Drug and Alcohol Review (I99i) IO, II5-H 9

Alcoholic beverage consumption prior to the onset of Wernicke's encephalopathy

JOHN PRICE, MAUREEN HICKS & MICHAEL DUNNE

Department of P~chiatry, University of Queensland, Herston, Brisbane, Queensland, Australia Abstract

Alcoholic beverage consumption prior to the onset of Wernicke's encephalopathy is shown to be, primarily, full strength beer, although not always in large quantity, by 9I% of 8o patients. Secondly, in order of frequency of consumption, was white wine sold in casks and consumed by 30% of patients. These findings have implications when decisions have to be made regarding which alcoholic beverages could be fortified with thiamine as a measure designed to prevent the development of the Wernicke-Korsakoff syndrome. [Price J, Hicks M, Dunne M. Alcoholic beverage consumption prior to the onset of Wernicke's encephalopathy. Drug Alcohol Rev I99I; io: i i5-II9]

Key words: alcohol abuse; prevention; thiamine; Wernicke-Korsakoff syndrome; Australia.

In Australia, the Wernicke-Korsakoff (WK) syn- drome remains commonplace, particularly in those consuming alcohol. In a I987 study, 2o patients with diagnosed Wernicke's encephalopathy (WE) were collected in a 6-month period through two Brisbane public hospitals serving a population of one million [i]. In addition, it is known that the diagnosis of WE is often missed [2]. The syndrome has two components: WE resulting from a state of acute thiamine deficiency and character- ized classically by one or more of the triad of symptoms: confusion, ataxia and ophthalmoplegia, and its common sequel when alcohol has been consumed, Korsakoffs psychosis (KP), character- ized by an often permanent impairment in short- term memory.

The fortification of alcoholic beverages with thiamine has been suggested as a public health measure which might prevent the WK syndrome [3,4]. Although this measure has had its pro-

portents and opponents in Australia, the National Health and Medical Research Council adopted a recommendation from a Working Party on Thiamine made in late i987 that full strength beers and wines sold in casks and flagons should be fortified with thiamine. The amount of thiam- ine recommended was three times the amount required for the metabolism of the carbohydrates contained in these beverages. This three-fold factor allows for some loss of thiamine on storage of the beverage and makes some allowance for the malabsorption of thiamine which is known to occur in some drinkers [5,6].

The choice by the NHMRC Working Party on Thiamine of beverages to be fortified was based to some extent on data presented in the present paper. This choice related to the concept that if those beverages most commonly consumed just prior to the onset of WE were fortified, then this would be more likely to prove cost-effective as a

John Price MD, FRCPsych, FRANZCP, Professor of Drug and Alcohol Studies, Maureen Hicks, RGN, RMN, Michael Dunne, BA (Hons), Department of Psychiatry, Clinical Sciences Building, Royal Brisbane Hospital, Herston, Queensland 4o29, Australia. Correspondence and requests for reprints to Professor Price.

u5

H6 John Price et al.

preventive measure than other beverage fortifica- tion measures. Additionally, it should prove more acceptable to the alcohol industry. Thus, if it were shown that whisky was a beverage never consumed at this time, it would be impossible to Convince distillers of the need for thiamine to be added to whisky. Likewise, there seems little point in adding thiamine to low alcohol beers if these beverages are rarely consumed just prior to the onset of WE. Furthermore, for each beverage, effects on taste and the stability of the added thiamine require consideration. Since there are very large numbers of alcoholic beverages on the market, the task of assessing taste and stability effects for every one of them is formidable. Hence, the need to focus on those beverages where fortification is likely to prove worthwhile.

In the present study, unlike the previous study of long-stay hospitalized Korsakoff patients, which yielded very incomplete data [3], the focus was not on Korsakoff patients, but on those with a recent history of WE. This cut the time interval between WE and enquiry considerably, and yielded data from every case. In addition, differ- ences in beverage consumption relating to age, sex and occupational class were examined.

