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Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.
Yang, K, Chen, J, Zhang, T, Yuan, X, Ge, A, Wang, S, Xu, H, Zeng, L, Ge, J
Frontiers in immunology. 2022;13:949746
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Non-alcoholic fatty liver disease (NAFLD) is characterised by fat accumulation in the liver that can result in liver damage. NAFLD affects approximately 25% of the global population. There is evidence that dietary polyphenols can improve metabolism and insulin resistance and reduce inflammation and oxidative stress, which are the mechanisms that lead to liver damage in NAFLD. This systematic review and meta-analysis aimed to assess the effectiveness of dietary polyphenols in the treatment of non-alcoholic fatty liver disease (NAFLD). Eight dietary polyphenols, such as curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein, were evaluated for their efficacy and safety. The administration of 80-3,000 mg of Curcumin for an 8-12 week duration is effective and safe for reducing body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), and insulin resistance (HOMA-IR). Compared with the placebo, Naringenin reduced the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol. Hesperidin may potentially decrease body mass index (BMI), AST, ALT, TG, TC, and HOMA-IR. Catechin is safe, and 500-1000 mg supplementation for 12 weeks may reduce BMI, HOMA-IR, and TG. NAFLD patients who received silymarin showed improvements in ALT and AST, as well as reductions in hepatic fat accumulation and liver stiffness. 94–2100 mg of Silymarin supplementation for 8–48 weeks may reduce liver enzyme levels. Researchers can use the results of this study to understand the clinical utility of different polyphenol supplements in the treatment of NAFLD. Because the current evidence is highly heterogeneous in nature and limited in scope, further robust research is required on various classes of polyphenols and their effectiveness in reducing the severity of NAFLD.
Abstract
Background: Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods: The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results: The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion: Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.
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Effects of camelina oil supplementation on lipid profile and glycemic control: a systematic review and dose‒response meta-analysis of randomized clinical trials.
Jalili, C, Talebi, S, Mehrabani, S, Bagheri, R, Wong, A, Amirian, P, Zarpoosh, M, Ghoreishy, SM, Kermani, MAH, Moradi, S
Lipids in health and disease. 2022;21(1):132
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Research indicates that alpha-linolenic acid (ALA) can reduce the risk of cardiovascular disease by improving blood lipids, blood pressure, and haemostatic factors, among others. Camelina oil, considered a good source of ALA compared to other edible oils, is one of the richest dietary sources of omega-3 fatty acids, with a polyunsaturated fatty acid content over 50%. The aim of this study was to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycaemic control in human studies. This study is a systematic review and meta-analysis of seven randomised controlled trials with a total of 428 individuals (202 participants in the COS group and 226 in the control group). Results did not show any affects of COS on lipid profile and glycaemic indices compared with placebo intake. However, subgroup analysis showed that COS for more than 8 weeks and at a dose lower than 30g/d could decrease total cholesterol. Authors conclude that COS may be a beneficial nonpharmacological strategy for the improvement of this lipid marker. However, further studies are required to confirm the findings of this study.
Abstract
BACKGROUND This systematic review and dose-response meta-analysis of published randomized controlled trials (RCTs) was conducted to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycemic indices. METHODS Relevant RCTs were selected by searching the ISI Web of Science, PubMed, and Scopus databases up to July 1, 2022. RTCs with an intervention duration of less than 2 weeks, without a placebo group, and those that used COS in combination with another supplement were excluded. Weighted mean differences and 95% confidence intervals were pooled by applying a random-effects model, while validated methods examined sensitivity analyses, heterogeneity, and publication bias. RESULTS Seven eligible RCTs, including 428 individuals, were selected. The pooled analysis revealed that COS significantly improved total cholesterol in studies lasting more than 8 weeks and utilizing dosages lower than 30 g/d compared to the placebo group. The results of fractional polynomial modeling indicated that there were nonlinear dose-response relations between the dose of COS and absolute mean differences in low-density cholesterol, high-density cholesterol, and total cholesterol, but not triglycerides. It appears that the greatest effect of COS oil occurs at the dosage of 20 g/day. CONCLUSION The present meta-analysis indicates that COS may reduce cardiovascular disease risk by improving lipid profile markers. Based on the results of this study, COS at dosages lower than 30 g/d may be a beneficial nonpharmacological strategy for lipid control. Further RCTs with longer COS durations are warranted to expand on these results.
