Targeting body composition in an older population: do changes in movement behaviours matter? Longitudinal analyses in the PREDIMED-Plus trial.

BACKGROUND: The optimal distribution between physical activity (PA) levels and sedentary behaviour (SB) for the greatest benefits for body composition among older adults with overweight/obesity and chronic health conditions remains unclear. We aimed to determine the prospective association between changes in PA and in SB with concurrent changes in body composition and to examine whether reallocating inactive time into different physical activity levels was associated with 12-month change to body composition in older adults. METHODS: Longitudinal assessment nested in the PREDIMED-Plus trial. A subsample (n = 1564) of men and women (age 55-75 years) with overweight/obesity and metabolic syndrome from both arms of the PREDIMED-Plus trial was included in the present analysis. Participants were followed up at 6 and 12 months. Physical activity and SB were assessed using validated questionnaires. Out of 1564 participants, 388 wore an accelerometer to objectively measure inactive time and PA over a 7-day period. At each time point, participants' body composition was measured using dual-energy X-ray absorptiometry (DXA). Standard covariate-adjusted and isotemporal substitution modelling were applied to linear mixed-effects models. RESULTS: Increasing 30 min of total PA and moderate-to-vigorous physical activity (MVPA) was associated with significant reductions in body fat (ß - 0.07% and - 0.08%) and visceral adipose tissue (VAT) (- 13.9 g, and - 15.6 g) at 12 months (all p values < 0.001). Reallocating 30 min of inactive time to MVPA was associated with reductions in body fat and VAT and with an increase in muscle mass and muscle-to-fat mass ratio (all p values < 0.001). CONCLUSIONS: At 12 months, increasing total PA and MVPA and reducing total SB and TV-viewing SB were associated with improved body composition in participants with overweight or obesity, and metabolic syndrome. This was also observed when substituting 30 min of inactive time with total PA, LPA and MVPA, with the greatest benefits observed with MVPA. TRIAL REGISTRATION: International Standard Randomized Controlled Trial (ISRCTN), 89898870 . Retrospectively registered on 24 July 2014.

Effect of changes in adherence to Mediterranean diet on nutrient density after 1-year of follow-up: results from the PREDIMED-Plus Study.

BACKGROUND: The prevalence of overweight/obesity and related manifestations such as metabolic syndrome (MetS) is increasing worldwide. High energy density diets, usually with low nutrient density, are among the main causes. Some high-quality dietary patterns like the Mediterranean diet (MedDiet) have been linked to the prevention and better control of MetS. However, it is needed to show that nutritional interventions promoting the MedDiet are able to improve nutrient intake. OBJECTIVE: To assess the effect of improving MedDiet adherence on nutrient density after 1 year of follow-up at the PREDIMED-Plus trial. METHODS: We assessed 5777 men (55-75 years) and women (60-75 years) with overweight or obesity and MetS at baseline from the PREDIMED-Plus trial. Dietary changes and MedDiet adherence were evaluated at baseline and after 1 year. The primary outcome was the change in nutrient density (measured as nutrient intake per 1000 kcal). Multivariable-adjusted linear regression models were fitted to analyse longitudinal changes in adherence to the MedDiet and concurrent changes in nutrient density. RESULTS: During 1-year follow-up, participants showed improvements in nutrient density for all micronutrients assessed. The density of carbohydrates (- 9.0%), saturated fatty acids (- 10.4%) and total energy intake (- 6.3%) decreased. These changes were more pronounced in the subset of participants with higher improvements in MedDiet adherence. CONCLUSIONS: The PREDIMED-Plus dietary intervention, based on MedDiet recommendations for older adults, maybe a feasible strategy to improve nutrient density in Spanish population at high risk of cardiovascular disease with overweight or obesity.

Ultra-processed food consumption and semen quality parameters in the Led-Fertyl study.

