Pre-Sleep Casein Supplementation,Metabolism, and Appetite: A Systematic Review

Protein intake is an important factor for augmenting the response to resistance training in healthy individuals. Although food intake can help with anabolism during the day, the period of time during sleep is typically characterized by catabolism and other metabolic shifts. Research on the application of nighttime casein protein supplementation has introduced a new research paradigm related to protein timing. Pre-sleep casein supplementation has been attributed to improved adaptive response by skeletal muscle to resistance training through increases in muscle protein synthesis, muscle mass, and strength. However, it remains unclear what the effect of this nutritional strategy is on non-muscular parameters such as metabolism and appetite in both healthy and unhealthy populations. The purpose of this systematic review is to understand the effects of pre-sleep casein protein on energy expenditure, lipolysis, appetite, and food intake in both healthy and overweight or obese individuals. A systematic review following PRISMA guidelines was conducted in CINAHL, Cochrane, and SPORTDiscus during March 2021, and 11 studies met the inclusion criteria. A summary of the main findings shows limited to no effects on metabolism or appetite when ingesting 24–48 g of casein 30 min before sleep, but data are limited, and future research is needed to clarify the relationships observed.     

Medical Treatments for Acromegaly: A Systematic Review and Network Meta-Analysis

Background

Acromegaly results from the hypersecretion of growth hormone. Because of the low incidence rates of this disease worldwide, few clinical trials evaluating drug treatments have been conducted.

Ghrelin as a Biomarker of Stress: A Systematic Review and Meta-Analysis

Introduction: Ghrelin is an orexigenic hormone which favors food-seeking behavior and has been postulated to be a biomarker of stress. We conducted a systematic review and meta-analysis on the evolution of ghrelin levels following acute stress. Methods: The PubMed, Cochrane Library, Embase, and ScienceDirect databases were searched for studies reporting ghrelin levels before and after acute stress in humans. Results: We included ten studies for a total of 348 patients. Acute stress (intervention) was always in a laboratory. Acute stress was psychological (Trier Social Stress Test), physical, or mixed (cold pressure test). The overall meta-analysis demonstrated an increase in ghrelin after the stress intervention (ES = 0.21, 95CI 0.09 to 0.34) compared with baseline levels. Stratification by time demonstrated an acute increase in ghrelin levels in the five minutes immediately following the initiation of stress (0.29, 0.10 to 0.48) but without any difference after. Obese individuals had a more significant (ES = 0.51, 95CI 0.18 to 0.84) and prolonged increase in ghrelin levels for up to 45 min compared with non-obese individuals who had a significant increase only five minutes after stress. Moreover, the ghrelin levels increased in response to stress with BMI (coefficient 0.028, 0.01 to 0.49; p = 0.013) and decreased with the time after the stress intervention (coefficient -0.007, −0.014 to −0.001; p = 0.025). Conclusion: Ghrelin is a biomarker of stress, with a short-term increase following acute stress. Obese individuals have both a higher and prolonged response, emphasizing the link between obesity and stress.     

Leptin as a Biomarker of Stress: A Systematic Review and Meta-Analysis

Background: Leptin is a satiety hormone mainly produced by white adipose tissue. Decreasing levels have been described following acute stress. Objective: To conduct a systematic review and meta-analysis to determine if leptin can be a biomarker of stress, with levels decreasing following acute stress. Methods: PubMed, Cochrane Library, Embase, and ScienceDirect were searched to obtain all articles studying leptin levels after acute stress on 15 February 2021. We included articles reporting leptin levels before and after acute stress (physical or psychological) and conducted random effects meta-analysis (DerSimonian and Laird approach). We conducted Meta-regressions and sensitivity analyses after exclusion of groups outside the metafunnel. Results: We included seven articles—four cohort and three case-control studies—(28 groups) from 27,983 putative articles. Leptin levels decreased after the stress intervention (effect size = −0.34, 95%CI −0.66 to −0.02) compared with baseline levels, with a greater decrease after 60 min compared to mean decrease (−0.45, −0.89 to −0.01) and in normal weight compared to overweight individuals (−0.79, −1.38 to −0.21). There was no difference in the overweight population. Sensitivity analyses demonstrated similar results. Levels of leptin after stress decreased with sex ratio—i.e., number of men/women—(−0.924, 95%CI −1.58 to −0.27) and increased with the baseline levels of leptin (0.039, 0.01 to 0.07). Conclusions: Leptin is a biomarker of stress, with a decrease following acute stress. Normal-weight individuals and women also have a higher variation of leptin levels after stress, suggesting that leptin may have implications in obesity development in response to stress in a sex-dependent manner.     

