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The use of magnesium stearate along with lactose in Dry Powder Inhaler (DPI) formulations is increasing. The impact of different conditions of high shear blending on the distribution of magnesium stearate on lactose particles was investigated in this study. The formulated blends were manufactured using high shear blending of pre-blended coarse and fine lactose particles with 1.0% (w/w) magnesium stearate under different blending conditions, specifically blending speed and time. The effects of blending conditions on the distribution of magnesium stearate on lactose particles were clearly identifiable by characterizing the formulated blends by means of rheological evaluations, scanning electron microscopy, and chemical surface analysis using time-of-flight secondary ion mass spectrometry (ToF-SIMS). Rheological properties were significantly affected in blends with magnesium stearate compared to blends without magnesium stearate. Blending speed exhibited a strong influence on the distribution of magnesium stearate on lactose surface, while blending time had relatively minor effect.
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Excipientes , Lactosa , Lactosa/química , Polvos/química , Excipientes/química , Cromatografía de Gases y Espectrometría de Masas , Administración por Inhalación , Tamaño de la Partícula , Inhaladores de Polvo Seco/métodosRESUMEN
OBJECTIVE: Increasing overnight fasting time seems a promising strategy to improve metabolic health in individuals with nonalcoholic fatty liver (NAFL). Mechanisms underlying the beneficial effects of fasting may be related to larger fluctuations in hepatic glycogen and higher fat oxidation. This study investigated whether prolonging an overnight fast depletes hepatic glycogen stores and improves substrate metabolism in individuals with NAFL and healthy lean individuals. METHODS: Eleven individuals with NAFL and ten control individuals participated in this randomized crossover trial. After a 9.5-hour or 16-hour fast, hepatic glycogen was measured by using carbon-13 magnetic resonance spectroscopy, and a meal test was performed. Nocturnal substrate oxidation was measured with indirect calorimetry. RESULTS: Extending fasting time led to lower nocturnal carbohydrate oxidation and higher fat oxidation in both groups (intervention × time, p < 0.005 for carbohydrate and fat oxidation). In both arms, the respiratory exchange ratio measured during the night remained higher in the group with NAFL compared with the control group (population p < 0.001). No changes were observed in hepatic glycogen depletion with a prolonged overnight fast in the group with NAFL or the control group. CONCLUSIONS: These results suggest that acutely prolonging the overnight fast can improve overnight substrate oxidation and that these alterations are not mediated by changes in hepatic glycogen depletion.
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Glucógeno Hepático , Enfermedad del Hígado Graso no Alcohólico , Humanos , Adulto , Glucógeno Hepático/metabolismo , Glucógeno Hepático/farmacología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Estudios Cruzados , Oxidación-Reducción , Carbohidratos/farmacología , Hígado/metabolismo , AyunoRESUMEN
BACKGROUND: Current guidelines aim to limit the dietary glycemic index (GI) and intake of saturated fatty acids (SFA). Several studies have shown favorable effects of low-GI or low-SFA diets on intrahepatic lipid content (IHL), but these studies were performed under overfeeding conditions or extreme differences in GI or SFA to maximize the contrast between diets. By combining changes in GI and SFA, we can mimic how people can improve their diet in a realistic setting. OBJECTIVES: We investigated the effect on liver fat content and substrate metabolism of both reducing GI and replacing SFA with polyunsaturated fat in practically realistic amounts under isocaloric conditions. DESIGN AND METHODS: In a randomized crossover study, thirteen overweight participants consumed two diets, one high in GI and SFA (high GI/SFA) and one low in GI and SFA (low GI/SFA) with identical macronutrient composition, for two weeks each. Diets were equal in caloric content, consisted of habitual food items, and had a macronutrient composition that can be easily achieved in daily life. At the end of each intervention, IHL content/composition and liver glycogen were measured by magnetic resonance spectroscopy. Additionally, fasted and postprandial hepatic de novo lipogenesis and glycemic and metabolic responses were investigated. RESULTS: IHL was significantly lower (-28%) after the two-week low-GI/SFA diet (2.4 ± 0.5% 95% CI [1.4, 3.4]) than after the two-week high-GI/SFA diet (3.3 ± 0.6% 95% CI [1.9, 4.7], p < 0.05). Although hepatic glycogen content, hepatic de novo lipogenesis, hepatic lipid composition, and substrate oxidation during the night were similar between the two diets, the glycemic response to the low-GI/SFA diet was reduced (p < 0.05). CONCLUSIONS: Changes in macronutrient quality can already have drastic effects on liver fat content and postprandial glycemia after two weeks and even when energy content and the percentage of total fat and carbohydrate remains unchanged.
