Substituting Low-Calorie Sweetened Beverages for Sugar-Sweetened Beverages to Prevent Obesity and Cardiometabolic Diseases: Still a Good Idea?

Low-calorie sweeteners (LCSs) and LCS-containing beverages have been proposed as appropriate substitutes for caloric sugars in recent years. In this Perspective, we highlight the recent findings from observational and interventional studies, focusing on obesity, gut microbiome, and cardiometabolic health. We provide public health actors and health care professionals with an insightful overview of recent evidence to bridge the gap between research and practice.

Two cosmoses, one universe: a narrative review exploring the gut microbiome's role in the effect of urban risk factors on vascular ageing.

In the face of rising global urbanisation, understanding how the associated environment and lifestyle impact public health is a cornerstone for prevention, research, and clinical practice. Cardiovascular disease is the leading cause of morbidity and mortality worldwide, with urban risk factors contributing greatly to its burden. The current narrative review adopts an exposome approach to explore the effect of urban-associated physical-chemical factors (such as air pollution) and lifestyle on cardiovascular health and ageing. In addition, we provide new insights into how these urban-related factors alter the gut microbiome, which has been associated with an increased risk of cardiovascular disease. We focus on vascular ageing, before disease onset, to promote preventative research and practice. We also discuss how urban ecosystems and social factors may interact with these pathways and provide suggestions for future research, precision prevention and management of vascular ageing. Most importantly, future research and decision-making would benefit from adopting an exposome approach and acknowledging the diverse and boundless universe of the microbiome.

Utility of iron biomarkers in differentiating menopausal status: Findings from CoLaus and PREVEND.

AIM: To examine the association of iron biomarkers with menopausal status and assess whether these biomarkers can help differentiate menopausal status beyond age. METHODS: In this cross-sectional study we included 1679 women from the CoLaus and 2133 from the PREVEND cohorts, with CoLaus used as primary cohort and PREVEND for replication. Ferritin, transferrin, iron, and transferrin saturation (TSAT) were used to assess iron status. Hepcidin and soluble transferrin receptor were assessed only in PREVEND. Menopausal status was self-reported and defined as menopausal or non-menopausal. Logistic regressions were used to explore the association of these iron biomarkers with menopause status. Sensitivity, specificity, area under the receiver operating characteristic curves (AUC), positive and negative predictive values as well as cut-off points for the iron biomarkers were calculated. The model with the highest AUC was defined as the best. RESULTS: In the CoLaus and PREVEND cohorts, respectively, 513 (30.6 %) and 988 (46.3 %) women were postmenopausal. Ferritin (OR, 2.20; 95 % CI 1.72-2.90), transferrin (OR, 0.03; 95 % CI 0.01-0.10), and TSAT (OR, 1.28; 95 % CI 1.06-1.54) were significantly associated with menopausal status in CoLaus, with the findings replicated in PREVEND. AUC of age alone was 0.971. The best model resulted from combining age, ferritin, and transferrin, with an AUC of 0.976, and sensitivity and specificity of 87.1 % and 96.5 %, respectively. Adding transferrin and ferritin to a model with age improved menopause classification by up to 7.5 %. In PREVEND, a model with age and hepcidin outperformed a model with age, ferritin, and transferrin. CONCLUSION: Iron biomarkers were consistently associated with menopausal status in both cohorts, and modestly improved a model with age alone for differentiating menopause status. Our findings on hepcidin need replication.

Endovascular revascularization strategies for aortoiliac and femoropopliteal artery disease: a meta-analysis.

