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Inefficacy of oxygenated drinking water in accelerating ethanol elimination in humans
Life Sciences, Vol, 25, pp . 1369-1372 Printed in the II .S .A .
Pergamon Press
INBT+FICACY OF mCYC~ipT$0 DIfQIIQNO WAT~t II~i ACCSI~iATDiO S'PHANOL TION II~T Hiß~fAN3
Maija Laakso, Timo Huopsniemi, Juiani HyvBrinsn, Ssi Lindroa, Risto Roine, Helmuth 31ppe1 and Reino itlikahri Institute of Physiology, IIaiwraity of üelsinki, 311tavuoren psngsr 20 J, 3F-00170 Aslainhi, R+*,i . ~ , Research laboratories of the State Alcohol Isaropoly (f11ko), Haat 350, 3F-00101 Hslsin]ti 10, Finland (Received in fuel form August 30, 1979)
3um4ary In our earlier sport it ~ found that after intrawaous iníhsiar of ethanol into monkeys the drinking of aogrgerytted water aaosleratwd their elimination rats of ethanol 6(ßi ar the average . The sowUntiar was assumed to be due to increased hepatic ~ tsnsiar through the portal blood flow . Now we haw repeated similar expsrimaits using humans as subjsote . In humans the elimination rate of ethanol was not changed by aatygenated drinks . We are nat abU to asplain the species difference, because the mechanism by which ooggenated water increased ethanol eliminatiar in moolteys is unsettled . In liver slices and in perfused livers the axidatiar of ethanol can bs enhanced by increasing aatygsn tenaiar (1,2) . Sxposur~e of ~r+~.~w to an atmosphere of increased ootygen tension doss not influence their eliminatiar rata of ethanol (3.x .5) " In order to increase ~ tsnsiar of the liver in vivo the ~n oartent of portal blood should bs increased since the liver receives approximately 7qß of its blood flow through the portal win (6) . 31nos is monkeys (!+lacaaa s soiop) mggenatsd drinking fluid inarwsed the eliminatiar rate of ethanol Î simiLr eapsrimenta with humans as subjects were undertaloen . IYlsthods Three aeries of experiments (I, II and III) with alight differences were performed . Thirteen healthy persona (10 males and 3 females, aged 20-35 gears) participated in the expsr~iments . Oos persar took part in two series of experiments (II and III) . Thus ailtogethsr 14 experiments were performed . Series I : Hefors the experiment the subjects hated at least three hours . They received 0 .8 g sthanol/kg body weight in physiological saline as an intravenous infuaiar during as hour . Thereafter blood samples for the dsterminatiar of ethanol aaaoentntiona were oollsated sorry 30 min during 5 hours . Starting at the beginning of the experiment the subjects drank 2 dl of ordinary tap water or aty~ted water every 30 min . O:ggerrted water was prepared as described earlier (7) . Ths blood samples were treated and ethanol measured with gas oh:wmatography as described earlier (7,8) . Ths elimit~atiar rate of ethanol in the subjects (mg/Ítg/h) was oaloulatsd from the leaataquarss regression liaee of the blood ethanol elimination by a~xtrapoLting the tide when the oaroentratiar of ethanol had hllen to sero (9) . 0024-3205/70/161369-03$02 .00/0 Copyright (c) 1979 Pergamon Press Ltd
1370
Elimination of Ethanol
Vol . 25, No . 16, 1979
aeries II : The experiments wero performed as in aeries I Kith the following differonaea : The subjects drank moro water or oxygenated water in a shorter time, about 2 dl every 10 min during 2-4 hours . This amount corresponds on the basis of body weight to the amount of oxygenated drinks ing~eated by monkeys in our provious work (7) . The drinking began one hour after the end of the ethanol infusion . The rate of diurosis was measured during the experiment~, it averaged 11 ml/min (range 8-16 ml/min) both in control and in oxygen experiments . The mean inaroase of the body weight of the subjects during an ezperiment was 1 .8 kg (range 0 .1-3 .1 kg) . Elimination rates of ethanol (mg/kg/h) wero computed fry the leastaquaroa rogrossiar lines of the blood oaroentratians of ethanol during the drinking . Widmark'e factor r was aalaulated from the control experiments . Its average value was 0 .78 ± 0 .04 (SD) Khioh was used in all computations for the estimation of ethanol elimination rates (9) . aeries III : The experiments Kero as in aeries II exeept that ethanol Kas infused in 5$ glucose solution instead of 0 .~ saline, and the subjeuta drank sugarod juice (natural or oxygenated) instead of Kater . Resulte (àygenated drinks did not inorsaae the elimination rate of ethanol in humane as seen in Table I . This is contrary to our earlier rosulta Kith monkeys . In the experiments of aeries II three times as mush water was ingested as in series I, but even this excasaive drinking of oxygenated water did not change the elimination rate of ethanol . In aeries III the subjects that had fasted rooeived sugars during the ezperiment both by mouth and as an intravenous infusion . The elimination of ethanol was more rapid than in the state of fasting, but no difference was observed between the control and oxygen experimanta . During fasting the eliminstiar rate of control experiments between 60 and 108 64 and 1dF mg/kg/h . Individual changes -7 or +12~ when aogrgenatsd drinks wero
ethanol varied in different subjects in mg/kg/h and in mprgen experiments between of the elimination rate did not exceed given instead of natural drinks .
