The Association between Vitamin D Status and Autism Spectrum Disorder (ASD): A Systematic Review and Meta-Analysis

The association between vitamin D status and autism spectrum disorder (ASD) is well-investigated but remains to be elucidated. We quantitatively combined relevant studies to estimate whether vitamin D status was related to ASD in this work. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to include eligible studies. A random-effects model was applied to pool overall estimates of vitamin D concentration or odds ratio (OR) for ASD. In total, 34 publications involving 20,580 participants were identified in this present study. Meta-analysis of 24 case–control studies demonstrated that children and adolescents with ASD had significantly lower vitamin D concentration than that of the control group (mean difference (MD): −7.46 ng/mL, 95% confidence interval (CI): −10.26; −4.66 ng/mL, p < 0.0001, I² = 98%). Quantitative integration of 10 case–control studies reporting OR revealed that lower vitamin D was associated with higher risk of ASD (OR: 5.23, 95% CI: 3.13; 8.73, p < 0.0001, I² = 78.2%). Analysis of 15 case–control studies barring data from previous meta-analysis reached a similar result with that of the meta-analysis of 24 case–control studies (MD: −6.2, 95% CI: −9.62; −2.78, p = 0.0004, I² = 96.8%), which confirmed the association. Furthermore, meta-analysis of maternal and neonatal vitamin D showed a trend of decreased early-life vitamin D concentration in the ASD group (MD: −3.15, 95% CI: −6.57; 0.26, p = 0.07, I² = 99%). Meta-analysis of prospective studies suggested that children with reduced maternal or neonatal vitamin D had 54% higher likelihood of developing ASD (OR: 1.54, 95% CI: 1.12; 2.10, p = 0.0071, I² = 81.2%). These analyses indicated that vitamin D status was related to the risk of ASD. The detection and appropriate intervention of vitamin D deficiency in ASD patients and pregnant and lactating women have clinical and public significance.     

Vitamin D and Graves’ Disease: A Meta-Analysis Update

The association between vitamin D levels and Graves’ disease is not well studied. This update review aims to further analyze the relationship in order to provide an actual view of estimating the risk. We searched for the publications on vitamin D and Graves’ disease in English or Chinese on PubMed, EMBASE, Chinese National Knowledge Infrastructure, China Biology Medical and Wanfang databases. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for the vitamin D levels. Pooled odds ratio (OR) and 95% CI were calculated for vitamin D deficiency. We also performed sensitivity analysis and meta-regression. Combining effect sizes from 26 studies for Graves’ disease as an outcome found a pooled effect of SMD = −0.77 (95% CI: −1.12, −0.42; p < 0.001) favoring the low vitamin D level by the random effect analysis. The meta-regression found assay method had the definite influence on heterogeneity (p = 0.048). The patients with Graves’ disease were more likely to be deficient in vitamin D compared to the controls (OR = 2.24, 95% CI: 1.31, 3.81) with a high heterogeneity (I² = 84.1%, p < 0.001). We further confirmed that low vitamin D status may increase the risk of Graves’ disease.     

The Impact of Selenium Supplementation on Trauma Patients—Systematic Review and Meta-Analysis

This study aimed to assess current evidence regarding the effect of selenium (Se) supplementation on the prognosis in patients sustaining trauma. MEDLINE, Embase, and Web of Science databases were searched with the following terms: “trace element”, “selenium”, “copper”, “zinc”, “injury”, and “trauma”. Seven studies were included in the meta-analysis. The pooled results showed that Se supplementation was associated with a lower mortality rate (OR 0.733, 95% CI: 0.586, 0.918, p = 0.007; heterogeneity, I² = 0%). Regarding the incidence of infectious complications, there was no statistically significant benefit after analyzing the four studies (OR 0.942, 95% CI: 0.695, 1.277, p = 0.702; heterogeneity, I² = 14.343%). The patients with Se supplementation had a reduced ICU length of stay (standard difference in means (SMD): −0.324, 95% CI: −0.382, −0.265, p < 0.001; heterogeneity, I² = 0%) and lesser hospital length of stay (SMD: −0.243, 95% CI: −0.474, −0.012, p < 0.001; heterogeneity, I² = 45.496%). Se supplementation after trauma confers positive effects in decreasing the mortality and length of ICU and hospital stay.     

