Concentrations of the dopamine metabolite homovanillic acid, or HVA, have been reported to be much higher in the urine of children with autism compared to controls. In the same study, severity of autism symptoms was directly related to the concentration of HVA. There was a relation between the urinary HVA concentration and increased agitation, stereotypical behaviors, and reduced spontaneous behavior. Furthermore, vitamin B6, which has been shown to decrease autistic symptoms, decreases urinary HVA concentrations. Excess dopamine has been implicated in the etiology of psychotic behavior and schizophrenia for over 40 years. Drugs that inhibit dopamine binding to dopaminergic receptors have been some of the most widely used pharmaceuticals used as antipsychotic drugs and have been widely used in the treatment of autism. Recent evidence reviewed below indicates that dopamine in high concentrations may be toxic to the brain.

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Dopamine is a very reactive molecule compared with other neurotransmitters, and dopamine degradation naturally produces oxidative species (Figure 1). More than 90 percent of dopamine in dopaminergic neurons is stored in abundant terminal vesicles and is protected from degradation. However, a small fraction of dopamine is cytosolic, and it is the major source of dopamine metabolism and presumed toxicity. Cytosolic dopamine (Figure 1) undergoes degradation to form 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) via the monoamine oxidase pathway. Alternatively, dopamine undergoes oxidation in the presence of excess iron or copper (common in autism and schizophrenia) to form dopamine cyclized o-quinone, which is then converted to dopamine cyclized o-semiquinone, depleting NADPH in the process. Dopamine cyclized o-semiquinone then reacts with molecular oxygen to form oxygen superoxide free radical, an extremely toxic oxidizing agent. In the process, dopamine cyclized o-quinone is reformed, resulting in a vicious cycle extremely toxic to tissues producing dopamine, including the brain, peripheral nerves, and the adrenal gland.

 It is estimated that each molecule of dopamine cyclized o-quinone produces thousands of molecules of oxygen superoxide free radical in addition to depleting NADPH. The o-quinone also reacts with cysteine residues on glutathione or proteins to form cysteinyl-dopamine conjugates (Figure 1). One of these dopamine conjugates is converted to N-acetylcysteinyl dopamine thioether, which causes apoptosis (programmed cell death) of dopaminergic cells. These biochemical abnormalities cause severe neurodegeneration in pathways that utilize dopamine as a neurotransmitter. Neurodegeneration is due to depletion of brain glutathione and NADPH as well as the overproduction of oxygen superoxide free radicals and neurotoxic N-acetylcysteinyl dopamine thioether. In addition, the depletion of NADPH also results in a diminished ability to convert oxidized glutathione back to its reduced form.

What is the likely cause of elevated dopamine in autism? A significant number of studies have documented increased incidence of stool cultures positive for certain species of Clostridia bacteria in the intestine in children with autism using culture and PCR techniques. All these studies have indicated a disproportionate increase in various Clostridia species in stool samples compared to normal controls. In addition, metabolic testing has identified the metabolites 3-(3-hydroxyphenl)-3-hydroxypropionic acid (HPHPA) and 4-cresol from Clostridia bacteria at significantly higher concentrations in the urine samples of children with autism and in schizophrenia.

Treatment with antibiotics against Clostridia species, such as metronidazole and vancomycin, eliminates these urinary metabolites with reported concomitant improvement in autistic symptoms. In addition, I had noticed a correlation between elevated HPHPA and elevated urine homovanillic acid (HVA). The probable mechanism for this correlation is that certain Clostridia metabolites have the ability to inactivate dopamine beta-hydroxylase, which is needed for the conversion of dopamine to norepinephrine (Figure 2).

Figure 2. Effect of  Clostridia  metabolites on human catecholamine metabolism. DHPPA, 4-cresol, HPHPA, HVA, and VMA are all measured in The Great Plains Laboratory organic acid test.