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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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The Effect of Yoga on the Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Ghazvineh, D, Daneshvar, M, Basirat, V, Daneshzad, E
Frontiers in nutrition. 2022;9:942702
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Modernisation has brought increased comforts and limited mobility in our lives at the cost of an increased prevalence of hypertension, diabetes mellitus, dyslipidaemia, and obesity, which are predecessors of major cardiovascular diseases. Prevention and control of coronary heart disease and its associated diseases are essential and can be achieved by modifying the lipid profile. The aim of this study was to systematically assess the effects of yoga on blood lipid levels. This study is a systematic review and meta-analysis of fifty-three randomised controlled studies. All studies employed a parallel design with a total of 13,191 participants whom were divided into 6,700 individuals in the control group and 6,517 in the intervention group. Results show that yoga had decreased total cholesterol, low-density lipoprotein cholesterol, triglycerides, and very low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol among yoga practitioners. Authors conclude that yoga had a striking effect on balancing lipid profiles.
Abstract
OBJECTIVES Yoga is a mind-body stress-relieving exercise that increases mental and physical health, which may have a role in the improvement of metabolic disorders. The present study has reviewed the effect of yoga on lipid profiles as a systematic review and meta-analysis. METHODS We evaluated the available randomized controlled trials on the effects of yoga-based programs, and lipid profiles by searching PubMed/Medline, Scopus, Web of Science, and the Cochrane central register of control trials up to January 2022. Both fixed and random effect analyses were used to find the relationships. Subgroup analysis was performed based on the continent, duration of the included studies, gender, and health condition of participants to discover the sources of heterogeneity. RESULT Fifty-three studies were included in the current systematic review and meta-analysis with a total sample size of 13,191. There was a striking association between yoga and total cholesterol (-10.31 mg/dl; 95% CI: -14.16, -6.45; I 2 = 82.5%, P < 0.001), low-density lipoprotein cholesterol (-8.64 mg/dl; 95% CI: -12.03, -5.25; I 2 = 75.0%, P < 0.001), high-density lipoprotein cholesterol (1.98 mg/dl; 95% CI: 0.81, 3.14; I 2 = 91.6%, P < 0.001), triglycerides (-13.50 mg/dl; 95% CI: -20.09, -6.92; I 2 = 90.7%, P < 0.001) and very low-density lipoprotein (-3.94 mg/dl; 95%CI: -6.31, -1.56; I 2 = 72.2%, P < 0.001). CONCLUSION It seems yoga interventions had a substantial effect on lipid profiles, however, more qualified trials or cohort studies are needed to conclude exactly.
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Efficacy and safety of oral alpha-lipoic acid supplementation for type 2 diabetes management: a systematic review and dose-response meta-analysis of randomized trials.
Jibril, AT, Jayedi, A, Shab-Bidar, S
Endocrine connections. 2022;11(10)
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Many studies have shown that type 2 diabetes is associated with increased formation of free radicals and decreased antioxidant potential, leading to oxidative damage of cell components. Increased formation of free radicals and decreased antioxidant potential, coupled with lipid abnormalities, are substantial risk factors for developing complications, especially microvascular ones. The aim of this study was to investigate the effect of oral supplementation of alpha-lipoic acid (ALA) on cardiometabolic risk factors in patients with type 2 diabetes. This study is a systematic review and dose–response meta-analysis of 16 randomised controlled trials with a total of 1035 patients with type 2 diabetes. Results show that: - each 500 mg/day oral ALA supplementation reduced haemoglobin A1c and body weight but did not affect low-density lipoprotein cholesterol concentration. - ALA supplementation reduced c-reactive protein, fasting plasma glucose, serum triglycerides, and diastolic blood pressure but it had no affect on serum total cholesterol and high-density lipoprotein cholesterol concentrations and systolic blood pressure. Authors conclude that their findings do not support ALA supplementation in clinical practice for patients with type 2 diabetes.
