The names of the diagnosis of Pyrrole Disorder have changed many times over the years!
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Starting with the initial Mauve Disorder, named after the colour the urine changed to when a testing reagent was added to it, in people with mental health and neurological conditions. Then came Malvaria, Kryptopyrrole and Haemopyrrole, Pyrrole Disorder (commonly used in Aus and UK) or Pyroluria (used in the USA), or other names!

All the names tend to suggest the relationship of the alleged pyrrole compound (ie, HPL) being found in the urine. The original doctors and scientists investigating this condition hypothesised that the HPL compound would bind to zinc and vitamin B6 and carry them out of the body to cause the chronic deficiencies of these nutrients, which in turn cause the Pyrrole Disorder symptoms. It was just a theory, and there was no evidence for this belief.

There are a number of issues I have with the concept of HPL binding to zinc and vitamin B6 in this condition, especially being in clinical practice and seeing thousands of people with this condition, including:

1. A study was conducted and shown to prove that vitamin B6 cannot actually bind to the HPL compound (Lambert, Semmler, Beer & Voisey, 2023), so that common belief is bust
2. I’ve never seen just deficiencies of zinc and B6 in those with the condition, but usually at least 6 deficiencies and sometimes 12… The more deficiencies that someone has, the more deficiency symptoms and the worse or more complex their health issues will be
3. These additional deficiencies are nothing to do with the HPL compound in the urine, but because of STRESS/trauma etc which causes increased use of these nutrients, being needed to make the stress hormones of cortisol and adrenaline, and more
4. The additional deficiencies in those with this condition are also due to reduced stomach function and digestion of foods, which causes reduced absorption of nutrients, leading to these nutrient deficiencies
5. The HPL test is very inaccurate due to being very sensitive to light, heat and time, from when the urine sample is taken to when it’s tested. All the while, the HPL level decreases and can give an inaccurate or even a negative result
6. The HPL result does not relate to severity of symptoms at all, so again it shouldn’t be used as a test for screening or even for checking on progress of the treatment plan.

Many published studies have shown that the urine test is inaccurate, inconsistent, and not related to the alleged mental health or neurological conditions that it is linked to, including of depression, anxiety, bipolar, schizophrenia and more (Warren, Sarris, Mulder, & Rucklidge, 2021). As such, these scientific studies recommend that the HPL urine test should not be used as a screening, diagnostic or treatment tool. And I agree, and why I haven’t used or recommended the HPL urine test for many years. I use a screening questionnaire as the first step, then blood tests to confirm my investigations, and further functional testing may be required too.

I believe the concept of the HPL in the urine being the cause of the nutrient deficiencies of Pyrrole Disorder is completely wrong! At best it might be a scapegoat, or perhaps because the original scientists investigating the condition were not actually clinicians or practitioners, and certainly hot holistic practitioners who use a root-cause focused approach to treating Pyrrole Disorder.

The many nutrient deficiencies of Pyrrole Disorder can be explained by the following 3 ways:

1. Stress and trauma, especially of chronic or long-term stress, causes many nutrient deficiencies due to the excess production of the stress hormones of cortisol and adrenaline, which can in turn strain the adrenal glands and cause reduced production of the stress hormones. The adrenal glands need all the B-vitamins, zinc, magnesium and more – all deficient in Pyrrole Disorder!

2. Stress and trauma affect stomach function and digestion, causing reduced digestion, which in turn causes reduced absorption of nutrients, then nutrient deficiencies and their deficiency symptoms. This causes deficiencies of all the B-vitamins, zinc, magnesium, iron, protein, and more – all are very commonly deficient in Pyrrole Disorder!

3. Many people with Pyrrole Disorder have high level of heavy metals, which can cause neuro-inflammation (of the brain and nervous system), oxidative damage, and the heavy metals can push out of the body many nutritional minerals and vitamins the brain and body needs, to cause many deficiencies including magnesium, zinc, copper, iron, calcium and more – again all very common deficiencies in Pyrrole Disorder.
Hence I believe the deficiencies of Pyrrole Disorder are NOTHING to do with the HPL compound in the urine, and also why the condition shouldn’t even be called as Pyrrole Disorder, Pyroluria, or its other names!

It’s much more important to find and treat all the root causes of the “Pyrrole Disorder” in each person, and not just use some standard protocol which is based on incorrect beliefs or outdated science. This is my approach as I specialise in mental health issues and Pyrrole Disorder – to find and treat all the root causes of all symptoms and conditions in each person. This is a real holistic approach which will give quick symptom relief, as well as the long-term resolution of symptoms, and even the long-term prevention so the issues don’t come back.

