CHICAGO – Diet plays a significantly less important role than genes in the development of high serum urate levels that typically precede gout, research from New Zealand has revealed.
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These findings stem from a first-ever systematic analysis of a large data set to “determine the relative contributions of inherited genetic variants and overall diet to variance in serum urate concentrations,” Tanya J. Major, PhD, of the University of Otago in Dunedin, New Zealand, and her colleagues first reported in The BMJ and then less than 2 weeks later at the annual meeting of the American College of Rheumatology.
Prior studies have estimated that genetic factors explain 25%-60% of the variability in serum urate levels, but diet also has long been considered a risk factor for gout, with certain diets such as the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet shown in studies to reduce serum urate levels and the risk of gout, the researchers noted.
The new study found that common genetic factors accounted for nearly 24% of the variation in serum urate levels, whereas diet accounted for less than 1%.
Before these findings, the impact of diet on hyperuricemia was known to be limited, but that doesn’t mean that diet is meaningless, Michael H. Pillinger, MD, who was not involved in the study, said in an interview at the ACR annual meeting.
“What this work does from a scientific point of view is underline the genetic basis [of hyperuricemia]. What it does from a practical and clinical point of view is tell us that diet is a meaningful thing to adjust. It will provide other health benefits, but it isn’t the solution, and we know that it rarely is,” said Dr. Pillinger, professor of medicine and biochemistry and molecular pharmacology at New York University. “We shouldn’t expect a really large impact from diet, and we shouldn’t make people feel guilty about their diets, and optimally you want to manage a diet that a patient can tolerate and not one that will be impossible to sustain.”
Dr. Tanya Major
Dr. Major had a similar message in an interview at the meeting: “By focusing on diet and treating urate levels through diet, you start to kind of get this blame element going on that the reason you’ve got gout is you’re eating the wrong foods, and so then it makes people less likely to want to go to see their doctor to start with. And then when they do try to follow their doctor’s advice about their diet, and nothing changes, then it starts to get frustrating for them as well.”
The research team analyzed dietary survey data from five U.S. cohort studies (Atherosclerosis Risk in Communities, Coronary Artery Risk Development in [Young] Adults, Cardiovascular Heart Study, Framingham Heart Study, and Third National Health and Nutrition Examination Survey [NHANES III]) that altogether included 16,760 individuals (8,414 men and 8,346 women) of European ancestry.
Participants were aged 18 years or older, did not have gout or kidney disease, and were not taking urate-lowering or diuretic drugs. Serum urate measurements, dietary survey data, and confounders such as gender, age, body mass index, smoking status, and average daily calorie intake were all recorded.
The results showed that 15 foods were significantly associated with serum urate levels. Six were established urate-modifying foods: beer, liquor, wine, soft drinks, skim milk, and meat (beef, pork, or lamb). The remaining nine foods included two less established urate-modifying foods (cheese and noncitrus fruit) and seven food items without established associations: poultry, potatoes, brown bread, peanuts, margarine, cold cereal, and eggs.
Beer and liquor had the strongest urate-raising effect, associated with a 1.38 micromol/L increase in serum urate per serving per week, equating to a 9.66 micromol/L (0.16 mg/dL) increase per daily serving.
The authors noted that the associations seen with known and confirmed serum urate–influencing foods were consistent with previously reported associations in terms of effect and magnitude. Nevertheless, they noted that “each of these established foods explained less than 1% of variation in serum urate levels within the full cohort.”
When the researchers analyzed the data according to three diet scores based on healthy diet guidelines, they found that diet explained “very little variance in serum urate levels (0.28% for the DASH diet, 0.15% for the Healthy Eating diet, 0.06% for the Mediterranean diet, and 0.16% for the data-driven diet pattern).”
However, they noted that even though their findings, along with previous research, suggest that a clinically relevant decrease in serum urate levels could be achieved with the DASH diet, the implementation of such a diet might not be “straightforward” because “the barriers to implementing this diet both at a population level and in a primary care setting are yet to be overcome.”
In contrast, when the research team looked at genes in the cohort they found that common genetic factors explained 23.9% of variation in serum urate levels in the full cohort (excluding the NHANES III study because of a lack of genotype data).
Baseline visit diet information for these cohort studies ranged from the mid-1980s to the early to mid-2000s, making it hard to account for changes in food composition over time. Dr. Major said that food compositions overall were likely to be more processed over time and contain more urate-raising foods. However, any effects of food composition changes on urate levels over time would be more likely be felt at the level of individual food products, not on diets overall, she said.
Dr. Michael Pillinger
The variability in the diet scores that the investigators noted across individuals and regions in these U.S. cohort studies did not appear to affect the results, Dr. Major noted. Furthermore, adjustment within models for these diet scores did not affect the degree of variation in urate levels that genetics accounted for, whereas adjustment for genetics lowered the amount of variation that diet contributed to urate levels.
The findings also don’t have any say on the relative contribution of diet versus genetics on gout flares, which is a separate issue. Many patients would agree that they suspect certain foods trigger gout flares even if they don’t affect baseline urate levels very much, Dr. Pillinger said.
The next steps for Dr. Major and her coinvestigators may be to see if diet is influencing urate levels to the same degree in people with gout as this study shows for the general population, she said.The investigators noted that the use of different food questionnaires between the five studies is one limitation of the analysis, and there should be some caution in generalizing the results to people with gout or those of non-European ancestry.
The study was supported by the Health Research Council of New Zealand and the University of Otago. One author reported receiving consulting and speaker fees or grants from several pharmaceutical companies that manufacture urate-lowering drugs.
This article was updated 10/25/18.
SOURCE: Major TJ et al. BMJ. 2018. doi: 10.1136/bmj.k3951.