What is pyrrole?

Understanding pyrrole aka pyroluria
by Sue Kira, Naturopath & Clinical Nutritionist

Introduction to pyrrole
– What is pyrrole or HPL?
– What is pyrrole disorder?
– Why is pyrrole called a disorder?

The history of pyrrole discovery

Signs and symptoms

Diagnosis and Testing
– Applied Analytical Laboratories
– What if you live in a remote area or overseas?
– Additional Testing for pyrrole

Treatment for pyrrole
– who do I go to for treatment?

Blocks to healing/clearing pyrrole disorder

Introduction to pyrrole

Pyrrole is a molecular compound occurring naturally in our bodies as part of haemoglobin synthesis. It is also the by-product of many other oxidative processes in the body. Pyroluria, or pyrrole disorder, is a condition where someone’s pyrrole levels are elevated beyond normal. This creates bio-chemical imbalances in the body,  leading to various aggravating symptoms.

Now some of the following information is quite technical but bear with me and you will have a better understanding of what pyrrole is and how it is best treated.

Pyrrole often goes by other names including pyrrole disorder, pyroluria, mauve disorder and kryptopyrrole (although pyrrole and kryptopyrrole are two different substances as seen in the figure above).

Then we have the spelling variations such as pyrolle, kryptopyrrole, kryptopyroluria and yes, even payroll. Some pronounce it ‘pie-roll’ others as ‘peeroll’ – both are ok

The most commonly accepted name is pyrrole, while the true name is hydroxyhemopyrroline-2-one, abbreviated to HPL.

What is pyrrole or HPL?

It’s a substance. Technically a heterocyclic aromatic organic compound, a molecular five-membered ring with the formula C4H4NH.

In our bodies, this chemical substance is quite normal and generated during the oxidative breakdown of heme and other substances in our blood such as biliverdin, bilirubin and urobilinogen.

Problems occur when HPL is elevated beyond the normal level.

In ‘normal people’ the amount of pyrrole or HPL is quite low (below 10ug/dl). Typically, those with levels between 10-40ug/dl have higher levels of oxidation in the body. When the score gets above 40ug/dl, there are more serious disturbances in the body.

What is pyrrole disorder?

As mentioned, Pyrrole disorder is a biochemical imbalance involving the abnormality in haemoglobin synthesis but is also the by-product of many other oxidative processes in the body.

Some say it is a purely genetic disorder, but many practitioners feel that although there are genetic influences, it is more accurate to say that it is an acquired condition relative to other things going on in the body. Having said that, there are certain genetic variants common to those who have pyrrole disorder.

Conditions such as ‘leaky gut syndrome’, heavy metal toxicity, mould illness, viral toxicity (e.g. EBV, RRV, CMV, herpes), bacterial imbalances in the gut, parasites, high stress levels and the overuse of antibiotics are common triggers for this imbalance.

In other words, there’s a cause for an elevated level of pyrrole in the body, it doesn’t just happen, even if you have inherited some dodgy genes.
Whatever the cause of this elevation, HPL is a biomarker for oxidative stress in the body and this oxidation is toxic to the body on many levels.

The main nutrients that are commonly deficient or poorly utilised by those with pyrrole disorder include zinc, B6, B12, folate (and the other B’s), magnesium, manganese, molybdenum, chromium and selenium as well as essential fatty acids such as EPA, DHA and GLA.

Zinc, one of the most common deficiencies seen in this condition, is essential for hundreds of processes in the body and is particularly important for healing, immune function, digestion, neurotransmitter activation, physical growth, memory, insulin sensitivity, co-factor in the production of melatonin for sleep, essential for all hormones, control of blood sugars, DNA replication and more.

B6 is another key nutrient prescribed with pyrrole disorder and together, Zinc and B6 are essential for production of neurotransmitters such as serotonin (our happy hormone), melatonin (our sleep hormone), GABA (our relaxation hormone), and acetyl choline which is important for memory.

Zinc and B6 are also involved in production of our steroid hormones such as cortisol (our anti-inflammatory, anti-allergy hormone and stress hormone) and the conversion of oils in the body (fat metabolism, liver and gall bladder issues and weight control).

