbleeds with vitamin supplementation, although these conditions were worse in placebo participants.47 These findings suggest that vitamin E may provide protective benefits in managing and potentially reducing the risk of DR progression.
Vitamin D
Vitamin D is an essential micronutrient that functions as a steroid hormone and is synthesized in the skin as cholecalciferol following sunlight exposure.48 Numerous studies have indicated an inverse relationship between vitamin D levels and DR, although the causal mechanisms remain uncertain.49-51 A meta-analysis revealed that diabetic individuals with vitamin D deficiency were at a significantly greater risk of developing DR.52 Similarly, a cross-sectional study involving 517 diabetic patients found that those with vitamin D deficiency had twice the prevalence of DR compared to those with adequate levels.53 Supporting this, a retrospective analysis of data from the National Health and Nutrition Examination Survey showed that patients with both insufficient vitamin D levels and poor disease management exhibited a higher prevalence of mild and severe DR.54
Emerging evidence suggests that vitamin D may help prevent the onset and progression of DR through its anti-inflammatory and antiangiogenic properties.55 It appears to modulate immune system activity and reduce the production of inflammatory proteins and proinflammatory cytokines, such as TNF-α and IL-6. Furthermore, vitamin D may inhibit angiogenesis, a critical process in the development of DR, as shown by studies where calcitriol supplementation reduced angiogenesis in the choroidal vasculature in both ex vivo and in vivo settings.55-57 A randomized trial involving 83 individuals with DME demonstrated that correcting vitamin D deficiency through oral supplementation, alongside intravitreal bevacizumab treatment, led to significant improvements in visual acuity and central macular thickness.58
Overall Diet
The relationship between overall diet and DR is less understood. In a clinical trial conducted by Diaz-Lopez et al, more than 3,600 individuals with T2DM and high cardiovascular risk were randomly assigned to follow 1 of 3 dietary patterns: a Mediterranean diet enriched with extra virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a low-fat control diet.59 Among these, only the Mediterranean diet with olive oil was linked to a greater than 40% risk reduction of developing DR. This diet, which emphasizes whole grains, fruits, vegetables, plant-based proteins, fish, olive oil, and low-fat dairy, has also been associated with a reduced risk of diabetes itself, while its individual components appear to offer protective effects against DR.59
Higher fruit consumption, specifically 170 grams or more per day, has been associated with a greater than 50% reduction in DR risk, likely due to the presence of antioxidants, vitamins C and E, carotenoids, and polyphenols.60,61 Similarly, consuming fatty fish at least twice a week has been associated with a 60% decrease in DR risk.32 Garlic has also been explored for its potential benefits in DR. A recent comprehensive review of in vitro, in vivo, and clinical studies identified garlic’s antidiabetic, antiangiogenic, and neuroprotective properties.50,62 In a clinical trial involving 91 diabetic patients, those who received garlic tablets (500 mg, 2 per day) for 4 weeks experienced significant improvements in visual acuity and reduced intraocular pressure compared to the placebo group.63 These findings suggest that garlic could serve as a safe and effective complementary treatment for DME.64
