Folic acid supplementation on inflammation and homocysteine in type 2 diabetes mellitus: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The beneficial effects of folate have been observed under different conditions, but the available evidence on inflammation and reduction of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) is limited. The study aimed to explore the effects of folate on inflammation and homocysteine amongst individuals with T2DM. METHODS: PubMed, Scopus, and Cochrane Library were used to search for evidence. A random-effect model meta-analysis through Review Manager (version 5.4) and metaHun was performed. Results were reported as standardized mean differences (SMD) and 95% confidence intervals graphically using forest and funnel plots. RESULTS: Data from 9 trials with 426 patients living with T2DM were analyzed. Folic acid supplementation significantly revealed a large effect size on homocysteine levels compared to placebo, SMD = -1.53, 95%CI (-2.14,-0.93), p < 0.05. Additionally, we observed a medium marginal effect size on C-reactive protein (SMD = -0.68, 95%CI (-1.34, -0.01), p = 0.05). However, no significant effect on tumor necrosis factor-α (SMD = -0.86, 95%CI (-2.65, 0.93), p = 0.34), and interleukin-6 (SMD = -0.04, 95%CI (-1.08, 1.01), p = 0.95) was observed. CONCLUSION: Evidence analyzed in this study suggests that folic acid supplementation in T2DM reduces homocysteine and may mitigate CVDs. However, its effect on inflammation is inconclusive.

Modulatory Properties of Vitamin D in Type 2 Diabetic Patients: A Focus on Inflammation and Dyslipidemia.

BACKGROUND: Evidence from preclinical studies has found a correlation between the development of type 2 diabetes (T2D) and vitamin D deficiency. However, evidence from randomized controlled trials (RCTs) revealed inconclusive results on vitamin D supplementation. We explored the effect of vitamin D on inflammation and dyslipidemia in T2D. METHODS: We comprehensively searched for RCTs evaluating the effect of vitamin D in T2D on PubMed. Data were analyzed using Review Manager 5.3 and reports, such as standardized mean difference (SMD) and 95% confidence intervals (CI) at a 5% significant level using a random effect model. RESULTS: This study revealed a significant reduction in tumor necrosis factor-alpha (TNF-α) SMD = (-0.51, 95%CI (-0.93, -0.09); p = 0.02), high sensitivity C-reactive protein (hs-CRP) SMD = (-1.06, 95%CI (-1.67, -0.45); p < 0.05) in vitamin D compared to placebo. Additionally, interleukin-6 (IL-6) exhibited a marginal effect SMD = (-0.52, 95%CI (-1.05, 0.01), p = 0.05). Furthermore, a significant reduction in the level of triglycerides SMD = (-0.65, 95%CI (-1.11, -0.18), p < 0.05) was observed, concomitant to a significantly increased high-density lipoprotein (HDL) level SMD = (0.53, 95%CI (0.08, 0.98), p = 0.02). However, no statistically significant changes were observed in total cholesterols SMD = (-0.16, 95%CI (-0.57, 0.24), p = 0.43) and low-density lipoprotein (LDL) SMD = (-0.06, 95%CI (-0.37, 0.24), p = 0.67). CONCLUSIONS: These findings suggest that vitamin D supplementation may be beneficial in ameliorating inflammation and dyslipidemia in T2D patients.

Comprehensive Overview of the Effects of Amaranthus and Abelmoschus esculentus on Markers of Oxidative Stress in Diabetes Mellitus.

The use of medicinal plants in the management of diabetes mellitus (DM) is extensively reported. However, there is still very limited information on the role of these plants as markers of oxidative stress in DM. This current review evaluated the effect of Amaranthus spinosus, Amaranthus hybridus, and Abelmoschus esculentus on markers of oxidative stress in rodent models of DM. Current findings indicate that these plants have the potential to reduce prominent markers of oxidative stress, such as serum malondialdehyde and thiobarbituric acid-reactive substances, while increasing enzymes that act as antioxidants, such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase. This may reduce reactive oxygen species and further ameliorate oxidative stress in DM. Although the potential benefits of these plants are acknowledged in rodent models, there is still a lack of evidence showing their efficacy against oxidative stress in diabetic patients. Therefore, we recommend future clinical studies in DM populations, particularly in Africa, to evaluate the potential effects of these plants. Such studies would contribute to enhancing our understanding of the significance of incorporating these plants into dietary practices for the prevention and management of DM.

Vitamin C intake potentially lowers total cholesterol to improve endothelial function in diabetic patients at increased risk of cardiovascular disease: A systematic review of randomized controlled trials.