Lycopene Supplement and Blood Pressure: An Updated Meta-Analysis of Intervention Trials

Epidemiological studies suggested that lycopene supplement could decrease blood pressure, but the results were conflicting. We conducted an updated meta-analysis by screening PubMed databases, and calculated the combined effect size using a random effect model. In addition, subgroup analysis stratified by baseline blood pressure, lycopene dosage, duration, study location and the funding support of the paper was also conducted. Six studies met our inclusion criteria, and the pooled analysis demonstrated a significant reduction of systolic blood pressure (SBP) (mean SBP = −4.953 [−8.820, −1.086], p = 0.012) with obvious heterogeneity (p = 0.034, I² = 58.5%). Subgroup analysis results showed that higher dosage of lycopene supplement (>12 mg/day) could lower SBP more significantly, especially for participants with baseline SBP >120 mmHg, or Asians, while lycopene intervention had no statistical effect on diastolic blood pressure (DBP) (mean DBP = −3.809 [−8.177, 0.560], p = 0.087), and obvious heterogeneity was also observed (p = 0.074, I² = 53.1%). Our present study suggests that lycopene supplement >12 mg/day might effectively decrease SBP, particularly among Asians or population with higher baseline SBP.     

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.     

The Impact on the Clinical Prognosis of Low Serum Selenium Level in Patients with Severe Trauma: Systematic Review and Meta-Analysis

This study was designed to examine the most up-to-date evidence about how low plasma selenium (Se) concentration affects clinical outcomes, such as mortality, infectious complications, and length of ICU or hospital stay, in patients with major trauma. We searched three databases (MEDLINE, EMBASE, and Web of Science) with the following keywords: “injury”, “trauma”, “selenium”, and “trace element”. Only records written in English published between 1990 and 2021 were included for analysis. Four studies were eligible for meta-analyses. The results of the meta-analysis showed that a low serum selenium level did not exert a negative effect on the mortality rate (OR 1.07, 95% CI: 0.32, 3.61, p = 0.91, heterogeneity, I² = 44%). Regarding the incidence of infectious complications, there was no statistically significant deficit after analyses of the four studies (OR 1.61, 95% CI: 0.64, 4.07, p = 0.31, heterogeneity, I² = 70%). There were no differences in the days spent in the ICU (difference in means (MD) 1.53, 95% CI: −2.15, 5.22, p = 0.41, heterogeneity, I² = 67%) or the hospital length of stay (MD 6.49, 95% CI: −4.05, 17.02, p = 0.23, heterogeneity, I² = 58%) in patients with low serum Se concentration. A low serum selenium level after trauma is not uncommon. However, it does not negatively affect mortality and infection rate. It also does not increase the overall length of ICU and hospital stays.     

Effects of Plant-Based Diets on Weight Status in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Excessive adiposity is a major risk factor for type 2 diabetes (T2D), and dietary patterns are important determinants of weight status. Plant-based dietary patterns (PBDs) are known for their therapeutic effects on T2D. The aim is to systematically review RCTs to investigate the effects of various PBDs compared to regular meat-eating diets (RMDs), in individuals who normally consume a RMD on body weight, BMI, and waist circumference in T2D. RCTs investigating PBDs and body weight, BMI, WC for ≥6 weeks in adults with T2D since 1980 were eligible for inclusion. Seven trials (n = 269) were included in the meta-analysis using random-effects models and expressed as MD (95%Cls). Compared to RMDs, PBDs significantly lowered body weight (−2.35 kg, 95% CI: −3.51, −1.19, p < 0.001), BMI (−0.90 kg/m², 95% CI: −1.42, −0.38, p = 0.001) and WC (−2.41 cm, 95% CI: −3.72, −1.09, p < 0.001). PBDs alone significantly reduced body weight by 5.1% (−4.95 kg, 95% CI: −7.34, −2.55, p < 0.001), BMI by 5.4% (−1.87 kg/m², 95% CI: −2.78, −0.95, p < 0.001) and WC by 4.3%(−4.23, 95% CI: −6.38, −2.07, p < 0.001). Interventions not limiting energy intake led to a significant reduction in body weight (−2.54 kg, 95% CI: −4.16, −0.92, p < 0.005) and BMI (−0.91 kg/m², 95% CI: −1.56, −0.25, p < 0.005). Trials ≥16 weeks had a pronounced reduction in body weight (−2.93 kg, 95% CI: −5.00, −0.87, p = 0.005) and BMI (−1.13 kg/m², 95% CI: −1.89, −0.38, p < 0.005). These findings provide evidence for the implementation of PBDs for better management of central adiposity in individuals with T2D.     

