An adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in familial hypercholesterolemia: A pilot study protocol

BACKGROUND AND AIMS: A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins. METHODS: A national, multicenter, factorial, and parallel placebocontrolled randomized clinical trial with a superiority design and 1:1:1:1 allocation rate will be conducted. The participants will undergo whole exome sequencing and be allocated into four treatment groups: 1) a cardioprotective diet adapted for FH (DICAFH) þ phytosterol placebo þ krill oil placebo; 2) DICA-FH þ phytosterol 2 g/day þ krill oil placebo; 3) DICA-FH þ phytosterol placebo þ krill oil 2 g/day; or 4) DICA-FH þ phytosterol 2 g/day þ krill oil 2 g/day. The primary outcomes will be low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels and adherence to treatment after a 120-day follow-up. LDL- and high-density lipoprotein (HDL)-cholesterol subclasses, untargeted lipidomics analysis, adverse events, and protocol implementation components will also be assessed. RESULTS: A total of 58 participants were enrolled between May e August 2023. After the end of the follow-up period, the efficacy and feasibility results of this pilot study will form the basis of the design of a large-scale randomized clinical trial. CONCLUSIONS: This study's overall goal is to recommend dietary treatment strategies in the context of FH.

Pre-exercise meal on oxidation of energy substrates during maximal exercise test in non-trained individuals.

Objective: This study aimed to compare the influence of a high carbohydrate meal versus high-fat meal on the oxidation of substrates during an exercise incremental test. Materials and methods: Ten untrained male subjects underwent two days of the protocol. Randomly, they received a high carbohydrate meal or a high-fat meal, receiving the other one in the next protocol. On both days, they performed an incremental treadmill test, with heart rate and maximal oxygen consumption to estimate the oxidation of substrates. Results: The high-fat meal showed an increase in the absolute amount of oxidized fat along with the incremental test (P < 0.05; effect size = 0.9528), and a reduction in the respiratory exchange ratio at low intensities (P < 0.05; effect size = 0.7765). Conclusion: The meals presented no difference when compared to maximum oxidation point of substrates, the oxidation rate of substrates over time, and heart rate. A pre-test high-fat meal in untrained individuals was shown to be a modulating factor of total oxidized fats throughout the exercise, although it did not exert a significant effect on the rate of this oxidation over time.

Pre-exercise meal on oxidation of energy substrates during maximal exercise test in non-trained individuals

ABSTRACT Objective: This study aimed to compare the influence of a high carbohydrate meal versus high-fat meal on the oxidation of substrates during an exercise incremental test. Materials and methods: Ten untrained male subjects underwent two days of the protocol. Randomly, they received a high carbohydrate meal or a high-fat meal, receiving the other one in the next protocol. On both days, they performed an incremental treadmill test, with heart rate and maximal oxygen consumption to estimate the oxidation of substrates. Results: The high-fat meal showed an increase in the absolute amount of oxidized fat along with the incremental test (P < 0.05; effect size = 0.9528), and a reduction in the respiratory exchange ratio at low intensities (P < 0.05; effect size = 0.7765). Conclusions: The meals presented no difference when compared to maximum oxidation point of substrates, the oxidation rate of substrates over time, and heart rate. A pre-test high-fat meal in untrained individuals was shown to be a modulating factor of total oxidized fats throughout the exercise, although it did not exert a significant effect on the rate of this oxidation over time.

Absolute and Relative Agreement between the Current and Modified Brazilian Cardioprotective Nutritional Program Dietary Index (BALANCE DI) and the American Heart Association Healthy Diet Score (AHA-DS) in Post Myocardial Infarction Patients.

