Dose-response Meta-analysis Research Articles

Effect of resting heart rate on the risk of metabolic syndrome in adults: a dose–response meta-analysis

Effect of resting heart rate on the risk of metabolic syndrome in adults: a dose–response meta-analysis

Effect of Phytosterols on Serum Levels of C-Reactive Protein: A Time- and Dose-Response Meta-analysis of Randomized Controlled Trial.

Phytosterols are recognized for their cholesterol-reducing effects and are commonly used as dietary supplements or added to foods due to their potential cardiovascular benefits. However, evidence regarding the impact of phytosterol supplementation on inflammatory markers remains inconclusive. This systematic review and meta-analysis aim to evaluate the effect of phytosterols in reducing levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP). A systematic literature search of the primary databases was conducted up to May 2024 to identify eligible studies. The measurement of effect sizes was determined using WMD (weighted mean difference) and 95% CI. For the meta-analysis, 14 publications (19 study arms) for hs-CRP and 10 publications (16 study arms) for CRP were included. The pooled analysis showed that the administration of phytosterol did not significantly reduce CRP compared to control with WMD= -0.04mg/l (95% CI: -0.28 to 0.20, P = 0.74). However, phytosterol supplementation significantly decreased the hs-CRP level compared to the control group with WMD of -0.25mg/l (95% CI: -0.42 to -0.07, P = 0.006). The WMD for hs-CRP reduction was - 0.36mg/l (95% CI: -0.53 to -0.18, P < 0.001) for supplementation with a phytosterol dose ≥ 2000mg/day compared to the control group. Phytosterol supplementation may be effective in reducing hs-CRP levels.

Cadmium exposure and hypertension: a systematic review and a dose-response meta-analysis

Abstract Background Since the shape of the relation between Cd exposure and risk of HTN has not been previously investigated, we aimed to perform a systematic review with dose-response meta-analysis in epidemiological studies. Methods After registration of the review in PROSPERO database (ID: CRD42022382030), we searched for eligible articles in online databases using Mesh-terms/keywords related to Cd, HTN, and BP. Eligible criteria were: adult population, assessment of exposure through Cd concentrations in blood or urine, risk estimates for HTN, observational design. Whenever possible, we computed summary odds ratio (OR) with 95% confidence interval (CI) and performed a dose-response meta-analysis on overall studies and subgroups. Results We eventually included 8 articles for both the qualitative and quantitative analysis published between 2006-2023 almost of cross-sectional design, 7 and 4 assessing blood and urine Cd concentrations, respectively. Comparing the highest versus lowest exposure, we found increased risk of HTN for both blood (OR = 1.12, 95% CI 0.92-1.36) and urine assessment (OR = 1.09, 95% CI 0.94-1.28). Dose-response meta-analysis showed an almost linear increased risk for blood Cd concentrations until 1.5 µg/L above with it plateaued. In contrast when using urine concentrations for exposure assessment, risk started to increase above 0.5 µg/g creatinine. Conclusions Our results confirm the recent findings of non-linear relation between Cd exposure and risk of both CVD and diabetes and the subsequent need to lower Cd exposure on a public health perspective. Key messages • Cadmium exposure showed positive association with risk of hypertension. • Public health efforts should be implemented to lowed cadmium exposure to decrease CVD risk.

Picking a bone with fluoride – dose-response meta-analysis on exposure to fluoride and bone density

