Pyroluria
Functional Urine Testing

Urine Kryptopyrrole Test
for Pyrrole Disorder

A simple urine test that identifies one of the most underdiagnosed and most treatable root causes of anxiety, depression, and stress intolerance.

Pyrrole disorder causes your body to excrete zinc and vitamin B6 in the urine before they can be absorbed — creating a double deficiency that impairs neurotransmitter production, stress tolerance, and immune function. Most doctors have never heard of it. I have spent over 20 years diagnosing and treating it.

This condition is also known as
Pyrrole Disorder Pyroluria Mauve Factor KPU Kryptopyroluria HPL Disorder Hydroxyhemopyrrolin-2-one
All of these names refer to the same condition — elevated urinary excretion of hydroxyhemopyrrolin-2-one (HPL), historically detected by its mauve color on testing paper.

"I've struggled with anxiety, anger issues, and a low tolerance for stress my entire life. My blood levels of zinc and B6 are always normal. Nobody has ever tested my pyrroles."

This is one of the most common patterns I see. Symptoms persist even when blood levels of zinc and vitamin B6 look normal because pyrrole disorder continually pulls both nutrients out of the body through the urine. Without identifying and addressing the underlying pyrrole excess, the deficiencies and symptoms will continue.

Pyrrole disorder is real, testable, and treatable. It was once recognized in the Merck Manual — the physician’s reference guide — as a verified medical condition. Most doctors today have never heard of it. That does not make it less real. It makes it one of the most important gaps in conventional mental health care.

Understanding Pyrrole Disorder

What is pyrrole disorder and how does it work?

Pyrrole disorder, also called pyroluria, is a metabolic and mood disorder in which the body overproduces a byproduct of hemoglobin synthesis called hydroxyhemopyrrolin-2-one (HPL) — commonly referred to as kryptopyrrole. All humans excrete pyrroles in urine in small amounts, which is normal and causes no harm. In an individual with pyrrole disorder, excessive amounts are produced.

The problem is that pyrroles (HPL) have a strong affinity for zinc and vitamin B6. These molecules latch onto zinc and B6 before the body can use them, and carry them out of the body in the urine. The result is a chronic double deficiency of zinc and vitamin B6 — two of the most critical nutrients for brain chemistry, stress response, immune function, and hormonal balance.

Pyrrole disorder is often inherited, though it can also be acquired during periods of significant stress, illness, injury, or trauma. I almost always see it in families with a strong history of alcoholism, depression, anxiety, and mental health struggles across multiple generations. It is frequently missed because most doctors have never heard of it and will not test for it.

For a deeper look at pyrrole disorder, including its connection to other biochemical imbalances, visit the pyrrole disorder page on this site.

The mechanism
How pyrroles create a double deficiency
1
HPL is overproduced The body produces excess hydroxyhemopyrrolin-2-one (HPL) as a byproduct of hemoglobin metabolism
2
HPL binds to zinc and B6 HPL molecules have a strong affinity for zinc and pyridoxine (vitamin B6) and attach to them before the body can absorb them
3
Nutrients excreted in urine The HPL-zinc-B6 complex is eliminated in the urine, constantly depleting the body of both critical nutrients
4
Arachidonic acid also depleted HPL disrupts the arachidonic acid (AA) pathway, an omega-6 fatty acid that is essential for brain function and normal development.
5
Stress worsens the cycle Emotional and physical stress increases HPL production further — creating a self-reinforcing loop that depletes these nutrients faster during the times you need them most
The result: severe ongoing depletion of zinc, vitamin B6, and arachidonic acid until the underlying pyrrole excess is identified and addressed.

A Condition with a Long History

Discovered in the 1950s.
Dismissed in the 1970s. Still real today.

Pyrrole disorder has a documented scientific history spanning over six decades. Its removal from mainstream medical references has more to do with shifts in the pharmaceutical model of psychiatry than with any failure of the underlying science.

58
1958

The Mauve Factor is discovered

Canadian psychiatrist Dr. Abram Hoffer, working with patients with schizophrenia, notices that a significant subset have urine that produces a distinctive mauve color on testing paper. He names the compound the Mauve Factor and begins investigating its relationship to psychiatric symptoms.

