D-BHB supplementation before moderate-intensity exercise suppresses lipolysis and selectively blunts exercise-induced long-chain acylcarnitine increase in pilot study of patients with long-chain fatty acid oxidation disorders.
Level 2 - randomized trial
Randomized, double-blind crossover pilot trial
PubMed 40048912 · doi:10.1016/j.ymgme.2025.109070
What was done
Five adult patients with long-chain fatty acid oxidation disorders (LC-FAOD; 1 VLCADD, 2 CPT2D, 2 LCHADD; mean age 33 years, 60% male) completed a randomized, double-blind crossover pilot study. Participants completed two moderate-intensity treadmill exercise sessions following oral supplementation with D-beta-hydroxybutyrate (D-BHB) salts or an isocaloric maltodextrin control beverage.
What was found
Oral D-BHB significantly increased post-exercise plasma D-BHB compared to maltodextrin (average concentration 0.43 mM, p < .001). During exercise, free fatty acids (p = .01), fold change in long-chain acylcarnitine species (p <= .03), and systolic blood pressure (p = .02) were significantly lower after D-BHB compared to maltodextrin. No differences between beverages were observed for acetylcarnitine, blood glucose, creatine kinase, VO2, heart rate, rating of perceived exertion, or respiratory exchange ratio. Mild to moderate gastrointestinal symptoms were associated with D-BHB ingestion.
Why it matters
Exogenous D-BHB supplementation safely induces mild ketosis and reduces the accumulation of potentially toxic long-chain acylcarnitines during exercise in LC-FAOD patients, providing mechanistic proof-of-concept for larger dosing trials.
Limits
The sample size is extremely small (n = 5) and aggregates three distinct enzyme deficiencies. The study examined only acute single-dose effects, achieving only mild ketosis without detectable improvements in functional exercise performance or energetic parameters.
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