Abstract
OBJECTIVE To examine the dose-dependent influence of oral alpha-lipoic acid (ALA) supplementation on cardiometabolic risk factors in patients with type 2 diabetes (T2D). DESIGN We followed the instructions outlined in the Cochrane Handbook for Systematic Reviews of Interventions and the Grading of Recommendations, Assessment, Development, and Evaluation Handbook to conduct our systematic review. The protocol of the study was registered in PROSPERO (CRD42021260587). METHOD We searched PubMed, Scopus, and Web of Science to May 2021 for trials of oral ALA supplementation in adults with T2D. The primary outcomes were HbA1c, weight loss, and LDL cholesterol (LDL-C). Secondary outcomes included fasting plasma glucose (FPG), triglyceride (TG), C-reactive protein (CRP), and blood pressure. We conducted a random-effects dose-response meta-analysis to calculate the mean difference (MD) and 95% CI for each 500 mg/day oral ALA supplementation. We performed a nonlinear dose-response meta-analysis using a restricted cubic spline. RESULTS We included 16 trials with 1035 patients. Each 500 mg/day increase in oral ALA supplementation significantly reduced HbA1c, body weight, CRP, FPG, and TG. Dose-response meta-analyses indicated a linear decrement in body weight at ALA supplementation of more than 600 mg/day (MD600 mg/day: -0.30 kg, 95% CI: -0.04, -0.57). A relatively J-shaped effect was seen for HbA1c (MD: -0.32%, 95% CI: -0.45, -0.18). Levels of FPG and LDL-C decreased up to 600 mg/day ALA intake. The point estimates were below minimal clinically important difference thresholds for all outcomes. CONCLUSION Despite significant improvements, the effects of oral ALA supplementation on cardiometabolic risk factors in patients with T2D were not clinically important.
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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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The Effect of Curcumin on Lipid Profile and Glycemic Status of Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.
Tian, J, Feng, B, Tian, Z
Evidence-based complementary and alternative medicine : eCAM. 2022;2022:8278744
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Dyslipidaemia is a common comorbidity of type 2 diabetes mellitus (T2DM), which is characterised by elevated triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) level, and/or decreased high-density lipoprotein cholesterol (HDL-c) concentrate serum. Dyslipidaemia and dysglycemia interact with each other, and they are the main risk factors of macro- and microvascular diseases in T2DM. The aim of this study was to outline curcumin’s efficacy and possible uses in clinical practice. This study is a meta-analysis of nine randomised controlled trials (RCTs). A total of 604 participants (284 in the curcumin group and 281 in the control group) were included in the selected studies. The design of all trials was parallel; seven of them were double-blind RCTs, and the other two were open label RCTs. Results show that curcumin significantly decreased TG, TC, fasting blood glucose, and haemoglobin A1C levels and also led to a reduction in LDL-c and an elevation in HDL-c concentration, although with no statistical difference. Authors conclude that curcumin has promising effects on the lipid profile and glycaemic status in patients with T2DM. It indicated that curcumin might be a favourable therapeutic option for T2DM patients with mixed dyslipidaemia.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Dyslipidemia and dysglycemia interact with each other, and are risk factors of macro- and microvascular diseases in T2DM.
Although effective intervention strategies exist for improving glycemic status of T2DM patients, they often need lipid-lowering drugs simultaneously to prevent CVD.
- Novel therapeutic interventions are needed to manage dyslipidemia and dysglycemia in diabetic patients, when statin therapy to treat dyslipidemia, may increase the risk of new-onset diabetes and myopathy.
- Other clinical studies have highlighted the benefits of curcumin supplementation on lipid profile and glycemic status. Clarifying its effects is important for assessing its potential as an alternative and complementary medicine on improving the metabolic status of T2DM patients.
- Overall there is limited evidence and further research is required.