References:
Lambert, B., Semmler, A., Beer, C., & Voisey, J. (2023). Pyrroles as a Potential Biomarker for Oxidative Stress Disorders. Integrated Journal of Molecular Sciences, 24 (3), 2712. DOI: 10.3390/ijms24032712

Warren, B., Sarris, J., Mulder, R.T, Rucklidge, J.J. (2021). Pyroluria: Fact or Fiction? Journal of alternative and complementary medicine (New York, N.Y.), 27(5), 407–415. DOI: 10.1089/acm.2020.0151

I often get questioned by patients or people with Pyrrole Disorder (Pyroluria) about whether they should reduce intake of copper-rich foods, to reduce their copper levels. Or even how to reduce copper levels. My answer is usually “it depends…”.

The same answer would be given if someone asked “should I eat more zinc-rich foods?” or “how can I increase my zinc levels?”. It depends…

This is because there is a huge assumption from people with Pyrrole Disorder, or even from most practitioners who follow the “official” (and outdated or wrong) guidelines, including and especially the Walsh Institute trained practitioners, that Pyrrole Disorder (Pyroluria) is just an issue of low zinc and high copper levels. Because it’s not!

If you get diagnosed with Pyrrole Disorder from the urine test, which I no longer recommend as it’s an outdated and inaccurate test, you MUST get a confirmation of this diagnosis from the serum zinc, serum copper and caeruloplasmin tests too. Actually, you also need other tests as well, to find other nutrient deficiencies and factors which are common in this condition. More on this another time.

Sadly, people and practitioners just assume that the urine test alone diagnoses this condition and indicates that someone has high copper and low zinc and therefore needs to supplement with zinc and vitamin B6 (the official guidelines), and avoid copper-rich foods, when this is not always accurate or enough.

Having Pyrrole Disorder doesn’t automatically mean that your zinc is low and copper is high! You can have LOW serum copper but high UNBOUND copper due to low caeruloplasmin. In this case you actually have LOW copper, but low production of the copper transport protein which is the caeruloplasmin, for a number of possible reasons. In this case, do you need to reduce or restrict your copper-rich foods? Absolutely NOT! Reducing your copper in this example will make your health WORSE!

Similar with zinc. Some people with this condition can have optimal zinc levels, but copper can either be too high or too low, together usually with low caeruloplasmin. It’s the imbalance between zinc and copper which is important to know from testing, and together with the caeruloplasmin level with respect to the copper level, which is driving most of the symptoms of Pyrrole Disorder.

Many people with this condition have low zinc and low copper levels, with low caeruloplasmin. This causes the high unbound copper % level, which is an indicator of high oxidative damage in the body, which will be causing many symptoms. Further investigation and testing is needed for people with this presentation of Pyrrole Disorder.

What YOU need in YOUR treatment plan depends on YOUR unique situation, causes, symptom presentation, and test results. Having a standard protocol (such as the Walsh Institute guidelines) is not going to help you and your unique situation. A one-size-fits-all approach never works! You need a personalised plan from a detailed investigation of your health.

1. This is what I do, after specialising in Pyrrole Disorder for many years.

One of the main alleged "official" nutrient recommendations for Pyrrole Disorder is vitamin B6, and the typical practitioner recommendation is to take vitamin B6 as pyridoxine hydrochloride (the inactive form) and P5P being the active form of this vitamin.

However, I do not recommend this...

Some years ago I read some published studies which found that taking the inactive form (pyridoxine hydrochloride) together with P5P caused the inactive form to inhibit the body's use of the P5P - the main one your body can use!

The pyridoxine hydrochloride form of B6 is also linked to causing peripheral neuropathy or nerve damage, which can cause symptoms of numbness or tingling in the extremities, loss of sensation, and also poor muscle control. This happens because of a deficiency of vitamin B6, but also in people who show very high levels of B6 in blood tests. This is likely as the body isn't able to use the B6, and causing the increasingly high levels on blood test, but at the same time as causing a functional deficiency of this vitamin and hence the deficiency symptoms. This neuropathy can take 2-3 months to start to develop after taking many of the usual compounded Pyrrole Primer or similar supplement products which are high in pyridoxine hydrochloride.

​Another reason why I don't recommend just taking B6 on its own, is that all the B-vitamins work together in many different biochemical pathways and reactions. Taking just one in a supplement may temporarily address that deficiency, but will quickly cause imbalances in the other Bs, to cause more symptoms. I believe these factors are why most people on the usual Primer or supplement protocols may get some initial improvements, but then plateau or collapse with the same or worse symptoms they had before taking the products.

