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Comparative effects of vitamin and mineral supplements in the management of type 2 diabetes in primary care: A systematic review and network meta-analysis of randomized controlled trials.
Xia, J, Yu, J, Xu, H, Zhou, Y, Li, H, Yin, S, Xu, D, Wang, Y, Xia, H, Liao, W, et al
Pharmacological research. 2023;188:106647
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Type 2 diabetes mellitus (T2DM), characterised by sustained hyperglycaemia and insulin resistance, remains a severe driver of chronic metabolic diseases such as cardiovascular diseases. The aim of this study was to investigate and compare the efficacy of vitamin and mineral supplements in the management of glycaemic control and lipid metabolism for type 2 diabetic patients to inform clinical practice. This study is a systematic review and meta-analysis of one hundred and seventy articles with a total of 4223 adults with T2DM. Participants were randomised to either the placebo/no treatment group (n= 6345) or to the treatment group (n= 7878). Results show that: - chromium was the most effective micronutrient for decreasing fasting blood glucose and insulin resistance. - vitamin K was the top-ranked micronutrient in reducing haemoglobin A1C and fasting insulin levels. - vanadium was the top-ranked micronutrient in total cholesterol reductions. - niacin was ranked as the most effective in triglycerides reductions and increasing high-density lipoprotein cholesterol levels. - vitamin E was the top-ranked micronutrient in low-density lipoprotein cholesterol reductions. Authors conclude that micronutrient supplements especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more effective in the management of T2DM compared with other micronutrients.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Clinicians could consider the adjunctive effect of micronutrients supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements in a nutrition protocol to manage T2DM and slow or prevent its complications.
- The study authors state that the vitamin and mineral supplements under review had a statistically significant improvement, however they did not reach the study threshold for clinical significance. Therefore they advise caution in utilising micronutrient supplements in the management of glucose and lipid metabolism for T2DM.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Objectives
The aim of this systematic review was to evaluate the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM).
Methodology
This systematic review is registered with PROSPERO and adhered to PRISMA-2020 guidelines for network meta-analysis
The Cochrane Collaboration’s risk-of-bias tool was used to assess eligible randomised trials
8 prespecified markers identified and assessed in this study : 1) HbA1c (%), 2) fasting blood glucose (mmol/L), 3) total cholesterol (mmol/L), 4) triglycerides (mmol/L), 5) fasting insulin (μIU/mL), 6) HOMA-IR, 7) LDL-c (mmol/L), and 8) HDL-c (mmol/L).
Results
- 170 RCT trials of 14223 participants with T2DM treated with vitamin supplements, mineral supplements, or placebo/no treatment were included
- Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively)
- Vitamin K supplements ranked best in reducing glycated haemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence
- Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%)
- Niacin supplements ranked best in triglyceride reductions and increasing high-density lipo-protein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively)
- Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%).
Conclusion
- Micronutrient supplements, such as chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be efficacious in managing T2DM
- It should be noted that the evidence certainty for all was low.
Clinical practice applications:
- Chromium plays an important role in carbohydrate and lipid metabolism and was the most effective micronutrient for decreasing fasting blood glucose, HbA1c, fasting insulin, and HOMA-IR reductions. More pronounced effects were seen for chromium than vitamin E, vitamin C, niacin, selenium, and magnesium supplements
- Vitamin K was the top-ranked micronutrient in reducing HbA1c and fasting insulin levels. The mechanism through which Vitamin K affects glucose metabolism is proposed as activation of the AMP-activated protein kinase/sirtuin 1, that in turn increases phosphocreatine 3-kinase and glucose transporter 2 to decrease insulin resistance and fasting glucose.
- Vanadium was the top-ranked micronutrient in total cholesterol (TC) reductions, where supplementation dosage should be carefully considered, as vanadium compounds can be moderately or highly toxic. Vanadium supplementation is only recommended in cases of vanadium deficiency or diabetes, hyperlipidemia, and hypertension, where the intake of vanadium from food should be enhanced in preference to supplementation
- Niacin was ranked as the most effective in triglyceride (TG) reductions and increasing HDL cholesterol levels. The dose of niacin could not be determined
- Vitamin E was the top-ranked micronutrient in low-density lipo- protein (LDL) cholesterol reductions.
