Glycaemic, gastrointestinal, hormonal and appetitive responses to pearl millet or oats porridge breakfasts: a randomised, crossover trial in healthy humans.

Whole-grain cereal breakfast consumption has been associated with beneficial effects on glucose and insulin metabolism as well as satiety. Pearl millet is a popular ancient grain variety that can be grown in hot, dry regions. However, little is known about its health effects. The present study investigated the effect of a pearl millet porridge (PMP) compared with a well-known Scottish oats porridge (SOP) on glycaemic, gastrointestinal, hormonal and appetitive responses. In a randomised, two-way crossover trial, twenty-six healthy participants consumed two isoenergetic/isovolumetric PMP or SOP breakfast meals, served with a drink of water. Blood samples for glucose, insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide (GIP), peptide YY, gastric volumes and appetite ratings were collected 2 h postprandially, followed by an ad libitum meal and food intake records for the remainder of the day. The incremental AUC (iAUC2h) for blood glucose was not significantly different between the porridges (P > 0·05). The iAUC2h for gastric volume was larger for PMP compared with SOP (P = 0·045). The iAUC2h for GIP concentration was significantly lower for PMP compared with SOP (P = 0·001). Other hormones and appetite responses were similar between meals. In conclusion, the present study reports, for the first time, data on glycaemic and physiological responses to a pearl millet breakfast, showing that this ancient grain could represent a sustainable alternative with health-promoting characteristics comparable with oats. GIP is an incretin hormone linked to TAG absorption in adipose tissue; therefore, the lower GIP response for PMP may be an added health benefit.

Glycaemic, gastrointestinal and appetite responses to breakfast porridges from ancient cereal grains: A MRI pilot study in healthy humans.

Cereal grain based porridges are commonly consumed throughout the world. Whilst some data are available for varieties that are popular in the Western world such as oats and rye, other 'ancient' grains used in the East and in Africa such as millets are thought to have beneficial health effects, such as a suppression of post prandial hunger and circulating glucose levels. These grains, a sustainable food source due to their tolerance of extreme weather and growing conditions, are commonly found throughout Asia and Africa. However, knowledge of the physiological responses to these grain varieties is very limited. This study aimed to collect initial pilot data on the physiological and gastrointestinal responses to breakfast porridges made with two millet varieties and oats and rye grains. A total of n=15 completed the oats and rye, n=9 the finger millet n=12 the pearl millet meals. MRI scans were undertaken at baseline, immediately after consumption and then hourly postprandially. Blood glucose was measured at baseline, immediately after consumption and then every 15min until t=80min, then every 20min until t=120min, followed on each occasion by completion of VAS. Seven participants completed the entire protocol and were included in the final analysis. A subgroup analysis with the n=10 paired comparison between the same individuals that completed the oats, rye and pearl millet was also considered. The gastric volume AUC was higher for pearl millet than oats and rye (n=10, p<0.001). The incremental area under the curve (iAUC) for blood glucose was not significantly different between the meals although this showed a trend to be lower for pearl millet. Hunger was lower for pearl millet compared to oats and rye (n=10, p=0.01). There was a significant correlation between total gastric volume AUC and average appetite AUC r=-0.47, p<0.010. Isoenergetic breakfast porridges from 'ancient' varieties of millet grains showed physiological responses that were comparable with those from common Western varieties known to have beneficial health effects. Pearl millet appeared to induce lower postprandial blood glucose response and appetite scores though the differences were not conclusive compared with the other porridges and further work is needed. Improved knowledge of the effects of different cereal grains could help direct dietary advice and ultimately improve health outcomes in the general population worldwide.

Magnetic Resonance Imaging Quantification of Fasted State Colonic Liquid Pockets in Healthy Humans.

