Effects of boron citrate supplementation on cardiometabolic factors, inflammatory biomarkers and anthropometric measures in obese patients: study protocol for a randomised, double-blind clinical trial.

INTRODUCTION: Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. The efficacy and safety of boron citrate (BC), a novel therapeutic approach, in patients with obesity are not known. The current trial will take place to determine the effects of BC supplementation on cardiometabolic factors, inflammatory biomarkers, anthropometric measures and body composition in obese patients. METHODS AND ANALYSIS: This double-blind, placebo-controlled, randomised clinical trial will involve 60 eligible obese participants aged 18-60 years. Participants will randomly be allocated to receive either BC capsules (containing 10 mg of boron) in the intervention group or placebo capsules (containing 10 mg of maltodextrin) in the placebo group for 12 weeks. Moreover, physical activity and dietary recommendations will be provided for both groups. To assess the dietary intakes of participants, a 3-day food record (2 days of the week and 1 day of the weekend) will be filled. Cardiometabolic factors, inflammatory biomarkers including tumour necrosis factor α, C reactive protein, interleukin-6 and interleukin-10 levels, anthropometric measures and body composition will be assessed at the baseline and end of the intervention. The findings of this study will provide evidence for the effectiveness of BC in the management of obesity. ETHICS AND DISSEMINATION: There are so far no reported adverse effects associated with the use of boron. This trial was approved by the Ethics Committee of Tabriz University of Medical Sciences (approval number: IR.TBZMED.REC.1401.350). Positive as well as negative findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: IRCT20220806055624N1.

Effects of oleoylethanolamide supplementation on the expression of lipid metabolism-related genes and serum NRG4 levels in patients with non-alcoholic fatty liver disease: A randomized controlled trial.

BACKGROUND: This study investigated the effects of oleoylethanolamide (OEA) supplementation on the expression levels of SIRT1, AMPK, PGC-1α, PPAR-γ, CEBP-α and CEBP-ß genes and serum neuregulin 4 (NRG4) levels in patients with non-alcoholic fatty liver diseases (NAFLD). METHODS: Sixty obese patients with NAFLD were equally allocated into either OEA or placebo group for 12 weeks. The mRNA expression levels of genes were determined using the reverse transcription polymerase chain reaction (RT-PCR) technique. Serum NRG4 level was also assessed using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: At the endpoint, mRNA expression levels of SIRT1(p = 0.001), PGC-1α (p = 0.011) and AMPK (p = 0.019) were significantly higher in the OEA group compared to placebo group. However, no significant differences were observed in the expression levels of PPAR-γ, CEBP-α and CEBP-ß between the two groups. Serum NRG4 levels significantly increased in the OEA group compared with the placebo group after controlling for confounders (p = 0.027). In the OEA group, significant relationships were found between percent of changes in the expression levels of the SIRT1, AMPK and PGC-1α as well as serum NRG4 level with percent of changes in some anthropometric measures. Moreover, in the intervention group, percent of changes in high-density lipoprotein cholesterol was positively correlated with percent of changes in the expression levels of the SIRT1 and AMPK. While, percent of changes in triglyceride was inversely correlated with percent of changes in the expression levels of SIRT1. CONCLUSION: OEA could beneficially affect expression levels of some lipid metabolism-related genes and serum NRG4 level. "REGISTERED UNDER IRANIAN REGISTRY OF CLINICAL TRIALS IDENTIFIER NO: IRCT20090609002017N32".

Dietary linoleic acid intake in relation to breast cancer: A case-control study.

Background: The present study aimed to investigate the association between dietary linoleic acid (LA) intake and breast cancer in women. Methods: In this population-based case-control study, we enrolled 350 pathologically confirmed breast cancer cases and 700 controls which were matched with cases in terms of age and socioeconomic status. Dietary intakes were assessed using a 106-item Willett-format semi-quantitative dish-based food frequency questionnaire (DS-FFQ). Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated. Results: A significant inverse association was found between LA intake and odds of breast cancer (OR: 0.41, 95% CI: 0.30-0.56). After adjusting for potential confounders, women in the highest tertile of dietary LA intake were 48% less likely to have breast cancer compared with those in the lowest tertile (OR: 0.52, 95% CI: 0.28-0.95). Such a significant inverse association was also seen among normal-weight women (OR: 0.29, 95% CI: 0.14-0.63), and premenopausal women (OR: 0.15, 95% CI: 0.02-0.95). Conclusion: The findings of current study provide evidence for a protective role of LA against breast cancer particularly among normal-weight and premenopausal women. Prospective studies are needed to confirm this association.

