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From the Townsend Letter
July 2017

Kryptopyrroluria (aka Hemopyrrollactamuria) 2017:
A Major Piece of the Puzzle in Overcoming Chronic Lyme Disease

by Scott Forsgren, FDN-P and Dietrich Klinghardt, MD, PhD
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Dietrich Klinghardt, MD, PhDDietrich Klinghardt, MD, PhD, is a practicing physician in Woodinville, Washington with a focus on the treatment of chronic neurological conditions such as Lyme disease, autism, and CFIDS. In the years that he has treated patients with chronic infections, he has observed that, for many, recovery is often elusive. Patients may plateau or find that their recovery is stalled. In other cases, patients may not succeed in their attempts to rid the body of a particular toxic or infectious burden, such as in patients with long-standing or therapy-resistant, late-stage Lyme disease.
In looking for possible explanations as to why some patients struggle more than others to regain their health, co-author Klinghardt has found a high correlation between patients with chronic Lyme disease and those with kryptopyrroluria (KPU), or more precisely hemopyrrollactamuria (HPU). The condition is alternatively known as the "mauve factor" or "malvaria."
KPU may be an inherited condition, but it can also be induced by psychological trauma or chronic infections. Epigenetic influences such as intrauterine, birth, childhood, or transgenerational trauma may trigger KPU; other triggers may include a car accident, divorce or emotional trauma, and physical or sexual abuse. Chronic infections, such as Lyme disease, may themselves serve as a trigger for the condition.
The HPU complex is a biochemical marker and neurotoxic substance frequently identified in the urine of patients with autism, learning disabilities, alcoholism, substance abuse, schizophrenia, ADHD, Down syndrome, depression, bipolar disorders, and even criminal behavior. Some estimate the incidence of KPU to be 40-70% in schizophrenia, 50% in autism, 30% in ADHD, and 40-80% in alcoholism and substance abuse.
Based on testing with Klinisch Ecologisches Allergie Centrum (KEAC; in Holland, Klinghardt has found the incidence of KPU in Lyme disease to be 80% or higher; in patients with heavy metal toxicity (lead, mercury, aluminum, cadmium, and others) over 75%; and in children with autism over 80%. These are very significant percentages of the patient population with chronic illness that may benefit from a treatment program that addresses KPU. Healthy controls do not test positive for KPU.

In 1958, a psychiatric research program in Saskatchewan, Canada, led by Abram Hoffer, MD, PhD, the father of orthomolecular psychiatry, was looking for the possible biochemical origin of schizophrenia and a lab marker that would make it easier to identify affected individuals. One study involved evaluating the urine for certain chemical fractions and evaluating those of schizophrenic patients and those of normal controls. The effort yielded "the mauve factor," a specific substance that reliably allowed the examiners to identify the schizophrenic patients, as it was not found in the normal controls.
CoreBioticEarly on, the substance was known as "the mauve factor" due to the mauve color that was observed on the stained paper. It was then termed "kryptopyrrole", later identified as hydroxyhemopyrrolin-2-one (HPL). The researchers first called the disease associated with this condition "malvaria," but it was renamed by Dr. Carl Pfeiffer, MD, PhD to "pyrolleuria" which was, for no obvious reason, consistently spelled "pyrroluria" in later publications. Today, the condition is generally referred to as "pyroluria." In the 1970s, Dr. Pfeiffer created an assay for the condition and was able to show clinical improvement in positive patients with high doses of zinc and vitamin B6 (between 400 mg and 3,000 mg B6).

Associated Conditions
A partial list of conditions where KPU may be a factor include ADHD, alcoholism, autism, bipolar disorders, criminal behavior, depression, Down syndrome, epilepsy, heavy metal toxicity, learning disabilities, Lyme disease, multiple sclerosis, Parkinson's disease, schizophrenia, and, substance abuse. The items listed in bold are those in which Klinghardt has observed a connection to KPU in his patient population.

