AUGMENTATION OF ETHANOL ABSORPTION BY MONO- AND DISACCHARIDES

GASTROENTEROLOGY 7:111-117,1976 Cpyright 1976 by The Williams & Wilkins C. Vl. 7, N.6 Printed in U.S.A. AUGMENTATION OF ETHANOL ABSORPTION BY MONO- AND DISACCHARIDES SELWYN A. BROITMAN, Ph.D., LEONARD S. GOTTLIEB, M.D., M.P.H., AND JOSEPH J. VITALE, Sc.D., M.D. Departments f Micrbilgy and Pathlgy, Bstn University Schl f Medicine and Nutritin-Pathlgy Unit, Mallry Institute f Pathlgy, Bstn City Hspital, Bstn, Massachusetts Assessment f the influence f nutritinal substrates n the dispsitin f ingested ethanl frm the bld requires, first, an understanding f the influence that these may exert upn ethanl absrptin frm the gastrintestinal tract. In this reprt, the effects f varius carbhydrates n the intestinal absrptin f ethanl were studied. When carbhydrates (5 mm) were perfused simultaneusly with ethanl (5 mm) in viv in the rat small bwel, ethanl absrptin increased up t 34% (P <.5) abve cntrls receiving ethanl alne. Of the mnsaccharides, fructse, 3--methylglucse, glucse, r galactse added t an ethanl perfusate, nly glucse r galactse increased ethanl absrptin ver cntrl animals receiving ethanl alne. Of the disaccharides tested, sucrse and maltse, but nt lactse, enhanced ethanl absrptin. Additin f varying cncentratins f maltse t an ethanl perfusate augmented ethanl absrptin in a direct prprtin t the quantity f glucse absrbed, rather than t the quantity f maltse hydrlyzed. Augmentatin f ethanl absrptin by carbhydrates appears t be dependent upn sugar-active transprt. Ethanl, disslved in intraluminal water, may crss the mucsa in water absrbed during sugar-active transprt. This quantity f ethanl is absrbed in additin t that which nrmally crsses the mucsa by diffusin dwn its cncentratin gradient. It is well appreciated that alchl taken with fd is better tlerated than when taken alne. 1 Althugh the mechanisms invlved have nt been ttally clarified, there is sme general agreement that at least ne mechanism invlves the effect ffd n delaying gastric emptying. In this regard, all majr fd cnstituents, fats, prteins, and carbhydrates exert similar effects. 2-6 After ingestin f alchl and fd simultaneusly-r separately with a shrt time span between-the peak bld alchf r urine alchls level is significantly lwer than when alchl alne is ingested. This peak, accrding t mst studies, als ccurs mre rapidly when alchl is taken with fd. Since this early wrk, little effrt has been directed t systematic studies cncerned with the relatinships f fd cnstituents t the intesti- Received June 12, 1975. Accepted December 11, 1975. This paper was presented in part at the American Sciety fr Clinical Nutritin's 13th Annual Meeting, April 29, 1973, Atlantic City, New Jersey. Address requests fr reprints t Dr. S. A. Britman, Department f Micrbilgy, Bstn University Schl f Medicine, Bstn, MA 2118. This study was supprted by Cntract HSM-42-72-195 with the Natinal Institute n Alchl Abuse and Alchlism. The authrs wuld like t acknwledge the skilled technical assistance f Ms. Maureen L. Kelly and Rberta M. 'Tawell and Messrs. Paul L. Cln and Gary Lucas. Their appreciatin is extended t Dr. Steven Shenker, Vanderbilt University, fr his cgent critique and suggestins and t Dr. T. Hastings Wilsn, Harvard Medical Schl, fr his helpful discussins f this wrk. nal absrptin f ethanl. Perhaps a deterrent t interest in this area has been the assumptin that mst ingested ethanl is absrbed in the stmach. Hwever, recent studies indicated 9, 1 that after ethanl ingestin, a significant prtin is absrbed in the small bwel. Thus, nutrients absrbed simultaneusly with ethanl may in sme manner effect ethanl absrptin. This reprt shws that certain carbhydrates may indeed augment the intestinal absrptin f ethanl. 