Pyrrole Disorder is an alternate name for the condition known as Pyroluria, which is also known by various other names including Kryptopyrrole, Kryptopyrroluria, Pyrroluria, Pyrolle Disorder, Mauve Factor and Hemepyrrole.
Pyrrole Disorder is the abnormal synthesis and metabolism of any heme producing molecule, including the oxygen-carrying molecule hemoglobin. All cells in the body consume nutrients and they also produce waste or by-products. The by-product of heme metabolism is a metabolite called hydroxyhemopyrrolin-2-one (HPL), AKA Mauve Factor. Originally HPL was thought to be the molecule Kryptopyrrole, but further studies have proven this is not to be the case.
Pyrrole Disorder sufferers produce excessive amounts of HPL, which renders the receptors on cells unable to utilize Zinc 1-8, Vitamin B6 1-8 and Biotin 9 while enhancing their excretion in the urine. HPL also prevents the proper manufacture of an important Omega 6 fat, Gamma Linolenic Acid (GLA).
Supplementation with these nutrients is essential to reduce the detrimental effects of elevated HPL and to reduce the severity of the symptoms and signs linked to Pyrrole Disorder.
There is some evidence that suggests Pyrrole Disorder is genetically based, especially if a parent, grandparent, aunt, uncle, brother or sister has suffered from major Depression, Bi-Polar Disorder, Alcoholism, Schizophrenia or has committed suicide.
What we have found through treating many sufferers of Pyrrole Disorder, is that certain lifestyle factors also contribute to, or exacerbate, the many associated signs and symptoms of Pyrrole Disorder. Addressing stress, improper diet, inadequate digestion, dysbiosis and leaky gut syndrome are essential in any treatment protocol for Pyrrole Disorder.
Poor diet and/or poor digestive health can lead to an increase in HPL levels 10. This makes sense as insufficient nutritional intake from a poor diet and malabsorption stemming from inadequate digestion, robs the body of essential nutrients creating deficiencies. These deficiencies, in turn, place a greater stress on the body, thus further increasing HPL levels.
Leaky Gut Syndrome or intestinal permeability is a condition whereby microscopic holes appear in the intestinal wall allowing bacterial by-products, food particles, poisons and toxins to pass into the bloodstream. Unfortunately, Leaky Gut Syndrome is commonly found in people suffering from Pyrrole Disorder and contributes to further elevation of HPL.
Studies have shown that zinc deficiency increases Leaky gut Syndrome in both animals and humans. 11-17 Stress is a major contributor to intestinal inflammation, which in turn increases the severity of Leaky Gut Syndrome. 10,18-20
Dysbiosis, also commonly found in Pyrrole Disorder, is an overgrowth of detrimental organisms and an undergrowth of the beneficial ones within the intestinal tract. Dysbiosis is linked to high HPL levels as well as a major cause of Leaky Gut Syndrome. 21, 22 Stress has been shown to increases the adherence of bad bacteria to the intestinal wall within 30 minutes further worsening Dysbiosis and Leaky Gut Syndrome. 23
Pioneering Pyrrole Disorder researcher, Dr Carl Pfeiffer, stated on more than one occasion that stress is a major driver behind elevated HPL. Further research confirms this and has shown that elevated stress levels can indeed increase the production of HPL 2,6,24. A non-published US navy study conducted in 1992 found a very rapid increase in HPL levels in healthy male volunteers who were subjected to the stress of a brief cold-water immersion 10.
Heavy metal exposure, smoking, drugs (medical or recreational) and alcohol can also increase HPL levels. This is why the symptoms of Pyrrole Disorder sufferers tend to get a worse for 24 to 72 hours after a big night out drinking or after recreational drug use.
HPL is classed as a 'nerve poison’ 25 and as such it can cause damage to nerves, nerve cells, tissue, the brain and also interrupt messages being sent along neuronal pathways especially within the brain.
Heme is a substance found in the body and has an iron atom at its core. The most commonly know heme molecule is hemoglobin, the oxygen-carrying red pigment of the blood. Heme is present in the liver, nerves and antioxidant enzymes.
The metabolic activity of nerves is highly dependent on heme for their function, and low levels of heme can lead to a metabolic crisis, resulting in neuronal or nerve cell death 26-28. The by-product of heme metabolism, HPL, is believed to further decrease heme levels in humans, thus worsening many of the signs and symptoms associated with Pyrrole Disorder.
Animal studies showed that HPL caused a decrease in liver heme and the heme-containing detoxification enzyme cytochrome P450, by up to 55% over a 48 hour period 29. Zinc, Vitamin B6, and Biotin are required for the production of heme and as such a reduction in these nutrients results in abnormal heme levels 27,30.
Heme is further depleted by stress and heavy metal exposure 27. Low levels of heme result in the excessive production of nitric oxide, which can cause serious damage to brain tissue and is suspected to play a role in schizophrenia, autism and Down Syndrome 31-35.
Oxidative stress or free radical damage can impair, injure and degenerate cells. Antioxidants are substances found in natural foods and are produced by the body to protect cells from damage, much like the way galvanized paint protects iron from rusting.
The body has three major antioxidant enzymes; Glutathione, Catalase and Superoxide Dismutase. All three of these enzymes rely on zinc or vitamin B6 in some part to assist in their production.
A marginal deficiency of vitamin B6 is linked to lower levels of Glutathione and cell mitochondrial decay 36-38. Catalase consists of four protein subunits, each requiring heme and as HPL suppresses heme, we can assume that Pyrrole Disorder is associated with lower catalase levels, as is the case with schizophrenia and autism 39-41. For Pyrrole Disorder sufferers the greater the HPL, the higher the level of oxidative stress.
The following table shows neurological and behavioral disorders along with the percentages of high HPL associated with those disorders (10).
| Diagnosed Ailment
|| % of HPL
|| Diagnosed Ailment
|| % of HPL
| Acute Intermittent Porphyria
||100|| Down's Syndrome
| Latent Acute Intermittent Porphyria
||70|| Schizophrenia Acute
|| 59 - 80
| Manic Depression
|| 47 - 50
|| Schizophrenia Chronic
|| 40 - 50
| Depression (Non Schizophrenic)
|| 12 - 46
|Autism|| 46 - 48
|| Learning Difficulties
||40 - 47
|| 40 - 47
|| Criminal Behavior
|Neurosis||20|| - Adults With Sudden Deviance
|| 20 - 84
|| - Youths, Violent Offenders
The reason for the variance in some of the above figures is that it depends which study the results have come from. For example one study may have found only 20% of alcoholics had high levels of HPL, whereas another study found that 84% of alcoholics had high levels of HPL.
Regrettably Pyrrole Disorder falls outside the realm of mainstream medicine because the only way to rectify the problem is by improving the sufferer's nutritional status, digestion, diet and stress levels. Thankfully there are a small group of GP's endeavoring to change this.
Mainstream medicine relies on drugs to suppress symptoms or relieve suffering. This form of treatment will not work on a person suffering from Pyrrole Disorder. Unfortunately Pyrrole Disorder sufferers tend to fall through the cracks of mainstream medicine, are often misdiagnosed and given medication that does nothing to rectify the underlying problem. Sadly these medications can lead to further deterioration of a person's health.
The Pyrrole Disorder test kit includes comprehensive instructions and an informative video on how to collect your urine sample and send it off to pathology for testing. Once we receive your Pyrrole Disorder test results from the laboratory, we will analyze these and send you a detailed Pyrrole Disorder Treatment Plan including suggested lifestyle, dietary and nutritional recommendations. You will also be enrolled in our FREE online Pyrrole Disorder Video Treatment Series, in which Dr Greg Newson explains Pyrrole Disorder treatment, diet, digestion, stress and the underlying causes. It's that easy!
We have a variety of options available;
1) Our Adult and Child, Positive and Borderline Pyroluria Treatment Plans (Pyrrole Disorder Treatment Plans) offer the latest up to date treatment information and contain advice and recommendation on nutritional supplementation, diet, lifestyle issues and the underlying causes.
2) Our Pyroluria Combo Packs (Pyrrole Disorder Combo Packs) are for adults and children diagnosed with Positive or Borderline Pyrrole Disorder and contain our recommended Treatment Plan and the nutritional supplements. This is a more economical way of purchasing nutritional supplements for the first 4 - 8 weeks of Pyrrole Disorder treatment.
As you can see Pyrrole Disorder is a complex health issue and treatment with the relevant nutrients will help to reduce the symptoms associated with Pyrrole Disorder, but it will not address the underlying causes. Any treatment protocol for Pyrrole Disorder needs to not only support the nutritional deficiencies, but also identify and treat what has caused Pyrrole Disorder in the first place.
1. Pfeiffer CC, Iliev V. Pyroluria, urinary mauve factor, cases double deficiency of B6 and zinc in schizophrenics. Fed Am Soc Exp Biol. 1973;32:276.
2. Pfeiffer CC, Sholer A, Jenny EH, et al. Treatment of pyroluric schizophrenia with large doses of pyridoxine and a dietary supplement of zinc. J Appl Nut. 1974;26:21-28.
3. Pfeiffer CC, Bacchi D, copper, zinc, manganese niacin and pyridoxine in schizophrenia J Appl Nutr. 1975;27:9-39.
4. Pfeiffer CC. Mental and elemental nutrients. New Canaan, CT: Keats publishing 1976.
5. Pfeiffer CC. The schizophrenia's ;76. Biol Psychiatry. 1976;11(6):773-775.
6. Pfeiffer CC. Extra nutrients and mental illness. Biol Psychiatry. 1981;16(9):797-799
7. Pfeiffer CC, Holford P. Mental Illness and Schizophrenia: The Nutritional Connection. Harper Collins Publishers, Great Britain;1987.
8. Pfeiffer CC. Nutrition and Mental Illness: An Orthomolecular Approach to Balancing Body Chemistry. Rochester, VT: Healing Arts Press;1987.
9. Kruesi O. Low plasma biotin levels in high mauve patients. Oral Communication 2005
10. Discercing the mauve factor, part 1: Alt Theapies, Mar/Apr 2008. Vol.14, No.2
11. Rohweder J, Runkel N, Fromm M, Schulzke JD, Buhr HJ. Zinc acts a protective agent on the mucosal barrier in experimental TNBS colitis [in German]. Langenbecks Arch Chir Suppl Kongressbd. 1998;12 5(Suppl 1):223-227.
12. Rodriguez P, Darmon N, Chappuis P, et al. Intestinal paracellular permeability during malnutrition in guinea pigs: effect of high dietary zinc. Gut. 1996;39(3):416-422.
13. Sturniolo GC, Fries W, Mazzon E, Di Leo V, Barollo M, D' Inca R. Effect of zinc supplementation on intestinal permeability in experimental colitis. J Lab Clin Med. 2002;139(5):311-315.
14. Mahmood A, Fitzgerald AJ, Marchbank T, et al. Zinc carnosine, a health food supplement that stabilizes small bowel integrity and stimulates gut repair processes. Gut. 2007;56(2):168-175. Epub 2006 Jun 15.
15. Bates CJ, Evans PH, Dardenne M, et al. A trial of zinc supplementation in young rural Gambian children. Br J Nutr. 1993;69(1):243-255.
16. Chen P, Soares AM, Lima AA, et al. Association of vitamin A and zinc status with altered intestinal permeability: analyses of cohort data from northeastern Brazil. J Health Popul Nutr. 2003;21(4):309-315.
17. Sturniolo GC, Di Leo V, Ferronato A, D Odorico A, D' Inca R. Zinc supplementation tightens leaky gut in Crohn's disease. Inflamm Bowel Dis. 2001;7(2):94-98.
18. Martínez-Augustín O, Sánchez de Medina F Jr, Sánchez de Medina F. Effect of psychogenic stress on gastrointestinal function. J Physiol Biochem. 2000;56(3):259-274.
19. Bhatia V, Tandon RK. Stress and the gastrointestinal tract. J Gastroenterol Hepatol. 2005;20(3):332-339. 20. Hart A, Kamm MA. Review article: mechanisms of initiation and perpetuation of gut inflammation by stress. Ailment Pharmacol Ther. 2002;16(12):2017-2028.
21. Irvine DG. Kryptopyrrole in molecular psychiatry. In: Hawkins D, Pauling L, eds. Orthomolecular Psychiatry: Treatment of Schizophrenia. San Francisco: WH Freeman and Company; 1973:146-178.
22. Irvine DG. Mauve factor and 6-sulfatoxy skatole: two biochemical abnormalities associated with specific measures of psychiatric disease. Clin Chem. 1963;9:444-445.
23. Chen C, Lyte M, Stevens MP, Vulchanova L, Brown DR. Mucosally-directed adrenergic nerves and sympathomimetic drugs enhance non-intimate adherence of Escherichia coli O157:H7 to porcine cecum and colon. Eur J Pharmacol. 2006;539(1-2):116-124.
24. Ward JL. Relationship of kryptopyrrole, zinc and pyridoxine in schizophrenics. JOrthomolec Psychiatr. 1975;4:27-31.
25. Corwin A M, et al. Encylopaedia Britannica 1960;18:801
26. Atamna H, Killilea DW, Killilea AN, Ames BN. Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging. Proc Nat Acad Sci U S A. 2002;99(23):14807-14812.
27. Atamna H. Heme, iron, and the mitochondrial decay of ageing. Ageing Res Rev. 2004;(3)3:303-318.
28. Lill R, Kispal G. Maturation of cellular Fe-S proteins: an essential function of mitochondria. Trends Biochem Sci. 2000;25(8):352-356.
29. Graham DJM, Thompson GG, Moore MR, Goldberg AA. The effects of selected monopyrroles on various aspects of heme biosynthesis and degradation in the rat. ArchBiochem Biophys. 1979;65(1):132-138.
30. Ames BN, Atamna H, Killilea DW. Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging. Mol Aspects Med. 2005;26(4-5):363-378.
31. Liu S, Kawai K, Tyurin VA, et al. Nitric oxide-dependent pro-oxidant and pro-apoptoticeffect of metallothioneins in HL-60 cells challenged with cupric nitrilotiracetate.Biochem J. 2001;354(pt 2):397-406.
32. Smith KJ, Kapoor R, Felts PA. Demyelination: the role of reactive oxygen and nitrogen species. Brain Path. 1999;9(1):69-92.
33. Shinkai T, Ohmori O, Hori H, Nakamura J. Allelic association of the neuronal nitricoxide synthatse (NOS1) gene with schizophrenia. Mol Psychiatry. 2002;7(6):560-563.
34. Sögüt S, Zoroglu SS, Ozyurt H, et al. Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved inautism. Clin Chim Acta. 2003;331(1-2):111-117.
35. De la Monte SM, Bloch KD. Aberrant expression of the constituitive endothelial nitricoxide synthase gene in Alzheimer disease Mol Chem Neuropathol. 1997;30(1-2):139-159.
36. Cabrini L, Bergami R, Fiorentini D, Marchetti M, Landi L, Tolomelli B. Vitamin B6 deficiency affects antioxidant defences in rat liver and heart. Biochem Mol Biol Int.1998;46(4):689-697. 107.
37. Park LC, Zhang H, Sheu KF, et al. Metabolic impairment induces oxidative stress, com-promises inflammatory responses, and inactivates key mitochondrial enzyme in micro-glia. J Neurochem. 1999;72(5):1948-1958. 108.
38. Atamna H, Walter PB, Ames BN. The role of heme and iron-sulfur clusters in mitochondrial biogenesis, maintenance, and decay with age. Archiv Biochem Biophys.2002;397(2):345-353.
39. Fendri C, Mechri A, Khiari G, Othman A, Kerkeni A, Gaha L. Oxidative stress involvement in schizophrenia pathophysiology: a review [in French]. Encephale. 2006;32(2 Pt 1):244-252.
40. Ranjekar PK, Hinge A, Hegde MV, et al. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res. 2003;121(2):109122.
41. Zoroglu SS, Armutcu F, Ozen S, et al. Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur Arch Psychiatry ClinNeurosci. 2004;254(3):143-147.