Coffee Itself, Not Caffeine, Reduces Risk of Gout

BOSTON, May 25 -- At relatively high daily doses, coffee -- whether regular or decaf -- may protect against gout, researchers here found.

In a large observational study, regular consumption of six or more cups a day was associated with 0.43 mg/dl lower serum uric acid levels compared with no coffee intake at all, said Hyon K. Choi, M.D., Dr.P.H., and Gary Curhan, M.D., Sc.D., both of Brigham and Women's Hospital in Boston.

While Americans average only two cups a day, the fact that coffee is readily available everywhere may make the findings important to public health, they wrote in the June issue of Arthritis Care & Research.

"This level of population mean difference of serum uric acid levels can be translated into a clinically relevant difference in the risk for incident gout," they said.

A previous study in middle-age Japanese men had established that coffee might lower gout risk, but it was not clear whether caffeine was responsible.

So the researchers looked at data from the National Health and Nutrition Examination Survey (NHANES III). Their analysis included a nationally representative sample of 14,758 men and women.

Participants underwent a medical examination and reported coffee and tea intake in a food frequency questionnaire administered during the home interview portion of the survey.

The mean age of participants was 45, and more than half of them drank at least one cup of coffee a day. Only 169 had six or more cups a day; 590 drank four or five cups a day.

The mean serum uric acid level was 5.32 mg/dl, and 18% of participants had hyperuricemia, the precursor of gout.

After adjusting for age and sex, the researchers found:

• Coffee intake of four to five cups daily was associated with 0.26 mg/dl lower serum uric acid levels compared with no intake (95% confidence interval 0.11 to 0.41).
• Six or more cups a day was associated with 0.43 mg/dl lower serum uric acid levels compared with no intake (95% CI 0.23 to 0.65, odds ratio 0.57, 95% CI 0.35 to 0.94).
• A significant trend for lower levels with higher intake, which remained significant after adjustment for decaffeinated coffee and tea intake (P<0.001 for trend).
• Decaffeinated coffee alone yielded a similar 0.39-mg/dl reduction in uric acid in the highest intake category (four cups or more a day) compared with no intake, but the difference was not significant.
• The trend for an inverse association between decaffeinated coffee intake and serum uric acid levels was significant, even when further adjusting for tea intake (P=0.035 for trend).
• Tea intake was not associated with any decrease in risk (P=0.71 for trend in even the least adjusted model).

Increasing total caffeine from coffee, tea, and other drinks was not associated with decreasing serum uric acid levels in a multivariate analysis (P=0.14 for trend).

Further adjusting the multivariate models for caffeine intake left the associations with coffee virtually unchanged.

"The inverse association with coffee appears to be via components of coffee other than caffeine," Drs. Choi and Curhan said.

The explanation for the findings may be that non-caffeine compounds in coffee, such as the antioxidant chlorogenic acid, lower insulin levels and increase insulin sensitivity. Insulin resistance has been strongly linked in other studies to elevated uric acid levels.

Whatever the mechanism, it is likely that the effects seen in the study would be clinically significant, the researchers noted.

In a previous study looking at Health Professionals Follow-up Study data, the researchers had found that an increase in mean serum uric acid level of 0.4 mg/dl-similar in magnitude, though in the opposite direction-was associated with a 50% increased risk of incident gout.

But, that doesn't necessarily mean patients should start drinking more coffee, Dr. Choi said.

The results suggest that there is no need to reduce or discontinue drinking coffee for those who have gout or are at elevated risk because of high serum uric acid or a strong family history of gout, he said.

Coffee is considered generally safe when consumed in moderation-typically defined as up to three cups a day-but higher intake may risk calcium loss and caffeine dependence, Dr. Choi cautioned.

While decaf coffee may yield similar benefits without the caffeine-induced risks, patients should be counseled based on an individual benefit-risk assessment, he said.