Metabolic Effects of Fructose and the Worldwide Increase in Obesity

Abstract

While virtually absent in our diet a few hundred years ago, fructose has now become a major constituent of our modern diet. Our main sources of fructose are sucrose from beet or cane, high fructose corn syrup, fruits, and honey. Fructose has the same chemical formula as glucose (C6H12O6), but its metabolism differs markedly from that of glucose due to its almost complete hepatic extraction and rapid hepatic conversion into glucose, glycogen, lactate, and fat. Fructose was initially thought to be advisable for patients with diabetes due to its low glycemic index. However, chronically high consumption of fructose in rodents leads to hepatic and extrahepatic insulin resistance, obesity, type 2 diabetes mellitus, and high blood pressure. The evidence is less compelling in humans, but high fructose intake has indeed been shown to cause dyslipidemia and to impair hepatic insulin sensitivity. Hepatic de novo lipogenesis and lipotoxicity, oxidative stress, and hyperuricemia have all been proposed as mechanisms responsible for these adverse metabolic effects of fructose. Although there is compelling evidence that very high fructose intake can have deleterious metabolic effects in humans as in rodents, the role of fructose in the development of the current epidemic of metabolic disorders remains controversial. Epidemiological studies show growing evidence that consumption of sweetened beverages (containing either sucrose or a mixture of glucose and fructose) is associated with a high energy intake, increased body weight, and the occurrence of metabolic and cardiovascular disorders. There is, however, no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects. There has also been much concern that consumption of free fructose, as provided in high fructose corn syrup, may cause more adverse effects than consumption of fructose consumed with sucrose. There is, however, no direct evidence for more serious metabolic consequences of high fructose corn syrup versus sucrose consumption.

Self-regulatory depletion in dogs: Insulin release is not necessary for the replenishment of persistence

“…Although the conclusions we draw from this study rest on the assumption that fructose and glucose differentially affect glucose and insulin levels, there is a large body of evidence that supports this assumption (for reviews see Riby et al, 1993;Tappy and Le, 2010).…”

“…Fructose does not directly provide energy for cellular processes, nor is it actively transported across the blood brain barrier like glucose (Simpson et al, 2007). In addition, it has little effect on blood glucose levels as it is digested primarily in the liver (Tappy and Le, 2010). The liver metabolizes fructose much like a lipid, and the energy is either converted to glucose or lactate (a process that takes hours, not minutes) or it is converted into glycogen (for a review see Sun and Empie, 2012).…”

“…The liver metabolizes fructose much like a lipid, and the energy is either converted to glucose or lactate (a process that takes hours, not minutes) or it is converted into glycogen (for a review see Sun and Empie, 2012). The stored glycogen then can be converted to glucose if necessary through glycogenolysis (Tappy and Le, 2010). Humans and dogs share this metabolic process (Shiota et al, 1998).…”

“…Humans and dogs share this metabolic process (Shiota et al, 1998). Furthermore, the consumption of fructose does not increase insulin synthesis or secretion like glucose does, because insulin is unnecessary for metabolizing fructose by humans (Tappy et al, 1986;Tappy, and Le, 2010) and nonhuman animals (Curry, 1989).…”

Sugar-sweetened beverages, vascular risk factors and events: a systematic literature review

“…Studies show that added sugar (over-) consumption, specifically in the form of sugar-sweetened beverages (SSB), seems to be linked to different harmful health outcomes such as obesity and diabetes (3)(4)(5) . SSB may also potentially increase the risk of CVD through their high amount of rapidly absorbable carbohydrates that may, via an elevated hepatic de novo lipogenesis, result in hypertension, accumulation of visceral and ectopic fat, and increased TAG and LDL cholesterol (LDL-C) and decreased HDL cholesterol (HDL-C) levels (6,7) . The increased glycaemic load caused by a high SSB intake may lead to inflammation, β-cell dysfunction and insulin resistance, as suggested by who, in their pooled meta-analysis from three prospective cohorts, reported that participants in the highest category of SSB intake had a 20 % greater risk of developing metabolic syndrome than those in the lowest category of intake (4) .…”