Effects of oleoylethanolamide supplementation on inflammatory biomarkers, oxidative stress and antioxidant parameters of obese patients with NAFLD on a calorie-restricted diet: A randomized controlled trial.

Background: Oxidative stress is considered a major factor in the pathophysiology of non-alcoholic liver disease (NAFLD). A growing body of evidence indicates that oleoylethanolamide (OEA), a bioactive lipid mediator, has anti-inflammatory and antioxidant properties. This trial investigated the effects of OEA administration on inflammatory markers, oxidative stress and antioxidant parameters of patients with NAFLD. Methods: The present randomized controlled trial was conducted on 60 obese patients with NAFLD. The patients were treated with OEA (250 mg/day) or placebo along with a low-calorie diet for 12 weeks. Inflammatory markers and oxidative stress and antioxidant parameters were evaluated pre-and post-intervention. Results: At the end of the study, neither the between-group changes, nor the within-group differences were significant for serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-1 beta (IL-1ß), IL-6, IL-10, and tumor necrosis-factor α (TNF-α). Serum levels of total antioxidant capacity (TAC) and superoxide dismutase (SOD) significantly increased and serum concentrations of malondialdehyde (MDA) and oxidized-low density lipoprotein (ox-LDL) significantly decreased in the OEA group compared to placebo at study endpoint (p = 0.039, 0.018, 0.003 and 0.001, respectively). Although, no significant between-group alterations were found in glutathione peroxidase and catalase. There were significant correlations between percent of changes in serum oxidative stress and antioxidant parameters with percent of changes in some anthropometric indices in the intervention group. Conclusion: OEA supplementation could improve some oxidative stress/antioxidant biomarkers without any significant effect on inflammation in NAFLD patients. Further clinical trials with longer follow-up periods are demanded to verify profitable effects of OEA in these patients. Clinical Trial Registration: www.irct.ir, Iranian Registry of Clinical Trials IRCT20090609002017N32.

Fruit and vegetable intake in relation to gastric cancer risk: A comprehensive and updated systematic review and dose-response meta-analysis of cohort studies.

Background: Since the release of previous meta-analyses, some studies on the associations between fruit and vegetable intake with gastric cancer risk have been published. Therefore, we aimed to update the previous meta-analyses on these associations by including recently published studies as well as considering the main limitations of those meta-analyses. Methods: A comprehensive search was conducted in online databases including PubMed, Scopus, ISI Web of Science, and Google Scholar to detect relevant prospective cohort studies published up to October 2021. Summary relative risks (RRs) were estimated using a random-effects model. Results: Overall, 17 articles containing 18 prospective studies with a total sample size of 1,527,995 participants, aged between 18 and 90 years, were included in the current meta-analysis. During the follow-up periods ranging between 4.5 and 21 years, 8,477 cases of gastric cancer were diagnosed. A higher intake of total fruit [RR: 0.87, 95% confidence interval (CI): 0.80 to 0.94, I 2 = 0%] and total fruit and vegetable (RR: 0.75, 95% CI: 0.61 to 0.93, I 2 = 55.2%) were associated with a lower risk of gastric cancer. For total vegetable intake, a significant inverse association was found among the studies that controlled their analysis for energy intake. Based on the linear dose-response analysis, each 100 g/day increase in total fruit intake (Pooled RR: 0.95, 95% CI: 0.90 to 0.99, I 2 = 49%) and 200 g/day increase in total fruit and vegetable intake (RR: 0.94, 95% CI: 0.88 to 0.99, I 2 = 37.6%) were associated with a 5 and 6% lower risk of gastric cancer, respectively. Conclusion: Fruit and vegetable consumption has a protective association with gastric cancer risk.

The association of dietary acid load (DAL) with estimated skeletal muscle mass and bone mineral content: a cross-sectional study.