Abstract There are still uncertainties around the effects, beneficial and adverse, of water fluoride exposure on bone density and strength. We selected bone mineral density (BMD) for investigation as it is recognized as the major non-invasive indicator of bone strength, representing its clinical assessment standard. The aim of this systematic review and meta-analysis was to characterize for the first time the relation between fluoride exposure and BMD through a dose-response approach, using a one-stage dose-response meta-analysis based on a cubic spline random-effects model. Out of 1201 potentially relevant literature records retrieved, after removing duplicates, title/abstract screening, and full-text evaluation, 16 studies were eligible for this review, 12 of which were also suitable for the dose-response meta-analysis. We observed an almost linear association between fluoride and BMD, yielding a mean difference of 2.60 (95% CI 0.17 to 0.40) at 4 mg/L of fluoride exposure. This pattern was also confirmed for hip BMD (MD = 2.83; 95% CI 0.11 to 0.40 at 4 mg/L). However, sex-specific analyses showed different patterns of association. In males, the relation between fluoride exposure and BMD was almost linear until 0.75 mg/L (MD = 0.24; 95% CI -0.22to 0.37), after which it plateaued. Females showed a slight increased BMD at 1 mg/L (MD = 0.05; 95% CI -0.02 to 0.16) but decreasing values above 2.5 mg/L (MD=-0.22; 95% CI -2.72 to 2.38 at 4 mg/L), with an indication of an inverted U-shaped association. This pattern was clearer when we restricted our analysis to hip BMD (MD=-0.56; 95% CI -2.98 to 1.85 at 4 mg/L). Sensitivity analyses examining both bone-specific BMD and conducting risk of bias assessments are currently underway. Moreover, imprecision of the estimates, especially in stratified analyses, and potential for residual confounding, underscore the need for further prospective studies, to more adequately assess the relation between fluoride exposure and bone density and strength. Key messages • At fluoride exposure below 1 mg/L, we observed a linear correlation between fluoride exposure and increase bone density in the overall pooled dose-response analysis of eligible studies. • Sex-specific patterns: males show positive response until certain exposure threshold; while females demonstrate an increase only at low doses of exposure and a downward trend at higher exposures.

Double-sided effect of selenium on blood lipids: A dose-response meta-analysis

Abstract Background Selenium, a trace element with both nutritional and toxicological properties, has been suggested to increase cardiovascular risk, particularly concerning diabetes and blood pressure levels. However, the impact of selenium exposure on the risk of dyslipidemia remains uncertain. This meta-analysis explored the shape of the relation between selenium exposure and its effects on lipid profiles in the most relevant experimental human studies, randomized controlled trials (RCTs). Materials and methods The review was registered in PROSPERO (ID: CRD42022380432). Through a bibliographic search conducted on PubMed, Web of Science, Embase, and the Cochrane Library, we identified RCTs investigating the impact of selenium supplementation on lipid profile. We then compared the results between intervention and control groups and, whenever possible, evaluated the non-linear relationship using a dose-response approach. Results We could include 26 RCTs involving different populations, i.e. healthy individuals, pregnant women, and subjects with health conditions such as cardiovascular diseases and Alzheimer’s dementia. Study endpoints were levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. Our dose-response analysis indicated that selenium supplementation exceeding 200 µg/day adversely affected total cholesterol, HDL, and triglyceride levels. Hence, a threshold for such a detrimental effect of selenium was observed on total and HDL cholesterol and triglycerides, while opposite and inconsistent results emerged for levels below 200 µg/day and for LDL-cholesterol. Blood selenium levels at the end of the studies were positively associated with adverse effects on all endpoints. Conclusions This first dose-response meta-analysis of the effects of selenium on blood lipids highlights the potentially adverse effects of this trace element, in the amount and the chemical forms used in the trials. Key messages • Elevated selenium levels correlated with adverse effects on lipid profile. • Selenium doses exceeding 200 µg/day showed adverse effects on total and HDL cholesterol and triglycerides levels.

Association between arterial oxygen tension with clinical outcomes in patients undergoing VA-ECMO support: a systematic review and dose-response meta-analysis

