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High Mauve, previously mistakenly associated with kryptopyrrole, is a condition characterized by elevated HPL, and associated with neurobehavioral disorders, and vitamin B6 and zinc deficiency.

Mauve Factor, Kryptopyrrole and Pyrroluria

“Mauve Factor,” or “Mauve”, was first detected in the urine of psychiatric patients in 1958 (R).

Mauve was identified mistakenly as kryptopyrrole (KP) in a high-profile scientific journal in 1969 (R). Improved technology, however, demonstrated that KP is not found in human urine (R,R), and Mauve was identified indisputably as hydroxyhemopyrrolin-2-one, or HPL (R,R).

Therefore, “High-Mauve” denotes subjects or groups with elevated HPL or with a tendency to excrete excess HPL, and should be used instead of the term “pyrroluria” which lacks specificity, as many pyrroles appear in urine (R).

What is HPL?

The exact biological origin of HPL (Mauve Factor) is unknown (R).

HPL may be a product of isocoproporphyrins, abnormal porphyrins (pigments) that result from altered heme production (R). Hemes are most commonly recognized as components of hemoglobin, the red pigment in blood, but are also found in a number of other biologically important hemoproteins such as myoglobin, cytochrome, catalase, heme peroxidase, and endothelial nitric oxide synthase.

The formation of isocoproporphyrin requires participation of gut bacteria. Evidence does suggest bacterial involvement in the formation of Mauve, as antibiotics reversibly abolish urinary HPL excretion (R).

Ingestion of large amounts of dietary sources of the pyrrole variety—coffee, tea, cola drinks, chlorophyll, tobacco, tryptophan, vitamin B12—does NOT increase HPL excretion (R).

HPL Levels

All humans seem to excrete small quantities of HPL in urine (R).

Normal concentration of HPL in urine is estimated at 2 to 25 μg/dL (R).

Urinary HPL levels over twice the upper limit of normal are considered highly elevated, butvery high HPL measurements—hundreds of micrograms per deciliter—are also reported (R).

HPL is also detectable in human blood and cerebrospinal fluid (R).

Why is too much of HPL Bad?

High-Mauve was reported in psychosis, alcoholism and substance abuse, psychoneurosis, and in many cognitive, affective, and neurobehavioral disorders (R).

Several findings suggest that HPL is neurotoxic in humans. As a class, pyrroles have been called “nerve poisons”, and HPL is from the subclass of monopyrroles, some of which cause acute neurobehavioral effects in animals (R).

Injection of HPL decreased activity in rats, while increasing aggressive behavior, while a higher dose of HPL increased head-twitch and backward locomotion, behaviors usually associated with hallucinogens (R).

Above-normal HPL excretion corresponds to subnormal vitamin B6 and zinc with remarkable consistency (R).

Individuals with high-Mauve cannot efficiently create serotonin –a neurotransmitter that contributes to feelings of well-being and happiness, and reduces anxiety and depression, since vitamin B6 is an important factor in the last step of serotonin production (R).

Furthermore, a pattern of low plasma biotin levels (vitamin B7) in high-Mauve patients was observed (R), and biotin deficiency is known to cause neurological disease in animals and humans (R,R).

Examination of laboratory records, however, found no association between HPL and markers for vitamins B1 (thiamine), B3, B9 (folate) and B12 (R).

HPL was shown to reduced heme in rats (R). Heme deficiency increases oxidative damage to cells (R,R).

Heme depression further results in excess nitric oxide (NO) (R), which is injurious to the brain (R,R) and is suspected to play a role in such high-Mauve disorders as schizophrenia and autism (R,R). Plasma NO and urinary HPL were positively associated (R).

HPL was also associated with lower catalase, an endogenous antioxidant. Lower catalase in blood has been reported in schizophrenia and autism (R,R).

Table 1. Neurobehavioral disorders associated with elevated HPL (R).

What are the Symptoms of High Mauve?

Numerous signs, symptoms, and traits have been observed in association with high-Mauve (R). Most of these are also symptoms of zinc and/or B6 deficiencies, and include:

  • poor stress control
  • nervousness, anxiety
  • mood swings
  • severe inner tension
  • episodic anger (explosive temper)
  • poor short-term memory
  • depression
  • poor dream recall
  • inability to tan
  • sensitivity to light and sound
  • morning nausea
  • very dry skin
  • white spots on the finger nails
  • stretch marks on the skin
  • poor growth
  • dyslexia
  • spleen area pain
  • joint pain
  • abnormal or absent menstrual periods

Poor dream recall and mild morning nausea/breakfast anorexia may relate especially to B6 deficiency. White flecks in the nails are responsive to zinc, while stretch marks result from a combined deficiency of B6 and zinc (R).

Table 2. Symptoms prevalent in high-Mauve patients (R).

Stress

Heightened HPL excretion is associated with emotional stress, which in turn is known to associate with oxidative stress in the body (R).

HPL excretion appears to be greater during waking hours than during sleep, which may also be stress associated (R).

