Organic Acid Test, Part 7: Amino Acid Metabolites

Please note: The content of this post is my own unless the technical terms are too hard to explain, then the content is copy and paste. I am not a medical professional and thus the post is my point of view. But the content is science-based and credible. Just because it is a new science, does not necessarily make it quackery.

Test results, part 4

Amino Acids

What is an amino acid, you ask? Amino acids are used in every cell of your body to build the proteins you need to survive. The best sources of essential amino acids are animal proteins like meat, eggs and poultry.

In the Great Plains Organic Acid test, there are about 15 markers that are tested for regarding amino acids. In the SA test, it is broken up into two categories.

Urine organic acids: Branched-chain amino acid intermediates

2-Ethylhydracrylic-/2-Ethyl-3-OH-propionic acid 0.35 < 2 mmol/mol creat
2-Hydroxyisocaproic acid 0.22 < 2 mmol/mol creat
2-Hydroxyisovaleric acid BDL < 2 mmol/mol creat
2-Oxoisovaleric acid / 3-Methyl-2-oxobutyric acid 0.22 < 1.1 mmol/mol creat
3-Hydroxy-2-methylbutyric acid 0.85 < 11 mmol/mol creat
3-Hydroxyisobutyric acid 5.48 L 20 – 118 mmol/mol creat
3-Hydroxyisovaleric acid 5.51 5.1 – 23.1 mmol/mol creat
3-Methyl-2-oxovaleric-/2-Keto-3-methylvaleric acid BDL < 4.8 mmol/mol creat
3-Methylglutaconic acid 2.89 < 20 mmol/mol creat
3-Methylglutaric acid 0.99 < 3.9 mmol/mol creat
4-Methyl-2-oxovaleric acid/2-Ketoisocaproic acid 0.16 < 0.86 mmol/mol creat
Malonic acid BDL < 5 mmol/mol creat

Urine organic acids: Other Amino acid intermediates

3-Hydroxyglutaric acid (Lysine Metabolism) 2.05 < 8 mmol/mol creat
Glutaconic acid (Lysine Metabolism) 0.58 < 3.1 mmol/mol creat
N-Acetylaspartic acid  (Aspartic Metabolism) 0.54 < 13 mmol/mol creat

This one is a bit more difficult to break down.

According to the Great Plains Lab break down:

2-Hydroxyisovaleric Acid

2-Oxoisovaleric Acid

3-Methyl-2-oxovaleric Acid

2-Hydroxyisocaproic Acid

2-Oxoisocaproic Acid

A moderate increase of branched-chain amino acid metabolites in urine may result from lactic acidosis, episodic ketosis, or deficiencies of the vitamins thiamine or lipoic acid.  Elevated 2hydroxyisocaproic acid in urine has also been linked to short bowel syndrome.  A significant increase of branched-chain amino acid metabolites is associated with the genetic disorders maple syrup urine disease (MSUD) or pyruvate dehydrogenase deficiency.  Patients with slight to moderate elevations may use dietary supplements containing thiamine to improve clinical symptoms.

2-Oxo-4-methiolbutyric Acid      Testing of plasma amino acids.        Elevated in an inborn error of methionine metabolism.  Confirmation of the genetic disorder requires

Malonic Acid Associated with the genetic disorders malonyl-CoA decarboxylase deficiency or malonic aciduria with normal malonyl-CoA decarboxylase activity.  Slightly elevated values in urine are unlikely to be clinically significant.

3-Methylglutaric Acid and 3-Methylglutaconic Significant increase are due to a reduced ability to metabolize the amino acid leucine.  This abnormality is found in the genetic disease methylglutaconic aciduria and in mitochondrial disorders.  3-Methylglutaconic acid may also be elevated.  Supplementation with coenzyme Q10, NAD+, L-carnitine and acetyl-L-carnitine, riboflavin, nicotinamide, biotin, and vitamin E may be useful.

Amongst the list were also markers found under Neurotransmitters which include Phenylalanine and Tyrosine Metabolites. But more about those in the next post.

So any reading in this section was the 3-Hydroxyisobutyric acid, which was low.

3-Hydroxyisobutyric acid (or 3-hydroxy-2-methylpropanoic acid) is an intermediate in the metabolism of Valine.

Just for fun: the chemical structure of 3-Hyrdoxyisobutyric acid

An interesting fact about Valine, it was first isolated from casein in 1901 by Hermann Emil Fisher. The name valine comes from valeric acid, which in turn is named after the plant valerian due to the presence of the acid in the roots of the plant. Casein which is present in milk.