Considerations for future research:
- Considering the clinical importance of these findings, new research is needed to get better insight into the efficacy of micronutrient supplements in managing T2DM
- Selenium homeostasis, selenoprotein, insulin signaling/secretion, and carbohydrate/lipid metabolism are linked in multiple and complex ways but the authors could not explain why chromium supplementation would lower blood glucose more effectively than selenium supplementation, and suggest more research is needed to clarify this
- While vitamin K status could be an emerging treatment target in T2DM prevention and management, it remains to be determined whether vitamin K supplementation has an advantage over other nutrients in terms of hypoglycemic effect, and further research is necessary
- The beneficial effect of vitamin E and niacin supplements regarding lipid metabolism warrant investigation through more rigorous comparative studies.
Abstract
Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.
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The Effect of Resveratrol on Blood Lipid Profile: A Dose-Response Meta-Analysis of Randomized Controlled Trials.
Cao, X, Liao, W, Xia, H, Wang, S, Sun, G
Nutrients. 2022;14(18)
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It is well known that cardiovascular disease is a leading cause of death. Imbalances in the blood lipid levels, such as elevation of total cholesterol, Triglycerides and LDL cholesterol, may increase the risk of cardiovascular disease. It has been shown that resveratrol, a polyphenol found in grapes, blueberries, mulberries, raspberries, peanuts, and knotweeds, has protective effects against cardiovascular disease. In this meta-analysis, 17 randomised controlled trials were included, with varying durations of 4 to 48 weeks and intervention dosages ranging from 10 to 3000 mg/day. According to the results of this meta-analysis, Resveratrol supplementation significantly reduced total cholesterol, triglycerides, and LDL cholesterol, but not HDL cholesterol. In addition, the reduction in LDL cholesterol was more significant in type 2 diabetic patients when resveratrol was supplemented for 12 weeks or more. A crucial factor in determining the effectiveness of resveratrol supplementation is its dosage. High doses over 500 mg/day were found to have the opposite effect of increasing body mass index and body weight and suppressing the cardioprotective effect. The effects of different dosages and durations of resveratrol supplementation on cardiometabolic health require further robust research. Healthcare professionals may use the results of this study to understand the importance of careful consideration when supplementing resveratrol as a nutraceutical.
Abstract
(1) Background: The effects of resveratrol on blood lipids are controversial. Whether there is a dose-response of the lipid profile upon resveratrol supplementation is unknown. (2) Methods: This dose-response meta-analysis of randomized controlled trials (RCTs) was performed to explore the effects of resveratrol supplementation on lipid profile. A systematical and comprehensive search of several databases was conducted by 30 June 2022. (3) Results: The results indicated that the intake of resveratrol could significantly decrease the total cholesterol (TC) (mean difference = -10.28; 95%CI: -13.79, -6.76, p < 0.001), triglyceride (TG) (Mean difference = -856; 95%CI: -12.37, -4.75, p < 0.001) and low-density lipoprotein cholesterol (LDL-C) (mean difference = -5.69; 95%CI: -11.07, -0.31, p = 0.038) level, but did not alter the level of high-density lipoprotein cholesterol (HDL-C). In the non-linear dose-response analysis, we observed a significant effect of the supplementation dosage on the level of LDL-C (p-nonlinearity = 0.002). Results from the sub-group analysis showed that the reduction of LDL-C was more significant in the trials with a duration of ≥12 weeks and in subjects with type 2 diabetes mellitus. (4) Conclusion: Findings from this study suggest that resveratrol may be beneficial to reduce TC, TG, and LDL-C levels in the blood. The dosage of the resveratrol intervention is an essential factor that affects the level of LDL-C.
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Nigella sativa supplementation improves cardiometabolic indicators in population with prediabetes and type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.