Treatment

Treatment with nutrients—particularly vitamin B6 and zinc—reduces urinary excretion of HPL and improves diverse neurobehavioral symptoms in high-Mauve subjects (R).

Neurobehavioral symptoms may improve after only a few days of therapy with B6 and zinc, but discontinuation may result in severe deterioration within 48 hours (R).

Vitamin B6 (200-800 mg daily) in combination with zinc (25-100 mg daily) usually is sufficient to suppress HPL and achieve optimal symptomatic response (R).

Long-term treatment with B6 and zinc is needed for ongoing HPL suppression and symptom management. Optimal initial dosages may be higher than maintenance dosages. Zinc requirements in high-Mauve subjects are noted to increase during growth spurts then decline abruptly (R).

Generally, higher urinary HPL suggests the need for proportionately higher dosing of zinc and B6, and repeated measurements of HPL should influence dosing decisions. Clinical symptoms and HPL suppression are the primary determinants of B6 dosing (R).

Sometimes, the optimal response to higher doses of B6 often is achieved with concurrent magnesium (R).

P5P may be effective in combination with B6 or instead of B6 in some high-Mauve subjects (R).

Caution

High urine pyrroles may not necessarily result in a deficiency of vitamin B6 or zinc (R). It is important to confirm their levels before supplementation.

Long-term treatment of high-Mauve patients with high dose vitamin B6 resulted in no cases of peripheral neuropathy, but reversible median nerve paresthesis (numbness and tingling) has been reported (R).

In adults receiving supplements, cellular or plasma zinc should not exceed upper limits of normal, and cellular or serum copper should not be below the normal range (R).

Suppression of manganese may result from aggressive zinc supplementation. Small dosages (approximately 5 mg manganese for each 30 mg of supplemental zinc) reportedly improve symptoms in some high-Mauve subjects. However, serum or red-cell levels should be monitored during supplementation with manganese, which in excess is pro-oxidant (R).

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8 COMMENTS

  • Lala

    So it’s possible that carrying tin, lead, aluminum, nickel that refuse to chelate… and now also high copper levels… in my blood, etc. are
    Ikely to have caused my now high pyroles, BUN and ch itloride levels? Thank you!

  • Tricia

    And causes? Genetics alone? Infection? Nutritional status?

  • Tricia

    Which tests would you recommend?

  • Dominic Pukallus

    Great article. I wish I’d come across this before writing my own, it would have saved me a lot of trouble. Having gone to the trouble here it is anyway, hopefully it may be of some use.

  • doug

    Joe, thanks, helpful article. Few comments/questions:

    1. Are you saying that B6 and Zinc supplementation actually reduce elevated HPL? I thought these supps were taken only to bring B6/Zinc levels up to normal.

    2. When you say “High urine pyrroles may not necessarily result in a deficiency of vitamin B6 or zinc (R). It is important to confirm their levels before supplementation.”… you are applying that only to Pyrroles and not HPU? Elevated HPU is a definitive diagnostic for Zinc, B6 deficiency correct?

    3. William Walsh in his book “Nutrient Power” still refers to the disorder as one of elevated Pyrroles.

    1. Dominic Pukallus

      1. They do, in that the elimination of psychiatric/mental symptoms tend to result in better stress response and avoidance strategies, thereby lowering the oxidative stress which is theorised to be a cause of the elevated HPL and nutrient deficiencies in the first place.My levels have gone from 40.6 ug/dL initially to 29.7 ug/dL after just over a year of heavy B6 and zinc supplementation (amongst other things). Symptoms had disappeared within 2 weeks.

      1. doug

        This gets confusing, in a chicken-egg sort of way. I have to wonder why is there high oxidative stress in the first place, which presumably is different for each person. If one is under high emotional stress or has high burden of toxic metals, for example, and this is causing increased oxidative stress and thus elevated HPU, then the high HPU would be a symptom, and the B6/zinc symptom management.

        1. Dominic Pukallus

          Exactly. An exerpt from my own article on the subject.

          In the 1980s, with Dr Hoffer having retired, Dr Pfeiffer was joined by Dr William Walsh who had met him on the very day that Dr Pfeiffer had been nominated for a Nobel prize by double Nobel laureate Linus Pauling. Together they made a number of findings about what eventually came to be called Pyrrole Disorder due to the fact that the symptoms that were associated with the elevated HPL were eventually theorised to be caused by oxidative stress.

          The HPL (“pyrrole”) was recast as mostly just a marker of this oxidative stress although it had also been shown to have neurotoxic effects of its own in animals. These symptoms were varied but were typically associated with diagnoses of depression, schizophrenia, and other brain, behavioural, and affective disorders.

          It has been reported recently that, as a metric of oxidative stress, HPL is found in elevated amounts in people with any kind of illness, stress, toxicity (especially heavy metal), or injury, though the levels are highest in those exhibiting symptoms of the mental or behavioural disorders mentioned previously.

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