Conclusion
Dietary nutrients have potent anti-inflammatory and antioxidant effects that make them promising candidates for retinoprotective prevention in nonproliferative, and possibly proliferative, diabetic retinopathy. Additional clinical research is necessary to clarify their benefits and confirm the effectiveness of nutrients and nutraceuticals in managing and preventing DR and DME. RP
References
1. D’Angelo A, Lixi F, Vitiello L, Gagliardi V, Pellegrino A, Giannaccare G. The role of diet and oral supplementation for the management of diabetic retinopathy and diabetic macular edema: a narrative review. Biomed Res Int. 2025;2025:6654976. doi:10.1155/bmri/6654976
2. Bryl A, Mrugacz M, Falkowski M, Zorena K. A Mediterranean diet may be protective in the development of diabetic retinopathy. Int J Mol Sci. 2023;24(13):11145. doi:10.3390/ijms241311145
3. Lem DW, Gierhart DL, Davey PG. A systematic review of carotenoids in the management of diabetic retinopathy. Nutrients. 2021;13(7):2441. doi:10.3390/nu13072441
4. Maiuolo J, Bulotta RM, Oppedisano F, et al. Potential properties of natural nutraceuticals and antioxidants in age-related eye disorders. Life (Basel). 2022;13(1). doi:10.3390/life13010077
5. Shivarudrappa AH, Ponesakki G. Lutein reverses hyperglycemia-mediated blockage of Nrf2 translocation by modulating the activation of intracellular protein kinases in retinal pigment epithelial (ARPE-19) cells. J Cell Commun Signal. 2020;14(2):207-221. doi:10.1007/s12079-019-00539-1
6. Nanjaiah H, Vallikannan B. Lutein upregulates the PGC-1α, NRF1, and TFAM expression by AMPK activation and downregulates ROS to maintain mtDNA integrity and mitochondrial biogenesis in hyperglycemic ARPE-19 cells and rat retina. Biotechnol Appl Biochem. 2019;66(6):999-1009. doi:10.1002/bab.1821
7. Muriach M, Bosch-Morell F, Alexander G, et al. Lutein effect on retina and hippocampus of diabetic mice. Free Radic Biol Med. 2006;41(6):979-984. doi:10.1016/j.freeradbiomed.2006.06.023
8. Kowluru RA, Menon B, Gierhart DL. Beneficial effect of zeaxanthin on retinal metabolic abnormalities in diabetic rats. Invest Ophthalmol Vis Sci. 2008;49(4):1645-1651. doi:10.1167/iovs.07-0764
9. Hanaguri J, Yokota H, Kushiyama A, et al. Beneficial effect of long-term administration of supplement with Trapa bispinosa Roxb. and lutein on retinal neurovascular coupling in type 2 diabetic mice. Front Physiol. 2022;13:788034. doi:10.3389/fphys.2022.788034
10. Xue C, Rosen R, Jordan A, Hu DN. Management of ocular diseases using lutein and zeaxanthin: what have we learned from experimental animal studies? J Ophthalmol. 2015;2015:523027. doi:10.1155/2015/523027
11. Moschos MM, Dettoraki M, Tsatsos M, Kitsos G, Kalogeropoulos C. Effect of carotenoids dietary supplementation on macular function in diabetic patients. Eye Vis (Lond). 2017;4:23. doi:10.1186/s40662-017-0088-4
12. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41(1):40-59. doi:10.1016/j.biocel.2008.06.010
13. Parsamanesh N, Moossavi M, Bahrami A, Butler AE, Sahebkar A. Therapeutic potential of curcumin in diabetic complications. Pharmacol Res. 2018;136:181-193. doi:10.1016/j.phrs.2018.09.012
14. Wang LL, Sun Y, Huang K, Zheng L. Curcumin, a potential therapeutic candidate for retinal diseases. Mol Nutr Food Res. 2013;57(9):1557-1568. doi:10.1002/mnfr.201200718
15. Khimmaktong W, Petpiboolthai H, Sriya P, Anupunpisit V. Effects of curcumin on restoration and improvement of microvasculature characteristic in diabetic rat’s choroid of eye. J Med Assoc Thai. 2014;97 Suppl 2:S39-46.
