Potential of Dietary Non-Provitamin A Carotenoids in the Prevention and Treatment of Diabetic Microvascular Complications

Abstract

Diabetes is a chronic metabolic disease that affects a substantial part of the population around the world. Whether type I or type II, this disease has serious macro- and microvascular complications that constitute the primary cause of death in diabetic patients. Microvascular complications include diabetic retinopathy, nephropathy, and neuropathy. Although these complications are clinically and etiologically diverse, they share a common factor: glucose-induced damage. In the progression of diabetic complications, oxidative stress, inflammation, and the formation of glycation end products play an important role. Previous studies have shown that a healthy diet is vital in preventing these complications; in particular, the intake of antioxidants has been studied for their potential effect in ameliorating hyperglycemic injuries. Carotenoids are lipid-soluble pigments synthesized by plants, bacteria, and some kinds of algae that are responsible for the yellow, red, and orange colors in food. These compounds are part of the antioxidant machinery in plants and have also shown their efficacy in quenching free radicals, scavenging reactive oxygen species, modulating gene expression, and reducing inflammation in vitro and in vivo, showing that they can potentially be used as part of a preventive strategy for metabolic disorders, including diabetes and its related complications. This review highlights the potential protective effects of 4 non-provitamin A carotenoids--lutein, zeaxanthin, lycopene, and astaxanthin--in the development and progression of diabetic microvascular complications.

Keywords: carotenoids; diabetes; inflammation; microvascular complications; oxidative stress.

FIGURE 1

Molecular structures of lycopene, astaxanthin, lutein, and zeaxanthin.

FIGURE 2

Proposed mechanisms by which non-provitamin A carotenoids may suppress glucose-induced damage and prevent microvascular complications in diabetes derived from cell and animal studies. Detrimental effects of hyperglycemia lead to microvascular complications in diabetes. High blood sugar causes oxidative stress, inflammation, and an uncontrolled production of advanced glycation products, all of which create a proinflammatory loop and cause the vascular permeability and dysfunction commonly seen in diabetic patients with retinopathy, nephropathy, or neuropathy. The carotenoids lutein, lycopene, zeaxanthin, and astaxanthin may ameliorate this glucose-induced damage by quenching free radicals, scavenging reactive oxygen species, blocking inflammatory pathways, AGE-RAGE engagement/signaling, and even decreasing plasma glucose concentrations. Arrows indicate a positive interaction, whereas bar-headed lines denote a blockage of a pathway or a decrease of a compound. Note that the mechanisms that are more strongly supported by the published evidence are shown with a dark arrow, whereas the ones shown with dotted lines represent weaker evidence. AGE, advanced glycation end product; ICAM, intercellular adhesion molecule 1; MDA, malondialdehyde; PVA, provitamin A; RAGE: receptor for advanced glycation end product; ROS, reactive oxygen species; VCAM-1, vascular adhesion protein 1; VEGF, vascular endothelial growth factor.