4-Hydroxyphenylacetic

Optimal Result: 1 - 27 mmol/mol creatinine.

3-Hydroxyphenylacetic acid and 4-hydroxyphenylacetic acid are produced by the bacterial fermentation of amino acids, much like Indoleacetic acid (IAA).

Common Dietary Sources:

Wine/grapes, cranberries, green/black tea, berries, orange juice, grape seed extract

References:

- Mora Brugues J, Gonzalez Sastre F. Influence of intestinal flora on the elimination of phenylacetic acid in urine. Clin Chem. 1986;32(1 Pt 1):223.

- Russell WR, Duncan SH, Scobbie L, et al. Major phenylpropanoidderived metabolites in the human gut can arise from microbial fermentation of protein. Mol Nutr Food Res. 2013;57(3):523-535.

- Sabelli H, Fawcett J, Gusovsky F, Edwards J, Jeffriess H, Javaid J. Phenylacetic acid as an indicator in bipolar affective disorders. J Clin Psychopharmacol. 1983;3(4):268-270.

- Sabelli HC, Fawcett J, Gusovsky F, et al. Clinical studies on the phenylethylamine hypothesis of affective disorder: urine and blood phenylacetic acid and phenylalanine dietary supplements. J Clin Psych. 1986;47(2):66-70.

- Sabelli HC, Javaid JI, Fawcett J, Kravitz HM, Wynn P. Urinary phenylacetic acid in panic disorder with and without depression. Acta Psych Scand. 1990;82(1):14-16.

- Henning SM, Wang P, Abgaryan N, et al. Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer. Mol Nutr Food Res. 2013;57(3):483-493.

- Jacobs DM, Fuhrmann JC, van Dorsten FA, et al. Impact of ShortTerm Intake of Red Wine and Grape Polyphenol Extract on the Human Metabolome. J Agr Food Chem. 2012;60(12):3078-3085.

- Zamora-Ros R, Achaintre D, Rothwell JA, et al. Urinary excretions of 34 dietary polyphenols and their associations with lifestyle factors in the EPIC cohort study. Sci Rep. 2016;6:26905-26905.

- Ward NC, Croft KD, Puddey IB, Hodgson JM. Supplementation with grape seed polyphenols results in increased urinary excretion of 3-hydroxyphenylpropionic Acid, an important metabolite of proanthocyanidins in humans. J Agric Food Chem. 2004;52(17):5545-5549.

- Amic A, Markovic Z, Markovic JMD, Jeremic S, Lucic B, Amic D. Free radical scavenging and COX-2 inhibition by simple colon metabolites of polyphenols: A theoretical approach. Comput Biol Chem. 2016;65:45-53.

- Manach C, Williamson G, Morand C, Scalbert A, Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr. 2005;81(1 Suppl):230s-242s.

- Selma MV, Espin JC, Tomas-Barberan FA. Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem. 2009;57(15):6485-6501.

What does it mean if your 4-Hydroxyphenylacetic result is too high?

Increased urinary para-hydroxyphenylacetate with:

  • Amphetamine use
  • Diet
    • High protein diet or amino acid supplementation
    • Diet high in plant materials
  • Gastrointestinal disorders

    • Dysbiosis

    • Gastric cancer

    • Giardia lamblia infection

    • Increased permeability

    • Lactose intolerance

    • Malabsorption (Celiac, IBD, etc.)

    • Short bowel syndrome

  • Plant flavonoid consumption

  • Parkinson’s disease

  • Inborn errors of metabolism

    • These disorders are usually diagnosed in infancy

      • PKU, tyrosinemia, hawkinsinuria, etc.

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Elevated levels of para-hydroxyphenylacetate may occur if there is a vitamin B2 deficiency or if the person is on a high-protein diet or a diet high in plant materials.

High levels may also occur if there is a large amount of undigested or poorly digested food left in the gastrointestinal tract for bacteria to ferment. The use of amino acid supplements (phenylalanine, tyrosine, tryptophan) may also increase para-hydroxyphenylacetate levels.

→ A chronic vitamin B2 deficiency may also increase levels of alpha-ketoglutarate, methylsuccinate, keto acids (alpha-ketoisovalerate, alpha-ketoisocaproate, alpha-keto-beta- methylvalerate, beta-hydroxyisovalerate), kyurenate, methylmalonate, and lower levels of cis-aconitate, isocitrate, succinate, fumarate, adipate, suberate, ethylmalonate, vanilmandelate, homovanillate, 5-hydroxyindoleacetate, and orotate.

→ Consider a stool test to evaluate the gut microbiome, digestion, and absorption.

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