Saadati, S, Naseri, K, Asbaghi, O, Abhari, K, Zhang, P, Li, HB, Gan, RY
Frontiers in nutrition. 2022;9:977756
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Chronic, non-infectious diseases contribute to nearly three-quarters of deaths worldwide. Type 2 diabetes mellitus (T2DM) together with cardiovascular disease, are the two most common conditions in this category. Insulin resistance, obesity, elevated blood fats, and high blood pressure are typical hallmarks of T2DM and its development and are also significant risk factors for diabetes-related cardiovascular events. The prolonged nature of T2DM and the complications that can go alongside make the condition one of the most costly diseases for healthcare systems hence finding cost-effective therapeutic strategies should be of high importance. Many functional plants and their bioactive components have shown to exert anti-diabetic effects, including Nigella sativa, commonly known as black cumin. Previous studies also reported promising benefits of Nigella on cardiometabolic health. How these effects manifest in individuals with T2DM and those who are prediabetic was analysed in this systematic review and meta-analysis. The review included 11 randomised controlled trials with a total of 666 subjects. The review focused on cardiometabolic measures such as body measurements, blood sugar control, insulin resistance and secretion, blood fats, and markers of inflammation and oxidative stress. Nigella supplementation appeared to have favourable effects on blood sugar control overall but with no changes in the outcomes of oral glucose tolerance tests. Furthermore, Nigella appeared to positively influence on various blood fats, and markers of inflammation and oxidative stress. There were no changes to fasting insulin, insulin resistance, triglyceride, high-density lipoprotein (HDL)-Cholesterol and body mass index (BMI) when compared to the control group. Yet, in a sub-analysis Nigella supplementation enhanced serum levels of 'good' HDL-Cholesterol in a particular group. An improvement in insulin resistance and a decrease in BMI were seen in supplementation trials lasting over 8-weeks with doses of over 1 g/day of Nigella. The authors concluded that Nigella has the potential to improve cardiometabolic parameters by favourably influencing blood sugar metabolism and blood fats, inflammation, and oxidative stress in individuals with prediabetes and T2DM. Hence Nigella supplementation has promsing potential as an adjunct therapeutic in the management of prediabetes and T2DM.
Abstract
OBJECTIVE Nigella sativa (N. sativa) from the family Ranunculaceae has medicinal properties. Previous studies have reported promising findings showing that N. sativa may benefit cardiometabolic health; however, current evidence on its cardiometabolic effects on those with prediabetes and type 2 diabetes mellitus (T2DM) is still unclear. Hence, we conducted a systematic review and meta-analysis to assess the efficacy of N. sativa on cardiometabolic parameters in population with prediabetes and T2DM. METHODS PubMed/Medline, ISI Web of Science, Scopus, and Cochrane library were systematically searched up to June 20, 2022. Meta-analyses using random-effects models were used. RESULTS Eleven randomized controlled trials (RCTs) were included in the meta-analysis. N. sativa intervention resulted in significant changes in fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), c-reactive protein (CRP), and malondialdehyde (MDA), without overall changes in glucose levels after oral glucose tolerance test (OGTT), fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride, high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI) when compared with the control group. In subgroup analyses, N. sativa supplementation enhanced serum levels of HDL-C in subjects with baseline HDL-C lower than 40 mg/dL. Furthermore, HOMA-IR and BMI values decreased in the N. sativa-supplemented group compared with the control group, when the length of follow-up was more than 8 weeks and the dose was more than 1 g/day for N. sativa supplementation, respectively. CONCLUSION Our findings indicate that N. sativa supplementation may effectively improve cardiometabolic profiles in individuals with prediabetes and T2DM.
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Effect of supplementation with Chlorella vulgaris on lipid profile in adults: A systematic review and dose-response meta-analysis of randomized controlled trials.
Sherafati, N, Bideshki, MV, Behzadi, M, Mobarak, S, Asadi, M, Sadeghi, O
Complementary therapies in medicine. 2022;66:102822
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Dyslipidaemia is a chronic metabolic disorder that is characterized by increased levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and reduced levels of high-density lipoprotein cholesterol (HDL-C). Patients with dyslipidaemia have an increased risk of coronary heart disease, stroke, non-alcoholic fatty liver disease, diabetes and even mortality. The aim of this study was to investigate the effect of Chlorella vulgaris supplementation on lipid profile in adults. This study is a systematic review and meta-analysis of ten randomised controlled trial studies. The studies included a total of 539 individuals (n= 264 in the Chlorella vulgaris group and n= 275 in the control group). Results show that Chlorella vulgaris supplementation resulted in a significant reduction in TC and LDL-C levels, while it had no significant effect on TG and HDL-C levels either in the overall analysis or in the subgroup analysis. Furthermore, the reducing effect of Chlorella vulgaris supplementation on LDL-C levels was significant between zero and 1500 mg/d and it was not significant at higher dosages. Authors conclude that future studies should examine the effect of Chlorella vulgaris supplementation on other biochemical parameters such as glycaemic measures and inflammatory biomarkers.