The oils EPA/DHA – but mostly GLA – are found to be low in those with pyrrole disorder and are damaged by oxidative stress/free radicals/toxins created by pyrrole.

Why is pyrrole called a disorder?

The definition of a disorder is a disruption of systematic order. In pyrrole disorder, there’s a disruption of the pathways that normally convert haemoglobin, associated with red cell production and destruction (our red cells have a lifespan of 120 days). Other systems can also be disrupted.

In simple terms, rather than a biochemical description, it means that certain pathways don’t work properly.

The history of pyrrole discovery

Pyroluria, was first noted by Abram Hoffer MD, PhD and Humphrey Osmond, MRCS, DPM in the early 1960’s in their research on metabolic imbalances in people with schizophrenia.

This condition was found to be relatively common in people with schizophrenia and bipolar disorder (manic depressive disease) by orthomolecular psychiatrists i.e. psychiatrists who focus on nutritional therapies. They found approximately 20% of schizophrenics have this condition and tend to respond well to treatment.

But Dr. Klinghardt and others found that not everyone with this condition suffers from such extreme psychiatric problems (though many may have a tendency towards anxiety and/or depression). Indeed, the breakthrough Dr. Klinghardt made is by recognizing how common this condition could be in other people with chronic illness.

In the early 1970’s Carl Pfieffer MD PhD found evidence of pyroluria in 5% of normal people he tested (people without serious psychiatric illness). This may represent the percentage of the population with a strong genetic tendency to pyroluria.

But it is quite possible the number of people with this problem has increased due to our increased exposure to environmental stressors (microbes and toxins) as well as increased emotional unrest (stress increases pyrroles) and more use of electronic devices.

Signs and symptoms

All my new clients, whether in-clinic or via skype or phone sessions, complete a client health history questionnaire prior to their consultation. This fact finder helps guide me towards extra questions that I may ask during the consult.

The following points are questions from my questionnaire where I screen for potential pyrrole disorder symptoms. Run through them and see how many you can relate to:

  • Moodiness/mood swings
  • Depression
  • Anxiety
  • Racing mind
  • Poor dream recall, or recall of vivid bizarre dreams only
  • Poor morning appetite, tendency to skip breakfast
  • Poor ability to tolerate stress
  • Night person
  • Insomnia or sleep problems
  • History of aggressive feelings or anger outbursts
  • Morning nausea (not pregnant)
  • Morning sickness during pregnancy
  • React unfavourably to the ‘pill’ or other HRT
  • React to any medications
  • Poor or deteriorating short term memory
  • Difficulty with concentration
  • Sensitive to bright lights, or loud noises, startle easily
  • Sensitive to tags on clothing &/or textures of clothing such as wool
  • Unstable blood sugars/carbohydrate craving/hypoglycaemia
  • White spots on fingernails (zinc deficiency sign)
  • Brittle or weak nails
  • Hypoglycaemia/sugar intolerance
  • Food allergies
  • Environmental allergies or chemical sensitivities
  • Joint pains, especially knee pain
  • Commonly fatigued
  • Headaches or migraines
  • Bowel dysfunction e.g. irritable bowel, constipation, leaky gut
  • Easily bruised
  • Cold hands/feet
  • Weight issues
  • Sensitive to alcohol
  • Get sick easily, or seem to ‘catch’ everything
  • Often have vitamin deficiencies

Obviously, many of these symptoms are common, and not everyone with them has pyroluria. Also, not everyone with pyrrole disorder has all the symptoms and may have a few but find it difficult to treat these symptoms with the usual methods.

Most who say something like, “I ticked most of the boxes for pyrrole” usually have elevated levels of HPL. Whereas those who only tick one or two boxes  and their symptoms are quite strong (such as anxiety which is a common symptom) may also have pyrrole disorder.

I mentioned the difficulty for some clients to treat their health symptoms with the usual methods. I have found clinically that clients who did not respond well to normal treatment protocols were often those with elevated levels of pyrrole.

This can be a good indicator for pyroluria. For example, a client may say, “I know you say I need B6 but whenever I take any B vitamins, especially B6 I feel worse”.

This may seem like a conundrum, but from the experience of treating clients with pyrrole disorder for the past 10 years I discovered that you usually have to treat the underlying condition first, such as leaky gut, infection, inflammation or toxicity, before using therapeutic levels of nutrients such as B6 and zinc.