Díaausaian It is not clear why oxygenated drinks inoreaaed the elimination rate of ethanol in manloeya but not in humans . Videla and Israel (2) have postulated that the elevating effect of molecular oxygen an the elimination rats of ethanol in vitro could be mediated by an inareaesd non-mitoohandrial oxidation of NADH under high oxygen partial proaauroa . We suggested that the inoroaae of ethanol elimintior rate in monkeys in vivo was due to inoroased oagrgen tension in the portal vein and the liver (7 . If the intrahepatic partial proaaure of oacygen ie the rate limiting factor of the ear-mitochardrial oxidation system, it is roaearable to assume that differoraea between the species in hepatic mioroairoulatior and portal blood flow, rogulated by neural and humoral fhctors, may affect the ethanol elimination by this system . This hypothesis doss not ezolude other possibilities, s .g . species differonaes in the hepatic or eztrahepatio oxidation systems such as gut wall or the role of intestinal bacteria in elimination of ethanol . However, Ke have no evidence about such differoncea . The sliminatiar of ethanol was moro rapid Khan subjects that had fasted rooeived sweetened juice and glucose as an intravenous infusion during the experiment . This is in aocordanoe with earlier findings (9) . No differonos was found between the control and oxygen groups in these experiments either .
Vol. 25, No . 16, 1979
Elimination of Ethanol
1371
TABTB I Rates of ethanol sliminstian (~) in three series of a~xperiments (see Methods) . In all series the aubjeots reoaived ethanol 0 .8 g/kg body weight i .v . In oortrol experiments they had drieka with atmosphsrio ~n pressure and in au~gsn experiments drinks from siphons with 8 stm of pure oxygen . N ~ number of experiments .
Bxp . series
N
I II III
5 7 2
Rate of ethanol elimination mg/kg/h Coatrol Oxygen experiments experiments ± 8 77 88 ± 14 120,180
Mean change
f2
79 ± 10 85 ± 13 133 .170
-3 +1
AolmowlsdBSmsnta W~ thank Mrs . Pirldco Johansaan and Mra . Katrüna Luren for their skilful technical assistance . Referenoea 1 . $.R . OORDOIi, Can. J . Physiol . Pharmaool. 4 6 609-616 (1969) . L . VIDßIA and Y. ISIiABy, Hioohem. J . 118 275-281 (1970) . F.W . 1C~II~TART, W .M . MoCORT and J .C . AUIL, Quart . J. Stud . Aloohol
2. 3. 4.
6. 7. 8. 9"
i79-i83
(1951) "
12
H. MÁ1'PIB, Aota Pl~yeiol . Pharmaool. Nssr . 12 1-11 (1963) . J.H . LAR.~T, Aota Physiol. Soand. ~ 186-195 (1968) . B.B . , PhysioloaP , ~Fth sd ., Little, Hrown ~ Co ., Hoaton, pp " 587603
(19T6) .
J. HYiÍÄRZN~T, M . IMRSO, H. SIPPSL, R . and V. H~9N~1, Lile Soi . 22 553-559 C .J .P . ERIICSSON, Hioohsm . Pharmao . 22 H. WAIZLÜiBrT and H. HAiûiY, III, Aotione Amats:dam, pp " 43-4~6, 100-103 1910 .