BACKGROUND & AIMS: Dietary patterns that promote mild metabolic acidosis may have a negative effect on bone and muscle, and a high dietary acid load (DAL) may be detrimental to skeletal muscle mass and bone mineral content. However, the association between skeletal muscle mass and bone mineral content with dietary acid load has not been consistently reported in previous studies. The objective of the study was to evaluate the association of potential renal net acid load (PRAL) and net endogenous acid production (NEAP) with bone mineral content and skeletal muscle mass in pre-menopause women with overweight or obesity in Iran. METHOD: Three hundred and ninety women with a body mass index (BMI) of 25 were included in this cross-sectional study. We used a validated 147-item semi-quantitative food frequency questionnaire (FFQ) for evaluating the dietary intake. Based on the dietary data, potential renal net acid load (PRAL) and net endogenous acid production (NEAP) were calculated. Muscle mass and bone mineral content were estimated by a bioelectrical impedance analyzer (BIA). RESULTS: After controlling for potential confounders, we discovered a significant linear relationship between PRAL (ß = -0.027, 95%CI = -0.049 to -0.004, P = 0.02) and NEAP (ß = -0.05, 95%CI = -0.097 to -0.003, P = 0.03) and skeletal muscle mass index. However, there was no significant difference between SMM and BMC across PRAL and NEAP tertiles. CONCLUSION: PRAL and NEAP were found to be inversely related to skeletal muscle mass index among overweight/obese women. Further research is required to establish whether this relationship is important for musculoskeletal health in these populations.

Soy isoflavone intake and risk of cardiovascular disease in adults: A systematic review and dose-response meta-analysis of prospective cohort studies.

We examined the association between soy isoflavone intake and risk of cardiovascular disease (CVD) outcomes in adults. We searched the online databases for relevant studies published up to September 2021. In total, 13 publications were included in the systematic review and 12 in the meta-analysis. We found that a high intake of soy isoflavones was significantly associated with a lower risk of coronary heart disease (CHD) among whole populations (Pooled RR: 0.92, 95% CI: 0.85-0.99, I2 = 41.0%, Pheterogeneity = 0.10) and a lower risk of overall CVD (Pooled RR: 0.91, 95% CI: 0.84-0.98, I2 = 30.7%, Pheterogeneity = 0.19) and CHD (Pooled RR: 0.89, 95% CI: 0.83-0.96, I2 = 14.4%, Pheterogeneity = 0.32) among Western population. In the linear dose-response analysis, a 3 mg/day increase in soy isoflavone intake was associated with 16% and 14% lower risks of overall CVD and CHD, respectively, among Western population. In conclusion, we found that soy isoflavone intake was associated with a lower risk of overall CVD and CHD in adults, particularly among Western population.

Yogurt consumption and risk of mortality from all causes, CVD and cancer: a comprehensive systematic review and dose-response meta-analysis of cohort studies.

OBJECTIVES: To quantify the dose-response relation between yogurt consumption and risk of mortality from all causes, CVD and cancer. DESIGN: Systematic review and meta-analysis. SETTING: We conducted a comprehensive search of PubMed/Medline, ISI Web of Science and Scopus databases through August 2022 for cohort studies reporting the association of yogurt consumption with mortality from all causes, CVD and cancer. Summary relative risks (RR) and 95 % CI were calculated with a random-effects model. PARTICIPANTS: Seventeen cohort studies (eighteen publications) of 896 871 participants with 75 791 deaths (14 623 from CVD and 20 554 from cancer). RESULTS: High intake of yogurt compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled RR 0·93; 95 % CI: 0·89, 0·98, I2 = 47·3 %, n 12 studies) and CVD (0·89; 95 % CI: 0·81, 0·98, I2 = 33·2 %, n 11), but not with cancer (0·96; 95 % CI: 0·89, 1·03, I2 = 26·5 %, n 12). Each additional serving of yogurt consumption per d was significantly associated with a reduced risk of all-cause (0·93; 95 % CI: 0·86, 0·99, I2 = 63·3 %, n 11) and CVD mortality (0·86; 95 % CI: 0·77, 0·99, I2 = 36·6 %, n 10). There was evidence of non-linearity between yogurt consumption and risk of all-cause and CVD mortality, and there was no further reduction in risk above 0·5 serving/d. CONCLUSION: Summarising earlier cohort studies, we found an inverse association between yogurt consumption and risk of all-cause and CVD mortality; however, there was no significant association between yogurt consumption and risk of cancer mortality.

