Testing for the Causes of Seizures-Great Plains Lab

[Guest guest]

I wrote to a couple of labs about what tests can help in finding

causes for Seizures. Great Plains wrote back and said " One of the

major causes of seizures that we have found is an increase in a

byproduct of clostridia bacteria in the intestinal tract. "

They sent a four page document on some of their testing posted

below. There is more information at their web site:

www.greatplainslaboratory.com

The Great PlainsLaboratory (GPL)

for Health, Metabolism, and Nutrition

11813 W. 77th

Street

Phone 913 341-8949

Lenexa, KS

66214

Fax 913 341-6207

Clinical Significance of The Organic Acid Test*

Glycolysis

Lactic, pyruvic – Elevated values (100-500 mmol/mol creatinine) may

indicate infection, recent vigorous exercise, B vitamin deficiency,

poor perfusion, or intestinal bacterial overgrowth.

Lactic, pyruvic – Extremely elevated values (500–100,000 mmol/mol

creatinine) indicate genetic diseases such as pyruvate dehydrogenase

deficiency, glycogen storage diseases, disorders of fructose

metabolism, severe trauma, or life-threatening infections.

2-hydroxbutyric – Slightly elevated values may indicate infection,

recent vigorous exercise, B vitamin deficiency, and poor perfusion.

2-hydroxybutyric – Significantly elevated values (> 25 mmol/mol

creatinine) may indicate genetic diseases such as pyruvate

dehydrogenase deficiency, glycogen storage disease, disorders of

fructose metabolism, severe trauma, and life-threatening infections.

Glyceric acid – Values greater than 150 mmol/mol creatinine may be

due to microbial sources such as yeast or due to dietary sources

containing glycerol.

Amino Acid Metabolites

2-hydroxyisovaleric, 2-oxoisovaleric, 3-methyloxovaleric, 2-

hydroxyisocaproic, 2-oxoisocaproic – Elevated values are associated

with maple syrup urine disease and pyruvate dehydrogenase deficiency

which are genetic diseases. Slight elevations may be due to

deficiencies of the vitamins thiamine or lipoic acid.

2-oxo-4-methiobutyric – Elevated in the genetic disease methioninemia

Phenyllactic, phenylpyruvic, mandelic – Elevated in the genetic

diseases PKU and tyrosinemia. Slight elevations may be due to

increased dietary intake of phenylalanine.

Homogentisic – elevated in the genetic disease homogentisic aciduria

(alkaptonuria).

4-hydroxyphenyllactic – Significantly elevated in the genetic

diseases tyrosinemia and in phenylketonuria. Slight increase may be

due to increased tyrosine intake.

Pyroglutamic – Pyroglutamic (oxoproline) is a metabolite of the

antioxidant gluthathione and is extremely elevated in the genetic

disease pyroglutamic acidurea and following the use of the

antibiotics flucloxacillin and netelmicin. Low values may be found

due to glutathione depletion following oxidative stress or after

exposure to toxic solvents or pesticides such as chloroform, DDT, or

polybrominated biphenyls (PBB's) and polychlorinatned biphenyls

(PCB's). Supplementation with glutathione, and N-acetyl cysteine are

useful to replenish glutathione.

3-indoleacetic – A metabolite of the amino acid tryptophan. Values

greater than 200 mmol/mol creatinine may be found in Hartnup's

disease, a genetic neurological disease due to defective renal and

intestinal transport of certain neutral amino acids. Elevations of

lesser magnitude appear to be of bacterial origin.

Kynurenic acid – Kynurenic is a tryptophan metabolite that may be

elevated with vitamin B-6 deficiency or due to excessive tryptophan

uptake. The reaction by which kynurenine is converted to

hydroxyanthranilate is catalyzed by an enzyme requiring vitamin B-6.

Thus, elevations of kynurenic may indicate a vitamin B-6 deficiency.

High values in individuals with the yeast overgrowth syndrome may be

due to yeast interference.