There is one other issue to be considered and that is vomiting. Vomiting in non-drinkers can precipitate acute thiamine deficiency and WE, for example in hyperemesis gravidarum. In drinkers also, because of vomiting, WE may develop at a time when blood alcohol levels are zero. If this happens, and if KP results from alcohol perma- nently damaging the thiamine-depleted brain [7], such vomiting patients could accordingly escape permanent damage: rather their condition would be understood as analogous to that of prisoners of war in Singapore who developed WE whilst on a diet of polished rice, had no exposure to alcohol and almost never went on to develop KP [8]. The vomiting issue is complex and, in this paper, will only be looked at in a limited way in relation to beverage preference.

Methods

Patients were recruited into the study by back- tracking from laboratory results indicative of thiamine deficiency obtained at two large Brisbane general hospitals. The corresponding case records were then perused. All those recruited into the

study had transketolase levels estimated before thiamine was given. They were diagnosed during life as having WE on the basis of two or three components of the clinical triad of confusion, ataxia and ophthalmoplegia plus, by definition, biochemical evidence of thiamine deficiency (a red cell transketolase level less than o.7o u/g Hb and/or a thiamine pyrophosphate (TPP) effect of greater than x70/0). Proceeding in this way will have led to cases being omitted since it is recognized that patients coming to post-mortem

with WE may lack all of the triad of features mentioned above [9]. It seems reasonable also to assume that some patients with WE recover from that disorder without that diagnosis being made.

Information in each instance was obtained from all available collateral sources (relatives, friends, fellow residents in boarding houses, landlords, etc.) regarding employment status, occupational status, marital status, living arrangements and alcoholic beverages being consumed in the 6-week period prior to the onset of WE. Each patient's beverage 'preference' (defined as the beverage most often consumed) was enquired about, but as there was often only one informant who could provide such information, these data should be regarded as of limited reliability. A beverage was only recorded in the data if it was consumed at least several times a week. Collateral information was checked against information available from the case record.

Results

A total number of 8o WE patients was studied. Of these 66 were male. The average age of the males was 57.o--+Io.5 (range 33-84), of the females 54.4-+x4.5 (range i6-72), the youngest female being an Aboriginal gift. At the time of the index admission, nine patients were employed, 22 unem- ployed and 49 on some form of pension. Occupa- tional status was managerial or executive in two instances, white collar in four, the services in eight, skilled blue collar in eight, semiskilled in i7, and labourer or equivalent in 22. Eleven were described as housewives and in eight instances no information was available. Regarding marital status, 17 were single, 19 married, 27 divorced or separated, Io living de facto, one a widow and five widowers. In one instance this information was unavailable. Regarding living arrangements at

/llcahol consumption and tVernicke's encephalopathy II 7

Table x. Beverages being consumed prior to the onset of lFernicke's eneephalopathy

M F TK Mean __+ SD

Beer only 29 Beer and spirits i2 Beer and table wine 7 Beer and fortified wine r Beer, spirits and table wine 9 Beer, spirits and fortified wine i Beer, table wine and fortified wine 3

Spirits only i Spirits and fortified wine t Spirits, fortified wine and table wine i

Table wine only x

Total 66

4 o.36+--o.I3 x o.4I +- o.I 4 3 °'36 + °'x2 3 0"35 o 0.42 +o.I8 o (o.3I) o (o.24, o.36, o.48)

2 (o.32, o.33, o.39 ) o (o.3I) o (0-64)

I (o.62, o.i2)

I4

the time of admission, 39 were stated to be living with their family, i i in boarding houses, one in a hostel, 22 alone and five with friends who were almost always drinking companions. One lived in his own home with a boarder and no information was available in one instance.

A breakdown of beverage consumption is provided in Table I. As far as beer is concerned, and where sufficient information was available, this was Australian-made full strength beer in every instance. As far as table wine is concerned, 24 subjects where this was their first preference drank white wine from casks. Thirteen also drank claret from flagons and six also drank wine from bottles. In one instance, this information was not available.

The preferred beverage being consumed up to the time of admission was stated to be beer in 62 instances, fortified wine in three, table wine in nine, spirits in six.

