Efficacy of dietary supplements on mortality and clinical outcomes in adults with sepsis and septic shock: A systematic review and network meta-analysis.

AIM: The aim of this network meta-analysis (NMA) was to investigate the effects of different dietary supplements on the mortality and clinical status of adults with sepsis. METHODS: We searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials until February 2023. The inclusion criteria were: 1) randomized controlled trials (RCT)s; 2) adults suffering sepsis or septic shock; 3) evaluation of short- or long-mortality; and 4) publications between 1994 and 2023. The general information of studies and details of interventions were extracted. The primary outcome was short-term mortality (<90 days), and the secondary outcomes were long-term mortality (≥90 days), length of ICU and hospital stays, and duration of mechanical ventilation (MV). The risk of bias of RCTs was assessed using the Cochrane risk of bias tool 2 (ROB2). A random effect NMA was performed to rank the effect of each intervention using a frequentist approach. RESULTS: Finally, 56 RCTs with 5957 participants met the criteria. Approximately, one-third of RCTs were low risk of bias. NMA analysis revealed that there was no treatment more effective in short- or long-term mortality than control or other interventions, except for magnesium (RR: 0.33, 95% CI: 0.14, 0.79; GRADE = low) and vitamin C (RR: 0.81, 95% CI: 0.67, 0.99; low certainty evidence), which had beneficial effects on short-term mortality. Moreover, eicosapentaenoic acid, gamma-linolenic acid, and antioxidants (EPA + GLA + AOs) combination was the most effective, and magnesium, vitamin D and vitamin C were the other effective approaches in terms of duration of MV, and ICU length of stay. There was no beneficial dietary supplement for hospital stay in these patients. CONCLUSIONS: In septic patients, none of the dietary supplements had a substantial effect on mortality except for magnesium and vitamin C, which were linked to lower short-term mortality with low certainty of evidence. Further investigation into high-quality studies with the use of dietary supplements for sepsis should be highly discouraged.

Nutritional interventions for the prevention and treatment of cancer therapy-induced oral mucositis: an umbrella review of systematic reviews and meta-analysis.

CONTEXT: To date, the efficacy of nutritional interventions on oral mucositis (OM) in patients with cancer, and the quality of this evidence have not been explored. OBJECTIVE: The goal of this umbrella review was to provide a comprehensive evaluation of nutritional interventions for patients with cancer with OM, as well as to assess the quality of this evidence. DATA SOURCES: Meta-analyses were searched for using PubMed, Scopus, and ISI Web of Science databases until December 2021, with no time restrictions. DATA EXTRACTION: Meta-analyses of randomized control trials that evaluated the effects of nutritional interventions on the incidence of OM in patients with cancer had inclusion criteria for this umbrella review. Data extraction, quality assessment of meta-analyses, and primary studies were done independently by 2 authors. The Grading of Recommendations Assessment, Development, and Evaluation technique was used to grade the certainty of evidence. DATA ANALYSIS: A total of 26 meta-analyses were included in this umbrella review. The results showed that honey, glutamine, and propolis can reduce the incidence of severe OM, based on moderate evidence quality. In addition, zinc supplementation significantly reduced the incidence of OM, regardless of symptom severity; however, low certainty of the evidence was observed. The effects of vitamin E, curcumin, and probiotics on OM were not statistically significant. CONCLUSION: This umbrella review shows that honey, glutamine, and propolis can significantly reduce the incidence of severe OM. These findings need to be confirmed with well-designed, longitudinal randomized controlled trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022301010.

Does folic acid supplementation have a positive effect on improving memory? A systematic review and meta-analysis of randomized controlled trials.

Introduction: The results of randomized controlled trials (RCTs) on the effect of folic acid supplementation on memory status due to various heterogeneity, dosage, duration, and cognitive function assessments were inconclusive. Therefore, we have performed a systematic review and meta-analysis to investigate the effect of folic acid supplementation on memory in RCTs. Method: Comprehensive computerized systematic searches were conducted throughout Scopus, PubMed/Medline, and Google Scholar from inception until February 2022 to investigate the effect of folic acid supplementation memory levels in RCTs. The standardized mean difference (SMD) and 95% confidence interval (CIs) were used to estimate the overall effect size using random-effects meta-analyses. Results: The overall results of nine trials with 641 participants, revealed that folic acid supplementation did not significantly change memory score compared to placebo (SMD: 0.12; 95% CI: -0.17, 0.40, p = 0.418; I 2 = 62.6%). However, subgroup analyses showed that supplementation with folic acid had favorable effects on memory levels considering the following conditions: (1) doses lower than 1 mg/day, (2) treatment lasting more than 6 months, (3) conducted in eastern countries, and (4) in participants equal to or older than 70 years old. The dose-response analysis suggested a significant favorable effect on memory status at doses of 6-11 mg/d and a significant decline at doses of 17-20 mg/d. Discussion: Although we did not find a significant effect of folic acid supplementation on memory, there were some suggestions of beneficial effects in the subgroup analyses.