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Ácidos Grasos , Índice Glucémico , Humanos , Estudios Cruzados , Ácidos Grasos/metabolismo , Grasas de la Dieta/metabolismo , Dieta con Restricción de Grasas , Hígado/metabolismo , Nutrientes , Carbohidratos de la Dieta/metabolismoRESUMEN
Lactose is the most commonly used excipient in carrier-based dry powder inhalation (DPI) formulations. Numerous inhalation therapies have been developed using lactose as a carrier material. Several theories have described the role of carriers in DPI formulations. Although these theories are valuable, each DPI formulation is unique and are not described by any single theory. For each new formulation, a specific development trajectory is required, and the versatility of lactose can be exploited to optimize each formulation. In this review, recent developments in lactose-based DPI formulations are discussed. The effects of varying the material properties of lactose carrier particles, such as particle size, shape, and morphology are reviewed. Owing to the complex interactions between the particles in a formulation, processing adhesive mixtures of lactose with the active ingredient is crucial. Therefore, blending and filling processes for DPI formulations are also reviewed. While the role of ternary agents, such as magnesium stearate, has increased, lactose remains the excipient of choice in carrier-based DPI formulations. Therefore, new developments in lactose-based DPI formulations are crucial in the optimization of inhalable medicine performance.
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Excipientes , Lactosa , Administración por Inhalación , Aerosoles , Química Farmacéutica , Portadores de Fármacos , Inhaladores de Polvo Seco , Humanos , Tamaño de la Partícula , PolvosRESUMEN
Dietary macronutrient composition may affect hepatic liver content and its associated diseases, but the results from human intervention trials have been equivocal or underpowered. We aimed to assess the effects of dietary macronutrient composition on liver fat content by conducting a systematic review and meta-analysis of randomized controlled trials in adults. Four databases (PubMed, Embase, Web of Science, and COCHRANE Library) were systematically searched for trials with isocaloric diets evaluating the effect of dietary macronutrient composition (energy percentages of fat, carbohydrates, and protein, and their specific types) on liver fat content as assessed by magnetic resonance techniques, computed tomography or liver biopsy. Data on change in liver fat content were pooled by random or fixed-effects meta-analyses and expressed as standardized mean difference (SMD). We included 26 randomized controlled trials providing data for 32 comparisons on dietary macronutrient composition. Replacing dietary fat with carbohydrates did not result in changes in liver fat (12 comparisons, SMD 0.01 (95% CI -0.36; 0.37)). Unsaturated fat as compared with saturated fat reduced liver fat content (4 comparisons, SMD -0.80 (95% CI -1.09; -0.51)). Replacing carbohydrates with protein reduced liver fat content (5 comparisons, SMD -0.33 (95% CI -0.54; -0.12)). Our meta-analyses showed that replacing carbohydrates with total fat on liver fat content was not effective, while replacing carbohydrates with proteins and saturated fat with unsaturated fat was. More well-performed and well-described studies on the effect of types of carbohydrates and proteins on liver fat content are needed, especially studies comparing proteins with fats.
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Dieta , Carbohidratos de la Dieta , Adulto , Humanos , Hígado , Nutrientes , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE OF REVIEW: Nonalcoholic fatty liver is the result of an imbalance between lipid storage [from meal, de novo lipogenesis (DNL) and fatty acid (FA) uptake] and disposal (oxidation and VLDL output). Knowledge on the contribution of each of these pathways to liver fat content in humans is essential to develop tailored strategies to prevent and treat nonalcoholic fatty liver. Here, we review the techniques available to study the different storage pathways and review dietary modulation of these pathways. RECENT FINDINGS: The type of carbohydrate and fat could be of importance in modulating DNL, as complex carbohydrates and omega-3 FAs have been shown to reduce DNL. No effects were found on the other pathways, however studies investigating this are scarce. SUMMARY: Techniques used to assess storage pathways are predominantly stable isotope techniques, which require specific expertise and are costly. Validated biomarkers are often lacking. These methodological limitations also translate into a limited number of studies investigating to what extent storage pathways can be modulated by diet. Further research is needed to elucidate in more detail the impact that fat and carbohydrate type can have on liver fat storage pathways and content.
