Nattokinase as an adjuvant therapeutic strategy for non-communicable diseases: a review of fibrinolytic, antithrombotic, anti-inflammatory, and antioxidant effects.

INTRODUCTION: Nattokinase (NK) is the primary ingredient of natto, a traditional Asian food made from fermented soybean by Bacillus subtilis natto. Studies have shown that natto reduces the risk of cardiovascular disease (CVD) mortality due to its fibrinolytic and antithrombotic properties. A new field of studies also demonstrates that NK can mitigate molecular pathways related to inflammation and oxidative stress and can be considered an adjuvant strategy for use in many non-communicable diseases (NCDs). This paper is a narrative review of the literature. A search was conducted in PubMed and ScienceDirect up to July 2024. AREAS COVERED: This review discusses the possible effects of NK on mitigating the common complications of NCDs, such as inflammation and oxidative stress. In addition, it provides an update on the most addressed areas related to NK's fibrinolytic and antithrombotic activities. EXPERT OPINION: Due to the fibrinolytic and antithrombotic activity of nattokinase, and more recently added to the anti-inflammatory and antioxidant effects, this enzyme can be used as a new adjuvant therapeutic strategy to mitigate inflammation and oxidative stress in NCDs, including CVD.

Unstressing the Reticulum: Nutritional Strategies for Modulating Endoplasmic Reticulum Stress in Obesity.

The progression of obesity involves several molecular mechanisms that are closely associated with the pathophysiological response of the disease. Endoplasmic reticulum (ER) stress is one such factor. Lipotoxicity disrupts endoplasmic reticulum homeostasis in the context of obesity. Furthermore, it induces ER stress by activating several signaling pathways via inflammatory responses and oxidative stress. ER performs crucial functions in protein synthesis and lipid metabolism; thus, triggers such as lipotoxicity can promote the accumulation of misfolded proteins in the organelle. The accumulation of these proteins can lead to metabolic disorders and chronic inflammation, resulting in cell death. Thus, alternatives, such as flavonoids, amino acids, and polyphenols that are associated with antioxidant and anti-inflammatory responses have been proposed to attenuate this response by modulating ER stress via the administration of nutrients and bioactive compounds. Decreasing inflammation and oxidative stress can reduce the expression of several ER stress markers and improve clinical outcomes through the management of obesity, including the control of body weight, visceral fat, and lipid accumulation. This review explores the metabolic changes resulting from ER stress and discusses the role of nutritional interventions in modulating the ER stress pathway in obesity.

Bisphenol S exposure induces cardiac remodeling and aggravates high-fat diet-induced cardiac hypertrophy in mice.

Bisphenol S (BPS) is widely used in the manufacture products and increase the risk of cardiovascular diseases. The effect of the association between obesity and BPS on cardiac outcomes is still unknown. Male C57BL/6 mice were divided into standard chow diet (SC; 15 kJ/g), standard chow diet + BPS (SCB), high-fat diet (HF; 21 kJ/g), and high-fat diet + BPS (HFB). Over 12 weeks, the groups were exposed to BPS through drinking water (dose: 25 µg/kg/day) and/or a HF diet. We evaluated: body mass (BM), total cholesterol, systolic blood pressure (SBP), left ventricle (LV) mass, and cardiac remodeling. In the SCB group, BM, total cholesterol, and SBP increase were augmented in relation to the SC group. In the HF and HFB groups, these parameters were higher than in the SC and SCB groups. Cardiac hypertrophy was evidenced by augmented LV mass and wall thickness, and ANP protein expression in all groups in comparison to the SC group. Only the HFB group had a thicker LV wall than SCB and HF groups, and increased cardiomyocyte area when compared with SC and SCB groups. Concerning cardiac fibrosis, SCB, HF, and HFB groups presented higher interstitial collagen area, TGFß, and α-SMA protein expression than the SC group. Perivascular collagen area was increased only in the HF and HFB groups than SC group. Higher IL-6, TNFα, and CD11c protein expression in all groups than the SC group evidenced inflammation. All groups had elevated CD36 and PPARα protein expression in relation to the SC group, but only HF and HFB groups promoted cardiac steatosis with increased perilipin 5 protein expression than the SC group. BPS exposure alone promoted cardiac remodeling with pathological concentric hypertrophy, fibrosis, and inflammation. Diet-induced remodeling is aggravated when associated with BPS, with marked hypertrophy, alongside fibrosis, inflammation, and lipid accumulation.