111 Materials and Methds An in viv small bwel perfusin system described by Shanker et al. 11 was used. Charles River rats weighing between 325 ± 25 g (except where nted) were fed Purina Lab Chw and maintained in a cnstant temperature animal f<trm at 7 ± 1 F. Rats were fasted 48 hr, but allwed water ad libitum. They were anesthetized with pentthal (5 mg per 1 g bdy weight), a midline abdminal incisin was made, and the small bwel was visualized. Ligatures were placed at the pylrus and ilececal valve; tw small transverse incisins were made in the bwel-distal t the tie at the pylrus and just prximal t the tie at the ilececal valve-and plyethylene cannulas were inserted int the dudenum and terminal ileum and tied securely in place. The prximal cannula was cnnected t a cnstant delivery Sigmamtr pump and the distal cannula was allwed t drain int a cllectin flask. A duble istpe intestinal perfusin technique described belw was adapted fr these studies. Pumps, perfusates, rats, and effluent cllectin vessels were all hused in a 37 C incubatr. Perfusates t assess the absrptin f ethanl alne cntained 5 t 4 mm ethanl and 2% plyethylene glycl

112 BROITMAN ET' AL. Vl. 7, N.6 (PEG), a nn absrbable marker, t mnitr water flux. 12 The influence f varius carbhydrates (fructse, 3--methylglucse, glucse, galactse, lactse, sucrse, and maltse) n ethanl absrptin was determined by adding each f these at 5 mm cncentratins t perfusates cntaining 5 mm ethanl and 2% PEG. With the exceptin f the 4 mm ethanl perfusate, all were adjusted t 3 millismles per liter with sdium chlride. Included als were trace quantities f l-hcethanl with a specific acitivity f.4 mc per mm and 2,3-3 H-PEG with a specific activity f.61 mc per g (New England Nuclear, Bstn, Mass.). Each was diluted t apprximately 4 dpm per ml f perfusate. Ethanl purity was greater than 98% as determined by gas liquid chrmatgraphy using tw clumns, a carbwax 4 r Durapak at 1 C and 21 % PEG-6 at 1 C. The 1,2-3 H-PEG marker was free f small mlecular weight cntaminants. Recvery after dialysis in Visking dialyzing bags against distilled water fr 12 hr was greater than 99%. Additinally, recvery f bth dialyzed and nndialyzed 1,2-3 H-PEG after intestinal perfusin f rats with saline r distilled water cntaining 2% PEG was apprximately 98%. Perfusates were pumped thrugh the small bwel at 1.5 ml per min. After a 3-min wash and equilibratin perid (except when nted), the effluent was cllected at 1-min intervals fr 6 min. One-milliliter aliquts, in duplicate, were added t 14 ml f scintillatin fluid cntaining 1 g f naphthalene and 5 g f PPO in a liter f l,4-dixane t which was added 2 ml f Tritn-Xl. Samples were assayed fr l4c and 3H in a Beckman 2 BL liquid scintillatin cunter. T crrect fr spillage f l4c cunts in the 3H channel, a quench curve was prepared in which the 14C ethanl cunts equivalent t the initial perfusate were serially quenched with CCl. (.1 ml t 1. ml). The rati f 14C cunts appearing in the 14C channel was crrelated with the S value. By utilizing this standard quench curve, S values btained with experimental perfusate and effluent samples cntaining bth 3H and l4c enabled the calculatin f the quantity f 14C cunts detected in the 3H channel. Apprpriate crrectins were then made fr each sample. It was unnecessary t crrect fr 3H spillage int the l4c channel, because