AIMS: Optimal endovascular management of intermittent claudication (IC) remains disputed. This systematic review and meta-analysis compares efficacy and safety outcomes for balloon angioplasty (BA), bare-metal stents (BMS), drug-coated balloons (DCB), drug-eluting stents (DES), covered stents, and atherectomy. METHODS AND RESULTS: Electronic databases were searched for randomized, controlled trials (RCT) from inception through November 2021. Efficacy outcomes were primary patency, target-lesion revascularization (TLR), and quality-of-life (QoL). Safety endpoints were all-cause mortality and major amputation. Outcomes were evaluated at short-term (<1 year), mid-term (1-2 years), and long-term (≥2 years) follow-up. The study was registered on PROSPERO (CRD42021292639). Fifty-one RCTs enrolling 8430 patients/lesions were included. In femoropopliteal disease of low-to-intermediate complexity, DCBs were associated with higher likelihood of primary patency [short-term: odds ratio (OR) 3.21, 95% confidence interval (CI) 2.44-4.24; long-term: OR 2.47, 95% CI 1.93-3.16], lower TLR (short-term: OR 0.33, 95% CI 0.22-0.49; long-term: OR 0.42, 95% CI 0.29-0.60) and similar all-cause mortality risk, compared with BA. Primary stenting using BMS was associated with improved short-to-mid-term patency and TLR, but similar long-term efficacy compared with provisional stenting. Mid-term patency (OR 1.64, 95% CI 0.89-3.03) and TLR (OR 0.50, 95% CI 0.22-1.11) estimates were comparable for DES vs. BMS. Atherectomy, used independently or adjunctively, was not associated with efficacy benefits compared with drug-coated and uncoated angioplasty, or stenting approaches. Paucity and heterogeneity of data precluded pooled analysis for aortoiliac disease and QoL endpoints. CONCLUSION: Certain devices may provide benefits in femoropopliteal disease, but comparative data in aortoiliac arteries is lacking. Gaps in evidence quantity and quality impede identification of the optimal endovascular approach to IC.

Prognostic models in COVID-19 infection that predict severity: a systematic review.

Current evidence on COVID-19 prognostic models is inconsistent and clinical applicability remains controversial. We performed a systematic review to summarize and critically appraise the available studies that have developed, assessed and/or validated prognostic models of COVID-19 predicting health outcomes. We searched six bibliographic databases to identify published articles that investigated univariable and multivariable prognostic models predicting adverse outcomes in adult COVID-19 patients, including intensive care unit (ICU) admission, intubation, high-flow nasal therapy (HFNT), extracorporeal membrane oxygenation (ECMO) and mortality. We identified and assessed 314 eligible articles from more than 40 countries, with 152 of these studies presenting mortality, 66 progression to severe or critical illness, 35 mortality and ICU admission combined, 17 ICU admission only, while the remaining 44 studies reported prediction models for mechanical ventilation (MV) or a combination of multiple outcomes. The sample size of included studies varied from 11 to 7,704,171 participants, with a mean age ranging from 18 to 93 years. There were 353 prognostic models investigated, with area under the curve (AUC) ranging from 0.44 to 0.99. A great proportion of studies (61.5%, 193 out of 314) performed internal or external validation or replication. In 312 (99.4%) studies, prognostic models were reported to be at high risk of bias due to uncertainties and challenges surrounding methodological rigor, sampling, handling of missing data, failure to deal with overfitting and heterogeneous definitions of COVID-19 and severity outcomes. While several clinical prognostic models for COVID-19 have been described in the literature, they are limited in generalizability and/or applicability due to deficiencies in addressing fundamental statistical and methodological concerns. Future large, multi-centric and well-designed prognostic prospective studies are needed to clarify remaining uncertainties.

Circulating lipoprotein (a) and all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis.

AIMS: To investigate the association between circulating lipoprotein(a) (Lp(a)) and risk of all-cause and cause-specific mortality in the general population and in patients with chronic diseases, and to elucidate the dose-response relations. METHODS AND RESULTS: We searched literature to find prospective studies reporting adjusted risk estimates on the association of Lp(a) and mortality outcomes. Forty-three publications, reporting on 75 studies (957,253 participants), were included. The hazard ratios (HRs) and 95% confidence intervals (95%CI ) for the top versus bottom tertile of Lp(a) levels and risk of all-cause mortality were 1.09 (95%CI: 1.01-1.18, I2: 75.34%, n = 19) in the general population and 1.18 (95%CI: 1.04-1.34, I2: 52.5%, n = 12) in patients with cardiovascular diseases (CVD). The HRs for CVD mortality were 1.33 (95%CI: 1.11-1.58, I2: 82.8%, n = 31) in the general population, 1.25 (95%CI: 1.10-1.43, I2: 54.3%, n = 17) in patients with CVD and 2.53 (95%CI: 1.13-5.64, I2: 66%, n = 4) in patients with diabetes mellitus. Linear dose-response analyses revealed that each 50 mg/dL increase in Lp(a) levels was associated with 31% and 15% greater risk of CVD death in the general population and in patients with CVD. No non-linear dose-response association was observed between Lp(a) levels and risk of all-cause or CVD mortality in the general population or in patients with CVD (Pnonlinearity > 0.05). CONCLUSION: This study provides further evidence that higher Lp(a) levels are associated with higher risk of all-cause mortality and CVD-death in the general population and in patients with CVD. These findings support the ESC/EAS Guidelines that recommend Lp(a) should be measured at least once in each adult person's lifetime, since our study suggests those with higher Lp(a) might also have higher risk of mortality.

