3 Commits

Author	SHA1	Message	Date
claude	5665d74e32	Deep dive: Rapamycin (Section 4.4, Tier 4 — Avoid) — replaces 5-line stub with full ~420-line analysis. Discovery from Streptomyces hygroscopicus on Rapa Nui (1972), CYP3A4 metabolism with CYP3A4*22 pharmacogenomic concern. FKBP12-FRB binding mechanism with full mTORC1 vs mTORC2 architecture diagram. Mouse evidence: Harrison 2009 ITP (9-14% lifespan extension), Miller 2011/2014 dose-dependent, Wilkinson 2012 female bias, Bitto 2016 brief treatment sufficient. Mouse-to-human translation problems: cancer-dominated mouse mortality, species-specific mTOR signaling differences, lab mouse environmental artifacts. Human evidence: PEARL trial (2023) NEGATIVE on primary endpoints, Mannick 2014/2018 RAD001 vaccine response (specific not generalizable), transplant cohort no anti-aging signal. Side effect profile (table): hyperlipidemia 50-80%, glucose intolerance, mouth ulcers 30-50%, edema, wound healing impairment, immunosuppression, pneumonitis, proteinuria. Framework's six mechanistic objections: anti-anabolic (Drummond 2009, Dickinson 2011), anti-glucose-oxidation (Lamming 2012, TCF7L2 TT amplification), anti-thyroid CR-mimetic profile (DIO2 het), anti-mitochondrial-biogenesis (Cunningham 2007, UA/cordyceps preferred), immunosuppression, wound healing/fertility. Blagosklonny hyperfunction theory critique. Genotype interaction table covering CYP3A4*22, TCF7L2, APOE ε4, DIO2, TNF-α, methylation hets, UCP2/J1c, FOXO3, COL1A1, 9p21, TERT. Low-dose intermittent defense and its limits. Stack interactions: metformin double-negative, statins additive, urolithin A preferred alternative, exercise adaptation abolished. Specific clinical scenarios where rapamycin IS appropriate (TSC, LAM, transplant, RCC, drug-eluting stents, HGPS). Evidence summary table 14 claims. 16 references. Harm reduction protocol if used against recommendation.	2026-05-10 09:18:52 +08:00
claude	6d88496404	Restore lost Tier 4 + Appendix A content (1231 sanitized lines). The original commit pushing SUPPLEMENTS.md to this repo was already missing this content (lost in upstream commit 1afbfe5 which dropped the file from 20,238 → 19,413 lines while adding the Alpha-Lipoic Acid section — the Tier 4 header was preserved but everything below it was truncated). Restored from upstream peak commit 264505c with personal references sanitized: Section 4.1 Statins (stub), Section 4.2 Metformin (full deep dive: Complex I/ND3 inhibition, Konopka 2019 exercise blunting, Aroda 2016 B12 depletion, mGPD inhibition, GI serotonin, TSH suppression, TAME framework interpretation, AMPK alternatives table), Section 4.3 High-Dose Antioxidants (stub), Section 4.4 Rapamycin (stub), Section 4.5 Fluoride (stub), Section 4.6 Iron — Dietary Yes Supplemental No (~254 lines), Section 4.7 GLP-1 Receptor Agonists (~420 lines: STEP/SELECT/SUSTAIN/FLOW trials, lean mass loss, MTC black box, GI pathology, metabolic suppression, TCF7L2 TT pharmacogenomic counterargument), Appendix A Excipients & Additives. Sanitized: 'this user' → 'someone with this profile', 'BMI 19.4 / 58 kg' → 'lean adult / low BMI', 'the user's X genotype' → 'X genotype (in carriers)', 36-year-old male → adult. File now 20,983 lines.	2026-05-10 09:08:04 +08:00
claude	181eb79b49	Add supplements deep-dive compendium — 35 Tier 1-3 sections + 7 Tier 4, covering 9 medicinal mushrooms, mitochondrial supplements, methylation support, metal detoxification agents, and more	2026-05-02 15:30:52 +08:00