STUDY QUESTION: Is ultra-processed food (UPF) consumption associated with semen quality parameters? SUMMARY ANSWER: Higher UPF consumption was inversely associated with total sperm count, sperm concentration, and total motility in men of reproductive age. WHAT IS KNOWN ALREADY: The consumption of UPF, which has been rising during the last decades, has been demonstrated to be positively associated with several chronic diseases such as diabetes or cardiovascular diseases. However, the scientific evidence on its potential impact on semen quality remains notably limited. STUDY DESIGN SIZE DURATION: A cross-sectional analysis was conducted using data from 200 healthy men (mean age 28.4 ± 5.5 years) enrolled in the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study between February 2021 and April 2023. PARTICIPANTS/MATERIALS SETTING METHODS: UPF consumption (% of energy from UPF) was estimated according to the NOVA classification system using a validated 143-item semi-quantitative food frequency questionnaire. Total sperm count, sperm concentration, sperm vitality, total motility, progressive motility, and normal sperm forms were set as the main outcomes. Microscopic parameters were analyzed using a phase-contrast microscope and a computer-assisted sperm analysis (CASA) system. Semen samples were collected and tested according to World Health Organization 2010 standards. Multivariable linear regression models were fitted to estimate the associations between UPF tertile and semen quality parameters. MAIN RESULTS AND THE ROLE OF CHANCE: Sperm concentration (ß: -1.42 × 106 spz./ml; 95% CI: -2.72 to -0.12) and motility (ß: -7.83%; 95% CI: -15.16 to -0.51) were lower in participants in the highest tertile of UPF compared to the lowest. A similar association was observed for sperm count when UPF was analyzed per 10% increment of energy from UPF consumption (ß: -1.50 × 106 spz.; 95% CI: -2.83 to -0.17). Theoretically replacing 10% of energy from UPF consumption with 10% of energy from unprocessed or minimally processed food consumption was associated with a higher total sperm count, sperm concentration, total motility, progressive motility, and normal sperm forms. LIMITATIONS REASONS FOR CAUTION: Cross-sectional studies do not permit the drawing of causal inferences. Measurement errors and reporting bias cannot be entirely ruled out. WIDER IMPLICATIONS OF THE FINDINGS: This work suggests that consumption of UPF may have an impact on certain semen quality parameters. Furthermore, opting for unprocessed or minimally processed foods instead of UPFs could potentially benefit semen quality. If these results are replicated in future epidemiological studies with different long-term designs, these novel findings could provide valuable insights for updating or even designing preventive and interventional programs to address infertility among men of reproductive age. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Spanish government's official funding agency for biomedical research, ISCIII, through the Fondo de Investigación para la Salud (FIS), the European Union ERDF/ESF, 'A way to make Europe'/'Investing in your future' [PI21/01447], and the Diputació de Tarragona (2021/11-No.Exp. 8004330008-2021-0022642). J.S.-S. gratefully acknowledges the financial support of ICREA under the ICREA Academia program. C.V.-H. received a predoctoral grant from the Generalitat de Catalunya (2022 FI_B100108). M.Á.M. was supported by the Sara Borrell postdoctoral fellowship (CD21/00045-Instituto de Salud Carlos III (ISCIII)). M.F.d.l.P. was supported by a predoctoral grant from the Rovira i Virgili University and Diputació de Tarragona (2020-PMF-PIPF-8). All authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Healthy and unhealthy dietary patterns and sperm quality from the Led-Fertyl study.

BACKGROUND: Dietary patterns may affect sperm quality, but the scientific evidence is limited. OBJECTIVE: To evaluate the association between adherence to different a-priori dietary patterns and sperm quality parameters in healthy reproductive-age men. MATERIALS AND METHODS: A cross-sectional analysis was conducted using data from 200 young men enrolled in the Led-Fertyl study. Tertiles of six a-priori dietary patterns were estimated: four healthy dietary patterns [Mediterranean Diet Adherence Screener (MEDAS), Dietary Approaches to Stop Hypertension (DASH), Healthful Plant-Based Diet Index (hPDI) and EAT-Lancet Score], and two unhealthy dietary patterns [Western Diet and Unhealthful Plant-Based Diet Index (uPDI)]. Sperm quality parameters (count, concentration, vitality, total and progressive motility, and normal morphology) were considered the main outcomes. RESULTS: Compared with the lowest tertile, participants in the highest MEDAS tertile had higher total sperm count (ß = 3.2;95%CI: 1.0, 5.5) and concentration (ß = 1.8;95%CI: 0.6, 3.0), and total (ß = 8.2;95%CI: 1.3, 15.1) and progressive motility (ß = 7.1;95%CI: 0.2, 14.0). Similarly, participants in the highest hPDI tertile had higher total sperm count (ß = 3.4;95%CI: 1.4, 5.5) and concentration (ß = 1.2;95%CI: 0.0, 2.3) compared with those in the lowest tertile. When these dietary patterns were modelled as continuous variables (for each 1-point increment in the specific score), an inverse association was found between the uPDI and Western and total sperm count [(ß = -2.7;95%CI: -4.8, -0.7) and (ß = -3.8;95%CI: -5.8, -1.7), respectively] and sperm concentration [(ß = -1.2;95%CI: -2.4, -0.1) and (ß = -1.7;95%CI: -2.8, -0.5), respectively]. Compared with participants in the lowest tertile, those in the highest uPDI tertile presented higher odds of abnormal sperm concentration (OR: 4.6;95%CI: 1.0, 19.9) and one or more seminogram abnormalities (OR: 2.3;95%CI: 1.1, 5.0). CONCLUSIONS: Our findings suggest that higher adherence to healthy dietary patterns (Mediterranean and healthful plant-based diet) was positively associated with better sperm quality parameters, in contrast, greater adherence to unhealthy dietary patterns was inversely associated.

