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Important Food Sources of Fructose-Containing Sugars and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Controlled Trials

ABSTRACT: Background: Fructose providing excess calories in the form of sugar sweetened beverages (SSBs) increases markers of non-alcoholic fatty liver disease (NAFLD). Whether this effect holds for other important food sources of fructose-containing sugars is unclear. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials of the effect of fructose-containing sugars by food source at different levels of energy control on non-alcoholic fatty liver disease (NAFLD) markers. Methods and Findings: MEDLINE, Embase, and the Cochrane Library were searched through 7 January 2022 for controlled trials ≥7-days. Four trial designs were prespecified: substitution (energy-matched substitution of sugars for other macronutrients); addition (excess energy from sugars added to diets); subtraction (excess energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients). The primary outcome was intrahepatocellular lipid (IHCL). Secondary outcomes were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE. We included 51 trials (75 trial comparisons, n = 2059) of 10 food sources (sugar-sweetened beverages (SSBs); sweetened dairy alternative; 100% fruit juice; fruit; dried fruit; mixed fruit sources; sweets and desserts; added nutritive sweetener; honey; and mixed sources (with SSBs)) in predominantly healthy mixed weight or overweight/obese younger adults. Total fructose-containing sugars increased IHCL (standardized mean difference = 1.72 [95% CI, 1.08 to 2.36], p < 0.001) in addition trials and decreased AST in subtraction trials with no effect on any outcome in substitution or ad libitum trials. There was evidence of influence by food source with SSBs increasing IHCL and ALT in addition trials and mixed sources (with SSBs) decreasing AST in subtraction trials. The certainty of evidence was high for the effect on IHCL and moderate for the effect on ALT for SSBs in addition trials, low for the effect on AST for the removal of energy from mixed sources (with SSBs) in subtraction trials, and generally low to moderate for all other comparisons. Conclusions: Energy control and food source appear to mediate the effect of fructose-containing sugars on NAFLD markers. The evidence provides a good indication that the addition of excess energy from SSBs leads to large increases in liver fat and small important increases in ALT while there is less of an indication that the removal of energy from mixed sources (with SSBs) leads to moderate reductions in AST. Varying uncertainty remains for the lack of effect of other important food sources of fructose-containing sugars at different levels of energy control.

SUBMITTER: Lee D

PROVIDER: S-EPMC9325155 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract Objectives Fructose as a source of excess calories increases non-alcoholic fatty liver disease (NAFLD) markers. Whether this effect is mediated by the food matrix is unknown. We thus conducted a systematic review and meta-analysis of controlled feeding trials assessing the effect of important food sources of fructose-containing sugars at different energy control levels on NAFLD markers. Methods MEDLINE, Embase, and Cochrane Library were searched through January 18, 2021 for controlled trials ≥7-days. Four trial designs were prespecified based on energy control: substitution (energy-matched replacement of sugars by other macronutrients); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients). The primary outcome was intrahepatocellular lipid (IHCL). Secondary outcomes were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed by GRADE. Results We included 44 trials (65 trial comparisons, n = 1941) assessing the effect of 8 food sources (sugar-sweetened beverages [SSBs]; sweetened dairy alternative [soy]; fruit juice; fruit; dried fruit; baked goods, desserts and sweets; added nutritive sweetener; and mixed sources) across 4 energy levels. Total fructose-containing sugars increased IHCL in addition trials (standardized mean difference = 1.69 [95% CI, 1.00–2.37], P < 0.001), but no effect in substitution, subtraction and ad libitum trials. There was evidence of interaction by food source in addition trials with SSBs increasing IHCL and ALT, and mixed sources increasing AST. The overall certainty of evidence was high for SSBs on IHCL and ALT in addition trials and high to very low for all other comparisons. Conclusions Energy control and food source appear to mediate the effect of fructose-containing sugars on NAFLD markers. High certainty evidence suggests that SSBs providing excess energy increase NAFLD markers, while the evidence is less certain that mixed sources share the same effect and other food sources do not. More high-quality randomized trials of different food sources are needed to improve our estimates (ClinicalTrials.gov identifier, NCT02716870). Funding Sources Primary funding: Diabetes Canada.

