McCarthy · The Journal of pharmacology and experimental therapeutics 2021 · Controlled animal dose-response experiment · n=?

Physiologic, Metabolic, and Toxicologic Profile of 1,3-Butanediol.

Cited 23 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Animal interventional study with no human data

PubMed 34521698 · doi:10.1124/jpet.121.000796 · record verified 2026-08-30

What was done

Adult male Wistar-Kyoto rats received 5%, 10%, or 20% 1,3-butanediol (1,3-BD) via drinking water for 4 weeks. Investigators measured systemic and urinary beta-hydroxybutyrate (βHB) concentrations alongside physiologic, metabolic, and toxicologic outcomes including body mass, food and fluid intake, hematologic markers (red blood cell count, hematocrit, urine volume), and liver histology.

What was found

Only the 20% 1,3-BD dose significantly elevated systemic and urinary βHB to levels comparable to a 24-hour fast. All doses decreased food consumption, but only 20% reduced fluid intake. Body mass rapidly and sustainably decreased in the 20% group. Markers of dehydration (urine volume, red blood cell count, hematocrit) appeared at 10% and 20% doses. Rats given 20% 1,3-BD developed metabolic acidosis and sinusoidal dilation without fatty liver or hepatotoxicity. No specific numeric values were reported in the abstract.

Why it matters

1,3-BD is commonly used to induce exogenous ketosis, but achieving target fasting levels of βHB required doses that produced notable adverse effects, including dehydration and metabolic acidosis in rodents.

Limits

This was an animal study conducted solely in male Wistar-Kyoto rats; results cannot be directly applied to humans. Sample size per group and quantitative numerical data are not reported in the abstract. Long-term effects beyond 4 weeks were not assessed.

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