ROII~, T . Hf10PAN10~lI, L . IBIIiWBrT (19t8) . 2283-229e
(1973) .
of Aloahol, Vol . I, Sisevier,
Pergamon Press
INBT+FICACY OF mCYC~ipT$0 DIfQIIQNO WAT~t II~i ACCSI~iATDiO S'PHANOL TION II~T Hiß~fAN3
Maija Laakso, Timo Huopsniemi, Juiani HyvBrinsn, Ssi Lindroa, Risto Roine, Helmuth 31ppe1 and Reino itlikahri Institute of Physiology, IIaiwraity of üelsinki, 311tavuoren psngsr 20 J, 3F-00170 Aslainhi, R+*,i . ~ , Research laboratories of the State Alcohol Isaropoly (f11ko), Haat 350, 3F-00101 Hslsin]ti 10, Finland (Received in fuel form August 30, 1979)
3um4ary In our earlier sport it ~ found that after intrawaous iníhsiar of ethanol into monkeys the drinking of aogrgerytted water aaosleratwd their elimination rats of ethanol 6(ßi ar the average . The sowUntiar was assumed to be due to increased hepatic ~ tsnsiar through the portal blood flow . Now we haw repeated similar expsrimaits using humans as subjsote . In humans the elimination rate of ethanol was not changed by aatygenated drinks . We are nat abU to asplain the species difference, because the mechanism by which ooggenated water increased ethanol eliminatiar in moolteys is unsettled . In liver slices and in perfused livers the axidatiar of ethanol can bs enhanced by increasing aatygsn tenaiar (1,2) . Sxposur~e of ~r+~.~w to an atmosphere of increased ootygen tension doss not influence their eliminatiar rata of ethanol (3.x .5) " In order to increase ~ tsnsiar of the liver in vivo the ~n oartent of portal blood should bs increased since the liver receives approximately 7qß of its blood flow through the portal win (6) . 31nos is monkeys (!+lacaaa s soiop) mggenatsd drinking fluid inarwsed the eliminatiar rate of ethanol Î simiLr eapsrimenta with humans as subjects were undertaloen . IYlsthods Three aeries of experiments (I, II and III) with alight differences were performed . Thirteen healthy persona (10 males and 3 females, aged 20-35 gears) participated in the expsr~iments . Oos persar took part in two series of experiments (II and III) . Thus ailtogethsr 14 experiments were performed . Series I : Hefors the experiment the subjects hated at least three hours . They received 0 .8 g sthanol/kg body weight in physiological saline as an intravenous infuaiar during as hour . Thereafter blood samples for the dsterminatiar of ethanol aaaoentntiona were oollsated sorry 30 min during 5 hours . Starting at the beginning of the experiment the subjects drank 2 dl of ordinary tap water or aty~ted water every 30 min . O:ggerrted water was prepared as described earlier (7) . Ths blood samples were treated and ethanol measured with gas oh:wmatography as described earlier (7,8) . Ths elimit~atiar rate of ethanol in the subjects (mg/Ítg/h) was oaloulatsd from the leaataquarss regression liaee of the blood ethanol elimination by a~xtrapoLting the tide when the oaroentratiar of ethanol had hllen to sero (9) . 0024-3205/70/161369-03$02 .00/0 Copyright (c) 1979 Pergamon Press Ltd
1370
Elimination of Ethanol
Vol . 25, No . 16, 1979
aeries II : The experiments wero performed as in aeries I Kith the following differonaea : The subjects drank moro water or oxygenated water in a shorter time, about 2 dl every 10 min during 2-4 hours . This amount corresponds on the basis of body weight to the amount of oxygenated drinks ing~eated by monkeys in our provious work (7) . The drinking began one hour after the end of the ethanol infusion . The rate of diurosis was measured during the experiment~, it averaged 11 ml/min (range 8-16 ml/min) both in control and in oxygen experiments . The mean inaroase of the body weight of the subjects during an ezperiment was 1 .8 kg (range 0 .1-3 .1 kg) . Elimination rates of ethanol (mg/kg/h) wero computed fry the leastaquaroa rogrossiar lines of the blood oaroentratians of ethanol during the drinking . Widmark'e factor r was aalaulated from the control experiments . Its average value was 0 .78 ± 0 .04 (SD) Khioh was used in all computations for the estimation of ethanol elimination rates (9) . aeries III : The experiments Kero as in aeries II exeept that ethanol Kas infused in 5$ glucose solution instead of 0 .~ saline, and the subjeuta drank sugarod juice (natural or oxygenated) instead of Kater . Resulte (àygenated drinks did not inorsaae the elimination rate of ethanol in humane as seen in Table I . This is contrary to our earlier rosulta Kith monkeys . In the experiments of aeries II three times as mush water was ingested as in series I, but even this excasaive drinking of oxygenated water did not change the elimination rate of ethanol . In aeries III the subjects that had fasted rooeived sugars during the ezperiment both by mouth and as an intravenous infusion . The elimination of ethanol was more rapid than in the state of fasting, but no difference was observed between the control and oxygen experimanta . During fasting the eliminstiar rate of control experiments between 60 and 108 64 and 1dF mg/kg/h . Individual changes -7 or +12~ when aogrgenatsd drinks wero
ethanol varied in different subjects in mg/kg/h and in mprgen experiments between of the elimination rate did not exceed given instead of natural drinks .
