Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis - PubMed (original) (raw)
Meta-Analysis
Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis
Mei Chung et al. Am J Clin Nutr. 2014 Sep.
Abstract
Background: Concerns have been raised about the concurrent temporal trend between simple sugar intakes, especially of fructose or high-fructose corn syrup (HFCS), and rates of nonalcoholic fatty liver disease (NAFLD) in the United States.
Objective: We examined the effect of different amounts and forms of dietary fructose on the incidence or prevalence of NAFLD and indexes of liver health in humans.
Design: We conducted a systematic review of English-language, human studies of any design in children and adults with low to no alcohol intake and that reported at least one predetermined measure of liver health. The strength of the evidence was evaluated by considering risk of bias, consistency, directness, and precision.
Results: Six observational studies and 21 intervention studies met the inclusion criteria. The overall strength of evidence for observational studies was rated insufficient because of high risk of biases and inconsistent study findings. Of 21 intervention studies, 19 studies were in adults without NAFLD (predominantly healthy, young men) and 1 study each in adults or children with NAFLD. We found a low level of evidence that a hypercaloric fructose diet (supplemented by pure fructose) increases liver fat and aspartate aminotransferase (AST) concentrations in healthy men compared with the consumption of a weight-maintenance diet. In addition, there was a low level of evidence that hypercaloric fructose and glucose diets have similar effects on liver fat and liver enzymes in healthy adults. There was insufficient evidence to draw a conclusion for effects of HFCS or sucrose on NAFLD.
Conclusions: On the basis of indirect comparisons across study findings, the apparent association between indexes of liver health (ie, liver fat, hepatic de novo lipogenesis, alanine aminotransferase, AST, and γ-glutamyl transpeptase) and fructose or sucrose intake appear to be confounded by excessive energy intake. Overall, the available evidence is not sufficiently robust to draw conclusions regarding effects of fructose, HFCS, or sucrose consumption on NAFLD.
© 2014 American Society for Nutrition.
Figures
FIGURE 1.
Summary of evidence search and selection. *Full-text articles of included studies in published systematic reviews and meta-analyses investigating effects of free fructose on body weight (27), uric acid (28), glycemic effects (29), blood pressure (30), and blood lipids (31) for our outcomes of interest. †Main rejection reasons were as follows: no exposures of interest (38 articles), no outcomes of interest (13 articles), fructose amount in the interventions cannot be quantified (8 articles), review article or letter to the editor (8 articles), liver cirrhosis patients (6 articles), animal study (1 article), alcoholic fatty liver disease (1 article), and not relevant (2 articles). **Two studies investigated both pure fructose and sucrose. All databases are available from
gateway.ovid.com
. CCRC, Cochrane Central Register of Controlled Trials; HFCS, high-fructose corn syrup.
FIGURE 2.
Evidence map of intervention studies that examined effects of fructose or sucrose on indexes of liver health. Open circles represent studies in adults without NAFLD, solid circles represent studies in adults with NAFLD, and a triangle represents a study in children with NAFLD. The size of each symbol (open circle, solid circle, or triangle) is proportional to the sample size (sample size in each study ranged from 7 to 64). _See_Table 3 for more-detailed characteristics of included studies represented here. DNL, de novo lipogenesis; HFCS, high-fructose corn syrup; IHCL, intrahepatocellular lipid; NAFLD, nonalcoholic fatty liver disease; WM, weight maintenance; (Negative), negative energy comparison; (Neutral), neutral energy comparison; (Positive), positive energy comparison.
FIGURE 3.
Random-effects meta-analysis of the comparison of effects of a hypercaloric fructose diet with a weight-maintenance diet (positive energy comparison) on liver fat measured by IHCLs 1H MRS. Each black box represents the individual study's effect estimate, and the horizontal line represents the 95% CI of the effect estimate. The diamond shape represents the meta-analysis pooled effect estimate and its CI. A vertical dashed line displays the location of the meta-analysis pooled effect estimate. DM, diabetes mellitus; IHCL, intrahepatocellular lipid; IHCLs 1H MRS, intrahepatocellular lipids by proton magnetic resonance spectroscopy; NR, not reported; RCT, randomized controlled trial; ROB, risk of bias; ww, wet weight; %Change, net percentage change in intrahepatocellular lipids from baseline between groups; %vol, percent volume.
FIGURE 4.
Random-effects meta-analysis of RCTs reporting liver enzyme outcomes. A: Hypercaloric fructose compared with WM diet: ALT outcome. B: Hypercaloric fructose compared with glucose: ALT outcome. C: Hypercaloric fructose compared with glucose: AST outcome. Each black box represents the individual study's effect estimate, and the horizontal line represents the 95% CI of the effect estimate. Within each panel, the diamond shape represents the meta-analysis pooled effect estimate and its CI. *Because the same 24 men were randomly assigned to receive 2 different doses of fructose or glucose, only results from one dose can be included in the meta-analysis. Results from 80 g fructose/d compared with glucose diets were included in the current meta-analysis. The use of results from 40 g fructose/d compared with glucose diets produced similar pooled-effect estimates. ALT, alanine aminotransferase; AST, aspartate aminotransferase; MD, mean difference between groups; ROB, risk of bias; T2DM, type 2 diabetes; WM, weight maintenance.
FIGURE 5.
Random-effects meta-analysis comparing effects of a hypercaloric fructose diet with a hypercaloric glucose diet (neutral energy comparison) on liver fat measured by IHCLs 1H MRS. Each black box represents the individual study's effect estimate, and the horizontal line represents the 95% CI of the effect estimate. The diamond shape represents the meta-analysis pooled effect estimate and its CI. A vertical dashed line displays the location of the meta-analysis pooled effect estimate. IHCL, intrahepatocellular lipid; IHCLs 1H MRS, intrahepatocellular lipids by proton magnetic resonance spectroscopy; RCT, randomized controlled trial; ROB, risk of bias; %Change, net percentage change in intrahepatocellular lipids from baseline between groups; %signal, percent signal; %vol, percent volume.
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