Fatty Acid Metabolites

3-hydroxybutyric, acetoacetic – Ketones derived from excessive fatty

acid oxidation may be elevated due to fasting or starvation, diabetes

mellitus, us of high fat (ketogenic) diets, and in several genetic

diseases.

Ethylmalonic, methylsuccinic, adipic, suberic, and sebacic – These

are fatty acid metabolites. Values may be elevated in ketosis,

fasting, deficiency of the fat-transporting molecule carnitine,

genetic deficiencies of fatty acid metabolism and the genetic disease

multiple acyl dehydrogenase deficiency, excessive intake of adipic

acid-containing foods such as Jell-O, and by increased intake of

foods containing medium chain triglycerides such as coconut oil.

Isolated high values of adipic acid only may be found in patients

with ADD, lethargy and seizures.

Miscellaneous

Glutaric – Elevated in the genetic diseases glutaric academia types 1

and II. Moderate increases may be to deficiencies in riboflavin and

coenzyme Q-10, or celiac disease. Moderate increases are common in

autism possibly due to defective vitamin absorption or microbial

production in the GI tract.

Methylmalonic – Values over 150 mmol/mol creatinine may be due to the

genetic disease methylmalonic aciduria. Moderate increases may be

due to vitamin B-12 deficiency, defective B-12 absorption, or

bacterial overgrowth of the GI tract that uses up vitamin B-12.

N-acetyl aspartic acid – High values are due to the genetic disease

Carnavan's disease, a potentially fatal disease causing spongy

degeneration of the brain.

Ascorbic –Vitamin C, and important antioxidant, with low values may

indicate dietary deficiency (scurvy) and is frequently low in chronic

fatigue syndrome. High values are usually of no concern except that

in individuals with bacteria overgrowth of the GI tract, ascorbic

acid may be converted to oxalic acid, which can lead to kidney

stones. There is a low probability that elevated vitamin C will cause

kidney stones if oxalic acid is in the normal range.

Orotic acid - Elevated orotic is most commonly associated with

ammonia toxicity. When ammonia is elevated, it is biochemically

converted to carbamyl phosphate and then orotic acid. Elevated

ammonia may occur due to liver toxicity, viral liver infection, GI

bleeding, portal systemic shunting of blood, drug toxicity, Reye's

syndrome, as well as inborn errors of ammonia metabolism. Elevated

orotic acid may also be found in leukemias and lymphomas, possibly

due to the increased production of pyrimidines.

3-hydroxy-3-methylglutaric (HMG) – HMG is a precursor in the

production of cholesterol in both humans and yeast. Moderate

increases as high as 300 mmol/mol creatinine are probably due to

yeast overgrowth of the GI tract and might also implicate yeast

overgrowth with elevated serum cholesterol.. Both yeast and humans

produce these same compounds as a precursor of steroid hormones.

Values from 200 – 11,000 mmol/mol creatinine are found in the genetic

disease 3-hydroxy-3-metylglutaric aciduria. .

Hydroxyhippuric – A conjugate of the amino acid glycine and

hydroxybenzoic acid (salicylic acid). Elevated values may be due to

the use of aspirin (salicylates) or due to the growth of GI bacteria

producing salicylates. Also increased after the ingestion of the

artificial sweetener aspartame (Nutrasweet).

Yeast/fungal

Citramalic (methylmalic) – Citramalic acid is a byproduct of

Saccharomyces yeast species as well as Propionibacterium acnes. This

metabolite was not found in the culture media of a wide number of

other anaerobic bacteria isolated from stool samples. Thus, an

increase in citramalic acid may indicate Propionibacteria overgrowth

rather than a yeast overgrowth of the intestinal tract. Citramalic

acid is a chemical relative (analog) of the Krebs cycle compound

malic acid. Presumably, this compound may interfere with the

production of malic acid in the Krebs cycle.

5-hydroxymethyl-2-furoic – A substituted furan that is a byproduct of

the fungus Aspergillus and probably other species of fungi and yeast

as well.

