Autism Recovery Stories

Citramalic (Methylmalic) Acid

• A byproduct of Saccharomyces yeast species, as well as Propionibacterium acnes.
• Suggests dysbiosis.
• An analog of the Krebs cycle compound malic acid; may interfere with the production of malic acid in the Krebs cycle.

5-hydroxymethyl-2-furoic Acid

• A byproduct of the fungus Aspergillus and probably other species of fungi and yeast as well.
• Suggests dysbiosis.

3-oxoglutaric Acid

• Slightly elevated values are found in autism and other disorders.
• An analog of the Krebs cycle compound 2-oxoglutaric (alpha-ketoglutaric) acid.
• Elevated 3-oxoglutaric acid may correlate with low 2-oxoglutaric acid, possibly indicating an interference with 3-oxoglutaric acid in the Krebs cycle.
• Presumably formed from the amino acids lysine and tryptophan.

Furan-2,5-dicarboxylic Acid

• A byproduct of the fungus Aspergillus and probably other species of fungi and yeast as well.
• Suggests dysbiosis.

Furancarbonylglycine

• A conjugate of furancarboxylic acid and the amino acid glycine.

Tartaric Acid (3-Hydroxymalic Acid or 2,3-Hydroxy-succinic acid)

• An analog of the Krebs cycle intermediate malic acid that inhibits the Krebs cycle enzyme fumarase that converts fumaric acid to malic acid [Shaw2008].
• A toxic fermentation product of Saccharomyces yeast species.
• High levels are associated with autism and fibromyalgia [Shaw2008].
• Damages muscles and kidney [Robertson1968].
• Suggests dysbiosis.
• Treatment with antifungal drugs can significantly lower level in urine (also consider naturopathic treatments).
• Also found in grapes, cream of tartar, and as a food additive. In low doses is Generally Recognized As Safe (GRAS) by the FDA, but a 12 g dose may be fatal [Shaw2008].

Arabinose

• A metabolite produced in the liver from arabitol (also called arabinitol), which is produced by various yeast species such as Candida albicans, Candida tropicalis, Candida parapsilosis, etc.
• Arabinose is a 5-carbon aldose sugar that is not made in significant quantity by human metabolism, but can be found in apples, grapes, and pears and can serve as a marker for yeast overgrowth [Kiehn1979] [Wong1990] [Larsson1994] [Roboz1992].
• Arabinose may be a particular problem for patients with a defect in their pentose metabolism; this defect can be tested for [Shaw2008].

Carboxycitric Acid

• An analog of the Krebs cycle compound citric acid; may interfere with the metabolism of citric acid in the Krebs cycle.

Bacterial Metabolites

2-hydroxyphenylacetic Acid

• Produced by overgrowth of several species of bacteria in the GI tract by metabolizing the amino acid tyrosine.
• Very elevated values are present in celiac disease and enteritis.

4-hydroxyphenylacetic Acid

• Produced by overgrowth of bacteria in the GI tract by metabolizing the amino acid tyrosine.
• Treatment with the antibiotic neomycin can significantly lower level in urine (also consider naturopathic treatments).
• Very elevated values are present in celiac disease, enteritis, and intestinal resection.

3-hydroxyphenyl-3-hydroxypropionic acid (HPHPA)

• Produced by Clostridia species, including but not limited to Clostridium difficile [GP].
• Elevated values are common in autism, depression, schizophrenia, seizures, and chronic fatigue syndrome colitis tic disorders muscle weakness or paralysis [Shaw2008] [GP].
• Treatment with the antibiotics vancomycin or metronidazole (Flagyl) can significantly lower the HPHPA level in urine [GP]. Addition of probiotics such as Lactobacillus acidophilus GG is also recommended [Shaw2008] (also consider naturopathic treatments).

According to [Shaw2008, page 14], Clostridia spp. deaminate the amino acid phenylalanine (which is the precursor of the important neurotransmitters dopamine, norepinephrine, and epinephrine) to form 3-phenyl-propionic acid, which is then hydroxylated in the meta position by Clostridia spp. to form 3-(3-hydroxyphenyl)-propionic acid [Elsden1976] [Bhala1993]. This intermediate is then subjected to human beta oxidation to form 3-(3-hydroxyphenyl)-3-hydroxy-propionic acid (HPHPA), which is detectable in the urine.

An alternative pathway for formation of HPHPA from phenylalanine is via microbial meta-hydroxylation of phenylalanine to form 3-hydroxyphenylalanine (an analog of tyrosine, which is 4-hydroxyphenylalanine), which is then deaminated to form 3-(3-hydroxyphenyl)-propionic acid, which then proceeds to HPHPA as above [Shaw2008].

Vanillylmandelic Acid (VMA) Analog

• Metabolite of the amino acid tyrosine produced by Clostridia species.
• Clostridial overgrowth may interfere with the body's production and metabolism of the important neurotransmitters dopamine and norepinephrine, which are made from tyrosine. Elevated values are common in autism, depression, schizophrenia, seizures, and chronic fatigue syndrome.
• Treatment with the antibiotics vancomycin or metronidazole (Flagyl) can significantly lower level in urine (also consider naturopathic treatments).

Oxalate Related

Glyceric Acid

• Elevated values may be due to microbial sources such as yeast or due to dietary sources containing glycerol (glycerine).
• Elevated values may also indicate an inborn error of metaboilism (see oxalaic acid).

