RESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently has no cure. Identifying biochemical changes associated with neurodegeneration prior to symptom onset, will provide insight into the biological mechanisms associated with neurodegenerative processes, that may also aid in identifying potential drug targets. The current study therefore investigated associations between plasma neurofilament light chain (NF-L), a marker of neurodegeneration, with plasma metabolites that are products of various cellular processes. Plasma NF-L, measured by ultrasensitive Single molecule array (Simoa) technology (Quanterix) and plasma metabolites, measured by mass-spectrometry (AbsoluteIDQ® p400HR kit, BIOCRATES), were assessed in the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort comprising 100 cognitively normal older adults. Metabolites belonging to biogenic amine (creatinine, symmetric dimethylarginine, asymmetric dimethylarginine; ADMA, kynurenine, trans-4-hydroxyproline), amino acid (citrulline, proline, arginine, asparagine, phenylalanine, threonine) and acylcarnitine classes were observed to have positive correlations with plasma NF-L, suggesting a link between neurodegeneration and biological pathways associated with neurotransmitter regulation, nitric oxide homoeostasis, inflammation and mitochondrial function. Additionally, after stratifying participants based on low/high brain amyloid-ß load (Aß ±) assessed by positron emission tomography, while creatinine, SDMA and citrulline correlated with NF-L in both Aß- and Aß+ groups, ADMA, proline, arginine, asparagine, phenylalanine and acylcarnitine species correlated with NF-L only in the Aß+ group after adjusting for confounding variables, suggesting that the association of these metabolites with neurodegeneration may be relevant to AD-related neuropathology. Metabolites identified to be associated with plasma NF-L may have the potential to serve as prognostic markers for neurodegenerative diseases, however, further studies are required to validate the current findings in an independent cohort, both cross-sectionally and longitudinally.
Assuntos
Doenças Neurodegenerativas/sangue , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/análise , Aminas Biogênicas/metabolismo , Biomarcadores/análise , Cognição , Estudos de Coortes , Encefalite/metabolismo , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/psicologia , Proteínas de Neurofilamentos/análise , Neurotransmissores/metabolismo , Óxido Nítrico/metabolismo , Tomografia por Emissão de Pósitrons , PrognósticoRESUMO
The structural similarity among lipid species and the low sensitivity and spectral resolution of nuclear magnetic resonance (NMR) have traditionally hampered the routine use of 1H NMR lipid profiling of complex biological samples in metabolomics, which remains mostly manual and lacks freely available bioinformatics tools. However, 1H NMR lipid profiling provides fast quantitative screening of major lipid classes (fatty acids, glycerolipids, phospholipids, and sterols) and some individual species and has been used in several clinical and nutritional studies, leading to improved risk prediction models. In this Article, we present LipSpin, a free and open-source bioinformatics tool for quantitative 1H NMR lipid profiling. LipSpin implements a constrained line shape fitting algorithm based on voigt profiles and spectral templates from spectra of lipid standards, which automates the analysis of severely overlapped spectral regions and lipid signals with complex coupling patterns. LipSpin provides the most detailed quantification of fatty acid families and choline phospholipids in serum lipid samples by 1H NMR to date. Moreover, analytical and clinical results using LipSpin quantifications conform with other techniques commonly used for lipid analysis.
