What is pyroluria?
Pyroluria (pyrrole disorder, kryptopyrrole, kryptopyrroluria, pyrroluria, mauve factor or hemepyrrole) is a common metabolic condition that occurs when pyrrol, a key component of haemoglobin, is overproduced by the liver.
As many as 10-15% of all people suffer from pyroluria. It is a lifelong condition, and symptoms tend to worsen with age and stress. Often people with pyroluria will suffer a variety of serious ailments and degenerative diseases for years, regardless of what therapies they try or how well they eat. It is only after diagnosis that they finally take the correct supplements and steps to manage their condition, usually with significant success. Disciplined supplementation and treatment can manage the condition to the point where there are virtually no symptoms.
Pyroluria is a metabolic condition long recognized by those who practice orthomolecular medicine and orthomolecular psychiatry. However most doctors’ medical associations do not recognise it because there are no pharmaceutical drugs to treat it, and it can be completely and effectively managed with basic supplements. Don’t be surprised if your doctor has not heard of pyroluria or disparages the condition. In Australia the AMA refuses to recognise the condition. However, an increasing number of doctors are starting to take pyroluria seriously.
With pyroluria, some of the by-products of the synthesis of haemoglobin called kryptopyrroles are produced in excess by the liver and not fully excreted in the urine. These kryptopyrroles (more specifically hydroxyhemoppyrrolin-2-one or HPL) are normally harmless. However, if the HPL in your body builds up to an excessive level, the HPL binds to zinc and vitamin B6, and also blocks the receptor sites for these two nutrients. The HPL-zinc-B6 complex is then excreted in the urine. The result is major deficiency in Vitamin B6 and Zinc, and to a lesser degree in other nutrients such as gamma linolenic acid (GLA), niacinamide, biotin, and sometimes manganese and other B-vitamins.
The deficiency in zinc and B6 is so large that it cannot be counterbalanced by foods high in these two nutrients. Zinc and B6 are critical nutrients for producing all proteins including enzymes, hormones and neurotransmitters required by all organs, muscle and connective tissue. This shortage affects the functioning of your entire body and mind, including immune system, digestion, cognitive functioning and emotions.
The onset commonly occurs during a stressful event during the late teens and it continues throughout a person’s life. Pyroluria is triggered and strongly aggravated by prolonged stress such as an injury, a debilitating illness, or severe mental stress. It occurs more frequently in women than in men.
Diagnosis of pyroluria
Most people with pyroluria suffer from some, but not all of the symptoms listed below. A more definitive diagnosis can be done with a urine test, showing an elevated level of kryptopyrroles. The HPL molecule is unstable and will disappear rapidly at room temperature or if exposed to bright light, so the urine to be tested may need to be chilled or transported quickly.
Normal: less than 10 micrograms of HPL per decilitre.
Borderline: 10 – 20 ug/dL of HPL.
Pyroluria: over 20 ug/dL.
Pyroluria should not be confused with histadelia (high histamine), histapenia (low histamine) and hypercupremia (high copper), which cause many of the same symptoms.
Causes of pyroluria
- Genetics, it can run in a family. If a parent, grandparent, uncle, aunt, brother or sister has suffered from major depression, schizophrenia, bi-polar disorder, alcoholism or has committed suicide, there is a higher risk of pyroluria in other family members.
Pyroluria is also an epigenetic condition in which severe stresses in childhood or adolescence can bring on heritable genetic changes.
- Childhood trauma.
- Stress is a trigger, and is one of the main factors that worsens pyroluria symptoms for those who already have it. (12,13) However, it is not clear if stress is an actual cause of the condition, especially in adults.
- Chronic infection in infancy, childhood or adolescence.
- Alcoholism of the sufferer or his/her parents.
- Environmental toxicity, particularly heavy metal poisoning.
- Other triggers or possible causes include sugar, processed foods, a poor diet high in wheat and other grains, and the stress of illness, particularly digestive problems that cause intestinal inflammation or leaky gut syndrome.
Conditions associated with pyroluria
A study (1) led by orthomolecular psychiatrist Abram Hoffer found that pyroluria was frequently present in people with the following conditions:
- Acute intermittent porphyria 100%.
- Latent acute intermittent porphyria 70%.
- Down’s syndrome 71%.
- Schizophrenia, acute 59-80%.
- Schizophrenia, chronic 40-50%.
- Criminal behaviour in adults (3), sudden deviance 71%.
- Criminal behaviour in youths (3), violent offenders 33%.
- Manic depression 47-50%.
- Depression, non-schizophrenic 12-46%.
- Autism 46-48%. (Including Asperger’s Syndrome, Tourette’s Syndrome).
- Epilepsy 44%.
- Learning difficulties and disability / ADHD / ADD 40-47%.
- Neuroses, neurotic behaviour 20%.
