The Mellanby Effect in Moderate and Heavy Drinkers Herbert Moskowitz,3b John Daily and Robert Henderson INTRODUCTION The Mellanby effect is named for E. Mellanby, who, in 1919, reported that the behavioural impairment at a given blood alcohol level was greater when the blood alcohol level was rising than when it was falling.2 While many subsequent studies have replicated this example of acute tolerance, estimates of its magnitude have been compromised by experimental prob- lems. For example, many studies have determined blood alcohol levels (BAC) using venous samples whose alcohol level lags in time compared to arterial and brain levels during the rising BAC phase. Other studies have failed to control for practice effects since, typically, they have measured subjects sequentially on a task — first during the rising and then on the falling phases of a single administration. Clearly, during the falling period, subjects will have been more practised on the task. Another problem has been that many of these studies have utilised extremely rapid rates of administration of alcohol with doses larger than 1 gm/kg bodyweight, given in five to twelve minutes. Since rapid intake is associated with an initially greater degree of impairment, it would be hard to estimate the additional deficits associated with the rising BAC phase in normal alcohol consumption. This current study attempted to control the factors discussed above. It had one additional feature. Half the subjects were very heavy drinkers and half were moderate drinkers, so as to determine whether there was an interaction between the development of acute tolerance to alcohol and the existence of chronic tolerance, typically found in the heavy drinker. In the study, practice effects were balanced by requiring subjects to attend two experimen- tal sessions, once for testing on a rising BAC curve and once for testing on a falling BAC curve. Half the subjects were first tested on a rising and then a falling BAC phase, and the opposite was done for the other half of the subjects. Accurate estimates of brain alcohol level were obtained by use of a breath sampling gas chromatograph. Breath alcohol levels are in equilibrium with arterial blood alcohol levels which are in turn in equilibrium with brain alcohol levels. Thus, Unbiased estimates of brain BAC were obtained for both rising and falling blood alcohol phases. Alcohol administration was given at rates more typical of social drinking situations, ranging between 0.32 and 0.35 g alcohol per kg bodyweight per hour. The «ttfdy utilised five behavioural performance measures: hand steadiness while stand- ing and sitting; body ss?ay in tjbe lateral and anterior-posterior planes; and finally, a divided attention task. Due to technical difficulties, the divided attention task produced unreliable data and results are not included. 8 California State University, Los Angeles and University of California, Los Angeles. bThis study was supported by the National Highway Traffic Safety Administration, U.S. Department of Transportation, and the National Institute of Alcohol Abuse and Alcoholism, U.S. Department of Health, Education, and Welfare. It was performed at the Systems Development Corporation. Opinions expressed are those of the authors and not necessarily the sponsors. 184
Transcript
The Mellanby Effect in Moderate and Heavy DrinkersHerbert Moskowitz,3 b John Daily and Robert Henderson
INTRODUCTION
The Mellanby effect is nam ed for E. Mellanby, who, in 1919, reported that the behavioural im pairm ent at a given blood alcohol level was greater when the blood alcohol level was rising than when it was falling.2 While many subsequent studies have replicated this example o f acute tolerance, estimates o f its magnitude have been compromised by experimental problems. For example, many studies have determ ined blood alcohol levels (BAC) using venous samples whose alcohol level lags in time compared to arterial and brain levels during the rising BAC phase. O ther studies have failed to control for practice effects since, typically, they have measured subjects sequentially on a task — first during the rising and then on the falling phases o f a single administration. Clearly, during the falling period, subjects will have been more practised on the task.
Another problem has been that many o f these studies have utilised extremely rapid rates o f adm inistration o f alcohol with doses larger than 1 gm /kg bodyweight, given in five to twelve minutes. Since rapid intake is associated with an initially greater degree of impairment, it would be hard to estimate the additional deficits associated with the rising BAC phase in norm al alcohol consumption.
This current study attem pted to control the factors discussed above. It had one additional feature. H alf the subjects were very heavy drinkers and half were moderate drinkers, so as to determine whether there was an interaction between the development o f acute tolerance to alcohol and the existence o f chronic tolerance, typically found in the heavy drinker.
In the study, practice effects were balanced by requiring subjects to attend two experimental sessions, once for testing on a rising BAC curve and once for testing on a falling BAC curve. H alf the subjects were first tested on a rising and then a falling BAC phase, and the opposite was done for the other half o f the subjects. Accurate estimates of brain alcohol level were obtained by use o f a breath sampling gas chromatograph. Breath alcohol levels are in equilibrium with arterial blood alcohol levels which are in turn in equilibrium with brain alcohol levels. Thus, Unbiased estimates o f brain BAC were obtained for both rising and falling blood alcohol phases. Alcohol adm inistration was given at rates more typical o f social drinking situations, ranging between 0.32 and 0.35 g alcohol per kg bodyweight per hour.
The «ttfdy utilised five behavioural performance measures: hand steadiness while standing and sitting; body ss?ay in tjbe lateral and anterior-posterior planes; and finally, a divided attention task. Due to technical difficulties, the divided attention task produced unreliable data and results are not included.
8 California State University, Los Angeles and University o f California, Los Angeles. bThis study was supported by the National Highway Traffic Safety Administration, U.S. Department of Transportation, and the National Institute o f Alcohol Abuse and Alcoholism, U.S. Department of Health, Education, and Welfare. It was performed at the Systems Development Corporation. Opinions expressed are those o f the authors and not necessarily the sponsors.
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The Mellanby Effect in Moderate and Heavy Drinkers 185
METHOD
Subjects
Forty male subjects were used: twenty moderate drinkers and twenty heavy drinkers. These categories were defined by alcohol quantity-frequency consumption scales and personal interviews regarding recent drinking history.
