Hippuric acid

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.

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.