Effect of Glycemic Index of Breakfast on Energy Intake at Subsequent Meal among Healthy People: A Meta-Analysis

Meals with low glycemic index (GI) may suppress short-term appetite and reduce subsequent food intake compared with high-GI meals. However, no meta-analysis has been conducted to synthesize the evidence. This meta-analytic study was conducted to assess the effect of high- and low-GI breakfast on subsequent short-term food intake. Trials were identified through MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled trials, and manual searches of bibliographies until May 2015. Randomized controlled and cross-over trials comparing the effect of low- with high-GI breakfast on subsequent energy intake among healthy people were included. Nine studies consisting of 11 trials met the inclusion criteria. Only one trial was classified with high methodological quality. A total of 183 participants were involved in the trials. The meta-analytic results revealed no difference in breakfast GI (high-GI vs. low-GI) on subsequent short-term energy intake. In conclusion, it seems that breakfast GI has no effect on short-term energy intake among healthy people. However, high quality studies are still warranted to provide more concrete evidence.     

Prevalence of Hyperhomocysteinemia in China: A Systematic Review and Meta-Analysis

Hyperhomocysteinemia (HHcy, total homocysteine concentrations > 15 μmol/L) has been associated with increased risk of many diseases. A systematic review was performed to summarize the prevalence of HHcy in China. We searched multiple international and Chinese scientific databases for relevant literature, and further manually screened reference lists and corresponded with original authors. Pooled prevalence of HHcy was calculated using random effects model. Subgroup analysis, meta-regression and sensitivity analysis were also performed. A total of 36 studies consisting 60,754 subjects (57.3% male; age range, 3–97 years) were finally included. The overall pooled prevalence of HHcy was 27.5%. Geographically, the prevalence was high in north areas, intermediate in central areas, and low in south areas, and was higher in inland versus coastal areas. The prevalence increased with age and was significantly higher in men than in women. Rural residents had a slightly higher HHcy prevalence than urban residents, and the studies conducted during 2006 to 2012 presented a higher HHcy prevalence than those during 1990 to 2005. In summary, the prevalence of HHcy in China is high, particularly in northern populations, the inlanders, males, and the elderly. Homocysteine-lowering strategies are necessary to reduce this highly preventable disorder.     

The Effect of Multivitamin/Mineral Supplements on Age-Related Cataracts: A Systematic Review and Meta-Analysis

Antioxidant vitamins supplements have been suggested as a strategy to decrease the risk of age-related cataract development. However, the results from observational studies and interventional trials of associations between antioxidant vitamins A, C, and E and cataract development have been inconsistent. We aim to evaluate the effectiveness of multivitamin/mineral supplements for decreasing the risk of age-related cataracts by conducting a systematic review and meta-analysis. In September 2013, we searched multiple databases to identify relevant studies including both cohort studies and randomized controlled trials (RCTs). A random-effects model was used to calculate the pooled relative risks (RR) with a 95% confidence interval (CI). Twelve prospective cohort studies and two RCTs were included. Pooled results from the cohort studies indicated that multivitamin/mineral supplements have a significant beneficial effect in decreasing the risk of nuclear cataracts (RR: 0.73; 95% CI: 0.64–0.82), cortical cataracts (RR: 0.81; 95% CI: 0.68–0.94), and any cataracts (RR: 0.66; 95% CI: 0.39–0.93). In addition, there were no decreases in the risk of posterior capsular cataracts (RR: 0.96; 95% CI: 0.72–1.20) or cataract surgery (RR: 1.00; 95% CI: 0.92–1.08). The two RCTs demonstrated that multivitamin/mineral supplements could decrease the risk of nuclear cataracts. There is sufficient evidence to support the role of dietary multivitamin/mineral supplements for the decreasing the risk of age-related cataracts.     

