Individual Variation in Tolerance to Alcohol

HENRY W. NEWMAN, M. D.Department of Medicine, Stanford University School of Medicine, San Francisco, California

We should not be surprised to find that different individuals are affected in different degree by the same con­centration of alcohol in their brains when we consider the universality of variability in response to drugs in ­dicated by Nelson (1), which extends to even such definite events as lethal doses, as for instance the variation of 2V2 to 1 for the fatal dose of digitalis in the cat. The importance of this variability is in connection w ith the validity of setting up of certain definite concentrations of alcohol in the blood as absolute evidence of in ­toxication, and it is because of this very practical application that we consider the point in detail.

The variation in inherent tolerance to alcohol is apparent in all the well- documented attempts to correlate the alcohol content of body fluids with drunkenness, although it is often neglected in a discussion of the results in favor of emphasis on the undeni­able correlation which exists in a majority of instances between alcohol concentration and inebriation. Bogen(2) tested 300 patients brought to the Cincinnati General Hospital on sus­picion of drunkenness, determining breath or urine alcohol concentrations and examining the patients clinically. A clinical diagnosis of drunkenness was made only in the presence of u n ­

mistakable loss of control of speech and movement. No patient w ith less than 1.0 mg. alcohol per cubic centi­m eter was adjudged intoxicated, while half of those w ith 1.0 to 2.0 mg., three-fourths of those w ith 3.0 mg., and almost every patient w ith 4.0 mg. or above were found to be drunk. Thus while a considerable num ber of subjects were considered drunk a t a concentration of 1.0 to 2.0 mg. per cubic centimeter, some few were not so considered at concentrations twice this great.

Je tter (3) examined 1,000 cases, a group similar to that of Bogen. Gross tests of inco-ordination were used in the clinical diagnosis to m ake the study as objective as possible. It was found that while 10.5% were diagnosed as drunk w ith a blood alcohol concentration of 50 mg.%, 6.7% of the group with blood alcohols of 400 mg.% were adjudged sober. To quote the author: “when it is realized that at 0.40% alcohol, a concentration close to the lethal point, an in­dividual may show so little effects as to be adjudged sober by our criteria, or on the other hand may be in a coma at this same level, it becomes evident that there exists a m arked variation in the individual’s reaction to alcohol.” Nor did this author change his opinion that individual tolerance

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to alcohol was a potent factor after study (4) of an additional 800 patients.

Bahnsen and Vedel-Petersen (5), studying the effect of the adm inistra­tion of alcohol on neurom uscular co­ordination, were impressed with the variation in degree from subject to subject. This variation was noted by Turner (6) in an experimental study of the relation of blood alcohol to intoxication in the dog. He admin­istered alcohol by stomach tube, and took samples of heart’s blood at 30 minutes and 1, 2, 3, 4, 5 and 6 hours thereafter. Blood alcohol concentra­tions and degrees of drunkenness were plotted in the case of 2 dogs, one of which received 2 gm. of alcohol per kilogram and the other 3 gm. The first dog showed loss of memory and equilibrium at blood alcohol con­centration of 285 mg.%, while the second showed perfectly normal be­havior.

Newman and Card (7, 8) and New­man and Lehman (9), working with dogs in a study of tolerance acquired on habituation to alcohol, found definite evidence of variation in the degree of drunkenness at a given level of blood alcohol concentration. This difference in tolerance within the group was present both when ab­stinent and when habituated. The range of blood alcohol concentrations at which all animals showed the same degree of inebriation amounted to as m uch as 75 to 100 mg.%, and was about equal to the increase in to le r­ance brought about by habituation.

Using rats, MacLeod (10) found that in 16 animals the blood alcohol con­centration at which failure of the test employed occurred, varied from 139 to 230 mg per 100 cc, Goldberg (11) esti­

mated that the variation between in­dividuals so far as the blood alcohol concentration at which signs of in­toxication occurred was about 30%. He found this tolerance to have normal distribution when plotted graphically, and concluded that toler­ance varies at random from individual to individual in a homogeneous group of individuals. Similar results were obtained by Newman, Fletcher, and Abramson (12) using tests of co­ordination.

Newman (13) gave repeated small doses of alcohol to a fairly homo­genous group of young male adults, testing their co-ordination on a com­mercial target-shooting device after each dose. When a significant lower­ing of score occurred, blood alcohol concentration was determined. These values fell in a bell-shaped distribu­tion curve, with its peak at the 100 to 119 mg. per 100 cc. level, but the spread was considerable, failure in 1 case occurring at the 40 to 59 mg. per 100 cc. level, while in another it did not occur until the 200 to 219 mg. per 100 cc. level was reached. Newman also investigated the effect of repeated doses of sodium amytal in the same manner, and found an even greater variation in tolerance.

One may ask why it has been necessary to do all of this difficult, carefully controlled experimentation when any layman knows that indi­viduals vary in their tolerance to liquor. The reason lies in the fact that what is known to every layman is apparently not known to some indi­viduals of scientific background who appear to believe that variation in tolerance to alcohol is a negligible factor, and that one may establish hard and fast limits of blood alcohol

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(or even breath alcohol) concentra­tion indicative of a specific degree of intoxication in all individuals.

