Hippurate

Sample type: Urine
Optimal result: 17.13 – 768.53 ug/mg creatinine

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.

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.

Microbes resident in the large intestine of the human body help to break down complex aromatic compounds in dietary plant matter (polyphenols), freeing up benzoic acid, which enters the bloodstream. The liver can add the amino acid glycine to benzoic acid to form hippuric acid, which re-enters the blood and is absorbed by the kidneys. As a result, the kidneys excrete hundreds of milligrams of hippuric acid into the urine every day.

Microbes resident in the large intestine of the human body help to break down complex aromatic compounds in dietary plant matter (polyphenols), freeing up benzoic acid, which enters the bloodstream. The liver can add the amino acid glycine to benzoic acid to form hippuric acid, which re-enters the blood and is absorbed by the kidneys. As a result, the kidneys excrete hundreds of milligrams of hippuric acid into the urine every day.

Dietary polyphenols include fruits, vegetables, whole grains, coffee, tea, and nuts. Abnormalities of urinary benzoate and hippurate may reveal detoxification or dysbiosis (=microbial imbalance) issues.

More on intestinal bacteria:

  • By acting on various dietary or endogenous substrates, intestinal bacteria or parasites can generate metabolic products that are absorbed and excreted in urine with or without further modification in the liver and kidney.

  • In health, the intestinal tract contains large amounts of beneficial bacteria that produce some B vitamins and provide stimulus for proper immune function. However, if your stomach acid is not adequate, if you fail to digest protein, or if your diet does not supply sufficient fiber, the resulting overgrowth of unfavorable bacteria can release toxic products that your body must remove. These products include hippurate.

Where is hippurate formed?

  • Hippurate is a glycine conjugate of benzoic acid formed in the mitochondria of the liver and kidneys

  • Bacteria also convert certain food components (polyphenols) into hippurate.

  • Hippurate is also derived from the metabolism of quinic acid and/or shikimic acid.

  • Hippurate is a bacterial product of phenylalanine metabolism.

What are polyphenols?

Polyphenols are micronutrients that we get through certain plant-based foods. They're packed with antioxidants and potential health benefits. It's thought that polyphenols can improve or help treat digestion issues, weight management difficulties, diabetes, neurodegenerative disease, and cardiovascular diseases.

What is benzoate?

Bacterial deamination of the amino acid phenylalanine forms benzoate, which is conjugated with another amino acid, glycine, to form hippurate. Elevated levels of benzoate compared to hippurate can indicate low levels of glycine and pantothenic acid (Vitamin B5). Benzoate can be increased due to dietary intake of certain foods.

Benzoate Hippurate Other bacterial markers Interpretation

Low

Low

No elevations Low intake of benzoate and precursors, plus normal or low dietary polyphenol conversion by intestinal mircrobes
Multiple elevations Low intake of benzoate and precursors with intestinal microbial overgrowth of species that do not metabolize dietary polyhenols (very rare)

High

Low

No elevations Glycine conjugation deficit (possibly genetic polymorphic phenotype if hippurate is very low); dietary benzoate or precursor intake.
Multiple elevations Glycine conjugation deficit; presume benzoate is at least partially from intestinal microbial action on dietary polyphenols.

Low

High

No elevations Normal hippurate production via active glycine conjugation; No indication of microbial overgrowth.
Multiple elevations Normal hippurate production via active glycine conjugation; Presume hippurate is at least partially derived from intestinal microbial action on dietary polyphenols.

High

High

No elevations Very high dietary benzoate or precursor intake with partial conversion to hippurate.
Multiple elevations Very high benzoate load, some, or all, of which is contributed by intestinal microbial action on dietary polyphenols.

Possible treatment options:

Take appropriate steps to ensure favorable gut microflora population to normalize gut permeability. Treatment can include diet changes, pre- and probiotics, mucosal support, and possibly further testing such as a stool test or immune reactions from food.

References:

http://www.altmedrev.com/archive/publications/13/4/292.pdf

Hippurate
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