Diagnosis and Testing

Pyroluria is diagnosed by a simple urine test which detects levels of pyrrole (HPL) in the urine. Most people have less than 10mcg/dL of HPL. Those with 10-20 mcg/dl were considered to have ‘borderline’ pyroluria but the reference range has changed over the years suggesting that a level above 40mcg/dl for an adult is more relevant (above 20 for a child under 14 is relevant). Some people have levels in the hundreds.

There are some with levels between 20 and 40 mcg/dl who still feel they have pyrrole disorder even though the reference leaves them outside of the range. To me, this indicates there is certainly something going on that needs balancing but pyrrole itself isn’t the focus and there is much that can be done to support them.

Pyrrole (HPL) is extremely sensitive to light and heat (especially heat) which means a urine sample must be collected in an environment with the least exposure to natural light as possible, in a container with a preserving agent such as vitamin C, wrapped in alfoil upon sample collection, snap frozen and then sent to the testing laboratory on dry ice.

For this reason, samples need to be delivered as fast as possible and it is not advisable to send your urine sample in the post even if frozen (because it won’t stay frozen). Many a person has been misdiagnosed this way and then missed out on appropriate treatment, not to mention the cost of the test.

Testing laboratory: Applied Analytical Laboratories

There are a few testing laboratories in Australia, but the most accurate and reliable one I have used is AAL, a lab that is dedicated solely to pyrrole testing. They are specialists in this field and dedicate all their time and resources to testing, pyroluria research, and the development of better collection systems. AAL is so far (as of March 2020) the only accredited testing laboratory for pyrrole (HPL).

For a list of places around Australia where a collection can be arranged and also for a practitioner request form, please email me and advise your location so I can respond with the correct information.

Brett from AAL has written a post about correct collection procedures and the science behind it. Well worth a read which you can find by clicking here.

The best time to do the test is the second morning urine sample of the day, so when booking with the collection centre please take this into account when choosing your time.

You do not have to be fasting, only off zinc, unless retesting to check if your dose is working. Previously it was considered advisable to be off B6, however that is now not necessary since AA labs discovered that B6 does not bind to pyrrole (which was quite a revolutionary turning point).

Please note that pyrrole screening is not covered by Medicare even if requested by a GP. I’m not aware of what happens in other countries, but I have not heard of any rebates available elsewhere.

What if you live in a remote area or overseas?

You may live overseas, in a remote area or simply cannot get to a suitable collection facility (or not confident in the lab near you).

It’s not ideal, but if you find you have many of the symptoms listed above, then the chance is high that you have pyrrole disorder. I used to have imaginary bets on myself that in a consultation, whether in-clinic, skype or phone, I could pick clients with pyrrole and I had a 99% success rate. But even if you work this out, please don’t self-medicate, it’s just too complex and you could harm yourself.

Incidentally, for other pathology tests, I can provide a pathology request form, but there is no current Medicare rebate from naturopath’s requests, however they are not very expensive. Generally, Medicare does not cover many nutrient tests (except iron which you can arrange with your doctor).  

Additional testing for pyrrole

Your health care provider may request other tests when pyrrole disorder has been picked up. These may include some of the following:

  1. Caeruloplasmin – copper binding capacity (blood)
  2. Copper (via serum, plasma, red cell or hair analysis)
  3. Zinc (via serum, plasma, red cell or hair analysis)
  4. Zinc to Copper ratio -ideal is 10:1 – (blood or hair)
  5. Vit D (blood)
  6. Histamine levels (blood)
  7. Homocysteine (blood)
  8. B12 and folate levels  (blood)
  9. MMA (Methyl Malonic acid – more accurate indication of B12 – blood)
  10. MTHFR gene SNP defects (blood or oral swab)
  11. Other genetic testing (oral swab)
  12. Neurotransmitter testing (urine)
  13. Amino Acid testing (urine or blood)
  14. Thyroid and other hormone testing such as adrenal

For more information go to, Tests relevant to Pyrrole

Treatment for pyrrole

Many practitioners treat pyrrole disorder by simply administering relatively high doses of various nutrients including: zinc; vitamin B6 and/or pyridoxal 5-phosphate (activated B6); GLA, an essential omega 6 fatty acid found in evening primrose, borage and black currant oil; Vitamin E; manganese, molybdenum and magnesium. But there is definitely more to it than using a few simple nutrients.

