PYROLURIA and CANDIDA

Twin Causes of Modern Diseases

by Walter Last

Introduction

This article shows that Pyroluria, an inherited or acquired liver defect, in combination with Candida overgrowth, are key factors in causing our modern diseases. Pyroluria is a common metabolic condition in which pyrrole, a key component of haem (as in haemoglobin), is overproduced in the liver, thereby causing a wide range of symptoms. The severity of this condition fluctuates widely as it is strongly related to stress levels. Symptoms range from liver and gastro-intestinal problems, to mental-emotional and neurological diseases, disorders of the blood and circulation, skin and muscle problems, and other connective tissue disorders.

Candida overgrowth, most commonly caused by antibiotic therapy, is the second factor. In this article the term "Candida" is only used as shorthand for a syndrome that includes intestinal dysbiosis; leaky gut syndrome or intestinal permeability caused by the invasive hyphal form of Candida; fungal metabolic chemicals affecting blood, muscles, nerves and brain, often blocking the oxidative energy metabolism in parts of the body, and a wide range of mycoplasmas and other pleomorphic microbes and parasites now invading the body as the immune system becomes increasingly ineffective due to the continuing assault by the hyphal Candida.

"Hyphae" are long, branching filamentous structures which grow through the intestinal wall, causing inflammation and making it permeable to intestinal toxins. In this fungal form Candida is much more dangerous than its easily treatable yeast-form.

Two Conditions Making Health Problems Much Worse    

Pyroluria and Candida, just like other modern diseases, have greatly increased in recent decades. However, I have now come to the conclusion that they are not just normal diseases but rather the underlying causes for the epidemic increase of many or most of our modern diseases. Pyroluria and Candida not only cause very similar disease symptoms, they also encourage each other's development, and if both are present together they make any health problems very much worse.

Pyroluria is a common metabolic condition in which pyrrole, a key component of haem as in haemoglobin, is overproduced in the liver and bone marrow. The surplus binds to vitamin B6 and zinc and is excreted in the faeces and urine, but part of it tends to remain in the body as obstructive waste residues. This creates severe deficiencies in B6 and zinc, and to a lesser degree in some other nutrients, such as niacinamide, gamma linolenic acid (GLA), biotin, and sometimes manganese; also other B-vitamins, especially vitamins B2, B3 and B5, may be low.

Vitamin B6 and zinc are essential for producing enzymes that are required for building all proteins, be they other enzymes, hormones, and neurotransmitters, components of the immune system, muscles, organs or connective tissue. Another major problem is that pyrrole waste chemicals tend to inhibit the conversion of pyridoxine, the common form of vitamin B6 in food, into its active form pyridoxal-5-phosphate or P5P. In a vicious circle deficiency of P5P reduces the synthesis of haem and haemoglobin, and increases formation of pyrrole wastes.

Other names for pyroluria are pyrroluria, pyrrole disorder, and mauve factor or Mauve. Initially it was thought that the compound causing the colour change in urine is Kryptopyrrole or KP, but newer research found the mauve factor to be the closely related derivative hydroxyhemopyrrolin-2-one or HPL. However, in addition many other pyrrole derivatives may be excreted as well.    

It has been estimated that the prevalence of pyroluria in the general population is about 10% and in those with chronic diseases and unexplained health problems closer to 50% and up to 80%, especially in the acute stages of mental-emotional problems such as ADHD/hyperactivity, anxiety disorders, autism/Asperger syndrome, bipolar disease, depression, obsessive compulsive disorder, and schizophrenia, but also with cancer, especially bowel cancer, dementia and liver diseases. With criminal behaviours it can test up to 71% (criminality a deficiency disease?), and with  all porphyrin diseases it is 100% (1). This reference also has a list of diagnostic laboratories.

Pyroluria is widely accepted and treated in natural medicine but not recognised by conventional medicine which basically ignores it. Conventional medicine uses instead the term "Porphyria" for a rare form of liver disease in which one of 8 different enzymes needed for the production of haemoglobin and other haem proteins is deficient, causing 7 different types of porphyria. These cause somewhat different sets of symptoms, mainly with abdominal pain, colic, neuropathy, psychiatric disorders, tachycardia (fast heartbeat), severe photosensitivity with erythema (skin redness or rash), purple skin lesions, swelling and blistering, haemolytic anaemia, enlarged spleen, developmental delay, gallstones, and liver dysfunction.

The term porphyria is derived from Greek and means "purple pigment". This refers to the purple discolouration of faeces and urine of patients when exposed to sunlight during an attack. This is also why the term "mauve factor" has been used for pyroluria. Conventional medicine generally distinguishes between acute porphyrias, mainly affecting the nervous system, often with severe abdominal pain, nausea, vomiting, neuropathy and acute mental-emotional problems, and cutaneous porphyrias with skin inflammations, often after exposure to the sun, due to the accumulation of excess porphyrins in the skin.

All or any of these symptoms can also be present with pyroluria. Pyroluria definitely belongs to the porphyrias but medical laboratories do not test for it, only relatively few specialised laboratories do this, and also porphyria enzymes are only tested in very few medical reference laboratories. These conventional enzyme deficiency tests are very ineffective and tend to work only during acute attacks. Repeat testing may be necessary to detect porphyria, and even in the initial stages of life-threatening attacks tests may fail (2). This makes it understandable why porphyria is regarded as a very rare disease in conventional medicine, while pyroluria, a form of porphyria which is much easier to detect, is so widespread. Pain and nausea during acute stages of porphyria can be very severe and out of proportion to any physical signs.

An Overview

The movie "The Madness of King George" relates the story of King George III's bouts with porphyria/pyroluria with his doctors chasing after him to examine his urine for signs of the mauve factor - deterioration of the disease is indicated when the urine develops a mauve colour as excreted pyrrole derivatives (HPL) are exposed to ultraviolet light.    