Buckwheat and Cardiometabolic Health: A Systematic Review and Meta-Analysis.

Buckwheat (BW) is suggested to have beneficial effects, but evidence on how it affects cardiometabolic health (CMH) is not yet established. We aimed to assess the effects of BW and/or its related bioactive compounds on cardiovascular disease (CVD) risk markers in adults. Five databases were searched for eligible studies. Observational prospective studies, nonrandomized or randomized trials were considered if they assessed BW, rutin or quercetin-3-glucoside intake and CVD risk markers. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting. We selected 16 human studies based on 831 subjects with mild metabolic disturbances, such as hypercholesterolemia, diabetes and/or overweight. Eight studies, investigating primarily grain components, were included in the meta-analyses (n = 464). High study heterogeneity was present across most of our analyses. Weighted mean difference (WMD) for subjects receiving BW supplementation, compared to controls, were - 0.14 mmol/L (95% CI: -0.30; 0.02) for total cholesterol (TC), -0.03 mmol/L (95% CI: -0.22; 0.16) for LDL cholesterol, -0.14 kg (95% CI: -1.50; 1.22) for body weight, -0.04 mmol/L (95% CI: - 0.09;0.02) for HDL cholesterol, -0.02 mmol/L (95% CI: -0.15; 0.11) for triglycerides and -0.18 mmol/L (95% CI: -0.36; 0.003) for glucose. Most of the studies (66.7%) had concerns of risk of bias. Studies investigating other CVD markers were scarce and with inconsistent findings, where available. Evidence on how BW affects CMH is limited. However, the available literature indicates that BW supplementation in mild dyslipidaemia and type 2 diabetes may provide some benefit in lowering TC and glucose, albeit non-significant. Our work highlights the need for more rigorous trials, with better methodological rigor to clarify remaining uncertainties on potential effects of BW on CMH and its utility in clinical nutrition practice.

Risk Prediction Models of Natural Menopause Onset: A Systematic Review.

CONTEXT: Predicting the onset of menopause is important for family planning and to ensure prompt intervention in women at risk of developing menopause-related diseases. OBJECTIVE: We aimed to summarize risk prediction models of natural menopause onset and their performance. METHODS: Five bibliographic databases were searched up to March 2022. We included prospective studies on perimenopausal women or women in menopausal transition that reported either a univariable or multivariable model for risk prediction of natural menopause onset. Two authors independently extracted data according to the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist. Risk of bias was assessed using a prediction model risk of bias assessment tool (PROBAST). RESULTS: Of 8132 references identified, we included 14 articles based on 8 unique studies comprising 9588 women (mainly Caucasian) and 3289 natural menopause events. All included studies used onset of natural menopause (ONM) as outcome, while 4 studies also predicted early ONM. Overall, there were 180 risk prediction models investigated, with age, anti-Müllerian hormone, and follicle-stimulating hormone being the most investigated predictors. Estimated C-statistic for the prediction models ranged from 0.62 to 0.95. Although all studies were rated at high risk of bias mainly due to the methodological concerns related to the statistical analysis, their applicability was satisfactory. CONCLUSION: Predictive performance and generalizability of current prediction models on ONM is limited given that these models were generated from studies at high risk of bias and from specific populations/ethnicities. Although in certain settings such models may be useful, efforts to improve their performance are needed as use becomes more widespread.

The effects of sesame, canola, and sesame-canola oils on cardiometabolic markers in patients with type 2 diabetes: a triple-blind three-way randomized crossover clinical trial.