The American Heart Association Diet Score (AHA-DS) defines the cardiovascular health, and the Brazilian Cardioprotective Nutritional Program Dietary Index (BALANCE DI) was designed to evaluate diet quality in secondary cardiovascular prevention settings. Our aim was to assess the absolute and relative agreement between both tools in Brazilian adults after a myocardial infarction (MI). In this cross-sectional study, 473 individuals were included and had their diet assessed by a 24 h food recall and a semi-quantitative Food Frequency Questionnaire. The weighted Kappa between BALANCE DI and primary AHA-DS was 0.66 (95% CI: 0.08-0.21), and between BALANCE DI and total AHA-DS was 0.70 (95% CI: 0.20-0.32). To improve the agreement between the tools, modifications were made to the BALANCE DI scoring system. The weighted Kappa between New BALANCE DI and primary AHA-DS was 0.77 (95% CI: 0.36-0.48), and between BALANCE DI and total AHA-DS was 0.76 (95% CI: 0.34-0.46). The mean bias observed between the New BALANCE DI as compared to the primary and total AHA-DS was -16% (-51 to 19) and -8% (-41 to 24), respectively. Our results suggest that the New BALANCE DI may be a useful tool to evaluate diet quality in post MI patients.

Efeito da Dieta Cardioprotetora Brasileira suplementada ou não com amendoins (Arachis hypogaea) sobre parâmetros cardiometabólicos no pós-infarto agudo do miocárdio / Effect of the Brazilian Cardioprotective Diet supplemented or not with peanuts on cardiometabolic parameters after acute myocardial infarction

Introdução: as doenças cardiovasculares (DCV) são responsáveis por quase 18 milhões de óbitos ao ano no mundo, sendo que o infarto agudo do miocárdio (IAM) acomete aproximadamente 300.000 brasileiros anualmente. A Dieta Cardioprotetora Brasileira (DICA-BR) foi projetada para facilitar a orientação nutricional à população brasileira, tendo por base as diretrizes clínicas nacionais, e como pano de fundo a dieta mediterrânea e as diretrizes da American Heart Association. O amendoim possui componentes como fibras, proteínas, arginina, compostos fenólicos, niacina, folato, magnésio, manganês e ácidos graxos mono e poli-insaturados, cuja composição nutricional apresenta potencial de modulação do risco cardiovascular. Objetivo: avaliar o efeito da DICA-BR, suplementada ou não com amendoim, sobre parâmetros cardiometabólicos em pacientes com IAM recente. Métodos: estudo caracterizado como um ensaio clínico randomizado, com um total de 100 indivíduos, alocados em dois grupos (taxa de alocação 1:1). Os critérios de inclusão são idade superior a 40 anos e ter episódio de IAM entre os últimos 60 e 180 dias. O grupo 1 recebeu orientação alinhada à DICA-BR enquanto o grupo 2 recebeu a orientação alinhada à DICA-BR e suplementação de 30 g/dia de amendoim. Os pacientes foram acompanhados por quatro meses, com as visitas ocorrendo aos 30, 60, 90 e 120 dias após o início do protocolo experimental. Ao longo do estudo, foram realizadas a avaliação antropométrica, recordatórios 24 horas, avaliação de medicação utilizada e dos hábitos de exercício físico e tabagistas, questionário socioeconômico e coleta de sangue para exames bioquímicos. O desfecho primário do estudo em tela foi a concentração plasmática de colesterol associado à lipoproteína de baixa densidade (LDL-c), e os secundários foram caracterizados como demais indicadores de perfil lipídico e controle glicêmico, ingestão alimentar, índices antropométricos, concentração de malondialdeído (MDA) e de antioxidantes totais (TAOC), atividade da enzima catalase e perfil de ácidos graxos na membrana plasmática de eritrócitos. Para as análises estatísticas foram efetuados testes t pareado. Resultados: não foi verificada diferença significativa referente à variação da concentração plasmática de LDL-c nos grupos 1 e 2 ao longo do protocolo. Foi constatada redução significativa da concentração plasmática de triacilgliceróis em indivíduos do grupo 1 (191 mg/dL [t=0] vs 160 mg/dL [t=1]; p = 0,03), bem como foi verificado aumento significativo da concentração plasmática de HDL-c no grupo 2 (40,3 mg/dL [t=0] vs 42,8 mg/dL [t=1]; p = 0,003). O grupo 2 apresentou redução no consumo energético total (1772 kcal/dia [t=0] vs 1374 kcal/dia [t=1]; p = 0,002) e ambos os grupos apresentaram diminuição das concentrações de MDA (Grupo 1: 0,63 µMol/mL [t=0] vs 0,4 µMol/mL [t=1]; p = 0,007 e grupo 2: 0,81 µMol/mL vs 0,4 µMol/mL; p = 0,038). Os demais biomarcadores não apresentaram diferença significativa. Conclusão: após 16 semanas de acompanhamento, os resultados obtidos evidenciam que a DICA-BR, de forma isolada, promove melhora do risco cardiovascular por meio da redução de biomarcadores plasmáticos, como concentração de triacilgliceróis e a razão triacilglicerol/HDL e diminuição de índices antropométricos, como o IMC e a circunferência da cintura. Não obstante, a DICA-BR, quando suplementada com amendoins, apresenta impacto positivo sobre a concentração plasmática de HDL-c, o que sugere potencial benefício dessa intervenção em relação ao transporte reverso do colesterol.

