Fructose Consumption and Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 723-745-Lipids: Fatty Liver Disease & Lipodystrophies
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-729
Mei Chung*1, Jiantao Ma2, Kamal Patel1, Samantha Berger1, Joseph Lau3 and Alice Lichtenstein2
1Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, 2Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 3Public Health Program, Brown University, Providence, RI
Background: There are growing concerns about the health effects of dietary fructose because the intakes appear to parallel trends in NAFLD and obesity prevalence in the United States.

Purpose: To examine the effect of different levels and sources of dietary fructose on the incidence or prevalence of NAFLD and on indices of liver health in humans.

Data Sources: English-language studies identified from MEDLINE (1946 to September 2012), Cochrane Central Register of Controlled Trials (through September 2012), CAB Abstracts (1973 to 2012 Week 39), and Global Health (1910 to September 2012) databases.

Study Selection: Human studies of any design in children and adults with low to no alcohol intake and reporting at least one predetermined measure of liver health.

Data Extraction: Study data was extracted by one investigator and corroborated by a second investigator.  Differences were resolved by consensus.

Data Synthesis: Twenty-two studies met the inclusion criteria, 3 reported NAFLD outcomes and 19 reported indices of liver health.  Of these, all but 1 study were rated at medium or high risk of bias. The overall strength of evidence for an association between fructose intake and incidence of NAFLD was rated insufficient because of the biases and confounding in the study results.  The 19 studies reporting indices of liver health were synthesized separately by each outcome: liver fat outcomes (7 studies), liver enzymes (11 studies), hepatic de novo lipogenesis rates (2 studies), and plasma bilirubin concentrations (2 studies).  The overall strength of evidence was rated insufficient for all outcomes, except for some plasma liver enzymes.  Our random-effects meta-analysis of 3 short-term RCTs (6 to 7 days) showed a significant increase in alanine aminotransferase (ALT) concentrations (+4.32 IU/L, 95% CI 0.20, 8.43, P=0.04) when a free fructose enriched excess energy diet was compared to a habitual weight maintenance diet.

Limitations: Most studies were rated at medium or high risk of bias, and were small in sample size, included healthy adult men only, and were highly heterogeneous in study design and intervention, and thus limiting comparability.

Conclusions: Due to scarce, poor-quality, and heterogenous data, we concluded that evidence is insufficient to draw conclusions regarding the effect of fructose consumption on NAFLD, while there is low level of evidence for a relationship between high free fructose intake in excess of energy needs and elevated liver enzyme concentrations. Large prospective cohort studies using standard NAFLD diagnosis are needed to examine the complex relationships between dietary factors and the risk of NAFLD.

Nothing to Disclose: MC, JM, KP, SB, JL, AL

*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: Funding for this systematic review was provided by the Technical Committee on Carbohydrates of the International Life Sciences Institute (ILSI) North American Branch.  ILSI North America’s participation was limited to discussion with the team about the initial formulation of systematic review key questions.  The sponsor had no role in study selection, quality assessment, synthesis or preparation of the manuscript.