Nutrigenomics and pyrroluria: a pathway to the lost diagnosis

Our resident nutrigenomics expert Anne Pemberton shares a case history in which a 23andme test finally unlocked a very difficult case being tackled by a multi-disciplinary team. The test results also stimulated an amazing response from a clients who had been withholding her background of severe stress from long-term abuse.

Linda is 32 years old, an actress who is too ill to work. She is desperate to get back to her acting career and motivated to do anything she can to get there. Sadly, when I meet her, she had been bed-bound for three years. She can’t have a bowel movement without enemas. She is receiving chiropractic care for severe TMJ. She can’t hold up her own head without a neck support.

She has been assessed by Dr Damien Downing and passed on to me for nutritional support. At this stage, my task is to introduce her to the PK protocol, assess her supplement intake and “hand hold” her and her partner. (The PK protocol is an extension of the ketogenic diet designed by Dr Patrica Kane of The Neurolipid Research Foundation.)
Linda had seen a number of practitioners, who all seemed to be apportioned a significant amount of blame for her demise. She was a carbohydrate junkie who had pushed her own adrenaline buttons in terms of her lifestyle and eating habits, such as getting too much sugar and eating on the hoof or skipping many meals. Working strange hours and eating after evening performances was also a key trigger. She didn’t give me much of a family history, other than she had a brother with Asperger’s syndrome who apparently “controlled” the family. As a result she was estranged from them.

Her overall aim was to get back on stage, but her main aim for our first session was to get some restful sleep. Despite trying 10mg amitryptiline, 5mg melatonin, 1mg diazepam, 5mg Valium and 4 x Zen capsules, her sleep pattern was a mess.


Running into trouble

We commenced the PK protocol and settled on weekly Skype calls, and face-to-face time with me every two-three months on my trips to London. We started slowly but very soon got into trouble, as she developed reflux and panic attacks once she reached a total of 100ml daily of the PK “power drink”. In Patricia Kane’s protocol, the fats and oils are delivered as a drink and are in ratios specific to the individual, based on their fatty acid analysis. (5). Clients also take a digestive supplement with food to support their production of digestive juices.

We know from previous experience that these responses can be the result of the gallbladder, in response to fats, swelling if it is unable to eject bile th

at is too thick (PK, personal communication, 2015). When the gallbladder swells, it puts pressure on the stomach, which in turn displaces upwards towards the lower oesophageal sphincter, giving rise to reflux, but also to possible hiatal hernia syndrome/vagus nerve imbalance.(3) As the vagus nerve is the key nerve associated with fight or flight and part of its role is to bring us back to parasympathetic dominance, it was imperative that we preserved its function. This was all being further exacerbated by her constipation – that failed to respond to the usual NT approaches such as linseed, magnesium and vitamin C. We did have some response to the colon-cleansing product Oxy-Powder®.

I added in my usual gallbladder support nutrients of beetroot complex, taurine, low-dose iodine, magnesium and B vitamins. After two months we did get natural bowel movements, but they were by no means normal and she still required occasional enemas. Linda piled on two stones in weight in ten weeks, which totally freaked her – and the fats came out of her diet. Six weeks later Linda had lost three stone and was now well below normal for her height and frame size. She had amenorrhoea, her blood glucose control was worse than ever, and she was more dependent on the benzodiazepines for sleep. Our major concern was that long-term use of benzodiazepines canlead to destruction of cell membranes, yet Linda was using these more and more to gain some small amount of sleep. Her melatonin levels were sky high at this point due to over-supplementation; this at least demonstrated that it needed to be discontinued. An MDT (multi-disciplinary team) meeting was scheduled to discuss Linda’s case.
It was very clear by this stage that Linda had a non-functioning gallbladder and that surgery was possibly her only option. There was no way she was going to subscribe to this, so we decided to encourage Linda’s partner to ferment vegetables with VSL#3 probiotics according to the later PK protocol. The rationale for the ferments was that these would encourage colon cleansing and a return of bowel movements. Usually patients respond within one to two weeks, so Linda was keen to try it. She reacted badly, and with no appreciable bowel improvement and now pain over the gallbladder, we stopped the ferments.


