BEER DRINKING AND ITS EFFECT ON URIC ACID

Transcription

1 British Journal of Rheumatology 1984;23:23-29 BEER DRINKING AND ITS EFFECT ON URIC ACID BY T. GIBSON, A. V. RODGERS, H. A. SIMMONDS AND P. TOSELAND Departments of Rheumatology, Medicine and Clinical Chemistry, Guy's Hospital, London SE1 9RT SUMMARY This study attempted to simulate the drinking habits of gout patients. Beer or squash was drunk over a 4-hour period on two successive days by five gouty and five normouricaemic men. Serum lactate increased with beer and squash, but elevation of plasma uric acid was confined to beer drinking. Urate clearance increased with both beverages, but 24-hour uric acid excretion was accentuated only by beer. The purine content of several beers was measured and the principal constituent found to be guanosine, which is probably the most readily absorbed dietary purine. It was concluded that the hyperuricaemic effect of beer was mediated by the digestion of purines contained by the beer and by an effect of ethanol on uric acid synthesis. There was no evidence that beer taken in usual quantities reduced the renal excretion of uric acid. KEY WORDS: Beer, Alcohol, Purines, Uric acid. THE long-cherished notion that habitual alcohol consumption is associated with hyperuricaemia (1) has been confirmed (2, 3). This relationship has been apparent in our own previous studies (4-6). Alcohol is thought to cause hyperuricaemia by reducing uric acid excretion. Lieber et al. (7) demonstrated a rise of serum urate, a 2-5% reduction of uric acid excretion and an elevation of serum lactate following ethanol. Infusion of sodium lactate can reduce renal urate clearance (8) and it is therefore reasonable to assume that the action of ethanol is mediated by lactate. However, Lieber et al. (7) were able to show an effect only by using alcohol over prolonged periods and in amounts which were in excess of those commonly consumed by gout patients in our experience (6). Maclachlan and Rodnan (9) found that ethanol given with food did not always result in reduced uric acid excretion despite elevation of serum lactate levels. Consistent diminution of urate clearance was confined to fasting patients so that the influence of alcohol could not be distinguished convincingly from that of fasting alone. Our own gout patients tend to drink a lot of beer but eat normally (6). We have, therefore, attempted to re-examine the effect of alcohol on uric acid metabolism by simulating their usual drinking and eating habits in a controlled environment. PATIENTS AND METHODS Five men with primary gout and five healthy controls of a similar age were studied in metabolic ward. The average body weight of the gouty was 88 kg and of the controls 81 kg. All subjects had normal blood urea and creatinine levels. Before admission, they were instructed to comply with a low purine, alcohol-free diet for one week. patients discontinued all drugs apart from colchicine. In hospital they were given an isocaloric and constant purine diet for 5 days. Meals were eaten at 8h, 12h and 18h each day. Fluid intake was controlled and on days 3 and 4 each subject drank 2.8 L (5 pints) of beer between 12h and 16h. On days 1, 2 and 5, an equivalent volume of squash (artificial fruit Submitted 5 October; revised 14 November; accepted 16 December Address correspondence to Dr. T. Gibson. 23

2 24 BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXIII NO. 3 juice sweetened with glucose) was consumed over the same time period. The daily intake of beer contained 53 g ethanol and 7.6 mg purine nitrogen. Venous blood samples were obtained at 12h on day 1 and at 8, 12, 14, 16, 18 and 2h on days 2 5. Timed urine collections were made throughout each day coinciding with blood samples whenever possible. Uric acid concentrations of blood and urine were measured by a uricase method (1). Serum lactate was estimated using the Calbiochem- Behring rapid lactate reagents in the Cobas-Bio centrifugal analyser (11) and blood alcohol by the method of Currey et al. (12). Urine ph was measured using a Beckman ph meter, and ammonium and titratable acid excretion were estimated by the method of Chan (13). Measurement of the urine oxypurines, xanthine and hypoxanthine, was confined to the non-gouty subjects (14). The purine nitrogen content of seven traditional British beers was estimated by the above method and compared with values obtained for cider, Guinness, home-brewed beer and a British-brewed lager. RESULTS Consumption of 2.8 L of beer over a 4 h period resulted in the anticipated rise of blood alcohol levels. These were similar for controls and patients. Serum lactate levels rose in parallel with those of alcohol and a similar rise of lactate was seen during squash ingestion on days 2 and 5 (Fig. 1). Individual peak alcohol values varied between 2 47 mmol/1 for gout patients and 13 4 mmol/1 for controls. The time of both peak alcohol and lactate levels varied between subjects, presumably because individuals drank at different rates. TABLE I MAXIMUM OF THE AVERAGE PLASMA URIC ACID AND URATE CLEARANCE VALUES OBTAINED OVER TIMED INTERVALS DURING EACH DAY OF THE STUDY; AVERAGE URINE ph AND 24 h EXCRETION OF URIC ACID, OXYPURINES, AMMONIUM AND TITRATABLE ACID Maximum plasma uric acid (mmol/1) Maximum urate clearance (ml/min) Uric acid excretion Urine hypoxanthine Urine xanthine Urine ph Ammonium excretion Titratable acid excretion 1 (Squash) (Squash) Day 3 (Beer) (Beer) (Squash) Plasma uric acid levels remained constant throughout day 2 during squash consumption. By contrast, beer ingestion on days 3 and 4 was associated with a modest rise of plasma urate in every individual (Table I, Fig. 2). The average increases for the gouty were

