gastric emptying and intestinal absorption of ingested fluids

Supplement Article

Fate of ingested fluids: factors affecting gastric emptying andintestinal absorption of beverages in humans

John B. Leiper

The volume of fluid ingested for rehydration is essential in determining therestoration of euhydration because it must be in excess of the water lost since theindividual was last euhydrated. The formulation of any ingested beverage is alsoimportant as this affects the rate at which the fluid is emptied from the stomach,absorbed in the small intestine, and hence assimilated into the body water pool.This review highlights the essential role of the gastrointestinal tract in themaintenance of hydration status.

INTRODUCTION

In everyday life, water is continually being lost in the

expired breath and by insensible sweating; it is also lostintermittently, mainly in urine, feces, and sweat.

Although these losses are, in themselves, relatively smallin comparison with total body water content,1 they are

cumulative, and the body’s ability to function normallyis measurably diminished both mentally2 and physi-

cally3,4 by being hypohydrated by as little as 2% of bodymass. Levels of dehydration >10% of body mass are

potentially fatal.5 In humans, the pattern of fluid con-sumption is usually periodic and in excess of that lostsince the last intake6; with thirst and habit being impor-

tant factors in controlling intake and the kidneys play-ing an important role in regulating excretion.7

FACTORS AFFECTING THE ASSIMILATION OF INGESTEDBEVERAGES INTO THE WATER POOLS

The absorption of water and solutes occurs predomi-nantly in the small intestine7; therefore, the rates of gas-

tric emptying and intestinal absorption, delivery of theabsorbed components to the circulation, and excretion

of ingested beverages are integral factors in determiningthe effectiveness of a beverage for hydrating an individ-

ual. The efficacy of any solution to rehydrate is criticallydependent on both the volume and formulation of the

beverage. While the amount of fluid ingested will ulti-mately determine how well the individual is hydrated,

the constituent solutes of the beverage markedly affectthe rate at which the beverage enters the body pool,8 the

duration of fluid retention,9–13 maintenance of the stim-ulus to drink,11,12 and restoration of electrolyte and sub-

strate deficits.5,11,14 While consumption of manybeverages occurs for pleasure or from habit,6,15 the re-

sultant intake of fluids will cause their water content toenter the body water pool following ingestion. How

quickly this occurs is dependent on many factors, ofwhich the 3 main elements are the rate of gastric empty-

ing, the rate of intestinal absorption of the ingested bev-erage, and the speed at which the absorbed water enters

the water pools.8,11

ROLE OF THE GASTROINTESTINAL TRACT INREGULATING WATER ABSORPTION

Formulation, palatability, and voluntary ingestion ofbeverages

Beverages range from distilled water, which containsonly trace amounts of solutes, to liquid meals, which

contain all the macronutrients, micronutrients, vita-mins, and minerals required for normal nutrition.

While there are various benefits to supplying nutrientsin liquid rather than in solid form, the main advantage

Correspondence: J.B. Leiper, 32 North Anderson Drive, Aberdeen, AB15 5DA, UK. Email: [email protected]. Phone: þ44-1224-310380.

Key words: energy density, gastric emptying, glucose, rehydration.

VC The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. ForPermissions, please e-mail: [email protected].

doi: 10.1093/nutrit/nuv032Nutrition ReviewsVR Vol. 73(S2):57–72 57

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lies in the faster absorption of fluids.16 The presence of

nutrients such as carbohydrates, fats, and proteins inbeverages not only supplies energy, it also affects the

solutions’ organoleptic properties and their rate of ab-sorption in the small intestine. Carbohydrates are the

most common energy source included in commercialbeverages, presumably because they are an adjunct tothe flavorings used to encourage voluntary fluid con-

sumption. It must also be recognized that the ingestionof beverages is very often associated with the consump-

tion of food, and it is the global solute mixture in thechyme that affects the rate of intestinal absorption.

Although humans appear to enjoy the taste of so-dium chloride, the human appetite for salt is appreciably

lower than that of many animals. In addition, relativelyhigh concentrations of sodium chloride are discerned as

being bitter and may cause nausea.15 Following exercise-induced dehydration, the thirst response increases, but

ingestion of electrolyte-free beverages can inhibit thisresponse by lowering blood osmolality and may result in

insufficient voluntary fluid intake to meet the water defi-cit–related rapid fall in plasma osmolality.17 Conversely,

the reduction in the volume-dependent dipsogenicstimulus that develops when fluids with a high sodium

chloride content are ingested is an important factor inlimiting ad libitum fluid intake during rehydration.17

Nevertheless, inclusion of electrolytes in rehydrationbeverages promotes retention of the fluid ingested.18

When hypohydrated individuals consume prescribedvolumes (amounting to 150% of their sweat loss) of

solutions containing relatively high (52–100 mmol/L)concentrations of sodium chloride, restoration of euhy-

dration is prolonged compared with that which occurswhen low-salt beverages are consumed.13,19 Because so-

dium is the main electrolyte in extracellular fluid, it isclosely involved in the homeostatic control of body wa-

ter. Consequently, many of the sensory signals andmechanisms that control water intake also influence so-

dium intake.20 Potassium, the main osmotically activecation in the intracellular space, does not play as pivotala role as sodium in the maintenance of water balance.5,21

Gastric emptying of fluids

Ingested fluids are not immediately available for assimi-

lation into the body. They are initially stored in thestomach, and there is little net absorption of water or sol-

ute across the gastric mucosa.22,23 Any delay in gastricemptying is detrimental to the effectiveness of a beverage

in situations where the constituents of the beverage areurgently needed by the body. In other circumstances, a

beverage that slowly empties would delay the integrationof its water content into the body water pool and, hence,

slow urine production might be preferred.

A variety of methods have been used to measure

gastric emptying of liquids in humans, and all havesome advantages and disadvantages.24–26 While most

claim that they have been validated, this generallymeans they have been compared with another “stan-

dard” method, usually scintigraphy, and that both haveshown some measure of agreement in assessment.Typically, the comparison between methodologies has

been assessed using correlation coefficients, with r val-ues �0.60 being accepted as indicators of reasonably

good agreement and, hence, validity. Much of the vari-ance seen between these techniques is undoubtedly due

to the large between-subject variability (�30%) seenamong techniques, while within-subject variability is on

the order of <10%.27–30 This would suggest that mosttechniques can be used to give an estimate of gastric

emptying rates of various solutions, but that poweranalysis indicates that for a sample size of 8 individuals,

there is an 80% chance of identifying a real differencein gastric emptying rates only when the emptying char-

acteristics of the beverages differ by �30%. For a samplesize of 10 individuals, the difference must be �27%.