The values for red cell transketolase (TK), are also included in Table x. Standard deviations are provided where there are sufficient numbers to make this meaningful. None of the differences between the larger individual groups depicted in Table i (i.e. where n ~ 9 ) are significant, but when those who drank some spirits are compared with those who did not (n=28, n = 5 z , respectively.) there is a significant difference (means = o.412 and 0.354, respectively, Student's t=2.o388, d f=78 p < o . o 5 ) , with those who drank spirits having

higher TK values. We will return to this point later.

Nine patients died before a 6-month follow-up. Eight of those were male, with an age range of 34-84. A further three patients in the series are known to have died subsequently.

Vomiting was not found to be associated with beverage preference.

Discussion

It is of intcrcst to comparc the present study with the necropsy study of Harper [9]. Particularly important in this study is a comment that WE may be missed at necropsy unless the brain is examined histologically.

Of those who die in Queensland hospitals only approximately one-third come to autopsy and, of those examined by the coroner, it has to be stated that the brains are not always examined in great detail (Dr Robin Cooke, personal communi- cation). Since Harper has indicated that the diagnosis is often missed during life, the question arises as to the extent to which our results, which deal only with cases diagnosed during life, might differ if the total Queensland picture were known. The total of all cases includes also those who recover undiagnosed and cases who receive thiam- ine before its deficiency has been established biochemically. There are also those who die where either there is no post-mortem or the brain is not

H8 lohn Price et al.

examined carefully enough for the characteristic histopathological lesions of WE to be recognized.

These questions are virtually unanswerable, but it is worth commenting that our male to female ratio (4.7:i) is somewhat greater than Harper's ratio of 2.9:I. Perhaps female cases of WE in Queensland are overlooked. On the other hand, the ratio differences may relate to a different decade (the late seventies in Harper's study, the late eighties in ours), or a different state--Western Australia and Queensland, respectively.

Because of the possibility that there may be bias in favour of male cases being diagnosed in Queensland, we have included data from the two sexes separately in Table i. Beverage consumption between the sexes may differ, but the most obvious comment that can be made is that the numbers are too small to justify any conclusion on this point. Beyond that we must simply admit the limitations of the data presented here.

It is quite clear from the present data (including those in Table I) that beer is the beverage being consumed by the vast majority of Queensland drinkers prior to the onset of hospital diagnosed acute WE. This mirrors the findings of Price & Theodoros [3] for chronic KP patients but the present data are complete, unlike those of the earlier study. That beer is the beverage preferred by those who go on to develop WE elsewhere in Australia receives some support from a study of the incidence of WE in an inner city district of Sydney, New South Wales, by Gold et al. [io].

The recommendation that full strength Austra- lian beers should be fortified with thiamine as a measure designed to reduce the incidence of WE in Australia is supported by the evidence in the present paper and also, less directly, by the study of Price et al. [r] which examined the dietary histories and drinking behaviour of a non-WE drinking population in Brisbane, Queensland. This determined that the fortification of full- strength beer with thiamine was the single measure which would be most likely to secure adequate thiamine intake for these drinkers, many of whom ate grossly inadequate diets. This measure remained superior to the fortification of flour even when the latter was enriched to the high US levels, according to these data.

Note that only seven of the 8o patients in the present study were reported to drink no beer at all. Because there was no way of accurately determin-

ing quantities consumed'in the pre-WE phase due to the subsequent memory impairment of the sufferers and the general absence of detailed information from informants, it is not possible to make predictions as to how many patients who drank beer as a second or third preference would have achieved adequate thiamine intake had beer been the only beverage fortified. However, even if the quantities had been known, the possibility of severe malabsorption in some patients remains. These considerations indicate that the levels of fortification with thiamine of alcoholic beverages would need to be generous if the population under consideration were to benefit maximally. Generous levels in beer could protect those with absorption difficulties as well as those for whom beer was only a small part of their alcoholic beverage consump- tion. Taste considerations are clearly not a limiting factor in how much thiamine might be added to beer [xz].

As far as the fortification of table wine with thiamine is concerned, the evidence that this might improve the WE situation substantially is much less compelling. The data do confirm that it is bulk table wine (particularly white wine sold in 4-1itre casks) which was being consumed in the pre-WE phase by the majority of our wine drinking patients.

