Dietary Supplements Potentially Target Plasma Glutathione Levels to Improve Cardiometabolic Health in Patients with Diabetes Mellitus: A Systematic Review of Randomized Clinical Trials
Abstract
:1. Introduction
2. Literature Search, Study Inclusion, and Quality Assessment
3. Results
3.1. Characteristic Features of the Included Studies
3.2. Evidence on the Effects of Dietary Supplements on Plasma Glutathione Levels and Cardiometabolic Health
3.2.1. Supplementation with CoQ10
3.2.2. Supplementation with Selenium
3.2.3. Supplementation with Melatonin and Curcumin
3.2.4. Supplementation with Omega-3 Fatty Acids and Vitamin E/D
3.2.5. Supplementation with Plant Extracts
4. Conclusions and Future Perspectives
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Author, Year | Country | Patients, Including Number and Average Age | Supplements, Dose and Intervention Period | Main Findings |
---|---|---|---|---|
Ceriello et al., 1991 [20] | Italy | Hypertensive and non-hypertensive diabetic patients (n = 20), with an age between 28 and 45 years | Received vitamin C, thiopronine and glutathione (GSH) at doses, reaching 6 and 12 mmol. Evaluation of blood pressure and heart rate was at 10/15 min intervals during a 1/2 h basal periods after intake of antioxidants | GSH and thiopronine displayed hypotensive effects at a dose of 12 mmol. However, all antioxidants had no effect on blood pressure in healthy normal subjects |
Knezević et al., 2000 [21] | Serbia | Patients with ischemic heart disease (n = 51), and some with diabetes mellitus (18%), age not reported | Received tocopherol (vitamin E) acetate at 450 mg for 3 months | Treatment improved blood glucose control and superoxide dismutase (SOD) levels in patients with diabetes. However, increased total antioxidant capacity in patients without diabetes. No effect was seen with glutathione-peroxidase (Gpx) |
Qian et al., 2012 [22] | China | Diabetic patients with chronic heart disease (n = 24), with an average age of 60 years | Received a tablet of Salvia miltiorrhiza hydrophilic extract at 5 g twice per day for 60 days in addition to their existing hypoglycemic therapy | Treatment did not affect lipid profiles but reduced markers of oxidative stress, including the levels of malondialdehyde (MDA). This was accompanied by increased serum GSH level, SOD, paraoxonase and GSH reductase |
Ramirez-Sanchez et al., 2013 [23] | Mexico | Patients with stable New York Heart Association stages II and III HF and T2D (n = 5), with an age between 47 and 70 years | Received Hershey’s extra dark 60% Cacao chocolate and cocoa beverages containing 18 g of natural cocoa powder (twice daily) for 3 months, with a total of 100 mg (-)-epicatechin | Treatment promoted recovery in GSH levels and reduced nitrotyrosilation and carbonylation of proteins within the skeletal muscle of patients, as well as transcriptional factors related to the enhancement of SOD2 and catalase protein expression |
Huguenin et al., 2015 [24] | Brazil | Hypertensive and dyslipidemic subjects (n = 52), with an average age of 62 years | Received a diet combined with granulated Brazil nut at 13 g per day (≈227.5 μg/day of selenium) for 3 months with 1 month washout interval | Treatment improved lipid profile by reducing low-density lipoprotein (LDL) levels and this was inversely linked with Gpx3 concentrations. However, did not affect the oxidative stress marker, 8-epi-prostaglandin F2alpha (8-epi PGF2α) |
Raygan et al., 2016 [25] | Iran | Overweight or obese patients with T2D and coronary heart disease (n = 30), with an age between 40 and 85 years | Received 100 mg coenzyme Q10 (CoQ10) supplementation for 2 months | Treatment improved metabolic profiles, including serum insulin levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Plasma total antioxidant capacity was neutralized after adjusting for age. However, GSH levels were increased, and MDA was reduced. However, treatment did not affect fasting plasma glucose, lipid concentrations and inflammatory markers |