Association of Adult Height with Cardiovascular Mortality: A Systematic Review and Meta-Analysis of Cohort Studies.

Background: Epidemiological studies on the association between adult height and cardiovascular disease (CVD) mortality have provided conflicting findings. We examined the association between adult height and the risk of CVD mortality. Methods: We searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar for relevant studies published up to September 2021. Prospective cohort studies that reported the risk estimates for death from CVD, coronary heart disease (CHD), and stroke were included. The random-effects model was used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs) for the highest vs. lowest categories of adult height. Results: In total, 20 prospective cohort publications were included in this systematic review and 17 in the meta-analysis. During 5 to 41 years of follow-up, the total number of deaths from CVD was 95,197 (51,608 from CHD and 20,319 from a stroke) among 2,676,070 participants. The summary RR comparing the highest and lowest categories of height was 0.80 (95% CI: 0.74-0.87, I 2 = 59.4%, n = 15 studies) for CVD mortality, 0.82 (95% CI: 0.74-0.90, I 2 = 70.6%, n = 12) for CHD mortality, 0.73 (95% CI: 0.67-0.80, I 2 = 0%, n = 10) for stroke mortality, 0.70 (95% CI: 0.61-0.81, I 2 = 0%, n = 4) for hemorrhagic stroke mortality, and 0.88 (95% CI: 0.72-1.08, I 2 = 0%, n = 4) for ischemic stroke mortality. Conclusion: The present comprehensive meta-analysis provides evidence for an inverse association between adult height and the risk of CVD, CHD, and stroke mortality.

Association of dietary phytochemical index with metabolically unhealthy overweight/obesity phenotype among Iranian women: A cross-sectional study.

Background: Phytochemicals have been recently studied as adjuvants for the treatment of obesity. No study has investigated the association of phytochemical-rich foods with metabolically unhealthy overweight/obesity phenotype (MUOW/O). This study aimed to determine the association of dietary phytochemical index (DPI) with MUOW/O based on Karelis criteria among Iranian female adults. Methods: In this cross-sectional study, a total of 228 overweight and obese women aged 18-48 years were included. Anthropometric measurements were evaluated for all participants. A validated 147-item Food Frequency Questionnaire (FFQ) was used for dietary assessment. DPI was calculated as [dietary energy derived from phytochemical-rich foods (kcal)/total daily energy intake (kcal)] × 100. Participants' body composition and biochemical parameters of Karelis criteria [triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), insulin, and high-sensitivity C-reactive protein (hs-CRP)] were determined. Results: The mean age of the study participants was 36.69 ± 9.20, and the mean DPI score was 26.23 ± 9.48 among participants with MUOW/O phenotype. After controlling for potential confounders, women in the highest tertile of DPI had lower odds for MUOW/O phenotype [odds ratio (OR): 0.23, 95% confidence interval (CI): 0.07-0.68, P = 0.008] compared to the lowest tertile. Among the components of Karelis criteria, homeostatic model assessment for insulin resistance (HOMA-IR) was significantly associated with MUOW/O phenotype in the fully adjusted model (OR: 0.29, 95% CI: 0.10-0.79, P = 0.01). Conclusion: We found a significant association between DPI and MUOW/O phenotype in Iranian women. Prospective studies are needed to confirm these findings.

Evaluation of the predictive value of different dietary antioxidant capacity assessment methods on healthy and unhealthy phenotype in overweight and obese women.

