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Pyroluria—A Hidden Disorder

Updated on July 21, 2016
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Natural Insight is a Qualified Naturopath. She has written about her experience with Pyroluria and neurological illness.

What Is Pyroluria?

Pyroluria is a genetic blood disorder and chemical imbalance, involving an abnormality in haemoglobin synthesis. Haemoglobin is a protein that holds iron in the red blood cell. During the production of haemoglobin a seemingly harmless byproduct is created called Kryptopyrrole, or what is now more specifically and accurately known as OHHPL, or HPL (hydroxyhemoppyrrolin-2-one). HPL is a chemical substance involved in the formation of heme, which makes blood red. In most individuals this by-product is harmless and excreted in the urine. For people with Pyroluria, levels of HPL multiply too rapidly and systemically bind and block receptor sites to the nutrients Zinc and Vitamin B6.

Kryptopyrroles (HPL) specifically seek out aldehydes to bind to, in this case Pyridoxine (vitamin B6). This duo does further damage by attaching itself to Zinc, forming a complex which is then eliminated via urine. The result is major deficiency in Vitamin B6 and Zinc. This presents a wide spectrum of mental/physical symptoms. The extent of the deficits are so large, they cannot be counterbalanced by foods high in these particular nutrients.

What This Article Will Cover

• Pyroluria Etiology and History
• Signs, Symptoms, and Associated Conditions
• Diagnosis
• Treatment
• An Inspiring True Story

Aetiology and History

A familial condition caused by poor genetics (such as familial alcoholism) and/or by environmental toxicity, Pyroluia can be induced by childhood trauma or chronic infection early in life. The onset commonly occurs during the late teens and continues throughout a person's life. It may be triggered by a traumatic incident, such as the death of a loved one, a parental divorce, or moving away to college. The disorder is highly aggravated by prolonged stress, for instance during injury, oxidative stress, or chronic or debilitating illness.

It is estimated that approximately 10% of the population have Pyroluria, with estimates as high as 20% of all psychiatric patients and 40% of all schizophrenic patients, with a higher prevalence in women than men.

Pyroluria was first discovered in the late 1950s in relation to schizophrenia by a Canadian research team led by psychiatrist Dr. Abram Hoffer. Hoffer was a pioneer of Orthomolecular Psychiatry and Orthomolecular Medicine, and became editor of the Journal of Orthomolecular Medicine. This was the first medical journal to bring attention to many important new treatments in medicine such as the yeast syndrome, the toxicity of mercury from amalgams, and the orthomolecular treatment of the schizophrenias.

In his research, Hoffer discovered a clear relationship between elevated urinary HPL, or as they called it then "the mauve factor," and patients with schizophrenic symptoms. According to Hoffer, 25% of nonpsychotic psychiatric patients, 50% of chronic schizophrenics, and 75% of acute (sudden-onset) schizophrenics exhibited "the mauve factor" in their urine, with 0% in the control group. They called it "mauve" due to the mauve colour that was observed on the paper chromatograms. All patients within the schizophrenic subgroup that were administered high dose niacinamide (Vitamin B3) converted from Mauve positive to Mauve negative. Discontinuation of the niacinamide was associated with the reappearance of Mauve. The researchers called this condition "Malvaria."

Malvaria was later renamed "Pyrolleuria" by Dr. Carl Pfeiffer of an American research team and later, for no obvious reason, consistently spelled "Pyrroluria" in later publications. It is also known as Kryptopyrroluria (KPU) and Haemopyrrollactamuria (HPU). In the 1970s Pfeiffer created a relatively simple, quantitative, colorimetric assay for the condition and was the first to show clinical improvement in positive patients using high doses of Vitamin B6 and Zinc.

The following statistics were obtained from the publication Discerning the Mauve Factor - Part 1 , by Woody R. McGinnis MD; Tapan Audhya PhD; William J. Walsh, PhD; James A. Jackson PhD; John McLaren-Howard, DSc, FACN; Allen Lewis, MD; Peter H. Lauda, MD; Douglas M. Bibus, PhD; Frances Jurnak, PhD; Roman Lietha, MD; Abram Hoffer, MD, PhD.

Neurobehavioral Disorders Associated with Elevated HPL:

  • Latent AIP 70%
  • Acute Intermittent Porphyria (AIP) 100%
  • Down Syndrome 71%
  • Schizophrenia (Acute) 59-80%
  • Schizophrenia (Chronic) 40-50%
  • Manic Depression 47-50%
  • Depression, non Schizophrenic 12-46%
  • Criminal Behaviour - Adults (Sudden deviance) - 71%; Youths (Violent Offenders) - 33%
  • Autism - 46-48%
  • Epilepsy 44%
  • Learning Disability/ADHD 40-47%
  • Neuroses 20%
  • Alcoholism 20-84%

In 1977, Irvine demonstrated the correlation between high HPL levels in urine and symptoms such as emotional withdrawal, motor retardation and severe depression in schizophrenia. He also experimented on rats by administering HPL resulting in hypothermia, locomotor aberration and ptosis (drooping eyelid). In 1990, Cutler and Graham reported an increase in head twitching and backward locomotion in mice after HPL administration. Graham suggested that HPL appears to exhibit excitotoxic properties, but it's yet to be investigated. There is a need for controlled therapeutic trials of existing treatments and potential new interventions, particularly anti-oxidants. The origin and genetics of HPL are important areas of inquiry.