Brazil nuts potential: effects on lipid peroxidation and heart health in nephrectomized rats.

OBJECTIVES: To investigate the effects of a Brazil nut-enriched diet on the wall thickness and the left ventricular chamber diameter of the heart, and lipid peroxidation in a CKD-induced model. METHODS: Male Wistar rats at 12 weeks of age were divided into two groups (n=16/group): the Nx group, which underwent 5/6 nephrectomy, and the Sham group, as a control. After 5 weeks, the groups were subdivided according to diet (n=8/group): the Nx and Sham groups received a control diet; the Nx5% and Sham5% groups received a diet enriched with 5 % Brazil nuts for 8 weeks. The left ventricular thickening and chamber diameter were determined. Plasma biochemical parameters were evaluated. Analysis of thiobarbituric acid reactive substances (TBARS) and antioxidant enzyme activity was performed in the plasma and the left ventricle (LV). LV mRNA expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by reverse transcription-polymerase chain reaction. RESULTS: The Nx5% group showed a remodeled LV wall with decreased thickness compared to the Nx group (p=0.016). Furthermore, LV TBARS concentration was reduced in the Nx5% group (p=0.0064). In addition, the Nx5% group showed an increase in plasma GPx activity (p=0.0431). No significant results were found concerning the LV mRNA expression of NF-κB and Nrf2 genes. CONCLUSIONS: A Brazil nut-enriched diet decreased LV thickness and LV TBARS concentration and increased GPx activity in a 5/6 nephrectomy experimental model, making it a promising adjuvant therapy to improve antioxidant status and cardiovascular outcomes in chronic kidney disease.

Brazil nut-enriched diet modulates bone mineral density and body composition in an experimental model of chronic kidney disease.

OBJECTIVE: This study investigates the effects of a Brazil nut-enriched diet on body composition and bone parameters in CKD animal model. METHODS: Male Wistar rats were assigned to the following groups: Sham (n=8), Nx (n=6), nephrectomized rats, and NxBN (n=6), nephrectomized rats and an enricheddiet with 5% Brazil nut. Body composition parameters were obtained by dual-energy X- ray absorptiometry (DXA). Bioclin kits determined plasmatic calcium. The femurs werecollected to determine absolute mass and length, bone mineral density, and biomechanical tests. RESULTS: The NxBN group exhibited a higher total body bone mineral density (BMD) value than the Nx group (0.177±0.004g/cm2vs 0,169±0.003g/cm2; p=0.0397). No significant differences were observed regarding absolute mass, length, BMD, and biomechanical parameters in the femurs of the groups. Moreover, no significant differences were found in plasmatic calcium levels among the groups. CONCLUSIONS: Brazil-nut enriched diet modulated BMD in CKD experimental model, and further studies are demanded to understand the pathways involved in this finding.

Is the enteric nervous system a lost piece of the gut-kidney axis puzzle linked to chronic kidney disease?

The enteric nervous system (ENS) regulates numerous functional and immunological attributes of the gastrointestinal tract. Alterations in ENS cell function have been linked to intestinal outcomes in various metabolic, intestinal, and neurological disorders. Chronic kidney disease (CKD) is associated with a challenging intestinal environment due to gut dysbiosis, which further affects patient quality of life. Although the gut-related repercussions of CKD have been thoroughly investigated, the involvement of the ENS in this puzzle remains unclear. ENS cell dysfunction, such as glial reactivity and alterations in cholinergic signaling in the small intestine and colon, in CKD are associated with a wide range of intestinal pathways and responses in affected patients. This review discusses how the ENS is affected in CKD and how it is involved in gut-related outcomes, including intestinal permeability, inflammation, oxidative stress, and dysmotility.

Brazil Nut-Enriched Diet Modulates Enteric Glial Cells and Gut Microbiota in an Experimental Model of Chronic Kidney Disease.

