Homovanillic acid (HVA), or 3-methoxy-4- hydroxyphenylacetic acid, is a metabolite of dopamine. Although dopamine is an important brain neurotransmitter, a substantial amount of dopamine is produced in the GI tract.
In neurotransmitter production, dopamine is formed from phenylalanine and tyrosine using several enzymes which require nutrient cofactors such as iron, tetrahydrobiopterin, and pyridoxal phosphate.
Dopamine then becomes norepinephrine using the enzyme dopamine beta-hydroxylase, which requires copper and ascorbic acid for optimal activity.
Dopamine can be metabolized to homovanillic acid using both monoamine oxidase (MAO) and catechol-Omethyltransferase (COMT).
MAO requires a vitamin B2 (FAD) cofactor, while the COMT enzyme requires SAM, magnesium, and vitamin B6.
References:
- Eisenhofer G, Aneman A, Friberg P, et al. Substantial production of dopamine in the human gastrointestinal tract. J Clin Endocrinol Metab. 1997;82(11):3864-3871.
- Schneider G, Kack H, Lindqvist Y. The manifold of vitamin B6 dependent enzymes. Structure. 2000;8(1):R1-6.
- Ash DE, Papadopoulos NJ, Colombo G, Villafranca J. Kinetic and spectroscopic studies of the interaction of copper with dopamine beta-hydroxylase. J Biol Chem. 1984;259(6):3395-3398.
- Ma Z, Liu H, Wu B. Structure-based drug design of catecholO-methyltransferase inhibitors for CNS disorders. Br J Clin Pharmacol. 2014;77(3):410-420.
- Gaweska H, Fitzpatrick PF. Structures and Mechanism of the Monoamine Oxidase Family. Biomol Concepts. 2011;2(5):365-377.
- Weldin J, Jack R, Dugaw K, Kapur RP. Quercetin, an over-thecounter supplement, causes neuroblastoma-like elevation of plasma homovanillic acid. Ped Dev Pathol. 2003;6(6):547-551.
- Combet E, Lean ME, Boyle JG, Crozier A, Davidson DF. Dietary flavonols contribute to false-positive elevation of homovanillic acid, a marker of catecholamine-secreting tumors. Int J Clin Chem. 2011;412(1-2):165-169.
- Nishi M, Miyake H, Takeda T, Takasugi N, Hanai J, Kawai T. Urinary vanillylmandelic acid and homovanillic acid levels in randomlysampled urine for the mass screening of neuroblastoma. Jap J Clin Oncol. 1990;20(3):268-270.
- Barco S, Gennai I, Reggiardo G, et al. Urinary homovanillic and vanillylmandelic acid in the diagnosis of neuroblastoma: report from the Italian Cooperative Group for Neuroblastoma. Clin Biochem. 2014;47(9):848-852.
- Baik J-H. Dopamine Signaling in reward-related behaviors. Front Neural Circ. 2013;7(152).
- Kaluzna-Czaplinska J, Socha E, Rynkowski J. Determination of homovanillic acid and vanillylmandelic acid in urine of autistic children by gas chromatography/mass spectrometry. Int Med J Exp Clin Res. 2010;16(9):Cr445-450.
- De Bellis MD, Lefter L, Trickett PK, Putnam FW. Urinary catecholamine excretion in sexually abused girls. J Am Acad Child Adoles Psych. 1994;33(3):320-327.
- Barthelemy C, Bruneau N, Cottet-Eymard J, et al. Urinary free and conjugated catecholamines and metabolites in autistic children. J Autism Develop Dis. 1988;18(4):583-591.
- Frankenhaeuser M, Lundberg U, Von Wright MR, Von Wright J, Sedvall G. Urinary monoamine metabolites as indices of mental stress in healthy males and females. Pharmacol Biochem Behav. 1986;24(6):1521-1525.
- Lykouras L, Markianos M, Hatzimanolis J, Malliaras D, Stefanis C. Association of biogenic amine metabolites with symptomatology in delusional (psychotic) and nondelusional depressed patients. Progr Neuro-Psychopharmacol Biol Psych. 1995;19(5):877-887.
- Agren H. Life at risk: markers of suicidality in depression. Psychiatr Dev. 1983;1(1):87-103.
- Linnoila M, Karoum F, Potter WZ. Effects of Antidepressant Treatments on Dopamine Turnover in Depressed Patients. Arch Gen Psych. 1983;40(9):1015-1017.
Low levels of urinary HVA imply deficient production of dopamine due to decreased amino acid precursors or lack of vitamin cofactors throughout the production cycle. It may also reflect impaired methylation of dopamine to HVA. Low dopamine turnover and low HVA levels are seen in some mood disorders and as an effect of various antidepressants.