Assuntos
Biologia Computacional/métodos , Ácidos Graxos/sangue , Fosfatidilcolinas/sangue , Espectroscopia de Prótons por Ressonância Magnética/métodos , Algoritmos , HumanosRESUMO
CONTEXT: In preclinical Alzheimer's disease (AD), the brain gradually becomes insulin resistant. As a result, brain glucose utilization is compromised, causing a cellular energy deficit that leads to the accumulation of free radicals, which increases inflammation and damages neurons. When glucose utilization is impaired, ketone bodies offer an alternative energy source. Ketone bodies are synthesized from fats, obtained from either the diet or adipose tissue. Dietary medium-chain fatty acids (MCFAs), which are preferentially metabolized into ketone bodies, have the potential to supply the insulin-resistant brain with energy. OBJECTIVE: This systematic review and meta-analysis aims to review the effect of MCFA supplements on circulating ketone bodies and cognition in individuals with subjective cognitive decline, mild cognitive impairment, and AD. DATA SOURCES: A comprehensive search of electronic databases was performed on August 12, 2019, to retrieve all publications meeting the inclusion criteria. Alerts were then set to identify any publications after the search date up until January 31, 2021. DATA EXTRACTION: Data were extracted by 2 authors and assessed by a third. In total, 410 publications were identified, of which 16 (nâ =â 17 studies) met the inclusion criteria. DATA ANALYSIS: All studies assessing change in levels of blood ketone bodies due to MCFA supplementation (n = 12) reported a significant increase. Cognition outcomes (measured in 13 studies), however, varied, ranging from no improvement (n = 4 studies) to improvement (n = 8 studies) or improvement only in apolipoprotein E allele 4 (APOE ε4) noncarriers (n = 2 studies). One study reported an increase in regional cerebral blood flow in APOE ε4 noncarriers and another reported an increase in energy metabolism in the brain. CONCLUSION: MCFA supplementation increases circulating ketone body levels, resulting in increased brain energy metabolism. Further research is required to determine whether this MCFA-mediated increase in brain energy metabolism improves cognition. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42019146967.
Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/prevenção & controle , Apolipoproteína E4 , Ácidos Graxos/metabolismo , Corpos Cetônicos/metabolismo , Corpos Cetônicos/uso terapêutico , Insulina , Glucose/metabolismoRESUMO
Alzheimer's disease (AD) is the most common form of dementia. AD is a progressive neurodegenerative disorder characterized by cognitive dysfunction, including learning and memory deficits, and behavioral changes. Neuropathology hallmarks of AD such as amyloid beta (Aß) plaques and neurofibrillary tangles containing the neuron-specific protein tau is associated with changes in fluid biomarkers including Aß, phosphorylated tau (p-tau)-181, p-tau 231, p-tau 217, glial fibrillary acidic protein (GFAP), and neurofilament light (NFL). Another pathological feature of AD is neural damage and hyperactivation of astrocytes, that can cause increased pro-inflammatory mediators and oxidative stress. In addition, reduced brain glucose metabolism and mitochondrial dysfunction appears up to 15 years before the onset of clinical AD symptoms. As glucose utilization is compromised in the brain of patients with AD, ketone bodies (KBs) may serve as an alternative source of energy. KBs are generated from the ß-oxidation of fatty acids, which are enhanced following consumption of ketogenic diets with high fat, moderate protein, and low carbohydrate. KBs have been shown to cross the blood brain barrier to improve brain energy metabolism. This review comprehensively summarizes the current literature on how increasing KBs support brain energy metabolism. In addition, for the first time, this review discusses the effects of ketogenic diet on the putative AD biomarkers such as Aß, tau (mainly p-tau 181), GFAP, and NFL, and discusses the role of KBs on neuroinflammation, oxidative stress, and mitochondrial metabolism.
RESUMO
Epidemiological and interventional studies have linked saturated fatty acids (SFA) with elevated levels of low-density lipoprotein cholesterol (LDL-C) and increased CVD risk. However, the effects of the SFA chain length on postprandial lipemia in humans are not well elucidated. The aim of this study was to investigate the impact of short, medium and long-chain SFA on postprandial blood lipids in healthy volunteers. Sixteen healthy volunteers consumed test biscuits containing 40 g of either butter (BB), coconut oil (CB) or lard (LB) in a single-blinded, randomized crossover design. Blood samples were collected fasting and 2, 3, 4, and 6 hours postprandially and assessed for blood lipids (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; LDL-C and triglyceride, TG). The postprandial TG response following CB was 59.8% lower than following BB (p < 0.01) and 58.8% lower than LB (p < 0.01), although no difference was observed between the BB and the LB responses. The net area under the LDL-C concentration curve was significantly larger after consumption of the CB compared to the BB, despite no significant differences in postprandial net area under the TC and HDL-C concentration curves. Consumption of medium-chain SFA as CB resulted in lower postprandial TG excursions compared to short-chain SFA as BB and long-chain SFA as LB, despite their identical fat and caloric content. These results suggest that SFA differ in their potential to elevate postprandial lipid levels, and that coconut oil, a rich source of medium-chain SFA may not be as hyperlipidemic as animal fats rich in long chain SFA. ANZCTR IDENTIFIER: 12617000903381. CLINICAL TRIAL REGISTRY NUMBER: The study was registered with the Australia New Zealand Trial registry as ACTRN12617000903381.