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Lipogénesis , Dieta , Humanos , Lipoproteínas VLDL , Hígado , Masculino , Enfermedad del Hígado Graso no AlcohólicoRESUMEN
The apicomplexan parasite Toxoplasma gondii, the causative agent of toxoplasmosis, can infect all warm-blooded animals. T. gondii can subtly alter host behaviors-either through manipulation to enhance transmission to the feline definitive host or as a side-effect, or "constraint," of infection. In humans, T. gondii infection, either alone or in association with other co-infecting neurotropic agents, has been reliably associated with both subtle behavioral changes and, in some cases, severe neuropsychiatric disorders, including schizophrenia. Research on the potential impact of T. gondii on the behavior of other long-lived naturally infected hosts is lacking. Recent studies reported a large number of wild red foxes exhibiting a range of aberrant behavioral traits, subsequently classified as Dopey Fox Syndrome (DFS). Here we assessed the potential association between T. gondii and/or other neurotropic agents with DFS. Live, captive foxes within welfare centers were serologically tested for T. gondii and, if they died naturally, PCR-tested for vulpine circovirus (FoxCV). Post-mortem pseudo-control wild foxes, obtained from pest management companies, were PCR-tested for T. gondii, FoxCV, canine distemper virus (CDV), canine adenovirus type (CAV)-1 and CAV-2. We also assessed, using non-invasive assays, whether T. gondii-infected foxes showed subtle behavioral alterations as observed among infected rodent (and other) hosts, including altered activity, risk, and stress levels. All foxes tested negative for CAV, CDV, CHV, and DogCV. DFS was found to be associated with singular T. gondii infection (captives vs. pseudo-controls, 33.3% (3/9) vs. 6.8% (5/74)) and singular FoxCV infection (66.7% (6/9) vs. 11.1% (1/9)) and with T. gondii/FoxCV co-infection (33.3% (3/9) vs. 11.1% (1/9)). Overall, a higher proportion of captive foxes had signs of neuroinflammation compared to pseudo-controls (66.7% (4/6) vs. 11.1% (1/9)). Consistent with behavioral changes seen in infected rodents, T. gondii-infected foxes displayed increased attraction toward feline odor (n=6 foxes). These preliminary results suggest that wild foxes with DFS are infected with T. gondii and likely co-infected with FoxCV and/or another co-infecting neurotropic agent. Our findings using this novel system have important implications for our understanding of both the impact of parasites on mammalian host behavior in general and, potentially, of the infectious causation of certain neuropsychiatric disorders.
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BACKGROUND: Current dietary recommendations for cardiovascular disease (CVD) prevention focus more on dietary patterns than on single nutrients. However, randomized controlled trials using whole-diet approaches to study effects on both fasting and postprandial CVD risk markers are limited. OBJECTIVE: This randomized parallel trial compared the effects of a healthy diet (HD) with those of a typical Western diet (WD) on fasting and postprandial CVD risk markers in overweight and obese adults. METHODS: After a 2-wk run-in period, 40 men and women (50-70 y; BMI: 25-35 kg/m2) consumed the HD (high in fruit and vegetables, pulses, fibers, nuts, fatty fish, polyunsaturated fatty acids; low in salt and high-glycemic carbohydrates; n = 19) or the WD (less fruit, vegetables, and fibers; no nuts and fatty fish; and more saturated fatty acids and simple carbohydrates; n = 21) for 6 wk. Fasting and postprandial cardiometabolic risk markers were assessed as secondary outcome parameters during a 5-h mixed-meal challenge, and a per protocol analysis was performed using 1-factor ANCOVA or linear mixed models. RESULTS: Differences in diet-induced changes are expressed relative to the HD group. Changes in fasting plasma total cholesterol (-0.57 ± 0.12 mmol/L, P < 0.001), LDL cholesterol (-0.41 ± 0.12 mmol/L, P < 0.01), apolipoprotein B100 (-0.09 ± 0.03 g/L, P < 0.01), and apolipoprotein A1 (-0.06 ± 0.03 g/L, P = 0.05) were significantly different between the diet groups. Changes in postprandial plasma triacylglycerol (diet × time, P < 0.001) and apolipoprotein B48 (P < 0.01) differed significantly between the groups with clear improvements on the HD, although fasting triacylglycerols (-0.24 ± 0.13 mmol/L, P = 0.06) and apolipoprotein B48 (1.04 ± 0.67 mg/L, P = 0.40) did not. Significant differences between the diets were also detected in fasting systolic (-6.9 ± 3.1 mmHg, P < 0.05) and 24-h systolic (-5.0 ± 1.7 mmHg, P < 0.01) and diastolic (-3.3 ± 1.1 mmHg, P < 0.01) blood pressure. CONCLUSION: A whole-diet approach targeted multiple fasting and postprandial CVD risk markers in overweight and obese adults. In fact, the postprandial measurements provided important additional information to estimate CVD risk. This trial is registered at clinicaltrials.gov as NCT02519127.