Figure 2. Effect of Clostridia metabolites on human catecholamine metabolism. DHPPA, 4-cresol, HPHPA, HVA, and VMA are all measured in The Great Plains Laboratory organic acid test.

Such metabolites are not found at only trace levels. The concentration of the Clostridia metabolite HPHPA in children with autism may sometimes exceed the urinary concentration of the norepinephrine metabolite vanillylmandelic acid (VMA) by a thousand fold on a molar basis and may be the major organic acid in urine in those with severe gastrointestinal Clostridia overgrowth, and even exceed the concentration of all the other organic acids combined. Dopamine beta hydroxylase that converts dopamine to norepinephrine in serum of severely retarded children with autism was much lower than in those who were higher functioning. Decreased urine output of the major norepinephrine metabolite meta-hydroxyphenolglycol (MHPG) was decreased in urine samples of children with autism, consistent with inhibition of dopamine beta hydroxylase.

Many physicians treating children with autism have noted that the severity of autistic symptoms is related to the concentration of the Clostridia marker 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) in urine. These are probably the children with autism with severe and even psychotic behavior treated with Risperdal® and other anti-psychotic drugs, which block the activation of dopamine receptors by excess dopamine. I have identified a number of species of Clostridia species that produce HPHPA including C. sporogenesC.botulinumC. caloritoleransC. mangenotiC. ghoniC.bifermentansC. difficile, and C. sordellii. All species of Clostridia are spore formers and thus may persist for long periods of time in the gastrointestinal tracts even after antibiotic treatment with oral vancomycin and metronidazole.

How do the changes in brain neurotransmitters caused by Clostridia metabolites alter behavior? The increase in phenolic Clostridia metabolites common in autism significantly decreases brain dopamine beta hydroxylase activity. This leads to overproduction of brain dopamine and reduced concentrations of brain norepinephrine, and can cause obsessive, compulsive, stereotypical behaviors associated with brain dopamine excess and reduced exploratory behavior and learning in novel environments that are associated with brain norepinephrine deficiency. Such increases in dopamine in autism have been verified by finding marked increases in the major dopamine metabolite homovanillic acid (HVA) in urine. The increased concentrations of HVA in urine samples of children with autism are directly related to the degree of abnormal behavior. The concentrations of HVA in the urine of some children with autism are markedly abnormal.

In addition to alteration of brain neurotransmitters, the inhibition of the production of norepinephrine and epinephrine by Clostridia metabolites may have a prominent effect on the production of neurotransmitters by the sympathetic nervous system and the adrenal gland. The major neurotransmitter of the sympathetic nervous system that regulates the eyes, sweat glands, blood vessels, heart, lungs, stomach, and intestine is norepinephrine. An inadequate supply of norepinephrine or a substitution of dopamine for norepinephrine might result in profound systemic effects on physiology. The adrenal gland which produces both norepinephrine and epinephrine might also begin to release dopamine instead, causing profound alteration in all physiological functions. In addition to abnormal physiology caused by dopamine substitution for norepinephrine and dopamine, dopamine excess causes free radical damage to the tissues producing it, perhaps leading to permanent damage of the brain, adrenal glands, and sympathetic nervous system if the Clostridia metabolites persist for prolonged periods of time, if glutathione is severely depleted, and if there is apoptotic damage caused by the dopamine metabolite N-acetylcysteinyl dopamine thioether.

Depletion of glutathione can be monitored in The Great Plains Laboratory organic acid test by tracking the metabolite pyroglutamic acid, which is increased in both blood and urine when glutathione is depleted. In addition, The Great Plains Laboratory also tests the other molecules involved in this toxic pathway, the dopamine metabolite homovanillic acid (HVA), the epinephrine and norepinephrine metabolite VMA and the Clostridia metabolites HPHPA and 4-cresol.