Introduction: cardiovascular diseases (CVD) are responsible for almost 18 million deaths a year worldwide, and acute myocardial infarction (AMI) affects approximately 300,000 Brazilians annually. The Brazilian Cardioprotective Diet (DICA-BR) was designed to facilitate nutritional guidance to the Brazilian population based on national clinical guidelines and the backdrop of the Mediterranean diet and the American Heart Association guidelines. Peanut has components such as fiber, proteins, arginine, phenolic compounds, niacin, folate, magnesium, manganese, and monounsaturated and polyunsaturated fatty acids, whose nutritional composition has the potential to modulate cardiovascular risk. Objective: to evaluate the effect of DICA-BR, supplemented or not with peanuts, on cardiometabolic parameters in patients with recent AMI. Methods: the study was a randomized clinical trial, with 100 individuals allocated into two groups (allocation ratio 1:1). Inclusion criteria are age over 40 years and having an AMI episode between the last 60 and 180 days. Group 1 received DICA-BR-aligned guidance while group 2 received DICA-BR-aligned guidance and peanut supplementation of 30 g/day. Patients were followed for four months, with visits occurring at 30, 60, 90, and 120 days after the start of the experimental protocol. Throughout the study, anthropometric assessment, 24-hour recalls, assessment of medication used and physical exercise and smoking habits, socioeconomic questionnaire, and blood collection for biochemical tests were performed. The primary outcome of the present study was the plasma concentration of cholesterol associated with low-density lipoprotein (LDL-c), and the secondary outcomes were characterized as other indicators of lipid profile and glycemic control, food intake, anthropometric indices, malondialdehyde concentration (MDA), and total antioxidants (TAOC), catalase enzyme activity and fatty acid profile in the plasma membrane of erythrocytes. For statistical analysis, paired t-tests were performed. Results: there was no significant difference regarding the variation of plasma LDL-c concentration in groups 1 and 2 throughout the protocol. A significant reduction in the plasma concentration of triacylglycerols was observed in individuals in group 1 (191 mg/dL [t=0] vs 160 mg/dL [t=1]; p = 0.03), as well as a significant increase in the concentration plasma HDL-c in group 2 (40.3 mg/dL [t=0] vs 42.8 mg/dL [t=1]; p = 0.003). Group 2 showed a reduction in total energy consumption (1772 Kcal/day [t=0] vs 1374 Kcal/day [t=1]; p = 0.002) and both groups showed a decrease in MDA concentrations (Group 1: 0, 63 µMol/mL [t=0] vs 0.4 µMol/mL [t=1]; p = 0.007 and group 2: 0.81 µMol/mL vs 0.4 µMol/mL; p = 0.038). The other biomarkers showed no significant difference. Conclusion: after 16 weeks of follow-up, the results show that in isolation, DICA-BR promotes an improvement in cardiovascular risk by reducing plasma biomarkers, such as triacylglycerol concentration and the triacylglycerol/HDL ratio, and reduction in anthropometric indices, such as BMI and waist circumference. However, when supplemented with peanuts, DICA-BR has a positive impact on plasma HDL-c concentration, suggesting a potential benefit of this intervention concerning reverse cholesterol transport.

Effects of a Brazilian cardioprotective diet and nuts on cardiometabolic parameters after myocardial infarction: study protocol for a randomized controlled clinical trial.

