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Ketogenic Approaches in Metabolic Health: Current Evidence, Sex-Informed Insights, and Clinical Prospects

A Special Issue of Nutrients (ISSN 2072-6643) belonging to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: 15 December 2026 | Viewed by 4785

Editors


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Guest Editor
Department of Human Sciences, The Ohio State University, Columbus, OH, USA
Interests: nutritional science; dietetics and nutrition; ketogenic diets; endocrinology; metabolic health; cognitive function

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Guest Editor
NIH Center for Scientific Review, Bethesda, MD, USA
Interests: nutritional neuroscience; ketogenic diets and supplements; cognitive and metabolic health; Alzheimer’s disease

Special Issue Information

Dear Colleagues,

This Special Issue invites original research, reviews, brief reports, and methodological papers that evaluate ketogenic approaches, such as dietary interventions and/or exogenous ketones, on metabolic health across diverse populations. We prioritize studies that incorporate sex as a biological variable and report sex-stratified outcomes where feasible, spanning adolescents to older adults and including pregnancy/postpartum, reproductive transitions, and aging. We welcome mechanistic and clinical investigations on obesity, insulin resistance, type 2 diabetes, NAFLD, dyslipidemia, neuro-metabolic and cardiovascular outcomes, renal and endocrine interfaces, body composition, performance, and quality of life. Submissions leveraging biomarkers and biowearables (e.g., β-HB exposure metrics, CGM coupling, HRV, and sleep) and omics or imaging are encouraged, as are implementation, safety, adherence, and real-world effectiveness studies. Comparative work (ketogenic diet vs. mixed diet, diet vs. exogenous ketones, dose–response relationship) and transparent reporting of energy availability, menstrual/androgen axis measures when applicable, and standardized ketone metrics (AUC, time-in-ketosis) are strongly encouraged. Studies in one sex are welcome with explicit rationale and discussion of generalizability.

Dr. Madison L. Kackley
Dr. Milene L. Brownlow
Guest Editors

Manuscript Submission Information

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Keywords

  • ketogenic diet
  • exogenous ketones
  • metabolic health
  • sex differences
  • life-cycle metabolism
  • insulin resistance
  • neuro-metabolic outcomes
  • biomarkers
  • body composition
  • clinical implementation

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Published Papers (1 paper)

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Research

15 pages, 1789 KB  
Article
Disparate Hepatic Mitochondrial and Inflammatory Effects of Ketone Supplements
by 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, Dallin S. Nevers, Dominic P. D’Agostino, Juan A. Arroyo, R. Ryley Parrish, Paul R. Reynolds and Benjamin T. Bikman
Nutrients 2026, 18(4), 675; https://doi.org/10.3390/nu18040675 - 19 Feb 2026
Cited by 1 | Viewed by 4202
Abstract
Background/Objectives: Beta-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) [...] Read more.
Background/Objectives: Beta-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. Methods: We 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). Results: Acute 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. Conclusions: This 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. Full article
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