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.
Alex’s Notes: I think I am going to keep this very brief. I’m tired of beating a dead-horse (although I will probably continue to do so indefinitely), and this latest meta-analysis really hits hard on sugar-haters when it concludes,
“On the basis of indirect comparisons across study findings, the apparent association between indexes of liver health (i.e., liver fat, hepatic DNL, ALT, AST, and GGT) and fructose or sucrose intake appear to be confounded by excessive energy intake. Current evidence does not allow us to discern the intertwined associations between excess body weight, monosaccharide fructose or sucrose intake, and NAFLD [non-alcoholic fatty liver disease]. Therefore, we concluded that, overall, the available evidence is not sufficiently robust to draw conclusions regarding effects of fructose, HFCS, or sucrose consumption on NAFLD.”
The researchers defined dietary fructose to include its free sugar form, as well as that in high-fructose corn syrup (HFCS), sucrose, and honey. Thus, many studies didn’t look at fructose in isolation, which is great because it never exists in food or even in sugary foods and beverages by itself. The researchers also excluded animal and in-vitro studies, ensuring these results are specific to humans. However, no human studies in which the participants had fructose intolerances, metabolic diseases or infections that affect the liver, Wilson’s disease, or cirrhosis were included. So for the most part, people had healthy livers. Overall, 27 studies were included in the review with six being observational and the remainder intervention studies.
For the intervention studies, it was interesting to find that 57% (12 studies) investigated the effects of pure fructose in almost exclusively healthy young men, and that 67% of these studies (eight) were conducted by the same researchers. Even worse is that every one of the 12 studies that looked at pure fructose did it in the context of a caloric surplus and compared it to a eucaloric diet without the fructose. Ignoring the obvious bias from the single group of researchers, how can pure fructose overfeeding be relevant to anything? In fact, only one study directly compared the isocaloric replacement of fructose and glucose (25% kcal) on liver fat and liver enzyme outcomes and showed that there was no difference between the two sugars. Even so, in the other studies on hypercaloric diets in healthy subjects the liver fat levels after the fructose interventions were still far below the concentrations of those with NAFLD (defined by IHCL ≥ 5.5%).
Bottom line: Get over it, fructose isn’t “evil.”