Effect of omega-3 supplementation on lipid profile in children and adolescents: a systematic review and meta-analysis of randomized clinical trials.

PURPOSE: Dyslipidemia is considered as a known risk factor for cardiovascular disease. Yet various trials with wide ranges of doses and durations have reported contradictory results. We undertook this meta-analysis of randomized controlled trials (RCTs) to determine whether omega-3 supplementation can affect lipid profile in children and adolescents. METHODS: Cochrane Library, Embase, PubMed, and Scopus databases were searched up to March 2021. Meta-analysis was performed using random-effect method. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was assessed using the I2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta-regression analysis was conducted. RESULTS: A total of 14 RCTs with 15 data sets were included. Based on the combination of effect sizes, there was a significant reduction in TG levels (WMD: -15.71 mg/dl, 95% CI: -25.76 to -5.65, P=0.002), with remarkable heterogeneity (I2=88.3%, P<0.001). However, subgroup analysis revealed that omega-3 supplementation significantly decreased TG only in studies conducted on participants ≤13 years old (WMD=-25.09, 95% CI: -43.29 to -6.90, P=0.007), (I2=84.6%, P<0.001) and those with hypertriglyceridemia (WMD=-28.26, 95% CI: -39.12 to -17.41, P<0.001), (I2=0.0%, P=0.934). Omega-3 supplementation had no significant effect on total cholesterol, HDL, and LDL levels. Also, results of nonlinear analysis showed significant effect of treatment duration on HDL status (Pnon-linearity=0.047). CONCLUSION: Omega-3 supplementation may significantly reduce TG levels in younger children and those with hypertriglyceridemia. Also, based on the HDL-related results, clinical trials with longer duration of intervention are recommended in this population.

Effects of omega-3 supplementation on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes mellitus: A randomized clinical trial.

Background: Vascular dysfunction is a major complication of diabetes mellitus that leads to cardiovascular disease (CVD). This study aimed to examine the effects of omega-3 consumption on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes mellitus (T1DM). Methods: In this randomized, double-blind, placebo-controlled clinical trial, 51 adolescents (10-18 years) with T1DM completed the study. Patients received 600 mg/day [containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA)] of omega-3 or placebo for 12 weeks. Flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, blood urea nitrogen (BUN), creatinine, fasting blood sugar (FBS), hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), serum insulin (SI), urine albumin-creatinine ratio (uACR), blood pressure, and anthropometric indices were assessed at the baseline and after the intervention. Results: Following supplementation, omega-3 significantly increased FMD (3.1 ± 4.2 vs. -0.6 ± 4%, p = 0.006) and decreased TG (-7.4 ± 10.7 vs. -0.1 ± 13.1 mg/dl, p = 0.022) in comparison with the placebo group. However, no significant difference was observed regarding CIMT (-0.005 ± 0.036 vs. 0.003 ± 0.021 mm, p = 0.33). Although hs-CRP was significantly decreased within the omega-3 group (p = 0.031); however, no significant change was observed compared to placebo group (p = 0.221). Omega-3 supplementation had no significant effect on other variables. Conclusion: Given the elevation in FMD and reduction in TG, omega-3 supplementation can improve vascular function and may reduce the risk of cardiovascular disease in adolescents with T1DM patients.

Study protocol of a randomized controlled clinical trial investigating the effects of omega-3 supplementation on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes.

BACKGROUND: Type 1 diabetes is a main health burden with several related comorbidities. It has been shown that endothelial function, vascular structure, and metabolic parameters are considerably disrupted in patients with type 1 diabetes. Omega-3 as an adjuvant therapy may exert profitable effects on type 1 diabetes and its complications by improving inflammation, oxidative stress, immune responses, and metabolic status. Because no randomized clinical trial has examined the effects of omega-3 consumption in children and adolescents with type 1 diabetes; the present study aims to close this gap. METHODS: This investigation is a randomized clinical trial, in which sixty adolescents with type 1 diabetes will be randomly assigned to receive either omega-3 (600 mg/day) or placebo capsules for 12 weeks. Evaluation of anthropometric parameters, flow-mediated dilation (FMD) as an endothelial function marker, carotid intima-media thickness (CIMT) as a vascular structure marker, proteinuria, biochemical factors including glycemic and lipid profile, blood urea nitrogen (BUN), creatinine, high-sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR), as well as blood pressure will be done at the baseline and end of the trial. Also, dietary intake and physical activity will be assessed throughout the study. Statistical analysis will be performed using the SPSS software (Version 24), and P < 0.05 will be considered statistically meaningful. DISCUSSION: It is hypothesized that omega-3 supplementation may be beneficial for the management of type 1 diabetes and its complications by reducing inflammation and oxidative stress and also modulating immune responses and glucose and lipid metabolism through various mechanisms. The present study aims to investigate any effect of omega-3 on patients with type 1 diabetes. ETHICAL ASPECTS: This trial received approval from Medical Ethics Committee of Iran University of Medical Sciences, Tehran, Iran (IR.IUMS.REC.1400.070). TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20210419051010N1 . Registered on 29 April 2021.

