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1.
JAMA Netw Open ; 3(11): e2025454, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33252690

RESUMO

Importance: Excess body weight and insulin resistance lead to type 2 diabetes and other major health problems. There is an urgent need for dietary interventions to address these conditions. Objective: To measure the effects of a low-fat vegan diet on body weight, insulin resistance, postprandial metabolism, and intramyocellular and hepatocellular lipid levels in overweight adults. Design, Setting, and Participants: This 16-week randomized clinical trial was conducted between January 2017 and February 2019 in Washington, DC. Of 3115 people who responded to flyers in medical offices and newspaper and radio advertisements, 244 met the participation criteria (age 25 to 75 years; body mass index of 28 to 40) after having been screened by telephone. Interventions: Participants were randomized in a 1:1 ratio. The intervention group (n = 122) was asked to follow a low-fat vegan diet and the control group (n = 122) to make no diet changes for 16 weeks. Main Outcomes and Measures: At weeks 0 and 16, body weight was assessed using a calibrated scale. Body composition and visceral fat were measured by dual x-ray absorptiometry. Insulin resistance was assessed with the homeostasis model assessment index and the predicted insulin sensitivity index (PREDIM). Thermic effect of food was measured by indirect calorimetry over 3 hours after a standard liquid breakfast (720 kcal). In a subset of participants (n = 44), hepatocellular and intramyocellular lipids were quantified by proton magnetic resonance spectroscopy. Repeated measure analysis of variance was used for statistical analysis. Results: Among the 244 participants in the study, 211 (87%) were female, 117 (48%) were White, and the mean (SD) age was 54.4 (11.6) years. Over the 16 weeks, body weight decreased in the intervention group by 5.9 kg (95% CI, 5.0-6.7 kg; P < .001). Thermic effect of food increased in the intervention group by 14.1% (95% CI, 6.5-20.4; P < .001). The homeostasis model assessment index decreased (-1.3; 95% CI, -2.2 to -0.3; P < .001) and PREDIM increased (0.9; 95% CI, 0.5-1.2; P < .001) in the intervention group. Hepatocellular lipid levels decreased in the intervention group by 34.4%, from a mean (SD) of 3.2% (2.9%) to 2.4% (2.2%) (P = .002), and intramyocellular lipid levels decreased by 10.4%, from a mean (SD) of 1.6 (1.1) to 1.5 (1.0) (P = .03). None of these variables changed significantly in the control group over the 16 weeks. The change in PREDIM correlated negatively with the change in body weight (r = -0.43; P < .001). Changes in hepatocellular and intramyocellular lipid levels correlated with changes in insulin resistance (both r = 0.51; P = .01). Conclusions and Relevance: A low-fat plant-based dietary intervention reduces body weight by reducing energy intake and increasing postprandial metabolism. The changes are associated with reductions in hepatocellular and intramyocellular fat and increased insulin sensitivity. Trial Registration: ClinicalTrials.gov Identifier: NCT02939638.


Assuntos
Dieta com Restrição de Gorduras , Dieta Vegana , Fígado/metabolismo , Músculo Esquelético/metabolismo , Obesidade/dietoterapia , Absorciometria de Fóton , Adulto , Idoso , Glicemia/metabolismo , Composição Corporal , Peso Corporal , Peptídeo C/metabolismo , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Ingestão de Energia , Metabolismo Energético , Feminino , Hemoglobina A Glicada/metabolismo , Hepatócitos/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal/diagnóstico por imagem , Metabolismo dos Lipídeos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/diagnóstico por imagem , Obesidade/metabolismo , Sobrepeso/dietoterapia , Sobrepeso/metabolismo , Período Pós-Prandial , Espectroscopia de Prótons por Ressonância Magnética , Triglicerídeos/metabolismo
2.
JAMA Netw Open ; 3(11): e2025466, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33211107

