Abstract

BACKGROUND & AIMS Serum 25-hydroxyvitamin D [S-25(OH)D] and nonalcoholic fatty liver disease (NAFLD) are correlated in many observational studies, whereas the causality of this association is uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to determine the association between S-25(OH)D and NAFLD. METHODS Seven and 6 independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide-significance level, respectively, were selected as instrumental variables. Summary-level data for S-25(OH)D were obtained from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium including 79,366 individuals. Summary-level data for NAFLD were available from a genome-wide association meta-analysis (1483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls), and the UK Biobank study (275 cases and 360,919 controls). Summary-level data for 4 liver enzymes were obtained from the UK Biobank. RESULTS There were genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes. Genetically predicted higher levels of S-25(OH)D were consistently associated with a decreased risk of NAFLD in the 3 sources. For a 1-SD increase in genetically predicted S-25(OH)D levels, the combined odds ratio of NAFLD was 0.78 (95% confidence interval [CI], 0.69 to 0.89). Genetically predicted higher levels of S-25(OH)D showed a borderline association with aspartate aminotransferase levels (change -1.17; 95% CI, -1.36 to 0.01). Genetic predisposition to NAFLD was not associated with S-25(OH)D (change 0.13; 95% CI, -1.26 to 0.53). CONCLUSIONS Our findings have clinical implications as they suggest that increased vitamin D levels may play a role in NAFLD prevention in European populations.

Abstract

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.

Abstract

Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.

Abstract

Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187) aimed to determine the levels of zinc intake at which adverse effects are observed in young children. Studies reporting potential adverse effects of zinc intake in children aged 0-3 y were identified (from inception to August 2020) in MEDLINE, Embase, and the Cochrane Library, with no limits on study design. Adverse clinical and physical effects of zinc intake were synthesized narratively, and meta-analyses of biochemical outcomes were conducted. Random effects models were used to generate forest plots to examine the evidence by age category, dose, dose duration, chemical formula of zinc, and zinc compared with placebo. The Joanna Briggs Institute Critical Appraisal Checklist, Cochrane Risk of Bias 2, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline were employed to assess risk of bias and to appraise the certainty of evidence. Fifty-eight studies assessed possible adverse effects of zinc doses ranging from 3 to 70 mg/d. Data from 39 studies contributed to meta-analyses. Zinc supplementation had an adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, hemoglobin, hematocrit, and the odds of anemia in ≥1 of the subgroups investigated. Lactulose:mannitol ratio was improved with zinc supplementation, and no significant effect was observed on C-reactive protein, erythrocyte superoxide dismutase, zinc protoporphyrin, blood cholesterol, and iron deficiency anemia. The certainty of the evidence, as assessed using GRADE, was very low to moderate. Although possible adverse effects of zinc supplementation were observed in some subgroups, it is unclear whether these findings are clinically important. The synthesized data can be used to undertake a dose-response analysis to update current guidelines of ULs of zinc intake for young children.

Abstract

BACKGROUND The aim of this systematic review and meta-analysis was to determine the effect of olive leaf extract (OLE) supplementation on cardiovascular-related variables, including lipid, glycemic, inflammatory, liver and renal-related factors, as well as blood pressure. METHODS PubMed, ISI Web of Science, Scopus, and Cochrane library were searched, up to October 2021, for relevant controlled trials. Mean differences and standard deviations were pooled for all outcomes, using a random-effects model. The methodological quality, as well as quality of evidence were assessed using standard tools. RESULTS Twelve studies (n = 819 participants) were included in our analyses. Overall analyses showed that OLE supplementation significantly decreased triglyceride (TG) levels (WMD = - 9.51 mg/dl, 95% CI - 17.83, - 1.18; P = 0.025; I2 = 68.7%; P-heterogeneity = 0.004), and systolic blood pressure (SBP) (WMD = - 3.86 mmHg, 95% CI - 6.44, - 1.28 mmHg; P = 0.003; I2 = 19.9%; P-heterogeneity = 0.28). Subgroup analyses also revealed a significant improvement in SBP (- 4.81 mmHg) and diastolic blood pressure (- 2.45 mmHg), TG (- 14.42 mg/dl), total cholesterol (TC) (- 9.14 mg/dl), and low-density lipoprotein-C (LDL-C) (- 4.6 mg/dl) measurements, in patients with hypertension. Significant reductions were also observed in TC (- 6.69 mg/dl), TG (- 9.21 mg/dl), and SBP (- 7.05 mmHg) in normal-weight individuals. However, no meaningful changes were seen in glucose hemostasis, liver and kidney, or inflammatory markers. CONCLUSION The present study revealed that supplementation with OLE yielded beneficial effects for blood pressure and lipid profile in adults, especially in patients with hypertension. As the quality of evidence for glucose hemostasis variables, liver, kidney, and inflammatory markers, were low-to-very low, higher quality RCTs may impact the overarching results. This study was registered at PROSPERO with the code CRD42022302395.