Certainly, these deficiencies are common in those with elevated pyrroles. But there is more going on in the body than just the elevated levels of HPL.

Elevation of HPL is a sign that there is an oxidative process going on in the body which needs investigation.

Some respond well to only taking nutrients because the cause of their HPL elevation has potentially healed, but they still remain deficient in these nutrients. For these people, rebalancing nutrients combined with a healthy diet and lifestyle keeps them on track.

However, most people find that taking these supplements seems to flare up their symptoms and they feel worse than before they started taking them. Sometimes they may feel better for a few days or even a few weeks before they crash.

This is partly because substances such as heavy metals and minerals like copper are released into the circulation, often called ‘copper dumping’. This can be addressed by reducing the dosage of zinc and progressing more slowly with treatment. Toxicity from heavy metals and general mineral imbalances can also play a role here.

For others who take nutrients prematurely, their immune system may be activated, causing microbial toxins to be released. This happens particularly for those who have a microbial imbalance or dysbiosis.

Dysbiosis is a blanket term that includes conditions such as bacterial overgrowth in the intestines such as SIBO (small intestine bacterial overgrowth), LIBO (large intestine bacterial overgrowth), parasites, fungal species such as candida or other mould types, viral infections, especially the remnants of old viruses such as glandular fever, herpes virus, Ross River virus or any other types or microbial imbalances.

Not having enough good bacteria or good microbial biodiversity can also have an impact, as can conditions like ‘leaky gut syndrome’.

So you can see from the above why it is important to address these imbalances, prior to some of the vitamin and mineral treatments, so you don’t have a toxic time bomb going off in your system.

When working systematically with a qualified and experienced practitioner it’s important to do things in the correct order. For this reason it is not advisable for people to self-medicate. So much can go wrong if not treated properly.

Who do I go to for treatment?

I am often asked if I know of a practitioner or integrative doctor I could recommend for treatment. I do not keep a list of practitioners. Pyrrole is a relatively ‘new’ condition and the levels of experience and expertise with pyrrole vary considerably amongst practitioners, particularly as treatment protocols can be quite complex.

Some year ago I set up the Pyrrole Australia Face Book page which has more than 7,500 followers (as of March 2020) where you can communicate with others. On this page there is also a link to join a closed pyrrole group which is more private.

However, I am available to provide consultations in-clinic or externally via skype or phone.

Blocks to healing/clearing pyrrole disorder

If someone has a poor response to treatment, then this is usually due to either not finding or treating the underlying causes, not having the right dosages of nutrients to suit the individual, or they have methylation issues.

Methylation is the combining of a methyl donor (a carbon with three hydrogen atoms) that joins to other compounds to make something else, such as hormones, neurotransmitters and enzymes.

Every process in the body requires methylation in order to work properly, including switching on and off certain genes. The process of methylation requires certain nutrients to work in concert with specific genes to perform properly.

The topic of methylation is quite complex, so here’s an article about methylation if you would like to read more.

There are several nutrients that help to support the process of methylation including vitamin B12, folate, SAMe, methionine, choline, B1, B2, B3, B5, B6, magnesium, betaine (TMG/DMG), vitamin D and even the spice turmeric. There are others, but these are the main ones.

It’s interesting to note that many people have intolerance or reactions to the very things that they need, such as these vitamins, and that’s because there is a ‘block’ in the methylation pathway.

The ‘blocks’ are those I referred to earlier in this article such as gut imbalances, be it viral, bacterial, fungal/mould or parasitic, heavy metal toxicity, mineral imbalances, chemical toxicity and inflammation.

Without clearing and healing these first, other treatments will invariably make things worse.

In summary, if you feel that you or a loved one has pyrrole, get tested for it, but more importantly – get tested for the potential causes of this imbalance and work with a practitioner who know and understands the imbalance and associated causes.

Resources:

http://www.walshinstitute.org/

http://www.biobalance.org.au/

http://mindd.org/

Click to see Case Studies

For any queries, please contact Sue

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