The double sampling aspiration method, althoughsubject to the same approximately 30% intersubject var-

iance, has the advantage of being able to provide the fol-lowing estimates: the change in emptying rate over

time, the volume of gastric secretions and their effecton total volume, and the content of liquid in the stom-

ach; endpoint gastric fluid volumes can be verified bothby aspiration and by dye dilution.30 This technique can

be used with individuals who are seated, standing, orexercising in a variety of modes and intensities. The dis-

advantages are that relatively large initial test volumes(usually between 400 and 600 mL) are ingested and that

not all individuals can tolerate the aspiration tube.26

Factors affecting gastric emptying

It is thought that the rate of gastric emptying is themain limiting factor in the assimilation of ingested flu-ids.8 Because of the complexity of the mechanisms that

control the gastric emptying process, it is not surprisingthat there is considerable interindividual variation in

emptying rates.24,28,29,31 However, most individualsdo appear to be relatively consistent in the rate at

which they empty the same solution on different occa-sions.27–29, Many factors have been shown to influence

the rate of gastric emptying of solutions.Apart from the receptors that respond to the vol-

ume of the stomach,32 the majority of receptors thatregulate gastric emptying are found in the duode-

num33,34 and ileum.35 These receptors appear to func-tion primarily by initiating neural and hormonal

responses that modify gastric and duodenal muscular

58 Nutrition ReviewsVR Vol. 73(S2):57–72



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tone and the frequency of contraction. The position of

the receptors in the small intestine suggests their mainfunction is to inhibit gastric emptying and, thus, pre-

vent the absorptive capacity of the intestine from beingoverwhelmed. Most of this information is derived from

studies on resting individuals that used either single-time-point or serial-time-point aspiration techniques.

The various factors that affect the rate of gastric empty-ing of ingested fluids are summarized in Table 1 and

described below.

Gastric volume as a regulator of gastric emptying

The negative exponential nature of the gastric empty-ing curve indicates the importance of the volume of

the stomach in controlling the rate of emptying(Figure 1). Because the stomach acts as a reservoir, it

must be able to distend to accommodate the ingestatewhile maintaining a relatively low intragastric pres-

sure. It is the slow, sustained contractions sweepingfrom the proximal to the distal regions of the stomach

that mainly influence the pressure in the antral area ofthe stomach, and these remain unaffected by the mus-

cle tone of the upper portion of the stomach.36

Increasing the pressure in the antral region increasesthe rate of gastric emptying of fluids.37 Increasing the

volume of the gastric contents stimulates the activityof the stretch receptors in the gastric mucosa; this, in

turn, raises the intragastric pressure and promotesfaster emptying.33,38 It is the total volume in the stom-

ach that is important, which includes the volume ofbeverage ingested plus the volume of gastric secretions

and swallowed saliva.Using the single-time-point technique, Costill and

Saltin39 measured the gastric volume 15 min after differ-ent volumes of a glucose solution were ingested. A

larger amount was emptied after ingestion of 600 mLcompared with 400 mL, which was greater comparedwith 200 mL. There was no difference in the volume

emptied when 600 mL was ingested compared with800 mL, but there was a tendency for less volume to be

emptied after ingestion of 1000 mL. This suggests theremay be an upper limit of gastric volume above which

emptying rates may plateau or even slow.38 It is also evi-dent that the volume required to promote the maxi-

mum gastric emptying rate for a given test solution willbe highly variable among individuals.39

Research has demonstrated that repeated ingestionof test solutions will maintain a high gastric volume

and result in faster rates of gastric emptying thanwould have been expected from the contents of the

beverages.38 Following ingestion of a single bolus of aliquid, there is an initial fast phase of gastric emptying

when the volume in the stomach is at its greatest. Theemptying rate then becomes progressively slower as

the volume in the stomach decreases. This means aconstant fraction of the volume in the stomach empties

per unit time.40 By refilling the stomach at intervals,the volume in the stomach can be kept high and rates

of gastric emptying equivalent to that of the ini-tial phase can be maintained for prolonged periods

(Figure 2).40,41

Energy density as a regulator of gastric emptying

Plain water empties rapidly from the stomach, while in-

creasing the energy content of ingested solutions slows

Table 1 Summary of the factors that affect the rate of gastric emptying of ingested beveragesFactor EffectVolume Increased intragastric volume speeds the rate of emptying up to a maximum capacityEnergy density High energy density of beverages reduces emptying ratesOsmolality High osmolality of beverages slows emptying rates, but the effect is much less than for energy densityTemperature Beverage temperature that differs markedly from normothermia has little effect on gastric emptying as intragastric

temperatures rapidly equilibratepH Beverage pH has little effect on emptying rates as buffering capacity is normally weak, and the type and concentration

of salts in beverages are not sufficient to influence emptying ratesExercise Steady-state exercise levels above 70% VO2max and high-intensity intermittent exercise can both slow gastric

emptying

0

100

200

300

400

500

600

0 10 20 30 40 50 60 70 80Time (min)

Single bolus

Initial fast emptying phase

Emptying rate slowing as

volume decreases

Figure 1 Typical gastric emptying pattern following ingestionof a single bolus of a dilute carbohydrate-containingbeverage.

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the rate of gastric emptying. Surprisingly, the rate of

gastric emptying is regulated such that approximatelyisoenergetic amounts of carbohydrates, proteins, fats,

and alcohol 34,42,43 are delivered into the duodenum. Itis widely accepted that the receptors that respond to en-

ergy density lie outside the stomach; however, it is notknown whether they are positioned on the luminal or

serosal side of the small intestine or whether they re-spond to the same stimulus for each nutrient.44 While

hyperglycemia can slow gastric emptying and hypogly-cemia can accelerate the emptying of nutrient solutions,

no hormone or gastrointestinal peptide has yet beenidentified as the unequivocal regulator of gastric empty-

ing of energy sources.45,46

The main nutrient source in most beverages is

carbohydrate, and the majority of studies that exam-ined the effects of energy content on gastric emptying

used carbohydrate solutions. It is now well recognizedthat solutions with a carbohydrate content of �2.5%empty from the stomach at essentially the same rate as

that of equal volumes of water,47 and most studieshave shown that carbohydrate levels �6% unequivo-

cally slow emptying.48 Even glucose concentrations of4%–5% produce small but significant slowing of gas-

tric emptying.39,49 Some studies have found no differ-ence in the gastric emptying rate of water and

carbohydrate solutions of up to 10%; however, most ofthis disparity is probably due to individual study de-

sign and participant population.48 Increasing the car-bohydrate content of solutions slows the rate of

emptying in proportion to the energy density, but itresults in faster rates of carbohydrate delivery to the

duodenum.25,49,50

Osmolality as a regulator of gastric emptying

While it is clear that osmolality is a major controlling

factor for solutions with no nutrient content, this is notthe case for fluids that contain energy.51 Substitution of

glucose polymers for glucose monomer can be used toreduce the osmolality of the solution while maintaining

the total carbohydrate content. Several studies have ex-amined the effect of replacing glucose monomer with

polymers on gastric emptying, but the findings are notconsistent. Most investigations have found little or no

difference in gastric emptying of isoenergetic solutionsof glucose monomers compared with glucose polymers,

despite the often large differences in osmolality.48,52

This lack of difference implies that hydrolysis of the

polymers occurs before reaching the small intestinalosmoreceptors. Therefore, the osmolality of the isoener-

getic solutions are, in fact, equal at the point at whichthey come in contact with the regulating osmorecep-

tors.34 In one study, a 15% glucose polymer solutionwas found to empty faster than a 15% glucose monomer

solution, but there was no difference in the emptyingrates of 5% and 10% solutions of glucose monomer and

polymer, respectively. Furthermore, the differences ingastric emptying could not be explained solely by thedifferences in the initial osmolality of the solutions.53

