Clinical Scorecard: Gender-Specific Factors Influencing Plasma Levels of β-Hydroxybutyrate in a General Population Cohort
At a Glance
Category
Detail
Condition
Plasma β-hydroxybutyrate (BHB) levels as a marker of ketosis
Key Mechanisms
Ketone bodies produced in liver; BHB acts as energy source and signaling molecule affecting oxidative stress, inflammation, and fibrosis
Target Population
General adult population aged 28-75 years without insulin-dependent diabetes
Care Setting
Population-based cohort study setting; relevant for metabolic, cardiology, nephrology, neurology, and oncology clinical research
Key Highlights
Women have significantly higher plasma BHB levels than men; hormonal status is the main determinant in women
In men, age is the primary determinant of BHB levels, increasing approximately 1% per year
Other factors associated with higher BHB in both sexes include lower protein intake, habitual alcohol use, higher NT-proBNP, and higher free thyroxine levels
Guideline-Based Recommendations
Diagnosis
Measure fasting plasma BHB using nuclear magnetic resonance spectroscopy for accurate ketone body quantification
Management
Consider sex-specific factors such as hormonal status in women (e.g., oral contraceptive use increases BHB; postmenopausal status decreases BHB)
Account for age-related increases in BHB in men when interpreting levels
Lifestyle factors including protein intake and alcohol use may modulate BHB levels and could be targeted in interventions
Monitoring & Follow-up
Monitor BHB levels in fasting state to assess ketosis status accurately
Adjust interpretation of BHB levels based on sex, hormonal status, age, and metabolic biomarkers
Risks
Nonfasting state or elevated insulin (>25 mIU/L) can confound BHB measurements and should be excluded
Patient & Prescribing Data
Predominantly healthy adults from a general population cohort
Oral contraceptive use in women is associated with a 45% increase in BHB levels; postmenopausal status decreases BHB by 11%; age increases BHB in men by 1% per year
Clinical Best Practices
Use fasting plasma samples and validated NMR spectroscopy for BHB measurement
Incorporate sex-specific hormonal status and age when evaluating ketone body levels
Consider lifestyle factors such as protein intake and alcohol consumption as modulators of BHB
Exclude participants with nonfasting status or high insulin to avoid confounding BHB results
Tailor ketogenic interventions considering distinct determinants of BHB in men and women
by Martine G E Knol, Amarens van der Vaart, Lyanne Kieneker, Margery A Connelly, Stephan J L Bakker, Roman-Ulrich Müller, Markus M Rinschen, Ron T Gansevoort, Maatje D A van Gastel
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