HPHPA stands for 3-(3-hydroxyphenyl)-3-hydroxypropionic acid.
The source of this compound appears to be multiple species of anaerobic bacteria of the Clostridium genus.
The biochemical role of Clostridia in altering brain neurotransmitters is due to the fact that Clostridia metabolites inactivate dopamine beta-hydroxylase, leading to an excess production of brain dopamine and reduced levels of the neurotransmitter norepinephrine. Excess dopamine is associated with abnormal or psychotic behavior. This imbalance can be demonstrated in the Organic Acids Urine Test by observing the ratio of the major dopamine metabolite, homovanillic acid (HVA), to that of the major norepinephrine metabolite, vanillylmandelic acid (VMA) when the Clostridia marker HPHPA is elevated.
The highest value of HPHPA was measured in the urine of a young woman with first onset of schizophrenia. Treatment of Clostridia bacteria resulted in loss of auditory hallucinations. In autism, children with gastrointestinal Clostridia commonly exhibit aggressive behavior, agitation, obsessive compulsive behavior, and irritability. They may have very foul stools with diarrhea with mucus in the stools although some individuals may be constipated. Stool testing for Clostridia is usually of limited usefulness since most Clostridia species are considered probiotics or beneficial. There are about 100 species of Clostridia that are commonly found in the gastrointestinal tract. Only seven of these species are producers of HPHPA including C. sporogenes, C.botulinum, C. caloritolerans, C. angenoti, C. ghoni, C.bifermentans, C. difficile, and C. sordellii while C. tetani,C. sticklandii, C. lituseburense, C. subterminale, C.putifaciens, C. propionicum, C. malenomenatum, C.limosum, C. lentoputrescens, C. tetanomorphum, C.coclearium, C. histolyticum, C. aminovalericum, and C.sporospheroides do not produce compounds that are converted to HPHPA.
References:
- https://www.ncbi.nlm.nih.gov/pubmed/20423563
- https://www.tandfonline.com/doi/abs/10.1179/147683010X12611460763968
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HPHPA elevated values indicate overgrowth of Clostridia in the GI tract including C. sporogenes, C. caloritolerans, and C. botulinum. This metabolite is commonly elevated in GAPS cases (=Gut and Psychology Syndrome). It inhibits the enzyme , leading to neurotransmitter imbalances.
HPHPA causes deactivation of an enzyme called dopamine-beta-hydroxylase so that dopamine cannot be converted to the neurotransmitter neuroepinephrine, and that causes a build-up of dopamine.
The major clinical impact that has been observed in patients with elevated HPHPA (as well as another clostridia bacteria toxin called 4-Cresol), particularly in individuals on the autism-spectrum, is erratic, aggressive and self-injurious behavior. Sometimes these behaviors are so severe the person is heavily medicated in attempts to control the problems. [L]
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2-Hydroxybutyric acid, 2-Hydroxyhippuric acid, 2-Hydroxyisocaproic acid, 2-Hydroxyisovaleric acid, 2-Hydroxyphenylacetic acid, 2-Oxo-4-methiolbutyric acid, 2-Oxoglutaric acid, 2-Oxoisocaproic acid, 2-Oxoisovaleric, 3-Hydroxy-3-methylglutaric, 3-Hydroxybutyric acid, 3-Hydroxyglutaric acid, 3-Indoleacetic acid (IAA), 3-Methyl-2-oxovaleric acid, 3-Methylglutaconic, 3-Methylglutaric acid, 3-Oxoglutaric acid, 4-Cresol, 4-Hydroxybenzoic acid, 4-Hydroxybutyric acid, 4-Hydroxyhippuric acid, 4-Hydroxyphenylacetic acid, 4-Hydroxyphenyllactic acid, 5-Hydroxyindoleacetic acid (5-HIAA), 5-Hydroxymethyl-furoic acid, Acetoacetic acid, Aconitic acid, Adipic acid, Arabinose, Ascorbic acid (Vitamin C), Carboxycitric acid, Citramalic acid, Citric acid, Creatinine, DHPPA (dihydroxyphenylpropionic acid), Dihydroxyphenylacetic acid (DOPAC), Ethylmalonic acid, Fumaric acid, Furan-2,5-dicarboxylic acid, Furancarbonylglycine, GABA, Glutaric acid (Vitamin B2), Glyceric acid, Glycolic acid, Hippuric acid, Homogentisic acid, Homovanillic acid (HVA), HPHPA (3-(3-hydroxyphenyl)-3-hydroxypropionic acid), HVA/DOPAC, HVA/DOPAC Ratio, Kynurenic acid, Lactic acid, Malic acid, Malonic acid, Mandelic acid, Methylcitric acid (Vitamin H), Methylmalonic acid (Vitamin B12), Methylsuccinic acid, N-Acetylaspartic acid, N-Acetylcysteine acid, Orotic acid, Oxalic acid, Pantothenic acid (Vitamin B5), Phenyllactic acid, Phenylpyruvic acid, Phosphoric acid, Pyridoxic acid (Vitamin B6), Pyroglutamic acid, Pyruvic acid, Quinolinic acid, Quinolinic acid/5-HIAA, Sebacic acid, Suberic acid, Succinic acid, Tartaric acid, Thymine, Tricarballyic acid, Uracil