this was a negligible quantity. Each lo-min effluent sample was crrected fr net water flux n the basis f dilutin r cncentratin f the 3H-PEG marker, and the quantity f ethanl absrbed was determined. A mean value was btained frm the six 1-min cllectins fr each animal and the results are expressed in terms f the quantity f ethanl absrbed per hur. Initially, estimates f the quantities f ethanl and PEG in perfusates and effluent samples btained by istpic assay were cmpared with the enzymatic assay (ADH) 13 fr ethanl and the chemical assay fr PEG. 14 Gd agreement was btained between each set f assay prcedures. Except where nted, the istpic prcedure was used thrughut. Maltse hydrlysis and absrptin was determined using the same in viv perfusin system described abve. Perfusates cntained 5, 1, r 25 mm maltse with r withut 5 mm ethanl and 2% PEG. All perfusates were adjusted t 3 millismles per liter with NaCl. 3H-PEG (as abve) and Ul4C-maltse (I.C.N., Cleveland, Ohi), specific activity.42 mc per mm, were added in trace quantities t yield apprximately 4 dpm per ml each f perfusate. Purity f U l4 C-maltse was assessed by paper chrmatgraphy utilizing tw slvent systems, BuOH:HAC:H2 and BuOH:EtOH:H2, and fund t be free f glucse r ther impurities. The ttal quantity f maltse which had been absrbed was determined frm the disappearance f the istpe frm the perfusate and crrected n the basis f the vlume indicatr, 3H-PEG. The quantity f maltse hydrlyzed, but remaining in the perfusate, was determined by enzymatic assay f glucse by the glucstat methd. 16 The quantity f maltse hydrlyzed, as determined enzymatically, was subtracted frm the apparent quantity f maltse in the perfusate assessed by istpic assay t yield the quantity f maltse remaining in the perfusate. All these values were crrected n the basis f dilutin r cncentratin f the 3H-PEG marker. Alchl absrptin in these studies was assessed by determinatin f the quantity f ethanl disappearing frm the perfusate by enzymatic assay (ADH) 15 and crrected als fr vlume changes n the basis f 3H-PEG. As a mrphlgical cntrl, the small bwel was immediately remved frm animals representative f each f the,varius grups after the 9-min perfusin and pened alng the line f the mesenteric attachment, rlled in a spl, fixed in frmalin, and stained with hematxylin and esin. Animals perfused with saline fr the same time perid were used as additinal cntrls. Results Figure 1 illustrates the intestinal absrptin f ethanl frm perfusates cntaining varius cncentratins f ethanl. With 4 mm ethanl perfusates, apprximately 3 mmles f ethanl were absrbed during the initial IO-min interval. Ethanl absrptin remained at this level fr the first 3 min, but decreased prgressively ver the duratin f the perfusin. A similar finding was nted when 2 mm ethanl was perfused. With 1 mm ethanl slutin, ethanl absrptin apprached steady state. At 5 mm ethanl cncentratin, the quantity f ethanl absrbed,.4 mmles per 1 min, remained at a steady state thrughut the duratin f the perfusin. Cnsequently, this cncentratin was used in the test perfusate in the remainder f the study. Histlgical sectins prepared fr light and electrn 3.5 3. en 2.5 UJ I- :> z 2 Q 2. " UJ III a: 1.5 III <t II) 1. I:) e.5 _--", '..",-" '\,, \ '1.."..._..._-...-_...- ( ) N. OF ANIMALS "-----. 4mM(4) 2mM(5) IOOmM(4).-... ------------ 5mM(l) 2 4 6 e 1 TIME IN MINUTES FIG. 1. Intestinal absrptin f ethanl frm perfusates cntaining varying cncentratins f ethanl. Results are expressed in lo-min intervals after a 2-min wash and equilibratin perid.

