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.
If Citrate is on the low end of the optimal range:
This key component of the citric acid cycle is formed inside the mitochondria from acetyl-coenzyme A and oxaloacetic acid by the enzyme citrate synthase. Succinate excess, as may occur with infection or intestinal dysbiosis (from bacterial transamination of non-absorbed glutamine), can inhibit citrate synthase. Citric acid can be low if cellular glucose or pyruvate is deficient or if pyruvate is elevated due to impairment of the pyruvate dehydrogenase complex that catalyzes the conversion of pyruvate into acetyl CoA. This transformation requires vitamin B1 as thiamin pyrophosphate, vitamin B2 as FAD, vitamin B3 as NAD, lipoic acid, magnesium and ATP.
Impaired beta-oxidation of fatty acids, as occurs with carnitine deficiency, can reduce levels of acetyl-CoA and citrate, especially in the early fasting state (12-48 hours after eating). Carnitine is necessary to transport long-chain fatty acids across the outer mitochondrial membrane for subsequent oxidation. Citric acid can also be low if oxaloacetic acid (its precursor) is insufficient. Oxaloacetic acid may be formed by oxidizing malic acid, or by transaminating aspartate. The first reaction requires B3 as NAD and the second requires B6 as pyridoxal 5-phosphate. Citric acid formation may also be low if pyruvate carboxylase is weak or in multiple carboxylase deficiency (pyruvic acid should be elevated). Pyruvate carboxylase requires biotin, ATP, magnesium and manganese. Additionally, low urinary citrate can occur with increased proximal tubular resorption in the kidneys that occurs in metabolic acidosis. This leads to hypocitraturia and can predispose the person to kidney stone formation.
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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:
Additional investigations:
Treatment considerations:
Anthony
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I have been using Healthmatters.io since 2021. I travel all over the world and use different doctors and health facilities. This site has allowed me to consolidate all my various test results over 14 years in one place. And every doctor that I show this to has been impressed. Because with any health professional I talk to, I can pull up historical results in seconds. It is invaluable. Even going back to the same doctor, they usually do not have the historical results from their facility in a graph format. That has been very helpful.
Karin
Advanced Plan Member since 2020
What fantastic service and great, easy-to-follow layouts! I love your website; it makes it so helpful to see patterns in my health data. It's truly a pleasure to use. I only wish the NHS was as organized and quick as Healthmatters.io. You've set a new standard for health tracking!
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Healthmatters Pro Member since 2024
As a PRO member and medical practitioner, Healthmatters.io has been an invaluable tool for tracking my clients' data. The layout is intuitive, making it easy to monitor trends and spot patterns over time. The ability to customize reports and charts helps me present information clearly to my clients, improving communication and outcomes. It's streamlined my workflow, saving me time and providing insights at a glance. Highly recommended for any practitioner looking for a comprehensive and user-friendly solution to track patient labs!
Citric Acid, or citrate, is measured to be low. This key component of the citric acid cycle is formed inside the mitochondria from acetyl-coenzyme A and oxaloacetic acid by the enzyme citrate synthase. Succinate excess, as may occur with infection or intestinal dysbiosis (from bacterial transamination of non-absorbed glutamine), can inhibit citrate synthase. Citric acid can be low if cellular glucose or pyruvate is deficient or if pyruvate is elevated due to impairment of the pyruvate dehydrogenase complex that catalyzes the conversion of pyruvate into acetyl CoA. This transformation requires vitamin B1 as thiamin pyrophosphate, vitamin B2 as FAD, vitamin B3 as NAD, lipoic acid, magnesium and ATP.
Impaired beta-oxidation of fatty acids, as occurs with carnitine deficiency, can reduce levels of acetyl-CoA and citrate, especially in the early fasting state (12-48 hours after eating). Carnitine is necessary to transport long-chain fatty acids across the outer mitochondrial membrane for subsequent oxidation. Citric acid can also be low if oxaloacetic acid (its precursor) is insufficient. Oxaloacetic acid may be formed by oxidizing malic acid, or by transaminating aspartate. The first reaction requires B3 as NAD and the second requires B6 as pyridoxal 5-phosphate. Citric acid formation may also be low if pyruvate carboxylase is weak or in multiple carboxylase deficiency (pyruvic acid should be elevated). Pyruvate carboxylase requires biotin, ATP, magnesium and manganese. Additionally, low urinary citrate can occur with increased proximal tubular resorption in the kidneys that occurs in metabolic acidosis. This leads to hypocitraturia and can predispose the person to kidney stone formation.
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Anthony
Unlimited Plan Member since 2021
I have been using Healthmatters.io since 2021. I travel all over the world and use different doctors and health facilities. This site has allowed me to consolidate all my various test results over 14 years in one place. And every doctor that I show this to has been impressed. Because with any health professional I talk to, I can pull up historical results in seconds. It is invaluable. Even going back to the same doctor, they usually do not have the historical results from their facility in a graph format. That has been very helpful.
Karin
Advanced Plan Member since 2020
What fantastic service and great, easy-to-follow layouts! I love your website; it makes it so helpful to see patterns in my health data. It's truly a pleasure to use. I only wish the NHS was as organized and quick as Healthmatters.io. You've set a new standard for health tracking!
Paul
Healthmatters Pro Member since 2024
As a PRO member and medical practitioner, Healthmatters.io has been an invaluable tool for tracking my clients' data. The layout is intuitive, making it easy to monitor trends and spot patterns over time. The ability to customize reports and charts helps me present information clearly to my clients, improving communication and outcomes. It's streamlined my workflow, saving me time and providing insights at a glance. Highly recommended for any practitioner looking for a comprehensive and user-friendly solution to track patient labs!
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2-Methylhippurate, 3,4-Dihydroxyphenylpropionate, 3-Hydroxybutyric acid, 5-Hydroxyindoleacetate, 8-Hydroxy-2-deoxyguanosine, Adipate, Alpha-Hydroxybutyrate, Alpha-Keto-Beta-Methylvalerate, Alpha-Ketoglutarate, Alpha-Ketoisocaproate, Alpha-Ketoisovalerate, Benzoate, Beta-Hydroxybutyrate, Beta-Hydroxyisovalerate, cis-Aconitate, Citrate, D-Arabinitol, D-Lactate, Ethylmalonate, Formiminoglutamate, Fumarate, Glucarate, Hippurate, Histamine, Homovanillate (Genova), Hydroxymethylglutarate, Indican, Isocitrate, Ketoisovalerate, Kynurenate, L-Lactate, Malate, Methylmalonate (Genova), Orotate, p-Hydroxybenzoate, p-Hydroxyphenylacetate, p-Hydroxyphenyllactate, Phenylacetate, Phenylpropionate, Picolinate, Pyroglutamate (Genova), Pyruvate (Genova), Quinolinic acid (Quinolinate) (Genova), Suberate, Succinate, Sulfate, Tricarballylate, Vanilmandelate (Genova), Xanthurenate (Genova)
