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MindCheck is the Weekly Wednesday Kids Mental Health series with Dr. Ray Pataracchia N.D.  MindCheck provides in depth information on the orthomolecular approach to coping with mood, behavior and psychotic disorders.  The MindCheck Health Series is endorsed by the  Mindful Network - ‘A Better Future for Children’s Mental Health’.

Pyroluria - the B6/zinc depletion state seen in teens that do not tolerate stress and in people with depression, anxiety, schizophrenia, ADD, and OCD.

Pyroluria Today: Optimal Orthomolecular Treatment

Pyroluria is a classic orthomolecular condition found in the general population and a wide variety of mental health conditions including schizophrenia, ADD, ADHD, OCD, depression, and anxiety.

(Our next blog discusses the High Histamine (Histadelia) Subtype, another classic orthomolecular syndrome.)

What is Pyroluria?

It is a condition that depletes zinc and vitamin B6 in the body and creates a deficiency state resulting in a plethora of symptoms.  Pyroluria may be obvious in patients having specific symptom profiles as we describe below.  The treatment rationale is to replenish the depleted nutrients with manganese.  Pyroluria is determined in cases with increased kryptopyrroles in the urine; tese elevated levels are considered a functional indirect indicator of vitamin B6 (pyridoxine) and zinc deficiency status.

The Case of Sara: Classic Pyroluria

The pyrrole excretion syndrome was documented by Carl Pfeiffer in the early 1970’s.  In 1971 he characterized a classic pyroluria patient (Sara) who responded well to B6, zinc, and manganese.

Pyroluria Characteristics

Pfeiffer determined that the pyroluria subtype was more likely to have the following profile of characteristics:

  • - inability to tolerate stress (teenagers and adults)
  • - poor wound healing
  • - nail white spots (these nail white spot are low in zinc; you can often trace a period of stress back to the time when the white spot emerged from the nail bed)
  • - no/little dream recall
  • - frequent infections
  • - tingling or tremors in limbs (in some cases seizures)
  • - light skin
  • - nausea
  • - dermatitis
  • - iron anemia
  • - knee aches/pains (compromise in cartilage formation)
  • - early hair greying
  • - teeth crowding, tooth decay
  • - cold feet/hands


The Modern Day Orthomolecular Approach to Pyroluria

The following two questions are often asked:

1. Why don’t we need to measure urinary pyrolles?


We provide optimal levels of vitamin B6, zinc, and manganese to all patients and the doses provided are dependent on several factors having nothing to do with whether pyrrole levels are high or not; simply stated, a positive or negative pyrrole result does not alter the treatment approach and, the cost benefit in ordering this test is negligible.

2. But cases that are really high in pyrroles may need more B6, zinc, and manganese, so it may be useful to measure it at baseline (i.e. before treatment)?


Yes, it can be argued that this is true however optimal response is often achieved by providing standard doses determined by factoring in body weight and patient sensitivity.  The dose of zinc provided is always dependent on how the patient tolerates zinc.  By going high with zinc in a case with heavy metals (copper, mercury) for example, you risk liberating metals from storage areas (brain and liver).

Optimal Zinc and B6 Treatment

An optimal orthomolecular clinical nutrition approach needs to respect the need for adequate zinc, B6, and manganese.

When B6 and zinc are provided, other competing diatomic minerals (especially copper, manganese, iron, and molybdenum) need to be provided to prevent secondary deficiency.

If there is a heavy metal that is being eliminated it is best to make the organs that eliminate that specific metal as efficient as possible before liberating it from storage.

Biochemical Details of Zinc and B6 Deficiency

For a full rendition of the symptoms and metabolic changes associated with zinc and B6 depletion, please read my orthomolecular review on schizophrenia or my orthomolecular review on mood and behavior disorders.

Here are some basics on zinc and B6 depletion states.

Zinc is important to several biochemical pathways as over 200 enzymes are zinc dependant. Zinc and iron are the most concentrated metals in the human brain. Zinc deficiency is very common and it is associated with schizophrenia, depression/anxiety, dementia, mental retardation, learning disability, lethargy and apathy. Zinc is essential for the synthesis of serotonin and melatonin. It is crucial to brain development because it plays a major role in protein synthesis. In the brain, zinc lowers excitability by moderating NMDA receptor release of excitatory glutamate. Zinc is involved in the synthesis of inhibitory GABA by the modulation of glutamate decarboxylase activity. Among the zinc-dependant proteins are metallothionein which is essential for heavy metal regulation and zinc bioavailability. The synthesis of Zn-thionein and CuZnSOD are essential in preventing oxidative damage. Zinc protects against fatty acid peroxidation which destroys neuron structure and function. Zinc is involved in neuronal plasma membrane structure and functioning and, may play a key role in blood-brain-barrier integrity. Zinc is involved in storing biogenic amines in synaptic vesicles and, in axonal transport. The biogenic amine histamine regulates nucleus accumbens activity, which is responsible for filtering sensory information and communicating with the amygdala, ventral tegmentum, and hypothalamus. In the limbic system, zinc is involved in the metabolism of emotional regulation. In the hypophysis and hypothalamus, zinc is involved in hormonal metabolism.

Vitamin B6 (pyridoxine) is involved in the decarboxylation of tyrosine, tryptophan, and histadine into the neurotransmitters nor-epinephrine, serotonin, and histamine respectively. B6 deficiencies are associated with schizophrenia, depression, and behavior disorders. It is a cofactor in homocysteine re-methylation. B6 has been found useful in memory acquisition, with just a 20mg dose. It has demonstrated usefulness in controlling neuroleptic-induced akathisia and drug-induced movement disorders. B6 is essential for the synthesis of antioxidants such as metallothionein, glutathione, and CoQ10 which help prevent neuronal oxidative stress. B6 (and zinc) are involved in the synthesis of glutamic acid decarboxylase (GAD) which blocks excitotoxicity with eventual secondary oxidative damage. B6 is essential for glutathione peroxidase and glutathione reductase which are helpful in preventing mitochondrial decay.