Depending on conditions, pyroluria is not only a main cause of mental-emotional disorders but may also be a leading cause of neurological dysfunctions, Type 1 diabetes, epilepsy, weak connective tissue, skin inflammations, poor muscle development and blood problems, especially clotting disorders. With severe vitamin B6 and zinc deficiency nothing works properly, and a wide range of chronic health problems is present as shown in Table 1. This is the common condition of most elderly individuals, but in the presence of pyroluria chronic health problems start much earlier, often already in childhood, and are more severe.

The main cause of pyroluria appears to be intestinal dysbiosis with overgrowth of Candida, pleomorphic (shape-changing) microbes, and possibly Lyme disease/Borreliosis. Any or all of these, in addition to viruses, may invade the liver and affect its functions. They also seem to be able to insert some of their own DNA into liver genes, especially changing our mitochondrial DNA involved with energy production. This then causes the acquired condition to be inheritable, and it often runs in families. Due to the overuse of antibiotics and other drugs, presently the original cause tends to be the fungal form of Candida, often in combination with the microbes of Lyme disease and parasites. Normal medical tests do not discover the fungal form of Candida in internal organs, only the less harmful yeast form.

Symptoms of Pyroluria

The symptoms of pyroluria generally fall into distinct groups. While commonly individuals experience problems with all groups, some symptoms may be rather mild while others can be rather severe. These main groups are liver and gastro-intestinal problems, mental-emotional and neurological problems, disorders of the blood circulation, skin problems, muscle problems, and above all connective tissue disorders. 

Some pyroluria symptoms, such as poor dream recall, are mainly functional and can improve rather quickly, but inherited conditions such as psoriasis, emotional or mental disorders, and weak connective tissue, can take a long time to improve. In advanced cases and in the presence of Candida, major improvements may take a long time to show up because all connective tissue needs to be rebuilt. Pyroluria difficulties commonly increase with age and especially with intestinal dysbiosis. In children, only certain acute symptoms may manifest: mainly digestive discomfort and abnormal brain activity such as hyperactivity and autism.

Many of the functional symptoms will only be present during acute stages, while long-term problems due to the accumulation of pyroluric and metabolic waste products in tissues may only show up with the inherited form of pyroluria. Newly acquired pyroluria may mainly affect the liver, and cause overacid, oxidative and inflammatory body conditions, often with arthritis, fatigue, and back or muscle pain. The presence of several of the symptoms and conditions shown in the following compilation may indicate pyroluria.

SYMPTOMS and CONDITIONS Associated with PYROLURIA

Blood, Circulation and Digestive Problems

Cold hands and feet, Carpal Tunnel Syndrome, Raynaud's Syndrome

Low blood pressure when young, BP may rise when older

Heart disease, enlarged heart, cardiovascular disease, aneurysms

poor brain blood supply, hypercoagulation, micro-clots, spider veins

Peripheral vascular disease, varicose veins, deep vein thrombosis, leg ulcers

Tendency toward anaemia and bleeding disorders, easily breaking capillaries

Problems with liver/gallbladder, pancreas, stomach and intestines

Fat malabsorption, poor fat metabolism, bloating, light coloured stool

Morning nausea or poor morning appetite, periods of abdominal pain

Difficulty digesting, especially proteins and fats, low gastric acid, acid reflux

Hormonal Problems and Deficiencies

Hormonal imbalances, puberty later than normal, menopausal problems

Problems with prostate or ovaries, male pattern baldness, miscarriage

Low enzyme activity, missing enzymes causing diseases

Problems with thyroid, parathyroid, adrenal and sex hormones,

Addictions, easily stressed due to weak adrenal glands (vitamin B5 helps)

Poor dream recall (vitamin B6 helps)

White spots on finger nails and stretch marks (zinc deficiency)

Poor sense of smell or taste (zinc deficiency)

Eye problems, sensitivity to bright light (vitamin B2 deficiency)

Hypersensitive to loud noise (magnesium helps)

Mental-Emotional and Neurological Conditions

Autism, hyperactivity, reading difficulty/dyslexia, Asperger syndrome

Family history of mental illness, suicide, addiction and psoriasis

Mood swings, temper outbursts, argumentative, dramatic tendency

Easily upset by criticism, "takes things to heart"

Bouts of depression or nervous exhaustion

Anxious, shy, worried, concerned, fearful, inner tensions

Stressed by new situations or changes in routine

May be a loner or avoids large groups of people, uneasy with strangers

Poor short term memory, dementia, Alzheimer's or Parkinson's disease

Difficulty recalling past events, names, people or finding things, mental block

Mental diseases or emotional problems, neurological disorders, epilepsy

Schizophrenia, bipolar disease, obsessive compulsive disorder

Paresthesia (tingly sensations or numbness), tremors in arms or legs

Skin and Connective Tissue Problems

Poor connective tissue & muscle development, hernias, cysts, crowded teeth

Prone to acne, eczema, psoriasis or other skin inflammations

Arthritis, especially rheumatoid and psoriatic arthritis, muscle pain

Skin depigmentation/vitiligo, purple skin spots, early greying hair

Dry, fragile or early aging skin, inelastic blood vessels, aneurisms

Pale or sensitive skin, poor tanning, burns easily in the sun

Problems with shoulders, arms, wrists, fingers, hands (also B6 deficiency)

Hypermobility of joints - Ehlers-Danlos syndrome, also Marfan syndrome 

Fibrosis/fibroids, Peyronie’s disease (fibrosis of the penis), distorted cornea

China doll syndrome/Moebius syndrome/facial paralysis

Others

Much more alert and capable in the evening than in the morning

When young prone to frequent colds, infections, and inflammations

Fatigue, tires easily, low energy, or low energy reserves

Bouts of hypoglycaemia, type1 diabetes, epilepsy, allergies, fainting

As a child had side-stitches when running

Overweight or persistent underweight

Abnormal body fat distribution around abdomen

May overreact to antibiotics, tranquilizers, alcohol or other drugs

Tendency to autoimmune diseases and cancer

Symptoms of Candida and intestinal dysbiosis

In the following I describe some key conditions in more detail based on published research (3,4,5) and my own experience.