AIMS: To compare the effects of replacing regular dietary oils intake with sesame (SO), canola (CO), and sesame-canola (SCO) oils (a novel blend), on cardiometabolic markers in adults with type 2 diabetes mellitus (T2DM), in a triple-blind, three-way, randomized, crossover clinical trial. METHODS: Participants were assigned to receive SO, CO, and SCO in three 9-week phases (4 weeks apart). Cardiometabolic makers (serum lipids, Apolipoprotein, cardiovascular risk scores, kidney markers, and blood pressure) were considered at the beginning and the end of intervention phases. RESULTS: Ninety-two, ninety-five, and ninety-five participants completed the SO, SCO, and CO periods, respectively. After CO consumption, serum Apo A-1 concentrations were significantly higher compared with the SCO period in the whole population (p < 0.05). A considerable reduction in visceral adiposity index values was seen in the CO compared with the SO period in males (p < 0.05). Serum high-density lipoprotein concentration was also significantly higher after the SO intake compared with SCO in females (p < 0.05). The between-period analysis showed a substantial reduction in diastolic blood pressure in the SCO period compared with the CO and SO periods and lower systolic blood pressure after SCO versus CO intake in males (p < 0.05). CONCLUSIONS: Canola oil might protect CVD through improving Apo A-1 levels in patients with T2DM (particularly in females) and visceral adiposity index in male patients. However, the blend oil might beneficially affect blood pressure in men. Future sex-specific studies might warrant the current findings. REGISTRY OF CLINICAL TRIALS: This trial was registered in the Iranian Registry of Clinical Trials (IRCT, registration ID: IRCT2016091312571N6).

Association Between Ultra-Processed Food Intake and All-Cause Mortality: A Systematic Review and Meta-Analysis.

Consumption of ultra-processed foods (UPF) has increased worldwide during the last decades because they are hyperpalatable, cheap, and ready-to-consume products. However, uncertainty exists about their impact on health. We conducted a systematic review and meta-analysis evaluating the association of UPF consumption with all-cause mortality risk. Five bibliographic databases were searched for relevant studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Of 6,951 unique citations, 40 unique prospective cohort studies comprising 5,750,133 individuals were included; publication dates ranged from 1984 to 2021. Compared with low consumption, highest consumption of UPF (RR = 1.29, 95% CI: 1.17, 1.42), sugar-sweetened beverages (RR = 1.11, 95% CI, 1.04, 1.18), artificially sweetened beverages (RR = 1.14, 95% CI, 1.05, 1.22), and processed meat/red meat (RR = 1.15, 95% CI, 1.10, 1.21) were significantly associated with increased risk of mortality. However, breakfast cereals were associated with a lower mortality risk (RR = 0.85, 95% CI, 0.79, 0.92). This meta-analysis suggests that high consumption of UPF, sugar-sweetened beverages, artificially sweetened beverages, processed meat, and processed red meat might increase all-cause mortality, while breakfast cereals might decrease it. Future studies are needed to address lack of standardized methods in UPF categorization.

Validity and Reproducibility of a Semiquantitative Multiple-Choice Food Frequency Questionnaire in Iranian Adults.

Previous multiple-choice food-based food frequency questionnaires (FFQs) were not validated against weighed dietary records (WDRs) in Iran. This study investigated the validity and reproducibility of a multiple-choice semi-quantitative food frequency questionnaire (SQ-FFQ) in adults living in central Iran. Patients with diabetes and their spouses were asked to complete 3 SQ-FFQs by interview, and nine 3-day WDRs, over 9 months. They provided 2 blood samples to assess serum calcium, magnesium, zinc, and vitamin C levels. The Pearson and intraclass correlation coefficients were calculated to assess reproducibility and validity. The degree of misclassification was explored using a contingency table of quartiles which compare the information between third FFQ and WDRs. The method of triads was incorporated to assess validity coefficients between estimated intakes using third FFQ, WDRs, and biochemical markers and assumed true intakes. A total of 180 participants aged 48.9 ± 8.4 years completed the study. Compared to WDRs, FFQs overestimated all nutrient intakes except for iron. The median intraclass correlation between FFQs was 0.56. The median de-attenuated, age, sex, and education adjusted partial correlation coefficients for validity were 0.17 and 0.26 for FFQ1-WDRs and FFQ3-WDRs, respectively. The FFQ3 validity coefficients for vitamin C, calcium, magnesium, and zinc were 0.13, 0.62, 0.89, and 0.66, respectively, using the triads method. The median exact agreement and complete disagreement between FFQ3 and WDRs were 33% and 6%, respectively. The SQ-FFQ seems to be an acceptable tool to assess the long-term dietary intake for future large-scale studies in this population.