16. Gupta SK, Kumar B, Nag TC, et al. Curcumin prevents experimental diabetic retinopathy in rats through its hypoglycemic, antioxidant, and anti-inflammatory mechanisms. J Ocul Pharmacol Ther. 2011;27(2):123-130. doi:10.1089/jop.2010.0123
17. Peddada KV, Brown A, Verma V, Nebbioso M. Therapeutic potential of curcumin in major retinal pathologies. Int Ophthalmol. 2019;39(3):725-734. doi:10.1007/s10792-018-0845-y
18. Wang L, Xu J, Yu T, Wang H, Cai X, Sun H. Efficacy and safety of curcumin in diabetic retinopathy: a protocol for systematic review and meta-analysis. PLoS One. 2023;18(4):e0282866. doi:10.1371/journal.pone.0282866
19. Chiosi F, Rinaldi M, Campagna G, et al. Effect of a fixed combination of curcumin, Artemisia, bromelain, and black pepper oral administration on optical coherence tomography angiography indices in patients with diabetic macular edema. Nutrients. 2022;14(7). doi:10.3390/nu14071520
20. Guarino O, Iovino C, Di Iorio V, et al. Anatomical and functional effects of oral administration of Curcuma longa and Boswellia serrata combination in patients with treatment-naïve diabetic macular edema. J Clin Med. 2022;11(15). doi:10.3390/jcm11154451
21. Haroyan A, Mukuchyan V, Mkrtchyan N, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018;18(1):7. doi:10.1186/s12906-017-2062-z
22. Soleimani V, Sahebkar A, Hosseinzadeh H. Turmeric (Curcuma longa) and its major constituent (curcumin) as nontoxic and safe substances: Review Phytother Res. 2018;32(6):985-995. doi:10.1002/ptr.6054
23. Arenas-Jal M, Suñé-Negre JM, García-Montoya E. Coenzyme Q10 supplementation: efficacy, safety, and formulation challenges. Compr Rev Food Sci Food Saf. 2020;19(2):574-594. doi:10.1111/1541-4337.12539
24. Rodríguez-Carrizalez AD, Castellanos-González JA, Martínez-Romero EC, et al. The antioxidant effect of ubiquinone and combined therapy on mitochondrial function in blood cells in non-proliferative diabetic retinopathy: a randomized, double-blind, phase 2a, placebo-controlled study. Redox Rep. 2016;21(4):190-195. doi:10.1179/1351000215Y.0000000032
25. Rodríguez-Carrizalez AD, Castellanos-González JA, Martínez-Romero EC, et al. The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: a phase 2a, randomized, double-blind, and placebo-controlled study. Redox Rep. 2016;21(4):155-163. doi:10.1179/1351000215Y.0000000040
26. Domanico D, Fragiotta S, Cutini A, Carnevale C, Zompatori L, Vingolo EM. Circulating levels of reactive oxygen species in patients with nonproliferative diabetic retinopathy and the influence of antioxidant supplementation: 6-month follow-up. Indian J Ophthalmol. 2015;63(1):9-14. doi:10.4103/0301-4738.151455
27. King JC, Shames DM, Woodhouse LR. Zinc homeostasis in humans. J Nutr. 2000;130(5S Suppl):1360S-6S. doi:10.1093/jn/130.5.1360S
28. Tabatabaei-Malazy O, Ardeshirlarijani E, Namazi N, Nikfar S, Jalili RB, Larijani B. Dietary antioxidative supplements and diabetic retinopathy; a systematic review. J Diabetes Metab Disord. 2019;18(2):705-716. doi:10.1007/s40200-019-00434-x
29. Roussel AM, Kerkeni A, Zouari N, Mahjoub S, Matheau JM, Anderson RA. Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus. J Am Coll Nutr. 2003;22(4):316-321. doi:10.1080/07315724.2003.10719310
30. Kheirouri S, Naghizadeh S, Alizadeh M. Zinc supplementation does not influence serum levels of VEGF, BDNF, and NGF in diabetic retinopathy patients: a randomized controlled clinical trial. Nutr Neurosci. 2019;22(10):718-724. doi:10.1080/1028415X.2018.1436236