Depressed Haem Production

Haem or heme (US spelling) is a heterocyclic ring system called porphyrin, which consists of four simple pyrrole groups joined together, and in the centre of the porphyrin ring is a ferrous or 2-valence iron ion. This is a haemoprotein. Haem is best known as a component of haemoglobin, the red pigment in blood, but is also present in muscles as myoglobin, in cytochrome needed for oxidative energy production, in catalase which prevents oxidative stress, in endothelial nitric oxide synthase which helps to relax blood vessels and muscles; thyroid peroxidase containing haem uses iodide ions and hydrogen peroxide to generate iodine, and plays a central role in the biosynthesis of thyroid hormones T3 and T4, and haems are also important for liver detoxification, the immune system and various other functions such as neuronal metabolic activity.

Without haem, cells cannot generate energy from oxidizing food. Depression of haem production leads to serious metabolic defects with anaemia, mitochondrial and neuronal decay, mental-emotional problems as well as overproduction of nitric oxide, causing slack and inelastic blood vessels. Underproduction of oxidative energy in muscles causes weakness, especially during extended exertion after glycogen has been used up and mainly lactic acid is generated. The combination of these factors can lead to fatigue and muscle pain. The heart is an essential muscle and may compensate for the lower output by becoming enlarged.

Another factor is a decreased generation of body heat. When the outside temperature drops so that hands and feet become cold, central body heat is preserved by greatly restricting blood-flow to the extremities, in extreme cases leading to Raynaud's Syndrome. 

From this it is easy to see how the disturbed production of haem has wide-ranging negative effects on all body functions, even before taking the serious vitamin B6 and zinc deficiencies into account that are created in this way. Deficiencies of vitamin B6, zinc and biotin also directly reduce the synthesis of haem, their deficiencies increase stress levels, causing weak adrenal glands, and stress independently degrades haem. It is all a vicious circle. Further, it is known that heavy metals, especially mercury, tend to disrupt the porphyrin metabolism and increase haem degradation. Haem depression increases leakage of oxidants from the mitochondria, thereby causing oxidative damage to cells and unsaturated oils.

Oxidative Stress

Oxidative stress also results from deficiency of zinc or P5P, the active form of vitamin B6. Glutathione is a key antioxidant inside cells, even marginal P5P deficiency is associated with lower glutathione enzymes, causing lower levels of reduced glutathione and higher levels of oxidized glutathione. There are also higher levels of oxidized oils and other lipids, and deterioration of energy-producing mitochondria. The P5P itself is highly vulnerable to oxidative damage. P5P protects neurons from oxidative stress, apparently by increasing energy production and lowering excitotoxicity as from MSG, while zinc supplementation decreases oxidized biomolecules. Since excretion of pyrrole derivatives is a marker for B6 and zinc deficiency, it is also a biomarker for oxidative stress.

Also other biomarkers for oxidative stress are known to be higher in high-pyrrole excretion disorders such as schizophrenia, autism, ADHD, Down syndrome, and alcoholism. Plasma levels of reduced glutathione are decreased in diseases associated with greater oxidative stress, such as Down syndrome and Alzheimer’s disease. Oxidative stress of the brain precedes the neurofibrillary tangles and plaque which indicate Alzheimer's disease. Low plasma glutathione correlates with increased levels of oxidized biomolecules in the brain. There is a very strong correlation of urinary pyrroles with plasma glutathione levels as biomarker for oxidative stress.

Pyrroles and Catalase

Catalase is a common enzyme which protects cells and biomolecules from oxidative damage. It causes the decomposition of hydrogen peroxide (H2O2) to water and oxygen. One catalase molecule can convert millions of hydrogen peroxide molecules to water and oxygen every second. It has four haem groups.

Excess pyrrole means reduced haem production and lower catalase levels. Catalase blood levels are low in schizophrenia and autism. A lower catalase level is associated with higher H2O2 levels and explains the hypopigmentation of the skin associated with excess pyrroles - such as pale, easily burning skin and the classic “china-doll” complexion.

In extreme cases low catalase and high H2O2 can lead to de-pigmentation of the skin as in vitiligo. This causes oxidative destruction of melanin and the pigment-producing melanocytes. This is also the mechanism by which high level pyroluria causes early greying of the hair. Excess H2O2 increases oxymelanin in hair and lightens it, similar to applying bleach. However, the type of melanin that produces blond or red hair colour (pheomelanin) is less affected than the eumelanin which colours hair brown to black.

Even zinc deficiency in itself leads to hypopigmentation, as melanin is rich in zinc and needs zinc for synthesis and maintenance. Zinc protects melanocytes from oxidation, and experimental zinc-deficiency greys the coats of rats. H2O2 displaces zinc from its binding proteins, and greater oxidative stress contributes to clinical zinc deficiency. In addition also copper (best supplied as organic copper complexes, see Copper Salicylate) is needed for melanin production.

A further consequence of low catalase activity and subsequent oxidative stress in the liver is the iron-storage disease haemochromatosis. Too much oxidised or ferric iron accumulates in the body and especially in liver and spleen, thereby greatly increasing oxidative stress. Most elderly individuals are affected. For being transported around the body to form red blood cells in bone marrow or to carry oxygen attached to haemoglobin, iron needs to be reduced by vitamin C from the 3-valence storage form to the 2-valence ferrous iron. But the small amount of vitamin C normally ingested is immediately oxidised in the liver and not able to reduce much 3-valence iron. Therefore the body is forced to absorb ever more iron to get what it needs. I found with several patients that 10 grams of vitamin C spaced out during the day quickly eliminates haemochromatosis (Natural Therapy for Haemochromatosis).

