Effect of adjuvant probiotic therapy (Lactobacillus reuteri) in the treatment of periodontitis associated with diabetes mellitus: clinical, controlled, and randomized study.

OBJECTIVES: Subgingival instrumentation (SI) with probiotics may be a proposal for the treatment of periodontitis (P), for patients with type 2 diabetes mellitus (T2DM). The Lactobacillus reuteri probiotic as an adjunctive therapy in the treatment of P associated with T2DM was evaluated. MATERIALS AND METHODS: Forty diabetic participants diagnosed with P (stage III and IV, grade B) were randomized into SI + Placebo (n = 20): subgingival instrumentation plus placebo lozenges and SI + Probi (n = 20): subgingival instrumentation plus probiotics. Probing depth (PD), gingival recession (GR), clinical attachment level (CAL), plaque index (PI), bleeding on probing (BoP), and PISA index were performed at baseline and 30, 90, and 180 days. Cytokine concentration in the gingival crevicular fluid, subgingival biofilm sample, and LDL and HDL subfractions were evaluated. RESULTS: In the deep pockets, PD in SI + Probi showed increased values (p = 0.02) compared to SI + Placebo at 90 days. For CAL, SI + Probi showed increased values compared to SI + Placebo, with a significant difference at 30 days (p = 0.03), 90 days (p = 0.02), and 180 days (p = 0.04). At #PD ≥ 7 mm, SI + Probi had a more frequent number of sites (p = 0.03) compared to SI + Placebo only at baseline. For the PISA, SI + Probi showed a significant difference (p = 0.04) compared to SI + Placebo at 90 days. For cytokines, SI + Probi showed higher quantification than SI + Placebo for IL-10 (p < 0.001) at 90 days, IL-12 (p = 0.010) at 90 days, IL-1ß (p = 0.035) at 90 days, and IL-8 (p = 0.003) at baseline. SI + Placebo showed higher quantification of IL-1ß (p = 0.041) compared to SI + Probi only at 30 days. There was a reduction in all microbial complexes. SI + Probi improved LDL size (246.7 nm vs 260.4 nm; p < 0.001), while large HDL subfractions were reduced aft 180 days of treatment (24.0% vs 20.3%; p = 0.022) when compared with SI + Placebo; this response was dependent of probiotics (1.0 mg/dL vs - 6.2 mg/dL; p = 0.002). CONCLUSION: Subgingival instrumentation improved the clinical periodontal parameters in patients with T2DM. The use of L. reuteri probiotics had no additional effects compared with the placebo; however, there was a positive effect on the lipoprotein subfraction. CLINICAL RELEVANCE: Scientific rationale for study: subgingival instrumentation with probiotics may be a proposal for the treatment of periodontitis (P), especially for patients with type 2 diabetes mellitus (T2DM). PRINCIPAL FINDINGS: the use of L. reuteri probiotics had no additional effects compared with the placebo; however, there was a positive effect on the lipoprotein subfraction.  Practical implications: L. reuteri as an adjunct to subgingival instrumentation may have significant therapeutic implications in dyslipidemia.

Higher bodily adiposity, fat intake, and cholesterol serum levels are associated with higher disease activity in psoriatic arthritis patients: is there a link among fat and skin and joint involvement?

INTRODUCTION/ OBJECTIVES: Assuming that there is a link between lipid and glucose metabolism and inflammation in patients with psoriatic arthritis (PsA), our aim was to evaluate the relationships among body composition measurements, food intake, and disease activity in patients with PsA. METHODS: A total of 97 patients with PsA, according to the CASPAR criteria, were included in this cross-sectional study. Body composition measurements (whole-body DXA, GE-Lunar), food intake (3-day registry) and biochemical and inflammatory serum markers were evaluated. Skin and joint disease activity were assessed by using PASI, BSA, DAS28, and minimal disease activity (MDA). The level of significance was set as p < 0.05. RESULTS: A higher prevalence of obesity, according to the fat mass index (FMI) (92.7%), and metabolic syndrome (MetS) (54%) were found, but no significant changes regarding lean or bone mass were found. Joint disease activity was positively correlated with total body fat (r = 0.4; p < 0.001), FMI (r = 0.33; p < 0.001), body mass index (r = 0.20; p < 0.049) and waist circumference (r = 0.27; p = 0.009). In addition, joint disease activity was negatively associated with muscle mass (r = - 0.38; p < 0.001). Skin disease activity was positively correlated with total cholesterol (r = 0.3; p = 0.003) and LDL-cholesterol (r = 0.28; p = 0.006). After multiple adjustments, patients with severe joint disease activity had higher body adiposity than patients in remission or with low disease activity. Skin disease activity was associated with higher trans-fat intake and lower omega-6 consumption. CONCLUSIONS: Our data suggest a possible harmful link among fat (body adiposity, saturated fat consumption, LDL-cholesterol serum levels) and joint and skin disease activity in patients with PsA.