RESUMO

Importance: Higher Mediterranean diet (MED) intake has been associated with reduced risk of type 2 diabetes, but underlying biological mechanisms are unclear. Objective: To characterize the relative contribution of conventional and novel biomarkers in MED-associated type 2 diabetes risk reduction in a US population. Design, Setting, and Participants: This cohort study was conducted among 25 317 apparently healthy women. The participants with missing information regarding all traditional and novel metabolic biomarkers or those with baseline diabetes were excluded. Participants were invited for baseline assessment between September 1992 and May 1995. Data were collected from November 1992 to December 2017 and analyzed from December 2018 to December 2019. Exposures: MED intake score (range, 0 to 9) was computed from self-reported dietary intake, representing adherence to Mediterranean diet intake. Main Outcomes and Measures: Incident cases of type 2 diabetes, identified through annual questionnaires; reported cases were confirmed by either telephone interview or supplemental questionnaire. Proportion of reduced risk of type 2 diabetes explained by clinical risk factors and a panel of 40 biomarkers that represent different physiological pathways was estimated. Results: The mean (SD) age of the 25 317 female participants was 52.9 (9.9) years, and they were followed up for a mean (SD) of 19.8 (5.8) years. Higher baseline MED intake (score ≥6 vs ≤3) was associated with as much as a 30% lower type 2 diabetes risk (age-adjusted and energy-adjusted hazard ratio, 0.70; 95% CI, 0.62-0.79; when regression models were additionally adjusted with body mass index [BMI]: hazard ratio, 0.85; 95% CI, 0.76-0.96). Biomarkers of insulin resistance made the largest contribution to lower risk (accounting for 65.5% of the MED-type 2 diabetes association), followed by BMI (55.5%), high-density lipoprotein measures (53.0%), and inflammation (52.5%), with lesser contributions from branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%), and minimal contribution (≤2%) from hemoglobin A1c. In post hoc subgroup analyses, the inverse association of MED diet with type 2 diabetes was seen only among women who had BMI of at least 25 at baseline but not those who had BMI of less than 25 (eg, women with BMI <25, age- and energy-adjusted HR for MED score ≥6 vs ≤3, 1.01; 95% CI, 0.77-1.33; P for trend = .92; women with BMI ≥25: HR, 0.76; 95% CI, 0.67-0.87; P for trend < .001). Conclusions and Relevance: In this cohort study, higher MED intake scores were associated with a 30% relative risk reduction in type 2 diabetes during a 20-year period, which could be explained in large part by biomarkers of insulin resistance, BMI, lipoprotein metabolism, and inflammation.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Dieta Mediterrânea/estatística & dados numéricos , Adiposidade , Adulto , Aminoácidos de Cadeia Ramificada/metabolismo , Apolipoproteína A-I/metabolismo , Apolipoproteína B-100/metabolismo , Apolipoproteínas/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Dieta/estatística & dados numéricos , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Inflamação/metabolismo , Resistência à Insulina , Molécula 1 de Adesão Intercelular/metabolismo , Lipoproteína(a)/metabolismo , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Lipoproteínas VLDL/metabolismo , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Proteção , Espectroscopia de Prótons por Ressonância Magnética , Triglicerídeos/metabolismo
3.
Nat Commun ; 11(1): 5559, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144569

RESUMO

Cholesterol import in mammalian cells is mediated by the LDL receptor pathway. Here, we perform a genome-wide CRISPR screen using an endogenous cholesterol reporter and identify >100 genes involved in LDL-cholesterol import. We characterise C18orf8 as a core subunit of the mammalian Mon1-Ccz1 guanidine exchange factor (GEF) for Rab7, required for complex stability and function. C18orf8-deficient cells lack Rab7 activation and show severe defects in late endosome morphology and endosomal LDL trafficking, resulting in cellular cholesterol deficiency. Unexpectedly, free cholesterol accumulates within swollen lysosomes, suggesting a critical defect in lysosomal cholesterol export. We find that active Rab7 interacts with the NPC1 cholesterol transporter and licenses lysosomal cholesterol export. This process is abolished in C18orf8-, Ccz1- and Mon1A/B-deficient cells and restored by a constitutively active Rab7. The trimeric Mon1-Ccz1-C18orf8 (MCC) GEF therefore plays a central role in cellular cholesterol homeostasis coordinating Rab7 activation, endosomal LDL trafficking and NPC1-dependent lysosomal cholesterol export.


Assuntos
Colesterol/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lisossomos/metabolismo , Multimerização Proteica , Proteínas rab de Ligação ao GTP/metabolismo , Transporte Biológico , Sistemas CRISPR-Cas/genética , LDL-Colesterol/metabolismo , Endossomos/metabolismo , Endossomos/ultraestrutura , Corantes Fluorescentes/metabolismo , Genoma Humano , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Células HEK293 , Células HeLa , Homeostase , Humanos , Hidroximetilglutaril-CoA Sintase/metabolismo , Lisossomos/ultraestrutura , Modelos Biológicos , Complexos Multiproteicos/metabolismo , Ligação Proteica
4.
Nat Commun ; 11(1): 4930, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004804

RESUMO

Inference of causality between gene expression and complex traits using Mendelian randomization (MR) is confounded by pleiotropy and linkage disequilibrium (LD) of gene-expression quantitative trait loci (eQTL). Here, we propose an MR method, MR-link, that accounts for unobserved pleiotropy and LD by leveraging information from individual-level data, even when only one eQTL variant is present. In simulations, MR-link shows false-positive rates close to expectation (median 0.05) and high power (up to 0.89), outperforming all other tested MR methods and coloc. Application of MR-link to low-density lipoprotein cholesterol (LDL-C) measurements in 12,449 individuals with expression and protein QTL summary statistics from blood and liver identifies 25 genes causally linked to LDL-C. These include the known SORT1 and ApoE genes as well as PVRL2, located in the APOE locus, for which a causal role in liver was not known. Our results showcase the strength of MR-link for transcriptome-wide causal inferences.


