Advertisement

Dietary antioxidative supplements and diabetic retinopathy; a systematic review

  • Ozra Tabatabaei-Malazy
  • Edris Ardeshirlarijani
  • Nazli Namazi
  • Shekoufeh Nikfar
  • Reza Baradar Jalili
  • Bagher LarijaniEmail author
Review article
  • 62 Downloads

Abstract

Purpose

There is controversial data regarding the effects of dietary antioxidative supplements on diabetic retinopathy (DR). We conducted a systematic review of both observational and randomized controlled clinical trials (RCTs) to clarify whether they are effective or not.

Methods

All observational and RCTs conducted by antioxidative supplements on DR published up to 1 January 2018 in PubMed, Web of Sciences, Scopus and Cochrane Library databases were included. Exclusion criteria were animal studies, and studies conducted in Type 1 diabetes mellitus (T1DM), children or pregnant women. Main outcome measures were reporting the incidence or progression of DR in T2DM by assessment of visual fields, and measurements of oxidative and antioxidative biomarkers. The quality of reporting of included articles and risk of bias were assessed.

Results

Finally, we reached 14 observational studies and 7 RCTs that conducted on 256,259 subjects. Due to severe methodological heterogeneity, only qualitative synthesis was carried. All studies were reported a significantly lower level of antioxidants and higher level of oxidative stress biomarkers in DR compared with others. There was an inverse significant correlation between vitamin C and malondialdehyde (MDA) (r = −0.81) or DNA damage (r = −0.41). These figures were statistically significant between vitamin E and MDA (r = 0.77) or superoxide dismutase (r = 0.44). Coefficient of correlation between MDA and zinc (−0.82), coenzyme Q10 (0.56), and magnesium (−0.73) was significant. Multi-oxidants trials were shown non-significant beneficial effects on DR.

Conclusions

Although our study supports the positive effects of antioxidative supplements on DR, more high quality studies are needed to confirm.

Keywords

Type 2 diabetes mellitus Diabetic retinopathy Oxidative stress Antioxidants 

Abbreviations

NPDR

Non-proliferative diabetic retinopathy

PDR

Proliferative diabetic retinopathy

DR

Diabetic retinopathy

IDF

International Diabetes Federation

PKC

Protein kinase C

AGEs

Advanced glycation end products

ROS

Reactive oxygen species

Mg

Magnesium

Zn

Zinc

MDA

Malondialdehyde

B1

Benfotiamine

ALA

Alpha lipoic acid

Se

Selenium

T2DM

Type 2 diabetes mellitus

RCTs

Randomized controlled trials

PRISMA

Preferred Reporting Items for Systematic reviews and Meta-Analyses

GPx

Glutathione peroxidase

SOD

Superoxide dismutase

TAS

Total antioxidant status

STROBE

Strengthening the reporting of observational studies in epidemiology

ADA

American Diabetes Association

VC

Vitamin C

VE

Vitamin E

VD

Vitamin D

BCVA

Best-corrected visual acuity

IOP

Intraocular pressure

RNFL

Retinal nerve fiber layer thickness

FORT

Free oxygen radical test

CMT

Central macular thickness

NF-κB

Nuclear translocation factor- κB

VEGF

Vascular endothelial growth factor

BAP

Biological antioxidant potential

OP

Oscillatory potential

Cu

Copper

Mn

Manganese

Notes

Acknowledgements

This paper is the outcome of an in-house study without any financial support.

Author’s contribution

Both OTM and NN helped to collect data, data interpretation, and drafting article. OTM and EAL equally designed, conceived of the study, data analysis and interpretation. SN and RBJ helped to written drafting article, and critical revision of the article. BL conceived of the study, helped to data interpretation, and drafting article. All authors read and approved the final draft of the article.

Funding

Any funding.

Compliance with ethical standards

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.

Supplementary material

40200_2019_434_MOESM1_ESM.docx (17 kb)
ESM 1 (DOCX 17 kb)

