Gender-Specific Factors Influencing Plasma β-Hydroxybutyrate Levels in a Population Cohort

Overview

This study analyzed plasma β-hydroxybutyrate (BHB) levels in 6102 individuals from the PREVEND cohort, revealing significant sex-specific determinants. Women exhibited higher BHB levels than men, with hormonal status being the primary factor in women and age in men. Additional factors influencing BHB included protein intake, alcohol use, natriuretic peptide levels, and free thyroxine.

Background

Ketone bodies such as β-hydroxybutyrate serve as alternative energy sources during low-carbohydrate states and have signaling roles that may reduce oxidative stress and inflammation. Ketosis is associated with improved metabolic health and is under investigation for therapeutic potential in various diseases including obesity, diabetes, kidney disease, and neurological disorders. Understanding non-dietary factors influencing ketone body levels is important to optimize ketogenic interventions and interpret variability in clinical studies.

Data Highlights

Key Findings

• Women have significantly higher fasting plasma BHB levels than men.
• In women, hormonal status is the strongest determinant: oral contraceptive use increases BHB by 45%, while postmenopausal status decreases it by 11% compared to premenopausal women without contraceptive use.
• In men, age is the primary determinant, with BHB levels increasing approximately 1% per year.
• Lower protein intake, habitual alcohol consumption, higher N-terminal pro-B-type natriuretic peptide, and elevated free thyroxine levels are associated with higher BHB levels in both sexes.
• The study highlights a complex interplay of metabolic, hormonal, and lifestyle factors influencing BHB concentrations with distinct sex differences.

Clinical Implications

Clinicians should consider sex-specific factors such as hormonal status in women and age in men when interpreting plasma BHB levels or designing ketogenic interventions. Lifestyle factors including protein intake and alcohol use also modulate BHB levels and may be targeted to optimize ketosis. Recognizing these determinants can improve personalization of ketogenic therapies and enhance understanding of metabolic health markers.

Conclusion

Plasma β-hydroxybutyrate levels in the general population are influenced by a multifactorial interplay of hormonal, metabolic, and lifestyle factors with clear sex-specific differences. Tailoring ketogenic strategies by accounting for these determinants may improve clinical outcomes.

References

1. PREVEND Study Group 2024 -- Gender-Specific Factors Influencing Plasma Levels of β-Hydroxybutyrate