Introduction: Chronic kidney disease (CKD) promotes gut dysbiosis, and enteric glial reactivity, a feature of intestinal inflammation. Brazil nut modulated enteric glial profile in healthy animals and could modulate these cells in 5/6 nephrectomized rats.Methods: A 5/6 nephrectomy-induced CKD and Sham-operated rats were divided as follows: CKD and Sham received a standard diet and CKD-BN and Sham-BN received a 5% Brazil nut enriched-diet. The protein content of glial fibrillary acid protein (GFAP), enteric glial marker, and GPx protein content and activity were assessed in the colon. The major phyla of gut microbiota were assessed.Results: CKD-BN group presented a decrease in GFAP content (p = 0.0001). The CKD-BN group modulated the abundance of Firmicutes, increasing its proportion compared to the CKD group. The CKD-BN group showed increased GPx activity in the colon (p = 0.0192), despite no significant difference in protein content.Conclusion: Brazil nut-enriched diet consumption decreased enteric glial reactivity and modulated gut microbiota in the CKD experimental model.

Is Trimethylamine N-oxide (TMAO) Associated with NF-κB mRNA Expression in Patients with Coronary Artery Disease?

Abstract Background: Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, is associated with cardiovascular disease (CVD) development. TMAO can trigger an inflammatory response by inducing the nuclear factor-kappa B (NF-κB) signaling cascade and increasing the expression of pro-inflammatory cytokines, contributing to the worsening of CVD. This study aimed to evaluate the association between TMAO plasma levels and inflammation in patients with coronary artery disease (CAD). Methods: A cross-sectional study was carried out including 29 patients with CAD. Peripheral blood mononuclear cells (PBMC) were isolated from fasting blood samples, and NF-κB and vascular cell adhesion protein 1 (VCAM1) mRNA expression were estimated using real-time quantitative PCR. We determined TMAO plasma levels by LC-MS/MS and TNF-α by ELISA. Routine biochemical parameters were evaluated using an automatic biochemical analyzer. Correlations were estimated by Spearman or Pearson test. Statistical significance was set at the level of p < 0.05. Results: All patients presented TMAO levels within the normal range according to EUTox (normal range: 2.83 ± 1.53 mg/L; CAD patients: 0.2 [0.1 to 0.2] ng/μL). TMAO plasma levels were positively correlated with NF-κB mRNA expression (0.555; p = 0.002). Conclusion: TMAO plasma levels may be associated with NF-κB mRNA expression in patients with CAD and may contribute to the pathogenesis of this disease.

Effects of Probiotic-Enriched Minas Cheese (Lactobacillus acidophilus La-05) on Cardiovascular Parameters in 5/6 Nephrectomized Rats.

Dairy foods have become an interest in chronic kidney disease (CKD) due to their nutritional profile, which makes them a good substrate for probiotics incorporation. This study evaluated the effect of probiotic-enriched Minas cheese with Lactobacillus acidophilus La-05 in an experimental rat model for CKD on cardiac, inflammatory, and oxidative stress parameters. Male Wistar rats were divided into 4 groups (n = 7/group): 5/6 nephrectomy + conventional Minas cheese (NxC); 5/6 nephrectomy + probiotic Minas cheese (NxPC); Sham + conventional Minas cheese (ShamC); Sham + probiotic Minas cheese (ShamPC). Offering 20 g/day of Minas cheese with Lact. acidophilus La-05 (108-109 log CFU/g) for 6 weeks. The cardiomyocyte diameter was determined. Superoxide dismutase (SOD) activity in plasma, heart, kidney, and colon tissue was performed. At the end of supplementation, no significant changes in lipid profile and renal parameters were found. The NxPC group showed a decrease in cardiomyocyte diameter compared to the NxC group (16.99 ± 0.85 vs. 19.05 ± 0.56 µm, p = 0.0162); also they showed reduced plasmatic SOD activity (502.8 ± 49.12 vs. 599.4 ± 94.69 U/mL, p < 0.0001). In summary, probiotic-enriched Minas cheese (Lact. acidophilus La-05) consumption suggests a promisor cardioprotective effect and was able to downregulate SOD activity in a rat model of CKD.

Consumo de Castanha-do-Brasil reduz o N-óxido de trimetilamina (TMAO) e a inflamação em um paciente com síndrome cardiorrenal: uma comunicação breve / Brazil nut consumption reduces trimethylamine-n-oxide (TMAO) and inflammation in a patient with cardiorenal syndrome: a brief communication

