Fructose and Gout Don't Mix

If you think you know what causes gout to flare up, think again. Gout sufferers have said for a long time that certain foods trigger their symptoms. And research has confirmed that alcohol and seafood, among other things, can increase serum urate levels. But the latest study by New Zealand researchers has muddied the picture considerably. The study shows that sugary beverages cause serum urate and gout risk to increase only in people who are overweight or obese – but not in skinnier folks. The finding adds to evidence that the genetic and lifestyle factors contributing to gout vary from one person to the next. “What you see as far as food that triggers gout is that it’s quite an individual thing,” says co-author Tony Merriman, PhD, an associate professor of biochemistry at the University of Otago in New Zealand. Previous research established that drinking sugar-sweetened beverages and being overweight both increase the risk of hyperuricemia and gout. But it wasn’t clear how these two effects related to each other. To get a better idea, Dr. Merriman and his colleagues conducted two lines of research. First they studied populations with data available on urate, gout and body mass index (BMI). Second they tried giving fructose to people with different BMIs to see if it affected them differently. For the first part, they analyzed data from the Atherosclerosis Risk in Communities and Framingham Heart Study, two longitudinal studies from the United States, along with the New Zealand dataset, a cross-sectional sample taken from 2007 to 2014. Together these populations added up to 12,870 people. Overall the people who consumed more sugary beverages had higher serum urate levels. But when the researchers divided the sample in two by (BMI), they found that the correlation only applied to the heavier people. In the New Zealand dataset, they compared 1,210 people with gout to 1,369 people without gout, as defined by the American Rheumatism Association preliminary gout classification criteria. There were differences between the groups in sex, age, ethnicity, serum urate, triglycerides, body mass index and history of hypertension and kidney disease.[[{"type":"media","view_mode":"media_crop","fid":"42459","attributes":{"alt":"©MarcosMesaSamWordley/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_599444233812","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4602","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":" ","typeof":"foaf:Image"}}]] After controlling for the other variables, the researchers found no increase in the risk of gout among the slimmer people who drank the most sugar-sweetened beverages (OR 0.64, P = 0.31). But among the heavier people, those who drank more sugar-sweetened beverages were more likely to have gout (OR 1.33, P = 0.033). In the second part of the study, the researchers asked 76 healthy volunteers to fast overnight, then gave them a sugar solution between 8 a.m. and 9 a.m. The researchers took blood and urine samples at 30, 60, 120 and 180 minutes afterward. Serum urate was higher in the high body mass index group at baseline and throughout the observation period (P <0.0001). Both low and high BMI groups experienced an increase in serum urate after drinking the fructose.  At baseline, both groups excreted similar amounts of uric acid. But the fractional excretion of uric acid in the low body mass index group increased significantly from baseline at 120 minutes (P = 0.003) and 180 minutes (P<0.0001). By contrast, the fractional excretion of uric acid in the high body mass index group decreased significantly from baseline to 60 minutes after drinking the fructose (P = 0.0002). And the excretion did not increase after that in this group, even at 180 minutes after the fructose intake. The difference in uric acid excretion after fructose intake was statistically significant between the two BMI groups (P <0.0001). These findings suggest that heavier people have more trouble clearing uric acid that builds up in response to consumption of sugary beverages. It’s not yet clear what underlies this difference, Dr. Merriman said. “That’s what future research should focus on,” he said. “What’s different about the metabolism of overweight and obese people? We don’t have an hypothesis yet about that.” Despite these differences between high- and low-BMI populations, the message for people with gout is fairly straight-forward, says Dr. Merriman’s co-author, Nicola Dalbeth, MBChB, MD, a rheumatologist and professor at the Faculty of Medical and Health Sciences in the University of Auckland, New Zealand.  “I think these data provide further evidence that sugary drinks should be avoided, particularly in people with overweight/obesity,” she said in an email. “The best strategy for long-term gout management is urate-lowering therapy, using medications such as allopurinol. Dietary modification can assist with gout management but for most people, is not sufficient without urate-lowering medications.” Other questions about diet and gout are more complex, Dr. Merriman acknowledges. When researchers have surveyed people with gout about what triggers their symptoms, sugary beverages rank No. 7 after seafood, alcohol, red meat, tomatoes, vegetables and fruit (and followed by poultry, dairy products and “other” foods).  Since fish, tomatoes, vegetables and fruit are considered healthy foods, clinicians may not want to recommend against them. And as the new study demonstrates, different foods may cause gout in different people. The answer, once again, is medication, says Dr. Merriman. People with gout don’t have to worry about foods that trigger their symptoms if they control the disease. What about patients who don’t want to take medication? Could they control their gout with lifestyle alone? That might depend on genes. In another study, Dr. Merriman and his colleagues showed that the SLC2A9 gene plays a role in the way sugary beverages affect gout. As further evidence of the genetic link, he points out that gout is more common and serum urate levels are higher in Māori and Pacific Islander people than in people of European heritage.  Since uric acid plays a role in the immune response to malaria, Dr. Merriman and others have hypothesized that the higher urate levels could be a genetic adaptation conferring resistance to this disease, much like sickle cell anemia, thalassemia  and other genetic conditions. (People with gout are also less likely to get Alzheimer’s and Parkinson’s diseases.) A Western diet may contribute to the risk of gout in people already susceptible to it. Māori and Pacific Islanders who live in urban environments, consuming a Western diet, have higher serum urate levels that people of the same ethnicity living in rural areas and eating more traditional foods, Dr. Merriman and his colleagues report. But even those in rural areas Māori and Pacific Islanders have relatively high serum urate. And there is evidence that their ancestors had high rates of gout even before contact with Europeans, he said. “Dig up bones, you see characteristic erosions,” he said. “Those people were having what one would consider a pretty good lifestyle with respect to food and they were getting gout.”  The bottom line, says Dr. Merriman: If you have gout, take gout medication. 

SERUM URATE BY BODY MASS INDEX

Sugar-Sweetened Beverage Drinks Per Day

Average Difference in Serum Urate Levels Compared to 0 Drinks Per Day (mmol/L)

P value

BMI < 25, n = 4,731

0

-

>0 - < 2

-.004

0.20

≥ 2

-.002

0.67

BMI ≥ 25, n = 7,350

0

-

>0 - < 2

0.010

9.4 x 10^-4

≥ 2

0.015

7.2 x 10^-6

References:

Flynn TJ, Cadzow M, et al.

"Positive association of tomato consumption with serum urate: support for tomato consumption as an anecdotal trigger of gout flares,"

BMC Musculoskeletal Disorders

2015, 16:196  doi:10.1186/s12891-015-0661-8 Dalbeth N, Phipps-Green A, et al.

"Body mass index modulates the relationship of sugar-sweetened beverage intake with serum urate concentrations and gout,"

Arthritis Res Ther

. 2015; 17(1): 263. Published online 2015 Sep 22. doi: 10.1186/s13075-015-0781-4 Caitlin Batt, Amanda J Phipps-Green, et al.

"Sugar-sweetened beverage consumption: a risk factor for prevalent gout with SLC2A9 genotype-specific effects on serum urate and risk of gout,"

Ann Rheum Dis

2014;73:2101-2106 doi:10.1136/annrheumdis-2013-203600 Gosling AL, Matisoo-Smith E, Merriman TR.

"Hyperuricaemia in the Pacific: why the elevated serum urate levels?"

Rheumatology International.

First online: 31 December 2013. June 2014, Volume 34, Issue 6, pp 743-757