In the JournalsPerspective

Sugar-sweetened beverages linked to 208% increase in incident gout

A “moderate certainty of evidence” showed that sugar-sweetened beverages are associated with a 208% increase in incident gout, when comparing intake levels, according to data published in BMJ Open.

The researchers also found a “very low” certainty of evidence that fruit juice was linked to a 77% increase in incident gout.

“Ingestion of large amounts of the monosaccharide fructose can increase uric acid production during its metabolism in the liver through unregulated phosphorylation of ATP into adenosine monophosphate (AMP) as demonstrated in randomized controlled trials,” John L. Sievenpiper, MD, PhD, FRCPC, of St. Michael’s Hospital, in Toronto, and colleagues said. “Similarly, in cohort studies, high intake of fructose-containing sugars in the form of sugar-sweetened beverages (SSBs) is associated with incident gout.

“It is unclear whether the association seen for SSBs intake holds for other important food sources of fructose-containing sugars, such as fruit and fruit-based products, grains and grain-based products, dairy and dairy-based products and sweets and desserts,” they added. “As dietary guidelines and public health policy move from nutrient-based recommendations toward food and dietary-based recommendations, it is important to understand the contribution of these different food sources of fructose-containing sugars to the association of incident gout.”

To evaluate the link between fructose-containing sugars and incident gout, Sievenpiper and colleagues conducted a systematic review and meta-analysis of prospective cohort studies. Searching Medline and the Cochrane Library through Sept. 13, 2017, the researchers initially identified 309 reports on the relationship between food sources of sugar and incident gout or hyperuricemia. Of those, 294 were excluded based on title or abstract, and 15 were read in full. Ultimately, the researchers included three articles in their analysis, representing 154,289 participants with 1,761 incident cases of gout.

Among the included articles, two each reported data on fruit intake, fruit juice and sugar-sweetened beverages, and none studied links to incident hyperuricemia. The researchers used these data to compare patients with the highest exposure levels for fruit, fruit juice and sugar-sweetened beverages with those reporting the lowest intake. They used pooled natural-log transformed risk ratios using the generic inverse variance method with random effects model. The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system.

According to the researchers, intake of fruit juice (RR = 1.77; 95%CI, 1.2-2.61) and sugar-sweetened beverages (RR = 2.08; 95%CI, 1.4-3.08) both demonstrated an adverse association with incident gout, when comparing the highest to lowest intake of the most adjusted models. Meanwhile, there was no significant link between fruit intake and gout. The strongest evidence — which was of a moderate certainty — pointed toward an adverse association with sugar-sweetened beverages and gout. The weakest evidence — a very low certainty — suggested an adverse association with fruit juice.

“The pooled analyses revealed that there was moderate certainty of evidence that SSB intake was associated with a 208% increase in incident gout when comparing the highest with the lowest intake,” Sievenpiper and colleagues wrote. “There was very low certainty of evidence that fruit juice intake was associated with a 77% increase in incident gout and that fruit intake was not associated with incident gout. There was no data available for other important food sources of fructose-containing sugars.”

“Given that incident gout is rising in many countries and that gout and hyperuricemia are both associated with metabolic syndrome, myocardial infarction, diabetes and premature death, it is becoming increasingly important to identify and understand risk factors for developing gout,” they added. “It is imperative for additional prospective studies to assess the intake of various food sources of fructose-containing sugars and their relationship with gout and hyperuricemia in diverse populations.” – by Jason Laday

Disclosure: Sievenpiper reports funding from a PSI Graham Farquharson Knowledge Translation Fellowship, a Canadian Diabetes Association (CDA) Clinician Scientist award, a Canadian Institutes of Health Research (CIHR) Institute of Nutrition, Metabolism and Diabetes (INMD)/Canadian Nutrition Society (CNS) New Investigator Partnership Prize and a Banting & Best Diabetes Centre Sun Life Financial New Investigator Award.

A “moderate certainty of evidence” showed that sugar-sweetened beverages are associated with a 208% increase in incident gout, when comparing intake levels, according to data published in BMJ Open.

The researchers also found a “very low” certainty of evidence that fruit juice was linked to a 77% increase in incident gout.

“Ingestion of large amounts of the monosaccharide fructose can increase uric acid production during its metabolism in the liver through unregulated phosphorylation of ATP into adenosine monophosphate (AMP) as demonstrated in randomized controlled trials,” John L. Sievenpiper, MD, PhD, FRCPC, of St. Michael’s Hospital, in Toronto, and colleagues said. “Similarly, in cohort studies, high intake of fructose-containing sugars in the form of sugar-sweetened beverages (SSBs) is associated with incident gout.

“It is unclear whether the association seen for SSBs intake holds for other important food sources of fructose-containing sugars, such as fruit and fruit-based products, grains and grain-based products, dairy and dairy-based products and sweets and desserts,” they added. “As dietary guidelines and public health policy move from nutrient-based recommendations toward food and dietary-based recommendations, it is important to understand the contribution of these different food sources of fructose-containing sugars to the association of incident gout.”

To evaluate the link between fructose-containing sugars and incident gout, Sievenpiper and colleagues conducted a systematic review and meta-analysis of prospective cohort studies. Searching Medline and the Cochrane Library through Sept. 13, 2017, the researchers initially identified 309 reports on the relationship between food sources of sugar and incident gout or hyperuricemia. Of those, 294 were excluded based on title or abstract, and 15 were read in full. Ultimately, the researchers included three articles in their analysis, representing 154,289 participants with 1,761 incident cases of gout.