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Enfermedades Cardiovasculares/sangre , Dieta , Ayuno , Enfermedades Metabólicas/sangre , Sobrepeso , Anciano , Biomarcadores/sangre , Presión Sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo PosprandialRESUMEN
BACKGROUND: Lower post-prandial glucose (PPG) and insulin (PPI) responses to foods are associated with reduced diabetes risk and progression. Several plant extracts have been proposed to reduce PPG or PPI by inhibiting enzymes or transporters involved in carbohydrate digestion and uptake. This study evaluates a range of such extracts, consumed with a carbohydrate load, for their effects on PPG, PPI and indicators of (gastrointestinal) tolerance. METHODS: Interventions were extracts of mulberry fruit (MFE, 1.5 g), mulberry leaf (MLE, 1.0 g), white bean (WBE, 3.0 g), apple (AE, 2.0 g), elderberry (EE, 2.0 g), turmeric (TE, 0.18 g), AE + TE, and EE + TE. Each of these 8 individual extracts or combinations were added to a rice porridge containing ~ 50 g available carbohydrate (control). In a within-subject (randomised, balanced incomplete block) design, individual subjects received the control and a subset of 4 of the 8 extracts or combinations. Participants were 72 apparently healthy adults (mean [SD] age 31.2 [5.5] yr, body mass index 22.1 [2.0] kg/m2). The primary outcome was the percentage change in 2-h PPG (positive incremental area under the curve) relative to control. Secondary measures were the 2-h PPI response, 7-h breath hydrogen, measures of gastrointestinal discomfort, and urine glucose. RESULTS: In the 65 subjects who completed the control and at least one intervention treatment, additions of AE, MFE and MLE produced statistically significant reductions in PPG vs control (p < 0.05; mean effect - 24.1 to - 38.1%). All extracts and combinations except TE and WBE significantly reduced PPI (p < 0.01; mean effect - 17.3% to - 30.4%). Rises in breath hydrogen > 10 ppm were infrequent, but statistically more frequent than control only for MLE (p = 0.02). Scores for gastrointestinal discomfort were extremely low and not different from control for any treatment, and no glucosuria was observed. CONCLUSIONS: Additions of AE, MFE and MLE to rice robustly reduced PPG and PPI. EE significantly reduced only PPI, while TE and WBE showed no significant efficacy for PPG or PPI. Breath hydrogen responses to MLE suggest possible carbohydrate malabsorption at the dose used, but there were no explicit indications of intolerance to any of the extracts. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04258501. Registered 6 February 2020 - Retrospectively registered.
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Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design (ClinicalTrials.gov ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (1H-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our 1H-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity.
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Ácidos Grasos/metabolismo , Resistencia a la Insulina/fisiología , Lipogénesis/fisiología , Hígado/metabolismo , Tejido Adiposo , Adulto , Anciano , Estudios Transversales , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Lípidos , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Triglicéridos/metabolismoRESUMEN
BACKGROUND & AIMS: Metabolic flexibility is the ability to adapt fuel oxidation to fuel availability. Metabolic inflexibility has been associated with obesity, the metabolic syndrome and insulin resistance, and can be improved by exercise or weight loss. Dietary changes can modulate metabolic flexibility; however, the effect of a whole diet approach on metabolic flexibility has never been studied. Therefore, our objective was to assess the effect of a healthy diet (HD), as compared to a typical Western diet (WD), on several fasting and postprandial markers of metabolic flexibility and insulin sensitivity. METHODS: In this parallel randomized trial, overweight or obese men and women (50-70 years; BMI 25-35 kg/m2) consumed a healthy diet (HD; high in fruits and vegetables, pulses, fibers, nuts, fatty fish, and low in high-glycemic carbohydrates; n = 19) or a typical Western diet (WD; n = 21) for six weeks, following a two-week run-in period. The change in respiratory quotient upon insulin stimulation (ΔRQ), and insulin sensitivity, expressed as the M-value, were both determined with a hyperinsulinemic euglycemic clamp. Additionally, other fasting and postprandial markers of metabolic flexibility were assessed during a 5-h high-fat high-glycemic mixed meal challenge. RESULTS: ΔRQ (p = 0.730) and insulin sensitivity (p = 0.802) were not significantly affected by diet. Postprandial RQ did also not show significant differences (p = 0.610), whereas postprandial glucose excursions were significantly higher in the HD group at T30 (p = 0.014) and T45 (p = 0.026) after mixed meal ingestion (p = 0.037). Fasting glucose (p = 0.530) and HbA1c (p = 0.124) remained unchanged, whereas decreases in fasting insulin (p = 0.038) and the HOMA-IR (p = 0.050) were significantly more pronounced with the HD. CONCLUSION: A healthy diet for six weeks, without further life-style changes, did not improve metabolic flexibility and whole-body insulin sensitivity, when compared to a Western-style diet. It remains to be determined whether the short time increase in postprandial glucose is physiologically relevant or detrimental to metabolic health. This trial was registered at clinicaltrials.gov as NCT02519127.
