Mechanism of gastric emptying of solid foods: biphasic nature
Gastric emptying results from the net effects of propulsive forces within the stomach and the resistance to flow offered by the narrowed gastroduodenal junction. The emptying rate is determined by the balance between driving and resistive forces (Vassallo and others 1992; Schulze 2006). Liquids, digestible solids, and indigestible solids are emptied with different mechanisms (Stotzer and Abrahamsson 2000). Liquid and semiliquid contents, as well as particles with a size of 1 to 2 mm, are emptied from the stomach into the duodenum during fed motility, whereas the contents of size > 1 to 2 mm are emptied during fasting motility (Hellström and others 2006). The proximal stomach has a major role in gastric emptying of liquids and the distal stomach a major role in gastric emptying of solids (Kelly 1980; Vassallo and others 1992).
After ingestion, liquids are rapidly distributed throughout the entire stomach. Emptying of liquids depends mainly on fundic pressure, through the “pressure pump” mechanism controlled by pyloric opening where the gastroduodenal pressure gradient is the driving force (Indireshkumar and others 2000; Stotzer and Abrahamsson 2000). Liquid meals empty from the stomach according to 1st-order kinetics; that is, the speed is directly proportional to the volume present in the stomach (Figure 9). It has an initial gastric emptying rate after ingestion of a meal, up to 10 to 40 mL/min, followed by a slower emptying rate of 2 to 4 mL/min. The halftime, t1/2, indicating when 50% ingested meal is emptied, ranges from 10 to 60 min (Fisher and others 1982; Versantvoort and others 2004; Hellström and others 2006).
Figure 9—. Gastric emptying curves for a solid and liquid meal in a healthy volunteer. Liquid emptying begins instantly in an exponential fashion, whereas the linear solid emptying begins after the lag phase. The emptying data is fitted with curves by power exponential model (Eq. 1). (Used with permission, Camilleri and others 1985).
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Ingested solids are stored initially in the proximal stomach and move gradually into the distal stomach. The propulsive contractions of the antral pump are the most important mechanisms underlying gastric emptying of solid food, where trituration is a rate-limiting step (Collins and others 1996; Cardoso-Júnior and others 2007). In the gastric antrum, mechanical (antral contractions) and chemical (acid, pepsin, and so on) factors work in coordination to grind and dissociate the solid particles. Solids are ground to particles of a size less than 1 to 2 mm before they are allowed to go through the pyloric opening. Indigestible material must wait for the interdigestive phase when the phase III contraction of the migrating motor complex empties the stomach (Poitras and others 1997; Stotzer and Abrahamsson 2000). The gastric emptying rate of solids, as indicated by the fraction of meal retention in the stomach compared with time, shows a biphasic pattern: a lag phase during which little emptying occurs, followed by a linear emptying phase during which solid particles empty from the stomach by mainly zero-order kinetics, that is, independent of gastric volume (Figure 9) (Siegel and others 1988; Hellström and others 2006; Schulze 2006). The stomach empties solids completely over approximately 3 to 4 h (Versantvoort and others 2004).
Since the early 1980s, scintigraphic imaging has been commonly used to evaluate gastric emptying rate. Various models and mathematical curves have been proposed for evaluation of gastric emptying rate, as indicated by fraction of food retention compared with time. With scintigraphic data, the food retention is assessed by the radioactivity remaining in the stomach. Two of the most popular models are Elashoff's power exponential curve (Elashoff and others 1982) and Siegel's modified power exponential curve (Siegel and others 1988).
Elashoff's power exponential equation is as follows (Marshall and others 2005):
where y(t) is the fractional meal retention at time t in minutes, T½ is the time required for the initial radioactivity to be reduced by half, and β is a constant that determines the shape of the curve. Siegel and others (1988) further modified Elashoff's model to account for the lag phase:
where k is the gastric emptying rate per minute, and β is the extrapolated y-intercept from the terminal portion of the curve. A value of β > 1.0 indicates an initial delay in emptying as for the solid foods, whereas a value of β < 1.0 indicates an initial rapid emptying as for liquid foods (Siegel and others 1988). The half-time (t1/2) can be calculated using y(t) = 0.5 and solving for t,
For solid foods, lag phase was defined as the time taken to achieve maximum rate of gastric emptying after ingestion of a test meal. This is usually correlated with the time when 90% of the test meal remained in the stomach. Despite some of the opposing arguments, it is commonly accepted that lag phase primarily reflects the time needed by the distal stomach to reduce ingested solid food into particles small enough to pass through the pylorus (Siegel and others 1988; Urbain and others 1989). Lag phase time (tlag) can be calculated by assuming that the 2nd derivative of the function is equal to zero,
Although the modified power exponential model is thought to be the best to fit experimental data and is commonly used to evaluate stomach emptying rate, the lag period calculated by Eq. 4 has been noted for its overestimation (Ziessman and others 1996; Hellström and others 2006).
