The effects of citrus flavonoids supplementation on endothelial function: A systematic review and dose-response meta-analysis of randomized clinical trials.

The present systematic review and dose-response meta-analysis was conducted to synthesize existing data from randomized clinical trials (RCTs) concerning the impact of citrus flavonoids supplementation (CFS) on endothelial function. Relevant RCTs were identified through comprehensive searches of the PubMed, ISI Web of Science, and Scopus databases up to May 30, 2023. Weighted mean differences and their corresponding 95% confidence intervals (CI) were pooled utilizing a random-effects model. A total of eight eligible RCTs, comprising 596 participants, were included in the analysis. The pooled data demonstrated a statistically significant augmentation in flow-mediated vasodilation (FMD) (2.75%; 95% CI: 1.29, 4.20; I2 = 87.3%; p < 0.001) associated with CFS compared to the placebo group. Furthermore, the linear dose-response analysis indicated that each increment of 200 mg/d in CFS led to an increase of 1.09% in FMD (95% CI: 0.70, 1.48; I2 = 94.5%; p < 0.001). The findings from the nonlinear dose-response analysis also revealed a linear relationship between CFS and FMD (Pnon-linearity = 0.903, Pdose-response <0.001). Our findings suggest that CFS enhances endothelial function. However, more extensive RTCs encompassing longer intervention durations and different populations are warranted to establish more precise conclusions.

The effects of coenzyme Q10 supplementation on biomarkers of exercise-induced muscle damage, physical performance, and oxidative stress: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

PURPOSE: This study aims to elucidate the dose-dependent effect of coenzyme Q10 supplementation (CoQ10) on exercise-induced muscle damage (EIMD), physical performance, and oxidative stress in adults. METHODS: A systematic search was conducted through PubMed, Scopus, and ISI Web of Science databases up to August 2023, focusing on randomized control trials (RCTs) that investigated the effects of CoQ10 supplementation on EIMD recovery, physical performance and oxidative stress mitigation in adults. The weighted mean difference (WMD) and 95 % confidence interval (95 %CI) were estimated using the random-effects model. RESULTS: The meta-analysis incorporated 28 RCTs, encompassing 830 subjects. CoQ10 supplementation significantly decreased creatine kinase (CK) (WMD: -50.64 IU/L; 95 %CI: -74.75, -26.53, P < 0.001), lactate dehydrogenase (LDH) (WMD: -52.10 IU/L; 95 %CI: -74.01, -30.19, P < 0.001), myoglobin (Mb) (WMD: -21.77 ng/ml; 95 %CI: -32.59, -10.94, P < 0.001), and Malondialdehyde (MDA) (WMD: -0.73 µmol/l; 95 %CI: -1.26, -0.20, P = 0.007) levels. No significant alteration in total antioxidant capacity was observed post-CoQ10 treatment. Each 100 mg/day increase in CoQ10 supplementation was correlated with a significant reduction in CK (MD: -23.07 IU/L, 95 %CI: -34.27, -11.86), LDH (WMD: -27.21 IU/L, 95 %CI: -28.23, -14.32), Mb (MD: -7.09 ng/ml; 95 %CI: -11.35, -2.83) and MDA (WMD: -0.17 µmol/l, 95 %CI: -0.29, -0.05) serum levels. Using SMD analysis, "very large" effects on LDH and "moderate" effects on CK and MDA were noted, albeit nonsignificant for other outcomes. CONCLUSION: CoQ10 supplementation may be effective in reducing biomarkers of EIMD and oxidative stress in adults. Nevertheless, given the preponderance of studies conducted in Asia, the generalizability of these findings warrants caution. Further RCTs, particularly in non-Asian populations with large sample sizes and extended supplementation durations, are essential to substantiate these observations.

Effect of soluble fiber on blood pressure in adults: a systematic review and dose-response meta-analysis of randomized controlled trials.

