Dietary Supplements

Acute exogenous ketone monoester supplementation decreases indices of cardiac vagal modulation in a dose-dependent manner in healthy adults.

TL;DR

Acute exogenous ketone monoester supplementation decreases HR variability measures associated with cardiac vagal modulation in a dose-dependent manner in healthy adults.

Key Findings

Both doses of ketone monoester increased plasma β-hydroxybutyrate compared to placebo.

  • Study involved 18 healthy adults (23 ± 3 years; n = 10 females)
  • Participants ingested 0.3 or 0.6 g/kg ketone monoester or placebo
  • Randomized crossover, double-blind design was used
  • Plasma β-hydroxybutyrate was elevated following both ketone doses relative to placebo

Both ketone monoester doses reduced pRR50 (percentage of successive R-R intervals differing by ≥50 ms) at 45 and 120 minutes post-ingestion.

  • Reductions in pRR50 were observed compared to placebo at both time points
  • Effect was statistically significant at 45 minutes post-ingestion (p < 0.02)
  • Effect was statistically significant at 120 minutes post-ingestion (p < 0.01)
  • Both the 0.3 g/kg and 0.6 g/kg doses produced this effect

Both ketone monoester doses reduced RMSSD (root mean square of successive differences) at 45 and 120 minutes post-ingestion.

  • Reductions in RMSSD were observed compared to placebo at both time points
  • Effect was statistically significant at 45 minutes post-ingestion (p < 0.02)
  • Effect was statistically significant at 120 minutes post-ingestion (p < 0.01)
  • Both the 0.3 g/kg and 0.6 g/kg doses produced this effect

Exogenous ketone monoester supplementation decreases heart rate variability measures associated with cardiac vagal modulation.

  • pRR50 and RMSSD are both indices associated with cardiac vagal modulation
  • Effects were observed at two time points: 45 minutes and 120 minutes post-ingestion
  • The supplementation also elevated heart rate, consistent with reduced vagal tone
  • Reductions occurred in a dose-dependent manner across 0.3 and 0.6 g/kg doses

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Citation

Thiessen J, Rourke A, Pocchi G, Yong C, Odisho A, Nash J, et al.. (2026). Acute exogenous ketone monoester supplementation decreases indices of cardiac vagal modulation in a dose-dependent manner in healthy adults.. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. https://doi.org/10.1139/apnm-2025-0394