Mediterranean Diet Maintained Platelet Count within a Healthy Range and Decreased Thrombocytopenia-Related Mortality Risk: A Randomized Controlled Trial

There is little information on the dietary modulation of thrombosis-related risk factors such as platelet count. We aimed to assess the effects of Mediterranean diet (MedDiet) on platelet count and related outcomes in an older population at high cardiovascular risk. In participants of the PREDIMED (PREvención con DIeta MEDiterránea) study, we assessed whether an intervention with a MedDiet enriched with extra-virgin olive oil or nuts, relative to a low-fat control diet, modulated platelet count (n = 4189), the risk of developing thrombocytosis and thrombocytopenia (n = 3086), and the association between these alterations and all-cause mortality (median follow-up time: 3.0 years). Although platelet count increased over time (+0.98·10⁹ units/L·year [95% confidence interval: 0.12; 1.84]), MedDiet interventions moderated this increase, particularly in individuals with near-high baseline count (both MedDiets combined: −3.20·10⁹ units/L·year [−5.81; −0.59]). Thrombocytopenia incidence was lower in the MedDiet interventions (incidence rates: 2.23% in control diet, 0.91% in MedDiets combined; hazard ratio: 0.44 [0.23; 0.83]). Finally, thrombocytopenia was associated with a higher risk of all-cause mortality (hazard ratio: 4.71 [2.69; 8.24]), but this relationship was attenuated in those allocated to MedDiet (p-interaction = 0.018). In brief, MedDiet maintained platelet counts within a healthy range and attenuated platelet-related mortality in older adults at high cardiovascular risk.     

Efficacy of Cognitive Behavioral Therapy in Adherence to the Mediterranean Diet in Metabolic Syndrome Patients: A Randomized Controlled Trial

Objective

Verify the efficacy of cognitive behavioral therapy (CBT) in adherence to the Mediterranean diet (MedDiet) in metabolic syndrome (MetS) patients.

Effect of Berberine on Cardiovascular Disease Risk Factors: A Mechanistic Randomized Controlled Trial

Cardiovascular disease (CVD) is a major contributor to the global burden of disease. Berberine, a long-standing, widely used, traditional Chinese medicine, is thought to have beneficial effects on CVD risk factors and in women with polycystic ovary syndrome. The mechanisms and effects, specifically in men, possibly via testosterone, have not been examined previously. To assess the effect of berberine on CVD risk factors and any potential pathway via testosterone in men, we conducted a randomized, double-blind, placebo-controlled, parallel trial in Hong Kong. In total, 84 eligible Chinese men with hyperlipidemia were randomized to berberine (500 mg orally, twice a day) or placebo for 12 weeks. CVD risk factors (lipids, thromboxane A2, blood pressure, body mass index and waist–hip ratio) and testosterone were assessed at baseline, and 8 and 12 weeks after intervention. We compared changes in CVD risk factors and testosterone after 12 weeks of intervention using analysis of variance, and after 8 and 12 weeks using generalized estimating equations (GEE). Of the 84 men randomized, 80 men completed the trial. Men randomized to berberine had larger reductions in total cholesterol (−0.39 mmol/L, 95% confidence interval (CI) −0.70 to −0.08) and high-density lipoprotein cholesterol (−0.07 mmol/L, 95% CI −0.13 to −0.01) after 12 weeks. Considering changes after 8 and 12 weeks together, berberine lowered total cholesterol and possibly low-density lipoprotein-cholesterol (LDL-c), and possibly increased testosterone. Changes in triglycerides, thromboxane A2, blood pressure, body mass index and waist–hip ratio after the intervention did not differ between the berberine and placebo groups. No serious adverse event was reported. Berberine is a promising treatment for lowering cholesterol. Berberine did not lower testosterone but instead may increase testosterone in men, suggesting sex-specific effects of berberine. Exploring other pathways and assessing sex differences would be worthwhile, with relevance to drug repositioning and healthcare.     

