Vitals Knowledge Vault

Vitals Knowledge Map

16 min read

Vitals Knowledge Map

What this is: The vault’s full topic index — use this to find any note by domain.

How to use it: Browse the sections below. Each domain has its own MOC (Map of Content) for focused navigation.

Start Here for New Agents

If you are an LLM or new visitor and want to find something fast, use the table below.

QuestionAnswer
”What peptides is Ben on?”Peptides MOC → Retatrutide, GHK-Cu, BPC-157, TB-500
”How does Retatrutide work?”Retatrutide hub in Peptides MOC
”Does cannabis affect HRV?”HRV signatures + Cannabis detection model
”How does alcohol mess up sleep?”Sleep architecture (alcohol) + Hangover mechanism
”What is the wearable signal for cannabis?”Cannabis detection model
”What mechanisms does GHK-Cu affect?”GHK-Cu hub → Genomic Remodeling, Tissue Repair
”How do I detect cannabis use from Apple Watch data?”Cannabis detection model
”What is the stack logic for X?”Peptides MOC → “Cross-Cutting Stacks” section
”What compounds affect HRV?”HRV → linked substance notes

🧪 Peptides and Compounds

Primary hub: Peptides MOC

Peptide Hub Notes

  • Retatrutide — GLP-1/GIP/Glucagon triple agonist (P1 anchor)
  • Survodutide — GLP-1/GCGR dual agonist (BI 456906); Phase 3 SYNCHRONIZE; GCGR energy-expenditure axis; MASH biopsy signal; investigational
  • Mazdutide — GLP-1/GCGR dual agonist (IBI-362 / LY3305677); NMPA-approved in China for obesity and T2D; no FDA/EMA approval; GLORY-1 phase 3 −14% at 48 wk in Chinese adults; no non-Chinese phase 3 data; no head-to-head vs semaglutide 2.4 mg, tirzepatide, or retatrutide
  • BPC-157 — tissue repair pentadecapeptide
  • GHK-Cu — copper tripeptide / genomic remodeler
  • SLU-PP-332 — ERR pan-agonist / exercise mimetic
  • Melanotan II PT-141 — melanocortin pan-agonist
  • Noopept Semax Selank — nootropic regulatory peptides
  • TB-500 — thymosin Beta-4 fragment
  • Tesamorelin — GHRH analog
  • CJC-1295 Ipamorelin — GHRH + GHSR stack
  • XW4475 — CRF2 receptor agonist
  • Epithalon — telomerase activator
  • Glutathione — endogenous antioxidant tripeptide
  • MOTS-c — mitochondrial-derived peptide
  • PCC1 — senolytic polyphenol
  • Fisetin — flavonoid senolytic
  • IGF-1 LR3 — synthetic IGF-1 analog; reduced IGFBP binding; research-only; WADA S2 prohibited; no human LR3 trials; primary acute risk: hypoglycemia; cancer risk confirmed epidemiologically
  • Protein Intake GLP-1 Glucagon — protein intake protocol for GLP-1 agonist users (1.8–2.2 g/kg), lean mass monitoring (DXA, grip strength), body composition outcomes by agent

Non-Peptide Compounds (in 01-Substances)