Every single case of a new Pyrrole Disorder client that comes to me, has a vitamin B12 deficiency, and over 50% have a vitamin B9 (Folate) deficiency too. Other B-vitamin deficiencies can also cause the common mental health symptoms and conditions seen in Pyrrole Disorder, as seen in the attached table. Again why those with this condition need ALL of the B-vitamins in a B-complex p just not necessarily a methylated B-complex, as many with this condition can be quite sensitive to the methylated forms of the Bs.

But that's not in the official Walsh guidelines... another reason why I think they are wrong, and why I treat this condition differently.

The generally recognised and recommended test for Pyrrole Disorder is the HPL urine test. However, I haven't used or recommended this test for a number of years because of the following reasons:

1. The test is inaccurate - the Pyrrole compound HPL is very sensitive to light, heat, and time from when the urine sample is taken to when it gets to the lab to be tested. If the urine sample is not handled properly, the HPL levels drop. Many times I have seen someone with all the PD symptoms get a "negative" or low HPL test result because of delays to the sample getting tested, which you typically have no idea whether this happens, and so they don't get the treatment they need. Unless you are physically at the lab and pee in the bottle and give it to them immediately for testing, the result will almost always be inaccurate.
2. There are over one dozen other conditions or causes to having high HPL levels in the urine, other than Pyrrole Disorder! So the HPL test isn't even specific for this condition anyway.
3. The HPL level isn't in any way related to the severity of the symptoms, as you would expect. I've seen patients with negative or only barely positive HPL results despite having all the symptoms in a severe way, or others with some mild symptoms having results 10x higher.
4. Even if you had a positive or high HPL test result, the condition needs to be confirmed with getting the serum zinc, serum copper and caeruloplasmin tests too! When you have the zinc, copper and caeruloplasmin test results, you can calculate the unbound copper % (or non-caeruloplasmin unbound copper) which is a marker of how much oxidative damage/stress is occurring because of the high copper level. The blood tests will always be more accurate.

As Pyrrole Disorder is NOT just a condition associated with zinc and copper, and there are many other symptoms and conditions present, other tests are needed to help identify those other issues and their causes. The HPL urine test cannot help at all with finding these things.
Hence why I recommend all of these additional tests as standard, to more holistically test for Pyrrole Disorder and its common related symptoms and conditions:

1. Full/Complete Blood Count (FBC/CBC) - This shows tests related to the red and white blood cells, as it is common to find issues related to anaemia in many people with PD
2. Iron studies - to check for iron deficiency anaemia which is common in approximately 50% of those with PD
3. Thyroid panel (TSH, and the T4 and T3 thyroid hormones) - as low thyroid function is seen in more than 50% with PD
4. E/LFT or Serum Biochemistry (electrolytes, liver and kidney functions, protein levels and more) - to check for many metabolic functions which can be affected by or contributing to the PD symptoms
5. Vitamin D - this "vitamin" acts in the body as an anti-inflammatory hormone to reduce the many inflammatory symptoms of the condition. The nutrient deficiencies of PD can affect the production of vitamin D.

These tests can be done through your doctor or practitioner, but with so few doctors understanding this condition, they may not approve some of these tests, so some may need to be done privately, which will include personally paying for those extra tests.
More important to getting these tests done is to make sure that you get an accurate analysis and interpretation of your results, as perhaps surprisingly, 99% of doctors (or other practitioners) do not interpret pathology results well.
Pathology analysis is an area of specialty that I do, after training over 900 other practitioners on this skill. More information on why doctors don't analyse blood tests properly can be explained here:
https://www.pathologyanalysis.com/pathology.html

The excess production of the "pyrrole" compound in the body, and the nutrient deficiencies and metabolic or biochemical dysfunctions of Pyrrole Disorder, are known to cause many symptoms and conditions.
There are many other conditions which are commonly found in those with Pyrrole Disorder which are not as well known, but can be caused by and/or associated with PD or having elevated pyrrole compounds (HPL) in the urine, including all those shown in the attached diagram.
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Some of these conditions may be a surprise to some, including Lyme disease, Parkinson's disease, and the Autism spectrum disorders, especially ADHD, and more. I have seen many similarities of ADHD with Pyrrole Disorder, or many people being diagnosed with ADHD as well as Pyrrole Disorder, suggesting that they are perhaps one and the same condition. This information and graphic was based on a published scientific article on the pyrrole compounds being found in 80% of patients with chronic Lyme disease (Forsgren, 2009) and these other conditions too.

​This gives some hope and additional treatment options for people with Lyme disease, ADHD, and other conditions shown in the graphic.
 
