Pharmacokinetics of Nitrate and Nitrite Following Beetroot Juice Drink Consumption

Background: Nitrate (NO₃⁻)-rich beetroot (BR) juice supplementation has been shown to improve cardiovascular function via reduction to nitrite (NO₂⁻) and then to the bioactive molecule nitric oxide (NO). However, limited research exists for the role of inorganic NO₂⁻ that is contained naturally within BR. Objective: As BR juice can naturally contain both NO₃⁻ and NO₂⁻ the objective of this study was to evaluate the individual effects of NO₃⁻ and NO₂⁻ consumed from BR on plasma [NO₃⁻]/[NO₂⁻] and their subsequent effects on various cardiovascular measures. Design: In four separate treatments, 11 healthy adults consumed 250 mL of BR containing one of the following: (i) high NO₃⁻, low NO₂⁻ (HL; 572 mg NO₃⁻, 32 mg NO₂⁻); (ii) medium NO₃⁻, medium NO₂⁻ (MM; 280 mg NO₃⁻, 237 mg NO₂⁻); (iii) low NO₃⁻, medium NO₂⁻ (LM; 43 mg NO₃⁻, 262 mg NO₂⁻); (iv) placebo (PL; low NO₃⁻, low NO₂⁻: 8 mg NO₃⁻, 5.8 mg NO₂⁻). Plasma [NO₃⁻]/[NO₂⁻], blood pressure, heart rate, mean arterial pressure (MAP), cardiac output and stroke volume were measured at baseline and every hour or second hour for 6 h post-BR consumption. Outcomes: Ingestion of the HL and MM BR increased plasma [NO₂⁻] and [NO₃⁻] after 2 h, with both remaining elevated after 6 h (p < 0.05). LM increased plasma [NO₃⁻] (p < 0.05) but did not increase plasma [NO₂⁻] compared to PL (p = 0.177). MAP was lower following the consumption of HL at 4 h and LM at 6 h (p < 0.05). Conclusion: Inorganic NO₃⁻ consumption is the critical factor in elevating plasma [NO₃⁻] and [NO₂⁻]; however, both NO₂⁻ and NO₃⁻ show potential to reduce MAP. The known reduction of systolic blood pressure (SBP)/diastolic blood pressure (DBP) following NO₃⁻ supplementation was not observed, making it unclear if NO₂⁻ contributes to a reduction in SBP/DBP alongside NO₃⁻.     

Acceptability and Feasibility of a 13-Week Pilot Randomised Controlled Trial Testing the Effects of Incremental Doses of Beetroot Juice in Overweight and Obese Older Adults

Nitrate-rich food can increase nitric oxide production and improve vascular and brain functions. This study examines the feasibility of a randomised controlled trial (RCT) testing the effects of prolonged consumption of different doses of dietary nitrate (NO₃⁻) in the form of beetroot juice (BJ) in overweight and obese older participants. A single-blind, four-arm parallel pilot RCT was conducted in 62 overweight and obese (30.4 ± 4 kg/m²) older participants (mean ± standard deviation (SD), 66 ± 4 years). Participants were randomized to: (1) high-NO₃⁻ (HN: 2 × 70 mL BJ/day) (2) medium-NO₃⁻ (MN: 70 mL BJ/day), (3) low-NO₃⁻ (LN: 70 mL BJ on alternate days) or (4) Placebo (PL: 70 mL of NO₃⁻-depleted BJ on alternate days), for 13 weeks. Compliance was checked by a daily log of consumed BJ, NO₃⁻ intake, and by measuring NO₃⁻ and NO₂⁻ concentrations in plasma, saliva, and urine samples. Fifty participants completed the study. Self-reported compliance to the interventions was >90%. There were significant positive linear relationships between NO₃⁻ dose and the increase in plasma and urinary NO₃⁻ concentration (R² = 0.71, p < 0.001 and R² = 0.46 p < 0.001, respectively), but relationships between NO₃⁻ dose and changes in salivary NO₃⁻ and NO₂⁻ were non-linear (R² = 0.35, p = 0.002 and R² = 0.23, p = 0.007, respectively). The results confirm the feasibility of prolonged BJ supplementation in older overweight and obese adults.     