Background: Vitamin C is one of the most consumed dietary compounds and contains abundant antioxidant properties that could be essential in improving metabolic function. Thus, the current systematic review analyzed evidence on the beneficial effects of vitamin C intake on cardiovascular disease (CVD)-related outcomes in patients with diabetes or metabolic syndrome. Methods: To identify relevant randomized control trials (RCTs), a systematic search was run using prominent search engines like PubMed and Google Scholar, from beginning up to March 2022. The modified Black and Downs checklist was used to assess the quality of evidence. Results: Findings summarized in the current review favor the beneficial effects of vitamin C intake on improving basic metabolic parameters and lowering total cholesterol levels to reduce CVD-risk in subjects with type 2 diabetes or related metabolic diseases. Moreover, vitamin C intake could also reduce the predominant markers of inflammation and oxidative stress like C-reactive protein, interleukin-6, and malondialdehyde. Importantly, these positive outcomes were consistent with improved endothelial function or increased blood flow in these subjects. Predominantly effective doses were 1,000 mg/daily for 4 weeks up to 12 months. The included RCTs presented with the high quality of evidence. Conclusion: Clinical evidence on the beneficial effects of vitamin C intake or its impact on improving prominent markers of inflammation and oxidative stress in patients with diabetes is still limited. Thus, more RCTs are required to solidify these findings, which is essential to better manage diabetic patients at increased risk of developing CVD.

Curcumin supplementation improves biomarkers of oxidative stress and inflammation in conditions of obesity, type 2 diabetes and NAFLD: updating the status of clinical evidence.

Oxidative stress and inflammation remain the major complications implicated in the development and progression of metabolic complications, including obesity, type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). In fact, due to their abundant antioxidant and anti-inflammatory properties, there is a general interest in understanding the therapeutic effects of some major food-derived bioactive compounds like curcumin against diverse metabolic diseases. Hence, a systematic search, through prominent online databases such as MEDLINE, Scopus, and Google Scholar was done focusing on randomized controlled trials (RCTs) reporting on the impact of curcumin supplementation in individuals with diverse metabolic complications, including obesity, T2D and NAFLD. Summarized findings suggest that curcumin supplementation can significantly reduce blood glucose and triglycerides levels, including markers of liver function like alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with T2D and NAFLD. Importantly, this effect was consistent with the reduction of predominant markers of oxidative stress and inflammation, such as the levels of malonaldehyde (MDA), tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP) and monocyte chemoattractant protein-1 (MCP-1) in these patients. Although RCTs suggest that curcumin is beneficial in ameliorating some metabolic complications, future research is still necessary to enhance its absorption and bioavailability profile, while also optimizing the most effective therapeutic doses.

Vitamin K: A vital micronutrient with the cardioprotective potential against diabetes-associated complications.

Cardiovascular disease (CVD) remains the leading cause of mortality in patients with type 2 diabetes (T2D). The conventional therapies seem to offer minimal long-term cardioprotection against diabetes-related complications in patients living with T2D. There is a growing interest in understanding the therapeutic effects of food-derived bioactive compounds in protecting or managing these metabolic diseases. This includes uncovering the therapeutic potential of fat-soluble micronutrients such as vitamin K, which are abundantly found in green leafy vegetables. We searched the major electronic databases including PubMed, Web of Sciences, Scopus, Google Scholar and Science direct. The search retrieved randomized clinical trials and preclinical studies, reporting on the impact of vitamin K on CVD-related complications in T2D. The current review updates clinical evidence on the therapeutic benefits of vitamin K by attenuating CVD-risk factors such as blood lipid profiles, blood pressure, as well as markers of oxidative stress and inflammation in patients with T2D. Importantly, the summarized preclinical evidence provides a unique perspective into the pathophysiological mechanisms that could be targeted by vitamin K in the primary prevention of T2D-related complications. Lastly, this review further explores the controversies related to the cardioprotective effects of vitamin K, and also provides the basic information such as the source and bioavailability profile of this micronutrient is covered to highlight its therapeutic potential.

Tea consumption and its effects on primary and secondary prevention of coronary artery disease: Qualitative synthesis of evidence from randomized controlled trials.

BACKGROUND AND AIMS: There is a general interest in understanding how the consumption of tea impacts cardiovascular function in individuals at risk of developing cardiovascular disease (CVD). The current review focuses on evidence from randomized controlled trials (RCTs) reporting on associations between tea consumption and endothelial function, in the primary and secondary prevention of coronary artery disease (CAD). METHODS: PubMed, EMBASE, and Google Scholar databases/search engines were used to identify eligible studies. Included studies had to report on the impact of tea supplementation of endothelial function or CAD related markers. In addition to flow-mediated dilation (FMD), makers of oxidative stress and inflammation such as oxidized low-density lipoprotein and C-reactive protein were considered as determinants of endothelial function. A total of 34 RCTs met the inclusion criteria, and these reported on the impact of tea consumption on endothelial function in individuals at risk of CVD or patients with CAD. RESULTS: The current qualitative synthesis of literature demonstrates that beyond enhancing nitric oxide bioavailability and lowering blood pressure, regular consumption of tea and its active ingredients such as epigallocatechin gallate may be beneficial in reducing markers of oxidative stress and inflammation. Moreover, the reduction of oxidized low-density lipoprotein and C-reactive protein levels, could be a sign of improved endothelial function in individuals at increased risk of developing CVD. CONCLUSIONS: The cumulative evidence also suggests that the development of epigallocatechin gallate as a nutraceutical or enriching foods with this bioactive compound could be a feasible strategy to improve endothelial function and lower CVD-risk. However, well-designed RCTs are still necessary to confirm long-term benefits of tea consumption on vascular health.