In summary, gastrointestinal Clostridia bacteria have the ability to markedly alter behavior in autism and other neuropsychiatric diseases by production of phenolic compounds that dramatically alter the balance of both dopamine and norepinephrine. Excess dopamine not only causes abnormal behavior but also depletes the brain of glutathione and NADPH and causes a vicious cycle producing large quantities of oxygen superoxide that causes severe brain damage. Such alterations appear to be a (the) major factor in the causation of autism and schizophrenia. The organic acid test (see sample organic acid test report below) now has the ability to unravel a major mystery in the causation of autism, schizophrenia, and other neuropsychiatric diseases, namely the reason for dopamine excess in these disorders.

In the past, some physicians would order the organic acid test once a year or less. With the new knowledge of the mechanism of Clostridia toxicity via inhibition of dopamine beta-hydroxylase, it seems that the control of such toxic organisms needs to monitored much more frequently to prevent serious brain, adrenal gland, and sympathetic nervous system damage caused by excess dopamine and oxygen superoxide. Below is a test report of a child with autism tested with The Great Plains Laboratory Organic acid test.

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In the graph above, the vertical bar is the upper limit of normal and the patient’s value is plotted inside a diamond (red for abnormal, black for normal). The above results were from a boy with severe autism. The HPHPA Clostridia marker was very high (979 mmol/mol creatinine), about 4.5 times the upper limit of normal. However, the metabolite due to Clostridium difficile was in the normal range, indicating that Clostridium difficile was unlikely to be the Clostridium bacteria producing the high HPHPA. In other words, a different Clostridia species was implicated. The major dopamine metabolite homovanillic acid (HVA) was extremely high (87 mmol/mol creatinine), almost 7 times the upper limit of normal. The major metabolite of epinephrine and norepinephrine, VMA was in the normal range. The HVA/VMA ratio was 15, more than five times higher than the upper limit of normal, indicating a severe imbalance in the production of epinephrine/norepinephrine and that of dopamine. The very high dopamine metabolite, HVA, indicates that the brain, adrenal glands, and sympathetic nervous system may be subject to severe oxidative stress due to superoxide free radicals and that brain damage due to severe oxidative stress might result if the Clostridia bacteria are left untreated. Below the same patient’s results are displayed in a form that is related to the metabolic pathways. This graphical result now appears on all organic acid results from The Great Plains Laboratory, Inc.

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  1. Shaw W. Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia. Nutr Neurosci. 2010 Jun;13(3):135-43.

The Clinical Significance of Organic Acids Testing to Mental Health – How Fungal, Bacterial, Mitochondrial, and Other Test Markers Influence the Brain

Kurt Woeller, D.O.

Organic acids testing is diagnostic tool that every healthcare practitioner should know about.  Whether you are a family practitioner, psychiatrist, a nutritionist, or other type of practitioner, the information provided by organic acids testing can help identify underlying causes of a variety of chronic illnesses, including the symptoms of autism, neuropsychiatric disorders like depression and anxiety, and neurodegenerative disorders like Alzheimer’s disease.  Below is a review of some of the most clinically significant markers measured with organic acids testing to mental health and the health of the brain in general. 

Many of the case studies reviewed in presentations about organic acids testing involve patients with autism.  While autism may not typically be considered a mental health disorder, it is a neurodevelopmental disorder and many autistic individuals suffer with mental symptoms such as anxiety and depression, along with associated behavioral problems.  Many patients with autism also have mitochondrial dysfunction and chronic infections (like Candida and clostridia), which are measured with organic acids testing. (1)

Mitochondria are linked to every organ system in the body, including the brain, and there markers for mitochondrial function in organic acids testing. Without adequate mitochondrial function, neurons cannot function appropriately to produce neurochemicals such as dopamine and serotonin.  Mitochondria are damaged by various endogenous toxins produced by Candida (a fungus) such as tartaric acid and citramalic acid. Also, certain clostridia bacteria produce propionic acid which damages mitochondria. Candida and clostridia are both measured with organic acids testing.  Mitochondria are also damaged by oxalate, which is produced by Candida and some molds, and is also measured with organic acids testing. Certain molds like Aspergillus produce mycotoxins which directly damage mitochondria. Organic acids testing specifically measures candida toxins, bacteria toxins, and mold toxins, along with mitochondria markers. (2, 3)