The Influence of Vitamin E and Omega-3 Fatty Acids on Reproductive Health Indices Among Male Workers Exposed to Electromagnetic Fields.

The present study aims to investigate the effects of using the supplementation of vitamin E and Omega 3 fatty acids on reproductive indices among workers in an automobile parts manufacturing plant. The effect of exposure to electromagnetic fields on certain sex hormones and sperm parameters will also be assessed. The participants were deployed into four groups as per the double-blind block randomization method. Semen parameters and sex hormones of the participants were analyzed before and after 3-month consumption of supplements. The level of workers' exposure to low-frequency magnetic and electrical fields was measured through the recommendation of National Institute for Occupational Safety and Health. Univariate analysis of variance indicated that exposure to electric fields had a statistically significant effect on sperm count, morphology, and motility. The simultaneous consumption of vitamin E + Omega 3 had a statistically significant effect on sperm morphology and motility.

Effect of L-Carnitine Supplementation on Inflammatory Markers and Serum Glucose in Hemodialysis Children: A Randomized, Placebo-Controlled Clinical Trial.

OBJECTIVES: Chronic inflammation is present in a high proportion of the chronic kidney disease (CKD) population, which can increase the risk of cardiovascular disease. Moreover, it is known as the leading cause of death in these patients. In addition, change in glucose metabolism is another common problem among CKD population. In this regard, it was found that insulin resistance and inflammation can perpetuate each other and simultaneously cause atherosclerosis. Because some studies have previously shown the positive effects of L-carnitine on reducing inflammation and controlling blood sugar, in the present study, we examined the effects of L-carnitine supplementation on serum inflammatory markers, fasting blood sugar (FBS), free carnitine (FC), albumin levels, and quality of life score among children on hemodialysis. METHOD: Twenty-four children on hemodialysis (aged between 6 and 18 years) were enrolled in this randomized clinical trial study. Thereafter, 12 patients received 50 mg/kg of L-carnitine and 12 patients received placebo for a 10-week period. Afterward, we determined serum FC, interleukin-6 (IL-6), high-sensitivity C-reactive protein, FBS, and albumin and Pediatrics Quality of Life scores once at the baseline and once after performing intervention for 10 weeks. Moreover, the one-way repeated measures analysis was used to evaluate the effects of L-carnitine supplementation. RESULTS: Although oral L-carnitine supplementation led to the decreased high-sensitivity C-reactive protein, this change was not significant compared with the placebo. Also, L-carnitine supplementation has significantly reduced serum levels of IL-6 and FBS, which has also raised serum FC and Pediatrics Quality of Life scores compared with the placebo. Notably, no significant change was observed in serum albumin levels. CONCLUSION: Given the significant reductions in IL-6 and FBS levels, L-carnitine supplementation appeared to have some positive effects on the inflammation, blood glucose control, and prevention of cardiovascular events in these patients, as well as the improvement of quality of life. In this regard, L-carnitine therapy with a longer duration is recommended to obtain more effective results.

Effect of L-carnitine supplementation on lipid profile and apolipoproteins in children on hemodialysis: a randomized placebo-controlled clinical trial.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in children with chronic kidney disease (CKD) and accounts for 40% of all deaths among pediatric patients with stage 5 chronic kidney disease (CKD 5). Dyslipidemia is common in children with CKD and is considered one of the major causes of CVD in these patients. As carnitine plays a key role in lipid metabolism and because plasma levels are reduced in hemodialysis patients, the aim of this study was to determine the effects of L-carnitine supplementation on serum lipid profiles, apolipoproteins, and free carnitine (FC) levels. METHODS: A total of 30 children on hemodialysis (6-18 years) were enrolled and 24 completed the study. Twelve patients received 50 mg/kg/day L-carnitine, while the other 12 patients received placebo for 10 weeks. Serum FC, total cholesterol (TC), LDL-C, HDL-C, TG, Apolipoprotein B (ApoB), and Apolipoprotein A1 (ApoA1) were determined at the baseline and after the intervention. One-way repeated measures analysis was used to evaluate the effects of L-carnitine supplementation. RESULTS: Oral L-carnitine supplementation led to decreased ApoB levels and ApoB/ApoA1 ratio, but these changes were not significant compared to placebo. Meanwhile, L-carnitine supplementation significantly reduced serum LDL-C and TC and increased serum FC compared to placebo. No significant changes were observed in serum TG and HDL-C levels. CONCLUSION: Given the significant reduction in LDL-C and TC levels, L-carnitine supplementation had positive effects on improving hyperlipidemia in children receiving hemodialysis. For more decisive results, studies with longer duration of L-carnitine therapy on children receiving hemodialysis with significant dyslipidemia are recommended. TRIAL REGISTRATION: We registered the present trial in the Iranian Registry of Clinical Trials website (available at: http://www.irct.ir , identifier: IRCT20170202032367N2).

