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.
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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.
- Check your serum homocysteine levels. If elevated disruptions in methylation ability or genetic SNPs in the CBS pathway (when homocysteine is broken down to create cysteine) should be explored. If the homocysteine value is low/normal, there is a need to explore the possibility of toxic exposure since the CBS pathway is upregulated. In cases of elevated 2HB and increased ketones or lactic acid (markers 43/44 and 22 on the OAT), also consider further testing regarding blood sugar regulation. At the very least, with this marker elevated, we know there is oxidative damage. Antioxidant support can be added to mitigate the stress as we explore all the possibilities of why it is elevated.
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There are no known clinical associations with low levels of α-hydroxybutyric acid.
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Anthony
Unlimited Plan Member since 2021
I have been using Healthmatters.io since 2021. I travel all over the world and use different doctors and health facilities. This site has allowed me to consolidate all my various test results over 14 years in one place. And every doctor that I show this to has been impressed. Because with any health professional I talk to, I can pull up historical results in seconds. It is invaluable. Even going back to the same doctor, they usually do not have the historical results from their facility in a graph format. That has been very helpful.
Karin
Advanced Plan Member since 2020
What fantastic service and great, easy-to-follow layouts! I love your website; it makes it so helpful to see patterns in my health data. It's truly a pleasure to use. I only wish the NHS was as organized and quick as Healthmatters.io. You've set a new standard for health tracking!
Paul
Healthmatters Pro Member since 2024
As a PRO member and medical practitioner, Healthmatters.io has been an invaluable tool for tracking my clients' data. The layout is intuitive, making it easy to monitor trends and spot patterns over time. The ability to customize reports and charts helps me present information clearly to my clients, improving communication and outcomes. It's streamlined my workflow, saving me time and providing insights at a glance. Highly recommended for any practitioner looking for a comprehensive and user-friendly solution to track patient labs!
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Age 13 and Over), Adipic (Males Under Age 13), Arabinose, Arabinose (Females Under Age 13), Arabinose (Males Age 13 and Over), Arabinose (Males Under Age 13), Ascorbic, Ascorbic (Males Age 13 and Over), Ascorbic (Males Under Age 13), Carboxycitric, Carboxycitric (Males Age 13 and Over), Carboxycitric (Males Under Age 13), Citramalic, Citramalic (Males Age 13 and Over), Citramalic (Males Under Age 13), Citric, Citric (Males Age 13 and Over), Citric (Males Under Age 13), DHPPA (Beneficial Bacteria), DHPPA (Beneficial Bacteria) (Males Age 13 and Over), DHPPA (Beneficial Bacteria) (Males Under Age 13), Dihydroxyphenylacetic (DOPAC), Dihydroxyphenylacetic (DOPAC) (Females Under Age 13), Dihydroxyphenylacetic (DOPAC) (Males Age 13 and Over), Dihydroxyphenylacetic (DOPAC) (Males Under Age 13), Ethylmalonic, Ethylmalonic (Males Age 13 and Over), Ethylmalonic (Males Under Age 13), Fumaric, Fumaric (Males Age 13 and Over), Fumaric (Males Under Age 13), Furan-2,5-dicarboxylic, 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Ratio (Males Age 13 and Over), HVA/ DOPAC Ratio (Males Under Age 13), Kynurenic, Kynurenic (Males Age 13 and Over), Kynurenic (Males Under Age 13), Lactic, Lactic (Males Age 13 and Over), Lactic (Males Under Age 13), Malic, Malic (Males Age 13 and Over), Malic (Males Under Age 13), Malonic, Malonic (Males Age 13 and Over), Malonic (Males Under Age 13), Mandelic, Mandelic (Males Age 13 and Over), Mandelic (Males Under Age 13), Methylcitric, Methylcitric (Males Age 13 and Over), Methylcitric (Males Under Age 13), Methylmalonic, Methylmalonic (Males Age 13 and Over), Methylmalonic (Males Under Age 13), Methylsuccinic, Methylsuccinic (Males Age 13 and Over), Methylsuccinic (Males Under Age 13), N-Acetylaspartic, N-Acetylaspartic (Males Age 13 and Over), N-Acetylaspartic (Males Under Age 13), N-Acetylcysteine (NAC), N-Acetylcysteine (NAC) (Males Age 13 and Over), N-Acetylcysteine (NAC) (Males Under Age 13), Orotic, Orotic (Females Under Age 13), Orotic (Males Age 13 and Over), Orotic (Males Under Age 13), Oxalic, Oxalic (Females Under Age 13), Oxalic (Males Age 13 and Over), Oxalic (Males Under Age 13), Pantothenic (B5), Pantothenic (B5) (Males Age 13 and Over), Pantothenic (B5) (Males Under Age 13), Phenyllactic, Phenyllactic (Males Age 13 and Over), Phenyllactic (Males Under Age 13), Phenylpyruvic, Phenylpyruvic (Males Age 13 and Over), Phenylpyruvic (Males Under Age 13), Phosphoric, Phosphoric (Males Age 13 and Over), Phosphoric (Males Under Age 13), Pyridoxic (B6), Pyridoxic (B6) (Males Age 13 and Over), Pyridoxic (B6) (Males Under Age 13), Pyroglutamic, Pyroglutamic (Males Age 13 and Over), Pyroglutamic (Males Under Age 13), Pyruvic, Pyruvic (Females Under Age 13), Pyruvic (Males Age 13 and Over), Pyruvic (Males Under Age 13), Quinolinic, Quinolinic (Males Age 13 and Over), Quinolinic (Males Under Age 13), Quinolinic / 5-HIAA Ratio, Sebacic, Sebacic (Males Age 13 and Over), Sebacic (Males Under Age 13), Suberic, Suberic (Males Age 13 and Over), Suberic (Males Under Age 13), Succinic, Succinic (Females Under Age 13), Succinic (Males Age 13 and Over), Succinic (Males Under Age 13), Tartaric, Tartaric (Males Age 13 and Over), Tartaric (Males Under Age 13), Thymine, Thymine (Males Age 13 and Over), Thymine (Males Under Age 13), Tricarballylic, Tricarballylic (Females Under Age 13), Tricarballylic (Males Age 13 and Over), Tricarballylic (Males Under Age 13), Uracil, Uracil (Males Age 13 and Over), Uracil (Males Under Age 13), Vanillylmandelic (VMA), Vanillylmandelic (VMA) (Males Age 13 and Over), Vanillylmandelic (VMA) (Males Under Age 13)