Introdução: A disbiose intestinal é uma característica comum na síndrome cardiorrenal e está associada ao aumento de toxinas urêmicas, como o N-óxido de trimetilamina (TMAO), que estão envolvidas com a inflamação e mortalidade cardiovascular. A castanha-do-Brasil (semente típica brasileira) possui propriedades anti-inflamatórias e antioxidantes, mas não há evidências dos seus efeitos na modulação da microbiota intestinal e redução de toxinas urêmicas. Objetivo: Avaliar o impacto do consumo de castanha-do-Brasil nos níveis de TMAO e marcadores de inflamação em um paciente com síndrome cardiorrenal. Métodos: Um paciente com doença arterial coronariana (66 anos e IMC, 26 kg/m2), estágio 3 da DRC (TFGe 36 mL/min), recebeu uma castanha-do-Brasil por dia durante três meses. Resultados: Os níveis plasmáticos de TMAO e a expressão de mRNA de NF-κB foram reduzidos e a atividade da glutationa peroxidase (GPx) aumentou após esta intervenção. Conclusão: A prescrição de castanha-do-Brasil pode ser uma estratégia promissora para mitigar as complicações relacionadas à síndrome cardiorrenal. Este caso apoia o conceito de "alimento como remédio" visando o fenótipo urêmico na síndrome cardiorrenal.

Introduction: Gut dysbiosis is a common feature in cardiorenal syndrome, and it is linked to increased uremic toxins, like trimethylamine-n-oxide (TMAO), which are involved with inflammation and cardiovascular mortality. Brazil nut (typical Brazilian seed) has anti-inflammatory and antioxidant properties, but there is no evidence of the effects of gut microbiota modulation and reduction of uremic toxins. Objective: To assess the impact of Brazil nut consumption on TMAO levels and inflammation markers in a patient with cardiorenal syndrome. Methods: Acoronary artery disease patient(66 years and BMI, 26 kg/m2),stage-3 of CKD (eGFR 36 mL/min), receivedone Brazil nut per day for three months. Results: TMAO plasma levels and NF-κB mRNA expression were reduced, and glutathione peroxidase (GPx) activity increased after this intervention. Conclusion: Brazil nut prescription may be a promising strategy to mitigate complications related tothe cardiorenal syndrome. This case supports the concept of "Food as medicine" targeting the uremic phenotype in cardiorenal syndrome.

Consumption of oils and anthocyanins may positively modulate PPAR-γ expression in chronic noncommunicable diseases: A systematic review.

Peroxisome proliferator-activated receptor-gamma (PPAR-γ) plays a central role in health and is an essential cardioprotective factor because of its effect on lipid and glucose metabolism, inflammation, and oxidative stress. We hypothesized that nutritional strategies positively regulate PPAR-γ expression in patients with noncommunicable diseases (NCDs). A systematic search was conducted using PubMed, Scientific Electronic Library Online (SciELO), and LILACS databases from May 2020 to January 2021. Eligibility criteria included placebo-controlled randomized clinical trials in adults with chronic diseases involving nutritional strategies, which performed PPAR-γ analysis (majority on mononuclear cells) before and after the intervention. The exclusion criteria included studies published more than 10 years ago, studies not published in English or Spanish, theses, reviews, and other study designs. The review was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methodological quality was assessed based on 7 criteria obtained from the Cochrane Handbook. A total of 7 studies were included that reported the effects of different nutritional strategies (such as anthocyanins, fish oil, Berberis vulgaris juice, ketogenic diet, flaxseed oil, olive oil) on 346 patients with NCDs (such as type 2 diabetes, hypertension, obesity, and cancer) between 18 and 85 years of age. These results suggest that anthocyanins, flaxseed oil, and olive oil may function as putative PPAR-γ agonists.

Supplementation of diet with Brazil nut modulates body composition, bone parameters, and lipid peroxidation in Wistar rats.

Oxidative stress, adipose tissue, and bone compartments can be disturbed in chronic diseases. Non-pharmacological strategies, such as Brazil nuts (BNs), can improve these parameters. This study evaluated the effects of BN supplementation at different concentrations on body composition, lipid profile, and peroxidation in healthy rats. Male Wistar rats were divided into three groups: control (CT), Brazil nut 5% (BN5), and Brazil nut 10% (BN10) groups. Body composition, brown adipose tissue (BAT), plasma lipid peroxidation, and lipid profile were evaluated in the three groups. The BN5 group showed an improvement in all bone parameters compared with that of the CT group (p  < .0001). The BN5 and BN10 groups showed reduced plasma lipid peroxidation compared with that of the CT group (p = .0009), whereas the BN10 group presented lower BAT lipid peroxidation than that of the other groups (p = .01). High-density lipoprotein-cholesterol (HDL-c) levels were higher in the BN5 group than in the CT group (p = .01). Conclusively, the use of BNs in a controlled manner promoted improvement in bone parameters, HDL-c levels, and lipid peroxidation in healthy rats. PRACTICAL APPLICATIONS: Nuts has been included in the diet because of their versatility, acceptance, and easy access. Among them, Brazil nut (BN) is considered one of the major known food sources of selenium as well as a source of fibers, unsaturated fatty acids, and phenolic compounds. Studies have shown that BN supplementation is effective in reducing oxidative stress, inflammation, lipid peroxidation, and selenium deficiency when used as a non-pharmacological strategy in experimental models of chronic diseases and in clinical trials. The present study showed that controlled administration of BN improved bone parameters, high-density lipoprotein-cholesterol levels, and lipid peroxidation in healthy rats. Therefore, BN is a promising non-pharmacological agent for the prevention of the onset of chronic non-communicable diseases.

