Pyrroles is also known as pyrrole disorder, kryptopyrrole, pyroluria, or Mauve Factor where urinary pyrrole concentrations known as HPL (hydroxyhemopyrrolin-2-one) are elevated and associated nutrient deficiencies such as zinc, vitamin B6 and vitamin C. Pyrroles is an abnormal metabolism of haemoglobin (oxygen-carrying pigment of the red blood cells). HPL when excreted (via urine) takes these vital nutrients with them – like “stripping” them from the body resulting in deficiencies. Elevated HPL is also found to be associated with high unbound copper levels which has been shown to be neurotoxic.
Symptoms and conditions which may be associated with high HPL (Pyrroles) levels:
- ADHD (attention deficit hyperactivity disorder)/learning disability
- Schizophrenia
- Depression
- Autism
- Epilepsy
- Poor dream recall
- Mild morning nausea/breakfast anorexia
- Allergies – food allergy
- Light, sound intolerance – background noises are distracting, irritating
- Stress intolerance, low tolerance to stressful situations, poor stress control
- Explosive anger
- Anxiety
- Nervousness
- Mood swings
- Severe inner tension
- Bipolar disorder
- Panic attacks
- Familial or social withdrawal
- Migraines, headaches
- Easy bruising
- Fatigue
- Poor memory, difficulty concentrating
- Gut symptoms – constipation
- White flecks in fingernails
- Elevated heavy metals
- Predisposition – may be heritable (elevated family member indication for family-wide testing – defective enzymes may be associated with HPL).
- Poor immune function, frequent colds, flu.
- Family history of depression, anxiety, bipolar or schizophrenia.
Supplementation with zinc and vitamin B6 has been shown to reduce elevated HPL levels and improve behavioural symptoms. HPL accumulation has been linked to intestinal hyper-permeability (“leaky gut”).
HPL (Hydroxyhemopyrrolin-2-one)
Elevated urinary HPL is associated with oxidative stress (poor antioxidant function) which combines with the structure of vitamin B6 and zinc. These deficiencies may present for example as ADHD (attention deficit hyperactivity disorder) due to the neurological impairment caused. Excess copper increases due to zinc deficiency reducing glutathione (antioxidant) possibly causing hyperactive behaviour.
HPL (the oxidative stress organic pyrrole-containing molecule detected in urine) has been shown to be linked with genetic variations in micronutrient metabolism. HPL has a high affinity to the structure of vitamin B6 and zinc which causes a deficiency as it is excreted with urine. Vitamin B6 deficiency affects the enzymes involved in protein metabolism and is a cofactor for biochemical reactions such as the synthesis of neurotransmitters, serotonin, dopamine and gamma-aminobutyric acid.
HPL accumulation can be associated with heme breakdown and altered heme biosynthesis. HPL is a metabolite of heme synthesis. Studies have suggested HPL is neurotoxic in humans and HPL is from the class of monopyrroles known for biotoxicity affecting the nervous system and neurotransmission. Elevated HPL has been shown to cause deficiencies of zinc, Vitamin B6 and biotin which are cofactors for heme synthesis.
Zinc and Copper
Zinc is a significant cofactor for metabolism of neurotransmitters (chemical messengers), prostaglandins, melatonin and affects dopamine metabolism. Zinc has antioxidant properties which protect proteins and enzymes from free radical damage (low antioxidant function). Zinc supplementation has been shown to improve the binding status of dopamine transporters. Zinc deficiency due to inadequate dietary intake, decreased absorption in the GIT and excessive losses inhibit the immune system where zinc is involved in the functioning of T cells, macrophages and natural killer cells (immune support cells). Immune function may be negatively affected with inadequate zinc levels.
Zinc acts in defence against copper by inhibiting absorption from the gastrointestinal tract however with zinc deficiency copper accumulates and can cause aggressive behaviour and hyperactivity. Excessive copper levels and copper-mediated neurotoxicity has been associated with oxidation (breaking down) of dopamine resulting in mental fatigue, hyperactivity and behavioural problems. Copper in excess is toxic and depletes glutathione increasing oxidative stress.
Low zinc levels may affect neurodevelopment, intellect and behaviour of children and adolescents. Zinc acts as a defence against copper by inhibiting its absorption from the GIT tract.
Pyrrole excretion can be an indication of heme breakdown due to emotional stress, oxidative stress or nutrient deficiencies. Heme is important for energy production and is required for detoxification and antioxidant defence. Low heme increases oxidative damage to cells. Lowered B6 is associated with low glutathione levels.
Pyrroles, Stress and the Gut
Elevated pyrroles has been related to gut issues such as intestinal bacterial overgrowth (“dysbiosis”) in human studies. Studies have shown correlation between elevated urinary pyrrole (HPL) and elevated urine indican levels. (Indican is an indicator of intestinal toxaemia and overgrowth of anaerobic bacteria). Indican is a product of bacterial tryptophan digestion while urobilinogen are products of intestinal bacteria that can build up if the liver is overburdened. Indican can also be an indicator of protein digestion efficiency. High indicans can present with symptoms such as insufficient gastric hydrochloric (HCL) acid, poor digestive enzymes, adverse food reactions, infections or bacterial overgrowth.