Nitrate Ingestion: A Review of the Health and Physical Performance Effects

This paper provides an overview of the current literature and scientific evidence surrounding inorganic nitrate (NO₃⁻) supplementation and its potential for improving human health and physical performance. As indicative of the ever-expanding organic and natural food consumer market, athletes and health enthusiasts alike are constantly searching for ingredient-specific “super foods” and dietary supplements capable of eliciting health and performance benefits. Evidence suggests that NO₃⁻ is the viable active component within beetroot juice (BRJ) and other vegetables, responsible for health-promoting and ergogenic effects. Indeed, multiple studies support NO₃⁻ supplementation as an effective method to improve exercise performance. NO₃⁻ supplementation (either as BRJ or sodium nitrate [NaNO₃⁻]) has also demonstrated modest benefits pertaining to cardiovascular health, such as reducing blood pressure (BP), enhancing blood flow, and elevating the driving pressure of O₂ in the microcirculation to areas of hypoxia or exercising tissue. These findings are important to cardiovascular medicine/exercise physiology and suggest a possible role for NO₃⁻ supplementation: (1) as a low-cost prevention and treatment intervention for patients suffering from blood flow disorders; and (2) an effective, natural ergogenic aid for athletes. Benefits have been noted following a single bolus, as well as daily supplementation of NO₃⁻. While results are promising, additional research is needed to determine the impact of NO₃⁻ supplementation on anaerobic exercise performance, to identify principle relationships between isolated nitrate and other ingredients found in nitrate-rich vegetables (e.g., vitamin C, polyphenols, fatty acids, thiocyanate), to explore the specific dose-response relationships needed to elicit health and ergogenic benefits, to prolong the supplementation period beyond a relatively short period (i.e., >15 days), to determine if more robust effects can be observed with longer-term treatment, and to fully examine the safety of chronic NO₃⁻ supplementation, as this continues to be a concern of some.     

Effect of Beetroot Juice Supplementation on Aerobic Response during Swimming

The beneficial effects of beetroot juice supplementation (BJS) have been tested during cycling, walking, and running. The purpose of the present study was to investigate whether BJS can also improve performance in swimmers. Fourteen moderately trained male master swimmers were recruited and underwent two incremental swimming tests randomly assigned in a pool during which workload, oxygen uptake (VO₂), carbon dioxide production (VCO₂), pulmonary ventilation (VE), and aerobic energy cost (AEC) of swimming were measured. One was a control swimming test (CSW) and the other a swimming test after six days of BJS (0.5l/day organic beetroot juice containing about 5.5 mmol of NO₃⁻). Results show that workload at anaerobic threshold was significantly increased by BJS as compared to the CSW test (6.3 ± 1 and 6.7 ± 1.1 kg during the CSW and the BJS test respectively). Moreover, AEC was significantly reduced during the BJS test (1.9 ± 0.5 during the SW test vs. 1.7 ± 0.3 kcal·kg⁻¹·h⁻¹ during the BJS test). The other variables lacked a statistically significant effect with BJS. The present investigation provides evidence that BJS positively affects performance of swimmers as it reduces the AEC and increases the workload at anaerobic threshold.     

Impact of Leucine Supplementation on Exercise Training Induced Anti-Cardiac Remodeling Effect in Heart Failure Mice

