Richard J. Johnson · Journal of Internal Medicine 2019 · Narrative review / evolutionary hypothesis · n=?

Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts

Cited 130 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and evolutionary hypothesis synthesis without primary experimental or human data

OpenAlex W2980939401 · doi:10.1111/joim.12993 · record verified 2026-08-31

What was done

The authors synthesized physiological, historical, and evolutionary literature to formulate a framework explaining how fructose metabolism—derived from dietary intake or endogenously via the polyol pathway—served as an adaptive survival mechanism during historical environmental crises such as food scarcity, drought, and hypoxia.

What was found

The abstract provides no empirical study data or quantitative measurements. It outlines a mechanistic model where fructose stimulates fat and glycogen storage, promotes sodium retention, elevates blood pressure, and shifts energy production from mitochondrial respiration to glycolysis to decrease oxygen demand. These adaptations are mediated partly through vasopressin and uric acid generation, reinforced historically by evolutionary mutations affecting vitamin C metabolism and uricase activity, but now drive obesity, diabetes, and hypertension under modern dietary patterns.

Why it matters

This evolutionary perspective offers a unifying mechanistic rationale for how pathways adapted for ancestral survival contribute to modern cardiometabolic disease when exposed to high-sugar diets.

Limits

The paper is a narrative theoretical review rather than an empirical trial or systematic review. It reports no new experimental or clinical measurements, quantitative risk estimates, or direct human outcome data.

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