31. Miao X, Sun W, Miao L, et al. Zinc and diabetic retinopathy. J Diabetes Res. 2013;2013:425854. doi:10.1155/2013/425854
32. Sala-Vila A, Díaz-López A, Valls-Pedret C, et al. Dietary marine ω-3 fatty acids and incident sight-threatening retinopathy in middle-aged and older individuals with type 2 diabetes: prospective investigation from the PREDIMED trial. JAMA Ophthalmol. 2016;134(10):1142-1149. doi:10.1001/jamaophthalmol.2016.2906
33. Carazo A, Macáková K, Matoušová K, Krčmová LK, Protti M, Mladěnka P. Vitamin A update: forms, sources, kinetics, detection, function, deficiency, therapeutic use and toxicity. Nutrients. 2021;13(5):1703. doi:10.3390/nu13051703
34. Choi YJ, Kwon JW, Jee D. The relationship between blood vitamin A levels and diabetic retinopathy: a population-based study. Sci Rep. 2024;14(1):491. doi:10.1038/s41598-023-49937-x
35. Rostamkhani H, Mellati AA, Tabaei BS, Alavi M, Mousavi SN. Association of serum zinc and vitamin A levels with severity of retinopathy in type 2 diabetic patients: a cross-sectional study. Biol Trace Elem Res. 2019;192(2):123-128. doi:10.1007/s12011-019-01664-z
36. Satyanarayana A, Balakrishna N, Pitla S, et al. Status of B-vitamins and homocysteine in diabetic retinopathy: association with vitamin-B12 deficiency and hyperhomocysteinemia. PLoS One. 2011;6(11):e26747. doi:10.1371/journal.pone.0026747
37. Cinici E, Dilekmen N, Senol O, Arpalı E, Cinici O, Tanas S. Blood thiamine pyrophosphate concentration and its correlation with the stage of diabetic retinopathy. Int Ophthalmol. 2020;40(12):3279-3284. doi:10.1007/s10792-020-01513-2
38. Horikawa C, Aida R, Kamada C, et al. Vitamin B6 intake and incidence of diabetic retinopathy in Japanese patients with type 2 diabetes: analysis of data from the Japan Diabetes Complications Study (JDCS). Eur J Nutr. 2020;59(4):1585-1594. doi:10.1007/s00394-019-02014-4
39. Ellis JM, Folkers K, Minadeo M, VanBuskirk R, Xia LJ, Tamagawa H. A deficiency of vitamin B6 is a plausible molecular basis of the retinopathy of patients with diabetes mellitus. Biochem Biophys Res Commun. 1991;179(1):615-619. doi:10.1016/0006-291x(91)91416-a
40. Smolek MK, Notaroberto NF, Jaramillo AG, Pradillo LR. Intervention with vitamins in patients with nonproliferative diabetic retinopathy: a pilot study. Clin Ophthalmol. 2013;7:1451-1458. doi:10.2147/OPTH.S46718
41. Chous AP, Richer SP, Gerson JD, Kowluru RA. The Diabetes Visual Function Supplement Study (DiVFuSS). Br J Ophthalmol. 2016;100(2):227-234. doi:10.1136/bjophthalmol-2014-306534
42. Monacelli F, Acquarone E, Giannotti C, Borghi R, Nencioni A. Vitamin C, aging and Alzheimer disease. Nutrients. 2017;9(7):670. doi:10.3390/nu9070670
43. Kumari S, Panda S, Mangaraj M, Mandal MK, Mahapatra PC. Plasma MDA and antioxidant vitamins in diabetic retinopathy. Indian J Clin Biochem. 2008;23(2):158-162. doi:10.1007/s12291-008-0035-1
44. Kundu D, Mandal T, Nandi M, Osta M, Bandyopadhyay U, Ray D. Oxidative stress in diabetic patients with retinopathy. Ann Afr Med. 2014;13(1):41-46. doi:10.4103/1596-3519.126951
45. Lam CS, Benzie IF, Choi SW, Chan LY, Yeung VT, Woo GC. Relationships among diabetic retinopathy, antioxidants, and glycemic control. Optom Vis Sci. 2011;88(2):251-256. doi:10.1097/OPX.0b013e318208494a
46. Bursell SE, Clermont AC, Aiello LP, et al. High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Diabetes Care. 1999;22(8):1245-1251. doi:10.2337/diacare.22.8.1245
47. Ho JI, Ng EY, Chiew Y, et al. The effects of vitamin E on non-proliferative diabetic retinopathy in type 2 diabetes mellitus: are they sustainable with 12 months of therapy. SAGE Open Med. 2022;10:20503121221095324. doi:10.1177/20503121221095324
