Optimal Result: 40 - 520 mmol/mol creatinine.

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.

What does it mean if your Citric Acid result is too low?

Possible causes:

Low or high pyruvic acid or low acetyCoA (from fatty acid oxidation)

What does it mean if your Citric Acid result is too high?

Citric Acid is measured to be high.

Citric acid is a key component of the citric acid cycle and is formed inside the mitochondria from acetyl coenzyme A and oxaloacetic acid. Citric acid is essential in the production of bicarbonate, a compound that helps to maintain proper pH in the body. Elevated urinary citrate may be a sign of a metabolic pH imbalance (metabolic acidosis), possibly due to damaged proximal tubular function in the kidney that results in urinary wasting of citrate. Another possible cause of elevated urine citrate is pancreatic dysfunction, as bicarbonate production would be reduced, leading to less utilization of citric acid. In this situation, cis-aconitic and isocitric acids may be also elevated. However, if cis-aconitic or isocitric acids are low, this may be indicative of impaired enzymatic conversion within the citric acid cycle. The enzyme cis-aconitase converts citric acid into cis-aconitic acid. This enzyme requires the presence of a sulfhydryl (-SH) group from cysteine or glutathione and it is activated by ferrous iron (Fe+2). Deficiencies of methionine, cysteine, glutathione, or iron, would result in sub-optimal enzyme efficiency. In addition, toxic elements with high sulfur affinity, like arsenic, antimony and mercury, may impair cis-aconitase activity. Also, xenobiotic toxicity, if it depletes glutathione, or increased oxidative stress from any cause may lead to elevated citrate. Excess fluorine can combine with acetate and, as fluoroacetate, can also inhibit the cis-aconitase enzyme. Any of the above situations may result in increased urinary citrate.

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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