Many great people in history have shown the signs of pyroluria. Among them are the poet Emily Dickinson and the scientific philosopher and discoverer Charles Darwin. Their life stories reflect many of the character traits associated with this condition. Pyroluria—the reason for adult withdrawal and seclusion? Reflections on the meaning of life and death were the two major influences in the life works of both Emily Dickinson and Charles Darwin.

— Dr. Carl C. Pfeiffer

Signs, Symptoms, and Associated Conditions

  • Signs

Characteristics commonly seen include white spots on fingernails, unusual fat distribution (larger mid section), increased incidence of stretch marks, pale skin that burns easily, sweet and fruity breath and body odour, overcrowded teeth, coarse eyebrows, poor appearance of tooth enamel, creaking knees, cold hands and feet, and stunted growth.

  • Symptoms

Anxiety, nervousness, pronounced mood swings, low stress tolerance, depression, panic attacks, motion sickness, general loss of appetite, social withdrawal, memory loss, episodic anger/temper outbursts, severe inner tension, insomnia, seizures, tremors, migraines, acne, irregular menstruation, impotence in males, disordered perception, eosinophilia, dyslexia, hallucinations, delusions, paranoia, loss of reality, increased sensitivity/intolerance to sound, light, smell and touch, frequent unexplained nausea, joint pain (specifically in the knee and leg), restless leg syndrome, fatigue, poor dream recall, stitch in side, digestive disturbances (abdominal tenderness, constipation), Irritable bowel syndrome, gluten intolerance, glucose intolerance/hypoglycaemia, anaemia, food/environmental allergies, delayed onset of puberty, suicidal tendencies, sensitivity to medications, pessimism, hyperactivity, emotional lability.

  • Conditions

Schizophrenia, bipolar disorder, ADHD, alcoholism, autism, Dissociative Identity Disorder, epilepsy, Asperger Syndrome, Obsessive-Compulsive Disorder, Multiple Sclerosis, Parkinson's disease, and Lyme disease.

There are varying degrees of Pyroluria. Expression of this condition can be mild, severe, or borderline, depending on genotypes, level of toxic environmental exposure, and complicated by the presence of other genetic defects such as Histadelia, Histapenia and Hypercupremia. Signs and symptoms will vary between individuals.


Upon consultation with a qualified practitioner, a thorough investigation into patient history coupled with a simple urine test for HPL will form the basis for diagnosis of Pyroluria.

The presence of HPL can be established using a colorimetric biochemical screening test adapted from Dr. Carl Pfeiffer’s method. Urine is collected in a vial containing ascorbic acid, wrapped in aluminium foil then frozen immediately for transport. The HPL molecule is unstable and will disappear rapidly at room temperature or if exposed to bright light.

Laboratory investigations including plasma zinc, serum copper, and ceruloplasmin (copper binding protein), along with HPL level and symptom picture, will be key in determining an individualised nutritional treatment regime.

Differential diagnosis is vitally important as many of the symptoms of Pyroluria present similarly to those of Histadelia (high histamine), Histapenia (low histamine) and Hypercupremia (high copper). The similar and also very severe, rare genetic condition known as, Acute Intermittent Porphyria (AIP) is commonly associated with Pyroluria with 100% of AIP patients tested exhibiting positive results for Pyroluria.


Nutrient Correction

The first line of treatment is to supplement with higher than the recommended daily average requirement of Zinc and Vitamin B6 to compensate for the deficits caused by the condition. These essential nutrients will reduce the excretion of HPL, improving all neurobehavioral symptoms associated with these deficits.

The favoured forms of these nutrients are Zinc picolinate and Pyridoxal-5-phosphate (P5P).

Not all Zinc supplements have equal bioavailability. Picolinic acid for example is a natural mineral chelate produced in the body from tryptophan. It makes its way to the pancreas where it is secreted during digestion into the small intestine, binding to minerals and facilitating their absorption. This makes Zinc picolinate the preferred supplement of choice.

There are three natural forms of Vitamin B6 found in food: Pyridoxine, Pyridoxine, and Pyridoxal. Pyridoxal joined with a phosphate is the metabolically active coenzyme form used within our bodies, also known as P5P. Pyridoxine hydrochloride is the more commonly used form of supplement for vitamin B6, and is well utilised in most individuals. However the body is then required to convert the pyridoxine into P5P in the small intestine so it can be utilised. The pyridoxine can not be used by the body directly. Two metabolic steps must first be performed: phosphorylation and oxidation. These processes require nutrients like Zinc, Magnesium and Riboflavin (Vitamin B2). If Riboflavin is low, P5P production can be reduced by up to 60%. For this reason in the treatment of Pyroluria it is important to administer the P5P form, as deficiencies in Zinc, Magnesium and B2 are most likely to be present.

Suggested Daily Dosage:

  • Vitamin B6 - 200mg Pyridoxine hydrochloride and 50mg P5P. I personally find taking smaller doses of P5P (20mg) every 3-4 hours throughout the day to be most affective. P5P is a water soluble vitamin that is not stored in the body and easily depleted, particularly if you drink tea/coffee or consume anything with a diuretic effect.
  • Zinc picolinate - anywhere from approximately 50 - 100mg for severe adult cases, taken in the morning after food. Zinc dosages are to be built up slowly in accordance with blood labs results for Zinc/Copper/Ceruloplasmin levels, HPL results, and general vitality/adaptive ability to cope with chelation.

