current progress toward the prevention of the wernicke-korsakoff ...

Alcohol for most of the population. Since magnesium is required for the conversion of thiamin to thiamin pyrophosphate, magnesium deficiency may contribute to thiamin deficiency (Ross and Birmingham, 1985). A recent case report of a patient with clinical signs of thiamin deficiency which responded to parenteral thiamin only when magnesium was added may help to substantiate this hypothesis (Dyckner et al., 1985). More data on the relation of magnesium status to thiamin metabolism is needed. SOCIOECONOMIC FEASIBILITY OF THIAMIN FORTIFICATION Aside from the considerations concerning thiamin fortification examined above, there are some socioeconomic issues to contend with. One possible undesired effect of thiamin fortification would be an increase in alcohol consumption by individuals perceiving alcoholic

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thiamin should be investigated in Korsakoff patients. This hypothesis may have some merit in view of the discovery of an abnormal transketolase isoenzyme with low affinity for thiamin pyrophosphate (Blass and Gibson, 1977). [The association of transketolase variant enzymes and brain damage has been recently reviewed in this journal (Pratt et al., 1985).] An alternative explanation for the Wernicke's patients' failure to absorb oral thiamin hydrochloride would be a possible gastric outlet obstruction as an acute concomitant of Wernicke's encephalopathy. A final technical consideration concerns the appropriate level of fortification of thiamin. There have been several previous recommendations concerning the required level for beer (Centerwall and Criqui, 1978; Price and Theodoras, 1979; Meilgaard, 1982). However, the available data tend to constrain the solution. For beer the flavor threshold of 10 mg/1 (Meilgaard, 1982) suggests a maximum level of fortification, and the requirement that the final concentration of thiamin in the jejunum when diluted with approximately 9 1. of gastrointestinal secretions per day be greater than 2 (i,m to achieve passive uptake, sets a lower limit of approximately 6.75 mg/1 of thiamin. Calculation assumes the molecular weight of thiamin to be 337 g/mol and a minimum daily 1 1. beer intake. Because of storage losses Meilgaard recommends adding 35% more thiamine than required (Meilgaard, 1982). This would lead us to revise the minimum level from 6.75 to 9.1 mg/1. The upper limit remains because of the concern for effects on flavor should the beer be •consumed earlier than its mean shelf-life of two months. Thus it would be best to add thiamin to beer at a concentration between 9.1 and 10 mg/1. Note that the narrow range produced by the constraints leaves little room for error in the data upon which the calculation is based. Similar calculations for wine and other beverages await data on the taste and stability of thiamin in these products.

PREVENTION OF THE W-K SYNDROME

the cost of the program to those who would ultimately benefit from it. Public reaction to the proposal to fortify beer with thiamin was surprisingly good. After being briefly educated about the involved issues only 1.3% of an Australian study population remained opposed to the measure. Those opposed to the measure tended to have significantly lower educational standards (Budge and Price, 1982). DISCUSSION This review of current progress toward the prevention of the Wernicke-Korsakoff syndrome has concentrated primarily on the policy of fortifying alcoholic beverages with thiamin. Although the Wernicke-Korsakoff syndrome is by no means common, the prospect of virtually eradicating a disease and its attendant financial burden without excessive health care expenditure merits close attention. The policy of thiamin fortification of alcoholic beverages arguably meets all of the food fortification guidelines laid down by the U.S. Food and Drug Administration. In particular: (1) The policy would address an identifiable problem in an identifiable population group. (2) Alcoholic beverages are generally not subject to any regulations requiring, permitting or prohibiting nutrient additions although labeling restriction prevent disclosure of vitamin content of alcoholic beverages. (3) The nutrient under consideration is stable in alcoholic beverages. (4) The nutrient is physiologically available in the presence of alcohol in chronic alcoholics according to the limited data from the Breen study, although data collected during episodes of Wernicke's encephalopathy do not corroborate this (Thomson et al., 1971a). (5) Toxicity from thiamin-fortified alcoholic beverages is highly unlikely. (6) Thiamin is a suitable nutrient with which to prevent to Wernicke-Korsakoff syndrome. Nevertheless, a number of theoretical objections to the policy remain. One very basic objection to the policy is that even if thiamin were adequately absorbed by alcoholics, the presence of an underlying genetic defect in thiamin metabolism would still allow the dis-