Assuntos
LDL-Colesterol/sangue , Regulação da Expressão Gênica , Predisposição Genética para Doença , Modelos Genéticos , Locos de Características Quantitativas , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , LDL-Colesterol/metabolismo , Simulação por Computador , Conjuntos de Dados como Assunto , Pleiotropia Genética , Humanos , Desequilíbrio de Ligação , Metabolismo dos Lipídeos/genética , Análise da Randomização Mendeliana , Redes e Vias Metabólicas/genética , Herança Multifatorial , Nectinas/genética , Nectinas/metabolismo , Países Baixos , Proteômica , RNA-Seq
5.
Sci Rep ; 10(1): 17162, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051566

RESUMO

Motivated by developments in information technology, recording personal parameters with health devices is effective in health promotion. Today's indoor individual lifestyles often involve using electrical appliances. We developed a health support system combined with wireless electricity monitoring and investigated whether electricity use is associated with residents' vital data and lifestyles. We recruited 116 participants in February 2013. Their vital and electricity use data were collected daily. They completed a self-administered questionnaire. Among participants living alone, electricity from 20 February to 11 March 2013 was negatively associated with high-density lipoprotein (HDL) (P = 0.008) and positively associated with low-density lipoprotein (LDL) (P = 0.007) and neutral fat (P = 0.020) levels. Among all participants, electricity use was negatively associated with vegetable intake (P = 0.044) and step count (P = 0.040). Temperature sensitivity in winter was negatively associated with the LDL/HDL ratio for both men and women. For men, temperature sensitivity in winter was negatively related with alcohol intake; for women, it was positively related to body fat percentage and abdominal circumference and negatively correlated to vegetable intake. Temperature sensitivity in summer was positively associated with vegetable intake for men and women. In conclusion, electricity use was related to vital data and lifestyles and influenced by temperature.


Assuntos
Monitorização Fisiológica/métodos , Tecido Adiposo/metabolismo , Adulto , Consumo de Bebidas Alcoólicas/metabolismo , Índice de Massa Corporal , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Planejamento em Saúde Comunitária/métodos , Eletricidade , Feminino , Humanos , Japão , Estilo de Vida , Lipoproteínas , Lipoproteínas HDL , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Tecnologia sem Fio , Adulto Jovem
6.
PLoS One ; 15(8): e0238388, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866186

RESUMO

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) in the non-obese population has increased and NAFLD is not always recognized in individuals with metabolic syndrome (MS). The risk of cirrhosis is higher in patients having NAFLD with elevated alanine aminotransferase (ALT) levels than in those having NAFLD with normal ALT levels. OBJECTIVE: To measure the differences in clinical factors associated with NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and to measure differences in metabolites between MS subjects with and without NAFLD having elevation of ALT. METHODS: Among 7,054 persons undergoing health check-ups, we included 3,025 subjects who met the selection criteria. We measured differences in clinical factors for NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and compared metabolites between subjects with and without NAFLD having elevation of ALT in 32 subjects with MS. RESULTS: The prevalence of NAFLD and NAFLD having elevation of ALT was significantly progressively greater in subjects with Non-MS, Pre-MS, and MS (p <0.001, respectively). In the Non-MS group, there were significant differences between subjects with and without NAFLD having elevation of ALT with respect to body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, hemoglobin A1c, uric acid, aspartate aminotransferase (AST); In the Pre-MS group, there were significant differences in BMI, hypertension, AST, and gamma-glutamyl transpeptidase (GGT); In the MS group, there were significant differences in HDL-C, impaired glucose tolerance, AST, and GGT. There were significant differences in levels of metabolites of nicotinamide, inosine, and acetyl-L-carnitine between MS subjects with and without NAFLD having elevation of ALT (all p <0.05). CONCLUSIONS: Although NAFLD having elevation of ALT is important for development of NAFLD, differences in factors associated with NAFLD having elevation of ALT at various stages of MS should be considered. Additionally, several metabolites may play roles in the identification of risk for NAFLD in individuals with MS.


Assuntos
Alanina Transaminase/metabolismo , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Aspartato Aminotransferases/metabolismo , Índice de Massa Corporal , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ácido Úrico/metabolismo , gama-Glutamiltransferase/metabolismo
7.
Am J Cardiol ; 134: 69-73, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32892993

RESUMO

Statin therapy is the gold standard for hypercholesterolemia. However, a significant number of patients cannot achieve their target low-density lipoprotein (LDL) levels despite a maximal dose of statin therapy, and some cannot tolerate statins at all. Approval of proprotein convertase subtilisin/kexin type 9 inhibitors has been revolutionary for those patients. However, the need for frequent injections limits patient compliance with their use. Recently, a twice-yearly injection of inclisiran, a small interfering RNA, has been shown to inhibit hepatic synthesis of proprotein convertase subtilisin/kexin type 9. However, patient randomized clinical trial has been underpowered for clinical end points, necessitating a meta-analysis of those trials. The weighted mean difference was used to describe continuous variables, and pooled risk ratios, calculated using a random effects model, were used to describe discrete variables. Data from 3 randomized clinical trials comprising 3,660 patients showed that inclisiran decreased LDL cholesterol levels by 51% (95% Confidence Interval, 48 to 53%; p < 0.001) compared with placebo. It was associated with a 24% lower major adverse cardiovascular events rate (risk ratios = 0.76; 95% Confidence Interval, 0.61 to 0.92). It also significantly decreased total cholesterol by 37%, apolipoprotein B by 41%, and non high-density lipoprotein (HDL) cholesterol by 45% (all p < 0.001). No differences were found in adverse events, abnormalities in liver function tests, or creatine kinase levels between the treatment strategies. However, a mild injection site reaction occurred more frequently in the inclisiran group. In conclusions, in patients with hypercholesterolemia, inclisiran decreased LDL level by 51% without significant adverse effects. Additionally, it was associated with a lower major adverse cardiovascular event rate.


