On the Metabolism of Exogenous Ketones in Humans

Matthew Stirling, Brianna J. Stubbs, Pete J. Cox, Rhys D. Evans, Peter Santer, Jack J. Miller, Olivia K. Faull, Snapper Magor-Elliott, Satoshi Hiyama, Kieran Clarke

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate "ketogenic" diet, but adherence to such diets can be difficult. An alternative way to increase blood D-ß-hydroxybutyrate (D-ßHB) concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE); (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, or ketone salts (KS); sodium plus potassium ßHB. Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of ßHB. Both drinks elevated blood D-ßHB concentrations (D-ßHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3-4 h. KS drinks were found to contain 50% of the L-ßHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-ßHB and L-ßHB was <1.5% of the total ßHB ingested and was in proportion to the blood AUC. D-ßHB, but not L-ßHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-ßHB concentrations was determined in 16 participants. Food lowered blood D-ßHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-ßHB concentrations greater than 1 mM. Both drinks and infusions gave identical D-ßHB AUC of 1.3-1.4 moles.min. Conclusion: We conclude that exogenous ketone drinks are a practical, efficacious way to achieve ketosis.

LanguageEnglish
Article number848
JournalFrontiers in Physiology
Volume8
Issue numberOCT
DOIs
Publication statusPublished - 30 Oct 2017

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Ketones
Hydroxybutyrates
Esters
Salts
Ketosis
Acetone
Area Under Curve
Ketogenic Diet
Carbohydrate-Restricted Diet
Nonesterified Fatty Acids
Electrolytes
Meals
Blood Glucose
Healthy Volunteers
Potassium
Protein Isoforms
Triglycerides

Cite this

Stirling, M., Stubbs, B. J., Cox, P. J., Evans, R. D., Santer, P., Miller, J. J., ... Clarke, K. (2017). On the Metabolism of Exogenous Ketones in Humans. Frontiers in Physiology, 8(OCT), [848]. https://doi.org/10.3389/fphys.2017.00848
Stirling, Matthew ; Stubbs, Brianna J. ; Cox, Pete J. ; Evans, Rhys D. ; Santer, Peter ; Miller, Jack J. ; Faull, Olivia K. ; Magor-Elliott, Snapper ; Hiyama, Satoshi ; Clarke, Kieran. / On the Metabolism of Exogenous Ketones in Humans. In: Frontiers in Physiology. 2017 ; Vol. 8, No. OCT.
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Stirling, M, Stubbs, BJ, Cox, PJ, Evans, RD, Santer, P, Miller, JJ, Faull, OK, Magor-Elliott, S, Hiyama, S & Clarke, K 2017, 'On the Metabolism of Exogenous Ketones in Humans', Frontiers in Physiology, vol. 8, no. OCT, 848. https://doi.org/10.3389/fphys.2017.00848

On the Metabolism of Exogenous Ketones in Humans. / Stirling, Matthew; Stubbs, Brianna J.; Cox, Pete J.; Evans, Rhys D.; Santer, Peter; Miller, Jack J.; Faull, Olivia K.; Magor-Elliott, Snapper; Hiyama, Satoshi; Clarke, Kieran.

In: Frontiers in Physiology, Vol. 8, No. OCT, 848, 30.10.2017.

Research output: Contribution to journalArticle

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T1 - On the Metabolism of Exogenous Ketones in Humans

AU - Stirling, Matthew

AU - Stubbs, Brianna J.

AU - Cox, Pete J.

AU - Evans, Rhys D.

AU - Santer, Peter

AU - Miller, Jack J.

AU - Faull, Olivia K.

AU - Magor-Elliott, Snapper

AU - Hiyama, Satoshi

AU - Clarke, Kieran

PY - 2017/10/30

Y1 - 2017/10/30

N2 - Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate "ketogenic" diet, but adherence to such diets can be difficult. An alternative way to increase blood D-ß-hydroxybutyrate (D-ßHB) concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE); (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, or ketone salts (KS); sodium plus potassium ßHB. Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of ßHB. Both drinks elevated blood D-ßHB concentrations (D-ßHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3-4 h. KS drinks were found to contain 50% of the L-ßHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-ßHB and L-ßHB was <1.5% of the total ßHB ingested and was in proportion to the blood AUC. D-ßHB, but not L-ßHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-ßHB concentrations was determined in 16 participants. Food lowered blood D-ßHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-ßHB concentrations greater than 1 mM. Both drinks and infusions gave identical D-ßHB AUC of 1.3-1.4 moles.min. Conclusion: We conclude that exogenous ketone drinks are a practical, efficacious way to achieve ketosis.

AB - Background and aims: Currently there is considerable interest in ketone metabolism owing to recently reported benefits of ketosis for human health. Traditionally, ketosis has been achieved by following a high-fat, low-carbohydrate "ketogenic" diet, but adherence to such diets can be difficult. An alternative way to increase blood D-ß-hydroxybutyrate (D-ßHB) concentrations is ketone drinks, but the metabolic effects of exogenous ketones are relatively unknown. Here, healthy human volunteers took part in three randomized metabolic studies of drinks containing a ketone ester (KE); (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, or ketone salts (KS); sodium plus potassium ßHB. Methods and Results: In the first study, 15 participants consumed KE or KS drinks that delivered ~12 or ~24 g of ßHB. Both drinks elevated blood D-ßHB concentrations (D-ßHB Cmax: KE 2.8 mM, KS 1.0 mM, P < 0.001), which returned to baseline within 3-4 h. KS drinks were found to contain 50% of the L-ßHB isoform, which remained elevated in blood for over 8 h, but was not detectable after 24 h. Urinary excretion of both D-ßHB and L-ßHB was <1.5% of the total ßHB ingested and was in proportion to the blood AUC. D-ßHB, but not L-ßHB, was slowly converted to breath acetone. The KE drink decreased blood pH by 0.10 and the KS drink increased urinary pH from 5.7 to 8.5. In the second study, the effect of a meal before a KE drink on blood D-ßHB concentrations was determined in 16 participants. Food lowered blood D-ßHB Cmax by 33% (Fed 2.2 mM, Fasted 3.3 mM, P < 0.001), but did not alter acetoacetate or breath acetone concentrations. All ketone drinks lowered blood glucose, free fatty acid and triglyceride concentrations, and had similar effects on blood electrolytes, which remained normal. In the final study, participants were given KE over 9 h as three drinks (n = 12) or a continuous nasogastric infusion (n = 4) to maintain blood D-ßHB concentrations greater than 1 mM. Both drinks and infusions gave identical D-ßHB AUC of 1.3-1.4 moles.min. Conclusion: We conclude that exogenous ketone drinks are a practical, efficacious way to achieve ketosis.

KW - (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

KW - D-ß-hydroxybutyrate

KW - Exogenous ketones

KW - Ketone ester

KW - Ketone salt

KW - Ketones

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Stirling M, Stubbs BJ, Cox PJ, Evans RD, Santer P, Miller JJ et al. On the Metabolism of Exogenous Ketones in Humans. Frontiers in Physiology. 2017 Oct 30;8(OCT). 848. https://doi.org/10.3389/fphys.2017.00848