Screenshot 2015-12-24 13.48.57


In an effort to regain control, we started her on BodyBio Balance Oil and this was a savior; 20ml per day re-established blood glucose control and a little energy. She could walk to the bathroom instead of using a commode, but that was the limit of her exercise. But she also now craved the fats her body required; her fatty acid analysis had shown she was 49% deficient in arachidonic acid.(1) BodyBio Balance Oil, another Patricia Kane “invention”, contains cold-pressed organic safflower and flax seed oils, blended to provide a 4:1 ratio of omega-6 linoleic to omega-3 linolenic fatty acids.

Having established that she could now tolerate the fats, we started to slowly put them back in her diet. She particularly wanted to try Coyo coconut yoghurt, and given the potential benefits of yoghurt for her gut health, we agreed. In less than a week, Linda started to get the old HHS/VNI symptoms again and I still suspected the ferments.

This changes everything…

Linda had been waiting for her 23andme results and luckily these arrived right at that moment. We had also run an organic acid test to check expression of her polymorphisms, and decided to marry up the two with her history in the hope of getting some answers.
What happened next changed my whole perspective on her case.
As I plotted her polymorphisms onto my pathway planner, I noticed that her key polymorphisms with expression were almost all affecting enzymes dependent on haem, vitamin B6, magnesium or zinc. (Haem, of course, is the iron compound responsible for transporting oxygen.) This led me to immediately suspect that her underlying problem was pyrroluria, aka kryptopyrroluria (KPU), as Mikirova notes many digestive symptoms as a result of pyrroluria.

Pyrroluria is a condition that affects haemoglobin synthesis. People with pyrroluria produce too much kryptopyrrole, a by-product of haemoglobin synthesis. 
It is thought to be “genetic”, but it seems clear that it can also be “acquired”. In natural medicine circles it is also often labelled as a stress-induced disorder – the stress causing depletion of key nutrients such as B6, magnesium and zinc. However, that is also just what kryptopyrroles do. So what comes first – a built-in genetic disorder/polymorphism that causes a build-up of kryptopyrrole(s) that depletes body and brain of vital nutrients; or a stress- or environmentally-induced depletion of nutrients such as B6, zinc and magnesium that triggers epigenetic changes that express as a haem disorder? Remember that zinc and copper are antagonists and that people with pyrroluria typically have high copper levels – unsurprisingly, since the pyrolles bind zinc.

Interestingly, Dr Dietrich Klinghardt says this is more important than other genes to support, but also I may not have thought of pyrroluria had I not seen the presentation of her polymorphisms plotted this way.


Screenshot 2015-09-01 22.44.19


My next task, after sharing my suspicions, was to send Linda some literature on pyrroluria. Her response was amazing.
A 90-page history of long-term abuse landed in my email box, describing family members just like her in personality. Her suspicious nature had kept all of that hidden until I was able to present her with something concrete that resonated with her.
At this point we commenced pyrroluria support with P-5-P, zinc, manganese, biotin, evening primrose oil, magnesium and a mineral base to buffer copper mobilisation. With specific instructions of signs and symptoms to look out for and a weekly Skype, Linda is coming through the worst of this. Her weight is now beginning to stabilise and blood glucose/energy are improving. Linda can now sit out for meals for about 20 minutes at a time. We have initiated chiropractic Network Spinal Analysis to help stabilise her nervous system, and the combined approach is proving invaluable. As part of my basic lifestyle advice, I now recommend all my highly-stressed females undertake NSA.

Key points

Many researchers talk about the Crystathione beta synthase enzyme (CBS), being an open gate leading to possible high ammonia and taurine. I am not seeing this in clinical practice and neither are my colleagues. I wonder if this is a reflection of the types of client we attract, or whether the big names are missing something crucial.
My second key point is that I now have other clients with similar genetic profiles. All have tested positive for pyrroluria, and none of them are the personality types we generally associate with pyrroluria. It has even made me reflect on previous cases that remain unresolved. I plan to run a clinical trial to see if I can identify key polymorphism patterns in patients with pyrroluria.

