What Is Kryptopyrroluria?

Kryptopyrroluria (KPU) is a condition in which zinc and pyridoxine (vitamin B6) are excreted in high amounts into the urine. Elevated kryptopyrroles (HPL) are found in the urine due to abnormality in the synthesis of heme (hemoglobin) in the body. Hemoglobin is a protein in the red blood cells that carries oxygen throughout the body.

Pyrroles are chemicals that are made up of a five-membered aromatic ring and are the byproducts of the hemoglobin synthesis which have no known function, so they are usually just excreted into the urine. Pyrroles have also been found to have an affinity to zinc and pyridoxine (vitamin B6) and may excrete these nutritional molecules into the urine in high amounts. The excretion of zinc and pyridoxine (vitamin B6) can result in a severe deficiency of these two important nutrients in the body.

HPL may also bind to biotin, manganese, chromium, magnesium, omega 6s (arachidonic acid) and other important nutrients, excreting them from the body via the kidneys causing further nutrient deficiencies. This condition can lead to a severe deficiency of nutrients throughout the body and may also result in poorly functioning enzymes. A deficiency of these nutrients may contribute to symptoms associated with:

• Neurological issues including:
  • Bipolar disorder
  • Other mood disorders
  • Autism
  • ADD/ADHD
  • Sensory Processing Disorder
  • PANS/PANDAS
• Psychiatric symptoms
• Reduced energy production
• Mitochondrial dysfunction
• Detoxification issues
• Thyroid imbalances
• Immune disorders
• Musculoskeletal issues
• Allergies
• Food intolerances and sensitivities
• Gynecological issues
• Gastrointestinal issues
• Blood sugar imbalances
• Methylation issues

Pyrrole disorder can affect children and teenagers as well as adults. Kryptopyrroluria has a variety of spellings and names that can be used interchangeably:

• Pyrole disease (pyrrole disease)
• Pyrole disorder (pyrrole disorder and pyrolle disorder)
• Kryptopyrroles
• Pyrroles or hydroxyhemophrrolin-2-one (HPL)
• Kryptopyroluria (Kryptopyrroluria) (KPU)
• Mauve factor
• Hemopyrrollactamuria (HPU)
• Hemepyrole (hemepyrrole, hemopyrrole, hemopyrole)

Negative effects of high pyrroles (HPL)

High pyrrole levels can:

• Damage nerve cells
• Decrease hemoglobin levels
• Increase free radical damage because three major antioxidants (glutathione, catalase and superoxide dismutase) require zinc or vitamin B6 in their production process.
• Reduce liver detoxification
• Cause stress which increases HPL levels
• Cause neuronal (nerve) cell death due to low levels of hemoglobin
• Potentially cause cell mitochondrial death
• Reduce hemoglobin levels due to deficiencies of vitamins B6, B7 (biotin) and zinc, which are required for hemoglobin production. Low levels of hemoglobin can result in an increased production of nitric oxide, a toxic free radical that can cause serious damage to brain tissue. This may play a role in schizophrenia, autism and Down syndrome.

Common Conditions and Disorders Associated with Kryptopyrroluria

• Schizophrenia (40% to 70%)
• Attention Deficient Hyperactivity Disorder (ADHD) (30%)
• Autism Spectrum Disorders (ASD) (50%)
• Acute intermittent porphyria
• Learning Disorders (LD)
• Temper Dysregulation Disorder (TDD)
• Tourette syndrome
• Down syndrome
• Type II diabetes
• Bipolar disorder
• Fibromyalgia
• Myalgic encephalomyelitis (ME)
• Chronic Fatigue Syndrome (CFS)
• Multiple Chemical Sensitivities (MCS)
• Multiple Sclerosis (MS)
• Hypothyroidism
• Hypoglycemia
• Hashimoto’s Thyroiditis
• Alcoholism/substance abuse (40% to 80%)
• Criminal behavior/violent offenses
• Neuroses
• Psychosis
• Lyme disease
• Macular degeneration
• Depression
• Manic depression
• Dyslexia
• Epilepsy/seizures
• Allergies
• Lung cancer
• Behavioral disorder
• Alzheimer’s
• Parkinson’s disease
• Post-Traumatic Stress Disorder (PTSD)
• Trauma
• Postnatal depression
• Anti-social personality disorder
• Oppositional Defiant Disorder (ODD)
• Short-term memory impairment
• Chronic infections
• Mold
• Anxiety disorder
• Mood swings
• Fears/phobias
• Sensory Processing Disorder (SPD)

