Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults
Abstract
Throughout history, the only way humans could raise their blood ketone levels was by several days of fasting or by following a strict low-carb, high-fat diet. A recently developed, dietary source of ketones, a ketone monoester, elevates d-β-hydroxybutyrate (βHB) to similar concentrations within minutes, with βHB remaining raised for several hours. To date, the longest human safety study of the exogenous ketone ester was for 5 days, but longer consumption times may be desired. Here we report results for 24 healthy adults, aged 18-70 years, who drank 25 ml (26.8 g) of the ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, three times a day for 28 days (a total of 2.1 L). Anthropomorphic measurements, plus fasting blood and urine analyses were made weekly. It was found that elevating blood βHB concentrations from 0.1 to 4.1 (±1.1) mM three times a day for 28 days had no effect on body weights or composition, fasting blood glucose, cholesterol, triglyceride or electrolyte concentrations, nor blood gases or kidney function, which were invariably normal. Mild nausea was reported following 6 of the 2,016 drinks consumed. We conclude that sustained exogenous ketosis using a ketone monoester is safe and well-tolerated by healthy adults.
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Recently developed ketone esters significantly increase circulating β-hydroxybutyrate in humans.
“These findings combined are particularly interesting when considering the availability of recently developed ketone esters known to significantly increase circulating β-hydroxybutyrate in humans [177].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [177]
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Cites
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Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging
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“These findings combined are particularly interesting when considering the availability of recently developed ketone esters known to significantly increase circulating β-hydroxybutyrate in humans [177].”
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- Authors
- Soto-Mota, A., Vansant, H., Evans, R. D., & Clarke, K.
- Affiliations
- University of Oxford (GB)
- Venue
- Regulatory Toxicology and Pharmacology
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 109
- Pages
- 104506
- ISSN
- 0273-2300 (ISSN-L)
- OpenAlex
- W2982272908
- Cited by
- 97
- References
- 17
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 16 · 2023: 10 · 2022: 17 · 2021: 18 · 2020: 16
- FWCI
- 8.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Regulatory Toxicology and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Consejo Nacional de Ciencia y Tecnología
- Fundación para la Salud y Educación Dr Salvador Zubirán
- Topics
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- ketone monoester, beta-hydroxybutyrate, safety, tolerability, long-term consumption, healthy adults, body weight, blood glucose, electrolytes, renal function, nausea
- MeSH terms
- Adolescent, Adult, Aged, Chronic Disease, Esters, Fasting, Humans, Hydroxybutyrates, Ketones, Ketosis, Male, Middle Aged, Dietary Supplements, Diet, Ketogenic, Young Adult, Toxicity Tests, Subacute, Healthy Volunteers
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