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Glucemia/análisis , Dieta Saludable , Resistencia a la Insulina/fisiología , Obesidad/metabolismo , Sobrepeso/metabolismo , Periodo Posprandial , Anciano , Dieta Occidental , Femenino , Técnica de Clampeo de la Glucosa , Índice Glucémico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: It is often assumed that lower postprandial glucose (PPG) and insulin (PPI) responses are induced by slower glucose influx from the gut (e.g., by delayed carbohydrate digestion). However, changes in the rate of appearance of glucose in the peripheral circulation [rate of appearance of exogenous glucose (RaE)] may be accompanied by changes in endogenous glucose production (EGP) and the rate of disappearance of total glucose into tissues (RdT). The quantitative relationships between reductions in RaE and PPG/PPI levels are unclear. OBJECTIVES: The objective was to perform a meta-analysis to quantify the effect of changes in RaE on changes in PPG and PPI levels (primary) and EGP and RdT (secondary). METHODS: We systematically searched the Scopus, Medline, and Cochrane library databases through 10 January 2019 for randomized, controlled, carbohydrate-rich interventions that aimed to reduce RaE in humans, measured using dual or triple stable isotope methods. The 2-h net incremental AUCs for all variables were extracted or calculated. Relationships between RaE and outcomes were quantified by weighted regression analyses. RESULTS: There were 12 articles, including 17 comparisons, that satisfied the inclusion criteria. The subjects were mainly men (60%), with age and BMI ranges of 18-40 y and 20.0-27.5 kg/m2, respectively. A 10% reduction in RaE was associated with reductions in PPG levels, PPI levels, and the RdT of 7% (95% CI: 2%, 12%; P = 0.010), 8% (95% CI: 2%, 13%; P = 0.012), and 11% (95% CI: 4%, 17%; P = 0.005), respectively, but was not significantly associated with a change in EGP (13%; 95% CI: -7%, 33%; P = 0.176). All fluxes together explained 70% and 26% of the variances in PPG and PPI levels, respectively. CONCLUSIONS: In adults, reducing glucose RaE by diet is associated with significant reductions in PPG levels, PPI levels, and the rate of glucose disposal. This trial was registered in the PROSPERO database with identifier CRD42018084824.
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Glucosa/metabolismo , Insulina/metabolismo , Periodo Posprandial/fisiología , Adulto , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/farmacocinética , Glucosa/biosíntesis , Humanos , Isótopos , CinéticaRESUMEN
We previously found that guar gum (GG) and chickpea flour (CPF) added to flatbread wheat flour lowered postprandial blood glucose (PPG) and insulin responses dose dependently. However, rates of glucose influx cannot be determined from PPG, which integrates rates of influx, tissue disposal and hepatic glucose production. The objective was to quantify rates of glucose influx and related fluxes as contributors to changes in PPG with GG and CPF additions to wheat-based flatbreads. In a randomised cross-over design, twelve healthy males consumed each of three different 13C-enriched meals: control flatbreads (C), or C incorporating 15 % CPF with either 2 % (GG2) or 4 % (GG4) GG. A dual isotope technique was used to determine the time to reach 50 % absorption of exogenous glucose (T 50 %abs, primary objective), rate of appearance of exogenous glucose (RaE), rate of appearance of total glucose (RaT), endogenous glucose production (EGP) and rate of disappearance of total glucose (RdT). Additional exploratory outcomes included PPG, insulin, glucose-dependent insulinotropic peptide and glucagon-like peptide 1, which were additionally measured over 4 h. Compared with C, GG2 and GG4 had no significant effect on T 50 %abs. However, GG4 significantly reduced 4-h AUC values for RaE, RaT, RdT and EGP, by 11, 14, 14 and 64 %, respectively, whereas GG2 showed minor effects. Effect sizes over 2 and 4 h were similar except for significantly greater reduction in EGP for GG4 at 2 h. In conclusion, a soluble fibre mix added to flatbreads only slightly reduced rates of glucose influx, but more substantially affected rates of postprandial disposal and hepatic glucose production.