Common Laboratory Symptoms of Kryptopyrroluria

• Elevated kryptopyrroles in urine
• Dark or mauve-colored urine
• Elevated eosinophils
• Abnormal EEG
• Severe oxidative stress
• Undermethylation
• Overmethylation
• Low ceruloplasmin
• Copper/zinc imbalance
• Hormonal imbalances
• Fungal infections, yeast, Candida
• Leaky Gut Syndrome/gut dysbiosis
• Small Intestinal Bacterial Organism (SIBO)
• Adrenal fatigue
• Heavy metal toxicity
• Allergies, food sensitivities and food intolerances
• Frequent infections
• Seizures
• High cortisol levels (excessive stress)
• Low vitamin D
• High homocysteine
• Elevated histamine levels
• Low white blood cells (WBC)
• High LDL/Low HDL cholesterol
• Low alkaline phosphatase
• Low omega-6 fatty acids in red cell membrane test
• Low taurine in amino acid profile
• High MCV (mean corpuscular volume) in red blood cells
• 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 – a reliable predictor of KPU
• Severe deficiencies of zinc, manganese, lithium, calcium, magnesium and molybdenum
• Alkaline Phosphatase (ALP) – a zinc and magnesium dependent enzyme. Low ALP may be low zinc if consuming adequate magnesium.

Common Body Signs of Kryptopyrroluria

• Abnormal fat distribution
• Acne, eczema or psoriasis
• Cold hands and feet
• Creaking in joints
• Delayed puberty
• Dry skin
• Early greying of hair
• Fluid retention
• Hypo pigmentation of skin
• Inability of skin to tan
• Knee ache or joint pain
• Lack of hair on head
• Lack of hair on head, eyebrows or eyelashes
• Malformed cartilage or tendons
• Overcrowding of teeth
• Pale skin
• Poor muscle development
• Poor tooth enamel
• Poor wound healing
• Poor sense of smell and taste
• Prone to “stitches” as a child and teenager
• Significant growth after age of 16
• Skin appears paper thin
• Skin burns easily in sun
• Skin disorders or rashes
• Hyperpigmentation of the skin
• Sneezes in sunlight
• Stretch marks / striae (may be misinterpreted as Bartonella in Lyme patients)
• Stunted growth
• Sweet, fruity or acetone body odor and breath
• Tingling in arms and legs
• Tremors, shaking, spasms
• Teeth prone to cavities
• Unexplained chills and fevers
• White spots on fingernails
• Delicate facial features
• Retracted gums
• Amenorrhea, irregular periods
• Abdominal tenderness/spleen area pain

Common Symptoms and Traits of Kryptopyrroluria in Children

• Poor ability to cope with stress
• Volatile, angry and cries easily
• Calm one minute and angry the next
• Inner tension and impulsivity
• High irritability, temper tantrums, outbursts
• Raging and inconsolable to calm down
• Poor short-term memory
• Sensory issues (doesn’t like clothing tags and certain clothes)
• Hypersensitive to loud noises
• Hypersensitive to light
• Prefers to be isolated
• Poor muscle development
• Poor wound healing
• Frequent infections
• Digestion difficulties
• Increased behaviors during growth spurts
• Child hallucinations
• Hyperactivity
• Multiple white spots on fingernails

Common Symptoms and Traits of Kryptopyrroluria in Teenagers and Adults

• Migraines and headaches
• Always sick
• Feelings of being overwhelmed
• Fear of airplane travel, tornadoes etc.
• Social withdrawal/antisocial behavior
• Delusions
• Paranoia/hallucinations
• Depression
• Emotional lability
• Perceptual disorganization
• Severe mood swings
• Hypoglycemia
• Glucose intolerance
• Crime and delinquency
• Pessimism (obsession of negative thoughts)
• Histrionic behavior (emotion-seeking)
• Emotional instability, mood swings, nervousness
• Dramatic tendencies
• Nervous exhaustion
• New situations stressful
• Severe inner tension
• Explosive
• Argumentative
• More energy in the evening than the morning
• Insomnia and abnormal sleep cycle (late nights)
• Poor appetite, especially in the morning
• Constipation
• Low tolerance for protein – favors vegetarian diets
• Preference for spicy and heavily flavored food
• Overeating
• Food sensitivities
• Poor dream recall
• Poor recall of past events
• Name recall difficulty
• Severe anxiety including panic attacks
• Uncomfortableness with strangers
• Poor wound healing
• Nausea, motion sickness especially in the morning
• Amnesia spells
• Crying spells
• Light, sound, odor intolerance
• All-girl family with look-alike sisters
• Delayed puberty
• Impotence
• Drug and alcohol intolerance
• History of reading disorder
• History of underachievement
• Low self esteem
• Frequent fatigue from anemia and low iron
• History of mental illness or alcoholism in the family
• Prone to frequent colds and infections
• Ear infections

