RESUMEN
(Poly)phenol (PP)-rich blackcurrant (BC) extracts reduce postprandial glucose concentrations. Combinations with other fruit (poly)phenols and fruit fibre may enhance the effect. This study investigated the acute effects of combinations of BC extracts, high (H-BC) and low (L-BC) (poly)phenol concentrations, sweet orange extracts (SO) and fibre-rich orange pulp (F) in reducing postprandial glycaemia. In two randomised, double-blind, crossover design studies, healthy participants consumed seven types of 200 mL beverages: in the GLU-FX trial, H-BC (1600 mg PP); L-BC (800 mg PP); SO (800 mg PP); BC + SO (1600 mg PP) or CON (placebo); in the GLU-MIX trial, BC + F (800 mg PP), F (1.5 g fibre), or CON2 (placebo), immediately followed by consumption of 75 g available carbohydrate (starch and sugars). Blood was sampled at baseline and postprandially to measure changes in glucose, insulin, and gut hormones; appetite changes were assessed by visual analogue scales and, in GLU-MIX, ad libitum food intake and cognitive function were assessed. Twenty-nine and thirty-seven adults completed GLU-FX and GLU-MIX, respectively. L-BC reduced early postprandial glycaemia (0-30 min) with no differences in glucose incremental Cmax or total glycaemic response. No significant effect was observed following other drinks relative to CON. L-BC and H-BC drinks inhibited insulin secretion up to 30 min and GIP up to 120 min. In GLU-MIX, BC + F improved some indicators of cognitive function but not all. Measures of appetite were unaffected. The impact of (poly)phenol-rich BC extracts on total postprandial glycaemia in healthy participants was minimal and not enhanced when administered in combination with an orange (poly)phenol extract or orange pulp. Clinical Trials registered at https://www.clinicaltrials.gov: NCT03184064 (GLU-FX) and NCT03572296 (GLU-MIX).
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Citrus , Hormonas Gastrointestinales , Humanos , Adulto , Apetito , Glucemia , Fenoles/farmacología , Fenol/farmacología , Glucosa/farmacología , Fibras de la Dieta/farmacología , Insulina , Cognición , Periodo Posprandial , Estudios Cruzados , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
As we continue to elucidate the mechanisms underlying age-related brain diseases, the reductionist strategy in nutritionbrain function research has focused on establishing the impact of individual foods. However, the biological processes connecting diet and cognition are complex. Therefore, consideration of a combination of nutritional compounds may be most efficacious. One barrier to establishing the efficacy of multi-nutrient interventions is that the area lacks an established set of evidence-based guidelines for studying their effect on brain health. This review is an output of the International Life Sciences Institute (ILSI) Europe. A multi-disciplinary expert group was assembled with the aim of developing a set of considerations to guide research into the effects of multi-nutrient combinations on brain functions. Consensus recommendations converged on six key issues that should be considered to advance research in this area: (1) establish working mechanisms of the combination and contributions of each individual compound; (2) validate the relevance of the mechanisms for the targeted human condition; (3) include current nutrient status, intake or dietary pattern as inclusion/exclusion criteria in the study design; (4) select a participant population that is clinically and biologically appropriate for all nutritional components of the combination; (5) consider a range of cognitive outcomes; (6) consider the limits of reductionism and the 'gold standard' randomised controlled trial. These guiding principles will enhance our understanding of the interactive/complementary activities of dietary components, thereby strengthening the evidence base for recommendations aimed at delaying cognitive decline.
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Envejecimiento Cognitivo , Nutrientes , Humanos , Alimentos , Encéfalo , Cognición , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The global increases in life expectancy and population have resulted in a growing ageing population and with it a growing number of people living with age-related neurodegenerative conditions and dementia, shifting focus towards methods of prevention, with lifestyle approaches such as nutrition representing a promising avenue for further development. This overview summarises the main themes discussed during the 3rd Symposium on "Nutrition for the Ageing Brain: Moving Towards Clinical Applications" held in Madrid in August 2018, enlarged with the current state of knowledge on how nutrition influences healthy ageing and gives recommendations regarding how the critical field of nutrition and neurodegeneration research should move forward into the future. Specific nutrients are discussed as well as the impact of multi-nutrient and whole diet approaches, showing particular promise to combatting the growing burden of age-related cognitive decline. The emergence of new avenues for exploring the role of diet in healthy ageing, such as the impact of the gut microbiome and development of new techniques (imaging measures of brain metabolism, metabolomics, biomarkers) are enabling researchers to approach finding answers to these questions. But the translation of these findings into clinical and public health contexts remains an obstacle due to significant shortcomings in nutrition research or pressure on the scientific community to communicate recommendations to the general public in a convincing and accessible way. Some promising programs exist but further investigation to improve our understanding of the mechanisms by which nutrition can improve brain health across the human lifespan is still required.