3 GIBSON ETAL.: BEER DRINKING AND ITS EFFECT ON URIC ACID 25 Day FIG. 1. Average serum lactate values during squash (S) and beer (B) drinking. (O patients; controls.).5 Day AVERACE BLOOD URIC ACID LEVELS FIG. 2. Average plasma uric acid levels during periods of squash (S) and beer (B) consumption. (O patients; controls.) 8% on day 3 and 18% on day 4. For the controls, plasma uric acid rose by 13% and 6%, respectively. Urate clearance could not be calculated on the morning of day 2 because urine was not collected at timed intervals. The single clearance values for day 1 are based on 24 h collections from 12h on that day. During the period of alcohol ingestion from 12h on days 3 and 4, average urate clearance values increased (Table I, Fig. 3). Clearance was consistently lower in the gouty subjects. Urate clearance estimations during these periods were similar to those during the same time interval when squash was drunk on day 2. Average urine output varied despite attempts to ensure that fluid input was the same each day and that exercise and diet were also controlled. On the first day (day 3) of beer

4 26 BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXIII NO. 3 AVERACE URATE CLEARANCE 12.- FIG. 3. Average urate clearance during periods of squash (S) and beer (B) drinking. (O patients; controls.) TABLE II AVERAGE PURINE CONTENT OF SEVEN TRADITIONAL BRITISH BEERS (EXPRESSED AS mg PURINE NITROGEN/I): RESULTS ARE COMPARED WITH VALUES FOR HOME-BREWED BEER, GUINNESS, CIDER AND LAGER BEER Beverage Adenine Hypoxanthine Xanthine Adenosine Guanosine Traditional British beers (range) Home-brewed beer Guinness Cider Lager beer 1.2 (.4-3.) (-2.5) ( ) (-6.) (1-17.3) Total purine 22.2 ( ) drinking, mean uric acid excretion increased 15% in the gouty and 2% in the controls. Hypoxanthine and xanthine excretion in the control subjects were not altered by beer consumption. During beer drinking, urine ph fell and titratable acid excretion increased markedly. Ammonium excretion was unaltered (Table I). The average purine nitrogen content of seven British beers was 22.2 mg/1. Of this, 61 % was present as guanosine, and similar values were seen for Guinness. The total purine nitrogen and guanosine content of lager was slightly lower but both cider and homebrewed beer contained negligible quantities of purines (Table II). The average total purine nitrogen content of American beers, calculated from published data (15), was found to be 22.3 mg/1, of which guanosine comprised 71%.

