Pyroluria: What It Is, How It Impacts Mental and Physical Health and Hope for Those Who Suffer
Hello, I am Julie Donaldson and I am a clinical nutritionist with functional health training. I specialize in restoring balance in complex, chronic and acute health conditions. I welcome you to peruse other articles that may be of interest to you in your health investigation!
“I struggled with my mental health, hormones and my immune system for decades, including all the judgments and stigma that goes with it. When Julie brought up the possibility of pyroluria with me, it felt foreign but with potential. In fact, I had it. And I had issues with estrogen and copper that were involved. Using the right approaches, life changed dramatically. I am forever grateful.”
Pyroluria is a condition, often inherited, that can affect persons of all ages including newborns. The condition is causative in multiple mood disorders and imbalances yet is quite unknown in both mainstream medicine and mental health care. In holistic health care practices, it is something we want to consider carefully. Topics of iron/heme regulation, copper toxicity, zinc and B6 depletion, oxidative stress gut health, nutrition and detoxification are covered in this article.
(This article was originally published n 2018 and is being re-published with new data/research just released in 2023. Over the last decades, there has been considerable dispute of pyroluria as a true condition - updates here will clarify this dispute.)
What is pyroluria?
Pyroluria is the disruption of synthesis of heme-producing molecules in the body, including hemoglobin. Pyrroles are a natural byproduct of the degradation of heme-containing molecules which accumulate in excess with the presence of this imbalance. Pyrrole disorder sufferers produce excessive amounts of the metabolite HPL (hydroxyhemopyrrolin-2-one). It was once thought that this renders normal cell receptors unable to properly utilize zinc, Vitamin B6 and biotin while at the same time enhancing their excretion in the urine when attached to the pyrroles (which have an affinity for these nutrients) But, new information and research suggests that pyrroles do not actually have the capacity to bind to these nutrients, but rather signal that the nutrients are being required and/or utilized in excess. In the new research, in fact, it is shown that elevated pyrroles are indeed found through proper urine testing (a fact that has been disputed over the last years), and those higher levels are associated with mental disorders over 70% of the time.
The depletion and/or high demand for these key nutrients (which are coenzymatic cofactors for mood and methylation modulation as well as for amino acid and neuromediator metabolism) contributes to the expression of the symptoms already defined in pyroluria. But the new understanding from the research is that elevated pyrroles signal 2 things: 1) the molecular origin is disruption of regulatory heme and 2) there is oxidative stress. These two things are interrelated and we’ll discuss that later in the article. Essentially, however, the research does prove that pyroluria is a legitimate condition.
Oxidative stress is defined as cellular/tissue damage caused by the body’s inability to keep up with free radical production. Here are the main sources of oxidative stress:
poor nutrition, especially the use of omega 6 processed oils
low antioxidant intake (this also damages the skin, our #1 line of defense and the body’s largest organ)
psychological stress
environmental toxin accumulation, including polluted air, water, homes (mold), heavy metals and plastics
disruption of circadian rhythms
iron overload
physical inactivity
What are the symptoms of pyroluria and how is it diagnosed?
Excess pyrroles and associated nutrient deficiencies can contribute to all types of mental health conditions, including depression, anxiety, OCD, ADHD, schizophrenia and suicidal tendencies. It is noted that there is a higher rate of pyroluria in people with autism and autism spectrum disorders.
Dr. Carl Pfeiffere was the primary pioneer in the arena of pyroluria, its impacts and its requirements for individual nutrient therapy. Dr. William Walsh and Dr. Albert Mensah have been modern-day champions and medical leaders in the effort to make the condition of pyroluria more well-known and accepted. At the right is a chart from Dr. Mensah with many of the common presenting symptoms of pyroluria:
It should be noted additionally that pyroluria does exist in people who are not symptomatic with mental/emotional conditions. Other possible symptoms include acne, nail spots, cold hands and feet, inability to tan, low morning appetite, constipation, joint pain, ADHD, dyslexia, food sensitivities/gut dysfunction, sensitivity to light, irritability and temper, prematurely gray hair, frequent infections, poor dream recall, poor short term memory and social withdrawal.
