Sweetened beverages consumption and NAFLD

The increasing incidence of Non Alcoholic Fatty Liver Disease (NAFLD) worldwide, and in particular in industrialized countries, has led to a growing interest in the pathogenetic mechanisms linked to this disease, with the ultimate goal of developing a causal therapy for this pathology. As is known, however, at present time the only recommendations on the treatment of NAFLD are related to the modifications of patients’ lifestyle, promoting changes in their diet and physical activity [Ref 1]. The consumption of industrial foods, in particular, represents a crucial point in the modification of the lifestyle of patients with NAFLD. The consumption of carbonated drinks is one of the focal points in this regard. Industrially produced sugary drinks are sweetened by adding fructose or polymeric sugars containing fructose (e.g. sucrose, which is a combination of glucose and fructose). This choice is however mainly based on economic reasons. In fact, the sweetening power of fructose is higher than that of glucose, so a smaller amount is needed to achieve the same degree of sweetness. This decision, that is purely based on profit, actually has catastrophic health implications. In fact, it is well known how the increased fructose intake is associated with obesity, metabolic syndrome and NAFLD [Ref 2], with increased hepatic de novo lipogenesis and hepatic fat content and reduced insulin sensitivity [Ref 3]. The increased fructose accumulation in hepatic cells stimulates the increase of lipogenesis through the overexpression of lipogenic enzymes like fatty acid synthase and acetyl-CoA carboxylase [Ref 4]. Furthermore, the continuous consumption of fructose-containing food and beverages brings to a metabolic adaptation in a lipogenic way [Ref 5].

While the effect of fructose is unfortunately well know, it is to date not clear the role of sucrose in lipogenesis and NAFLD.

Geidl-Flueck B et al. recently tried to investigate the metabolic effects of moderate fructose, sucrose and glucose intake and to compare them [Ref 6]. In their study, they enrolled 126 healthy male volunteers with a Body Mass Index (BMI) within normal limits and divided them in four different groups of 24 participants each. The first group received a thrice daily dose of 200 ml of a beverage containing fructose for seven weeks. The second group received the same amount of beverages containing sucrose and the third group the same quantity of beverages containing glucose instead. The fourth group was asked to maintain abstinence from the consumption of sweetened beverages of any kind.

The average body weight and percentage of body fat increased during the period of beverages consumption in all groups, being significant however only in the subjects that were assuming glucose. Fasting plasmatic triglycerides, glucose and insulin concentrations did not change throughout the study. However, subjects that consumed fructose and sucrose-added beverages showed a significant increase in hepatic fatty acids synthesis. While the role of fructose was well know, this study shows new perspectives regarding the role of sucrose. The notion of sucrose having the same potential role of fructose in lipogenesis can be possibly explained intracellular mechanisms in which glucose and fructose enhance each other. In fact, glucose enhances intestinal fructose uptake while fructose stimulates hepatic glucose uptake  through  glucokinase  activation,  enhancing hepatic glucose uptake and consequently increasing the concentration of lipogenic substrates.

In summary, this study demonstrates that even normal-to moderately elevated quantities of sweetened beverages containing both fructose and sucrose can alter hepatic metabolism increasing fatty acids synthesis. This notion is fundamental because it has a strong impact on everyday dietary choices. Therefore, dietary advice on food selection and not just caloric restriction should be offered to all NAFLD patients.

REFERENCES

1. Cardoso AC, de Figueiredo-Mendes C, A Villela-Nogueira C. Current management of NAFLD/NASH. Liver Int. 2021 Jun;41 Suppl 1:89-94.
2. Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL et al.  consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest 2009;119:1322–1334.
3. Schwarz  JM,  Noworolski  SM,  Wen  MJ,  Dyachenko  A,  Prior  JL, Weinberg ME, et al. Effect of a high-fructose weight-maintaining diet on lipogenesis and liver fat. J Clin Endocrinol Metab 2015;100:2434–2442.
4. Janevski M, Ratnayake S, Siljanovski S, McGlynn MA, Cameron-Smith D, Lewandowski P. Fructose containing sugars modulate mRNA of lipogenic genes ACC and FAS and protein levels of transcription factors ChREBP and SREBP1c with no effect on body weight or liver fat. Food Funct 2012;3:141–149.
5. Hudgins LC, Hellerstein M, Seidman C, Neese R, Diakun J, Hirsch J. Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet. J Clin Invest 1996;97:2081– 2091.
6. Geidl-Flueck B, Hochuli M, Németh Á, Eberl A, Derron N, Köfeler HC et al. Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial. J Hepatol. 2021 Jul;75(1):46-54.