OBJECTIVES: Pervious epidemiologic evidence indicates that soluble fiber is protective against hypertention: however, randomized controlled trials (RCTs) have presented varying results. In the present study, we aimed to conduct a systematic review and dose-response meta-analysis to summarize published RCTs which assess the effect of soluble fiber supplementation on systolic blood pressure (SBP) and diastolic blood pressure (DBP). METHODS: Scopus, PubMed, and ISI Web of Sciences were searched to identify relevant studies up to Aug 2022. We estimated the change in blood pressure for each 5 g/d increment in soluble fiber supplementation in each trial and then calculated the weighted mean difference (WMD) and 95%CI using a random-effects model. We estimated dose-dependent effects using a dose-response meta-analysis of differences in means. The risk of bias for study was assessed using the Cochrane tool. Publication bias was evaluated via funnel plot and Begg's test and Egger's test. RESULTS: Eighty-three eligible studies with total sample size of 5,985 participants were included in the meta-analysis. Soluble fiber supplementation significantly decreased SBP (WMD: -1.36 mmHg, 95% CI: -2.13 to -0.60, P < 0.001; I2 = 47.1%, P < 0.001) and DBP (WMD: -0.72 mmHg, 95% CI: -1.26 to -0.18, P = 0.009; I2 = 45.4%, P < 0.001). Each 5 g/d increment in soluble fiber supplementation had a significant reduction in SBP (WMD: -0.54 mmHg; 95%CI: -0.86, -0.22, P = 0.001; I2 = 52.2, Phet < 0.001) and DBP (WMD: -0.28 mmHg; 95%CI: -0.49, -0.80, P = 0.007; I2 = 43.1%, Phet < 0.001). The levels of SBP decreased proportionally with the increase in soluble fiber supplementation up to 20 g/d (MD20g/d: -1.79 mmHg, 95%CI: -2.86, -0.71). CONCLUSION: Current evidence indicated the beneficial effect of soluble fiber supplementation on blood pressure. Our findings suggest that soluble fiber supplementation could contribute to the management of hypertension and the reduction of cardiovascular disease risk.

The effects of spirulina supplementation on serum iron and ferritin, anemia parameters, and fecal occult blood in adults with ulcerative colitis: A randomized, double-blinded, placebo-controlled trial.

BACKGROUND & AIMS: The present clinical trial aimed to evaluate the efficacy of spirulina administration on serum iron, ferritin, anemia parameters, and fecal occult blood test (FOBT) in adults with ulcerative colitis (UC). METHODS: Eighty participants with UC were randomly assigned to take, either 1 g/day (two 500 mg capsules) spirulina (n = 40) or placebo (n = 40) in a double-blinded clinical trial for eight weeks. Dietary intake, physical activity status, serum iron and ferritin levels, anemia parameters, and FOBT were assessed in each participant at baseline and following the intervention. Seventy-three participants completed the trial. RESULTS: Our results indicated significantly increased (p = 0.04) serum iron after eight weeks of spirulina supplementation compared to the placebo group. The spirulina group also demonstrated significantly increased mean corpuscular volume (p = 0.004) whereas red blood cell count (p = 0.01) and hematocrit (p = 0.03) were significantly lowered in the placebo group. No significant changes in FOBT outcomes were seen between groups at baseline (p = 0.12) and the end of the trial (p = 0.34). Eight weeks of 1 g/day spirulina supplementation improved anemia parameters in adults with UC compared to placebo. CONCLUSIONS: These outcomes suggest that spirulina administration may be beneficial in the management of anemia in UC. Further clinical trials of longer duration are necessary to corroborate and expand our findings. Registered at: http://www.IRCT.ir (code: IRCT20170802035460N3).

The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Imbalances in immune regulation are important features of migraine pathophysiology. In line with this, the current study investigated the efficacy of omega-3 fatty acids supplementation on inflammatory and anti-inflammatory markers in patients with migraines. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial consisted of 40 patients that were prone to experiencing episodic migraines. For two months, participants were randomized into one group that received omega-3 supplementation (n= 20), 600 mg of EPA and 300 mg of DHA, twice daily) or another group that received a placebo (n= 20). Transforming growth factor ß (TGF-ß), interleukin (IL)-4, interferon-gamma (IFN-γ), and interleukin (IL)-17 serum levels were assessed using enzyme-linked immunosorbent assay methods at baseline and following the intervention. The current study was registered on ClinicalTrials.gov with the registration number NCT02532023. RESULTS: After two months of intervention, the administration of omega-3 fatty acids resulted in a significant rise in the concentrations of anti-inflammatory cytokine IL-4 (p=0.010) as well as a significant reduction in concentrations of pro-inflammatory cytokine IFN-γ (p=0.001) compared with the placebo. However, no significant changes were observed in serum TGF-ß and IL-17 levels. DISCUSSION: Our findings indicated consumption of omega-3 fatty acids may have a potentially beneficial response on the inflammatory immune response in patients with migraines. Larger trials are needed to corroborate these findings.