Connective Tissue Problems

Major health problems are caused by weak connective tissue, and especially poorly constructed and inelastic collagen. With inherited pyroluria we may find blood clotting disorders and weak blood vessel development such as peripheral vascular disease (PVD) leading to varicose veins, deep vein thrombosis, leg ulcers potentially requiring leg amputation in diabetes, and poor blood supply to the brain.

Many common conditions such as arthritis, degenerative eye changes (e.g. cataracts, macular degeneration), migraines, and multiple sclerosis are aggravated by circulation problems. Capillaries get easily congested from clotting or hypercoagulation and break easily with bruising and bleeding, aneurisms or ballooning arteries may be present as well as slack veins that do not properly pump blood back to the heart. Blood and metabolic wastes pool in the lower veins, contributing to cold hands and feet as well as prostate problems and haemorrhoids.

Muscles and joints may be underdeveloped, and the skin is not tight and elastic, but stretches too much and ages too early. Because tendons are too slack there may be hyper-mobility of joints - Ehlers-Danlos Syndrome, joints easily get out of the socket, the body does not have sufficient stability. Also Marfan Syndrome - tall individuals with long, slender limbs, is mainly a connective tissue disease.

Tissue fibrosis is common, a rarer form is Peyronie’s Disease with fibrosis in the penis. Another frequent effect is keratosis, hardening of skin and mucous membranes, also causing weakness, distortions and infections (keratitis) of the cornea with visual problems. Serious connective tissue diseases are mainly present in inherited forms but not normally in the acquired condition of pyroluria.

Accumulating Pyrrole Residues

While connective tissue problems are mainly due to deficiency of P5P and zinc, a set of other problems is caused by the accumulation of pyrrole residues in different parts of the body. Some of the excess pyrrole derivatives are excreted through the bowels and bladder, but others remain in the body, in muscles, skin, brain and joints, and clog up blood vessels. This is a main contributor to the development of autoimmune diseases, especially rheumatoid and infectious forms of arthritis, psoriasis and psoriatic arthritis, inflammatory skin problems and other inflammatory conditions, circulation problems, dementia, immune dysfunction, fibromyalgia, pain and chronic fatigue.

I assume that also problems related to sexual hormones and functions, such as prostate enlargement, male pattern baldness, erectile difficulties, problems with conception, postnatal depression, and polycystic ovary syndrome, are often due to an interaction of two factors: disturbances in the production of sex hormones related to deficiencies of P5P and zinc, and accumulation of waste residues from pyrrole derivatives and other dead proteins. Again, the underlying cause of both of these factors can be traced back to the liver, and specifically to difficulties with haem production.

A major problem with these residues are their neurotoxic and tissue-irritating properties which are strongly pro-inflammatory, pro-oxidative and acidic. These residues are unstable, reacting with each other and other body molecules to become difficult to dissolve and expel with the urine. Pyrolurics also do not normally have the capacity to process and expel them through the liver. This leaves mainly the skin as a viable alternative. This is what the body tries to do with psoriasis and other inflammatory skin conditions.

More problems arise because these pyrrolic wastes form an ideal environment for microbial colonies. The irritating and inflammatory effect of pyrrole residues on the inner lining of blood vessels invites microbes present in the blood to infiltrate, and cholesterol to attach to soothe the condition. This, then, in combination with vitamin C deficiency, may be the true cause of cardiovascular disease, with heart infarcts and strokes to follow. Due to the slack venous system the blood pressure is often low in younger years while increasing arterial congestion may raise blood pressure with advancing age.

Removing the Residues

Removing these waste residues through the skin is the fastest but also the most uncomfortable way of cleansing because of the intense itching that it causes. Anything that strongly activates the immune system, such as high doses of ascorbate/vitamin C, P5P or fresh raw juices may cause cleansing with outbreaks of itchy pimples, blisters and other inflammatory skin conditions, basically causing an acute attack of psoriasis. This can be managed to some degree by reducing the amounts of vitamin C and P5P, heavily alkalising with oral sodium bicarbonate and soaking in alkaline water in a bathtub, glycerine skin rubs, blue light therapy, high intake of water and other suitable liquids combined with fasting periods.

A good cleansing method is with a high intake of alkaline ionised water. The main benefit of ionised water comes from its content of negative hydrogen ions if produced at a high setting. While this water also tends to have a high pH, there is usually not much alkalinity from alkaline minerals in it. Therefore 2-3 teaspoons of sodium bicarbonate may still be added to 2-3 litres of ionised water, drinking it mainly on rising and before meals. Alternatively high amounts of Microhydrin or Megahydrin/Megahydrate and/or vitamin C may be used in combination with sodium bicarbonate added to normal water.

Repeated fasting periods with high intakes of alkaline water and green juices or fresh green leaves pureed in a high-speed blender are very effective and great for overweight or even normal weight individuals, but unfortunately not so suitable for underweight/slender individuals with fat malabsorption. These may experiment with all available methods to find the right mix for their individual requirements but focus especially on proteolytic enzymes.

High amounts of proteolytic enzymes are most comfortable for advanced and inherited conditions. These are serrapeptase for cleaning skin, muscles, joints and other tissue from pyrrole residues and other accumulated wastes, nattokinase for cleaning the blood vessels, and at times additional bromelain and possibly papain for general clean-up of protein residues. Take these on an empty stomach several times daily. Serrapeptase and nattokinase may be taken together but at separate times from bromelain or papain as the latter may digest the former. For an impressive account of the healing benefits of serrapeptase see the free download "The Miracle Enzyme" at www.serrapeptase.info.