The addition of salts with a combined osmolality of�336 mosmol/kg to a 15% glucose polymer solution

with an initial osmolality of 114 mosmol/kg did not sig-nificantly affect gastric emptying compared with the

glucose polymer solution without electrolytes.51

Consensus opinion at present is that the energy density

of a solution exerts a greater effect than osmolality inthe regulation of gastric emptying and that the substitu-

tion of glucose polymer for monomer may slightly in-crease the rate of gastric emptying, but only at high

energy densities.54

Beverage temperature as a regulator of gastricemptying

Nerve conduction and muscle motility are both sensi-

tive to changes in temperature, which implies that gas-tric emptying may be affected by the temperature of an

ingested beverage. Several studies have shown that bev-erage temperature can slightly affect the gastric empty-

ing rate, but only for about 10 min post-ingestion.39,55,56

The intragastric temperature appears to rapidly return

to normal core levels,56,57 and the beverage temperaturehas little effect on overall rates of gastric emptying. The

rate of recovery of intragastric temperature depends onthe temperature of the beverage, the volume consumed,

and the thermal capacity of the solution.

0

100

200

300

400

500

600

0 10 20 30 40 50 60 70 80Time (min)

Single bolus

Repeat boli

Figure 2 The effect on gastric emptying of maintaining a highgastric volume by repeated ingestion compared with a singlebolus of the same carbohydrate beverage. Reproduced fromRehrer et al.40 with permission




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Beverage pH as a regulator of gastric emptying

The pH within the stomach is strongly acidic; as the

chyme moves into and along the proximal small intes-tine, the acid is neutralized by the duodenal and pancre-

atic secretions. In a series of experiments, Hunt andKnox34 demonstrated that it was not the pH of the fluid

that affected the rate of gastric emptying but the con-centration and type of acids present. Low-molecular-

weight acids were associated with greater inhibition ofgastric emptying than high-molecular-weight acids.34

The type and concentration of acids commonly used inbeverages are not thought to influence gastric emptying

to a measurable extent.26

Beverage carbonation as a regulator of gastricemptying

Many commercial beverages are carbonated to varyingdegrees. An early study suggested that carbonation of

beverages enhances gastric emptying due to the increasein intragastric pressure caused by the release of carbon

dioxide from the beverage.58 The technique used in thatstudy is now thought to be qualitative at best33 andprobably inappropriate for measuring the emptying rate

of beverages. While ad libitum ingestion of carbonatedbeverages during running exercise tends to be less than

that of a noncarbonated beverage,59 the differences aresmall and not always apparent.60 Several studies have

shown that carbonation has little effect on gastric emp-tying at rest61 or during exercise.59,60,62 However, the

majority of studies that investigated the effect of car-bonation on gastric emptying used single endpoint

measurement, which is liable to miss subtle differencesin emptying rates. The lack of an effect of carbonation

on gastric emptying is likely due to either the carbon di-oxide being rapidly removed by eructation or the com-

pressibility of the gas, making it ineffective instimulating the stretch receptors.63

EXERCISE AS A REGULATOR OFGASTRIC EMPTYING

Several mechanisms have been proposed whereby exer-cise intensity may affect gastric emptying, but there is

little evidence to suggest which of these factors plays themajor role.64 When discussing the possible effects of ex-

ercise on gastric emptying, the mode, intensity, and du-ration of the exercise are of fundamental importance. A

number of studies have confirmed the findings ofCostill and Saltin39 that steady-state cycle exercise at an

intensity below about 70% of an individual’s VO2max

has little effect on gastric emptying; increasing the in-

tensity above this level produces progressive, significant

slowing of the emptying rates of ingested fluids.14 To

date, the gastric emptying characteristics of elite endur-ance athletes exercising at their race intensity have not

systematically been investigated. The majority of studiesthat have examined the effect of prolonged moderate

exercise of up to 3 h on gastric emptying have been car-ried out on recreationally active individuals, and theyhave shown that high gastric emptying rates can be sus-

tained during this type of exercise14 even in the heat.65

Other studies, however, have indicated that both hypo-

hydration and hyperthermia can slow gastricemptying.66,67

Upright exercise undertaken between 28% and 70%of VO2max has been demonstrated to stimulate gastric

emptying compared with rest, but emptying was slowerwhen running at 75% VO2max.66 Other researchers,

however, have found little effect during running atmoderate exercise levels compared with rest.14 The dif-

ferences in findings among studies may be due to thebeverages used or the study protocols. There appears to

be no significant difference in gastric emptying betweencycling and running exercise.40

At high exercise intensities known to inhibit gastricemptying, the duration is usually too short for any ben-

efit to be derived from the fluid ingested during the ex-ercise.14,68 During most sports and other forms of

physical activity, however, the period spent exercising isprolonged while the exercise is intermittent and the in-

tensity is varied. Many of the factors that have beenshown to induce fatigue during prolonged constant-

intensity exercise have the same effect on intermittentexercise of sufficient duration.68 It has been assumed,

however, that in most forms of intermittent exercise,the time spent at relatively low levels of activity is suffi-

cient to allow appropriate amounts of any ingested bev-erage to be emptied and absorbed.

It has been shown in a series of studies that inter-mittent, variable-intensity exercise significantly slows

gastric emptying, even when the overall energy ex-penditure is not much greater than that of steady-state exercise, which had no measurable effect on

emptying.30,69,70 Overall, these studies demonstratedthat intermittent, variable-intensity exercise signifi-

cantly slows gastric emptying of fluids, but that inges-tion of dilute carbohydrate–electrolyte solutions

(CESs) can still enhance exercise performance and ca-pacity as enough carbohydrate can be absorbed to be

effective.

INTESTINAL ABSORPTION

The structure and functional architecture of the smallintestine is adapted for absorption while presenting a

barrier to potential noxious chemicals and organisms.