61
1961

First published research

Dr. D. Irvine publishes the first description of Ehrlich-positive substances in psychiatric patients' urine, beginning the peer-reviewed documentation of the Mauve Factor and its relationship to mental health conditions.

70s
1970s

Recognized in the Merck Manual — then removed

The Mauve Factor (pyroluria) is listed in the Merck Manual — the physician's standard reference guide — as a verified medical condition. During the 1970s, as the pharmaceutical industry's influence over mainstream psychiatry grows and drug-based treatment models become dominant, the condition is removed from the Merck Manual. Its removal reflects a shift in the economic model of psychiatry, not a scientific disproof of the condition.

90s
1990s onward

Walsh and Pfeiffer develop clinical protocols

Dr. William Walsh and Dr. Carl Pfeiffer develop and refine clinical testing protocols and nutrient-based treatment approaches for pyrrole disorder at the Pfeiffer Treatment Center. Walsh's subsequent decades of research establish pyrroles as a clinically significant biomarker connected to behavioral disorders, schizophrenia, and violent behavior.

08
2008

Mauve Factor clarified by peer-reviewed research

Walsh, McGinnis, Audhya, and colleagues publish "Discerning the Mauve Factor" in Alternative Therapies in Health and Medicine — clarifying that the active compound is HPL (hydroxyhemopyrrolin-2-one), not kryptopyrrole as was initially believed. Treatment with zinc and vitamin B6 is confirmed to reduce urinary HPL and improve neurobehavioral symptoms.

📖

On the Merck Manual removal

The fact that pyroluria was removed from the Merck Manual in the 1970s is frequently cited as evidence that it is not a real condition. This misunderstands how medical reference guides work. The Merck Manual reflects what mainstream medicine chooses to recognize and treat — which is heavily influenced by what is profitable to treat pharmaceutically. The removal of pyroluria coincided with a broader shift toward drug-based psychiatric treatment and away from nutritional approaches. The underlying biochemistry did not change. The peer-reviewed research has continued to accumulate. And the clinical results — patients whose decades-long anxiety, depression, and stress intolerance resolve when their pyrroles are identified and treated — speak for themselves.

Who Should Consider This Test

Symptoms that strongly suggest elevated pyrroles

These symptoms reflect the downstream effects of chronic zinc and vitamin B6 depletion. They frequently overlap with anxiety, depression, OCD and ADHD presentations — which is why pyrrole disorder is so often missed.

Mood and neurological
Severe anxiety and stress intolerance The hallmark symptom — an inability to handle stress that feels disproportionate to circumstances
Explosive anger or irritability Often described as a short fuse — rage that feels uncontrollable and is followed by remorse
Depression and low mood Neurotransmitter production depends on both zinc and B6 — their depletion directly impairs serotonin and dopamine synthesis
Poor short-term memory Difficulty retaining new information, forgetting what was just said or read
Sensitivity to light, sound (misophonia), textures and smell A heightened nervous system response that makes ordinary sensory input overwhelming
Difficulty recalling dreams A classic marker of pyroluria — B6 is required for dream recall and its deficiency consistently impairs it
Night Owl tendencies More energy to get things done after the sun goes down
Physical
White spots on fingernails Leukonychia — a reliable physical sign of zinc deficiency
Nausea in the morning, poor appetite Low stomach acid related to zinc deficiency frequently causes morning nausea and skipping breakfast
Frequent infections and poor immune function Zinc is foundational to immune response — its depletion leaves the immune system chronically undermanned
Stretch marks and pale skin Zinc deficiency impairs collagen production, leading to stretch marks and reduced skin integrity
Severe blood sugar dysregulation Zinc and B6 play critical roles in regulating insulin and glucose metabolism
Why stress makes pyrrole disorder so much worse

Emotional and physical stress directly increases HPL production in the body. This means every stressful event — an argument, an illness, a difficult period at work — causes a fresh surge of zinc and B6 loss. This is why pyroluric individuals seem to fall apart during stress in ways that others do not, and why recovery after stressful periods takes far longer than it should.

Both inherited and acquired forms exist. The acquired form is triggered by acute stress, trauma, illness, or injury — which is why pyrrole disorder sometimes appears to develop in adulthood in people who previously felt well.

