Rankings / Mitochondria & Cellular Energy

Methylene blue

Mitochondria & Cellular Energy · Alternative electron carrier / MAOI / tau aggregation inhibitor

Tier C

mitochondrialmao-inhibitortau-aggregation-inhibitoralzheimerprescriptionotcawaiting-readout
4.9 / 10
Tier C
Ev 6.0 Bn 5.0 Sf 3.5

What this is

Hormetic dose-response is the central decision input — biohacker sweet spot is 0.5-2 mg/kg PO. Only USP/pharmaceutical grade is safe orally (industrial/aquarium/photographic grades contain heavy-metal contaminants). Mechanism updated in light of newer literature: MB acts as an alternative electron carrier between NADH and cytochrome c, bypassing complex I deficits common in aging and neurodegeneration. **2024-2025 development — major reversal of prior framing**: TauRx LUCIDITY Phase 3 of hydromethylthionine mesylate (HMTM, the reduced LMTX form) at 16 mg/day in MCI and mild-to-moderate AD reported 82% reduction in ADAS-cog13 decline at 18 months (115% reduction in early-AD subgroup); 71% of patients had same or better global CDR at 2 years vs 52% for matched placebo; 35% reduction in brain atrophy. **Caveat**: independent analysts (Clinical Trials Arena AD/PD 2025 commentary) flag that LUCIDITY's "placebo" arm received background standard-of-care AD therapy rather than true placebo — making the effect-size estimate disputed. TauRx submitted UK marketing application July 2024; US/Canada filings announced for 2026. This **supersedes** the prior framing — the 2016 Gauthier TRx0237 Ph3 (higher 75-125 mg BID dose) failed primary endpoint and was the earlier disappointment; the dramatically lower 16 mg/day appears critical to LMTX's signal. Industry-funding caveat: all LMTX/HMTM trials are TauRx-funded; independent replication remains the open question. For biohacker cognitive use (vs. AD), the Rodriguez 2016 fMRI signal at 280 mg ≈ 4 mg/kg remains the best human anchor — modest and short-term.

Mechanism

Hormetic dose-response: at low doses (~0.5-4 mg/kg) reroutes electrons from NADH directly to cytochrome c, increasing complex IV activity and ATP synthesis (~30-40% in vitro) while reducing oxidative stress; at high doses becomes pro-oxidant and can paradoxically cause methemoglobinemia; reversible MAO-A inhibitor (~700x more potent than linezolid); MAO-B inhibitor; tau aggregation inhibitor; crosses BBB; reduces β-amyloid and phospho-tau via enhanced mitophagy in preclinical models

Dose & route

0.5-4 mg/kg PO (hormetic — higher doses counterproductive for cognition; LUCIDITY used 16 mg/day fixed dose ≈ 0.2 mg/kg in 70 kg adult)

Citations

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