Project description:Abstract Objectives Overconsumption of fructose-containing sugars may increase blood pressure. Whether this effect is mediated by the food matrix is unclear. We conducted a systematic review and meta-analysis of controlled feeding trials of the effect of food sources of fructose-containing sugars at different levels of energy control on blood pressure (NCT02716870). Methods We searched MEDLINE, Embase and the Cochrane Library through January, 2020 for controlled trials ≥7d. Trial designs were prespecified based on energy control: substitution (energy matched replacement of sugars in the diet); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in the diet) trials. Outcomes were systolic blood pressure (SBP) and diastolic blood pressure (DBP). Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed by GRADE. Results We included 76 trials (121 trial comparisons, N = 4 302) assessing 9 food sources (sugar-sweetened beverages [SSBs], sweetened dairy alternatives, 100% fruit juice, fruit, dried fruit, sweets, added nutritive sweetener, sweetened cereal grains/bars, and mixed sources) across the 4 levels of energy control. Total fructose-containing sugars decreased SBP (mean difference, −2.76 mmHg [95% CI, −4.36, −1.16], P = 0.001) and DBP (−1.26 mmHg [−2.29, −0.23], P = 0.016) in addition trials and the removal of these sugars decreased SBP (−1.79 mmHg [−3.36, −0.21], P = 0.026) in subtraction trials. There was evidence of interaction by food source with fruit decreasing and sweets and mixed sources increasing SBP and DBP in addition trials and the removal of SSBs decreased SBP in subtraction trials. The certainty of evidence was generally moderate to low for all food source-outcome relationships, except for the decreasing-effect of fruit on DBP in addition trials (high). Conclusions Food source and energy control appear to mediate the effect of fructose-containing sugars on blood pressure. The evidence provides a good indication that fruit decreases while excess calories from SSBs, sweets and mixed sources increase blood pressure. More high-quality trials of different food sources are needed to improve our estimates. Funding Sources Diabetes Canada.

Project description:Abstract Objectives Fructose providing excess calories has been shown to increase postprandial triglycerides (TAG). Whether this effect holds for different food sources of fructose-containing sugars is unclear. We conducted a systematic review and meta-analysis of controlled feeding trials on the effect of different food sources of fructose-containing sugars at different levels of energy control on postprandial blood lipids (NCT02716870). Methods MEDLINE, EMBASE, and Cochrane Library were searched through June 1st, 2020 for controlled feeding trials ≥7-days assessing the effect of food sources of fructose-containing sugars on postprandial lipids. Trial designs were prespecified based on energy control: substitution (energy matched replacement of sugars by other macronutrients); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients) trials. Independent reviewers extracted data and assessed risk of bias. Outcomes were postprandial TAG and apoB48. Certainty of evidence was assessed using GRADE. Results We included 29 trials (60 trial comparisons, N = 943) assessing 5 food sources (SSBs, fruit, sweets and desserts, added caloric sweetener and mixed sources) across 4 levels of energy control. Total fructose-containing sugars increased postprandial TAG in substitution (MD: 0.17 mmol/L [95% CI: 0.05, 0.30], P = 0.007), addition (0.38 mmol/L [0.13, 0.62], P = 0.003), and ad libitum (0.17 mmol/L [0.02, 0.31], P = 0.024) trials and increased apoB48 in addition trials (0.12 g/L [0.07, 0.18], P < 0.001).There was evidence of interaction by food source with SSBs increasing postprandial TAG and apoB48 in addition trials and mixed sources increasing postprandial TAG in ad libitum trials. The certainty of the evidence was “moderate” for SSBs increasing TAG in addition trials and mixed sources increasing TAG in ad libitum trials and “low” for all other comparisons. Conclusions Food source more than energy control appears to mediate fructose-containing sugars on postprandial lipids. Good evidence suggests that SSBs and mixed sources increase postprandial lipids while evidence is less certain for the lack of effect of other food sources. More high-quality trials of different food sources are needed. Funding Sources Primary: Diabetes Canada.