NOTE: All supplements should be titrated to the individuals age, body weight, laboratory results, severity of symptoms and ability to absorb supplements, i.e. underlying digestive malabsorptive disorders such as Crohn's disease, Irritable Bowel Syndrome, Inflammatory Bowel Disease, Coeliac disease, Leaky gut syndrome, Intestinal dysbiosis (an imbalance of bowel flora), GIT infections (parasites, yeast, clostridia, H. pylori), Gastritis, Peptic ulcer, and food allergies/intolerances.

Secondary deficiencies will also need to be addressed as a result of pre-existing deficiencies of B6 and Zinc. These nutrients are crucial for the production of other nutrients, neurotransmitters, hormones, and over 100 enzymes in the body: Manganese, Magnesium, Biotin, Vitamin B complex, Omega 6 essential fatty acids (EFA) in particular Arachidonic acid, 5 Hydroxy Tryptophan (5HTP), Vitamins A, C, E, Glutamine, Gamma Amino Butyric Acid (GABA), Inositol, Taurine, and Glycine are some examples of nutrients that may need to be included in your initial treatment regime. Due to alterations in the fatty acid pathways, deficiency in arachidonic acid (Omega 6) is most common. It is important to note that omega 3 EFA's (EPA/DHA) must also be avoided, as they compete with omega 6 in enzymatic pathways. In this case it is the enzyme delta 5,6 desaturase that is required to convert omega 6 to arachidonic acid.

Chelation Therapy

Chelation therapy may also be necessary for those with long standing Pyroluria who exhibit high copper levels. Copper levels can be tested utilising hair and blood analysis. Copper and Zinc compete for cellular uptake on receptor sites, so when Zinc levels are low, Copper will be high. Copper is neurotoxic to the body in higher than normal amounts, exhibiting similar chemical behaviour as an equivalent dose of the psycho-stimulant drug D-amphetamine. High copper levels can also be initiated by long term stress, a common state for the Pyroluric.

During emotional, mental or physical stress the body releases Aldosterone, Cortisol and Adrenaline. Aldosterone, in particular increases the retention of copper and sodium to protect us from the perceived threat, producing a neuro-excitatory effect and simultaneously releases Zinc and Magnesium (our calming nutrients). The body retains excess copper causing further neurotoxicity. Chelation therapy involves the use of high dose Vitamin C, Zeolite (Volcanic ash), Copper antagonists such as Zinc, Manganese and Molybdenum. Nutrients that encourage the formation of Metallothionein (Copper binding protein) such as Selenium, Vitamin B6, Zinc and Folinic acid will further assist in balancing copper levels in the body. Chelation must be taken slowly to prevent exacerbation of symptoms. Copper removal commonly creates an initial aggravation of copper related symptoms, so care must be taken during this process.

Diet and Digestion

It's vitally important to treat Pyroluria from a holistic standpoint. Addressing only the nutrient deficiencies, and copper chelation, may not be enough. Long standing deficiency, chronic adrenal stress, high copper, and poor diet can contribute to digestive disorders and intestinal dysbiosis that may further affect absorption of the nutrients required to reestablish optimum health. Investigations and corrections of diet and digestion form an important part of long term treatment success.

Diet has a profound effect and behave. There is a tendency in Pyroluria towards high consumption of sugar/refined carbohydrate foods and alcohol, to compensate for low serotonin levels. Serotonin is the body's natural anti-depressant, inducing a sense of well-being, calm, and confidence. Low serotonin levels are comomonly seen in Pyroluria due to the Vitamin B6 deficiency. Vitamin B6 (P5P) is a necessary coenzyme in the conversion of tryptophan to serotonin. Eating foods like cakes, chocolate, potato chips or ice-cream and drinking alcohol, are usually the first things we reach for when we are anxious, depressed, or sad. These high sugar substances increase insulin production in order to lower our blood sugar levels. The high levels of insulin produced, flush out competing amino acids, allowing higher levels of the amino acid tryptophan to reach the brain. The end result is a boost of serotonin to elevate mood and reduce anxiety. There is some therapeutic benefit in treating Pyroluria with Tryptophan or 5HTP supplementation, especially if the patient suffers from depression and insomnia and craves sweets and carbohydrates.

Marked improvements have been seen in pyroluric patients embracing gluten free and low- no-grain and no-sugar diets. Decreasing sugar and refined carbohydrates and opting for gluten free wholegrains can further improve recovery when an underlying digestive disorder is present. Some interesting insights have been discovered by British neurologist and nutritionist Dr Natasha Campbell-McBride who developed the GAPS diet, Gut and Psychology Syndrome. Her book outlines the relationship and importance between our mental and gastrointestinal health. There is an emphasis on maintaining the intricate balance of our intestinal flora, without which we can not digest food or absorb nutrients. When we consume large amounts of sugar, refined carbohydrates, alcohol, yeast containing foods, or food we are allergic/intolerant to (gluten, dairy, wheat, fructose, salicylates, yeasts, sulfur, caffeine etc) we provide the perfect breeding ground for opportunistic organisms. Intestinal dysbiosis will develop with the most common culprits being yeast (candida) and the Clostridia family. These organisms produce their own toxins. Yeasts create acetaldehyde and alcohol, causing liver damage, with an inability to remove old neurotransmitters, hormones and other byproducts of normal metabolism from the body. These substances accumulate in the body causing behavioural abnormalities. Pancreatic damage with a reduced ability to produce pancreatic enzymes; brain damage with loss of memory, impaired coordination, stupor, mental retardation, are also side effects of these yeast producing toxins. Clostridia produces neurotoxins which have been seen in patients with Schizophrenia, Autism, and severe depression.

