α-hydroxybutyric acid (2-hydroxybuturic acid [2-HB]) is a marker that relates to oxidative stress. 2-HB is an organic acid produced from α-ketobutyrate via the enzymes lactate dehydrogenase (LDH) or α-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 2-HB. Being that 2-HB’s precursor α-ketobutyrate is a byproduct in the glutathione (GSH) synthesis pathway, an increased demand for GSH may ultimately result in increased 2-HB. Increased oxidative stress associated with insulin resistance increases the rate of hepatic glutathione synthesis. Plasma 2-HB 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.
There are no known clinical associations with low levels of α-hydroxybutyric acid.
All of the conditions associated with increased 2-Hydroxybutyric acid (aka α-Hydroxybutyrate) excretion may be related to increased rates of hepatic glutathione synthesis from methionine. Elevated 2-Hydroxybutyric acid thus shows increased flow through the hepatic glutathione synthesis pathway as required during times of increased oxidative stress or for detoxification functions.
- Smoking, poor diet, and lack of exercise significantly inhibit the activity of AHBD (=Alpha-Hydroxybutyrate dehydrogenase catalyzes oxidation of AHB to acetate), suggesting that urinary elevation of Alpha-Hydroxybutyrate may be related to these factors via increased glutathione demand.
- High 2-Hydroxybutyric acid is also found during phases of increased lymphocyte destruction in infectious diseases such as measles.
- Elevated 2-Hydroxybutyric acid is found in birth asphyxia and in inherited metabolic diseases such as “cerebral” lactic acidosis, glutaric aciduria type II, dihydrolipoyl dehydrogenase deficiency, and propionic acidemia.
- 2-Hydroxybutyric acid is also an early marker for both insulin resistance and impaired glucose regulation that appears to arise due to increased lipid oxidation and oxidative stress.
- Elevated levels of 2-Hydroxybutyric acid in the plasma is a good marker for early-stage type II diabetes.
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2-Hydroxybutyric, 2-Hydroxyhippuric, 2-Hydroxyisocaproic, 2-Hydroxyisovaleric, 2-Hydroxyphenylacetic, 2-Oxo-4-methiolbutyric, 2-Oxoglutaric, 2-Oxoisocaproic, 2-Oxoisovaleric, 3-Hydroxy-3-methylglutaric (HMG), 3-Hydroxybutyric, 3-Hydroxyglutaric, 3-Indoleacetic, 3-Methyl-2-oxovaleric, 3-Methylglutaconic, 3-Methylglutaric, 3-Oxoglutaric, 4-Cresol, 4-Hydroxybenzoic, 4-Hydroxybutyric, 4-Hydroxyhippuric, 4-Hydroxyphenylacetic, 4-Hydroxyphenyllactic, 5-Hydroxyindoleacetic (5-HIAA), 5-Hydroxymethyl-2-furoic, Acetoacetic, Aconitic, Adipic, Arabinose, Ascorbic, Carboxycitric, Citramalic, Citric, DHPPA (Beneficial Bacteria), Dihydroxyphenylacetic (DOPAC), Ethylmalonic, Fumaric, Furan-2,5-dicarboxylic, Furancarbonylglycine, Glutaric, Glyceric, Glycolic, Hippuric, Homogentisic, Homovanillic (HVA), HPHPA, HVA / VMA Ratio, HVA/ DOPAC Ratio, Kynurenic, Lactic, Malic, Malonic, Mandelic, Methylcitric, Methylmalonic, Methylsuccinic, N-Acetylaspartic, N-Acetylcysteine (NAC), Orotic, Oxalic, Pantothenic (B5), Phenyllactic, Phenylpyruvic, Phosphoric, Pyridoxic (B6), Pyroglutamic, Pyruvic, Quinolinic, Quinolinic / 5-HIAA Ratio, Sebacic, Suberic, Succinic, Tartaric, Thymine, Tricarballylic, Uracil, Vanillylmandelic (VMA)
