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Food Addiction Institute
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The fructose survival hypothesis proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biologic response (survival switch) that aims to protect animals in advance of crisis. The response is characterized by hunger, thirst, foraging, weight gain, fat accumulation, insulin resistance, systemic inflammation and increased blood pressure. The process is initiated by the ingestion of fructose or by stimulating endogenous fructose production via the polyol pathway. Unlike other nutrients, fructose reduces the active energy (adenosine triphosphate) in the cell, while blocking its regeneration from fat stores. This is mediated by intracellular uric acid, mitochondrial oxidative stress, the inhibition of AMP kinase and stimulation of vasopressin. Mitochondrial oxidative phosphorylation is suppressed, and glycolysis stimulated. While this response is aimed to be modest and short-lived, the response in humans is exaggerated due to gain of ‘thrifty genes’ coupled with a western diet rich in foods that contain or generate fructose. We propose excessive fructose metabolism not only explains obesity but the epidemics of diabetes, hypertension, non-alcoholic fatty liver disease, obesity-associated cancers, vascular and Alzheimer’s dementia, and even ageing. Moreover, the hypothesis unites current hypotheses on obesity. Reducing activation and/or blocking this pathway and stimulating mitochondrial regeneration may benefit health-span. This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Food addiction is an emerging area of both clinical and research interest. The current review discussed several definitional and conceptual categorisations that have been put forth to quantify food addiction. However, the YFAS 2·0 concept predominates the literature. Similarly, evidence shows some similarities of food addiction with established eating disorders, particularly BED. Thus, the current review supports two main areas of contention that warrant much more research; considering food addiction as a substance-related addiction or a behavioural-related addiction and if food addiction is distinct from established eating disorders. Further research is needed to continue to delineate and clarify controversies about similarities and differences in food addiction with other concepts and established disorders.
The fructose survival hypothesis for obesity
Johnson, R. J., Lanaspa, M. A., Sanchez-Lozada, L. G., Tolan, D., Nakagawa, T., Ishimoto, T., Andres-Hernando, A., Rodriguez-Iturbe, B., & Stenvinkel, P. (2023). The fructose survival hypothesis for obesity. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 378(1885), 20220230.
The fructose survival hypothesis for obesity

Fructose is a simple sugar that is the primary nutrient in fruit and honey. However, in the western diet, its main source is table sugar (sucrose), which consists of fructose and glucose bound together, and high fructose corn syrup (HFCS), which consists of a blended mixture of fructose and glucose, often with slightly higher concentrations of fructose as testing has suggested humans prefer slightly more fructose as it is sweeter than glucose. Today these ‘added sugars’ account for ≈15% of overall energy intake, with some groups ingesting as much as 20% or more [6].

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