When there is evidence of digestive abnormalities, with symptoms such as constipation, excessive flatulence, diarrhoea, intestinal cramps, epigastric pain, irregular bowel motions, reflux, heartburn, nausea and vomiting, a comprehensive Gastrointestinal profile via DNA stool analysis can be utilised to investigate the presence of digestive disease, yeast, parasites, bacteria, intestinal dysbiosis or leaky gut syndrome. Any of these conditions can further complicate and slow recovery in Pyroluria. Treatment may include high dose probiotics, glutamine, deglycyrrhizinated licorice (DGL), hydrochloric acid, pancreatic enzymes, anti-parasitic and anti-fungal herbs/nutrients - Black Walnut, Pau d'arco, Saccharomyces boulardii, Methylsulfonylmethane for those who are not sulfur sensitive (CBS, SUOX polymorphisms), Wormwood, Caprylic acid, Cloves, Goldenseal, Oregon grape and Citrus seed extract. Diet change will be at the core of treatment success in these cases.

Hormone Regulation

Hormonal balance is another aspect worth mentioning. It is intricately tied into digestive and neurobehavioral health and heavily influenced by deficiencies of Zinc, B6 and high copper levels. High oestrogen levels overstimulate aldosterone receptors, which in turn leads to copper retention, similarly to the stress response. Symptoms of high blood pressure, fluid retention through an increase in blood volume may be evident; common side effects seen in those taking the Oral Contraceptive Pill (OCP). Interestingly the OCP has been associated with exacerbation in patients suffering from Schizophrenia, with complete remission of their schizophrenic symptoms once the OCP was stopped.

Conditions that may ensue from estrogen imbalance/dominance include PMS, ovarian cysts, miscarriage, Polycystic Ovarian Syndrome (PCOS), Uterine fibroids, sexual dysfunction. High oestrogen levels can occur as a result of toxic exposure to xeno-estrogens within the environment/food. Xeno-estrogens chemically mimic our natural estrogen hormones and replace them on receptor sites within our cells. This unnatural replacement creates imbalance within estrogen levels and ratios between other hormones within the body - progesterone, thyroid hormones etc. Xeno-estrogen's can be avoided; they are present in pesticides, plastics - especially soft plastics (food wrap), volatile organic compounds (VOC's), growth hormones used in animals, and all petrochemical waste products used in the manufacture of plastics, gasoline and petrochemical derivatives. Estrogen imbalance can also occur from inside the body; this is where hormones and digestion are intricately involved. When our digestive processes slow down, and we adopt unhealthy dietary principles, or ones that do not suit our genotype/constitution, our intestines can become a compost heap and putrefaction/fermentation ensues. Bacterial imbalance within our intestinal microbiota leads to production of toxic metabolites and a great deal of metabolic activity that is detrimental to our health. During putrefaction, the bacterial enzyme beta-glucuronidase is produced, causing an enterohepatic recirculation of estrogen, rather than elimination of excess levels, placing extra strain on the liver's role of conjugating and eliminating oestrogen. This disease causing biochemical pathway, induced by poor diet, creates a state of oestrogen dominance within the body, increasing the risk of hormonally dependant cancers, hormonal disease, obesity, diabetes, circulatory disorders and much more. Supplementation with Calcium d-glucarate can support oestrogen reduction through inhibition of beta-glucuronidase activity. Diindolylmethane (DIM) is another natural compound obtained from the Brassica family, which can be used to inhibit oestrogen's dominant effect in the body. It works by adjusting the pathways of oestrogen metabolism in favour of 2-hydroxy oestrone production, whilst simultaneously decreasing 16-alpha hydroxy oestrone levels. 2-hydroxy oestrone has been indicated through clinical studies as a protective biomarker against hormonally dependant cancers.

Symptoms of hypothyroidism; fatigue, depression, brain fog, constipation, dry skin, dry, thinning hair, weight gain, intolerance to cold, excessive menstrual flow, can also be seen in oestrogen dominant states. Estrogen has a similar chemical structure to the active thyroid hormone Triiodothyronine (T3) and can block receptors sites on the cell membrane, inducing a hypothyroid state. Copper also plays a part by disrupting the conversion of Thyroxine (T4) to T3. Addressing Copper, Oestrogen and stress levels can have a positive impact on regulating metabolic activity of the thyroid gland.

