Beta-Hydroxybutyrate (BHB): Medical Uses and Dosing
Beta-hydroxybutyrate (BHB) is primarily indicated for diagnosis and monitoring of diabetic ketoacidosis (DKA), with emerging applications in cardiac imaging and potential therapeutic uses in various metabolic conditions. While traditional ketone testing methods using nitroprusside reactions fail to detect BHB (the predominant ketone in DKA), specific BHB measurement provides superior clinical utility.
Diagnostic Applications
- BHB is the predominant ketone body in diabetic ketoacidosis (DKA) and specific measurement in blood should be used for diagnosis of DKA and monitoring during treatment 1
- Blood ketone determinations that rely on nitroprusside reaction should NOT be used to monitor DKA treatment as they measure acetoacetate but not BHB 1
- DKA diagnosis requires the presence of hyperglycemia, increased blood ketone bodies (specifically BHB), and acidosis with increased anion gap 1
Monitoring Recommendations
- Individuals prone to ketosis (type 1 diabetes, history of DKA, or those treated with SGLT2 inhibitors) should measure ketones in urine or blood if they have unexplained hyperglycemia or symptoms of ketosis 1
- SGLT2 inhibitors increase DKA risk in type 2 diabetes and even higher risk in off-label use for type 1 diabetes, requiring vigilant ketone monitoring 1
- For blood collection to measure BHB, samples can be collected into heparin, EDTA, fluoride, citrate, or oxalate 1
Specimen Handling
- Whole blood specimens for BHB testing are stable at 4°C for up to 24 hours 1
- Serum/plasma specimens are stable for up to 1 week at room temperature, 2 weeks at 4°C, and at least several weeks at -20°C 1
- Ascorbic acid and acetoacetate may interfere with some BHB assay methods 1
Cardiac Imaging Applications
- BHB is used in myocardial suppression protocols for [18F]FDG PET/CT imaging when evaluating cardiac sarcoidosis and infective endocarditis 1
- Protocols typically include prolonged fasting (≥12 hours) preceded by high fat-low/no carbohydrate diet for 24-48 hours, with or without intravenous heparin administration 1
- BHB serum levels can be used to confirm adequate ketosis following myocardial suppression preparation for cardiac imaging 1
Emerging Therapeutic Applications
Exogenous BHB Supplementation
- Free D-BHB (the biologically active isoform) has been studied as a safe and well-tolerated intervention for inducing sustained exogenous ketosis 2
- BHB acts as both an efficient fuel and signaling molecule that may help circumvent metabolic malfunctions in various diseases 3
- BHB supplementation offers a way to induce nutritional ketosis without requiring strict dietary adherence 4
Safety Profile
- Free D-BHB supplementation has shown minimal side effects, with only 6.2% of administrations resulting in reported symptoms, most commonly mild gastrointestinal discomfort (2.6%), headache (1%), and loss of appetite (1%) 2
- Being bioidentical and salt-free, free D-BHB may have a better safety profile than ketone salts or esters 2
Potential Applications Under Investigation
- BHB has potential applications in neurodegenerative disorders, cardiovascular diseases, cancer, and inflammatory conditions 4
- BHB acts through multiple mechanisms including interactions with cell surface receptors, intracellular enzymes, transcription factors, and epigenetic modifications 5
Important Distinctions
- Do not confuse β-hydroxybutyrate (BHB) with β-hydroxy-β-methylbutyrate (HMB), which is a different compound 6
- HMB is a metabolite of leucine used as a dietary supplement, typically at doses of 3g/day, with limited evidence for improving fat-free mass 1
- HMB has shown inconsistent results in clinical trials for cancer cachexia and has compliance issues with long-term use 1
Cautions and Contraindications
- GHB (gamma-hydroxybutyrate), which sounds similar to BHB, is a controlled substance with sedative effects and has been used as a "date-rape drug" - this is NOT the same as BHB 1
- Optimal dosing regimens for therapeutic BHB supplementation are still being established, with ongoing research needed to determine long-term safety and efficacy 4