June 1976 CARBOHYDRATES AND ETHANOL ABSORPTION micrscpy examinatin frm animals perfused with 4 mm ethanl slutins fr 9 min revealed significant mrphlgical alteratin. These changes resemble thse reprted by Barna et al. 16 after intra gastric intubatin f 2% ethanl in the rat, and were assciated with the hypertnicity f the slutin. Similar findings, but t a lesser degree, were bserved in rats perfused with 2 mm ethanl (fig. 2). The brush brder and clumnar epithelial cells were intact and appeared nrmal. Dilatin f endthelial-lined vessels within the lamina prpria f the villi was als nted and was cnsidered t be cnsistent with the ccurrence f fluid absrptin. Ethanl absrptin frm perfusates f 5 t 4 mm ethanl, based nly n the first 3 min f perfusin, were reasnably cnstant. In ther rats perfused fr this time perid at these cncentratins f ethanl, minimal histlgical abnrmalities were nted. Values are pltted in figure 3. As ethanl cncentratin was increased frm 5 t 4 mm, the quantity f ethanl absrbed increased prprtinately and is cnsistent with the ft-reprted finding that ethanl absrptin ccurs by a diffusinal prcess. Because ethanl is freely diffusable thrughut tissue 113 fluids, animal size has an effect n the quantity f ethanl absrbed using this in viv intestinal perfusin technique. T define this relatinship fr the purpses f this study, rats weighing between 125 and 525 g were perfused with 5 mm ethanl and the rate f ethanl absrptin was determined. Abslute quantities f ethanl absrbed increased with bdy weight. Because bdy mass influences the absrptin f ethanl, individual animals selected fr the rest f these studies were cnfined t a relatively narrw weight range f 325 ± 25 g after fasting 48 hr. Weight variatins between grups f animals were maintained at less than 5 g. Results f absrptin fr the remainder f these studies are expressed as the quantity f ethanl absrbed per animal ver a given time perid. Figure 4 illustrates the influence f mn- and disaccharides n ethanl absrptin. In these studies, the 5 mm ethanl perfusate was supplemented with 5 mm f each f the varius carbhydrates depicted. Frm a cntrl vlaue f 2.45 mmles f ethanl absrbed per hr per animal, glucse, sucrse, galactse, and maltse augmented ethanl absrptin frm 18 t 33%. Althugh values btained with these sugars were significantly FIG. 2. A, lw pwer view f dudenum f rat receiving 5 mm ethanl perfusate adjusted t 3 millismles per liter. Mucsa appears nrmal. Lymphatic vessels f lamina prpria are prminent. H & E. x 1. B. dudenum f rat receiving 2 rm ethanl perfusate adjusted t 3 millismles per liter. Sme villus tips shw exfliatin f lining cells. Sme lymphatic channels are cllapsed. H & E. x 1. C, dudenum f rat receiving 4 mm ethanl perfusate. Villus tips all shw marked exfliatin f epithelial cells. Lymphatics are nt evident. H & E. x 1. D. high pwer f fig. 2 C. shwing exfliatin f villus tips. H & E. x 3.