Abstract Background Arterial hyperoxia has been associated with a worse prognosis in critically ill patients. However, studies conducted in patients undergoing Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) used inconsistent and arbitrary thresholds for defining hyperoxia, which impeded the determination of the optimal target for arterial oxygen tension (PaO2) in this population. Purpose To investigate and visualise the dose-response relationship between post-ECMO level of PaO2 with early mortality (in-hospital and 1-month) and poor neurological outcomes in adult patients undergoing VA-ECMO support, including Extracorporeal Cardiopulmonary Resuscitation (ECPR). Methods A systematic search was conducted through Pubmed and Embase to include studies that stratified patients based on PaO2 levels and evaluated relevant outcomes. We utilised either adjusted Odds Ratio (OR) with 95% Confidence Interval (CI) when available, or unadjusted OR against the lowest exposure category. The median, mean, or midpoint value of PaO2 was assigned as the corresponding dose. A random-effects one-stage dose-response meta-analysis was performed to assess linear association for every 10 mmHg increase in PaO2, while potential non-linear relationship was explored with restricted cubic splines at 3 knots (10th, 50th, and 90th percentile). Non-linearity was assessed by using Wald test with p value &amp;lt;0.05 considered significant. Statistical analyses were performed using STATA 17.0. Results Fourteen eligible records were identified (cardiogenic shock/CS = 5 records; ECPR = 8 records; both = 1 record). Only four studies classified a separate category for hypoxemic patients (&amp;lt;60 mmHg). PaO2 levels were measured within 24-72 hours of VA-ECMO initiation, except in one study. PaO2 level was not associated with early mortality (9 studies; OR 1.021 [95% CI 0.988–1.055]; p for non-linearity = 0.893), but found to have a linear association with composite poor neurological outcomes (6 studies; OR 1.016 [1.009–1.024]; p for non-linearity = 0.346). Subgroup analysis of CS patients revealed a linear association between PaO2 &amp;gt;100 mmHg and early mortality (4 studies; OR 1.025 [95%CI 1.018–1.032]; p for non-linearity = 0.255). For ECPR patients, a J-shaped relationship was observed between PaO2 and early mortality (5 studies; p for non-linearity = 0.004), with the lowest odds being at PaO2 level of 110-210 mmHg, while PaO2 level &amp;gt;110 mmHg showed a linear trend towards higher odds of poor neurological function (4 studies; OR 1.091 [95%CI 0.938–1.269]; p for non-linearity = 0.257). Conclusion Pooled data from observational studies suggest that PaO2 &amp;gt;100 mmHg should be avoided in CS patients on VA-ECMO support, given its linear association with mortality, but it cannot be extrapolated to hypoxemic patients. In ECPR patients, PaO2 level around 110-210 mmHg conferred the best clinical outcomes. However, these findings should be confirmed through randomised controlled trials.

Red blood cell distribution width to albumin ratio as novel prognostic biomarker in cardiovascular disease

Abstract Background The red blood cell distribution width-to-albumin ratio (RAR) is a novel, cost-effective, and accessible biomarker for inflammation. Although numerous studies have investigated the relationship between RAR values and mortality in cardiovascular diseases (CVD), the generalizability and robustness of these individual studies' results remain uncertain, underscoring the necessity for a meta-analysis. Purpose To explore the pooled association between RAR and all-cause mortality in several CVDs. Methods A systematic search for eligible studies was conducted across scientific databases, including Scopus, Web of Science, PubMed, and ProQuest, up to February 1, 2024. Mortality hazard ratios (HRs) for the highest versus lowest RAR categories were pooled using the Generic Inverse Variance method. A dose-response meta-analysis was performed using generalized least-squares regression to estimate trends of HRs across dose categories. Publication bias was assessed by inspecting funnel plots and performing Egger's test. Subgroup analyses were based on the underlying CVDs. Statistical analyses were executed in RStudio software, with the significance threshold set at p &amp;lt; 0.05. Results This systematic review and meta-analysis reviewed 16 high-quality studies published between 2021 and 2024 with 30,933 participants. The underlying diseases in the included studies were Acute Myocardial Infarction (AMI), Heart Failure (HF), Atrial Fibrillation (AF), aortic valvular disease, stroke and pulmonary embolism. The lowest quartile range for RAR was 0.80–1.20 ml/g, while the highest quartile ranged from 6.09 to 15.45 ml/g. Pooled results with a random-effect model showed that patients with higher RAR had significantly increased risk of all-cause mortality (HR 1.88, 95%CI 1.59–2.23, p&amp;lt;0.0001, I² = 91%). Non-linearity was observed in the dose-response relationship; thus, it was primarily illustrated using the restricted cubic spline model, with the linear model provided for comparison. A 1 ml/g increase in RAR corresponded to a 27% rise in the predicted HR for all-cause mortality (HR 1.27, 95%CI 1.16–1.39; p &amp;lt; 0.0001). Subgroup analyses based on the primary CVD diagnoses in the included studies confirmed a significant association between RAR values and all-cause mortality across all subgroups (AMI: HR 2.43, 95%CI 1.52–3.87, I² = 45%; HF: HR 1.78, 95%CI 1.13–2.81, I² = 94%; Stroke: HR 1.58, 95%CI 0.94–2.67, I² = 90%; Other CVD: HR 1.97, 95%CI 1.34–2.89, I² = 57%; p for interaction 0.24). Conclusion This is the first meta-analysis demonstrating the positive dose-response association between RAR values and all-cause mortality in CVD. Thus, RAR may be considered as a simple and practical prognostic biomarker in CVD.Forest plot based on CVD diagnosisDose-response RAR value to HR

