Benzoic acid and hippuric acid are formed from the bacterial metabolism of polyphenols. Urinary benzoic acid may also come from ingestion of food preservatives such as sodium benzoate. Hippuric acid is made when sodium benzoate is conjugated with glycine.
Common Dietary Sources:
Orange juice, elderberry, huckleberry, food preservative, berries, other flavonoids
References:
- Badenhorst CP, Erasmus E, van der Sluis R, Nortje C, van Dijk AA. A new perspective on the importance of glycine conjugation in the metabolism of aromatic acids. Drug Metab Rev. 2014;46(3):343- 361.
- Lees HJ, Swann JR, Wilson ID, Nicholson JK, Holmes E. Hippurate: the natural history of a mammalian-microbial cometabolite. J Proteome Res. 2013;12(4):1527-1546.
- Loo RL, Zou X, Appel LJ, Nicholson JK, Holmes E. Characterization of metabolic responses to healthy diets and association with blood pressure: application to the Optimal Macronutrient Intake Trial for Heart Health (OmniHeart), a randomized controlled study. Am J Clin Nutr. 2018;107(3):323-334.
- Williams HR, Cox IJ, Walker DG, et al. Differences in gut microbial metabolism are responsible for reduced hippurate synthesis in Crohn’s disease. BMC Gastroenterol. 2010;10:108.
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Clinical Associations: Elevated levels of urinary hippuric acid have been associated with several clinical conditions that may be linked to dysbiosis. For example, elevated urinary hippurate was associated with an increase in blood pressure, likely due to the direct effect of gut-microbial products on blood pressure. However, in other studies low hippuric acid excretion has also been attributed to dysbiosis, which supports its use as a biomarker for general microbial alterations.
→ Increased metabolism by imbalanced gut flora may increase levels.
→ Dietary intake of polyphenols or food preservatives can also increase levels of these organic acids.
→ High levels of hippurate may occur if there is high consumption of whole grains or other plant foods (flavonoids, tea, coffee) or if there are higher levels of its precursor benzoate.
→ Liver conversion of benzoate into hippurate usually occurs within 3-4 hours.
→ Hippurate levels may also reflect liver protein metabolism, and hippurate levels may increase on a high protein diet or with amino acid supplementation.
→ Toxic exposures (toluene, benzenes, gasoline) may increase hippurate levels.
→ Hippurate may also increase if type II diabetes is present, or if the patient is highly stressed or anxious.
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Low levels of hippurate may occur if there are nutritional enzyme inhibitions or inherited low-activity enzyme variants present in the synthesis pathway, or if there are low levels of its precursor (plant materials). Hippurate is synthesized in the liver and kidney mitochondria from benzoate on a pathway that requires minerals and glycine. A low hippurate level with a higher benzoate level may indicate a glycine insufficiency or a defect in the glycine deportation system. Low levels of hippurate may also occur if the diet is poor in plant compounds or if there are too few beneficial bacteria in the gut. Comorbid conditions that may be associated with lower hippurate levels include inflammatory bowel disease (IBD) parasites, and obesity. Some toxic chemical exposures (hydrazine, methylene dianiline, galactosamine, chlorophenoxyacetic acid herbicides) may also decrease hippurate levels.
→ Low hippurate with increased benzoate may indicate a glycine deficiency or a defect in the glycine deportation system
- If indicated, consider supporting the glycine deportation system with magnesium, manganese (if deficient), potassium, rubidium and glycine.
- Poor methylation may inhibit serine/glycine interconversion. If indicated, consider checking methylation status.
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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-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