References

  1. 1.
    IDF diabetes atlas, 8th edition (2017). Available at: www.IDF.org/e-library/epidemiology-research/diabetes-atlas.html. Date access: 29 Aug.
  2. 2.
    Hendrick AM, Gibson MV, Kulshreshtha A. Diabetic retinopathy. Prim Care. 2015;42(3):451–64.  https://doi.org/10.1016/j.pop.2015.05.005.CrossRefPubMedGoogle Scholar
  3. 3.
    Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother. 2005;59:365–73.CrossRefGoogle Scholar
  4. 4.
    Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. CardiovascDiabetol. 2005;4:5.  https://doi.org/10.1186/1475-2840-4-5.CrossRefGoogle Scholar
  5. 5.
    Saeidnia S, Abdollahi M. Toxicological and pharmacological concerns on oxidative stress and related diseases. Toxicol Appl Pharmacol. 2013;273:442–55.CrossRefGoogle Scholar
  6. 6.
    Khodaeian M, Tabatabaei-Malazy O, Qorbani M, Farzadfar F, Amini P, Larijani B. Effect of vitamins C and E on insulin resistance in diabetes: a meta-analysis study. Eur J Clin Investig. 2015;45(11):1161–74.  https://doi.org/10.1111/eci.12534.CrossRefGoogle Scholar
  7. 7.
    Tabatabaei-Malazy O, Nikfar S, Larijani B, Abdollahi M. Influence of ascorbic acid supplementation on type 2 diabetes mellitus in observational and randomized controlled trials; a systematic review with meta-analysis. J Pharm Pharm Sci. 2014;17(4):554–82.CrossRefGoogle Scholar
  8. 8.
    Kowluru RA, Mishra M. Oxidative stress, mitochondrial damage and diabetic retinopathy. BiochemicaBiophysicaActa. 1852;2015:2474–83.Google Scholar
  9. 9.
    Ola MS, Nawaz MI, Siddiquei MM, Al-Amro S, Abu El-Asrar AM. Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy. J Diabetes Complicat. 2012;26:56–64.CrossRefGoogle Scholar
  10. 10.
    Kumari S, Panda S, Mangaraj M, Mandal MK, Mahapatra PC. Plasma MDA and antioxidant vitamins in diabetic retinopathy. Indian J Cli Biochem. 2008;23:158–62.CrossRefGoogle Scholar
  11. 11.
    Ates O, Bilen H, Keles S, Alp HH, Keles MS, Yildirim K, et al. Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy. Int J Ophthalmol. 2013;6:675–9.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Kumari S, Pradhan T, Panda TK. Trace minerals and oxidative stress in diabetic retinopathy. BJMS. 2014;13:175–9.Google Scholar
  13. 13.
    Jee D. Han Kd, Kim EC. Inverse association between high blood 25-hydroxyvitamin D levels and diabetic retinopathy in a representative Korean population. PLoS One. 2014;9:e115199.  https://doi.org/10.1371/journal.pone.0115199.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Madsen-Bouterse SA, Kowluru RA. Oxidative stress and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Rev Endocr Metab Disord. 2008;9(4):315–27.  https://doi.org/10.1007/s11154-008-9090-4.CrossRefPubMedGoogle Scholar
  15. 15.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred Reporting Items for Systematic Reviewsand Meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.  https://doi.org/10.1371/journal.pmed.1000097.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, et al. STROBE Initiative. Strengthening the reporting of observational studies in epidemiology (STROBE): Explanation and elaboration. PLoS Med. 2007;4:e297.  https://doi.org/10.1371/journal.pmed.0040296.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Halpern SH, Douglas MJ. Jadad scale for reportingrandomized controlled trials. Evidence-based Obstetric Anesthesia. 2005:237–8.  https://doi.org/10.1002/9780470988343.app1.
  18. 18.
    Sinclair AJ, Girling AJ, Gray L, Lunec J, Barnett AH. An investigation of the relationship between free radical activity and vitamin C metabolism in elderly diabetic subjects with retinopathy. Gerontology. 1992;38(5):268–74.CrossRefGoogle Scholar
  19. 19.
    Gürler B, Vural H, Yilmaz N, Oguz H, Satici A, Aksoy N. The role of oxidative stress in diabetic retinopathy. Eye (Lond). 2000;14(Pt 5):730–5.CrossRefGoogle Scholar
  20. 20.
    Gupta MM, Chari S. Lipid peroxidation and antioxidant status in patients with diabetic retinopathy. Indian J Physiol Pharmacol. 2005;49(2):187–92.PubMedGoogle Scholar
  21. 21.