114 BROITMAN ET AL. Vl. 7, N. 6 Vl ILl I- :;) 3. (4) 2.5 2. z :::E Q "- Cl 1.5 ILl m a: Vl m 1... <I WI " E E.5 ( ) N. OF ANIMALS 35 9 MINUTES ** 3 25 2 * 15 *PCO.OI 1 **PCO.3 5... 6 MINUTES E 1l 1111111 MEAN ts.e. :I: I- w rfl 2 3 MINUTES N. OF ANIMALS 15 ( ) 1 1 2 3 4 ETHANOL CONCENTRATION IN mm FIG. 3. Influence f cncentratin n intestinal absrptin f ethanl in rats perfused with 5 t 4 mm ethanl slutins. Pints shwn are the means ± standard errrs f the means. Values shwn are thse frm figure 1 and represent ethanl absrptin during the first 3 min nly, after a 2-min wash and equilibratin perid. 4l 3 UJ<L (f)a: "': ::! l3 2 "': I at!? w 1 z 4. a: I "- 3. UJ CD a: (f) 2. CD...: I g 1. w III G> C C * * P>.5 MEAN S.E. N. OF ANIMALS ( ) FIG. 4. Influence f mn- and disaccharides n ethanl absrptin. Cntrl perfusate cntained 5 mm ethanl; test perfusates cntained 5 mm ethanl and 5 mm f each carbhydrate listed; all perfusates were adjusted t 3 mijiismles per liter with sdium chlride. different frm cntrls (P <.5), nly the value btained with maltse was significantly different frm the ther three carbhydrates (P <.5). Bld ethanl levels after intestinal perfusin with the varius carbhydrates are shwn in figure 5. In cntrl animals, bld ethanl levels were apprximately 5, 16, and 25 mg per 1 ml at 3, 6, and 9 min after the start f the perfusin. Althugh glucse, sucrse, galactse, FIG. 5. Bld ethanl levels 3, 6, and 9 min after intestinal perfusin f ethanl with varius carbhydrates. Tail bld frm rats used in figure 5 was taken fr bld ethanl levels at the varius time intervals depicted. and maltse augmented the intestinal absrptin f ethanl, nly galactse was assciated with an increase in bld ethanl abve cntrl levels. Of the remaining carbhydrates, which had n significant effect n ethanl absrptin, 3--methylglucse and lactse had n effect n bld ethanl levels, whereas fructse was assciated with bld ethanl levels lwer than cntrls at 9 min. The relatinship f augmentatin f ethanl absrptin t the quantity f water absrbed r lst (net water flux) during the perfusin f ethanl with varius carbhydrates is depicted in figure 6. The crrelatin cefficient f.94 (P <.1) implies that the ability f the varius carbhydrates t augment ethanl absrptin is related t the ability f that sugar t prmte water absrptin. Because maltse was mre effective than actively transprted mnsaccharides in augmenting the intestinal absrptin f ethanl, it was f interest t determine whether maltse hydrlysis, per se, influenced ethanl absrptin. By adding varying cncentratins f maltse, 2 mm t 25 mm, t a 5 mm ethanl perfusate, it was pssible t demnstrate a dse-respnse relatinship f the ability f maltse t augment ethanl absrptin (fig. 7). By measuring maltse hydrlysis and glucse absrptin under these cnditins, it was bserved that augmentatin f ethanl absrptin was directly related t the quantity f glucse absrbed, rather than t maltse hydrlysis per se. There was n evidence that unhydrlyzed maltse was absrbed and/r excreted in the urine under the cnditins f the experiment. Discussin Enhanced ethanl absrptin was bserved when carbhydrates were administered simultaneusly with

June 1976 CARBOHYDRA TES AND ETHANOL ABSORPTION n5 6 _I I/) I/), FRUCTOSE...J...J- y =.18 x -.37 r =.935 t MEAN! S.E.M. L- w % INCREASE IN ETHANOL ABSORPTION FIG. 6. Relatinship between net water flux and augmentatin f ethanl absrptin by carbhydrates. Six rats per grup were perfused with 5 mm ethanl alne (cntrl) r 5 mm ethanl and 5 mm f each carbhydrate shwn. All perfusates were adjusted t 3 millismles per liter with sdium chlride. ethanl in an in viv small bwel perfusin system in the rat. When mnsaccharides, fructse, 3--methylglucse, glucse, r galactse were added t an ethanl perfusate, nly glucse r galactse increased ethanl absrptin ver the absrptin in cntrl animals receiving ethanl alne. Of the disaccharides tested, maltse and sucrse, but nt lactse, enhanced ethanl absrptin. - It is suggested that the augmentatin f ethanl absrptin by carbhydrates is dependent upn sugaractive transprt. Glucse r galactse alne, r glucse derived frm disaccharide hydrlysis, is transprted by its sdium-dependent carrier against the cncentratin gradient. 