beverages as health-promoting. It is difficult to imagine a way in which data on this possible effect could ever transcend the level of opinion. Two considerations are pertinent: (1) at least in the U.S.A., current laws interpret the disclosure of the vitamin contents of alcoholic beverages as tending 'to create a misleading impression' and disclosing them is thus illegal (U.S. Government, 1985b); (2) the fundamental behavior disturbance in alcoholism is an inability to control drinking behavior despite the occurrence of alcohol-related life problems (Shuckit, 1986). Whether rationalization of drinking behavior is a cause or a symptom of the lack of control remains unclear. A related consideration is that by preventing symptoms, thiamin fortification will enable alcoholics to continue drinking longer and reduce the frequency with which they present for alcoholism treatment. Here it should be noted: (1) in the case of the Wernicke-Korsakoff syndrome, the lesions are often irreversible and ought to be prevented rather than allowed to progress to the acute stage, and (2) liver damage (Lieber and deCarli, 1974), inebriation, withdrawal symptoms, and alcohol-related life problems, etc., will continue at the same rate despite thiamin fortification and ought to provide ample motivation for alcoholic rehabilitation. Other considerations are those of cost and public acceptance. The cost of fortifying all the alcoholic beverages in the U.S.A. with thiamin hydrochloride would have been $17 million in 1977 (Centerwall and Criqui, 1978). Since the cost-benefit ratio is better than 1:1, the savings realized by averted long-term care costs would more than pay for the cost of fortification. There are indications that alcoholic beverage preferences of patients with thiamin deficiency are not so broad and that only selected beverages would need to be fortified, thus further decreasing the estimated cost of fortification. In Australia, beer has been implicated as the primary beverage of WernickeKorsakoff patients (Price and Kerr, 1985). One suggestion for financing the fortification of alcoholic beverages would be for bottlers to receive a tax rebate of 0.15 cents per liter, thus both offsetting the cost and providing producers with an incentive to fortify (Weinstein, 1978). This policy would ostensibly distribute

