Jun 9 • General discussion
5 AMINO 1 MQ CAN YOU TELL ME IF THIS IS TRUE
Dosing Protocol
Why Most Protocols Online Do Not Make Sense
The mouse study used doses that translate to roughly 400 mg per day for humans using allometric scaling. Online you will find recommendations ranging from 150 to 600 micrograms per day (microdosing) up to 50 to 150 mg per day. That is a 2,500x difference between the low end and what the science suggests should work.
For a drug to actually do its job, you need enough of it in your bloodstream to block at least 50% of the target enzyme. This is called IC50 coverage. If you are below that threshold, the drug is not doing much. Based on pharmacokinetic analysis using metformin as a structural analog (similar molecular weight, charge, oral bioavailability, and half-life), to achieve 50% NNMT inhibition you need roughly 50 to 100 mg per day. To achieve near-complete inhibition you need 400 to 600 mg per day.
Microdoses of 150 to 600 micrograms per day get you roughly 400 times below the threshold needed for 50% inhibition. You cannot outsmart pharmacology. Either you are achieving effective concentration or you are not.
There is another reason microdose protocols do not make sense. The enzyme that actually makes NAD+ from nicotinamide is called NAMPT, and NAMPT has 430 times higher affinity for nicotinamide than NNMT does. Under normal conditions, nicotinamide preferentially flows toward NAD+ synthesis anyway. NNMT only becomes a significant drain when it is massively overexpressed. If you want NAD+ support, taking a direct precursor like NMN or using injectable NAD+ makes more sense than taking a microdose of an enzyme inhibitor that does not achieve meaningful tissue concentrations.
Why do these smaller protocols exist? Follow the economics. A 10 mg vial at 150 micrograms per day lasts about 66 days. That same vial at 5 mg per day lasts 2 days. The true effective dose never gets tested because it is economically prohibitive outside of funded clinical trials.
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5 AMINO 1 MQ CAN YOU TELL ME IF THIS IS TRUE
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