Benzoate
Benzoate, was one of the compounds first found to be elevated in urine from patients with intestinal bacterial overgrowth of various origins. Many people with intestinal bacterial overgrowth resulting from cystic fibrosis, unclassified enteritis, celiac disease, or short bowel syndrome have elevated benzoate along with varying degrees of elevated phenylacetate, p-hydroxybenzoate, and p-hydroxyphenylacetate.
Benzoic acid, a common food component used as a preservative in packaged foods such as pickles and lunch meats, also occurs naturally in cranberries and other fruits, a factor to take into account when interpreting elevated hippurate levels in urine. Whether the source is dietary intake or jejunal bacterial metabolism, benzoate should be rapidly converted to hippurate by conjugation with glycine.
What is Hippurate?
Hippurate is produced by the conjugation of Benzoate and glycine, found as a normal component in urine as a metabolite of aromatic compounds from food. Increased urine hippuric acid content may have antibacterial effects.
What is Glycine?
Glycine is an amino acid serving several important purposes within the body, including:
- Detoxification,
- DNA formation,
- The synthesis of hemoglobin,
- and as a part of brain neurotransmission pathways.
- In the liver, glycine helps to convert many potentially harmful substances, including toxic materials such as benzoic acid (benzoate) into harmless forms.
References:
– van der Heiden C, Wauters EA, Duran M, et al. Gas chromatographic analysis of urinary
tyrosine and phenylalanine metabolites in patients with gastrointestinal disorders. Clin Chim Acta, 1971;34:289-296.
– Temellini A, Mogavero S, Giulianotti PC, et al. Conjugation of benzoic acid with glycine in human liver and kidney: a study on the interindividual variability. Xenobiotica 1993;23:1427-1433.
What does it mean if your Benzoate result is too high?
High levels of benzoate may occur if there are inherited low-activity enzyme variations on its breakdown pathway or if there are high levels of substrate for conversion into benzoate. Benzoate occurs naturally in plant foods and is a common preservative in foods, cosmetics, and medications. Bacteria in the gut microbiome can convert plant flavonoids and some amino acids (tyrosine, phenylalanine, tryptophan) into benzoate or its precursors, which are then transported across the gut barrier into circulation. The precursors are converted into benzoate via the beta-oxidation pathway in the liver and liver conversion of benzoate into hippurate usually occurs within 3-4 hours. Liver disorders or inherited problems in the beta-oxidation pathway may increase benzoate and decrease hippurate levels. The conversion of benzoate into hippurate requires glycine; low glycine levels may also increase benzoate levels. Exposure to the toxic metal cadmium may also increase benzoate levels. Other toxicants that may increase benzoate levels include ethylene glycol, toluene, and ammonia.
- High levels of tyrosine in the gut can also increase para-hydroxyphenyllactate, para-hydroxybenzoate, and para-hydroxyphenylacetate. High levels of phenylalanine may also increase 2-hydroxyphenylacetate.
- Low hippurate with increased benzoate may indicate a liver disorder, 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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What does it mean if your Benzoate result is too low?
Low levels of benzoate 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 precursors available. The avoidance of benzoate preservatives found in processed foods, cosmetics, and medications may decrease benzoate levels. Liver conversion of benzoate into hippurate usually occurs within 3-4 hours. Plant compounds are converted into benzoate via the beta-oxidation pathway in the liver. A diet poor in plant materials or an inhibition of the beta-oxidation pathway can decrease benzoate levels.
- Review diet for fruit and vegetable intake.
- Beta-oxidation defects will increase levels of adipate and suberate and may decrease levels of citrate or succinate. If indicated, consider supporting fatty oxidation with: L-carnitine, Vitamins B2, B3, B5 CoQ10 (ubiquinone), magnesium, and molybdenum, Omega-3 fatty acids to support mitochondrial membranes, Resveratrol and sulforaphane may upregulate fatty oxidation pathways.
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