Effect of French maritime pine bark extract supplementation on metabolic status and serum vascular cell adhesion molecule-1 levels in patients with type 2 diabetes and microalbuminuria.

OBJECTIVES: This study investigated the effect of French maritime pine bark extract (PBE) supplementation on metabolic parameters, vascular cell adhesion molecule 1 (VCAM-1), urinary albumin-to-creatinine ratio (UACR), and anthropometric indexes in patients with type 2 diabetes (T2DM) and microalbuminuria. DESIGN: This randomized, double-blind, placebo-controlled clinical trial was conducted on 46 patients with T2DM and the evidence of microalbuminuria aged 30-65 years. SETTING: Patients were recruited from the endocrinology clinic of Sina hospital (Tabriz, Iran) from March 2018 to April 2019. INTERVENTIONS: The subjects were randomly assigned to receive two capsules/day each containing 50mg of PBE or placebo for eight weeks. MAIN OUTCOME MEASURES: Glycemic parameters, serum VCAM-1 and lipid profile, UACR, and anthropometric indexes were measured for all patients at baseline and the end of the study. RESULTS: PBE supplementation significantly reduced glycosylated hemoglobin, VCAM-1, total cholesterol, UACR, waist circumference, and waist-to-height ratio compared to the placebo group at the end of the study (all P < 0.05). Changes in fasting blood glucose, insulin, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were not significant between the two groups (all P > 0.05). CONCLUSIONS: The study findings demonstrated some favorable effects of PBE supplementation on glycemic control, serum VCAM-1 and total cholesterol levels, and microalbuminuria, as well as abdominal obesity in patients with T2DM.

Effect of l-arginine on cardiac reverse remodeling and quality of life in patients with heart failure.

BACKGROUND & AIMS: Heart failure (HF), as a major cardiac disease, is associated with considerable mortality, morbidities and poor quality of life. The aim of this study was to investigate the effect of l-arginine supplementation on cardiac outcomes and quality of life in patients with ischemic HF. METHODS: This double-blind randomized controlled clinical trial was conducted in 50 patients with ischemic HF. Patients were randomly assigned to receive either 3 gr/d l-arginine or placebo, for 10 weeks. Cardiac function (based on echocardiography and six-minute walk test), blood pressure, and quality of life (based on the Minnesota living with heart failure questionnaire) were assessed. RESULTS: The results showed significant improvements in ejection fraction (-6.5 ± 8.7 vs. -0.7 ± 7.8%, P = 0.037), left ventricular function (P = 0.043), diastolic dysfunction (P = 0.01) and marginally improvement in changes of left ventricular dimension during diastole (LVDd) (4 ± 6 vs. 0.3 ± 6.9 mm, P = 0.065) in the l-arginine compared to the placebo group. At the end of the study, physical aspect (5.7 ± 3.3 vs. 1.2 ± 6.1, P = 0.002) and total score (10 ± 6.7 vs. 4.1 ± 9.4, P = 0.011) of quality of life improved significantly in the l-arginine compared with the placebo group. Additionally, pre-to post-values of diastolic blood pressure, mean arterial pressure, LVDd, LV ejection fraction, left ventricular function, diastolic dysfunction as well as physical and total scores of quality of life improved significantly within the intervention, but not the placebo, group (all P < 0.05). CONCLUSION: This study showed that 3 gr/d l-arginine supplementation for 10 weeks could improve cardiac recovery and function, and quality of life in patients with HF. This study was registered at the Iranian Clinical Trial Registration Center (www.irct.ir) with IRCT20170202032367N4 code.

The effect of vitamin E supplementation on biomarkers of endothelial function and inflammation among hemodialysis patients: A double-blinded randomized clinical trial.