Fluoride exposure and risk of fractures: a systematic review and dose-response meta-analysis

Abstract Introduction Fluoride (F) is a widespread natural element, whose exposure occurs mostly through drinking water, fluoridated foods and use of toothpastes. At high levels, it may adversely affect human health by altering thyroid and cognitive function in children, and inducing dental and skeletal fluorosis. Since bone health significantly impacts quality of life, we performed a systematic review and meta-analysis to evaluate the effect of F exposure on risk of bone fractures. Methods We conducted a literature search in online databases and selected studies that were carried out in humans and reported risk estimates with 95% confidence intervals for bone fractures according to F exposure. We eventually performed a meta-analysis using a random effects model, comparing the highest versus the lowest exposure, and one-stage dose-response model, to explore the shape of the association. Results Of the 1052 potentially eligible articles, 28 were included in the quantitative analyses. Most studies were conducted in adults (n = 26) and in Western countries (North America=16, Europe=11) and assessed fluoride exposure in drinking water, urine, serum, toenail or diet. The preliminary dose-response curve showed a positive non-linear relation between F exposure through drinking water and bone fracture risk, regardless of site, starting at 1.5 mg/L. Sex-stratified analyses, based on a lower number of studies, showed similar trends, with an indication of higher susceptibility in males compared with females. Conclusions Overall, risk of bone fractures appears to non-linearly increase along with exposure to fluoride in drinking water, regardless of bone site and sex, at levels of exposure above the WHO standard and similar to those that have associated to altered thyroid and cognitive function. Under a public health perspective, fluoride in drinking water should be kept below 1.5 mg/L to prevent bone fractures. Key messages • Our analysis revealed a positive non-linear association between fluoride in drinking water and bone fracture risk. • Public Health actions should be oriented in keeping fluoride in drinking water below 1.5 mg/L to prevent bone fractures.

Ultra-processed food intake and type 2 diabetes: A dose-response meta-analyses of prospective studies

Abstract Studies suggested a positive association between ultra-processed food (UPF) intake and risk of type 2 diabetes (T2DM). However, the magnitude of association varies across studies due to differences in population characteristics and methodological issues. It is also unclear about the exact shape of the association and whether the association is independent of diet quality and adiposity. We conducted a dose-response meta-analysis of prospective studies to summarize the association between UPF intake and T2DM risk. PubMed/MEDLINE, Web of Science, and Embase were searched through Jan. 2024 to identify relevant studies. Using random-effects models, summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated for each of the following unit increment in UPF intake: 10% (of total g/d), 100-g/d, and 1-serving/d. A non-linear dose-response meta-analysis was conducted using restricted cubic spline analysis. After screening 569 publications, 12 prospective cohort studies were included in this study. The summary RRs associated with every 10%, 100-g, and 1-serving increment in UPF intake were 1.13 (95% CI = 1.10-1.16), 1.05 (95% CI = 1.03-1.06), and 1.04 (95% CI = 1.03-1.05), respectively. The positive associations remained statistically significant after additional adjustment for diet quality, BMI, and total energy intake. The dose-response curve for g/d of UPF intake suggested evidence of nonlinearity (p-nonlinearity=0.0005), showing a steeper increase in risk at UPF intake &amp;gt;300 g/d. However, evidence for non-linearity was not observed with % and serving/d of UPF intake. The association did not significantly vary by method and timing of UPF assessment. Higher summary RRs were observed among studies from Europe and North America compared with those from other countries (p-heterogeneity=0.048). Our data suggest that higher UPF intake may increase T2DM risk, independent of diet quality and adiposity. Key messages • Higher intake of ultra-processed food is positively associated with the risk of type 2 diabetes. • Public health strategies should encourage healthier dietary choices by emphasizing reduction of UPF intake in dietary guidelines and implementing regulations on manufacturing and labeling of UPF.