Feasibility and Acceptability of a Healthy Nordic Diet Intervention for the Treatment of Depression: A Randomized Controlled Pilot Trial

Healthy diet interventions have been shown to improve depressive symptoms, but there is a need for randomized controlled trials (RCTs) that are double blind and investigate biological mechanisms. The primary objectives of this randomized controlled pilot trial were to test the palatability of the meals and the acceptability of the intervention in preparation for an 8-week RCT in the future, which will investigate whether a healthy Nordic diet improves depressive symptoms in individuals with major depressive disorder, and associated biological mechanisms. Depressed (n = 10) and non-depressed (n = 6) women and men were randomized to receive either a healthy Nordic diet (ND) or a control diet (CD) for 8 days. Participants were blinded to their diet allocation and the study hypotheses. Health questionnaires were completed before and after the intervention and, throughout the study, questionnaires assessed participants’ liking for the meals, their sensory properties, adherence, and open-ended feedback. In the ND group, 75% of participants consumed only the provided foods, as instructed, compared to 50% of CD participants. The meals of both diets, on average, received good ratings for liking and sensory properties, though the ND ratings were somewhat higher. Overall, results were positive and informative, indicating that the planned RCT will be feasible and well-accepted, with some proposed modifications.     

The Effect of the Mediterranean Diet on Serum Total Antioxidant Capacity in Obese Patients: A Randomized Controlled Trial

Objective: The aim of this work was to evaluate the combined effect of physical activity and 1 and 12 months’ adherence to Mediterranean diet (MD) on serum total antioxidant capacity (TAC) in obese patients, as well as factors contributing to TAC.

Methods: One hundred twenty-four patients were randomly assigned to either MD combined with physical activity or standard hypolypemic diet (SHD) with physical activity. Both groups received counseling and education during the initial week and were invited for the follow-up visits, where data on body weight and blood samples were collected. TAC was determined by Trolox equivalent antioxidant capacity and urate was determined using a uricase spectrophotometric method at the initial visit and after 1 and 12 months.

Results: Eighty-four patients finished the 12-month program and were analyzed. The baseline and 1- and 12-month mean (±SD) TAC values in the MD group (n = 40) were 2.38 ± 0.48, 2.51 ± 0.47, and 2.47 ± 0.45 mmol Trolox equivalent (TE)/L, respectively. In the SHD group (n = 44), TAC values were 2.37 ± 0.49, 2.48 ± 0.49, and 2.31 ± 0.51 mmol TE/L, respectively. There was a statistically significant main effect for time (p < 0.001), as well as statistically significant time–diet interaction effect (p = 0.009). There was no statistically significant correlation between TAC and uric acid after 1 month (p = 0.733) or 12 months (p = 0.844) of the intervention. Based on the regression model, which included gender, diet, physical activity level, and percentage body weight change, the type of diet was the only significantly contributing factor to TAC change after the 12-month period, F = 3.867, df = 3, p = 0.012, R = 0.358, R² = 0.128.

Conclusion: This randomized controlled trial with diet and physical activity intervention and TAC as a primary outcome demonstrated initial antioxidant improvement in both MD and SHD groups and a long-term beneficial effect of MD. The results imply that diet composition—olive oil, nuts, and fish in particular—combined with physical activity modify antioxidant capacity.     

The Effect of Weaning with Adult Food Typical of the Mediterranean Diet on Taste Development and Eating Habits of Children: A Randomized Trial

Mediterranean Diet (Med Diet) is one of the healthiest dietary patterns. We aimed to verify the effects of weaning (i.e., the introduction of solid foods in infants previously fed only with milk) using adult foods typical of Med Diet on children eating habits, and on the microbiota composition. A randomized controlled clinical trial on 394 healthy infants randomized in a 1:1 ratio in a Med Diet group weaned with fresh; seasonal and tasty foods of Med Diet and control group predominantly weaned with industrial baby foods. The primary end point was the percentage of children showing a good adherence to Med Diet at 36 months. Secondary end points were mother’s changes in adherence to Med Diet and differences in children gut microbiota. At 36 months, children showing a good adherence to Med Diet were 59.3% in the Med Diet group and 34.3% in the control group (p < 0.001). An increase in adherence to the Med Diet was observed in the mothers of the Med Diet group children (p < 0.001). At 4 years of age children in the Med Diet group had a higher gut microbial diversity and a higher abundance of beneficial taxa. A Mediterranean weaning with adult food may become a strategy for early nutritional education, to develop a healthy microbiota, to prevent inflammatory chronic diseases and to ameliorate eating habits in children and their families.     