Elevated urinary pyrroles has been associated with other stress factors and can be an indicator of metabolic stress in the body. Stress related changes in intestinal permeability have shown to be associated with elevated HPL. Zinc deficiency is known to result in intestinal epithelial damage and increased permeability (“leaky gut”).
Studies have shown a reduction in vitamin C, vitamin B3 red blood cell, zinc and zinc to copper ratios with elevated pyrrole levels. Pyrrole excretion is a component of illness in general and is not strictly associated with psychiatric disorders. Pyrrole levels have shown to reduce in studies after prolonged supplementation therapy. Pyrrole disorder or pyroluria has been demonstrated to be an indicator of oxidative stress, infection, intoxication or poor digestion.
Deficiency of vitamin B6 and zinc deficiency, elevated free copper and elevated HPL has been associated with explosive anger. Vitamin B6 is needed by more than 100 enzymes associated with protein metabolism including neurotransmitters serotonin, dopamine and gamma-aminobutryic acid (GABA – helps relax and sleep). These deficiencies can lead to ADHD, depression, anxiety, sleep disorders and mental illnesses.
Elevated HPL has also been associated with a deficiency of other micronutrients, including vitamin B6, P5P, zinc, biotin, manganese and GLA.
Enquire at your next consultation if you should be tested for elevated pyrroles (HPL), zinc: copper ratios, unbound copper or intestinal permeability.
Testing Costs:
- Urinary Pyrroles (HPL) testing is $75 for lab test ($60 for pensioner/concession) plus $35 QML collection fee (results take approximately 7 days). This is a urine sample given at the lab (not at home) and is the second void of the morning. If this is the first time being tested zinc and vitamin B6 supplements need to cease two weeks prior to the test to ensure accuracy.
- Pfeiffer Profile: (plasma zinc, serum copper, % free copper, zinc:copper ratio, ceruloplasmin, histamine, homocysteine, Vitamin D3 (see testing page). Fasting blood test (Results take 2-3 weeks).
- These tests cannot be claimed via Medicare.
Further Testing:
- After a pyrrole positive test, further blood tests are recommended to determine and measure zinc and copper imbalances known as the “pfeiffer protocol”.
- The Pfeiffer testing determines the extent of these imbalances and helps guide treatment protocols and manage dosages.
- Family members and siblings with similar symptoms due possible genetic predisposition are encouraged to undergo pyrrole testing.
Treatment:
- Nutritional deficiencies and imbalances are addressed by supplementation together with dietary changes in conjunction with a health professional to reduce the HPL levels. Reduction of free unbound copper levels (where required) are also pivotal in treatment.
- Lifestyle changes and recommendations are also combined with the pyrrole nutritional treatment protocol to address emotions such as stress, anger or low mood where required.
References:
Elbaz, F, Zahra, S & Hanafy, H 2017, ‘Original article: magnesium, zinc and copper estimation in children with attention deficit hyperactivity disorder (ADHD)’, Egyptian Journal of Medical Human Genetics, vol. 18, pp. 153-63.
Hambly, J, Francis, K, Khan, S, Gibbons, K, Walsh, W, Lambert, B, Testa, C & Haywood, A 2017, ‘Micronutrient therapy for violent and aggressive male youth: an open-label trial’, Journal of Child and Adolescent Psychopharmacology, vol. 1, pp. 1-10.
Heilskov Rytter, M, Andersen, L, Houmann, T, Bilenberg, N, Hvolby, A, Mølgaard, C, Michaelsen, K & Lauritzen, L 2015, ‘Diet in the treatment of ADHD in children – a systematic review of the literature’, Nordic Journal of Psychiatry, vol. 69, no. 1, pp. 1-18.
McGinnis, W, Audhya, T, Walsh, W, Jackson, J, McLaren-Howard, J, Lewis, A, Lauda, P, Bibus, D, Jurnak, F, Lietha, R & Hoffer, A 2008, ‘Discerning the mauve factor’, Alternative Therapies in Health and Medicine, vol. 14, no. 2, pp. 40-50.
Mikirova, N 2015, ‘Cross-sectional analysis of pyrroles in psychiatric disorders: association with nutritional and immunological markers’, Journal of Orthomolecular Medicine, vol. 30, no. 1, pp. 25-31.
Viktorinova, A, Ursinyova, M, Trebaticka, J, Uhnakova, I, Durackova, Z & Masanova, V 2016, ‘Changed plasma levels of zinc and copper to zinc ratio and their possible associations with parent and teacher-rated symptoms in children with attention-deficit hyperactivity disorder’, Biological Trace Element Research, vol. 169, no. 1, pp. 1-7.