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:
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Higher levels:
| Benzoate | Hippurate | Other bacterial markers | Interpretation |
| 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. |
- Generally, high hippurate is a marker for bacterial overgrowth in the intestines.
- Higher levels indicate GI bacterial overgrowth that can be reduced with natural antibacterial agents and/or high-potency multi-strain probiotics.
- Higher circulating levels of the benzoate metabolite, hippurate, were also associated with higher fruit and whole grains intake. [L]
- Higher baseline intakes of whole grains, coffee and fruit significantly predicted increasing hippurate trends. [L]
- Hippurate in particular was strongly associated to increased gut microbiome diversity and consumption of polyphenol-rich foods including coffee, whole grains and fruit and reduced odds of metbolic syndrome. [L]
Possible treatment options:
Take appropriate steps to ensure favorable gut microflora population to normalize gut permeability. Treatment for can include diet changes, pre- and probiotics, mucosal support, and possibly further testing such as a stool test or immune reactions from food.
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| 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. |
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2-Hydroxyphenylacetic Acid, 3-Hydroxyisovaleric Acid, 3-Hydroxyphenylacetic Acid, 3-Hydroxypropionic Acid, 3-Methyl-4-OH-phenylglycol, 4-Hydroxyphenylacetic Acid, 5-OH-indoleacetic Acid, a-Hydroxyisobutyric Acid (from MTBE), a-Keto-b-Methylvaleric Acid, a-Ketoadipic Acid, a-Ketoglutaric Acid (AKG), a-Ketoisocaproic Acid, a-Ketoisovaleric Acid, a-Ketophenylacetic Acid (from Styrene), Adipic Acid, Arabinose, B-OH-B-Methylglutaric Acid (HMG), Benzoic Acid, Beta-OH-Butyric Acid (BHBA), Cis-Aconitic Acid, Citramalic Acid, Citric Acid, Dihydroxyphenylpropionic Acid (DHPPA), Formiminoglutamic Acid (FIGlu), Glutaric Acid, Hippuric Acid, Homogentisic Acid, Homovanillic Acid, Indoleacetic Acid (IAA), Isocitric Acid, Isovalerylglycine, Kynurenic / Quinolinic Ratio, Kynurenic Acid, Lactic Acid, Malic Acid, Methylmalonic Acid, Orotic Acid, Phenylacetic Acid (PAA), Pyroglutamic Acid, Pyruvic Acid, Quinolinic Acid, Suberic Acid, Succinic Acid, Tartaric Acid, Vanilmandelic Acid, Xanthurenic Acid
