Antioxidant effects of astaxanthin and metformin combined therapy in type 2 diabetes mellitus patients: a randomized double-blind controlled clinical trial

Abstract

Background and purpose: Since the critical role of oxidative stress in the pathogenesis and complications of type 2 diabetes mellitus (T2DM) has been proven, antioxidant therapy is considered an applicable strategy to control T2DM development. This study aimed at evaluating the effect of astaxanthin (AST) supplementation combined with metformin on oxidative indices and antioxidant defenses in T2DM patients. Experimental approach: In this randomized, double-blind placebo-controlled trial, 50 T2DM subjects receiving metformin were supplemented with 10 mg/day AST or placebo for 12 weeks. Malondialdehyde concentration and serum total antioxidant capacity (TAC) were assessed as oxidative indices. We also evaluated NF-E2-related factor2 (Nrf2) as the most critical transcription factor of antioxidant defense. Moreover, the activity of antioxidant enzymes, superoxide dismutase (SOD), and catalase were calculated. Findings/Results: AST supplementation-metformin combination caused a significant increase in SOD and catalase activities, as well as inducing Nrf2 protein expression compared to the placebo group. Significant changes in serum malondialdehyde and TAC between the AST group and placebo group after supplementation were not observed, although a significant increase was observed in TAC within the AST group after supplementation (32.67 ± 6.73) to before (25.86 ± 5.98). These results remained without change after adjustment for potential confounders. Conclusion and implications: Our study demonstrated that AST supplementation controlled oxidative stress through a synergistic effect with metformin and ameliorated overall antioxidant capacity by inducing Nrf2 transcription factor and activating SOD and catalase in T2DM patients. As a result, AST and metformin combination therapy can be considered beneficial in modifying oxidative stress and preventing T2DM complications.

Effects of Astaxanthin supplementation on selected metabolic parameters, anthropometric indices, Sirtuin1 and TNF-α levels in patients with coronary artery disease: A randomized, double-blind, placebo-controlled clinical trial

“…Alike our results, Roustae Rad et al investigated that lipid profile did not change significantly through consuming 10 mg AX after 12 weeks in T2DM subjects receiving metformin ( 26 ). Also, administration of 12 mg AX for 12 weeks in healthy volunteers including subjects with prediabetes exhibit the same outcomes ( 19 ).…”

Microalgae as a Nutraceutical Tool to Antagonize the Impairment of Redox Status Induced by SNPs: Implications on Insulin Resistance

“…Thus, carotenoids not only directly scavenge ROS, but they also indirectly counteract oxidative stress by inducing genes involved in the cellular machinery responsible for detoxifying ROS [ 190 ]. In support of this, supplementation of astaxanthin in subjects affected by T2DM resulted in the upregulation of NRF2 [ 135 ]. The induction of this transcription factor in response to carotenoids also holds true for β-carotene [ 129 ], lutein [ 133 ], zeaxanthin [ 138 ], fucoxanthin [ 141 ], and β-cryptoxanthin [ 136 ] ( Figure 2 ).…”