Chronic Lyme & Tick-Borne Diseases Q & A


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How Our Program Works

When treating tick-borne disease there is more involved than simply trying to eradicate pathogens. Firstly, it is almost impossible to know all the pathogens which have invaded the body and it is equally difficult to determine which ones are responsible for what symptoms. 

Our approach assumes that a healthy body can defend itself against disease and that the natural tendency of our body is to heal. Unfortunately, many factors can interfere or even prevent the natural patterns of our body from taking place.

Using the five steps to health we can help the body find the balance it needs to heal.

Modulate Immune System

The immune system consists of an array of cells, which need to be present in a specific ratio to one another for the system to function in a coordinated fashion. An imbalance of immune sysytem occurs through mental and environmental stress, environmental challenges, inproper nutrition and  resulting chronic inflammation when total body burden exceeds individual capacity in the presence of poor nutrition.

Damage to the immune sysytem occurs whic monitors body's neuro-immune endocrine responses. Thymus  gland which monitors and    controls the immune cell ratios can also play an important role. By using immunotherapy and other trace elements, it is possible to help restore immune function and restore healthy ratios of the immune cells. This allows the immune system to detect and destroy microbes effectively.

Establish Homeostasis

To reestablish a healthy Homeostasis many steps are needed. When there is inflammation, the cells aref often deprived of oxygen. This hypoxic state interferes with many basic functions of the cell. Cells need glucose as food. In the mitochondria this glucose is converted into something called pyruvate. Pyruvate in needed to power the so-called Krebs cycle. The Krebs cycle is the powerhouse of the cell. Where there is a lack of oxygen, glucose is converted to lactate instead of pyruvate. This lack of pyruvate essentially suffocates the Krebs cycle. It prevents the cell performing its basic functions including ending its life through apoptosis. Apoptosis is necessary to protect our organism from being overtaken by abnormal or infected cells.

The conversion of pyruvate into lactate causing the cells to become acidic. This, in turn, has adverse effect on the electrical potential  of the cell surface. When electrical potential changes it makes it difficult for a cell to effectively absorb nourishment or to discharge its waste. The key to reestablishing homeostasis is to  maintain health of matrix.When homeostasis return to normal mitochondrial function returns to normal which sometimes take very long time when damage may be more . We give specific substances which in themselves  help to reduce mitochondrial dysfunction and helps to converte lactate to pyruvate, automatically feeding the Krebs cycle to activate the metabolism of the cell.

Additional IV treatments are given to neutralize the acid between the cells, thus depolarizing the cell membrane. This, coupled with the application further substances can selectively open the cell membrane, allowing the cell to take in nutrients and to let out waste. In this state,

It is now possible to reach the cell and the intracellular space with IV nutrients such as vitamins, minerals, amino acids and trace elements. The tissue can also be flooded with NAD this replenishing the ATP of the cells.

Through the activation of the Krebs cycle and the increased energy through feeding the cell, damaged or infected cells are able to perish through apoptosis. Additionally, transcription factors, which are healing, and anti-inflammatory are released. Some of these factors are antimicrobial, providing a natural defense mechanism within the cell. This in a cellular level, homeostasis can be achieved.

Through the immune modulation, the immune system is now able to start a coordinated response to microbes in the system. The support of neuro-immune -endocrine system also start to increase and help support homeostasis. In this state, the select use of antimicrobial agents may also be effective. 

On another front, the application of  photobiomodulation helps replenish the cells with energy. Photobiomodulation helps rid the body of oxidative stress and free radicals. A similar effect is achieved with the application of intravenous ozone.

It is theorized that Lyme and co-infections also hijack certain processes in the cells, making it difficult for the body to retain zinc, vitamin b6, biotin and other essential factors. This state is called KPU. 

For many,patients with chronic infections,  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. 

Some patients struggle more than others to regain their health. There is high correlation between patients with chronic Lyme disease and those with kryptopyrroluria (KPU), or more precisely hemopyrrollactamuria (HPU). 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 lyme disease. 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.

These nutrients can be replenished through IV cocktails and post treatment supplements. The lack of zinc can cause the cells to hoard heavy metals in its place. With the cellular terrain now functioning, it is relatively easy for the cells to release these metals. To avoid them triggering high amounts of oxidative stress, which in turn causes inflammation (restarting the whole cycle), select chelating agents are carefully applied.

The KPU condition results in a significant loss of zinc, vitamin B6, biotin, manganese, arachidonic acid (omega-6), and other nutrients from the body via the kidneys. There are many symptoms of KPU, which may result from deficiencies of these nutrients. This leads to a significant depletion of these nutrients throughout the body and to the synthesis of non-functioning or poorly functioning enzymes. 