  • NMN NAD+ — NAD+ precursor / sirtuin activator
  • Rapamycin — mTORC1 inhibitor
  • Ecnoglutide — GLP-1/GIP agonist
  • Orforglipron — oral non-peptide GLP-1 RA; Eli Lilly (LY3502970; Foundayo); FDA approved April 2026 for chronic weight management; no fasting/SNAC requirement; moderate −9 to −11% weight loss; GI tolerability, body-composition protection, and pending CV outcomes are the key boundaries
  • Cagrilintide — long-acting amylin analog (DACRA); AMY1/3 + CTR agonism; ~9.7% monotherapy weight loss at 26 weeks (Phase 2, PMID 34798060); monotherapy program discontinued; investigational; only the CagriSema combo was filed; amylin receptor pathway genuinely distinct from GLP-1
  • CagriSema — semaglutide 2.4mg + cagrilintide 2.4mg (GLP-1 + amylin dual); Phase 3 REDEFINE-1 -20.4% at 68 weeks; filed-not-approved; critical gap: zero DXA lean mass data; 79.6% GI AEs; dual injection burden; compare to Tirzepatide, Retatrutide
  • Amycretin — zenagamtide / NN9487; unimolecular GLP-1 + amylin receptor co-agonist; investigational; Phase 1b/2a −24.3% at 36 weeks with 60mg SC (PMID 40550231); Phase 2 T2D −14.5% is press-release-only; AMAZE Phase 3 program includes AMAZE 8 vs semaglutide
  • Difamilast — topical PDE4B-selective inhibitor; FDA approved 2/12/2026 for mild-moderate AD; Phase 3 IGA 38.5% vs 12.6% vehicle at 4 weeks (P<0.0001); first PDE4B-selective topical approved in US; rapid onset from week 1; no boxed hypersensitivity warning (vs crisaborole); no head-to-head vs crisaborole; no validated wearable biomarker for treatment response
  • Urolithin A — mitophagy inducer
  • Lion’s Mane — neurotrophic fungus
  • Dihexa — HGF/c-Met agonist
  • 9-MBC — neurogenic compound
  • Methylene Blue — phenothiazine redox agent; FDA-approved acute methemoglobinemia/ifosfamide neurotoxicity; investigational cognitive/mitochondrial use; serotonin-syndrome safety gate
  • Berberine — AMPK activator + GLP-1 secretagogue; “natural metformin” with distinct lipid and microbiome mechanisms
  • Suzetrigine — Nav1.8 sodium channel inhibitor; FDA approved January 2025; first non-opioid acute pain mechanism; opioid-sparing, non-NSAID option
  • NPR1 Agonists — natriuretic peptide receptor 1 agonist drug class; XXB750 (terminated) as anchor case study; paradoxical functional antagonism in HFrEF; safety signal in Phase 2 NCT06142383
  • Asundexian — first-in-class oral FXIa inhibitor; 26% RRR in recurrent non-cardioembolic ischemic stroke (OCEANIC-STROKE, Phase 3); no excess major bleeding; not yet approved; Factor XIa mechanism note

Investigational / Muscle

  • Follistatin Gene Therapy FST-344 — AAV1/minicircle myostatin inhibitor; NOT FDA-approved; male-only Phase 1/2a trials in BMD and sIBM only; no healthy-adult data; oxidative capacity trade-off; NCT07285629 active trial
  • Myostatin-Follistatin Axis — TGF-β family muscle preservation axis; myostatin (GDF8), activin A, follistatin, ActRII blockade; central mass-without-function pattern across domagrozumab, bimagrumab, landogrozumab, ACE-083; no FDA/EMA-approved agent; apitegromab nearest to approval (SMA, CRL 2025 manufacturing issue); bimagrumab + GLP-1 obesity combo fastest-moving frontier; coaching: resistance training + protein as primary evidence anchor