Conditions commonly associated with elevated pyrroles
Bipolar disorder Autism spectrum Schizophrenia OCD ADD/ADHD DMDD Tourette syndrome Multiple sclerosis Parkinson's disease Asperger syndrome Alcoholism Epilepsy Down syndrome Porphyria Postpartum depression Family history of anxiety Family history of alcoholism

Pyrrole disorder is especially common when there is a strong multi-generational family history of depression, anxiety, and alcoholism. I almost always test for pyrroles when I see this pattern — because the link between family alcoholism and pyroluria is well established clinically.

What Copper/Zinc Imbalance Drives

Three nutrients lost in every pyroluric individual

This is what makes pyrrole disorder so biochemically significant. It is not a single deficiency — it is a simultaneous, ongoing loss of three nutrients that collectively affect almost every aspect of brain and body function.

Zinc

The master mineral — required for 300+ enzymes

Zinc is essential for neurotransmitter synthesis, immune function, antioxidant production (particularly glutathione and metallothionein), hormone regulation, gene expression, and gut integrity. Its chronic loss in pyrrole disorder impairs virtually every system in the body. Zinc is also the primary check on copper — when zinc falls, copper rises, adding another layer of biochemical disruption.

🧠

Vitamin B6

Pyridoxine — the neurotransmitter cofactor

Vitamin B6 is a cofactor required for the synthesis of serotonin, dopamine, norepinephrine, GABA, and melatonin. It is essential for dream recall, stress response, and the conversion of homocysteine to cysteine. Its depletion directly impairs mood regulation and stress tolerance. B6 deficiency is also a contributing factor in pyrrole-related anxiety, irritability, and sleep disruption.

🌿

Arachidonic Acid

An omega-6 fatty acid essential for brain development

Arachidonic acid (AA) is a polyunsaturated omega-6 fatty acid that is a critical structural component of brain cell membranes and is required for normal brain development and function. Its depletion in pyroluria contributes to cognitive symptoms, developmental issues, and impaired neurological resilience.

Important: Individuals with pyrrole disorder should avoid fish oils. AA replenishment requires high-quality omega-6 sources — not omega-3. This is one of the most commonly misunderstood aspects of pyrrole disorder nutrition. Fish oil is not for everyone, despite what mainstream sources suggest.

Published Research

The science behind
the Mauve Factor

Pyrrole disorder is supported by decades of peer-reviewed research — much of it from Dr. William Walsh and colleagues at the Walsh Research Institute, whose work has been central to my clinical training and practice.

Walsh Institute — Peer-reviewed publication

Discerning the Mauve Factor, Part 1

This landmark paper by Walsh, McGinnis, Audhya, and colleagues definitively identified the Mauve Factor as HPL (hydroxyhemopyrrolin-2-one) rather than kryptopyrrole — correcting a decades-old misidentification. It established the biochemical basis for urinary pyrrole testing and confirmed that treatment with vitamin B6 and zinc reduces HPL excretion and improves neurobehavioral symptoms.

McGinnis WR, Audhya T, Walsh WJ, et al. Discerning the Mauve Factor, Part 1. Alternative Therapies in Health and Medicine. 2008;14(2):40-50. Read the study
Walsh Institute — Peer-reviewed publication

Discerning the Mauve Factor, Part 2

The follow-up paper expanded on the biochemical mechanisms of HPL, its relationship to oxidative stress and homocysteine dysregulation, and its clinical significance across a range of neurobehavioral conditions. It further established HPL as a biomarker with broad applicability in nutritional psychiatry and confirmed the clinical validity of urine pyrrole testing.

McGinnis WR, Audhya T, Walsh WJ, et al. Discerning the Mauve Factor, Part 2. Alternative Therapies in Health and Medicine. 2008;14(3):50-56. Read the study

About the Urine Kryptopyrrole Test

A urine test with strict collection requirements

The urine kryptopyrrole test measures the level of HPL in a urine sample. It is the primary and only direct test for pyrrole disorder. The test itself is straightforward — but the collection process has specific requirements that are critical for accurate results.