Abstract
OBJECTIVE To summarize available findings on the effect of Chlorella vulgaris supplementation on lipid profile in adults. DESIGN Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING This study followed 2020 PRISMA guideline. We performed a systematic search in the online databases to identify relevant articles and then, extracted required data from each paper for the meta-analysis. Random-effects models were used to obtain overall mean difference (MD) comparing Chlorella vulgaris supplementation with a control group. MAIN OUTCOME MEASURES Blood lipids including triglyceride (TG), total cholesterol (TC), LDL-C, and HDL-C. RESULTS In total, 10 RCTs with a total sample size of 539 adults (264 in the Chlorella vulgaris group and 275 in the control group) were included. Of the 10 RCTs, four had a low risk of bias for all aspects of the Cochrane risk of bias tool. Also, only two studies determined the chlorella content, purity, potency, and contamination of the supplements used in the intervention. Combining results from these studies showed a summary MD of -2.11 mg/dL (95% CI: -7.28 to 3.06) for TG, -7.47 mg/dL (95% CI: -12.98 to -1.96) for TC, -7.71 mg/dL (95% CI: -14.05 to -1.37) for LDL-C, and -0.45 mg/dL (95% CI: -0.67 to 1.57) for HDL-C, indicating a beneficial effect of Chlorella vulgaris supplementation on TC and LDL-C levels. Based on the dose-response analysis, the reducing effect of Chlorella vulgaris supplementation on LDL-C levels was seen at the dosages between zero and 1500 mg/d (P for non-linearity= 0.01), whereas in higher amounts, this effect was not significant. CONCLUSION We found that Chlorella vulgaris supplementation had a beneficial effect on TC and LDL-C levels with no significant effect on TG and HDL-C levels.
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Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials.
Zhu, J, Xun, PC, Kolencik, M, Yang, KF, Fly, AD, Kahe, K
Nutrients. 2022;14(8)
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Dietary intake of B-vitamins or omega-3 polyunsaturated fatty acids (PUFAs) has been found to be inversely related to cardiovascular disease (CVD). The aim of this study was to examine whether the combined supplementation of B-vitamins and omega-3 PUFAs could provide additional beneficial effects on improving risk factors to prevent CVD beyond the effects of either of them alone. This study is a systematic review of fifteen studies. The sample sizes ranged from 12 to 2501 participants with study duration ranging from 4 weeks to 4.7 years. Results show that the combined supplementation with B-vitamins and omega-3 PUFAs may be promising and more effective at reducing plasma homocysteine, triglycerides and low-density lipoprotein cholesterol than each supplementation alone. Authors conclude that: - there is no solid evidence that the joint supplementation of B-vitamins and omega-3 PUFAs can offer a synergistic effect on preventing CVD and decreasing the relevant morbidity and/or mortality in susceptible populations. - dietetic strategies for preventing CVD need to focus more on the importance of considering effects at the whole food and dietary patterns level. - further well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are required.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Combined vitamin B and n3 PUFA supplementation might have favourable health effects
- Combined vitamin B and n3 PUFA supplementation could help in the primary and secondary prevention of cardiovascular disease
- The suggested favourable dose ranges are vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day, and n3 PUFA 0.2–2) g/day.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- The paper reviews whether combined supplementation of vitamin B (B2, B6, B9, and B12) and omega-3 polyunsaturated fatty acids (n3 PUFA) outweighs the individual cardiovascular benefits of each supplement. Registered in PROSPERO under CRD42018085993
- A total of 15 clinical studies including 8,263 individuals published from December 2021, that investigated the combined effects of the supplements met inclusion criteria and were included in the review
- Although the results indicate the beneficial effects of combined supplementation in primary and secondary cardiovascular prevention, firm conclusions cannot be drawn from the existing data, and more studies are needed in this area.