The effect of sesame, canola, and sesame-canola oils on cardiometabolic risk factors in overweight adults: a three-way randomized triple-blind crossover clinical trial.

Limited data exist on the cardiometabolic effects of sesame oil compared with canola oil. In the present study, 77 overweight adults were randomized to replace their regularly consumed oils with canola (CO), sesame (SO), and sesame-canola oils (SCO, 40% SO, and 60% CO) in three 9-week phases. Blood pressure, visceral adiposity index, serum apo-proteins (APOs) and lipid profile, glycemic control markers, kidney markers, liver enzymes, and cardiovascular disease risk scores were assessed at baseline and endline. After adjustment for confounders, SO significantly reduced serum alkaline aminotransferase (ALT) compared to CO (p ≤ 0.05) in all participants, increased serum urea compared to SCO in males, and decreased serum alkaline phosphatase compared to other oils in males, and improved serum high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) compared to SCO, and eGFR compared with CO in females (p ≤ 0.05). Canola oil significantly improved serum Apo A1 and APO B/A ratio compared with SO, in males (p ≤ 0.05). Sesame-canola oil significantly reduced serum urea compared to other oils in all participants (p ≤ 0.05). Sesame oil and SCO might beneficially affect serum ALT and urea, respectively. Intervention oils might have different cardiometabolic effects in each gender. Further studies are needed to confirm our results (Trial registration code: IRCT2016091312571N6).

The effects of propolis supplementation on metabolic parameters: A systematic review and meta-analysis of randomized controlled clinical trials.

OBJECTIVE: Propolis is a sticky, resinous substance produced by honeybees from various plants. Various biological properties of propolis and its extracts have been recognized in previous studies including the antiseptic, anti-inflammatory, antioxidant, antiviral, hepatoprotective, antitumor, antibacterial and antimycotic properties. This study aimed to summarize the effect of propolis on metabolic parameters in human adults using systematic review and meta-analysis. MATERIALS AND METHODS: A comprehensive systematic search was performed in ISI Web of Science, PubMed, Scopus, and Google Scholar up to July 2020 for controlled clinical trials evaluating the impact of propolis on lipid profile and liver enzyme biomarkers. A random effects model was used to calculate the weighted mean difference (WMD) and 95% confidence interval (CI) as the difference between the mean for the intervention and control groups. RESULTS: The present meta-analysis included six randomized controlled trials. There was significant reduction in Aspartate Aminotransferase (AST) in comparison to the control groups (WMD=-2.01; 95% CI: -3.93--0.10; p=0.039). However, a non-significant effect was observed in Triglycerides (TG), Total cholesterol (TC), low-density lipoprotein (LDL), High-density lipoprotein (HDL) (WMD=-0.05 mg/dl; 95% CI: -0.27-0.18; p=0.688; WMD=7.08 mg/dl; 95% CI: -37.31-51.46; p=0.755; WMD=-0.94 mg/dl; 95% CI: -6.64-4.77; p=0.747; WMD=3.14 mg/dl; 95% CI: -1.84-8.13; p=0.216, respectively). CONCLUSION: Current meta-analysis revealed that propolis supplementation can reduce AST; nevertheless, there was no significant effect on lipid profile indices and ALT.

Effects of sesame, canola and sesame-canola oils on body weight and composition in adults with type 2 diabetes mellitus: a randomized, triple-blind, cross-over clinical trial.

BACKGROUND: Recent investigations have proposed that sesame and canola oils might affect body fat distribution. The present study aimed to examine the effects of sesame, canola and sesame-canola (a blend of sesame and canola oils) oils on body weight and composition in adults with type 2 diabetes mellitus in the context of a randomized, triple-blind, three-way, cross-over clinical trial. RESULTS: Eligible participants were randomized to replace their regular dietary oil with sesame oil (SO), canola oil (CO) and sesame-canola oil (SCO) (with 40% SO and 60% CO). Treatment periods lasted 9 weeks and were separated by 4-week wash-out periods. Body weight and composition were measured at the beginning, in the middle and at the end of each intervention phase. In total, 93 participants completed the study. After adjustment for confounders, within-period changes were observed following SO and CO intake for body weight (0.34 ± 0.16 kg and 0.33 ± 0.17 kg) and visceral fat (0.13 ± 0.06% and 0.13 ± 0.05%, P < 0.05), respectively. Body mass index was increased within SO intake (0.13 ± 0.05 kg m-2 , P = 0.031). All of the treatment oils resulted in reduced waist circumference and index of central obesity (P < 0.05). A significant difference in change values was observed for visceral fat between SCO (-0.14 ± 0.07%) and SO (0.12 ± 0.08%) treatment periods in females (P = 0.02). CONCLUSION: Sesame and canola oils might lead to a modest favorable body fat redistribution by reducing central adiposity, particularly in females; however, the changes were of little clinical importance. © 2021 Society of Chemical Industry.

