Pyrroluria is a common feature of many behavioral and emotional disorders. It belongs to the non-acute porphyrias—large amounts of porphyrins in the blood. It is said that an inborn error of pyrrole chemistry results in a dramatic deficiency of zinc, vitamin B6, and usually arachidonic acid. More likely it is the result of mercury and other heavy metal toxicity. This observation on porphyrin aberrances brings into consideration other possible effects of mercury toxicity that are secondary to porphyrin depletion. Porphyrins are the precursors to heme synthesis. Heme is the oxygen-binding prosthetic group in hemoglobin, and depletion of heme would affect oxygen delivery to the mitochondria and decrease energy production. Heme is also a component of the electron-transport system of mitochondria and a prosthetic group in the P450 enzymes that are fundamental in the detoxifying of the body from many organic toxicants including pesticides and PCBs.
Just recently, a report was released implying that lack of heme was the major reason why ß-amyloid plaques build up in the brains of Alzheimer's diseased subjects. It seems that heme attaches to ß-amyloid helping it remain soluble and excretable-Boyd Haley, PhD.).
Pyrroluria suppresses Cytochrome p450 (Phase I) liver
enzymes, leading to a build up of toxins within the body that accounts for
many symptoms. The result is a genetic-stress disorder associated with
severe mood swings, high anxiety, and depression. Pyrrolurics are devastated
by stresses including physical injury, emotional trauma, illness, and sleep
deprivation. A more severe form of Pyrroluria symptoms include explosive
temper (rage), poor short-term memory, inability to tan the face,
sensitivity to light and sound, a tendency to skip breakfast, dry skin,
abnormal fat distribution, little or no dream recall, reading disorders,
under-achievement, histrionic behaviors, and frequent infections. They
usually respond quickly to supplements of zinc, manganese, vitamin B6,
Evening Primrose Oil, and augmenting nutrients. Selection of high AA-content
foods (farmed salmon, tilapia, organ meats, turkey, fat pork, and eggs) can
be most helpful in these instances. There may be a need for a niacin
supplement to prevent pellagra because B6 is required to convert tryptophan
into niacin. In porphyrias, there is elevated porphyrin in the urine. The
decisive laboratory test is analysis for kryptopyrroles in the urine. You
can get a urinary screen for elevated pyrroles for $32 from BioCenter
Laboratory in
Pyrroluria or Hemopyrrollactam Uria (HPU) is a toxin that interferes with liver detoxification (blocks cytochrome p450 – phase I liver enzymes) and with heme production. Schizophrenia (20%), Autism (53%), and Multiple Chemical Sensitivity (MCS) also has been linked to porphyrin metabolism problems. Many of the children with HPU have low levels of histamine (overmethylated), which may make them more sensitive to allergies. One source of this endogenous pyrrole is thought to arise from an aberrant, breakdown product of hemoglobin. Another source of the elevated hemopyrrollactam (pyrroles) is intestinal bacteria (Irvine and Wilson 1976). Sometimes, a form of the antibiotics tetracycline and kanamycin turn off the production of pyrrole. Porphyrin is the killing chemical inside NK-cells, and when these cells are destroyed, it releases higher rates of the porphyrins in the blood (possibly leading to Pyrroluria -WSL).
Porphirine and porphyrins are diagnostic indicators of toxic-cell damage effects from metals and chemicals. CFS causes lowered NK-cell population, and this is a result of their porphyrin content and RNase L ineffectivity toward viral infections.
(Corroborating insert: Most recently, a study showed that 53% of autistic children had aberrant prophyrin profiles similar to mercury toxic individuals. Treatment of these children with a mercury chelator brought these porphyrins back towards normal levels indicating mercury toxicity was the cause, not genetic impairment. Porphyrin profiles are one of the most sensitive methods of measuring toxic mercury exposures. Recently, in a major advance, it was shown that about 15% of individuals in one population displayed a marked sensitivity to mercury exposure in their porphyrin physiology, again supporting the concept of a genetically-susceptible (?) population that is more sensitive to mercury than the general population.
Heme production is promoted by the enzyme
delta-aminolevulinic acid synthase (
About one third of porphyrics accumulate iron, and this
is bound in a very tight fashion making it impossible to remove via
bloodletting. Therefore, it has to be removed via iron chelation, and this
may take 18 months according to Prof Chaim Hershko of the
Symptoms of HPU are: paleness of the skin, especially of the face (pallor, a China Doll appearance, in summer the skin is yellowish or golden brown), recurrent ear infections, colds, allergies, hay fever, skin reactions, hyperreactivity, dermatografy, headache, migraine, easy bruising, anemia; inability to climb a rope, climbing rack, or flying rings; abdominal pain in the upper left side, convulsions, a bad set of teeth, hypermobility of the joints, growing pains, especially of the knee (left), changes in handwriting, white marks on their nails, sensitivity to sunlight and sound, loss of appetite, nausea, stretch marks on the skin, sweetish breath odor, constipation, but more often an excessive stool mucus with bloating and a light colored stool, learning and behavioral problems, and high internal tension. Depression can lead to suicide. Mental symptoms are aggravated when undergoing stress. In fact, pyrroluria flares up when the individual is undergoing prolonged stress, such as during a chronic and debilitating illness. The nutrient dosage usually must be increased when the pyrroluric is under increased stress. Some depression patients have a genetic pyrrole disorder. Many of these persons report benefits from Prozac™, Paxil™, Zoloft™, or other serotonin-enhancing medications. However, similar benefits may be achieved by simply giving these patients sufficient amounts of vitamins B6 and niacin, with Evening Primrose Oil, magnesium, manganese, and zinc. Actually, most or all these symptoms indicate the vitamin B6 and zinc deficiencies.