Effect of chemotherapy on dietary glycemic index and load in patients with breast cancer and their relationships to body fat and phase angle.

Dietary glycemic index (GI) and glycemic load (GL) are indicators of carbohydrate consumption and widely used in studies evaluating the risk for breast cancer. However, the effect of chemotherapy on these indices has been scarcely studied. The aim of this study was to evaluate dietary levels of GI and GL in women with breast cancer during chemotherapy treatment and their relationships to body fat and phase angle. Twenty-five patients were assessed according to demographic, clinical, anthropometric, and food consumption data. Dietary intake was assessed by 24-h dietary recalls applied on nonconsecutive days. Anthropometric measures and body composition were determined at all study timepoints: prior to the first chemotherapy cycle (T0), immediately after the last chemotherapy cycle (T1), and 2 months after T1 (T2). There was no difference in mean GI and GL among study timepoints. However, a high prevalence of inadequate GI and GL values was noted, independent of study timepoint. GI and GL were associated with phase angle at T1. GI was associated with percentage fat at T0 only. Dietary GI and GL were unchanged during chemotherapy, but were associated with indicators of clinical outcome, such as percentage fat and phase angle.

Ketogenic diet in epileptic children: impact on lipoproteins and oxidative stress.

OBJECTIVES: Ketogenic diet (KD) is an important therapy used in the control of drug-refractory seizures. The major goal of this review is to update the knowledge about the adverse effects of KD on lipoproteins, lipid profile, and cardiometabolic risk. METHODS: Articles on the effect of the KD on plasma lipoproteins of children and adolescents with refractory epilepsy, which were published in the past 15 years and indexed in the PubMed and MedLine databases, were included. RESULTS: Dyslipidemia was recurrent in children, and adolescents treated with KD. Evidence suggests that hypercholesterolemia promotes structural modifications in low-density lipoprotein particles. Such modifications possibly favor oxidative processes and contribute to changes in the size of lipoproteins, particularly related to small and denser LDL. However, oxidative modifications in LDL of children on KD are not described in the literature. DISCUSSION: The positive effects of KD on the health of children and adolescents with refractory epilepsy are unquestionable. Conversely, this positive role is associated with significant and negative changes in lipid metabolism. Moreover, the positive effects are possibly related to oxidative reactions and unbalance of antioxidants that can contribute to an increased cardiometabolic risk. Therefore, this review invites clinicians and researchers to investigate the lipid and oxidative metabolism in their clinical practice and trials, respectively.

Effects of phytosterol supplementation on lipoprotein subfractions and LDL particle quality.

Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein subfractions and the quality of the LDL particle have not been studied in greater detail. We aimed to evaluate the effects of phytosterols supplements on lipids, lipoproteins subfractions, and on the quality of LDL. A prospective, pilot-type, open label, cross-over study, randomized 23 males in primary prevention of hypercholesterolemia to receive diet or diet plus phytosterol (2.6 g in 2 doses, with meals) for 12 weeks, when treatments were switched for another 12 weeks. Lipoprotein subfractions were analyzed by electrophoresis in polyacrylamide gel (Lipoprint System®). The Sampson equation estimated the small and dense (sd) and large and buoyant (lb) LDL subfractions from the lipid profile. Quality of LDL particle was analyzed by Z-scan and UV-vis spectroscopy. Primary outcome was the comparison of diet vs. diet plus phytosterols. Secondary outcomes assessed differences between baseline, diet and diet plus phytosterol. Non-parametric statistics were performed with p < 0.05. There was a trend to reduction on HDL-7 (p = 0.05) in diet plus phytosterol arm, with no effects on the quality of LDL particles. Heatmap showed strong correlations (ρ > 0.7) between particle size by different methods with both interventions. Diet plus phytosterol reduced TC, increased HDL-c, and reduced IDL-B, whereas diet increased HDL7, and reduced IDL-B vs. baseline (p < 0.05, for all). Phytosterol supplementation demonstrated small beneficial effects on HDL-7 subfraction, compared with diet alone, without effects on the quality of LDL particles.This trial is registered in Clinical Trials (NCT06127732) and can be accessed at https://clinicaltrials.gov .

Stearic Acid, but not Palmitic Acid, is Associated with Inflammatory and Endothelial Dysfunction Biomarkers in Individuals at Cardiovascular Risk. / Ácido Esteárico (mas não o Ácido Palmítico) está Associado a Biomarcadores Inflamatórios e de Disfunção Endotelial em Indivíduos em Risco Cardiovascular.

