Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts

Abstract

ObjectiveTo systematically test dietary components for association with serum urate levels and to evaluate the relative contributions of estimates of diet pattern and inherited genetic variants to population variance in serum urate levels.DesignMeta-analysis of cross sectional data from the United States.Data sourcesFive cohort studies.Review methods16 760 individuals of European ancestry (8414 men and 8346 women) from the US were included in analyses. Eligible individuals were aged over 18, without kidney disease or gout, and not taking urate lowering or diuretic drugs. All participants had serum urate measurements, dietary survey data, information on potential confounders (sex, age, body mass index, average daily calorie intake, years of education, exercise levels, smoking status, and menopausal status), and genome wide genotypes. The main outcome measures were average serum urate levels and variance in serum urate levels. β values (95% confidence intervals) and Bonferroni corrected P values from multivariable linear regression analyses, along with regression partial R2 values, were used to quantitate associations.ResultsSeven foods were associated with raised serum urate levels (beer, liquor, wine, potato, poultry, soft drinks, and meat (beef, pork, or lamb)) and eight foods were associated with reduced serum urate levels (eggs, peanuts, cold cereal, skim milk, cheese, brown bread, margarine, and non-citrus fruits) in the male, female, or full cohorts. Three diet scores, constructed on the basis of healthy diet guidelines, were inversely associated with serum urate levels and a fourth, data driven diet pattern positively associated with raised serum urate levels, but each explained ≤0.3% of variance in serum urate. In comparison, 23.9% of variance in serum urate levels was explained by common, genome wide single nucleotide variation.ConclusionIn contrast with genetic contributions, diet explains very little variation in serum urate levels in the general population.

Population Impact Attributable to Modifiable Risk Factors for Hyperuricemia

“…In contrast, the serum urate variance explained by these risk factors was very small. In particular, the serum urate variance explained by adherence to the DASH diet was very small (0.1%), similar to findings from a recent study that examined 5 US cohorts (variance ≤0.3%) .…”

“…The current study also demonstrated that, among the 4 hyperuricemia risk factors examined, the most important factor was BMI, with a PAR of 44%. Because diet (along with physical activity) plays a critical role in the risk of obesity and the subsequent risk of hyperuricemia and gout (Figure ), the net total effect of diet is greater than the PAR estimated for the isocaloric DASH diet alone (direct effect, measured independently of BMI), as shown in a previous study . To that end, the large PAR associated with BMI suggests large indirect effects of diet and exercise on the risk of hyperuricemia at the population level.…”

“…This historical background and epidemiologic data are at odds with a recent study that showed ≤0.3% of serum urate variance in the US to be explained by dietary components, particularly when compared with the variance explained by common genome‐wide genes (i.e., genome‐wide association study heritability estimate of 23.9%) . However, because the variance depends on the degree of variability of the exposure without incorporating the exposure's prevalence in the population, it can be highly misleading as a measure of relative importance among risk factors .…”

“…To properly examine the theoretical population impact that can be attributed to modifiable risk factors (i.e., obesity, alcohol intake, diet, and diuretic use) for hyperuricemia in the US, thereby overcoming the critical limitations of the variance explained , we calculated the population attributable risk (PAR) percentage for each risk factor, assuming exposures were causal . The same approach has been used to estimate the population impact of lifestyle factors for myocardial infarction , hypertension , and type 2 diabetes mellitus , as well as for genetic factors discovered in genome‐wide association studies on hyperuricemia and gout .…”

The role of diet in serum urate concentration

“…In a linked article, Major and colleagues (doi: 10.1136/bmj.k3951) report a meta-analysis of cross sectional food frequency questionnaire data from five US cohort studies to test individual foods for associations with serum urate and to compare the variance in serum urate levels explained by dietary factors with heritable factors 4. Their findings replicate the results of previous epidemiological studies, identifying seven foods associated with raised serum urate levels (beer, spirits, wine, potatoes, poultry, soft drinks, and meat) and eight foods associated with reduced serum urate levels (eggs, peanuts, cold cereal, skimmed milk, cheese, brown bread, margarine, and non-citrus fruit).…”