Effects of body weight regain on leptin levels: A systematic review and meta-analysis.

BACKGROUND: There are different changes observed before and after diet therapy, and also after weight regain. However, there is not sufficient information regarding weight regain and hormonal changes. PURPOSE: The purpose of this study was to review the connection between weight regain and leptin concentration levels. METHODS: MEDLINE, SCOPUS, Web of Science, and the Cochrane Library were searched for interventional articles published from January 1, 1980, to June 30, 2020. Randomized clinical trials with parallel or cross over design assessing leptin concentrations at the baseline and at the end of study were reviewed. Two independent reviewers extracted data related to study design, year of publication, country, age, gender, body mass index (BMI), duration of the following up period and mean ± SD of other intended variables. RESULTS: Four articles were included, published between 2004 and 2016. Three of them were conducted in the US and one of them in Netherland. Sample size of the studies ranged between 25 and 148 participants. The range of following up period was from13 to 48 weeks. The age range of participants was from 34 to 44 years. Our analysis shows that weight regain could reduce leptin levels, but this change is not statistically significant. CONCLUSION: This review suggests that weight regain may induce a non-significant reduction in leptin level. However, the limited number and great heterogeneity between the included studies may affect the presented results and there are still need to well-designed, large population studies to determine the relationship between weight regain and leptin levels.

Effect of bariatric surgery on endogenous sex hormones and sex hormone-binding globulin levels: a systematic review and meta-analysis.

BACKGROUND: Most studies have shown beneficial effect of bariatric surgery (BS) on serum levels of sex hormones. OBJECTIVE: A systematic review and meta-analysis was conducted to examine the magnitude of possible changes in levels of sex hormones following BS. SETTINGS: Electronic databases were searched, including PubMed, Scopus, Web of Science, and Embase, for relevant studies. METHODS: The heterogeneity of the studies was examined by χ2 tests and the degree of heterogeneity was estimated using I2 statistic. RESULTS: The results of pooled analyses revealed that BS caused a significant increase in luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), and sex hormone binding globulin (SHBG) levels and conversely, decreased dehydroepiandrosterone (DHEA) and estradiol (E2) levels in males. For females, BS significantly increased LH, FSH, and SHBG levels and conversely, decreased androstenedione (AE), E2 and TT levels. Additionally, the level of progesterone (P), prolactin (PRL), free testosterone (FT) and dehydroepiandrosterone sulfate (DHEA-S) showed no significant changes in patients who had undergone BS. CONCLUSION: BS changed most sex hormones levels including LH, FSH, TT, SHBG, AE, DHEA, and E2. It seems that BS is able to exert substantial impacts on sex hormones levels and as well as sexual function, however, larger, and more precise trials are required to specifically focus on these claims.

Effect of extra virgin olive oil consumption on glycemic control: A systematic review and meta-analysis.

AIMS: Several health benefits are contributed to extra virgin olive oil (EVOO). The polyphenol fraction of EVOO may be responsible for its cardioprotective impacts. This systematic review and meta-analysis aimed to investigate the effect of EVOO intake on glycemic parameters. Electronic literature searched through 1 September 2020 across MEDLINE/PubMed, Web of Science, and SCOPUS databases to find all clinical trials that reported the effect of EVOO intake on glycemic parameters [FBS(fasting blood glucose), insulin, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) and HbA1c (glycated hemoglobin A1c)] vs. control. DATA SYNTHESIS: We pooled standardized mean differences (SMD) and 95% confidence intervals (CIs) from randomized clinical trials (RCTs) using random-effects models. Heterogeneity was assessed by Cochran Q-statistic and quantified (I2). We found 13 related trials comprising a total of 633 subjects. In pooled analysis, EVOO intake had no effect on FBS (SMD: -0.07; 95% CI: -0.20, 0.07; I2 = 0.0%), insulin (SMD: -0.32; 95% CI: -0.70, 0.06; I2 = 38.0%), and HOMA-IR (SMD: -0.32; 95% CI: -0.75, 0.10; I2 = 51.0%). However, a decreasing trend was observed in these effects. Subgroup analysis based on age, health status, dose, and EVOO intake duration also did not significantly change results. CONCLUSION: Although EVOO seems a promising hypoglycemic effects, we did not find any significant evidence that EVOO consumption impacts glucose homeostasis. Furthermore, well-designed RCTs with longer durations are still needed to evaluate the EVOO's efficacy on glycemic parameters.