BACKGROUND: Several studies have associated dietary saturated fatty acids (SFAs) with cardiovascular risk but there are still many controversies. Most of these studies have focused on the effects of palmitic acid on circulating lipids. Stearic acid usually shows a neutral effect on blood lipids, however, there is a lack of clinical studies assessing the link with inflammatory and endothelial dysfunction markers. OBJECTIVE: To evaluate the association of red blood cell (RBC) SFA (palmitic and stearic acids) with circulating inflammatory and endothelial dysfunction biomarkers. METHODS: Cross-sectional study of 79 adults of both sexes with at least one cardiovascular risk factor but without previous events (acute myocardial infarction or stroke). Plasma biomarkers - lipids, glucometabolic markers, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) - and RBC palmitic and stearic fatty acids were analyzed. The associations were assessed by correlation and multiple linear regression analyses, with statistical significance set at p < 0.05. RESULTS: Palmitic acid showed no significant associations with traditional cardiovascular risk factors or inflammatory markers. Stearic acid, on the other hand, was inversely correlated with blood cholesterol and triglycerides, but independently associated with hs-CRP, IL-6, and TNF-α. CONCLUSION: Stearic acid is associated with inflammatory and endothelial dysfunction biomarkers in individuals with at least one cardiovascular risk factor.

FUNDAMENTO: Vários estudos têm associado o consumo de ácidos graxos saturados (AGSs) com risco cardiovascular, mas ainda existem muitas controvérsias. A maioria desses estudos avaliou os efeitos do ácido palmítico sobre lipídios circulantes. O ácido esteárico geralmente apresenta um efeito neutro sobre os lipídios sanguíneos, mas faltam estudos clínicos avaliando sua relação com marcadores de inflamação e de disfunção endotelial. OBJETIVOS: Avaliar a associação de AGSs das hemácias (ácido palmítico e ácido esteárico) com biomarcadores inflamatórios e de disfunção endotelial circulantes. MÉTODOS: Estudo transversal que incluiu 79 adultos de ambos os sexos com pelo menos um fator de risco cardiovascular, mas sem eventos prévios (infarto agudo do miocárdio ou acidente vascular cerebral). Biomarcadores plasmáticos ­ lipídios, marcadores glicometabólicos, proteína C ultrassensível (PCR-us), Interleucina 6 (IL-6), Interleucina 10 (IL-10), Fator de Necrose Tumoral-α (TNF-α), Proteína quimioatraente de Monócitos 1 (MCP-1) ­ e ácidos graxos das hemácias (ácidos palmítico e esteárico) foram analisados. As associações foram avaliadas por análises de correlações e regressões lineares múltiplas, com significância estatística estabelecida em p<0,05. RESULTADOS: O ácido palmítico não apresentou associações com fatores de risco cardiovasculares ou com marcadores inflamatórios. Por outro lado, o ácido esteárico foi inversamente correlacionado com PCR-us, IL-6 e TNF-α, mas independentemente associado com PCR-us, IL-6, e TNF-α. CONCLUSÃO: O ácido esteárico está associado com biomarcadores inflamatórios e disfunção endotelial em indivíduos com um ou mais fatores de risco cardiovascular.

Red Blood Cells' Omega-6 and Omega-3 Polyunsaturated Fatty Acids Have a Distinct Influence on LDL Particle Size and its Structural Modifications. / Os Ácidos Graxos Poli-insaturados Ômega-6 e Ômega-3 Presentes nas Hemácias Exercem uma Influência Distinta sobre o Tamanho das Partículas de LDL e suas Alterações Estruturais.

BACKGROUND: While Omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs) have established effects on cardiovascular disease (CVD) risk factors, little is known about their impacts on LDL quality markers. OBJECTIVE: To assess the associations of n-3 and n-6 PUFA within red blood cells (RBC) with LDL particle size, small dense LDL-c (sdLDL-c), and electronegative LDL [LDL(-)] in adults with CVD risk factors. METHODS: Cross-sectional study involving 335 men and women aged 30 to 74 with at least one cardiovascular risk factor. Analyses were conducted on biochemical parameters, such as glucose, insulin, HbA1c, C-reactive protein (CRP), lipid profile, lipoprotein subfractions, electronegative LDL particle [LDL(-)] and its autoantibody, and RBC n-3 and n-6 PUFAs. Independent t-test/Mann-Whitney test, one-way ANOVA/Kruskal-Wallis test, and multiple linear regressions were applied. All tests were two-sided, and a p-value of less than 0.05 was considered statistically significant. RESULTS: The RBC n-6/n-3 ratio was associated with increased LDL(-) (ß = 4.064; 95% CI = 1.381 - 6.748) and sdLDL-c (ß = 1.905; 95% CI = 0.863 - 2.947) levels, and reduced LDL particle size (ß = -1.032; 95% CI = -1.585 - -0.478). Separately, n-6 and n-3 PUFAs had opposing associations with those parameters, reinforcing the protective effects of n-3 and showing the potential negative effects of n-6 on LDL particle quality. CONCLUSION: RBC n-6 PUFA was associated with increased cardiometabolic risk and atherogenicity of LDL particles, while n-3 PUFA was associated with better cardiometabolic parameters and LDL particle quality.