The KPU condition results in a significant loss of zinc, vitamin B6, biotin, manganese, arachidonic acid, and other nutrients from the body via the kidneys. There are many symptoms of KPU, which may result from deficiencies of these nutrients. Those in bold are tell-tale signs of the condition. Klinghardt finds that depression is often a leading symptom of the condition. Symptoms may include the following:

Abdominal tenderness
Abnormal fat distribution
Acne, allergy
Amenorrhea, irregular periods
Anxiety / Nervousness
Attention Deficit / ADHD
B6-responsive anemia
Cold hands or feet
Course eyebrows
Crime and delinquency
Delayed puberty, impotence
Emotional liability
Explosive or episodic anger
Hypoglycemia, glucose intolerance
Knee and joint pain
Light, sound, odor intolerance
Mood swings
Nail spots (Leukodynia)
Pale skin, poor tanning
Paranoia / Hallucinations
Perceptual disorganization
Poor breakfast appetite
Poor Dream Recall
Poor short-term memory
Stress intolerance
Stretch marks (striae)
Substance abuse
Tremor, shaking, spasms

Impact of Nutrient Loss
Elevated levels of HPL found in urine are the result of an abnormality in heme synthesis. Hemoglobin is the substance that holds iron in the red blood cells. Heme is also the principal building block of many enzymes involved in detoxification (cytochromes), enzymes involved in healthy methylation (MSR and CBS), and NOS – a significant enzyme in the urea/BH4-cycle. HPL is a byproduct of dysfunctional heme synthesis and can be identified in the urine. HPL binds to zinc, vitamin B6, biotin, manganese, arachidonic acid (omega-6), and other important compounds that, as a result, are excreted via the urine. This leads to a significant depletion of these nutrients throughout the body and to the synthesis of non-functioning or poorly functioning enzymes. Turning to the importance of zinc, vitamin B6, biotin, manganese, and arachidonic acid in the body, it becomes clear how widespread the problems may be that are created by this condition.
Zinc deficiency may result in emotional disorders, food allergies, insulin resistance, delayed puberty, rough skin, delayed wound healing, growth retardation, hypogonadism, hypochlorhydria, men-tal lethargy, short stature, diarrhea, stretch marks or striae (which may be misinterpreted as Bartonella in some patients with Lyme disease), white spots on the fingernails, reduction in collagen, macular degeneration, dandruff, skin lesions such as acne, hyperactivity, loss of appetite, reduced fertility and libido, transverse lines on the fingernails, defective mineralization of the bones leading to osteoporosis, and many others.
Zinc is a powerful antioxidant, and lower levels lead to an increase in oxidative stress. Lower levels are correlated with lowered glutathione, an important part of the detoxification system. Zinc is required to support proper immune function. "White blood cells without zinc are like an army without bullets," says Klinghardt.
Vitamin B6 deficiency is thought to be a rare occurrence. However, in those with KPU, this is not the case. B6 deficiency may lead to nervousness, insomnia, irritability, seizures, muscle weakness, poor absorption of nutrients, decrease of key enzymes and cofactors involved in amino acid metabolism, impairment in the synthesis of neurotransmitters, impairment in the synthesis of hemoglobin, seborrheic dermatological eruptions, confusion, and neuropathy. Like zinc, B6 is an antioxidant and correlates to levels of glutathione.
Biotin deficiency may be evidenced by rashes, dry skin, seborrheic dermatitis, brittle nails, fine or brittle hair, and hair loss. More importantly, however, it may be associated with depression, lethargy, hearing loss, fungal infections, muscle pain, and abnormal skin sensations such as tingling. Biotin is an important co-factor in the production of energy in the mitochondria. Biotin is essential for a healthy brain and nervous system. Biotin deficiency is associated with many aspects of the aging process.
Manganese deficiency may be associated with joint pain, inflammation, and arthritis. Deficiency may result in a change in hair pigment or a slowing of hair growth. It is essential for normal growth, glucose utilization, lipid metabolism, and production of thyroid hormone. It may be associated with diseases such as diabetes, dyslipidemia, Parkinson's disease, osteoporosis, and epilepsy.

