Ketone Body Salts
Also known as: Ketone body salts, Exogenous ketone salts, Ketone salt supplements, βHB salts, beta-hydroxybutyrate salts
Overview
Ketone body salts are synthetic supplements designed to acutely elevate blood levels of β-hydroxybutyrate (βHB), the primary ketone body, by binding it to mineral salts like sodium, potassium, calcium, or magnesium. Unlike naturally occurring ketones produced during endogenous ketosis, these are consumed externally. They are primarily used to mimic a state of ketosis, with purported benefits for enhancing physical performance, cognitive function, and metabolic health. Ketone salts are orally bioavailable and typically raise circulating ketone concentrations modestly, usually below 1 mmol/L, which is lower than the levels achieved with ketone esters. Research into their efficacy is an emerging field, with a growing body of evidence from randomized controlled trials and systematic reviews, though results are often mixed and heterogeneous.
Benefits
Ketone salt supplementation reliably increases blood βHB concentrations, typically ranging from 0.88 to 1.03 mmol/L. However, this modest increase has not consistently translated into improved physical exercise performance in healthy, non-endurance trained individuals, with systematic reviews showing mixed effects (3 positive, 10 null, 3 negative outcomes across 16 performance metrics). The increases in blood ketones are often insufficient to significantly shift energy metabolism during exercise. Preclinical models suggest potential neuroprotective and cognitive benefits, including the inhibition of inflammatory pathways (NLRP3 inflammasome) and reduction of amyloid-β plaques in Alzheimer's disease mouse models. While ketone esters show some evidence for improved neuronal energetic efficiency, it is unclear if ketone salts offer similar benefits. Most studies focus on healthy adults, with limited data on clinical populations. Benefits are acute and transient, with chronic effects less studied.
How it works
Ketone body salts deliver β-hydroxybutyrate (βHB) directly into the bloodstream. Once absorbed, βHB serves as an alternative fuel source for mitochondria, particularly in the brain and muscle tissues. Beyond its role as a fuel, βHB also acts as a signaling molecule, influencing various biological pathways. It is known to modulate energy metabolism, reduce inflammation by inhibiting pathways such as the NLRP3 inflammasome, and potentially impact cognitive function. βHB can also affect histone deacetylases, further contributing to its signaling properties. Oral ketone salts are absorbed and increase plasma βHB concentrations, though their bioavailability is generally lower compared to ketone esters, resulting in more modest increases in blood ketone levels.
Side effects
Ketone body salts are generally considered safe for healthy adults at recommended doses. The most common side effects, reported in some individuals, are gastrointestinal discomfort, including nausea and diarrhea. These symptoms are often dose-dependent and can be mitigated by starting with lower doses or consuming with food. Uncommon side effects may include electrolyte imbalances due to the significant mineral load (sodium, potassium, calcium, magnesium) associated with these supplements. Individuals with pre-existing kidney disease or electrolyte disorders should exercise caution and consult a healthcare professional before use, as the added mineral load could exacerbate their conditions. No serious adverse events have been reported in randomized controlled trials. There are no well-documented drug interactions, but caution is advised for individuals on medications that affect mineral balance. Limited data exist for special populations such as pregnant women, children, or those with specific clinical conditions, and use in these groups is not recommended without medical supervision.
Dosage
Dosage for ketone body salts varies, with studies often employing 0.5 to 0.75 grams per kilogram of body weight to achieve blood βHB levels of approximately 0.8-1.0 mmol/L. Optimal dosage ranges typically fall between 10-25 grams per single dose. The maximum safe dose is not well-defined, as higher doses can increase the risk of gastrointestinal side effects and potential electrolyte disturbances. For acute effects, ketone salts are commonly taken 30-60 minutes before exercise or cognitive tasks. The specific mineral content (sodium, potassium, calcium, magnesium) of the ketone salt product should be considered, especially for individuals monitoring mineral intake. Co-ingestion with food may slow the absorption rate. No specific cofactors are required for their efficacy.
FAQs
Do ketone salts improve athletic performance?
Current high-quality evidence does not consistently support performance enhancement in healthy, non-endurance trained individuals, with mixed results across studies.
Are ketone salts safe for daily use?
Generally safe at studied doses, but long-term safety data are limited. Gastrointestinal issues and potential electrolyte imbalances are possible with high or frequent doses.
How quickly do ketone salts raise blood ketones?
Peak blood βHB concentrations typically occur within 30-60 minutes after ingestion, providing a transient increase in ketone levels.
Can ketone salts replace ketogenic diets?
No, ketone salts provide only transient ketosis and do not induce the metabolic adaptations or sustained ketone levels achieved through a strict ketogenic diet.
Are ketone salts better than ketone esters?
Ketone esters generally raise ketone levels more substantially. Ketone salts produce lower ketone levels but may be more palatable and cost-effective than esters.
Research Sources
- https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.663206/full – This high-quality randomized controlled trial and systematic review found that ketone salts raised blood βHB levels (approx. 0.88 mmol/L) in healthy, non-endurance trained adults. However, this increase did not translate into improved exercise time trial performance, nor did it significantly alter glucose or lactate levels during exercise.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7442417/ – This systematic review analyzed 16 randomized controlled trials on ketone body salts and physical performance. It reported mixed effects, with 3 studies showing positive outcomes, 10 showing null effects, and 3 showing negative effects, highlighting significant heterogeneity and limiting clear conclusions on performance enhancement.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC10337131/ – This meta-regression of βHB infusion studies, including both clinical and healthy subjects, identified a strong dose-response relationship between infused βHB and blood βHB levels. While primarily focused on infusions rather than oral salts, it provides valuable insights into the pharmacokinetics and dosing principles of βHB.
- https://www.nature.com/articles/s44324-024-00029-y – This high-quality review synthesized preclinical and clinical data, linking ketone bodies to improved cognitive and cardiometabolic outcomes. It highlighted that ketone salts can inhibit inflammatory pathways, such as the NLRP3 inflammasome, in preclinical models, suggesting potential neuroprotective benefits, though human data are still limited.