FUNDAMENTO: Embora os ácidos graxos poli-insaturados ômega-3 e ômega-6 (AGPIs n-3 e n-6) tenham efeitos bem conhecidos sobre os fatores de risco de doenças cardiovasculares (DCV), ainda existe um conhecimento limitado sobre como eles afetam os indicadores de qualidade da LDL. OBJETIVO: Avaliar as associações dos AGPIs n-3 e n-6 de hemácias com o tamanho da partícula da LDL, LDL-c pequena e densa (sdLDL-c) e com LDL eletronegativa [LDL(-)] em adultos com fatores de risco para DCV. MÉTODOS: Estudo transversal com 335 homens e mulheres de 30 a 74 anos com, pelo menos, um fator de risco cardiovascular. Foram realizadas análises de parâmetros bioquímicos, como glicose, insulina, HbA1c, proteína C reativa (PCR), perfil lipídico, subfrações de lipoproteínas, partícula eletronegativa de LDL [LDL(-)] e seu autoanticorpo, e os AGPIs n-3 e n- 6 de hemácias. Os testes t independente/teste de Mann-Whitney, ANOVA unidirecional/teste de Kruskal-Wallis e regressões lineares múltiplas foram aplicados. Todos os testes foram bilaterais e um valor de p inferior a 0,05 foi considerado estatisticamente significativo. RESULTADOS: A relação n-6/n-3 de hemácias foi associada ao aumento dos níveis de LDL(-) (ß = 4,064; IC de 95% = 1,381 ­ 6,748) e sdLDL-c (ß = 1,905; IC de 95% = 0,863 ­ 2,947), e redução do tamanho das partículas de LDL (ß = -1,032; IC de 95% = -1,585 − -0,478). Individualmente, os AGPIs n-6 e n-3 apresentaram associações opostas com esses parâmetros, realçando os efeitos protetores do n-3 e evidenciando os possíveis efeitos adversos do n-6 na qualidade das partículas de LDL. CONCLUSÃO: O AGPI n-6, presente nas hemácias, foi associado ao aumento do risco cardiometabólico e à aterogenicidade das partículas de LDL, enquanto o AGPI n-3 foi associado a melhores parâmetros cardiometabólicos e à qualidade das partículas de LDL.

[Meat consumption by adults and the elderly in a city colonized by Germans in the south of Brazil: a population-based study]. / Consumo de carnes por adultos e idosos de uma cidade de colonização alemã do sul do Brasil: estudo de base populacional.

Excessive meat consumption, especially red and processed meats, is associated with increased morbidity and mortality. The pattern of meat consumption varies in Brazil and is influenced by economic and cultural factors in the world. The study aimed to analyze the consumption of meat by adults and the elderly in a city colonized by Germans in the south of Brazil. It involved a cross-sectional population study. Sociodemographic and meat consumption data were collected using a previously validated Food Frequency Questionnaire. Frequencies and amounts were analyzed by type of meat and processing. The association between excessive meat consumption and the study variables was estimated by Prevalence Ratio. Among the 1,941 participants, the average amount of meat consumed was 250 g/day, the most consumed being white unprocessed meat (138 g/day), especially poultry (80 g/day). The prevalence of excessive consumption of red and processed meat (more than 500 g/week) was 63%, mainly among men (PR=1.6; 95%CI 1.5-1.8), aged 20 to 29 years (PR=1.4; 95%CI 1.2-1.5), and higher economic class (PR=1.2; 95%CI 1.0-1.3). Excessive consumption of red and processed meat among young men of upper economic class should be the target of public health actions for the adequacy of food consumption.

O consumo excessivo de carnes, em especial as vermelhas e processadas, está associado ao aumento da morbi-mortalidade. O padrão de consumo de carnes varia no Brasil e no mundo influenciado por fatores econômicos e culturais. O estudo buscou analisar o consumo de carnes por adultos e idosos de uma cidade de colonização alemã do sul do Brasil. Trata-se de estudo populacional seccional. Foram coletados dados sociodemográficas e de consumo de carne por Questionário de Frequência Alimentar previamente validado. Foram analisadas as frequências, e as quantidades por tipo de carne e processamento. A associação entre o consumo excessivo de carne e as variáveis de estudo foi estimada por Razão de Prevalência. Entre os 1.941 participantes, a média de carne consumida foi de 250 g/dia, sendo a carne não processada branca (138 g/dia) a mais consumida, com destaque para as aves (80 g/dia). A prevalência de consumo excessivo de carne vermelha e processada (mais que 500 g/semana) foi de 63%, principalmente entre os homens (RP=1,6; IC95% 1,5-1,8), de 20 a 29 anos (RP=1,4; IC95% 1,2-1,5), e mais alta classe econômica (RP=1,2; IC95% 1,0-1,3). O consumo excessivo de carne vermelha e processada entre homens jovens de classe econômica alta deve ser alvo de ações de saúde pública para a adequação no consumo alimentar.

Effect of Nuts on Markers of Inflammation and Oxidative Stress: A Narrative Review.