Soluble Fiber Supplementation and Serum Lipid Profile: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

To present a comprehensive synthesis of the effect of soluble fiber supplementation on blood lipid parameters in adults, a systematic search was undertaken in PubMed, Scopus, and ISI Web of Science of relevant articles published before November 2021. Randomized controlled trials (RCTs) evaluating the effects of soluble fibers on blood lipids in adults were included. We estimated the change in blood lipids for each 5 g/d increment in soluble fiber supplementation in each trial and then calculated the mean difference (MD) and 95% CI using a random-effects model. We estimated dose-dependent effects using a dose-response meta-analysis of differences in means. The risk of bias and certainty of the evidence was evaluated using the Cochrane risk of bias tool and the Grading Recommendations Assessment, Development, and Evaluation methodology, respectively. A total of 181 RCTs with 220 treatment arms (14,505 participants: 7348 cases and 7157 controls) were included. There was a significant reduction in LDL cholesterol (MD: -8.28 mg/dL, 95% CI: -11.38, -5.18), total cholesterol (TC) (MD: -10.82 mg/dL, 95% CI: -12.98, -8.67), TGs (MD: -5.55 mg/dL, 95% CI: -10.31, -0.79), and apolipoprotein B (Apo-B) (MD: -44.99 mg/L, 95% CI: -62.87, -27.12) after soluble fiber supplementation in the overall analysis. Each 5 g/d increase in soluble fiber supplementation had a significant reduction in TC (MD: -6.11 mg/dL, 95% CI: -7.61, -4.61) and LDL cholesterol (MD: -5.57 mg/dl, 95% CI: -7.44, -3.69). In a large meta-analysis of RCTs, results suggest that soluble fiber supplementation could contribute to the management of dyslipidemia and the reduction of cardiovascular disease risk.

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.

L-Arginine is a feasible supplement to heal chronic anal fissure via reducing internal anal sphincter pressure: a randomized clinical trial study.

The hypertonicity of internal anal sphincter resting pressure is one of the main causes of chronic anal fissure. Therefore, the aim of this study was to assess the effect of oral administration of L-arginine on the improvement of the anal fissures by relaxing the internal anal sphincter. Seventy-six chronic anal fissure patients (aged 18-65 years) who were referred to Rasoul-e-Akram Hospital, Tehran, Iran from February 2019 to October 2020 participated in this randomized, double-blind, placebo-controlled trial. Participants were allocated into treatment (L-arginine) and placebo groups. They took a 1000 mg capsule three times a day for 1 month, and then we followed them at the end of the first and third months after the intervention. Clinical symptoms, anal sphincter resting pressure, and quality of life (QoL) were completed at baseline and the end of the study. The analysis of data showed a significant decrease in bleeding, fissure size, and pain for each group; however, in the L-arginine group was more than the control group at the end of the study (P values < 0.001). Following that, a significant increase in QoL was seen just in patients treated with L-arginine (P value = 0.006). In addition, the comparison of anal pressures at baseline and, between groups at the end of the study showed a significant reduction in sphincter pressure in patients treated with L-arginine (P value < 0.001, = 0.049; respectively). The oral administration of 3000 mg L-arginine can heal chronic anal fissures by reducing internal anal sphincter pressure with more negligible side effects. However, we recommend long-term study with more extended follow-up.Clinical trial registry: IRCT20190712044182N1 at Iranian clinical trials, date: 2019-08-27.

The Effect of Oral Magnesium Supplementation on Inflammatory Biomarkers in Adults: A Comprehensive Systematic Review and Dose-response Meta-analysis of Randomized Clinical Trials.

This is a comprehensive systematic review and dose-response meta-analysis evaluating the effects of oral magnesium supplementation on inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) among adults. The major databases including PubMed, Web of Science, Embase, and Google Scholar were searched for relevant publications until December 14, 2020, using appropriate keywords. The Cochrane Collaboration tool was used to assess the quality of each study. We also performed a subgroup analysis to identify probable sources of heterogeneity. A total of 18 studies with 927 participants fulfilled the eligibility criteria and included in this meta-analysis. Our results indicate that the supplementation with magnesium had no statistically significant effect on serum concentrations of CRP (WMD, - 0.49; 95% CI, - 1.72 to 0.75 mg/L; P = 0.44), IL-6 (WMD, - 0.03; 95% CI, - 0.40 to 0.33 pg/mL; P = 0.86), and TNF-α (WMD, 0.12; 95% CI, - 0.08 to 0.31 pg/mL; P = 0.24) compared with controls. In addition, based on dose-response assessment, no significant non-linear association was found between magnesium supplementation dosage or duration on serum CRP and IL-6 concentrations. The findings of the present systematic review and meta-analysis did not support the notion that oral magnesium supplementation could have favorable effects on CRP, IL-6, and TNF-α in the adult population.