3-oxoglutaric acid – A chemical relative (analog) of the Krebs cycle

compound 2-oxoglutaric (alpha-ketoglutaric). Presumably, this

compound is a byproduct of the amino acids lysine and tryptophan.

The highest value was found in a child with a severely malformed

brain. Slightly elevated values are found in autism and other

disorders. 2-oxoglutaric, the normal Krebs cycle metabolite may be

low when 3-oxoglutaric is elevated, possibly indicating an

interference of 3-oxoglutaric in the Krebs cycle.

Furan-2,5-dicarboxylic – A substituted furan that is a byproduct of

the fungus Aspergillus and probably other species of fungi and yeast

as well.

Furancarbonylglycine – A conjugate of furancarboxylic acid and the

amino acid glycine.

Tartaric (hydroxymalic acid) – Tartaric acid is a toxic metabolite of

Saccharomyces yeast species, the same species of yeast that is used

in baking and brewing industries. Saccharomyces species may be

important organisms in the immuno-compromised person. The fungal

origin of this compound was confirmed in my laboratory by showing

that this compound decreased dramatically in the urine after the use

of antifungal drugs. Tartaric acid is also found in grapes, grape

products, and as a food additive. Cream of tartar, used in baking,

is basically tartaric acid.

Arabinose – Arabinose (a five carbon sugar or pentose) is not

produced by yeast directly. A closely related sugar derivative

called arabitol is produced by Candida species including Candida

albicans, Candida tropicalis, and Candida parapsilosis. Arabitol

produced in the gastrointestinal tract is absorbed into the portal

circulation, converted to arabinose by the liver, and then released

into the circulation. Since arabinose is also a major sugar in

apples, apple juice, and all apple products must be avoided 24 hour

prior to urine collection to prevent test interference.

Carboxycitric – A chemical relative (analog) of the Krebs cycle

compound citric acid. Presumably, this compound may interfere with

the metabolism of citric acid in the Krebs cycle.

Bacterial

2-hydroxyphenylacetic – A metabolites of tyrosine produced by

overgrowth of several species of bacteria in the GI tract.

4-hydroxyphenylacetic – Also a metabolite of tyrosine and the

bacterial origin of this compound was confirmed by the finding that

this compound in urine decreased significantly after the use of the

antibiotic neomycin. Very elevated values for these compounds are

present in celiac disease (gluten sensitivity), enteritis, and

intestinal resection.

Anaerobic Bacterial

HPHPA, 3- (3-hydroxyphenyl-3-hydroxypropionic acid - This is the

compound produced by Clostridia species including Clostridium

difficile. There are approximately 100 species of Clostridia in the

gastrointestinal tract so that this marker is NOT specific for

Clostridium difficile. Elevated values are common in autism,

depression,

schizophrenia, seizures, and in chronic fatigue syndrome. This

compound is reduced by treatment with vancomycin, Flagyl

(metronidazole), an herbal product called Biocidin, and by probiotics.

VMA analog – Derivatives of the amino acid tyrosine produced by

species of the Clostridia genus. This byproduct may be important for

two reasons: First, dietary tyrosine which is the raw material for

the production of the neurotransmitters dopamine and norepinephrine

may be diverted into the production of these microbial compounds so

that there is not enough tyrosine available for neurotransmitters.

Second, these compounds may act as inhibitors of neurotransmitter

production or metabolism. Elevated values are common in autism,

depression, schizophrenia, seizures, and in chronic fatigue

syndrome. This compound is reduced by treatment with vancomycin,

Flagyl (metronidazole), an herbal product called Biocidin, and by

probiotics.

Krebs Cycle

Succinic acid – A Krebs cycle compound that may be elevated due to a

deficiency or riboflavin or coenzyme Q-10. Values greater than 50

mmol/mol creatinine may be due to genetic diseases. High values may

also be due to bacterial conversion of glutamine to succinic acid in

the gastrointestinal tract.