Project description:Abstract Objectives Excess calories as fructose may initiate pathways increasing biomarkers of inflammation. Whether this effect is mediated by the food matrix at different energy levels is unknown. We conducted a systematic review and meta-analysis of controlled feeding trials of the effect of food sources of fructose-containing sugars at different energy control levels on biomarkers of inflammation (NCT02716870). Methods We searched MEDLINE, Embase, and the Cochrane Library through January 15 2020 for controlled trials ≥7d. Trial designs were prespecified based on energy control: substitution (energy-matched replacement of sugar in the diet); addition (excess energy from sugar added to diets); subtraction (energy from sugar subtracted from diets); ad libitum (energy from sugar freely replaced in the diet). The primary outcome was C-reactive protein (CRP). Secondary outcomes were tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Independent reviewers extracted data and assessed the risk of bias. Certainty of evidence was assessed by GRADE. Results We included 48 trials (109 trial comparisons, n = 2108) assessing the effect of 10 food sources (SSBs, sweetened dairy, sweetened dairy alternatives (soy), fruit, 100% fruit juice, dried fruit, sweetened cereal grains/bars, sweets, added nutritive sweetener, and mixed sources) across the 4 levels of energy control. Total fructose-containing sugars had no effect on any outcome in any level of energy control. There was evidence of interaction by food source; in substitution trials, sweetened dairy alternative (soy) decreased CRP. In addition trials, fruit decreased while added nutritive sweetener increased TNF-α. The certainty of evidence was low for the effect of sweetened dairy alternative (soy) on CRP in substitution trials, and generally moderate for all other comparisons. Conclusions Food source more than energy control appears to mediate the effect of fructose-containing sugars on inflammation. The evidence provides some indication that sweetened dairy alternatives (soy) and fruit decrease and added nutritive sweeteners increase biomarkers of inflammation. More high-quality randomized trials of different fructose containing food sources are needed to improve our estimates. Funding Sources Diabetes Canada.

Project description:Abstract Objectives Fructose as a source of excess calories increases uric acid. Whether this effect is mediated by the food matrix at different levels of energy is unknown. We aim to conduct a systematic review and meta-analysis of controlled feeding trials on the effect of food sources of fructose-containing sugars at different energy levels on uric acid (NCT02716870). Methods MEDLINE, Embase and the Cochrane Library were searched through January 27, 2020 for controlled trials ≥7-days assessing the effect of food sources of fructose-containing sugars on uric acid. Trial designs were prespecified based on energy control: substitution (energy matched replacement of sugars by other macronutrients); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients) trials. Independent reviewers extracted data and assessed risk of bias. Certainty of evidence was assessed using the GRADE approach. Results Eligibility was met by 41 trials (72 trial comparisons, N = 2109) assessing the effect of 9 food sources (sugar-sweetened beverages [SSBs], sweetened dairy, fruit drink [lemonade], 100% fruit juice, fruit, dried fruit [raisins], baked goods desserts and sweets, added nutritive [caloric] sweetener and mixed sources) across the 4 energy levels. Total fructose-containing sugars increased uric acid in substitution trials (mean difference, 0.15 mg/dL [95% confidence interval, 0.03 to 0.27 mg/dL], P = 0.012) with no effect in addition, subtraction or ad libitum trials. There was evidence of interaction by food source with SSBs and baked goods, desserts and sweets increasing uric acid in substitution and SSBs increasing and 100% fruit juice decreasing uric acid in addition trials. The overall certainty of evidence was moderate for the increasing effect of SSBs in substitution and addition trials and low to very low for all other comparisons. Conclusions Food source more than energy control mediate the effect of fructose-containing sugars on uric acid. SSBs and baked goods, desserts and sweets appear to increase, and 100% fruit juice appear to decrease uric acid. More high-quality trials of different food sources of fructose-containing sugars are needed to improve our estimates. Funding Sources Diabetes Canada.