Low-Glycemic Index Diets as an Intervention in Metabolic Diseases: A Systematic Review and Meta-Analysis

We aimed to investigate the effects of a low-glycemic index (GI) diet on the body mass and blood glucose of patients with four common metabolic diseases by conducting a systematic review and meta-analysis of studies comparing a low-GI diet (LGID) and other types of diet. Search terms relating to population, intervention, comparator, outcomes, and study design were used to search three databases: PubMed, Embase, and the Cochrane Library. We identified 24 studies involving 2002 participants. Random-effects models were used for 16 studies in the meta-analysis and stratified analyses were performed according to the duration of the intervention. The systematic review showed that LGIDs slightly reduced body mass and body mass index (BMI) (p < 0.05). BMI improved more substantially after interventions of >24 weeks and there was no inter-study heterogeneity (I² = 0%, p = 0.48; mean difference (MD) = −2.02, 95% confidence interval (CI): −3.05, −0.98). Overall, an LGID had superior effects to a control diet on fasting blood glucose (FBG) and glycosylated hemoglobin. When the intervention exceeded 30 days, an LGID reduced FBG more substantially (MD = −0.34, 95% CI: −0.55, −0.12). Thus, for patients with metabolic diseases, an LGID is more effective at controlling body mass and blood glucose than a high-GI or other diet.     

Efficacy of Vitamin D Supplements in Prevention of Acute Respiratory Infection: A Meta-Analysis for Randomized Controlled Trials

Background: Previous systematic reviews and meta-analyses of randomized controlled trials (RCTs) have reported inconsistent results regarding the efficacy of vitamin D supplements in the prevention of acute respiratory infections (ARIs). Methods: We investigated these efficacy results by using a meta-analysis of RCTs. We searched PubMed, EMBASE, and the Cochrane Library in June 2021. Results: Out of 390 trials searched from the database, a total of 30 RCTs involving 30,263 participants were included in the final analysis. In the meta-analysis of all the trials, vitamin D supplementation showed no significant effect in the prevention of ARIs (relative risk (RR) 0.96, 95% confidence interval (CI) 0.91–1.01, I² = 59.0%, n = 30). In the subgroup meta-analysis, vitamin D supplementation was effective in daily supplementation (RR 0.83, 95% CI, 0.73–0.95, I² = 69.1%, n = 15) and short-term supplementation (RR 0.83, 95% CI, 0.71–0.97, I² = 66.8%, n = 13). However, such beneficial effects disappeared in the subgroup meta-analysis of high-quality studies (RR 0.89, 95% CI, 0.78–1.02, I² = 67.0%, n = 10 assessed by the Jadad scale; RR 0.87, 95% CI, 0.66–1.15, I² = 51.0%, n = 4 assessed by the Cochrane’s risk of bias tool). Additionally, publication bias was observed. Conclusions: The current meta-analysis found that vitamin D supplementation has no clinical effect in the prevention of ARIs.     