Always start with low doses and gradually increase as much as you comfortably can. I have been experimenting with 4 x 250,000 units of serrapeptase a day with good results and not noticed any problems. Cut back if any reaction develops, later increase again. An important requirement for high-dose clean-outs is a high fluid intake and the ability for unrestricted urination. If this is not possible due to kidney disease or other factors then this should be improved while remaining on a lower dose of serrapeptase that does not cause problems. Nattokinase seems to depend less on urination for removing residues. Improvements are gradual and may be noticed within weeks, but completely cleaning out a heavily congested body takes much longer.  

During cleansing periods also heavy metals, such as mercury, as well as pesticides and other toxins get into the circulation and temporarily can cause increased pain and discomfort. With severe conditions, especially if elderly, this process may take years to bring to a successful end, and it can only work if the formation of new pyrrole residues has been stopped with suitable supplements as well as intestinal sanitation to eliminate the fungal form of Candida and with this the leaky gut syndrome.

Pyroluria and Candida

It is difficult and often not possible to differentiate between effects caused by pyroluria and Candida as both tend to affect the same systems, although usually in different ways. Even without entering the blood itself, Candida can produce these effects with the chemicals it releases into the blood via the intestinal tract, vagina, mouth and lungs. The main chemicals have been identified as acetaldehyde, tartaric acid, and arabinose, an abnormal 5-carbon sugar (6).

The more serious conditions commonly arise from an uncontrolled Candida overgrowth coming on top of inherited pyroluria. Candida toxins absorbed from the intestines into the blood disable much of the energy production in brain, muscles and connective tissue, thereby reinforcing similar problems due to deficient haem production, accumulating protein wastes, and vitamin B6 and zinc deficiency caused by pyroluria. This partnership between inherited pyroluria and acquired Candida overgrowth in combination with leaky gut syndrome underlies most of our modern diseases. Which parts and functions of the body become affected depends mostly on other acquired or inherited weaknesses.

Cachexia with severe muscle wasting, weakness and anaemia is the last stage of cancer, AIDS, tuberculosis and other deadly infections. In my understanding this is due to extreme liver stress causing pyroluria and an inability to produce haem, in addition to fungal/microbial/pleomorphic destruction of red blood cells, severe energy deficiency, and overacidity from blockage of oxidative energy production.

A further factor is the observation that there usually do not seem to be any serious or obvious symptoms from pyroluria until intestinal dysbiosis develops. The main cause of intestinal dysbiosis and overgrowth with Candida is the use of medical drugs, mainly broad-spectrum antibiotics, steroids and chemotherapy, that kill our good intestinal bacteria. Initially this causes proliferation of the yeast form of Candida which morphs into the invasive fungal or hyphal form with long, branching filamentous tentacles. These tentacles then grow within the intestinal wall, causing inflammation and making it permeable for toxins from the intestinal tract. With this we have now the leaky gut syndrome, in conventional medicine called intestinal permeability. This is the basis for the development of allergies, of microbial toxins getting into the blood and seriously weakening the immune system, and Candida chemicals affecting the brain and other organs.

With healthy intestinal bacteria pyrrole chemicals are generally fat-soluble, mainly excreted through the gallbladder into the intestines, and then expelled with bowel movements. However, with intestinal dysbiosis some of these excretions are being reduced by pathological microbes into water-soluble forms. These can be re-absorbed into the blood from where they are partly expelled with the urine and partly accumulate in tissues. Normally P5P and zinc deficiencies are mainly restricted to the liver but after re-absorption of pyrrole residues these deficiencies directly affect the whole body.

Mental-Emotional and Other Brain Problems

There are several ways in which pyroluria and Candida, individually and jointly, affect the brain to cause mental-emotional diseases and other brain problems. There is the deficiency of neurotransmitters caused by P5P and zinc deficiency, the blockage of the mitochondrial oxidative energy generation by chemicals produced by Candida and other microbes, and there is the clogging up of capillaries and brain cells with inflammatory and acidic pyrrole-based waste protein. The combined effect of these assaults is severe energy deficiency in parts of the brain in addition to a lack of proper nerve transmissions. Problems are intensified by commonly existing multiple allergies and mercury toxicity. Even relatively young individuals with severe inherited pyroluria may accumulate high levels of waste proteins in brain cells as is typical for individuals with dementia, Alzheimer's or Parkinson's disease.

Pyroluria, which was then called 'mauve factor', was discovered in the 1960's by Abram Hoffer, MD, PhD, a Canadian psychiatrist, while working with schizophrenics, bipolar patients, mentally retarded or disturbed children, and criminals. In addition to using ascorbate/vitamin C, he successfully treated schizophrenia with very high doses of niacinamide/vitamin B3. This is the main vitamin to increase oxidative energy production. All of the recovered schizophrenics also converted from Mauve-positive to Mauve-negative, indicating a link between defective oxidative energy production and pyroluria. When niacinamide was discontinued, Mauve reappeared. 

In the early 1970's Carl Pfeiffer, MD, PhD, introduced a relatively simple quantitative colorimetric test for Mauve in urine. Pfeiffer worked with schizophrenia when he discovered the suppression of urinary Mauve and subsequent clinical improvement with high-doses of vitamin B6 and zinc. This has more recently been modified by using mainly activated vitamin B6 or P5P.

Blackouts or 'grey-outs' tend to be a common stress response of sensitive individuals with uncontrolled pyroluria. Stress, just like coffee or sweet food, strongly increases the blood sugar level in preparation for physical action. But if no such action happens, the pancreas releases an excessive amount of insulin in response to the elevated blood sugar level. This drives the blood sugar down too low which, in association with the resulting low blood pressure, causes severe lack of energy in the brain. Affected individuals may end up in the medical system with lots of X-rays, scans and other tests without finding a cause.

