BMJ Open 2019; 9:e024171. doi:10.1136/bmjopen-2018-024171
Ayoub-Charette S, Liu Q, Tauseef AK, et al.
Objective
- To conduct a systematic review and meta-analysis of prospective cohort studies to assess the relation of important food sources of fructose-containing sugars with incident gout and hyperuricaemia.
Background
- Foods that increase net adenosine triphosphate (ATP) degradation including alcohol and high purine meats are risk factors for 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.
- The results of cohort studies indicate that high intake of fructose-containing sugars in the form of sugar-sweetened beverages (SSBs) is also associated with incident gout.
- However, 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, sweets and desserts.
Methods
- The Cochrane Handbook for Systematic Reviews of Interventions was utilized to conduct a systematic review and meta-analysis. Results were reported according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.
- Studied included in this review were prospective cohort studies of ≥1-year duration that assessed the association of important food sources of fructose-containing sugars including non-alcoholic beverages (SSBs), cereal grain and grain-based products, fruit and fruit-based products, dairy and dairy-based products and sweets, chocolate and desserts with incident gout or hyperuricaemia in participants free from gout or hyperuricaemia at the start of the study.
- Extracted data included sample size, subject characteristics, sources of fructose-containing sugars, exposure levels, duration of follow-up, number of gout or hyperuricaemia cases, model adjustments and the risk ratio (RR) with 95% confidence intervals (CIs) per quantile of intake.
- Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) for prospective cohort studies.
- Primary pooled, sensitivity and dose response analyses were conducted. Interstudy heterogeneity and interactions between food sources were assessed. The overall certainty and the strength of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
Findings
- Of the 309 reports identified by the literature search, three reports with data from three prospective cohort studies met our inclusion criteria, including the Nurses’ Health Study (NHS), Health Professionals Follow-up Study (HPFS) and the National Runner’s Health Study (NRHS). All three reports reported the association of food sources of fructose-containing sugars on incident gout but none did on incident hyperuricaemia.
- The researchers were unable to identify prospective cohort studies reporting the association of other food sources of fructose-containing sugars (eg, cereal grain and grain-based products, sweets and desserts, dairy and dairy based products and chocolate) with incident gout fitting our inclusion criteria.
- There was significant interaction between the food sources (p=0.02). When comparing the highest to the lowest fruit intake, no association was shown for fruit intake on incident gout (RR=0.85 [95% CI 0.63 to 1.14]).
- When comparing the highest to lowest intake, an adverse association was shown for fruit juice intake on incident gout (RR 1.77 [95% CI 1.20 to 2.61]). When comparing the highest with the lowest intake, an adverse association was shown for SSB intake on incident gout (RR=2.08 [95% CI 1.40 to 3.08]). A random effect GLST model showed a significant dose–response relationship between fruit juice intake and incident gout per serving/week (RR=1.03, 95% CI 1.02 to 1.05, p<0.001) (online supplementary figure 1) and for SSB intake (RR=1.04, 95% CI 1.02 to 1.07, p<0.001).
Conclusions
- The researcher report that their findings are consistent with the literature that certain food sources of fructose-containing sugars, especially SSBs, are a risk factor for the development of gout.
- Future directions will aid in identifying the extent to which foods mediate the risk for hyperuricaemia and gout and will further inform healthcare professionals, policymakers, and aid in the development of improved dietary guidelines for the prevention and management of gout and hyperuricaemia.
Points to Consider
- Dietary intake assessments were done with self-reported, validated food frequency questionnaires (FFQs) in all studies. The ascertainment of incident gout in both HPFS and NHS Cohorts was through self-report, followed by supplementary surveys of the subjects based on the American College of Rheumatology gout survey criteria to confirm the diagnosis. As for the NRHS cohort, incident gout was self-reported based on physician diagnosis. Each of these methods are subject to recall and/or self-report bias.
- The certainty of the evidence for an adverse association of both fruit and fruit juice intake with incident gout was rated as very low, and the certainty of the evidence for an adverse association of SSB intake with incident gout was rated as moderate.
- The specific nature of the included studies’ population limits the generalizability of the results to other populations and geographical locations.