Pyroluria - A Hidden Disorder

"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. Pyroluriathe 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
What is Pyroluria?
Pyroluria is a genetic blood disorder, a chemical imbalance, involving an
abnormality in haemoglobin synthesis. Haemoglobin is a protein in the body, that
holds iron in the red blood cell. During production of haemoglobin, there is a
seemingly harmless byproduct created called Kryptopyrrole or what is now more
specifically and accurately known as OHHPL, or HPL (hydroxyhemoppyrrolin-2one). HPL is a chemical substance involved in the formation of heme, what
makes blood red. In most individuals this byproduct is harmless and excreted in
the urine. In 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, with 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.
Aetiology and History of Pyroluria
A familial condition, caused by poor genetics (such as familial alcoholism) and/or
by environmental toxicity. It 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, triggered by a traumatic incident - death of a
loved one, parental divorce, 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 discoverd in the late 1950's 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 he 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, 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 by Dr. Carl Pfeiffer of an American research team to
"Pyrolleuria" which was, for no obvious reason, consistently spelled "Pyrroluria"
in later publications. It is also known as Kryptopyrroluria (KPU) and
Haemopyrrollactamuria (HPU). In the 1970's 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.
Signs, Symptoms And Conditions Associated with Pyroluria
Signs
Characteristics commonly seen are: white spots on fingernails, unusual fat
distribution (larger mid section), increased incidence of stretch marks, pale skin
that burns easily, sweet, fruity breath and body odour, overcrowded teeth, coarse
eyebrows, poor appearance of tooth enamel, creaking knees, cold hands and
feet, stunting of 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 knee/leg pain,
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, Aspergers, Obsessive Compulsive Disorder, Multiple

Sclerosis, Parkinson's disease, Lyme disease.
There are varying degrees of Pyroluria; expression of this condition can be mild
to 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.
Diagnosis of Pyroluria
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 Pfeiffers 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.
Treatment of Pyroluria
NUTRIENT CORRECTION
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-5phosphate (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 it's 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 3 natural forms of Vitamin B6 found in food - Pyridoxine, Pyridoxamine
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 - ie
underlying digestive malabsorptive disorders: 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, 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, 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 neuroexcitatory 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 & 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 affect on how you feel 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 icecream 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, insomnia and craves sweets/carbohydrates.

Marked improvements have been seen in pyroluric patients embracing gluten
free and low/no grain/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 over stimulate
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 so 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.
Copyright Insight Naturopathy 2012
A Real Life Inspiring Story
Extract from Direct Health Care Access Laboratory website
http://www.kryptopyrrole.com/
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 consistant 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