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,"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.

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 80% of patients KPU is  triggered by infection with Lyme organisms,  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.Patients with intractable chronic infections have experienced significant improvements in immune function and a resulting lowering of total microbial burden.

Always  treat KPU first,  balancing the zinc and B6-dependent enzymes indirectly without the addition of methyl groups is generally a safer way to restore healthy methylation on all fronts as opposed to directly supporting methylation with methyl donors. 

Both zinc and vitamin B6 deficiencies, which are important cofactors in the methylation cycle, reduce levels of glutathione in the body. Glutathione is important for the detoxification of heavy metals and other toxins.
Replacing missing zinc and vitamin B6 increases glutathione. This, in turn, increases the rate of detoxification of heavy metals and other body burdening toxins. However, it is also the case that incorporating the KPU protocol  giving high dse zinc and B6 will liberate additional heavy metals within the body, thus additional detoxification support is generally needed.

This is, in part, due to the fact that when the body has been deficient in zinc for a long period of time, it may retain heavy metals much more readily. When zinc is missing from the body, it is replaced in our bones with lead. If zinc is supplemented, lead is expelled. Secondly, the enzymes needed to detoxify these metals are heme-dependent enzymes, and these metals accumulate when heme synthesis is abnormal. The biomarkers of  porphyrin metablosm are present, like uroporphyrin is an indicator for aluminum, coproporphyrin for lead, and precoproporphyrin for mercury. 

KPU and Histamine

When a KPU patient is having a good day, low histamine levels are observed; on a bad day, higher histamine levels are observed. It is the relative elevation of histamine in response to foods, inhalants, allergens, emotional stressors, and electrosmog that is problematic and causes the allergic phenomena, not the absolute histamine level. When histamine levels rise from a low level to a moderate level, the reactions are often severe. 

When exploring histamine levels in a KPU patient at a time when they are experiencing hives or asthma, the histamine levels are elevated, but not to levels that would create a problem for others. The relative rise in histamine, however, in KPU patients is experienced in a far more significant way. 

The medical professionals  are beginning to link KPU with mastocytosis or mast cell activation syndrome (MCAS). They have observed that KPU treatment repairs the heme molecule, which notably stabilizes the mast cells and lowers the response to these relative rises in histamine.In patients with KPU, absolute histamine levels are almost always low.

Within the United States, two of the available labs for testing include the following:

  • DHA Laboratory (https://www.pyroluriatesting.comuses a frozen one-time collection at a cost of $80. They recommend the collection be the second urination of the day. They suggest a. The lab is testing for hydroxyhemopyrrolin-2-one (HPL).
  • Health Diagnostics and Research Institute (http://www.hdri-usa.comcharges $140 for a 24-hour collection and $90 for a random collectionHDRI suggests stopping zinc and B6 as well as antidepressant medications for 48 hours prior to the collection. They suggest not smoking or consuming caffeine for 24 hours prior. While there is no additional cost for testing the hydroxyhemopyrrolin-2-one (HPL) compound, this must be specifically ordered on the requisition form as it is not part of their KPU assay by default. If you do not specify HPL as an add-on, you will get kryptopyrrole (2,4 dimethyl-3-ethyl pyrrole) only.
  • To further maximize the sensitivity of testing, it may be best for the patient to be under stress at the time the test is being performed as HPL excretion is known to increase during times of stress.
  • WBC (not RBC) intracellular zinc may be a useful tool for exploring the potential for zinc deficiency where it matters most - in the white blood cells.
  • Other laboratory indicators that may be suggestive of KPU include the following:
    • WBC < 5000/mcL (due to low levels of zinc)
    • High LDL / Low HDL
    • Low normal alkaline phosphatase (<60U/L)
    • Low omega-6 fatty acids in red cell membrane test
    • Low taurine in amino acid profile
    • High MCV
    • Low glutathione
    • Low ATP
    • WBC and RBC zinc and manganese levels may be normal while biopsies from bone and CNS are completely deficient.
    • Bone biopsies are a reliable predictor of KPU. Severe deficiencies of zinc, manganese, lithium, calcium, magnesium, and molybdenum are often found.
    • Alkaline phosphatase (ALP) is a zinc and magnesium dependent enzyme. When someone is consuming adequate magnesium and is still presenting with low ALP, zinc deficiency is a likely consideration, and this may represent another indication for KPU.
    • When ALP is below 55, zinc deficiency can be suspected; when below 40, it is likely.
    • A consequence of KPU is low glutathione and low ATP. In the realm of chronic illnesses, low reduced glutathione and low ATP are common and should alone trigger the suspicion that KPU may be a factor.