The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent on the volume of liquid in the gastrointestinal tract (GIT). However, little is known about the time course of GIT liquid volumes after drinking a glass of water (8 oz), particularly in the colon, which is a targeted site for both locally and systemically acting drug products. Previous magnetic resonance imaging (MRI) studies offered novel insights on GIT liquid distribution in fasted humans in the stomach and small intestine, and showed that freely mobile liquid in the intestine collects in fairly distinct regions or "pockets". Based on this previous pilot data, we hypothesized that (1) it is possible to quantify the time course of the volume and number of liquid pockets in the undisturbed colon of fasted healthy humans following ingestion of 240 mL, using noninvasive MRI methods; (2) the amount of freely mobile water in the fasted human colon is of the order of only a few milliliters. Twelve healthy volunteers fasted overnight and underwent fasted abdominal MRI scans before drinking 240 mL (∼8 fluid ounces) of water. After ingesting the water they were scanned at frequent intervals for 2 h. The images were processed to quantify freely mobile water in the total and regional colon: ascending, transverse, and descending. The fasted colon contained (mean ± SEM) 11 ± 5 pockets of resting liquid with a total volume of 2 ± 1 mL (average). The colonic fluid peaked at 7 ± 4 mL 30 min after the water drink. This peak fluid was distributed in 17 ± 7 separate liquid pockets in the colon. The regional analysis showed that pockets of free fluid were found primarily in the ascending colon. The interindividual variability was very high; the subjects showed a range of number of colonic fluid pockets from 0 to 89 and total colonic freely mobile fluid volume from 0 to 49 mL. This is the first study measuring the time course of the number, regional location, and volume of pockets of freely mobile liquid in the undisturbed colon of fasted humans after ingestion of a glass of water. Novel insights into the colonic fluid environment will be particularly relevant to improve our understanding and design of the in vivo performance of controlled release formulations targeted to the colon. The in vivo quantitative information presented here can be input into physiologically based mechanistic models of dissolution and absorption, and can be used in the design and set up of novel in vitro performance tools predictive of the in vivo environment.

Fat emulsion intragastric stability and droplet size modulate gastrointestinal responses and subsequent food intake in young adults.

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.

Aerated drinks increase gastric volume and reduce appetite as assessed by MRI: a randomized, balanced, crossover trial.

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.

Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state.

The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent upon the volumes and distribution of gastric and small intestinal water. However, little is known about the time courses and distribution of water volumes in vivo in an undisturbed gut. Previous imaging studies offered a snapshot of water distribution in fasted humans and showed that water in the small intestine is distributed in small pockets. This study aimed to quantify the volume and number of water pockets in the upper gut of fasted healthy humans following ingestion of a glass of water (240 mL, as recommended for bioavailability/bioequivalence (BA/BE) studies), using recently validated noninvasive magnetic resonance imaging (MRI) methods. Twelve healthy volunteers underwent upper and lower abdominal MRI scans before drinking 240 mL (8 fluid ounces) of water. After ingesting the water, they were scanned at intervals for 2 h. The drink volume, inclusion criteria, and fasting conditions matched the international standards for BA/BE testing in healthy volunteers. The images were processed for gastric and intestinal total water volumes and for the number and volume of separate intestinal water pockets larger than 0.5 mL. The fasted stomach contained 35 ± 7 mL (mean ± SEM) of resting water. Upon drinking, the gastric fluid rose to 242 ± 9 mL. The gastric water volume declined rapidly after that with a half emptying time (T50%) of 13 ± 1 min. The mean gastric volume returned back to baseline 45 min after the drink. The fasted small bowel contained a total volume of 43 ± 14 mL of resting water. Twelve minutes after ingestion of water, small bowel water content rose to a maximum value of 94 ± 24 mL contained within 15 ± 2 pockets of 6 ± 2 mL each. At 45 min, when the glass of water had emptied completely from the stomach, total intestinal water volume was 77 ± 15 mL distributed into 16 ± 3 pockets of 5 ± 1 mL each. MRI provided unprecedented insights into the time course, number, volume, and location of water pockets in the stomach and small intestine under conditions that represent standard BA/BE studies using validated techniques. These data add to our current understanding of gastrointestinal physiology and will help improve physiological relevance of in vitro testing methods and in silico transport analyses for prediction of bioperformance of oral solid dosage forms, particularly for low solubility Biopharmaceutics Classification System (BCS) Class 2 and Class 4 compounds.

Calibrated BOLD using direct measurement of changes in venous oxygenation.