Below is a list indicating urine measurements of HPL in numerous challenging conditions of mental illness as well as criminal behavior. HPL is placed in relationship to creatinine, a waste product produced from kidney filtration:
Diagnosed Ailment/% of HPL in urine (as ratio to creatinine):
Acute Intermittent Porphyria/100
Down's Syndrome/77
Latent Acute Intermittent Porphyria/70
Acute schizophrenia/59-80
Chronic schizophrenia/40-50
Manic depression/47-50
Depression (Non Schizophrenic)/12-46
Epilepsy/44
Autism/46-48
Learning Difficulties/40-47
ADD/ADHD/40-47
Criminal behavior, adults with sudden deviance/71
Criminal behavior, youth violent offenders/33
Alcoholism/20-84
Clearly, there are high levels of HPL in the majority of these conditions. Fortunately, testing for pyroluria is quite simple using a urine sample with both corrected and uncalculated kryptopyrrole results that delivers high reliability. The test is also quite affordable and easy for children to use. In the research cited in this article revision, it is also clearly stated that only the Lambert study method validated pyrrole results properly and classified them as a marker of oxidative stress. The Lambert study method corrected to creatinine to adjust for hydration. This is the only method that the Mensah organization condones and here at True Nature we only use this approved method. The level of pyrroles in the urine is provoked by the application of a chemical called DMAB. The reactive intermediate is stable enough to remain in the bladder to be detected.
There is also an online questionnaire which can be helpful to have some assessment of pyroluria risk. Here is the link to that questionnaire: https://www.keac.nl/hpu-2/vragenlijst/?lang=en A score of 10-14 is positive and may not require any further testing. Lower scores should be evaluated for borderline possibilities and should include individual symptom assessment.
What causes pyroluria?
Stressful events and/or environmental exposures are known to precipitate pyroluria. Heightened emotional states lead to the release of certain hormones and neurotransmitters which causes a cascade effect in neural chemistry. This can include the chemistry of a developing fetus in response to maternal biochemistry. These hormones and neurotransmitters often have an epigenetic effect that shifts the capacity of an individual to cope with oxidative stress. Pyroluria is essentially a biological event referred to as an oxidative burst.
In some cases, pyrrole disorder has been linked to environmental factors such as exposure to certain chemicals, foods or stressors. Additionally, certain genetic mutations may play a role in its development.
As we dive deeply into the cascade effects of an oxidative burst, we see many reasons that the typical therapies recommended for pyroluria work. Namely, B6 is a primary therapy. Through the most current research, we understand that rather than being cleaved, it is an important, often depleted antioxidant. B6 plays critical roles in oxidative stress as well as in the balance of numerous neurotransmitters, including GABA, serotonin and tryptophan. These neurotransmitters are also associated with numerous mental disorders and ADHD. The link between B6 and improvement in symptoms with pyroluria is clear.
In the case of zinc, which is another major nutrient utilized in balancing pyroluria, we see several important connections. In pyroluria, as stated above, heme dysregulation is the molecular origin. When iron is out of balance, copper is also out of balance. And when copper is out of balance, zinc is also imbalanced. Zinc is the antagonist to copper, and as you can see from the chart below, copper moves out of balance with iron (in the opposite direction):
copper and iron relationships
The most common finding with copper in pyroluria is toxicity. Copper requires zinc to be cleared/antagonized. Due to their intricate relationship, sources of iron depletion must also be identified, including immune/pathogenic stress, spleen stress, poor diet, etc. Copper toxicity also interferes with proper neurotransmission, so the utilization of zinc becomes an important procedure for supporting mental health. The Weston A. Price organization has published an important article on contributing factors to zinc depletion, including improper diets and pyrloruia. Copper toxicity incites numerous processes of oxidative stress as well.
Zinc is also key to the successful resolution of oxidative stress which, as we’ve discussed, appears to be the true “cause” of pyroluria in conjunction with heme dysregulation. A chronic state of oxidative stress will lower zinc levels. Zinc is also a key cofactor in methylation and those with impaired methylation and toxin recycling/reabsorption tendencies will also have depleted reservoirs of zinc. Of course, once again, diets low in zinc will add to these challenges.
As noted previously, mental illness and ADHD are common conditions in those with pyroluria. Copper toxicity is also associated with these conditions.
Pyroluria and Gut Health
Individuals with pyroluria and associated higher levels of HPL also have much higher risk for leaky gut syndrome. Many people know that leaky gut syndrome involves damage to the very delicate lining of the digestive tract called the mucosal barrier. The barrier, aptly named, is responsible for protecting the digestive tract from pathogen invasion. When damaged, a person is much more susceptible to all types of pathogenic infections. Unfortunately, leaky gut syndrome also contributes to further elevation of HPL - it is a double-edged sword in this scenario..
With pyroluria, there are also associated changes in fatty acid metabolism, causing lower levels of arachidonic acid, a polyunsaturated fatty acid present in the phospholipids of cell membranes. Its presence is high in the brain, muscles and liver, all of which have roles in healthy digestion. HPL also prevents the proper utilization of Gamma Linolenic Acid (GLA), an important Omega 6 fat.Thus, careful attention to nutrition, gut repair, and stabilization of HPL production are all necessary with pyroluria.