Díaausaian It is not clear why oxygenated drinks inoreaaed the elimination rate of ethanol in manloeya but not in humans . Videla and Israel (2) have postulated that the elevating effect of molecular oxygen an the elimination rats of ethanol in vitro could be mediated by an inareaesd non-mitoohandrial oxidation of NADH under high oxygen partial proaauroa . We suggested that the inoroaae of ethanol elimintior rate in monkeys in vivo was due to inoroased oagrgen tension in the portal vein and the liver (7 . If the intrahepatic partial proaaure of oacygen ie the rate limiting factor of the ear-mitochardrial oxidation system, it is roaearable to assume that differoraea between the species in hepatic mioroairoulatior and portal blood flow, rogulated by neural and humoral fhctors, may affect the ethanol elimination by this system . This hypothesis doss not ezolude other possibilities, s .g . species differonaes in the hepatic or eztrahepatio oxidation systems such as gut wall or the role of intestinal bacteria in elimination of ethanol . However, Ke have no evidence about such differoncea . The sliminatiar of ethanol was moro rapid Khan subjects that had fasted rooeived sweetened juice and glucose as an intravenous infusion during the experiment . This is in aocordanoe with earlier findings (9) . No differonos was found between the control and oxygen groups in these experiments either .
Vol. 25, No . 16, 1979
Elimination of Ethanol
1371
TABTB I Rates of ethanol sliminstian (~) in three series of a~xperiments (see Methods) . In all series the aubjeots reoaived ethanol 0 .8 g/kg body weight i .v . In oortrol experiments they had drieka with atmosphsrio ~n pressure and in au~gsn experiments drinks from siphons with 8 stm of pure oxygen . N ~ number of experiments .
Bxp . series
N
I II III
5 7 2
Rate of ethanol elimination mg/kg/h Coatrol Oxygen experiments experiments ± 8 77 88 ± 14 120,180
Mean change
f2
79 ± 10 85 ± 13 133 .170
-3 +1
AolmowlsdBSmsnta W~ thank Mrs . Pirldco Johansaan and Mra . Katrüna Luren for their skilful technical assistance . Referenoea 1 . $.R . OORDOIi, Can. J . Physiol . Pharmaool. 4 6 609-616 (1969) . L . VIDßIA and Y. ISIiABy, Hioohem. J . 118 275-281 (1970) . F.W . 1C~II~TART, W .M . MoCORT and J .C . AUIL, Quart . J. Stud . Aloohol
2. 3. 4.
6. 7. 8. 9"
i79-i83
(1951) "
12
H. MÁ1'PIB, Aota Pl~yeiol . Pharmaool. Nssr . 12 1-11 (1963) . J.H . LAR.~T, Aota Physiol. Soand. ~ 186-195 (1968) . B.B . , PhysioloaP , ~Fth sd ., Little, Hrown ~ Co ., Hoaton, pp " 587603
(19T6) .
J. HYiÍÄRZN~T, M . IMRSO, H. SIPPSL, R . and V. H~9N~1, Lile Soi . 22 553-559 C .J .P . ERIICSSON, Hioohsm . Pharmao . 22 H. WAIZLÜiBrT and H. HAiûiY, III, Aotione Amats:dam, pp " 43-4~6, 100-103 1910 .
ROII~, T . Hf10PAN10~lI, L . IBIIiWBrT (19t8) . 2283-229e
(1973) .
of Aloahol, Vol . I, Sisevier,