17. 18 As a result f the increased cncentratin f glucse in the cell r within the intercellular spaces, the smtic pressure increases, activating the bulk flw f water acrss the mucsa. As bulk flw f water ccurs, water-sluble electrlytes and nn electrlytes f small mlecular diameter disslved in the intraluminal water are carried acrss the mucsa by slvent drag. Ethanl disslved in the intraluminal water als enters in a manner analagus t that f ther nnelectrlytes. As substrate cncentratin is increased (within physilgical limits), the flw f bulk water and the frce f slvent drag increase the augmentatin f ethanl absrptin prprtinately. Thus, fructse, which des nt participate in the sugar-active transprt f ther hexses tested, is nt assciated with enhanced ethanl absrptin frm the bwel when perfused simultaneusly. 4 r - - - - - - - - - - - - - - - - - - - - - - i=!l. :: 3 «:J: W 2 Z W (/) :: U Z * O 1 +MEAN!S.E. MALTOSE (hyd) GLUCOSE (abs)...j- L- -J 2 4 6 8 1 MALTOSE HYDROLYZED (J'mles Ihr) GLUCOSE ABSORBED (J'mles/hr) FIG. 7. Relatinship f increased ethanl absrptin t maltse hydrlysis and glucse absrptin. Three rats in each grup were perfused with 5 mm ethanl alne r with 5 mm ethanl and 5, 1, r 25 rnm maltse. All perfusates were adjusted t 3 millismles per liter with sdium chlride. 3--Methylglucse is transprted actively, but prlyl9 relative t glucse. Its slwer rate f transprt (reflected als in part by relatively lw net water flux) may be inadequate t prvide significant augmentatin f ethanl absrptin. Of the carbhydrates evaluated, maltse was mst effective in augmenting ethanl absrptin frm the small bwel. This may relate t the fact that the hydrlytic activity f maltase in the rat gut, fr its respective substrates, is greater than sucrase r lactase 2 fr each f their respective substrates. Cnsequently, it is likely that maltse, upn hydrlysis, yields a greater quantity f actively transprted hexse than either f the ther disaccharides. Furthermre, maltse was mre effective than the same cncentratin f glucse in augmenting ethanl absrptin. An explanatin fr this finding is nt readily apparent since maltse hydrlysis, at the cncentratins used, apprached but did nt exceed 5% f the perfused substrate-when administered with ethanl. Cnsequently, the luminal cncentratin f glucse derived frm maltse was less when the same cncentratin f glucse was perfused. Given the same cncentratin f maltse r glucse perfused with ethanl, it is pssible that the frmer delivers a greater cncentratin f glucse lcally at the brush brder during maltse hydrlysis. Such an event culd be accmpanied by a relative increase in bulk water flw, and with it, greater augmentatin f ethanl absrptin than that ccurring frm an ethanl-glucse perfusate f the same cncentratin. Althugh net water flux frm the lumen is greater frm an ethanl-maltse perfusate than frm an ethanl-glucse perfusate, n evidence cncerning differences in bulk water flw r glucse cncentratin at the brush brder frm either perfusate is available frm these studies t substantiate this cnsideratin. The failure f lactse t stimulate ethanl absrptin may be due t the lw hydrlytic activity f lactase in the rat gut fr its substrate, relative t the hydrlytic activity

116 BROITMAN ET AL. Vl. 7, N.6 f the ther disaccharidases fr each f their respective substrates. 