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The major barrier for transport across the intestinal

mucosa is the phospholipid bilayer of the enterocytes ofthe villi and the intercellular junctions between those

cells.71 Lipid-soluble solutes can readily permeate cellmembranes, are translocated through the cell, and pass

across the basal membrane on the serosal side into thelymphatics or portal vein.72,73 Water and water-solublesolutes require different mechanisms to cross the intes-

tinal mucosa. Embedded in the brush-border mem-brane of the enterocytes are various transport carriers

with different degrees of specificity. These transportcarriers unidirectionally translocate carbohydrate

monomers, amino acids, dipeptides, and tripeptidesfrom the luminal surface into a cell’s cytoplasm.73–76

This transport is often linked with sodium uptake,which plays a pivotal role in the absorption of many or-

ganic and inorganic solutes71,77; as an osmotically activetransportable solute, it has a major influence on water

absorption.71 The current concept of net water move-ment across the intestinal wall is that water flux is pas-

sive and dependent on osmotic, hydrostatic, andfiltration pressures. Water absorption from the intestine

is considered to be a passive consequence of solute ab-sorption, resulting from local osmotic gradients that

promote net uptake of water from the lumen across theintestinal mucosa.71,78,79

MEASUREMENT OF INTESTINAL ABSORPTION

Many methods have been described to study intestinal

absorption in animals and humans.26,71 Both in vitroand in vivo techniques have been used in intestinal

studies. Generally, studies that use the steady-state intu-bation method have been the most productive. All intu-

bation methods require the participant to pass an oraltube into the intestinal region of interest to allow fluid

and solute absorption to be measured over a prescribedlength of the tract. Absorption is measured as the differ-

ence between the amount of test substance introducedinto the intestinal segment and the amount that is sub-sequently recovered further down the lumen. The use of

nonabsorbable markers allows studies to be made with-out quantitative recovery of all luminal contents.71 The

results are expressed per unit length of intestine per-fused (cm) per unit time (h).

There is fairly large between-subject variability inintestinal water and solute absorption, but intrasubject

variability is much smaller. In one study in which 6 in-dividuals were perfused with the same CES 7 times, the

intersubject range for water absorption using thesteady-state perfusion technique was 2.6–7.2 mL/cm/h

with a coefficient of variance (cv) of 22%, but thewithin-subject variability had a minimum cv of 3% and

a maximum of 12%.80

The steady-state perfusion method has been used

to study mechanisms of water absorption and solute ex-change throughout the intestine both at rest71 and dur-

ing exercise.81 The method is limited by therequirement to minimize the radiation dose given dur-

ing fluoroscopic positioning of the perfusion set in theintestine and by the ability of individuals to successfullypass the perfusion set into their intestine and to tolerate

its presence in their gastrointestinal tract, particularlyduring exercise.8 This technique has also been criticized

because steady-state conditions are unlikely to be nor-mally maintained in the small intestine for extended pe-

riods following ingestion of beverages and that the highrates of perfusion (5–20 mL/min) used to establish

steady-state usually only occur in the initial stages ofgastric emptying after swallowing 500–600 mL of flu-

ids.8,26 Nevertheless, to date, the perfusion model hasbeen used to establish our understanding of many of

the parameters that regulate intestinal absorption.

REGIONAL DIFFERENCES IN INTESTINALFUNCTION

The stomach contents delivered to the duodenum are

rapidly brought into osmotic equilibrium with the cir-culating plasma.7,82 This appears to be brought about by

bidirectional movement of water and electrolytes acrossthe intestinal lumen along osmotic and electrochemical

gradients.7,71 The proximal small intestine is relativelypermeable to water and electrolytes, and movement in

either direction across the mucosa is dependent on theprevailing gradient for the specific molecules. The ileum

is less permeable to water and electrolytes, and the co-lon is less permeable than the ileum.

One study investigated fluid absorption from dif-ferent segments of the upper small intestine (total

length of perfused gut was 75 cm) during cycle exer-cise.83 In this steady-state study, water absorption was

fastest from the first 25 cm of intestine perfused (duode-num), followed by the adjacent 25 cm of the proximaljejunum, with the slowest water uptake from the next

25-cm segment of the perfused jejunum. Water flux wasdifferent from perfused plain water and a CES, with up-

take being faster from plain water in the duodenum butslower than that of the CES in the first part of the jeju-

num. Total solute absorption (carbohydrate and elec-trolytes) was not significantly different between

segments for a given solution or between solutions for agiven segment.83

In the human jejunum, net sodium absorption oc-curs only when the sodium chloride concentration of

an isotonic solution is �127 mmol/L, with net efflux ofsodium occurring into the lumen at lower concentra-

tions. In the ileum, however, sodium is absorbed when




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the luminal concentration is �115 mmol/L.82 The addi-

tion of relatively small amounts of actively transportedsugars enhanced sodium uptake by the jejunal but not

by the ileal mucosa.82 In the jejunum, absorption ofchloride appears to be determined by water and sodium

transport rather than by a specific transport mecha-nism. In the ileum, however, chloride is actively ab-sorbed even against strong chemical gradients by a

linked anion-exchange mechanism, with chloride beingexchanged for bicarbonate.7 This exchange mechanism

does not operate in the jejunum, which is the predomi-nant site of both chloride and bicarbonate absorption.71

ABSORPTIVE MECHANISMS

Two transcellular routes and 1 intercellular route have

been proposed to explain the absorption of water andhydrophilic solutes across the intestinal mucosa of the

proximal small intestine.71,82 One transcellular route isvia aquaporins that penetrate the enterocyte membrane.

Because the inner surface of these aquaporins carries anelectrical charge, both the 3-dimensional size and the

charge of the molecule will influence the effective per-meability.84,85 These aquaporins are known to be im-

portant routes that allow water and electrolytes to crossthe mucosal barrier by osmotic and hydrostatic gradi-

ents and by diffusion along electrochemical gradients.85

The comparatively large physical size of monosaccha-

rides and amino acids prevents their access via thisroute. Aquaporins comprise a family of highly efficient

water-transporting membrane proteins that span thecell membrane of a variety of different cells throughout

the body. Aquaporin-10 appears to be expressed exclu-sively in the duodenum and jejunum, with the highest

expression in absorptive enterocytes at the tips of villiin the jejunum.86,87 One isoform is also permeated by

neutral solutes such as urea and glycerol, but not ade-nine,87 while the other isoform appears to transport

only water.86

The second transcellular route involves the carrier-mediated transporter systems that are embedded in the

brush-border membrane of the enterocytes. Carriertransport is specific to individual molecules or to a

group of similar molecules. For example, the carriermechanism that transports glucose (sodium-dependent

glucose transporter [SGLT]) is equally effective in trans-porting galactose but is not involved in the transport of

fructose or lactose. There are families of carrier mecha-nisms that have different specificities for neutral, acidic,

and branched-chain amino acids and for small pep-tides.75 Movement of solute against an electrical or con-

centration gradient requires energy; active transportersare carrier-mediated systems that are energy dependent

and capable of moving solute against a concentration

gradient. Active transporters use the electrochemical

potential gradient of a cotransported cation, which isusually sodium, to supply the required energy.