Individuals affected by KPU usually carry about 50% of all these symptoms.

The History of Kryptopyrroluria

In 1958, Abram Hoffer MD PhD, the father of orthomolecular psychiatry, led a psychiatric research program in Saskatchewan, Canada in search of any possible biochemical etiology for schizophrenia or biomarkers (lab markers) he might find in the urine of these individuals. The urine of his schizophrenia patients was found to be purple or mauve on the testing paper of the analysis; hence the name the “mauve factor.” Dr. Hoffer’s research identified excessive kryptopyrroles in the urine.

By the 1970s, these kryptopyrroles were renamed hydroxyhemophrrolin-2-one (HPL) by Carl C. Pfeiffer MD PhD, who was the first to identify KPU as pyroluria. Dr. Pfeiffer found KPU to be an underlying factor in a range of medical conditions. He was also able to show clinical improvement in positive patients with high doses of zinc and vitamin B6 (between 400 mg and 3,000 mg of vitamin B6). Many studies in the 1970s discredited the Hoffer hypothesis: “Hoffer decided that he was not the victim of a failed hypothesis, but rather the victim of a conspiracy of mainstream psychiatry that was simply closed to his revolutionary ideas.”

Understandably today, this disorder is not commonly known among pediatricians and other medical physicians because many of the symptoms are emotional and psychiatric, and the physiological symptoms are often identified with other medical conditions. Consequently, this disorder is very poorly understood, rarely treated and not even considered as a medical condition since emotional and psychiatric symptoms are traditionally psychiatric and not seen as having any connection to the physiological symptoms.

Further discredit also arises because the treatment protocol involves nutritional supplementation and not pharmaceutical drugs. However, for countless integrative doctors and naturopaths, kryptopyrroluria is widely considered an underlying factor in many medical conditions and disorders, and the strong body/mind connection is revealed in the many symptoms associated with this disorder. The magnitude of potential health problems and negative health implications that could arise from this one condition due to the number of nutritional deficiencies, is overwhelming and devastating. It is no wonder that KPU is often described as the “elephant in the room.”

What Causes Kryptopyrroluria?

Kryptopyrroluria (KPU) disorder can be a genetically acquired inherited abnormality (fault in the genes passed down through the generations) in the biochemistry. Most people have very few pyrroles at any given time in their system. However, about 65% of individuals who have high levels of pyrroles in their bodies are believed to have a lifestyle-generated pyrrole disorder (KPU). KPU may be triggered by:

• Psychological trauma
• Conditions with chronic infections such as:
  • Lyme disease
  • Epstein-Barr virus
  • Other bacterial and viral pathogens
• Epigenetic factors such as:
  • Use of intrauterine device
  • Childbirth, childhood or transgenerational trauma passed down through families
• Excessive stress from events such as:
  • Car accident
  • Divorce
  • Emotional trauma
  • Physical abuse
  • Sexual abuse
• Lifestyle factors such as:
  • Drug use
  • Alcohol use
  • Unhealthy lifestyle
• Food allergies, intolerances and sensitivities
• Insufficient liver detoxification
• Oxidative stress
• Nutritional deficiencies
• Poor dietary choices
• Poor digestive health
• Stress
• Toxic exposure such as:
  • Heavy metals
  • Chemical exposures

Children with parents or grandparents or siblings with any of the above disorders or associating conditions are at greater risk of getting KPU.

The role of the gut:

Zinc deficiency can increase bowel permeability, which may lead to a condition called Leaky Gut Syndrome (LGS). A leaky gut can increase pyrroles in individuals who suffer from KPU. Stress damages the intestinal wall and can trigger intestinal inflammation which can lead to LGS. Stress can cause bad bacteria in the intestines to migrate to the brain via the vagus nerve and cross the blood-brain barrier, triggering aggressive behaviors, depression, anxiety, mood swings and other neurological symptoms.