Sex-specific dietary patterns and their association with metabolic syndrome: Insights from a cross-sectional analysis.

AIMS: This study aims to identify a posteriori dietary patterns with a sex approach and to evaluate their association with metabolic syndrome criteria. METHODS: Cross-sectional study conducted in 6821 men and women between 55 and 75 years of age. Forty-two food groups were analyzed from dietary information collected with food frequency questionnaires, using principal component analysis and cluster analysis and then information from both statistical methods was compared. Prevalences were calculated foreach cluster group, based on the number and types of metabolic syndrome criteria they met. RESULTS: Following principal component analysis, two dietary patterns labeled "healthy" and "unhealthy" were identified in both men and women, due to the presence of foods that are considered more or less healthy. These same dietary patterns were found in cluster analysis plus an "intermediate" cluster consisting of both healthy and unhealthy foods. The presence of metabolic syndrome is related to the "healthy" dietary pattern in women and to the "unhealthy" dietary pattern in men. Comparison of the two statistical approaches showed a high level of correlation between them (weighted Kappa = 0.703 in women and weighted Kappa = 0.691 in men). CONCLUSIONS: Adherence to both healthy and unhealthy dietary pattern appears to be related to the development of MS. The differences found by sex make it necessary to develop interventions with a sex-specific approach.

Association of monetary diet cost of foods and diet quality in Spanish older adults.

Background: A major barrier to a healthy diet may be the higher price of healthy foods compared to low-quality foods. Objectives: This study aimed to assess the association between the monetary cost of food and diet quality in Spanish older adults at high risk of cardiovascular disease. Methods: Cross-sectional analysis was carried out in Spanish older adults (n = 6,838; 48.6% female). A validated food frequency questionnaire was used to assess dietary intake. Metabolic syndrome severity, adherence to the Mediterranean diet (MedDiet), adherence to a provegetarian dietary pattern, and dietary inflammatory index were assessed. The economic cost of the foods was obtained from the Spanish Ministry of Agriculture Fisheries and Food database (2015-2017, the period of time when the participants were recruited). The total cost of diet adjusted per 1,000 kcal was computed. Results: The healthier dietary pattern was associated with a higher cost of the diet. Higher adherence to the MedDiet, anti-inflammatory diet, and the healthy version of the provegetarian dietary pattern were related to higher costs of the diet. Conclusion: Higher diet quality was associated with a higher dietary cost of the diet per 1,000 kcal/day. Food prices can be an important component of interventions and policies aimed at improving people's diets and preventing diet-related chronic diseases. Clinical trial registry number: The trial was registered in 2014 at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870) with the number 89898870.

Adopting a High-Polyphenolic Diet Is Associated with an Improved Glucose Profile: Prospective Analysis within the PREDIMED-Plus Trial.

Previous studies suggested that dietary polyphenols could reduce the incidence and complications of type-2 diabetes (T2D); although the evidence is still limited and inconsistent. This work analyzes whether changing to a diet with a higher polyphenolic content is associated with an improved glucose profile. At baseline, and at 1 year of follow-up visits, 5921 participants (mean age 65.0 ± 4.9, 48.2% women) who had overweight/obesity and metabolic syndrome filled out a validated 143-item semi-quantitative food frequency questionnaire (FFQ), from which polyphenol intakes were calculated. Energy-adjusted total polyphenols and subclasses were categorized in tertiles of changes. Linear mixed-effect models with random intercepts (the recruitment centers) were used to assess associations between changes in polyphenol subclasses intake and 1-year plasma glucose or glycosylated hemoglobin (HbA1c) levels. Increments in total polyphenol intake and some classes were inversely associated with better glucose levels and HbA1c after one year of follow-up. These associations were modified when the analyses were run considering diabetes status separately. To our knowledge, this is the first study to assess the relationship between changes in the intake of all polyphenolic groups and T2D-related parameters in a senior population with T2D or at high-risk of developing T2D.