All pronouncements regarding the variability of tolerance to alcohol have not been based on experimental evidence, as may be attested by the following quotations from a paper by Meerloo (14). “Alcohol forms a com­pound with hemoglobin in the blood. Oxygen helps to burn the alcohol al­most immediately, tha t is why the blood alcohol values decrease rather soon. There exists a normal alcohol- emia of 0.03 mg.%, depending on the transformation of carbohydrates by fermentation. Eating large quantities of fru it may increase it to 0.3 mg.%. There are special m ixtures that make people more or less intolerant for drinks. Perhaps the m ixture of alcohol w ith some proteins sensitize the or­ganism (lobster cocktail). It is still a problem, why the different mixtures have such a different reaction on soma and psyche”. This fragment is quoted not because of virtue, bu t to demonstrate the type of superstition that frequently takes the place of scientific investigation in the field of alcohol research.

In addition to variations in inherent tolerance to alcohol, the question of tolerance acquired by habituation m ust be considered. In our opinion it has been demonstrated that in animals prolonged ingestion of large doses of alcohol is capable of producing a re ­sistance of the nervous system to the effect of this substance. There are two possible mechanisms whereby this improved performance may eventuate. Either the metabolic processes in the nerve cell which are disturbed by alcohol become resistant to the sub­stance and able to take place in the

presence of increasing concentrations, or conceivably by some sort of psycho­logical process the animal may learn to compensate, by using more or dif­ferent nerve pathways, for the de­terioration in performance brought

* about by alcohol. The latter process has been invoked to explain the re ­puted “pulling himself together” said to be shown by an intoxicated indi­vidual involved in an accident. There is not the slightest doubt tha t an in­dividual who knows the effect of alcohol, as an habitué does, can compensate to some degree for its inebriating effect when it seems ex ­pedient to do so, as when under ob­servation. This is accomplished by greater attention and care in perform ­ance, and by limiting the type of ac­tivity undertaken to tha t which is less liable to show the effect of alcohol. Thus the experienced drinker learns to avoid tongue-twisting phrases, con­versation in which poor recall will be noticeable, and skilled acts in which incoordination would be obvious. This will certainly provide an adequate explanation for increased tolerance of experienced drinkers for the re la­tively low blood alcohol concentra­tions associated w ith mild inebriation. That such mechanisms can be invoked to explain the larger dose of alcohol required in habituated rats to produce anesthesia, or the ability of dogs to walk about at blood alcohol con­centrations at which before habitua­tion they could not arise from the ground, seems entirely unreasonable. In our opinion this change can only be attributed to a true tissue tolerance of the nervous system to alcohol, so that the nerve cells when habituated are able to function at a concentration of alcohol at which previously they were narcotized. The most reasonable

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explanation for such an effect is that w hatever metabolic processes in the cell adversely affected by alcohol must after prolonged exposure to the sub­stance become resistant thereto. It is equally apparent tha t this resist­ance is lost after a period of abstin­ence. This is fu rther evidence that the whole of tolerance to alcohol is not of a psychological nature, since one would not expect such a psycho­logical process to disappear so quickly.

Actually, the practical importance of acquired tolerance to alcohol does not seem great to us. It is not of sufficient magnitude to necessitate dangerously high doses in the habitu­ate in order to produce a desirable degree of inebriation. H o w e v e r , coupled w ith differences in inherent susceptibility to the substance, it is responsible for the widely divergent blood alcohol concentrations required in different individuals to produce the same degree of intoxication, and is thus of some importance in any con­sideration of the chemical tests for drunkenness.

It should be unnecessary to do more than note in passing tha t other factors tending to reduce neurom uscular con­trol, such as shock, drugs, carbon- monoxide, low-oxygen tension, and so on, may be additive to the effects of alcohol, so that an individual having to cope w ith one or more of these as well may show much more evidence of drunkenness at the same blood alcohol concentration than he would under more favorable circumstances. That changes in the blood metabolites, notably blood sugar concentration, may also play a part in determining tolerance to alcohol at any particular time is indicated by the work of Hag­gard and Greenberg (15), who found

the fatal dose of alcohol to vary di­rectly with the blood sugar concentra­tion, an increase in the blood sugar of the ra t from 70 to 200 mg.% in­creasing the fatal dose from 6.5 to11.0 gm. per kilogram. Should this effect also apply to the sublethal in ­toxicating doses, it might be expected to result in an individual tolerance to alcohol varying considerably from hour to hour, depending on the blood sugar level, which varies in relation to meals and exercise. Further work on the point is needed, and the technic used by Turner and by Newman and his co-workers noted above should be applicable to the problem.