Leucine supplementation potentiates the effects of aerobic exercise training (AET) on skeletal muscle; however, its potential effects associated with AET on cardiac muscle have not been clarified yet. We tested whether leucine supplementation would potentiate the anti-cardiac remodeling effect of AET in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α_2A/α_2CARKO). Mice were assigned to five groups: wild type mice treated with placebo and sedentary (WT, n = 11), α_2A/α_2CARKO treated with placebo and sedentary (KO, n = 9), α_2A/α_2CARKO treated with leucine and sedentary (KOL, n = 11), α_2A/α_2CARKO treated with placebo and AET (KOT, n = 12) or α_2A/α_2CARKO treated with leucine and AET (KOLT, n = 12). AET consisted of four weeks on a treadmill with 60 min sessions (six days/week, 60% of maximal speed) and administration by gavage of leucine (1.35 g/kg/day) or placebo (distilled water). The AET significantly improved exercise capacity, fractional shortening and re-established cardiomyocytes’ diameter and collagen fraction in KOT. Additionally, AET significantly prevented the proteasome hyperactivity, increased misfolded proteins and HSP27 expression. Isolated leucine supplementation displayed no effect on cardiac function and structure (KOL), however, when associated with AET (KOLT), it increased exercise tolerance to a higher degree than isolated AET (KOT) despite no additional effects on AET induced anti-cardiac remodeling. Our results provide evidence for the modest impact of leucine supplementation on cardiac structure and function in exercised heart failure mice. Leucine supplementation potentiated AET effects on exercise tolerance, which might be related to its recognized impact on skeletal muscle.     

Effect of Vitamin D Supplementation on Skeletal Muscle Volume and Strength in Patients with Decompensated Liver Cirrhosis Undergoing Branched Chain Amino Acids Supplementation: A Prospective,Randomized, Controlled Pilot Trial

Background: Sarcopenia worsens patient prognoses in chronic liver disease. This study aimed to elucidate the effects of vitamin D supplementation on skeletal muscle volume and strength in patients with decompensated cirrhosis. Methods: Thirty-three patients were entered into the study based on the criteria and then randomly assigned to two groups: Group A (n = 17), the control group, and Group B (n = 16), those who received oral native vitamin D3 at a dose of 2000 IU once a day for 12 months. Results: SMI values in Group B were significantly increased at 12 months (7.64 × 10⁻³). The extent of changes in the SMI and grip strength in Group B were significantly greater than that in Group A at 12 months (p = 2.57 × 10⁻³ and 9.07 × 10⁻³). The median change rates in the SMI were +5.8% and the prevalence of sarcopenia was significantly decreased from 80.0% (12/15) to 33.3% (5/15; p = 2.53 × 10⁻²) in Group B. Conclusions: Vitamin D supplementation might be an effective and safe treatment option for patients with decompensated cirrhosis to increase or restore the skeletal muscle volume and strength or prevent the muscle volume and strength losses.     

Effects of Milk Protein in Resistance Training-Induced Lean Mass Gains for Older Adults Aged ≥ 60 y: A Systematic Review and Meta-Analysis

This review evaluated the effects of milk-based protein supplementation on resistance training (RT)-induced gains in lean body mass or fat free mass (LBM/FFM) and muscle strength for older adults. A systematic search of PubMed, Scopus and EBSCOhost/SPORTDiscus was conducted. Eligibility criteria: Randomized controlled trials comparing all types of milk-based protein supplements with control supplements for the training older adults at mean age ≥ 60 y. Twenty studies were included in the qualitative synthesis, whilst seventeen studies were included in the quantitative synthesis. A dose of 10–15 g of milk protein supplementation was sufficient to augment RT-induced LBM/FFM. Intriguingly, four out of five studies show negative effect of whey protein supplementation at the same dose range (or even higher) compared with control supplementation (−0.49 kg, 95% CI: −0.69, −0.29, I² = 14%, Z = 4.82, p < 0.001). For milk-based protein supplementation, RT-induced improvements in muscle strength were observed only when the protein doses ≥22 g (+0.66 kg, 95% CI: 0.07, 1.25, I² = 0%, Z = 2.18, p = 0.03). Conclusion: Milk protein is superior to whey protein in enhancing RT-induced LBM/FFM gains for older adults. Optimal daily protein intake can dilute the protein supplementation effect.     

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth

Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m²: adjusted mean difference (aMD) −0.11[95% CI −0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.     

