Genova Diagnostics Blog

Exploring Health and Healing with Laboratory Testing


Ammonia Overload Anyone?


Patterns within the Organix Profile: Many of the analytes in the Organix Profile have more than one meaning, especially in combination with other analytes. There are patterns of elevated analytes you can learn to recognize and which can help you more specifically identify and understand your patients’ issues. All of the markers work in overlapping pathways, and understanding analyte patterns can give details to the stories the Organix Profile tells.

Doctor checking organic acids.

Part 1: Ammonia is not just a hazardous chemical, it’s also a natural by-product of our biochemistry that is tightly regulated by the urea cycle. Do your patients have ammonia system overload? Well, one way to check is looking at orotate, citrate, cis-aconitate, and isocitrate in the Organix Profile.

Why are these markers important?

The protein you eat will catabolize into individual amino acids which are used to build new proteins; the nitrogen is used, and the waste gets excreted. The end products of protein catabolism include carbon dioxide, water, adenosine triphosphate (ATP), urea, and ammonia. Ammonia from protein breakdown, both from diet and body metabolism, goes into the urea cycle.

The urea cycle operates to form and eliminate urea. When ammonia enters the urea cycle, citrulline is produced and orotate is given off. Next arginine enters, generates urea, and the cycle runs again. If arginine amounts are insufficient, the cycle can’t produce urea, and the cycle backs up and orotate increases. Citrate, cis-aconitate, and isocitrate from the Krebs cycle bind to excess ammonia to aid its excretion, avoiding ammonia overload. If orotate, citrate, cis-aconitate, and isocitrate are all above the reference intervals, there may be an ammonia issue. Both decreasing the production of ammonia and adding arginine can help to increase the function of the urea cycle and reduce the levels of these markers.

Interpreting the changes

You’ll want to note that ammonia levels are constantly changing. When dietary proteins increase significantly, ammonia rises and then declines again once protein intake is lowered. Intestinal bacterial action on protein and fasting can also lead to increases in ammonia. So, looking at orotate, citrate, cis-aconitate, and isocitrate can give a picture of how your body is handling your ammonia load.

Additionally, you can also check the amino acids that are involved in urea cycle and ammonia detoxification: arginine, citrulline, ornitine, asparagine, aspartic acid, and glutamine.

Join me next week for Part 2 as I continue to guide you through the use of organic acid testing, and how targeted treatment can help maximize patient responses and lead to improved patient outcomes.

Additional Resources:

Comments (4) -

United States Tony Giancarlo

Dr. Redmond,

You mentioned that fasting can increase ammonia levels. Would this tend to happen over very short-term fasts or more so during an extended fast? Or is it simply a matter of degree, i.e. it will increase during any sort of fasting with the increase in ammonia mirroring the duration of the fasting period?


United States Dr. Redmond

The response would certainly have significant variables. Ammonia is a byproduct of fasting due to an increase in glucogneogenesis; Gluconeogenesis is often associated with ketosis. Urinary ammonia excretion correlates with ketosis. The use of keone bodies, can be detected in the Organix marker β-Hydroxybutyrate. So a short fast maybe insignificant on most people, and become more significant as time goes on.
Ammonia is often detected in the sweat of athletes when they do a hard workout; A workout that requires glucogneogenesis.


Dr. Redmond,

How sensitive are the markers for Ammonia? e.g. if a patient has problems with low level ammonia production only when they consume higher amounts of protein, would Organix pick this type of activity?

I am concerned that the test may not pick the ammonia burden which may be occurring upon extra protein intake only.


I think this is quite interesting! I salute your ingenuity and am grateful for this enjoyable post. Happily anticipating future information!


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