Can vitamin E supplementation affect obesity indices? A systematic review and meta-analysis of twenty-four randomized controlled trials.

BACKGROUND: Several mechanisms have been proposed for the effect of vitamin E on weight loss. Yet various interventional studies with wide ranges of doses and durations have reported contradictory results. METHODS: Cochrane Library, PubMed, Scopus, and Embase databases were searched up to December 2020. Meta-analysis was performed using random-effect method. Effect size was presented as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was evaluated using the I2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta regression analyses was conducted. RESULTS: A total of 24 studies with 33 data sets were included. There was no significant effect of vitamin E on weight (WMD: 0.15, 95% CI: -1.35 to 1.65, P = 0.847), body mass index (BMI) (WMD = 0.04, 95% CI: -0.29 to 0.37, P = 0.815), and waist circumference (WC) (WMD = -0.19 kg, 95% CI: -2.06 to 1.68, P = 0.842), respectively. However, subgroup analysis revealed that vitamin E supplementation in studies conducted on participants with normal BMI (18.5-24.9) had increasing impact on BMI (P = 0.047). CONCLUSION: There was no significant effect of vitamin E supplementation on weight, BMI and WC. However, vitamin E supplementation might be associated with increasing BMI in people with normal BMI (18.5-24.9).

The effect of Alpha-lipoic acid supplementation on endothelial function: A systematic review and meta-analysis.

There is evidence that alpha-lipoic acid (ALA) supplementation plays an important role in preventing cardiovascular diseases. However, its effect, specifically, on endothelial function (EF) is unclear. Therefore, this systematic review and meta-analysis aimed to evaluate the effects of ALA supplementation on EF. Databases including PubMed/Medline, Scopus, and ISI Web of Science were searched to identify eligible publications from inception up to April 2020. Randomized controlled trials assessing the effect of ALA supplementation on flow-mediated dilation (FMD) levels in adults were included. The pooled results were obtained using the random-effects model and are expressed as weighted mean differences (WMD) with 95% confidence intervals (CI). Five studies including six effect sizes and 300 participants were included. ALA supplementation significantly increased FMD levels by 2.36% (95% CI: 1.21-3.51; p < .001), compared with the control. Subgroup analyses suggested that the effects of ALA on FMD could be changed by age and health status of the participants. Dose-response analysis also showed that ALA dosage had a significant non-linear effect on FMD levels. The results showed that ALA supplementation appears to improve the EF. However, the role of ALA supplementation in improving other biomarkers of EF requires further research.

Spirulina supplementation and anthropometric indices: A systematic review and meta-analysis of controlled clinical trials.

Obesity and overweight are associated with the burden of chronic diseases. The aim of the present meta-analysis is to determine the efficacy of spirulina in reducing of obesity indices. PubMed, Web of Science, Scopus, EMBASE and Cochrane library databases were searched up to November 2019. Randomized controlled trials comparing spirulina supplementation with a placebo or no treatment for anthropometric indices were included. Meta-analysis was performed using random-effects model. Subgroup analysis and meta-regression were carried out. Publication bias was evaluated using standard methods. Spirulina had ameliorative effects on weight (WMD = -1.85 Kg; 95% CI: -2.44, -1.26; p < .001; I2 = 82.4%, p < .001), and waist circumference (WMD = -1.09 cm; 95% CI: -2.16, -0.01; p = .046; I2 = 0.0%, p = .757) while no significant effect was shown on body mass index, even after sensitivity analysis (SMD = -0.53 Kg/m2 ; 95% CI: -1.25, 0.19; p = .149; I2 = 92.9%, p < .001); however, spirulina was effective in studies lasted for at least 12 weeks (SMD = -1.25 Kg/m2 ; 95% CI: -2.21, -0.28; p = .011; I2 = 90.8%, p < .001). Spirulina supplementation exerts beneficial effects on weight and waist circumference. The ameliorative effect of spirulina on body mass index was revealed in longer duration of supplementation.