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:
Introduction
This meta-analysis aimed to evaluate the effects of curcumin on lipid profile in patients with type 2 diabetes mellitus (T2DM), including: serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-c), and/or high-density lipoprotein cholesterol (HDL-c). Fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were also assessed.
Methods
A search was performed on Pubmed, Embase, Web of Sciences, and the Cochrane Library up to March 2022. Quality assessment of all included studies was performed.
Results
9 studies were included in the review, with a total of 604 participants (284 in the curcumin group and 281 in the control group) of mean age from 41 to 60.95 years. Curcumin forms varied among the studies including, turmeric, curcuminoids, and curcumin. The dosage of curcumin in the intervention group ranged from 80 to 2100 mg/day. The duration of intervention was between 4 weeks and 3 months in different studies.
- Effect of Curcumin on TG: A difference was observed between curcumin supplementation and control (p = 0.03), indicating curcumin could reduce serum TG.
- Effect of Curcumin on TC: The mean difference in net changes of TC between intervention and control groups was −8.91mg/dL (p = 0.001), suggesting that curcumin could decrease serum TC.
- Effect of Curcumin on LDL-C: No difference in the net change of LDL-c between intervention and control groups (p = 0.26).
- Effect of Curcumin on HDL-C: No difference in HDL-c between intervention and control groups (p = 0.56).
- Effect of Curcumin on FBG: Curcumin reduced blood glucose levels compared with control treatment (p = 0.002). The effect was greater in trials with the treatment duration >8w (p = 0.037), curcumin dose >100mg/day (p = 0.004), and with the participants receiving the other therapy (p = 0.002).
- Effect of Curcumin on HbA1c: HbA1c (%) decreased in the intervention group compared with the control group (p ≤ 0.001).
Conclusion
Curcumin has promising effects on the lipid profile and glycemic status of T2DM patients and might be a therapeutic option for T2DM patients with mixed dyslipidemia.
Clinical practice applications:
- Limitations were the small number of included studies, mostly with small sample sizes. In some studies, treatment duration was short (<2 months) and may be insufficient to see a difference in some metabolic parameters.
- The reduction of FBG and HbA1c after treatment with curcumin suggested that it improved the glycemic metabolism in the T2DM patients studied.
- Studies have shown that curcumin could promote insulin release through inducing β-cell electrical activity and lower serum glucose level via decreasing the production of hepatic glucose and increasing glucose uptake. While changes of LDL-c and HDL-c was not statistically significant, the authors note the effect of curcumin on LDL-c/HDL-c and its potential clinical significance could not be neglected.
- The reduction of dyslipidemia by curcumin supplementation could improve the glucose metabolic status of T2DM patients, and multiple molecular targets including PPAR-c, cholesteryl ester transfer protein, and lipoprotein lipase contribute to the beneficial effects of curcumin.
Considerations for future research:
- While significant heterogeneity was found in pooled analyses of TG, LDL-c, FBG, and Hb1Ac, a random-effects model revealed that trial duration, curcumin dosage, and other therapy may contribute to the variation in pooled effects, and these aspects could be discussed in future studies.
- The study found that a higher dose of curcumin was more powerful in reducing plasma TG and FBG concentrations, but further large-scale multicenter RCTs are required to confirm the clinical improvement of curcumin.