Abstract

Numerous clinical trials have examined the beneficial effects of Juglans regia leaf extract (JRLE) in patients with type 2 diabetes mellitus (T2DM); however, the results of these studies are inconsistent. Therefore, we conducted the current systematic review and meta-analysis to evaluate the effect of JRLE on glycemic control and lipid profile in T2DM patients. We searched online databases including PubMed, Scopus, EMBASE, and Web of Science for randomized controlled clinical trials that examined the effect of JRLE on glycemic and lipid indices in T2DM patients. Data were pooled using both fixed and random-effect models and weighted mean difference (WMD) was considered as the overall effect size. Of the total records, 4 eligible studies, with a total sample size of 195 subjects, were included. The meta-analysis revealed that JRLE supplementation significantly reduces fasting blood glucose (WMD, -18.04; 95% confidence interval [CI], -32.88 mg/dL, -3.21 mg/dL; p = 0.017) and significantly increases fasting insulin level (WMD, 1.93; 95% CI, 0.40 U/L, 3.45 U/L; p = 0.014). Although the overall effect of JRLE supplementation on hemoglobin A1c was not significant, a significant reduction was seen in studies with an intervention duration of > 8 weeks (WMD, -0.64; 95% CI, -1.16%, -0.11%; p = 0.018). Moreover, we also found no significant change in lipid parameters. Our findings revealed a beneficial effect of JRLE supplementation on glycemic indices in T2DM patients, but no significant improvement was found for lipid profile parameters.

Abstract

PURPOSE Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT). METHODS We conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane's Q test and I2 statistic, respectively. RESULTS Six retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44-1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9-1.68). CONCLUSION We found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.

Abstract

OBJECTIVE This study aimed at comparing sperm parameters and hormonal levels with L-carnitine vs. CoQ10 and Vitamin E therapy for patients with asthenozoospermia and teratozoospermia. PATIENTS AND METHODS A single-blind randomized controlled trial (RCT) was designed wherein patients were randomly allocated to receive L-carnitine complex nutrient treatment (study group - 15 g/bag, orally one bag at a time, twice a day) or CoQ10 (control group - 10 mg tablet orally, thrice daily) with Vitamin E (100 mg tablet orally, thrice daily) for three months. Outcome variables were sperm concentration, progressive sperm motility, normal sperm morphology, testosterone, follicle-stimulating hormone, luteinizing hormone (LH), and prolactin levels. RESULTS 143 patients were analyzed (73 in study and 70 in control group). Compared to baseline, sperm count, progressive sperm motility, and morphology improved significantly in the study group, but only progressive sperm motility and morphology improved in the control group. Serum testosterone levels significantly increased both in the study and control groups, while LH increased only in the study but not in the control group. All sperm parameters showed significantly better improvement in the study group, compared to the control group. Testosterone and LH levels were also higher in the study group compared to the control group. CONCLUSIONS L-carnitine significantly improves sperm motility, morphology, and concentration, while also improving testosterone and LH levels. Use of CoQ10 and Vitamin E resulted in improvement of only sperm motility, morphology, and testosterone levels. L-carnitine was found to be superior to the combination of CoQ10 and Vitamin E in improving sperm parameters. Further studies examining clinical pregnancy rates are needed to strengthen the evidence.

