Johnson · Philosophical transactions of the Royal Society of London. Series B, Biological sciences 2023 · narrative review / theoretical framework · n=?

The fructose survival hypothesis for obesity.

Cited 56 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and theoretical hypothesis paper based on mechanistic reasoning without new empirical data.

PubMed 37482773 · doi:10.1098/rstb.2022.0230 · record verified 2026-08-27

What was done

This theoretical review outlines the fructose survival hypothesis, synthesizing evolutionary concepts and biochemical pathways to explain how dietary fructose ingestion and endogenous polyol pathway production drive obesity and metabolic disorders.

What was found

The abstract reports no numerical or quantitative data. It outlines a proposed mechanism wherein fructose metabolism depletes cellular adenosine triphosphate (ATP) and blocks fat breakdown via intracellular uric acid, mitochondrial oxidative stress, AMP kinase inhibition, and vasopressin stimulation, shifting metabolism toward glycolysis and fat accumulation.

Why it matters

The paper provides a unifying evolutionary framework linking dietary and endogenous fructose metabolism to obesity, diabetes, hypertension, non-alcoholic fatty liver disease, and related chronic conditions.

Limits

This is a conceptual narrative hypothesis without original human experimental or observational data. No quantitative effect sizes, clinical outcomes, or empirical sample sizes are presented in the abstract.

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