The Effects of L-Carnitine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-response Meta-analysis.

PURPOSE: Hypertension stands as a prominent risk factor for cardiovascular disease, making it of utmost importance to address. Studies have shown that L-carnitine supplementation may lower blood pressure (BP) parameters in different populations. Therefore, we have conducted a systematic review and dose-response meta-analysis of published Randomized Controlled Trials (RCTs), including the most recent articles on the effect of L-carnitine supplementation on BP. METHODS: PubMed, ISI Web of Science, Cochrane databases, and Scopus were used to collect RCT studies published up to October 2022 without limitations in language. Inclusion criteria were adult participants and recipients of L-carnitine in oral supplemental forms. The funnel plot test, Begg's test, and Egger's test were used to examine publication bias. FINDINGS: After the search strategy, 22 RCTs (n = 1412) with 24 effect sizes fulfilled the criteria. It was found L-Carnitine supplementation did not have a significant effect on systolic blood pressure (SBP) (mm Hg) (weighted mean difference [WMD] = -1.22 mm Hg, 95% CI: -3.79, 1.35; P = 0.352; I2 = 85.0%, P < 0.001), and diastolic blood pressure (mm Hg) (WMD = -0.50 mm Hg, 95% CI: -1.49, 0.48; P = 0.318; I2 = 43.4%, P = 0.021) in the pooled analysis. Subgroup analyses have shown that L-carnitine supplementation had no lowering effect on SBP in any subgroup. However, there was a significant reduction in diastolic blood pressure in participants with a baseline body mass index >30 kg/m2 (WMD = -1.59 mm Hg; 95% CI: -3.11, -0.06; P = 0.041; I2 = 41.3%, P = 0.164). There was a significant nonlinear relationship between the duration of L-carnitine intervention and changes in SBP (coefficients = -6.83, P = 0.045). IMPLICATIONS: L-carnitine supplementation in adults did not significantly affect BP. But anyway, more studies should be done in this field on different individuals.

Zinc Supplementation in Individuals with Prediabetes and type 2 Diabetes: a GRADE-Assessed Systematic Review and Dose-Response Meta-analysis.

Zinc supplementation has therapeutic effects on cardiovascular disease (CVD) risk factors, including dyslipidemia, hyperglycemia, and inflammation as the main contributors to CVD pathogenesis. Since CVD is a major cause of mortality among people with type 2 diabetes mellitus (T2DM), this study aimed to overview the potential effects of zinc supplementation on CVD risk factors in T2DM patients. To determine appropriate randomized clinical trials (RCTs) investigating the effects of zinc supplementation on CVD risk factors, electronic sources including PubMed, Web of Science, and Scopus were systematically searched until January 2023. The heterogeneity of trials was checked using the I2 statistic. According to the heterogeneity tests, random-effects models were estimated, and pooled data were defined as the weighted mean difference (WMD) with a 95% confidence interval (CI). Of the 4004 initial records, 23 studies that met inclusion criteria were analyzed in this meta-analysis. The pooled findings indicated the significant lowering effects of zinc supplementation on triglycerides (TG), total cholesterol (TC), fasting blood glucose (FBG), hemoglobin A1C (HbA1C), and C-reactive protein (CRP), while high-density cholesterol (HDL) concentrations showed an elevation after zinc supplementation. In addition to statistical significance, the effect of zinc supplementation on most of the variables was clinically significant; however, the quality of evidence in the included studies is regarded as low or very low for most variables. Our study demonstrated that zinc supplementation has beneficial effects on glycemic control markers, lipid profile, and CRP levels as a classic marker of inflammation in T2DM. Due to the high degree of heterogeneity between studies and the low rate of quality in them, further well-designed studies are necessitated to strengthen our findings.

The effects of L-carnitine supplementation on inflammatory and anti-inflammatory markers in adults: a systematic review and dose-response meta-analysis.

L-carnitine supplementation may be beneficial in improving inflammatory conditions and reducing the level of inflammatory cytokines. Therefore, according to the finding of randomized controlled trials (RCTs), the systematic review and meta-analysis aimed to investigate the effect of L-carnitine supplementation on inflammation in adults. To obtain acceptable articles up to October 2022, a thorough search was conducted in databases including PubMed, ISI Web of Science, the Cochrane Library, and Scopus. A random-effects model was used to estimate the weighted mean difference (WMD). We included the 48 RCTs (n = 3255) with 51 effect sizes in this study. L-carnitine supplementation had a significant effect on C-reactive protein (CRP) (p < 0.001), interleukin-6 (IL-6) (p = 0.001), tumor necrosis factor-α (TNF-α) (p = 0.002), malondialdehyde (MDA) (p = 0.001), total antioxidant capacity (TAC) (p = 0.029), alanine transaminase (ALT) (p < 0.001), and aspartate transaminase (AST) (p < 0.001) in intervention, compared to the placebo group. Subgroup analyses showed that L-carnitine supplementation had a lowering effect on CRP and TNF-α in trial duration ≥ 12 weeks in type 2 diabetes and BMI ≥ 25 kg/m2. L-carnitine supplementation reduced ALT levels in overweight and normal BMI subjects at any trial dose and trial duration ≥ 12 weeks and reduced AST levels in overweight subjects and trial dose ≥ 2 g/day. This meta-analysis revealed that L-carnitine supplementation effectively reduces the inflammatory state by increasing the level of TAC and decreasing the levels of CRP, IL-6, TNF-α and MDA in the serum.