Calibration of the BOLD signal is potentially of great value in providing a closer measure of the underlying changes in brain function related to neuronal activity than the BOLD signal alone, but current approaches rely on an assumed relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF). This is poorly characterised in humans and does not reflect the predominantly venous nature of BOLD contrast, whilst this relationship may vary across brain regions and depend on the structure of the local vascular bed. This work demonstrates a new approach to BOLD calibration which does not require an assumption about the relationship between cerebral blood volume and cerebral blood flow. This method involves repeating the same stimulus both at normoxia and hyperoxia, using hyperoxic BOLD contrast to estimate the relative changes in venous blood oxygenation and venous CBV. To do this the effect of hyperoxia on venous blood oxygenation has to be calculated, which requires an estimate of basal oxygen extraction fraction, and this can be estimated from the phase as an alternative to using a literature estimate. Additional measurement of the relative change in CBF, combined with the blood oxygenation change can be used to calculate the relative change in CMRO(2) due to the stimulus. CMRO(2) changes of 18 ± 8% in response to a motor task were measured without requiring the assumption of a CBV/CBF coupling relationship, and are in agreement with previous approaches.

Preventing gastric sieving by blending a solid/water meal enhances satiation in healthy humans.

Separation of solids and liquids within the stomach allows faster gastric emptying of liquids compared with solids, a phenomenon known as sieving. We tested the hypothesis that blending a solid and water meal would abolish sieving, preventing the early rapid decrease in gastric volume and thereby enhancing satiety. We carried out 2 separate studies. Study 1 was a 2-way, crossover, satiety study of 22 healthy volunteers who consumed roasted chicken and vegetables with a glass of water (1008 kJ) or the same blended to a soup. They completed satiety visual analogue scales at intervals for 3 h. Study 2 was a 2-way, crossover, mechanistic study of 18 volunteers who consumed the same meals and underwent an MRI to assess gastric emptying, gallbladder contraction, and small bowel water content (SBWC) at intervals for 3 h. In Study 1, the soup meal was associated with reduced hunger (P = 0.02). In Study 2, the volume of the gastric contents after the soup meal decreased more slowly than after the solid/liquid meal (P = 0.0003). The soup meal caused greater gallbladder contraction (P < 0.04). SBWC showed a biphasic response with an initial "gastric" phase during which SBWC was greater when the solid/liquid meal was consumed (P < 0.001) and a later "small bowel" phase when SBWC was greater when the soup meal was consumed (P < 0.01). Blending the solid/liquid meal to a soup delayed gastric emptying and increased the hormonal response to feeding, which may contribute to enhanced postprandial satiety.

The effects of morphine-neostigmine and secretin provocation on pancreaticobiliary morphology in healthy subjects: a randomized, double-blind crossover study using serial MRCP.

BACKGROUND: Secretin-stimulated magnetic resonance cholangiopancreatography (MRCP) is used for the diagnosis of sphincter of Oddi dysfunction (SOD), but it does not correlate well with sphincter of Oddi manometry. Serial MRCP following morphine-neostigmine provocation may be of value in the assessment of SOD, but the effects of these pharmacological agents on pancreaticobiliary morphology in healthy subjects have not been studied. The aim of the present study was to use serial MRCP to characterize the effects of morphine-neostigmine and secretin provocation on serum pancreatic enzyme responses and pancreaticobiliary ductal morphology in healthy subjects. METHODS: Following a baseline scan and serum lipase and amylase assays, 10 healthy subjects were randomized in a double-blind manner to receive morphine (10 mg intramuscularly [IM]), neostigmine (1 mg IM) and saline (intravenously [IV]); OR saline (IM), saline (IM) and secretin (1 U/kg IV). A MRCP study was performed at 5, 30, 60, 90, 120, 150, and 180 min thereafter, with blood samples taken every 60 min for 4 h. Pancreatic duct (PD) diameter, visible PD length, common bile duct (CBD) diameter, and gallbladder volume were recorded. Crossover studies were performed 10 days later. RESULTS: Serum pancreatic enzyme concentrations were significantly greater (amylase, P = 0.003; lipase, P = 0.04) after morphine-neostigmine than after secretin. Following morphine-neostigmine and secretin provocation, the mean (SEM) percentage increase in PD diameter was 28.7 (7.2) versus 12.9 (3.3); P < 0.0001, and visible PD length was 49.4 (11.5) versus 28.1 (8.2); P < 0.0001, respectively. CONCLUSIONS: The effects of morphine-neostigmine were more pronounced than those of secretin in healthy subjects. The diagnostic utility of morphine-neostigmine stimulated serial MRCP for SOD merits further evaluation.