Assuntos
Anticolesterolemiantes/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Reação no Local da Injeção/epidemiologia , RNA Interferente Pequeno/uso terapêutico , Idoso , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Apolipoproteínas B/metabolismo , Aspartato Aminotransferases/metabolismo , Bilirrubina/metabolismo , Doenças Cardiovasculares/mortalidade , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Creatina Quinase/metabolismo , Quimioterapia Combinada , Ezetimiba/uso terapêutico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/metabolismo , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/epidemiologia
8.
Med Hypotheses ; 144: 110128, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758903

RESUMO

It has been proposed that a degraded immune system is (one of) the condition(s) that predispose certain subjects to fatal consequences from infection by SARS-CoV-2. It is unknown whether therapeutic regimens to which these patients may have been subjected to in the months/years preceding the infection could be immunocompromising. Statins are among the most widely prescribed cholesterol-lowering drugs. As competitive inhibitors of HMG-CoA-reductase, the key enzyme of the "mevalonate pathway" through which essential compounds, not only cholesterol, are synthesized, statins decrease the levels of cholesterol, and thus LDLs, as an innate defense mechanism, with controversial results in decreasing mortality from cardiovascular disease. Moreover, statins have pleiotropic, mostly deleterious effects on many cell types, including immune cells. In the attempt to decipher the enigma of SARS-CoV-2 infectivology, the hypothesis should be tested whether the population of subjects who succumbed to Covid-19 may have developed a compromised immunity at sub-clinical levels and have become more susceptible to fatal consequences from SARS-Cov-2 infection due to statin therapy.


Assuntos
/tratamento farmacológico , Ácido Mevalônico/química , Oxirredução , Selenoproteínas/química , Colesterol/metabolismo , LDL-Colesterol/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Sistema Imunitário , Imunidade Inata , Inflamação , Lipoproteínas LDL/metabolismo , Modelos Teóricos , Estresse Oxidativo
9.
Proc Natl Acad Sci U S A ; 117(31): 18521-18529, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32690708

RESUMO

Animal cells acquire cholesterol from receptor-mediated uptake of low-density lipoprotein (LDL), which releases cholesterol in lysosomes. The cholesterol moves to the endoplasmic reticulum (ER), where it inhibits production of LDL receptors, completing a feedback loop. Here we performed a CRISPR-Cas9 screen in human SV589 cells for genes required for LDL-derived cholesterol to reach the ER. We identified the gene encoding PTDSS1, an enzyme that synthesizes phosphatidylserine (PS), a phospholipid constituent of the inner layer of the plasma membrane (PM). In PTDSS1-deficient cells where PS is low, LDL cholesterol leaves lysosomes but fails to reach the ER, instead accumulating in the PM. The addition of PS restores cholesterol transport to the ER. We conclude that LDL cholesterol normally moves from lysosomes to the PM. When the PM cholesterol exceeds a threshold, excess cholesterol moves to the ER in a process requiring PS. In the ER, excess cholesterol acts to reduce cholesterol uptake, preventing toxic cholesterol accumulation. These studies reveal that one lipid-PS-controls the movement of another lipid-cholesterol-between cell membranes. We relate these findings to recent evidence indicating that PM-to-ER cholesterol transport is mediated by GRAMD1/Aster proteins that bind PS and cholesterol.


Assuntos
Membrana Celular/metabolismo , LDL-Colesterol/metabolismo , Retículo Endoplasmático/metabolismo , Lisossomos/metabolismo , Fosfatidilserinas/metabolismo , Animais , Transporte Biológico , Linhagem Celular , Colesterol/metabolismo , Humanos
10.
Am J Clin Nutr ; 112(1): 19-24, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32491166

RESUMO

The proposition that dietary SFAs should be restricted to the maximal extent possible (e.g., to achieve approximately half of current consumption) is based primarily on observational and clinical trial data that are interpreted as indicating a benefit of such limitation on cardiovascular disease (CVD) risk. Further support is believed to derive from the capacity of SFAs to raise LDL cholesterol, and the evidence that LDL-cholesterol lowering reduces CVD incidence. Despite their apparent merit, these arguments are flawed. In fact, although it is possible that dietary intake of SFAs has a causal role in CVD, the evidence to support this contention is inconclusive. Moreover, other considerations argue against a guideline focused primarily on limiting SFA intake, including the heterogeneity of individual SFAs, the likelihood of clinically meaningful interindividual variation in response to SFA reduction, the potential for unintended health consequences of population-wide promotion of severe restriction, and the critical differences in health impacts among individual SFA-containing foods.