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Pan , Cicer , Cyamopsis , Fibras de la Dieta/farmacología , Glucosa/metabolismo , Índice Glucémico , Periodo Posprandial , Adulto , Área Bajo la Curva , Glucemia/metabolismo , Isótopos de Carbono , Harina , Galactanos , Polipéptido Inhibidor Gástrico/sangre , Péptido 1 Similar al Glucagón/sangre , Gluconeogénesis/efectos de los fármacos , Glucosa/farmacocinética , Humanos , Insulina/sangre , Absorción Intestinal/efectos de los fármacos , Hígado , Masculino , Mananos , Gomas de Plantas , Preparaciones de Plantas/farmacología , Triticum , Adulto JovenRESUMEN
Currently it is estimated that about 1 billion people globally have non-alcoholic fatty liver disease (NAFLD), a condition in which liver fat exceeds 5 % of liver weight in the absence of significant alcohol intake. Due to the central role of the liver in metabolism, the prevalence of NAFLD is increasing in parallel with the prevalence of obesity, insulin resistance and other risk factors of metabolic diseases. However, the contribution of liver fat to the risk of type 2 diabetes mellitus and CVD, relative to other ectopic fat depots and to other risk markers, is unclear. Various studies have suggested that the accumulation of liver fat can be reduced or prevented via dietary changes. However, the amount of liver fat reduction that would be physiologically relevant, and the timeframes and dose-effect relationships for achieving this through different diet-based approaches, are unclear. Also, it is still uncertain whether the changes in liver fat per se or the associated metabolic changes are relevant. Furthermore, the methods available to measure liver fat, or even individual fatty acids, differ in sensitivity and reliability. The present report summarises key messages of presentations from different experts and related discussions from a workshop intended to capture current views and research gaps relating to the points above.
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Background: We investigated whether substituting sitting with standing and self-perceived light walking in free-living conditions would improve cardiometabolic risk factors, mood, and cognition in overweight/obese adults. Methods: In a randomized, cross-over study, 24 (m/f: 13/11) sedentary overweight/obese participants (64 ± 7 years, BMI 29 ± 2 kg/m2) followed two activity regimens of each 4 days in free-living conditions: "Sit": sitting 13.5 h/day, standing 1.4 h/day, self-perceived light-intensity walking 0.7 h/day; for "SitLess" these activities lasted 7.6, 4.0, and 4.3 h/day, respectively. Meals were standardized and physical activity was assessed by accelerometry (activPAL). Insulin sensitivity (expressed as Matsuda-index based on an oral glucose tolerance test), circulating lipids, blood pressure, mood (pleasantness and arousal), and cognition were assessed on the morning after the activity regimens. Quality of life and sleep were assessed on the last day of the activity regimens. Results: We observed that AUC (0-190 min) for insulin decreased by 20% after SitLess vs. Sit [10,125 (656) vs. 12,633 (818); p = 0.006]. Insulin sensitivity improved by 16% after SitLess vs. Sit [Matsuda-index, mean (SEM): 6.45 (0.25) vs. 5.58 (0.25) respectively; p = 0.007]. Fasting triglycerides, non-HDL-cholesterol, and apolipoprotein B decreased by 32, 7, and 4% respectively, whereas HDL-cholesterol increased by 7% after SitLess vs. Sit (all p < 0.01). Diastolic blood pressure was lower after SitLess vs. Sit (p < 0.05). Pleasantness (as one marker of mood status) after the oral glucose tolerance test was higher after SitLess vs. Sit (p < 0.05). There was no significant difference between regimens for cognition, quality of life and sleep. Conclusions: Reducing sitting time in free-living conditions markedly improved insulin sensitivity, circulating lipids, and diastolic blood pressure. Substituting sitting with standing and self-perceived light walking is an effective strategy to improve cardiometabolic risk factors in overweight/obese subjects.
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PURPOSE: Type 2 diabetes (T2DM) is increasing, particularly in South-East Asia. Intake of high-glycaemic foods has been positively associated with T2DM, and feasible routes to reduce the glycaemic response to carbohydrate-rich staple foods are needed. The research question was whether different fibre and legume flour mixes in flatbreads lower postprandial glucose (PPG) responses. METHODS: Using a balanced incomplete block design, we tested the inclusion of guar gum (GG), konjac mannan (KM) and chickpea flour (CPF) in 10 combinations (2/4/6 g GG; 2/4 g KM; 15 g CPF, and 10 or 15 g CPF plus 2 or 4 g GG) in 100 g total of a control commercial high-fibre flatbread flour mix ("atta") on PPG in 38 normal-weight adults. Self-reported appetite was an additional exploratory outcome. An in vitro digestion assay was adapted for flatbreads and assessed for prediction of in vivo PPG. RESULTS: Flatbreads with 6 g GG, 4 g KM, and 15 g CPF plus 2 or 4 g GG reduced PPG ≥30 % (p < 0.01), while no other combinations differed significantly from the control. A statistical model with four in vitro parameters (rate of digestion, %RDS, AUC, carbohydrate level) was highly predictive of PPG results (adjusted R 2 = 0.89). Test products were similar to the control for appetite-related measures. CONCLUSIONS: The results confirm the efficacy of specific additions to flatbread flour mixes for reducing PPG and the value of the in vitro model as a predictive tool with these ingredients and product format. This trial is registered at ClinicalTrials.gov with identifier NCT02671214.