Zinc supplementation and cardiovascular disease risk factors: A GRADE-assessed systematic review and dose-response meta-analysis.

BACKGROUND AND OBJECTIVE: A deficit in zinc has been related to a higher probability of developing cardiovascular diseases (CVDs). The anti-inflammatory and anti-oxidative capabilities of zinc may have a wide range of therapeutic impacts on CVDs. We conducted a comprehensive systematic review and meta-analysis of the possible impacts that zinc supplementation may have on the risk factors associated with CVDs. METHODS: To identify eligible randomized clinical trials (RCTs) evaluating the effects of zinc supplementation on CVDs risk factors, electronic databases including PubMed, Web of Science, and Scopus were systematically searched up to January 2023. The heterogeneity of trials was checked using the I2 statistic. According to the heterogeneity tests, random effects models were estimated and pooled data were defined as the weighted mean difference (WMD) with a 95% confidence interval (CI). RESULTS: Of 23165 initial records, 75 studies that met inclusion criteria were analyzed in this meta-analysis. The pooled findings indicated the significant lowering effects of zinc supplementation on triglycerides (TG), total cholesterol (TC), fasting blood glucose (FBG), Hemoglobin A1C (HbA1C), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein (CRP), interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC), and glutathione (GSH), with no noticeable effects on low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate transaminase (AST), and Alanine aminotransferase (ALT). CONCLUSION: Overall, zinc supplementation may boost recognized coronary risk factors that contribute to the development of CVDs. Future research should be conducted to bolster our results.

Propolis supplementation in obese patients with non-alcoholic fatty liver disease: effects on glucose homeostasis, lipid profile, liver function, anthropometric indices and meta-inflammation.

This study assessed the effects of propolis supplementation on glucose homeostasis, lipid profile, liver function, anthropometric indices and meta-inflammation in patients with non-alcoholic fatty liver disease (NAFLD). In this double-blind placebo-controlled randomized clinical trial, 44 patients with NAFLD confirmed by ultrasonography findings were randomly allocated into either the "propolis" (n = 23) or "placebo" (n = 21) group along with a calorie-restricted diet (-500 kcal d-1) for 8 weeks. Fasting serum levels of metabolic factors, liver enzymes, and inflammatory factors, as well as anthropometric indices, dietary intake and appetite status were assessed pre-and post-intervention. The liver fibrosis score, homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were also calculated. The weight, body mass index (BMI), waist and hip circumferences, and waist to height ratio significantly decreased in both groups (p < 0.001), while the waist to hip ratio (p = 0.006) and serum level of total cholesterol (p = 0.038) decreased only in the propolis arm. However, no significant changes in anthropometric measurements and lipid profile were found between the groups at the end of the intervention. Fasting blood sugar (p = 0.037), the serum insulin level (p = 0.040), HOMA-IR (p = 007), desire to eat sweet foods (p = 0.005) and the NAFLD fibrosis score (p = 0.013) decreased significantly in the propolis group compared to the placebo group, post-intervention after adjusting for baseline values and potential confounders. However, QUICKI showed a significant increase (p = 0.015) in the propolis arm compared to the placebo at the study endpoint. Although there were significant reductions in the serum levels of inflammatory factors including tumor necrosis factor-α (TNF-α), toll-like receptor-4 (TLR-4) and monocyte chemoattractant protein-1 (MCP-1), as well as liver enzymes and severity of fatty liver, between-group differences were not statistically significant after adjusting for the potential confounding factors. The estimated number needed to treat (NNT) due to 8-week propolis supplementation (510 mg per day) for at least 1-point improvement in NAFLD severity was found to be approximately 3. In conclusion, propolis supplementation along with a calorie-restricted diet for 8 weeks could significantly improve the glucose homeostasis, hepatic fibrosis score and liver function in patients with NAFLD. Further clinical trials are encouraged to study the effects of propolis supplementation in patients with long-term NAFLD.