Purpose: Predictive value of different dietary antioxidant capacity assessment methods on healthy and unhealthy phenotypes in overweight and obese women is still unclear. This study aimed to evaluate the predictive value of different dietary antioxidant capacity assessment methods on healthy and unhealthy phenotypes in overweight and obese women. Methods: A total of 290 overweight and obese women were included in this cross-sectional study. Food intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). Dietary antioxidant capacity was calculated using valid databases of antioxidant value. The receiver operating characteristic (ROC) curve method was used to evaluate the predictive value of antioxidant capacity indices, including dietary antioxidant quality score (DAQS), ferric reducing ability of plasma (FRAP), total reactive antioxidant potential (TRAP), and trolox equivalent antioxidant capacity (TEAC). Results: The results showed that the highest area under the ROC curve for predicting metabolically healthy obesity (MHO) belongs to the TRAP method (area under the curve (AUC) = 0.53). In addition, this method had the highest AUC for predicting inflammatory marker of C-reactive protein (hs-CRP) (AUC = 0.54) and the index of the homeostatic model assessment for insulin resistance (HOMA-IR) (AUC = 0.59). The highest AUC for triglyceride prediction was related to the DAQS method (AUC = 0.56). Moreover, a significant correlation of FRAP (r = -0.15, P = 0.02), TRAP (r = -0.19, P < 0.001), TEAC (r = -0.18, P< 0.001) with HOMA-IR was reached. Conclusion: The findings of this study show that the best way to predict the status of MHO is TRAP method. This method is also the best predictor of hs-CRP and HOMA-IR. DAQS method is the best predictor for TG.

Association between dietary antioxidant index and risk of Helicobacter pylori infection among adults: a case-control study.

BACKGROUNDS AND AIMS: One of the most important risk factors for Helicobacter pylori (H. pylori) infection is nutrition. Balanced diets with high antioxidant properties may have protective effects against the consequences of this infection. In the current study, we aimed to investigate the association between the dietary antioxidant index and the risk of H. pylori infection among adults. METHODS: In a case-control study the dietary intake of patients with H. pylori infection was compared with healthy subjects. The dietary antioxidant index (DAI) was calculated using dietary intakes derived from a validated food frequency questionnaire (FFQ). Demographic information was obtained by a related questionnaire and Physical Activity was measured by International Physical Activity Questionnaire (IPAQ) were used to obtain information. Using logistic regression models, we evaluated the association between the DAI and H. pylori infection risk. The significance level was determined as P < 0.05. RESULTS: Finally, dietary data of 148 cases and 302 controls (mean age: 38.72 ± 10.61 (were analyzed. The mean of total DAI was significantly higher in controls (7.67) when compared with H. pylori cases (3.57) (P < 0.001). After adjustment for covariates, participants with less than median DAI values had an increased risk of H. pylori onset (adjusted OR 1.08, 95% CI: 1.02-1.12, P < 0.001). CONCLUSIONS: Appropriate intake of nutrient antioxidants may have a role in decreasing the likelihood of H. pylori infection risk.

Relationship between maternal caffeine and coffee intake and pregnancy loss: A grading of recommendations assessment, development, and evaluation-assessed, dose-response meta-analysis of observational studies.

Background: Numerous studies report an association between coffee or caffeine consumption and pregnancy loss; however, the nature and strength of this relationship have not been clearly established. Based on recent studies, our meta-analysis aimed to test whether a dose-response relationship between coffee or caffeine consumption and pregnancy loss exists. Methods: We searched for articles in PubMed, Web of Science, and Scopus published until May 2022. Two independent reviewers extracted data and rated the quality of the evidence using the GRADE approach. We applied a random-effects, one-stage dose-response meta-analysis. Results: A total of 34 articles (18 cohort studies and 16 case-control studies) were included in this review. Results showed a significantly higher risk of pregnancy loss for coffee consumption before (Pooled ES: 1.21; 95% CI: 1.01-1.43) and during pregnancy (Pooled ES: 1.26; 95% CI: 1.04-1.57), and for coffee consumption during pregnancy in case-control studies (Pooled ES: 1.20; 95% CI: 1.19-6.41). Findings from this meta-analysis demonstrated that caffeine intake during pregnancy was associated with a significantly higher risk of pregnancy loss in cohort (Pooled ES: 1.58; 95% CI: 1.23-2.01) and case-control studies (Pooled ES: 2.39; 95% CI: 1.69-3.37, P < 0.001), respectively. A dose-response analysis suggested that an increase of a cup of coffee per day during pregnancy was associated with 3% increased risk of pregnancy loss; 100 mg of caffeine per day during pregnancy was also associated with 14 and 26% increased risk of pregnancy loss in cohort and case-control studies, respectively. A non-linear dose-response association was observed between coffee intake and the risk of pregnancy loss. Conclusion: This study confirms that coffee or caffeine consumption raises the risk of pregnancy loss. Researchers are encouraged to conduct more studies to explore the underlying mechanisms and active compounds in coffee and caffeine. Systematic Review Registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42021267731].