Safety

  • GLP-1 RA NAION Safety Signal — GLP-1 RA associated with NAION (OR 1.70); absolute risk small; FDA/EMA no action; patient counseling warranted; no wearable detection; disc-at-risk patients highest priority; practical triage note: GLP-1 NAION Risk
  • GLP-1 RA Skeletal Safety — Population-specific fracture risk: neutral/protective in T2D, elevated in elderly 65+ and non-diabetic patients (HR ~1.11); Wegovy hip/pelvis fracture label (Confirmed); 25–40% lean mass loss (Confirmed); mitigation: resistance training + protein + calcium/vitamin D + DXA; AAOS 2026 abstract Contested until peer-reviewed; GLP-1 Agonist Muscle Atrophy Sarcopenia Adverse Events for full muscle/bone evidence
  • GLP-1 Non-Responder Genetic Variants — GLP1R missense variant (rs1030559, Nature 2026): −0.76 kg/copy; ARRB1 β-arrestin-1 HbA1c signal; GIPR tirzepatide nausea variant; complementary to GLP-1 Agonist Pharmacogenomics Non-Response
  • GLP-1 Agonist Pharmacogenomics Non-Response — GLP1R rs6923761 (most-studied, failed to replicate); MC4R deficiency does NOT contraindicate GLP-1; early response trajectory is best current predictor; no clinical utility trial; GLP-1 Non-Responder Genetic Variants for Nature 2026 GLP1R missense data
  • GLP-1 Agonist Muscle Atrophy Sarcopenia Adverse Events — FAERS 142-case muscle atrophy signal (semaglutide ROR=2.39, tirzepatide ROR=1.69); AAOS 2026 +29% osteoporosis risk; FDA hip/pelvis fracture label (semaglutide); Hansen 2024 RCT −2.6% hip BMD; 25–43% FFM proportion overlapping caloric restriction; indirect (caloric deficit) mechanism primary; older adults >65 highest risk; Incretin Sarcopenia GLP-1 Prevention Protocol for countermeasures and coaching protocol
  • Ozempic FDA Warning Letter 2026 — FDA Warning Letter MARCS-CMS 717576 (March 5, 2026): Novo Nordisk failed to submit serious adverse-event reports within the 15-day window; cited examples include semaglutide death/suicide reports and a liraglutide stroke report; regulatory reporting failure ≠ semaglutide caused the events; no recall or new safety finding from this letter alone; coaches: frame accurately, do not advise self-discontinuation, screen/escalate mood symptoms.
  • NMN NAD+ — cancer chemo interaction: preclinical safety signal (PMID 41724424); oncologist consultation required for active cancer patients on chemo

Metabolic / Liver

  • Linvesirixibat — ASBT inhibitor; FDA approved March 2026 for cholestatic pruritus in PBC (first drug for this indication); GLISTEN Phase 3 WI-NRS −0.71 vs placebo (p=0.001); modest absolute benefit; high placebo response; diarrhea dominant AE; 20–50/month generic; no validated wearable pruritus monitor; sleep disruption from nocturnal itch is the tractable wearable proxy
  • Semaglutide Liver Health MASLD MASH — FDA-accelerated approved for MASH F2–F3 (Aug 2025); MASH resolution 63% vs 34% placebo; weight-independent mechanism NOT established; NOT for cirrhosis; oral formulation no data
  • CagriSema — semaglutide + cagrilintide coadministration; GLP-1 + amylin dual mechanism; -20.4% in Phase 3 REDEFINE-1; filed-not-approved; no DXA body composition data — lean mass impact completely unknown

Stack Logic

See Peptides MOC → “Cross-Cutting Stacks” section for:

  • Metabolic Resurrection Stack (Retatrutide + SLU-PP-332 + GHK-Cu + BPC-157)
  • Wolverine Stack (BPC-157 + TB-500) — research-only; human efficacy unproven
  • GH Amplification Stack (Tesamorelin + CJC-1295 Ipamorelin)
  • Ultimate Recomposition Stack (Retatrutide + XW4475)
  • Senolytic Regeneration Stack (PCC1/Fisetin + NMN NAD+ + Glutathione + GHK-Cu)

🌿 Substances (Non-Peptide)

Hub notes in 01-Substances/

Recreational / Behavioral

  • Cannabis — THC, CB1, edible metabolism, biometric signatures
  • Alcohol — GABA-A, NMDA, CYP2E1, biometric signatures
  • Cocaine — DAT blockade, crash, risk profile