The effects of berberine supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis.

Cardiovascular disease (CVD) is a major concern today. Herbal medicine is one helping way to control CVD risks. One conclusive of herbal medicine is Berberine (BBR) and converse about it still exists, to clarify this issue, this meta-analysis was performed. PubMed/Medline, Scopus, and Web of Science were searched for RCTs in adults on the effect of BBR supplementation on CVD risk factors up to July 2022. The pooled results showed BBR significantly reduced triglyceride (WMD = -23.70 mg/dl; 95%CI -30.16, -17.25; P < 0.001), total cholesterol (WMD = -20.64 mg/dl; 95%CI -23.65, -17.63; P < 0.001), low-density lipoprotein WMD = -9.63 mg/dl; 95%CI, -13.87, -5.39; P < 0.001), fasting blood glucose (FBG) (WMD = -7.74 mg/dl; 95%CI -10.79, -4.70; P < 0.001), insulin (WMD = -3.27 mg/dl; 95%CI -4.46,-2.07; P < 0.001), HbA1c (WMD = -0.45%; 95%CI -0.68, -0.23; P < 0.001), HOMA-IR (WMD = -1.04; 95%CI -1.55, -0.52; P < 0.001), systolic blood pressure (WMD = -5.46 mmHg; 95%CI -8.17, -2.76; P < 0.001), weight (WMD = -0.84; 95%CI -1.34,-0.34; P < 0.001), body mass index (WMD = -0.25 kg/m2; 95%CI -0.46, -0.04; P = 0.020), while increased high-density lipoprotein (HDL) (WMD = 1.37 mg/dl; 95%CI 0.41,2.23; P = 0.005). The optimal dose of BBR was 1 g/day for TG, TC, and weight, 1.8 g/day for insulin and HOMA-IR, and 5 g/day for HDL. FBG's most efficient time frame was 40 weeks from the beginning of supplementation, whereas DBP and waist circumference was 50 weeks. In conclusion, the lipid profile, FBG balance, obesity parameters, and SBP were improved with BBR supplementation. Systematic review registration: CRD42022347004.

The effects of L-carnitine supplementation on glycemic markers in adults: A systematic review and dose-response meta-analysis.

Background and aims: Hyperglycemia and insulin resistance are concerns today worldwide. Recently, L-carnitine supplementation has been suggested as an effective adjunctive therapy in glycemic control. Therefore, it seems important to investigate its effect on glycemic markers. Methods: PubMed, Scopus, Web of Science, and the Cochrane databases were searched in October 2022 for prospective studies on the effects of L-carnitine supplementation on glycemic markers. Inclusion criteria included adult participants and taking oral L-carnitine supplements for at least seven days. The pooled weighted mean difference (WMD) was calculated using a random-effects model. Results: We included the 41 randomized controlled trials (RCTs) (n = 2900) with 44 effect sizes in this study. In the pooled analysis; L-carnitine supplementation had a significant effect on fasting blood glucose (FBG) (mg/dl) [WMD = -3.22 mg/dl; 95% CI, -5.21 to -1.23; p = 0.002; I 2 = 88.6%, p < 0.001], hemoglobin A1c (HbA1c) (%) [WMD = -0.27%; 95% CI, -0.47 to -0.07; p = 0.007; I 2 = 90.1%, p < 0.001] and homeostasis model assessment-estimate insulin resistance (HOMA-IR) [WMD = -0.73; 95% CI, -1.21 to -0.25; p = 0.003; I 2 = 98.2%, p < 0.001] in the intervention compared to the control group. L-carnitine supplementation had a reducing effect on baseline FBG ≥100 mg/dl, trial duration ≥12 weeks, intervention dose ≥2 g/day, participants with overweight and obesity (baseline BMI 25-29.9 and >30 kg/m2), and diabetic patients. Also, L-carnitine significantly affected insulin (pmol/l), HOMA-IR (%), and HbA1c (%) in trial duration ≥12 weeks, intervention dose ≥2 g/day, and participants with obesity (baseline BMI >30 kg/m2). It also had a reducing effect on HOMA-IR in diabetic patients, non-diabetic patients, and just diabetic patients for insulin, and HbA1c. There was a significant nonlinear relationship between the duration of intervention and changes in FBG, HbA1c, and HOMA-IR. In addition, there was a significant nonlinear relationship between dose (≥2 g/day) and changes in insulin, as well as a significant linear relationship between the duration (weeks) (coefficients = -16.45, p = 0.004) of intervention and changes in HbA1C. Conclusions: L-carnitine could reduce the levels of FBG, HbA1c, and HOMA-IR. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022358692.