Oxidative stress and inflammation are mediators in the pathophysiology of several non-communicable diseases (NCDs). Tree nuts and peanuts lower risk factors of cardiometabolic disease, including blood lipids, blood pressure and insulin resistance, among others. Given their strong antioxidant/anti-inflammatory potential, it is plausible that nuts may also exert a favorable effect on inflammation and oxidative stress. Evidence from systematic reviews and meta-analyses of cohort studies and randomized controlled trials (RCTs) suggest a modest protective effect of total nuts; however, the evidence is inconsistent for specific nut types. In this narrative review, the state of evidence to date is summarized for the effect of nut intake on biomarkers of inflammation and oxidative stress, and an attempt is made to define the gaps in research while providing a framework for future research. Overall, it appears that some nuts, such as almonds and walnuts, may favorably modify inflammation, and others, such as Brazil nuts, may favorably influence oxidative stress. There is a pressing need for large RCTs with an adequate sample size that consider different nut types, and the dose and duration of nut intervention, while evaluating a robust set of biomarkers for inflammation and oxidative stress. Building a stronger evidence base is important, especially since oxidative stress and inflammation are mediators of many NCDs and can benefit both personalized and public health nutrition.

Influence of polymorphisms in IRS1, IRS2, MC3R, and MC4R on metabolic and inflammatory status and food intake in Brazilian adults: An exploratory pilot study.

Polymorphisms in genes of leptin-melanocortin and insulin pathways have been associated with obesity and type 2 diabetes. We hypothesized that polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory markers and food intake composition in Brazilian subjects. This exploratory pilot study included 358 adult subjects. Clinical, anthropometric, and laboratory data were obtained through interview and access to medical records. The variants IRS1 rs2943634 A˃C, IRS2 rs1865434 C>T, MC3R rs3746619 C>A, and MC4R rs17782313 T>C were analyzed by real-time polymerase chain reaction. Food intake composition was assessed in a group of subjects with obesity (n = 84) before and after a short-term nutritional counseling program (9 weeks). MC4R rs17782313 was associated with increased risk of obesity (P = .034). Multivariate linear regression analysis adjusted by covariates indicated associations of IRS2 rs1865434 with reduced low-density lipoprotein cholesterol and resistin, MC3R rs3746619 with high glycated hemoglobin, and IRS1 rs2943634 and MC4R rs17782313 with increased high-sensitivity C-reactive protein (P < .05). Energy intake and carbohydrate and total fat intakes were reduced after the diet-oriented program (P < .05). Multivariate linear regression analysis showed associations of IRS2 rs1865434 with high basal fiber intake, IRS1 rs2943634 with low postprogram carbohydrate intake, and MC4R rs17782313 with low postprogram total fat and saturated fatty acid intakes (P < .05). Although significant associations did not survive correction for multiple comparisons using the Benjamini-Hochberg method in this exploratory study, polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory status in Brazilian adults. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acid intakes in response to a diet-oriented program in subjects with obesity.

Tumor aggressiveness is associated with cell integrity changes in breast cancer-surviving women: a follow-up study.

INTRODUCTION: Introduction: cell integrity and fat mass had been studied as a prognostic marker for cancer survival. Objective: our aim was to evaluate the association between tumor aggressiveness and cell integrity changes and adiposity in breast cancer (BC) survivors. Methods: women with BC (n = 114) were evaluated at diagnosis and 5 years later. Percentage of lean mass, fat mass, phase angle (PA), resistance (R) and reactance (Xc) were obtained by bioimpedance (450-50 kHz). Plasma leptin was assessed by immunoassay. Changes in body composition were assessed by the paired t-test or Wilcoxon's test. The disease effect associated with the time of diagnosis was assessed by a generalized linear model. Regression models were structured to assess the prevalence ratio between tumor aggressiveness and body composition changes adjusted for age, income, and level of schooling. Results: patients with N+ (p = 0.02) and % Ki67 > 14 (p = 0.00) show a reduction in Xc. Patients with advanced clinical staging (CS) (p = 0.02), tumors > 2 cm (p = 0.01), N+ (p = 0.01), non-luminal tumors (p = 0.02), ER- (p = 0, 00) and PR- (p = 0.02) show a PA reduction, and N+ patients (p = 0.01) show a reduction in leptin during follow-up. Tumors  2 cm (CI: 0.33-0.95; p = 0.03), initial CS (CI: 0.20-0.93; p = .0.03), and luminal tumors (CI: 0.01-0.95; p = 0.04) are related to a lower reduction in PA. Initial CS (CI: 0.00-0.00; p = 0.00) are related to increased leptin. Conclusion: tumor aggressiveness is associated with cell integrity changes in women who are BC survivors.