Abstract
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder, some natural compounds are thought to be beneficial in improving the metabolic status of patients with T2DM. Curcumin is the main bioactive agent of turmeric, the impact of curcumin on T2DM is still controversial. This meta-analysis aimed to evaluate the effects of curcumin on lipids profile and glucose status in patients with T2DM. Randomized controlled trials (RCTs) examining the effects of curcumin on lipids profile and glycemic control of T2DM patients were searched in PubMed, Embase, Web of Science and Cochrane Library. Pooled estimates of weighted mean difference (WMD) were calculated between intervention and control groups using random-effects or fixed-effects model. Subgroup and sensitivity analyses were conducted to assess the effects. Nine eligible RCT with 604 subjects were included. The estimated pooled mean changes with curcumin were -18.97 mg/dL (95% CI: -36.47 to -1.47; P=0.03) for triglyceride (TG), -8.91 mg/dL (95% CI: -14.18 to -3.63, P=0.001) for total cholesterol (TC), -4.01 mg/dL (95% CI: -10.96 to 2.95, P=0.259) for low density lipoprotein cholesterol (LDL-c), 0.32 mg/dL (95% CI: -0.74 to 1.37, P=0.557) for high density lipoprotein cholesterol (HDL-c), -8.85 mg/dL (95% CI: -14.4 to -3.29, P=0.002) for fasting blood glucose (FBG), -0.54 (95% CI: -0.81 to -0.27, P ≤ 0.001) for glycated hemoglobin (HbA1c) (%) compared with controls. There was a significant heterogeneity for the influence of curcumin on TG, LDL-c, FBG and HbA1c. Subgroup analysis revealed that the heterogeneity mainly attributed to trial period, curcumin dosage and other therapy. The results of this study showed that curcumin supplementation had beneficial effects on glycemic status and some lipid parameters in patients with T2DM. Further studies with large-scale are still needed to confirm the results.
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8.
Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis.
Whittaker, J, Harris, M
Nutrition and health. 2022;28(4):543-554
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Testosterone is the primary male sex hormone, and vital for reproductive development and function. Moreover, low endogenous testosterone is associated with an increased risk of chronic disease, including type 2 diabetes and cardiovascular disease. The aim of this study was to investigate the effects of low- versus high-carbohydrate diets on mens' testosterone and cortisol. This study is a systematic review and meta-analysis of twenty-seven studies with a total of 309 participants. Twelve of these studies were randomised trials whilst the rest were non-randomised. Results show an increase in resting and post-exercise cortisol on short-term low-carbohydrate diets (<3 weeks). In fact, resting cortisol levels return to baseline after <3 weeks on a LC diet, whilst post-exercise cortisol remains elevated. Furthermore, high-protein diets cause a large decrease in resting total testosterone. Authors conclude that further research is required in order to warrant their findings.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Short-term LC-diets diets cause a moderate increase in resting and post-exercise cortisol however this effect is not seen in LC-diets followed for great than 3 weeks
- HP-LC diets caused a statistically significant decrease in resting TT, suggesting caution in relation to endocrine effects of LC diets
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:
Introduction:
A systematic review and network meta-analysis was conducted on the effects of low-carbohydrate (LC) versus high-carbohydrate (HC) diets on men’s testosterone and cortisol.
The review was registered with PROSPERO and reported using PRISMA 2020 checklists.
Methods:
A comprehensive search strategy was used to find intervention studies looking at healthy adult males and LC diets of <35% carbohydrate. Studies were assessed for quality using the Cochrane Risk of Bias tool. Sub-group analyses was conducted for diet duration, protein intake and exercise duration.
Results:
The literature search resulted in 27 studies with a total of 309 healthy adult male participants, age: 27.3 ± 4.7 (to minimise variation in steroid hormone metabolism), body mass: 78.6± 7.1kg and BMI: 24.8 ±1.6. 12 randomised and 15 non-randomised controlled trials were analysed. 21 studies were considered low risk bias, 5 medium and 1 high risk.
- Short-term (<3 weeks) LC diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01) when compared to HC diets.
- Long-term (≥3 weeks) LC diets had no consistent effect on resting cortisol
- LC diets resulted in higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01).
- The overall results for resting total testosterone (TT) showed a significant decrease on LC versus HC diets (SMD = −0.48, p = 0.01. However, subgroup analyses revealed this effect to be limited to high-protein (HP) LC diets, which yielded a very large decrease in TT (SMD = −1.08, p < 0.01; ∼5.23 nmol/L), albeit in a small sample (n = 26).
- Moderate protein (MP) (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (−1.08 [−1.67, −0.48], p < 0.01) and post-exercise total testosterone (−1.01 [−2, −0.01] p = 0.05).