Arachidonic acid (from omega-6) deficiency may lead to the impairment of white blood cell function, primarily the leukocytes, which may lead to one being more vulnerable to infection. It may lead to neuropathy, neural and vascular complications in preterm babies, skin eruptions, behavior changes, sterility in males, arthritic conditions, dry eyes, growth retardation, dry skin and hair, slow wound healing, hair loss, kidney dysfunction, heart beat abnormalities, and miscarriages.
When one considers the magnitude of potential health problems that may be present when a single condition leads to a deficiency in zinc, vitamin B6, biotin, manganese, arachidonic acid, and other nutrients simultaneously, the negative implications on health are almost endless.

KPU and Lyme Disease
Three possible origins of KPU are discussed in the literature: genetics, trauma, and chronic infections. The connection between KPU and many of the illnesses previously discussed has been known for quite some time. However, prior to Klinghardt's early work in treating Lyme disease, never before had a connection been observed or published between KPU and Lyme disease. This discovery has been a key for Klinghardt to return his patients to an improved state of health and wellness, and the changes he has observed have been profound.
Klinghardt has found that 4 of 5 patients with chronic or persistent Lyme disease test highly positive for this condition (when tested with KEAC). That suggests that 80% or more of patients with symptoms of chronic Lyme disease may benefit from a treatment protocol that addresses KPU.
Klinghardt finds that it is rare for a patient to have chronic symptomatic Lyme disease as an adult without the patient having developed KPU. He postulates that the biotoxins from microbes block one or more of the eight enzymes of heme synthesis. This leads to a significant loss of key minerals in the white blood cells, which effectively disarms cellular immunity.
In those where KPU was triggered by infection with Lyme organisms, Klinghardt has observed that the KPU is often an unstable form of the condition where there are times of higher levels of pyrroles being excreted and times when this is not observed. If a person has episodes of depression, these episodes generally correlate to times when pyrroles are being released in higher levels in the urine.
One young adult female struggling with Lyme for several years had severe multiple chemical sensitivities (MCS) that were not improved by any previous treatment. After starting the KPU protocol, she noticed improvements in her MCS for the first time since she became ill. Other patients with intractable chronic infections have experienced significant improvements in immune function and a resulting lowering of total microbial burden.
Klinghardt has observed numerous patients that have struggled to rid the body of parasitic infestations. In these patients, regardless of the interventions used, the patient continues to expel these parasites on an ongoing basis. Therapy-resistant infections are a hallmark sign of KPU. Klinghardt has found that once the KPU protocol is put in place, there is often swift resolution of long-standing infections and infestations. This includes patients who have failed years of antibiotic therapy for chronic or late-stage Lyme disease.
Sandeep Gupta, MD, from Australia has stated that parasites and pyroluria almost always go together. He has observed that almost every chronically unwell individual seems to have both; one opens the door to the other. Chronically low levels of zinc allow parasites to invade the mucosal layer of the gut. Parasites may then move to the liver and gallbladder. They interfere with mood, energy levels, and sleep. Addressing the parasites while restoring zinc and B6 often makes a tremendous difference in his patients.
Chronic Lyme disease patients often suffer from severe jawbone infections that may require cavitation surgery, which often tends to fail in this population. When the clients are pre-treated for KPU, the outcome of the surgical procedure is generally much better. In some mild cases, ozone treatment of the jaw may be sufficient to turn things around.
Klinghardt has followed the interest in HLA-DR genetic typing in regard to biotoxin illnesses such as Lyme disease and mold. Prior to KPU, patients with certain haplotypes were considered more difficult to treat as the body could not properly and effectively respond to and remove biotoxins from Lyme disease, molds, or in the worst cases, both. In his experience, once the KPU issue is addressed, these HLA types become far less of a concern in most patients and no longer hold them back on their road to regaining health.
Once bodily systems are back online and functioning properly, a few months after introducing the KPU protocol, patients become less vulnerable to Lyme disease, to mold, and even to heavy metals. Their bodies are now much better equipped to deal with these conditions when they have appropriate levels of zinc, vitamin B6, biotin, manganese, and arachidonic acid to support optimal functioning of numerous bodily processes.

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