BACKGROUND: Nut consumption has been related to improvements on cardiometabolic parameters and reduction in the severity of atherosclerosis mainly in primary cardiovascular prevention. The objective of this trial is to evaluate the effects of the Brazilian Cardioprotective Diet (DIeta CArdioprotetora Brasileira, DICA Br) based on consumption of inexpensive locally accessible foods supplemented or not with mixed nuts on cardiometabolic features in patients with previous myocardial infarction (MI). METHODS: DICA-NUTS study is a national, multicenter, randomized 16-week follow-up clinical trial. Patients over 40 years old with diagnosis of previous MI in the last 2 to 6 months will be recruited (n = 388). A standardized questionnaire will be applied to data collection and blood samples will be obtained. Patients will be allocated in two groups: Group 1: DICA Br supplemented with 30 g/day of mixed nuts (10 g of peanuts, 10 g of cashew, 10 g of Brazil nuts); and Group 2: only DICA Br. The primary outcome will consist of LDL cholesterol means (in mg/dL) after 16 weeks of intervention. Secondary outcomes will consist of other markers of lipid profile, glycemic profile, and anthropometric data. DISCUSSION: It is expected that DICA Br supplemented with mixed nuts have superior beneficial effects on cardiometabolic parameters in patients after a MI, when compared to DICA Br. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03728127 . First register: November 1, 2018; Last update: June 16, 2021. World Health Organization Universal Trial Number (WHO-UTN): U1111-1259-8105.

Effects of extra virgin olive oil and pecans on plasma fatty acids in patients with stable coronary artery disease.

OBJECTIVE: The aim of this study was to determine the effects of a healthy diet supplemented with extra virgin olive oil or pecans on plasma fatty acids (PFAs) in patients with stable coronary artery disease (CAD). METHODS: Patients 40 to 80 y of age were randomized to one of three dietary interventions (allocation ratio 1: 1: 1): healthy diet based on guidelines (control group [CG]), healthy diet supplemented with 30 g/d of pecans (PNG), or a healthy diet supplemented with 30 mL/d of extra virgin olive oil (OOG). PFAs were identified at baseline and at the end of follow-up (12 wk), and correlations between dietary fatty acids intake, PFAs, and clinical biomarkers of the lipid profile were also assessed before and after the interventions. RESULTS: Among 149 participants included in the analysis (43 CG; 51 PNG; and 55 OOG), correlations were observed between food intake, PFAs, and lipid profile before and after interventions independent of statins used, but all were considered weak. At the end of the study, the OOG showed increased concentrations of oleic fatty acid independently of the type of statin in use (1.49%; 95% confidence interval, 0.08-2.89; P = 0.029); however, there were no significant differences between the groups regarding the final mean values of oleic fatty acid or in the other PFAs. CONCLUSIONS: In patients with stable CAD, there were no significant differences in PFAs after 12 wk according to dietary interventions evaluated.

Effects of aerobic and resistance exercise training associated with carnosine precursor supplementation on maximal strength and V̇O2max in rats with heart failure.

BACKGROUND: Combined exercise training (CET) has been associated with positive responses in the clinical status of patients with heart failure (HF). Other nonpharmacological tools, such as amino acid supplementation, may further enhance its adaptation. The aim was to test whether CET associated with supplementing carnosine precursors could present better responses in the functional capacity and biochemical variables of rats with HF. METHODS: Twenty-one male Wistar rats were subjected to myocardial infarction and allocated to three groups: sedentary (SED, n = 7), CET supplemented with placebo (CETP, n = 7), and CET with HF supplemented with ß-alanine and L-histidine (CETS, n = 7). The trained animals were submitted to a strength protocol three times per week. Aerobic training was conducted twice per week. The supplemented group received ß-alanine and L-histidine orally (250 mg/kg per day). RESULTS: Maximum oxygen uptake, running distance, time to exhaustion and maximum strength were higher in the CET-P group than that in the SED group and even higher in the CET-S group than that in the CET-P group (P < 0.01). CET-S showed lower oxidative stress and inflammation markers and higher heat shock protein 72 kDa content and mRNA expression for calcium transporters in the skeletal muscle compared to SED. CONCLUSION: CET together with ß-alanine and L-histidine supplementation in rats with HF can elicit adaptations in both maximum oxygen uptake, running distance, time to exhaustion, maximum strength, oxidative stress, inflammation and mRNA expression. Carnosine may influence beneficial adjustments in the cell stress response in the skeletal muscle and upregulate the mRNA expression of calcium transporters.