Efficacy of Low-Carbohydrate Ketogenic Diet as an Adjuvant Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: The role of low-carbohydrate ketogenic diet (LCKD) as an adjuvant therapy in antitumor treatment is not well established. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the efficacy of LCKD as an adjuvant therapy in antitumor treatment compared to non-ketogenic diet in terms of lipid profile, body weight, fasting glucose level, insulin, and adverse effects; Methods: In this study, databases such as PubMed, Web of Science, Scopus, CINAHL, and Cochrane trials were searched. Only RCTs that involved cancer participants that were assigned to dietary interventions including a LCKD group and a control group (any non-ketogenic dietary intervention) were selected. Three reviewers independently extracted the data, and the meta-analysis was performed using a fixed effects model or random effects model depending on the I² value or p-value; Results: A total of six articles met the inclusion/exclusion criteria. In the overall analysis, the post-intervention results = standard mean difference, SMD (95% CI) showed total cholesterol (TC) level = 0.25 (−0.17, 0.67), HDL-cholesterol = −0.07 (−0.50, 0.35), LDL-cholesterol = 0.21 (−0.21, 0.63), triglyceride (TG) = 0.09 (−0.33, 0.51), body weight (BW) = −0.34 (−1.33, 0.65), fasting blood glucose (FBG) = −0.40 (−1.23, 0.42) and insulin = 0.11 (−1.33, 1.55). There were three outcomes showing significant results in those in LCKD group: the tumor marker PSA, p = 0.03, the achievement of ketosis p = 0.010, and the level of satisfaction, p = 0.005; Conclusions: There was inadequate evidence to support the beneficial effects of LCKDs on antitumor therapy. More trials comparing LCKD and non-KD with a larger sample size are necessary to give a more conclusive result.     

Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials

Background: Recent systematic reviews and meta-analyses of randomized, double-blind, placebo-controlled trials (double-blind, placebo-controlled RCTs) have reported controversial findings regarding the associations between calcium supplements on the risk of cardiovascular disease (CVD). This meta-analysis aimed to investigate the association between them. Methods: We searched PubMed, EMBASE, the Cochrane Library, and the bibliographies of relevant articles for double-blind, placebo-controlled RCTs in November, 2020. Relative risks (RRs) with 95% confidence intervals (CIs) for the risk of cardiovascular disease were calculated using a random effects model. The main outcomes were CVD, coronary heart disease (CHD), and cerebrovascular disease. Results: A total of 13 double-blind, placebo-controlled RCTs (n = 28,935 participants in an intervention group and 14,243 in a control group)) were included in the final analysis. Calcium supplements significantly increased the risk of CVD (RR 1.15, 95% CI 1.06–1.25], I2 = 0.0%, n = 14) and CHD (RR 1.16, 95% CI 1.05–1.28], I2 = 0.0%, n = 9) in double-blind, placebo-controlled RCTs, specifically in healthy postmenopausal women. In the subgroup meta-analysis, dietary calcium intake of 700–1000 mg per day or supplementary calcium intake of 1000 mg per day significantly increased the risk of CVD and CHD. Conclusions: The current meta-analysis found that calcium supplements increased a risk of CVD by about 15% in healthy postmenopausal women.     

Effectiveness of an Intervention Programme on Adherence to the Mediterranean Diet in a Preschool Child: A Randomised Controlled Trial

Background: The Mediterranean diet is considered one of the dietary patterns with the most accumulated scientific evidence on health benefits. In children, it has positive effects in the prevention of obesity and cardiovascular diseases, as well as in the prevention of diabetes. We aimed to evaluate the medium-term efficacy of an intervention programme, targeting adherence to the Mediterranean diet among preschool children. Methods: In a randomised, parallel trial of participants aged 3–5 years, a school garden was attended in the experimental group, and in the control group, the usual content on the human body and health were taught. Adherence to the Mediterranean diet was assessed using the KIDMED questionnaire, controlling for weight, height, body mass index (BMI) and socio-demographic variables. Results: A reduction in BMI was found in the experimental group after one year and at the end of the follow-up period. In the overall score obtained in the KIDMED survey, a statistical trend was found between the two groups (p = 0.076). In multivariate analysis, consumption of pulses more than once a week’ was predictive of improved diet quality, with an Odds Ratio (OR) in the experimental group of 1.382 (95% CI 1.126–1.695; p = 0.009). Conclusions: The experimental approach improved the quality of the participants’ diet, increasing adherence to the Mediterranean diet due to increased consumption of plant-based protein.     

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.     