The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: a systematic review of current evidence on human studies.

BACKGROUND: Cytochrome P450s (CYPs) are a class of hemoproteins involved in drug metabolism. It has been reported that body composition, proportion of dietary macronutrients, fasting and nutritional status can interfere with the activity of drug-metabolizing CYPs. OBJECTIVES: The present systematic review was conducted to summarize the effect of obesity, weight reduction, macronutrients, fasting and malnutrition on the CYP-mediated drug metabolism. METHODS: PubMed (Medline), Scopus, Embase and Cochrane Library databases and Google Scholar were searched up to June 2020 to obtain relevant studies. The PRISMA guidelines were employed during all steps. Two reviewers independently extracted the information from the included studies. Studies investigating CYPs activity directly or indirectly through pharmacokinetics of probe drugs, were included. Increase in clearance (CL) or decrease in elimination half-life (t½) and area under the curve (AUC) of probe drugs were considered as increase in CYPs activity. RESULTS: A total of 6545 articles were obtained through searching databases among which 69 studies with 126 datasets fully met the inclusion criteria. The results indicated that obesity might decrease the activity of CYP3A4/5, CYP1A2 and CYP2C9 and increase the activity of CYP2E1. The effect of obesity on CYP2D6 is controversial. Also, weight loss increased CYP3A4 activity. Moreover, CYP1A2 activity was decreased by high carbohydrate diet, increased by high protein diet and fasting and unchanged by malnutrition. The activity of CYP2C19 was less susceptible to alterations compared to other CYPs. CONCLUSION: The activity of drug-metabolizing CYPs are altered by body composition, dietary intake and nutritional status. This relationship might contribute to drug toxicity or reduce treatment efficacy and influence cost-effectiveness of medical care.

Effects of hydroalcoholic extract of Berberis Integerrima on the anthropometric indices and metabolic profile in active rheumatoid arthritis patients.

OBJECTIVES: Since, the main cause of death in Rheumatoid arthritis (RA) patients is the presence of type 2 diabetes, abnormal increase in blood lipids, blood pressure and obesity, the aim of this study was to assess the effects of Barberry on the anthropometric indices and metabolic profile in patients with RA. DESIGN: present study was a double-blinded, placebo-controlled randomized clinical trial. SETTING: 70 active RA patients were randomly allocated into intervention or placebo group INTERVENTION: Participants received 6 capsules of 500 mg barberry extract or placebo for 3 months. MAIN OUTCOME MEASURES: Serum levels of fasting blood sugar (FBS), triglyceride (TG), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C), systolic and diastolic blood pressure and anthropometric factors were assessed at baseline and at the end of the trial. RESULTS: The results of intervention on 62 patients showed that weight, BMI, and conicity index increased in both groups, but this was significant only in the placebo group (p < 0.001). Waist and hip circumference were decreased in the intervention group and increased significantly in the placebo group (p < 0.001). Body fat percent (p = 0.04), LDL-C (p = 0.05) and SBP (p = 0.02) significantly were decreased in the intervention group. The results showed a significant decrease in body fat percent (p = 0.05), hip circumference (p < 0.001), FBS (p = 0.03) and HDL-C (p = 0.03) in the intervention group compared to the placebo. CONCLUSIONS: Overall, the results of this study demonstrated that the extract of Berberis Integerrima had beneficial effects on metabolic profile and anthropometric indices in RA patients.

Effect of evening primrose oil supplementation on lipid profile: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Studies have shown that evening primrose oil (EPO) supplementation might be effective in improving lipid profile, however, the results are inconsistent. This study was performed to determine the direction and magnitude of the EPO effect on the lipid profile. METHODS: PubMed, Scopus, Cochrane Library, Embase and Web of Science databases and Google Scholar were searched up to September-2019. Meta-analysis was performed using the random-effects model. Lipid profile including high-density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) was considered as the primary outcome. RESULTS: A total of 926 articles were identified through database searching, of which, six RCTs were included in the meta-analysis. There were six studies on HDL, TC, and TG and four studies on LDL. EPO supplementation had no significant effect on TC, TG, LDL, and HDL. However, in subgroup analysis, a significant reduction in TG at a dose of ≤4 g/day (weighted mean difference [WMD] = -37.28 mg/dl; 95% CI: -73.53 to -1.03, p = .044) and a significant increase in HDL in hyperlipidemic subjects (WMD = 5.468 mg/dl; 95% CI: 1.323 to 9.614, p = .010) was found. CONCLUSION: Oral intake of EPO at a dose of ≤4 g/day significantly reduces serum TG levels and significantly increases HDL levels in hyperlipidemic subjects.