Gastric emptying is regulated by both gastric factors and, to a greater extent, duodenal factors. Gastric factors include the food volume, fluid viscosity, caloric content, acidity, and food physical properties such as texture and density (Arora and others 2005). Duodenal gastric feedback is the major control mechanism for gastric emptying. The duodenum contains receptors that respond to distention, the presence of acid, carbohydrate, fat, and protein digestion products, and osmolarity differences from that of plasma (Versantvoort and others 2004). Chemical composition of the meal and the physical nature of the food remain crucial in regulating emptying rate. This information, important for understanding relationships between the physical and chemical properties of foods and digestion, is introduced in the following sections.
Biological factors such as age, body mass index, hormonal factor, gender, the blood glucose level, posture, stress and depression, and diseased states also influence gastric emptying (Amidon and others 1991; Darwiche and others 2003; Arora and others 2005; Hellström and others 2006). For example, gastric emptying is slower in elders and females. This could be related to the weaker antrum contractions in elders and women, because emptying rate is inversely correlated with the rate of antrum contractions (Houghton and others 1988). Emptying rate increases under stress and decreases in depression (Amidon and others 1991; Arora and others 2005). Fluids ingested at body temperature are emptied faster than colder or warmer fluids (Arora and others 2005). An increase in the osmolarity of the stomach contents decreases gastric emptying rate (Versantvoort and others 2004). The influence of biological factors on gastric emptying is not directly related to the theme of this review; therefore, it is not discussed here.
Influence of food caloric content, macronutrients, and volume on gastric emptying
Gastric emptying is so controlled that about 2 to 4 kcal/min (8.4 to 16.8 kJ/min) caloric content is delivered to the duodenum through a negative feedback mechanism mediated by the duodenal receptors. Meals with similar energy content are emptied from the stomach at similar rates (Faas and others 2002; Gentilcore and others 2006; Hellström and others 2006). In this context, meal calories, compositions, and size are important for gastric emptying. Meals of larger weight and kcal content are associated with longer emptying time for both solids and liquids (Horowitz and others 1986; Hadi and others 2002). Liquids with a calorie density of 1 kcal/mL are emptied at about 2 to 2.5 mL/min, whereas liquids of 0.2 kcal/mL are emptied at about 10 mL/min (Dressman and others 1998). The rate of energy delivery is faster with the larger meal. For example, a 150-mL meal containing 10% dextrose combined with 400 g ground beef was delivered at 4.8 kcal/min, whereas that with 100 g beef was delivered at only 2.5 kcal/min. Meanwhile, a delay in the lag phase of emptying was observed: 56 min for the large meal and 31 min for the small meal, respectively (Collins and others 1996). Moore and others (1984) determined that 900 g lettuce and water meals adjusted to either 68, 208, or 633 kcal with added salad are emptied at 3.18, 2.56, and 1.46 grams/min, corresponding to 0.48, 1.18, and 2.04 kcal/min, respectively. Christian and others (1980) showed that the average t1/2 for emptying meals consisting of meats, vegetables, and beverages were 277, 146, and 77 min, respectively, for 1692, 900, and 300 g meals. The t1/2 for the liquid part of these meals was 178, 81, and 38 min, respectively.
Among the major components of foods, fat is emptied more slowly than carbohydrates and proteins. Emptying 4 g of fat emulsion takes the same time as for a solution of 9 g of carbohydrate or protein. This is primarily because of its high caloric density, roughly 9 kcal/g in fat and 4 kcal/g in carbohydrate or protein (Versantvoort and others 2004; Gentilcore and others 2006). In addition, density difference causes phase separation of chyme in stomach, leading to the layering of fat above water that may also contribute to the longer emptying time of fat (Versantvoort and others 2004). Another possible reason is that fat absorption rate in the intestine is relatively slower that delays emptying speed (Gentilcore and others 2006).