Studies of the human oropharyngeal airspaces using magnetic resonance imaging. III. The effects of device resistance with forced maneuver and tidal breathing on upper airway geometry.

The anatomical geometry of the upper airways of five healthy volunteers were studied using three-dimensional inhalation-gated magnetic resonance imaging (MRI) for two dummy inhalation devices of varying airflow resistances (0.049(0.5) and 0.004(0.5) kPa(0.5)(L/min)(1)) using a forced maneuver (sharp inhalation) and tidal breathing. The range of maximum inspiratory pressures (MIP) was 0.02-6 kPa. Significant airway expansion occurred for the lower resistance device with forced maneuver compared with tidal breathing. The mean upper airway volume for forced maneuver through a low-resistance device was 60 (SD 15) cm(3) compared with 38 (SD 9) cm(3) for tidal breathing through the same device. Regionally, these increases occurred in the oropharynx (factor of three increase) and the laryngo-pharynx (factor of two increase). Significant changes did not occur for the buccal and laryngeal regions. No significant airway volume change occurred between the two breathing modes using the high-resistance device. In contrast to an earlier study using tidal breathing, device-related volume changes occurred with forced maneuvers in the oropharynx and laryngopharynx. For the low resistance device, significant differences for the minimum airway equivalent radius at the epiglottis occurred between forced maneuver (8.0 mm) and tidal breathing (5.2 mm), and for the maximum airway diameter in the laryngo-pharynx (12.4 mm vs 9.1 mm). For forced maneuvers, significant differences in maximum airway diameter in the oropharynx were also apparent between the devices (12.6 mm low vs. 9.1 mm high) and also in the laryngopharynx (12.4 mm low vs. 9.4 mm high). The minimum radius at the epiglottis varied significantly between devices under forced maneuver breathing (8.0 mm low vs. 8.3 mm high). There was no correlation between airway expansion or contraction and MIP. A linear relationship was found between airway volume changes and maximum calculated volumetric airflow. This work has implication for the modeling of inhaled aerosol dynamics and in vitro particle impaction studies.

Studies of the human oropharyngeal airspaces using magnetic resonance imaging. II. The use of three-dimensional gated MRI to determine the influence of mouthpiece diameter and resistance of inhalation devices on the oropharyngeal airspace geometry.

The anatomical geometry of the upper airways of 20 volunteers has been studied using three-dimensional (3D)inhalation-gated magnetic resonance imaging (MRI)for four separate dummy inhalation devices of varying diameters and resistances. The only anatomical parameters showing a consistent dependence upon device characteristics were the total airway and buccal volumes between large and small mouthpieces and the distance from the back of the teeth to the first solid obstacle encountered. Individual subjects showed varied device dependent changes: 45% having an increase in regional airway volumes, particularly in the nasopharynx (+46% volume increase)and laryngo-pharynx (+36% volume increase)for the high-resistance devices compared with the low-resistance ones. However, 30% of subjects showed the opposite behavior, a reduction in naso-pharynx volume (-17%), laryngo-pharynx volume (-17%), and laryngeal cavity (-11%). 25% showed no significant difference in airway volume between high- and low-resistance devices. There was a correlation between maximum inspiratory pressure (MIP)and change in airway volume for high-resistance devices, with those exhibiting expansion having generally lower MIP than the group showing contraction (with the non-responders intermediate). Mean airway minimum and maximum cross-sectional areas and radii were not influenced by device. The geometric mean radius at the epiglottis was 5.1 mm (standard deviation [SD] 1.1) and 5.7 mm (SD 1.1) at the vocal cords. Significant differences observed between males and females included MIP for high-resistance devices, the volume and minimum and maximum radii of the laryngeal and laryngeo-pharynx regions, and total airway volume. A cadaver cast exhibited a number of striking differences in comparison with the in vivo data, most notably a significantly greater total volume.