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It’s often said that there’s no biomarker for ME/CFS, Long Covid, Post Vaccine Syndrome, PSSD, Lyme Disease, etc. I strongly disagree. However, it helps to have the right data and tools to visualise it. To help people explore the Born Free disease model and better understand the connections between the minerals deficiencies, metal toxicities and disease model processes, I've added 10 random example pairs of Oligoscan (corrected, skin minerals + toxic metals) + Theriome Aristotle Plus data (296 metabolites) to the Metabolic Pathway Overlay tool. bornfree.life/learn/metaboli… Some common patterns to observe across these patient profiles: 1) Elevated toxic metals, with mineral and electrolyte deficiencies, relating to pathway alterations. 2) A reduced total NADP/NADPH pool size and impaired conversion of NADP to NADPH (low NADPH), with broad effects. The reported exception (#4) is where aluminium is not elevated. 3) Constraints on glycolysis and glycogen synthesis, gluconeogenesis. 4) Altered pyruvate and/or lactate levels, ratio. 5) Constraints on the pentose phosphate pathway and downstream PRPP synthesis. 6) Impairments in purine and pyrimidine metabolism, Cell Danger Response. 7) Oxidative stress. 8) TCA cycle alterations and constraints. 9) Issues with NAD+ synthesis and redox. 10) Reduced carnitine synthesis and associated carnitine-shuttle constraints. 11) Elevated glutamate relative to low GABA, except where severe induced malnutrition constrains glutamate synthesis. 12) Issues with glutathione metabolism. 13) Issues involving magnesium and Mg-ATP. 14) Urea-cycle and nitric oxide synthase impairments, with potential effects on vascular tone. 15) Dysregulated neurotransmitter synthesis and degradation. 16) Impaired conversion of choline to betaine. 17) Impaired methylation and associated SAMe, glycine, and cysteine metabolism. 18) Impaired creatine synthesis. Importantly, you can see coherence between the tests and inferred causality for pathway alterations. When you consider these metabolic alterations in specific cells / tissues - brain, liver, kidneys, thyroid, immune, etc., it becomes much easier to understand how mitochondrial dysfunction creates systemic impacts and a progressive cascade.

Hi Jack, I can describe this one in quite some detail and the data is highly repeatable: The “missing piece of the puzzle” is the ionome -> metalloproteome in the context of mitochondrial and related metabolism.. and this is anecdotally now much easier to restore, with recent improvements in intervention, especially with regards to the accumulated toxic metals. Glutathione metabolism includes synthesis, peroxidase activity and (NAPD) redox. The synthesis side takes outputs of the methylation and transsulfuration pathways - glycine and cysteine. Zinc, folate, choline and thiamine have important roles here. NADPH:NADP also regulates folate -> THF (and BH4). Glutathione peroxidase requires selenium, which is antagonised by silver and mercury accumulation. If glutathione metabolism is inhibited, mitochondrial ROS is not regulated and Complex I inhibition follows, impairing NAD+:NADH. Glutathione reductase activity requires sufficient oxidised glutathione and NADPH, making NADP. It requires FAD (riboflavin, zinc and magnesium, ATP sensitive) and is inhibited by cadmium and lead. It also needs a NADP:NADPH redox partner - G6PD is the main one. G6PD is inhibited by aluminium and poor glycolysis -> glucose-6-phosphate. Aluminium also inhibits glucokinase, affecting this. Low magnesium, chromium, phosphate, gluconeogenesis (for non-hepatic tissues) are also relevant. In this way, impaired NADP redox leads to a spiral of oxidative stress, impaired NAD redox, impaired mitochondrial metabolism, pathological glutamate metabolism, impaired glycogen synthesis and glycolysis, low lactate threshold, cell danger response dysregulation, impaired methylation, low BH4, impaired histamine degradation with dysregulated mast cell degranulation and an array of other measurable problems. This also creates a dysregulated stress response. TCA cycle flux -> oxidative stress -> Complex I inhibition -> NAD+ redox inhibition promotes intracellular glutamate, normally used to promote glutathione. When this fails, glutamate becomes elevated inside the cells. (see figure 14) Sympathetic signalling (adrenaline -> cAMP-PKA) triggers these cells to export that now elevated glutamate pool, where it now becomes a ligand, signalling for calcium influx -> triggering already overloaded cells to ramp up metabolism, creating excitotoxicity / nerve pain / visual and auditory intolerance, etc. Progressive loss of glycogen stores and parasympathetic balance biases sympathetic metabolism as compensation, compounding this issue. (see figure 18) A number of these issue create a loop, under mitochondrial flux - exertion, immune activity. eg. The minerals become depleted and metals accumulate in specific tissues, as part of an inflammatory cascade. PEM, POTS, MCAS, hEDS, immune dysfunction, autonomic dysfunction - sympathetic dominance / loss of parasympathetic tone, brain fog, fatigue, chronic viral reactivation, microbiome dysbiosis (fermentation syndrome, loss of butyrate production), hyperoxaluria and a long list of other issues are created as part of this progressive cascade. Various other issues can appear, relating to the status of different minerals and metals, eg. hypothyroidism, impaired hepatic gluconeogenesis. (see figure 12) More on the cascade, here - bornfree.life/learn/ If you want to “see” all of this using your own data with these and other diagrams, you can now take eg. Theriome Aristotle Plus and Oligoscan data and run it through the Metabolic Pathway Overlay tool - bornfree.life/learn/metaboli…