Reference:
Forsgren, S. (2009). Kryptopyrroluria (aka Hemopyrrollactaminuria): A major piece of the puzzle in overcoming chronic Lyme Disease. Explore, 18 (6), 1-7. 

Methylation is a biochemical process (involving chemistry of compounds and chemical reactions) involving the transfer of a methyl group (one carbon atom connected to 3 hydrogen atoms, or -CH3) to another chemical compound, for activation of the resulting compound or to cause some action.

Of more relevance to health in general, methylation is also used for gene expression - methylation turns on or off the genes which can affect your health. This is called epigenetics - how your environmental factors turn on or off genes, without affecting the DNA underneath. For example, stress, your diet (and deficiencies), chemicals and toxins, lifestyle factors, sleep, etc, will either turn on or off genes to improve your health or to cause symptoms.

With regard to Pyrrole Disorder, there is a belief that people with this condition are categorised into being an overmethylator or undermethylator, to explain how well (or not) the many body methylation processes are occuring. Some practitioners use a questionnaire of symptoms to determine if someone is one or the other, but I've never seen someone who has just symptoms of under vs over, so I question how true this classification really is. Other practitioners test histamine levels as a marker of over vs under, and others use different testing - there is no gold standard. Some genetic testing of genes such as MTHFR and others are sometimes used to check for methylation status too. Vitamin B12 and folate in your diet are methylation factors and do affect methylation, but should be taken into account for assessing methylation status, but these are typically not used for some strange reason. Many other nutrients are needed for methylation, or their deficiencies can affect methylation too.

​The thyroid function of controlling your metabolic rate will also affect methylation, and typically isn't taken into account either! I seriously question this methylation classification and I do not feel it is relevant for health in general or for pyrrole disorder. I do not believe that EVERY chemical process of methylation in the body is somehow running under or over! Some will likely be under and some being overmethylating and this will regularly change, because of many factors, hence why people with pyrroles have symptoms of both!

In undermethylated people, the problem is usually due to a lack of methyl group production in methylation pathways from the abovementioned causes.

It actually isn't possible to be an overmethylator as methyl groups and donors are available, but the cells or processes cannot actually use them, leading to high methyl levels hence the term "overmethylation", but causing a functional deficiency of methylation and LOW methylation symptoms. Hence "overmethylation" is just UNDERmethylation but having high availability of methyl groups.
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Hence don't worry about your alleged methylation status!

​What is Pyrrole Disorder? It is a little known condition which can be initiated from severe or chronic stress or emotional trauma, which then triggers a genetic predisposition for excess production of a compound called HPL, which causes nutrient deficiencies. Because food nutrients are needed for a lot of functions and processes in your body, a deficiency in more than one nutrient will cause many seemingly separate symptoms. Specific nutrient deficiencies cause symptoms which result in Pyrrole Disorder (PD).
Many GPs and doctors don't know about or recognise PD, as it just looks like you have a bunch of fairly common symptoms, including:

• headaches and migraines
• digestive complaints - constipation, reflux, bloating
• poor tolerance to stress
• depression and/or anxiety
• sleep issues (can't get to sleep, or interrupted sleep)
• poor immune system and lots of infections
• allergies and intolerances to foods or environmental substances
• sensitivity to light, sounds, tastes
• and many more symptoms (as shown in the above picture).
  

 You don't need to have all these symptoms, but having more increases the likelihood. When I see some or all of these symptoms together as I do in many clients, I look for the root causes for them all. I also use a screening questionnaire, analysis of pathology results, and specific pyrrole tests.
Pyrroles is nothing to be worried about! If anything it is great to have this diagnosis, as it is very easily treatable mainly with nutritional medicine! I've seen the condition in children as well as adults over 60 years of age, and it's always a relief to finally have an answer to their health issues!
​Pyrroles causes nutritional deficiencies mainly in zinc and vitamin B6, but also of lesser deficiencies in other B-vitamins, magnesium, omega-6 fats and others. Multiple deficiencies lead to all of the symptoms above, and more. Pyrroles is very frequently seen running in families across multiple generations. It is VERY common in those with Irish and Celtic family history, and the reasons for this are unknown.
Some research shows that PD itself is very commonly linked to, and probably even a cause of bipolar disorder, schizophrenia, some autism disorders and other neurological and behavioural conditions.
If you recognise many of the above symptoms (in the picture) in yourself, your children, or other people you know, it would be a good idea to see if Pyrroles may be the cause! I have seen substantial reductions of symptoms with the nutritional medicine treatment for this condition! And those who have improved feel like they have their life (and health) back again!