Cahill · Transactions of the American Clinical and Climatological Association 2003 · narrative review · n=?

Ketoacids? Good medicine?

Cited 200 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing mechanistic reasoning and preclinical animal/in vitro models without human trial data.

PubMed 12813917 · record verified 2026-08-30

What was done

This narrative review summarizes the physiological role of D-beta-hydroxybutyrate during human starvation and evaluates preclinical evidence (perfused rat heart preparations, neuronal tissue cultures, and rodent models of hypoxia and hemorrhagic shock) assessing its energetic efficiency and potential therapeutic applications.

What was found

The abstract reports qualitative observations without specific statistical metrics. D-beta-hydroxybutyrate displaces glucose as the primary fuel for the brain during starvation, reducing hepatic/renal glucose synthesis and sparing muscle amino acids, thereby enabling prolonged starvation survival (2–3 months in a normal 70 kg individual and up to over a year in obesity). In preclinical models, D-beta-hydroxybutyrate increased myocardial contractility while decreasing oxygen consumption in perfused rat hearts, protected cultured neurons against toxins associated with Alzheimer's and Parkinson's diseases, reduced lung cell death in rodent hemorrhagic shock, and prolonged survival in mice subjected to hypoxia.

Why it matters

It outlines the metabolic rationale for developing oral or parenteral beta-hydroxybutyrate esters to treat conditions where tissue oxygenation or substrate utilization is compromised.

Limits

The paper is a narrative review relying entirely on evolutionary reasoning, in vitro cell cultures, ex vivo organs, and rodent models; no human clinical trial data or quantitative statistical estimates are provided in the abstract.

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