Vitamin D Deficiency and Comorbidities as Risk Factors of COVID-19 Infection: A Systematic Review and Meta-analysis

ObjectivesExtensive evidence links low vitamin D status and comorbidities with coronavirus disease 2019 (COVID-19) outcomes, but the results of published studies are contradictory. Therefore, we investigated the association of lower levels of vitamin D and comorbidities with the risk of COVID-19 infection.MethodsWe searched MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for articles published until August 20, 2021. Sixteen eligible studies were identified (386 631 patients, of whom 181 114 were male). We included observational cohort and case-control studies that evaluated serum levels of vitamin D in COVID-19-positive and COVID-19-negative patients. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated.ResultsSignificantly lower vitamin D levels were found in COVID-19-positive patients (MD, −1.70; 95% CI, −2.74 to −0.66; p=0.001), but with variation by study design (case-control: −4.04; 95% CI, −5.98 to −2.10; p<0.001; cohort: −0.39; 95% CI, −1.62 to 0.84; p=0.538). This relationship was more prominent in female patients (MD, −2.18; 95% CI, −4.08 to −0.28; p=0.024) than in male patients (MD, −1.74; 95% CI, −3.79 to 0.31; p=0.096). Male patients showed higher odds of having low vitamin D levels (odds ratio [OR], 2.09; 95% CI, 1.38 to 3.17; p<0.001) than female patients (OR, 1.17; 95% CI, 0.74 to 1.86; p=0.477). Comorbidities showed inconsistent, but generally non-significant, associations with COVID-19 infection.ConclusionsLow serum vitamin-D levels were significantly associated with the risk of COVID-19 infection. This relationship was stronger in female than in male COVID-19 patients. Limited evidence was found for the relationships between comorbidities and COVID-19 infection, warranting large population-based studies to clarify these associations.     

Lower Fiber Consumption in Women with Polycystic Ovary Syndrome: A Meta-Analysis of Observational Studies

Polycystic ovary syndrome is a common endocrine disorder associated with metabolic abnormalities and gut microbiota dysbiosis. The deficiency of dietary fiber, a crucial nutrient in the daily diet, is also associated with a wide range of metabolic and reproductive abnormalities, as well as an altered gut microbial ecosystem. This study is a meta-analysis to summarize the available evidence on the dietary fiber intake level in PCOS patients. Databases of PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched for observational studies, and 13 studies were finally included. The pooled standardized mean difference (SMD) with the 95% confidence interval (CI) of daily dietary fiber intake and total energy intake were calculated using the random-effects model. The pooled result (12 studies) on absolute dietary fiber intake showed that while there was no significant difference in the total energy intake [−0.17 (−0.44, 0.09), p = 0.208], the dietary fiber intake was significantly lower in PCOS women than those of controls [−0.32 (−0.50, −0.14), p < 0.001]. However, significant heterogeneity was detected across the studies (I² = 65.6%, p = 0.001). Meta-regression suggested that geographic region and dietary assessment method may confer borderline significance of influence on the heterogeneity. The pooled result (two studies) on dietary fiber intake which adjusted for total energy intake, however, showed no significant difference [−2.11 (−4.77, 0.56), p = 0.122]. In subgroup analyses based on absolute dietary fiber intake, a lower dietary fiber intake in PCOS was observed in studies conducted in Asia, adopted food diary or records or food recall as the dietary assessment method, had a case–control study design, or used Rotterdam criteria for PCOS diagnosis. The difference in SMD was still significant in the adult subgroup or in studies matched or unmatched for age.     