The Effects of a Low-Carbohydrate Diet vs. a Low-Fat Diet on Novel Cardiovascular Risk Factors: A Randomized Controlled Trial

Increasing evidence supports a low-carbohydrate diet for weight loss and improvement in traditional cardiovascular disease (CVD) markers. Effects on novel CVD markers remain unclear. We examined the effects of a low-carbohydrate diet (<40 g/day; n = 75) versus a low-fat diet (<30% kcal/day from total fat, <7% saturated fat; n = 73) on biomarkers representing inflammation, adipocyte dysfunction, and endothelial dysfunction in a 12 month clinical trial among 148 obese adults free of diabetes and CVD. Participants met with a study dietitian on a periodic basis and each diet group received the same behavioral curriculum which included dietary instruction and supportive counseling. Eighty percent of participants completed the intervention. At 12 months, participants on the low-carbohydrate diet had significantly greater increases in adiponectin (mean difference in change, 1336 ng/mL (95% CI, 342 to 2330 ng/mL); p = 0.009) and greater decreases in intercellular adhesion molecule-1 concentrations (−16.8 ng/mL (−32.0 to −1.6 ng/mL); p = 0.031) than those on the low-fat diet. Changes in other novel CVD markers were not significantly different between groups. In conclusion, despite the differences in weight changes on diets, a low-carbohydrate diet resulted in similar or greater improvement in inflammation, adipocyte dysfunction, and endothelial dysfunction than a standard low-fat diet among obese persons.     

Effects of Vitamin D Supplementation on Surrogate Markers of Fertility in PCOS Women: A Randomized Controlled Trial

Vitamin D (VD) might play an important role in polycystic ovary syndrome (PCOS) and female fertility. However, evidence from randomized controlled trials (RCT) is sparse. We examined VD effects on anti-Müllerian hormone (AMH) and other endocrine markers in PCOS and non-PCOS women. This is a post hoc analysis of a single-center, double-blind RCT conducted between December 2011 and October 2017 at the endocrine outpatient clinic at the Medical University of Graz, Austria. We included 180 PCOS women and 150 non-PCOS women with serum 25-hydroxyvitamin D (25(OH)D) concentrations <75 nmol/L in the trial. We randomized subjects to receive 20,000 IU of VD3/week (119 PCOS, 99 non-PCOS women) or placebo (61 PCOS, 51 non-PCOS women) for 24 weeks. Outcome measures were AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, dehydroepiandrosterone sulfate, and androstenedione. In PCOS women, we observed a significant treatment effect on FSH (mean treatment effect 0.94, 95% confidence interval [CI] 0.087 to 1.799, p = 0.031) and LH/FSH ratio (mean treatment effect −0.335, 95% CI −0.621 to 0.050, p = 0.022), whereas no significant effect was observed in non-PCOS women. In PCOS women, VD treatment for 24 weeks had a significant effect on FSH and LH/FSH ratio but no effect on AMH levels.     

Effect of the Intake of Isoflavones on Risk Factors of Breast Cancer—A Systematic Review of Randomized Controlled Intervention Studies

Epidemiological studies suggest that high intake of soy isoflavones may protect against breast cancer, but causal relationships can only be established by experimental trials. Thus, we aimed to provide a systematic review of randomized controlled trials (RCTs) on the effect of an isoflavone intake on risk factors of breast cancer in healthy subjects. After a systematic literature search in PubMed, 18 different RCTs with pre- and/or postmenopausal women were included and investigated for details according to the PRISMA guideline. In these studies, isoflavones were provided by soy food or supplements in amounts between 36.5–235 mg/d for a period of 1–36 months. Breast density, estrogens including precursors, metabolites, estrogen response such as length of menstrual cycle, and markers of proliferation and inflammation were considered. However, in most studies, differences were not detectable between isoflavone and control/placebo treatment despite a good adherence to isoflavone treatment, irrespective of the kind of intervention, the dose of isoflavones used, and the duration of isoflavone treatment. However, the lack of significant changes in most studies does not prove the lack of effects as a sample size calculation was often missing. Taking into account the risk of bias and methodological limitations, there is little evidence that isoflavone treatment modulates risk factors of breast cancer in pre- and postmenopausal women. Future studies should calculate the sample size to detect possible effects and consider methodological details to improve the study quality.     

Effect of Five-Year Supplementation of Vitamin C on Serum Vitamin C Concentration and Consumption of Vegetables and Fruits in Middle-Aged Japanese: A Randomized Controlled Trial

Objective: This study was aimed at evaluating the effect of long-term vitamin C supplementation on serum and dietary vitamin C and identifying the factors associated with change in serum concentration.

Methods: A total of 439 subjects with atrophic gastritis initially participated in a randomized clinical trial using vitamin C and β-carotene to prevent gastric cancer. We originally randomized the participants into four treatment groups using a 2×2 factorial design, whereby 0 or 15 mg/day β-carotene and 50 or 500 mg/day vitamin C were administered in a double-blind manner. The β-carotene component was terminated early after a mean treatment duration of four months. Before and upon early termination of β-carotene supplementation, 134 subjects dropped out this trial, while 120 and 124 subjects took the vitamin C supplement at either 50 mg or 500 mg daily for five years.