As a precaution these individuals may carry a little bottle of glycerine with them and take a good sip when they feel a problem coming on, or before an expected stressful event, preferably swishing part of it in the mouth for a minute for immediate absorption before swallowing. Glycerine is best suited because it provides quick energy without affecting the insulin response. If it gets bad lie down or stay close to the floor, and if you are on the road definitely stop driving. 

The Cause of Autism

Autism and hyperactivity have been cured, controlled or greatly improved by treating either Candida, or pyroluria, or brain-mercury pollution. For best results preferably all three factors should be treated. Vaccination is commonly seen by parents and activists as a main cause of autism, but it needs to be explained why only some of the vaccinated children develop autism. My understanding of the interaction of factors leading to autism is as follows.

All three of the mentioned factors have a strong negative impact on the brain and on mental and emotional activities. But there is a fourth factor - vitamin C. When there is an immune challenge, be it from an infection or vaccination, the body needs a high amount of vitamin C; it is the ammunition of immune cells to produce intracellular hydrogen peroxide for killing invaders. Candida overgrowth, pyroluria, and leaky gut syndrome are like chronic infections causing persistently low vitamin C levels. This causes individuals on a diet low in vitamin C to be permanently close to acute vitamin C deficiency or scurvy.

Haemorrhaging is typical with scurvy, this is not only the trade-mark of haemorrhaging viruses such as Ebola but also of infants dying a few weeks after vaccinations. Dr Archie Kalokerinos worked as a General Practitioner in outback Aboriginal communities and wrote that after vaccinations every second child used to die about 3 weeks after vaccination with signs of severe scurvy (7). Many parents were imprisoned for allegedly shaking the infant to cause spot bleeding on the brain (8).

Only later was it shown by some pioneering doctors that this brain haemorrhage was caused by severe scurvy as a result of vaccinations, but even today this is not accepted by the medical orthodoxy. When Dr Kalokerinos gave aboriginal infants high-dose vitamin C not a single child died anymore from vaccinations. Fifty percent is about the same death rate as presently from Ebola in similarly malnourished African populations. Also it is claimed that typically Ebola patients die with signs of haemorrhage, commonly about 3 weeks after some kind of Red Cross vaccinations.

I interpret all of this to mean that whether an infant dies after vaccination, or from an acute viral disease, or survives with hyperactivity or autism, depends on the interaction of several factors, such as vitamin C status, mercury toxicity, Candida activity, pyroluria, and leaky gut syndrome.

Causes of Pyroluria

While the more serious forms of pyroluria seem to be inherited, also most liver diseases and advancing age may cause symptoms of porphyria and pyroluria, even in the absence of a genetic predisposition. Such liver diseases include haemochromatosis, hepatitis B and C, liver cirrhosis, fat malabsorption and other problems with the fat metabolism. Many medical drugs cause liver damage, not only 'powerful' ones but also commonly used pain relievers, especially Panadol/Tylenol/Paracetamol/Acetaminophen, and Ibuprofen/Advil. However, most liver disease seems to be caused by antibiotics and related drugs, statins, and epilepsy drugs (9).

An additional problem is that all medical drugs need to be detoxified in the liver but with pyroluria this detoxifying ability is greatly reduced. This leads to accumulation of toxins from the drugs and further deterioration. 

Another crucial factor is an invasion of the liver by other pathogens, such as the fungal form of Candida, mycoplasmas, mycobacteria and parasites. With severe or chronic intestinal dysbiosis such microbial invasions tend to occur very frequently. I believe that in former centuries pyroluria was mainly caused by the pleomorphic forms of mycobacteria and spirochetes which include tuberculosis, syphilis and Borreliosis/Lyme disease.  

Fungal or myco-type microbes (e.g. pleomorphic forms of mycobacteria) produce energy mostly anaerobically, and if they or even just their chemicals invade the liver, then oxidative energy production will be reduced, causing energy deficiency in the liver. This condition can also be inherited as these pathogens are able to change the DNA of energy-producing mitochondria in the liver. Therefore porphyria/pyroluria appears to start with inherited or acquired energy deficiency in the liver which prevents it from effectively producing haem and other essential biochemicals.   

In susceptible individuals stress may be the main trigger for bringing a latent energy deficiency into the open by disrupting the synthesis of haem in the liver, possibly by interfering with the conversion of normal vitamin B6/pyridoxine into its activated form P5P. Activated B6, in addition to zinc, is essential for most enzymatic steps of haem formation. In the presence of ample activated B6 and zinc there is no clinical pyroluria activity, although problems due to weak connective tissue, clogged blood vessels and other waste accumulations still remain.

A main biochemical effect of stress is a greatly increased requirement of the adrenal glands for pantothenate or vitamin B5. This is also the key vitamin to produce coenzyme A and further acetyl coenzyme A or acetyl-CoA. Acetyl-CoA is needed in many biochemical reactions as it feeds the breakdown products from carbohydrates and fats into the citric acid cycle for oxidative energy production. Therefore acetyl-CoA is sometimes called the "Hub of Metabolism". It also assists in transferring fatty acids from the cytoplasm of cells to mitochondria and, important for this discussion, acetyl-CoA and with this vitamin B5 are essential for normal liver functions and the synthesis of haem. 

In addition acetyl-CoA is needed for the synthesis of the major neurotransmitter acetylcholine. It regulates muscle activity as well as nerve and brain functions, especially in regard to memory, arousal and reward. Organic mercury compounds, such as methylmercury, inhibit the formation of acetyl-CoA. All this lets us understand why stress, especially in the presence of low vitamin B5 levels, leads not only to liver dysfunction but also to general lack of energy, muscle weakness, and disturbances of nerve and brain functions. More stress means less available vitamin B5 and acetyl-CoA, and greater disruption of haem production.