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Butters, N. (1984) Alcoholic Korsakoffs syndrome: an update. Seminars in Neurology 4, 226-244. Centerwall, B. S. and Criqui, M. H. (1978) Prevention of the Wernicke-Korsakoff syndrome. New England Journal of Medicine 299, 285-289. Centerwall, B. S. and Criqui, M. H. (1979) Prevention of the Wernicke-Korsakoff syndrome, an updated costbenefit analysis (Letter). New England Journal of Medicine 300, 320-321. Cowgill, R. (1939) The need for the addition of Vitamin B, to staple American foods. Journal of the American Medical Association 113, 2146-2151. Crane, S. and Price, J. (1983) The attempted enrichment of beer with thiamine alkyl disulfides. Journal of Nutritional Science and Vitaminology 29, 381-387. Danford, P. E. and Munro, H. N. (1980) Water-soluble vitamins. In The Pharmacological Basis of Therapeutics, 6th edn, Gilman, A. G., Goodman, L. S., Gilman, A. eds, pp. 1560-1582. Macmillan, New York. Davis, R. E., Icke, G. C , Thorn, J. and Riley, W. J. (1984) Intestinal absorption of thiamin in man compared with folate and Pyridoxal and its subsequent urinary excretion. Journal of Nutritional Science and Vitaminology 30, 475-482. Desmond, P. V., Lourenzs,-C. and Breen, K. J. (1976) Thiamine hydrochloride absorption in man: normal kinetics and absence of acute effect of ethanol. Australian and New Zealand Journal of Medicine 6, 264. Dyckner, T., Ek, B., Nyhlin, H. and Wester, P. O. (1985) Aggravation of thiamin deficiency by magnesium depletion. Ada Medica Scandinavica 218, 129-131. Halstead, C. H., Bhanthumnavin, K. and Mezey, E. (1974) Jejunal uptake of tritiated folic acid in the rat studied by in vivo perfusion. Journal of Nutrition 104, 1674-1680. Harper, C. (1979) Wernicke's encephalopathy: a more common disease than realised. Journal of Neurology, Neurosurgery, and Psychiatry 42, 226-231. Hillman, R. S. (1980) Vitamin B12, folic acid, and the treatment of megaloblastic anemias. The PharmacolREFERENCES ogical Basis of Therapeutics, 6th edn, Gilman, A. G., Goodman, L. S., Gilman, A. eds, pp. 1331-1346. American Medical Association, Council on Foods and Macmillan, New York. Nutrition (1968) Improvement of the nutritive quality of foods — Council Statement. Journal of the American Hoyumpa, A. M., Middleton, H. M., Wilson, F. A. and Medical Association 205, 160-161. Schenker, S. (1975) Thiamine transport across the rat intestine. Gastroenterology 68, 1218-1227. American Medical Association, Council on Scientific Affairs (1982) Addition of thiamine to alcoholic bever- Hoyumpa, A. M., Nichols, S., Henderson, G. I. and ages. Council on Scientific Affairs Report: D(I-82), pp. Schenker, S. (1978) Intestinal thiamin transport: effect 1-3. of chronic ethanol administration in rats. American Journal of Clinical Nutrition 31, 938-945. Basu, T. K. and Chakraborty, J. C. (1982) The protective effect of hymochromone against ethanol-induced thia- Hoyumpa, A. M., Strickland, R., Sheehan, J. J., Yarbormine deficiency. Drug-Nutrient Interactions 1, 271-274. ough, G. and Nichols, S. (1982) Dual system of intestinal transport in humans. Journal of Laboratory Blass, J. P. and Gibson, G. E. (1977) Abnormality of a and Clinical Medicine 99, 701-708. thiamine requiring enzyme in patients with WernickeKorsakoff syndrome. New England Journal of Medicine Jones, G. and Briscoe, M. (1979) Prophylactic thiamine in 297, 1367-1370. liquor (Letter). British Medical Journal 2, 1294. Breen, K. J., Buttigieg, R., Iossifidis, S., Lourensz, C. and Katz, D., Metz, J. and Van der Westhuyzen, J. (1985) Wood, B. (1985) Jejunal uptake of thiamin hydroIntestinal absorption of thiamin from yeast-containing chloride in man: influence of alcoholism and alcohol. sorghum beer. American Journal of Clinical Nutrition American Journal of Clinical Nutrition 42, 121-126. 42, 666-670. Budge, M. and Price, J. (1982) Public reaction to a Kaunitz, J. D. and Lindenbaum, J. (1977) The bioavailability of folic acid added to wine. Annals of Internal proposal to fortify beer with thiamin. Journal of Food Medicine 87, 542-545. and Nutrition 39, 147-151.

ease to occur. Although the administration of thiamin can reverse many of the symptoms of Wernicke's encephalopathy there is still room for doubt as to the linkage between thiamin status and the development of Korsakoffs psychosis. Another area of doubt surrounds the issue of gastrointestinal absorption of thiamin especially in view of the possibility that patients who get Wernicke's encephalopathy may represent a subpopulation of poor thiamin-absorbers, as is suggested by their refractoriness to oral thiamin (Thomson et al., 1971a, b). A study of thiamin absorption in Korsakoff s patients given beer fortified by thiamin in a range of 9.5 mg/1 would be helpful in resolving this issue. Social and political problems which need to be considered include the potential for increased consumption of alcoholic beverages should the thiamin status of alcoholic beverages become widely appreciated and misperceived and the bureaucratic problems of instituting thiamin fortification without violating alcoholic beverage labeling regulations. Currently one can say in favor of the policy that it might easily prevent a devastating and costly albeit rare disease and, if done quietly, would probably do no harm. The need for more research into the pathophysiology of this disease is apparent.

PREVENTION OF THE W-K SYNDROME

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