5 GIBSON ETAL.: BEER DRINKING AND ITS EFFECT ON URIC ACID 27 DISCUSSION The results of our study showed that the leisurely drinking of beer by subjects who were not fasting increased plasma uric acid. The investigation differed from some earlier studies in that the quantity of alcohol was relatively small and the subjects were eating regular meals (7, 9). Beer and squash induced virtually identical increases of serum lactate, the magnitude of which was similar to that achieved by Maclachlan and Rodnan (9) when larger amounts of alcohol were given with food. However, an increase of plasma urate was confined to periods of beer drinking, indicating that some mechanism other than an increase of serum lactate was responsible. Furthermore, despite the elevation of circulating lactate, ingestion of beer was associated with an increase of urate clearance which was roughly equivalent to the values seen during squash consumption. There is evidence that urate clearance follows a circadian rhythm with a peak in the afternoon (16). It is thus possible that the increase of urate clearance seen during the periods of both squash and beer drinking was a natural phenomenon. However, there are convincing data which indicate that urate clearance is enhanced by increased fluid intake (17) and this alone might have accounted for the rise in urate clearance. It is surprising that clearance was not further accentuated in response to the rise of plasma uric acid associated with beer. However, the increase of 24 h urine uric acid left little doubt that an excretory response did occur. The increase of plasma urate was marginally greater in the gouty subjects although in neither group was the change very striking. A relatively low urate clearance of the gouty subjects was apparent throughout the study and is a well-documented characteristic of such patients (18). There was some evidence that amongst the gouty at least, the second day of beer drinking had a more pronounced influence on plasma urate. A cumulative effect might account for the pronounced hyperuricaemia so often seen in habitual drinkers with gout. The fall of urine ph, the increase of titratable acid and the lack of change in ammonium excretion following beer were striking observations. These could not be attributed entirely to the increase of uric acid excretion which did not correlate with titratable acid. It is possible that hydrogen ion excretion and ammonia synthesis are linked with uric acid metabolism by some as yet obscure mechanism (18, 19). Reduced ammonium excretion in gout has been attributed to diversion of glutamine from ammonia to uric acid production (21), a hypothesis which has been criticized (22, 23). Nevertheless, in the present study, increased uric acid synthesis and excretion may have taken place at the expense of ammonia production and could explain the exclusive disposal of increased hydrogen as titratable acid. It is not clear whether the increased plasma and urine uric acid associated with beer were wholly, or partly, due to increased uric acid production. The contribution of purines contained by the beer could not be quantified. There was no increase of xanthine or hypoxanthine excretion in the control subjects with beer and this usually accompanies increased uric acid synthesis. However, there is good evidence that ingested alcohol will increase uric acid production (24) and infusion may stimulate urate production in the liver (25) as well as the excretion of urine oxypurines (26). Chronic ethanol exposure will increase liver metabolism and thereby reduce its ATP content (27). This may explain the reported increase of adenine nucleotide turnover, the degradation of which may accelerate uric acid synthesis (26). Beer is the only acknowledged alcoholic beverage with a measurable purine content and our results showed that this varied between products. Home-brewed beer and cider contained small quantities of total purine nitrogen, lager rather more, but Guinness

6 28 BRITISH JOURNAL OF RHEUMATOLOGY VOL. XXIII NO. 3 resembled the average values of the seven traditional domestic beers. A similarity between British and American beers was apparent and the predominance of guanosine was striking in both. Estimation from dietary tables (28) suggests that the total purine nitrogen of a liver portion weighing 17 g would be 244 mg (contained mainly as nucleic acids). This is roughly equivalent to 11 1 of beer, a volume which even well practised beer drinkers would be incapable of consuming in one sitting. In man, the ability to absorb dietary purines depends on their nature (29). AnimaJ studies have demonstrated that guanosine is more readily absorbed than other nucleosides, nucleotides or bases (3) and in man, dietary ribomononucleotides are digested more efficiently than nucleic acids (31). This implies that although beer contains less purine than liver, its presence as guanosine may allow more ready absorption. Our attempts to reproduce the drinking pattern of typical patients with gout provided no evidence that the hyperuricaemic effect of beer was mediated by a net diminution of renal urate excretion. The increase of plasma and urine uric acid was consistent with the ingestion of dietary purines contained by the beer. However, the foregoing discussion makes it clear that an effect of alcohol on uric acid synthesis may also be implicated. It is likely that both mechanisms contribute to the association of beer drinking with gout. ACKNOWLEDGEMENTS We are most grateful to the Arthritis and Rheumatism Council for financial support and to Courage Breweries Ltd. for their interest and help. REFERENCES 1. Copeman WS. A short history of the gout London: Cambridge University Press, 1974; Brochner-Mortensen, Heberden Oration. Ann Rheum Dis 1958; 17: Drum DE, Goldman PA, Jankowski CB. Elevation of serum uric acid as a clue to alcohol abuse. Arch Intern Med 1981 ;141: Gibson T, Grahame R. and hyperlipidaemia. Ann Rheum Dis 1974;33: Gibson T, Kilbourn K, Horner I, Simmonds HA. Mechanism and treatment of hypertriglyceridaemia in gout. Ann Rheum Dis 1979;38: Gibson T, Rodgers AV, Simmonds HA, Court Brown F, Todd E, Meilton V. A controlled study of diet in patients with gout. Ann Rheum Dis 1983;42: Lieber CS, Jones DP, Losowsky KS, Davidson CS. Inter-relation of uric acid and ethanol metabolism in man. J Clin Invest 1962;41: Yu TF, Sirota JH, Berger L, Halpern M, Gutman AB. Effect of sodium lactate infusion on urate clearance in man. Proc ExpBiol Med 1957;96:8O Maclachlan- MJ, Rodnan FP. Effects of food, fast and alcohol on serum uric acid and acute attacks of gout. Am J Med 1967;42: Simmonds HA. A method of estimation of uric acid in urine and other body fluids. Clin Chim Ada 1967;15: Jung G, Kaufman S, Ferard G. Determination du lactate sur analyseur centrifuge par la lactate dehydrogenase en presence d'alanine aminotransferase. Ann Biol Chem 1977,35: Curry AS, Walker GS, Simpson G. The determination of ethanol in blood using gas chromatography. Analyst 1966;91: Chan JCM. The rapid determination of urinary titratable acid and ammonium and evaluation of freezing as a method of preservation. Clin Biochem 1972^5: Simmonds HA. Two-dimensional thin layer high voltage electrophoresis and chromatography for the separation of urinary purines, pyrimidines and pyrizolo-pyrimidines. Clin Chim Ada 1979,23: Charalambous G, Bruckner KJ, Hardwick WA, Lunnebach A. Separation, identification and determination of beer flavour compounds by high pressure liquid chromatography. Tech Q Master Brew Assoc Am 1974;11:15 4.