Treatment for hormonal balancing will focus largely on correcting nutritional imbalances and dietary change; reduction and in some cases elimination of sugar, grains, alcohol, excessive fat/protein intake from animal sources (meat, dairy). Simultaneously increasing fibre and vegetable content and shaping your diet around vegetables/fruits/nuts/seeds/lean meat as your core will provide the quickest results to eliminate the state of putrefaction. Diet coaching with an understanding of how to eat; being in a relaxed, present state, no fluids with meals, small portion sizes, chewing well, and possible use of aperitifs, will improve hormonal balance. Increasing transit time of stool is vitally important with the concurrent use of probiotics, certain fibres and cultured foods.

Lifestyle Considerations

Treatment will always vary depending on the individual. We are biochemically and genetically unique. No treatment would be complete without addressing one's lifestyle and the need to discover and implement stress reducing strategies. And these strategies will indeed be different for everyone. Some people will find exercise helpful: yoga, swimming, kick boxing, martial arts, pilates, dance, gym. Other's may find relaxation in practices like meditation, breathing techniques (Uijayi breathing), sound healing and music. Other ideas include support/social groups, emWave (biofeedback personal stress reducer), retreats, massage, emotional freedom technique (EFT), neuro-emotional technique (NET), neurolink. Lifestyle changes and stress reducing activities will help you develop internal resources and healthier coping mechanisms, that you can incorporate into your daily life. Balancing your daily stress levels is key to keeping copper levels down, and maximising the calming benefits of zinc supplementation.

The encouraging part about Pyroluria treatment is that in patients with uncomplicated Pyroluria (no food allergy/digestive disorder/methylation issues), improvement can be seen within a few days, with only taking Zinc and Vitamin B6. In more complicated cases, where diet and digestion need addressing, it may take 3-6 months to reach a consistently stable level. This will be dependant on patient compliance with new diet change, and also allowing for an adjustment period of learning new information, new ways of cooking, techniques for stress reduction etc. Because of the varying presentations and severities of pyroluria, each person does best with a treatment plan specifically tailored to them. It is important to note that discontinuation of a treatment regime may result in deterioration of the patient within as little as 48 hours.

Pyroluria has only begun to be recognised as a medical condition for about 10 years now and many health practitioners are still not taught about it in school. Due to a lack of knowledge, awareness, research, and complete acceptance within the mainstream medical profession, unfortunately most people with Pyroluria go undiagnosed. On a positive note, I am continuously becoming aware of more and more doctors and psychiatrists worldwide accepting the validity of Pyroluria and changing the lives of those suffering from mental illness. Though without proper identification and treatment, those affected tend to become loners in order to avoid stressful situations in life. Their lives become an ongoing struggle to protect themselves from too much emotional and physical stress. Let's spread the word and openly share our experiences with others, and start support groups within our communities. Let us find ways for Pyroluria to become known and accepted within our society, so we are no longer hiding behind a veil.

An Inspiring True Story

Extracted from Direct Health Care Access Laboratory website:

A classic case involved an 11 year old girl diagnosed with Schizophrenia. Her history included chronic insomnia, loss of reality, attempted suicide, amnesia, seizures, nausea, vomiting and debilitating pain in her extremeties. She was misdiagnosed by a series of physicians, labelled as "schizophrenic," "paranoid" and "schizophrenic with convulsive disorder." Psychotherapy and medications were ineffective. Her physical debilitation was almost total.

Everything changed when a Kryptopyrrole Quantitative Urine Test, demonstrated that her symptoms were consistent with elevated kyptopyrrole levels. Indeed, her urinary kryptopyrrole level was at times as high as 1,000mcg (the normal range is less that 15mcg). She was diagnosed as vitamin B6 and zinc deficient and treatment commenced immediately.

In just three months her pain disappeared, the depression subsided and the seizures and nausea vanished. In effect, all of her symptoms were gone! Since then, she has experienced no recurrence of her grave illness. She has finished college and now works in New York. She takes zinc and B6 daily. When under stress of any kind, she increases her intake of vitamin B6. All indications are that she has been completely cured as a direct result of correct diagnosis and proper treatment.

Pyroluria Quiz

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  1. Hoffer, A. and Osmond, H., Malvaria: A New Psychiatric Disease, Acta Psychiatrica Scandanivica, 1963.
  2. Ward, J.L., Relationship of Kryptopyrrole, Zinc and Pyridoxine in Schizophrenics,Journal of Orthomolecular Psychiatry, 1975.
  3. Pfeiffer, C.C., Sohler, A., and Jenney, E.H., Treatment of Pyroluric Schizophrenia (Malvaria) with large doses of pyridoxine and a dietary supplement of zinc, Journal of Applied Nutrition, 1974.
  4. Pfeiffer, C.C. and Holford, P., Mental Illness and Schizophrenia: the Nutritional Connection, Harper Collins, 1987.
  5. McGinnis, W.R., Discerning the Mauve Factor Part 1 and 2, In Press, 2007.
  6. Hoffer, A., The Discovery of Kryptopyrrole and it's importance in diagnosis of biochemical imbalances in Schizophrenia and in criminal behaviour, Journal of Orthomolecular Medicine, 1995.
  7. Cutler, M.G., Graham, D.J., and Moore, M.R., The Mauve Factor of Porphyria, 3-ethyl-5-hydroxy-4,5-dimethyl-delta-3-pyrrolline-2-one: effects on behaviour of rats and mice,Pharmacology & Toxicology, 1990.
  8. Pfeiffer, C.C., Mailloux, R., and Forsythe, L., The Schizophrenias: ours to conquer, Biocommunications Press, 1988.
  9. Irvine, D.G., Pyrroles in Neuropyschiatric and Porphyric disorders: confirmation of a metabolite structure by synthesis, Life Sci, 1978.
  10. Campbell-McBride.N., Gut and Psychology Syndrome, Medinform Publushing, 2004.
  11. Forsgren.S., 2010, Kryptopyrroluria (aka hemopyrrollactamuria): A major piece of the puzzle in overcoming Lyme disease, Public Health Alert, vol. 5, no. 5, viewed 23rd January 2011.
  12. McGinnis, W.R., 2004, Pyroluria - Hidden Cause of Schizophrenia, Bipolar, Depression and Anxiety Symptoms, International Guide to the World of Alternative Health, viewed 24th January 2011.
  13. Heleniak, E.P., Lamola, S.W., 1986, A new prostanglandin disturbance syndrome in Schizophrenia, Pub Med, viewed 25th January 2011.