Assuntos
Ácidos Graxos/farmacologia , Hiperlipidemias/sangue , Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , Adolescente , Adulto , Estudos Cross-Over , Ácidos Graxos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Método Simples-Cego , Adulto JovemRESUMO
Dietary supplementation with curcumin has been previously reported to have beneficial effects in people with insulin resistance, type 2 diabetes (T2D) and Alzheimer's disease (AD). This study investigated the effects of dietary supplementation with curcumin on key peptides implicated in insulin resistance in individuals with high risk of developing T2D. Plasma samples from participants recruited for a randomised controlled trial with curcumin (180 mg/day) for 12 weeks were analysed for circulating glycogen synthase kinase-3 ß (GSK-3ß) and islet amyloid polypeptide (IAPP). Outcome measures were determined using ELISA kits. The homeostasis model for assessment of insulin resistance (HOMA-IR) was measured as parameters of glycaemic control. Curcumin supplementation significantly reduced circulating GSK-3ß (-2.4 ± 0.4 ng/mL vs. -0.3 ± 0.6, p = 0.0068) and IAPP (-2.0 ± 0.7 ng/mL vs. 0.4 ± 0.6, p = 0.0163) levels compared with the placebo group. Curcumin supplementation significantly reduced insulin resistance (-0.3 ± 0.1 vs. 0.01 ± 0.05, p = 0.0142) compared with placebo group. Dietary supplementation with curcumin reduced circulating levels of IAPP and GSK-3ß, thus suggesting a novel mechanism through which curcumin could potentially be used for alleviating insulin resistance related markers for reducing the risk of T2D and AD.
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Doença de Alzheimer/prevenção & controle , Curcumina/administração & dosagem , Curcumina/farmacologia , Diabetes Mellitus Tipo 2/prevenção & controle , Suplementos Nutricionais , Glicogênio Sintase Quinase 3 beta/química , Resistência à Insulina , Polipeptídeo Amiloide das Ilhotas Pancreáticas/sangue , Doença de Alzheimer/etiologia , Diabetes Mellitus Tipo 2/etiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Fatores de TempoRESUMO
Targeting kinases linked to insulin resistance (IR) and inflammation may help in reducing the risk of type 2 diabetes (T2D) and Alzheimer's disease (AD) in its early stages. This study aimed to determine whether DHA-rich fish oil supplementation reduces glycogen synthase kinase (GSK-3), which is linked to both IR and AD. Baseline and post-intervention plasma samples from 58 adults with abdominal obesity (Age: 51.7 ± 1.7 years, BMI: 31.9 ± 0.8 kg/m2) were analysed for outcome measures. Participants were allocated to 2 g DHA-rich fish oil capsules (860 mg DHA + 120 mg EPA) (n = 31) or placebo capsules (n = 27) per day for 12 weeks. Compared to placebo, DHA-rich fish oil significantly reduced GSK-3ß by -2.3 ± 0.3 ng/mL. An inverse correlation (p < 0.05) was found between baseline insulin and IR and their changes following intervention only in participants with C-reactive protein levels higher than 2.4 mg/L. DHA-rich fish oil reduces GSK-3 and IR, suggesting a potential role of long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) in ameliorating AD risk.
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Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Óleos de Peixe/administração & dosagem , Resistência à Insulina , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Adolescente , Adulto , Idoso , Doença de Alzheimer , Índice de Massa Corporal , Diabetes Mellitus Tipo 2 , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Quinase 3 da Glicogênio Sintase , Glicogênio Sintase Quinase 3 beta , Humanos , Insulina , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Alzheimer's disease (AD) is the most common form of dementia. Currently, there is no effective medication for the prevention or treatment of AD. This has led to the search for alternative therapeutic strategies. Coconut oil(CO) has a unique fatty acid composition that is rich in medium chain fatty acids(MCFA), a major portion of which directly reaches the liver via the portal vein, thereby bypassing the lymphatic system. Given that brain glucose hypometabolism is a major early hallmark of AD, detectable well before the onset of symptoms, ketone bodies from MCFA metabolism can potentially serve as an alternative energy source to compensate for lack of glucose utilisation in the brain. Additionally, neuroprotective antioxidant properties of CO have been attributed to its polyphenolic content. This review discusses how the metabolism of CO and MCFA may aid in compensating the glucose hypometabolism observed in the AD brain. Furthermore, we present the current evidence of the neuroprotective properties of CO on cognition, amyloid-ß pathogenicity, inflammation and oxidative stress. The current review addresses the influence of CO/MCFA on other chronic disorders that are risk factors for AD, and addresses existing gaps in the literature regarding the use of CO/MCFA as a potential treatment for AD.
