Pyroluria, drugs, and psychoneuroimmunology

Pyroluria is a genetic condition seen in roughly 11% of the population where the blood contains an excess of compounds called pyrroles. These bind with vit B6 and zinc which are expressed in urine, depleting the brain of these essentials, which results in many symptoms that are easily misdiagnosed as depressive or psychiatric illness. Other symptoms may include mood swings, sensitivity to light, flashes of extreme and inappropriate anger, anaemia, fatigue, general malaise, stiches in the side after moderate exertion, pain in the chest under stress, and the inability to remember dreams. It is not uncommon for people to be inappropriately administered anti-depressive medication when in fact they have pyroluria. Even short term use of anti-depressant medications alters brain chemistry to such an extent that withdrawal is dangerous. For these people, supervised withdrawal from medication should be undertaken at the same time as remedial measures for pyroluria, and this must be done in consultation with a doctor or naturopath who has experience and competency in this area.

An easy diagnostic for pyroluria is thin, pale nails, with or without white spots or half moons due to an overall zinc deficiency (though white spots may also be due to damage to the nail bed, or general systemic shock especially when accompanied by ridges from bed to tip). Where this occurs with symptoms of depression or other similar conditions, or any of the symptoms listed above, a urine test should be given to rule out pyroluria first. Treatment can be as simple as supplements of B6, zinc, and manganese. The methylated form of B vitamins should only ever be taken (otherwise you are wasting your money, the methylated form of B6 is pyridoxal-5-phosphate), and consideration to a methyl donor (trimethylglycine) and RDA supplementation of magnesium may be wise because methylation issues often occur side by side with pyroluria. Restoration of GABA (a neuro-relaxant) levels is also good either by supplementing GABA, or its precursor. GABA production in the body can be enhanced by drinking green tea, especially fermented green tea in the form either of puh erh, or kombucha or jun made with green tea. The other GABA enhancers are oats, particularly if you ferment them for 24 hours before use, traditional kimchi with fish sauce, and Japanese or Korean style fermented fish or fish gut.

Many strains of probiotic bacteria have been found to produce the same compounds we use in the body to regulate neural function and mood – things like serotonin, dopamine, and gamma-aminobutyric acid (GABA) – and this production works to not only maintain normal gut function, but to regulate mood as well, postulating a gut/brain axis. Serotonin is important in the regulation of many bodily functions, including mood, though this action is poorly understood, and data indicates that serotonin must work in concert with other neurotransmitters and compounds within the brain. Strains of Bifidobacterium, Streptococcus, Enterococcus, and Escherichia have been found to produce serotonin, with Bifidobacterium infantis also producing tryptophan, the amino acid precursor to serotonin. Bifidobacterium and Lactobacillus produce GABA (the body’s main neural relaxant) from glutamate, one Lactobacillus strain has been identified as a producer of the neurotransmitter acetylcholine, Bacillus, Esherichia and Saccharomyces produce norepinephrine, while Bacillus and Serratia produce dopamine.

The most likely route for communication between the brain and substances consumed or produced in the gut (as indicated in the literature) is the vagus nerve, which directly connects the two. Some mechanisms proposed for this (dietary sources of substances such as GABA cannot cross the blood brain barrier) are translocation along the vagus nerve; that the nerve signals to the brain that these neurotransmitters are in the body, and the brain either acts as if they were within it (rather than in the gut); or the brain is prompted to produce the substance itself. Other proposed communication/translocation routes of the gut/brain axis are the spinal cord, and the neuroendocrine system. One further suggested mechanism for the relaxing effect of dietary GABA may be that when ingested, GABA acts not on the central nervous system, but on the peripheral nervous system, where it appears to inhibit perivascular nerve stimulation and noradrenaline release. Therefore, neuroexitotoxicity is assisted not directly, but indirectly through the action of overall bodily relaxation and reduction in hypertension. The positive results of probiotic therapy and restoration of gut health in areas of mental health as diverse as interferon-induced depression, obsessive-compulsive disorder, and post-traumatic stress disorder are being reported not only in scientific literature, but anecdotally from doctors and their patients. So much so that terms like 'psychobiotics' and 'psychoneuroimmunology' are frequently encountered in journal articles, and even in the mainstream press.

How does this work? Well, it's early days, but as with most human dysfunction, it appears to come down to our old friends gut dysbiosis and inappropriate bodily inflammation (dysbiosis is defined as a microbial imbalance that detrimentally impacts on normal function). Lipopolysaccharides (LPS) function in the body as endotoxins, and are produced by many gram-negative bacterial pathogens. LPS are used to create a depressive state model in rodents for clinical studies. Mice engineered to lack a cytokine responsible for mediating inflammatory response are resistant to the artificial depressed state induced by LPS, which indicates the role of inflammation in the regulation of mood. Western diets tend to promote inflammation and elevated LPS levels, whereas studies on traditional or ancestral diets that utilise fermented foods show elevated antioxidant and anti-inflammatory activity in the body, concomitant with reductions in gut wall permeability and LPS levels. Fermented foods (including the live organisms contained therein) also enable production of essential enzymes, vitamins, neurotransmitters and neuropeptides, modulate function of the adrenal cortex toward a relaxed bodily state, confer improved glycemic control and cholesterol management within the body, produce GABA and other beneficial bioactive compounds directly, and help restore optimal balance within the microbiota, all of which have positive effects on our mental state.