Supplementation of Omega 3 during Pregnancy and the Risk of Preterm Birth: A Systematic Review and Meta-Analysis

Preterm birth (PTB) is a major cause of neonatal death and long-term consequences for the newborn. This review aims to update the evidence about the potential benefit of pharmacological supplementation with omega 3 fatty acids during pregnancy on the incidence of PTB. The Medline, Embase, Cochrane Library and Central databases were searched until 28 June 2020 for RCTs in which omega 3 supplementation was used versus placebo to reduce PTB risk. Data from 37 trials were analyzed. We found an 11% reduction in PTB risk (RR(risk ratios), 0.89; 95% CI (confidence intervals), 0.82 to 0.97) in trials using omega 3 supplements versus placebo. Regarding early PTB (ePTB), there was a 27% reduction in the risk of ePTB (RR, 0.73; 95% CI, 0.58 to 0.92). However, after sensitivity analyses, there were no significant differences in PTB and ePTB risk (PTB RR, 0.92; 95% CI, 0.83 to 1.01, ePTB RR, 0.82; 95% CI, 0.61 to 1.09). We conclude that omega 3 supplementation during pregnancy does not reduce the risk of PTB and ePTB. More studies are required to determine the effect of omega 3 supplementations during pregnancy and the risk of detrimental fetal outcomes.     

Effect of a Ketogenic Diet on the Nutritional Parameters of Obese Patients: A Systematic Review and Meta-Analysis

The effect of a ketogenic diet (KD) on biochemical parameters and nutritional status has been the subject of debate over the years, as several randomized clinical trials (RCTs) obtained different results. Method: A systematic review and random-effects meta-analysis of RCTs comparing KD with a balanced diet was performed by means of a search of PubMed, Cochrane Library, Scopus, and Web of Science. Trials where the method for measuring the response variables was unclear, those that considered pathologies other than chronic non-communicable diseases and those with participants receiving pharmacological treatment for obesity were excluded from the comparison. Results: Of the studies included in the meta-analysis, no statistically significant standardized mean differences were observed for body mass index (BMI) (d = −0.457, p = 0.359), total cholesterol, COL-T (d = 0.230, p = 0.591), high-density lipoprotein, HDL (d = −0.028, p = 0.934), low-density lipoprotein, LDL (d = 0.528, p = 0.173), or triglycerides, TG (d = −0.283, p = 0.222), with high values of heterogeneity. The percentage of women included in the studies is a significant moderating variable in terms of BMI ratio (z = −6.68, p < 0.001) and TG (z = −2.27, p = 0.023). Conclusion: A KD shows no more benefits on nutritional parameters than a balanced diet, and adverse effects of being on the diet are sometimes reported.     

Effect of Calcifediol on Physical Performance and Muscle Strength Parameters: A Systematic Review and Meta-Analysis

There is general agreement that optimal vitamin D status is necessary for bones, muscles, and general health, particularly in older adults, who are at higher risk of negative consequences of vitamin D deficiency, including sarcopenia; vitamin D supplementation is proposed as a potential intervention to mitigate sarcopenia. Several RCTs have reported that calcifediol (25(OH)D) was more potent than cholecalciferol in increasing plasma 25(OH)D. The present systematic review and meta-analysis aimed to summarize the effects of calcifediol on physical performance and muscle strength. We searched databases from inception to 1 January 2022 for studies investigating calcifediol on physical performance or muscle strength parameters. We calculated the difference between the means of follow-up vs. baseline data using standardized mean differences (SMD) and their 95% confidence intervals (CIs); a random-effect model was considered for all of the analyses. Seven RCTs were included in the meta-analysis. Calcifediol significantly improved gait speed (SMD = 2.500; 95%CI = 1.768–3.223; p < 0.0001); handgrip strength (n = 5446 participants, SMD = 0.532; 95%CI: 0.305–0.758; p < 0.0001; I² = 20.2%); and leg extension (n = 4318 participants, SMD = 0.641; 95%CI: 0.346 to 0.935; p < 0.0001; I² = 18.8%;) vs. baseline values. In conclusion, in this systematic review and meta-analysis, we observed that calcifediol may have a positive effect on muscle strength parameters, with less evidence on physical performance. These data further indicate the importance of vitamin D and, in particular, of calcifediol, not only on bone metabolism but also on muscle parameters and sarcopenia.     

Residential Pesticides and Childhood Leukemia: A Systematic Review and Meta-Analysis

Objective

We conducted a systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during critical exposure time windows (preconception, pregnancy, and childhood) and childhood leukemia.