INTRODUCCIÓN: Introducción: se han estudiado la integridad celular y la masa grasa como marcadores pronósticos de supervivencia al cáncer. Objetivo: nuestro objetivo fue evaluar la asociación entre la agresividad del tumor y los cambios en la integridad celular y la adiposidad en supervivientes de cáncer de mama (CM). Métodos: las mujeres con CM (n = 114) se evaluaron al diagnóstico y 5 años después. El porcentaje de masa magra, masa grasa, ángulo de fase (PA), resistencia (R) y reactancia (Xc) se obtuvo mediante bioimpedancia (450-50 kHz). La leptina plasmática se evaluó mediante inmunoensayo. Los cambios en la composición corporal se evaluaron mediante la prueba de la t pareada o la prueba de Wilcoxon. El efecto de la enfermedad asociado con el momento del diagnóstico se evaluó mediante un modelo lineal generalizado. Los modelos de regresión se estructuraron para evaluar la razón de prevalencia entre la agresividad del tumor y los cambios en la composición corporal ajustados por edad, ingresos y nivel de escolaridad. Resultados: las pacientes con N+ (p = 0,02) y % Ki67 > 14 (p = 0,00) muestran una reducción de Xc. Las pacientes con estadificación clínica (EC) avanzada (p = 0,02), tumores > 2 cm (p = 0,01), N+ (p = 0,01), tumores no luminales (p = 0,02), ER- (p = 0, 00) y PR- (p = 0,02) muestran una reducción de la AP, y los pacientes N+ (p = 0,01) muestran una reducción de la leptina durante el seguimiento. Los tumores  2 cm (IC: 0,33-0,95; p = 0,03), el EC inicial (IC: 0,20-0,93; p = 0,03) y los tumores luminales (IC: 0,01-0,95; p = 0,04) se relacionan con un menor reducción de la PA. Los EC iniciales (IC: 0,00-0,00; p = 0,00) están relacionados con un aumento de leptina. Conclusión: la agresividad del tumor se asocia con cambios en la integridad celular en las mujeres que sobreviven al CM.

Reply to Ravnskov, U. Is High Cholesterol Deleterious? An Alternative Point of View. Comment on "Burén et al. A Ketogenic Low-Carbohydrate High-Fat Diet Increases LDL Cholesterol in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial. Nutrients 2021, 13, 814".

We thank Ravnskov [...].

A Ketogenic Low-Carbohydrate High-Fat Diet Increases LDL Cholesterol in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial.

Ketogenic low-carbohydrate high-fat (LCHF) diets are popular among young, healthy, normal-weight individuals for various reasons. We aimed to investigate the effect of a ketogenic LCHF diet on low-density lipoprotein (LDL) cholesterol (primary outcome), LDL cholesterol subfractions and conventional cardiovascular risk factors in the blood of healthy, young, and normal-weight women. The study was a randomized, controlled, feeding trial with crossover design. Twenty-four women were assigned to a 4 week ketogenic LCHF diet (4% carbohydrates; 77% fat; 19% protein) followed by a 4 week National Food Agency recommended control diet (44% carbohydrates; 33% fat; 19% protein), or the reverse sequence due to the crossover design. Treatment periods were separated by a 15 week washout period. Seventeen women completed the study and treatment effects were evaluated using mixed models. The LCHF diet increased LDL cholesterol in every woman with a treatment effect of 1.82 mM (p < 0.001). In addition, Apolipoprotein B-100 (ApoB), small, dense LDL cholesterol as well as large, buoyant LDL cholesterol increased (p < 0.001, p < 0.01, and p < 0.001, respectively). The data suggest that feeding healthy, young, normal-weight women a ketogenic LCHF diet induces a deleterious blood lipid profile. The elevated LDL cholesterol should be a cause for concern in young, healthy, normal-weight women following this kind of LCHF diet.

Omega-3 Fatty Acids Improve Functionality of High-Density Lipoprotein in Individuals With High Cardiovascular Risk: A Randomized, Parallel, Controlled and Double-Blind Clinical Trial.

Omega-3 (ω-3) fatty acids have been extensively studied for primary and secondary prevention of cardiovascular health, but their ability to modulate HDL functionality remains unclear. The purpose of this study was to investigate the role of ω-3, rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA), on HDL functionality. For that, 147 individuals with high cardiovascular risk were randomized in ω-3 (1 g of fish oil each - 370 mg of EPA and 230 mg of DHA, 3 times per day total EPA+DHA = 1,800 mg) or ω-6 groups (1 g of sunflower oil each - 760 mg of linoleic acid, 3 times per day; total linoleic acid = 2,280 mg). Fasting blood samples were collected at baseline time and after 8 weeks of follow-up and, and the lipid profile and glucose metabolism were evaluated from plasma. From HDL, the fatty acid profile, apolipoproteins (Apo AI, CII and CIII), paraoxonase-1 (PON1), cholesteryl ester transfer protein (CETP), subfractions and antioxidant activity were investigated. Omega-3 improved large HDL (HDL = 28.7%) and reduced small HDL (HDL10 = -10.6%) and the non-esterified fatty acids in HDL (NEFAs-HDL) level (-16.2%). A significant reduction in CETP activity was observed in the ω-3group (Δ ω-6 = 3.60 pmol/ul/h and Δ ω-3 = -1.99 pmol/ul/h; p = 0.044). The antioxidant capacity estimated by Lag time analysis did not change after the ω-3intervention. Changes in PON1 and Apo AI were inversely associated with increased incorporation of EPA (AOR = 0.446; IC = 0.200-0.994) and DHA (AOR = 0.351; IC = 0.150-0.821) in HDL, respectively. Cardioprotective profile obtained by pooled fatty acids analysis was related to a decrease in Apo CIII (r = -0.638; p = 0.002) and CETP (r = -0.341; p = 0.012) and an increase in Apo CII (r = 0.448; p = 0.042) and PON1 (r = 0.388; p = 0.003). In conclusion, omega-3 was effective in the reduction of cardiovascular risk associated with HDL functionality by size improvement and changes in its lipid, antioxidant and enzyme composition.