This outline also shows the importance of acetyl groups or acetate for producing energy. "Acetyl" refers to a two-carbon group as in acetic acid or vinegar. Acetate is said to be the most common building block for biosynthesis and for producing energy. In a well functioning metabolism acetate is mainly formed from the metabolic breakdown of carbohydrates and fats. However, if oxidative energy production is weak, then the breakdown of carbohydrates produces too much lactic acid and too little acetate, while a weak liver has difficulties metabolising fats. With this a deficiency of acetate and acetyl-CoA may develop, leading to chronic lack of energy or fatigue.

What to do about it

On the Internet it is often recommended to have an HPL urine test done to find out if one really has pyroluria and how severe it is. I do not regard this test as being very helpful because results can fluctuate greatly depending on the stress level at the time of urine collection. Such stress may be from emotional causes or nutritional deficiencies, allergies, acidity level, electromagnetic and chemical pollution, so that a positive or negative test result may not apply to normal or long-term conditions.

 Therefore, if some key conditions are present, such as problems with blood circulation, skin or connective tissue, arthritis, muscle and joint diseases, enzyme deficiencies, or mental-emotional issues, I would just suspect that pyroluria and dysbiosis/Candida may be present and treat accordingly, always starting with a very low dose and increasing gradually but steadily to an optimal level. After some time it will become apparent, especially in periods of stress, whether this approach is helpful.

To show the difference of reactions: one young woman with anxiety problems had a frightening panic attack after taking only a very low dose of P5P and zinc, while someone with Asperger syndrome (an autism spectrum disorder) wrote that he felt completely normal after rapidly increasing P5P up to 500mg daily. However, after several months he did develop some gastro-intestinal problems (cleansing or detoxification?) and had to reduce the dose. If there is a reaction, the first one is usually the strongest.

P5P is a brain stimulant, and initially it can make problems worse, such as hyperactivity in children or causing sleeplessness when taken in the evening. It is common for the body to overreact initially, that is why one should always start with low levels, and if a reaction happens, further reduce or stop until the reaction is gone, and then start again at a much lower level. However, also the chemicals produced by Candida tend to produce anxiety attacks, and there may be an interaction between Candida and P5P in causing an attack. Controlling Candida may reduce or avoid such problems.

Niacinamide (B3) and pantothenate (B5) can usually be taken in reasonably high amounts for improving energy and stress response without causing any reactions. Also other secondary nutrients such as biotin, vitamin B12, magnesium, manganese, and gamma linolenic acid or GLA do not seem to cause problems. With low energy try using more acetic acid or vinegar in a drink during or before meals or as salad dressing. This may require occasionally checking the pH of the urine to see if more bicarbonate is needed to keep it generally neutral or slightly alkaline. Some bicarb may also be mixed with diluted vinegar and ingested while it still bubbles.

Vitamin C in any form stimulates the immune system which may produce strong inflammatory cleansing reactions. This is the normal way the body heals itself - by causing an inflammation in a diseased part of the body to kill microbes and remove toxins. Unfortunately this is a problem with psoriasis and sometimes also with other autoimmune diseases. In this case increase vitamin C only very slowly, pull back during reactions and keep alkaline with sodium bicarbonate. Also detoxify with increasing doses of serrapeptase and nattokinase, focus on intestinal sanitation and antimicrobial therapy, increase the amount of energised water, herb teas, diluted lemon juice or vinegar, fresh salads, juiced and blended fresh green leaves and other raw vegetables. Drink liquids mainly before rather than with or after meals, except if using lemon juice or vinegar to improve stomach acidity.

Most books and Internet articles also mention that copper must be avoided as blood levels are too high as a side effect of pyroluria, but I believe this is not quite correct. High copper blood levels are present with all conditions of inflammation, including cancer and infections, and are not specific for pyroluria. When the inflammation decreases then blood copper levels drop as copper returns to its usual storage place in the liver. However there may be a problem with high levels of inorganic copper or an inability of a defective liver to produce enough organic carrier and storage molecules for copper, but this should improve with additional P5P and zinc.

A problem area for skin-sensitive pyrolurics is the use of sunscreen. Commercial sunscreens may not be safe to use. Gradually expose the skin to more sunshine. With sufficient P5P, zinc, sodium ascorbate, serrapeptase, and sodium bicarbonate there should be much less of a tendency to get a sunburn. As sunscreen dissolve 1 level tsp each of PABA, sodium bicarbonate and possibly sodium ascorbate in several tablespoons of water (it fizzes when PABA and bicarbonate react). Rub on the skin exposed to the sun. It needs to be reapplied after getting wet as it washes off.  

How much to take

P5P is normally sold as enteric coated tablets, apparently to protect it from stomach acid, but I am not aware of evidence that this is needed, and coating may actually hinder absorption for individuals with poor digestive ability. Therefore I prefer to cut such tablets to make them easier to absorb. It is also possible to buy P5P cheaper in powder form (www.strideintohealth.com), and take it dissolved in an alkaline drink (by adding some sodium bicarbonate) before meals or mixed with food at the beginning of meals.

Zinc, on the other hand, like magnesium and other 2-valence minerals, is best absorbed from acidic stomach content, preferably containing protein, vegetables or fruit but not grains or other seeds. With indications of low gastric acid such as soft fingernails and other signs of mineral deficiencies, add a hydrochloric acid supplement, lemon juice or vinegar. Do not use the sulphate or sulfate form of zinc as in higher doses it may cause gastric or abdominal discomfort.

A normal starting dose may be half of a 50mg tablet of P5P and about 20mg of zinc with breakfast; if there is no unfavourable reaction then after a few days double these doses by taking them at the start of breakfast and lunch, and later also at dinner. Gradually, over several weeks or months, increase both P5P and zinc to an optimal dose at which symptoms start improving or disappearing. In mild conditions this may be almost immediately, even with a relatively low dose, in severe cases much higher doses may be needed for several months before good progress is made.