Relaxing the "second brain": nutrients and bioactive compounds as a therapeutic and preventive strategy to alleviate oxidative stress in the enteric nervous system.

The enteric nervous system (ENS) regulates several functional and immunological processes in the gastrointestinal tract. However, some diseases can disrupt the ENS functionality, impacting the behavior of enteric neurons and enteric glial cells by increasing the accumulation of reactive oxygen species. Oxidative stress is considered to be a trigger for alterations in these cells' morphology, density, and neurochemical patterns. In light of this, nutritional strategies are a growing field of investigation regarding their potential to modulate enteric neurons and enteric glial cells through reduced reactive oxygen species production. Moreover, several lines of evidence show that nutrients are related to counteracting oxidative stress. Some studies have evaluated the potential of nutrients with antioxidant roles (such as amino acids, polyphenols, prebiotics, vitamins, and specific extracts obtained from foods) to modulate the ENS. Thus, this review discusses how bioactive compounds and nutrients can impact the ENS by alleviating oxidative stress.

Brazil nut supplementation does not affect trimethylamine-n-oxide plasma levels in patients with coronary artery disease.

The purposes of this study were to assess the effect of Brazil nut supplementation on trimethylamine N-oxide (TMAO) levels and glutathione peroxidase (GPx) activity in patients with coronary artery disease (CAD). Patients with CAD were randomly assigned to two groups, Brazil nut group (23 patients, 48% male, 62.7 ± 6.8 years, 29.4 ± 5.8 kg/m2 ), which received one Brazil nut per day for 3 months, and the control group (14 patients, 43% male, 63.7 ± 8.7 years, 28.4 ± 4.2 kg/m2 ) who did not receive any supplementation. After 3 months, TMAO levels and their precursors did not change in either group. Although not significant, GPx activity increased by 41% in the Brazil nut group. TMAO levels were negatively associated with total fiber intake (r = -0.385 and p = .02). A 3-month Brazil nut supplementation did not change TMAO levels and GPx activity in CAD patients. PRACTICAL APPLICATIONS: Trimethylamine N-oxide (TMAO) has been associated with oxidative stress and cardiovascular disease risk. Thus, the increase in antioxidants enzymes production could be a promising strategy to reduce TMAO-mediated oxidative stress. In this context, nutritional strategies are well-known as activators of cellular antioxidant responses. As Brazil nuts have a known role in reducing oxidative stress by increasing glutathione peroxidase (GPx) activity (a selenium-dependent antioxidant enzyme), this study hypothesized that Brazil nuts could be a strategy that, via antioxidant capacity, would reduce TMAO plasma levels. Although no changes in TMAO levels and GPx activity can be observed in this study, it is believed that other results can be obtained depending on the dosage used. Thus, this study can open new paths and direct other studies with different doses and treatment times to evaluate the effects of Brazil Nuts on TMAO levels.

5/6 nephrectomy affects enteric glial cells and promotes impaired antioxidant defense in the colonic neuromuscular layer.

