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What is pyroluria?

Pyroluria is a genetic disorder caused by abnormal hemoglobin synthesis.  Hemoglobin is the protein in red blood cells that contains iron and carries oxygen throughout the body.  During hemoglobin synthesis, by-product compounds called kryptopyrroles are formed.  This is a normal process even though there is no known function of kryptopyrroles in the body.  However, in people with pyroluria, these compounds are produced to excess, especially under stress, and create deficiencies of vitamin B6 (pyridoxine) and zinc.  Because of this, most of the signs and symptoms associated with pyroluria are due to deficiencies of B6 and zinc.

Vitamin B6 and zinc are essential in the body.  Vitamin B6 is required for more than 100 enzyme reactions in the body.  It is specifically required for:

  • Converting food into glucose for energy;
  • Niacin production;
  • lipid metabolism,
  • carnitine synthesis,
  • production of neurotransmitters serotonin, dopamine, norepinephrine, histamine, and GABA;
  • functioning of the immune system;
  • formation of red blood cells;
  • control of homocysteine (along with B12 and folate); and
  • hormone modulation.


Zinc is also essential for enzyme function and more than 50 enzymes in the body contain zinc.  Zinc is important for:

  • cell growth and replication;
  • hormone activity and reproduction;
  • vision, especially night vision;
  • immune function;
  • protein metabolism;
  • wound healing and blood clot formation;
  • breakdown of carbohydrates;
  • thyroid function;
  • resistance to stress;
  • maintaining cognitive function, memory, and learning; and
  • normal appetite, taste, and smell.


Moderate zinc deficiency is also associated with disorders of the intestine which interfere with food absorption (malabsorption syndromes), which can cause additional symptoms and health conditions.  This may be why tendency to iron deficiency or low iron levels can be seen in patients with pyroluria.


Signs and symptoms of pyroluria

This condition is important to know about because a high incidence of pyrrole disorder is found in individuals with many conditions, including:

  • Autism spectrum disorders
  • anxiety
  • depression
  • tics/Tourette’s
  • epilepsy
  • obsessive-compulsive disorder
  • schizophrenia
  • bipolar disorder
  • Asperger’s
  • alcoholism and addictions
  • Multiple sclerosis
  • Parkinson’s
  • Lyme disease


“As many as 50% of those with autism, 40% of alcoholics, 70% of schizophrenics, 70% of persons with depression and 30% of persons struggling with ADD may have pyroluria underlying these conditions and make them very difficult to reach with traditional and even holistic therapies.  –But pyroluria isn’t limited to these populations.  As much as 10% of the population may have this metabolic condition and not know it…but may have lifelong symptoms associated with it that tend to worsen with age…and stress.” (


In general, the symptoms of pyroluria can have a mysteriously intractable quality to them, and primarily relate to the B6 and/or zinc deficiencies.  One source also indicated that accumulated pyrroles can also interfere with the conversion of B6 (pyridoxine) to its active form, pyridoxine-5-phosphate (P5P).  The deficiency of P5P can then reduce hemoglobin synthesis, worsening many symptoms.  Lower levels of P5P are also associated with lower glutathione levels, which will further increase oxidative stress and decrease detoxification in the body, causing additional symptoms.

I have listed symptoms gathered from a variety of sources and they may include:


  • poor stress tolerance
  • all symptoms worse with stress
  • nervousness
  • anxiety
  • mood swings or instability
  • inner tension
  • irritability or emotional reactivity
  • episodic anger or aggressiveness
  • depression
  • very sensitive to criticism



  • difficulty concentrating
  • poor short-term memory
  • learning problems, especially with information in written format



  • headaches, especially blinding or cluster type
  • tics
  • poor night vision
  • poor dream recall
  • restless leg syndrome, tingling or tremors
  • motion sickness
  • sensitivity to light, smell, sound, and/or touch



  • frequent or chronic infections
  • slow wound healing
  • tendency to autoimmune disorders