Assuntos
Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Saúde Pública/normas , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/metabolismo , Gorduras na Dieta/análise , Ácidos Graxos/análise , Humanos , Política Nutricional
11.
Am J Clin Nutr ; 112(1): 25-26, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32491172

RESUMO

There is ongoing debate as to whether public health guidelines should advocate reducing SFA consumption as much as possible to reduce the risk of chronic diseases, especially cardiovascular disease (CVD). In considering both sides of this question, we identified a number of points of agreement, most notably that the overall dietary patterns in which SFAs are consumed are of greater significance for cardiometabolic and general health than SFA intake alone. Nevertheless, there remained significant disagreements, centered largely on the interpretation of evidence bearing on 4 major questions: 1) does reducing dietary SFAs lower the incidence of CVD, 2) is the LDL-cholesterol reduction with lower SFA intake predictive of reduced CVD risk, 3) do dietary SFAs affect factors other than LDL cholesterol that may impact CVD risk, and 4) is there a sufficient rationale for setting a target for maximally reducing dietary SFAs? Finally, we identified specific research needs for addressing knowledge gaps that have contributed to the controversies.


Assuntos
Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Saúde Pública/normas , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/metabolismo , Consenso , Gorduras na Dieta/análise , Gorduras na Dieta/normas , Ácidos Graxos/análise , Ácidos Graxos/normas , Humanos , Política Nutricional
12.
Am J Clin Nutr ; 112(1): 13-18, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32491173

RESUMO

Based on decades of research, there is strong evidence that supports ongoing dietary recommendations to decrease intakes of SFAs and, more recently, to replace SFAs with unsaturated fat, including PUFAs and MUFAs. Epidemiologic research has shown that replacement of SFAs with unsaturated fat, but not refined carbohydrate and added sugars, is associated with a reduction in coronary heart disease events and death. There is much evidence from controlled clinical studies demonstrating that SFAs increase LDL cholesterol, a major causal factor in the development of cardiovascular disease. When each (nonprotein) dietary macronutrient isocalorically replaces SFA, the greatest LDL-cholesterol-lowering effect is seen with PUFA, followed by MUFA, and then total carbohydrate. New research on full-fat dairy products high in saturated fat, particularly fermented dairy foods, demonstrates some benefits for cardiometabolic diseases. However, compared with food sources of unsaturated fats, full-fat dairy products increase LDL cholesterol. Thus, current dietary recommendations to decrease SFA and replace it with unsaturated fat should continue to the basis for healthy food-based dietary patterns.


Assuntos
Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/metabolismo , Ácidos Graxos/análise , Ácidos Graxos Insaturados/análise , Ácidos Graxos Insaturados/metabolismo , História do Século XXI , Humanos , Saúde Pública/história , Saúde Pública/normas , Ensaios Clínicos Controlados Aleatórios como Assunto , Recomendações Nutricionais/história
14.
Nutr. hosp ; 37(3): 465-473, mayo-jun. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-193853

RESUMO

INTRODUCTION: the composition of snack foods likely influences the overall effect that snacking has on metabolism and obesity. The objective of the current study was to assess the responses to two different snacks, one of them supplemented with wakame and carobs, on cardiovascular risk factors, satiety, and subsequent food intake in obese subjects with metabolic syndrome. MATERIAL AND METHODS: forty patients were randomized in a clinical trial (NCT03420989, clinicaltrial.gov) to group I (enriched snack, n = 16) or group II (control snack, n = 16). At baseline and after 8 weeks biochemical parameters, dietary intakes, and nutritional status were assessed. The subjects also rated their feelings of satiety/hunger with a test meal. RESULTS: no differences were detected in anthropometric parameters between both snacks. Changes in other parameters were detected in patients with enriched snacks, with a significant decrease in LDL-cholesterol by 7.4 % (intervention snack, -8.9 ± 2.3 mg/dL vs control snack, -0.9 ± 3.3 mg/dL; p = 0.03), in total cholesterol by 5.8 % (intervention snack, -10.4 ± 2.9 mg/dL vs control snack, -1.4 ± 3.2 mg/dL; p = 0.02), and in resistin level by 15.9 % (intervention snack, -1.0 ± 0.2 mg/dL vs control snack, -0.1 ± 0.3 mg/dL: p = 0.03). After the test meal, satiety scores (after 20 min and 40 min) were higher than fasting levels in both groups. The same results were obtained with the 100-mm, 5-point visual satiety scale. CONCLUSION: our study indicates that a wakame- and carob-enriched snack induces a significant decrease in total cholesterol, LDL-cholesterol, and resistin levels when compared to a control snack, without effects on food consumption, other cardiovascular parameters, or anthropometric parameters