- There was no overall effect of LC versus HC diets on 0 h post-exercise TT (SMD = −0.03, p = 0.95). However, subgroup analysis showed 0 h post-exercise was non-significantly higher on long-term LC versus HC diets (SMD = 0.44, p = 0.18), and much lower on short-term LC versus HC diets (SMD = −1.01, p = 0.05)
Conclusion:
This systematic review and metanalysis found an increase in resting and post-exercise cortisol on short-term LC diets. Cortisol does return to baseline in the first 3 weeks of a low-carbohydrate (LC) diet. The same response is, however, not seen in post-exercise cortisol, which remains elevated. In addition, the review showed that compared to moderate-protein diets, HP diets were found to cause a large decrease in resting and post-exercise TT (∼5.23 nmol/L).
Clinical practice applications:
The results of this review suggest that exercising whilst following a LC diet can increase cortisol in the short term, but not long-term. This suggests a period of diet adaptation. The effects of long-term LC diets on cardiovascular disease risk is uncertain and healthcare practitioners should monitor client responses and keep up-to-date with new research in this area
Since HP-LC diets were found to significantly decrease resting testosterone it highlights the need to ensure that protein intake does not exceed the urea cycle’s capacity due to potential adverse endocrine effects.
For clients where there is a desire to increase strength, power and hypertrophy, a MP-LC diet could be of benefit, as it showed potential to signal an increased anabolic state post exercise..
NB: Since the review only included a low number of studies and saw within these some heterogeneity that could not be explained, more research is needed before the paper’s findings can be conclusive. The above potential practice applications should therefore be seen as something to be mindful of when working with clients where cortisol and testosterone levels are relevant to their protocol.
Considerations for future research:
Future research should consider:
- Since LC diets have been shown to have a positive effect on health – decreased triglycerides, increased high density lipoprotein cholesterol and weight loss - future studies would benefit from including these markers so any positive and negative impacts can be monitored directly.
- Despite extensive analysis including sensitivity analysis to reduce bias and heterogeneity of the results, the paper highlights a need for further research to ensure consistency in key parameters e.g., exercise duration and intensity, carbohydrate supplements inclusion and period of dietary intervention. Since it was identified that HP-LP diets impact post exercise and resting TT, follow up studies would benefit from consistency in participants diets. This would help to reduce any potential confounding results.
Abstract
Background: Low-carbohydrate diets may have endocrine effects, although individual studies are conflicting. Therefore, a review was conducted on the effects of low- versus high-carbohydrate diets on men's testosterone and cortisol. Methods: The review was registered on PROSPERO (CRD42021255957). The inclusion criteria were: intervention study, healthy adult males, and low-carbohydrate diet: ≤35% carbohydrate. Eight databases were searched from conception to May 2021. Cochrane's risk of bias tool was used for quality assessment. Random-effects, meta-analyses using standardized mean differences and 95% confidence intervals, were performed with Review Manager. Subgroup analyses were conducted for diet duration, protein intake, and exercise duration. Results: Twenty-seven studies were included, with a total of 309 participants. Short-term (<3 weeks), low- versus high-carbohydrate diets moderately increased resting cortisol (0.41 [0.16, 0.66], p < 0.01). Whereas, long-term (≥3 weeks), low-carbohydrate diets had no consistent effect on resting cortisol. Low- versus high-carbohydrate diets resulted in much higher post-exercise cortisol, after long-duration exercise (≥20 min): 0 h (0.78 [0.47, 1.1], p < 0.01), 1 h (0.81 [0.31, 1.31], p < 0.01), and 2 h (0.82 [0.33, 1.3], p < 0.01). Moderate-protein (<35%), low-carbohydrate diets had no consistent effect on resting total testosterone, however high-protein (≥35%), low-carbohydrate diets greatly decreased resting (-1.08 [-1.67, -0.48], p < 0.01) and post-exercise total testosterone (-1.01 [-2, -0.01] p = 0.05). Conclusions: Resting and post-exercise cortisol increase during the first 3 weeks of a low-carbohydrate diet. Afterwards, resting cortisol appears to return to baseline, whilst post-exercise cortisol remains elevated. High-protein diets cause a large decrease in resting total testosterone (∼5.23 nmol/L).