Mindfulness Practice for Glycemic Control: Could it be a New Strategy for an Old Problem? A Systematic Review and Meta-Analysis.

BACKGROUND: The management of type 2 diabetes mellitus (T2DM) requires a complex and organized care that includes patient's lifestyle change. Additionally, emotional well-being is an important part of self-management, and it may impair the individual's adherence. Therefore, equipping the patients with the necessary coping and self-care techniques may be an important step in managing diabetes. OBJECTIVE: To evaluate the effect of interventions using established mindfulness-based protocols on glycemic control of individuals with T2DM. METHODS: Data sources: Two electronic databases (PubMed and EMBASE) were searched from inception to December 2019. We limited our search to published studies in English, Spanish and Portuguese languages. STUDY SELECTION: Randomized clinical trials that assessed the effects of mindfulness in individuals with T2DM were selected. DATA EXTRACTION: Two authors independently assessed the risk of bias and extracted data from the included trials. Data were pooled using inverse-variance random-effects meta-analyses. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Four randomized trials were included. There were no differences in blood glucose change (mean difference between groups (MD) -0.73mg/dl; 95% CI, -10.49; 9.02; I2 =0%; very low quality of evidence) or glycated hemoglobin (MD 0.05%; 95%CI -0.22 to 0.32; I2 =29%; very low quality of evidence). CONCLUSION: Although the quality of current evidence is very low, our findings suggest that established protocols involving mindfulness have no effect on blood glucose or glycated hemoglobin in individuals with T2DM. Indeed, large-scale trials are needed to evaluate the contribution of mindfulness to glycemic control in clinical practice. PROSPERO Registration ID: RD42020161940.

ß-Alanine and l-histidine supplementation associated with combined training increased functional capacity and maximum strength in heart failure rats.

NEW FINDINGS: What is the central question of the study? Does ß-alanine with l-histidine supplementation associated with endurance and strength training improve echocardiographic parameters, functional capacity, and maximum strength in rats with chronic heart failure? What is the main finding and its importance? ß-Alanine with l-histidine supplementation associated with endurance and strength training increased functional capacity and maximum strength through increasing exercise capacity peripherally but did not affect echocardiographic parameters in rats with chronic heart failure. Combined training (CT) has been associated with positive responses in the clinical status of patients with chronic heart failure (CHF). Other non-pharmacological tools, such as amino acid supplementation, may further enhance its adaptation. However, the effects of ß-alanine and l-histidine supplementation in CHF remain unclear. In the present study, the aim was to test whether supplementing carnosine precursors with CT could give improved responses in the functional capacity and echocardiographic variables of rats with CHF. Twenty-four Wistar rats, were submitted to myocardial infarction and allocated to three groups: animals with CHF kept in sedentary conditions (SED, n = 8), animals with CHF submitted to CT in strength and aerobic exercise supplemented with placebo (CT-P, n = 8) and animals with CHF submitted to CT in strength and aerobic exercise supplemented with ß-alanine and l-histidine (CT-S, n = 8). The trained animals were submitted to a strength protocol three times per week with intensity of 65-75% of one repetition maximum test. Aerobic training was conducted two times per week (50 min, 15 m min-1 ). The supplemented group received ß-alanine and l-histidine orally (each 250 mg kg-1  day-1 ). No changes in echocardiographic and morphological parameters were found among the groups (P > 0.05). Functional capacity, Δ V̇O2max and maximum strength were higher in CT-P than in SED and even higher in CT-S than in CT-P (P < 0.01). The CT was able to improve functional capacity, but the supplementation was shown to enhance these parameters even further in the CHF rats. We conclude that the increase in functional capacity and strength gained through CT and supplementation were associated with the improvement in peripheral parameters with no changes in cardiac variables.