    Yildirim Z, Uçgun NI, Kiliç N, Gürsel E, Sepici-Dinçel A. Antioxidant enzymes and diabetic retinopathy. Ann N Y Acad Sci. 2007;1100:199–206.CrossRefGoogle Scholar
  22. 22.
    Samuel TV, Murthy DSJ, Dattatreya K, Babu PS, Johncy SS. Impaired antioxidant defence mechanism in diabetic retinopathy. J Clin Diagn Res. 2010;4:3430–6.Google Scholar
  23. 23.
    Aldebasi Y, Mohieldin A, Almansour Y, Almoteri B. Imbalance of oxidant/antioxidant status and risk factors for Saudi type 2 diabetic patientswith retinopathy. Br J Med Med Res. 2011;1:371–84.CrossRefGoogle Scholar
  24. 24.
    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):251–6.  https://doi.org/10.1097/OPX.0b013e318208494a.CrossRefPubMedGoogle Scholar
  25. 25.
    Kulkarni RP, Kodliwadmath MV. Oxidative stress and high sensitivity c-reactive protein in diabetic retinopathy. Int J Pharm Bio Sci. 2013;4:1306–10.Google Scholar
  26. 26.
    Said NS, Hadhoud KM, Nada WM, El Tarhouny SA. Superoxide dismutase, glutathione peroxidase and vitamin E in patients with diabetic retinopathy. Life Sci. 2013;1:1851–6.Google Scholar
  27. 27.
    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):41–6.  https://doi.org/10.4103/1596-3519.126951.CrossRefPubMedGoogle Scholar
  28. 28.
    Longo-Mbenza B, MvituMuaka M, Masamba W, MuizilaKini L, Longo Phemba I, Kibokela Ndembe D, et al. Retinopathy in non diabetics, diabetic retinopathy and oxidative stress: a new phenotype in Central Africa? Int J Ophthalmol. 2014;7(2):293–301.  https://doi.org/10.3980/j.issn.2222-3959.2014.02.18.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Hu BJ, Hu YN, Lin S, Ma WJ, Li XR. Application of lutein and zeaxanthin in nonproliferative diabetic retinopathy. Int J Ophthalmol. 2011;4(3):303–6.  https://doi.org/10.3980/j.issn.2222-3959.2011.03.19.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Garcia-Medina JJ, Pinazo-Duran MD, Garcia-Medina M, Zanon-Moreno V, Pons-Vazquez S. A 5-year follow-up of antioxidant supplementation in type 2 diabetic retinopathy. Eur J Ophthalmol. 2011;21(5):637–43.  https://doi.org/10.5301/EJO.2010.6212.CrossRefPubMedGoogle Scholar
  31. 31.
    Nebbioso M, Federici M, Rusciano D, Evangelista M, Pescosolido N. Oxidative stress in preretinopathic diabetes subjects and antioxidants. Diabetes Technol Ther. 2012;14(3):257–63.  https://doi.org/10.1089/dia.2011.0172.CrossRefPubMedGoogle Scholar
  32. 32.
    Domanico D, Fragiotta S, Cutini A, Carnevale C, Zompatori L, Vingolo EM. Circulating levels of reactive oxygen species in patients with nonproliferativediabetic retinopathy and the influence of antioxidant supplementation: 6-monthfollow-up. Indian J Ophthalmol. 2015;63(1):9–14.  https://doi.org/10.4103/0301-4738.151455.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Roig-Revert MJ, Lleó-Pérez A, Zanón-Moreno V, Vivar-Llopis B, Marín-Montiel J, Dolz-Marco R, et al. Valencia Study On Diabetic Retinopathy (VSDR). Enhanced oxidative stress and other potential biomarkers for retinopathy in type 2 diabetics: beneficial effects of the nutraceutic supplements. Biomed Res Int. 2015:408180.  https://doi.org/10.1155/2015/408180.
  34. 34.
    Rodríguez-Carrizalez AD, Castellanos-González JA, Martínez-Romero EC, Miller-Arrevillaga G, Pacheco-Moisés FP, Román-Pintos LM, et al. The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: a phase IIa, randomized, double-blind, and placebo-controlled study. Redox Rep. 2016;21(4):155–63.  https://doi.org/10.1179/1351000215Y.0000000040.CrossRefPubMedGoogle Scholar
  35. 35.
    Chatziralli IP, Theodossiadis G, Dimitriadis P, Charalambidis M, Agorastos A, Migkos Z, et al. The effect of vitamin E on oxidative stress indicated by serum malondialdehyde in insulin-dependent type 2 diabetes mellitus patients with retinopathy. Open Ophthalmol J. 2017;11:51–8.  https://doi.org/10.2174/1874364101711010051.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Tabatabaei-Malazy O, Larijani B, Abdollahi M. A systematic review of in vitro studies conducted on effect of herbal products on secretion of insulin from Langerhans islets. J Pharm Pharm Sci. 2012;15:447–66.CrossRefGoogle Scholar
  37. 37.