Effects of Mediterranean Diet on plasma metabolites and their relationship with insulin resistance and gut microbiota composition in a crossover randomized clinical trial.

BACKGROUND & AIMS: The Mediterranean Diet (MedDiet) may decrease the cardiometabolic risk through modulation of metabolic pathways. Furthermore, the interplay between MedDiet, metabolites and microbial metabolism may improve our understanding on the metabolic effects of this diet. We aimed to evaluate the effect of the MedDiet compared to nuts supplementation on circulating metabolites and their relationship with cardiometabolic health. We further examined whether changes in the metabolomic profiles were associated with changes in gut microbiota composition in a multi-omics integrative approach. METHODS: Forty-four adults with Metabolic Syndrome (MetS), (aged 37-65) participated in a randomized controlled, crossover 2-months dietary-intervention trial with a 1-month wash-out period, consuming a MedDiet or a non MedDiet plus nuts (50 g/day). Nutritional data were collected at the beginning and the end of each intervention period using 3-day dietary records, as well as fasting blood and fecal samples. Plasma metabolites (m = 378) were profiled using targeted metabolomics. Associations of these metabolites with the interventions were assessed with elastic net regression analyses. Gut microbiota composition was assessed by 16S rRNA sequencing. A sparse least regression analysis combined with a canonical correlation analysis was conducted between the plasma selected metabolites and genera in order to identify the relevant dual-omics signatures discriminating the dietary interventions. RESULTS: Changes in 65 circulating metabolites were significantly associated with the MedDiet (mainly lipids, acylcarnitines, amino acids, steroids and TCA intermediates). Importantly, these changes were associated with decreases in glucose, insulin and HOMA-IR. The network analysis identified two main clusters of genera with an opposite behaviour towards selected metabolites, mainly PC species, ChoE(20:5), TGs and medium/long-chain acylcarnitines. CONCLUSION: Following a MedDiet, rather than consuming nuts in the context of a non-MedDiet was associated with a specific plasma metabolomic profile, which was also related to metabolic improvements in adults with MetS. The identified correlated network between specific bacteria and metabolites suggests interplay between diet, circulating metabolites and gut microbiota. The trial was registered in the ISRCTN with identifier ISRCTN88780852, https://doi.org/10.1186/ISRCTN88780852.

Examining the Interaction of the Gut Microbiome with Host Metabolism and Cardiometabolic Health in Metabolic Syndrome.

(1) Background: The microbiota-host cross-talk has been previously investigated, while its role in health is not yet clear. This study aimed to unravel the network of microbial-host interactions and correlate it with cardiometabolic risk factors. (2) Methods: A total of 47 adults with overweight/obesity and metabolic syndrome from the METADIET study were included in this cross-sectional analysis. Microbiota composition (151 genera) was assessed by 16S rRNA sequencing, fecal (m = 203) and plasma (m = 373) metabolites were profiled. An unsupervised sparse generalized canonical correlation analysis was used to construct a network of microbiota-metabolite interactions. A multi-omics score was derived for each cluster of the network and associated with cardiometabolic risk factors. (3) Results: Five multi-omics clusters were identified. Thirty-one fecal metabolites formed these clusters and were correlated with plasma sphingomyelins, lysophospholipids and medium to long-chain acylcarnitines. Seven genera from Ruminococcaceae and a member from the Desulfovibrionaceae family were correlated with fecal and plasma metabolites. Positive correlations were found between the multi-omics scores from two clusters with cholesterol and triglycerides levels. (4) Conclusions: We identified a correlated network between specific microbial genera and fecal/plasma metabolites in an adult population with metabolic syndrome, suggesting an interplay between gut microbiota and host lipid metabolism on cardiometabolic health.

Effects of the Mediterranean Diet or Nut Consumption on Gut Microbiota Composition and Fecal Metabolites and their Relationship with Cardiometabolic Risk Factors.