To minimise supplementation, eating plenty of raw, organic, whole foods is best. Conventional argricultural production methods lead to vitamin and mineral depletion within foods, which are also selected (bred) for bulk and appearance over nutrirional content. Chemical residues within conventionally farmed foods work to chelate minerals essential for human enzyme production, interfere with gut-based bacterial neurotransmitter production, and contribute greatly to gut dysbiosis.

Pyroluria is exaccerbated by stress. The condition normally presents during the teenage years, but dormant pyroluria can be awakened at any age if stress levels are high enough. Techniques to deal with stress such as yoga or meditation are important for everyone, but most especially anyone with pyroluria.
These words do not constitute medical advice in any way. Remember that as with any condition, consultation with a qualified professional such as an holistic doctor or naturopath should be undertaken, and seek professional help also if you suffer any of the symptoms of depression or anxiety mentioned here.

“How (these) differences in our microbial world influence the development of brain and behavior will be one of the great frontiers of clinical neuroscience in the next decade.” - Thomas Insel, Director of the (US) National Institute of Mental Health

References

Cakmak I, Yazici A, Tutus Y, Ozturk L (2009) Glyphosate reduced seed and leaf concentrations of calcium, magnesium, manganese, and iron in non-glyphosate resistant soybean. European Journal of Agronomy 31:114-119.

Davis, D. R. (2009) Declining Fruit and Vegetable Nutrient Composition: What is the Evidence? Horticultural Science 44 (1):15-19.

Dheen ST, Kaur C, Ling EA (2007) Microglial activation and its implication in the brain diseases. Current Medical Chemistry 14(11):1189-97.

Dinan TG, Cryan JF (2013) Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterology and Motility 25(9):713-719.

Dinan TG, Stanton C, Cryan JF (2013) Psychobiotics: a novel class of psychotropic. Biological Psychiatry 74(10):720-726.

Eker S, Ozturk L, Yazici A, et al. (2006) Foliar applied glyphosate substantially reduced uptake and transport of iron and manganese in sunflower (Helianthus annuus L.) plants. Journal of Agricultural and Food Chemistry 54:10019-10025.

Grandjean P, Landrigan PJ (2014) Neurobehavioural effects of developmental toxicity. Lancet Neurology 13:330-8.

Hayakawa K, Kimura M, Kamata K (2002) Mechanism underlying gamma-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats. European Journal of Pharmacology 438:107-113.

Hyman SE, Nestler EJ (1996) Initiation and adaptation: a paradigm for understanding psychotropic drug action. American journal of Psychiatry 153(2):151-62.

Inoue K, Shirai T, Ochiai H, et al. (2003) Blood pressure lowering effect of a novel fermented milk containing γ-aminobutyric acid (GABA) in mild hypertensives. European Journal of Clinical Nutrition 57:490-495.

Krüger M, Schledorn P, Schrödl W, et al. (2014) Detection of glyphosate residues in animals and humans. Journal of Analytical Toxicology 4:2.

Kuriyama K, Sze Y (1971) Blood – brain barrier to H3-γ-aminobutyric acid in normal and amino oxyacetic acid-treated animals. Neuropharmacology 10:103 -108.

Mesnage R, Defarge N, de Vendômois JS, Séralini GE (2014) Major pesticides are more toxic to human cells than their declared active principles. BioMed Research International, 2014, Article ID: 179691.

Samsel A, Seneff S (2013) Glyphosate’s suppression of cytochrome P450 enzymes and amino acid biosynthesis by the gut microbiome: pathways to modern diseases. Entropy 15:1416-1463.

Santos MS, Ferreira F, Cunha AP, et al. (1994) Synaptosomal GABA release as influenced by valerian root extract – involvement of the GABA carrier. Archives of International Pharmacodynamic Therapy 327(2):220-31.

Seneff S, Swanson N, Li C (2015) Aluminum and glyphosate can synergistically induce pineal gland pathology: connection to gut dysbiosis and neurological disease. Agricultural Sciences 6:42-70.

Sohler A, Holsztyimska E, Pfeiffer CC (1974) A rapid screening test for pyroluria; useful in distinguishing a schizophrenic sub-population. Orthomolecular Psychiatry 3(4):273-279.

Susilowati A, Aspiyanto, Melanie H, Maryati Y (2010) Green tea (Camellia assamica) concentrate as a source of L-theanine used in kombucha fermentation for relaxation drink. Menara Perkebunan 78(2):75-83.

Tolonen M, Tiapale M, Viander B, Pihlava J-M, Korhonen H, Ryhänen E-L (2002) Plant-derived biomolecules in fermented cabbage. Journal of Agricultural and Food Chemistry 50(23):6798-6803.
van Donkelaar EL et al. (2011) Mechanism of acute tryptophan depletion: is it only serotonin? Molecular Psychiatry 16(7):695-713.

Bio

Tom Rothsey is an ecologist, environmental scientist, reflexologist, energy worker, health and lifestyle coach, writer, researcher, and teacher of the fermented arts in all their forms. He lives with his wife Christy Lavers, and their son Jasper Blue in a pole house, in a rainforest in North Eastern New South Wales, Australia.

Links

www.facebook.com/celestialroots



tom@celestialroots.com http://www.celestialroots.com/ http://celestialroots.tumblr.com/ https://twitter.com/celestialroots1