INTRODUCCIÓN: la composición de los "snacks" probablemente influya en el efecto que produce su consumo sobre los marcadores metabólicos y la obesidad. El objetivo del presente estudio fue evaluar las respuestas a dos snacks, uno de ellos suplementado con wakame y algarroba, sobre factores de riesgo cardiovascular, saciedad y posterior ingesta de alimentos, en sujetos obesos con síndrome metabólico. MATERIAL Y MÉTODOS: se aleatorizaron 40 pacientes en el ensayo clínico NCT03420989 (clinicaltrial.gov) para participar en el grupo I (snack enriquecido, n = 16) o el grupo II (snack de control, n = 16). Antes y después de 8 semanas se determinaron los parámetros bioquímicos, las ingestas dietéticas y el estado nutricional. A los sujetos también se les evaluó la saciedad y el apetito con una comida de prueba. RESULTADOS: no se detectaron diferencias en los parámetros antropométricos con ambos snacks. Se detectaron cambios en los parámetros bioquímicos de los pacientes que recibieron snacks enriquecidos, con una disminución significativa del colesterol-LDL del 7,4 % (snack de intervención, -8,9 ± 2,3 mg/dl vs. snack de control, -0,9 ± 3,3 mg/dl; p = 0,03), del colesterol total del 5,8 % (snack de intervención, -10,4 ± 2,9 mg/dl vs. snack de control, -1,4 ± 3,2 mg/dl; p = 0,02) y de los niveles de resistina del 15,9 % (snack de intervención, -1,0 ± 0,2 mg/dl vs. snack de control, -0,1 ± 0,3 mg/dl; p = 0,03). Después de la comida de prueba, las puntuaciones de saciedad (a los 20 min y 40 min) fueron más altas que el nivel de ayuno en ambos grupos. Los resultados fueron similares con la escala de saciedad visual de 5 puntos y 100 mm. CONCLUSIÓN: nuestro estudio muestra que un snack enriquecido con wakame y algarroba produce una disminución significativa de los niveles de colesterol total, colesterol-LDL y resistina frente a un snack de control, sin efectos sobre el consumo de alimentos, otros parámetros cardiovasculares y los parámetros antropométricos


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Lanches/fisiologia , Ingestão de Energia/fisiologia , Undaria , Método Duplo-Cego , Obesidade/dietoterapia , Extratos Vegetais/farmacologia , Fatores de Risco , Doenças Cardiovasculares/prevenção & controle , Síndrome Metabólica/dietoterapia , LDL-Colesterol/metabolismo , Antropometria , Receptores de Adipocina/administração & dosagem , Undaria/química , Galactanos/farmacologia , Extratos Vegetais/uso terapêutico
15.
Am J Med ; 133(10): 1126-1134, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32569590

RESUMO

Cardiovascular disease remains one of the most prevalent and preventable chronic conditions worldwide. Diet modification is the foundation of cardiovascular disease prevention. Several dietary approaches have emerged to promote better cardiovascular health. The rapid dissemination of anecdotal and observational data through the internet and social media has caused confusion amongst providers and patients. The aim of this comprehensive review is to present objective insights into 2 of today's most popular fad diets: ketogenic diet and intermittent fasting. We will evaluate the performance of these diets based on their impact on cardiovascular risk factors.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Cetogênica/métodos , Dislipidemias/metabolismo , Jejum , Fibrilação Atrial , Glicemia/metabolismo , Pressão Sanguínea , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/prevenção & controle , Dietas da Moda , Humanos , Resistência à Insulina , Metabolismo dos Lipídeos , Obesidade/metabolismo , Comportamento de Redução do Risco , Triglicerídeos/metabolismo , Perda de Peso
16.
Life Sci ; 254: 117756, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32389832

RESUMO

Polydatin (PD) is a monocrystalline metabolite from the underground parts of Polygonum cuspidatum Sieb. et Zucc., a member of the Polygonaceae family, which has been traditionally used in Asian countries as both foodstuffs and medicine. PD, also reckoned as pieceid, 3,4',5-trihydroxystilbene-3-ß-D-glucoside, (E)-piceid, (E)-polydatin, and trans-polydatin. It possesses potent biological activities i.e. analgesic, anti-inflammatory, antidiabetic, anticancer, and anti-atherosclerotic properties. The initial part of this report specifically explains distinct sequential mechanisms underlying the initiation and development of atherosclerotic plaques and later part deals with the pharmacological efficacy of PD in the management of major cardiac event i.e. atherosclerotic cardiovascular diseases (ASCVD) via modulation of a set of molecular mechanisms i.e. antioxidant potential, lipid and lipoprotein metabolism including total cholesterol (TC) and low density lipoprotein (LDL) levels, ß-hydroxy-ß-methyl-glutaryl-CoA reductase (HMG-R) expression and functionality, SIRT signalling, LDL-receptor (LDL-R), LDL oxidation status (Ox-LDL), effects on endothelial cells (ECs), smooth muscle cells (SMCs), macrophage, foam cell formation and plaque stabilization, inflammatory signalling pathways and hypertension. In contrast, one of the major insight into the potential cardioprotective molecular mechanism is the PD-mediated targeting of proprotein convertase subtilisin/kexin type-9 (PCSK-9) and LDL-R pathway, both at transcriptional and protein functional level, which makes it a better alternative therapeutic medicinal candidate to treat hypercholesterolemia, especially for the patients facing inadequate lipid lowering with classical HMG-R inhibitors (statins) and statin intolerance. Finally, to sum up the whole, we concluded that PD may be promoted from alternative to mainstream medicine in targeting risk factors mediated ASCVD.