As indicated above, beverage preference did not relate to the level of thiamine deficiency except that those who drank spirits tended towards better thiamine status. This finding indirectly confirms the finding of a previous study [i3] which showed that spirit drinkers ate more meals than beer drinkers, an effect which held for the midday meal, but not for breakfast or the evening meal.

We are able to comment anecdotally on factors that appeared to determine beverage preference in this group of drinkers. For these drinkers, very few of whom were employed, spirits were too expen- sive. Some found wine and more particularly beer to be very bloating and might then, if they could afford to do so, use small quantities of spirits as occasional supplements. Many spent at least some time drinking beer in hotels and while there would purchase supplies for home consumption. How- ever, only three of them were customarily driving at this time and cheap bulk wine was, therefore, often purchased because patients preferred to carry an unbreakable cask when walking and using public transport. This was in preference to beer

Alcohol consumption and I4,'ernicke's encephalopathy n 9

which was relatively more bulky, heavier and more expensive.

One aspect of the situation remains elusive: dietary thiamine intake immediately prior to the onset of WE. From such information could be determined whether the enrichment of flour with thiamine would be likely to succeed as a preventive measure. In order to answer this question one would need to obtain detailed dietary histories for the weeks leading up to the onset of WE. In the majority of cases, we found that there was nobody to supply such information.

In summary, this paper demonstrates that it is feasible to pinpoint certain alcohol beverages as worthy of thiamine supplementation as a measure designed to prevent WE. If one assumes that on the whole patients just prior to the development of WE are drinking no less and eating no more than other very heavy drinkers, then previous data [i,rr] would indicate that the thiamine supplementation of beer would have a better preventive effect that the thiamine enrichment of flour even to the high US levels. It seems unlikely, however, that further studies of WE sufferers will provide evidence regarding the quantity of alcohol consumed or enough details of diet to enable the consequences of fortification to be more accurately predicted; because of the memory impairment of WE patients and imprecise nature of collateral evi- dence, such information is unlikely ever to be forthcoming.

References

[x] Price J, Kerr R, Hicks M, Nixon PF. The Wernicke-Korsakoff Syndrome: a reappraisal in

Queensland with Special reference to prevention. Med J Aust 1987~i47:56i- 5.

[2] Harper CG, Giles M, Finlay-Jones R. Clinical signs in Wernicke-Korsakoff complex: a retro- spective analysis of i3i cases diagnosed at nec- ropsy. J Neurol Neurosurg Psychiat 1986;49:34x- 5.

[3] Price J, Theodoros MT. The supplementation of alcoholic beverages with thiamine--a necessary preventive measure in Queensland? Aust NZ J Psychiat i979;13:315-2o.

[4] Centerwall BS, Criqui MH. Prevention of the Wernicke-Korsakoff Syndrome. New Eng J Med I978~ 299:285-289.

[5] Thomson AD, Baker H, Leery CM. Patterns of 35 S thiamine hydrochloride absorption in the malnourished alcohol patient. J Lab Clin Med I97o~76:36-44.

[6] Breen KJ, Buttigieg R, lossifidis S. Jejunal uptake of thiamine hydrochloride in man: influence of alcoholism and alcohol. Am J Clin Nutr I985;42:12I-6.

r7] Phillips SC. Structural assessment of the experi- mental alcohol-treated brain. Aust Drug Alcohol Rev 1988~7:69-73.

[8] de Wardener HE, Lennox B. Cerebral beri-beri (Wernicke's encephalopathy). Lancet 1947;i:H- 7.

[93 Harper CG. Wernicke's encephalopathy: a more common diagnosis than realised. J Neurol Neuro- surg Psychiat 1979;42:226-3i.

[~o] Gold J, Peridices M, Lardner K, Makinson R, Mahoney D. The Wernicke-Korsakoffprojectma preliminary report of the National Health and Medical Research Council of Australia, i985 .

[ii] Price J, Kerr R. Thiamin: to add or not to add? Med J Aust i989ii5o:~23- 4.

1I5] Price J. The taste of thaimine-fortified beer. J Food Nutr 198i;38:66- 9.

[i3] Price J, Kerr R, Williams G. The diet of steady drinkers with special reference to social variables. Br J Addict ~989;84:i65-72.