Higher dietary inflammatory index linked to increased risk of hypertension: a systematic review and dose-response meta-analysis.

The relationship between dietary inflammation index (DII) and the risk of hypertension is inconsistent across published epidemiological studies. This meta-analysis aimed to investigate the dose-response relationship between DII score and the risk of hypertension. A systematic search for relevant studies was conducted in PubMed, Web of Science, and Embase databases until January 9, 2024. After data extraction, the summarized relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using the Der Simonian and Laird random effect model, and dose-response analyses were performed using restricted cubic splines. A total of six studies with 120,294 participants and 36,725 cases of hypertension were included. The pooled relative risk (RR) for hypertension risk was 1.15 (95% CI: 1.06, 1.26) for the highest DII score compared with the lowest, and 1.10 (95% CI: 1.03, 1.18) for higher DII score compared with the lower. The dose-response meta-analysis further demonstrated a positive association between elevated DII scores and hypertension risk. For each one-unit increase in the DII score, the incidence of hypertension increased by 4% (RR = 1.04, 95% CI: 1.00, 1.07). Pro-inflammation dietary increases the risk of hypertension. Therefore, reducing pro-inflammatory components in the diet may be beneficial for the prevention and control of hypertension.

Mediterranean Diet and Risk of Hip Fracture: A Systematic Review and Dose-Response Meta-Analysis.

Hip fractures are a major public health concern. Understanding their epidemiologic and biological links with diet and cardiovascular risk may have important implications for prevention. To assess the dose-response association of Mediterranean diet (MD) adherence with the risk of hip fracture. A systematic search was conducted in the PubMed, Scopus, and Web of Science databases for prospective studies. Search terms were "Mediterranean Diet" and "Fracture." Data were extracted from 8 studies, encompassing 15 cohorts that included 503 174 individuals. Methodological quality was assessed using the Risk of Bias in Nonrandomized Studies of Interventions. The "meta" and "dosresmeta" packages were used in R Studio Software. The results demonstrated that high and moderate MD adherence were associated with a reduced risk of hip fracture (relative risk [RR] = 0.71 [95% CI, 0.55-0.91]; and RR = 0.78[(95% CI, 0.65-0.93], respectively). The effect of the association was similar in men and women. The dose-response pattern of the association was linear: each point increase in MD adherence was associated with a 5.25% reduction in hip fracture risk. Adherence to MD is associated with a reduction in hip fracture risk, following a linear dose-response pattern. This supports the promotion of this dietary pattern for improving bone health. PROSPERO registration no. CRD42023402284.

The effects of conjugated linoleic acid supplementation on cardiovascular risk factors in patients at risk of cardiovascular disease: A GRADE-assessed systematic review and dose-response meta-analysis.

The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on cardiovascular risk factors in patients at risk of CVD. Relevant studies were obtained by searching the PubMed, SCOPUS and Web of Science databases (from inception to January 2023). Weighted mean differences (WMD) and 95% CI were pooled using a random-effects model. Heterogeneity, sensitivity analysis and publication bias were reported using standard methods. A pooled analysis of 14 randomised controlled trials (RCT) with 17 effect sizes revealed that CLA supplementation led to significant reductions in body weight (WMD: -0·72 kg, 95% CI: -1·11, -0·33, P < 0·001), BMI (WMD: -0·22 kg/m2, 95% CI: -0·44, -0·00, P = 0·037) and body fat percentage (BFP) (WMD: -1·32 %, 95% CI: -2·24, -0·40, P = 0·005). However, there was no effect on lipid profile and blood pressure in comparison with the control group. In conclusion, CLA supplementation may yield a small but significant beneficial effect on anthropometric indices in patients at risk of CVD. Moreover, CLA seems not to have adverse effects on lipid profiles and blood pressure in patients at risk of CVD. It should be noted that the favourable effects of CLA supplementation on anthropometric variables were small and may not reach clinical importance.