Different sugars empty from the stomach at different rates. Lavin and others (2002) showed that the t1/2 values for 575 mL lemon-flavored drink of sucrose or maltose (125 g + 450 mL water + 50 mL lemon juice, 516 kcal) are 86 ± 5 min and 115 ± 2 min, respectively, whereas that for an unsweetened 575 mL lemon-flavored drink (525 mL water + 50 mL lemon juice, 16 kcal) was only 39 ± 2 min.
Complex interactions occur when different types of solids and liquids are consumed simultaneously (Collins and others 1996). For example, distinct t1/2 were observed for 10 mm chicken liver when ingested with 2 different meals: 117 min for a meal of 200 mL of water + 213 g of beef stew + 52 g of chicken liver, compared with 82 min for a meal of 200 mL of water + 75 g of noodles + 30 g of chicken liver (Moore and others 1981). Eggs and liver cubes have different emptying rates when they were ingested individually, but were emptied at a similar rate when ingested together (Poitras and others 1997). Ingested solid and liquid foods affect each other. Simultaneous ingestion of solids slowed significantly the gastric emptying rate of the liquid component (Fisher and others 1982). The liquid composition also affects solid emptying. Houghton and others (1988) showed that when the liquid component of the meal changed from normal saline to 25% dextrose, the lag period for solid emptying increased from 40 to 87 min. Meanwhile, liquid emptying t1/2 increased from a median of 8 to 40 min. However, the slope of solid emptying did not change, implying that the rate of coordinated contractions involving the antrum did not alter during the solid emptying period (Houghton and others 1988).
Influence of food viscosity on gastric emptying
Increasing the viscosity of liquid meals delays gastric emptying and increases satiety (Ehrlein and Pröve 1982; Benini and others 1995). An experiment on dogs showed that t1/2 was 4.5 ± 2.2 min with a low viscosity liquid meal (10−3 Pa.s), 28.9 ± 9.5 min with a test meal of medium viscosity (102 Pa.s), and 43 ± 11.8 min with a test meal of high viscosity (103 Pa.s) (Ehrlein and Pröve 1982). Studies have shown that addition of soluble fibers such as pectin (Di Lorenzo and others 1988), guar gum (Blackburn and Johnson 1981; Leclère and others 1994), and locust bean gum (Marciani and others 2001; Darwiche and others 2003) reduces the gastric emptying rate, delays absorption, reduces the plasma glucose response, and slows down the return of hunger. For this reason, soluble fibers have been combined in diet for treating pathological conditions such as obesity, hypercholesterolemia, and diabetes.
The mechanisms governing delayed stomach emptying with increased viscosity of meal are thought to be related to the negative feedback from the intestine when fiber arrives in the distal ileum or in the colon (the “ileal brake”) (Darwiche and others 2003). It may be also related to the greater resistance of fiber containing food to the intragastric movement of the meal toward antrum and grinding action of the antrum (Benini and others 1995). However, despite an increase in the apparent viscosity of the gastric contents after ingestion of a high viscosity meal (Blackburn and Johnson 1981), the increase in the chyme viscosity is not proportional to the meal viscosity. A rapid intragastric dilution in the stomach occurs after a high viscosity meal is ingested to reduce the meal viscosity and minimize delay in gastric emptying (Meyer and Doty 1988; Marciani and others 2000). This may partly explain the much smaller change in emptying rates compared to the increase in viscosity in the meal. Marciani and others (2000) showed that 1000-fold viscosity variation between meals caused changes in emptying rates by a factor of only 1.3. Guerin and others (2001) studied the influence of meal viscosity on chyme and emptying on conscious pigs, and found that the reduced emptying rate is more associated with changes in intragastric distribution of the meal rather than meal viscosity. They concluded that viscosity of the gastric contents is a better predictor of emptying than the viscosity of the meal. Furthermore, gastric emptying is not only directly related to gastric digesta viscosity but it also depends on the type of dietary fiber (Guerin and others 2001).
The effect of dietary fiber on the gastric emptying rate of solids is controversial. Although different authors have reported a delayed emptying by the fibers added manually (Di Lorenzo and others 1988) or naturally present in food (Benini and others 1995), accelerated gastric emptying was also reported. Meyer and others (1986) documented that the addition of guar gum significantly increased the emptying of 3.2-mm Teflon spheres in a meal consisted of steak and saline. They also observed an increased passage of large, poorly digestible pieces of foods through pylorus: the size of food particles emptied from the stomach increased from < 1 mm to 1 to 4 mm, leading to a reduced absorption in intestine. This phenomenon could be related to the viscosity-induced change in hydrodynamic factors that disrupted gastric sieving (Meyer and Doty 1988).