KPU is a severe but reversible deficiency of zinc, vitamin B6 (or P5P), biotin, manganese, arachidonic acid, and other co-factors. It is important to recognize, however, that treatment with zinc and vitamin B6 does not result in fewer pyrroles being excreted in the urine. KPU orthomolecular treatment does not fix the underlying condition; it substitutes what is being lost as a result of the condition such that the person is no longer deficient in key nutrients needed by the body to move towards health. 
The general KPU substitution treatment that Klinghardt uses in his practice is as follows (dosages for 160 lb. adult and should be adjusted based on weight; may be customized for specific patient needs):

With Breakfast

  • Zinc 25-30 mg (as picolinate, gluconate, sulfate, or zinc l-carnosine). Nausea after zinc supplementation may be a sign of hypochlorhydria or low stomach acid; this often resolves after a few months on treatment.
  • Vitamin B6 50-100 mg (split between pyridoxine HCl and P5P, with P5P being the predominant form)
  • Biotin 3-5 mg for brain, skin, hair, and nails
  • Magnesium 100 mg (glycinate, bisglycinate, or malate) – or titrate to bowel tolerance.
  • Arachidonic acid from omega-6 oils (Ghee such as Mt. Capra Goat Milk Ghee, Evening Primrose Oil, Hemp Seed Oil, Black Currant Oil, Borage Oil, Pumpkin Seed Oil; 4-6 capsules of Evening Primrose Oil per day is commonly used.)
  • With Dinner
  • Zinc 25-30 mg
  • Vitamin B6 50-100 mg
  • Biotin 3-5 mg
  • Magnesium 100 mg
  • Omega-6 Oils

This is the core treatment Klinghardt utilizes for KPU.

Additional Support

  • Vitamin A 1,500-3,000 IU per day to improve the absorption of zinc in the gut
  • Niacin 40-50 mg per day for psychiatric symptoms. (Abram Hoffer used up to 3000 mg per day.)
  • Taurine 100 mg twice per day (up to 2,000 mg at bedtime) for brain-related symptoms such as seizures, brain fog, and memory loss. Supports elimination of neurotoxins, improves bile quality, increases glutathione, and normalizes brain rhythms.
  • Lithium 5-10 mg per day (Orotate or Aspartate); lithium is lost in the urine in some patients with KPU.
  • Manganese 2-5 mg per day (Patients with joint problems may require additional manganese above the dosages recommended here; see additional considerations later in this article on manganese for patients with Lyme disease.)
  • Chromium 250-500 mcg per day
  • Molybdenum 100-500 mcg per day
  • Boron 1-3 mg per day
  • Trace Minerals - As more is learned about KPU, additional elements are found to be lower in those with the condition. Thus, supplementing trace minerals may be a supportive strategy. BioPure MicroMinerals, Quinton Isotonic, or similar mineral products may be helpful.

As compared to the first version of this article which was published in 2009, Klinghardt has found that many of his patients do quite well with lower dosages of some of these key nutrients than were originally utilized. 
In Europe, Depyrrol is one product which provides support for KPU. Additionally, and in the United States, BioPure CORE and CORE-S are available to support those dealing with the condition. Another product in this realm is Mensah Medical's Pyrrole Pak. These products serve as a solid foundation for KPU treatment; though additional co-factors may be needed for a given patient. Some patients may not tolerate both vitamin B6 and P5P as contained in some products and may find it necessary to take each component of the KPU program separately. 
In terms of BioPure's CORE and CORE-S, CORE-S is a recent reformulation of the CORE product which has been available for many years. While either may be an appropriate option, CORE-S generally results in less nausea, better absorption, and is often better tolerated by those patients with Lyme disease as it does not contain manganese. While many with pyroluria may benefit from manganese, it may act as a growth factor for untreated Lyme disease, and thus, some may prefer to avoid its use in this patient population. The reformulated CORE-S contains horsetail as people with KPU excrete higher levels of silica in the urine, which leads to higher levels of aluminum toxicity. With either CORE or CORE-S, two capsules twice daily are a common target dose for a 160 lb. adult. When first starting to introduce products in support of KPU, it is best to start with lower dosages and to take them towards the end of a meal and to gradually work up to the target dosage. Levels of B6, taurine, or biotin may be additionally and individually titrated upwards depending on the patient's symptoms and needs.
With the introduction of zinc, it is best to monitor copper levels after a few months on the protocol as copper replacement may also be needed. Zinc, vitamin B6, and manganese are copper antagonists. Thus, monitoring levels of copper and supplementing where needed is an important part of the treatment protocol.
Copper deficiency can lead to hemorrhoids, varicose veins, fatigue, edema, hair loss, anorexia, skin problems, osteoporosis, cardiovascular disease, aneurisms, and many other undesired conditions. Current nutritional teachings are misinformed on the topic of copper toxicity. The immune system uses copper and iron to fight infections associated with Lyme disease. As a result, oxidized copper is displaced in the connective tissue and may appear as though the patient is copper toxic by some testing methods when in fact copper supplementation may be appropriate. High dose Vitamin C has the effect of reducing oxidized copper to a form that can be reused by the body.