Effects of selected dietary supplements on migraine prophylaxis: A systematic review and dose-response meta-analysis of randomized controlled trials.

The existing evidence on the effect of dietary supplements for preventing migraines has generated conflicting results. We assessed alterations in migraine clinical features corresponding to the intake of dietary supplements. Our main outcomes included the frequency (number of attacks), duration (in hours), the severity (intensity) and the monthly migraine days. Using a dose-response meta-analysis, we estimated the dose-dependent impact. The certainty of evidence was evaluated using the GRADE tool. Finally, twenty-two trials were included in the systematic review and meta-analysis. Magnesium supplementation reduced migraine attacks (mean difference (MD) = -2.51), severity (MD = -0.88), and the monthly migraine days (MD = -1.66) compared with the control group. CoQ10 decreased the frequency (MD = -1.73), severity (MD = -1.35), and duration of migraine (MD = -1.72). Riboflavin decreased attack frequency (MD = -1.34). Alpha-lipoic acid decreased attack frequency (MD = -1.24) and severity (MD = -0.38). Probiotics decreased the frequency (MD = -1.16), severity (MD = -1.07) and the monthly migraine days (MD = -3.02). Vitamin D reduced migraine frequency (MD = -1.69) and the monthly migraine days (MD = -2.41). In adults, compared with placebo, these supplements did not significantly affect other outcomes, and omega-3 supplementation did not yield a statistically significant reduction in any of these outcomes. The use of certain dietary supplements has resulted in a significant decrease in migraine prophylaxis. Further clinical trials of high quality appear to be beneficial.

A dose-response meta-analysis of the relationship between number of pregnancies and risk of gynecological cancers.

Despite several investigations, the association between the number of pregnancies and gynecological cancers remains inconclusive. To address this issue, we conducted a dose-response meta-analysis of observational studies. We searched PubMed, Web of Science, and Scopus databases up to Jun 8, 2023, to identify observational studies that examined the association between the number of pregnancies and gynecologic cancers. To assess the heterogeneity across studies, we used the χ2 test and I2 statistics. We also explored the possibility of publication bias using Begg's and Egger's tests. The overall effect sizes were reported as odds ratios (ORs) with a 95% confidence interval (CI) using a random-effects model. Out of the 87,255 studies initially identified, a total of 101 studies involving 8,230,754 participants were included in the final meta-analysis. Our analysis revealed a positive trend between the number of pregnancies and cervical cancer; however, this association was not found to be statistically significant except for fifth pregnancy. Conversely, our findings showed a significant decreasing trend between the number of pregnancies and the risk of endometrial and ovarian cancers. There was insufficient evidence to establish a relationship between the number of pregnancies and the risk of vaginal, vulvar, and fallopian tube cancers. Our study found a positive trend between the number of pregnancies and cervical cancer and a significant decreasing trend between the number of pregnancies and endometrial and ovarian cancers. These findings may have implications for counseling women about their reproductive health and the potential risks and benefits of pregnancy.

Serum glycosylated hemoglobin and prostate cancer risk: Results from a systematic review and dose-response meta-analysis

ObjectivesTo evaluate the correlation between serum glycosylated hemoglobin (HbA1c) levels and the risk of prostate cancer incidence and mortality, providing a comprehensive analysis to inform preventative and clinical strategies. MethodsA systematic review and meta-analysis was conducted including studies based on their documentation of prostate cancer incidence and mortality related to HbA1c levels, with a minimum of 3 risk-related data levels. The Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used for quality assessment and risk of bias evaluation. We employed generalized least squares (GLS) to assess the linear trend within individual studies and combined these estimates using a random effects model. Additionally, we utilized a restricted cubic spline (RCS) model to investigate potential nonlinear trends. ResultsA total of 13 studies were included in the quantitative synthesis ultimately. The quantitative analysis did not find a significant association between HbA1c levels and prostate cancer incidence. However, a significant positive correlation was revealed between HbA1c levels and both cancer-specific mortality (CSM) and all-cause mortality (ACM), with a 1% increase in HbA1c levels associated with a 26% increase in CSM and a 21% increase in ACM. ConclusionThe HbA1c level is significantly associated with increased prostate cancer mortality. The results highlight the importance of considering blood sugar control in the comprehensive risk assessment for prostate cancer, particularly among the nondiabetic population.