This result should be right because Alex does not drink milk or eat any dairy products, not because he is allergic to it or on a casein-free diet, but because he does not like it.

Dr Lindenberg comments: “Branched-chain amino acids OK with relatively low tyrosine metabolism.”

Interesting read: An Amino-Acid Deficiency That Causes Neurological Problems

There is a condition called 3-hydroxyisobutyric aciduria. In many affected people, the exact underlying cause of 3-hydroxyisobutyric aciduria is poorly understood. Scientists believe that some cases are caused by changes (mutations) in the ALDH6A1 gene. This gene encodes an enzyme called methylmalonate semialdehyde dehydrogenase, which helps the body break down certain amino acids (the building blocks of protein) found in food. If this gene isn’t working properly, the body is unable to break down the amino acids valine and thymine which leads to a build-up of toxic substances in the body and the many signs and symptoms of 3-hydroxyisobutyric aciduria. There is no cure for 3-hydroxyisobutyric aciduria. Because it is so rare, there is limited evidence to support the effectiveness of treatment. However, affected people have been treated with a protein-restricted diet and carnitine supplementation with varying degrees of success. (


Organic Acid Test: Part 6, Pyrimidine Metabolites

Please note: The content of this post is my own unless the technical terms are too hard to explain, then the content is copy and paste. I am not a medical professional and thus the post is my point of view. But the content is science-based and credible. Just because it is a new science, does not necessarily make it quackery.

Pyrimidine Metabolites – Folate Metabolism

Remember this picture? This is from the series on MTHFR (methylation cycle)

The Pyrimidine metabolites in the Organic Acid test also points to your folate cycle. In the Organic acid test, there are two acids they look for :

  1. Uracil
  2. Thymine

Folate acts as a methyl donor in converting uracil to thymine.

Elevated Uracil could also indicate MTHFR homozygous gene mutation and methylation problems including high homocysteine. High levels of uracil are found with folate (vitamin B9) deficiencies.

High levels of thymine indicate a deficiency in vitamin B1. Low B1 is common with alcoholics, and for people who are on very high carbohydrate, low-nutrient diet.  Very high levels are associated with inflammatory diseases and cancer.

This is why the MTHFR/ Methylation test and the Organic acid test goes hand in hand.

According to some studies, around 10% of autistic children have elevated uracil acid. Great Plain Laboratories has a specific test testing Uric acids, click here and here

From earlier blood tests (2016 and 2018) you can see that Alex has an issue with processing folic acid as you would get if from your multivitamins and supplements and your pregnancy supplement. Most doctors recommend women wanting to get pregnant and those that are pregnant to take a folic acid supplement to prevent this like spinal bifida and cognitive disorders in their babies, but if genetically you have a disposition to not be able to process that folic acid it can build up and cause more harm. That is why taking folinic acid or folate instead is more beneficial. Folinic acid and folate has already been through the methylation process to make are more useful to the body.

2016 vs 2018 Blood test – folic acid:
E-folaat (RBS) 1305 >285.0 2859 > 500

A slight increase, but apparently this is normal as your levels are not always the same every day.

Organic acid test results:
Thymine BDL < 0.8 mmol/mol creat
Uracil 0.71 < 6.8 mmol/mol creat

It was too low to measure. (I am yet to find a doctor to explain this to me – the reason why the blood test shows elevation and the organic acid test was too low).

Foods to eat that increase folinic acid or folate:

Another acid that is part of the methylation cycle and which is also picked up on the Organic acid test is Vitamin B12 or Methylmalonic Acid. But more about it later in the section on Nutritional Markers.




Organic Acid Test: Part 5, Ketones and Fatty Acids

Please note: The content of this post is my own unless the technical terms are too hard to explain, then the content is copy and paste. I am not a medical professional and thus the post is my point of view. But the content is science-based and credible. Just because it is a new science, does not necessarily make it quackery.