Detoxification and Course of Treatment

As treatment for KPU is implemented, this often can result in toxin mobilization as the body begins to release heavy metals. Symptoms may include muscle aches, bowel problems, or those normally associated with cleansing or detoxification reactions. Additionally, the immune system begins to become more active which can result in a Herxheimer-like reaction as the immune system begins to better respond to the backlog of microbes that it was previously unable to adequately address.
One approach for minimizing these reactions is to start slowly with introduction of the KPU nutrients and work up over time. In most cases, there is no reason that the treatment course must be an aggressive one. Nonetheless, this treatment should always be guided by a knowledgeable practitioner. In addition to the KPU treatment discussed earlier, consideration should be given to detoxification support and to protection of the red blood cells as the treatment is initiated. 
According to Klinghardt, many of our metabolic enzymes use zinc as part of their molecular makeup. However, in patients with KPU, there is not enough zinc available to satisfy the need. In these cases, lead, mercury, and other 2-valent metals bind to these sites instead in a poor attempt to fulfill the role of zinc. 
Once zinc is reintroduced into the body, 2-valent metals such as mercury, cadmium, aluminum, and lead are liberated. The patient may now have dislodged heavy metals circulating throughout the body. These may be competing for the already overtaxed detoxification pathways or may be redistributed to places where they may be more problematic. Lead moves back into the blood, which can cause problems including damage to red blood cells. To protect the red blood cells, freeze-dried garlic and Vitamin E are often used.
Incorporation of known toxin binders further supports the detoxification process. Some of the binders that Klinghardt uses in his practice include chlorella, Ecklonia cava, zeolite, and chitosan. Silica from horsetail supports binding of aluminum, and thus, the use of a high-silica zeolite such as BioPure ZeoBind is often utilized. It is critical to support the kidneys with specific drainage and organ support remedies in order to optimize the removal of heavy metals and to avoid stressing the kidneys.
An interesting observation has been that patients with KPU often get worse when an attempt is made to incorporate detoxification agents or antimicrobial agents prior to having first addressed the KPU condition. Once KPU has been addressed, other treatment options are often much more effective and better tolerated.

Additional Considerations

Many patients with chronic Lyme disease have issues with sulfur intolerance. This leads to a patient being unable to effectively utilize a number of detoxification agents such as alpha-lipoic acid, DMSA, DMPS, and glutathione; as well as supplements such as garlic. This may be related to genetic predisposition, but some of the enzymes involved in sulfur metabolism (CBS and others) are heme and B6 dependent; both of which are depleted in KPU. As patients are treated for KPU, these sulfur tolerance issues may resolve. Klinghardt has found that molybdenum at a dose of 100-500 mcg per day may correct sulfur intolerance in patients with KPU, as molybdenum may also be lost in these patients.
Ammonia is generally high in patients with KPU. As KPU is treated, high levels of ammonia tend to normalize. To bind and excrete ammonia, zeolite may be used.

Resolution of KPU

For most with the condition, supplementation will be required for life. However, Klinghardt has seen complete resolution of the condition after having addressed epigenetic influences, trauma, or unresolved conflicts using tools such as mental field therapy, family constellation work, or EMDR. By resolving trauma in the ancestry, the epigenetics are influenced in a positive way and the condition resolves. Klinghardt has also observed complete resolution of Lyme-induced KPU when the infection is managed successfully with biological interventions.  


Final Thoughts

Once patients are on the KPU protocol and mobilized metals have been addressed, the body begins to respond to backlogged infections and significant improvements in the patient's condition are often observed. Hormonal status often improves. Some patients who have been on thyroid medication for years may even become hyperthyroid as the body begins to function more optimally. Other patients may lose weight. Symptoms directly related to low levels of zinc, vitamin B6, biotin, manganese, and arachidonic acid often resolve.
Just as homes are built by first laying a solid foundation, addressing KPU and the deficiencies in zinc, vitamin B6, biotin, manganese, and arachidonic acid are key pieces of the puzzle in addressing the complexities of chronic Lyme disease and many other conditions. 
Evaluation for KPU is one of the first things that Klinghardt pursues in working with patients with chronic illnesses. Implementing the KPU protocol often yields progress that had not previously been possible, and patient recovery is accelerated in a very deep and profound way.3. 

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