Dietary calcium intake in relation to metabolic syndrome in adults: A systematic review and dose-response meta-analysis of epidemiological studies with GRADE assessment.

Numerous studies have examined the relationship of calcium intake and metabolic syndrome (MetS) in adults in previous decades; but the results were inconsistent across different societies. This systematic review and dose-response meta-analysis assessed the relation between calcium consumption and MetS in adults. We did a systematic search of all articles published up to July 2023 in Scopus, PubMed/Medline, ISI Web of Science electronic databases, and Google Scholar. Observational studies investigated the association between dietary calcium (Ca) intake and MetS in adults were eligible to be included. For computing the estimates, a random effects model was applied. Combining 24 effect size from 17 investigations (15 cross-sectional and two cohort studies) with 74,720 participants and 18,200 cases showed that highest versus lowest level of dietary Ca intake was related to 23% significant decreased odds of MetS (OR = 0.77; 95% CI: 0.66, 0.89). Linear dose-response analysis of estimates from 12 investigations showed that each 100 mg/day increment in dietary Ca intake was associated with 3% marginally significant decreased odds in MetS (OR = 0.97; 95%CI: 0.93, 1.01). In nonlinear dose-response analysis of 12 studies with 67,896 participants, a significant association between dietary calcium intake and MetS was found (Pnonlinearity <0.001); such that 500 mg/day dietary calcium intake was related to maximum decrease in odds of MetS. According to this meta-analysis, the likelihood of MetS was significantly lower in adults with higher level of dietary calcium intake. Further large-scale prospective cohort investigations are needed to obtain stronger and more accurate results.

Unveiling the Effects of Cruciferous Vegetable Intake on Different Cancers: A Systematic Review and Dose-Response Meta-analysis.

Epidemiological studies indicated that cruciferous vegetable intake is associated with positive health outcomes. However, the role of cruciferous vegetables may have differential impacts on various cancers. This meta-analysis aims to review recent epidemiological studies on the link between cruciferous vegetables and various cancers. It seeks to identify the optimal intake dose and timing of cruciferous vegetables influencing their association with cancer risk. Studies on cruciferous vegetables and cancer were searched in PubMed, NCBI, Web of Science, and Elsevier databases from 1978 to June 2023. Extracted data from 226 relevant case-control and cohort studies were expressed by standardized mean difference and 95% CI, followed by the subgroup analysis to eliminate heterogeneity. Intake of cruciferous vegetables can prevent cancers, with an odds ratio of 0.77 and risk ratio (RR) of 0.96. The intake levels of cruciferous vegetables associated with the risk of colorectal cancer, lung cancer, upper gastrointestinal cancer, gynecological cancer (ovarian cancer and endometrial cancer), bladder cancer, renal cancer, and prostate cancer were found to be 5.41 servings/week, 5.41 servings/week, 5.5 servings/week, 7.4 servings/week, 5.5 servings/week, 4.85 servings/week, and 3 servings/week, respectively. In a cohort followed for 2 to 15 years, limited consumption of cruciferous vegetables was correlated with a higher cancer RR. In the Asian population, cruciferous vegetables had a significant relationship with lung cancer, head and neck squamous cell carcinoma, and esophageal cancer. Conversely, cruciferous vegetables are predominantly associated with colorectal, renal, gynecological, and prostate cancer in the American population. This study highlights the complex link between cruciferous vegetables and cancer, influenced by factors such as cancer type, region, intake level, and follow-up duration.