Vitamin C supplementation and C-reactive protein levels: Findings from a systematic review and meta-analysis of clinical trials.

Background and purpose C-reactive protein (CRP) is an inflammatory biomarker which prognosticates cardiovascular disease. Previous studies have reached mixed conclusions regarding the effect of vitamin C on reducing CRP or hs-CRP level. The present systematic review and meta-analysis was conducted to resolve these inconsistencies. Materials and methods: Related articles published up to August 2018 were searched through PubMed, Scopus, Ovid, ISI web of science, Embase, and Cochrane databases by relevant keywords. Clinical trials which examined the effect of either vitamin C supplementation or vitamin C-enriched foods on CRP and hs-CRP levels were included. A total of 11 studies with 14 data sets involving 818 subjects were included. Results Overall, the pooled analysis revealed that vitamin C could decrease CRP level relative to placebo group (Weighted mean difference [WMD]=-0.73 mg/L: 95% CI: -1.30 to -0.15, p=0.013) with a considerable heterogeneity (I2=98%, p<0.001). Moreover, subgroup analyses revealed that the beneficial effect of vitamin C on CRP level alternation only was found in male (p=0.003), non-smoker (p=0.041), healthy (p=0.029) and younger participants (p=0.010). Vitamin C could improve CRP level only at doses of less than 500 mg/day (p=0.009). Regarding hs-CRP changes, the pooled analysis did not show any significant effect of vitamin C (WMD=-0.65 mg/L: 95% CI: -2.03 to 0.72, p=0.35). This finding was confirmed by all subgroup analyses expect for high quality articles in which hs-CRP level was elevated after vitamin C supplementation (p=0.026). Conclusion In conclusion, supplementation with vitamin C might have a significant effect only on CRP reduction. Further studies are needed to confirm this effect.

Melatonin supplementation and pro-inflammatory mediators: a systematic review and meta-analysis of clinical trials.

BACKGROUND: Inflammatory processes are involved in chronic diseases. It has been suggested that melatonin reduces inflammation by its radical scavenging properties; however, the results of the previous studies are inconclusive. The objective of the present meta-analysis is to determine the direction and magnitude of melatonin supplementation effect on inflammatory biomarkers. METHODS: Databases including PubMed, Scopus, Cochran Library, Embase, and Google Scholar were searched up to April 2019. Meta-analysis was performed using random-effect model. Subgroup analysis, sensitivity analysis, and meta-regression were also carried out. RESULTS: Thirteen eligible studies with 22 datasets with total sample size of 749 participants were included in the meta-analysis. Melatonin supplementation significantly decreased TNF-α and IL-6 levels [(WMD = - 2.24 pg/ml; 95% CI - 3.45, - 1.03; P < 0.001; I2 = 96.7%, Pheterogeneity < 0.001) and (WMD = - 30.25 pg/ml; 95% CI - 41.45, - 19.06; P < 0.001, I2 = 99.0%; Pheterogeneity < 0.001)], respectively. The effect of melatonin on CRP levels was marginal (WMD = - 0.45 mg/L; 95% CI - 0.94, 0.03; P = 0.06; I2 = 96.6%, Pheterogeneity < 0.001). CONCLUSION: The results of the present meta-analysis support that melatonin supplementation could be effective on ameliorating of inflammatory mediators.

