Citric acid, cis-aconitic acid, and isocitric acid are the first three metabolites in the Krebs Citric Acid energy production cycle, which operates in the mitochondria of your cells.
Citrate, cis-Aconitate (and Isocitrate) are involved in both energy production and removal of toxic ammonia.
High levels can indicate ammonia toxicity. Chronic loss of these valuable compounds can contribute to loss of organ reserve and disturbances in neurological function. If they are low they can indicate a need for essential amino acids, especially arginine.
References:
- Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid
metabolism in bipolar disorder [https://dash.harvard.edu/bitstream/handle/1/26860076/4832124.pdf?sequence=1]
Lower levels:
- Might be due to low or high pyruvic acid or low acetyCoA (from fatty acid oxidation)
- 2° to subnormal upstream metabolites.
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Impaired metabolism due to toxic metals (Fl, Hg, As, Sb) OR low cofactors (Fe, GSH— depleted in oxidative stress); OR high amounts of dietary citric acid; OR metabolic acidosis (if mildly increased cis-aconitic acid but markedly increased citric acid). High Citrate and Cis-aconitate can indicate arginine insufficiency for ammonia clearance through the Urea Cycle.
- Consider supplementing with arginine
- Rule out toxic metals; glutathione, N-acetylcysteine, Mg, or L-glutamine;
- Consider antioxidants;
- Rule out pancreatic insufficiency (can lead to metabolic acidosis from deficient bicarbonate).
Possible causes:
- Impaired metabolism due to toxic metals (Fl, Hg, As)
- Low glutathione
- High amounts of dietary citric acid
- Metabolic acidosis (if mildly increased cis-aconitic acid but markedly increased citric acid)
Additional investigations:
- Comprehensive Urine Elements Profile
- Functional Liver Detoxification Profile
- Complete Digestive Stool Analysis
Treatment considerations:
- Rule out toxic metals
- Glutathione
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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