Opium Use and Cancer Risk: A Comprehensive Systematic Review and Meta-Analysis of Observational Studies.

Background: Epidemiological studies have reported inconsistent associations between opium use and cancer risk. We therefore conducted a systematic review and meta-analysis to investigate the relationship between opium use and cancer risk. Methods: We searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until February 2021 and references of retrieved relevant articles for observational studies that reported the risk of cancer in relation to opium use. Random-effects models were used to calculate pooled effect sizes (ESs) as well as 95% confidence intervals (CIs) for the association between opium use and cancer risk by considering opium doses and types, duration of consumption, and routes of opium use. Results: In total, 21 observational articles, with a total sample size of 64,412 individuals and 6,658 cases of cancer, were included in this systematic review and meta-analysis. Ever opium users, compared with never opium users, had 3.53 times greater risk of overall cancer (pooled ES: 3.53, 95% CI: 2.60-4.79, P ≤ 0.01). This positive association was also seen for some individual types of cancers except for esophageal and colon cancers. Also, we found that higher opium doses and higher duration of consumption were associated with an increased risk of overall and individual types of cancer. However, the associations between opium doses and the risk of head and neck and larynx cancers were not significant. In terms of the routes of opium use, both opium ingestion and smoking were positively associated with the risk of cancer. Regarding opium types, we found that using teriak, but not shireh, could increase the risk of cancer. Conclusions: Our findings showed that opium use, particularly in the form of teriak, is a risk factor for cancer.

Egg and Dietary Cholesterol Intake and Risk of All-Cause, Cardiovascular, and Cancer Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Objective: This systematic review and meta-analysis of prospective cohort studies examined the associations between egg and dietary cholesterol intake and the risk of mortality from all causes, including cardiovascular disease (CVD) and cancer. Methods: We searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until April 2021, as well as references to the relevant articles retrieved. Random-effects models were used to calculate summary relative risk (RR) and 95% confidence intervals (CIs) for the highest vs. lowest categories of egg and dietary cholesterol intake. Also, linear and non-linear dose-response analyses were conducted to examine the dose-response relationships. Results: We included 55 studies, comprising data from 2,772,486 individuals with 228,425, 71,745, and 67,211 cases of all-cause, CVD, and cancer mortality, respectively. Intake of each additional egg per day was associated with a 7% higher risk of all-cause (1.07, 95% CI: 1.02-1.12, I2 = 84.8%) and a 13% higher risk of cancer mortality (1.13, 95% CI: 1.06-1.20, I2 = 54.2%), but was not associated with CVD mortality (1.00, 95% CI: 0.92-1.09, I2 = 81.5%). Non-linear analyses showed increased risks for egg consumption of more than 1.5 and 0.5 eggs/day, respectively. Each 100 mg/day increment in dietary cholesterol intake was associated with a 6% higher risk of all-cause mortality (1.06, 95% CI: 1.03-1.08, I2 = 34.5%) and a 6% higher risk of cancer mortality (1.06, 95% CI: 1.05-1.07, I2 = 0%), but was not associated with CVD mortality (1.04, 95% CI: 0.99-1.10, I2 = 85.9%). Non-linear analyses demonstrated elevated risks of CVD and cancer mortality for intakes more than 450 and 250 mg/day, respectively. Conclusions and Relevance: High-dietary intake of eggs and cholesterol was associated with all-cause and cancer mortality. Little evidence for elevated risks was seen for intakes below 0.5 egg/day or 250 mg/day of dietary cholesterol. Our findings should be considered with caution because of small risk estimates and moderate between-study heterogeneity. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=252564, PROSPERO, identifier: CRD42021252564.

Dietary Acid Load and Bone Health: A Systematic Review and Meta-Analysis of Observational Studies.