Therefore, they are ultimately dependent on the activityof the sodium–potassium–ATPase pump located in the

basolateral membrane of the enterocytes.73–76 Othercarriers, termed facilitated transporters, are driven byconcentration differences that favor absorption of a spe-

cific solute; however, the carrier mechanism increasesthe rate of transport compared with simple diffu-

sion.75,88 Facilitated transporters are energy and sodiumindependent but they are less efficient, especially at rela-

tively low solute concentrations, than the active trans-porters. While glucose is mainly absorbed when it is

actively cotransported with sodium by the transporterSGLT1, the facilitated transporter GLUT5 absorbs

fructose. In addition to the brush-border transportersystems, there are a number of electrically neutral ion-

exchange mechanisms and ion-cotransport systemssited in the enterocyte membrane. In the jejunum, so-

dium and chloride are transported into the enterocytevia a dual-coupled antiport system that involves hydro-

gen and bicarbonate ions.77 In the ileum, chloride en-ters the enterocyte in exchange for bicarbonate.77

The intercellular route occurs through the tightjunctions between the enterocytes at the luminal side of

the lateral edge of the cells. Below this junction, the lat-eral membranes diverge to form the intracellular lateral

space that opens into the interstitial space of the villuscore. The perijunctional actomycin ring of the intestinal

tight junctions can be activated to increase or decreasethe permeability of the intercellular junction. Initiation

of any of the active transporters causes the tight junc-tions to become more permeable to water and solute.89

Water absorption from isotonic luminal fluid ismainly a passive consequence of solute absorption that

establishes a local osmotic gradient that promotes thenet uptake of water from the intestine. A number of dif-

ferent models have been proposed that couple soluteand water absorption in the absence of, or against,moderate osmotic gradients. In each paradigm, active

uptake of nutrients and/or sodium initiates an osmoticgradient, which causes an increase in the lumen-to-mu-

cosa water flux.39,78,90,91 It has been clearly establishedthat the intestinal absorption of solutes such as glucose

promote net water uptake, which in turn increases thenonselective transport of additional solute from the in-

testinal lumen.89,91

FACTORS THAT AFFECT INTESTINAL ABSORPTION

Most studies that have investigated the factors that af-fect intestinal absorption in humans have used steady-

state perfusion methods in a segment of intestine.8,71




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Absorption of solute by active and passive means pro-

motes water absorption,8,71,74,75,79 and the flow of waterthrough the tight junction can act as a conduit, convey-

ing a heterogeneous sample of the intestinal contentsacross the intestinal mucosa by solvent drag.89,91

Therefore, absorption of both water and solute areclosely related, and each can assist the absorption of the

other.8,26 The factors that affect the rate of intestinal ab-sorption of water from ingested beverages are summa-

rized in Table 2.

Effect of intestinal flow rate on absorption

Because the normal pattern of gastric emptying of solu-

tions is not linear, the flow rate through the intestine isvariable. In the steady-state perfusion method, althoughthe rates of perfusion used (5–15 mL/min) are similar to

normal gastric emptying rates of liquids in humans, theflow rate is held constant. It is possible for individuals

to ingest beverages at a frequency and volume thatmaintains relatively constant rates of gastric emptying,

which can be used to calculate fluid and solute flux inthe proximal small intestine. However,92 this is not a

usual occurrence in life. Studies have shown that in-creasing the perfusion rate in the intestinal segment

produces greater absorption of water and solute; how-ever, this appears to be due to the increase in the abso-

lute solute load in the lumen rather than the greaterfluid volume.93

Effects of nutrient type and concentration onintestinal absorption

The major nutrient source in most beverages is carbo-

hydrate in the form of sucrose, glucose monomer,

maltodextrins, fructose, or cornstarch. Several studies

have shown that the rate of glucose absorption in thehuman jejunum appears to plateau as the glucose

monomer content in the lumen approaches about200 mmol/L.71,93 Although greater glucose monomer

concentrations are associated with luminal hypertonic-ity and reductions in water absorption, rates of glucose

absorption still tend to increase, at least up to a glucoseconcentration of around 555 mmol/L.91 It is thought

that the majority of glucose absorption up to the200-mmol/L concentration is due to the SGLT1, which

becomes fully saturated above this concentration.Thereafter, the more gradual increase in glucose ab-

sorption is caused by diffusion down the concentrationgradient and/or by solvent drag.91 Although glucose ab-

sorption tends to increase with increasing luminal con-centration, the main effect on glucose and water

absorption occurs with perfusion solutions that have aglucose content of approximately 200 mmol/L (i.e.,

3.6% glucose w/v).The substitution of disaccharides or maltodextrins

for equimolar amounts of glucose monomers has been

reported to increase glucose absorption.75,94 Whilemost hypotheses have stressed that this effect is due to

an improved rate of binding between SGLT1 and thehydrolysis products of maltodextrins, others have sug-

gested that membrane-bound digestion results in a highlocal concentration of glucose monomer from which

nonspecific paracellular absorption occurs. However, itis not a universal finding that glucose absorption is

faster from maltodextrins than from equivalent concen-trations of glucose monomers.68,95 Because solutions

containing maltodextrins have a lower osmolalitythan those of equivalent amounts of glucose monomer,

water uptake is usually reported as being faster from the

Table 2 Summary of the factors that affect the rate of intestinal absorption of water from ingested beveragesFactor EffectGastric emptying rate Fast rates of emptying increase intestinal absorptionOsmolality Water absorption rates are faster from moderately hypotonic beverages (200–260 mosmol/kg), but in the

duodenum marked hypotonicity may be more effective; hypertonicity retards water absorptionCarbohydrate content Active cotransport of glucose and sodium facilitates the absorption of glucose and promotes osmotic

gradients that support water absorption; facilitated transport of fructose is slower and is less effective insupporting water uptake; high concentrations of maltodextrins may assist absorption by producingrelatively lower beverage osmolality than would occur with the same glucose monomer content

Other activelytransported solutes

Actively transported amino acids, peptides, and organic acids that are linked with sodium absorptionpromote intestinal water uptake

Sodium concentration Intestinal sodium absorption is closely linked with water transport, but it is not clear if it is required inrehydration beverages, as sodium from the blood rapidly effluxes into lumen; no other ion has been shownto be as crucial for water absorption

pH It is unlikely that commercial beverage formulations will affect the pH buffering capacity of the intestine; anacidosis appears to enhance water and sodium absorption but not that of glucose

Temperature Because the stomach rapidly equilibrates the temperature of beverages, it is predicable that the luminalcontents are always at body temperature

Exercise Steady-state exercise levels below 70% VO2max have little effect on intestinal absorption of carbohydratesolutions; however, exercise-induced changes in perfusion of the capillary bed may interfere with isotopicwater tracers measured in the blood