A Meta-Analysis of the Impact of Resveratrol Supplementation on Markers of Renal Function and Blood Pressure in Type 2 Diabetic Patients on Hypoglycemic Therapy.

Evidence on the beneficial effects of resveratrol supplementation on cardiovascular disease-related profiles in patients with type 2 diabetes (T2D) is conflicting, while its impact on renal function and blood pressure measurements remains to be established in these patients. The current meta-analysis included randomized controlled trials (RCTs) reporting on the impact of resveratrol supplementation on markers of renal function and blood pressure in patients with T2D on hypoglycemic medication. Electronic databases such as MEDLINE, Cochrane Library, Scopus, and EMBASE were searched for eligible studies from inception up to June 2020. The random and fixed effects model was used in the meta-analysis. A total of five RCTs met the inclusion criteria and involved 388 participants with T2D. Notably, most of the participants were on metformin therapy, or metformin in combination with other hypoglycemic drugs such as insulin and glibenclamide. Pooled estimates showed that resveratrol supplementation in patients with T2D lowered the levels of fasting glucose (SMD: -0.06 [95% CI: -0.24, 0.12]; I2 = 4%, p = 0.39) and insulin (SMD: -0.08 [95% CI: -0.50, 0.34], I2 = 73%, p = 0.002) when compared to those on placebo. In addition, supplementation significantly lowered systolic blood pressure (SMD: -5.77 [95% CI: -8.61, -2.93], I2 = 66%, p = 0.02) in these patients. Although resveratrol supplementation did not affect creatinine or urea levels, it reduced the total protein content (SMD: -0.19 [95% CI: -0.36, -0.02]; I2 = 91%, p = 0.001). In all, resveratrol supplementation in hypoglycemic therapy improves glucose control and lowers blood pressure; however, additional evidence is necessary to confirm its effect on renal function in patients with T2D.

The prophylactic effects of vitamin K supplementation on coagulopathies associated with type 2 diabetes mellitus: A protocol for a systematic review and meta-analysis.

BACKGROUND: The impact of vitamin K in ameliorating diabetes-associated complications, especially those linked with platelet activation and coagulation remains unclear. The current study aims to systematically explore and discuss the available evidence on the impact of vitamin K on the diabetes-cardiovascular disease (CVD)-associated complications. METHODS: A systematic review of studies published on the MEDLINE (PubMed), EMBASE, and Google Scholar electronic database will be conducted. The review will include studies published from inception until May 25, 2020, reporting on the effect of vitamin K on CVD-related markers, especially coagulation factors and platelet activation in type 2 diabetes mellitus. Before the full-text screening, all studies will be screened by title, abstract, and keywords. The Downs and Black checklist will be used to assess the quality of the studies. Additionally, the Cochrane collaboration tool will also be used to evaluate the risk of bias across the included studies. Kappa Cohen's calculator will be used to assess the level of agreement between the authors. DISCUSSIONS: This systematic review will not require ethical approval, and the results will be distributed through conference and peer-reviewed publications. Our results will assist current and future research scientists on the potential use of vitamin K as a protective therapy against CVD-related complications. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered on the International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42020151667.

Coenzyme Q10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials.

Evidence from randomized controlled trials (RCTs) suggests that coenzyme Q10 (CoQ10) can regulate adipokine levels to impact inflammation and oxidative stress in conditions of metabolic syndrome. Here, prominent electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible RCTs reporting on any correlation between adipokine levels and modulation of inflammation and oxidative stress in individuals with metabolic syndrome taking CoQ10. The risk of bias was assessed using the modified Black and Downs checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to evaluate the quality of evidence. Results from the current meta-analysis, involving 318 participants, showed that CoQ10 supplementation in individuals with metabolic syndrome increased adiponectin levels when compared to those on placebo (SMD: 1.44 [95% CI: -0.13, 3.00]; I2 = 96%, p < 0.00001). Moreover, CoQ10 supplementation significantly lowered inflammation markers in individuals with metabolic syndrome in comparison to those on placebo (SMD: -0.31 [95% CI: -0.54, -0.08]; I2 = 51%, p = 0.07). Such benefits with CoQ10 supplementation were related to its ameliorative effects on lipid peroxidation by reducing malondialdehyde levels, concomitant to improving glucose control and liver function. The overall findings suggest that optimal regulation of adipokine function is crucial for the beneficial effects of CoQ10 in improving metabolic health.