Oral Ketone Supplementation Acutely Increases Markers of NLRP3 Inflammasome Activation in Human Monocytes
Bibliographic record
Abstract
SCOPE: Cell culture studies indicate that the ketone β-hydroxybutyrate (β-OHB) directly inhibits the NLRP3 inflammasome, a key regulator of inflammation. However, direct evidence demonstrating this effect in humans is lacking. METHODS AND RESULTS: To determine the effects of acutely raising blood β-OHB in healthy humans, two separate randomized double-blind placebo-controlled experiments are conducted using similar methods but each employed different exogenous ketone supplements. Participants' blood β-OHB is directly elevated by ketone salts (0.3 g β-OHB per kg; Study 1, N = 10 males) or ketone monoester (0.482 g β-OHB per kg; Study 2, N = 18, equal males/females). Markers of NLRP3 inflammasome activation include caspase-1, IL-1β secretion, and IL1B and NLRP3 mRNA in LPS-stimulated whole blood collected at the baseline and 30 minutes following supplementation. Caspase-1 activation increases after ketone salt (Study 1: condition × time interaction, p = 0.012) and monoester supplementation (Study 2: condition × time interaction, p = 0.016) compared to placebo. IL-1β secretion increases (main effect of condition, p = 0.024; Study 2) while IL1B and NLRP3 mRNA remain unchanged. CONCLUSION: Measures of NLRP3 activation increases when blood β-OHB is elevated using ketone supplements, suggesting that increasing β-OHB exogenously may have unintended effects that augment inflammatory activation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".