Glycolic Acid

• Elevated glycolic acid without elevated oxalic acid is most likely a result of GI yeast overgrowth.
• Elevated values may also indicate an inborn error of metaboilism (see oxalaic acid).

Oxalic Acid

• Elevated values may be due to many causes, including:
  • primary hyperoxaluria,
  • diabetes mellitus,
  • cirrhosis,
  • vitamin B-6 deficiency,
  • sarcoidosis,
  • steatorrhea due to pancreatic insufficiency,
  • celiac disease,
  • bacteria overgrowth,
  • ileal resection,
  • biliary tract disease,
  • small bowel disease,
  • ethylene glycol poisoning,
  • increased intake of foods high in oxalate including rhubarb, spinach, raspberries, and peanuts,
  • increased vitamin C intake.
• If glycolic acid is also elevated, it may indicate the genetic disease hyperoxaluria type I.
• If glyceric acid is also elevated, it may indicate the genetic disease hyperoxaluria type II.

Glycolysis Intermediates

Lactic Acid

• Elevated values may indicate infection, recent vigorous exercise, B vitamin deficiency, poor perfusion, or intestinal bacterial overgrowth.
• Extremely elevated values indicate genetic diseases such as pyruvate dehydrogenase deficiency, glycogen storage diseases, and disorders of fructose metabolism, severe trauma, or life-threatening infections.

Pyruvic Acid

• Elevated values may indicate infection, recent vigorous exercise, B vitamin deficiency, poor perfusion, or intestinal bacterial overgrowth.
• Extremely elevated values indicate genetic diseases such as pyruvate dehydrogenase deficiency, glycogen storage diseases, and disorders of fructose metabolism, severe trauma, or life-threatening infections.

2-hydroxbutyric Acid

• Slightly elevated values may indicate infection, recent vigorous exercise, B vitamin deficiency, or poor perfusion.
• Significantly elevated values may indicate genetic diseases such as pyruvate dehydrogenase deficiency, glycogen storage disease, or disorders of fructose metabolism, or be the result of severe trauma or life-threatening infections.

Krebs Cycle Intermediates

Succinic Acid

• A Krebs cycle compound that may be elevated due to a deficiency in riboflavin or coenzyme Q10, bacterial conversion of glutamine to succinic acid in the gastrointestinal tract, or inborn error of metabolism.

Fumaric Acid

• A Krebs cycle compound produced by the dehydrogenation of succinic acid by the enzyme succinic acid dehydrogenase.

2-oxoglutaric Acid (Alpha-ketoglutaric Acid, AKG)

• A Krebs cycle compound.
• 2-oxoglutaric acid may be derived from the conversion of glutamic acid to 2-oxoglutaric by deamination or transamination.
• Very low values may sometimes be encountered in chronic fatigue syndrome.
• Anecdotal reports indicate that autistic symptoms sometimes improve with AKG supplementation in response to low values of this metabolite.

Aconitic Acid

• A Krebs cycle compound.
• May be elevated as a result of a deficiency in glutathione since the enzyme aconitase requires reduced glutathione to metabolize aconitic to citric acid.

Citric Acid

• A Krebs cycle compound.
• Do not confuse citric acid with ascorbic acid (vitamin C). They are both found in citrus fruit, but are not the same compound.

Amino Acid Metabolites

2-hydroxyisovaleric Acid

• Slight elevations may be due to deficiencies of the vitamins thiamine or lipoic acid.
• Elevated values are also associated with the genetic diseases maple syrup urine disease or pyruvate dehydrogenase deficiency.

2-oxoisovaleric Acid

• Slight elevations may be due to deficiencies of the vitamins thiamine or lipoic acid.
• Elevated values are also associated with the genetic diseases maple syrup urine disease or pyruvate dehydrogenase deficiency.

3-methyloxovaleric Acid

• Slight elevations may be due to deficiencies of the vitamins thiamine or lipoic acid.
• Elevated values are also associated with the genetic diseases maple syrup urine disease or pyruvate dehydrogenase deficiency.

2-hydroxyisocaproic Acid

• Slight elevations may be due to deficiencies of the vitamins thiamine or lipoic acid.
• Elevated values are also associated with the genetic diseases maple syrup urine disease or pyruvate dehydrogenase deficiency.

2-oxoisocaproic Acid

• Slight elevations may be due to deficiencies of the vitamins thiamine or lipoic acid.
• Elevated values are also associated with the genetic diseases maple syrup urine disease or pyruvate dehydrogenase deficiency.

2-oxo-4-methiobutyric Acid

• Elevated in the genetic disease methioninemia.

Phenyllactic Acid

• Elevated in the genetic diseases PKU and tyrosinemia.
• Slight elevations may result from increased dietary intake of phenylalanine.

Phenylpyruvic Acid

• Elevated in the genetic diseases PKU and tyrosinemia.
• Slight elevations may result from increased dietary intake of phenylalanine.

Mandelic Acid

• Elevated in the genetic diseases PKU and tyrosinemia.
• Slight elevations may result from increased dietary intake of phenylalanine.

Homogentisic Acid

• Elevated in the genetic disease homogentisic aciduria (alkaptonuria).

4-hydroxyphenyllactic Acid

• Significantly elevated in the genetic diseases tyrosinemia and in phenylketonuria.
• Slight increase may be due to increased tyrosine intake.

Autism Recovery Stories