SCOPE: To examine whether a Mediterranean Diet (MedDiet) compared to the consumption of nuts in the context of a habitual non-MedDiet exerts a greater beneficial effect on gut microbiota and fecal metabolites; thus, contributing to explain major benefits on cardiometabolic risk factors. METHODS AND RESULTS: Fifty adults with Metabolic Syndrome are randomized to a controlled, crossover 2-months dietary-intervention trial with a 1-month wash-out period, following a MedDiet or consuming nuts (50 g day-1 ). Microbiota composition is assessed by 16S rRNA gene sequencing and metabolites are measured using Nuclear Magnetic Resonance (NMR) and liquid chromatography coupled to triple quadrupole mass spectrometry (LC-qTOF) platforms in a targeted metabolomics approach. Decreased glucose, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) is observed after the MedDiet compared to the nuts intervention. Relative abundances of Lachnospiraceae NK4A136 and an uncultured genera of Ruminococcaceae are significantly increased after the MedDiet compared to nuts supplementation. Changes in Lachnospiraceae NK4A136 are inversely associated with insulin levels and HOMA-IR, while positively and negatively with changes in cholate and cadaverine, respectively. CONCLUSIONS: Following a MedDiet, rather than nuts, induces a significant increase in Lachnospiraceae NK4A136 and improves the metabolic risk. This genera seems to affect the bile acid metabolism and cadaverine which may account for the improvement in insulin levels.

Baseline drinking water consumption and changes in body weight and waist circumference at 2-years of follow-up in a senior Mediterranean population.

BACKGROUND & AIMS: The association between drinking water consumption and adiposity has been poorly explored. Therefore, we aimed to analyse the associations between the frequency of drinking water consumption and body weight and waist circumference changes in an elderly Mediterranean cohort. METHODS: A total of 1832 elderly participants (aged 55-75 years) with metabolic syndrome from the PREDIMED-Plus study with baseline data on drinking water and other beverages assessed by a validated 32-item Spanish fluid-intake questionnaire and with data on body weight (BW) and waist circumference (WC) at 1-year and 2-year were included in these prospective analyses. Multivariable linear regression models were fitted to assess the ß-coefficients and 95% confidence interval (CI) for BW and WC changes in terms of categories of baseline drinking water consumption (tap water and bottled water). The theoretical effect on BW and WC of replacing several beverages with drinking water was assessed using mathematical models. RESULTS: The baseline frequency of drinking water consumption was inversely associated with 1-year and 2-year changes in BW. ß-coefficients (95%CI) across categories of water consumption (<2.5, 2.5 to <5, 5 to < 7.5, ≥7.5 servings/d) expressed in % of weight changes at 2 years of follow-up were 0.0, -0.80 (-1.48, -0.12), -1.36 (-2.18, -0.54), and -1.97 (-3.09, -0.86), respectively. Individuals in the two highest categories of drinking water consumption (5 to < 7, and ≥7.5 servings/d) also showed a higher decrease in WC (expressed as % of change) after 2 years of follow-up: -1.11 (-1.96, -0.25) and -1.45 (-2.66, -0.24) compared to the reference intake (<2.5 servings/day), after adjustment for potential confounding factors. The theoretical replacement of soups, beers, spirits, hot beverages, dairy beverages, and other beverages group with drinking water was associated with greater reductions in BW at one- and two-years of follow-up. CONCLUSIONS: Drinking water consumption was inversely associated with 2-year adiposity changes in an elderly Mediterranean cohort at high cardiovascular risk. Our results also suggest that the consumption of drinking water instead of energy-containing beverages is associated with lower weight gain. THE TRIAL REGISTRATION: ISRCTN89898870.

The Effect of Physical Activity and High Body Mass Index on Health-Related Quality of Life in Individuals with Metabolic Syndrome.

The main objective of this study was to examine the relationship between the level of physical activity (PA) and the degree of obesity with health-related quality of life (HRQoL) in individuals with metabolic syndrome (MetS) who participated in the Predimed-Plus study. A total of 6875 subjects between 55 and 75 years of age with MetS were selected and randomized in 23 Spanish centers. Subjects were classified according to categories of body mass index (BMI). PA was measured with the validated Registre Gironí del Cor (REGICOR) questionnaire and subjects were classified according to their PA level (light, moderate, vigorous) and the HRQoL was measured with the validated short-form 36 (SF-36) questionnaire. By using the ANOVA model, we found a positive and statistically significant association between the level of PA and the HRQoL (aggregated physical and mental dimensions p < 0.001), but a negative association with higher BMI in aggregated physical dimensions p < 0.001. Furthermore, women obtained lower scores compared with men, more five points in all fields of SF-36. Therefore, it is essential to promote PA and body weight control from primary care consultations to improve HRQoL, paying special attention to the differences that sex incurs.

