Why Every Protocol Stops Working After Two Weeks: The Mechanistic Pattern Hiding in Plain Sight in Chronic SIBO, MCAS, and Long COVID — Part 2: The Mechanistic Reality — Why Interventions Plateau

The two-week arc has multiple distinguishable mechanisms depending on the intervention class. Each is a specific case of the same general principle: a downstream lever can deflect the system briefly, and homeostatic loops will reorganize around the deflection within ten to twenty-one days. The deflection is real. The reorganization is the plateau. Mechanism One: The Substrate Ceiling When you supply a missing cofactor — NAD precursor, glycine, CoQ10, riboflavin, alpha-lipoic acid, methylene blue, glutathione substrate — you raise the ceiling on a single biochemical reaction. The reaction's flux increases. Downstream pathways that were starved of the product of that reaction can run. You feel better. But every cofactor sits inside a regulated pool. Serum NAD rises within forty-eight hours of NR or NMN dosing. Mitochondrial NAD, which is the pool that matters for sirtuin-mediated control of the matrix proteome and for Complex I substrate availability, takes longer to fill — and continues to be drained at a rate set by CD38, PARP, and SARM1, none of which the supplement addresses. Within roughly fourteen days, supply and consumption reach a new steady state. The pool stabilizes at a slightly higher level than baseline, but the rate of demand has not changed. The system has reached a new equilibrium, and the equilibrium is no longer producing dynamic improvement. The same logic gov