Ancient Medicine Systems

Adaptogens / Nootropics

Metabolic / Longevity

  • ER-100 — partial epigenetic reprogramming gene therapy; first OSK human trial (NCT07290244); Phase 1 initiated Jan 2026; zero human efficacy/safety data; DO_NOT_OPERATIONALIZE_YET
  • Metformin Longevity — AMPK activator; pre-clinical longevity case coherent; TAME trial still pending; B12 depletion is most important long-term risk
  • SGLT2 Inhibitors, Imeglimin, Berberine
  • Insulin Icodec — Awiqli once-weekly basal insulin for adults with T2D; convenience advantage, CGM/TIR relevance, and day-2-to-4 hypoglycemia monitoring window; uses Albumin Binding Half-Life Extension
  • Testosterone Optimization — TRT for pathological hypogonadism; FDA-approved indication only for classical (not age-related) hypogonadism; TRAVERSE CV non-inferiority confirmed (HR 0.96); polycythemia is primary safety concern; wearable HRV cannot track testosterone status; exercise is foundational over TRT for body composition and longevity
  • Alpha-Klotho — aging-suppressor protein; FGF23 co-receptor; zero human efficacy data; SGLT2 inhibitors are the only FDA-approved Klotho-axis intervention; monitor Phase 1 trials (AKL003 NCT07544420, Minicircle NCT07285629)
  • Bimagrumab Semaglutide Combo — ActRII blockade + GLP-1 combo; lean mass preservation during GLP-1-induced fat loss; Phase 2 RCT; investigational
  • Incretin Sarcopenia GLP-1 Prevention Protocol — GLP-1 agonist lean mass loss prevention; 25–40% of WL as LBM (DEXA-confirmed); resistance training + protein (1.2–1.6 g/kg) only evidence-based prevention; BIMZ + semaglutide Phase 2 with 92.8% fat mass and lean preserved; older adults ≥60 highest risk; bone monitoring warranted; Vitals coaching note
  • Semaglutide Liver Health MASLD MASH — FDA-accelerated approved for MASH F2–F3 (Aug 2025); MASH resolution 63% vs 34% placebo; weight-independent mechanism NOT established; NOT for cirrhosis; oral formulation no data
  • GLP-1 FFM Systematic Review ACP 2026 — ACP 2026 systematic review: 34.9% median FFM proportion; zero RCTs with physical function primary endpoints; CagriSema approaching approval
  • Amyloid-Beta Monoclonal Antibodies — Cochrane meta-analysis (PMID 41985900): class-level clinical benefit trivially small (SMD −0.11 ADAS-Cog); amyloid clearance ≠ meaningful benefit; only lecanemab/donanemab approved (2026); ARIA is primary safety risk; Vitals: cognitive decline prevention should foreground lifestyle over anti-amyloid strategies
  • ApoB Lipoprotein Coaching — ApoB particle number principle; non-HDL-C and TG/HDL-C as Vitals proxies; coaching for atherogenic particle burden in dysmetabolic patients; no wearable measures ApoB directly; highest-value scenario: normal LDL-C + elevated TG/HDL ratio
  • Beetroot Nitrate — dietary nitrate (beetroot juice); entero-salivary nitrate-nitrite-NO pathway; SBP ↓4–8 mmHg in hypertensives; VO₂max ↑3–5%, TTE ↑6–20% in recreational athletes; cycling required (5 on/2–3 off); PDE5i/organic nitrates contraindicated
  • Lactate Metabolism — lactate as training load biomarker; individualized LT1/LT2 via fingerstick GXT (ModDmax method); metabolic clearance rate (Lt50 ~14 min, trainable); active recovery at 80% LT1 optimal; resting lactate trending for metabolic fitness; no consumer wearable measures lactate directly as of 2026
  • CoQ10 Ubiquinol — mitochondrial electron carrier + antioxidant; ubiquinone has stronger trial evidence than ubiquinol; Supported for HF NYHA II–III and BP adjunct; Contested for statin-associated muscle symptoms; no performance or longevity benefit in healthy populations
  • Brown Adipose Tissue Activation — BAT thermogenesis via UCP1 uncoupling; cold exposure +188 kcal/day EE (Supported); mirabegron 200 mg +203 kcal/day (Reported, off-label CV risk); no weight loss despite EE increase (Gap); all wearable BAT signals exploratory (Gap); complements Zone 2 and metabolic flexibility goals; no FDA-approved BAT drug for metabolic indication

⚙️ Mechanisms

Reusable notes in 02-Mechanisms/

Receptor / Signaling

Metabolic / Cellular

Substance-Specific Metabolites

Cardiovascular

  • Respiratory Sinus Arrhythmia — HRV physiology
  • Mayer Waves — blood pressure regulation
  • Factor XIa — intrinsic coagulation amplification; biological rationale for FXIa as anticoagulant target; asundexian and milvexian mechanism
  • XXB750 NPR1 Agonist — terminated NPR1 agonist antibody; paradoxical functional antagonism in HF; cardiac safety case study
  • Elastin Degradation — initiating event in arterial aging; MMP-mediated elastin fragmentation; elastin has ~70-year half-life and is not meaningfully replaced in adults
  • AGE-RAGE Axis — advanced glycation end-products form non-enzymatic collagen cross-links; causal role established via ALT-711 breaker studies
  • VSMC Phenotype Switch — transition from contractile to synthetic VSMC state; high collagen I/III production; drives arterial fibrosis
  • Arterial Calcification — medial elastocalcinosis; hydroxyapatite deposition around elastin lamellae; VSMC osteoblastic differentiation; suppressed by MGP, fetuin, klotho, FGF-23