Test Results, Part 3

Urine organic acids: Fatty acid oxidation intermediates

3-Hydroxybutyric  acid BDL < 10 mmol/mol creat
Acetoacetic acid BDL < 24.9 mmol/mol creat
Adipic acid 9.43 < 37 mmol/mol creat
Ethylmalonic acid 3.49 < 17 mmol/mol creat
Methylsuccinic acid BDL < 6.05 mmol/mol creat
Sebacic acid 0.11 < 16 mmol/mol creat
Suberic acid 28.9 H < 20 mmol/mol creat

The markers measured here will show how well your body can process fat. These markers are sometimes elevated for persons on the Ketogenic diet or Low-carbs diet, but if there is an elevation in the results and a person is not on a Ketogenic diet it means that the body is not processing that fat too well.

If you are unable to process fat effectively your cells cannot put out the energy needed to function optimally.  Candida, bacterial toxins, and high oxalates can contribute to fat malabsorption. An anti-inflammatory nutrition plan is critical for improving these markers, along with targeted supplementation as indicated by other abnormal markers.

If you want to read more about Ketones, follow the link here.

Many people are following the Ketogenic diet, many dieticians or functional medicine practitioners have suggested the Ketogenic diet for Autistic people. Click here.

On the Great Plains lab results they list the following under Ketone and Fatty Acid Oxidation:

  1. 3-Hydroxybutyric Acid & Acetoacetic Acid
Ketones, such as 3-hydroxybutyric and acetoacetic acids, are the end-products of rapid or excessive fatty-acid breakdown.  Common causes of elevated ketones are prolonged fasting, protein malnutrition, high fat diet, vitamin B12 deficiency, severe GI Candida overgrowth, and pulmonary infections.  Dietary supplements containing L-carnitine or acetyl-L-carnitine may be beneficial.
2. 4-Hydroxybutyric Acid A moderate urinary increase in 4-hydroxybutyric acid may be due to intake of dietary supplements containing 4-hydroxybutyric acid, also known as gamma-hydroxybutyric acid.  Very high results may indicate the genetic disorder involving succinic semialdehyde dehydrogenase deficiency.

3. Adipic Acid Slightly elevated adipic acid may result from excessive ingestion of gelatin or other “junk” food containing adipic acid as an additive.  Elevated adipic acid may also indicate an abnormality in fatty acid metabolism.  Dietary supplements containing L-carnitine or L-acetyl-carnitine may be beneficial.  

4. Suberic Acid, Sebacic Acid, Ethylmalonic Acid & Methylsuccinic Acid Increased urinary products of omega- fatty acid metabolism pathway may be due to carnitine deficiency, fasting, or increased intake of triglycerides from coconut oil, or some infant formulas.  Very elevated values may indicate a genetic disorder.  Fatty acid oxidation defects are associated with hypoglycemia and lethargy.  Regardless of the cause, intake of dietary supplements containing L-carnitine, or acetyl-L-carnitine may improve clinical symptoms.

On Alex’s test, the Suberic Acid was elevated 28.9/ 20.  This is a very interesting acid, as it can indicate some-one was fasting overnight or AN INCREASE IN OIL USE.

The comments from the Lab technician stated: “The isolated increase in Suberic acid is likely dietary in origin and not suggestive of compromised beta-oxidation capacity.” 

The reason why I said that this result is interesting is that because we have been struggling with Alex to pick up weight, we started to give Alex food with a higher fat content like full cream yoghurt and using spread that 70% more fat spread than the more plastic margarine.  Also, and I know this is maybe THE reason why this acid is so elevated is that his chicken patties and french fries have been fried, even if it is only a little bit of oil, and not baked.

Organic Acid Test: part 4, Glycolytic Cycle and Krebs Cycle Metabolites

Please note: The content of this post is my own unless the technical terms are too hard to explain, then the content is copy and paste. I am not a medical professional and thus the post is my point of view. But the content is science-based and credible. Just because it is a new science, does not necessarily make it quackery.

Test Results, Part 2

In our South African test, the Glycolytic Cycle and Krebs Cycle results are combined, whereas in the Great Plains test it is separate.

Glycolysis is the metabolic pathway by which we convert glucose into lactate and pyruvate to form energy. If levels of lactic and pyruvic acids are elevated, a person has mitochondrial dysfunction.

High values for these markers may indicate that environmental toxins, particularly mold, are affecting your mitochondria. High lactic acid is commonly elevated with mold issues.