Prebiotic Inulin Supplementation and Peripheral Insulin Sensitivity in adults at Elevated Risk for Type 2 Diabetes: A Pilot Randomized Controlled Trial

Prediabetes affects 84.1 million adults, and many will progress to type 2 diabetes (T2D). The objective of this proof-of-concept trial was to determine the efficacy of inulin supplementation to improve glucose metabolism and reduce T2D risk. Adults (n = 24; BMI: 31.3 ± 2.9 kg/m²; age: 54.4 ± 8.3 years) at risk for T2D were enrolled in this controlled feeding trial and consumed either inulin (10 g/day) or placebo (maltodextrin, 10 g/day) for six weeks. Assessments included peripheral insulin sensitivity, fasting glucose, and insulin, HOMA-IR, in vivo skeletal muscle substrate preference, Bifidobacteria copy number, intestinal permeability, and endotoxin concentrations. Participant retention was 92%. There were no baseline group differences except for fasting insulin (p = 0.003). The magnitude of reduction in fasting insulin concentrations with inulin (p = 0.003, inulin = Δ-2.9, placebo = Δ2.3) was attenuated after adjustment for baseline concentrations (p = 0.04). After adjusting for baseline values, reduction in HOMA-IR with inulin (inulin = Δ-0.40, placebo=Δ0.27; p = 0.004) remained significant. Bifidobacteria 16s increased (p = 0.04; inulin = Δ3.1e⁹, placebo = Δ-8.9e⁸) with inulin supplementation. Despite increases in gut Bifidobacteria, inulin supplementation did not improve peripheral insulin sensitivity. These findings question the need for larger investigations of inulin and insulin sensitivity in this population.     

Traffic-Related Air Pollution and Congenital Anomalies in Barcelona

Background: A recent meta-analysis suggested evidence for an effect of exposure to ambient air pollutants on risk of certain congenital heart defects. However, few studies have investigated the effects of traffic-related air pollutants with sufficient spatial accuracy.Objectives: We estimated associations between congenital anomalies and exposure to traffic-related air pollution in Barcelona, Spain.Method: Cases with nonchromosomal anomalies (n = 2,247) and controls (n = 2,991) were selected from the Barcelona congenital anomaly register during 1994–2006. Land use regression models from the European Study of Cohorts for Air Pollution Effects (ESCAPE), were applied to residential addresses at birth to estimate spatial exposure to nitrogen oxides and dioxide (NO_x, NO₂)_, particulate matter with diameter ≤ 10 μm (PM₁₀), 10–2.5 μm (PM_coarse), ≤ 2.5 μm (PM_2.5), and PM_2.5 absorbance. Spatial estimates were adjusted for temporal trends using data from routine monitoring stations for weeks 3–8 of each pregnancy. Logistic regression models were used to calculate odds ratios (ORs) for 18 congenital anomaly groups associated with an interquartile-range (IQR) increase in exposure estimates.Results: In spatial and spatiotemporal exposure models, we estimated statistically significant associations between an IQR increase in NO₂ (12.2 μg/m³) and coarctation of the aorta (OR_{spatiotemporal} = 1.15; 95% CI: 1.01, 1.31) and digestive system defects (OR_{spatiotemporal} = 1.11; 95% CI: 1.00, 1.23), and between an IQR increase in PM_coarse (3.6 μg/m³) and abdominal wall defects (OR_{spatiotemporal} = 1.93; 95% CI: 1.37, 2.73). Other statistically significant increased and decreased ORs were estimated based on the spatial model only or the spatiotemporal model only, but not both.Conclusions: Our results overall do not indicate an association between traffic-related air pollution and most groups of congenital anomalies. Findings for coarctation of the aorta are consistent with those of the previous meta-analysis.Citation: Schembari A, Nieuwenhuijsen MJ, Salvador J, de Nazelle A, Cirach M, Dadvand P, Beelen R, Hoek G, Basagaña X, Vrijheid M. 2014. Traffic-related air pollution and congenital anomalies in Barcelona. Environ Health Perspect 122:317–323; http://dx.doi.org/10.1289/ehp.1306802     

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.     