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9.
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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Plain language summary
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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The Effects of Intermittent Fasting and Continuous Energy Restriction with Exercise on Cardiometabolic Biomarkers, Dietary Compliance, and Perceived Hunger and Mood: Secondary Outcomes of a Randomised, Controlled Trial.
Keenan, S, Cooke, MB, Chen, WS, Wu, S, Belski, R
Nutrients. 2022;14(15)
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Obesity plays an important role in the development of cardiometabolic diseases. Excess body weight contributes to insulin resistance, unfavourable patterns of blood lipids and systemic inflammation, which are significant risk factors for cardiovascular disease and type 2 diabetes. Lifestyle modifications that restrict energy intake are an effective approach to attaining weight loss and reducing fat mass; however, continuous energy restrictions (CER) often have poor compliance in the long run. Intermittent fasting (IF) approaches present a promising alternative to CER and may promote increased compliance. The favourable changes in cardiometabolic health attained by an energy-restricted diet can be further amplified when combined with exercise. This paper is a secondary analysis from a 12-week intervention investigating the effects of a twice-weekly fast (5:2 IF; IFT group) and CER (CERT group) in 34 young, overweight but metabolically healthy participants when combined with resistance training. The analysis focused on changes in cardiometabolic blood markers, ratings of hunger, mood, energy and compliance as well as the participant's intention to continue with their prescribed diets post-intervention. Both dietary patterns improved blood lipids, namely reductions in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol over 12 weeks. Reductions in TC and LDL-C were more pronounced in the IFT group. No remarkable differences or changes in triglycerides, the inflammatory marker C-reactive Protein or markers of insulin resistance were seen in either group. Both groups reported high levels of dietary compliance and low levels of hunger, suggesting that both diets are well adhered to in the short to medium term. Some gender-specific differences were seen, but the author was unable to make conclusions due to the small study size. The analysis demonstrated that IF and CER, combined with resistance exercise, can improve some cardiometabolic risk biomarkers in overweight but metabolically healthy adults, independent of weight loss, with greater improvements with IF approaches.
Abstract
(1) Background: Excess weight in the form of adiposity plays a key role in the pathogenesis of cardiometabolic diseases. Lifestyle modifications that incorporate continuous energy restriction (CER) are effective at inducing weight loss and reductions in adiposity; however, prescribing daily CER results in poor long-term adherence. Over the past decade, intermittent fasting (IF) has emerged as a promising alternative to CER that may promote increased compliance and/or improvements in cardiometabolic health parameters independent of weight loss. (2) Methods: This paper presents a secondary analysis of data from a 12-week intervention investigating the effects of a twice-weekly fast (5:2 IF; IFT group) and CER (CERT group) when combined with resistance exercise in 34 healthy participants (17 males and 17 females, mean BMI: 27.0 kg/m2, mean age: 23.9 years). Specifically, changes in cardiometabolic blood markers and ratings of hunger, mood, energy and compliance within and between groups were analysed. Dietary prescriptions were hypoenergetic and matched for energy and protein intake. (3) Results: Both dietary groups experienced reductions in total cholesterol (TC; mean reduction, 7.8%; p < 0.001), low-density lipoprotein cholesterol (LDL-C; mean reduction, 11.1%; p < 0.001) and high-density lipoprotein cholesterol (mean reduction 2.6%, p = 0.049) over the 12 weeks. Reductions in TC and LDL-C were greater in the IFT group after adjustment for baseline levels and change in weight. No significant changes in markers of glucose regulation were observed. Both groups maintained high levels of dietary compliance (~80%) and reported low levels of hunger over the course of the intervention period. (4) Conclusions: Secondary data analysis revealed that when combined with resistance training, both dietary patterns improved blood lipids, with greater reductions observed in the IFT group. High levels of compliance and low reported levels of hunger throughout the intervention period suggest both diets are well tolerated in the short-to-medium term.