- Alcoholism 20-84%.
Other studies (6,10,11) have noted that it is frequently associated with other ailments:
- Lyme disease.
- Post Natal Depression.
- Substance Abuse (apart from alcohol).
- Cancers, particularly lung Cancer.
- Bi-Polar Disorder.
Symptoms – physical signs and appearance
- Characteristic breath and body odour, smells like sweet ripe fruit.
- Immune system weak or stressed, causing frequent colds, infections; more likely to suffer from acne, eczema or herpes.
- White flecks or spots on finger nails (zinc deficiency).
- Cold hands and feet.
- Crowded teeth (need to ask if orthodontic treatment has been used to correct crowded teeth).
- Skin. A variety of chronic skin conditions that have not responded to previous treatments.
- Skin is prone to stretch marks.
- Skin appears paper thin.
- Skin. If the patient’s family has black skin, theirs will be lighter than other members of the family who do not have pyroluria.
- Hair. Reduced hair on head, eyebrows and eyelashes.
- Tooth enamel – poor quality or appearance.
- Fat tends to distribute in the middle of the body.
Symptoms and other indications of pyroluria
Pyroluria can vary from mild borderline cases to severe. It is often complicated by the presence of other ailments or genetic defects. Signs and symptoms will vary greatly between different individuals. Only a few of the symptoms listed below may be present in mild cases.
- Nervous exhaustion, severe inner tension (highly strung), anxiety, mood swings, low stress tolerance, low motivation, pessimism, episodic anger/temper outbursts, panic attacks, memory loss, dyslexia, hallucinations, delusions, paranoia, loss of reality, suicidal tendencies, hyperactivity, histrionic (dramatic) tendency, argumentative (enjoys argument), easily upset by criticism.
- Social withdrawal, tendency to be a loner who avoids large groups of people, loud noise, new situations, new routines, travelling and stressful situations.
- Skin conditions such as dry skin, chronic acne, eczema or dermatitis, psoriasis.
- Pale skin that is prone to sunburn.
- Poor dream recall.
- Tinnitus (whistle or ringing in the ears).
- Poor tolerance of alcohol, drugs and medications. A little produces a powerful response.
- Increased sensitivity/intolerance of sound, light, smells and touch. Poor sense of taste or smell.
- Digestive disturbances, irritable bowel syndrome, abdominal pain.
- A history of being a vegetarian or vegan.
- Gluten intolerance.
- Glucose intolerance with hypoglycaemia. Craving for high-sugar and high-carbohydrate foods.
- Allergies to food or environment.
- Prone to frequent colds or other infections.
- Poor appetite, especially in the morning.
- Early morning nausea.
- More capable and alert in the evening rather than in the morning.
- As a child, often got a stitch when running.
- Delayed onset of puberty.
- Irregular menstrual periods.
- Progesterone deficiency.
- Impotence, erectile dysfunction.
- Joint pain, usually in the knees/legs, creaking knees, restless leg syndrome.
- Seizures, tremors.
- Motion sickness (gets carsick or seasick).
Consequences of pyroluria
- Depression, ADD, ADHD, Autism, Asperger’s syndrome, anxiety disorders, Tourette’s syndrome, bipolar disorder, schizophrenia, dissociative identity disorder, epilepsy, obsessive compulsive disorder, multiple sclerosis, Parkinson’s disease. (2,4,5,9)
- Those affected tend to become loners. They withdraw socially in order to avoid stressful situations both socially and physically. New situations or changes in routine such as travelling are particularly stressful.
- Weak immune system or immune problems causing frequent or chronic bacterial, fungal or viral infections.
- Poor memory, poor learning ability, confusion, mood swings.
- Tendency to alcoholism or other substance abuse and addictions.
Remedies / treatment for pyroluria
The symptoms and conditions for each individual can vary, so a laboratory test including plasma zinc, serum copper and ceruloplasmin (copper binding protein) and HPL level are used to determine the patient’s specific treatment needs.
In mild cases, improvement can be seen in a few days. With severe cases, symptoms may take 3-6 months to abate. If treatment stops, symptoms can return within a couple of days or weeks.
Zinc and vitamin B6 need to be supplemented, usually for the remainder of one’s life.
- Zinc. Take from 25 mg up to 100 mg for severe adult cases. The dose should be increased slowly over weeks, especially if other digestive or mineral-deficiency ailments are present. Take it in the morning after food. It is best to take zinc in an absorbable liquid form rather than as tablets. The best form is zinc picolinate. Not all Zinc supplements have equal bioavailability. Zinc sufficiency can be determined with a zinc taste test.
- Vitamin B6. Up to 200mg of Pyridoxine hydrochloride or 50mg of P5P for a severe adult case. Reduce for children and less severe cases. Ideally, spread throughout the day every 3-4 hours.