Raygan et al., 2018 [26,27] | Iran | Patients with congestive heart failure and impaired fasting plasma glucose (n = 26), with an average age between 45 and 85 years | Received selenium at 200 µg/d for 3 months | Treatment improved insulin metabolism and reduced cardiometabolic risk by decreasing LDL-cholesterol and hs-CRP, while increasing plasma total antioxidant capacity and total GSH levels |
Raygan et al., 2019 [28] | Iran | Patients with T2D and coronary heart disease (n = 30), with an average age of 65 years | Received omega-3 fatty acids from fish oil at 1000 mg or omega-3 fatty acids from flaxseed oil at 1000 mg twice a day for 3 months | Treatment improved metabolic profile, including decreasing insulin and hs-CPR levels, while increasing the total antioxidant capacity, including GSH levels |
Raygan et al., 2019 [29] | Iran | Patients with T2D and coronary heart disease (n = 27), with an average age of 65 years | Received selenium at 200 μg/day plus 8 × 109 CFU/day probiotic for 3 months | Treatment improved metabolic profiles such as fasting plasma glucose, and serum insulin levels. In fact, co-supplementation improved lipid profiles by reducing triglycerides, total cholesterol, and hs-CRP, while enhancing levels of nitric oxide, total antioxidant capacity and total GSH |
Raygan et al., 2019 [30] | Iran | Patients with T2D and coronary heart disease (n = 27), with an average age of 65 years | Received melatonin capsules at 10 mg (2 melatonin capsules, 5 mg each) once a day for 3 months | Treatment improved metabolic and lipid profiles by decreasing fasting plasma glucose, HOMA-IR, and total cholesterol. In addition, reduced blood pressure and markers of inflammation and oxidative stress like MDA, hs-CRP and increasing plasma GSH levels |
Shafabakhsh et al., 2020 [31] | Iran | Patients with T2D and coronary heart disease (n = 27), with an average age between 45 and 85 years | Received curcumin at 1000 mg/day for 3 months | Treatment improved sleep quality, by reducing Pittsburgh Sleep Quality Index. This was accompanied by reduced markers of oxidative stress like MDA. Furthermore, total antioxidant capacity and GSH levels were also increased. In addition, the expression of peroxisome proliferator-activated receptor gamma from mononuclear cells from peripheral blood was increased |
Hoseini et al., 2022 [32] | Iran | Patients with T2D (n = 40), with an average age between 35 and 50 years | Received vitamin D at 50,000 IU for 2 months, with aerobic training program executed for 20–40 min/day, at 60–75% of heart rate maximum, for 3 days/week | Improved metabolic profile like fasting plasma glucose, insulin, and HOMA-IR; and reduced markers of oxidative stress (MDA and 8-OHdG). Markers of inflammation were also reduced, including hs-CRP, and gene expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), mitogen-activated protein kinases 1, nuclear factor kappa B (NF-κB) 1. This was consistent with elevated levels of total GSH, Gpx, SOD, catalase, and total antioxidant capacity |
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Dludla, P.V.; Ziqubu, K.; Mabhida, S.E.; Mazibuko-Mbeje, S.E.; Hanser, S.; Nkambule, B.B.; Basson, A.K.; Pheiffer, C.; Tiano, L.; Kengne, A.P. Dietary Supplements Potentially Target Plasma Glutathione Levels to Improve Cardiometabolic Health in Patients with Diabetes Mellitus: A Systematic Review of Randomized Clinical Trials. Nutrients 2023, 15, 944. https://doi.org/10.3390/nu15040944
Dludla PV, Ziqubu K, Mabhida SE, Mazibuko-Mbeje SE, Hanser S, Nkambule BB, Basson AK, Pheiffer C, Tiano L, Kengne AP. Dietary Supplements Potentially Target Plasma Glutathione Levels to Improve Cardiometabolic Health in Patients with Diabetes Mellitus: A Systematic Review of Randomized Clinical Trials. Nutrients. 2023; 15(4):944. https://doi.org/10.3390/nu15040944
Chicago/Turabian StyleDludla, Phiwayinkosi V., Khanyisani Ziqubu, Sihle E. Mabhida, Sithandiwe E. Mazibuko-Mbeje, Sidney Hanser, Bongani B. Nkambule, Albertus K. Basson, Carmen Pheiffer, Luca Tiano, and André P. Kengne. 2023. "Dietary Supplements Potentially Target Plasma Glutathione Levels to Improve Cardiometabolic Health in Patients with Diabetes Mellitus: A Systematic Review of Randomized Clinical Trials" Nutrients 15, no. 4: 944. https://doi.org/10.3390/nu15040944