Clinical practice applications:
In comparison with a single supplement alone, the combined administration of vitamin B and n3 PUFA might have:
- Hypolipidemic effects, by reducing triglycerides and LDL-cholesterol. Some of the studies indicate a lowering of LDL-c up to 13% and triglycerides up to 24%
- Anti-inflammatory effects, by reducing homocysteine. Based on some of the studies, the lowering effects might go up to 39%.
Dietary practice might benefit from the following:
- The authors highlighted food-based and healthy dietary pattern-based strategies should include food sources rich in these nutrients such as fish, vegetables, fruit, legumes, nuts, and eggs
- The authors conclude that intake of whole foods and whole diets rich in desirable foods (such as MedDiet) should be encouraged
- The supplementation dose ranges in the studies covered by the review were the following: vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day and n3 PUFA 0.2–2) g/day
- Limitations of the systematic review include different supplementation regimens, variability of study designs in terms of duration of the intervention, existence of placebo group, dosages and the inability to monitor study subjects’ habitual diet.
Considerations for future research:
- Future studies should be designed regarding the need for a uniform methodological approach in testing the combined effects of vitamin B complex and n3 PUFA supplements
- The studies should investigate supplementation strategies and dietary patterns rich in both nutrients.
Abstract
Studies have suggested that B vitamins or omega-3 polyunsaturated fatty acids (PUFAs) may deter the development of cardiovascular disease (CVD). This systematic review aims to examine whether the combined supplementation of both B vitamins and omega-3 PUFAs could provide additional beneficial effects to prevent CVD beyond the effect of each supplement based on clinical trials published up to December 2021. The overall findings are inconsistent and inconclusive, yet the combined supplementation of these two nutrients may be more effective at reducing plasma homocysteine, triglyceride, and low-density lipoprotein-cholesterol than the individual components. The underlying mechanisms mainly include alleviating endothelial dysfunction, inhibiting atherosclerosis and lesion initiation, reducing oxidative stress, suppressing activation of pro-inflammatory cytokines, regulating endothelial nitric oxide synthase, and interfering with methylation of genes that promote atherogenesis. Although biologically plausible, the existing literature is insufficient to draw any firm conclusion regarding whether B vitamins can further enhance the potential beneficial effects of omega-3 PUFA intake on either primary or secondary prevention of CVD. The inconsistent findings may be largely explained by the methodological challenges. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.
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Effects of the Treatment with Flavonoids on Metabolic Syndrome Components in Humans: A Systematic Review Focusing on Mechanisms of Action.
Gouveia, HJCB, Urquiza-Martínez, MV, Manhães-de-Castro, R, Costa-de-Santana, BJR, Villarreal, JP, Mercado-Camargo, R, Torner, L, de Souza Aquino, J, Toscano, AE, Guzmán-Quevedo, O
International journal of molecular sciences. 2022;23(15)
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Metabolic syndrome is a condition characterised by at least three of the five risk factors, such as abdominal obesity, elevated fasting glucose, blood pressure and triglycerides and reduced high-density lipoprotein cholesterol (HDL-c). There is a strong link between metabolic syndrome and the development of cardiovascular disease and Type 2 diabetes. Research suggests that increasing consumption of flavonoid-rich foods can be beneficial in reducing cardiovascular morbidity and mortality. Flavonoids are bioactive compounds that possess antioxidative, anti-inflammatory, anti-cancerous, anti-mutagenic, and enzymatic properties. This systematic review of 29 randomised controlled trials evaluated the beneficial effects of long-term flavonoid supplementation in reducing the risk factors of metabolic syndrome. This review included a variety of flavonoid supplements, such as anthocyanin, hesperidin, quercetin, epigallocatechin gallate (egcg), genistein, theaflavin, catechin, and eriocitrin. Additionally, this research investigated the mechanisms behind the beneficial effects of flavonoid supplementation. Results showed that flavonoid supplementation for at least three weeks improved metabolic parameters and inflammatory markers, with hesperidin showing the greatest improvements in metabolic parameters. Healthcare professionals can use these findings to understand the potential benefits of long-term flavonoid supplementation in improving metabolic parameters. However, more robust studies are needed to determine the therapeutic dosages of different flavonoids.
