Oral Ketone Supplementation Acutely Increases Markers of NLRP3 Inflammasome Activation in Human Monocytes
Bibliographic record
Abstract
Recent cell culture studies indicate that the ketone body β‐hydroxybutyrate (β‐OHB) directly inhibits the NLRP3 inflammasome, which plays an important role in regulating inflammation. However, there is limited direct evidence demonstrating this effect in humans. Objectives To determine the effects of acutely raising blood β‐OHB on NLRP3 inflammasome activation in healthy humans. Methods We conducted two randomized double‐blind placebo‐controlled experiments wherein participants' blood β‐OHB levels were directly elevated by ingesting supplements containing ketone salts (0.3 g β‐OHB/kg; Study 1, N = 10 males) or ketone monoesters (0.482 g β‐OHB/kg; Study 2, N = 20, 50% females). Blood samples were obtained in the fasted state and 30‐minutes following ingestion of ketones or placebo. Markers of NLRP3 inflammasome activation included monocyte caspase‐1 (flow cytometry) and interleukin (IL)‐1β secretion (ELISA) in LPS‐stimulated whole blood cultures, and IL1B and NLRP3 mRNA expression (qPCR) from whole blood. Results Blood β‐OHB was significantly raised from baseline following both ketone salt (0.2 ± 0.1 mM to 0.9 ± 0.2 mM; P < 0.001) and ketone monoester (0.2 ± 0.1 mM to 3.2 ± 0.6 mM; P < 0.001) ingestion with no change in placebo. Caspase‐1 activation increased 30 minutes after consuming both ketone salt (condition X time interaction, P = 0.012) and ketone monoester (condition X time interaction, P = 0.016) supplements but not placebo. IL‐1β secretion from stimulated whole blood cultures was increased following ketone monoester consumption (9.1 ± 7.6 pg/mL to 10.9 ± 6.5 pg/mL; main effect of condition, P = 0.024) with no change in placebo. There were no significant effects of ketone supplementation on IL1B and NLRP3 mRNA expression. Conclusions Measures of NLRP3 activation increased when blood β‐OHB was acutely elevated using ketone supplements, suggesting that artificially increasing β‐OHB may have unintended metabolic effects that augment activation of circulating immune cells. Support or Funding Information This study was funded by a Natural Sciences and Engineering Research Council (NSERC) of Canada Discovery Grant (Grant number 435807). JPL is supported by a Canadian Institutes of Health Research (CIHR) New Investigator Salary Award (MSH‐141980) and a Michael Smith Foundation for Health Research (MSFHR) Scholar Award (16890). H.N. was supported by a NSERC Undergraduate Student Research Award. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".