Meta-analysis of vitamin D supplementation and hemoglobin concentration: methodological faults obscure the interpretation of the data.

We read the review by Arabi et al. with great interest which tried to examine the effects of vitamin D supplementation on hemoglobin concentration. It seems that the article suffers from fundamental methodological issues and the conclusions are likely to be erroneous. In this regard, we would like to ask the authors to address the mentioned limitations and to update the analysis in order to provide robust and trustful results. We are concerned that such meta-analyses may lead to the biased findings and conclusions.

Canola oil compared with sesame and sesame-canola oil on glycaemic control and liver function in patients with type 2 diabetes: A three-way randomized triple-blind cross-over trial.

BACKGROUND: This study aimed to compare the effects of sesame (SO), canola (CO), and sesame-canola (SCO: a blend) oils on glycaemic control markers and liver function enzymes in adults with type 2 diabetes. METHODS: In this randomized, triple-blind, three-way, cross-over clinical trial, participants replaced their usual oil with the intervention oils for 9 weeks. Serum fasting blood sugar, fasting serum insulin (FSI), insulin resistance (HOMA2-IR), beta-cell function (HOMA2-%B), insulin sensitivity (HOMA2-%S), quantitative insulin sensitivity check index (QUICKI), as well as serum liver function enzymes were measured at baseline and end of intervention periods. RESULTS: Ninety-two participants completed all treatment periods. After adjusting for confounders, all treatment oils resulted in significant improvements in FSI and HOMA2-%S (p < 0.05). SO and SCO led to favourable changes in HOMA2-IR and QUICKI (p < 0.05). Following CO and SCO, there was a significant decrease in HOMA2-%B (p < 0.05). The sex-stratified analysis revealed that FSI and HOMA2-IR were decreased after SO compared to CO in males (p = 0.024). Serum gamma-glutamyltransferase (GGT) was significantly lower following SO compared to CO in females (p = 0.02), however, the difference in change values was not significant (p = 0.058). CONCLUSIONS: SO consumption appears to improve glycaemic control markers in males and serum GGT in females compared with CO in patients with type 2 diabetes (registration code: IRCT2016091312571N6).

The effect of canola, sesame and sesame-canola oils on body fat and composition in adults: a triple-blind, three-way randomised cross-over clinical trial.

The present study aimed to examine the effect of replacing edible oils with sesame oil (SO), canola oil (CO) and sesame-canola oil (SCO) on body weight and composition in adults. Adults without any chronic diseases (n = 77) were entered a 4-week run-in period and then were randomised to receive SO, CO and SCO for their household use in 9-week intervention periods (separated by 4-week washout intervals). Anthropometric measurements, as well as body composition markers, were assessed at baseline, middle and after each intervention period. In total, 73 participants completed the study. Although significant time effects were seen for waist and hip circumference, waist-to-hip ratio, central obesity index, body adiposity index, muscle mass and body fat percent (ptime<.05), the treatment and treatment × time effects were not significant (p>.05). The present clinical trial revealed that CO, SO and SCO might not differently affect body fat and composition. Trial registration code: IRCT2016091312571N6 (http://en.irct.ir/trial/12622).

Double-counting of effect sizes and inappropriate exclusion of studies in "The influence of vitamin D supplementation on IGF-1 levels in humans: A systematic review and meta-analysis".

We read with interest the review by Kord-Varkaneh et al. which examined the effects of vitamin D supplementation on IGF-1 levels in humans. We believe that the article suffers from severe methodological faults and subsequently the conclusions are likely to be biased. Thus, the authors should address the mentioned limitations and update the analyses to provide robust and trustful estimates. We are concerned that without correction, the analyses may lead to erroneous findings and conclusions.