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



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.


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.


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.


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


Type 2 diabetes mellitus Diabetic retinopathy Oxidative stress Antioxidants 



Non-proliferative diabetic retinopathy


Proliferative diabetic retinopathy


Diabetic retinopathy


International Diabetes Federation


Protein kinase C


Advanced glycation end products


Reactive oxygen species










Alpha lipoic acid




Type 2 diabetes mellitus


Randomized controlled trials


Preferred Reporting Items for Systematic reviews and Meta-Analyses


Glutathione peroxidase


Superoxide dismutase


Total antioxidant status


Strengthening the reporting of observational studies in epidemiology


American Diabetes Association


Vitamin C


Vitamin E


Vitamin D


Best-corrected visual acuity


Intraocular pressure


Retinal nerve fiber layer thickness


Free oxygen radical test


Central macular thickness


Nuclear translocation factor- κB


Vascular endothelial growth factor


Biological antioxidant potential


Oscillatory potential







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.


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)


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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

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