In this large prospective cohort study involving men, we found an increased risk of gout with higher meat consumption or seafood consumption but not with higher consumption of animal or vegetable protein or purine-rich vegetables. Furthermore, we found a strong inverse association between the consumption of dairy products, especially low-fat dairy products, and the incidence of gout. These associations were independent of both the other dietary factors we studied and other purported risk factors for gout, such as high body-mass index, older age, hypertension, alcohol use, use of diuretics, and chronic renal failure.

The suspicion that there is a link between purine-rich diets and gout has been based on metabolic experiments in animals and humans that examined the effect of the artificial short-term loading of purified purine on the serum uric acid level (not on gouty arthritis).17-20 Although these studies provide a theoretical basis for the effect of a purine-rich diet on hyperuricemia and, conceivably, on the eventual development of gout, several important hurdles remain before these data can be applied to clinical practice or public health efforts.

First, little is known about the precise identity and quantity of individual purines in most foods, especially when they are cooked or processed.5 In addition, the bioavailability of various purines contained in different foods varies substantially. For example, dietary experiments have shown that the bioavailability is greater for RNA than for an equivalent amount of DNA,20 greater for ribonucleotides than for nucleic acid,21 and greater for adenine than for guanine.17 Finally, the outcome examined in these metabolic studies was hyperuricemia, rather than gout,17-21 and a substantial proportion of patients with hyperuricemia will not have gouty arthritis.22,23 Thus, it has been difficult to predict whether a certain “purine-rich” food or food group that is commonly consumed actually affects the risk of gout and, if it does, to what extent.

Our study overcame these hurdles by examining common foods or food groups and new cases of gout, and it provides clinically relevant information: each additional daily serving of meat was associated with a 21 percent increase in the risk of gout, and each additional weekly serving of seafood was associated with a 7 percent increase in risk. This effect may be greater in patients who already have gout: because renal urate clearance is relatively impaired in most patients with gout, the absorption of dietary purines causes a steeper increase in the blood uric acid level than do equivalent quantities in persons with normouricemia.24,25

We found that the risk of gout associated with seafood intake was significantly higher among men who were not overweight than among men who were overweight. These results suggest that there may be a substantial difference between these subgroups in purine-to-uric-acid metabolism, uric acid excretion specifically related to seafood intake, or both. It remains to be elucidated how these findings are related to hyperuricemia associated with overweight that may occur through both increased production and decreased renal excretion of uric acid3,4,26; it is also unclear why the interaction appears to be limited to seafood intake. Confirmation of these findings by future studies might result in more refined and comprehensive dietary recommendations for the prevention of gout, given the emerging role of fish intake in the prevention of coronary heart disease.27

We did not find a significant association between gout and the consumption of purine-rich vegetables, either as a group or individually. The variation in the risk of gout associated with different purine-rich foods may be explained by the variation in the amounts and types of purine content and their bioavailability for purine-to-uric-acid metabolism.5,17-21 It has been suggested that moderation in dietary purine consumption is indicated for patients who habitually eat large amounts of purine-containing foods, of either animal or vegetable origin3,4; however, our results suggest that this type of dietary restriction may be applicable to purines of animal origin but not to purine-rich vegetables.

We found a strong inverse relation between consumption of dairy products, especially low-fat dairy products, and the incidence of gout. The ingestion of milk proteins (casein and lactalbumin) has been shown to reduce serum uric acid levels in healthy subjects because of the uricosuric effect of these proteins.8 Conversely, a significant increase in the uric acid level was induced by a dairy-free diet in a four-week randomized clinical trial.9 Since dairy products are low in purine content, dairy protein may exert its urate-lowering effect without providing the concomitant purine load contained in other protein sources such as meat and seafood. Although other nutrients in dairy products may be responsible for the inverse association, there is currently no relevant biologic or metabolic evidence available.

A higher total intake of animal or vegetable protein was not associated with an increased risk of gout. Actually, our results regarding vegetable-protein intake suggest that protein from vegetable sources may have a protective effect, although its magnitude appeared to be smaller than that provided by dairy protein. High-protein diets are associated with increased urinary uric acid excretion and may reduce the blood uric acid level.5,6,28-30 In a recent open-label study involving 13 patients, a dietary intervention was used that included an increased proportional intake of protein; the study showed a significant reduction in the rate of recurrent attacks of gout.31 These data support our findings that the consumption of protein does not increase the risk of gout but, rather, may actually decrease the risk and that the protein content of foods may not be a good surrogate for their purine content.

Several strengths and potential limitations of our study deserve comment. Our study was substantially larger than previous studies concerning gout,1,5,23,32-35 and dietary data were prospectively collected and validated.10,12 Potentially biased recall of diet was avoided, because the intake data were collected before gout was diagnosed. Our findings are most directly generalizable to men 40 years of age or older (the population with the highest prevalence of gout23) who have no history of gout. As in other epidemiologic studies of gout,1,23,32-34 our primary case definition of gout did not require the observation of urate crystals in joint fluid. Although the presence of a tophus or urate crystals in joint fluid would be diagnostic of gout,13 the sensitivity of these findings is too low, especially in a population-based study, because arthrocentesis is performed infrequently.

In our study, fulfillment of 6 of the 11 American College of Rheumatology survey criteria for gout13 showed a high degree of concordance with reviews of the medical records, and the incidence of gout fulfilling these criteria in our cohort agreed closely with the estimated incidence among male physicians in the Johns Hopkins Precursor Study1 (1.5 and 1.7 per 1000 person-years, respectively). Furthermore, when we evaluated the effect of various definitions of gout, our findings appeared to be robust, and the magnitude of the associations tended to increase with increasing specificity of the case definition.

Our study was observational; thus, we cannot rule out the possibility that unmeasured factors might contribute to the observed associations. Overall, however, our findings provide prospective evidence that meat consumption and seafood consumption are associated with an increased risk of gout, whereas consumption of dairy products, especially low-fat dairy products, is associated with a substantially reduced risk of gout. In contrast, moderate intake of purine-rich vegetables or protein is not associated with an increased risk of gout.