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Envejecimiento Saludable , Estado Nutricional , Envejecimiento , Encéfalo , Dieta , HumanosRESUMEN
BACKGROUND: Ageing is a highly complex process marked by a temporal cascade of events, which promote alterations in the normal functioning of an individual organism. The triggers of normal brain ageing are not well understood, even less so the factors which initiate and steer the neuronal degeneration, which underpin disorders such as dementia. A wealth of data on how nutrients and diets may support cognitive function and preserve brain health are available, yet the molecular mechanisms underlying their biological action in both normal ageing, age-related cognitive decline, and in the development of neurodegenerative disorders have not been clearly elucidated. OBJECTIVES: This review aims to summarise the current state of knowledge of vulnerabilities that predispose towards dysfunctional brain ageing, highlight potential protective mechanisms, and discuss dietary interventions that may be used as therapies. A special focus of this paper is on the impact of nutrition on neuroprotection and the underlying molecular mechanisms, and this focus reflects the discussions held during the 2nd workshop 'Nutrition for the Ageing Brain: Functional Aspects and Mechanisms' in Copenhagen in June 2016. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). CONCLUSION: Coupling studies of cognitive ageing with studies investigating the effect of nutrition and dietary interventions as strategies targeting specific mechanisms, such as neurogenesis, protein clearance, inflammation, and non-coding and microRNAs is of high value. Future research on the impact of nutrition on cognitive ageing will need to adopt a longitudinal approach and multimodal nutritional interventions will likely need to be imposed in early-life to observe significant impact in older age.
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Envejecimiento Cognitivo/fisiología , Envejecimiento Cognitivo/psicología , Dietoterapia/métodos , Estado Nutricional/fisiología , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Animales , Encéfalo/metabolismo , Cognición/fisiología , Trastornos del Conocimiento/dietoterapia , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/psicología , Dietoterapia/tendencias , Humanos , Nutrientes/administración & dosificación , Nutrientes/metabolismo , Obesidad/dietoterapia , Obesidad/metabolismo , Obesidad/psicologíaRESUMEN
Differentiated human neural stem cells were cultured in an inert three-dimensional (3D) scaffold and, unlike two-dimensional (2D) but otherwise comparable monolayer cultures, formed spontaneously active, functional neuronal networks that responded reproducibly and predictably to conventional pharmacological treatments to reveal functional, glutamatergic synapses. Immunocytochemical and electron microscopy analysis revealed a neuronal and glial population, where markers of neuronal maturity were observed in the former. Oligonucleotide microarray analysis revealed substantial differences in gene expression conferred by culturing in a 3D vs a 2D environment. Notable and numerous differences were seen in genes coding for neuronal function, the extracellular matrix and cytoskeleton. In addition to producing functional networks, differentiated human neural stem cells grown in inert scaffolds offer several significant advantages over conventional 2D monolayers. These advantages include cost savings and improved physiological relevance, which make them better suited for use in the pharmacological and toxicological assays required for development of stem cell-based treatments and the reduction of animal use in medical research. Copyright © 2015 John Wiley & Sons, Ltd.
