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The phosphorylation leads downregulation of MTHFR activity and upregulation of allosteric inhibition by SAM

39 These acquired resistant mechanisms are often employed in conjunction with other mechanisms of antibiotic resistance

Medications: Certain drugs, including birth control pills and hormone replacement therapies, can increase melanin levels and contribute to pigmentation changes

The reduction in AUC after oral administration can result from numerous mechanisms including: pH or bacterial-mediated metabolism of the drug within the GI tract, incomplete drug absorption from the GI tract, metabolism within the GI epithelium (which contains CYP3A4), excretion back into the GI tract by P-glycoprotein in the GI epithelium, hepatic metabolism, or biliary excretion into the GI tract

Over time, this can lessen these uncomfortable sensations and improve overall nerve sensitivity