Clostridia bacteria can produce various compounds like HPHPA, 4-Hydroxyphenylacetic acid and 4-Cresol (all measured with organic acids testing), and are known to inhibit dopamine metabolism. These chemicals inhibit Dopamine-Beta Hydroxylase which causes neuronal dopamine levels to rise. This has been associated with paranoia and schizophrenia. Also, the breakdown products of dopamine are neurotoxic and cause brain receptor damage.  Chronic infections and the compounds produced from them such as bacteria lipopolysaccharides (LPS), along with elevated cortisol (seen in hypothalamic-pituitary-adrenal dysfunction), viral infections, and beta-amyloid and niacin deficiency (seen in schizophrenia) can trigger tryptophan metabolism problems. Tryptophan is the amino acid precursor to serotonin. In the presence of these chronic stressors, tryptophan conversion to serotonin is reduced. This can lead to depression and anxiety. Elevated tryptophan metabolites can lead to increased quinolinic acid (QA).  (4)

Quinolinic acid is neurotoxic and measured with organic acids testing. It is an NDMA receptor agonist, which is linked to various mental health disorders (anxiety, depression, suicidal ideation) and chronic neurodegenerative diseases (Alzheimer’s, Huntington’s). Quinolinic acid can also block acetylcholine production (linked to memory) and gamma-amino-butyric acid (which can trigger anxiety and panic). (5)

The aforementioned markers in organic acids testing are some of the most clinically significant to mental health and brain function, though there are many other examples.  This information is critical for mental health professionals to help deepen their knowledge about sophisticated testing and advanced solutions for patient intervention. 


  1. Shaw, W., et. al. Increased Urinary Excretion of Analogs of Krebs Cycle Metabolites and Arabinose in Two Brothers with Autistic Features. Clin Chem 41:1094-1104, 1995.
  2. Shaw, W., et. al. Assessment of antifungal drug therapy in autism by measurement of suspected microbial metabolites in urine with GC/MS. Clinical Practice of Alternative Medicine: 15-26.
  3. Persico AM, et. al. Urinary p-cresol in autism spectrum disorders, Neurotoxicol Teratol. 2013 Mar-Apr;36:82-90, 2012 Sep 10.
  4. Heyes MP, et. al. A mechanism of quinolinic acid formation by brain in inflammatory neurological disease. Attenuation of synthesis from L-tryptophan by 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate. Brain. 1993 Dec;116 (pt 6):1425-50.
  5. Ganiyu Oboh, et. al. Anticholinesterase and Antioxidative Properties of Aqueous Extract of Cola acuminata Seed In Vitro. Int J Alzheimers Dis. 2014; 2014: 498629.

A New Generation of Organic Acid Testing: Pushing the Limits of Detection with New Technology

Shaw, William Ph.D

More than 50 phenotypically different organic acidemias have been discovered since the first known disease of this type, isovaleric academia, was described in 1966. An organic acid is any compound that generates protons at the prevailing pH of human blood. Although some organic acidemias result in lowered blood pH, other organic acidemias are associated with relatively weak organic acids that do not typically cause acidosis.

Organic acidemias are disorders of intermediary metabolism that lead to the accumulation of toxic compounds that derange multiple intracellular biochemical pathways, including glucose catabolism (glycolysis), glucose synthesis (gluconeogenesis), amino acid and ammonia metabolism, purine and pyrimidine metabolism, and fat metabolism. The accumulation of an organic acid in cells and fluids (plasma, cerebrospinal fluid, or urine) leads to a disease called organic academia, or organic aciduria.