Cross-Sectional Study of the Prevalence of Cobalamin Deficiency and Vitamin B12 Supplementation Habits among Vegetarian and Vegan Children in the Czech Republic

Vegetarian (VG) and vegan (VN) diets in childhood are of growing interest due to their perceived health and environmental benefits. Concerns remain due to the possible disruption of healthy growth and development of children because of the scarcity of evidence-based studies. Among the nutrients of special concern is vitamin B12. Therefore, the Czech Vegan Children Study (CAROTS) decided to examine the relationship between B12 metabolism parameters and B12 intake through diet and supplementation. We analyzed laboratory parameters within n = 79 VG, n = 69 VN, and n = 52 omnivores (OM) children (0–18 years old). There were no significant differences in levels of holotranscobalamin (aB12), folate, homocysteine (hcys), or mean corpuscular volume. However, there was a significant difference in levels of cyanocobalamin (B12) (p = 0.018), even though we identified only n = 1 VG and n = 2 VN children as B12 deficient. On the other hand, we identified n = 35 VG, n = 28 VN, and n = 9 OM children with vitamin B12 hypervitaminosis (p = 0.004). This finding was related to a high prevalence of over-supplementation in the group (mean dose for VG 178.19 ± 238.5 µg per day; VN 278.35 ± 394.63 µg per day). Additionally, we found a significant (p < 0.05) difference between B12, aB12, and hcys levels of supplemented vs. non-supplemented VG/VN children. This can show that the intake of vitamin B12 via diet in the VG group might not be sufficient. Secondly, we analyzed a relation between supplement use in pregnancy and breastfeeding and its impact on vitamin B12 levels of children aged 0–3 years. Out of n = 46 mothers, only n = 3 (e.g., 6.5%) were not supplemented at all. We have not identified any clinical manifestation of B12 deficiency and only n = 1 child with low serum cobalamin, a child who did not receive vitamin B12 supplementation and whose mother took only low doses of vitamin B12 (25/µg/day).To conclude, we did not observe any life-threatening or severe consequences of laboratory-stated vitamin B12 deficiency; thus, our group was well supplemented. On the other hand, we have identified many subjects with vitamin B12 hypervitaminosis of unknown impact on their health. Further research and new guidelines for B12 supplementation among VG and VN children are needed.     

Effect of Omega-3 Supplementation on Self-Regulation in Typically Developing Preschool-Aged Children: Results of the Omega Kid Pilot Study—A Randomised,Double-Blind,Placebo-Controlled Trial

Supplementation of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) may enhance self-regulation (SR) and executive functioning (EF) in children of preschool age. The aim of the Omega Kid Study was to investigate the effect of n-3 LCPUFA supplementation on SR and EF in typically developing preschool-aged children. A double-blind placebo-controlled pilot trial was undertaken, the intervention was 12 weeks and consisted of 1.6 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day compared to placebo. The HS-Omega-3 Index^® was assessed by capillary blood samples at baseline and post-intervention. Seventy-eight children were enrolled and randomised to either the n-3 LCPUFA treatment (n = 39) or placebo (n = 39) group. Post intervention, there was a significant three-fold increase in the HS-Omega-3 Index^® in the n-3 LCPUFA group (p < 0.001). There were no improvements in SR or EF outcome variables for the n-3 LCPUFA group post intervention compared to the placebo group determined by linear mixed models. At baseline, there were significant modest positive Spearman correlations found between the HS-Omega-3 index^® and both behavioural self-regulation and cognitive self-regulation (r = 0.287, p = 0.015 and r = 0.242, p = 0.015 respectively). Although no treatment effects were found in typically developing children, further research is required to target children with sub-optimal self-regulation who may benefit most from n-3 LCPUFA supplementation.     

