Component

D-(R)-beta-hydroxybutyrate

Context-specific entity; species, compartment and exposure are stated on each claim.

11 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. BDH1 interconverts D-beta-hydroxybutyrate and acetoacetate using the NAD+/NADH redox pair.

    D-(R)-beta-hydroxybutyrate → Acetoacetate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Reactome curated reaction and its primary-study attribution
    experimental_model
    Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work.
    limitations
    Reversible reaction; redox state and compartment determine net direction.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    Ketone interconversion connects to niacin-derived redox chemistry.
    primary_references
    BDH1: D-beta-hydroxybutyrate + NAD+ ⇌ acetoacetate + NADH + H+ · 2003 · https://reactome.org/content/detail/R-HSA-73920

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 128–134

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work. · source_derived_draft · unverified_draft

    ## fast-bdh-reaction Ketone interconversion connects to niacin-derived redox chemistry. BDH1 interconverts D-beta-hydroxybutyrate and acetoacetate using the NAD+/NADH redox pair. Model: Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work. Limitations: Reversible reaction; redox state and compartment determine net direction. Evidence access: Reactome curated reaction and its primary-study attribution BDH1: D-beta-hydroxybutyrate + NAD+ ⇌ acetoacetate + NADH + H+ · 2003 · https://reactome.org/content/detail/R-HSA-73920
    Complete structured claim and evidence

  2. BHB reduced ASC oligomerization and speck formation.

    D-(R)-beta-hydroxybutyrate → ASC oligomerization and speck formation source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    NLRP3 activation models.
    limitations
    Effect did not require HCAR2, AMPK, autophagy or ketone oxidation.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    The inflammatory complex assembled less effectively.
    primary_references
    The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 376–382

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · NLRP3 activation models. · source_derived_draft · unverified_draft

    ## fast-bhb-asc The inflammatory complex assembled less effectively. BHB reduced ASC oligomerization and speck formation. Model: NLRP3 activation models. Limitations: Effect did not require HCAR2, AMPK, autophagy or ketone oxidation. Evidence access: Primary abstract The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804
    Complete structured claim and evidence

  3. BHB reduced NLRP3-mediated IL-1beta and IL-18 production in human monocytes.

    D-(R)-beta-hydroxybutyrate → Human monocyte IL-1beta and IL-18 production source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human monocyte experiments.
    limitations
    Not universal anti-inflammatory activity or a clinical fasting outcome.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    The cellular signal changed selected cytokine outputs.
    primary_references
    The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 384–390

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human monocyte experiments. · source_derived_draft · unverified_draft

    ## fast-bhb-cytokines The cellular signal changed selected cytokine outputs. BHB reduced NLRP3-mediated IL-1beta and IL-18 production in human monocytes. Model: Human monocyte experiments. Limitations: Not universal anti-inflammatory activity or a clinical fasting outcome. Evidence access: Primary abstract The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804
    Complete structured claim and evidence

  4. D-beta-hydroxybutyrate activated human HM74a/HCAR2 and its mouse orthologue.

    D-(R)-beta-hydroxybutyrate → Human hydroxycarboxylic acid receptor 2 / HCAR2 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human and mouse receptor pharmacology.
    limitations
    Shared receptor does not imply identical exposures or clinical effects.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    A fasting-associated ketone uses a receptor also used by nicotinic acid.
    primary_references
    (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 352–358

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human and mouse receptor pharmacology. · source_derived_draft · unverified_draft

    ## fast-bhb-hcar2 A fasting-associated ketone uses a receptor also used by nicotinic acid. D-beta-hydroxybutyrate activated human HM74a/HCAR2 and its mouse orthologue. Model: Human and mouse receptor pharmacology. Limitations: Shared receptor does not imply identical exposures or clinical effects. Evidence access: Primary abstract (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200
    Complete structured claim and evidence