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low-osmolality maltodextrin solution, and more carbo-

hydrate may be nonspecifically absorbed by solventdrag.91,96

Sucrose has been suggested as a disaccharide thatmay potentiate carbohydrate absorption because fruc-

tose, 1 of its 2 hydrolysis products, is absorbed by a fa-cilitated transport mechanism (GLUT5) that is notutilized for glucose uptake.68,97,98 Therefore, it is less

likely that the SGLT1 will become saturated and each ofthe 2 monosaccharides will not interfere with the ab-

sorption of the other. However, results from perfusionstudies that used sucrose or mixtures of glucose and

fructose have been equivocal on this issue. Total carbo-hydrate uptake from sucrose or the monosaccharide

mixtures tends to be similar to that from equimolaramounts of glucose monomer.94,96,97 One study, how-

ever, reported faster uptake from a glucose–fructosemixture than from an equivalent amount of either glu-

cose or sucrose.68 Some studies have shown that waterabsorption from sucrose solutions is slower than from

equimolar glucose solutions.96,99 This may result froman increase in luminal osmolality produced by an accu-

mulation of fructose (fructose is absorbed at about two-thirds the rate of an equivalent concentration of glu-

cose) or because GLUT5 does not cotransport sodium,resulting in less total solute absorption and a reduced

osmotic gradient. This is not a universal finding, how-ever, as others have reported faster water uptake from

sucrose solutions than from solutions with an equiva-lent amount of glucose.68

Effect of intestinal osmolality on absorption

In a fasted individual, the normal osmolality of the lu-

minal contents of the small intestine is usually be-tween 270 and 290 mosmol/kg, which is approximately

isotonic with human serum.26 Following ingestion offood and/or beverages, the osmolality of the duode-

num and jejunum changes in accordance with the os-molality of the gastric contents and the rate at whichthose contents are emptied into the small intestine.

Thereafter, luminal osmolality is eventually returnedto isotonicity due to the bidirectional movement of

water and electrolytes across the proximal intestine.After the luminal contents have been made isotonic,

they remain so during the remaining process ofabsorption.7

The time required to achieve isotonicity varies withthe osmolality and nutrient load of the gastric efflux.

For example, water is rapidly made isotonic within theduodenum and proximal jejunum by the influx of elec-

trolytes, whereas hypertonic beverages such as fruit jui-ces and soft drinks require a greater period of time and,

thereby, traverse a greater length of small intestine

before the luminal contents regain isotonicity. Solutions

with an osmolality of >290 mosmol/kg initially cause anet efflux of water from the body water pool into the in-

testinal lumen. The time required to achieve isotonicityreduces the rate of net water absorption as water efflux

increases in proportion to the level of hyperosmolalityof the luminal contents.100 Hypertonic solutions areeventually absorbed, but this occurs further down the

small intestine, after the solution has been made iso-tonic. This delay coupled with the initial net movement

of water from the circulation to dilute the luminal con-tents renders hypertonic solutions less effective in pro-

moting rapid rehydration than beverages with a lowerosmolality.101

Absorption of solute from isotonic solutions canproduce local osmotic gradients that are sufficient to

promote net water absorption from the intestinal lu-men. However, if the luminal contents have an osmolal-

ity of <270 mosmol/kg, water will follow the osmoticgradient and move from the lumen across the mucosa.

Hypotonicity of the luminal contents can be an additivefactor to that of solute absorption for promoting net

water absorption.63,68,71,102 Many studies have demon-strated that faster rates of water absorption occur in the

jejunum from hypotonic compared with isotonicCES.68,102,103 This would suggest that drinking water or

mineral waters that are markedly hypotonic (i.e., withan osmolality generally between 5 and 15 mosmol/kg)

would promote high rates of water absorption.However, water absorption is faster from isotonic CES

than from plain water in the jejunum.71,81 Water ab-sorption from plain water in the duodenum has been

reported as being more rapid than that from CES83,104

but slower than from CES in the jejunum.104 This same

group found that water absorption rates were fasterfrom plain water with an osmolality of about

30 mosmol/kg than from a hypotonic 6% carbohydratesolution entering the duodenum with an osmolality of

approximately 200 mosmol/kg, but the rates were simi-lar to those from a 4% carbohydrate solution with anosmolality of 260 mosmol/kg.105

In the absence of actively transported molecules(e.g., carbohydrates, amino acids), net sodium absorp-

tion from the duodenum and jejunum occurs onlywhen the luminal concentration of this cation is about

127 mmol/L.106,107 This is thought to be the main rea-son for the relatively poor rate of water absorption

from the infusion of plain water; the resulting effluxof electrolytes, mainly sodium, down concentration

gradients will cause some body water to cross the mu-cosa into the jejunal lumen,71 thereby reducing the

villous tip osmolality and, hence, the lumen-to-villiosmotic gradient.79 It has been proposed that it is the

reabsorption of previously secreted endogenous




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bicarbonate from the luminal contents linked with so-

dium cotransport that creates osmotic gradients suit-able for water absorption from plain water in the

jejunum.107 As such, water absorption from plain wa-ter is considered to be relatively slower than from CES

along the majority of the length of the proximal smallintestine.

Most studies have shown that both glucose solu-

tions and nutrient-free solutions with an osmolality of<200 mosmol/kg produce slower rates of water absorp-

tion in the jejunum than do similar solutions with an os-molality of between 200 and 260 mosmol/kg.108,109

Therefore, the most effective osmolality range for rehy-dration solutions appears to be relatively narrow because

even small differences in osmolality have marked effectson water absorption. For example, in one study in which

the total carbohydrate and sodium content of the perfu-sion solutions were similar, but osmolality differed, net

water absorption was about twice as fast from a moder-ately hypotonic (229 mosmol/kg) solution than from an

isotonic (277 mosmol/kg) solution, which was fasterthan from a moderately hypertonic (352 mosmol/kg) so-

lution110 (Figure 3).

Effect of electrolyte content on intestinal absorption

In the human jejunum, sodium is actively cotransported

with a variety of sugars, amino acids, peptides and py-rimidines, organic acids, and bile salts.71 Bicarbonate

ions promote sodium absorption in the jejunum by apH-independent, dual-coupled antiport system that in-

volves chloride and hydrogen ions.77 Because of the es-sential role of sodium in active nutrient transport and

water absorption, it has been thought necessary to have

it included in oral rehydration solutions used to replace

fecal losses in diarrheal disease.8,21 However, because so-dium from the blood rapidly effluxes into the proximal

small intestine, it has been argued that exogenous so-dium is not required to activate nutrient transporters.

Perfusion studies have shown that the exclusion of so-dium from glucose solutions does not have amarked detrimental effect on water absorption.111

Nevertheless, substitution of mannitol or magnesium forsodium results in 23% and 45% reductions in glucose up-

take, respectively.112 In addition, enhanced carbohydrateabsorption from maltose and maltodextrin solutions has

been associated with luminal sodium concentrations of>100 mmol/L.94

The other major electrolytes of the body (e.g.,potassium, magnesium, calcium) are absorbed down

electrochemical gradients or by carrier-mediated pro-cesses.77 The inclusion of electrolytes in rehydration so-

lutions increases the osmolality of the solution and,with the exception of sodium, the presence of electro-

lytes does not enhance water absorption. Most studiesthat have investigated the effect of sodium on water ab-

sorption have used chloride as the accompanying anion.Nevertheless, other anions such as acetate or citrate can

enhance water absorption from glucose–sodium solu-tions.113 In all of these studies, however, the major an-

ion in the intestinal lumen was chloride. For reasons ofpalatability, chloride is probably the anion of choice in

beverages that contain sodium.