OBJECTIVES: The present study was aimed to investigate the effect of alpha-tocopherol supplementation on biomarkers of endothelial function (Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Protein 1) and inflammatory markers (Interleukin 6 and high-sensitivity C-reactive protein) among the hemodialysis patients. METHODS: To conduct this randomized, double-blinded, and placebo-controlled clinical trial, 49 hemodialysis patients, aged 20-60 years, were recruited and randomly divided into the intervention and control groups. The intervention group (n = 25) received 600 IU alpha-tocopherol soft gels (200 IU three times daily), while the controls (n = 24) consumed the identical placebo soft gels for 10 weeks. At the baseline and end of the study, 7 ml pre-dialysis blood samples were taken from all participants to measure their serum concentrations of ICAM-1, VCAM-1, IL-6, and hs-CRP. RESULTS: Alpha-tocopherol supplementation reduced the serum levels of ICAM-1 and VCAM-1 significantly (-140.67 ± 57.25 ng/ml vs. -15.97 ± 79.19 ng/ml, P = 0.001 for ICAM-1 and --6.79 ± 4.76 ng/ml vs. 1.02 ± 3.22 ng/ml, P = 0.019 for VCAM-1). However, no significant difference was observed between the two groups regarding the serum levels of hs-CRP (-0.15 ± 0.19 mg/l vs. 0.02 ± 0.12 mg/l; P = 0.32) and IL-6 (-0.03 ± 0.1 pg/ml vs. - 0.06 ± 0.11 pg/ml; P = 0.65). CONCLUSIONS: Our results showed that 10 weeks of supplementation with 600 IU alpha-tocopherol improved ICAM-1 and VCAM-1 levels, but did not have any effect on the serum concentration of IL-6 and hs-CRP in hemodialysis patients. Further studies are required to confirm these findings.

The effect of hesperidin supplementation on metabolic profiles in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: Hesperidin as an antioxidant flavonoid exerts anti-adipogenic, anti-inflammatory, anti-oxidant and anti-hypercholesterolemic effects. Besides, the increasing prevalence of metabolic syndrome (MetS) and its allied complications, on the one hand, and the willingness of individuals to use natural products for curing their diseases, on the other hand, led to the design of this study to evaluate the efficacy of hesperidin in normalizing the metabolic abnormalities in patients with MetS. METHODS: In this clinical trial with a parallel-group design, 49 patients with MetS received either 500-mg hesperidin or placebo, twice daily, for 12 weeks. Number of participants with treated MetS was considered as a primary end point. Anthropometric parameters, dietary intake, physical activity, lipid profile, glucose homeostasis parameter, tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP) were assessed at the beginning and at the end of the study. This trial is registered at clinicaltrials.gov as NCT03734874. RESULTS: Compared with the placebo group, hesperidin decreased fasting glucose level (- 6.07 vs. - 13.32 mg/dL, P = 0.043), triglyceride (- 8.83 vs. - 49.09 mg/dL, P = 0.049), systolic blood pressure (- 0.58 vs. - 2.68 mmHg, P = 0.048) and TNF-α (- 1.29 vs. - 4.44 pg/mL, P = 0.009). Based on the within-group analysis, hesperidin led to significant decrease in serum levels of glucose, insulin, triglyceride, total cholesterol, low density lipoprotein cholesterol, TNF-α and hs-CRP, while in control group only glucose and insulin significantly decreased. CONCLUSIONS: The results indicate that hesperidin supplementation can improve metabolic abnormalities and inflammatory status in patients with MetS.

Hesperidin improves hepatic steatosis, hepatic enzymes, and metabolic and inflammatory parameters in patients with nonalcoholic fatty liver disease: A randomized, placebo-controlled, double-blind clinical trial.

This study aimed to evaluate the effects of hesperidin on nonalcoholic fatty liver disease (NAFLD) characteristics. In this randomized, double-blind, controlled clinical trial, 50 NAFLD patients were supplemented with either 1-g hesperidin capsule or identical placebo capsule for 12 weeks. During the intervention, both groups were advised to follow healthy lifestyle habits including dietary and physical activity recommendations. At the end of the study, hesperidin supplementation, compared with placebo, was associated with a significant reduction in alanine aminotransferase (p = .005), γ-glutamyltransferase (p = .004), total cholesterol (p = .016), triglyceride (p = .049), hepatic steatosis (p = .041), high-sensitivity C-reactive protein (p = .029), tumor necrosis factor-α, and nuclear factor-κB (NF-κB). In conclusion, our results indicate that hesperidin supplementation accompanied with lifestyle modification is superior to lifestyle modification alone in management of NAFLD at least partially through inhibiting NF-κB activation and improving lipid profile. Further studies with higher dose of hesperidin are required to find the optimal dose.