There is a widespread belief among aviators that a dose of alcohol which will not produce symptoms of intoxi­cation at sea level will do so at high altitudes. Newman (16) investigated this problem with the divided dose technic, using a pursuit meter as the test of co-ordination. Identical experi­ments were run with the subject breathing room air on one occasion and a mixture of 10% oxygen and 90% nitrogen on another, the latter simu­lating an altitude of 18,000 feet, at least so far as oxygen pressure is concerned. In 3 of the 5 subjects there was a striking reduction of the alcohol concentration in the blood at which a significant deterioration in perform­ance took place when the low oxygen m ixture was breathed, while the other two subjects showed no significant change. Thus it is apparent that alti­tude does reduce alcohol tolerance, but when one considers that even with an altitude of 18,000 feet, far above that at which oxygen is routinely used, only 3 out of 5 subjects showed a significant reduction, the effect must be considered slight and of little practical importance.

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We know that individuals suffering from psychiatric disease usually de­veloping in definitely divergent p er­sonality types react quite differently to alcohol. No work has been done on individuals w ithin the normal range of personality variation; bu t it is reasonable to assume that they also might be expected to be differently affected by alcohol according to their makeup, as G antt has shown to occur in dogs. These changes in general be­havior, mood, and emotional stability are all factors difficult of appraisal but nevertheless of importance, particu­larly from the medicolegal aspect; for it is just such changes which, equally w ith interference w ith neurom uscular co-ordination, are responsible for bringing the individual into conflict w ith the law. As a m atter of fact, in respect to most crimes in which alco­hol plays a part it is entirely the change in personality which is respon­sible, the depression of co-ordination frequently being the factor which limits the seriousness of the act by interfering w ith its execution. Motor co-ordination, however, lends itself much more readily to scientific in ­vestigation; and since it m ust be con­ceded to play an im portant part in the effect of alcohol on such skilled acts as driving a motor car, it is natural tha t in this particular connec­tion stress has been laid on this aspect almost to the exclusion of the effect on personality. Nor is there any very good evidence to show w hether or not there is any degree of parallelism be­tween the effect of alcohol on the p er­sonality and tha t on neurom uscular co-ordination; and it is only when objective tests have shown that cer­tain individuals do not show signifi­cant changes in co-ordination at blood alcohol values generally shown to pro­

duce a greatly increased hazard in driving a car that these other effects of alcohol are invoked to explain the discrepancy, in spite of the fact that they have been studied little if at all. Such studies, on a quantitative, scien­tific basis, are a necessary complement to already initiated studies of the effect of alcohol on neurom uscular co-ordination if we are to have any rational basis for the chemical diag­nosis of drunkenness.

References1. Nelson, E. E., “Variability in Re­

sponse to Drugs,” J. Am. Med. Assoc., 113: 1373, 1939.

2. Bogen, E., “Drunkenness: a Quan­titative S tudy of Acute Alco­holic Intoxication” J. Am. Med. Assoc., 89: 1508, 1927.

3. Jetter, W. W., “Studies in Alco­h o l I . The Diagnosis of Acute Intoxication by a Correlation of Clinical and Chemical Find­i n g s Am. J. Med. Sc., 196; 475, 1938.

4. Jetter, W. W., “Chemical andClinical Diagnosis of AcuteAlcoholism ,” New Eng. J. Med., 221: 1019, 1939.

5. Bahnsen, P., and Vedel-Petersen,K., “Alcohol Studies. I. Experi­m ents on Drivers of MotorVehicles” J. Ind. Hyg., 16: 304, 1934.

6. Turner, R. G., “Blood Alcohol andIts Relation to Intoxication,” J. Pharmacol., 44: 305, 1932.

7. Newman, H. W., and Card, J., “TheNature of Tolerance to Ethyl Alcohol,” J. Nerv, and Ment. Dis., 86: 428, 1937.

8. Newman, H. W., and Card, J.,“Duration of Acquired Tolerance to Alcohol,” J. Pharmacol., 59: 249, 1938.

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9. Newman, H. W., and Lehman, A. J., “Nature of Acquired Tolerance to Alcohol,” J. Pharmacol., 62: 301, 1938.

10. MacLeod, L. D., “The ControlledAdministration of Alcohol to E x­perimental A n im als” Brit. J. Addiction, 45: 112, 1948.

11. Goldberg, L., “Quantitative Studieson Alcohol Tolerance in Man: The Influence of Ethyl Alcohol on Sensory, Motor and Psycho­logical Functions referred to Blood Alcohol in Normal and Habituated Individuals,” Acta Physiol. Scand. vol. 5, supp. XVI, 1943.

12. Newman, H., Fletcher, E. andAbramson, M., “Alcohol and Driving,” Quart. J. Stud. Alcohol, 3: 15, 1942.

13. Newman, H. W., “Variability inTolerance to Depressant Drugs,” Stanford Med. Bull., 5: 12, 1947.

14. Meerloo, A. M., “Variable Toler­ance for Alcohol,” J. Nerv, and Ment. Dis., 105: 590, 1947.

15. Haggard, H. W., and Greenberg,L. A., “The Effects of Alcohol as Influenced by Blood Sugar,” Science, 85: 608, 1937.

16. Newman, H. W., “The Effect ofA ltitude on Alcohol Tolerance,” Quart. J. Stud. Alcohol, 10: 398, 1949.

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