Project description:ObjectiveSugar-sweetened beverages (SSBs) are associated with hyperuricaemia and gout. Whether other important food sources of fructose-containing sugars share this association is unclear.DesignTo assess the relation of important food sources of fructose-containing sugars with incident gout and hyperuricaemia, we conducted a systematic review and meta-analysis of prospective cohort studies.MethodsWe searched MEDLINE, Embase and the Cochrane Library (through 13 September 2017). We included prospective cohort studies that investigated the relationship between food sources of sugar and incident gout or hyperuricaemia. Two independent reviewers extracted relevant data and assessed the risk of bias. We pooled natural-log transformed risk ratios (RRs) using the generic inverse variance method with random effects model and expressed as RR with 95% confidence intervals (CIs). The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system.ResultsWe identified three studies (1 54 289 participants, 1761 cases of gout), comparing the highest with the lowest level of exposure for SSBs, fruit juices and fruits. No reports were found reporting incident hyperuricaemia. Fruit juice and SSB intake showed an adverse association (fruit juice: RR=1.77, 95% CI 1.20 to 2.61; SSB: RR=2.08, 95% CI 1.40 to 3.08), when comparing the highest to lowest intake of the most adjusted models. There was no significant association between fruit intake and gout (RR 0.85, 95% CI 0.63 to 1.14). The strongest evidence was for the adverse association with SSB intake (moderate certainty), and the weakest evidence was for the adverse association with fruit juice intake (very low certainty) and lack of association with fruit intake (very low certainty).ConclusionThere is an adverse association of SSB and fruit juice intake with incident gout, which does not appear to extend to fruit intake. Further research is needed to improve our estimates.Trial registration numberNCT02702375; Results.

Project description:BackgroundAlthough fructose as a source of excess calories increases uric acid, the effect of the food matrix is unclear.ObjectivesTo assess the effects of fructose-containing sugars by food source at different levels of energy control on uric acid, we conducted a systematic review and meta-analysis of controlled trials.MethodsMEDLINE, Embase, and the Cochrane Library were searched (through 11 January 2021) for trials ≥ 7 days. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars in diets); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in diets) designs. Independent reviewers (≥2) extracted data and assessed the risk of bias. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the certainty of evidence.ResultsWe included 47 trials (85 comparisons; N = 2763) assessing 9 food sources [sugar-sweetened beverages (SSBs), sweetened dairy, fruit drinks, 100% fruit juice, fruit, dried fruit, sweets and desserts, added nutritive sweetener, and mixed sources] across 4 energy control levels in predominantly healthy, mixed-weight adults. Total fructose-containing sugars increased uric acid levels in substitution trials (mean difference, 0.16 mg/dL; 95% CI: 0.06-0.27 mg/dL; P = 0.003), with no effect across the other energy control levels. There was evidence of an interaction by food source: SSBs and sweets and desserts increased uric acid levels in the substitution design, while SSBs increased and 100% fruit juice decreased uric acid levels in addition trials. The certainty of evidence was high for the increasing effect of SSBs in substitution and addition trials and the decreasing effect of 100% fruit juice in addition trials and was moderate to very low for all other comparisons.ConclusionsFood source more than energy control appears to mediate the effects of fructose-containing sugars on uric acid. The available evidence provides reliable indications that SSBs increase and 100% fruit juice decreases uric acid levels. More high-quality trials of different food sources are needed. This trial was registered at clinicaltrials.gov as NCT02716870.