Assuntos
Aterosclerose/tratamento farmacológico , Glucosídeos/farmacologia , Estilbenos/farmacologia , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/metabolismo , Células Endoteliais/metabolismo , Fallopia japonica/metabolismo , Glucosídeos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Lipoproteínas LDL , Placa Aterosclerótica/tratamento farmacológico , Receptores de LDL/metabolismo , Fatores de Risco , Estilbenos/uso terapêutico
17.
Lancet Child Adolesc Health ; 4(5): 359-369, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32333883

RESUMO

BACKGROUND: Primordial and primary prevention is the cornerstone for cardiometabolic health. In the randomised, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP; n=1116), a 20-year dietary counselling intervention was given to children biannually from infancy, and cardiometabolic health benefits had been observed among the participants in the intervention group. Here, we report on the key results of the first follow-up done 6 years after the end of the intervention, at age 26 years. METHODS: The randomised controlled STRIP study recruited children at age 5 months from well-baby clinics in Turku, Finland, and randomly assigned them to either an intervention or control group; group allocation was unmasked. The intervention introduced participants to a heart-healthy diet, characterised by low proportional intake of saturated fat and cholesterol, by dietary counselling and nutrition education sessions to parents and children from the age of 7 months to 20 years. Children in the control group received only the basic health education given at Finnish well-baby clinics and school health care. We assessed diet, lifestyle, and cardiometabolic risk factor data, including blood pressure, anthropometry, serum biochemistry (lipids, apolipoproteins, glucose, and insulin), and homoeostatic model assessment of insulin resistance (HOMA-IR) in the participants at age 26 years. FINDINGS: 1116 children were included in the original STRIP study, of whom 551 provided data at the age 26 years follow-up, and data for 507 participants were analysed (243 in the intervention group and 264 in the control group). At follow-up, those who had been in the intervention group had slightly lower mean intake of saturated fat as a proportion of total energy intake than the control group (13·0% [SD 3·3] vs 13·7% [3·6], p=0·049). A higher proportion of participants in the intervention group achieved the targeted monounsaturated and polyunsaturated fat to saturated fat ratio of more than 2:1 than the control group (78 [39%] of 200 vs 70 [30%] of 235; risk ratio [RR] 1·16 [95% CI 1·01-1·33]; p=0·035). A higher proportion of intervention group participants met the ideal total cholesterol concentration of less than 5·17 mmol/L (194 [81%] of 240 vs 187 [72%] of 261; RR 1·45 [1·05-2·01], p=0·024) and optimal LDL cholesterol concentration of less than 3·0 mmol/L (166 [69%] of 240 vs 158 [61%] of 251; RR 1·30 [1·03-1·66], p=0·031). Those who received the intervention had lower glucose (5·00 mmol/L [SD 0·43] vs 5·07 mmol/L [0·46], p=0·040) and HOMA-IR (median 1·44 [IQR 1·09-1·91] vs 1·62 [1·22-2·09], p=0·037) than the participants in the control group. INTERPRETATION: Previously observed intervention effects during the 20-year counselling were largely maintained into adulthood 6 years after the withdrawal of the intervention. Dietary counselling introduced in infancy thus provided a sustained benefit to diet quality and cardiometabolic risk factor levels. FUNDING: Academy of Finland, Juho Vainio Foundation, Finnish Foundation for Cardiovascular Research, Finnish Ministry of Education and Culture, Finnish Cultural Foundation, Sigrid Jusélius Foundation, Special Governmental grants for Health Sciences Research (Turku University Hospital), Yrjö Jahnsson Foundation, Finnish Medical Foundation, and Turku University Foundation.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Aconselhamento/métodos , Dieta Saudável/métodos , Síndrome Metabólica/prevenção & controle , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Doenças Cardiovasculares/metabolismo , Colesterol/metabolismo , Colesterol na Dieta , LDL-Colesterol/metabolismo , Gorduras na Dieta , Gorduras Insaturadas na Dieta , Ingestão de Energia , Feminino , Finlândia , Seguimentos , Humanos , Insulina/metabolismo , Resistência à Insulina , Estudos Longitudinais , Masculino , Síndrome Metabólica/metabolismo , Prevenção Primária/métodos , Fatores de Risco
18.
Nutrients ; 12(4)2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32231085