  • muscle weakness
  • joint pain or stiffness, especially knee or leg
  • hypermobile joints, muscle pain
  • gets stitch in the side when running,

especially in children



  • hair loss
  • premature graying of hair
  • white spots on nails
  • rough and dry skin
  • tendency to acne, eczema, or psoriasis
  • being pale, having an inability to tan, or sun burning easily



  • irritable bowel syndrome
  • allergies
  • gluten intolerance
  • hypoglycemia
  • nausea
  • difficulty digesting protein and fat
  • fat distribution around abdomen
  • diarrhea or constipation
  • abdominal tenderness
  • loss of appetite
  • poor sense of taste or smell



  • easy bruising/bleeding
  • low blood pressure
  • cold hands and feet, Raynaud’s syndrome
  • spider veins, varicose veins
  • heart disease
  • higher clotting risk
  • tendency to anemia, especially iron deficiency



  • fatigue and low energy reserves
  • slow growth
  • sensitivity to medications
  • wide variety of hormonal symptoms or imbalances- thyroid, adrenal, sex hormones



I have also found two slightly different pyroluria symptom questionnaires that may also be helpful at:




One important factor in pyroluria is that the doses of zinc and vitamin B6 required for treatment may be toxic for someone with a normal metabolism.  Therefore, testing prior to initiating treatment is important.  False negative results are possible and there is a higher incidence of false negative results in children because they have faster metabolisms than adults.   Children can still be tested; the practitioner just needs to be aware of potential false negatives and a closely monitored trial of B6 and zinc may still be warranted with a negative result but strong clinical indications.  Additionally, because pyroluria is a genetic disorder, other family members should also be tested.

Because pyrroles are excreted in the urine, testing for pyroluria is an easy urine test.  Prior B6 and zinc supplements need to be avoided for 24 to 48 hours prior to testing.  It is important to choose a lab that corrects for the concentration or dilution level of the sample.  Additionally, kryptopyrroles are light sensitive, so the lab should include methods used to prevent the degradation prior to the sample analysis.


Fortunately, pyroluria is manageable with the use of regular supplements, typically high doses of zinc and B6, higher than what can be obtained from food.  The type of supplement is important so they can be effectively absorbed; zinc picolinate or gluconate and pyridoxal-5-phsphate (P5P) tend to be the best forms of these nutrients.  However, some patients may do best with a combination of P5P and standard B6.  Supplementation may need to start at low levels and gradually increase.  Supplementation does need to be monitored to avoid toxic levels, as well as ensuring patients are avoiding competing nutrients.  For example, copper-rich foods and copper-containing supplements should be avoided because they are antagonistic to zinc.

People with pyroluria also have a higher than normal need for omega-6 fatty acids, particularly arachidonic acid and gamma linolenic acid (GLA).  Arachidonic acid is found in eggs, butter, red meat and liver, and GLA is found in supplements like black currant seed oil and evening primrose oil.  Other helpful nutrients may include high doses of probiotics; other B vitamins; antioxidants, including glutathione and vitamins A, C, and E; other minerals, including manganese and magnesium; and amino acids, including cysteine, 5-hydroxy tryptophan (5HTP), glutamine, taurine, or glycine.  Proteolytic enzymes may be needed to break up accumulated pyrroles.  Patients will also need digestive, liver, and brain support as well because the effects of zinc and B6 deficiencies can be wide spread through the body.

Ongoing treatment is required and symptom relapses will occur usually within several weeks of stopping supplementation.  Because people with pyroluria have difficulty dealing with the effects of stress, relapses may also occur under different types of mental, emotional, and/or physical stress, including illness, lack of sleep, or injury.  However, with proper, continued supplementation, patients with pyroluria can improve their health.

References (Walter Last)

Dr. Renee Schwartz. Seminar: Nutritional Approaches to Treating Pyroluria and Other Depression Biotypes. November 2014.

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