Vertical Divider

Summary
A large percentage of individuals with diabetes type 2 are affected by diabetic retinopathy. In this condition, local vasculature pathology and fluid buildup damage the retina of the eye with vision loss and even blindness as consequences. DHA has been shown to be inversely correlated with diabetic retinopathy risk and severity, highlighting the importance of DHA in this condition.

Introduction
Diabetic retinopathy is one of the most common complications in persons with diabetes, affecting up to 50% of individuals with diabetes type 2. In this condition, the retina of the eyes are damaged leading to symptoms such as vision loss and blindness. The retina lie in the back of the eye and contain the photoreceptor cells that take up light signal, allowing us to see. Two forms of this condition exist: non-proliferative diabetic retinopathy, which can develop into proliferative diabetic retinopathy. The former variant is defined by local dilation and damage to blood vessels, leading to bleeding and fluid buildup in the retina, resulting in an obstructed blood flow in the retina. Proliferative diabetic retinopathy is characterized by abnormal development of blood vessels in the retina in addition to the previous symptoms. Furthermore, diabetic retinopathy can lead to a condition called diabetic macular edema. Here, extracellular fluid accumulates in the macula as a result of the blood vessels there, and the retina of the macular area thickens, causing further vision problems.

The systematic inflammation and oxidative stress at play in diabetes are thought to be major factors of influence in diabetic retinopathy. Diabetes is associated with elevated levels of Vascular Endothelial Growth Factor (VEGF), a protein that stimulates the production of new blood vessels. Current medicinal treatments for diabetic retinopathy such as Ranibizumab are given to counteract diabetesassociated increase in VEGF and the consequent production of new blood vessels. DHA has been shown to reduce oxidative stress, inflammation and the abnormal formation of new blood vessels. Hence, studies on the effects of DHA in the context of diabetic retinopathy have been conducted, as discussed below.

Research findings
In a 2023 study by Weir and colleagues, the levels of DHA and EPA were assessed in relation to risk and severity of retinopathy in 1356 persons with type 2 diabetes. Blood plasma analysis was conducted on omega-3 fatty acids such as DHA and EPA, together with measurements of diabetic retinopathy incidence and severity. To analyze the effects of DHA and EPA, the authors divided the plasma DHA and EPA level of the subjects in 4 quartiles from lowest to highest. From this analysis, they found that persons in the quartile with the highest DHA plasma levels had 17% lower risk of diabetic retinopathy and 38% lower severity of retinopathy, compared to persons in the lowest plasma DHA quartile (Weir et al., 2023). No associations were found between EPA plasma levels and risk or severity of diabetic retinopathy.

Saenz de Viteri and colleagues researched the effects of EPA and DHA on human retinal cells in the context of oxidative stress and inflammation, typical stressors in diabetic retinopathy (Saenz de Viteri et al., 2020). The researchers assessed the cell health and function of the human retinal pigment epithelium cell line during induced conditions of oxidative stress and inflammation, examining the effects of DHA and EPA supplementation. They found that EPA + DHA together protected human retinal pigment epithelium cells against induced oxidative damage as seen in inflammation. Furthermore, they reported that this effect of the omega-3 fatty acids was more pronounced when they were in triglyceride or phospholipid confirmation, rather than in ethyl-ester confirmation.

Lafuente and colleagues conducted a study on the effects of DHA supplementation in 62 diabetes type 2 patients with diabetic macular edema receiving Ranibizumab treatment. Patients received either Ranibizumab alone (control group) or Ranibizumab + 1050mg DHA per day (DHA group) for a period of 3 years (Lafuente et al., 2019). The DHA supplementation pill also contained low doses of EPA, vitamins and minerals. The Ranibizumab was given for a minimum of 4 months and was afterwards only administered when required by a medical professional. The authors reported that from 2 years to the end point of the study, the DHA + Ranibizumab group showed a decrease in macular thickness compared to the control group. Thickening of the macula is a symptom of diabetic macular edema, a decrease in thickness is thus considered a positive effect in this context. Furthermore, the DHA group had lower serum levels of inflammatory cytokine IL-6 at the end of the study compared to the start of the study, whereas the control group showed an increased in IL-6 serum levels.

Conclusion
DHA has been shown to be inversely correlated with severity and risk of developing diabetic retinopathy in persons with diabetes type 2. This means that diabetes type 2 patients with the highest levels of blood plasma DHA have substantially lower risks of developing diabetic retinopathy and suffering from severe forms of diabetic retinopathy. In human retinal pigment epithelium cells, DHA together with EPA have been shown to protect against oxidative (inflammatory) damage seen in diabetic retinopathy. Diabetic retinopathy can develop into diabetic macular edema; a common medicine given to diabetes type 2 patients with this condition is Ranibizumab, which aims to reduce the pathogenic macular thickness. When this treatment is combined with DHA supplementation, treatment effectiveness is enhanced. In summation, individuals suffering from diabetes type 2 may choose to take DHA supplementation to reduce their risk of diabetic retinopathy development and severity.

References
Lafuente, M., Ortín, L., Argente, M., Guindo, J. L., López-Bernal, M. D., López-Román, F. J., Domingo, J. C., & Lajara, J. (2019). THREE-YEAR OUTCOMES IN A RANDOMIZED SINGLE-BLIND CONTROLLED TRIAL OF INTRAVITREAL RANIBIZUMAB AND ORAL SUPPLEMENTATION WITH DOCOSAHEXAENOIC ACID AND ANTIOXIDANTS FOR DIABETIC MACULAR EDEMA. Retina (Philadelphia, Pa.), 39(6), 1083–1090.     https://doi.org/10.1097/IAE.0000000000002114

Saenz de Viteri, M., Hernandez, M., Bilbao-Malavé, V., Fernandez-Robredo, P., González-Zamora, J., Garcia-Garcia, L., Ispizua, N., Recalde, S., & Garcia-Layana, A. (2020). A Higher Proportion of Eicosapentaenoic Acid (EPA) When Combined with Docosahexaenoic Acid (DHA) in Omega-3 Dietary Supplements Provides Higher Antioxidant Effects in Human Retinal Cells. Antioxidants, 9(9), Article 9.
​https://doi.org/10.3390/antiox9090828

Weir, N. L., Guan, W., Karger, A. B., Klein, B. E. K., Meuer, S. M., Cotch, M. F., Guo, X., Li, X., Tan, J., Genter, P., Chen, Y.-D. I., Rotter, J. I., Ipp, E., & Tsai, M. Y. (2023). OMEGA-3 FATTY ACIDS ARE ASSOCIATED WITH DECREASED PRESENCE AND SEVERITY OF DIABETIC RETINOPATHY: A Combined Analysis of MESA and GOLDR Cohorts. RETINA, 43(6), 984.   https://doi.org/10.1097/IAE.000000000000374

Vertical Divider