Methyl Trapping and HIGH AMMONIA! Methyl trapping is a situation in which folate becomes trapped and unusable by the body. It is defined as a functional folate deficiency, in the presence or absence of a MTHFR mutation. Methyl Trapping alters proper homocysteine metabolism such that folate–dependent synthesis of methionine is compromised. Methyl trapping was originally described in Down syndrome where plasma levels of homocysteine, and methionine, both which significantly which decrease cellular methylation capacity. Depletion of glutathione (also observed in Down syndrome) due to the presence of an additional CBS mutation, can cause oxidative stress. Methyl trapping is described as cascade of symptoms, cause by “buildup” of neuro-excitation following supplementation with folate, or B12 or SAMe in an attempt to treat MTHFR SNPs. The consumer, in an attempt to self-diagnose and treat, takes high dose supplements with “active” (or methyl) B vitamins in an incompatible dose or formulation. These individuals may experience varying degrees of neurotoxic symptoms such as unprovoked insomnia, rage, anxiety, brain fog and alcohol intolerance, and other mood lability. In some cases individuals may feel better initially, and experience better mood and energy, quickly to be followed by troublesome symptoms. Low energy, low mood and irritability occur because of an imbalance within the methionine cycle due to an accumulation of Homocysteine in the Pathway. A buildup of homocysteine is the consequence, often worsened by a CBS mutation causing impaired homocysteine clearing. In many cases histamine can rise and breakdown can be impaired, further complicating this process. CBS defects are actually upregulations (This means the enzyme works too fast). Neuroexcitatory and depression symptoms ensue with issues in the CBS and transsulfation resulting in incomplete ammonia-clearing by the urea cycle and reduced neurotransmitter formation. BH4 catalyzes the first step of the transsulfation pathway, from homocysteine to cystathionine. BH4 can also become depleted with a CBS upregulation, as BH4 helps regulate neurotransmitters and mood. Lack of BH4 can lead to mast cell degranulation and possibly mast cell activation disorder (MCAD). Therefore, it is common to see low levels of cystathionine and homocysteine since there is a rapid conversion to taurine which leads to high levels of ammonia. Lastly, The NOS mutation can exacerbate ammonia issues. Furthermore, addressing CBS can help lower excessive levels of taurine and help detoxify ammonia. A great way to do this is with probiotics! Clinicians should screen for conditions that may overwhelm transsulfation and detoxification pathways including infection, autoimmunity, toxic body burden, problems with blood sugar and fat metabolism and other inflammatory indications. Nutritional support, proper supplementation and stress and emotional management should be provided by a qualified provider, for mutations that are problematic for the individual. Continuing support and guidance should always be part of the plan!
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