Omega-3 Fatty Acids in Erythrocyte Membranes as Predictors of Lower Cardiovascular Risk in Adults without Previous Cardiovascular Events.

Background: This study investigated the association of omega-3 polyunsaturated fatty acids (n-3 PUFA) within erythrocyte membranes and cardiovascular risk assessed by three different estimates. Methods: Inclusion criteria were individuals of both sexes, 30 to 74 years, with at least one cardiovascular risk factor, and no previous cardiovascular events (n = 356). Exclusion criteria were individuals with acute or chronic severe diseases, infectious diseases, pregnant, and/or lactating women. Plasma biomarkers (lipids, glucose, and C-reactive protein) were analyzed, and nineteen erythrocyte membrane fatty acids (FA) were identified. The cardiovascular risk was estimated by Framingham (FRS), Reynolds (RRS), and ACC/AHA-2013 Risk Scores. Three patterns of FA were identified (Factor 1, poor in n-3 PUFA), (Factor 2, poor in PUFA), and (Factor 3, rich in n-3 PUFA). Results: Total cholesterol was inversely correlated with erythrocyte membranes C18:3 n-3 (r = -0.155; p = 0.004), C22:6 n-3 (r = -0.112; p = 0.041), and total n-3 (r = -0.211; p < 0.001). Total n-3 PUFA was associated with lower cardiovascular risk by FRS (OR = 0.811; 95% CI= 0.675-0.976). Regarding RRS, Factor 3 was associated with 25.3% lower odds to have moderate and high cardiovascular risk (OR = 0.747; 95% CI = 0.589-0.948). The ACC/AHA-2013 risk score was not associated with isolated and pooled FA. Conclusions:n-3 PUFA in erythrocyte membranes are independent predictors of low-risk classification estimated by FRS and RRS, which could be explained by cholesterol-lowering effects of n-3 PUFA.

Micronutrient supplementation needs more attention in patients with refractory epilepsy under ketogenic diet treatment.

OBJECTIVES: This study evaluated the adequacy of micronutrient intake from the ketogenic diet (KD) with and without micronutrient supplementation according to age in Brazilian children and adolescents with refractory epilepsy undergoing KD treatment. METHODS: This study enrolled children and adolescents with refractory epilepsy who were up to 19 y of age. Nutrient intakes were monitored using 3 d food records before introducing micronutrient supplementation and 3 mo after starting KD treatment. The prevalence of micronutrient inadequacy was estimated by sex and age according to the estimated average requirement cutoff values. RESULTS: This study included 39 children and adolescents. The KD did not provide enough content of folate, calcium, and magnesium in all patients according to the dietary reference intake. Even after starting supplementation, calcium, phosphorus, and magnesium intake remained inadequate in the majority of patients. The supplementation effectively met the vitamin B12 recommendation in all age groups. CONCLUSIONS: KD treatment did not provide adequate levels of the monitored micronutrients. The supplementation improved but did not prevent the inadequacy of micronutrients such as calcium, magnesium, and phosphorus. The results highlight the importance of individual supplementation protocols and the need to monitor micronutrient intake according to age and sex.

Cardiovascular risk estimated in individuals with multiple sclerosis: A case-control study.

BACKGROUND: Patients with multiple sclerosis (MS) had a 1.5-fold increase in cardiovascular diseases (CVD) mortality, compared with those without MS. Therefore, the aim of this study was to assess the CVD risk in MS patients by multiple cardiometabolic indexes and to investigate associated factors. METHODS: The MS group included 57 patients matched for age and sex to 57 healthy controls. They were evaluated for physical activity, smoking, anthropometric indices, blood pressure, and plasma biomarkers. Framingham risk score (FRS) and multiple cardiovascular risk indexes were calculated. Clinical course of disease, age at onset, disease duration, disease-modifying therapy, relapse rate, EDSS, physical and functional impairment were investigated. RESULTS: The mean age was 34.6 years old. The majority (89.5%) in the MS group had a RRMS clinical course and a mild level of disability (EDSS=1.0). WC (p = 0.022) and FM% (p = 0.007) were different between the MS and control groups. The FRS was higher in the MS group (10% versus 0%) and this was related with high prevalence of dyslipidemia (43.8% versus 36.8%). The atherogenic index of plasma (AIP) (0.013) and Castelli risk indexes I (CRI-I) (p = 0.017) and II (CRI-II) (p = 0.008) and non-HDL-C (p = 0.044) were higher in the MS group. CONCLUSION: MS patients, with controlled disease course, have a higher cardiovascular risk than comparable healthy individuals. We emphasize that the use of FRS, and the monitoring of CRI-I and II, as well as AIP, are important lipid markers to manage CVD risk in individuals with MS.