At True Nature, the first step in stabilizing any condition is the assessment of metabolic nutrition needs and initiation of a personalized nutrition program. This is necessary in order to generate the energy to produce healing/repair of the gut and is the most effective nutritional approach I have seen in decades of practice.
Pyroluria and Heme Synthesis
Remember that pyroluria involves the malfunction of heme-containing molecule degradation and excess production of HPL. Animal studies have shown that excess levels of HPL cause a decrease in liver heme and the heme-containing detoxification enzyme cytochrome P450. It is estimated that this decrease can measure up to 55%. Zinc, vitamin B6, and biotin are all required for the production of heme. The loss of these nutrients through pyrrole affinity and excretion creates a major disruption in heme levels. Proper balances of heme are required for many other body functions as well, including oxygen regulation and electron transfer, two very critical homeostatic functions.
It has also been discovered that heme is depleted by stress and heavy metal exposure. Notably also, vitamin B6 and zinc are two of the most critical cofactors for detoxification/methylation. This brings us to our next topic around pyroluria...
Pyroluria and Methylation
With an increased risk for heavy metal accumulation in pyroluria (due to low cofactors), we now have to consider increased risks for overall toxicity and possibly impaired detoxification.
The cytochrome P450 enzymes utilize the majority of synthesized haem. These enzymes are responsible for detoxification of toxic estrogen metabolites, xenobiotic compounds (such as petrochemicals, plastics and perfumes) as well as pharmaceutical compounds. Without proper balance in CYP function, risks for all kinds of toxic buildups increase, many of which have associations with cancer risks as well.
Also affected are the stores of the antioxidants glutathione, superoxide dismutase (SOD), and catalase, through the loss of vitamin B6 and zinc. All three enzymes rely on these nutrients to some degree for production and successful detoxification. Glutathione is the major antioxidant required for the removal of non water-soluble, toxic molecules such as heavy metals.
Next, as we know, heme dysregulation is at the heart of pyrrole disorder. Heme is catabolized by bilirubin. Bilirubin is derived from two main sources. Roughly, 80% of bilirubin is made from the breakdown of hemoglobin in aging red blood cells plus prematurely destroyed erythroid cells in the bone marrow. The remainder originates from the turnover of various heme-containing proteins found in other tissues, primarily the liver and muscles. One half of bilirubin is absorbed and taken up by the portal vein to the liver where it is used to make bile. The liver stores a percentage of toxins in the bile which is released from the gallbladder during digestion. This is a supportive mechanism for detox, giving the body a path to clear some toxic burden at every meal. If bilirubin and bile are compromised due to heme dysregulation, this mechanism also becomes compromised.
Summations and Solutions - Shifting the Paradigm to Whole Person Therapy
Pyroluria is a condition that is relatively simple to work with, once identified and dealt with in a whole person paradigm. Not only is it important to confirm the condition with appropriate, reliable testing, but also to look at the whole person in the process. Our paradigms in medicine and mental health care are often very limited, scoping through a myopic lens which separates the person's behavior from their overall health and integrated physical function. That lens is also quite small as it relates to pigeonholing mental illness. If we are to create more and better opportunities for those who suffer with mental illness and possibly with pyroluria, it requires a rather wide lens, and one that includes addressing gut health, detoxification, personalized nutrition and the immune system along with the emotional aspects.
Many children and adults have had dramatic improvement in their lives as a result of easy testing and safe therapeutic application to correct the problem. Clearly, also, there could be direct and positive impacts for our correctional and mental health services systems, reducing burden and lack of effective therapeutic and rehabilitative approaches.
I have tested and supported many clients, both children and adults, who displayed pyroluria-based symptoms. To date, not one single client who has been adequately tested and supported with a proper targeted protocol has failed to heal and move on to lead a much more normal life. Some people are able to recover from pyroluria, especially with comprehensive nutritional and stress management practices. Others need to continue with ongoing specific nutrient therapy, while yet others will require nutrient therapies only in times of very high stress. Professional monitoring of long-term therapies is important, as other nutrient deficiencies can occur with high-dose therapies.
It is natural that our beliefs/thoughts/feelings and behaviors become intertwined with our biochemistry. Hence the saying that our biography is our biology, and vice versa. A new paradigm of comprehensive physical healing along with the restructuring of beliefs and habits will allow much greater potential for all of us around conditions like pyroluria. For more information on mind/body and core belief work, please read here
At True Nature Health Consulting, every person is respected in this type of paradigm. If I may help you with a suspected case of pyroluria and the creation of a fresh perspective, please email me at Julie@truenaturehealthconsulting.com. We provide holistic teleheath services.