THE EFFECT OF ALCOHOL CONSUMPTION ON SERUM URIC ACID LEVEL

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1 THE EFFECT OF ALCOHOL CONSUMPTION ON SERUM URIC ACID LEVEL Raut Sayali E, Pagar Atish B, Kowale Arun N ABSTRACT BACKGROUND : Association between alcoholism and hyperuricemia has been suggested. Very few studies are done correlating e quantity of alcohol consumed wi serum uric acid (UA) level. As alcoholism is also associated wi end organ damage, it will be interesting to see correlation between quantity of alcohol consumption, serum UA levels and end organ damage markers(serum creatinine, SGOT, SGPT), so at some light can be rown on understanding e mechanism of hyperuricemia in alcoholics. METHODS : Sample: 30 light, 27 moderate, 30 heavy alcoholic male subjects and 30 age matched non alcoholics of age between 30 & 60 years. Details about amount, type & frequency of alcohol intake and diet were gaered by history given by subjects. Blood samples were collected wiin 24 hours of last drink and serum UA, serum bilirubin, SGPT & SGOT were estimated. RESULTS : Consistent and very significant (P<0.0001) increase in serum UA wi increasing quantity of alcohol consumption was observed. Serum creatinine showed positive correlation wi quantity of alcohol intake at is significant (P<0.001) only in heavy alcoholics. Positive correlation between serum UA and serum creatinine observed was significant (P<0.001) only in moderate and heavy alcoholics. Correlation between serum UA and SGOT was positive and significant (<0.05) only in heavy alcoholics. CONCLUSION : Regular moderate alcohol consumption promotes hyperuricemia because of increased urate production by accelerating hepatic breakdown of ATP and decreased urate excretion by conversion to lactic acid. Along wi ese, renal impairment causing decreased urate excretion and hepatic impairment affecting urate metabolism may be involved in e mechanism of hyperuricemia associated wi heavy alcoholism. Regular alcohol consumption in any amount promotes hyperuricemia. KEY WORDS: Alcohol, End organ damage markers, Serum uric acid. INTRODUCTION Alcoholism is one of e principle medical and social problems in e world. Alcohol consumption can give rise to psychological as well as medical problems involving [1] virtually every system. Implications of hyperuricemia are well known in past and present literature of medicine. In addition to risk of gout and nephroliiasis, ere is increasing evidence at hyperuricemia may also be involved in e paogenesis [2] of hypertension, vascular diseases and renal failure. Many previous studies have pointed out e risk factors [3,4,5,6] for hyperuricemia. The association between alcohol consumption and hyperuricemia has also been [7,,8,9] suggested But, is association was confirmed only recently in 2004 in prospective study conducted by Dr. Choi and Dr. Atkinson et al. They found a strong association between alcohol consumption and incident [10] gout. In humans, uric acid is synesized in liver and small intestines as e final breakdown product of purine nucleotide metabolism and excreted by kidney. Blood levels of urate are maintained by e balance between [2] e generation and e excretion. As in alcoholism ere is definite evidence of increased blood urate levels and it is also associated wi e end organ damage, e present study was conducted to find out e correlation between quantity of alcohol consumption, serum uric acid levels and end organ damage markers. MATERIAL & METHODS Selection of subjects: Present study was conducted in four groups: light (n=30), moderate(n=27), heavy alcoholics(n=30) taking absolute alcohol regularly for at least one year and non-alcoholics (n=30) as controls of age between 30 & 60 years. 1&2 Assistant Professor, Department of Physiology, GMC Miraj, Maharashtra. Professor & Head, Department of Physiology, R. C. S. M. Medical College & C. P. R. Hospital, Kolhapur, Maharashtra