Dietary Diversity and Nutritional Adequacy among an Older Spanish Population with Metabolic Syndrome in the PREDIMED-Plus Study: A Cross-Sectional Analysis.

Dietary guidelines emphasize the importance of a varied diet to provide an adequate nutrient intake. However, an older age is often associated with consumption of monotonous diets that can be nutritionally inadequate, increasing the risk for the development or progression of diet-related chronic diseases, such as metabolic syndrome (MetS). To assess the association between dietary diversity (DD) and nutrient intake adequacy and to identify demographic variables associated with DD, we cross-sectionally analyzed baseline data from the PREDIMED-Plus trial: 6587 Spanish adults aged 55-75 years, with overweight/obesity who also had MetS. An energy-adjusted dietary diversity score (DDS) was calculated using a 143-item validated semi-quantitative food frequency questionnaire (FFQ). Nutrient inadequacy was defined as an intake below 2/3 of the dietary reference intake (DRI) forat least four of 17 nutrients proposed by the Institute of Medicine (IOM). Logistic regression models were used to evaluate the association between DDS and the risk of nutritionally inadequate intakes. In the higher DDS quartile there were more women and less current smokers. Compared with subjects in the highest DDS quartile, those in the lowest DDS quartile had a higher risk of inadequate nutrient intake: odds ratio (OR) = 28.56 (95% confidence interval (CI) 20.80-39.21). When we estimated food varietyfor each of the food groups, participants in the lowest quartile had a higher risk of inadequate nutrient intake for the groups of vegetables, OR = 14.03 (95% CI 10.55-18.65), fruits OR = 11.62 (95% CI 6.81-19.81), dairy products OR = 6.54 (95% CI 4.64-9.22) and protein foods OR = 6.60 (95% CI 1.96-22.24). As DDS decreased, the risk of inadequate nutrients intake rose. Given the impact of nutrient intake adequacy on the prevention of non-communicable diseases, health policies should focus on the promotion of a healthy varied diet, specifically promoting the intake of vegetables and fruit among population groups with lower DDS such as men, smokers or widow(er)s.

Effect of Functional Bread Rich in Potassium, γ-Aminobutyric Acid and Angiotensin-Converting Enzyme Inhibitors on Blood Pressure, Glucose Metabolism and Endothelial Function: A Double-blind Randomized Crossover Clinical Trial.

Because it has been suggested that food rich in γ-aminobutyric acid (GABA) or angiotensin-converting enzyme inhibitor (ACEI) peptides have beneficial effects on blood pressure (BP) and other cardiovascular risk factors, we tested the effects of low-sodium bread, but rich in potassium, GABA, and ACEI peptides on 24-hour BP, glucose metabolism, and endothelial function.A randomized, double-blind, crossover trial was conducted in 30 patients with pre or mild-to-moderate hypertension, comparing three 4-week nutritional interventions separated by 2-week washout periods. Patients were randomly assigned to consume 120 g/day of 1 of the 3 types of bread for each nutritional intervention: conventional wheat bread (CB), low-sodium wheat bread enriched in potassium (LSB), and low-sodium wheat bread rich in potassium, GABA, and ACEI peptides (LSB + G). For each period, 24-hour BP measurements, in vivo endothelial function, and biochemical samples were obtained.After LSB + G consumption, 24-hour ambulatory BP underwent a nonsignificant greater reduction than after the consumption of CB and LSB (0.26 mm Hg in systolic BP and -0.63 mm Hg in diastolic BP for CB; -0.71 mm Hg in systolic BP and -1.08 mm Hg in diastolic BP for LSB; and -0.75 mm Hg in systolic BP and -2.12 mm Hg in diastolic BP for LSB + G, respectively). Diastolic BP at rest decreased significantly during the LSB + G intervention, although there were no significant differences in changes between interventions. There were no significant differences between interventions in terms of changes in in vivo endothelial function, glucose metabolism, and peripheral inflammatory parameters.Compared with the consumption of CB or LSB, no greater beneficial effects on 24-hour BP, endothelial function, or glucose metabolism were demonstrated after the consumption of LSB + G in a population with pre or mild-to-moderate hypertension. Further studies are warranted to clarify the effect of GABA on BP, preferably using a specific design for noninferiority trials and ambulatory BP monitoring as a measure of BP.This study was registered at Current Controlled Trials as ISRCTN31436822.