Changes in the Gut Bacteria Composition of Healthy Men with the Same Nutritional Profile Undergoing 10-Week Aerobic Exercise Training: A Randomized Controlled Trial

Nutrient consumption and body mass index (BMI) are closely related to the gut microbiota, and exercise effects on gut bacteria composition may be related to those variables. Thus, we aimed to investigate the effect of 10-week moderate aerobic exercise on the cardiorespiratory fitness and gut bacteria composition of non-obese men with the same nutritional profile. Twenty-four previously sedentary men (age 25.18 [SD 4.66] years, BMI 24.5 [SD 3.72] kg/m²) were randomly assigned into Control (CG; n = 12) or Exercise Groups (EG; n = 12). Body composition, cardiorespiratory parameters, blood markers, dietary habits and gut bacteria composition were evaluated. EG performed 150 min per week of supervised moderate (60–65% of VO₂peak) aerobic exercise, while CG maintained their daily routine. The V4 16S rRNA gene was sequenced and treated using QIIME software. Only EG demonstrated marked improvements in cardiorespiratory fitness (VO₂peak, p < 0.05; Effect Size = 0.971) without changes in other gut bacteria-affecting variables. Exercise did not promote clustering based on diversity indices (p > 0.05), although significant variations in an unclassified genus from Clostridiales order and in Streptococcus genus were observed (p < 0.05). Moreover, α-diversity was correlated with VO₂peak (Pearson’s R: 0.47; R² 0.23: 95%CI: 0.09 to 0.74, p = 0.02) and BMI (Pearson’s R: −0.50; R² 0.25: 95%CI: −0.75 to −0.12, p = 0.01). Roseburia, Sutterella and Odoribacter genera were associated with VO₂peak, while Desulfovibrio and Faecalibacterium genera were associated with body composition (p < 0.05). Our study indicates that aerobic exercise at moderate intensity improved VO₂peak and affected gut bacteria composition of non-obese men who maintained a balanced consumption of nutrients.     

Effects of poly-gamma-glutamic acid and vitamin B6 supplements on sleep status: a randomized intervention study

BACKGROUD/OBJECTIVESData regarding the effects of poly-γ-glutamic acid (γ-PGA) on sleep status are limited. This study aimed to test whether γ-PGA and vitamin B₆ (VitB6) supplements improve sleep duration and quality.SUBJECTS/METHODSA factorial randomized, double-blinded, placebo-controlled crossover study included 47 adults (25 men and 22 women) who were free of chronic disease. Stratified randomized allocation considered age and gender for three interventions, group A (supplementation with γ-PGA 600 mg; n = 16), group B (supplementation with VitB6 100 mg; n = 14), and group C (dual supplementation of both γ-PGA 600 mg and VitB6 100 mg; n = 17). Participants underwent a 1-mon intervention period, followed by a 1-mon washout period, and then a second 1-mon intervention period. Differences (mean ± SD) in nighttime sleep status before and after supplementation were compared between the placebo and intervention groups using nonparametric tests.RESULTSSignificant changes in sleep duration (0.27 ± 0.98 h, P < 0.05) and the Pittsburgh Sleep Quality Index global score (−0.52 ± 1.58, P < 0.05) indicating improved sleep status were observed in the intervention compared with the placebo of group C while no significant changes were observed in groups A and B. No statistical significance was detected between the intervention and the placebo; however, there was a greater increase in the group C intervention (4.59 ± 38.5 ng/mL) in serum serotonin concentrations than the groups A and B interventions. No side effects were observed.CONCLUSIONSOn the basis of these findings, the dual supplementation of γ-PGA and VitB6 may be effective as functional food components to improve nighttime sleep status.Trial RegistrationClinical Research Information Service Identifier: KCT0005083     

Repeated Nitrogen Dioxide Exposures and Eosinophilic Airway Inflammation in Asthmatics: A Randomized Crossover Study

