Fructose and Cardiometabolic Disorders: The Controversy Will, and Must, Continue

Abstract

The present review updates the current knowledge on the question of whether high fructose consumption is harmful or not and details new findings which further pushes this old debate. Due to large differences in its metabolic handling when compared to glucose, fructose was indeed suggested to be beneficial for the diet of diabetic patients. However its growing industrial use as a sweetener, especially in soft drinks, has focused attention on its potential harmfulness, possibly leading to dyslipidemia, obesity, insulin resistance/metabolic syndrome and even diabetes. Many new data have been generated over the last years, confirming the lipogenic effect of fructose as well as risks of vascular dysfunction and hypertension. Fructose exerts various direct effects in the liver, affecting both hepatocytes and Kupffer cells and resulting in non-alcoholic steatotic hepatitis, a well known precursor of the metabolic syndrome. Hepatic metabolic abnormalities underlie indirect peripheral metabolic and vascular disturbances, for which uric acid is possibly the culprit.Nevertheless major caveats exist (species, gender, source of fructose, study protocols) which are detailed in this review and presently prevent any firm conclusion. New studies taking into account these confounding factors should be undertaken in order to ascertain whether or not high fructose diet is harmful.

Hepatic function and the cardiometabolic syndrome

“…Fructose is present as concentrated corn syrup in many sodas, and there is presently a lively debate about its importance in the epidemic of hepatic steatosis, particularly in the US 23. Indeed, a high fructose intake leads rapidly to hepatic inflammation, stress on the endoplasmic reticulum, and lipoapoptosis, in addition to de novo lipogenesis 24.…”

“…Patients with a fatty liver index >60 show an increased risk of atherosclerosis, which is tentatively explained by incorporation of GGT into plaques, where it might trigger iron-dependent oxidation of low-density lipoprotein 79. A high fructose intake is also linked with an elevated incidence of cardiovascular disease 23. There is likely a prominent role for high triglycerides, in that while inert triglycerides are harmless, triglycerides containing saturated fatty acids are harmful 80.…”

Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice

“…Consumption of high levels of fructose in humans and animals leads to insulin resistance, obesity, hypertension, autonomic dysfunction, and lipid and renal abnormalities (1,5,8,10,13). The cluster of metabolic and hemodynamic alterations, known as metabolic syndrome, has reached epidemic levels worldwide (1,17,48).…”

High Sugar Intake May Increase Cardiovascular Disease Risk

“…4,5 There is a striking parallel between the prevalence of obesity and the consumption of high fructose corn syrup, the major source of sugar added to beverages and foods in the American diet. 7 The current study is limited by its cross-sectional design and the fact that the data were derived in most cases from a single 24-hour dietary recall. 7 The current study is limited by its cross-sectional design and the fact that the data were derived in most cases from a single 24-hour dietary recall.…”