The effect of zinc supplementation in children with attention deficit hyperactivity disorder: A systematic review and dose-response meta­analysis of randomized clinical trials.

OBJECTIVE: The present systematic review and dose-response meta-analysis was conducted to quantify the efficacy of zinc supplementation on clinical symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. METHODS: Electronic databases including PubMed, Scopus, ISI web of science, and Google Scholar were searched until January 2021. Results were reported as standardized mean difference (SMD) with a 95% confidence interval (CI) using Hedges's adjusted g method. RESULTS: six randomized clinical trials with 489 school-aged children were identified for the meta-analysis. Our findings showed a significant effect of zinc supplementation on ADHD total scores (SMD: -0.62 Hedges' g; 95% CI: -1.24 to -0.002, p = 0.04) but not in hyperactivity scores (SMD: -0.93 Hedges' g; 95% CI: -3.31 to 1.45, p = 0.44) and inattention scores (SMD: 0.21 Hedges' g; 95% CI: -0.09 to 0.51, p = 0.17) compared to the control group. Besides, the dose-response analysis did not find any significant non-linear association between zinc supplementation dosage or duration on ADHD total scores. The certainty of the evidence was rated moderate to very low for all outcomes. CONCLUSION: Zinc supplementation may have beneficial effects in improving ADHD symptoms in children with ADHD. Future well-designed, large-scale randomized controlled trials are needed to establish the benefit of zinc supplementation for ADHD.

Effects of zinc supplementation on inflammatory biomarkers and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & OBJECTIVE: Current evidence is debatable regarding the feasible effects of zinc supplementation on the inflammation and oxidative stress status of adults. This systematic review and meta-analysis aimed to clarify this inconclusiveness. MATERIALS AND METHODS: Literature search was conducted via online databases such as PubMed, Scopus, ISI Web of Science, Cochrane Library, and Google Scholar until June 2020. The overall effect was presented as the weighted mean difference (WMD) at 95 % confidence interval (CI) in a random-effects meta-analysis model. Publication bias was also assessed using Egger's and Begg's statistics. RESULTS: In total, 25 clinical trials (n = 1428) were reviewed, which indicated that zinc supplementation significantly affects the concentration of C- reactive protein (WMD: -0.03 mg/l; 95 % CI: -0.06, 0.0; P = 0.029), interlukin-6 (WMD: -3.81 pg/mL; 95 % CI: -6.87, -0.76; P = 0.014), malondialdehyde (WMD: -0.78 µmol/l; 95 % CI: -1.14, -0.42; P < 0.001), and total antioxidant capacity (WMD: 95.96 mmol/l; 95 % CI: 22.47, 169.44; P = 0.010). In addition, a significant between-study heterogeneity and a non-significant increment was reported in nitric oxide (WMD: 1.47 µmol/l; 95 % CI: -2.45, 5.40; P = 0.461) and glutathione (WMD: 34.84 µmol/l; 95 % CI: -5.12, 74.80; P = 0.087). CONCLUSION: According to the results, zinc supplementation may have beneficial anti-inflammatory and anti-oxidative effects in adults.

The effects of magnesium and vitamin E co-supplementation on some cardiovascular risk factors: A meta-analysis.