Abstract
Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa. Studies have already demonstrated the benefits of flavonoids on the cardiovascular and nervous systems, as well as cancer cells. The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose. Only theaflavin and catechin were unable to affect metabolic parameters. Moreover, only body weight and body mass index were unaltered. Thus, the evidence presented in this systematic review offers bases in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and, consequently, reduce the risk of diseases associated with MetS. This fact becomes stronger due to the rare side effects reported with flavonoids.
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Cinnamon as a Complementary Therapeutic Approach for Dysglycemia and Dyslipidemia Control in Type 2 Diabetes Mellitus and Its Molecular Mechanism of Action: A Review.
Silva, ML, Bernardo, MA, Singh, J, de Mesquita, MF
Nutrients. 2022;14(13)
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Diabetes is a metabolic disorder resulting from defects in insulin secretion and/or action, leading to chronic hyperglycaemia, which has an adverse impact on health. The aim of this study was to provide an overview of the beneficial effects of cinnamon in exerting dysglycemia and dyslipidaemia control in type 2 diabetic patients and a summary of its mechanisms of action. This study is a narrative review of twenty-three articles. Results showed that: - in diabetic patients with dyslipidaemia, the lipid profile could be modulated with cinnamon supplementation as it seems to decrease serum triglycerides, total cholesterol and low-density lipoprotein levels. - cinnamon seems to exert beneficial and protective anti-inflammatory and antioxidant effects. - cinnamon seems to be effective as an antihyperlipidemic agent – through the regulation of lipid metabolism in enterocyte [a cell of the intestinal lining]. Authors conclude that targeted cinnamon-based therapy can provide an opportunity to modulate glucose and lipid dysregulation to avoid the progression of T2DM. Thus, future research studies should investigate the effect of cinnamon by employing a larger number of standardized randomized clinical trials to provide a comprehensive impact of cinnamon on diabetic patients.
Abstract
The scientific evidence that cinnamon may exert beneficial effects on type 2 diabetes mellitus due to the biological activity of its bioactive compounds has been increasing in recent years. This review provides an overview of the effects of cinnamon on clinical parameters of diabetes and summarizes the molecular mechanisms of action of cinnamon on glucose and lipid metabolism. Search criteria include an electronic search using PubMed, Medline, and Cochrane Library databases. English literature references from 2000 up to 2022 were included. Following title and abstract review, full articles that met the inclusion criteria were included. The results from the available evidence revealed that cinnamon improved glycemic and lipidemic indicators. Clinical trials clarified that cinnamon also possesses an anti-inflammatory effect, which may act beneficially in diabetes. Based on in vitro and in vivo studies, cinnamon seems to elicit the regulation of glucose metabolism in tissues by insulin-mimetic effect and enzyme activity improvement. Furthermore, cinnamon seems to decrease cholesterol and fatty acid absorption in the gut. The current literature search showed a considerable number of studies on diabetic subjects. Some limitations in comparing published data should be highlighted, including variability in doses, extracts and species of cinnamon, administration forms, and antidiabetic therapy.
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Adiponectin-leptin ratio: A promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk.
Frühbeck, G, Catalán, V, Rodríguez, A, Gómez-Ambrosi, J
Adipocyte. 2018;7(1):57-62
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Obesity is medically defined as a condition of abnormal or excessive fat accumulation in adipose tissue, of sufficient extent to produce adverse health consequences. Presently, adipose tissue has emerged as an extremely active endocrine organ, based on its ability to secrete a plethora of biologically active adipokines [a class of cytokine mediators that are predominantly secreted by adipose cells] such as leptin and adiponectin. Furthermore, obesity is characterized by an increase in circulating leptin concentrations, in parallel to a decrease in blood levels of adiponectin. Thus, the adiponectin/leptin ratio has been suggested as a marker of adipose tissue dysfunction. A dysfunctional adipose tissue, evidenced by a lower adiponectin/ leptin ratio, is a clear contributor to the low-grade chronic inflammation associated with metabolic syndrome. Authors conclude that this ratio is highly and negatively correlated with markers of low-grade chronic inflammation emerging as a useful estimator of obesity- and metabolic syndrome- associated cardiometabolic risk.
