Kurt Woeller DO

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. 

References

  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.

Clostridia difficile - The Role of Toxin A and B in its Pathogenicity

Kurt Woeller, DO

There are approximately 100 species of clostridia bacteria that can inhabit the gastrointestinal tract of humans. Not all of these clostridia are disease causing, but a certain few can lead to serious illness in susceptible individuals. There are 5 main species of clostridia known to cause disease: Clostridia botulinum, Clostridia perfringens, Clostridia tetani, Clostridia sordellii, and Clostridia difficile. This article will focus on the role of Clostridia difficile (C. difficile), and its production of various gastrointestinal toxins in human illness.

What Are Clostridia Bacteria?
Clostridia difficile, like all clostridia bacteria, is an obligate anaerobe. This means it is an organism that thrives in an oxygen devoid environment and is susceptible to being killed by normal atmospheric oxygen. It is unique in its ability to survive in hostile environments in part because of its spore development. Clostridia spores, the reproductive cell of clostridia, have thick cell walls which resist heat and antimicrobial compounds. These spores of clostridia are highly contagious and can be spread person to person even from individuals without symptoms of clostridia overgrowth.

C. difficile is a complex species of clostridia because of the various toxins it can produce. There are certain strains of C. difficile that produce compounds known to alter mitochondrial function by interfering with various steps in Kreb Cycle metabolism decreasing the amount of nicotinamide adenine-dinucleotide (NADH) used by the electron transport chain for adenosine-triphosphate (ATP) production (1). Other C. difficile strains create neurochemical compounds that disrupt dopamine production leading to various issues with regards to mental health. However, the most commonly known toxins produced by C. difficile are those that disrupt gastrointestinal function and in some individuals can lead to serious health problems.

The Prevalence of C. difficile Associated Disease
The rates of C. difficile infections leading to serious illness and death have been on the rise. According to the Centers for Disease Control even as recent as 2011 there were approximately 450,000+ documented case of Clostridium difficile infections (CDI) and upwards of 29,000 deaths (2). A large number of individuals who have an initial episode of CDI will develop at least one recurrence of the disease. The recurrence rates for CDI are high, in part because of the complex nature of C. difficile, and its spore forms that resist antibiotic intervention.

One of the problems with C. difficile is that not only can it lead to serious illness in susceptible individuals, but that it can be found in people, even children, who may not necessarily be suffering with primary issues related to C. difficile. For example, a paper in 2010 out of Poland (3) discussed the prevalence of C. difficile in fecal samples taken from 178 children ages 2 months to 2 years who were hospitalized for a variety of reasons. Their stools where examined for the presence of C. difficile Toxin A and B, the two main intestinal toxins known to trigger chronic diarrhea and bowel inflammation. The percentage of children infected with C. difficile was 68.6% and many of these children were not acutely sick from C. difficile. However, as mentioned previously, toxin A and toxin B from certain strains of C. difficile can lead to serious problems.

The Role of Toxin A and Toxin B
These two toxins are the main virulence factors related to mucosal damage from C. difficile. Toxin A and B are capable of causing mucosal damage resulting in digestive tract inflammation leading to either clostridia difficile associated diarrhea (CDAD) or Pseudomembranous colitis (4).

Toxin A is categorized as an enterotoxin, which means it is a toxin released by microorganisms that target the digestive system. It functions by changing host cell metabolism and tight junction formation. This can lead to mucosal cell damage, fluid accumulation and even cell death. Toxin A is considered to be the main cause of CDAD as it causes intestinal villi and brush border destruction. In severe cases of Toxin A production, it can lead to ulceration formation seen in Pseudomembranous colitis.

Pseudomembranous colitis is a type of inflammatory bowel disease of the colon that manifests with various ulcerations from mucosal damage and the development of a “pseudo” membrane (aka. ‘inflammatory membrane’), that overlays the site of mucosal injury. This inflammatory membrane is an accumulation of fibrin and inflammatory and necrotic cells that appear as a yellowish globule spread throughout the colon. In the late 1970s it was determined that C. difficile via the production of various toxins, was the causative organism for Pseudomembranous colitis.

Like Toxin A, Toxin B also plays a significant role in damage to the mucosal lining of the digestive system. Toxin B is categorized as a cytotoxin which means it is toxic to cells. Examples of cytotoxins would be chemicals produced by the immune system that damage other cells in the body. Bee venom, as well as poisons from spiders or snakes, are all classified as cytotoxins.

Toxin B causes major cellular disruption by interfering with signaling pathways, tight junction formation, formation of the cytoskeleton of the cell, and derangement of overall cell structure. It is a major virulence factor of C. difficile leading to vascular swelling and hemorrhaging. Also, Toxin B can not only have local inflammatory effects in the digestive system, but also systemic effects through its production of proinflammatory cytokines such as Tumor Necrosis Factor-αlpha.

It was felt for many years that serious bowel inflammation from C. difficile was generated by a single toxin, but both toxins are now known to be capable of causing mucosal damage.

Treatment and Testing
Treatment of C. difficile infections are mostly done by antibiotics. The two most common antibiotics are oral Flagyl (metronidazole) and oral Vancomycin (vancocin). Traditional intervention calls for 7 to 10 days of either antibiotic. As mentioned previously recurrence rates for C. difficile can be high, primarily because of C. difficile spore formation. There is a trend in C. difficile treatment to use cyclical courses of either antibiotic to aide in reduction of recurrence rates and increase clinical outcomes.

Stool testing for C. difficile is effective and is used as a primary diagnostic tool analyzing for the presence of Toxin A and Toxin B. Prior to stool testing direct visualization of inflammatory membranes was used through colonoscopy or sigmoidoscopy.

If either Toxin A or B is detected on stool pathogen screening the practitioner needs to correlate the information to the clinical presentation of the individual and treat accordingly or refer to a specialist for further evaluation. Not everyone with C. difficile will be symptomatic of intestinal disease so each situation needs to be evaluated individually. However, the presence of Toxin A or Toxin B found on stool pathogen testing certainly documents the presence of a strain of C. difficile. The individual should be treated appropriately.

Dr. Kurt N. Woeller is an author, international speaker, practicing clinician and founder of Integrative Medicine Academy (www.IntegrativeMedicineAcademy.com), which is an online training academy that provides various courses for health practitioners interested in integrative medicine.


REFERENECS

1.      Richard E. Frye, et. al. Gastrointestinal dysfunction in autism spectrum disorders: the role of the mitochondria and the enteric microbiome. Microbial Ecology in Health and Disease. Volume 26, 2015.

2.      Lessa, FC, et.al. Burden of Clostridium difficile infection in the United States. N. Engl J Med, 2015;372:825-834.

3.      Prevalence of Clostridium difficile in the gastrointestinal tract of hospitalized children under two years of age. Med Dosw Mikrobiol; 2010;62(1):77-84 (Poland).

4.      (Kuehne SA, Cartman ST, Heap JT, Kelly ML, Cockayne A, Minton NP; October 2010. "The role of toxin A and toxin B in Clostridium difficile infection". Nature 467 (7316): 711–3.