Finding the optimal dose of P5P and zinc is not easy as this depends strongly on stress levels which may change daily. Therefore try to find a dose that feels right for your normal daily activities, but when stressed or expecting stress temporarily double the amounts, or during peaceful and relaxed periods reduce the normal amounts.  

Mild conditions can be managed with 50mg of P5P/day while more severe conditions may require 3 x 50 to 100mg of P5P and 3 x 20mg of zinc, although much higher doses have sometimes been taken. Experiment occasionally to find any variations in the optimal dose for your condition. Initially too much P5P may cause overstimulation or bouts of overactivity in children, and difficulty falling asleep, especially if taken in the evening.

Highly sensitive individuals may start with a quarter tablet of P5P in the morning and remain on this for a week or two until gradually increasing to a quarter tablet with 2 and then with 3 meals. If a strong reaction develops stop intake until the reaction is over and then start slowly increasing again. Finally gradually increase further to half or even full tablets. A reaction confirms that you are on the right track, and that this remedy is the key to your recovery.

Recommended as supportive nutrient is a B-complex with most meals, whether high, medium or low potency depends on the condition, and you may need to experiment. Also with weak adrenal glands and during stressful periods pantothenate/vitamin B5 may be temporarily increased up to 3x500mg with meals. Niacinamide is mainly useful to increase energy, e.g. with schizophrenia, depression, Alzheimer's disease, chronic fatigue and advanced cancer; try up to 1 gram with each meal.

Other important supplements are up to 10 grams of ascorbate and up to 20 grams of MSM (well spaced out during the day (see www.health-science-spirit.com/morenergy.htm), magnesium chloride (orally and transdermally), manganese, biotin, alpha lipoic acid, vitamins A, D and E (orally take opened and emulsified with lecithin, additionally also rubbed onto sensitive skin areas), Lugol's solution (1-2 drops/day - iodine is needed, not just iodide), selenium, borax/boron, copper salicylate, especially with inflammations, aging skin or grey hair, and also serrapeptase up to 4 x 250,000 Units and nattokinase up to 8 x 2,000 FU.

As with any health improvement, cleansing reactions may occur, temporarily causing skin problems or aggravating other existing conditions. In this case make a special effort to use sufficient bicarbonate to keep the urine alkaline, greatly reduce the dosage of all remedies, keep the bowels clean, drink a lot of healthy fluids, and when the problem has subsided gradually increase supplementation again.

Afterthoughts

In addition to providing missing nutrients also focus on intestinal sanitation with psyllium therapy, anti-Candida therapy, cleansing and activating the liver. All problems are much worse if there is in addition mercury toxicity, but attempt mercury removal only after pyroluria and Candida are under control. See www.the-heal-yourself-series.com/TowardsRadiantHealth.html for details.

Even without pyroluria body builders prefer P5P because of its superior qualities in building muscles and connective tissue. This may also indicate that most elderly individuals or anyone with liver problems would benefit from P5P and zinc.

The FDA has been petitioned by a drug company to ban the general sale of P5P so that it can be sold as a drug. The FDA has done this before with another natural form of vitamin B6, pyridoxamine, which is no longer available in the US (10). Pyridoxamine was mainly used as an anti-aging remedy, to reduce diabetic neuropathy, nephropathy, retinopathy, and it can block the formation of advanced glycation end-products, but P5P can do the same.

Individuals with advanced pyroluria may need P5P for the rest of their lives, although I am hopeful that the program outlined in this article, in addition to energy meditation and guided imagery, will eventually overcome also the serious inherited form of pyroluria. Pyroluria is an important health indicator because it shows that the liver does not have enough energy to work efficiently, especially in stressful situations, and that means the whole body is in danger. For aware young couples it is preferable to get any pyroluria and Candida under control before trying to conceive children to break the chain of transmitting pyroluria in the family tree. For further information see Managing the Immune System.


End Notes

(1) Pyroluria - A Hidden Disorderhttp://naturalinsight.hubpages.com/hub/Pyroluria-A-Hidden-Disorder.

(2) Porphyria - http://en.wikipedia.org/wiki/Porphyria

(3) Caryn Talty & Matthew Dahlitz: Pyrrole Disorder For Therapistshttp://www.neuropsychotherapist.com/pyrrole-disorder-for-therapists/

(4) Woody R. McGinnis, MD, et al: Discerning the Mauve Factor, Part 1Altern Ther Health Med. 2008;14(2):40-50;

 http://www.biobalance.org.au/_downloads/discerning-mauve-factor-part-1-galley-feb-2008.pdf

(5) Woody R. McGinnis, MD, et al: Discerning the Mauve Factor, Part 2Altern Ther Health Med. 2008;14(3):50-56;

http://www.biobalance.org.au/_downloads/discerning-the-mauve-factor-part-ii-galley.pdf

(6) William Shaw et al: Assessment of Antifungal Drug Therapy in Autism by Measurement of Suspected

Microbial Metabolites in Urine with Gas Chromatography-Mass Spectrometry; Clinical Practice of Alternative Medicine 1(1): 15-26, 2000. http://www.greatplainslaboratory.com/newevidence/antifungal.pdf

(7) Archie Kalokerinos: Every Second Child; Keats Publishing (1981), free download from http://www.soilandhealth.org/copyform.aspx?bookcode=020341

(8) Archie Kalokerinos: Shaken Baby Syndrome: An Abusive Diagnosis (2008); free download from http://www.beyondconformity.org.nz/hilarys-desk/archie_kalokerinos_-_this_is_your_life

(9) John Gever: Antibiotics Top Cause of Drug-Induced Liver Failure; Nov 4, 2009; http://www.medpagetoday.com/MeetingCoverage/AASLD/16791

(10)  Alliance for Natural Health (USA); Breaking News: FDA’s Sneak Attempt to Ban Another B Vitamin

March 11, 2014; http://www.anh-usa.org/fdas-sneak-attempt-to-ban-another-b-vitamin/


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