Of all the diabetic complications, retinopathy is among the most serious and progressive, leading to blindness because it is characterised by vascular lesions, retinal detachment, capillary occlusion, vitreous haemorrhage, macular oedema and lipid exudates. Diagnosis and prevention, given the increasing prevalence of type 2 diabetes in the population, have become essential, as is understanding the different mechanisms of action by which a wide variety of phytochemicals can be used as therapeutically active agents.
These compounds, derived from natural products, include flavonoids, terpenoids, polyphenols, alkaloids, tannins and steroids and have pharmacological properties of great interest because they target several metabolic pathways simultaneously.
Numerous in vivo studies using animal models and in vitro studies on cell cultures have revealed that phytochemicals can alter the disruption of the blood-retinal barrier (Brb), improve oxidative status, decrease the release of proinflammatory mediators and restore retinal thickness by suppressing neurodegeneration and apoptosis.
There are several clinical studies demonstrating that the administration of polyphenols through supplements and the diet has favourable effects at various stages that may reduce the development of retinopathy in diabetic patients. In 2002, a clinical study was conducted in which 564 out of 10,054 subjects were selected to analyse the likelihood of developing diabetes mellitus. The results revealed that one year’s consumption of the flavonoids myricetin and quercetin significantly reduced the incidence of diabetes. In addition, quercetin shows protective activity against several lesions in the retina of diabetic patients: it reduces glucose-induced inflammation and apoptosis by decreasing Il-6 levels, the production of monocyte chemoattractant protein-1 (Mcp-1) and free radicals.
A 2013 meta-analysis studied the efficacy of catechins, with or without caffeine, on diabetes biomarkers in 1,584 patients. The data described that consumption of catechin from green tea significantly decreased fasting blood glucose levels, while showing no effect on fasting blood glycated haemoglobin (HbA1c) and insulin.
Another trial, which included 70 patients with type 2 diabetes, explored the effect of flavonoid supplementation from melilotus and centella asiatica in the management of diabetic cystoid macular oedema. The study described that flavonoid treatment preserved retinal sensitivity, while no substantial differences were observed in blood pressure, HbA1c levels, central retinal thickness, visual acuity and microalbuminuria.
In 2020, however, it was observed that after administration of purified anthocyanins for 12 weeks in 160 patients, fasting glucose was significantly reduced and serum adiponectin increased in diabetic patients.
In 2014, a study carried out on the Nhanes (National health and nutrition examination survey) epidemiological sample between 2003 and 2006 investigated the effect of a flavonoid-rich diet on diabetic retinopathy and diabetes-associated biomarkers using results from 381 patients. Consumption of a flavonoid-rich diet decreased the development of retinopathy by 30% and there was also a significant decrease in glucose, HbA1C and C-reactive protein levels. Another comparative study, conducted over one year, described that regular consumption of green tea reduced the occurrence of diabetic retinopathy by 50%.
A multicentre field study evaluated the impact of a standardised extract of the bark of the French maritime pine (Pinus pinaster, pignogenol) on the development of visual acuity in diabetic patients with diabetic retinopathy, and after 6 months, in 1,169 subjects, supplementation prevented loss of vision, although no significant improvement was observed in the patients’ visus.
It should be noted that pycnogenol has been tested for the treatment and prevention of retinopathy in five clinical trials with a total number of 1,289 patients since the late 1960s and is being re-evaluated in recent years with better-designed clinical trials. The data show a reduction in oxidative stress and central macular thickness, and treatment for two months significantly improved vision in the primary phase of diabetic retinopathy.
Despite many favourable therapeutic effects of these phytochemicals in diabetic patients, studies continue to emphasise the management of patients with distinct phases of the disease, making the correlation between the administration of phytochemicals and the management of diabetic retinopathy still complex.
In conclusion, data from preclinical and clinical studies have revealed that dietary consumption of polyphenols may be a safer, more effective and economical way to reduce the development of diabetic retinopathy and other visual lesions, whereas nutraceuticals can only be an additional weapon when administered as supplements to a balanced and complete diet.
Bibliography
Unveiling the role of polyphenols in diabetic retinopathy. Journal of functional foods, Volume 85, October 2021.
Flavonoid intake and risk of chronic diseases. The american journal of clinical nutrition, 76 (3) (2002), pp. 560-568.
Anthocyanins increase serum adiponectin in newly diagnosed diabetes but not in prediabetes: a randomized controlled trial. Nutrition & Metabolism, 17 (1) (2020).
Regular chinese green tea consumption is protective for diabetic retinopathy: a clinic-based case-control study. Journal of diabetes research, 2015 (2015), pp. 1-7.
Influence of flavonoid-rich fruit and vegetable intake on diabetic retinopathy and diabetes-related biomarkers. Journal of diabetes and its complications, 28 (6) (2014), pp. 767-771.
Pycnogenol® for diabetic retinopathy. International ophthalmology, 24 (3) (2001), pp. 161-171.
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