© 2012 Natural Insight


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    • profile image

      Zarah 12 months ago

      Hi Do you have a reference for oestrogen disturbance due to poor digestion/putrification?

    • profile image

      Susan Bunt 17 months ago

      You say in this report that you recommend taking 200mg of Pyridoxine hydrochloride AND P5P. Do you mean Or P5P?

      Thank you

    • profile image

      EB 21 months ago

      I've just been diagnosed with pyroluria by the BrainBio Centre in Putney (London UK). They specialise in nutritional and functional treatment of mental/brain problems and I can highly recommend the centre. They see people in London but they also do phone/ skype consultations. For those who are interested, the test is £47 and I'm sure you can do the test from abroad and just send it to the lab in London by special post. This could help people who live somewhere where it's hard to find testing. It's changed my life and I hope this information might help other people. Good luck!

    • profile image

      Deirdre 2 years ago

      Could you please put the link to the facebook page?

    • profile image

      Alethea Black 2 years ago

      Thank you, Helen. This is a truly wonderful article, and treating Pyroluria has been life-changing for me. I believe this illness is especially common among artists (it is associated with high copper; copper conducts energy in the body, just as if does in copper wires), and perhaps pyroluria's copper dysregulation may help explain the historical associations between creativity and madness.

      But independent of that, I would love to see a non-profit set up to increase awareness of this under recognized, under diagnosed illness and perhaps provide support to sufferers. I have also floated this idea to Trudy Scott, another source of great knowledge on this topic. If anyone is interested, please let her or me know. I have no experience with 501©s, but would love to donate, if one were set up.

    • lyoness913 profile image

      Summer LeBlanc 3 years ago from H-Town

      Something that really helps Pyroluria is a good, medical grade infrared sauna which helps you sweat out toxins like copper and heavy metals. Excellent, well researched article. Fascinating- voted up and interesting


    • profile image

      Pauline 3 years ago

      my daughter has recently been diagnosed with Pyroluria and has also has chronns disease which is in remission and was wondering if there is a connection between the two

    • profile image

      veronick 3 years ago

      can i have this full tests done in Singapore ??????? where ?? which clinic or hospital

      or in Bangkok ?????

      please help me. txs.

    • profile image

      Nicole Harris2 4 years ago

      Mensah Medical should be listed as a resource on here -- Pfeiffer Treatment Center is CLOSED -- they no longer do the work of William J. Walsh. Drs. Mensah and Bowman were trained under William J. Walsh, PhD of the Walsh Research Institute. They are physicians that specialize in biochemical imbalances including pyroluria, methylation (histamine), copper/zinc and other nutritional deficiencies/overloads including gut health. Their website is They are doing a FREE webinar too!

    • profile image

      Cheryl 4 years ago

      Nev - this is the link to one of the FB Pyroluria pages.

    • profile image

      Nev 4 years ago

      Hi I have searched facebook cannot fing Pyroluria page

      Can you helpme please

    • profile image

      Ruth 4 years ago

      What a great article! Thank you so much for being so thorough and concise. I have read some speculation on and statements claiming that pyroluria is caused by an infection which can be passed on from mother to child. Dr. Klinghardt, Dr. Campbell Mcbride and others have made such statements. as such it is possible to heal the pyroluria. Are you aware of specifically what infections may causeit?

      I have pyroluria, and as a consequence have had a Lyme test which came back negative. I don't know much about Lyme disease, but I do know that some lab tests for different things are inconclusive. For some you can easily get a false positive so if you get a positive result you might have it or you might not, but if you get a negative you don't have it. For some you can easily get a false negative so if you get a negative result you might have it or you might not, but if you get a positive, you have it. So I'm still wondering if I might have it, although my doctor stated I'm the least likely person to have it. I take the supplements as originally prescribed, but rarely have a lot of money, so have not received further treatment. They keep me sane, but I still have problems with hypothyroidism, inflammation, craving sweets, high levels of c reactive protein. Any suggestions?

    • profile image

      Martina 4 years ago

      My son was diagnosed when he was 13. He is 24 now. Due to the move to the USA we first didn't find much info. I am happy to have found this site. Where do we get good supplements? And does he have to redo the urine test? I still got the information of the original dosage of supplements.

      Thank you so much.