7 GIBSON ETAL.: BEER DRINKING AND ITS EFFECT ON URIC ACID Lang F, Greger R, Oberleithner H, et al. Renal handling of urate in healthy man in hyperuricaemia and renal insufficiency: circadian fluctuation, effect of water diuresis and of uricosuric agents. EurJ Clin Invest 198O;lO: Diamond HS, Lazarus R, Kaplan D, Halberstam D. Effect of urine flow rate on uric acid excretion in man. Arthritis Rheum 1972;15: Gibson T, Highton J, Potter C, Simmonds HA. Renal impairment and gout. Ann Rheum Dis 198;39: Gibson T, Hannon SF, Hatfield P, et al. The effect of acid loading on renal excretion of uric acid and ammonium in gout. Adv Exp MedBiol 1977;76B: Gibson T, Rodgers V, Potter C, Simmonds HA. Allopurinol treatment and its effect on renal function in gout: a controlled study. Ann Rheum Dis 1982;41: Gutman AB, Yu TSF. An abnormality of glutamine metabolism in primary gout. Am J Med 1963;35:82O Vogler WR, Drane JW. Effect of allopurinol on urinary ammonia excretion in patients with gout. Metabolism 1969;18: Swales JD, Kopstein J, Wrong OM. Renal excretion of ammonia and urate production: examination of Gutman-Yu hypothesis. Metabolism 1972;21: Delbarre F, Auscher C, Brouilhet H, de Gery A. Action de Pethanol dans la goutte et sur la metabolisme de 1'acide urique. Sem Hdp Paris 1967;43: Grunst J, Dietze J, Wicklmayr M. Effect of metabolic changes on uric acid production of human liver. In: Fleisch H, Robertson WG, Smith LH, Vahlinsiek V, eds. Urolithiasis research, New York: Plenum Press, 1976; Faller J, Fox I. Ethanol induced hyperuricaemia. Evidence for increased urate production by activation of adenine nucleotide turnover. N Engl J Med 1982;3O7:1598-6O Israel Y, Videla L, Bernstein J. Liver hypermetabolic state after chronic ethanol consumption: hormonal interrelations and pathogenic implications. FedProc 1975;34: McCance RA, Widdowson EM. The composition of foods, London: H.M.S.O., Clifford AJ, Riumallo JA, Young VR, Scrimshaw NS. Effect of oral purines on serum and urinary uric acid of normal, hyperuricaemic and gouty humans. / Nutr 1976;1O6:428-5O. 3. Potter C, Cadenhead A, Simmonds HA, Cameron JS. Differential absorption of purine nucleotides, nucleosides and bases. A dv Exp Med Biol 198;122A: Griebsch A, Zollner N. Effect of ribomononucleotides given orally on uric acid production in man. Adv Exp Med Biol 1974;41B:435^2.