RESUMO

Traditionally, nutritional epidemiologists have utilized single nutrient or dietary pattern approaches to examine diet-health relationships. However, the former ignores that nutrients are consumed from foods within dietary patterns, and, conversely, dietary patterns may provide little information on mechanisms of action. Substitution provides a framework for estimating diet-health relationships while holding some nutrient intakes constant. We examined substitution effects of polyunsaturated fatty acids (PUFAs) in the SEARCH Nutrition Ancillary Study in the context of food group source. PUFAs were calculated from fatty acids 18:3, 20:5, and 22:6 (n-3), and 18:2 and 20:4 (n-6) from a food frequency questionnaire, quantified by food group. Models were adjusted for other fat intake, carbohydrates, protein, age, race, gender, and diabetes duration. Participants (n = 1441) were 14 years old on average, 51% female, with type 1 diabetes for 3.6 years. Mean intake of PUFAs was 14.9 g/day, and the highest PUFA sources were nonsolid fats, nuts, grains, red/processed meats, sweets/desserts, and high-fat chicken. PUFAs from nuts were inversely associated with low-density lipoprotein cholesterol (LDL) (p = 0.03) and PUFAs from high-fat chicken were positively associated with LDL (p < 0.01). Substituting nuts for chicken was associated with -7.4 mg/dL in LDL. These findings illustrate the importance of considering food group-based sources of nutrients when examining diet-health relationships.


Assuntos
Fenômenos Fisiológicos da Nutrição do Adolescente , LDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Dieta Saudável , Ácidos Graxos Insaturados/administração & dosagem , Alimentos , Nutrientes , Adolescente , Animais , Galinhas , Feminino , Análise de Alimentos , Humanos , Masculino , Nozes , Produtos Avícolas , Prognóstico
19.
Nutrients ; 12(4)2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32231103

RESUMO

Increased consumption of plant-based foods and decreased consumption of animal-based foods is recommended for healthy diets and sustainable food production. We investigated the effects of partial replacement of dietary animal proteins with plant-based ones on intake of energy-yielding nutrients, fibre, and plasma lipoproteins. This 12-week randomised clinical intervention comprised 107 women and 29 men (20-69 years) in three diet groups with different dietary protein compositions ("ANIMAL": Animal 70%/plant 30%; "50/50": Animal 50%/plant 50%; "PLANT": Animal 30%/plant 70%; all: Protein intake 17 E%). Nutrient intakes were assessed by 4-day food records. Saturated fat intake (E%) was lower and polyunsaturated fatty acid intake (E%) higher in the PLANT and 50/50 groups compared to the ANIMAL group (p < 0.001 for all). Fibre intake was higher in the PLANT (p ˂ 0.001) and 50/50 (p = 0.012) groups. Total and LDL cholesterol were lower in the PLANT than in the ANIMAL group (p = 0.003 for both) but no differences in HDL cholesterol or triglycerides were observed (p > 0.05). Replacing animal protein with plant protein sources in the diet led to an increased fibre intake and improved dietary fat quality as well as blood lipoprotein profile. Flexitarian diets could provide healthy and more sustainable alternatives for the current, predominantly animal-based diets.


Assuntos
Proteínas Animais da Dieta/administração & dosagem , Dieta Saudável , Dieta , Proteínas na Dieta/administração & dosagem , Ingestão de Alimentos/fisiologia , Voluntários Saudáveis , Fenômenos Fisiológicos da Nutrição/fisiologia , Proteínas de Vegetais Comestíveis/administração & dosagem , Adulto , Idoso , LDL-Colesterol/metabolismo , Fibras na Dieta/administração & dosagem , Ácidos Graxos Insaturados/administração & dosagem , Feminino , Finlândia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
J Am Coll Cardiol ; 75(16): 1945-1955, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32327106

RESUMO

Mendelian randomization studies and randomized trials have conclusively demonstrated that lower low-density lipoprotein (LDL) cholesterol results in fewer cardiovascular events. This review describes key stages in the evolution of LDL cholesterol-lowering treatment. Data from over 25 cardiovascular outcome trials confirm that, within a few years, statins lower the relative risk of major atherosclerotic events by about 22% per 38.7 mg/dl (1 mmol/l) reduction in LDL cholesterol, with similar benefit across patient subgroups. Meta-analyses of these trials have established the safety of statins with regard to nonvascular mortality and cancer. Other agents available for prescription include ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which both reduce major atherosclerotic events in proportion to their effects on LDL cholesterol and have good safety profiles, though PCSK9 inhibitors remain costly. Investigational LDL cholesterol-lowering agents currently being tested in cardiovascular outcome studies are bempedoic acid, an adenosine triphosphate-citrate lyase inhibitor that reduces cholesterol synthesis, and inclisiran, a double-stranded small interfering ribonucleic acid that inhibits PCSK9 synthesis.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , LDL-Colesterol/metabolismo , Anticolesterolemiantes/classificação , Anticolesterolemiantes/farmacologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Humanos , Análise da Randomização Mendeliana
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