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Red Nerviosa/fisiología , Células-Madre Neurales/citología , Ingeniería de Tejidos/métodos , Potenciales de Acción/fisiología , Algoritmos , Diferenciación Celular/genética , Forma de la Célula , Células Cultivadas , Electrodos , Regulación de la Expresión Génica , Humanos , Inmunohistoquímica , Aprendizaje Automático , Células-Madre Neurales/ultraestructura , FenotipoRESUMEN
Blackcurrants are rich in polyphenolic glycosides called anthocyanins, which may inhibit postprandial glycemia. The aim was to determine the dose-dependent effects of blackcurrant extract on postprandial glycemia. Men and postmenopausal women (14M, 9W, mean age 46 years, S.D.=14) were enrolled into a randomized, double-blind, crossover trial. Low sugar fruit drinks containing blackcurrant extract providing 150-mg (L-BE), 300-mg (M-BE) and 600-mg (H-BE) total anthocyanins or no blackcurrant extract (CON) were administered immediately before a high-carbohydrate meal. Plasma glucose, insulin and incretins (GIP and GLP-1) were measured 0-120min, and plasma 8-isoprostane F2α, together with arterial stiffness by digital volume pulse (DVP) was measured at 0 and 120min. Early plasma glucose response was significantly reduced following H-BE (n=22), relative to CON, with a mean difference (95% CI) in area over baseline (AOB) 0-30min of -0.34mmol/l.h (-0.56, -0.11, P<.005); there were no differences between the intermediate doses and placebo. Plasma insulin concentrations (AOB 0-30min) were similarly reduced. Plasma GIP concentrations (AOB 0-120min) were significantly reduced following H-BE, with a mean difference of -46.6ng/l.h (-66.7, -26.5, P<.0001) compared to CON. Plasma GLP-1 concentrations were reduced following H-BE at 90min. There were no effects on 8-isoprostane F2α or vascular function. Consumption of blackcurrant extract in amounts roughly equivalent to 100-g blackcurrants reduced postprandial glycemia, insulinemia and incretin secretion, which suggests that inclusion of blackcurrant polyphenols in foods may provide cardio-metabolic health benefits. This trial was registered at clinicaltrials.gov as NCT01706653.
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Antocianinas/uso terapéutico , Bebidas , Frutas/química , Hiperglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Extractos Vegetales/uso terapéutico , Ribes/química , Adulto , Antocianinas/administración & dosificación , Glucemia/análisis , Estudios Cruzados , Dieta de Carga de Carbohidratos/efectos adversos , Dieta Baja en Carbohidratos , Método Doble Ciego , Femenino , Alimentos Funcionales , Humanos , Hiperglucemia/sangre , Hiperglucemia/metabolismo , Hiperinsulinismo/sangre , Hiperinsulinismo/metabolismo , Hiperinsulinismo/prevención & control , Hipoglucemiantes/administración & dosificación , Incretinas/antagonistas & inhibidores , Incretinas/sangre , Incretinas/metabolismo , Masculino , Comidas , Persona de Mediana Edad , Extractos Vegetales/administración & dosificación , Periodo PosprandialRESUMEN
Epidemiological studies suggest that fruits and vegetables may play a role in promoting bone growth and preventing age-related bone loss, attributable, at least in part, to phytochemicals such as flavonoids stimulating osteoblastogenesis. Through systematically screening the effect of flavonoids on the osteogenic differentiation of human mesenchymal stem cells in vitro and correlating activity with chemical structure using comparative molecular field analysis, we have successfully identified important structural features that relate to their activity, as well as reliably predicted the activity of compounds with unknown activity. Contour maps emphasized the importance of electronegativity, steric bulk, and a 2-C-3-C double bond at the flavonoid C-ring, as well as overall electropositivity and reduced steric bulk at the flavonoid B-ring. These results support a role for certain flavonoids in promoting osteogenic differentiation, thus their potential for preventing skeletal deterioration, as well as providing a foundation for the lead optimization of novel bone anabolics.
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Flavonoides/farmacología , Osteogénesis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Flavonoides/química , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Estructura Molecular , Transducción de Señal/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
Reviewed here is the existing evidence for the effects of ginseng extracts and isolated ginsenosides relevant to cognition in humans. Clinical studies in healthy volunteers and in patients with neurological disease or deficit, evidence from preclinical models of cognition, and pharmacokinetic data are considered. Conditions under which disease modification may indirectly benefit cognition but may not translate to cognitive benefits in healthy subjects are discussed. The number of chronic studies of ginseng effects in healthy individuals is limited, and the results from acute studies are inconsistent, making overall assessment of ginseng's efficacy as a cognitive enhancer premature. However, mechanistic results are encouraging; in particular, the ginsenosides Rg3 , Rh1 , Rh2 , Rb1 , Rd, Rg2 , and Rb3 , along with the aglycones protopanaxadiol and protopanaxatriol, warrant further attention. Compound K has a promising pharmacokinetic profile and can affect neurotransmission and neuroprotection. Properly conducted trials using standardized tests in healthy individuals reflecting the target population for ginseng supplementation are required to address inconsistencies in results from acute studies. The evidence summarized here suggests ginseng has potential, but unproven, benefits on cognition.
