Para-Hydroxyphenylacetate
Para-hydroxyphenylacetate, often referred to as P-Hydroxyphenylacetate or PARA, is a diagnostic tool used in functional medicine and clinical assessments. PARA is a key intermediate in the degradation pathway of the amino acid tyrosine and is produced during the breakdown of tyrosine in the body. Elevated levels of PARA on the panel can provide valuable insights into various metabolic and enzymatic processes. An abnormal PARA level can be indicative of issues related to tyrosine metabolism, such as deficiencies in enzymes like phenylalanine hydroxylase or tyrosine aminotransferase. It can also suggest disruptions in gut microbiota, as some bacteria produce PARA as a metabolic byproduct.
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What does it mean if your Para-Hydroxyphenylacetate result is too high?
Elevated urinary para-hydroxyphenylacetate with:
1. Amphetamine use
2. Diet
- High protein diet or amino acid supplementation
- Diet high in plant materials
3. Gastrointestinal disorders
- Dysbiosis
- Gastric cancer
- Giardia lamblia infection
- Increased permeability
- Lactose intolerance
- Malabsorption (Celiac, IBD, etc.)
- Short bowel syndrome
4. Plant flavonoid consumption
5. Parkinson’s disease
6. Inborn errors of metabolism
- These disorders are usually diagnosed in infancy (PKU, tyrosinemia, hawkinsinuria, etc.)
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Elevated levels of para-hydroxyphenylacetate may occur if there is a vitamin B2 deficiency or if the patient is on a high-protein diet or a diet high in plant materials. High levels may also occur if there is a large amount of undigested or poorly digested food left in the gastrointestinal tract for bacteria to ferment.
The use of amino acid supplements (phenylalanine, tyrosine, tryptophan) may also increase para-hydroxyphenylacetate levels.
- A chronic vitamin B2 deficiency may also increase levels of alpha-ketoglutarate, methylsuccinate, keto acids (alpha-ketoisovalerate, alpha-ketoisocaproate, alpha-keto-beta-methylvalerate, beta-hydroxyisovalerate), kyurenate, methylmalonate, and lower levels of cis-aconitate, isocitrate, succinate, fumarate, adipate, suberate, ethylmalonate, vanilmandelate, homovanillate, 5-hydroxyindoleacetate, and orotate.
- Consider a stool test to evaluate the gut microbiome, digestion, and absorption.
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What does it mean if your Para-Hydroxyphenylacetate result is too low?
Decreased urinary para-hydroxyphenylacetate if:
- Medical conditions (Kidney disorders)
- Pesticide exposure
- Whole-grain diet
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Low levels of para-hydroxyphenylacetate may occur if the patient is on a low-protein diet or a diet low in plant materials. Nutritional deficiencies may prevent the synthesis of para-hydroxyphenylacetate from the aromatic amino acids phenylalanine or tyrosine in the liver. Amino acid breakdown uses many of the same enzymes that break down the neurotransmitters vanilmandelate and homovanillate. Large amounts of whole grains may shift the gastrointestinal bacteria in the gut microbiome and lower levels of para-hydroxyphenylacetate. Antibiotic use may decrease the number and type of bacteria in the microbiome and result in lower levels of para-hydroxyphenylacetate.
Exposure to rotenone or other pesticides may also prevent the synthesis of para-hydroxyphenylacetate and decrease levels.
- Liver disorders or early-stage liver disease may instead increase the levels of adipate and suberate, while blocking the synthesis of ketones such as beta-hydroxybutyrate.
- Levels of alpha-keto-isovalerate, hydroxymethylglutarate, pyroglutamate, benzoate, and 3-indoleacetate may be elevated, while vanilmandelate, 5-hydroxyindolacetate, and orotate may be lower than expected.
- If indicated, consider supporting the liver metabolism of amino acids with vitamins B2, B3, B6, calcium and copper.
- Consider a stool test or other evaluation of the gut microbiome. Environmental or chronic psychological stress can not only decrease the number of beneficial bacteria in the gut, but it can increase the levels of neurotransmitter metabolites (vanilmandelate, homovanillate, 5-hydroxyindoleacetate), para-hydroxyphenyllacetate, and hippurate.
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