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Glucemia/metabolismo , Pan/análisis , Fibras de la Dieta/análisis , Harina/análisis , Periodo Posprandial , Adulto , Asia Sudoriental , Índice de Masa Corporal , Peso Corporal , Cicer/química , Diabetes Mellitus Tipo 2 , Digestión , Método Doble Ciego , Femenino , Manipulación de Alimentos , Galactanos/química , Voluntarios Sanos , Humanos , Insulina/sangre , Masculino , Mananos/química , Persona de Mediana Edad , Gomas de Plantas/químicaRESUMEN
Triggering of gastro-intestinal bitter taste receptors might have implications for appetite and food intake, but the evidence in humans is mixed and limited to acute studies. We previously reported that 15-days consumption of drinks with purified Hoodia gordonii extract and its taste-matched control both produced similar, significant energy intake (EI) reductions in females in an in-patient setting, with no significant differences between treatments. In that study the control was matched to Hoodia flavour and bitterness using Raisin Flavour (RF), Sucrose Octa Acetate (SOA) and Quassia Extract (QE). As triggering of gastrointestinal bitter receptors might have produced shared effects on EI, our objective here was to assess the effects of sustained exposure to capsules containing the same bitter RF + SOA + QE mix itself on EI, compared to a non-bitter placebo. In this randomized, double-blind study, sixty slightly overweight women in parallel groups consumed twice-daily capsules without (placebo) or with the tastant mixture (0.88 mg SOA, 0.088 mg QE, 0.22 mg RF) on days 1-14. On day 0 all subjects received placebo capsules at 0800 and 1600, ad libitum meals at 0900, 1300, 1700, and snacks after 1900. On day 14 these test procedures were repeated. Changes in EI on days 14 versus 0 between treatment groups were assessed using ANCOVA. Total EI differences on days 14 versus 0 were not significant (mean active-placebo treatment difference -109 kcal, SE 71, P = 0.13), nor was this significant when analyzed separately for each meal within the test day. Body weight changes were negligible. In conclusion, sustained exposure to these encapsulated bitter tastants did not significantly affect EI in overweight females.
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Ingestión de Energía , Sobrepeso/dietoterapia , Gusto , Adolescente , Adulto , Apetito , Índice de Masa Corporal , Cápsulas , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Extractos Vegetales/administración & dosificación , Quassia/química , Bocadillos , Sacarosa/administración & dosificación , Sacarosa/análogos & derivados , Resultado del Tratamiento , Vitis/química , Adulto JovenRESUMEN
BACKGROUND: Intragastric creaming and droplet size of fat emulsions may affect intragastric behavior and gastrointestinal and satiety responses. OBJECTIVES: We tested the hypotheses that gastrointestinal physiologic responses and satiety will be increased by an increase in intragastric stability and by a decrease in fat droplet size of a fat emulsion. METHODS: This was a double-blind, randomized crossover study in 11 healthy persons [8 men and 3 women, aged 24 ± 1 y; body mass index (in kg/m(2)): 24.4 ± 0.9] who consumed meals containing 300-g 20% oil and water emulsion (2220 kJ) with 1) larger, 6-µm mean droplet size (Coarse treatment) expected to cream in the stomach; 2) larger, 6-µm mean droplet size with 0.5% locust bean gum (LBG; Coarse+LBG treatment) to prevent creaming; or 3) smaller, 0.4-µm mean droplet size with LBG (Fine+LBG treatment). The participants were imaged hourly by using MRI and food intake was assessed by using a meal that participants consumed ad libitum. RESULTS: The Coarse+LBG treatment (preventing creaming in the stomach) slowed gastric emptying, resulting in 12% higher gastric volume over time (P < 0.001), increased small bowel water content (SBWC) by 11% (P < 0.01), slowed appearance of the (13)C label in the breath by 17% (P < 0.01), and reduced food intake by 9% (P < 0.05) compared with the Coarse treatment. The Fine+LBG treatment (smaller droplet size) slowed gastric emptying, resulting in 18% higher gastric volume (P < 0.001), increased SBWC content by 15% (P < 0.01), and significantly reduced food intake by 11% (P < 0.05, equivalent to an average of 411 kJ less energy consumed) compared with the Coarse+LBG treatment. These high-fat meals stimulated substantial increases in SBWC, which increased to a peak at 4 h at 568 mL (range: 150-854 mL; P < 0.01) for the Fine+LBG treatment. CONCLUSION: Manipulating intragastric stability and fat emulsion droplet size can influence human gastrointestinal physiology and food intake.