Background: Nitrogen dioxide (NO₂), a ubiquitous atmospheric pollutant, may enhance the asthmatic response to allergens through eosinophilic activation in the airways. However, the effect of NO₂ on inflammation without allergen exposure is poorly studied.Objectives: We investigated whether repeated peaks of NO₂, at various realistic concentrations, induce changes in airway inflammation in asthmatics.Methods: Nineteen nonsmokers with asthma were exposed at rest in a double-blind, crossover study, in randomized order, to 200 ppb NO₂, 600 ppb NO₂, or clean air once for 30 min on day 1 and twice for 30 min on day 2. The three series of exposures were separated by 2 weeks. The inflammatory response in sputum was measured 6 hr (day 1), 32 hr (day 2), and 48 hr (day 3) after the first exposure, and compared with baseline values measured twice 10–30 days before the first exposure.Results: Compared with baseline measurements, the percentage of eosinophils in sputum increased by 57% after exposure to 600 ppb NO₂ (p = 0.003) but did not change significantly after exposure to 200 ppb. The slope of the association between the percentage of eosinophils and NO₂ exposure level was significant (p = 0.04). Eosinophil cationic protein in sputum was highly correlated with eosinophil count and increased significantly after exposure to 600 ppb NO₂ (p = 0.001). Lung function, which was assessed daily, was not affected by NO₂ exposure.Conclusions: We observed that repeated peak exposures of NO₂ performed without allergen exposure were associated with airway eosinophilic inflammation in asthmatics in a dose-related manner.Citation: Ezratty V, Guillossou G, Neukirch C, Dehoux M, Koscielny S, Bonay M, Cabanes PA, Samet JM, Mure P, Ropert L, Tokarek S, Lambrozo J, Aubier M. 2014. Repeated nitrogen dioxide exposures and eosinophilic airway inflammation in asthmatics: a randomized crossover study. Environ Health Perspect 122:850–855; http://dx.doi.org/10.1289/ehp.1307240     

High Blood Pressure and Long-Term Exposure to Indoor Noise and Air Pollution from Road Traffic

Background: Traffic noise has been associated with prevalence of hypertension, but reports are inconsistent for blood pressure (BP). To ascertain noise effects and to disentangle them from those suspected to be from traffic-related air pollution, it may be essential to estimate people’s noise exposure indoors in bedrooms.Objectives: We analyzed associations between long-term exposure to indoor traffic noise in bedrooms and prevalent hypertension and systolic (SBP) and diastolic (DBP) BP, considering long-term exposure to outdoor nitrogen dioxide (NO₂).Methods: We evaluated 1,926 cohort participants at baseline (years 2003–2006; Girona, Spain). Outdoor annual average levels of nighttime traffic noise (L_night) and NO₂ were estimated at postal addresses with a detailed traffic noise model and a land-use regression model, respectively. Individual indoor traffic L_night levels were derived from outdoor L_night with application of insulations provided by reported noise-reducing factors. We assessed associations for hypertension and BP with multi-exposure logistic and linear regression models, respectively.Results: Median levels were 27.1 dB(A) (indoor L_night), 56.7 dB(A) (outdoor L_night), and 26.8 μg/m³ (NO₂). Spearman correlations between outdoor and indoor L_night with NO₂ were 0.75 and 0.23, respectively. Indoor L_night was associated both with hypertension (OR = 1.06; 95% CI: 0.99, 1.13) and SBP (β = 0.72; 95% CI: 0.29, 1.15) per 5 dB(A); and NO₂ was associated with hypertension (OR = 1.16; 95% CI: 0.99, 1.36), SBP (β = 1.23; 95% CI: 0.21, 2.25), and DBP (β⊇= 0.56; 95% CI: –0.03, 1.14) per 10 μg/m³. In the outdoor noise model, L_night was associated only with hypertension and NO₂ with BP only. The indoor noise–SBP association was stronger and statistically significant with a threshold at 30 dB(A).Conclusion: Long-term exposure to indoor traffic noise was associated with prevalent hypertension and SBP, independently of NO₂. Associations were less consistent for outdoor traffic L_night and likely affected by collinearity.Citation: Foraster M, Künzli N, Aguilera I, Rivera M, Agis D, Vila J, Bouso L, Deltell A, Marrugat J, Ramos R, Sunyer J, Elosua R, Basagaña X. 2014. High blood pressure and long-term exposure to indoor noise and air pollution from road traffic. Environ Health Perspect 122:1193–1200; http://dx.doi.org/10.1289/ehp.1307156     

