Pyroglutamate (or Pyroglutamic acid) is an intermediate in the glutathione metabolism and a marker of glutathione deficiency.
Pyroglutamate is a step in the production/recycling of glutathione. Glutathione is one of the most potent anti-oxidants in the human body. It is especially important in getting rid of toxins, including the harmful metabolites of estrogen detoxification 4-OH-E1 and 4-OH-E2.
In healthy individuals, a very modest amount of Pyroglutamate is spilled in the urine.
Though it does not directly look at glutathione status, it measures the activity of the rate limiting enzymatic process in the production of glutathione. Thus, it is assessing the process of antioxidant production, and when upregulated informs us of increased stress on the system.
Glutathione, itself, is the major antioxidant produced in abundance in the liver. It is composed of three amino acids: cysteine, glycine, and glutamate. In periods of nutritional deficiency, stress, increased reactive oxygen species (ROS), toxicity, mitochondrial dysfunction, cellular proliferation, Phase 2 detoxification, etc. glutathione stores are depleted, and the production status is upregulated. Prolonged glutathione depletion leads to mitochondrial dysfunction and is directly supported with glutathione administration.
If there is little glutathione available to be recycled, pyroglutamate will be low. Low values may indicate glutathione deficiency due to oxidative stress or chemical exposure. Supplementation with reduced glutathione, N-acetyl L-cysteine, lipoic acid, and vitamin C (buffered) can raise glutathione levels. Selenium is essential to the antioxidant activity of glutathione; usually, adequate selenium can be obtained from a quality multivitamin.
Additional investigations:
- Functional Liver Detoxification Profile
- Total Antioxidant Status
Treatment considerations:
- Identify & correct toxicity
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If the body cannot convert pyroglutamate forward, it will show up elevated in the urine. Pyroglutamate elevation indicates the body is using up glutathione to keep from losing amino acids. Supplementation with various amino acids, especially methionine and glycine, can help rebuild total body glutathione.
Possible causes:
- Impaired recycling to glutathione due to cofactor insufficiencies (Mg, cysteine, glycine, glutamine)
- Consistent with impaired GSH
- Elevated values may be due to supplementation with glutathione or N-acetyl cysteine.
- Elevated pyroglutamic acid may also result from a genetic disorder, metabolic effects of certain antibiotics, or intake of certain infant formulas.
Additional investigations:
- Vitamins & Minerals Analysis
- Urinary Amino Acids
Treatment considerations:
- Supplement Mg, glycine, glutamine, N-acetylcysteine (NAC)
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