| Description |
- Background
Short-term nutritional ketosis may be associated with prolonged latency to central nervous system oxygen toxicity (CNSOT). Ketone food product administration may raise ketone levels more quickly and predictably than dietary modification, supporting a regimen to be tested for CNSOT mitigation.
Methods
16.2g beta-hydroxybutyrate (BHB) ketone salts, 10g medium chain triglyceride (MCT) oil powder, and increasing regimens (6-33g) of 1,3-butanediol acetoacetate diester (KDE) were given to the first 15 healthy volunteers and side effects were documented. A weight-based response was noted, and 0.5g/kg and 0.6g/kg regimens of the KDE were additionally evaluated. Point-of-care BHB and Acetone, plus UPLC-MS/MS BHB and acetoacetate (AcAc) levels were assessed for 6 hours post-ingestion. Side effects and pre/post study blood counts, metabolic panels, and urine were analyzed.
Results
Nineteen subjects (mean±SD: age 25.8±5.6 years, BMI 24.1±2.2) completed evaluation. Plasma AcAc and BHB AUC increased in stepwise fashion with increasing regimens (adjusted R2=0.55; p<0.001; adjusted R2=0.76, p<0.001). Peak plasma AcAc and BHB levels rose significantly with increases in KDE regimen (adjusted R2=0.50; p<0.001, adjusted R2=0.60, p<0.001). No clinically significant changes in blood, metabolic, or urine studies were observed. Mean (SD) time to peak acetoacetate occurred at 74.2 (45.1) minutes, and for BHB, occurred at 83.7 (41.9) minutes. Self-limited adverse effects were mild and included fatigue (31.6%), headache (31.6%), brief stomach discomfort (26.3%), and diarrhea (10.5%). Only one subject, who had received the highest (0.6 g/kg) regimen, experienced mission-limiting adverse effects including diarrhea during the trial and moderate nausea that required treatment.
Conclusions
Plasma ketones were elevated in a weight-based fashion and maintained long enough to perform a dive. No mission-limiting side effects were observed at/below 0.5g/kg KDE over 6 hours and no significant electrolyte or metabolic abnormalities were observed. A regimen of 16.2g BHB salts, 10g MCT oil powder, and 0.5g/kg KDE is hypothesized to delay CNSOT and was selected to compare against placebo in a randomized, double-blind, crossover trial of in- water, exercising divers at 2.06 ATA breathing 100% O2.
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