ArticleNutrients2026
Disparate Hepatic Mitochondrial and Inflammatory Effects of Ketone Supplements.
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.
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16 authors.
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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.
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