The Relationship between Serum Zinc Level and Preeclampsia: A Meta-Analysis

The association between serum zinc level and preeclampsia (PE) remains controversial. A systematic literature search was performed in PubMed, Web of Science and Embase for relevant available articles. The articles were limited to those in English from January 1990 to April 2015. Observational studies evaluating the association between serum zinc level and PE were included. The I² was used to assess heterogeneity and the random effect model (REM) was adopted as the pooling method. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was used to estimate the association between serum zinc level and PE. Seventeen observational studies were included. Compared with healthy pregnancy controls, PE patients have lower serum zinc level in 14 studies about total PE (SMD (95% CI): −0.587 (−0.963, −0.212), Z = 3.06, p for Z = 0.002; I² = 88.4%, p for I² < 0.0001). In subgroup analysis, a lower serum zinc level in PE patients compared with healthy pregnancy controls was observed in studies conducted in Asia, studies with zinc level measured in serum, and studies involving fasting participants. The SMD did not differ significantly between studies with healthy pregnancy controls matched by individual age (yes or no), and by individual gestational age (yes or no), respectively. Results from this meta-analysis indicate that serum zinc level in PE patients is significantly lower than that in healthy pregnancy controls. A moderate amount of zinc supplementation during pregnancy is advocated to reduce the incidence of PE.     

Inositol Nutritional Supplementation for the Prevention of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

This study was aimed at assessing the efficacy and safety of inositol nutritional supplementation during pregnancy for the prevention of GDM. PubMed, Embase, MEDLINE, and Cochrane library were systematically searched for randomized controlled trails (RCTs) in this field until May 2022. Primary outcomes were the incidence for GDM and plasma glucose levels by oral glucose tolerance test (OGTT). Pooled results were expressed as relative risk (RR) or mean difference (MD) with a 95% confidence interval (95% CI). Seven RCTs with 1321 participants were included in this study. Compared with the control group, 4 g myo-inositol (MI) supplementation per day significantly decreased the incidence of GDM (RR = 0.30, 95% CI (0.18, 0.49), p < 0.00001). It significantly decreased the plasma glucose levels of OGTT regarding fasting-glucose OGTT (MD = −4.20, 95% CI (−5.87, −2.54), p < 0.00001), 1-h OGTT (MD = −8.75, 95% CI (−12.42, −5.08), p < 0.00001), and 2-h OGTT (MD = −8.59, 95% CI (−11.81, −5.83), p < 0.00001). It also decreased the need of insulin treatment, and reduced the incidence of preterm delivery and neonatal hypoglycemia. However, no difference was observed between 1.1 g MI per day plus 27.6 mg D-chiro-inositol (DCI) per day and the control group regarding all evaluated results. In conclusion, 4 g MI nutritional supplementation per day during early pregnancy may reduce GDM incidence and severity, therefore may be a practical and safe approach for the prevention of GDM.     

Effect of Vitamin D Supplementation in Early Life on Children’s Growth and Body Composition: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Vitamin D deficiency during pregnancy or infancy is associated with adverse growth in children. No systematic review has been conducted to summarize available evidence on the effect of vitamin D supplementation in pregnancy and infancy on growth and body composition in children. Objective: We aim to summarize the available evidence on the effect of vitamin D supplementation in pregnancy and infancy on child growth and body composition. Method: A systematic review and meta-analysis were performed on the effects of vitamin D supplementation during early life on children’s growth and body composition (bone, lean and fat). A literature search of randomized controlled trials (RCTs) was conducted to identify relevant studies on the effects of vitamin D supplementation during pregnancy and infancy on children’s body composition (bone, lean and fat) in PubMed, EMBASE and Cochrane Library from inception to 31 December 2020. A Cochrane Risk Assessment Tool was used for quality assessment. The comparison was vitamin D supplementation vs. placebo or standard care. Random-effects and fixed-effect meta-analyses were conducted. The effects are presented as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Results: A total of 3960 participants from eleven randomized controlled trials were eligible for inclusion. Vitamin D supplementation during pregnancy was associated with higher triceps skinfold thickness (mm) (MD 0.33, 95% CI, 0.12, 0.54; I² = 34%) in neonates. Vitamin D supplementation during pregnancy or infancy was associated with significantly increased length for age z-score in infants at 1 year of age (MD 0.29, 95% CI, 0.03, 0.54; I² = 0%), and was associated with lower body mass index (BMI) (kg/m²) (MD −0.19, 95% CI −0.34, −0.04; I² = 0%) and body mass index z-score (BMIZ) (MD −0.12, 95% CI −0.21, −0.04; I² = 0%) in offspring at 3–6 years of age. Vitamin D supplementation during early life was not observed to be associated with children’s bone, lean or fat mass. Conclusion: Vitamin D supplementation during pregnancy or infancy may be associated with reduced adiposity in childhood. Further large clinical trials of the effects of vitamin D supplementation on childhood body composition are warranted.     

Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of probiotics supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis (SpA), or psoriatic arthritis). Methods: A systematic literature review and meta-analysis from RA and SpA randomized controlled trials were conducted searching for articles in MEDLINE/PubMed and abstracts from recent international rheumatology meetings. The control group was a placebo or another dietary intervention. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration tool and the Jadad scale. Results: The initial search yielded 173 articles. Of these, 13 studies were included in the qualitative synthesis, 8 concerning a total of 344 RA patients and 2 concerning a total of 197 SpA patients. Three meta-analyses were also analyzed. Probiotic strains and quantities used were different among trials (5 studies using Lactobacillus sp., 1 trial Bacillus coagulans and the others a mix of different probiotic strains). Time to assess response ranged from 8 weeks to one year. Two studies associated probiotic supplementation with a dietary intervention. Meta-analysis showed a statistically significant decrease of C-reactive protein (CRP) concentration (mean difference (MD)) −3.04 (95% CI −4.47, −1.62) mg/L, p < 0.001; I² = 20%, n patients = 209) with probiotics in RA. However, after excluding high-risk-of-bias trials of meta-analysis, there was no difference between probiotics and placebo on DAS28 (standard MD −0.54; 95% CI −1.94 to 0.85, p = 0.45, I² 93%, n patients = 143). The two studies on SpA patients showed no efficacy of probiotics. Conclusions: Probiotic supplementation might decrease RA activity with a moderate decrease effect on CRP, but lack of evidence and studies’ heterogeneity do not allow us to propose them to patients with inflammatory arthritis to control their disease. Further RCTs are required in the future to determinate the efficacy of probiotics and the optimal administration design.     

Effect of Camel Milk on Glucose Homeostasis in Patients with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The effects of camel milk (CM) intake on glycemic control in patients with diabetes are controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of CM intake on glucose homeostasis parameters in patients with both types of diabetes mellitus; T1DM and T2DM. We searched Google Scholar, PubMed/MEDLINE, EBSCO host, CINAHL, ScienceDirect, Cochrane, ProQuest Medical, Web of Science, and Scopus databases from inception until the end of November 2021. Relevant RCTs were identified, and the effect size was reported as mean difference (MD) and standard deviation (SD). Parameters of glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), postprandial blood glucose (PBG), fasting serum insulin (FI), insulin resistance (expressed in terms of HOMA-IR), insulin dose (ID) received, serum insulin antibody (IA), and C-peptide (CP) were tested. Out of 4054 collected articles, 14 RCTs (total 663 subjects) were eligible for inclusion. The pooled results obtained using a random-effects model showed a statistically significant decrease in HbA1c levels (MD, −1.24, 95% confidence interval (CI): −2.00, −0.48, p < 0.001 heterogeneity (I²) = 94%) and ID received (MD, −16.72, 95% CI: −22.09, −11.35 p < 0.00001, I² = 90%), with a clear tendency was shown, but non-significant, to decrease FBG (MD, −23.32, 95% CI: −47.33, 0.70, p = 0.06, I² = 98%) in patients with diabetes who consumed CM in comparison to those on usual care. Conversely, the consumption of CM did not show significant reductions in the rest of the glucose homeostasis parameters. Subgroup analysis revealed that patients with T2DM were more beneficially affected by CM intake than those with T1DM in lowering FBG, while patients with T1DM were more beneficially affected by CM intake than those with T2DM in lowering HbA1c. Both fresh and treated (pasteurized/fermented) CM gave similar beneficial effects in lowering HbA1c. Lastly, a relatively superior effect for longer duration on shorter duration (>6 months, ≤6 months, respectively) of CM intake is found in lowering HbA1c. To conclude, long-term consumption of CM by patients with diabetes could be a useful adjuvant therapy alongside classical medications, especially in lowering the required insulin dose and HbA1c. Due to the high heterogeneity observed in the included studies, more controlled trials with a larger sample size are warranted to confirm our results and to control some confounders and interfering factors existing in the analyzed articles.     

