Mitochondria as the ultimate drivers of health and disease
By Gilian Crowther MA (Oxon) ND/NT
Kryptopyrroluria – KPU – is a metabolic disorder that is still practically unknown in the UK, despite the fact that Dr. Carl C. Pfeiffer identified it back in the 1970s as being prevalent in the west, and an underlying factor in a vast range of conditions, from ME, fibromyalgia and multiple chemical sensitivity to thyroid disorders, ADHD, depression and epilepsy. Dr. Pfeiffer found that around 30% of patients labelled schizophrenic were suffering from KPU, and that targeted support of their broken metabolic pathways could relieve the condition – often very fast.
In KPU, a chemical substance involved in the formation of haem multiplies too rapidly, and binds to zinc and B6 forming a complex that is excreted in the urine. Manganese is also lost via the kidneys as a result – as well as biotin and chromium, according to various sources. This complex that is excreted was identified in 1969 by Dr. D. G. Irvine as 2,4-dimethyl-3-ethylpyrrole. Known initially as the mauve factor (because it stained mauve with Ehrlich's reagent), this can be detected in a urine test, though it needs conducting very carefully as this pyrrole is so extremely sensitive to light, temperature and oxygen. Labs in Germany and Holland have developed special highly sensitive tests, since this condition has been recognised there for so much longer. According to Dr. Dietrich Klinghardt, even if it cannot be picked up in the KPU test (he says the more sensitive test is for HPU – hemopyrrollactamuria – only available in Holland), one should treat for it anyway if a sufficient cluster of symptoms indicates the condition. (See below for symptoms of KPU)
Losing all your B6 in the urine so that it is unavailable to the many pathways where it is required is a metabolic catastrophe. B6 in its active form – pyridoxal-5-phosphate (P5P) – is a coenzyme in over 100 metabolic processes. Without it, you cannot form haem, as the first step in haem synthesis (a-aminolevulinic acid) is B6-dependent. Without haem, your haemoglobin formation will be compromised, so your cells cannot transport oxygen sufficiently (anaemia that does not respond to simply giving iron). All compounds that require haem will become dysfunctional.
The CYP450 enzymes crucial for Phase I detoxification all have haem at their centre, and cannot work without it, so every form of detoxification will be impaired. Likewise cytochrome c – the electron carrier in our mitochondria – meaning our mitochondria are disrupted, and hence our energy levels as well as cellular signalling. That first step in haem synthesis that is broken in KPU is also the first step in forming tetrapyrroles, of which B12 is one: B12 synthesis will also be impeded as a result. This in turn affects the methylation cycle, with multiple knock-on effects, such as hyperhomocsyteinemia.
Myoglobin also contains a haem group, so this protein in heart and skeletal muscles will be weakened. And haem is a cofactor in the urea cycle, so you cannot process and eliminate ammonia, instead creating peroxynitrite, a very toxic substance. The conversion of protein and carbohydrate stores into glucose (gluconeogenesis) requires B6, as does the synthesis of neurotransmitters (serotonin, dopamine, noradrenaline) and proteins (which even means you cannot form antibodies properly, which are formed from amino acids). Fat metabolism needs P5P, so you will have difficulty synthesizing the myelin sheath around nerves.
Symptoms of KPU
Physical appearance: Pale, sallow skin, pale lips, pruritis either in certain areas or all over (anal pruritis is particularly prevalent in children); light intolerance, rash in sunlight, yellowish-brown pigmentation after being in the sun, slight puffiness of the face, especially around the cheeks and eyes. Dark rings around the eyes, eyes sunk deep into their sockets; soft gums; striae on the skin similar to stretch marks; white spots on the nails (leukodynia), sometimes hair loss, acne, eczema and dandruff; poor tooth enamel
Neurological issues, often labelled psychiatric: Memory and concentration difficulties, problems with short-term memory, "brain fog", poor dream recall, low mood, fear, panic attacks, withdrawal from social activities, hallucinations, apparent schizophrenia/psychosis, ADHD
Impaired energy production: Fatigue, may be severe
Detoxification issues, resulting in intolerance to medications and chemicals (MCS)
Thyroid disorders: Hypothyroidism, Hashimoto's thyroiditis
Immune disorders, particularly bronchial infections, cystitis and urinary infections, sinusitis particularly in children
Musculoskeletal symptoms: Hypermobility, pelvic instability, weak muscles. Often muscle and joint pain (due to myoglobin being affected, because it has a haem group)
Allergies, food intolerances, lactose intolerance (lactoperoxidase contains haem)
Gynaecological issues: Menstrual disorders, fertility issues, complications in pregnancy
Gastrointestinal disorders: Bloating, pain, nausea, especially in the morning. Alternating diahorrea and constipation, halitosis, aversion to meat (because the conversion of muscle protein to our own protein is B6-dependent)
Blood sugar disorders: Hypoglycaemia (because gluconeogenesis is B6-dependent); diabetes type II
Methylation issues, hyperhomocysteinaemia
Source: Joachim Strienz, Leben mit KPU Kryptopyrrolurie (Living with KPU – Kryptopyrroluria, only available in German)
Blocking uptake of zinc is equally dramatic. Zinc is a coenzyme in over 300 enzymatic reactions, especially in the immune system, and in cell division, growth and differentiation. Without it, our cells will insert whatever heavy metals they find – cadmium, lead, mercury, or nickel – into the bonds where zinc would normally be needed. This is a toxic load that is rarely evidenced in heavy metals tests, but these metals start being excreted when you correct KPU.
