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Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohort studies.
Jamnik, J, Rehman, S, Blanco Mejia, S, de Souza, RJ, Khan, TA, Leiter, LA, Wolever, TM, Kendall, CW, Jenkins, DJ, Sievenpiper, JL
BMJ open. 2016;(10):e013191
Abstract
BACKGROUND The prevalence of hyperuricemia and gout has increased in recent decades. The role of dietary fructose in the development of these conditions remains unclear. OBJECTIVE To conduct a systematic review and meta-analysis of prospective cohort studies investigating the association fructose consumption with incident gout and hyperuricemia. DESIGN MEDLINE, EMBASE and the Cochrane Library were searched (through September 2015). We included prospective cohort studies that assessed fructose consumption and incident gout or hyperuricemia. 2 independent reviewers extracted relevant data and assessed study quality using the Newcastle-Ottawa Scale. We pooled natural-log transformed risk ratios (RRs) using the generic inverse variance method. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS 2 studies involving 125 299 participants and 1533 cases of incident gout assessed the association between fructose consumption and incident gout over an average of 17 years of follow-up. No eligible studies assessed incident hyperuricemia as an outcome. Fructose consumption was associated with an increase in the risk of gout (RR=1.62, 95% CI 1.28 to 2.03, p<0.0001) with no evidence of interstudy heterogeneity (I2=0%, p=0.33) when comparing the highest (>11.8% to >11.9% total energy) and lowest (<6.9% to <7.5% total energy) quantiles of consumption. LIMITATIONS Despite a dose-response gradient, the overall quality of evidence as assessed by GRADE was low, due to indirectness. There were only two prospective cohort studies involving predominantly white health professionals that assessed incident gout, and none assessed hyperuricemia. CONCLUSIONS Fructose consumption was associated with an increased risk of developing gout in predominantly white health professionals. More prospective studies are necessary to understand better the role of fructose and its food sources in the development of gout and hyperuricemia. PROTOCOL REGISTRATION NUMBER NCT01608620.
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'Catalytic' doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials.
Sievenpiper, JL, Chiavaroli, L, de Souza, RJ, Mirrahimi, A, Cozma, AI, Ha, V, Wang, DD, Yu, ME, Carleton, AJ, Beyene, J, et al
The British journal of nutrition. 2012;(3):418-23
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Abstract
Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, 'catalytic' doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of 'catalytic' doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring 'catalytic' fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I 2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. 'Catalytic' doses of fructose significantly reduced HbA1c (MD - 0·40, 95 % CI - 0·72, - 0·08) and fasting glucose (MD - 0·25, 95 % CI - 0·44, - 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that 'catalytic' fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using 'catalytic' fructose to confirm these results.
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Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials.
Cozma, AI, Sievenpiper, JL, de Souza, RJ, Chiavaroli, L, Ha, V, Wang, DD, Mirrahimi, A, Yu, ME, Carleton, AJ, Di Buono, M, et al
Diabetes care. 2012;(7):1611-20
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OBJECTIVE The effect of fructose on cardiometabolic risk in humans is controversial. We conducted a systematic review and meta-analysis of controlled feeding trials to clarify the effect of fructose on glycemic control in individuals with diabetes. RESEARCH DESIGN AND METHODS We searched MEDLINE, EMBASE, and the Cochrane Library (through 22 March 2012) for relevant trials lasting ≥7 days. Data were aggregated by the generic inverse variance method (random-effects models) and expressed as mean difference (MD) for fasting glucose and insulin and standardized MD (SMD) with 95% CI for glycated hemoglobin (HbA(1c)) and glycated albumin. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I(2) statistic. Trial quality was assessed by the Heyland methodological quality score (MQS). RESULTS Eighteen trials (n = 209) met the eligibility criteria. Isocaloric exchange of fructose for carbohydrate reduced glycated blood proteins (SMD -0.25 [95% CI -0.46 to -0.04]; P = 0.02) with significant intertrial heterogeneity (I(2) = 63%; P = 0.001). This reduction is equivalent to a ~0.53% reduction in HbA(1c). Fructose consumption did not significantly affect fasting glucose or insulin. A priori subgroup analyses showed no evidence of effect modification on any end point. CONCLUSIONS Isocaloric exchange of fructose for other carbohydrate improves long-term glycemic control, as assessed by glycated blood proteins, without affecting insulin in people with diabetes. Generalizability may be limited because most of the trials were <12 weeks and had relatively low MQS (<8). To confirm these findings, larger and longer fructose feeding trials assessing both possible glycemic benefit and adverse metabolic effects are required.
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Heterogeneous effects of fructose on blood lipids in individuals with type 2 diabetes: systematic review and meta-analysis of experimental trials in humans.
Sievenpiper, JL, Carleton, AJ, Chatha, S, Jiang, HY, de Souza, RJ, Beyene, J, Kendall, CW, Jenkins, DJ
Diabetes care. 2009;(10):1930-7
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OBJECTIVE Because of blood lipid concerns, diabetes associations discourage fructose at high intakes. To quantify the effect of fructose on blood lipids in diabetes, we conducted a systematic review and meta-analysis of experimental clinical trials investigating the effect of isocaloric fructose exchange for carbohydrate on triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol in type 1 and 2 diabetes. RESEARCH DESIGN AND METHODS We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant trials of > or =7 days. Data were pooled by the generic inverse variance method and expressed as standardized mean differences with 95% CI. Heterogeneity was assessed by chi(2) tests and quantified by I(2). Meta-regression models identified dose threshold and independent predictors of effects. RESULTS Sixteen trials (236 subjects) met the eligibility criteria. Isocaloric fructose exchange for carbohydrate raised triglycerides and lowered total cholesterol under specific conditions without affecting LDL cholesterol or HDL cholesterol. A triglyceride-raising effect without heterogeneity was seen only in type 2 diabetes when the reference carbohydrate was starch (mean difference 0.24 [95% CI 0.05-0.44]), dose was >60 g/day (0.18 [0.00-0.37]), or follow-up was < or =4 weeks (0.18 [0.00-0.35]). Piecewise meta-regression confirmed a dose threshold of 60 g/day (R(2) = 0.13)/10% energy (R(2) = 0.36). A total cholesterol-lowering effect without heterogeneity was seen only in type 2 diabetes under the following conditions: no randomization and poor study quality (-0.19 [-0.34 to -0.05]), dietary fat >30% energy (-0.33 [-0.52 to -0.15]), or crystalline fructose (-0.28 [-0.47 to -0.09]). Multivariate meta-regression analyses were largely in agreement. CONCLUSIONS Pooled analyses demonstrated conditional triglyceride-raising and total cholesterol-lowering effects of isocaloric fructose exchange for carbohydrate in type 2 diabetes. Recommendations and large-scale future trials need to address the heterogeneity in the data.