Effects of Flaxseed Oil on Serum Bone Turnover Markers in Hemodialysis Patients: a Randomized Controlled Trial.

INTRODUCTION: Chronic kidney disease-mineral and bone disorder is a common complication in hemodialysis patients. The present study was designed to investigate the effects of flaxseed oil, a rich source of plant omega-3 fatty acid alpha-linolenic acid, on serum markers of bone formation and resorption in hemodialysis patients. MATERIALS AND METHODS: In this randomized controlled trial, 34 hemodialysis patients were randomly assigned to either the flaxseed oil or the control group. The patients in the flaxseed oil group received 6 g/d of flaxseed oil for 8 weeks, whereas the control group received 6 g/d of medium chain triglycerides oil. At baseline and the end of the 8th week, 7 mL of blood was obtained from each patient after a 12- to 14-hour fast and serum concentrations of osteocalcin, osteoprotegerin, N-telopeptide, and receptor activator of nuclear factor kappa B ligand were measured. RESULTS: Serum N-telopeptide concentration decreased significantly up to 17% in the flaxseed oil group at the end of week 8, as compared to baseline (P < .01), and the reduction was significant in comparison with the control group. There were no significant differences between the two groups in the mean changes of serum osteocalcin, osteoprotegerin, or receptor activator of nuclear factor kappa B ligand. CONCLUSIONS: This study indicates that daily consumption of 6 g/d of flaxseed oil may reduce bone resorption in hemodialysis patients.

Effects of Ginger on Serum Lipids and Lipoproteins in Peritoneal Dialysis Patients: A Randomized Controlled Trial.

UNLABELLED: ♦ BACKGROUND: In peritoneal dialysis (PD) patients, one of the major risk factors for cardiovascular disease is lipid abnormalities. This study was designed to investigate the effects of ginger supplementation on serum lipids and lipoproteins in PD patients. ♦ METHODS: In this randomized, double-blind, placebo-controlled trial, 36 PD patients were randomly assigned to either the ginger or the placebo group. The patients in the ginger group received 1,000 mg ginger daily for 10 weeks, while the placebo group received corresponding placebos. At baseline and at the end of week 10, 7 mL of blood were obtained from each patient after a 12- to 14-hour fast, and serum concentrations of triglyceride, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and lipoprotein (a) [Lp (a)] were measured. ♦ RESULTS: Serum triglyceride concentration decreased significantly up to 15% in the ginger group at the end of week 10 compared with baseline (p < 0.01), and the reduction was significant in comparison with the placebo group (p < 0.05). There were no significant differences between the 2 groups in mean changes of serum total cholesterol, LDL-C, HDL-C, and Lp (a). ♦ CONCLUSION: This study indicates that daily administration of 1,000 mg ginger reduces serum triglyceride concentration, which is a risk factor for cardiovascular disease, in PD patients.

Effects of ginger on serum glucose, advanced glycation end products, and inflammation in peritoneal dialysis patients.

OBJECTIVE: The aim of this study was to investigate the effects of ginger supplementation on serum glucose, advanced glycation end products, oxidative stress, and systemic and vascular inflammatory markers in patients on peritoneal dialysis (PD). METHODS: In this randomized, double-blind, placebo-controlled trial, 36 patients on PD were randomly assigned to either the ginger or the placebo group. The patients in the ginger group received 1000 mg/d ginger for 10 wk, whereas the placebo group received corresponding placebos. At baseline and the end of week 10, serum concentrations of glucose, carboxymethyl lysine, pentosidine, malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and sE-selectin were measured after a 12- to 14-h fast. RESULTS: Serum fasting glucose decreased significantly up to 20% in the ginger group at the end of week 10 compared with baseline (P < 0.05), and the reduction was significant in comparison with the placebo group (P < 0.05). There were no significant differences between the two groups in mean changes of serum carboxymethyl lysine, pentosidine, MDA, hs-CRP, sICAM-1, sVCAM-1, and sE-selectin. CONCLUSION: This study indicated that daily administration of 1000 mg ginger reduces serum fasting glucose, which is a risk factor for hyperinsulinemia, dyslipidemia, peritoneal membrane fibrosis, and cardiovascular disease, in patients on PD.