Effects of probiotics supplementation on glycemic profile in adults with type 2 diabetes mellitus: A grade-assessed systematic review and dose–response meta-analysis of randomized controlled trials

BackgroundDisturbed glycemia and the resulting type 2 diabetes (T2D) are significant health concerns. Various approaches have been examined to improve glycemic control in patients with T2D. Modification of gut microbiome via administering probiotics has been extensively studied. The present study aims to sum up the existing literature which investigated the effect of probiotics on glycemic indices in individuals with T2D in the format of randomized controlled trials (RCTs). MethodsOnline medical databases (PubMed, Scopus, and Web of Science) were searched from inception to January 2024. Eligible studies were included using pre-defined inclusion and exclusion criteria. Outcome variables included fasting blood sugar (FBS), insulin, hemoglobin A1c (HbA1c), and homeostatic model of insulin resistance (HOMA-IR). Weighted mean differences (WMDs) were estimated. Subgroup and dose-response analyses were conducted. P-values <0.05 were considered as statistically significant. ResultsOut of 5,636 records retrieved by the initial search, thirty-two RCTs were included in the final analyses. Supplementation with probiotics was observed to significantly improve indices of glycemic control; including FBS (WMD: -13.27 mg/dl; 95% CI: -18.31, -8.22), HbA1c (WMD: -0.44 %; 95% CI: -0.59, -0.28), insulin (WMD: -1.33 μIU/ml; 95% CI: -2.57, -0.08), and HOMA-IR (WMD: -0.95; 95% CI: -1.71, -0.18). Dose-response analysis revealed that increased duration of intervention results in a larger reduction only in FBS. ConclusionSupplementation with probiotics seems to improve indices of glycemic control. Nonetheless, taken into account the notable heterogeneity (with regard to dosage, duration, and the species/strains used) between the included studies and low quality of evidence, caution must be considered, especially when long-term clinical implications are intended.

Role of physical activity and sedentary behavior in venous thromboembolism: a systematic review and dose-response meta-analysis

Increasing studies have investigated the link between physical activity (PA) and sedentary behavior with venous thromboembolism (VTE) but the existing findings are not consistent and the independent relationship is uncertain. This meta-analysis aimed to comprehensively assess the shape of dose-response relationship between PA and sedentary behavior with VTE and further explore whether the relationship is independent after mutual adjustment. We systematically searched PubMed, Embase and Web of Science from inception to August 1, 2024. PA exposures were converted into MET-h/wk. Categorical meta-analyses and a cubic spline model were performed to evaluate the association between PA, sedentary behavior and VTE. Twenty-five articles including 31 studies were included. A curvilinear dose-response relationship between PA and VTE was observed, with steeper gradients even at lower PA levels. After adjustment for sedentary behavior, higher level of PA was independently associated with a reduced VTE risk (OR = 0.83, 95%CI:0.77–0.89). Based on population attributable fraction analyses, 2.37% (95%CI: 1.90-2.85%) of incident VTE could have been prevented if all adults had achieved half the PA minimum recommended level. A linear dose-response relationship between sedentary behavior and VTE risk was found, and there was a 2% higher risk of VTE (OR = 1.02, 95%CI: 1.00-1.03) for 1 h increment of sedentary behavior per day. After adjustment for PA, sedentary behavior was independently associated with an increased VTE risk (OR = 1.19, 95CI%:1.01–1.39). Our analyses demonstrated PA and sedentary time were indeed independently associated with the risk of VTE after mutually adjusting for sedentary time or PA, highlighting a unique perspective on their individual contributions. Further studies assessing the effects of different combinations of PA and sedentary time for assessing joint effects on VTE are needed.

Folate intake and the risk of endometrial cancer: A dose-response meta-analysis.

The relationship between folate intake and risk of endometrial cancer (EC) is debatable. The goal of this study was to examine the relationship between folate consumption and EC and then conduct a dose-response analysis in accordance with this. Up until February 1, 2024, we conducted a thorough search using PubMed, EMBASE, the Cochrane Library, and Web of Science. Stata 14 software was used to analyze the findings of the article. The study protocol was registered in PROSPERO (CRD42024505943), and the meta-analysis was conducted in accordance with PRISMA guidelines. Nine case-control studies and 6 cohort studies were included, comprising 379,570 participants and 8660 EC cases. The highest level of folate consumption was associated with a 10% reduction in the occurrence of EC (relative risk [RR] = 0.90, 95% confidence intervals [CIs]: 0.78-1.05, I2 = 63.2%) compared to the lowest level of intake. The association exhibited a statistically significant linear trend (P = .231), with a combined RR of 0.974 (95% CI: 0.968-0.981) for each daily intake of 50 µg folate. Folate intake may reduce the risk of EC.