Effect of beverage temperature on intestinalabsorption

The stomach rapidly equilibrates the temperature of in-gested beverages to approximate internal body tempera-

ture.56,57 Consequently, it is unlikely that significantamounts of markedly hot or cold fluid are emptied into

the duodenum.

Effect of beverage pH on intestinal absorption

Several studies in animals have examined the effect of

alterations in acid–base balance on water and solute ab-sorption in the small intestine; changes in intestinal lu-

minal pH are known to affect mucosal ion transport.114

Little work has been carried out in humans, in one

study, perfusing the jejunum with a CES containing23 mmol/L bicarbonate produced a mean luminal pH of

6.6, which was higher than that produced when tartratewas used.115 Water and glucose absorption was

faster from the bicarbonate solution than from the tar-trate.115 However, it is unclear from this study whether

the improved absorption rates were due directly to

0

2

4

6

8

10

12

14

Hypotonic CES Isotonic CES Hypertonic CES

Figure 3 Net water absorption (median [range] in the 30-cm je-junal test segment from 3 CESs with the same carbohydrateand electrolyte concentrations but differing in osmolality).Abbreviation: CES, carbohydrate–electrolyte solution. Reproducedfrom Leiper et al.96 with permission.




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bicarbonate uptake that enhanced intestinal transport

or to a buffering effect that increased active absorptionof glucose.

Most commercial beverages are acidic, in part, toextend their shelf life and to improve their palatability.6

However, these beverages have little buffering capacity,and the pH of the intestinal luminal contents is proba-

bly little affected by the levels of acidity present in mostbeverages.

Effect of exercise on intestinal absorption

Few studies have investigated the effect of exercise on

intestinal absorption. This is largely due to the practicaldifficulties associated with perfusing the small intestinein individuals who are exercising. In an early study,

treadmill exercise at 70% of VO2max was shown to haveno discernible effect on intestinal absorption of water

or solute.116 Another investigation found no differencein absorption rates between rest and moderate cycle ex-

ercise (30–70% VO2max) from either water or a CES.81

In a series of studies using a triple lumen perfusion

model sited in the duodeno–jejunum, with gastric emp-tying controlled at a steady rate, the effects of beverage

osmolality, sodium concentration, and carbohydratecontent on fluid absorption during constant load cycle

exercise at or below 70% VO2 max was investigated.These studies indicated that net water absorption was

fastest in the duodenum from plain water than from

any of the three 6% CES tested. However, over the en-

tire 50 cm of perfused intestinal segment, no differencesin water uptake could be detected among plain

water and hypotonic, isotonic, or hypertonic CES.104

Increasing the sodium concentration over the range

0–50 mmol/L in 6% carbohydrate beverages failed toimprove water uptake, but luminal sodium concentra-

tion increased markedly along the length of perfusedsegment.115 In exercising individuals who were previ-

ously hypohydrated by 2.7%, net water uptake was fast-est from plain water and an isotonic 6% carbohydrate

solution compared with a hypertonic 8% carbohydratesolution, which was greater than from a hypertonic 9%

carbohydrate solution.117 While the gastric emptyingrate of all solutions was fixed, which is not what wouldhave been expected to happen if the beverages had been

normally ingested, the same group of investigatorsshowed that individuals can repeatedly ingest carbohy-

drate beverages in quantities that maintain gastric emp-tying rates at a relatively fixed rate similar to that used

in perfusion studies.92

Using a water tracer technique, the accumulation

rate of the isotopic label in the circulation decreased inproportion to exercise intensity (40%–80% VO2max),

and the time to peak tracer concentration in the bloodwas longer with increasing exercise intensities118

(Figure 4). These results suggest a decreased availabilityof ingested fluids during exercise; however, whether

this was due to changes in intestinal absorption or

0

50

100

150

200

250

300

350

1 6 11 16 21 26 31Time (min)

Rest 42% Vo2max61% Vo2max80% Vo2max

0 5 10 15 20 25 30

Figure 4 Plasma deuterium accumulation at rest and during exercise at 42%, 61%, or 80% VO2max after ingestion of the same carbo-hydrate–electrolyte solution containing deuterium oxide. Reproduced from Lambert et al.130 with permission.




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perfusion of the splanchnic vascular bed could not be

ascertained.118 It is likely that intermittent high-inten-sity sprinting will reduce absorption to at least the same

extent as it affects gastric emptying.30,69,70

INTEGRATION OF MEASURES OF GASTRIC EMPTYINGAND INTESTINAL ABSORPTION

Several studies have directly measured both gastricemptying and intestinal absorption rates separately and

have derived estimates of the relative importance ofeach in determining the incorporation of beverage con-

stituents in the body water pools.92,116 These studies arerather artificial as the conditions of the model are never

likely to occur naturally in the gastrointestinal tract, yetthey have produced important basic information re-

garding factors that affect intestinal absorption of in-gested solutions.

Isotopic tracers were used in perfusion studies in

the early 1960s to differentiate the effects of the bidirec-tional fluxes of water and sodium on the specific rates

of the net absorption of each.119 Although the isotopicwater tracer technique does not determine net rates of

gastric emptying and/or intestinal fluid absorption,comparison of the unidirectional flux of the tracer ap-

pears to give a measure of the relative rates of absorp-tion from different beverages.8 In addition, this

technique has demonstrated differences among bever-ages that reflect the known combined gastric emptying

and intestinal absorption patterns of those bever-ages.8,55,120,121 While some investigations have cast

doubt on the usefulness of the isotopic technique forcomparing water uptake from beverages,122,123 the dis-

parities in the studies’ findings have been explained bytechnical difficulties in the respective experimental

protocols.24

USE OF ISOTOPIC TRACERS TO ASSESS UPTAKE OFWATER FROM THE GASTROINTESTINAL TRACT INTO

THE BODY WATER POOLS

The stable isotope deuterium oxide (2H2O) and the ra-

dioactive isotope tritium oxide appear to be appropriatetracers for water124,125 and have been used in studies

that investigated the total body water content, body wa-ter turnover, water exchange between tissues,124,125 and

water availability from ingested beverages.8,120,121,126–128

Tritium oxide is radioactive, and its use raises health is-

sues. However, it can be utilized in small doses, and ithas a biological half-life of 7–14 days in the human

body.125 The stable isotope oxygen-18 has also beenused to determine total body water in humans129; it

could be used to assess water uptake from the

gastrointestinal tract, and it has the advantage that it

can be detected in breath samples.129

These tracers are easily incorporated into bever-

ages, are tasteless and odorless, and are distributed intothe body water pools from ingested beverages at a rate

that is comparable to water. The volume of test beverageconsumed in investigations can be similar to that usu-ally ingested by euhydrated individuals.55,130