Although this technology has commonly been used for diagnosing genetic disease in children, genetic diseases in adults have also been detected with it. New applications of organic acid testing include detection of factors in psychiatric disorders, mitochondrial disease and dysfunction, and exposure to a wide variety of toxic chemicals from the environment, and assessment of inflammation due to overproduction of quinolinic acid from tryptophan.

Testing now includes markers for the following metabolites:

  • Glycolysis
  • Krebs Cycle
  • Amino acid Metabolism
  • DNA, RNA metabolism
  • Neurotransmitter metabolism
  • Organophosphate metabolism
  • Yeast, fungal markers
  • Markers for beneficial bacteria
  • Oxalate markers for kidney stones, genetic disease
  • Specific marker for ammonia toxicity
  • Markers of fatty acid catabolism
  • Metabolic diseases causing autism spectrum disorders
  • Phthalates
  • Solvents
  • Pyrethrins
  • Dry cleaning solvents
  • Preservatives
  • Vinyl chloride
  • Specific Clostridia marker
  • Specific mitochondrial disease markers
  • Vitamin deficiency markers
  • Phosphate marker of bone function
  • Marker for glutathione precursor
  • Genetic screening with extremely sensitive markers

Organic acids are most commonly analyzed in urine because they are not extensively reabsorbed in the kidney tubules after glomerular filtration. Thus, organic acids in urine are often present at 100 times their concentration in the blood serum and thus are detected in urine with greater accuracy and precision than with blood samples. The number of organic acids found in urine is enormous: over 1000 have been detected since this kind of testing started 25 years ago. The challenge of dealing with so many compounds led to the use of gas chromatography-mass spectrometry (GC/MS) to analyze these complex body fluids.

With GC/MS, organic acids are chromatographically separated on the basis of their polarity and volatility and then bombarded by an electron beam that fragments the eluting molecules in a characteristic pattern. The patterns, or spectra, are stored by a computer system and then compared with known spectra that are compiled in a spectral "library." The software then compares an unknown spectrum to all the spectra on the hard drive and prints out those with the best fit. Since a single organic acid analysis generates over 1000 spectra, and each spectrum may consist of 600 ions, the software must be optimized to analyze the data in the most efficient and clinically relevant manner. Recently, the Great Plains Laboratory Inc. increased the sensitivity of this technology by approximately 1000-fold with the use of new triple-quadrupole MS technology so that a large number of toxic compounds can be measured at levels of micromoles/mole creatinine compared with urine compounds, such as vanillylmandelic (VMA), which is measured at levels of millimoles/mole creatinine.

The scope of organic acid testing has been markedly widened by commercial laboratories such that it can monitor physiological changes in nongenetic diseases and offer tremendous help in diagnosis and treatment of most chronic illnesses. Some examples are given below:

An adult with a movement disorder and bilateral temporal arachnoid cysts by brain imaging was found to have very elevated glutaric acid, indicating the presence of the genetic disease glutaric aciduria type 1.1Symptoms of this potentially fatal disorder include headaches, ataxia, memory loss, and many other neurological effects. Treatment with high doses of carnitine may be helpful in relieving symptoms in such cases, and of course such information is important for genetic counseling.

High levels of urine oxalates in an adult with frequent kidney stones led to a closer examination of the patient's dietary history. The patient ate a large spinach salad with pecans almost every day. Spinach is one of the foods highest in oxalates, and all nuts are high in oxalates as well. Treatment is directed at reducing dietary oxalates as well as calcium citrate and vitamin B6 supplementation.

After organic acid testing, a child with autism was found to have very high values (more than four times the upper limit of age-appropiate normals) of the catecholamine metabolites VMA and HVA, indicating a possible neuroblastoma. Follow-up imaging near the spine confirmed the presence of a previously undiagnosed neuroblastoma, likely saving the child's life.