Findings on the association between dietary acid load (DAL) and bone health are conflicting. This study aimed to summarize available studies on the association between DAL and risk of fractures or bone mineral density (BMD) in adults. Online databases including PubMed, Scopus, and Embase were searched for relevant studies published up to June 2021, using pertinent keywords. We identified observational studies (cohort, case-control, and cross-sectional) investigating the association between DAL and risk of fractures or BMD, then selected studies following these reported criteria: RRs with corresponding 95% CIs for the relationship between DAL and fracture risk; correlation coefficients for the association between DAL and BMD; and mean ± SD of BMD values across the categories of DAL. Overall, 17 studies with 80545 individuals were included. There was no significant relationship between the PRAL and fracture risk (Pooled RR: 1.18; 95% confidence interval 0.98 to 1.41, I 2 = 60.6%). Moreover, a similar association was observed between the NEAP and fracture risk (Pooled RR: 1.41, 95% CI: 0.79 to 2.52, I 2 = 54.1%). The results of five studies from four publications revealed no significant association between dietary PRAL score and femoral and spinal BMD (WMD femoral = -0.01, 95% confidence interval: -0.02 to 0.01, I 2 = 76.5%; WMD spinal = -0.01, 95% CI: -0.03 to 0.01, I 2 = 56.7%). However, being in the highest category of NEAP was significantly associated with a lower femoral and spinal BMD (WMD femoral = -0.01, 95% CI: -0.02 to -0.00, I 2 = 82.1%; WMD spinal = -0.02, 95% CI: -0.03 to -0.01, I 2 = 93%). It was showed that adopting diets high in acidity was not associated with risk of fractures. We also found a significant negative relationship between NEAP and BMD. However, DAL based on PRAL was not associated with BMD.

High vs. low-fat dairy and milk differently affects the risk of all-cause, CVD, and cancer death: A systematic review and dose-response meta-analysis of prospective cohort studies.

Considerable controversy exists regarding the association between milk and dairy consumption and mortality risk. The present systematic review and meta-analysis of prospective studies was undertaken to examine the association of high vs. low-fat dairy and milk consumption with mortality. We searched PubMed/Medline, ISI Web of Science, and Scopus databases through February 2020 for prospective cohort studies that reported the association between milk and dairy consumption and mortality risk. High-fat milk consumption was significantly associated with a greater risk of all-cause (Pooled ES: 1.15; 95% CI: 1.09-1.20, I2=24.5%, p = 0.22), CVD (Pooled ES: 1.09; 95% CI: 1.02-1.16, I2=4.5%, p = 0.38) and cancer mortality (Pooled ES: 1.17; 95% CI: 1.08-1.28, I2=30.1%, p = 0.19). However, total dairy consumption was associated with a lower risk of CVD mortality (Pooled ES: 0.93; 95% CI: 0.88-0.98, I2=59.7%, p = 0.001). Dose-response analysis revealed a significant non-linear association of total dairy consumption with all-cause and CVD mortality. Moreover, high-fat milk consumption was significantly associated with risk of cancer mortality in linear and non-linear dose-response analysis. In conclusion, we found high-fat milk consumption was associated with a higher risk of all-cause, CVD, and cancer mortality. However, total dairy consumption was associated with a lower risk of CVD mortality.

The effect of ketogenic diet on body composition and anthropometric measures: A systematic review and meta-analysis of randomized controlled trials.

This study aimed to summarize earlier randomized controlled trials on the effects of ketogenic diet (KD) on body composition and anthropometric measures. Four databases were searched from inception to May 2020 using relevant keywords. All clinical trials investigating the effects of KD on body weight (BW), body mass index (BMI), waist circumference (WC), fat mass (FM), fat-free mass (FFM), lean body mass (LBM), visceral adipose tissue (VAT) and percentage body fat (PBF) in adults were included. Overall, 18 trials were included in the review. Pooled effect sizes revealed a significant effect of KD on BW (weighted mean differences [WMD]: -2.87 kg, 95% confidence interval [CI]: -3.84 to -1.89), BMI (WMD: -1.44 kg/m2, 95% CI: -2.07, -0.81), FM (WMD: -1.40 kg, 95% CI: -2.50, -0.30), FFM (WMD: -0.81 kg, 95% CI: -1.32, -0.30), LBM (WMD: -0.63 kg, 95% CI: -1.21, -0.06), WC (WMD: -3.23 cm, 95% CI: -4.38, -2.09), VAT (WMD: -28.91 g, 95% CI: -50.57, -7.24) and PBF (WMD: -2.81 kg, 95% CI: -3.82, -1.80), respectively. Taken together, the data suggest that KD has beneficial effects on BW, BMI, FM, FFM, LBM, WC, VAT, and PBF. However, the effectiveness of the long term effect of this dietary pattern is unclear.