HPL is extremely light-sensitive and temperature-sensitive. Exposure to light degrades the compound rapidly. The sample must be collected in a light-protected container and frozen immediately after collection. Failure to follow these collection protocols is one of the most common reasons for false-negative results — which is why detailed instructions are included with the kit to ensure every client understands the process before collection.

Result interpretation matters enormously. Pyrroles fluctuate with stress. A result taken during a calm period may read lower than one taken during a stressful week. I assess results in the context of your full symptom picture, family history, and other lab findings — not as a standalone number.

Please note: During your consultation, I will advise on the testing process based on your individual situation.

Sample collection requirements
What makes this test different
🔒
Light-protected container required HPL degrades rapidly when exposed to light. The collection container should wrapped with a towel to block all light exposure during and after collection
❄️
Frozen immediately after collection The sample must be frozen right after collection and kept frozen until shipped.
🏠
Home collection The sample is collected at home using the provided collection materials, then shipped according to the lab's frozen sample instructions
🔄
Repeat testing is important Because HPL fluctuates with stress levels, retesting after treatment helps confirm whether intervention is working and whether ongoing monitoring is needed
Critical: Incorrect collection (especially light exposure or failure to freeze immediately) is the primary cause of false-negative results. Follow all instructions carefully.

How It Works

Simple collection at home. Life-changing clarity.

Here is what the process looks like from your first discovery call to your personalized treatment plan.

01

Free Discovery Call

We spend 20 minutes talking through your symptoms, family history, and health goals to determine whether pyrrole testing is the right starting point — and what other testing may be relevant alongside it.

02

Initial Consultation and Test Order

After sign-up, we complete a full intake session. I order your urine kryptopyrrole test, which comes with complete collection instructions, including which days to ship your sample back to the lab.

03

Collect at Home and Ship

You collect your urine sample at home using the provided collection materials, following the instructions sent with the kit. You then ship the frozen sample to the lab in the provided packaging.

04

Your Personalized Treatment Plan

Once all results are in, I build your starting treatment plan. We meet to review your HPL level and what it means for your specific symptoms, then I build your targeted zinc, B6, and nutritional protocol. We meet monthly with updates and you can message me between sessions (included with 3 and 6-month programs only).

20+

years in practice

Why Work With Samantha

Pyrrole disorder has been central
to my practice for over two decades

I have specialized in pyrrole disorder since the beginning of my practice. It is one of the most consistently rewarding conditions to work with — because when it is identified and properly treated, the results can be dramatic. Clients who have struggled with anxiety, anger, and stress sensitivity their entire lives often experience significant relief within weeks of beginning targeted treatment.

But getting the treatment right requires clinical experience. The specific forms of zinc and B6 matter. The dosing needs to be individualized. And pyrrole disorder rarely exists in isolation — it almost always coexists with copper toxicity, methylation imbalances, gut dysfunction, or other biochemical factors that must be addressed alongside the pyrroles for the full picture to come together.

  • I treat pyrrole disorder as part of a whole biochemical picture — connecting it to zinc and copper status (internal link to copper/zinc panel page), methylation (internal link to methylation profile page), gut health (internal link to GI Map page), and hormonal influences so nothing is missed.
  • I guide you through the collection process personally — because incorrect sample handling is the most common reason for false-negative results, and I want your test to give you the most accurate picture possible.

  • All sessions are virtual — I work with clients across the United States and internationally. Sample collection and shipping can be arranged from most locations.

Common Questions

Everything you need to
know before you start

Pyrrole disorder (also called pyroluria, KPU, or Mauve Factor disorder) is a metabolic condition in which the body overproduces a compound called hydroxyhemopyrrolin-2-one (HPL). HPL has a strong affinity for zinc and vitamin B6, binding to them and carrying them out of the body in the urine before they can be absorbed. The result is a chronic double deficiency of both nutrients regardless of diet or supplementation — because the underlying excess HPL production keeps pulling them out. The deficiencies then impair neurotransmitter production, stress response, immune function, and hormone regulation.

The test requires a urine sample collected at home using a light-protected container. HPL degrades rapidly when exposed to light and temperature changes — so the sample must be protected from light during and immediately after collection, then frozen right away. It is shipped to the lab in frozen condition. Complete instructions are included with the kit to ensure accurate results. Incorrect handling — particularly light exposure or failure to freeze — is the most common cause of false-negative results.