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Elevations of homovanillic acid can be seen with lack of vitamin cofactors for enzymes within the metabolism of dopamine or the production of norepinephrine. Quercetin supplementation can elevate plasma HVA and perhaps urinary excretion.
Dietary flavanols, such as tomatoes, onions, and tea are also known to elevate urinary HVA. Like VMA, urinary HVA is elevated in conditions such as neuroblastoma and neural crest tumors. And, since dopamine regulates emotional and motivational behavior, changes in dopamine levels, and subsequent HVA levels, have been studied in the overall stress response, PTSD, mood disorders, and autism.
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% Omega-3s, % Omega-6s, % Omega-9s, % Saturated Fats, 1-Methylhistidine, 3-Hydroxyisovaleric Acid, 3-Hydroxyphenylacetic Acid, 3-Hydroxypropionic Acid, 3-Methyl-4-OH-phenylglycol, 3-Methylhistidine, 4-Hydroxyphenylacetic Acid, 5-OH-indoleacetic Acid, 8-OHdG (urine), a-Amino-N-butyric Acid, a-Aminoadipic Acid, a-Hydroxybutyric Acid, a-Hydroxyisobutyric Acid (from MTBE), a-Keto-b-Methylvaleric Acid, a-Ketoadipic Acid, a-Ketoglutaric Acid, a-Ketoisocaproic Acid, a-Ketoisovaleric Acid, a-Ketophenylacetic Acid (from Styrene), a-Linolenic (ALA) 18:3 n3, AA / EPA (20:4 n6 / 20:5 n3), Adipic Acid, Alanine, Aluminum, Anserine (dipeptide), Antimony, Arachidic C20:0, Arachidonic (AA) 20:4 n6, Arginine, Arsenic, Asparagine, Aspartic Acid, b-Alanine, b-Aminoisobutyric Acid, b-OH-b-Methylglutaric Acid, b-OH-Butyric Acid, Barium, Behenic C22:0, Benzoic Acid, Bismuth, Cadmium, Calcium, Carnosine (dipeptide), Cesium, Chromium, cis-Aconitic Acid, Citramalic Acid, Citric Acid, Citrulline, Cobalt, Copper, Creatinine, Creatinine Concentration (Amino Acids FMV), Cystathionine, Cysteine, Cystine, D-Arabinitol, Dihomo-g-linolenic (DGLA) 20:3 n6, Dihydroxyphenylpropionic Acid (DHPPA), Docosahexaenoic (DHA) 22:6 n3, Docosapentaenoic (DPA) 22:5 n3, Docosatetraenoic (DTA) 22:4 n6, Eicosadienoic 20:2 n6, Eicosapentaenoic (EPA) 20:5 n3, Elaidic 18:1 n9t, Ethanolamine, Formiminoglutamic Acid (FIGlu), g-Aminobutyric Acid, g-Linolenic (GLA) 18:3 n6, Gadolinium, Gallium, Glutamic Acid, Glutamine, Glutaric Acid, Glyceric Acid, Glycine, Glycolic Acid, Hippuric Acid, Histidine, Homovanillic Acid, Indoleacetic Acid, Iron, Isocitric Acid, Isoleucine, Isovalerylglycine, Kynurenic / Quinolinic Ratio, Kynurenic Acid, Lactic Acid, Lead, Leucine, Lignoceric C24:0, Linoleic (LA) 18:2 n6, Linoleic / DGLA (18:2 n6 / 20:3 n6), Lipid Peroxides (urine), Lithium, Lysine, Magnesium, Malic Acid, Manganese, Margaric C17:0, Mercury, Methionine, Methylmalonic Acid, Molybdenum, Nervonic 24:1 n9, Nickel, Niobium, Oleic 18:1 n9, Omega-3 Index, Omega-6s /Omega-3s, Ornithine, Orotic Acid, Oxalic Acid, Palmitic C16:0, Palmitoleic 16:1 n7, Pentadecanoic C15:0, Phenylacetic Acid, Phenylalanine, Phosphoethanolamine, Phosphoserine, Platinum, Potassium, Proline, Pyroglutamic Acid, Pyruvic Acid, Quinolinic Acid, Rubidium, Sarcosine, Selenium, Serine, Stearic C18:0, Strontium, Suberic Acid, Succinic Acid, Sulfur, Tartaric Acid, Taurine, Thallium, Thorium, Threonine, Tin, Tricosanoic C23:0, Tryptophan, Tungsten, Tyrosine, Uranium, Urea, Urine Creatinine, Vaccenic 18:1 n7, Valine, Vanadium, Vanilmandelic Acid, Xanthurenic Acid, Zinc