A posteriori dietary patterns and risk of inflammatory bowel disease: a meta-analysis of observational studies.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder which affects the gastrointestinal tract. Many factors, such as genetics, stress, and dietary patterns have been related to the risk of this disease. Adherence to a prudent/healthy dietary pattern, due to its antioxidant and anti-inflammatory properties, help to reduce the risk of many chronic diseases such as IBD. The results from previous studies regarding the association between dietary patterns and risk of IBD, including Crohn's disease (CD) and ulcerative colitis (UC), are inconsistent. This meta-analysis was performed to evaluate the potential relations between dietary patterns and risk of CD and UC. PubMed and Scopus were searched up to October 2017 for eligible studies. Random-effects or fixed-effects models were used to pool the estimated risks for the highest versus the lowest category of extracted dietary patterns. A total of six studies, including four case-control and two cohort studies with 1099 cases and 263112 controls/participants were included in the meta-analysis. A decreased risk of CD was seen for the highest compared with the lowest categories of healthy dietary pattern (OR/RR = 0.39, 95%CI = 0.16-0.62), while no significant association with western dietary pattern was observed (OR/RR = 0.78, 95% CI: 0.51-1.04). Furthermore, no significant relationship was found between healthy (OR/RR = 0.61, 95%CI = 0.04-1.18, random effects) and western/unhealthy (OR/RR = 0.97, 95% CI: 0.67-1.26) dietary patterns and risk of UC. The results of the current meta-analysis showed that a healthy dietary pattern is associated with a lower risk of CD. Further studies are warranted to confirm these findings.

The Effect of Zinc Supplementation on Serum Leptin Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Recently, obesity has become a common worldwide concern. Leptin, as an adipocytokine, plays a major role in the etiology of obesity. Prior studies have demonstrated that zinc potentially affects serum leptin levels. However, clinical trials carried out in this regard are not consistent. Therefore, current meta-analysis was conducted to ascertain the actual effect of zinc supplementation on serum leptin levels in adults. Databases of PubMed, SCOPUS, and Google Scholar were methodically searched to identify relevant articles up to April 2018. Clinical trials that examined the effect of zinc supplementation on serum leptin concentrations as outcome variables in human adults were included. The mean difference (SD) of leptin changes in the intervention and placebo groups were used to calculate the overall effect size. Totally, 663 articles were identified, of which 6 studies were eligible randomized controlled trials (RCTs) with 7 treatment arms. The analysis suggested that zinc supplementation exerts no significant effect on overall serum leptin (WMD: 0.74 ng/ml; 95% CI: -1.39 to 2.87, p=0.49). Nevertheless, sex and duration of intervention seemed to impact the extent of zinc's influence. In trials with female subjects, zinc consumption led to a significant decrease in serum leptin level (WMD: -1.93 ng/ml; 95% CI: -3.72 to -0.14, p=0.03) as well as trials that lasted for more than 6 weeks (WMD: -1.71 ng/ml; 95% CI: -3.07 to -0.35, p=0.01), in comparison to the control group. Zinc supplementation did not significantly improve leptin concentrations, but it may result in a decreased circulating leptin level in studies with a duration of more than 6 weeks especially among females.

Effects of L-citrulline supplementation on blood pressure: A systematic review and meta-analysis.

OBJECTIVE: We aimed to conduct a systematic review and meta-analysis of clinical trials that examined the effects of L-citrulline supplementation on blood pressure (BP). MATERIALS AND METHODS: We searched MEDLINE, SCOPUS, PUBMED and Google scholar databases from inception to November 16, 2017 and 811 papers were identified, of which 8 trials with 10 data sets met the inclusion criteria. Inclusion criteria were: (1) application of randomized clinical trial with either crossover or parallel designs; (2) studies conducted in adults (≥18 y); (3) oral supplementation with L-citrulline compared to control group; (4) expression of sufficient data about systolic and diastolic BP at baseline and at the end of the study in each group. BP effects were pooled by random-effects models, with trials weighted by inverse variance. RESULTS: The included studies' sample size ranged between 12 and 34 subjects. The mean age of the participants in these trials ranged between 22 and 71 years. Dosage of L-citrulline supplementation varied from 3 to 9 g/day. Duration of the intervention ranged between 1 and 17 weeks. The pooled changes in systolic and diastolic BP were (MD, -4.10 mm Hg; 95% CI [-7.94, -0.26]; p=0.037) and (MD -2.08 mm Hg; 95% CI [-4.32, 0.16]; P=0.069), respectively. The subgroup analysis showed a significant diastolic BP reduction in studies that used doses of ≥6 g/day (MD -2.75 mm Hg; 95% CI [-5.37, -0.12]; p=0.04). CONCLUSION: Our results suggest that L-citrulline supplementation may reduce systolic BP. A significant reduction in diastolic BP was observed only in the studies that used doses ≥ 6 g/day.