    • profile image

      CAWS 4 years ago

      Can you tell me which SNPs are related to this disorder? I have access to 23and me raw data. Interesting most of the syptoms align with metal poisoning & the porphrins test [along with hair & urine] is considered a confirmation of this. The "white lines in the fingernails" symptoms are a specific marker for arsenic intoxication. Hg,Pb,Cd,Al are also known to cause mineral derangement, hormone disruption, & mental disorders. Safe, effective, & cheap chelation protocols can be found at no amalgams dot com.

    • profile image

      5 years ago


      I have just learnt about this and would like to be tested, but I live in the UK. I have heard that it is the Hemopyrrole test that needs doing but all I can find here is the Kryptopyrrole test. The lady who wrote the Cure for Mood book said in a radio interview that it should be the former test. I only found out about this yesterday and I am desperate to get tested as I really think I could have it. Also, I've read that they now think it's a bacteria? Is that right? Thanks for any help you can give :)

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      Emma T 5 years ago

      Dr Wood in Bowral NSW Australia who works at East Brooke Medical Center is onto it. He is a very good doctor.

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      Fiona hall 5 years ago

      Thanks for info , will email you now.

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      Natural Insight 5 years ago from Western Australia

      Fiona, if you want me to analyse your 23andme results you can join the wait list...just email me at I don't offer consultations anymore, I only specialise in SNP analysis. Otherwise I can suggest Dr. Nancy Mullan who is based in the states...she does Skype sessions and is also very well versed in understanding methylation SNP testing. Warmest wishes x

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      Fiona hall 5 years ago

      Thanks for the great article! I just found out today that I am positive to pyroluria, and am wondering how to go about treating it, maybe not as simple as taking a few supplements! I have digestive issues and methylation problems also, starting to all come together now. I am in Australia in sydney, can you recommend a knowledgeable doctor to work with? I'm just waiting on results from 23andme also. Many thanks

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      Dick 5 years ago

      My daughter was just diagnosed with this disorder (today in fact). Reading this article explains the long road she (we) have been traveling the past 15 years. We look forward to her getting the treatment that she needs so that she can enjoy the life she is deserves/

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      Natural Insight 5 years ago from Western Australia

      petluvr10 I'm unable to answer all your questions here.. I prefer yasko, more accurate and focuses on what is needed. I'd be careful with fats until bile is sorted. Cholacol is my choice of supp here. I'd look at phosphatidylserine or a combo of PC/PS/PE for your adrenal issues and more. It will gently open up short route pathway of methylation. RNA, cholacol and PS combo is avail through Dr. Yasko's holistic heal site. Wishing you well on your journey to whole health.

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      Petluvr10 5 years ago

      Sorry, my comment sent too soon...

      Is it best to be on the supps for a few months first, before doing genetic testing?

      What thorough testing do u recommend for the gut issues, bile problems, and sibo and such?

      Lastly, is ox bile good for bile? Betaine hcl for low stomach acid? Have u heard of NOW brands super enzyme... It has these but also has animal based pancreatic... Or is a plant based pancreatic better?

      Where do I get those RNa supps and are they expensive? I've taken betaine hcl and enzymes in the past, but hey didn't seem to help enough.

      Thanks for the macro suggestion. I've been on a high carb low fat diet for a long time and it is not serving me well... Catch 22 is that I don't digest pro and fat well.

      What do u recommend for adrenal fatigue with issues of no energy, intolerance to exercise (it makes me anxious), can't sleep, gaining fat around midsection, painful joints and skin, round face, water retention, massive cravings for sweets (for me, it's dates), reversal of circadian rhythm into a night owl, hot flashes (in my 20s...I not menopausal), no period, anxious and depressed. Etc? I was the complete opposite a for several years but this changed a couple months ago fast. I used to not be able to gain wt and would wake up early and always be cold. Complete opposite now. ;(

      Thanks so much for ur amazing knowledge :n) this is so hard to navigate thru

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      Petluvr10 5 years ago

      Thank so much!! I'm currently seeing practitioners who use the Walsh/Pfeiffer method for biochemical imbalacnces, so I had those tests done, as well an oaT and a stool test. I'm in the USA. I've seen a lot of people get the genetic tests done (23andme or yasko). Which of these tests is best and why?


      My doctors have not order any genetic testing yet. Is this a common test for the walsh/Pfeiffer method? Also, how do these differ from the OAT?

      Mind u, I just started on this path and just got my RX for my supplements. is it best to be on the supps for a few months first before doing the genetic test

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      Natural Insight 5 years ago from Western Australia

      @petluvr10 I'd look at bile insufficiency and consider support here as well as for the pancreas. Low elastase can indicate bile insufficiency. Stomach pH RNA by Dr. Yasko is great for balancing stomach, which in turn helps the rest of digestion. Bile salts can assist GB. Definitely use pancreatic enzymes...trienza are my favourite. Specific methylation work would help with long term gut issues (for instance if BH4 is low, highly prone to GI infections and SIBO) much to consider, so thorough testing would be advised. I don't have specific suggestions for macro ratios. I'm very much into individualised diet to suit a person. Some need far more carbs, fats or protein than others. I personally eat more fats and slightly more carbs (mostly veg sources) than protein...maybe 50 fats, 30 carbs and 20 protein. There will surely be times where the carb/protein levels are very on par with one another. I'm very slim and my nervous system feels well nourished with good quality fats so I keep those high.