  5. R-beta-hydroxybutyrate increased histone beta-hydroxybutyrylation despite absent detectable HDAC inhibition.

    D-(R)-beta-hydroxybutyrate → Histone lysine beta-hydroxybutyrylation source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Cultured-cell comparison with butyrate.
    limitations
    Beta-hydroxybutyrylation and acetylation are different modifications.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    A distinct histone modification can occur without proving the proposed HDAC route.
    primary_references
    Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30679586/ · DOI 10.1038/s41598-018-36941-9

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 408–414

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cultured-cell comparison with butyrate. · source_derived_draft · unverified_draft

    ## fast-bhb-histone-mark A distinct histone modification can occur without proving the proposed HDAC route. R-beta-hydroxybutyrate increased histone beta-hydroxybutyrylation despite absent detectable HDAC inhibition. Model: Cultured-cell comparison with butyrate. Limitations: Beta-hydroxybutyrylation and acetylation are different modifications. Evidence access: Primary abstract Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30679586/ · DOI 10.1038/s41598-018-36941-9
    Complete structured claim and evidence

  6. D-beta-hydroxybutyrate inhibited mouse adipocyte lipolysis in an Hcar2-dependent manner.

    D-(R)-beta-hydroxybutyrate → Mouse adipocyte lipolysis source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse adipocyte experiments.
    limitations
    Whole-body ketone feedback was proposed; magnitude in human fasting was not established.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    A ketone could feed back on its upstream fuel supply.
    primary_references
    (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 360–366

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse adipocyte experiments. · source_derived_draft · unverified_draft

    ## fast-bhb-lipolysis-feedback A ketone could feed back on its upstream fuel supply. D-beta-hydroxybutyrate inhibited mouse adipocyte lipolysis in an Hcar2-dependent manner. Model: Mouse adipocyte experiments. Limitations: Whole-body ketone feedback was proposed; magnitude in human fasting was not established. Evidence access: Primary abstract (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200
    Complete structured claim and evidence

  7. BHB prevented potassium efflux in the tested NLRP3 activation experiments.

    D-(R)-beta-hydroxybutyrate → Macrophage potassium efflux source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Stimulated innate immune cells; both BHB enantiomers were active.
    limitations
    Not evidence that BHB corrects systemic potassium deficiency.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    A ketone altered an ion movement involved in inflammatory signaling.
    primary_references
    The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 368–374

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Stimulated innate immune cells; both BHB enantiomers were active. · source_derived_draft · unverified_draft

    ## fast-bhb-potassium A ketone altered an ion movement involved in inflammatory signaling. BHB prevented potassium efflux in the tested NLRP3 activation experiments. Model: Stimulated innate immune cells; both BHB enantiomers were active. Limitations: Not evidence that BHB corrects systemic potassium deficiency. Evidence access: Primary abstract The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804
    Complete structured claim and evidence

  8. The later study detected no HDAC inhibition with 10 mM sodium R-BHB in its nuclear-extract assay; multiple cell models lacked histone hyperacetylation up to 40 mM.

    D-(R)-beta-hydroxybutyrate → Class I histone deacetylase activity source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract and indexed full-text Figure 2/Discussion, PMC6346118
    experimental_model
    Nuclear-extract assay and HEK293, HMEC-1, rat and human myotube experiments.
    limitations
    Different preparations/readouts may matter; the discrepancy is unresolved. Concentrations are experimental, not target blood levels.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    Another study did not reproduce the proposed direct effect.
    primary_references
    Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30679586/ · DOI 10.1038/s41598-018-36941-9

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 400–406

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Nuclear-extract assay and HEK293, HMEC-1, rat and human myotube experiments. · source_derived_draft · unverified_draft

    ## fast-hdac-negative Another study did not reproduce the proposed direct effect. The later study detected no HDAC inhibition with 10 mM sodium R-BHB in its nuclear-extract assay; multiple cell models lacked histone hyperacetylation up to 40 mM. Model: Nuclear-extract assay and HEK293, HMEC-1, rat and human myotube experiments. Limitations: Different preparations/readouts may matter; the discrepancy is unresolved. Concentrations are experimental, not target blood levels. Evidence access: Primary abstract and indexed full-text Figure 2/Discussion, PMC6346118 Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30679586/ · DOI 10.1038/s41598-018-36941-9
    Complete structured claim and evidence

  9. The study reported direct class-I HDAC inhibition by D-beta-hydroxybutyrate, alongside increased histone acetylation in mouse tissues.