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Doença de Alzheimer , Encéfalo , Óleo de Coco/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Humanos , Nootrópicos/farmacologiaRESUMO
BACKGROUND/OBJECTIVE: Hepcidin, an iron-regulating hormone, suppresses the release of iron by binding to the iron exporter protein, ferroportin, resulting in intracellular iron accumulation. Given that iron dyshomeostasis has been observed in Alzheimer's disease (AD) together with elevated serum hepcidin levels, the current study examined whether elevated serum hepcidin levels are an early event in AD pathogenesis by measuring the hormone in cognitively normal older adults at risk of AD, based on high neocortical amyloid-ß load (NAL). METHODS: Serum hepcidin levels in cognitively normal participants (nâ=â100) aged between 65-90 years were measured using ELISA. To evaluate NAL, all participants underwent 18F-florbetaben positron emission tomography. A standard uptake value ratio (SUVR)<1.35 was classified as low NAL (nâ=â65) and ≥1.35 (nâ=â35) was classified as high NAL. RESULTS: Serum hepcidin was significantly higher in participants with high NAL compared to those with low NAL before and after adjusting for covariates: age, gender, and APOEÉ4 carriage (pâ<â0.05). A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished high from low NAL (area under the curve, AUCâ=â0.766), but was outperformed when serum hepcidin was added to the base model (AUCâ=â0.794) and further improved with plasma Aß42/40 ratio (AUCâ=â0.829). CONCLUSION: The present findings indicate that serum hepcidin is increased in individuals at risk for AD and contribute to the body of evidence supporting iron dyshomeostasis as an early event of AD. Further, hepcidin may add value to a panel of markers that contribute toward identifying individuals at risk of AD; however, further validation studies are required.
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Peptídeos beta-Amiloides/sangue , Cognição/fisiologia , Hepcidinas/sangue , Neocórtex/metabolismo , Fragmentos de Peptídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Humanos , Masculino , Tomografia por Emissão de Pósitrons/métodosRESUMO
As the food matrix is a determinant of the rate of fat digestion and absorption, it is important for the modulation of postprandial triglyceridaemia. High postprandial triglyceride levels are associated with an increase in inflammation, oxidative stress, an imbalance in the lipoprotein profile and an increase in the risk of developing chronic diseases. This study was designed to assess the in vitro digestion patterns and the postprandial lipaemic responses to test foods with the same nutrient composition but differing in the form and structure. A liquid, a semi-solid and a solid test food with the same nutrient and energy composition were designed. The digestion profiles of the three foods were assessed using a dynamic in vitro model. The foods were also consumed by healthy young adults who donated blood samples after an overnight fast and again 0.5, 1, 2, 3, 4 and 6 h after consuming each of the test foods and who were also assessed for appetite sensations. The solid food showed phase separation during gastric digestion and a lower release of fatty acids during intestinal digestion than the liquid and semi-solid foods. During the postprandial feeding experiments, the solid food caused a lower increase in serum triglycerides than the liquid food and produced higher fullness and satisfaction. In conclusion, the food form and structure modulated fat release, postprandial triglyceridaemia and appetite sensations independent of the nutrient and energy content. Thus, manipulation of the food structure and form may be used in designing strategies for improving metabolic markers and satiety.
