Substances MOC
Hub notes in 01-Substances/
Metabolic / Cardiovascular
- Alpha-Klotho — aging-suppressor protein; preclinical only; SGLT2 inhibitors are the only FDA-approved Klotho-axis intervention
- Berberine — AMPK activator + GLP-1 secretagogue
- Lactate Metabolism — lactate as training load biomarker; LT1/LT2 individualized thresholds via fingerstick GXT; metabolic clearance rate (Lt50, MCR) as trainable adaptation; no consumer wearable measures lactate directly as of 2026
- Glycine NAC Sleep Stack — glycine + NAC combination; glycine Supported for SOL; NAC evidence limited to oxidative-stress populations; combination is Gap (no human studies)
- SGLT2 Inhibitors — cardiovascular and renal protection
- Imeglimin — mitochondrial-targeted T2D agent
- Insulin Icodec — Awiqli once-weekly basal insulin for adults with T2D; convenience advantage with CGM/TIR relevance and hypoglycemia risk window
- Asundexian — Factor XIa inhibitor for stroke prevention
- Semaglutide Liver Health MASLD MASH — FDA-accelerated approved for MASH
- CagriSema — semaglutide + cagrilintide combo; filed-not-approved
- Difamilast — topical PDE4B-selective inhibitor for atopic dermatitis
- Amyloid-Beta Monoclonal Antibodies — Cochrane class-level review
- ApoB Lipoprotein Coaching — ApoB particle number principle; coaching protocol for atherogenic lipid burden
- Bimagrumab Semaglutide Combo — ActRII + GLP-1 combo; lean mass preservation during GLP-1-induced fat loss
- CoQ10 Ubiquinol — mitochondrial electron carrier + antioxidant; ubiquinone preferred over ubiquinol (stronger trial evidence); Supported for HF NYHA II–III and BP adjunct; Contested for statin-associated muscle symptoms
- Methylene Blue — phenothiazine redox agent; FDA-approved acute methemoglobinemia/ifosfamide neurotoxicity only; investigational cognitive/mitochondrial use; hard safety gate for Serotonin Syndrome with serotonergic drugs
- NAD Precursor Stacking — NMN+NR co-administration boundary; monotherapy raises blood NAD+ but stacking superiority, muscle benefit, and longevity claims remain unproven
GLP-1 / Incretin Agents
- See Peptides MOC for full peptide index
- GLP-1 FFM Systematic Review ACP 2026 — FFM proportion 34.9% median
- GLP-1 Non-Responder Genetic Variants — pharmacogenomics
- Orforglipron — Eli Lilly LY3502970 / Foundayo; FDA-approved oral non-peptide GLP-1 RA for chronic weight management; no fasting/SNAC requirement; −9 to −11% label-aligned weight loss range; GI tolerability, body-composition protection, and pending CV outcomes are the key boundaries
- Amycretin — zenagamtide / NN9487; investigational unimolecular GLP-1 + amylin receptor co-agonist; Phase 1b/2a −24.3% at 36 weeks with 60mg SC (PMID 40550231); Phase 2 T2D −14.5% is Reported/press-release-only; not CagriSema
- GLP-1 Agonist Muscle Atrophy Sarcopenia Adverse Events — FAERS 142-case signal; AAOS 2026 osteoporosis (+29%); FDA hip fracture label; 25–43% FFM proportion; caloric deficit primary mechanism; older adults >65 highest risk; GLP-1 Muscle Preservation for countermeasures
- Ozempic FDA Warning Letter 2026 — FDA MARCS-CMS 717576 pharmacovigilance reporting failure; not proof of semaglutide causation; coaching: do not advise self-discontinuation, screen/escalate mood symptoms.
Recreational / Behavioral
- Cannabis — THC, CB1 receptor, edible metabolism
- Alcohol — GABA-A, NMDA, CYP2E1
- Cocaine — DAT blockade, crash, risk profile
Hormone / Endocrine
- Testosterone Optimization — TRT for pathological hypogonadism; not approved for age-related decline; polycythemia is primary safety concern; exercise is foundational over TRT for body composition and longevity
Relaxants / Nootropics / Adaptogens
- L-Theanine — GABA/glutamate modulator + alpha wave inducer; best-supported as L-theanine + caffeine cognitive stack; not established for clinical GAD; no tolerance or dependence; wearable detection experimental
- Ashwagandha — AMPK activator + GLP-1 secretagogue
- Ayurveda, Bacopa monnieri, Rhodiola rosea, Spermidine, Astragalus, Cordyceps, Alpha-Ketoglutarate, Alpha-Ketoglutarate Longevity
Index
- Hub notes are the primary retrieval point for each substance
- Mechanism notes live in 02-Mechanisms/
- Coaching protocols live in 04-Protocols-and-Recovery/
- See Vitals Knowledge Map for the full cross-domain graph