Another child thought to have autism had very low amino acids, and the neurologist recommended high doses of amino acid supplements, which made the child severely ill. Organic acid testing revealed a massive excretion of methylmalonic acid, indicating that the child had methlmalonic aciduria, a severe genetic disorder. Treatment of this disorder requires extensive supplementation with vitamin B12 and a low-protein diet. Continued amino acid supplementation or a high-protein diet might have been fatal.

A person with severe depression was found to have low amounts of the serotonin metabolite 5-hydroxy-indoleacetic acid, which is derived from tryptophan. Depression is associated with decreased brain serotonin. However, the tryptophan metabolite by an alternate pathway, quinolinic acid, was much higher. Quinolinic acid is associated with inflammation such as arthritis and is considered to be neurotoxic, with a probable role in Parkinson's syndrome, Alzheimer's disease, Huntington's disease, and schizophrenia.2,3 The condition eosinophilia myalgia syndrome (EMS), associated with excessive tryptphan intake, is probably not due to tryptophan itself but to the inflammatory effects of its major metabolite quinolinic acid. Quinolinc acid administered by itself generated all of the symptoms of EMS.4,5 This research indicates that various conspiracy theories about contaminated tryptophan batches as the cause of EMS are unnecessary and probably wrong. 100% pure tryptophan at high enough doses will produce significant quantities of toxic quinolinic acid and EMS in susceptible individuals. Administration of 5-hydroxytryptophan (5-HT or 5-HTP) is a much safer option than tryptophan since 5-HT cannot be converted to the neurotoxic quinolinic acid, whereas only about 1% of tryptophan is converted to serotonin.6 Both the serotonin metabolite and quinolinic acid are measured by organic acid testing (Figure 1).

I recently proved that the dibiosis marker 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), the predominant dihydroxy-phenylpropionic acid isomer in urine measured in the organic acid test, is due to a combination of human metabolism and the metabolism by a group of Clostridia species, including but not limited to C. difficile.7 The same article indicates that 3,4-dihydroxyphenylpropionic acid (DHPPA) is a marker for beneficial bacteria in the gastrointestinal tract such as Lactobacilli, Bifidobacteria, and E. coli. The exception is one species of Clostridia orbiscindens that can convert the flavonoids luteolin and eriodictyol (which occur only in a relatively small food group that includes parsley, thyme, celery, and sweet red pepper) to DHPPA. The quantity of C. orbiscindens in the gastrointestinal tract is negligible (approximately 0.1% of the total bacteria) compared with the predominant flora of Lactobacilli, Bifidobacteria, and E. coli.7 DHPPA is an antioxidant that lowers cholesterol, reduces proinflammatory cytokines, and protects against pathogenic bacteria.

Outdated literature has referred to HPHPA as due to dietary origin based mainly on conjecture, but this conjecture was clearly disproved by my 2010 article which indicates that the metabolite is abolished by the antibiotic metronidazole.8 DHPPA, a different isomer, has been claimed to be a metabolite of Pseudomonas species, but the literature indicates that this compound is formed by the in vitro action of these species on quinolone, a component of coal tar – a substance missing from the diet of virtually all humans.9

HPHPA has been one of the most useful clinical markers in recent medical history. Treatment of individuals with high urinary values with metronidazole, vancomycin, or high doses of probiotics has led to significant clinical improvements or remissions of psychosis, tic disorders, seizures, autistic behaviors, hyperactivity, chronic fatigue syndrome, and obsessive compulsive behavior.

One of the newest aspects of organic acid testing is the screening for 74 different toxic chemicals in the environment by testing their organic acid metabolites. Solvents such as benzene, toluene, styrene, and others may be present for only short periods in body fluids and may also be lost in transit due to their volatility, but their metabolites are very stable. Using this screening technique, most metabolites of different organophosphates and pyrethrins can be measured as well as trichloroethylene, tetrachloroethylene, and vinyl chloride. Phthalates, an extremely toxic group of compounds implicated in infertility and abnormal sexual development in both males and females, can be measured by their metabolite phthalate, a specific chemical entity.