Kryptopyrrole is an avid aldehyde-reacting agent that has been shown to combine irreversibly with Pyridoxal 5’ Phosphate (a metabolite of vitamin B6). The resulting kryptopyrrole-pyridoxal complex binds voraciously with zinc, and the combined product is excreted. (I understand the compound is actually hydroxy-hemopyrrolenone and not kryptopyrrole. See Clinical Chemistry 24(11)2069-2070 1978). This condition is termed Pyrroluria (or Malvaria) and affects 20% to 30% of Autistics. It has been identified as a form of psychosis that accounts for about 30 percent of psychotic patients (Pfeiffer, 1975). These patients are vitamin B6 and zinc dependent and respond readily to zinc and vitamin B6 therapy, however, experience shows it will take 6-months of supplementation at high levels.
Acetaldehyde (AH) also induces a deficiency of
Pyridoxal 5` Phosphate (P5P), the major coenzyme necessary to form virtually
all major-brain neurotransmitters. AH is known to strongly combine with the
protein portion of P5P enzymes in a way that displaces the P5P portion of
the molecule. This subjects P5P to an increased rate of destruction, and
results in abnormally-low, blood and tissue levels of this coenzyme that is
involved in all transamination reactions whereby cells may convert many
different amino acids into each other to satisfy their ever-shifting,
amino-acid needs. P5P also is necessary to convert essential fatty acids
into their final-use forms, and to turn linoleic acid into the key,
nerve-cell-regulating biochemical, Prostaglandin E1. P5P helps regulate
magnesium entry into cells, and the ideal level of excitability of nerve
cells is strongly dependent upon their magnesium level. P5P is also
necessary to convert tryptophan into serotonin and niacin, and
niacin/niacinamide into the active, coenzyme-form, NAD. Niacin participates
in the enzymatic breakdown of sugar at several places in the energy cycles.
A deficiency of niacin slows down brain metabolism to the point of causing
what appears to be mental illness. Pellagra can be a result of this lack of
vitamin B6.
Acetaldehydes also unfavorably influence prostaglandin metabolism by deactivating Delta-6-Desaturase, the enzyme that converts the Omega-6 fatty acid, linoleic acid (LA), into gamma linolenic acid (GLA), that is totally absent from a typical diet. GLA is the only material that can be converted into prostaglandin E1 (PgE1), a key regulatory biochemical for both nerve cells and the immune system. Conditions that promote production of PgE1 prevent excessive production of the inflammatory prostaglandin E2 from the dietary fatty acid, arachidonic acid that is plentiful in meat, poultry, farmed salmon, and dairy products.
The first indication of pellagra is depression and perceptual disturbances, which can affect hyperactive and hypoactive, and autistic children. Like people with schizophrenia, affected children may hear voices and foods may taste different to them. Letters appear upside down, and words slip around the page. Children may see objects or creatures among the shadows in the semi-dark. Usually, children are unable to describe these changes in their perceptions without help. Pellagra is characterized by a pigmented rash that develops symmetrically in areas exposed to sunlight. Changes in the digestive tract that are associated with vomiting, constipation, or diarrhea, and a bright red tongue with a shiny tip; and neurological symptoms including depression, apathy, headache, fatigue, loss of memory, loss of appetite, diarrhea, deficient stomach acid, fatigue, insomnia, apathy, encephalopathy, disorientation, confusion, amnesia, and manic-depressive psychosis.
Dr. Hoffer’s “ABC of Natural Nutrition for Children” includes a hundred-question, Perceptual Dysfunction Test that can be completed by young children with the help of a parent. The PD Test was adapted by Dr. Glen Green from the HofferOsmond Diagnostic Test (HOD), which Dr. Hoffer and Dr. Humphrey Osmond developed in 1960 to screen for schizophrenia. The HOD test can be used to evaluate mental health in children over 10 years old although Hoffer says that some children may have difficulty with some of the vocabulary. The HOD test is available as a computer program at www.softtac@islandnet.com.
In addition to these questionnaires, a urine test can identify krytopyrrolle (KP), a substance commonly found in the urine of schizophrenic patients. This substance causes a deficiency of B6 and zinc by latching onto these nutrients and removing them from the body via urine. Hoffer has noticed that children with positive KP results also respond to B3. While all of these tests and questionnaires may point to vitamin deficiency, the primary test is to give the child large doses of niacinamide (often starting with 1 gram twice daily) (and B2, B6 and zinc). If the child’s perceptual and behavioral problems are caused by a deficiency, Hoffer says that improvement will be noticed within months (or sooner).
“If your child has a low arachidonic acid (AA) on the membrane fatty acid test, I would get a urinary pyrrole test. We have good data from the Hormel Institute on consistently low AA levels in autistic children with elevated urinary pyrrole levels. At least a third of autistic and ADHD children have high pyrrole. When you see pyrroles elevated in a child, you know two things right away: 1) very high zinc requirement, 2) very high B6 (prefer P5P) requirement. The higher the pyrroles, the greater these two are needed. Zinc picolinate may be preferred to other zinc supplements for the lack of B6 may cause the formation of picolinate to be suboptimal. Manganese (and perhaps copper and iron) will be required to balance the zinc. This is such key information; I always get this urinary screen. Sixty percent of Down’s kids have pyrroluria. I have all Pyrrolurics (low AA) on Evening Primrose Oil.”—Dr. Woody McGinnis (compressed). Walsh finds biotin very useful in “slender malabsorber group”. Those with low levels of Arachidonic Acid may benefit by supplementing DHA that is converted to AA in endothelial cells—PMID 3080955.
In the section of the book, “Gliotoxins, and Other Immunotoxins Produced by Yeast and Fungi”, Dr. William Shaw writes:
“A second toxic effect of gliotoxins (an antibiotic that is toxic to higher animals, and that is produced by various fungi—WSL) is probably due to their action on the sulfhydryl (mercapto) group of proteins, which they inactivate. These sulfhydryl groups are necessary for the functioning of a wide variety of enzymes. Supplements of glutathione, N-acetyl cysteine, and lipoic acid might be useful to prevent this toxic action of gliotoxins since they help regenerate free sulfhydryl groups.
“A third way that gliotoxins may be causing their damage is by the generation of compounds called free radicals...Many of these harmful reactions can be counteracted by compounds called antioxidants such as vitamin C, vitamin E, lipoic acid, glutathione, or N-acetylcysteine. Several physicians who treat large numbers of children with autism have indicated to me significant improvement of symptoms in some children with autism after treatment with the nutritional supplements of glutathione or N-acetylcysteine.” Dr. Shaw often recommends 500 mg of NAC for thirty days when beginning yeast therapy.
Research indicates that NAC is a selective immune system enhancer, improving symptoms and preventing recurrences of common lung-related illnesses such as chronic bronchitis. It is a vital antioxidant whose beneficial characteristics include scavenging of potent, hydroxyl radicals and diminished production of hydrogen peroxide. It has been used with observed benefit in neurodegenerative conditions such as Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Diabetic Neuropathy, and Alzheimer’s disease. It has been effective in treating liver failure from causes of drug toxicity and hepatitis. Oral NAC reduced 86% of the incidence of kidney damage in people undergoing tests that injected dye into the blood vessels. It thins body fluids that sometimes congeal (as in blepharitis). Nevertheless, see cautions elsewhere in this paper about using NAC.
The petrochemical AH is used in perfumes, flavors, dyes, plastics and synthetic rubber, and is present in fermented products. It has a general narcotic effect with symptoms of chronic intoxication and “hangover”. The difficulties discussed above that are caused by chronic AH toxicity should indicate that AH has a significant ability to compromise the brain function. A partial summary of AH’s damaging effects on brain function includes: impaired memory, decreased ability to concentrate (“brain fog”), depression, slowed reflexes, lethargy and apathy, heightened irritability, decreased mental energy, increased anxiety and panic reactions, decreased sensory acuity, increased tendency to alcohol, sugar, and cigarette addiction, decreased sex drive, and increased PMS with breast swelling/tenderness in women.
I recite these biochemical effects of acetaldehyde again to stress that allowing Candida overgrowth to continue is a dreadful mistake. To drag out efforts to eliminate it is equally unfortunate for the child. These effects of acetaldehyde are multiplied many times over when Candida die-off occurs, but they can be minimized or eliminated by adequate supplements of the affected vitamins and minerals, and by use of Alka-Seltzer Gold™ and N-acetylcysteine (as outlined elsewhere in this paper). Charcoal and or bentonite clay orally bind toxins preventing reabsorption also.
These children likely have a family history of food intolerance, and Candida predisposes to rampant allergies; so, in addition to clearing Candida, they may need Enzyme Potentiated Desensitization (EPD) therapy, or NAET, because allergies can cause many of these children’s symptoms, including hypoglycemia that mimics a multitude of diseases. Food allergies and sensitivities can be avoided by changing the foods one eats, thus it would seem relatively easy to eliminate food-related problems. Unfortunately, when one food is removed, other allergies become apparent or develop, until often it seems there are no foods that are safe to eat. Nevertheless, when these foods are avoided, other contributing factors, if present, will be much more easily discerned and addressed. Nevertheless, many, if not all, of these problems will disappear only when healing of the digestion and gut progresses. This is most quickly accomplished by homeopathic vaccine detoxification and mercury removal for these poisons are the root cause of these problems. Whether Pyrroluric or not, if fighting Candida, you must significantly supplement vitamin B6/P5P and zinc.