Assuntos
Análise de Alimentos , Metabolismo dos Lipídeos , Período Pós-Prandial , Adolescente , Adulto , Apetite , Estudos Cross-Over , Digestão , Feminino , Humanos , Lipídeos/química , Masculino , Triglicerídeos/sangue , Adulto JovemRESUMO
BACKGROUND: Aberrant amyloid-ß (Aß) deposition in the brain occurs two decades prior to the manifestation of Alzheimer's disease (AD) clinical symptoms and therefore brain Aß load measured using PET serves as a gold standard biomarker for the early diagnosis of AD. However, the uneconomical nature of PET makes blood markers, that reflect brain Aß deposition, attractive candidates for investigation as surrogate markers. OBJECTIVE: Investigation of plasma Aß as a surrogate marker for brain Aß deposition in cognitively normal elderly individuals. METHODS: Plasma Aß40 and Aß42 concentrations were measured using the ultrasensitive Single Molecule Array (Simoa) assay in 95 cognitively normal elderly individuals, who have all undergone PET to assess brain Aß deposition. Based on the standard uptake value ratios (SUVR) obtained from PET imaging, using the tracer 18F-Florbetaben, plasma Aß was compared between 32 participants assessed to have low brain Aß load (Aß-, SUVR <1.35) and 63 assessed to have high brain Aß load (Aß+, SUVR ≥1.35). RESULTS: Plasma Aß42/Aß40 ratios were lower in the Aß+ group compared to the Aß-group. Plasma Aß40 and Aß42 levels were not significantly different between Aß-and Aß+ groups, although a trend of higher plasma Aß40 was observed in the Aß+ group. Additionally, plasma Aß42/Aß40 ratios along with the known AD risk factors, age and APOEÉ4 status, resulted in Aß+ participants being distinguished from Aß-participants based on an area under the receiver operating characteristic curve shown to be 78%. CONCLUSION: Plasma Aß ratios in this study are a potential biomarker for brain Aß deposition and therefore, for preclinical AD. However, this method to measure plasma Aß needs further development to increase the accuracy of this promising AD blood biomarker.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/sangue , Biomarcadores/sangue , Cognição , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Apolipoproteínas E/sangue , Apolipoproteínas E/genética , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Fragmentos de Peptídeos/sangue , Tomografia por Emissão de Pósitrons , RiscoRESUMO
Background: Medium-chain saturated fatty acids (MCFAs) may affect circulating lipids and lipoproteins differently than long-chain saturated fatty acids (LCSFAs), but the results from human intervention trials have been equivocal. Objective: The aim of this study was to determine whether MCFAs and LCSFAs have differential impacts on blood lipids and lipoproteins. Design: Five databases were searched (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus) until April 2018, and published clinical trials investigating the differential effects of dietary MCFAs and LCSFAs on blood lipids were included. Searches were limited to the English language and to studies with adults aged >18 y. Where possible, studies were pooled for meta-analysis using RevMan 5.2. The principle summary measure was the mean difference between groups calculated using the random-effects model. Results: Eleven eligible crossover and 1 parallel trial were identified with a total of 299 participants [weighted mean ± SD age: 38 ± 3 y; weighted mean ± SD body mass index (kg/m2): 24 ± 2]. All studies were pooled for the meta-analysis. Diets enriched with MCFAs led to significantly higher high-density lipoprotein (HDL) cholesterol concentrations than diets enriched with LCSFAs (0.11 mmol/L; 95% CI: 0.07, 0.15 mmol/L) with no effect on triglyceride, low-density lipoprotein (LDL) cholesterol, and total cholesterol concentrations. Consumption of diets rich in MCFAs significantly increased apolipoprotein A-I (apoA-I) concentrations compared with diets rich in LCSFAs (0.08 g/L; 95% CI: 0.02, 0.14 g/L). There was no evidence of statistical heterogeneity for HDL cholesterol, apoA-I, and triglyceride concentrations; however, significant heterogeneity was observed for the total cholesterol (I2 = 49%) and LDL cholesterol analysis (I2 = 58%). Conclusion: The findings of this research demonstrate a differential effect of MCFAs and LCSFAs on HDL cholesterol concentrations. Further investigations are warranted to elucidate the mechanism by which the lipid profile is altered. This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42017078277.