Total, dietary, and supplemental calcium intake and risk of all-cause cardiovascular, and cancer mortality: a systematic review and dose-response meta-analysis of prospective cohort studies.

Considerable controversy exists regarding the association between calcium intake and mortality risk. Therefore, this study aimed to summarize available findings on the associations of total, dietary and supplemental calcium intake with all-cause, CVD, and cancer mortality. We searched PubMed, Scopus, Embase, and ISI Web of Knowledge until February 2020 to identify eligible publications. Random-effects models were used to calculate pooled effect sizes (ESs) and 95% confidence intervals (CIs) for highest versus lowest categories of calcium intake and to incorporate variation between studies. Linear and non-linear dose-response analyses were done to evaluate the dose-response relations between calcium intake and mortality. 36 publications were included in this systematic review and 35 in the meta-analysis. During the follow-up periods ranging from 4.2 to 28 years, the total number of deaths from all causes was 163,657 (83703 from CVD and 83929 from cancer). Total calcium intake was associated with a lower risk of CVD mortality (Pooled ES for highest v lowest category: 0.91; 95% CI: 0.83-0.99, I2=68.1%, P < 0.001). Dietary calcium intake was associated with a lower risk of all-cause mortality (Pooled ES for highest v lowest category: 0.95; 95% CI: 0.92-0.99, I2=62.1%, P < 0.001). Supplemental calcium intake was not significantly associated with risk of all-cause, CVD and cancer mortality. In the dose-response analysis, there was evidence of nonlinear association between calcium intake and risk of all-cause, CVD, and cancer mortality. In conclusion, a non-linear association between calcium intake with all-cause, CVD, and cancer mortality risk was observed in this meta-analysis. Moderate intake of total (1000-1800), dietary (600-1200), and supplemental calcium (600-1200) was inversely significantly associated with mortality risk but higher calcium intake was not associated with a lower risk of mortality.

The Association of Dietary Energy Density and Body Composition Components in a Sample of Iranian Adults.

Background: We aimed to investigate the association between the energy density (ED) of diet and body composition components in Iranian adults. Methods: We conducted a cross-sectional study on 267 adults in Tehran. We obtained ED (kcal/g) using the two most common methods: ED1, ED from foods only with the exclusion of all beverages and ED2, from foods and all beverages. Body composition was measured using a multifrequency bio-impedance analysis. To find a strong association, we used both the linear and binary regression analysis in the three adjusted models. Results: The mean of ED1 and ED2 was 1.34 ± 0.23 and 0.89 ± 0.20 kcal/g, respectively. Increasing the ED of diet in both methods was associated with a high intake of dietary fat, of saturated fatty acid (SFA), of monounsaturated fatty acid (MUFA), of polyunsaturated fatty acid (PUFA), of oleic and linoleic acids, accompanied by a low intake of fruits, vegetables, and some vitamins and minerals. There was a significant positive relationship between fat-free mass index (FFMI) and ED1 (ß = 4.44, p = 0.02). However, we found no significant association between the consumption of ED1 and fat mass index (FMI) (0.28; 95% CI 0.08, 0.98; p = 0.07), and abdominal obesity (0.91; 95% CI 0.43, 1.94; p = 0.82). Also, ED2 had no association with FMI (0.86; 95% CI 0.26, 2.80; p = 0.81) and abdominal obesity (0.78; 95% CI 0.35, 1.72; p = 0.54). No significant associations were found between ED and other anthropometric indices and body composition components after considering the confounders. Conclusion: This study supports the positive association between ED and poor dietary quality. However, our findings did not show significant associations of dietary energy density (DED) with anthropometric indices and body composition components. Further well-designed studies are required to investigate the exact link between DED and body composition.