AIMS: Chronic kidney disease (CKD) produces multiple repercussions in the gastrointestinal tract (GIT), such as alterations in motility, gut microbiota, intestinal permeability, and increased oxidative stress. However, despite enteric glial cells (EGC) having important neural and immune features in GIT physiology, their function in CKD remains unknown. The present study investigates colonic glial markers, inflammation, and antioxidant parameters in a CKD model. MAIN METHODS: A 5/6 nephrectomized rat model was used to induce CKD in rats and Sham-operated animals as a control to suppress. Biochemical measures in plasma and neuromuscular layer such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were carried out. Kidney histopathology was evaluated. Colon morphology analysis and glial fibrillary acid protein (GFAP), connexin-43 (Cx43), nuclear factor-kappa B (NF-κB) p65, and GPx protein expression were performed. KEY FINDINGS: The CKD group exhibited dilated tubules and tubulointerstitial fibrosis in the reminiscent kidney (p = 0.0002). CKD rats showed higher SOD activity (p = 0.004) in plasma, with no differences in neuromuscular layer (p = 0.9833). However, GPx activity was decreased in the CKD group in plasma (p = 0.013) and neuromuscular layer (p = 0.0338). Morphological analysis revealed alterations in colonic morphometry with inflammatory foci in the submucosal layer and neuromuscular layer straightness in CKD rats (p = 0.0291). In addition, GFAP, Cx43, NF-κBp65 protein expression were increased, and GPx decreased in the neuromuscular layer of the CKD group (p < 0.05). SIGNIFICANCE: CKD animals present alterations in colonic cytoarchitecture and decreased layer thickness. Moreover, CKD affects the enteric glial network of the neuromuscular layer, associated with decreased antioxidant activity and inflammation.

High-fat diets on the enteric nervous system: Possible interactions and mechanisms underlying dysmotility.

Obesity is a chronic disease that affects various physiological systems. Among them, the gastrointestinal tract appears to be a main target of this disease. High-fat diet (HFD) animal models can help recapitulate the classic signs of obesity and present a series of gastrointestinal alterations, mainly dysmotility. Because intestinal motility is governed by the enteric nervous system (ENS), enteric neurons, and glial cells have been studied in HFD models. Given the importance of the ENS in general gut physiology, this review aims to discuss the relationship between HFD-induced neuroplasticity and gut dysmotility observed in experimental models. Furthermore, we highlight components of the gut environment that might influence enteric neuroplasticity, including gut microbiota, enteric glio-epithelial unit, serotonin release, immune cells, and disturbances such as inflammation and oxidative stress.

Brazil Nut Supplementation Does Not Regulate PPARß/δ Signaling Pathway in Peripheral Blood Mononuclear Cells from Coronary Artery Disease Patients.

Background: Peroxisome proliferator-activated receptor (PPAR)ß/δ activation is a potential target for modulation of inflammation in cardiovascular disease. PPARß/δ activation depends on the presence of a ligand, which may be pharmacological or natural, such as bioactive compounds and nutrients. Due to its composition, rich in selenium and unsaturated fatty acids, Brazil nuts have been related to reduced oxidative stress and inflammation in chronic non-communicable diseases and could regulate PPARß/δ. This study aimed to evaluate the effects of Brazil nut supplementation on PPARß/δ mRNA expression in patients with Coronary Artery Disease (CAD).Methods: A secondary analysis of a randomized controlled clinical trial was performed with 36 CAD patients. Patients were randomly assigned to either the Supplementation group or the control group and followed up for three months. The Supplementation group consumed 1 Brazil nut/day; the control group did not receive any intervention. At the baseline and after three months, analysis of gene expression and biochemical parameters linked to inflammatory biomarkers and oxidative stress was carried out.Results: In the supplementation group, no significant change was observed in PPARß/δ (0.9 ± 0.5 vs 1.2 ± 0.6; p = 0.178) and NF-κB (1.6 ± 1.5 vs 0.8 ± 0.30, p = 0.554) mRNA expression. There were no significant changes in both groups concerning all the other biochemical parameters.Conclusion: One Brazil nut per day for three months was not able to increase the PPARß/δ expression in CAD patients.

Brazil Nut (Bertholletia excelsa H.B.K) Retards Gastric Emptying and Modulates Enteric Glial Cells in a Dose-Dependent Manner.