48. Bouillon R, Carmeliet G, Verlinden L, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29(6):726-776. doi:10.1210/er.2008-0004
49. Alcubierre N, Valls J, Rubinat E, et al. Vitamin D deficiency is associated with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus. J Diabetes Res. 2015;2015:374178. doi:10.1155/2015/374178
50. Afarid M, Ghattavi N, Johari M. Serum levels of vitamin D in diabetic patients with and without retinopathy. J Ophthalmic Vis Res. 2020;15(2):172-177. doi:10.18502/jovr.v15i2.6734
51. Shimo N, Yasuda T, Kaneto H, et al. Vitamin D deficiency is significantly associated with retinopathy in young Japanese type 1 diabetic patients. Diabetes Res Clin Pract. Nov 2014;106(2):e41-3. doi:10.1016/j.diabres.2014.08.005
52. Zhao WJ, Xia XY, Yin J. Relationship of serum vitamin D levels with diabetic microvascular complications in patients with type 2 diabetes mellitus. Chin Med J (Engl). 2021;134(7):814-820. doi:10.1097/CM9.0000000000001364
53. Kaur H, Donaghue KC, Chan AK, et al. Vitamin D deficiency is associated with retinopathy in children and adolescents with type 1 diabetes. Diabetes Care. 2011;34(6):1400-1402. doi:10.2337/dc11-0103
54. Binkley N, Dawson-Hughes B, Durazo-Arvizu R, et al. Vitamin D measurement standardization: the way out of the chaos. J Steroid Biochem Mol Biol. 2017;173:117-121. doi:10.1016/j.jsbmb.2016.12.002
55. Gverović Antunica A, Znaor L, Ivanković M, Puzović V, Marković I, Kaštelan S. Vitamin D and diabetic retinopathy. Int J Mol Sci. 2023;24(15) :12014. doi:10.3390/ijms241512014
56. Imanparast F, Javaheri J, Kamankesh F, et al. The effects of chromium and vitamin D. Appl Physiol Nutr Metab. 2020;45(5):471-477. doi:10.1139/apnm-2019-0113
57. Fernandez-Robredo P, González-Zamora J, Recalde S, et al. Vitamin D protects against oxidative stress and inflammation in human retinal cells. Antioxidants (Basel). 2020;9(9):838. doi:10.3390/antiox9090838
58. Fekri S, Soheilian M, Roozdar S, Abtahi SH, Nouri H. The effect of vitamin D supplementation on the outcome of treatment with bevacizumab in diabetic macular edema: a randomized clinical trial. Int Ophthalmol. 2022;42(11):3345-3356. doi:10.1007/s10792-022-02333-2
59. Díaz-López A, Babio N, Martínez-González MA, et al. Mediterranean diet, retinopathy, nephropathy, and microvascular diabetes complications: a post hoc analysis of a randomized trial. Diabetes Care. 2015;38(11):2134-2141. doi:10.2337/dc15-1117
60. Tanaka S, Yoshimura Y, Kawasaki R, et al. Fruit intake and incident diabetic retinopathy with type 2 diabetes. Epidemiology. 2013;24(2):204-211. doi:10.1097/EDE.0b013e318281725e
61. Schwingshackl L, Missbach B, König J, Hoffmann G. Adherence to a Mediterranean diet and risk of diabetes: a systematic review and meta-analysis. Public Health Nutr. 2015;18(7):1292-1299. doi:10.1017/S1368980014001542
62. Sanie-Jahromi F, Zia Z, Afarid M. A review on the effect of garlic on diabetes, BDNF, and VEGF as a potential treatment for diabetic retinopathy. Chin Med. 2023;18(1):18. doi:10.1186/s13020-023-00725-9
63. Afarid M, Sadeghi E, Johari M, Namvar E, Sanie-Jahromi F. Evaluation of the effect of garlic tablet as a complementary treatment for patients with diabetic retinopathy. J Diabetes Res. 2022;2022:6620661. doi:10.1155/2022/6620661
64. Iso H, Date C, Wakai K, Fukui M, Tamakoshi A, Group JS. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med. 2006;144(8):554-562. doi:10.7326/0003-4819-144-8-200604180-00005