Fumaric acid - A Krebs cycle compound produced by the dehydrogenation

of succinic acid by the enzyme succinic acid dehydrogenase.

2-oxoglutaric acid – A Krebs cycle compound that is also called alpha-

ketoglutaric acid. 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

improvement of some autistic symptoms are associated with low values.

Aconitic, Citric – These Krebs cycle compounds may be elevated due to

a deficiency of glutathione since the enzyme aconitase requires

reduced glutathione.

Neurotransmitters

HVA – A metabolite of the neurotransmitter dopamine. Elevated values

are encountered in the tumors neuroblastoma, ganglioblastoma, and

pheochromacytoma. Values may also be elevated due to L-DOPA

administration or after IV dopamine drips.

VMA – Elevated values are found in the tumors pheochromacytoma,

neuroblastoma, ganglioneuroma, and carcinoid tumors. May be elevated

after catecholamine L-DOPA administration.

5-hydroxyindoleacetic acid – A metabolite of tryptophan that is

commonly elevated in carcinoid syndrome, celiac sprue, tropical

sprue, Whipple's disease, oat cell carcinoma of the bronchus, and in

bronchial adenoma of carcinoid type. May be elevated to intake of

foods high in hydroxyindoles such as walnuts, bananas, avocados,

eggplants, pineapples, plums and tomatoes. Low values may be found

in depressive illnesses, small intestine resection, mastocytosis,

PKU, and Hartnup's disease.

Pyrimidines

Uracil – A pyrimidine (DNA building block) that is elevated in the

genetic disease dihydropyrimidine dehydrogenase deficiency. In this

genetic disease, the pyrimidine thymine is also elevated. Elevations

of uracil and orotic acid are found in the genetic diseases OTC

deficiency and citrullinemia.

Thymine – Thymine is a pyrimidine (DNA building bock) that is

elevated in the genetic disease dihydropyrimidine dehydrogenase

deficiency. In this genetic disease, the pyrimidine uracil is also

elevated.

Miscellaneous

Glycolic – Elevated glycolic may be due to the genetic disease

hyperoxaluria type I, if oxalic acid is also elevated. Elevated

glycolic without elevated oxalic is most likely a result of GI yeast

overgrowth.

Oxalic – Elevated values may be due to 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 rhubarbs, strawberries, spinach, and tomatoes, and

increased vitamin C intake. Hyperoxaluria type I is associated with

elevated glycolic acid while hyperoxaluria type II is associated with

elevated glyceric acid.

Malonic – Elevated values may be associated with the genetic disease

malonyl CoA decarboxylase deficiency.

Methylglutaric – Elevated values may be associated with the genetic

deseases 3-hydroxy-3-methylglutaric aciduria and in 3-

methylglutaconic aciduria.

Hippuric - Hippuric acid is a conjugate of benzoic acid and glycine

formed in the liver. Hippuric acid may be elevated due to bacteria

overgrowth of the GI tract. Benzoic acid formed in the

gastrointestinal tract by bacteria is absorbed into the portal

circulation. In the liver, it is conjugated with the amino acid

glycine to form benzoylglycine (huppuric acid). Other sources that

increase benzoic acid are the solvent toluene and the food

preservative sodium benzoate. Toluene exposure may occur due to

industrial exposure or due to out gassing from new carpets. Low

values of hippuric acid may be due to depletion of glycine die to

competing detoxification reactions or due to low amounts of bacteria

after antibiotic use.

4-hydroxybutyric – Elevated values indicate the rare genetic disease

3-methylglutaconic aciduria or after the intake of the muscle builder

4-hydroxybutyric (also called gamma-hydroxybutyric acid) which can

cause severe myalgia or death.

Phenylcarboxylic –Elevated values indicate overgrowth of GI bacteria

Indole-like compound - Most likely derived from tryptophan. Elevated

values indicate overgrowth of GI bacteria and is commonly elevated

along with 3-indoleacetic.