2 Only males were selected for e present study, as it was difficult to get females as regular drinkers in light, moderate and heavy quantities. Also e level of drinking to call it as light, moderate and heavy has not been clearly defined for women. It is known at higher levels of alcohol are achieved in females an in males for e same dose of eanol due to less gastric dehydrogenase and less volume of distribution in females as compared to males. That is why same criteria could not be applied for males and females. Among e alcoholic groups, people consuming any type of alcoholic beverage were taken as subjects, because it was e absolute eanol intake which was taken into e consideration (irrespective of type of beverage) and not e amount of beverage. A criterion for dividing e drinkers in different groups is based on amount of absolute eanol taken in grams per day according to [11,12] British Heart Foundation and The Royal College. Thus, different alcoholic groups are : Light alcoholic group: intake of < 30 g/d of absolute eanol. Moderate alcoholic group: intake of g/d of absolute eanol. Heavy alcoholic group: intake of > 50 g/d of absolute eanol. In order to maintain uniformity in e study, taking into consideration at serum uric acid level is affected by dietary purine content which is high in non-vegetarian diet; subjects having mixed diet were selected. Patients suffering from or on treatment for gout, hyperuricemia, psoriasis, cancers (leukemia, polycyemia, lymphomas), diabetes and hypertension; subjects having history of increased tissue breakdown like major trauma, starvation etc. in recent past, were excluded from e study. The subjects taking illicit liquor were excluded, as is type of liquor is not licensed by e government and because of e lack of standardization, it was not possible to calculate e intake of eanol in grams per day for ese beverages. Study protocol: The study was conducted at e B J Medical College & Sasoon General Hospital, Pune, Maharashtra, India. Written informed consent was taken from each subject. All e information about e alcohol intake, diet, any oer illnesses, recent operations or accidents was noted in e form of history in a questionnaire. Absolute eanol intake was calculated as follows: A) Malted liquors : alcohol content is low (3 6% v/v) eg Beers, Stout. B) Wines : Light wines: Alcohol content 9 12% v/v. eg Cider, Claret. Fortified wines: Alcohol content 16 22% v/v. eg Port, Sherry. Effervescent wines: Alcohol content 12 16% v/v. eg Champagne. C) Spirits : Though e alcohol content can vary from 40 55% v/v in India (and almost internationally) for all licensed brands it is standardized to 42.8% v/v or 37%w/w. eg Rum, Gin, Whisky, Brandy, Vodka etc. [14] D) COUNTRY LIQUOR : Eanol content may vary from 11% to 45% v/v. Different types of drinks contain different percentage of eanol. Beers range from 3 8% v/v of eanol in eir alcohol content i.e. on an average 5% v/v of eanol. This means 5 ml of absolute alcohol (5 X 0.79 = 3.95 g of eanol) per 100 ml of drink, e rest being water. Similarly, Wines contain on an average 12% of eanol v/v i.e. 12 ml of absolute eanol (corresponds to 9.48 g of eanol) per 100 ml of wine. Spirits contain about 43% v/v of eanol i.e. 43 ml of absolute eanol (corresponds to about g of absolute eanol) per 100 ml of spirits. So, one unit or drink which corresponds to ingestion of 10 g of absolute eanol corresponds approximately to intake of 250 ml of beer, 30 ml of spirits and 105 ml of wine. Similarly unit for country liquor (28% of eanol v/v i.e g of eanol per 100 ml) was calculated according to e percentage of eanol present in it. Six to seven ml of blood was collected under all aseptic precautions by venepuncture using disposable syringes and needles. Care was taken to see at blood samples were collected wiin 24 hours of e last drink to avoid e waning off effect of alcohol on e blood parameters. Blood sample was taken into e plane bulb and serum obtained was used for manual estimation of serum uric [15] acid by Meod of Caraway, serum bilirubin by 370