Among the included articles, two each reported data on fruit intake, fruit juice and sugar-sweetened beverages, and none studied links to incident hyperuricemia. The researchers used these data to compare patients with the highest exposure levels for fruit, fruit juice and sugar-sweetened beverages with those reporting the lowest intake. They used pooled natural-log transformed risk ratios using the generic inverse variance method with random effects model. The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system.

According to the researchers, intake of fruit juice (RR = 1.77; 95%CI, 1.2-2.61) and sugar-sweetened beverages (RR = 2.08; 95%CI, 1.4-3.08) both demonstrated an adverse association with incident gout, when comparing the highest to lowest intake of the most adjusted models. Meanwhile, there was no significant link between fruit intake and gout. The strongest evidence — which was of a moderate certainty — pointed toward an adverse association with sugar-sweetened beverages and gout. The weakest evidence — a very low certainty — suggested an adverse association with fruit juice.

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“The pooled analyses revealed that there was moderate certainty of evidence that SSB intake was associated with a 208% increase in incident gout when comparing the highest with the lowest intake,” Sievenpiper and colleagues wrote. “There was very low certainty of evidence that fruit juice intake was associated with a 77% increase in incident gout and that fruit intake was not associated with incident gout. There was no data available for other important food sources of fructose-containing sugars.”

“Given that incident gout is rising in many countries and that gout and hyperuricemia are both associated with metabolic syndrome, myocardial infarction, diabetes and premature death, it is becoming increasingly important to identify and understand risk factors for developing gout,” they added. “It is imperative for additional prospective studies to assess the intake of various food sources of fructose-containing sugars and their relationship with gout and hyperuricemia in diverse populations.” – by Jason Laday

Disclosure: Sievenpiper reports funding from a PSI Graham Farquharson Knowledge Translation Fellowship, a Canadian Diabetes Association (CDA) Clinician Scientist award, a Canadian Institutes of Health Research (CIHR) Institute of Nutrition, Metabolism and Diabetes (INMD)/Canadian Nutrition Society (CNS) New Investigator Partnership Prize and a Banting & Best Diabetes Centre Sun Life Financial New Investigator Award.

    Perspective
    Michael Strachan

    Michael Strachan

    As it has been described that sugar-sweetened beverages are associated with hyperuricemia and gout, the authors of this paper pose the question whether there are food sources of fructose containing sugars which also have a similar association.

    Excess intake of fructose can increase uric acid through an unregulated phosphofructose kinase pathway that uses substantial amounts of ATP to convert fructose-1-phosphate in the liver. Net ATP degradation leads to accumulation of AMP which is subsequently degraded to uric acid. Fructose can also increase de nova purine synthesis which further produces uric acid. Foods that increase net ATP degradation including alcohol and high purine meats are risk factors for gout.

    The pooled analysis of this study revealed a moderate certainty of evidence that sugar sweetened beverage intake was associated with a 208% increase in incident gout from highest to the lowest level. There was a very low certainty of evidence that fruit juice intake was associated with a 77% increase in incident gout and that fruit intake was not associated with incident gout. There was no reported incidence of hyperuricemia in these studies. The authors point out that dietary recommendations for gout have focused on restricted purine intake diets, which are often high in carbohydrates including fructose rich foods.

    There were notable limitations to this systematic review and meta-analysis due to potential for unmeasured and residual confounding as the studies were observational. All studies were U.S.-based and two of the three were conducted on health professionals. Two cohorts included only middle-aged and older people, who were predominantly white, working in health care.

    The authors note that dietary guidelines have shifted from nutrient based recommendations to food and dietary pattern-based recommendations. The interaction between nutrients in foods can be complex and the food matrix works as a whole to increase or decrease disease risk.

    • Michael Strachan, MD
    • Premier HealthCare Associates, Inc.
      Member, Medical Policy Committee
      United Rheumatology

    Disclosures: Strachan reports no relevant financial disclosures.

    Perspective
    Eileen McCullagh

    Eileen McCullagh

    Although this paper contributes to the widening body of knowledge that ingesting certain food sources of fructose-containing sugars is associated with gout, we as health care providers are left with more questions than answers.

    There were several limitations to this analysis, as noted by the researchers. Out of 309 initially identified studies, only three prospective cohorts were included in the analysis; all three reported on the incidence of gout and none on hyperuricemia.

    Additionally, all the fructose data in the included studies was derived from sugar-sweetened beverages (SSBs). There was some association of fruit juice intake with incident gout, but two of the three prospective cohorts did not differentiate between fruit drinks and pure fruit juice. No association between actual fruit intake and incident gout was found. Lastly, two of the cohorts consisted of largely Caucasian populations, which can also limit the generalizability of the results to other populations and geographical areas.

    I suggest that health care providers continue what they have been doing all along: Educating their patients on the relationship between fructose and purine metabolism. They should also be reinforcing the benefits of following a low purine diet along with limiting the consumption of SSBs and fruit juices, as well as bakery foods and cereals — this will go a long way in helping them control their gout along with taking their medication. However, more studies need to be conducted in different populations to clarify the association between fructose intake and gout.

    • Eileen McCullagh, BSN, RN, ONC, CCRC
    • Board member, Rheumatology Nurses Society
      Clinical research manager
      Hospital for Special Surgery

    Disclosures: McCullagh reports no relevant financial disclosures.