BACKGROUND: The role of food and nutrients in the regulation of enteric glial cell functions is unclear. Some foods influence enteric neurophysiology and can affect glial cell functions that include regulation of the intestinal barrier, gastric emptying, and colonic transit. Brazil nuts are the most abundant natural source of selenium, unsaturated fatty acids, fibers, and polyphenols. OBJECTIVE: The study investigated the effects of a Brazil nut-enriched diet on enteric glial cells and gastrointestinal transit. METHODS: Two-month-old male Wistar rats were randomized to a standard diet (control group, CG), standard diet containing 5% (wt/wt) Brazil nut (BN5), and standard diet containing 10% (wt/wt) Brazil nut (BN10) (n = 9 per group). After eight weeks, the animals underwent constipation and gastric emptying tests to assess motility. Evaluations of colonic immunofluorescence staining for glial fibrillary acidic protein (GFAP) and myenteric ganglia area were performed. RESULTS: The BN5 group showed increased weight gain while the BN10 group did not (p < 0.0001). The BN10 group showed higher gastric residue amounts compared to the other groups (p = 0.0008). The colon exhibited an increase in GFAP immunoreactivity in the BN5 group compared to that in the other groups (p = 0.0016), and the BN10 group presented minor immunoreactivity compared to the CG (p = 0.04). The BN10 group presented a minor ganglia area compared to the CG (p = 0.0155). CONCLUSION: The Brazil nut-enriched diet modified the gastric residual, colonic GFAP immunoreactivity, and myenteric ganglia area after eight weeks in healthy male Wistar rats.

Impact of Brazil Nut (Bertholletia excelsa, H.B.K.) Supplementation on Body Composition, Blood Pressure, and the Vascular Reactivity of Wistar Rats When Submitted to a Hypersodium Diet.

Introdution: Endothelium integrity is a key that maintains vascular homeostasis but it can suffer irreversible damage by blood pressure changes, reflecting an imbalance in the maintenance of vascular homeostasis.Objective: The aim of this study was to investigate the impact of Brazil nut (Bertholletia excelsa, H.B.K.) (BN) supplementation (10% in chow, wt/wt) on the vascular reactivity of Wistar rats during chronic exposure to a sodium overload (1% in water).Methods: First, male Wistar rats were allocated into two groups: Control Group (CG) and the Hypersodic Group (HG) for 4 weeks. Afterward, the CG was divided into the Brazil Nut Group (BNG) and the HG Group into the Hypersodic Brazil Nut Group (HBNG) for a further 8 weeks, totaling 4 groups. Blood pressure was measured during the protocol. At the end of the protocol, the vascular reactivity procedure was performed. Glucose, lipid profile, lipid peroxidation, and platelet aggregation were analyzed in the serum. Body composition was determined by the carcass technique.Results: The groups that were supplemented with the BN chow presented less body mass gain and body fat mass, together with lower serum glucose levels. The HG Group presented an increase in blood pressure and a higher platelet aggregation, while the BN supplementation was able to blunt this effect. The HG Group also showed an increase in contractile response that was phenylephrine-induced and a decrease in maximum relaxation that was acetylcholine-induced when compared to the other groups.Conclusion: The BN supplementation was able to prevent an impaired vascular function in the early stages of arterial hypertension, while also improving body composition, serum glucose, and platelet aggregation.

Can diet modulate trimethylamine N-oxide (TMAO) production? What do we know so far?

BACKGROUND: Trimethylamine N-oxide (TMAO) is a metabolite that has attracted attention due to its positive association with several chronic non-communicable diseases such as insulin resistance, atherosclerotic plaque formation, diabetes, cancer, heart failure, hypertension, chronic kidney disease, liver steatosis, cardiac fibrosis, endothelial injury, neural degeneration and Alzheimer's disease. TMAO production results from the fermentation by the gut microbiota of dietary nutrients such as choline and carnitine, which are transformed to trimethylamine (TMA) and converted into TMAO in the liver by flavin-containing monooxygenase 1 and 3 (FMO1 and FMO3). Considering that TMAO is involved in the development of many chronic diseases, strategies have been found to enhance a healthy gut microbiota. In this context, some studies have shown that nutrients and bioactive compounds from food can modulate the gut microbiota and possibly reduce TMAO production. OBJECTIVE: This review has as main objective to discuss the studies that demonstrated the effects of food on the reduction of this harmful metabolite. METHODS: All relevant articles until November 2020 were included. The articles were searched in Medline through PubMed. RESULTS: Both the food is eaten acutely and chronically, by altering the nature of the gut microbiota, influencing colonic TMA production. Furthermore, hepatic production of TMAO by the flavin monooxygenases in the liver may also be influenced by phenolic compounds present in foods. CONCLUSION: The evidence presented in this review shows that TMAO levels can be reduced by some bioactive compounds. However, it is crucial to notice that there is significant variation among the studies. Further clinical studies should be conducted to evaluate these dietary components' effectiveness, dose, and intervention time on TMAO levels and its precursors.