Bioelectrical impedance vector applied to body composition evaluation of women survivors of breast cancer: A longitudinal study.

BACKGROUND AND AIMS: Thus, the aim of this study was to assess the changes in the body composition of the women survivors of breast cancer and its association with clinical staging, using the bioelectrical impedance vector analysis (BIVA), over five years of follow-up. METHODS: At baseline time 114 patients (T0) were selected and after 5 years (T1) of follow-up (n = 35) data of weight, body mass index, waist circumference, phase angle, resistance/height, reactance/height, %fat free mass and %fat mass were monitored. Bioelectrical impedance vector analysis (BIVA) and the vector displacement assessment took place according to the initial and advanced clinical staging (CS 1 and 2, respectively) and time of follow-up and have been showed using mean graph and RXc score graph. RESULTS: Patients on CS 1 showed a reduction in reactance/height, phase angle, %fat free mass and an increase in %fat mass. The same group presented during the follow-up significant vector displacement by mean graph and a change to the 95% ellipse by the RXc score graph. CONCLUSIONS: Women with breast cancer in the initial CS showed a more significant displacement of bioelectric vectors, indicating worsening in body composition.

OxLDL alterations in endothelial cell membrane dynamics leads to changes in vesicle trafficking and increases cell susceptibility to injury.

Plasma membrane repair (PMR) is an important process for cell homeostasis, especially for cells under constant physical stress. Repair involves a sequence of Ca2+-dependent events, including lysosomal exocytosis and subsequent compensatory endocytosis. Cholesterol sequestration from plasma membrane causes actin cytoskeleton reorganization and polymerization, increasing cell stiffness, which leads to exocytosis and reduction of a peripheral pool of lysosomes involved in PMR. These changes in mechanical properties are similar to those observed in cells exposed to oxidized Low Density Lipoprotein (oxLDL), a key molecule during atherosclerosis development. Using a human umbilical vein endothelial cell line (EAhY926) we evaluated the influence of mechanical modulation induced by oxLDL in PMR and its effect in endothelial fragility. Similar to MßCD (a drug capable of sequestering cholesterol) treatment, oxLDL exposure led to actin reorganization and de novo polymerization, as well as an increase in cell rigidity and lysosomal exocytosis. Additionally, for both MßCD and oxLDL treated cells, there was an initial increase in endocytic events, likely triggered by the peak of exocytosis induced by both treatments. However, no further endocytic events were observed, suggesting that constitutive endocytosis is blocked upon treatment and that the reorganized cytoskeleton function as a mechanical barrier to membrane traffic. Finally, the increase in cell rigidity renders cells more prone to mechanical injury. Together, these data show that mechanical modulation induced by oxLDL exposure not only alters membrane traffic in cells, but also makes them more susceptible to mechanical injury, which may likely contribute to the initial steps of atherosclerosis development.

Comparison of early cardiovascular risk among Brazilian and African university students.

Cardiovascular diseases are among the main causes of mortality worldwide, and dyslipidemia is a principal factor risk. Hence the study of biochemical markers is necessary for early diagnosis. OBJECTIVES: Evaluate biomarkers to diagnose the risks of cardiovascular diseases in healthy Brazilian and African young adults. DESIGN & METHODS: Weight, height, waist circumference, percentage of body fat and systemic blood pressure were measured; and fasting blood samples were taken for biochemical analysis. Triglycerides, total cholesterol, HDL-c, and apolipoproteins A-I and B were measured on automated equipment using commercially available kits, in addition to the tests of antioxidant capacity of HDL and the enzymatic activity of Paraoxonase 1. RESULTS: After statistical analysis, it was found that BMI, WC, fat (%), triglycerides, ApoB/ApoA-I ratio and Vmax were higher in Brazilians, while HDL-c, ApoA-I, Lag Time, Vmax and PON1 activity were higher in Africans. In Brazilians, the ApoB/ApoA-I ratio was related to obesity factors and lipid profile, but in Africans it was related only to lipids. The antioxidant capacity of HDL and PON1 activity was better in Africans. Through independence testing, we observed an association with moderate risk of myocardial infarction with gender in Africans. In the binary logistic regression analysis, it was found that men in general - and particularly African men - have higher risk of myocardial infarction than women; Odds Ratio 2144 (CI95%: 1343-3424) and 2281 (CI95%: 1082-4811), respectively. CONCLUSIONS: The anthropometric and biochemical parameters of Brazilians, especially men, predispose them to greater risks of cardiovascular diseases.