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Trastornos del Conocimiento/tratamiento farmacológico , Cognición/efectos de los fármacos , Ginsenósidos/farmacología , Panax/química , Extractos Vegetales/farmacología , Cognición/fisiología , Humanos , Fármacos Neuroprotectores/farmacología , Fitoterapia , Sapogeninas/farmacologíaRESUMEN
RATIONALE: Increased food consumption following ∆(9)-tetrahydrocannabinol-induced cannabinoid type 1 receptor agonism is well documented. However, possible non-∆(9)-tetrahydrocannabinol phytocannabinoid-induced feeding effects have yet to be fully investigated. Therefore, we have assessed the effects of the individual phytocannabinoids, cannabigerol, cannabidiol and cannabinol, upon feeding behaviors. METHODS: Adult male rats were treated (p.o.) with cannabigerol, cannabidiol, cannabinol or cannabinol plus the CB(1)R antagonist, SR141716A. Prior to treatment, rats were satiated and food intake recorded following drug administration. Data were analyzed for hourly intake and meal microstructure. RESULTS: Cannabinol induced a CB(1)R-mediated increase in appetitive behaviors via significant reductions in the latency to feed and increases in consummatory behaviors via increases in meal 1 size and duration. Cannabinol also significantly increased the intake during hour 1 and total chow consumed during the test. Conversely, cannabidiol significantly reduced total chow consumption over the test period. Cannabigerol administration induced no changes to feeding behavior. CONCLUSION: This is the first time cannabinol has been shown to increase feeding. Therefore, cannabinol could, in the future, provide an alternative to the currently used and psychotropic ∆(9)-tetrahydrocannabinol-based medicines since cannabinol is currently considered to be non-psychotropic. Furthermore, cannabidiol reduced food intake in line with some existing reports, supporting the need for further mechanistic and behavioral work examining possible anti-obesity effects of cannabidiol.
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Cannabidiol/farmacología , Cannabinoides/farmacología , Cannabinol/farmacología , Ingestión de Alimentos/efectos de los fármacos , Animales , Antagonistas de Receptores de Cannabinoides/farmacología , Conducta Alimentaria/efectos de los fármacos , Masculino , Piperidinas/farmacología , Pirazoles/farmacología , Ratas , Receptor Cannabinoide CB1/efectos de los fármacos , Receptor Cannabinoide CB1/metabolismo , Rimonabant , Factores de TiempoRESUMEN
Cannabinoid type 1 receptor-mediated appetite stimulation by Δ9tetrahydrocannabinol (Δ9THC) is well understood. Recently, it has become apparent that non-Δ9THC phytocannabinoids could also alter feeding patterns. Here, we show definitively that non-Δ9THC phytocannabinoids stimulate feeding. Twelve male, Lister-Hooded rats were prefed to satiety prior to administration of a standardized cannabis extract or to either of two mixtures of pure phytocannabinoids (extract analogues) comprising the phytocannabinoids present in the same proportions as the standardized extract (one with and one without Δ9THC). Hourly intake and meal pattern data were recorded and analysed using two-way analysis of variance followed by one-way analysis of variance and Bonferroni post-hoc tests. Administration of both extract analogues significantly increased feeding behaviours over the period of the test. All three agents increased hour-one intake and meal-one size and decreased the latency to feed, although the zero-Δ9THC extract analogue did so to a lesser degree than the high-Δ9THC analogue. Furthermore, only the analogue containing Δ9THC significantly increased meal duration. The data confirm that at least one non-Δ9THC phytocannabinoid induces feeding pattern changes in rats, although further trials using individual phytocannabinoids are required to fully understand the observed effects.
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Dronabinol/farmacología , Ingestión de Alimentos/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Relación Dosis-Respuesta a Droga , Masculino , RatasRESUMEN
The herb Cannabis sativa (C. sativa) has been used in China and on the Indian subcontinent for thousands of years as a medicine. However, since it was brought to the UK and then the rest of the western world in the late 19th century, its use has been a source of controversy. Indeed, its psychotropic side effects are well reported but only relatively recently has scientific endeavour begun to find valuable uses for either the whole plant or its individual components. Here, we discuss evidence describing the endocannabinoid system, its endogenous and exogenous ligands and their varied effects on feeding cycles and meal patterns. Furthermore we also critically consider the mounting evidence which suggests non-Δ(9) tetrahydrocannabinol phytocannabinoids play a vital role in C. sativa-induced feeding pattern changes. Indeed, given the wide range of phytocannabinoids present in C. sativa and their equally wide range of intra-, inter- and extra-cellular mechanisms of action, we demonstrate that non-Δ(9) tetrahydrocannabinol phytocannabinoids retain an important and, as yet, untapped clinical potential.