Vitamin D Status and Gestational Diabetes in Russian Pregnant Women in the Period between 2012 and 2021: A Nested Case–Control Study

Several meta-analyses found an association between low maternal serum 25-hydroxyvitamin D (25(OH)D) level and gestational diabetes mellitus (GDM). However, some of them reported significant heterogeneity. We examined the association of serum 25(OH)D concentration measured in the first and in the second halves of pregnancy with the development of GDM in Russian women surveyed in the periods of 2012–2014 and 2018–2021. We conducted a case–control study (including 318 pregnant women) nested on two previous studies. In 2012–2014, a total of 214 women (83 GDM and 131 controls) were enrolled before 15 weeks of gestation and maternal serum 25(OH)D concentrations were measured twice: at 8th–14th week of gestation and simultaneously with two-hour 75 g oral glucose tolerance test (OGTT) at 24th–32nd week of gestation. In the period of 2018–2021, 104 women (56 GDM and 48 controls) were included after OGTT and 25(OH)D concentrations were measured at 24th–32nd week of gestation. Median 25(OH)D levels were 20.0 [15.1–25.7] vs. 20.5 [14.5–27.5] ng/mL (p = 0.565) in GDM and control group in the first half of pregnancy and 25.3 [19.8–33.0] vs. 26.7 [20.8–36.8] ng/mL (p = 0.471) in the second half of pregnancy, respectively. The prevalence rates for vitamin D deficiency (25(OH)D levels < 20 ng/mL) were 49.4% and 45.8% (p = 0.608) in the first half of pregnancy and 26.2% vs. 22.1% (p = 0.516) in the second half of pregnancy in women who developed GDM and in women without GDM, respectively. The frequency of vitamin D supplements intake during pregnancy increased in 2018–2021 compared to 2012–2014 (p = 0.001). However, the third trimester 25(OH)D levels and prevalence of vitamin D deficiency (25.5 vs. 23.1, p = 0.744) did not differ in women examined in the periods of 2012–2014 and 2018–2021. To conclude, there was no association between gestational diabetes risk and maternal 25(OH)D measured both in the first and in the second halves of pregnancy. The increased prevalence of vitamin D supplements intake during pregnancy by 2018–2021 did not lead to higher levels of 25(OH)D.     

A Systematic Review,Meta-Analysis and Meta-Regression on the Effects of Carbohydrates on Sleep

This study aimed to assess the effects of quantity, quality and periodization of carbohydrates consumption on sleep. PubMed, SCOPUS and Cochrane Library were searched through October 2020. Data were pooled using random-effects meta-analysis. Eleven articles were included in the meta-analysis which consisted of 27 separate nutrition trials, resulting in 16 comparison data sets (sleep quantity n = 11; sleep quality n = 5). Compared to high carbohydrate (HCI), low carbohydrate intake (LCI) moderately increased duration and proportion of N3 sleep stage (ES = 0.37; 95% CI = 0.18, 0.56; p < 0.001 and ES = 0.51; 95% CI = 0.33, 0.69; p < 0.001, respectively). HCI prolonged rapid eye movement (REM) stage duration (ES = −0.38; 95% CI = 0.05, −8.05; p < 0.001) and proportion (ES = −0.46; 95% CI = −0.83, −0.01; p < 0.001), compared to LCI. The quality of carbohydrate intake did not affect sleep stages. Meta-regression showed that the effectiveness of carbohydrate quantity and quality in sleep onset latency was significantly explained by alterations of carbohydrate intake as a percentage of daily energy intake (R² = 25.87, p = 0.018) and alterations in the glycemic load (R² = 50.8, p = 0.048), respectively. Alterations in glycemic load partially explained the variance of the effectiveness of carbohydrate quality in sleep efficiency (R² = 89.2, p < 0.001) and wake after sleep onset (R² = 64.9, p = 0.018). Carbohydrate quantity was shown to affect sleep architecture, and especially N3 and REM sleep stages. Alterations in both quantity and quality of carbohydrate intake showed a significant effect on sleep initiation. Variations in carbohydrate quality significantly affected measures of sleep continuation. Further studies are needed to assess the effect of long-term carbohydrate interventions on sleep.     