Assuntos
Colesterol/sangue , Dieta , Gorduras na Dieta/farmacologia , Ácidos Graxos/farmacologia , Triglicerídeos/sangue , Adulto , Idoso , Apolipoproteína A-I/sangue , Índice de Massa Corporal , Humanos , Pessoa de Meia-Idade , Adulto JovemRESUMO
In the current study, we aimed to evaluate the effects of a single dose of curcumin and/or fish oil on postprandial glycaemic parameters in healthy individuals. This was a randomised, placebo-controlled and crossover study. Sixteen (n = 16) volunteers were randomised to receive placebo, curcumin (180 mg) tablets, fish oil (1.2 g long chain omega-3 polyunsaturated fatty acids) capsules and curcumin + fish oil prior to a standard meal on 4 test days separated by a week. Blood glucose, serum insulin and triglycerides were measured at intervals between 0-120 min. Difference between the treatments was measured using two-way repeated measures analysis of variance and pair-wise comparisons using Wilcoxon signed-rank or paired t-test as appropriate. Postprandial glucose concentrations were significantly lower in the curcumin (60.6%, P = 0.0007) and curcumin + fishoil group (51%, P = 0.002) groups at 60 min from baseline. Compared with placebo, area under the curve (AUC) for change in blood glucose concentration was reduced by curcumin (36%, P = 0.003) and curcumin + fishoil (30%, 0.004), but not fish oil alone (p = 0.105). Both curcumin (P = 0.01) and curcumin + fishoil (P = 0.03) treatments significantly lowered postprandial insulin (AUC) by 26% in comparison with placebo. Curcumin, but not fish oil, reduces postprandial glycaemic response and insulin demand for glucose control.
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Glicemia/efeitos dos fármacos , Curcumina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Período Pós-Prandial/efeitos dos fármacos , Adulto , Estudos Cross-Over , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ácidos Graxos Ômega-3/metabolismo , Feminino , Óleos de Peixe/uso terapêutico , Humanos , Insulina/metabolismo , Masculino , Triglicerídeos/metabolismoRESUMO
Lower incidence of cardiovascular disease (CVD) in the Greenland Inuit, Northern Canada and Japan has been attributed to their consumption of seafood rich in long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA). While a large majority of pre-clinical and intervention trials have demonstrated heart health benefits of LCn-3PUFA, some studies have shown no effects or even negative effects. LCn-3PUFA have been shown to favourably modulate blood lipid levels, particularly a reduction in circulating levels of triglycerides. High density lipoprotein-cholesterol (HDL-C) levels are elevated following dietary supplementation with LCn-3PUFA. Although LCn-3PUFA have been shown to increase low-density lipoprotein-cholesterol (LDL-C) levels, the increase is primarily in the large-buoyant particles that are less atherogenic than small-dense LDL particles. The anti-inflammatory effects of LCn-3PUFA have been clearly outlined with inhibition of NFkB mediated cytokine production being the main mechanism. In addition, reduction in adhesion molecules (intercellular adhesion molecule, ICAM and vascular cell adhesion molecule 1, VCAM-1) and leukotriene production have also been demonstrated following LCn-3PUFA supplementation. Anti-aggregatory effects of LCn-3PUFA have been a subject of controversy, however, recent studies showing sex-specific effects on platelet aggregation have helped resolve the effects on hyperactive platelets. Improvements in endothelium function, blood flow and blood pressure after LCn-3PUFA supplementation add to the mechanistic explanation on their cardio-protective effects. Modulation of adipose tissue secretions including pro-inflammatory mediators and adipokines by LCn-3PUFA has re-ignited interest in their cardiovascular health benefits. The aim of this narrative review is to filter out the reasons for possible disparity between cohort, mechanistic, pre-clinical and clinical studies. The focus of the article is to provide possible explanation for the observed controversies surrounding heart health benefits of LCn-3PUFA.