    de Lopes JCC, Atallah AN, Valente O, Fernandes MTV. Vitamin C and superoxide dismutase (SOD) for diabetic retinopathy. Cochrane Database Syst Rev. 2008;1.  https://doi.org/10.1002/14651858.CD006695.pub2.
  38. 38.
    Li C, Miao X, Li F, Wang S, Liu Q, Wang Y, et al. Oxidative stress-related mechanisms and antioxidant therapy in diabetic retinopathy. Oxidative Med Cell Longev. 2017;2017:9702820–15.  https://doi.org/10.1155/2017/9702820.CrossRefGoogle Scholar
  39. 39.
    Tabatabaei-Malazy O, Larijani B, Abdollahi M. A novel management of diabetes by means of strong antioxidants’combination. Journal of Medical Hypotheses and Ideas 2013;7:25–30.CrossRefGoogle Scholar
  40. 40.
    Kowluru RA, Tang J, Kern TS. Abnormalities of retinal metabolism in diabetes and experimental galactosemia, VII, effect of long-term administration of antioxidants on the development of retinopathy. Diabetes. 2001;50:1938–42.CrossRefGoogle Scholar
  41. 41.
    Hathcock JN, Azzi A, Blumberg J, Bray T, Dickinson A, Frei B, et al. Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr. 2005;81:736–45.CrossRefGoogle Scholar
  42. 42.
    Steinberg D. Clinical trials of antioxidants in atherosclerosis: are we doing the right thing? Lancet. 1995;346:36–8.CrossRefGoogle Scholar
  43. 43.
    Kowluru RA, Odenbach S. Effect of long-term administration of alpha lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes. 2004;53:3233–8.CrossRefGoogle Scholar
  44. 44.
    Barlett HF, Eperjesi F. Nutritional supplementation for type 2 diabetes: a systematic review. Ophthalmic Physiol Opt. 2008;28:503–23.CrossRefGoogle Scholar
  45. 45.
    Gębka A, Serkies-Minuth E, Raczyńska D. Effect of the administration of alpha-lipoic acid on contrast sensitivity in patients with type 1 and type 2diabetes. Mediat Inflamm. 2014;2014:131538–7.  https://doi.org/10.1155/2014/131538.CrossRefGoogle Scholar
  46. 46.
    Stahl W, Sies H. Effects of carotenoids and retinoids on gap junctional communication. BioFactors. 2001;15:95–8.CrossRefGoogle Scholar
  47. 47.
    Kvansakul J, Rodriguez-Carmona M, Edger DF, Barker FM, Kopoke W, Schalch W, et al. Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance. Ophthalmic Physiol Opt. 2006;26:362–71.CrossRefGoogle Scholar
  48. 48.
    Kalariya NM, Ramana KV, Srivastava SK, van Kuijk FJ. Carotenoid derived aldehydes-induced oxidative stress causes apoptotic cell death in human retinal pigment epithelial cells. Exp Eye Res. 2008;86:70–80.CrossRefGoogle Scholar
  49. 49.
    Littarru GP, Langsjoen P. Coenzyme Q10 and statins: biochemical and clinical implications. Mitochondrion. 2007;7(Suppl):S168–74.CrossRefGoogle Scholar
  50. 50.
    Hamilton SJ, Chew GT, Watts GF. Coenzyme Q10 improves endothelial dysfunction in statin-treated type 2 diabetic patients. Diabetes Care. 2009;32:810–2.CrossRefGoogle Scholar
  51. 51.
    Gao L, Mao Q, Cao J, Wang Y, Zhou X, Fan L. Effects of coenzyme Q10 on vascular endothelial function in humans: a meta-analysis of randomized controlled trials. Atherosclerosis. 2012;221:311–6.CrossRefGoogle Scholar
  52. 52.
    Sourris KC, Harcourt BE, Tang PH, Morley AL, Huynh K, Penfold SA, et al. Ubiquinone (coenzyme Q10) prevents renal mitochondrial dysfunction in an experimental model of type 2 diabetes. Free Radic Biol Med. 2012;52:716–23.CrossRefGoogle Scholar
  53. 53.
    American Diabetes Association. Standards of medical care in diabetes-2019. Diabetes Care. 2019;42(Suppl 1):S1–S193.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
  2. 2.Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
  3. 3.Simon Fraser UniversityBurnabyCanada
  4. 4.Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
  5. 5.Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
  6. 6.Evidence-based Evaluation of Cost-Effectiveness and Clinical Outcomes Group, The Institute of Pharmaceutical Sciences (TIPS)Tehran University of Medical SciencesTehranIran
  7. 7.Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy and Pharmaceutical Policy Research CenterTehran University of Medical SciencesTehranIran
  8. 8.Department of SurgeryUniversity of British ColumbiaVancouverCanada

Personalised recommendations