Getting the lipids right

The PK protocol is an extension of the ketogenic diet designed by Dr Patrica Kane of The Neurolipid Research Foundation ( The fats and oils in the protocol are delivered as a power drink in ratios specific to the individual, based on their fatty acid analysis.

The Power Drink can be flavoured, but the key to making it palatable is several minutes in a blender, which makes it a smoothie. The main ingredients are;

nut and seed cream
BodyBio Balance Oil or hemp seed oil

optional flavouring.

The drink provides saturated fats and omega-3, -6 and -9 fatty acids. Many people have intolerances or other digestive problems which make it difficult or impossible to deal with some of these ingredients, but there is reasonable adaptability in this system. Any one of several forms of milk is acceptable, for example organic whole milk or yoghurt – cow’s, sheep’s or goat’s, unsweetened coconut milk, seed or nut milk (almond, hazelnut, hemp), or unsweetened soya milk.

The stress and detox connection

Stress is a strong contributor for increased urinary levels of HPL, the “mauve factor” that causes strangely-coloured urine in patients with pyrroluria, says Dr William Walsh, PhD, author of The Nutrient Factor and recent CAM Conference speaker.
As a result, he says, pyrroluria can be induced early in life by childhood trauma or chronic infection.“Stress will not only worsen symptoms, but may also make it a chronic condition when the digestive system gets compromised, especially the intestines”, he says. “Then it tends to persist throughout a person’s life, or until your digestive system is healed. That´s why for most people the onset of pyrroluria symptoms only occurs after late teens, triggered by a traumatic event such as the death of a loved one, parental divorce or moving away to college.
“Other external factors that contribute for pyrroluria are poor diet, environmental toxicity (heavy metals) and drug abuse (alcohol, marihuana etc), as [they]put your body under stress and remove its ability to recover.”
In a 2008 review article (Altern Ther 2008, 14: 3) authors including Dr Walsh, Dr Abram Hoffer, MD, PhD, and Dr John McLaren-Howard, DSc, state: “Treatment with nutrients, particularly vitamin B6 and zinc, reduces urinary excretion of HPL and improves diverse neurobehavioral symptoms in subjects with elevated urinary HPL. Heightened HPL excretion classically associates with emotional stress, which in turn is known to associate with oxidative stress.”
As Anne’s polymorphism plot highlighted, the cytochrome P450 enzymes are haem proteins, which means that they contain iron surrounded by porphyrin compounds. According to Dr Stephen Rochlitz, PhD, writing in CAM in October 2013, “Some 40% of the body’s manufactured haem goes into creating the cytochrome P450 enzymes. These crucial enzymes metabolise cholesterol and some hormones, detoxify external chemicals, and process or create some vitamins. By ‘external chemicals’ I mean naturally-occurring toxins, drugs, man-made toxins and compounds in foods.”}     Simon Martin


Alijamali NM and Jwad, SM, Survey in pyrrole compounds and biological activity. International Technology and Innovation Research J 2015, 1:1.

Mirikova N. Clinical test of pyrroles: usefulness and association with other biochemical markers. Clin Med Rev Case Rep 2015, 2:2

Rochlitz S (2012). Hiatus Hernia syndrome, Vagus nerve imbalance; a missing link to chronic illness, allergies and other problems:

Rochlitz S (2011). Porphyria: the ultimate case of common, chronic and environmental illnesses:

 About the author

Anne Pemberton, BSc (Hons), PGCE (Autism), RGN, DipION, mBANT, CNHC, NMC, RCN, RSM, was an Intensive Therapy Unit nurse trainer until 2003, then retrained as a nutritional therapist.
She is course director on the MSc/PGDip Nutritional Therapy course at the Northern College of Acupuncture in York. She works as a nurse and nutritional therapist with the ecological medicine practice Nutrition Associates, has a special interest in ASDs, CFS and cancer, and has recently co-authored a book with Dr Damien Downing.
* Join Anne at a Genesnippers four-day course on genetic polymorphisms: / December 2015