Data sources

Searches of MEDLINE and other electronic databases were performed (1950–2009). Reports were included if they were original epidemiologic studies of childhood leukemia, followed a case–control or cohort design, and assessed at least one index of residential/household pesticide exposure/use. No language criteria were applied.

Data extraction

Study selection, data abstraction, and quality assessment were performed by two independent reviewers. Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs).

Data synthesis

Of the 17 identified studies, 15 were included in the meta-analysis. Exposures during pregnancy to unspecified residential pesticides (summary OR = 1.54; 95% CI, 1.13–2.11; I² = 66%), insecticides (OR = 2.05; 95% CI, 1.80–2.32; I² = 0%), and herbicides (OR = 1.61; 95% CI, 1.20–2.16; I² = 0%) were positively associated with childhood leukemia. Exposures during childhood to unspecified residential pesticides (OR = 1.38; 95% CI, 1.12–1.70; I² = 4%) and insecticides (OR = 1.61; 95% CI, 1.33–1.95; I² = 0%) were also positively associated with childhood leukemia, but there was no association with herbicides.

Conclusions

Positive associations were observed between childhood leukemia and residential pesticide exposures. Further work is needed to confirm previous findings based on self-report, to examine potential exposure–response relationships, and to assess specific pesticides and toxicologically related subgroups of pesticides in more detail.     

Manganese Exposure and Metabolic Syndrome: A Systematic Review and Meta-Analysis

Manganese (Mn) is an essential element acting as a co-factor of superoxide dismutase, and it is potentially beneficial for cardiometabolic health by reducing oxidative stress. Although some studies have examined the relationship between Mn and metabolic syndrome (MetS), no systematic review and meta-analysis has been presented to summarize the evidence. Therefore, the present review examined the association between dietary and environmental Mn exposure, and MetS risk. A total of nine cross-sectional studies and three case-control studies were included, which assessed Mn from diet, serum, urine, and whole blood. The association of the highest Mn level from diet (three studies, odds ratio (OR): 0.83, 95% confidence interval (C.I.) = 0.57, 1.21), serum (two studies, OR: 0.87, 95% C.I. = 0.66, 1.14), urine (two studies, OR: 0.84, 95% C.I. = 0.59, 1.19), and whole blood (two studies, OR: 0.92, 95% C.I. = 0.53, 1.60) were insignificant, but some included studies have suggested a non-linear relationship of urinary and blood Mn with MetS, and higher dietary Mn may associate with a lower MetS risk in some of the included studies. While more evidence from prospective cohorts is needed, future studies should use novel statistical approaches to evaluate relative contribution of Mn on MetS risk along with other inter-related exposures.     

Effect of Protein-Rich Breakfast on Subsequent Energy Intake and Subjective Appetite in Children and Adolescents: Systematic Review and Meta–Analysis of Randomized Controlled Trials

Breakfast has been labeled “the most important meal of the day”, especially for children and adolescents. Dietary protein intake may benefit and regulate appetite and energy balance. However, few meta–analyses have been conducted to examine the effect of protein–rich (PR) breakfast on both children and adolescents. This meta–analytic study was conducted to examine the effect of consuming a PR breakfast on short–term energy intake and appetite in children and adolescents. PubMed, Embase, Cochrane Central Register of Controlled Trials, China Biology Medicine disc (CBM), and China National Knowledge Infrastructure (CNKI) were searched for randomized controlled trials (RCTs) published in January 1990–January 2021. The inclusion criteria applied were RCTs in children and adolescents (7–19 year) comparing PR breakfast consumption with normal protein (NP)/traditional breakfast consumption. Finally, ten studies were included in the analysis, eight studies examined the effect of consuming PR breakfast on SEI (n = 824), and nine studies examined the effect on appetite (fullness = 736, hunger = 710). Our meta-analysis using the random–effects model shows that participants assigned to consume PR breakfast had lower SEI (MD, −111.2 kcal; 95% CI: −145.4, −76.9), higher fullness (MD, 7.4 mm; 95% CI: 6.0, 8.8), and lower hunger (MD, −8.5 mm; 95% CI: −9. 7, −7.3) than those assigned to consume NP/traditional breakfast. However, there was considerable inconsistency across the trial results. Our review suggests that the consumption of PR breakfast could be an excellent strategy for weight management by declining SEI and suppressing appetite, and provides new evidence of the relationship between energy balance and obesity. However, since most eligible studies were of low quality, the results ought to be interpreted cautiously.     