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Doenças Cardiovasculares/prevenção & controle , Ácidos Graxos Ômega-3/administração & dosagem , Animais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , LDL-Colesterol/metabolismo , Ensaios Clínicos como Assunto , Suplementos Nutricionais/análise , Humanos , Agregação Plaquetária/efeitos dos fármacos , Resultado do Tratamento , Triglicerídeos/metabolismoRESUMO
BACKGROUND AND AIMS: Dietary fat composition is known to modulate circulating lipid and lipoprotein levels. Although supplementation with long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to reduce plasma triglyceride levels, the effect of the interactions between LCn-3PUFA and the major dietary fats consumed has not been previously investigated. METHODS: In a randomized controlled parallel design clinical intervention, we examined the effect of diets rich in either saturated fatty acids (SFA) or omega-6 polyunsaturated fatty acids (n-6PUFA) on plasma lipid levels and lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) in subjects with an adequate omega 3 index. Twenty six healthy subjects went through a four-week pre-supplementation period with LCn-3PUFA and were then randomized to diets rich in either n-6PUFA or SFA both supplemented with LCn-3PUFA. RESULTS: The diet rich in n-6PUFA decreased low density lipoprotein (LDL) particle concentration (-8%, p=0.013) and LDL cholesterol (LDL-C) level (-8%, p=0.021), while the saturated fat rich diet did not affect LDL particle concentration or LDL-C levels significantly. Nevertheless, dietary saturated fatty acids increased LCn-3PUFA in plasma and tissue lipids compared with n-6PUFA, potentially reducing other cardiovascular risk factors such as inflammation and clotting tendency. CONCLUSION: Improvement on the omega 3 index of healthy subjects did not alter the known effects of dietary saturated fats and n-6PUFA on LDL profiles.
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LDL-Colesterol/sangue , Gorduras na Dieta/farmacologia , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Insaturados/sangue , Ácidos Graxos/farmacologia , Lipoproteínas LDL/sangue , Adulto , Idoso , Coagulação Sanguínea , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/epidemiologia , Dieta , Suplementos Nutricionais , Eritrócitos/química , Eritrócitos/metabolismo , Feminino , Humanos , Inflamação/epidemiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
Dietary saturated fat (SFA) intake has been associated with elevated blood lipid levels and increased risk for the development of chronic diseases. However, some animal studies have demonstrated that dietary SFA may not raise blood lipid levels when the diet is sufficient in omega-3 polyunsaturated fatty acids (n-3PUFA). Therefore, in a randomised cross-over design, we investigated the postprandial effects of feeding meals rich in either SFA (butter) or vegetable oil rich in omega-6 polyunsaturated fatty acids (n-6PUFA), in conjunction with n-3PUFA, on blood lipid profiles [total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triacylglycerol (TAG)] and n-3PUFA incorporation into plasma lipids over a 6-h period. The incremental area under the curve for plasma cholesterol, LDL-C, HDL-C, TAG and n-3PUFA levels over 6 h was similar in the n-6PUFA compared to SFA group. The postprandial lipemic response to saturated fat is comparable to that of n-6PUFA when consumed with n-3PUFA; however, sex-differences in response to dietary fat type are worthy of further attention.
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Gorduras na Dieta/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Metabolismo dos Lipídeos , Lipídeos/sangue , Óleos de Plantas/metabolismo , Período Pós-Prandial , Adolescente , Adulto , Idoso , Manteiga/análise , Estudos Cross-Over , Dieta , Ácidos Graxos Ômega-3/sangue , Feminino , Humanos , Masculino , Refeições , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: Absorption of long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to be potentiated when consumed with a high fat meal. However, the effect of different dietary fats on n-3PUFA absorption and postprandial kinetics has not been previously studied. METHOD: In a randomized cross-over design intervention, postprandial incorporation of LCn-3PUFA into plasma lipids following consumption of a meal rich in either saturated fat or omega-6 polyunsaturated fatty acids (n-6PUFA) was investigated. Healthy adult male and female subjects (n=26) were fed an isocaloric meal containing equivalent amount of either butter or sunflower seed oil supplemented with 1.8grams of LCn-3PUFA (300mg eicosapentaenoic acid, 20:5n-3 and 1500mg docosahexaenoic acid, 22:6n-3). RESULTS: Postprandial plasma lipids were enriched with saturated fatty acids and linoleic acid (18:2n-6) following consumption of the butter and the sunflower oil containing meals respectively. The increase in plasma 20:5n-3 and 22:6n-3 levels over the 6hour study period was similar in both the saturated and the n-6 fat groups. CONCLUSION: These results suggest that the expected competition between LCn-3PUFA and n-6PUFA at the absorption level is unlikely; therefore competition at the enzymatic level should be primarily responsible for differences in their metabolic and clinical effects. Trial registered with the Australia New Zealand Trial registry as ACTRN12612000654853.