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KSR Number: KSRA14426

Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohort studies

Risk of Bias Assessment

Overall summary: Low risk of bias in the review

Bottom Line

The available evidence supports the association between fructose intake and increased risk of incidence of gout. However, there is a lack of evidence to determine the association between intake and increased risk of hyperuricemia. All domains were considered at low concern. The authors have already acknowledged that publication bias could not be assessed as the number of studies included was small. Further research with more prospective studies is needed to understand better the role of fructose and its food sources in the development of gout and hyperuricemia.

Risk of Bias Assessment

Overall summary Low risk of bias in the review

Low

All domains were considered at low concern. The authors have already acknowledged that publication bias could not be assessed as the number of studies included was small.

A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4? Probably yes
B. Was the relevance of identified studies to the review's research question appropriately considered? Probably yes
C. Did the reviewers avoid emphasizing results on the basis of their statistical significance? Probably yes
Risk of bias in the review Low

Details of Review

Number of studies 2
Number of participants 125,299
Last search date September 2015
Review type Aetiological
Objective To determine the prospective cohort studies investigating total fructose consumption and its association with incident hyperuricemia and gout.
Population Patients with gout, assessed using self-report of a physician diagnosis and hyperuricemia assessed using serum uric acid measurements.
Outcome Incidence of hyperuricemia and gout.
Study design Prospective cohort studies.
Exposure Total dietary fructose intake.

Results

The pooled analysis of two studies reported a significant association between fructose intake and increased risk of incidence of gout (risk ratio (RR) 1.62, 95% confidence interval (CI) 1.28 to 2.03, n = 125,299 patients). Multivariate models adjusted for percentage of energy from non-fructose carbohydrates and protein, a significant association was reported between fructose Intake and the risk of gout (RR 1.34, 95% CI 1.05 to 1.72, two studies, n = 125,299 patients).

The pooled analysis of the least-adjusted models (adjusted for age, total energy intake, body mass index (BMI) and alcohol consumption in both studies) reported no significant association between fructose intake and incidence of gout (RR 1.10, 95% CI 0.88 to 1.39, two studies, n = 125,299 patients). There was a lack of prospective studies to identify the association between total fructose intake and incident hyperuricemia.

Full Risk of Bias Assessment

The research objective was clearly stated and appropriate inclusion criteria were defined. No restrictions were applied based on the source of information and study characteristics.

1.1 Did the review adhere to pre-defined objectives and eligibility criteria? Probably yes
1.2 Were the eligibility criteria appropriate for the review question? Probably yes
1.3 Were eligibility criteria unambiguous? Probably yes
1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)? Probably yes
1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)? Probably yes
Concerns regarding specification of study eligibility criteria Low

Literature searches were conducted in MEDLINE, Cochrane Library and EMBASE databases. Additionally, reference lists of retrieved articles were manually reviewed for potentially relevant information and the authors were contacted for missing information. The search strategy was reported in full and appeared to be adequate. The searches were not restricted to date, publication format or language. Two review authors were independently involved in the study selection process.

2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports? Yes
2.2 Were methods additional to database searching used to identify relevant reports? Probably yes
2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible? Probably yes
2.4 Were restrictions based on date, publication format, or language appropriate? Probably yes
2.5 Were efforts made to minimise error in selection of studies? Yes
Concerns regarding methods used to identify and/or select studies Low

Two review authors independently extracted data from included studies using a standard data extraction form. Sufficient study characteristics have been extracted to allow interpretation of the results. Details of the confounders adjusted were provided. The study results were appropriately collected for the synthesis. The methodological quality assessment was performed by two reviewers independently using the Newcastle-Ottawa Quality Assessment Scale and disagreements were resolved through discussion.

3.1 Were efforts made to minimise error in data collection? Yes
3.2 Were sufficient study characteristics considered for both review authors and readers to be able to interpret the results? Probably yes
3.3 Were all relevant study results collected for use in the synthesis? Probably yes
3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria? Probably yes
3.5 Were efforts made to minimise error in risk of bias assessment? Yes
Concerns regarding methods used to collect data and appraise studies Low

The synthesis included all relevant studies and was appropriate. All predefined analyses were explained in the methodology section. The method used to pool the data was appropriate. There was no evidence of significant heterogeneity among the studies. Appropriate attempts were not made to explore the possible source of heterogeneity due to few studies. Publication bias could not be assessed due to the low number of studies included in the review. The quality of individual studies was considered in the synthesis.

4.1 Did the synthesis include all studies that it should? Probably yes
4.2 Were all pre-defined analyses reported or departures explained? Probably yes
4.3 Was the synthesis appropriate given the degree of similarity in the research questions, study designs and outcomes across included studies? Probably yes
4.4 Was between-study variation minimal or addressed in the synthesis? Probably yes
4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses? Probably yes
4.6 Were biases in primary studies minimal or addressed in the synthesis? Probably yes
Concerns regarding synthesis and findings Low

Keywords

  • gout
  • hyperuricemia
  • fructose