Poor coping abilities and an inability to handle stress are major symptoms of KPU. Irritable Bowel Syndrome (IBS) and digestive disorders such as gut dysbiosis and Small Intestinal Bacterial Overgrowth (SIBO) in the intestinal tract may also increase HPL levels and can be major contributors to a leaky gut.

The role of toxins:

Heavy metal and chemical exposures dramatically increase HPL in blood levels. The enzymes needed to detoxify heavy metals are enzymes that are dependent on the heme synthesis. Heavy metals will accumulate if heme synthesis is abnormal and if KPU causes the heme synthesis to be abnormal.

The role of dietary choices:

Phytate-containing foods in the diet such as unsoaked and unsprouted grains, legumes and soy can also contribute to KPU. Phytic acids in these foods bind to major minerals like zinc, vitamin B6 and other nutrients, causing them to be depleted in the body.

Testing for KPU

There are varied types of tests that can determine KPU:

• Laboratory analysis of the urine for kryptopyrroles
• Metabolic testing for elevated pyrroles
• The Pfeiffer Protocol (Mensah Medical)
• Nutrient and mineral testing for deficiencies

Because symptomology is just not accurate enough, proper testing for identification of KPU is very important and necessary for an appropriate treatment protocol and to resolve the underlying factors involved. For example: Too much vitamin B6 can cause nerve damage. In addition, too much zinc can suppress immune functioning and then be in competition with copper, manganese and iron, resulting in deficiencies.

Many health conditions such as SIBO, gut dysbiosis, Leaky Gut Syndrome, adrenal fatigue and excessive stress can all resemble symptoms of KPU/pyrrole disorder. Therefore, see the recommended laboratories below and seek out and consult with a good integrative practitioner or naturopath who can help you with proper testing. In some cases, individuals will test negative even when KPU is suspected; retesting two to three times may show results.

Pyrrole-testing laboratories:

• DHA Laboratory (the Pfeiffer Protocol and whole-blood histamine)
• Great Plains Laboratory
• Health Diagnostics and Research Institute
• Integrative Psychiatry
• Klinisch Ecologisches Allergie Centrum in Holland (KEAC)
• Mensah Medical (the Pfeiffer Protocol)
• Quest Diagnostics
• Riordan Clinic

Dietrich Klinghart’s KPU Treatment Protocol

Dietrich Klinghardt MD PhD recommends a questionnaire used by many doctors worldwide to help determine KPU. If the score is 10-14, Klinghardt often will proceed with treatment; if the score is 0-9, then he may suggest additional lab testing. Klinghardt found that 80% or higher of his chronic Lyme disease patients had KPU, 75% of patients with heavy metal toxicity such as lead, mercury, aluminum, cadmium and others had KPU, and 80% or more of children with autism also had this condition. Once KPU has been identified, supplementation of vitamin B6 or the metabolic form of B6, known as P5P, or both, and zinc (in the form of picolinate, gluconate, sulfate, or zinc l-carnosine) are crucial. In addition, an individual protocol of supplementation depending on the results of individual testing may be required.

Zinc

Klinghardt recommends supplementing with CORE (made Dr. Klinghardt’s company), which also includes many of the co-factors that may also be deficient in KPU in addition to B6 and zinc. CORE supplementation should be started at a low dose because treatment will begin to release heavy metals, and this could affect behaviors in children.

Main considerations of Klinghardt’s protocol:

Two main considerations in Klinghardt’s KPU protocol are detoxification support and protection of red blood cells. Toxin binders such as chlorella, zeolite, activated charcoal, and chitosan support detoxification. Silica from horsetail will bind aluminum. Drainage and organ support remedies will help protect and avoid stressing the kidneys.

Freeze dried garlic and vitamin E protect the red blood cells especially if lead moves back into the body if zinc levels are low. Zinc is replaced in the bones with lead if there is a zinc deficiency in the body; when zinc is supplemented, then bones expel lead.

Klinghardt’s findings have lead him to believe that the biotoxins from microbes block one or more of the eight enzymes needed for the heme synthesis. This leads to a significant loss of key minerals in the white blood cells which dramatically reduces cellular immunity.