Response Measures
Hand steadiness was measured by am ount of time a metal stylus inserted in a hole made contact with the metal plate. This measure was taken both while standing and while sitting. Body sway was measured by attaching two strings at chest height to the subject’s side and back and measuring the excursions o f the string in the subject’s anterior-posterior plane and in the lateral plane.
Alcohol Treatments
Alcohol was administered in mixed drinks containing 80-proof vodka. It was intended that moderate drinkers consume sufficient alcohol to achieve a BAC of 0.10% and heavy drinkers achieve 0.15%. The alcohol treatments administered were designed to produce increases of roughly 0.02% BAC per hour in moderate drinkers. In heavy drinkers the treatments were also designed to produce increases of 0.02% BAC per hour until they reached 0.10% BAC, and then the alcohol rate was increased slightly so BACs were to increase 0.025% per hour. Thus, moderate drinkers reached their BAC levels in, roughly, five hours, arfd heavy drinkers in, roughly, seven hours, during the day when testing was on the rising BAC. BAC samples were taken at frequent intervals. Behavioural testing was timed by frequent breath sampling so as to produce performance measures at 0.01% BAC.
RESULTS
BAC levels dropped 0.020% per hour for heavy drinkers and 0.017% per hour for moderate drinkers on the falling BAC test days. This difference is to be expected in terms of the increased metabolism rate for alcohol typically found in chronically tolerant heavy drinkers.
It was desired that the rate of change o f alcohol levels be similar during7the behavioural testing on the rising and fiftlling phases. During the rising BAC test days, BAC levels rose0.023% per hour Strt the moderale drinkers aad 0.024% for the heavy drinkers. Thus, the rates o f change o f alcohol level during the rising BAC test sessions were, roughly, 20 to 25 per cent jgreater fhan on the falling “BAS test lays.
Figure 1 shows performance scores for all subjects, both heavy and moderate drinkers, on the four behavioural response measures for the conditions of rising and falling BAC at increments o f 0.01% changes in BAC level plus an initial pretest level. It can be seen that the data supports the existence o f the Mellenby effect in that performance decrement was always greater at every BAC level during the rising BAC test days in contrast to the falling BAC test days. The data was tested for statistical significance using a repeated measures m ultivariant analysis o f variance based on a linear hypothesis model, and the difference due to the rising and falling curve was found significant for all response measures. It should be noted, however, that the difference in resistance to im pairment produced by testing on the falling versus the rising BAC phase is quite small, equivalent in effect to between 0.01% and 0.02% differences in BAC level.
186 H. Moskowitz, J. Daily and R. Henderson
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Performance o f fo u r behavioural measures as a function o f BA C fo r rising and fa llin g BA C phases.
Figure 2 shows differences in performance decrements at various BAC levels as a function o f whether the subject is a heavy or moderate drinker. It can be seen that the experienced drinker is more resistant to the effects o f alcohol.
It might be asked whether the existence of chronic tolerance in the heavy drinker would affect the development o f acute tolerance, as expressed in the Mellanby phenomenon.
The Mellanby Effect in Moderate and Heavy Drinkers 187
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Performance o f heavy and moderate drinkers as a function o f BA C.
Figure 3 shows performance during the rising and falling BAC phases separately for heavy and moderate drinkers on one o f the measures, i.e. lateral sway. The results here are typical o f all the performance measures. It can be seen that there is as much or greater development o f acute tolerance in the chronically tolerant heavy drinkers as in the non-tolerant
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moderate drinkers. Clearly, there is evidence for the development of acute tolerance as expressed in the Mellenby phenom enon, and the acute tolerance occurs independently of the existence o f the chronic tolerance in the heavy drinker.
Figure 3 Rising and falling BA C performance o f heavy and moderate drinkers on LateralSway.
The results o f this aspect o f the study are in conflict with the suggestion offered by Jellinek (1960) that chronic heavy drinkers would be expected to show less acute tolerance and specifically a smaller M ellanby effect than moderate drinkers. This suggestion was based on the belief that the chronic tolerance induced by heavy drinking would have protected the drinker from some o f the impairing effects o f alcohol from the very start of the drinking session. The results herein obtained conform more closely with the expectations o f the theory o f tolerance developed by LeBlanc, Kalant, LeBlanc, and Gibbins.2 They propose that the result o f the development o f tolerance by heavy chronic drinking is a change in the rate and degree o f final am ount o f acute tolerance exhibited at each drinking session, in comparison with that shown by a naive or moderate drinker. Thus both moderate and heavy drinkers would begin to exhibit behavioral im pairm ent at approximately the same threshold level in the rising BAC curve. However, the rate of increase in impairment for the heavy
L A T E R A L SWAY
The Mellanby Effect in Moderate and Heavy Drinkers 189
drinker would be slower and reach a lower level at a given BAC level than for a moderate drinker.
It might be wondered why the Mellanby effect is quite small in size in this study, in comparison with larger differential effects for rising and falling BAC curves reported in other studies. It was our hypothesis that this was due to the difference in the rate of administration of alcohol. To test this, Moskowitz and Burns3 performed an additional study in which performance decrement under alcohol was examined as a function of the rate of drinking for five different groups. The study determined that the more rapid the rate of drinking the greater the degree of performance decrements at the same BAC level.
REFERENCES
1. Kalant, H., LeBlanc, A. E., and Gibbins, R. J. Tolerance to, and dependence on, some non-opiate psychotropic drugs. Pharmacological Review 23, 135-191, 1971.
2. Mellanby, E., Alcohol: its absorption into and disappearance from blood under different conditions. British Medical Research Committee, Special Report Series, No. 31. London: H.M.S.O., 1919.
3. Moskowitz, H. and Burns, M., Effects of rate of drinking on human performance. Journal of Studies on Alcohol 37, 598-605, 1976.
