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.

Effect of Important Food Sources of Fructose-Containing Sugars on Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Controlled Feeding Trials

“…Our findings, similar to our previous systematic reviews and meta-analyses on the importance of food sources of fructose-containing sugars on other cardiometabolic outcomes [ 8 , 11 , 124 , 125 , 139 ], suggest that the focus of dietary guidelines [ 151 ] should be on dietary patterns, recognizing the importance and complex interactions of the food matrix and the energy conditions under which foods are consumed, rather than limited to single nutrients, like total fructose-containing sugars. Our present results demonstrating the benefit of fruit on inflammation are also supported by the Global Burden of Disease Study which showed the most important contributors to the global burden of morbidity and mortality are foods we should increase intake of, include increased intake of fruit [ 152 ].…”

“…The lack of harm observed for SSBs alone at all levels of energy control is supported by a previous systematic review and meta-analysis including 7 trial comparisons of fructose versus glucose which showed no overall effect [ 121 ]. Previous systematic reviews and meta-analyses exploring the effect of different food sources of fructose containing sugars on cardiometabolic outcomes in controlled trials have demonstrated harm when SSBs are consumed as a source of excess calories, including on glycemic control, adiposity, blood pressure and uric acid [ 8 , 11 , 139 , 140 ]. It is possible that the lack of harm observed in the present analysis may be the result of fewer trials and those which only comprised of healthy participants free of chronic diseases and with low baseline CRP levels (median 0.4 mg/L, range 0.2–1.22 mg/L).…”

Dietary patterns and risk of non-alcoholic fatty liver disease in Korean adults: a prospective cohort study

“…30 A systematic review was agree with this speculation that food source may mediate the effect of nutrients on NAFLD development. 39 The white rice pattern was characterised by high rice consumption in the present study. Chung et al also identified a similar dietary pattern, named the 'simple meal pattern', and reported no association with NAFLD risk.…”

“… 30 A systematic review was agree with this speculation that food source may mediate the effect of nutrients on NAFLD development. 39 …”

Kommentar zu „Zusammenhang zwischen Fruktosekonsum und intrahepatischem Fett untersucht“

“…Die Ergebnisse einer kürzlich veröffentlichen Meta-Analyse, die den Einfluss der Quelle der Fruktose (z. B. zuckergesüßte Getränke, Obstsaft, Süßwaren, gesüßte Milchprodukte) und des Energiegehalts auf Marker der NAFLD in 51 Studien untersuchte, weisen ebenfalls darauf hin, dass vor allem eine überschüssige Energieaufnahme aus zucker- (fruktose-) gesüßten Getränken mit dem Anstieg des Leberfetts und der ALT Aktivität im Blut einhergeht 5 . In dieser Untersuchung fand sich auch ein positiver Effekt auf den Leberfettgehalt bei einer Reduktion der Aufnahme von Fructose aus gesüßten Getränken.…”