2 Althugh n attempt was made t assess lactse hydrlysis, and subsequent hexse absrptin, it is pssible that insufficient hydrlysis ccurred t prvide ample quantities f hexses t elicit a stimulatry effect upn ethanl absrptin. A clse crrelatin was nted between the ability f a given c a r b h t y dprmte r a t net water flux frm the small bwel and its ability t augment ethanl absrptin. Hwever, standard errrs f the means f pints expressing net water flux exhibited wide variatins, while thse depicting the percentage increase in ethanl absrptin tended t be reasnably cnfined t the mean values. Variatins abut the frmer are nt the result f methdlgical prcedures, because the same vlume marker was used in calculating ethanl absrptin. It is likely, but nt prven, that the ability f these sugars t augment ethanl absrptin is mre clsely allied t their ability t prmte the flw f bulk water, which is reflected in part by net water flux. It is als pssible that the stimulatin f ethanl absrptin by carbhydrates may be secndary t the lss f water frm the lumen assciated with carbhydrate absrptin. Under these cnditins, water lss (net water flux) frm the gut lumen wuld have the effect f increasing gut luminal ethanl cncentratins. The subsequent increase in the ethanl cncentratin gradient between the gut lumen and the mucsa culd prvide a driving frce t accunt fr a prtin, but nt the ttal quantity, f augmented ethanl absrptin. Permeability characteristics f the small bwel vary accrding t anatmic segment. Thus, sugar-stimulated sdium and water absrptin, while ccurring readily in the dudenum and jejunum, des nt ccur appreciably in the ileum. 21 In this reprt, findings were btained utilizing perfusin f the entire small bwel. Cnsequently, augmentatin f ethanl absrptin by carbhydrates wuld prbably be mre prnunced if assessed nly in the prximal small bwel. Fr similar reasns it is pssible that the failure t bserve a significant effect f ther carbhydrates like 3-- methylglucse r lactse n ethanl absrptin may be the result f perfusin f the entire small bwel rather than restrictin f the perfusin t the jejunum. Of the carbhydrates which did nt influence ethanl absrptin, ne, fructse, was assciated with bld ethanl levels lwer than cntrls at the end f perfusin. Effects f intravenus fructse n lwering bld ethanl in humans are well dcumented,22-24 the present studies are additinal cnfirmatin f this effect f fructse after its intestinal absrptin. Of thse mn- and disaccharides which augmented the intestinal absrptin f ethanl, nly ne, galactse, was assciated with bld ethanl levels abve cntrl values at 9 min after the start f perfusin. Galactse metablism is knwn t be inhibited in the presence f ethanl; 25. 26 hwever, there is n evidence that the cnverse is true. Thus, elevated bld levels may merely reflect increased ethanl absrptin. The finding that ethanl levels in animals shwing augmented ethanl absrptin with glucse, sucrse, and maltse were n greater than in cntrls implies (1) that the dispsitin f ethanl frm the bld f these animals ccurred at a mre rapid rate, r (2) that the distributin f ethanl in bdy fluids was different than in cntrls. This finding appears discrdant with studies in humans indicating that the rate f ethanl disappearance frm the bld is unaltered by glucse infusins. 24 Hwever, cntrlled studies in humans r experimental animals cncerning the influence f glucse, r any nutritinal substrate, n the disappearance f ethanl frm the gastrintestinal tract and its simultaneus dispsitin frm the bld are nt presently available. As mentind previusly, when ethanl is cnsumed with fd, peak bld ethanl levels ccur earlier and are cnsiderably lwer than when ethanl is cnsumed alne. Ascribing this phenmenn t delayed stmach emptying assciated with eating-even thugh ethanl diffuses readily acrss the gastric wall-has been a cnvenient albeit nt ttally tenable explanatin. In the present study, ethanl was mre rapidly absrbed frm the small bwel in the presence f an actively transprted hexse and was assciated with lwer bld ethanl levels than when absrbed alne. These findings imply that an alternative mechanism(s) may be perative t explain the actin f fd n ethanl absrptin. REFERENCES 1. Tuvinen PI: Uber den alkhlgehalt des blutes unter verschieden en bedingungen. Skand Arch Physil 6:1-134, 193 2. Mellanby E: Alchl: its absrptin int and disappearance frm the bld under different cnditins. Med Res Cunc Spec Rep Ser (Lnd) n. 31, His Majesty's Statinery Office, 191 3. 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