The Impact of Alcohol on Hyperuricemia and Gout
For centuries, alcohol has long been associated with hyperuricemia and gout. In 1876, Alfred Garrod wrote that 'the use of fermented liquors is the most powerful of all the predisposing causes of gout, nay so powerful that it may be a question whether gout would ever have been known to mankind had such beverages not be indulged in'. Increased uric acid production and decreased uric acid excretion have both been implicated in the pathogenesis of alcohol-induced hyperuricemia. Specifically, alcohol metabolism produces net adenosine triphosphate degradation to adenosine monophosphate, which is subsequently converted to uric acid. In addition, lactate generated via alcohol consumption increases proximal tubular urate re-absorption while interfering with urinary urate secretion.[36,37] Chronic heavy use of alcohol also has the potential to inhibit conversion of the pro-drug allopurinol to its active metabolite oxypurinol.
Recent advances in molecular biology have defined the cellular mechanisms behind the long-recognized capacity of ketosis to markedly raise serum uric acid level. Urate transporter-1 (URAT1) is an electroneutral transporter that is centrally involved in urate re-absorption at the proximal tubule lumen membrane. Alcohol ingestion directly induces temporary lactate generation and also potentially indirectly triggers ketoacidosis through the fasting often associated with heavy alcohol ingestion. Ketoacids not only compete with urate for secretion but also activate proximal tubular urate re-absorption by activating the organic anion exchange function of URAT1[15**,36,37,39,40] (Fig. 1). URAT1 is located on the apical plasma membrane of proximal tubular cells in human kidneys and is the central factor in reabsorbing tubular uric acid (as urate anion) from the lumen in exchange for intracellular organic anions. The urate re-absorption transport process via URAT1 is triggered by high loads of lactate and several other organic anions. Hence, intense alcohol use, dietary ketosis and prolonged anaerobic muscular activity are among the activities that promote renal urate re-absorption.
The hyperuricemic effect of alcohol has since been observed in many studies. Most recently, NHANES III[6*] was used to assess the impact of various alcoholic beverages on the serum uric acid level. Consistent with previous studies, the serum uric acid level increased with increasing total alcohol intake. This association was only notable with beer and liquor consumption where those with the highest intake (at least one serving per day) had serum uric acid levels of 0.99 mg/dl (95% CI 0.82-1.17) and 0.58 mg/dl (95% CI 0.36-0.80) higher than non-drinkers, respectively. This difference became more prominent among women and those with BMIs of less than 25 kg/m2. Surprisingly, an inverse relationship was noted with wine intake, with those drinking at least one serving per day having a lower serum uric acid level (-0.23 mg/dl; 95% CI -0.48 to -0.03). The mechanism for this protective effect of wine remains unknown. It has been postulated, however, that antioxidants contained in wine, or greater attention to diet and health issues in wine drinkers, may mitigate the potential deleterious effects of alcohol.
Another small study also noted differing effects of different types of alcohol on serum uric acid. Four gout patients were given regular beer, liquor (vodka with orange juice), non-alcoholic beer or orange juice on separate occasions. Patients were monitored for both serum and urine urate levels. The serum uric acid rose significantly only after the ingestion of regular beer. In addition, both regular and non-alcoholic beer reduced the urinary excretion of urate.
In addition to hyperuricemia, the Health Professionals Follow-Up Study[7*] also found that alcohol was associated with an increased risk of developing gout. The risk of gout increased with increasing intake of total alcohol, with the greatest association with beer, followed by spirits. Compared with those who did not drink, men who drank more than two drinks per day had the multivariate RRs of 2.51 and 1.60 for beer and wine, respectively. The risk of gout increased by 1.17 (95% CI 1.11-1.22) per 10 g increase in daily alcohol intake. Similarly to the results from the NHANES III, wine was not association with an increased risk of gout. Beer, unlike most other forms of alcohol, has a high content from malt of the readily absorbable purine guanosine, which can further increase uric acid production. This problem is not avoided by the use of reduced-carbohydrate 'light beer'.
Curr Opin Rheumatol. 2006;18(2):193-198. © 2006 Lippincott Williams & Wilkins
Cite this: Recent Developments in Diet and Gout - Medscape - Mar 01, 2006.