Biotoxin illnesses such as Lyme disease and mold as well as heavy metals are much less resistant after being treated for KPU. Hence, children or adults with chronic infections will benefit from a KPU treatment protocol. Many people have experienced significant improvements in immune functioning as well as finding a lower microbial load.

Klinghardt states that therapy-resistant infections are a hallmark of KPU. Long-term infections, parasitic infestations or years of antibiotic therapy for chronic or late-stage Lyme disease or PANDAS or PANS could benefit from KPU treatment so that the microbes, heavy metals, infections and parasites become much less resistant. Chronically low levels of zinc allow parasites to invade the mucosal lining of the gut; from there they may migrate to the liver and gallbladder, interfering with mood, energy levels and sleep. Parasite treatment and supplementation with zinc and vitamin B6 can make a difference.

Bouts of depression (or anger in children with autism) generally correlate to times when pyrroles (HPL) are released in high numbers in the urine. Many children and adults with KPU also have high levels of ammonia; treatment with alpha ketoglutaric acid, ornithine or zeolite can reduce and normalize the ammonia levels.

KPU and Lyme disease:

Klinghardt was the first to discover the connection between KPU and Lyme disease; he found that it was rare to have chronic symptomatic Lyme disease in adults and not to have KPU. He has stated that microbes begin to be less resistant after implementation of his KPU protocol.

KPU and methylation:

Zinc and vitamin B6 are important cofactors in the methylation cycle. Treating KPU first without adding a methyl group is a safer way to support and restore methylation than to directly support methylation with methyl donors such as methylcobalamin and folinic acid (folate).

KPU and heavy metal toxicity:

Zinc and vitamin B6 increase glutathione, an antioxidant that is important for the detoxification of heavy metals and environmental toxins. Treating KPU first assists in facilitating the detoxification process by reducing the total load.

KPU and porphyrin disorders:

Dutch lab KEAC has established that elevated porphyrins decrease with KPU treatment. Porphyrin testing shows that levels of aluminum, lead and mercury excrete more readily from the body when KPU is corrected.

KPU and histamine:

An increase in histamine levels can be particularly bad for KPU individuals, especially when they are experiencing hives or asthma. Biochemists in Germany are beginning to link mastocytosis or mast cell activation syndrome (MCAS) with KPU. They have seen that KPU treatment repairs the heme molecule and stabilizes the mast cells and reduces histamine levels.

KPU and multiple sclerosis:

Multipe sclerosis (MS) patients appear to have KPU as a familiar co-factor. They frequently have low histamine, so KPU treatment with histamine can improve outcomes of MS.

William Walsh’s (Pfeiffer Center) KPU Treatment Protocol

The role of copper:

A long-term history of zinc deficiency can result in high copper levels, potentially resulting in:

• Anxiety
• Depression
• Mood swings
• Postpartum depression
• Skin issues
• Hormonal imbalances

Copper is transported around the body by a protein called ceruloplasmin that delivers the copper in trace amounts to the cells. Low ceruloplasmin may indicate “elevated free copper or unbound copper”, which can lead to a greater risked of toxic copper symptoms. Therefore, simple copper testing does not give the whole picture; instead serum copper, zinc plasma and ceruloplasmin testing also need to be tested.

Additional tests for that can round out the KPU picture are whole-blood histamine, homocysteine and vitamin D. High copper levels can be balanced by increasing zinc levels; however, copper levels must continue to be monitored because low copper can cause deficiency symptoms such as:

• Hemorrhoids
• Varicose veins
• Fatigue
• Edema
• Hair loss
• Anorexia
• Skin problems
• Osteoporosis
• Cardiovascular disease
• Aneurisms

Some individuals have displaced oxidized copper in the connective tissue which may appear as copper toxicity but is really a deficiency. High dosages of vitamin C can reduce the negative effect of oxidized copper by transforming it into a reusable form that can be used by the body. William Walsh MD PhD performed clinical research for the Pfeiffer Center, and he developed the Pyrrole Pak to correct the abnormality in the biochemistry caused by KPU.

Kryptopyrroluria Healing Checklist

Find a practitioner that can help your child heal the gut microbiome, rebuild and strengthen the immune system, and address nutritional deficiencies.

Still Looking for Answers?

Visit the Epidemic Answers Practitioner Directory to find a practitioner near you.

Join us inside our online membership community for parents, Healing Together, where you’ll find even more healing resources, expert guidance, and a community to support you every step of your child’s healing journey.