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Studies show this is because oral supplements are broken down by the digestive system, meaning only a small amount actually reaches your joints

Sci Rep 15(1):12914 Mohyeldin RH, Abdelzaher WY, Sharata EE, Mohamed HM, Ahmed MY, Attia JZ, Atta M, Saleh RK, Ghallab EA, Marey H (2024) Aprepitant boasted a protective effect against olanzapine-induced metabolic syndrome and its subsequent hepatic, renal, and ovarian dysfunction

The 21-28 day recommendation accounts for this additional degradation pathway

(In essence, FOXO4 holds p53 so it cannot execute the death program)

It is also not yet known whether such dysbiosis leads to ME/CFS, or whether it is a consequence of the metabolic and immunologic changes that occur in the disease (201)