Asunto(s)
Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/farmacocinética , Tracto Gastrointestinal/metabolismo , Saciedad/fisiología , Adulto , Índice de Masa Corporal , Estudios Cruzados , Digestión , Método Doble Ciego , Emulsiones/química , Ingestión de Energía , Femenino , Vaciamiento Gástrico/fisiología , Contenido Digestivo/química , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética , Masculino , Comidas , Tamaño de la Partícula , Periodo Posprandial/fisiología , Respuesta de Saciedad/fisiología , Adulto JovenRESUMEN
BACKGROUND: Compared with nonaerated, isocaloric controls, aerated foods can reduce appetite throughout an entire dieting day. Increased gastric volumes and delayed emptying are possible but unexplored mechanisms. OBJECTIVE: We tested the hypothesis that aerated drinks (foams) of differing gastric stability would increase gastric distension and reduce appetite compared with a control drink. DESIGN: In a randomized, balanced, crossover trial, 18 healthy male participants consumed the following 3 skimmed-milk-based test products (all 110 kcal): 2 drinks aerated to foams by whipping (to 490 mL), one drink that was stable in the stomach [stable foam (SF)], and one drink that was less stable in the stomach [less-stable foam (LSF)], and a nonaerated drink [liquid control (LC); 140 mL]. Over 4 h, stomach contents (foam, air, and liquid) were imaged using magnetic resonance imaging (MRI), and self-reported appetite ratings were collected and quantified by the area under the curve or time to return to baseline (TTRTB). RESULTS: Compared with the LC, both foams caused significantly increased gastric volumes and reduced hunger (all P < 0.001). Compared with the LSF, SF further produced a significantly slower decrease in the total gastric content (P < 0.05) and foam volume (P < 0.0001) and a longer TTRTB (197 compared with 248 min, respectively; P < 0.05), although the hunger AUC was not statistically different. Results for other appetite scales were similar. CONCLUSIONS: With this MRI trial, we provide novel insights on the gastrointestinal behavior of aerated drinks by measuring separate volumes of foam, liquid, and air layers in the stomach. Appetite suppression induced by foams could largely be explained by effects on gastric volumes and emptying, which may be further enhanced by foam stability. This trial was registered at clinicaltrials.gov as NCT01690182.
Asunto(s)
Apetito/fisiología , Bebidas/análisis , Imagen por Resonancia Magnética , Adolescente , Adulto , Regulación del Apetito/fisiología , Índice de Masa Corporal , Estudios Cruzados , Ingestión de Energía , Mucosa Gástrica/metabolismo , Voluntarios Sanos , Humanos , Hambre/fisiología , Masculino , Persona de Mediana Edad , Autoinforme , Adulto JovenRESUMEN
The aim of the study was to investigate how the fine particle content of lactose carriers prepared with different types of lactose fines regulates dry powder inhaler (DPI) formulation performance of a cohesive batch of micronised budesonide. Budesonide formulations (0.8 wt%) were prepared with three different lactose carriers (Lactohale (LH) LH100, 20 wt% LH210 in LH100 and 20 wt% LH300 in LH100). Fine particle fraction of emitted dose (FPFED) and mean mass aerodynamic diameter (MMAD) of budesonide was assessed with a Next Generation Impactor (NGI) using a Cyclohaler at 90 l/min. Morphological and chemical characteristics of particles deposited on Stage 2 were determined using a Malvern Morphologi G3-ID. The results indicate that increasing concentration of lactose fines (<4.5 µm) not only increased the FPFED but also the MMAD of budesonide, suggesting drug deposition in agglomerates. Presence of agglomerates on Stage 2 was confirmed by morphological analysis of particles. Raman analysis of material collected on Stage 2 indicated that the more fine lactose particles were available the more agglomerates of budesonide and lactose were delivered to Stage 2. These results suggest drug-fines agglomerate formation is an important mechanism for how lactose fines improve and regulate DPI formulation performance.