The chemical structure of phthalic acid (or phthalates) is nearly identical to quinolinic acid. A toxic effect occurs when phthalic acid competitively inhibits the reaction by which quinolinic acid is converted to the beneficial coenzyme NAD. High concentrations of phthalic acid or quinolinic acid may be associated with increased toxicity due to phthalate blockage of NAD formation and potential mitochondrial dysfunction due to deficient NAD for mitochondrial energy production.

One of the most important advances in the organic acid test is the addition of a biochemical marker, tiglylglycine, as a specific indicator for mitochondrial dysfunction.11 Mitochondrial dysfunction has been implicated in Parkinson's and Alzheimer's syndromes, diabetes, autism, chronic fatigue syndrome, aging, and many others. Tiglylglycine has been shown to be elevated in the urine in mitochondrial disorders involving defects of complexes I, II, III, and IV, protein complexes attached to the mitochondrial membrane that are involved in energy production. In addition to mutations in mitochondrial or nuclear DNA, mitochondrial dysfunction may also be due to exposures to toxic chemicals such as organophosphates and the solvent trichloroethylene. The advantage of the organic acid test is that if a mitochondrial dysfunction is detected, a number of different toxic chemicals implicated in mitochondrial damage can be reviewed to find the potential cause. Trichloroethylene has been found as a contaminant in the municipal water supply of many cities in both the US and Canada, and is used as a degreaser military bases and as a common solvent throughout the chemical industry. Mitochondrial disorders can be treated with a cocktail of nutritional substances including coenzyme Q10, carnitine, riboflavin, and others, when chemical exposure is not detected. If toxic chemicals are found, treatment with the Hubbard protocol can be highly successful for the removal of a wide array of toxic substances.12

Clinical References:

  • 1. Martinez-Lage J et al. Macrocephaly, dystonia, and bilateral temporal arachnoid cysts: glutaric aciduria type 1. Childs Nerv Sys. 1994;10(3): 198-203.
  • 2. Guillemin GJ et al. Quinolinic acid in the pathogenesis of Alzheimer's disease. Adv Exp Med Biol. 2003;527:167-176.
  • 3. Stoy N et al. Tryptophan metabolism and oxidative stress in patients with Huntington's disease. J Neurochem. 20015;93:611-623.
  • 4. Silver RM et al. Scleroderma, fasciitis, and eosinophilia associated with the ingestion of tryptophan. N Engl J Med. 1990;322(13):874-881.
  • 5. Noakes R, Spelman L, Williamson R. Is the L-tryptophan metabolite quinolinic acid responsible for eosinophilic fasciitis? Clin Exp Med. 2006;6(2):60-64.
  • 6. Shah GM et al. Biochemical assessment of niacin efficiency among carcinoid cancer patients. Am J Gastroenterol. 2005;100:2307-2314.
  • 7. Shaw W. Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia species in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia. Nutr Neurosci. 2010;13(3):1-10.
  • 8. Kumps A, Duez P, Mardens Y. Metabolic, nutritional, latrogenic, and artifactual sources of urinary organic acids: a comprehensive table. Clin Chem. 2002,48:708-717.
  • 9. Shukla OP. Microbial transformation of quinolone by a pseudomonas sp. Appl Environ Microbiol. 1986;51(6):1332-1342.
  • 10. Fukuwatari T et al. Phthalate esters enhance quinolinate production by inhibiting alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarbocylase (ACMSD), a key enzyme of the tryptophan pathway. Toxicol Sci. 2004;81:302-308.
  • 11. Bennett M et al. Tiglylglycine excreted in urine in disorders of isoleucine metabolism and the respiratory chain measured by stable isotope dilution GC-MS. Clin Chem. 1994;40(10):1879-1833.
  • 12. Shaw W. The unique vulnerability of the human brain to toxic chemical exposure and the importance of toxic chemical evaluation and treatment in orthomolecular psychiatry. J Orthomol Med. 2010;25(3).