3 [16] Malloy and Evelyn meod and for estimating serum creatinine, SGPT and SGOT by autoanalyser of SuperStat 919 company. We took levels of serum creatinine; serum bilirubin, SGOT and SGPT as tissue damage markers for kidney and liver respectively. Serum uric acid levels and levels of ese tissue damage markers were compared wi age matched controls in different study groups. The experiment protocol was approved by e Research and Human Eics Committee of B J Medical College & Sasoon General Hospital, University of Pune, Maharashtra, India. Statistical analyses: Analysis was done by Statistical Package for Social Sciences (SPSS) software version 9, by using 't' test, 'Z' test. A 'P' value of < 0.05 was considered statistically significant. RESULTS & DISCUSSION Table 1 : Comparison of Blood Parameters in study groups. Table 3 : Correlation between quantity of Alcohol Intake and Serum Uric Acid in alcoholic groups. Table 4 : Correlation between quantity of Alcohol Intake and Serum Creatinine in alcoholic groups. Table 5 : Correlation between quantity of Alcohol Intake and Serum Bilirubin in alcoholic groups. Table 6 : Correlation between quantity of Alcohol Intake and SGPT in alcoholic groups. *P<0.05, ** P<0.01, # P< Table 2 : Comparison of Serum Uric Acid in study groups. Table 7 :Correlation between quantity of Alcohol Intake and SGOT in alcoholic groups. Light Vs Moderate = 5.53, P< Light Vs Heavy = 13.03, P< Moderate Vs Heavy = 6.56, P<

4 Table 8 : Correlation between Serum Uric Acid and Serum Creatinine in study groups. Table 9 : Correlation between Serum Uric Acid and Serum Bilirubin in study groups. Table 10 : Correlation between Serum Uric Acid and SGPT in study groups. Table 11 : Correlation between Serum Uric Acid and SGOT in study groups. Definite hyperuricemia has been observed in moderate and heavy alcoholics (table 1, 2). Statistical analysis reveals significant increase in serum uric acid levels in light, moderate and heavy alcoholic subjects as compared to control group (table 2). Serum uric acid level also increases in correlation wi e amount of absolute alcohol intake per day wi P < (very significant) (table 2, 3). Comparison of serum creatinine levels wi quantity of alcohol intake per day revealed increasing positive correlation at is statistically significant only in heavy alcoholic group (table 4). Positive correlation between serum uric acid level and serum creatinine has been observed in alcoholics. It was statistically significant only in moderate and heavy alcoholics but, not in light alcoholics (table 8). It is observed at increasing alcohol intake up to moderate quantity does not impair renal function as serum creatinine levels are not significantly altered. But serum uric acid levels are consistently increasing wi quantity of alcohol intake. Similar finding were observed by Faller et al (1982) in eir study and found at eanol administration has been shown to increase uric acid production by increasing ATP degradation to AMP, a uric [7] acid precursor. Puig et al (1984) in eir study wi similar findings showed at, eanol induced increase in uric acid production involve acetate conversion to acetyl [17] CoA in e metabolism of eanol. It is seen at ere is no statistically significant correlation between quantity of alcohol intake and serum bilirubin levels. In fact, e correlation is negative ough insignificant in light and heavy alcoholic group (table 5). The correlation between serum bilirubin level and serum uric acid is also statistically insignificant and is negative in light alcoholics (table 9). There is a negative correlation between quantity of alcohol intake and SGPT and SGOT in light alcoholics. It's statistical significance is only marginal. This means ere is no increase in SGPT and SGOT levels wi increasing alcohol intake. The correlation of quantity of alcohol intake wi SGPT is negative and at wi SGOT is positive in moderate alcoholics but bo are statistically insignificant. Whereas e correlations between quantity of alcohol intake and SGPT and SGOT are positive in heavy alcoholics wi no statistical significance (table 6, 7). The correlation between SGPT and serum uric acid is negative 372