BACKGROUND: Growing attention has been paid to use the combination of magnesium and vitamin E, which might improve metabolic profiles in patients with metabolic diseases. Consequently, we conducted a meta-analysis of published randomized controlled trials (RCTs) to systematically analyze the effects of magnesium and vitamin E co-supplementation on some cardiovascular risk factors in patients with metabolic disorders. METHODS: We searched the National Library of PubMed, Scopus, Web of Science, the Cochrane library and Embase databases for studies published before February 2020 and included controlled trials in which used mentioned intervention. Finally, we extracted 4 trials satisfying our selection criteria. Two reviewers selected studies independently of each other and if they disagreed, was asked a third reviewer. The risk of bias of individual studies was assessed using the Cochrane Collaboration risk of bias tool. Data were pooled using the random-effects method and were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI). RESULTS: A total of 4 studies meet the eligibility criteria. 119 individuals allocated to intervention and 118 participants allocated to control group. Our meta-analysis indicated that the co-supplementation with magnesium and vitamin E resulted in a significant decrease in FPG, Insulin, HOMA-IR, TG, TC, and LDL-C in comparison with placebo. The co-supplementation with magnesium and vitamin E had no significant effects on the body weight, BMI, and HDL. However, there were no significant heterogeneity for all of the variables except for FPG (I2 = 56.0%, P = 0.103) and TG (I2 = 80.7%, P = 0.006). CONCLUSIONS: Our meta-analysis indicated that the co-supplementation with magnesium and vitamin E resulted in a significant decrease in FPG, Insulin, HOMA-IR, TG, LDL-C. Moreover, no significant effects on the body weight, BMI and HDL were observed. However, the glycemic-improving properties of magnesium and vitamin E co-supplementation were small and may not reach clinical importance.

The effect of green coffee extract supplementation on anthropometric measures in adults: A comprehensive systematic review and dose-response meta-analysis of randomized clinical trials.

BACKGROUND AND AIM: Two meta-analyses summarized data on the effects of green coffee extract (GCE) supplementation on anthropometric measures. However, the accuracy of those meta-analyses is uncertain due to several methodological limitations. Therefore, we aimed to conduct a comprehensive systematic review and dose-response meta-analysis to summarize all available evidence on the effects of GCE supplementation on anthropometric measures by considering the main limitations in the previous meta-analyses. METHODS: We searched available online databases for relevant publications up to January 2020, using relevant keywords. All randomized clinical trials (RCTs) investigating the effects of GCE supplementation, compared with a control group, on anthropometric measures [including body weight, body mass index (BMI), body fat percentage, waist circumference (WC) and waist-to-hip ratio (WHR)] were included. RESULTS: After identifying 1871 studies from our initial search, 15 RCTs with a total sample size of 897 participants were included in the systematic review and meta-analysis. We found a significant reducing effect of GCE supplementation on body weight (weighted mean difference (WMD): -1.23, 95 % CI: -1.64, -0.82 kg,P < 0.001), BMI (WMD: -0.48, 95 % CI: -0.78, -0.18 kg/m2, P = 0.001), and WC (WMD: -1.00, 95 % CI: -1.70, -0.29 cm, P = 0.006). No significant effect of GCE supplementation on body fat percentage and WHR was seen. In the dose-response analyses, there was no significant association between chlorogenic acid (CGA) dosage, as the main polyphenol in green coffee, and changes in anthropometric measures. CONCLUSION: We found that GCE supplementation had a beneficial effect on body weight, BMI and WC. It provides a cost-effective and safe alternative for the treatment of obesity. Additional well-designed studies are required to further confirm our findings.

The effect of synbiotic supplementation on anthropometric indices, appetite, and constipation in people with hypothyroidism: A randomized, double-blind, placebo-controlled trial.

Hypothyroidism and obesity are two highly prevalent conditions that appear to be closely related. Hypothyroidism is correlated with weight gain, loss of appetite, constipation, and a higher incidence of obesity. The present study aimed to investigate the effects of synbiotic supplementation on anthropometric indices, appetite, and constipation in subjects with hypothyroidism. Sixty subjects with hypothyroidism were assigned into two groups to receive either 500 mg/day of synbiotic (n = 30) or a placebo (n = 30) per day for 8 weeks. Anthropometric indices, appetite, and constipation were assessed at study baseline and end of the trial. At the end of trial, waist-to-hip ratio was significantly decreased in the synbiotic group (p = .030), whereas there were no significant differences between groups. We did not observe any statistically significant change in appetite or other anthropometric indices (p > .05). Compared with the placebo synbiotic supplementation led to a significant reduction in constipation (p = .048). The results of the present trial indicated that synbiotic supplementation may have favorable results in constipation among subjects with hypothyroidism for 8 weeks. Further studies with larger sample size and longer duration are needed to confirm our findings.

The beneficial effects of nutraceuticals and natural products on small dense LDL levels, LDL particle number and LDL particle size: a clinical review.