Manganese, which also seeps out of the system without being able to be utilised, is a trace element required in more than 100 enzymatic processes. It is involved in coagulation, gluconeogenesis, the urea cycle, the synthesis and regulation of insulin production in the pancreas, the development of cartilage and bones, and much more. It is also an essential cofactor for superoxide dismutase, our key antioxidant within the mitochondria.
It was previously thought that KPU was a genetic disease only, but it is now known that it can also be acquired. One of the factors that can trigger it is excess nitric oxide, upregulated in the NO/ONOO– (nitric oxide/peroxynitrite) cycle on which Professor Martin Pall has done so much research. Dr. Dietrich Klinghardt also argues convincingly that spirochetes have found that the ideal method to generate a comfortable existence for themselves in the human body is to cut off our supply of zinc, disarming our immune system. His first-line therapy is to treat KPU, with an awareness that Lyme Disease is often an underlying factor. And then of course in many cases the condition is genetic, maternally inherited (since our mitochondria are all inherited from our mothers, and the inherited form is most likely due to that broken first step in haem synthesis, a-aminolevulinic acid, which is located in the mitochondria).
Ultimately, whatever the cause of KPU, the first stage of therapy is to provide P5P, zinc and manganese in physiologically effective quantities. Lab tests will help to establish the doses required, and remedies exist that contain synergistic combinations of the deficient nutrients for both intravenous and oral use. Good food sources of B6, zinc and manganese are also important (though they will rarely be enough to make up for such a metabolic deficit, unless it is very mild). (See below for food sources of these nutrients)
A great deal more fine-tuning is required, especially later down the line when the heavy metals sequestered in the tissues start being excreted as the detoxification pathways begin to open up: more of that in a later AONM Spotlight Topic.
Pfeiffer, C.C., et al. (1975). Mental and Elemental Nutrients, A Physician's Guide to Nutrition and Health Care. Keats Publishing, Inc, New Haven, Connecticut.
Irvine, D.G. et al (1969). Identification of Kryptopyrrole in Human Urine and its Relation to Psychosis. Nature 224, 811-813
Kuklinski, Bodo: Cryptopyrroluria, nitrosative stress and mitochondrial disease:
http://www.kpu-berlin.de/en/Cryptopyrroluria-nitrosative_stress_and_mitochondrial_disease.htm
Hoffmann, Kyra:Â Die Kryptopyrrolurie "Ein typisches Beispiel einer mitochondrialen Funktionsstrung (Kryptopyrroluria" A typical example of a mitochondrial dysfunction), CST Newsletter 2014-02: www.akademie-cst.de
Hoffmann, Kyra und Kauffmann, Sascha: Kryptopyrrolurie – ein bewahrtes Therapiekonzept für die haufigste Form der Porphyrie (Kryptopyrroluria A tried-and-test therapeutic concept for the most frequent form of porphyria), Comed 12/2013
What is KPU? And HPU?, CST Newsletter 2013_01: www.cst-academy.co.uk
Strienz, Joachim: Leben mit KPU Kryptopyrrolurie, Ein Ratgeber für Patienten, Germe-ring/München 2011 (Living with KPU Kryptopyrroluria, only available in German)
O'Reilly, P., et al. (1965). The Incidence of Malvaria. British Journal of Psychiatry. August; 111:741-4
Irvine, D.G. (1974). Kryptopyrrole and other monopyrroles in molecular neurobiology International Review of Neurobiology. 16:145-82
Dr. Dietrich Klinghardt discusses Kryptopyrolluria: http://www.youtube.com/watch?v=THZhANfFnyY
Scott Forsgren, Kryptopyrroluria (aka Hemopyrrollactamuria): A Major Piece of the Puzzle in Overcoming Chronic Lyme Disease http://www.betterhealthguy.com/images/stories/PDF/PHA/2010_05.pdf
Food sources of B6, zinc and manganese
Some good sources of B6:
Chicken, Hazelnuts, Potatoes
Tuna, Pinto beans, Sardines
Walnuts, Halibut, Brussel sprouts
Salmon, Avocados, Cod
Lentils, Chestnuts, Sweet potatoes
Lima beans, Kale, Cauliflower
Blackeyed peas, Whole grain rye, Red cabbage
Brown rice, Spinach, Leeks
Some rich food sources of zinc:
Oysters, Lima beans, Shrimp
Ginger roots, Almonds, Turnips
Pecans, Walnuts, Black pepper
Split peas, Clams, Paprika
Whole grain wheat, Tuna, Chili powder
Whole grain rye, Haddock, Thyme
Whole grain oats,Green peas, Cinnamon
Some food sources of manganese:
Wheat germ, Brussel sprouts, Grapefruit
Green leafy vegetables, Blueberries, Apricots
Spinach, Oranges, Kelp