Abstract

Background and aims: Dietary regimens are crucial in the management of non-alcoholic fatty liver disease (NAFLD). The effects of intermittent fasting (IF) have gained attention in this regard, but further research is warranted. Thus, we aimed to ascertain the overall effects of the 5:2 IF diet (5 days a week of normal food intake and 2 consecutive fasting days) in patients with NAFLD compared to a control group (usual diet). Methods and results: A 12-week randomized controlled trial was performed to evaluate the effects of the 5:2 IF diet on anthropometric indices, body composition, liver indices, serum lipids, glucose metabolism, and inflammatory markers in patients with NAFLD. The IF group (n = 21) decreased body weight (86.65 ± 12.57-82.94 ± 11.60 kg), body mass index (30.42 ± 2.27-29.13 ± 1.95 kg/m2), waist circumference (103.52 ± 6.42-100.52 ± 5.64 cm), fat mass (26.64 ± 5.43-23.85 ± 5.85 kg), fibrosis (6.97 ± 1.94-5.58 ± 1.07 kPa), steatosis scores/CAP (313.09 ± 25.45-289.95 ± 22.36 dB/m), alanine aminotransferase (41.42 ± 20.98-28.38 ± 15.21 U/L), aspartate aminotransferase (34.19 ± 10.88-25.95 ± 7.26 U/L), triglycerides (171.23 ± 39.88-128.04 ± 34.88 mg/dl), high-sensitivity C-reactive protein (2.95 ± 0.62 -2.40 ± 0.64 mg/L), and cytokeratin-18 (1.32 ± 0.06-1.19 ± 0.05 ng/ml) values compared to the baseline and the end of the control group (n = 23)-p ≤ 0.05 were considered as significant. However, the intervention did not change the levels of high-density lipoprotein cholesterol, total cholesterol, low-density lipoprotein cholesterol, fasting blood sugar, insulin, HOMA-IR, and total antioxidant capacity. Conclusion: Adhering to the 5:2 IF diet can reduce weight loss and related parameters (fat mass and anthropometric indicators of obesity), as well as hepatic steatosis, liver enzymes, triglycerides, and inflammatory biomarkers in patients with NAFLD.

Abstract

BACKGROUND Circulating methionine components have been reported to be associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI), although outcomes are not always consistent. MATERIALS AND METHODS Database searching was conducted using PubMed, Embase, Cochrane Library, and Web of Science from inception to 26 December 2021. In this study, two reviewers independently identified eligible articles and extracted the data. We used Joanna Briggs Institute (JBI) Critical Appraisal tools to assess the overall quality of the included studies. STATA software was employed to perform meta-analysis evaluating the standardized mean difference (SMD) with its 95% confidence intervals (CIs) using random-effects models. Evidence quality was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RESULTS Totally, 30 observational studies were eligible for inclusion. Compared with cognitively normal controls, patients with AD had increased homocysteine (Hcy) levels in the blood [standardized mean difference (SMD) = 0.59, 95% confidence interval [CI]: 0.36-0.82, P = 0.000], plasma (SMD = 0.39, 95% CI: 0.23-0.55, P = 0.000), and serum (SMD = 1.56, 95% CI: 0.59-2.95, P = 0.002). Patients with MCI were not significantly different from controls (SMD = 0.26, 95% CI: -0.07-0.58, P = 0.127). Patients with AD or MCI did not significantly differ from controls of blood vitamin B12 levels, AD (SMD = -0.05, 95% CI: -0.19-0.08, P = 0.440), or MCI (SMD = 0.01, 95% CI: -0.16-0.17, P = 0.94). Some cohort studies have suggested that higher Hcy, methionine, and S-adenosylmethionine levels may accelerate cognitive decline in patients with MCI or AD, and vitamin B12 deficiency is a risk factor for the disease; however, the results of other studies were inconsistent. According to the GRADE system, all these outcomes scored very low to low quality, and no high-quality evidence was found. CONCLUSION Only Hcy levels in the plasma and serum were found to be inversely related to the risk of AD. However, due to the low quality of supporting these results, high-quality studies are needed to verify these findings. SYSTEMATIC REVIEW REGISTRATION http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022308961.