Dietary Supplements Potentially Target Plasma Glutathione Levels to Improve Cardiometabolic Health in Patients with Diabetes Mellitus: A Systematic Review of Randomized Clinical Trials

Abstract

Cardiovascular diseases (CVDs) continue to be the leading cause of death in people with diabetes mellitus. Severely suppressed intracellular antioxidant defenses, including low plasma glutathione (GSH) levels, are consistently linked with the pathological features of diabetes such as oxidative stress and inflammation. In fact, it has already been established that low plasma GSH levels are associated with increased risk of CVD in people with diabetes. Dietary supplements are widely used and may offer therapeutic benefits for people with diabetes at an increased risk of developing CVDs. However, such information remains to be thoroughly scrutinized. Hence, the current systematic review explored prominent search engines, including PubMed and Google Scholar, for updated literature from randomized clinical trials reporting on the effects of dietary supplements on plasma GSH levels in people with diabetes. Available evidence indicates that dietary supplements, such as coenzyme Q₁₀, selenium, curcumin, omega-3 fatty acids, and vitamin E or D, may potentially improve cardiometabolic health in patients with diabetes. Such beneficial effects are related to enhancing plasma GSH levels and reducing cholesterol, including biomarkers of oxidative stress and inflammation. However, available evidence is very limited and additional clinical studies are still required to validate these findings, including resolving issues related to the bioavailability of these bioactive compounds.

Keywords: antioxidants; cardiometabolic health; cardiovascular diseases; diabetes mellitus; glutathione; inflammation; oxidative stress.

Figure 1

An overview of the glutathione biosynthesis pathway and its influence from external factors like free radical species. Briefly, the diabetic state is associated with depleted intracellular antioxidants (including glutathione) and increased risk of developing of atherosclerosis and cardiovascular disease. Both oxidative stress and inflammation are implicated in this process. Abbreviations; AR: aldose reductase, CAT: catalase, GCL: γ-glutamyl cysteine synthetase, GS: glutathione synthetase, GSH: glutathione, GR: glutathione reductase, GPx: glutathione peroxide, GSH: glutathione, GSSG: glutathione disulfide, NADPH: nicotinamide adenine dinucleotide phosphate, SOD, superoxide dismutase, ROS: reactive oxygen species.

Figure 2

An overview of the flow diagram representing study inclusion.

Figure 3

Dietary supplements such as coenzyme Q₁₀, selenium, curcumin, omega-3 fatty acids, and vitamin E or D can potentially enhance intracellular antioxidants (including glutathione) to improve cardiometabolic health in diabetic patients. These effects are associated with reduced low-density lipoprotein-cholesterol, oxidative stress, and inflammation, while improving blood glucose control and blocking the destructive effects of sorbitol. Abbreviations; GSSG: glutathione disulfide, GSH: glutathione, MDA: malondialdehyde, 8-OHdG: 8-hydroxyguanosine, NADP(H): nicotinamide adenine dinucleotide phosphate, hs-CRP: high sensitivity C-reactive protein, LDL: low-density lipoprotein, ROS: reactive oxygen species.