a-hydroxybutyric acid (2-hydroxybuturic acid [2-HB]) is a marker that relates to oxidative stress.
a-hydroxybutyric acid is an organic acid produced from a-ketobutyrate via the enzymes lactate dehydrogenase (LDH) or a-hydroxybutyrate dehydrogenase (HBDH).
These enzymes are catalyzed by NADH. Oxidative stress creates an imbalance in NADH/NAD ratios, which leads directly to the production of a-hydroxybutyric acid. Being that a-hydroxybutyric acid’s precursor a-ketobutyrate is a byproduct in the glutathione (GSH) synthesis pathway, an increased demand for GSH may ultimately result in increased a-hydroxybutyric acid.
Increased oxidative stress associated with insulin resistance increases the rate of hepatic glutathione synthesis. Plasma a-hydroxybutyric acid is highly associated with insulin resistance and may be an effective biomarker for prediabetes.
A study on type 2 diabetics showed that GSH infusion restored the NADH/NAD balance and resulted in improvement of insulin sensitivity and beta cell function.
References:
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565252/
- https://pubmed.ncbi.nlm.nih.gov/20526369/
There are no known clinical associations with low levels of a-hydroxybutyric acid.
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Higher circulating levels of a-Hydroxybutyric Acid are associated with insulin resistance and prediabetes.
Elevated a-hydroxybutyric acid may be seen with oxidative stress.
Treatment options:
Evaluate oxidative stress markers such as lipid peroxides and 8-hydroxydeoxyguanosine (8-OHdG) and ensure adequate antioxidant intake and glutathione status. Hard physical exercise can result in lactic acidosis and accumulation of 2-HB.
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