Cardiovascular diseases (CVDs) are globally the major causes of morbidity and mortality. Evidence shows that smaller and denser low-dense lipoprotein (sdLDL) particles are independent atherogenic risk factors for CVD due to their greater susceptibility to oxidation, and permeability in the endothelium of arterial walls. sdLDL levels are an independent risk factor and of more predictive value than total LDL-C for the assessment of coronary artery disease and metabolic syndrome. Functional food ingredients have attracted significant attention for the management of dyslipidemia and subsequently increase cardio-metabolic health. However, to date there is no study that has investigated the effect of these bioactive natural compounds on sdLDL levels. Therefore, the aim of the present review is to summarize the evidence accrued on the effect of special dietary ingredients such as omega-3 polyunsaturated fatty acids, nutraceuticals and herbal medicines on the levels of sdLDL, LDL particle number, and LDL particle size. Based on the results of the existing clinical trials this review suggests that natural products such as medicinal plants, nutraceuticals and omega-3 fatty acids can be used as adjunct or complementary therapeutic agents to reduce sdLDL levels, LDL particle numbers or increase LDL particle size and subsequently may prevent and treat CVD, with the advantage that theses natural agents are generally safe, accessible, and inexpensive.

The effects of synbiotic supplementation on thyroid function and inflammation in hypothyroid patients: A randomized, double­blind, placebo­controlled trial.

BACKGROUND: There is a positive link between thyroid homeostasis and the composition of gut microbiota. A limited number of studies have suggested the efficacy of probiotic products on levothyroxine metabolism and thyroid hormone activity. Therefore, the purpose of this study was to investigate the effect of synbiotic supplementation on thyroid function, inflammation markers, and blood pressure in subjects with hypothyroidism. METHODS: This study was conducted as a randomized, double-blind, placebo-controlled trial involving 60 patients with hypothyroidism. Participants were randomly recruited into two groups to receive either 500 mg/day of synbiotic (n = 30) or a placebo (n = 30) for 8 weeks. RESULTS: Thyroid-stimulating hormone concentration, levothyroxine dose, and fatigue severity scale score were significantly decreased after the 8-week intervention in the synbiotic group (P < 0.05), while there were no significant differences seen in the placebo group. In addition, FT3 at the end of intervention was significantly higher (P = 0.001) in both groups, although these changes were not significant between the two groups (P = 0.259). Synbiotic supplements led to a significant elevation in serum CRP (P = 0.006), but this increase was not significant between groups (P = 0.699). Moreover, no statistical significance was observed within or between groups in terms of anti-thyroid peroxidase, systolic blood pressure and diastolic blood pressure (P > 0.05). CONCLUSION: Synbiotic supplementation among hypothyroid patients for 8 weeks may have beneficial effects on thyroid function. Further studies with larger sample size and longer duration are needed to confirm the current findings.

Trace Element Status and Hypothyroidism: A Systematic Review and Meta-analysis.

The relationship between thyroid hormones metabolism and trace element levels has biological plausibility; however, previous reports that compared trace element levels in patients with hypothyroidism and healthy individuals yielded conflicting results. Therefore, the aim of this meta-analysis was to investigate the association between selected trace elements (i.e., selenium (Se), zinc (Zn), iron (Fe), manganese (Mn), copper (Cu), lead (Pb)), and magnesium (Mg) concentrations in patients with hypothyroidism and healthy controls. Electronic databases, including PubMed, Scopus, Embase, and Science Direct, were searched systematically until September 2019. Thirty-two observational studies were included in the final analyses. Hedges' g tests were used to estimate effect sizes, as trace element concentrations were reported using different measurement units across the studies. Selenium (Hedges' g = - 0.52; 95% CI = [- 1.05, - 0.002]; P = 0.049) and Zn (Hedges' g = - 0.86; 95% CI = [- 1.66, - 0.06]; P = 0.035) concentrations were significantly lower, whereas Pb concentrations were significantly higher (Hedges' g = 0.34; 95% CI = [0.10, 0.59]; P = 0.006) in patients with hypothyroidism compared with healthy controls. There were no differences in the concentrations of Fe, Cu, Mn, and Mg between the groups. Patients with hypothyroidism exhibited lower Se and Zn and increased Pb concentrations compared with healthy controls. High-quality studies with larger sample sizes are required to explicate the link between trace element status and hypothyroidism.