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Regulación del Apetito/efectos de los fármacos , Cannabis/química , Dronabinol/farmacología , Animales , Sistema Nervioso Central/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Receptores de Cannabinoides/efectos de los fármacosRESUMEN
Appetite stimulation via partial agonism of cannabinoid type 1 receptors by Δtetrahydrocannabinol (ΔTHC) is well documented and can be modulated by non-ΔTHC phytocannabinoids. ΔTHC concentrations sufficient to elicit hyperphagia induce changes to both appetitive (reduced latency to feed) and consummatory (increased meal one size and duration) behaviours. Here, we show that a cannabis extract containing too little ΔTHC to stimulate appetite can induce hyperphagia solely by increasing appetitive behaviours. Twelve, male Lister hooded rats were presatiated before treatment with a low-ΔTHC cannabis extract (0.5, 1.0, 2.0 and 4.0 mg/kg). Hourly intake and meal pattern data were recorded and analyzed using one-way analyses of variance followed by Bonferroni post-hoc tests. The cannabis extract significantly increased food intake during the first hour of testing (at 4.0 mg/kg) and significantly reduced the latency to feed versus vehicle treatments (at doses ≥1.0 mg/kg). Meal size and duration were unaffected. These results show only the increase in appetitive behaviours, which could be attributed to non-ΔTHC phytocannabinoids in the extract rather than ΔTHC. Although further study is required to determine the constituents responsible for these effects, these results support the presence of non-ΔTHC cannabis constituent(s) that exert a stimulatory effect on appetite and likely lack the detrimental psychoactive effects of ΔTHC.
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Agonistas de Receptores de Cannabinoides/toxicidad , Dronabinol/toxicidad , Hiperfagia/inducido químicamente , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Masculino , RatasRESUMEN
RATIONALE: The hyperphagic effect of Delta9-tetrahydrocannabinol (Delta9THC) in humans and rodents is well known. However, no studies have investigated the importance of Delta9THC composition and any influence other non-Delta9THC cannabinoids present in Cannabis sativa may have. We therefore compared the effects of purified Delta9THC, synthetic Delta9THC (dronabinol), and Delta9THC botanical drug substance (Delta9THC-BDS), a Delta9THC-rich standardized extract comparable in composition to recreationally used cannabis. METHODS: Adult male rats were orally dosed with purified Delta9THC, synthetic Delta9THC, or Delta9THC-BDS, matched for Delta9THC content (0.34-2.68 mg/kg). Prior to dosing, subjects were satiated, and food intake was recorded following Delta9THC administration. Data were then analyzed in terms of hourly intake and meal patterns. RESULTS: All three Delta9THC substances tested induced significant hyperphagic effects at doses >or=0.67 mg/kg. These effects included increased intake during hour one, a shorter latency to onset of feeding and a greater duration and consumption in the first meal. However, while some differences in vehicle control intakes were observed, there were significant, albeit subtle, differences in pattern of effects between the purified Delta9THC and Delta9THC-BDS. CONCLUSION: All Delta9THC compounds displayed classical Delta9THC effects on feeding, significantly increasing shortterm intake whilst decreasing latency to the first meal. We propose that the subtle adjustment to the meal patterns seen between the purified Delta9THC and Delta9THC-BDS are due to non-Delta9THC cannabinoids present in Delta9THC-BDS. These compounds and other non-cannabinoids have an emerging and diverse pharmacology and can modulate Delta9THC-induced hyperphagia, making them worth further investigation for their therapeutic potential.
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Cannabis/química , Dronabinol/administración & dosificación , Dronabinol/química , Ingestión de Alimentos/efectos de los fármacos , Hiperfagia/inducido químicamente , Animales , Cannabis/fisiología , Relación Dosis-Respuesta a Droga , Dronabinol/efectos adversos , Ingestión de Alimentos/fisiología , Hiperfagia/fisiopatología , Masculino , Ratas , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiologíaRESUMEN
We have designed and implemented a low-cost digital system using closed-circuit television cameras coupled to a digital acquisition system for the recording of in vivo behavioral data in rodents and for allowing observation and recording of more than 10 animals simultaneously at a reduced cost, as compared with commercially available solutions. This system has been validated using two experimental rodent models: one involving chemically induced seizures and one assessing appetite and feeding. We present observational results showing comparable or improved levels of accuracy and observer consistency between this new system and traditional methods in these experimental models, discuss advantages of the presented system over conventional analog systems and commercially available digital systems, and propose possible extensions to the system and applications to nonrodent studies.