Effect of Oral Nutritional Supplementation on Growth in Children with Undernutrition: A Systematic Review and Meta-Analysis

Oral nutritional supplements (ONS) are used to promote catch-up growth in children with undernutrition. We conducted a systematic review and meta-analysis to summarize the evidence of ONS intervention effects on growth for 9-month- to 12-year-old children who were undernourished or at nutritional risk. Eleven randomized controlled trials met the inclusion criteria; trials compared changes in anthropometric measures in children using ONS or ONS + DC (dietary counselling) to measures for those following usual diet or placebo or DC alone. The RCTs included 2287 children without chronic diseases (mean age 5.87 years [SD, 1.35]; 56% boys). At follow-up time points up to 6 months, results showed that children in the ONS intervention group had greater gains in weight (0.423 kg, [95% confidence interval 0.234, 0.613], p < 0.001) and height (0.417 cm [0.059, 0.776], p = 0.022) versus control; greater gains in weight (0.089 kg [0.049, 0.130], p < 0.001) were evident as early as 7–10 days. Longitudinal analyses with repeated measures at 30, 60, and 90 days showed greater gains in weight parameters from 30 days onwards (p < 0.001), a trend towards greater height gains at 90 days (p = 0.056), and significantly greater gains in height-for-age percentiles and Z-scores at 30 and 90 days, respectively (p < 0.05). Similar results were found in subgroup analyses of studies comparing ONS + DC to DC alone. For children with undernutrition, particularly those who were mildly and moderately undernourished, usage of ONS in a nutritional intervention resulted in significantly better growth outcomes when compared to control treatments (usual diet, placebo or DC alone).     

Effect of Low FODMAPs Diet on Irritable Bowel Syndromes: A Systematic Review and Meta-Analysis of Clinical Trials

We conducted a meta-analysis exploring the effect of a low fermentable oligo-, di-, monosaccharides, and polyols diet (LFD) on the overall symptoms, quality of life, and stool habits of irritable bowel syndrome (IBS) patients. The meta-analysis was performed using a random-effects method. The effect size was presented as weighted standardized mean difference (SMD) and 95% confidence interval (CI). Subgroup analyses were conducted to determine the potential effects of covariates on the outcome. Twenty-two papers were included. The LFD group showed a moderate reduction in symptom severity and a slight improvement in quality of life compared to the control group (SMD, −0.53 and 0.24; 95% CI, −0.68, −0.38 and 0.02, 0.47, respectively). IBS symptom improvement was consistent between subgroups stratified according to proportions of female patients, study durations, IBS subtypes, assessment methods, and control interventions. Three studies regarding stool habits change in IBS-D patients showed a significant decrease in stool frequency (mean differences [MD], −5.56/week; 95% CI, −7.40, −3.72) and a significant improvement in stool consistency (MD, −0.86; 95% CI, −1.52, −0.19) in the LFD group compared to the control group. This is the most updated meta-analysis including studies that adopted diverse control interventions such as dietary interventions, supplementation, habitual diets, and lifestyle changes.     

Effect of Flaxseed Intervention on Inflammatory Marker C-Reactive Protein: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Functional food-flaxseed and its derivatives (flaxseed oil or lignans) are beneficial for human health, possibly because of their anti-inflammatory effects. C-reactive protein (CRP), a sensitive marker of inflammation was chosen to evaluate the anti-inflammatory effects of flaxseed. We searched randomized controlled trials from PubMed and the Cochrane Library in October 2015 and conducted a meta-analysis to evaluate the effectiveness of flaxseed and its derivatives on CRP. The mean differences (net change) in CRP (mg/L) concentrations were pooled with a random- or a fixed-effects model depending on the results of heterogeneity tests. Overall, flaxseed interventions had no effects on reduction of CRP (p = 0.428). The null effects were consistent in the subgroup analysis with multiple studies and population characteristics. Significant heterogeneity was observed in most of the analyses. Meta-regression identified baseline body mass index (BMI) as a significant source of heterogeneity (P-interaction = 0.032), with a significant reduction in CRP of 0.83 mg/L (95% confidence interval −1.34 to −0.31; p = 0.002) among subjects with a BMI of ≥30 kg/m². In conclusion, our meta-analysis did not find sufficient evidence that flaxseed and its derivatives have a beneficial effect on reducing circulating CRP. However, they may significantly reduce CRP in obese populations.