Vitamin C Supplementation Slightly Improves Physical Activity Levels and Reduces Cold Incidence in Men with Marginal Vitamin C Status: A Randomized Controlled Trial

The early indications of vitamin C deficiency are unremarkable (fatigue, malaise, depression) and may manifest as a reduced desire to be physically active; moreover, hypovitaminosis C may be associated with increased cold duration and severity. This study examined the impact of vitamin C on physical activity and respiratory tract infections during the peak of the cold season. Healthy non-smoking adult men (18–35 years; BMI < 34 kg/m²; plasma vitamin C < 45 µmol/L) received either 1000 mg of vitamin C daily (n = 15) or placebo (n = 13) in a randomized, double-blind, eight-week trial. All participants completed the Wisconsin Upper Respiratory Symptom Survey-21 daily and the Godin Leisure-Time Exercise Questionnaire weekly. In the final two weeks of the trial, the physical activity score rose modestly for the vitamin C group vs. placebo after adjusting for baseline values: +39.6% (95% CI [−4.5,83.7]; p = 0.10). The number of participants reporting cold episodes was 7 and 11 for the vitamin C and placebo groups respectively during the eight-week trial (RR = 0.55; 95% CI [0.33,0.94]; p = 0.04) and cold duration was reduced 59% in the vitamin C versus placebo groups (−3.2 days; 95% CI [−7.0,0.6]; p = 0.06). These data suggest measurable health advantages associated with vitamin C supplementation in a population with adequate-to-low vitamin C status.     

Role of Whole Grain Consumption in Glycaemic Control of Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Observational studies have indicated beneficial effects of whole grain consumption on human health. However, no evidence based on randomized controlled trials has been established. Our objective was to perform a systematic review and meta-analysis of randomized controlled trials to assess the effects of whole grain consumption in glycaemic control of diabetic patients. Methods: A comprehensive search in four databases (Web of Science, Pubmed, Scopus and Cochrane library) was conducted to collect potential articles which measured the roles of whole grain consumption on glycaemic control up to October 2021. Results: A total of 16 eligible trials involving 1068 subjects were identified to evaluate the pooled effect. The overall results indicated that compared with the control group, whole grain intake presented a significantly reduced concentration in fast plasma glucose (WMD = −0.51 mmol/L, 95% CI: −0.73, −0.28; I2 = 88.6%, p < 0.001), a homeostasis model assessment of insulin resistance (WMD = −0.39 μU × mol/L², 95% CI: −0.73, −0.04; I2 = 58.4%, p = 0.014), and glycosylated haemoglobin (WMD = −0.56%, 95% CI: −0.88, −0.25, I2 = 88.5%, p < 0.001), while no significant difference was observed in fast plasma insulin level between groups (SMD = −0.05, 95% CI: −0.25, 0.14; I2 = 40.7%, p = 0.120). In terms of incremental area under the curve (iAUC), data suggested that whole grain effected a significant decrease in Glucose-iAUC (WMD = −233.09 min × mmol/L, 95% CI: −451.62, −14.57; I2 = 96.1%, p < 0.001) and Insulin-iAUC (SMD = −4.80, 95% CI: −8.36, −1.23; I2 = 89.9%, p = 0.002), although only in a small number of studies. Of note, there is evidence for modest unexplained heterogeneity in the present meta-analysis. Conclusion: Whole grain consumption confers a beneficial effect on glucose metabolism in patients with diabetes. Regrettably, since relevant studies were scarce, we failed to provide confident evidence of whole grain consumption on acute effects including Glucose-iAUC and Insulin-iAUC, which should be addressed in further trials.