Project description:ObjectiveTo assess the effect of different food sources of fructose-containing sugars on glycaemic control at different levels of energy control.DesignSystematic review and meta-analysis of controlled intervention studies.Data sourcesMedine, Embase, and the Cochrane Library up to 25 April 2018.Eligibility criteria for selecting studiesControlled intervention studies of at least seven days' duration and assessing the effect of different food sources of fructose-containing sugars on glycaemic control in people with and without diabetes were included. Four study designs were prespecified on the basis of energy control: substitution studies (sugars in energy matched comparisons with other macronutrients), addition studies (excess energy from sugars added to diets), subtraction studies (energy from sugars subtracted from diets), and ad libitum studies (sugars freely replaced by other macronutrients without control for energy). Outcomes were glycated haemoglobin (HbA1c), fasting blood glucose, and fasting blood glucose insulin.Data extraction and synthesisFour independent reviewers extracted relevant data and assessed risk of bias. Data were pooled by random effects models and overall certainty of the evidence assessed by the GRADE approach (grading of recommendations assessment, development, and evaluation).Results155 study comparisons (n=5086) were included. Total fructose-containing sugars had no harmful effect on any outcome in substitution or subtraction studies, with a decrease seen in HbA1c in substitution studies (mean difference -0.22% (95% confidence interval to -0.35% to -0.08%), -25.9 mmol/mol (-27.3 to -24.4)), but a harmful effect was seen on fasting insulin in addition studies (4.68 pmol/L (1.40 to 7.96)) and ad libitum studies (7.24 pmol/L (0.47 to 14.00)). There was interaction by food source, with specific food sources showing beneficial effects (fruit and fruit juice) or harmful effects (sweetened milk and mixed sources) in substitution studies and harmful effects (sugars-sweetened beverages and fruit juice) in addition studies on at least one outcome. Most of the evidence was low quality.ConclusionsEnergy control and food source appear to mediate the effect of fructose-containing sugars on glycaemic control. Although most food sources of these sugars (especially fruit) do not have a harmful effect in energy matched substitutions with other macronutrients, several food sources of fructose-containing sugars (especially sugars-sweetened beverages) adding excess energy to diets have harmful effects. However, certainty in these estimates is low, and more high quality randomised controlled trials are needed.Study registrationClinicaltrials.gov (NCT02716870).

Project description:ImportanceSugar-sweetened beverages (SSBs) are associated with increased risk of metabolic syndrome (MetS). However, the role of other important food sources of fructose-containing sugars in the development of MetS remains unclear.ObjectiveTo examine the association of major food sources of fructose-containing sugars with incident MetS.Data sourcesMEDLINE, Embase, and Cochrane Library were searched from database inception to March 24, 2020, in addition to manual searches of reference lists from included studies using the following search terms: sugar-sweetened beverages, fruit drink, yogurt, metabolic syndrome, and prospective study.Study selectionInclusion criteria included prospective cohort studies of 1 year or longer that investigated the association of important food sources of fructose-containing sugars with incident MetS in participants free of MetS at the start of the study.Data extraction and synthesisStudy quality was assessed using the Newcastle-Ottawa Scale. Extreme quantile risk estimates for each food source with MetS incidence were pooled using a random-effects meta-analysis. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Dose-response analyses were performed using a 1-stage linear mixed-effects model. The certainty of the evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Results were reported according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines.Main outcomes and measuresPooled risk ratio (RR) of incident MetS (pairwise and dose response).ResultsThirteen prospective cohort studies (49 591 participants [median age, 51 years; range, 6-90 years]; 14 205 with MetS) that assessed 8 fructose-containing foods and MetS were included. An adverse linear dose-response association for SSBs (RR for 355 mL/d, 1.14; 95% CI, 1.05-1.23) and an L-shaped protective dose-response association for yogurt (RR for 85 g/d, 0.66; 95% CI, 0.58-0.76) and fruit (RR for 80 g/d, 0.82; 95% CI, 0.78-0.86) was found. Fruit juices (mixed and 100%) had a U-shaped dose-response association with protection at moderate doses (mixed fruit juice: RR for 125 mL/d, 0.58; 95% CI, 0.42-0.79; 100% fruit juice: RR for 125 mL/d, 0.77; 95% CI, 0.61-0.97). Honey, ice cream, and confectionary had no association with MetS incidence. The certainty of the evidence was moderate for SSBs, yogurt, fruit, mixed fruit juice, and 100% fruit juice and very low for all other food sources.Conclusions and relevanceThe findings of this meta-analysis suggest that the adverse association of SSBs with MetS does not extend to other food sources of fructose-containing sugars, with a protective association for yogurt and fruit throughout the dose range and for 100% fruit juice and mixed fruit juices at moderate doses. Therefore, current policies and guidelines on the need to limit sources of free sugars may need to be reexamined.

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Important Food Sources of Fructose-Containing Sugars and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Controlled Trials

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