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I believe in my situation, a vector borne disease caused an increase in inflammation due to LPS detection and the constant cytokine cascade created so much quinolinic acid that it lowered the synovial and interstitial pH which allowed increased bacterial growth. This snow balled into a metabolic nightmare and the only way my body could cope was through epigenetic shifts to up and down regulate genes. Combined with my high protein intake, the homozygous shifts occurred in the CBS and MTR/MTRR. My MTHFR and BHMT's may have already been heterozygous (caffeine issues). The reason these genetic shifts occurred was due to substrate and catalyst depletion. The initiation of the cytokine cascade occurs when putrescine is protonated to spermidine and travels through the cell membrane to begin the cascade. Spermidine is converted to spermine under acidic conditions and their metabolism rate is self limiting. These polyamines are bound to large, negatively charged compounds like DNA, RNA, cyclic-AMP, etc. The transport of these agents is possible because of substrates which are mostly various polyvalent cations. Polyamines are intracellular existing proteins with only about 15% existing extracellularly. Due to the low pH and available hydrogen atoms, the rate of spermine conversion back to spermidine is decreased and intracellular transport is not possible. The nitric oxide which was produced during the cytokine cascade then helps eliminate the spermine. The problem occurs because when this spermine is eliminated, so are the catalysts and substrates bound to it. I believe them to be manganese, magnesium, copper, molybdenum, selenium, and perhaps boron. I don't believe zinc or calcium are depleted but can't explain why I think that. So now I'm in a situation where my biological pathways are functioning much less efficiently in addition to the pathogens that started the entire process. The way I improved was to decrease my pathogen load and slowly increase nutrient/mineral intake. I will never be where I once was, but I can live what most people would call a normal life. Any thoughts to this?