Abstract
Obesity is currently the most extended metabolic disturbance worldwide favoring the development of cardiometabolic alterations such as type 2 diabetes, hypertension, and dyslipidemia. Obesity and the metabolic syndrome (MS) are characterized by an increase in circulating leptin concentrations, in parallel to a decrease in blood levels of adiponectin. Consequently, the adiponectin/leptin ratio has been suggested as a maker of adipose tissue dysfunction. This emerging biomarker correlates with insulin resistance better than adiponectin or leptin alone, or even HOMA and is decreased with increasing number of metabolic risk factors having been proposed as a predictive marker for the MS. Moreover, the adiponectin/leptin ratio is negatively correlated with markers of low-grade chronic inflammation. In this sense, an increase in this ratio has been related with reduced atherosclerosis risk as well as with a decreased risk of some types of cancer in epidemiological studies. In this commentary we propose new cutoffs to estimate obesity- and MS-associated cardiometabolic risk according to the adiponectin/leptin ratio and discuss different therapeutic strategies to increase this promising biomarker of metabolic risk.
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Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis.
Manheimer, EW, van Zuuren, EJ, Fedorowicz, Z, Pijl, H
The American journal of clinical nutrition. 2015;102(4):922-32
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Metabolic syndrome is a cluster of 5 risk factors, including waist circumference, blood pressure, and serum concentrations of glucose, triglycerides, and high-density lipoprotein (HDL) cholesterol in the fasting condition. These often occur in concert and predispose people to type 2 diabetes and cardiovascular disease. The aim of this study was to evaluate whether current evidence supports the idea that Paleolithic nutrition improves risk factors for chronic disease more than do other dietary interventions in people with one or more components of the metabolic syndrome. The study is a systematic review and meta-analysis of 4 randomized controlled trials that compared Paleolithic nutrition with any other dietary intervention in participants with one or more of the 5 components of the metabolic syndrome. Results indicate that Paleolithic nutrition resulted in greater short-term pooled improvements on each of the 5 components of metabolic syndrome than did currently recommended guideline-based control diets. However, the greater pooled improvements did not reach significance for 2 of the 5 components (i.e., HDL cholesterol and fasting blood sugar). Authors conclude that the available data warrant additional evaluations of the health benefits of Paleolithic nutrition.
Abstract
BACKGROUND Paleolithic nutrition, which has attracted substantial public attention lately because of its putative health benefits, differs radically from dietary patterns currently recommended in guidelines, particularly in terms of its recommendation to exclude grains, dairy, and nutritional products of industry. OBJECTIVE We evaluated whether a Paleolithic nutritional pattern improves risk factors for chronic disease more than do other dietary interventions. DESIGN We conducted a systematic review of randomized controlled trials (RCTs) that compared the Paleolithic nutritional pattern with any other dietary pattern in participants with one or more of the 5 components of metabolic syndrome. Two reviewers independently extracted study data and assessed risk of bias. Outcome data were extracted from the first measurement time point (≤6 mo). A random-effects model was used to estimate the average intervention effect. The quality of the evidence was rated with the use of the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS Four RCTs that involved 159 participants were included. The 4 control diets were based on distinct national nutrition guidelines but were broadly similar. Paleolithic nutrition resulted in greater short-term improvements than did the control diets (random-effects model) for waist circumference (mean difference: -2.38 cm; 95% CI: -4.73, -0.04 cm), triglycerides (-0.40 mmol/L; 95% CI: -0.76, -0.04 mmol/L), systolic blood pressure (-3.64 mm Hg; 95% CI: -7.36, 0.08 mm Hg), diastolic blood pressure (-2.48 mm Hg; 95% CI: -4.98, 0.02 mm Hg), HDL cholesterol (0.12 mmol/L; 95% CI: -0.03, 0.28 mmol/L), and fasting blood sugar (-0.16 mmol/L; 95% CI: -0.44, 0.11 mmol/L). The quality of the evidence for each of the 5 metabolic components was moderate. The home-delivery (n = 1) and dietary recommendation (n = 3) RCTs showed similar effects with the exception of greater improvements in triglycerides relative to the control with the home delivery. None of the RCTs evaluated an improvement in quality of life. CONCLUSIONS The Paleolithic diet resulted in greater short-term improvements in metabolic syndrome components than did guideline-based control diets. The available data warrant additional evaluations of the health benefits of Paleolithic nutrition. This systematic review was registered at PROSPERO (www.crd.york.ac.uk/PROSPERO) as CRD42014015119.