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 Started
Monthly plan
Annual plan
Own it for life
Our exclusive data entry service is a convenient way to get your results into your private dashboard. Simply attach an image or a file of your lab test results, and one of our qualified data entry team members will add the results for you. We support all sorts of files, whether PDFs, JPGs, or Excel. This service is excellent whether you have a lot of reports to upload or are too busy to do the data entry yourself.
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.
$15 /month
billed every month
Most popular
Data entry included
$79 /year
$6.60/month billed annually
Data entry included
$250 /once
own it for life
Are You a Health Professional?
Get started with our professional plan
Welcome to Healthmatters Pro.
Save time on interpreting lab results with the largest database of biomarkers online. In-depth research on any test at your fingertips, all stored and tracked in one place. Learn more
Pro Monthly Plus
for health professionals
$75 per month
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.
3,4-Dihydroxyphenylpropionate, 3-Methyl-4-OH-phenylglycol, 5-Hydroxyindoleacetate, 8-Hydroxy-2-deoxyguanosine, a-Hydroxybutyrate, a-Hydroxyisobutyrate, a-Keto-b-Methylvalerate, a-Ketoadipate, a-Ketoglutarate, a-Ketoisocaproate, a-Ketoisovalerate, a-Ketophenylacetate, Adipate, b-Hydroxybutyrate, b-Hydroxyisovalerate, b-Hydroxypropionate, Benzoate, Cis-Aconitate, Citramalate, Citrate, Creatinine, D-Arabinitol, Formiminoglutamate, Glutarate, Glycerate, Glycolate, Hippurate, Homovanillate, Hydroxymethylglutarate, Indoleacetate, Isocitrate, Isovalerylglycine, Kynurenate, Kynurenate/Quinolinate, Lactate, m-Hydroxyphenylacetate, Malate, Methylmalonate, Orotate, Oxalate, p-Hydroxyphenylacetate, Phenylacetate, Pyroglutamate, Pyruvate, Quinolinate, Suberate, Succinate, Tartarate, Vanilmandelate, Xanthurenate