Effects of Probiotic Supplementation on Exercise with Predominance of Aerobic Metabolism in Trained Population: A Systematic Review,Meta-Analysis and Meta-Regression

The scientific literature about probiotic intake and its effect on sports performance is growing. Therefore, the main aim of this systematic review, meta-analysis and meta-regression was to review all information about the effects of probiotic supplementation on performance tests with predominance of aerobic metabolism in trained populations (athletes and/or Division I players and/or trained population: ≥8 h/week and/or ≥5 workouts/week). A structured search was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA^®) statement and PICOS guidelines in PubMed/MEDLINE, Web of Science (WOS), and Scopus international databases from inception to 1 November 2021. Studies involving probiotic supplementation in trained population and execution of performance test with aerobic metabolism predominance (test lasted more than 5 min) were considered for inclusion. Fifteen articles were included in the final systematic review (in total, 388 participants were included). After 3 studies were removed due to a lack of data for the meta-analysis and meta-regression, 12 studies with 232 participants were involved. With the objective of assessing the risk of bias of included studies, Cochrane Collaboration Guidelines and the Physiotherapy Evidence Database (PEDro) scale were performed. For all included studies the following data was extracted: authors, year of publication, study design, the size of the sample, probiotic administration (dose and time), and characteristics of participants. The random effects model and pooled standardized mean differences (SMDs) were used according to Hedges’ g for the meta-analysis. In order to determine if dose and duration covariates could predict probiotic effects, a meta-regression was also conducted. Results showed a small positive and significant effect on the performance test with aerobic metabolic predominance (SMD = 0.29; CI = 0.08–0.50; p < 0.05). Moreover, the subgroup analysis displayed significant greater benefits when the dose was ≥30 × 10⁹ colony forming units (CFU) (SMD, 0.47; CI, 0.05 to 0.89; p < 0.05), when supplementation duration was ≤4 weeks (SMD, 0.44; CI, 0.05 to 0.84; p < 0.05), when single strain probiotics were used (SMD, 0.33; CI, 0.06 to 0.60; p < 0.05), when participants were males (SMD, 0.30; CI, 0.04 to 0.56; p < 0.05), and when the test was performed to exhaustion (SMD, 0.45; CI, 0.05 to 0.48; p < 0.05). However, with references to the findings of the meta-regression, selected covariates did not predict probiotic effects in highly trained population. In summary, the current systematic review and meta-analysis supported the potential effects of probiotics supplementation to improve performance in a test in which aerobic metabolism is predominant in trained population. However, more research is needed to fully understand the mechanisms of action of this supplement.     

Tomato (Lycopersicon esculentum) Supplementation Induces Changes in Cardiac miRNA Expression,Reduces Oxidative Stress and Left Ventricular Mass,and Improves Diastolic Function

The aim of this study was to evaluate the effects of tomato supplementation on the normal rat heart and the role of oxidative stress in this scenario. Male Wistar rats were assigned to two groups: a control group (C; n = 16), in which animals received a control diet + 0.5 mL of corn oil/kg body weight/day, and a tomato group (T; n = 16), in which animals received a control diet supplemented with tomato +0.5 mL of corn oil/kg body weight/day. After three months, morphological, functional, and biochemical analyses were performed. Animals supplemented with tomato had a smaller left atrium diameter and myocyte cross-sectional area (CSA) compared to the control group (C group: 474 (415–539); T group: 273 (258–297) µm²; p = 0.004). Diastolic function was improved in rats supplemented with tomato. In addition, lipid hydroperoxide was lower (C group: 267 ± 46.7; T group: 219 ± 23.0 nmol/g; p = 0.039) in the myocardium of rats supplemented with tomato. Tomato intake was also associated with up-regulation of miR-107 and miR-486 and down-regulation of miR-350 and miR-872. In conclusion, tomato supplementation induces changes in miRNA expression and reduces oxidative stress. In addition, these alterations may be responsible for CSA reduction and diastolic function improvement.