    D-(R)-beta-hydroxybutyrate → Class I histone deacetylase activity source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Biochemical/cellular experiments; mouse fasting, calorie restriction or exogenous BHB.
    limitations
    Later direct testing challenged HDAC inhibition; see the linked research disagreement.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    One study proposed a direct route from ketones to gene regulation.
    primary_references
    Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23223453/ · DOI 10.1126/science.1227166

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 392–398

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Biochemical/cellular experiments; mouse fasting, calorie restriction or exogenous BHB. · source_derived_draft · unverified_draft

    ## fast-hdac-positive One study proposed a direct route from ketones to gene regulation. The study reported direct class-I HDAC inhibition by D-beta-hydroxybutyrate, alongside increased histone acetylation in mouse tissues. Model: Biochemical/cellular experiments; mouse fasting, calorie restriction or exogenous BHB. Limitations: Later direct testing challenged HDAC inhibition; see the linked research disagreement. Evidence access: Primary abstract Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23223453/ · DOI 10.1126/science.1227166
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Human-heart mitochondrial BDH1 was described as specifically requiring phosphatidylcholine for enzymic activity.

    Phosphatidylcholine → Human mitochondrial D-beta-hydroxybutyrate dehydrogenase / BDH1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Primary human-heart enzyme cloning and characterization.
    limitations
    Does not establish that supplemental choline increases ketone use.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    A membrane lipid linked to choline supports a ketone enzyme.
    primary_references
    Molecular cloning and characterization of (R)-3-hydroxybutyrate dehydrogenase from human heart. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1639787/

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 136–142

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Primary human-heart enzyme cloning and characterization. · source_derived_draft · unverified_draft

    ## fast-bdh-choline A membrane lipid linked to choline supports a ketone enzyme. Human-heart mitochondrial BDH1 was described as specifically requiring phosphatidylcholine for enzymic activity. Model: Primary human-heart enzyme cloning and characterization. Limitations: Does not establish that supplemental choline increases ketone use. Evidence access: Primary abstract Molecular cloning and characterization of (R)-3-hydroxybutyrate dehydrogenase from human heart. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1639787/
    Complete structured claim and evidence

  2. Beta-hydroxybutyrate and acetoacetate became predominant cerebral fuels after prolonged starvation.

    Fasting / abstention from energy intake → Cerebral ketone-body utilization source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Three obese patients; cerebral catheterization after 5–6 weeks of starvation.
    limitations
    This prolonged, small historical study does not establish a 16-hour switch.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    The brain can use ketones while retaining a glucose requirement.
    primary_references
    Brain metabolism during fasting. · 1967 · https://pubmed.ncbi.nlm.nih.gov/6061736/ · DOI 10.1172/JCI105650

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 88–94

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Three obese patients; cerebral catheterization after 5–6 weeks of starvation. · source_derived_draft · unverified_draft

    ## fast-brain-ketones The brain can use ketones while retaining a glucose requirement. Beta-hydroxybutyrate and acetoacetate became predominant cerebral fuels after prolonged starvation. Model: Three obese patients; cerebral catheterization after 5–6 weeks of starvation. Limitations: This prolonged, small historical study does not establish a 16-hour switch. Evidence access: Primary abstract Brain metabolism during fasting. · 1967 · https://pubmed.ncbi.nlm.nih.gov/6061736/ · DOI 10.1172/JCI105650
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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