Ketone bodies are produced by the liver from fatty acids under the following conditions:
- low food intake (fasting)
- low carbohydrate diets (ketogenic diet)
- prolonged intense exercise
There are three water soluble ketone bodies:
- beta-hydroxybutyric acid
Figure 1. Ketone bodies (Source)
Ketone bodies are converted to acetyl-CoA in the mitochondria which is then oxidized in the citric acid cycle to produce energy in the form of ATP.
Beta-hydroxybutyrate (Beta-Hydroxybutyric acid)
Beta-Hydroxybutyric acid is synthesized in the liver from acetoacetate. Beta-Hydroxybutyric acid is able to cross the blood-brain-barrier into the central nervous system.
Figure 1. Beta-hydroxybutyric acid molecule
It has been determined that beta-hydroxybutyric acid has clinical relevance in a number of health related matters:
- found to act as a histone deacetylase (HDAC) inhibitor. 1
- found to increase brain-derived neurotrophic factor (BNDF) levels 2
- found to increase TrkB signaling in the hippocampus 3
Beta-Hydroxybutyric acid extends lifespan in C. elegans
A study published in the Journal Aging in August 2014 demonstrated that beta-hydroxybutyric acid (BHB) supplementation extended mean lifespan of the worm C. elegans by approximately 20%. 4
Figure 3. Caenorhabditis elegans nimatode (roundworm); C. elegans has been a model organism for research into ageing
What the researchers of this study discovered was that supplementing with BHB had the same effect as caloric restriction. Caloric restriction has been known to activate longevity genes such as:
The finding of the researchers in this study was that BHB supplementation also activated these longevity gene pathways. 5
In addition to activating these longevity gene pathways, the researchers found that BHB supplementation also had the following effects:
- increased worm thermotolerance
- partially prevented glucose toxicity
- delayed Alzheimer’s amyloid-beta toxicity
- decreased Parkinson’s alpha-synuclein aggregation
The researchers administered the toxic protein amyloid-beta to the nimatode worms and found that they stopped moving only hours after being given the protein. However, when the nimatodes were supplemented with BHB, the time to stop moving took longer.
Alpha-synuclein accumulates in the brains of people suffering from Parkinson’s disease. Researchers in this study found that BHB supplementation inhibited the accumulation of alpha-synuclein in NL5901 nematodes.
The researchers concluded that:
“Beta-HB (BHB) treatment extended lifespan and protected against metabolic, proteotoxic and thermal stress in Caenorhabditis elegans. Our data support the hypothesis that beta-HB is a dietary restriction mimetic and that beta-HB treatment will likely be useful in the treatment of many human aging-associated disorders.”
Beta-hydroxybutyric acid is synthesized in the liver under the conditions of low food intake and/or the consumption of a low carbohydrate diet (ketogenic diet).
However, it is possible to supplement with Beta-hydroxybutyric acid (BHB) which is known as exogenous BHB Ketone salt. Exogenous BHB is beta-hydroxybutyric acid attached to a mineral salt, such as, sodium, potassium, calcium, or magnesium, in order that the body can adequately metabolize the beta-hydroxybutyric acid.