Results: Changes in serum vitamin C were significantly higher in the high-dose group (38.5% increase, 95% CI = 27.0–49.9) than in the low-dose group (13.0% increase, 5.1–20.9) or in the dropout group (3.3% increase, ?2.1–8.6) after five-year supplementation. The serum vitamin C at baseline was negatively associated with changes in serum vitamin C (p < 0.0001), while high-dose (p < 0.0001) and low-dose (p < 0.05) supplementation and female gender (p < 0.001) were positively associated. Dietary intake of vitamin C in the supplementation group was almost identical before and after five-year supplementation of vitamin C (2.31 mg/day decrease, 95% CI = ?15.3–10.7), while a 17.7 mg/day decrease (95% CI = ?44.2–8.86) was observed in the drop-out group.

Conclusion: Five-year vitamin C supplementation induces a remarkable increase in serum vitamin C concentration, and our intervention program appears to have no effect on dietary vitamin C intake.     

Education to Reduce Potentially Harmful Medication Use Among Residents of Assisted Living Facilities: A Randomized Controlled Trial

ObjectivesThe objectives of this study were (1) to investigate the effect of nurse training on the use of potentially harmful medications; and (2) to explore the effect of nurse training on residents' health-related quality of life (HRQoL), health service utilization, and mortality.DesignA randomized controlled trial.Setting and participantsIn total, 227 residents in 20 wards of assisted living facilities in Helsinki were recruited. The 20 wards were randomized into those in which (1) staff received two 4-hour training sessions on appropriate medication treatment (intervention group), and (2) staff received no additional training and continued to provide routine care (control group).InterventionTwo 4-hour interactive training sessions for nursing staff based on constructive learning theory to recognize potentially harmful medications and corresponding adverse drug events.MeasurementsUse of potentially harmful medications, HRQoL assessed using the 15 dimensional instrument of health-related quality of life, health service utilization, and mortality assessed at baseline, and 6 and 12 months.ResultsDuring the 12-month follow-up, the mean number of potentially harmful medications decreased in the intervention wards [−0.43, 95% confidence interval (CI) −0.71 to −0.15] but remained constant in the control wards (+0.11, 95% CI −0.09 to +0.31) (P = .004, adjusted for age, sex, and comorbidities). HRQoL declined more slowly in the intervention wards (−0.038 (95% CI −0.054 to −0.022) than in the control wards (−0.072 (95% CI −0.089 to −0.055) (P = .005, adjusted for age, sex, and comorbidities). Residents of the intervention wards had significantly less hospital days (1.4 days/person/year, 95% CI 1.2–1.6) than in the control wards (2.3 days/person/year; 95% CI 2.1–2.7) (relative risk 0.60, 95% CI 0.49–0.75, P < .001, adjusted for age, sex, and comorbidities).ConclusionsActivating learning methods directed at nurses in charge of comprehensive care can reduce the use of harmful medications, maintain HRQoL, and reduce hospitalization in residents of assisted living facilities.     

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.     

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.     

The Health Effects of Vitamin D and Probiotic Co-Supplementation: A Systematic Review of Randomized Controlled Trials

Evidence of synergic health effects of co-supplementation with vitamin D and probiotics is emerging. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statement, scientific databases and the grey literature were searched, and a narrative review and risk of bias assessment were conducted. Seven randomized controlled trials were included, which had low risk of bias. Six studies were double-blind, and once single-blind, extended over 6–12 weeks, and included 50–105 participants. Conditions explored included schizophrenia, gestational diabetes, type 2 diabetes and coronary heart disease, polycystic ovarian syndrome, osteopenia, irritable bowel syndrome (IBS), and infantile colic. Supplementation frequency was daily or bi-monthly, with mainly vitamin D3, and Lactobacillus, Bifidobacterium, and Streptococcus. Comparators were placebo, vitamin D, lower vitamin D dose, and probiotics and lower vitamin D dose. The co-supplementation yielded greater health benefits than its comparators did in all studies except in one assessing IBS. Beneficial effects included decreased disease severity, improved mental health, metabolic parameters, mainly insulin sensitivity, dyslipidemia, inflammation, and antioxidative capacity, and lower use of healthcare. Co-supplementation of vitamin D and probiotics generated greater health benefits than its comparators did. More studies in other diseases and various populations are needed to confirm these findings and to elucidate the optimal form, composition, and frequency of this co-supplementation.