Pyridoxine hydrochloride is the most common form of supplementary vitamin B6. However, Pyridoxal-5-phosphate or P5P is more biologically available for those suffering acute pyroluria. P5P is a water soluble vitamin that is not stored in the body and is easily depleted, particularly if you drink tea, coffee or anything with a diuretic effect.
- Pyrolurics need more omega-6 fatty acids than other people, particularly dietary arachidonic acid (AA) and gamma linolenic acid (GLA). Good food sources of AA include eggs, butter, red meat and liver. GLA is found in black currant seed oil and evening primrose oil. Note: omega-3 oils compete with omega-6 oils in enzymatic pathways, so omega-3 oils should not be supplemented. (5,14)
Most people have an excess of omega-6 oils in their diet, and a deficiency is very rare except in the case of pyrolurics. Deficiency causes a dry scaly skin, with a rash or eczema.
- The following supplements also help with pyroluria: vitamin B complex (especially biotin, niacinamide, Vitamin B12), Vitamin A, Manganese, (8) Magnesium.
- Hair tests for copper are not reliable. It is possible to have a high level of copper in the hair while being copper-deficient in the body. In particular, those who have been supplementing with copper antagonists such as zinc, iron, vitamin C, manganese, molybdenum and possibly selenium may be copper-deficient. Those with pyroluria who have been supplementing with zinc for a long period are at high risk of copper deficiency.
- Diet. No grain, no sugar. A wheat-free, gluten-free and preferably grain-free diet will improve digestion significantly, better enabling the absorption of minerals that are so lacking under pyroluria. Barley and oats are the most acceptable grains, as they are good sources of gamma linolenic acid. I suspect some kinds of millet may also be acceptable.
- Probiotics, particularly if there are symptoms of digestive problems.
- Minimise stress. Various techniques are discussed in Grow Youthful, including how to meditate, exercises in accepting life and people as they are, breathing techniques, massage and bodywork, and social support.
- Exercise – any form of enjoyable regular exercise.
- Treat symptoms of estrogen dominance, if present. Stop taking the oral contraceptive pill.
- Treat symptoms of hypothyroidism if present.
- Treat symptoms of adrenal stress if present.
- See details of remedies recommended by Grow Youthful visitors, and their experience with them.
1. Woody R. McGinnis, Tapan Audhya, William J. Walsh, James A. Jackson, John McLaren-Howard, Allen Lewis, Peter H. Lauda, Douglas M. Bibus, Frances Jurnak, Roman Lietha, Abram Hoffer. Discerning the Mauve Factor, Part 1. Alternative Therapies, Mar/apr 2008, VOL. 14, NO. 2.
2. Pfeiffer C.C., Holford P. Mental Illness and Schizophrenia: the Nutritional Connection. Harper Collins, 1987.
3. Abram Hoffer. The Discovery of Kryptopyrrole and its Importance in Diagnosis of Biochemical Imbalances in Schizophrenia and in Criminal Behavior. J. Orthomolecular Medicine 10(1):3 1995.
4. Woody McGinnis. Pyroluria: Hidden Cause of Schizophrenia, Bipolar, Depression, and Anxiety Symptoms. International Guide to the World of Alternative Health, Orlando, 21 May 2004.
5. William Walsh. Fatty Acid Profiles of Schizophrenic Phenotypes. Pfeiffer Treatment Center, 91st AOCS Annual Meeting and Expo San Diego, California 2000.
6. Scott Forsgren. Kryptopyrroluria (aka hemopyrrollactamuria): A major piece of the puzzle in overcoming Lyme disease. Public Health Alert, vol. 5, no. 5. May 2010.
7. Carl Pfeiffer, Arthur Sohler. Treatment of pyroluric schizophrenia (malvaria) with large doses of pyridoxine and a dietary supplement of zinc. J. Orthomolecular Psychiatry3(4):292, 1974.
8. Carl Pfeiffer, Scott LaMola. Zinc and Manganese in the Schizophrenias. J. Orthomolecular Psychiatry 12(3):215, 1983.
9. Carl Pfeiffer, Arthur Sohler. Treatment of pyroluric schizophrenia (malvaria) with large doses of pyridoxine and a dietary supplement of zinc. J. Orthomolecular Psychiatry3(4):292, 1974.
10. Pfeiffer CC, Bacchi D. Copper, zinc, manganese, niacin and pyridoxine in schizophrenia. J Appl Nutr. 1975;27:9-39.
11. 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.
12. Bhatia V, Tandon RK. Stress and the gastrointestinal tract. J Gastroenterol Hepatol. 2005;20(3):332-339.
13. 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.
14. 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.
15. 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.
16. Ward JL. Relationship of kryptopyrrole, zinc and pyridoxine in schizophrenics. JOrthomolec Psychiatr. 1975;4:27-31.