Influence of physical properties of food on gastric emptying
During gastric digestion, solid foods are ground down to 1 to 2 mm size by the action of gastric peristalsis before being discharged to the duodenum. The physical properties such as size, density, texture, and microstructure of the food are important in determining how easily it can be fragmented in the stomach. Food particles with large size and density need more time for size reduction in the antrum, consequently requiring long time for emptying. The t1/2 was 70 ± 10 min for the 0.25 mm chicken liver and 117 ± 19 min for the 10 mm liver particles (Moore and others 1981). Spheres with specific gravity greater than 1 or less than 1 may sink or float out of the central moving stream in the stomach; both are emptied more slowly than spheres of the same size with a specific gravity of 1 (Meyer and others 1985). This principle has been used in the design of floating dosage form, which has a density less than that of the gastric fluids and therefore can be retained in the stomach for a prolonged period (Arora and others 2005).
Hardness of solids affects stomach-emptying rates. Soft particles emptied significantly faster than hard ones. When noodle and liver are ingested simultaneously, noodle was emptied faster (52 ± 8 compared with 82 ± 5 in t1/2) (Moore and others 1981). Another study showed a longer t1/2 for chicken liver than egg (Siegel and others 1988). Based on this fact, Poitras and others (1997) proposed using liver rather than egg as a radiolabeled tracer in scintigraphy to improve the sensitivity for detection of gastroparesis.
Contrary to intuition, consistency of foods may not make significant difference on emptying. Mashed potato was found to empty from the stomach at a similar rate with meals of a more particulate consistency (rice, hamburger meal), although it did not require trituration in stomach as a homogeneous meal (Faas and others 2002). This may be due to a longer period of time needed for gastric secretions to penetrate and liquefy the meal with denser consistency (Marciani and others 2001; Faas and others 2002).
Food processing affecting digestion
Food processing (during manufacturing or cooking) modifies physical and chemical properties of food, and thus may influence the release and uptake of nutrients from the food matrix. Comminution reduces food size, which significantly improves gastric emptying rates and nutrient absorption (Bjorck and others 1994; Pera and others 2002). The lag phase and half emptying time (t1/2) were significantly shorter for the homogenized egg meal than for the 2.5 mm and 5.0 mm cubed egg particles, with the lag phase 29 ± 19 min compared with 55 ± 26 and 64 ± 24 min, and the t1/2 71 ± 30 min compared with 91 ± 26 and 104 ± 30 min, respectively (Urbain and others 1989). An in vitro digestion study showed that 3% of the carotenoid content was released from raw carrots in pieces, whereas 21% was released from the homogenized (pulped) carrots (Hedrén and others 2002).
Thermal processing can significantly affect digestion of protein (Ruales and Nair 1994), starch (Lee and others 2005), fat (Benini and others 1994), and vitamins (Yeum and Russell 2002). Heat treatment significantly improves bioavailability of carotenoid and lycopene in vegetables (Yeum and Russell 2002). Fried meal showed significantly delayed emptying time (317.1 ± 24.12 compared with 226.7 ± 18.4 min) and caused a longer persistence of satiety and epigastric fullness in human trials, which could be attributed to the effect of thermal oxidation on fat absorption (Benini and others 1994). Cooking improves bioavailability of starch by splitting the starch granules and increasing the availability of the starch to amylase (Brand and others 1985). Lee and others (2005) studied the effects of various cooking methods on rice texture, microstructure, and digestion in rats. Cooking methods studied included microwave oven, electric cooker, autoclaving, and a stone pot. Scanning electronic microscopy showed a more compact structure in the samples heated by microwave and electric cooker compared to those treated in an autoclave or stone pot, corresponding to a higher firmness in the samples heated by microwave and electric cooker. Cooking increased pasting temperatures and decreased peak viscosity. The starch hydrolysis rates of cooked rice samples increased with an increase in gelatinization. Holm and others (1989) also documented that incompletely gelatinized starch products were digested more slowly in vitro and elicited lower glucose responses in rats compared with completely gelatinized samples.