Glycolytic Cycle

Urine organic acids: Glycolysis and Krebs Cycle intermediates

2-Oxoglutaric acid/2-Ketoglutaric acid 1.72 L 36 – 103 mmol/mol
Aconitic acid 24.67   17.3 – 63.3 mmol/mol
Citric acid 31.44   < 656 mmol/mol
D/L-2-Hydroxyglutaric acid 2.47   < 35 mmol/mol
DL-Lactic acid 3.4 L 20 – 346 mmol/mol
Fumaric acid BDL   2 – 42 mmol/mol
Isocitric acid 12.97   < 99 mmol/mol
Malic acid 0.13   < 73 mmol/mol
Pyruvic acid 0.05   < 19 mmol/mol
Succinic acid 10.09 L 16 – 156 mmol/mol

In the Glycolytic we look at the following markers

  1. Lactic acidLactic acid is produced as part of the cycle when your body takes food, or sugars, and process it for energy. You know that burn you feel in your muscles after some exercises, that is lactic acidosis. In Afrikaans, we speak of “miltsteek”, that sharp pain you somethings get in your side after exercising especially when you are unfit. Elevations of lactic acid and/or pyruvic acid can also be caused by many nonspecific factors, such as vigorous exercise, bacterial overgrowth, shock, anaemia, mitochondrial dysfunction, or other causes.
  2. Pyruvic acid – Pyruvic acid can be made from glucose (sugar) through glycolysis, converted back to carbohydrates (such as glucose) via gluconeogenesis, or to fatty acids through a reaction with acetyl-CoA.
  3. 2-Hydroxybutyric acid – 2-Hydroxybutyric acid is a ketone body produced as a by-product of fatty acids oxidation for energy. This acid will be elevated if there is a yeast overgrowth.

Elevated levels of these three acids might indicate there are inborn errors of metabolism, including disorders of sugar metabolism and pyruvate dehydrogenase deficiency. The possibility of an inborn error of metabolism increases as the lactic acid value exceeds 300 mmol/mol creatinine and when pyruvic acid exceeds 100 mmol/mol creatinine.

Krebs Cycle

For more details on the Krebs Cycle, you can read more about it as part of the MTHFR series, click here.

Like previously mentioned the Glycolytic Cycle and the Krebs cycle is actually part of the same process. The Krebs cycle uses sugars to create lactic acid and pyruvic acid to produce energy for the cells.

In the Krebs Cycle they look at these markers:

  1. SuccinicLow levels could indicate a need for the branch chain amino acids leucine and isoleucine. An elevated result may also indicate a relative deficiency of riboflavin and/or coenzyme Q10.  Suggest supplementation with a minimum of 20 mg riboflavin and/or 50 mg per day of coenzyme Q10.  Also produced by bacterial degradation of unabsorbed glutamine supplement. Foods that contains Succinic acid include broccoli, rhubarb, sugar beets, fresh meat extracts, various cheeses, and sauerkraut.  
  2. Fumaric (Increased urinary fumaric acid may be due to impaired Krebs cycle function, a defect in the enzyme fumarase or in mitochondrial function.)
  3. Malic (Slightly elevated values usually indicate a higher need for nutrients such as niacin and coenzyme Q10.When malic acid is simultaneously elevated with citric, fumaric and 2-ketoglutaric acids, a mitochondrial energy pathway dysfunction is strongly suggested.)
  4. Citric (Elevations may be due to increased intake of citric acid containing foods or result from intestinal yeast producing citric acid or perhaps inhibiting the human citric acid cycle.  Increased citric acid may also indicate depletion of glutathione, which is required for the enzyme aconitase to metabolize both aconitic and citric acids.  If pyroglutamic acid values are low, consider supplements containing glutathione, n-acetyl cysteine, or lipoic acid.)
  5. 2-Ketoglutaric acids/ 2-Oxoglutaric acid – Increased values in urine may be due to dietary vitamin deficiencies or the intake of 2-ketoglutaric acid as a supplement.  The conversion of 2-oxoglutaric acid to succinyl-CoA requires coenzyme A (derived from pantothenic acid), lipoic acid, flavin adenine dinucleotide (FAD) derived from riboflavin (B2), and thiamine (B3).
  6. Aconitic Acid (Aconitase, the enzyme that metabolizes citric and aconitic acids, is dependent upon glutathione. Elevated in mitochondrial disorders (e.g. Complex I and Pierson Syndrome).  Elevated aconitic acid may indicate an additional requirement for reduced glutathione.)

Elevations in Krebs Cycle metabolites are commonly due to environmental toxins such as heavy metals or mold, yeast/fungal or bacterial overgrowth, high oxalate levels, or high oxidative stress. A less common indication of high levels would be a genetic issue.