You can supplement, but without identifying and addressing the pyrrole excess that is causing the depletion, the deficiencies will keep returning. Many clients come to me having supplemented zinc and B6 for years without lasting effect — because the underlying HPL overproduction keeps pulling both nutrients out of the body. Testing also matters for dosing: the forms and amounts of zinc and B6 appropriate for pyrrole disorder are specific, and supplementing incorrectly — particularly with the wrong form of zinc — can actually worsen some symptoms. Testing removes the guesswork.

Pyroluria was listed in the Merck Manual — the physician’s standard reference guide — as a verified medical condition before being removed in the 1970s as pharmaceutical approaches to psychiatry became dominant. Its removal reflects a shift in the economic model of psychiatry rather than a scientific disproof of the condition. The peer-reviewed research has continued to accumulate, including the landmark “Discerning the Mauve Factor” papers published by Walsh and colleagues in 2008. Most conventional doctors today are unfamiliar with it — which is exactly why most people with pyrrole disorder go undiagnosed for years or decades.

Many pyroluric individuals experience noticeable improvement within the first few weeks of properly dosed and correct forms of zinc and B6. More substantial recovery typically occurs over three to six months. Treatment for pyrrole disorder is ongoing — those who discontinue treatment typically experience a return of symptoms because the underlying HPL overproduction does not go away. It is a lifelong management process rather than a one-time cure. Regular monitoring and periodic retesting help ensure the protocol remains appropriately calibrated as circumstances change.

The Mauve Factor is the original name for pyrrole disorder, given by Dr. Abram Hoffer in the 1950s when he noticed that patients with schizophrenia had urine that produced a mauve color on testing paper. The condition was listed in the Merck Manual as a verified medical condition before being removed in the 1970s as pharmaceutical approaches to psychiatry became dominant. The Mauve Factor, HPL, kryptopyrrole, pyroluria, and pyrrole disorder all refer to the same underlying condition — elevated urinary excretion of HPL causing zinc and B6 depletion.

Yes — pyrrole disorder is often inherited and tends to run strongly in families. I almost always see it when there is a multi-generational history of anxiety, depression, and alcoholism in a family. Alcoholism in particular has a well-documented clinical association with pyroluria, which may partly explain why alcohol temporarily relieves the anxiety and stress intolerance that pyroluric individuals experience. An acquired form also exists — triggered by significant acute stress, trauma, illness, or injury, which causes a surge in HPL production that depletes zinc and B6 rapidly.

Pyrrole disorder disrupts the arachidonic acid (AA) pathway, a critical omega-6 fatty acid that is essential for brain function and normal development. The appropriate way to restore it is through high-quality omega-6 sources — not omega-3 fatty acids like those found in fish oil. Taking fish oil can actually worsen the arachidonic acid deficiency by further tilting the omega-6 to omega-3 ratio. This is one of the most important and most commonly misunderstood aspects of pyrrole disorder nutrition, and it is why dietary guidance from someone experienced with pyroluria is so important.

Pyrrole disorder rarely exists in isolation. Because it depletes zinc, it frequently contributes to copper toxicity — since zinc and copper are biological antagonists and low zinc allows copper to rise. It also connects to methylation imbalances (zinc is required for methylation), gut dysfunction (zinc is essential for gut lining integrity), and hormonal symptoms (zinc regulates estrogen metabolism). I almost always assess pyrrole disorder alongside copper and zinc bloodwork, methylation status, and GI health — because treating the pyrroles while ignoring the downstream imbalances gives only partial results. Internal links to relevant test pages.

The urine kryptopyrrole test is a specialty functional test and is not covered by insurance. It is an out-of-pocket cost. During your free discovery call I can walk you through current pricing and help you determine whether this test is the right starting point, or whether we should begin with a broader panel of testing based on your symptom picture and history.

Ready to finally test
for pyrrole disorder?

Schedule your free 20-minute discovery call with Samantha. We will talk through your symptoms, your family history, and whether the urine kryptopyrrole test is the right next step for you.