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.
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.
Understand and improve your laboratory results with our health dashboard.
Upload your lab reports and get your interpretation today.
Our technology helps to understand, combine, track, organize, and act on your medical lab test results.
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:
Interpret Your Lab Results
Upload your lab report, and we'll interpret and provide you with recommendations today.
Get StartedOur specialized data entry service is designed to seamlessly integrate your laboratory results into your private dashboard. Just send in your lab test results—whether it's an image or a file—and our skilled data entry team will handle the rest. We accommodate various file formats like PDFs, JPGs, and Excel.
The first report is complimentary. After that, the data entry service is priced at $15 per report, unless it's part of your subscribed plan. It's an ideal solution whether you have numerous reports to upload or if your schedule doesn't permit self-data entry.
We strive to make the data entry process easy for you. Whether by offering dozens of templates to choose from that pre-populate the most popular laboratory panels or by giving you instant feedback on the entered values. Our data entry forms are an easy, fast, and convenient way to enter the reports yourself. There is no limit on how many lab reports you can upload.
Personal plans
track personal results
Professional Plan
track multiple client's results
$15/month
$250/once
own it for life
$45/month
for health professionals
Personal Account
$15/month
for personal lab results
$250/once
own it for life
Level up your lab report analysis with our Pro plan, built for health practitioners like you.
Health Business Account
$45/month
Unlock additional Pro plans when you sign up.
At HealthMatters, we're committed to maintaining the security and confidentiality of your personal information. We've put industry-leading security standards in place to help protect against the loss, misuse, or alteration of the information under our control. We use procedural, physical, and electronic security methods designed to prevent unauthorized people from getting access to this information. Our internal code of conduct adds additional privacy protection. All data is backed up multiple times a day and encrypted using SSL certificates. See our Privacy Policy for more details.
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)