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1.
Nutr Rev ; 81(9): 1144-1162, 2023 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-36633304

RESUMEN

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 (n = 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.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/prevención & control , Apolipoproteína E4 , Ácidos Grasos/metabolismo , Cuerpos Cetónicos/metabolismo , Cuerpos Cetónicos/uso terapéutico , Insulina , Glucosa/metabolismo
2.
Nutrients ; 12(6)2020 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-32486256

RESUMEN

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.


Asunto(s)
Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Aceites de Pescado/administración & dosificación , Resistencia a la Insulina , Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Adolescente , Adulto , Anciano , Enfermedad de Alzheimer , Índice de Masa Corporal , Diabetes Mellitus Tipo 2 , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Glucógeno Sintasa Quinasa 3 , Glucógeno Sintasa Quinasa 3 beta , Humanos , Insulina , Masculino , Persona de Mediana Edad , Adulto Joven
3.
Nutrients ; 12(4)2020 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-32283762

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer/prevención & control , Curcumina/administración & dosificación , Curcumina/farmacología , Diabetes Mellitus Tipo 2/prevención & control , Suplementos Dietéticos , Glucógeno Sintasa Quinasa 3 beta/química , Resistencia a la Insulina , Polipéptido Amiloide de los Islotes Pancreáticos/sangre , Enfermedad de Alzheimer/etiología , Diabetes Mellitus Tipo 2/etiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Factores de Tiempo
4.
Sci Rep ; 8(1): 13679, 2018 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-30209353

RESUMEN

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.


Asunto(s)
Glucemia/efectos de los fármacos , Curcumina/uso terapéutico , Hipoglucemiantes/uso terapéutico , Periodo Posprandial/efectos de los fármacos , Adulto , Estudios Cruzados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ácidos Grasos Omega-3/metabolismo , Femenino , Aceites de Pescado/uso terapéutico , Humanos , Insulina/metabolismo , Masculino , Triglicéridos/metabolismo
5.
Food Funct ; 9(7): 3576-3596, 2018 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-29904777

RESUMEN

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.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Ácidos Grasos Omega-3/administración & dosificación , Animales , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/fisiopatología , LDL-Colesterol/metabolismo , Ensayos Clínicos como Asunto , Suplementos Dietéticos/análisis , Humanos , Agregación Plaquetaria/efectos de los fármacos , Resultado del Tratamiento , Triglicéridos/metabolismo
6.
Metabolism ; 68: 11-19, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28183443

RESUMEN

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.


Asunto(s)
LDL-Colesterol/sangre , Grasas de la Dieta/farmacología , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Insaturados/sangre , Ácidos Grasos/farmacología , Lipoproteínas LDL/sangre , Adulto , Anciano , Coagulación Sanguínea , Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/epidemiología , Dieta , Suplementos Dietéticos , Eritrocitos/química , Eritrocitos/metabolismo , Femenino , Humanos , Inflamación/epidemiología , Lípidos/sangre , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto Joven
7.
Metabolism ; 64(12): 1658-66, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26386693

RESUMEN

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.


Asunto(s)
Ácidos Grasos Omega-3/farmacocinética , Ácidos Grasos Omega-6/administración & dosificación , Adolescente , Adulto , Anciano , Estudios Cruzados , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Humanos , Cinética , Lípidos/sangre , Masculino , Persona de Mediana Edad , Caracteres Sexuales
8.
Lipids ; 50(4): 339-47, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25753895

RESUMEN

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.


Asunto(s)
Grasas de la Dieta/metabolismo , Ácidos Grasos Omega-3/metabolismo , Metabolismo de los Lípidos , Lípidos/sangre , Aceites de Plantas/metabolismo , Periodo Posprandial , Adolescente , Adulto , Anciano , Mantequilla/análisis , Estudios Cruzados , Dieta , Ácidos Grasos Omega-3/sangre , Femenino , Humanos , Masculino , Comidas , Persona de Mediana Edad , Adulto Joven
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