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      Petluvr10 5 years ago

      Thanks.... I do have bad gut infections (yeast and bacteria like klebsiella), am slightly under methylated (histamine at 61), copper toxic and low zinc at 69. I've been on a fruit based raw vegan diet for over a year. My elastase is low so my pancreatic enzyme production isn't great. I'm prettysure I have sibo and low hcl. So, based on this, what are ur thoughts?

      Lastly. In general, what macronutrient ratios are optimal... There are so many theories on this, from high carb to really high fat and everything in between, but for gi and kpu, what tends to be the best?

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      Natural Insight 5 years ago from Western Australia

      Linda - yes you can share this. Please site my name Helen Janneson Bense as author. Thank you :)

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      Natural Insight 5 years ago

      @Petluvr10 diet is individual and needs to be based on more than just pyrrole results. I'd be looking at methylation, ammonia levels, possible GI infections/leaky gut/dysbiosis and food intolerance - amines, phenols, sals, etc. There is a lot to consider. Legumes are not ok for some, depends on GI stability. I'd recommend a more paleo style diet and focus on good fats, protein and vegetable sources of carbohydrates. Too many grains are irritating for the gut and for most pyrroles GI inflammation is a big aggravating factor.

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      Petluvr10 5 years ago

      Can u elaborate more on diet? Do u recommend a vegetarian diet or more of a paleo diet? Are legumes ok and what should the optimal ratio of carb, fat, protein be to best nourish a person with this disorder?

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      Linda Purdy 5 years ago

      Am I allowed to share this article on facebook?

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      Natural Insight 5 years ago from Western Australia

      Isabella try the facebook Pyroluria page. there are many helpful people there :)

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      Isabellak 5 years ago

      This is the best info I have found on Pyroluria on the net! Thanks for putting it together. I have an 11yo daughter who has been diagnosed with the disorder and since starting her course of primer pyrrole capsules the difference has been amazing but we still have a long way to go. I am in Australia and am having trouble finding support groups. Do you know of any? Thanks :-)

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      Natural Insight 5 years ago from Western Australia

      Yes I agree Caryn. I have had to address diet, emotions and environmental issues. Regular testing to check zinc/copper/ceruloplasmin is also important. There is much to consider, as well as overlapping methylation issues.

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      Natural Insight 5 years ago from Western Australia

      Thanks so much Jane. Appreciate your feedback and hopefully you'll get the answers you need. Take care and all the best on your healing journey :)

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      Jane 5 years ago

      I really appreciate this incredible summary. I have been recently told by a family member that she has this condition and it could be an issue with me. Reading this page is like reading my life, and I'm hoping that I can work with my naturopath on exploring this possibility. Thank you so much. I hope you will leave this page up forever!

    • profile image 5 years ago

      Our family has been dealing with pyroluria too. In our case our son has a motor tic disorder. Once on supplements there are no symptoms. I think it is important for people to understand that you can't just take supplements. Dr. McGinnis told us to watch for tissue saturation. Once the tissues get saturated the patient will start to have nausea from the zinc. You really need to be under doctor supervision, especially at the start. Here's our story:

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      Natural Insight 6 years ago from Western Australia

      Lizzie I know how it feels. I have pyroluria and methylation issues and it's been a long road to recovery, but you will get there. There is a great Facebook group we all support each other on. I highly recommend getting on there. I offer my guidance on there as well as a wonderful biomedical doctor here in Australia. There is so much information we have collected in documents too. Look forward to seeing you on there :)

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      Lizzie 6 years ago

      Thanks so much for your impute i'm just so sick of feeling so horrible and want to find a way to get someone who specializes in it. I appreciate your feedback greatly!! It feels good to connect with someone who might have it or knows of it.. Otherwise, I feel so alone in the situation. Thanks again. Blessings.

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      Natural Insight 6 years ago

      Pfeiffer Treatment Centre is great if you are in the states. Expensive though. Direct Health Care Access II Laboratory do the testing as well. I recommend every few months doing the Plasma zinc, serum copper and ceruloplasmin (copper binding protein) to assess where your free copper and zinc/copper ratio is at. This helps to determine the right doses of zinc. B6 is harder to work out as it can be impacted by methylation pathway defects. Getting zinc right though lowers copper and that helps immensely. Take care

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      Lizzie 6 years ago

      This is such a great summarization of this disorder and extremely thorough. I really appreciate this information. I'm wondering if you know anything about Pfeiffer Treatment Center? And, if you would highly recommend getting testing from them.. I was diagnosed with mild pyroluria, but have yet to find the right dose of b6 and zinc that was right for me. I worked with a naturopath, but no longer able to see this person. I feel so lost in finding a doctor that specializes in this.. and have been suffering greatly from it.

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      Natural Insight 6 years ago

      That's wonderful to hear. I am too so grateful for all the progress I've made with the pyrrole treatment regime. Thanks for your feedback :)

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      Harry777 6 years ago

      That is an awesome post about Pyroluria. I have suffered from this disease and it took me 8 years to work out what was wrong with me.

      The supplements I take for this condition have been a real lifesaver to me. Nearly all my symptoms have been resolved and I'm very close to being in perfect health now.


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