Added Fructose in Non-Alcoholic Fatty Liver Disease and in Metabolic Syndrome: A Narrative Review

Abstract

Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease and it is considered the hepatic manifestation of metabolic syndrome (MetS). Diet represents the key element in NAFLD and MetS treatment, but some nutrients could play a role in their pathophysiology. Among these, fructose added to foods via high fructose corn syrup (HFCS) and sucrose might participate in NAFLD and MetS onset and progression. Fructose induces de novo lipogenesis (DNL), endoplasmic reticulum stress and liver inflammation, promoting insulin resistance and dyslipidemia. Fructose also reduces fatty acids oxidation through the overproduction of malonyl CoA, favoring steatosis. Furthermore, recent studies suggest changes in intestinal permeability associated with fructose consumption that contribute to the risk of NAFLD and MetS. Finally, alterations in the hunger–satiety mechanism and in the synthesis of uric acid link the fructose intake to weight gain and hypertension, respectively. However, further studies are needed to better evaluate the causal relationship between fructose and metabolic diseases and to develop new therapeutic and preventive strategies against NAFLD and MetS.

A Low Daily Intake of Simple Sugars in the Diet Is Associated with Improved Liver Function in Cirrhotic Liver Transplant Candidates

“…Our results demonstrating the beneficial effect on the prognosis of cirrhotic patients of reducing the dietary intake of simple sugars, especially fructose, find support in data published in the field of NAFLD and MAFLD. Indeed, high fructose consumption exerts a negative metabolic effect in these patients on hepatic lipid synthesis, visceral adipose tissue accumulation, insulin resistance, increased uric acid and inflammation, and fibrosis progression [ 25 , 26 , 27 , 28 , 29 ]. Furthermore, it is known that patients with NAFLD and high amounts of visceral fat are at increased risk of insulin resistance [ 38 ].…”

“…First, because patients with cirrhosis related to non-alcoholic fatty liver disease (NAFLD) or metabolic associated fatty liver disease (MAFLD) are steadily increasing overall and among LT candidates [ 19 , 20 , 21 , 22 , 23 , 24 ]. Secondly, because it is increasingly evident that in patients with NAFLD or MAFLD in the noncirrhotic phase, hepatic fat accumulation, inflammation, and hepatic fibrosis are associated with the consumption of simple sugars, in particular fructose and sucrose [ 25 , 26 , 27 , 28 , 29 ].…”

A Comparison of Primary Human Hepatocytes and Hepatoma Cell Lines to Model the Effects of Fatty Acids, Fructose and Glucose on Liver Cell Lipid Accumulation

“…While it is well established that NAFLD is associated with insulin resistance there is also evidence that specific components of the diet can contribute to its development. Animal [ 6 ] and human [ 7 , 8 , 24 ] studies have suggested that diets rich in fructose may promote hepatic steatosis and its progression to steatohepatitis, to a greater extent than glucose. Multiple mechanisms have been suggested for this response including direct effects on hepatic lipogenesis [ 13 ].…”

Impact of Dietary Fructose and High Salt Diet: Are Preclinical Studies Relevant to Asian Societies?

“…This review focuses on the impact of fructose and salt consumption on the development of hypertension, independent or preceding the full expression of metabolic syndrome, which may lead to heightened cardiovascular risk. The influence of fructose on metabolic syndrome is well recognized and reviewed in detail in several recent reviews [20][21][22][23].…”