LIMITATIONS OF WATER TRACER METHODOLOGY

Measurement of 2H2O by mass spectrometry has a sen-

sitivity of approximately 0.2 ppm131 and a cv of <2%.132

Determination by infrared spectrometry can reliably

detect differences of �10 ppm and a cv of 4.8%.17

Between-subject variance in deuterium (2H) accumula-

tion rates in the circulation from an ingested CES was38% measured by mass spectrometry132 and 40% by in-

frared spectrometry.130 Power analysis indicates that fora sample size of 10 individuals, there is an 80% chance

of identifying a real difference in water absorption ratesonly when the fluid absorption characteristics of the

beverages differ by �35%. Quantification of the tritiumtracer can be made using liquid scintillation counters,

with assay sensitivity similar to that of mass spectrome-try. The radioactive dose received by individuals can be

maintained within normal background radiationlevels.125

Several methods have been used to model the ab-sorption of water tracers from ingested solutions. In

many studies investigating unidirectional 2H fluxes, thetemporal appearance of the tracer in the circulation

over the whole of the sampling period has been incor-porated into the comparison.120,123,126–128 Davis

et al.120,127,128 used blood 2H enrichment area-under-the-curve (AUC) profiles produced by their different

test beverages sampled over 180 min post-ingestion.While they found that the 2H AUC was less for bever-

ages containing 40% and 15% glucose than from hypo-tonic saline or a 6% glucose solution, they could notidentify differences between the 2 beverages with the

highest levels of carbohydrate nor between the salineand the 6% glucose solution. Currell et al.126 demon-

strated a smaller AUC following ingestion of a 6% glu-cose beverage compared with that from water or a 6%

glucose–fructose solution. This group also showed thatthe 2H AUC was greater from a 3% glucose solution

than from water, which was greater than from a 6% or a9% glucose solution.133 The addition of sodium (range

0–60 mmol/L) to a 6% glucose solution did not notice-ably affect the enrichment curve.133 In another study,

no differences in 2H AUC profiles were found betweenwater and 4 different CESs containing various carbohy-

drates ranging in concentration from 6% to 8%.127




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The use of the AUC measure, which can include a dis-

proportionally large section of the dissipation and equil-ibration phases of the tracer contained in the ingested

beverages, is likely to decrease the sensitivity of compar-isons of absorption rates between solutions (Figure 5).

A more rational comparison for evaluating water ab-sorption rates from ingested beverages would appear to

be the accumulation slope to peak concentration of thetracer in the circulation.8

The slope of the 2H accumulation rate in the circu-lation to time to peak enrichment (Tmax), calculated by

linear regression from samples collected before and af-ter ingestion of the test beverages, was found to be faster

following consumption of a 3.6% CES than from wa-ter.132 However, no differences were detected in AUC

enrichment post-ingestion or in peak concentration be-tween the 2 solutions. Using the same measure, 2H en-

richment in the circulation was faster from diluteglucose solutions than from fructose solutions with the

same carbohydrate concentration,134 and from a 2%glucose solution compared with a 10% glucose solu-

tion.135 The use of the parameters Tmax, Pmax, and rateof deuterium accumulation to Tmax, appear to ade-quately model the known gastric emptying and

intestinal absorption rates of most of the carbohydrate

solutions tested to date.28

CONCLUSION

The volume of fluid ingested for rehydration is essential

in determining the restoration of euhydration.However, the formulation of beverages is also important

as it affects the rate at which the beverage’s water con-tent enters the body water pool and, hence, its effect onthe hydration status of an individual. Because there is

no net absorption of water in the stomach, the gastricemptying and small intestinal absorption rates of con-

sumed beverages critically affect the speed at which theaqueous portion of a beverage is assimilated into the

body. Both a high volume and a low energy content of abeverage improve the rate of gastric emptying. Low os-

molality also speeds emptying from the stomach; never-theless, it is energy density that has the greater effect.

Water is rapidly emptied, but 2%–4% glucose solutionsappear to leave the stomach just as quickly. Net water

uptake from the proximal intestinal lumen occurs alongosmotic gradients that are promoted by the absorption

of solute. The active cotransport of glucose and amino

0

50

100

150

200

250

300

1 6 11 16 21 26 31 360 30 60 90 120 150 180 210Time (min)

Peak of 2H enrichment in the circulation (Cmax)

(Influx = Eflux)

Initial rapid rate of 2H appearance inthe circulation - (Influx > Efflux)

2H dispersal into the body water pool - (Influx < Efflux)

Region where 2H has effectively equilibrated with the Total Body Water pool

Tmax

2H accumulation rate to Cmax in the circulation

Area under the curve (AUC).180 min

Ingestion of labelled drink

Figure 5 Typical plasma deuterium enrichment curve following ingestion of a dilute carbohydrate–electrolyte solution labelled withthe tracer. Influx is the net movement of deuterium from the small intestine into the circulation. Efflux is the movement of deuterium fromthe circulation into the extravascular water pools.




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acids with sodium enhances water absorption.

Moderate hypotonicity of the luminal contents en-hances water absorption.

Measurement of gastric emptying rates of solu-tions indicates between-subject variability to be about

30%, while within-subject variability is <10%.Intestinal perfusion techniques that bypass the stom-ach have between-subject variability levels of approxi-

mately 22% and within-subject variability of �12%.Whether it is learned responses based on the dietary

habits of the individual or the individual’s geneticmakeup that determines the specific gastric emptying

and intestinal absorption rates is, at present, un-known. The mechanisms that establish the relatively

small within-subject variance compared with that ofbetween-subject variance requires further research.

Studies have been carried out using a combination ofgastric emptying and intestinal perfusion to try to de-

termine overall rates of water assimilation from bever-ages. Although each of these techniques is rather

artificial, they have produced important basic infor-mation regarding factors that affect absorption of in-

gested solutions. The unidirectional accumulation rateof isotopic water tracers into body fluids broadly fol-

lows the pattern of the integrated effects of gastricemptying and intestinal absorption of these labeled

beverages.Further research is needed to identify the interac-

tion of neurotransmitters and hormone responses fol-lowing consumption of beverages and their relative

influence on the control of net absorption of water andsolute from ingested solutions.

Acknowledgments

The author thanks the staff of the European Hydration

Institute for their hard work in setting up and runningthe Workshop on Human Hydration, Health and

Performance.

Funding. J.B.L was contracted and funded by the

European Hydration Institute. He received financial re-imbursement for travel and accommodation expenses

and an honorarium from the European HydrationInstitute for his participation in the conference and for

writing this manuscript.

Declaration of interest. The author has no relevant inter-ests to declare.

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