anecdotal report. TDLR : using 24.3mcg/kg scaled HED value from rat studies with Elamipretide / Bendavia / SS-31, there is anecdotal observation suggesting that MB donor/acceptor usage declines as SS-31 dosing approaches (rodent) study effective value.
Full-story for the curious
did quite a few months on methylene blue, maxed daily 210mg, while up on a 140mg plateau. along the journey i noticed that "clearance" matched some studies, with concentration in kidneys surpassing serum, evidenced by near blue urine. i drove above the plateau as work was beyond obnoxious requiring sustained 14hr+ days, during which time i used the bio indicator as a gauge of utilization, specifically if it didn't "drop" in the kidneys i interpreted as MB was needed some place else. hit pure blue at 210mg aka 1.67mg/kg and figured i found personal max. takeaway is: the lack of blue-ness' suggests MB donor/acceptor electron utilization.
documentation stated no heavy ox (hormesis curve bad side) noted historically up to 2mg/kg (some literature puts that at 4mg/kg), but for me I suspect overspin and have set personal limit at 1.6mg.kg
Speculative observation(s)
MB is purely nootropic prior to 25mg absolute, relative 0.2mg/kg; clarity in vision is a pretty notable effect, and ease of mental focus. above this point it goes energetic, and above 0.75mg/kg...food becomes optional. above 1.1mg/kg the expression "zero fuzz coke buzz" fits well, and i recommend keto shooters above 0.5mg/kg to utilize fat stores and maintain rad mental clarity (haven't rolled semax/selank, closest comparison is 'amplified racetam' effect.
ok, done with that MB rabiit trail, and back to anecdotal point: with SS-31 24.3mcg/kg (scaled lab allometric) HED defines beneficial effect mapping, and lowest effective dose is lowest recurring cost.
at my mass, that is all of 3mg. i'm using 2mg now, about to step up to 3mg on Sunday. not even at the effective dosage, while using 20-25mg MB, urine is leaning 'pure blue'. I have fortified the cardolipin substrate with addition of Geranylgeraniol (GGOH) on top of long-term 200-400mg ubiquionol on the daily.
Recap of human use case data
Across multiple studies, the only issue uncovered after 192 weeks of CONTINUOUS elamipretide 40 mg once-daily SQ within human youth population afflicted with Barth syndrome (BTHS) was statistically significant rise (upper value-shift) in mean hemoglobin level 14.62-15.16 mg/dL (normative: 11.0-14.5 mg/dL). most researchers aren't keeping an eye on this, but i know from personal experience that no significant risk unfolds until serum tests reveal 18.5g/dL+ for Hemoglobin WITH concurrent elevated RBC and hematocrit
recap: the fact human case studies with genetic mitochondrial defective population used 40mg SQ daily, simply does not mandate use of this high dosage to correct mitochondial dysfunction in a normal population, whether metabolically challenged or not.
my assertion would be that parallel or series cycles with MOTS-C, Humanin/HNG, and NNMTi's would be better research than high dose SS-31