5 in light and moderate alcoholics showing no statistical significance in any group. That between SGOT and serum uric acid is positive and statistically significant only in heavy alcoholic group. That is, ere is no increase in SGPT wi increasing serum uric acid level and increase in SGOT wi increase in uric acid level is observed only in heavy alcoholics (table 10, 11). This indicates at hepatic impairment has least role in hyperuricemia observed in light and moderate alcoholics and to some extent may be involved in e mechanism of hyperuricemia seen in heavy alcoholics. When e alcohol intake exceed above 50g/d, ere is definite evidence of impaired renal function as indicated by increased serum creatinine levels. So, hyperuricemia observed in heavy alcoholics can be attributed to 1) Increased ATP degradation, 2) Decreased urate excretion via conversion of alcohol to lactic acid, which reduces renal uric acid excretion by competitively inhibiting uric [18,19,20] acid secretion by e proximal tubules and 3) To some extent impaired renal function leading to decreased urate excretion. Alough we got ese results, we recognize at we should estimate our results carefully because of some limitations. 1) We could not assess e association between e type of alcoholic beverage and hyperuricemia. 2) Information on alcohol consumption was obtained by an interview using a questionnaire wiout verification using biological markers. 3) Subjects reported only one beverage at ey usually consumed. Many of e subjects might have consumed more an one kind of beverages. Also a prospective study wi a larger population will be expected to investigate e association between e type of alcoholic beverage and hyperuricemia. REFERENCE 1. Lloyd GG. Principles of Medical Psychiatry. In: Davidson's Principles and Practice of Medicine. 18 edition, Edited by: Haslett C, Chilvers ER, Hunter JAA, Boon NA. Published by Churchchill Livingstone, International Publication; Hediger MA, Johnson RJ, Miyazaki H, Endou H. Molecular Physiology of Urate Transport. Physiology 2005; 20: Steel TH. Control of uric acid excretion. N Engl J Med 1971; 284: Bonora E, Targher G, Zener MB, Saggiani F, Cacciatory V, Tosi F, et al. Relationship of uric acid concentration to cardiovascular risk factors in young men. Role of obesity and central fat distribution. The Verona Young Men Aerosclerosis Risk Factors Study. Int J Obes Relat Metab Disord 1996; 20: Carneon MR, Fortmann SP, Palaniappan L, Duncan BB, Schmidt MI, Chambless LE. Risk factors for progression to incident hyperuricemia: The aerosclerosis risk in communities study, Am J Epidemiol 2003; 158: Nicholls A, Scott JT. Effect of weight loss on plasma and urinary levels of uric acid. Lancet 1972; 2: Faller J, Fox IH. Eanol induced hyperuricemia: evidence for increased urate production by activation of adenine nucleotide turnover. N Engl J Med 1982; 307: Johnson RJ, Rideout BA.Uric acid and diet: Insights into e epidemic of cardiovascular disease. N Engl J Med 2004; 350: Kono S, Shinchi K, Imanishi K, Honjo S, Todoroki I. Behavioural and biological correlates of serum uric acid: A study of self defense officials in Japan. Int J Epidemiol 1994; 23: Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G. Alcohol intake and risk of incident gout in men: a prospective study. Lancet 2004; 363: Hein HO et al. Alcohol consumption, serum LDL cholesterol concentration and risk of ischaemic heart disease. Brit Med J 1996; 312: Preedy VR et al. Eanol induced cardiovascular disease. Brit Med Bulletin 1994; 50: Tripai KD. Eyl and Meyl Alcohols. In: Essentials of Medical Pharmacology. 5 edition, 2003 Reprint 2004 Edited by: Tripai KD.Published by Jaypee Broers Medical Publishers (P) Ltd, New Delhi, India; Parikh CK. Arrack (Country Liquor). In: Parikh's Textbook of Medical Jurisprudence, Forensic Medicine and Toxicology. 6 edition, 1999 Reprint 2007 Edited by: Parikh CK. Published by CBS Publishers and Distributors, India; Varley H. Non Protein Nitrogen. In: Practical Clinical Biochemistry. 4 edition, Edited by: Varley H. Published by CBS Publishers and Distributors, India; Varley H. Tests in Liver and Biliary Tract Disease. In: Practical Clinical Biochemistry. 4 edition, Edited by: Varley H. Published by CBS Publishers and Distributors, India; Puig JG, Fox IH. Eanol induced activation of adenine nucleotide turnover. Evidence for role of acetate. J Clin Invest 1984; 74: Yu TF, Sirota JH, Berger L. Effect of sodium lactate infusion on urate clearance in man. Proc Soc Exp Biol Med 1957; 96: Beck LH. Clinical disorder of uric acid metabolism. Med Clin Nor Am 1981; 65: Fam GA. Gout, diet and insulin resistance syndrome. J Rheumatol 2002; 29: