Pyroluria is known by many different names including Pyrrole Disorder, Kryptopyrrole, Kryptopyrroluria, Pyrroluria, Pyrolle Disorder, Mauve Factor and Hemepyrrole.
Pyroluria is best described as the abnormal synthesis and metabolism of any heme producing molecule, including the oxygen-carrying molecule hemoglobin. All cells in the body produce by-products (waste) and the by-product of heme metabolism is a metabolite called hydroxyhemopyrrolin-2-one (HPL), also known as Mauve Factor. The metabolite was originally thought to be a Kryptopyrrole, but further studies have proven that this is not the case.
Pyroluria sufferers produce excessive amounts of HPL, which renders the receptors on cells unable to utilize Zinc (1-8), Vitamin B6, Biotin (9). HPL also prevents the proper manufacture of Gamma Linolenic Acid (GLA), an important Omega 6 fat.
Supplementation with these nutrients is essential to reduce the detrimental effects of elevated HPL and to reduce the severity of the signs and symptoms associated with Pyroluria.
There is some evidence that suggests Pyroluria 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 suicided. What we have found through treating many sufferers of Pyroluria, is that certain lifestyle factors also contribute to or exacerbate Pyroluria, and it's associated signs and symptoms. Addressing inadequate digestion, leaky gut syndrome, dysbiosis, an improper diet and stress are essential in any treatment protocol in addressing Pyroluria.
Poor diet and digestive health can lead to an increase in HPL levels (10). This makes sense as insufficient nutritional intake from a poor diet and inadequate digestion, robs the body of essential nutrients causing deficiencies. This places greater stress on the body and further inflates HPL levels.
Leaky Gut Syndrome or intestinal permeability is a condition whereby microscopic holes occur in the intestinal wall allowing undigested food, bacterial by-products, poisons and toxins to pass into the bloodstream. Leaky Gut Syndrome is commonly found in Pyroluria sufferers and further contributes to the elevation of HPL.
Studies have shown that zinc deficiency increases Leaky gut Syndrome in animal and humans (11-17).
It is a well-known fact that stress damages the intestinal wall causing intestinal inflammation, which leads to an increase in Leaky Gut Syndrome (10, 18-20).
Dysbiosis, frequently found in Pyroluria sufferers, is an overgrowth of detrimental organisms within the intestinal tract. Dysbiosis is linked to increased HPL levels as well as a cause of Leaky Gut Syndrome (21, 22). Stress increases the adherence of bad bacteria to the intestinal wall within 30 minutes (23).
Pioneering Pyroluria researcher, Dr Carl Pfeiffer, stated on more than one occasion that stress is a major driver behind elevated HPL. 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 male volunteers who were subjected to the stress of a brief cold-water immersion (10).
Alcohol, smoking, drugs and heavy metal exposure also increase HPL levels. This is why sufferers of Pyroluria tend to get a worsening of their symptoms 24 to 48 hours after a big night out drinking or after recreational drug use.
HPL is classed as 'nerve poisons' (25) and as such it can cause damage to nerves, nerve cells and tissue, the brain and also interrupt messages being sent along nerve pathways especially within the brain.
Heme, a substance found in the body, has an iron atom at its core. The most commonly know heme is hemoglobin, the oxygen-carrying red pigment of the blood. Heme is not only found in the blood but in other areas including the liver and nerves. The metabolic activity of nerves is highly dependent on heme for their function, and low levels of heme leads to a metabolic crisis, resulting in neuronal or nerve cell death (26-28). The by-product of heme metabolism, Hydroxyhemopyrrolin-2-one (HPL), is believed to further decrease heme levels in humans, thus worsening the signs and symptoms associated with Pyroluria.
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 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 excess 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 produced by the body and are found
in foods that protect cells from oxidative stress, much like the way galvanised paint protects iron from rusting. The body has three major
antioxidant enzymes; Glutathione, Catalase and Superoxide Dismutase and these enzymes rely on zinc or vitamin B6 in some part to assist in
their production. A marginal deficiency of vitamin B6 is associated with lower levels of Glutathione production and cell
The table below 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 Pyroluria falls outside the realm of mainstream medicine because the only way to rectify the problem is by improving the sufferer's nutritional status, diet, digestion 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 for a person with Pyroluria and sadly these Pyroluria sufferers tend to fall through the cracks of mainstream medicine and are often misdiagnosed and given medication that does nothing to rectify the underlying problem. Unfortunately these medications can lead to a further deterioration of a person's health.
The Pyroluria test kit includes comprehensive instructions and a informative video on how to collect your urine sample and send it off to pathology for testing. Once we receive your Pyroluria test results we will analyse these and send you a detailed Pyroluria Treatment Plan including suggested lifestyle, dietary and nutritional recommendations. You will also be enrolled in our FREE online Pyroluria Video Treatment Series, in which Dr Greg Newson explains Pyroluria treatment, diet, digestion, stress and the underlying causes. It's that easy!
We can have variety of options available;
1) Our Adult and Child, Positive and Borderline treatment Plans offer the latest up to date treatment information and contain advice and recommendation on nutritional supplementation, diet, lifestyle issues and underlying causes.
2) Our Pyoluria Combo Packs are for adults and children diagnosed with Positive or Borderline Pyroluria and contain our recommended treatment plan and nutritional supplements. This is a more economical way of purchasing nutritional supplements for the first 4 - 8 weeks of Pyroluria treatment.
As you can see Pyroluria is a complex health issue and treatment with the relevant nutrients will help to reduce the symptoms associated with Pyroluria, but it will not address the underlying causes. Any treatment protocol for Pyroluria needs to not only support the nutritional deficiencies, but also identify and treat what has caused Pyroluria in the first place.
This article was last updated 20/02/17 by Greg Newson ND
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):109122br /> 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.