Evidence map›Paper›PMID 41754192›Full record

ArticleNutrients2026

Disparate Hepatic Mitochondrial and Inflammatory Effects of Ketone Supplements.

Tyson J Morris, Madeline D Morris, Andrew J Parker, Jeter R Heggie, Eliza J Roeth, Genevieve Parker, Matthew K Beus, Rachel Ricks, T Luke Shafer, Tyler S Poulos and 6 more

Abstract read
In one paragraph

Article in Nutrients, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Tyson J MorrisDepartment of Hematology and Oncology, Creighton University School of Medicine, Phoenix, AZ 85012, USA.ORCID 0009-0008-1457-591X
Madeline D MorrisDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Andrew J ParkerDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Jeter R HeggieDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Eliza J RoethDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.ORCID 0009-0006-5299-7887
Genevieve ParkerDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Matthew K BeusDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Rachel RicksDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.ORCID 0009-0005-4508-7490
T Luke ShaferDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Tyler S PoulosDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Dallin S NeversDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Dominic P D'AgostinoLaboratory of Metabolic Medicine, Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33612, USA.ORCID 0000-0001-9652-181X
Juan A ArroyoDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.ORCID 0000-0002-8818-8786
R Ryley ParrishDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.ORCID 0000-0001-6798-6140
Paul R ReynoldsDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.ORCID 0000-0002-0931-3025
Benjamin T BikmanDepartment of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

objectivesBeta-hydroxybutyrate (BHB) exists as two enantiomers with potentially distinct biological activities. While D-BHB is the physiological form produced during ketogenesis, L-BHB is present in equal amounts in racemic supplements, yet its biological effects remain poorly understood. Additionally, the ketone precursor 1,3-butanediol (BD) is used in some formulations despite limited safety data.

methodsWe investigated acute (single gavage, 2-h time course) and short-term (daily gavage for 8 days) hepatic effects of D-BHB, L-BHB, and 1,3-butanediol compared to a vehicle control in male C57BL/6 mice. Acute studies assessed hepatic ATP dynamics and lipid peroxidation (MDA) at multiple timepoints. Eight-day protocols evaluated mitochondrial function (oxygen consumption, Complex II activity, SDH activity), lipid accumulation (triglycerides), and inflammatory markers (IL-1β, TNF-α, CRP).

resultsAcute ATP responses differed markedly among treatments. Compared to the baseline and the control, L- and D-BHB elicited significant increases in ATP, while BD caused sustained ATP depletion. Over this same time, oxidative stress markers remained stable in the control and both BHB groups but increased dramatically with BD. After 8 days, the mitochondrial effects of BD were more apparent with a significant reduction in complex II-supported respiration and activity. Both forms of BHB maintained control levels of inflammation and BD showed significant effects on all inflammatory markers. Hepatic triglycerides increased only with BD treatment.

conclusionsThis study reveals striking hepatic effects of various ketone supplements. In contrast to the positive or inert effects of BHB enantiomers, 1,3-butanediol induces significant hepatic stress. These findings have implications for ketone supplement formulation and highlight the therapeutic potential of D- and L-BHB.

Indexed as

3-Hydroxybutyric AcidButylene GlycolsDietary SupplementsInflammationKetonesLiverMitochondria, LiverAdenosine TriphosphateAnimalsLipid PeroxidationMaleMiceMice, Inbred C57BLOxidative StressOxygen Consumption1,3-butylene glycol3-Hydroxybutyric AcidAdenosine TriphosphateButylene GlycolsKetones1,3-butanediolD-beta-hydroxybutyrateenantiomershepatic metabolisminflammationketonesL-beta-hydroxybutyratemitochondrial functionoxidative stress

Identifiers

PMID41754192
PMCPMC12942913

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.