🟡 Sleep / Recovery

Hub notes in 01-Substances; mechanism notes in 02-Mechanisms; biometric notes in 03-Biometrics

📊 Biometrics

Signal notes in 03-Biometrics/

Core Wearable Signals

  • HRV — heart rate variability (primary recovery signal)
  • HRV — Myths and Overmarketed Claims — common HRV misinterpretations (LF/HF, breathwork)
  • HRV — Apple Watch Limits — what Watch HRV can and can’t tell us
  • Sleep Onset Latency — sleep onset latency as coaching endpoint; primary signal for glycine intervention
  • REM suppression — cannabis primary sleep signature
  • Sleep architecture — general sleep stage patterns
  • Cardiovascular signatures — RHR, BP, HRV combined
  • Blood Pressure Response Nitrate — systolic BP response to beetroot nitrate supplementation; 4–8 mmHg SBP reduction in hypertensive adults; 2–4 h post-dose peak; chronic effect after 2–4 weeks; morning fasting seated measurement protocol; key confounders: oral microbiome, mouthwash, antihypertensives, PPIs
  • Arterial Stiffness — arterial stiffness as cardiovascular aging biomarker; cfPWV gold standard; wearable-accessible proxies (HRV, resting HR); vascular age precision limits; coaching decision algorithm

Substance-Specific Biometrics

🛡️ Protocols and Recovery

Risk / recovery notes in 04-Protocols-and-Recovery/

Withdrawal

Acute Harm

Recovery Modalities

  • Microcurrent Electrical Stimulation — MENS/MCT; moderate evidence wound healing, low-null evidence DOMS; pacemaker EMI risk; dose-response (50 µA > 500 µA for tendinopathy)

Training Load Protocols

  • Lactate Threshold Field Protocol — supervised GXT with POC lactate meter for individualized LT1/LT2 (ModDmax method, ICC=0.96); active recovery at 80% LT1 is evidence-based optimal clearance intensity; zone derivation from lactate thresholds; key caveats: same device, same time of day, individual thresholds not population averages

Ayurvedic / Traditional

🔍 Detection Models

Wearable inference logic in 05-Detection-Models/

  • Cluster Headache Detection Model — sleep-timing correlation + attack logging; no real-time attack detection validated
  • Cannabis detection model — HR delta + REM + motion; AUC ~0.75–0.85
  • Alcohol detection model — HRV suppression + elevated RHR + sleep efficiency drop
  • Cocaine detection model — RHR elevation + sleep fragmentation + next-day HRV depression
  • Arterial Stiffness Wearable Detection Model — HRV, resting HR, and PPG-derived proxies for arterial stiffness; vascular age trend tracking with 6–7 year MAE; coaching signal algorithm with measurement noise floor
  • Lactate Wearable Detection Model — no consumer wearable measures blood lactate directly as of 2026; smartwatch “lactate threshold” features (Huawei 78%, Garmin 65%, Coros 47% success) estimate from HR/pace, not blood lactate; sweat lactate breaks down in hot/humid conditions; microneedle ISF sensors (NCT04238611) promising but not yet commercial; POC fingerstick meters (StatStrip, Lactate Plus) are the practical option
  • NAD precursor detection model — coaching/interpretation model for NMN/NR use; wearables cannot detect NAD+ directly; rejects unproven stacking, muscle, longevity, and disease-modification claims

🏥 Body Systems / Safety

Condition and safety notes in 02-Body-Systems/

  • Cluster Headache — severe unilateral orbital pain phenotype, red-flag differential, acute vs preventive treatment split, Vitals boundaries

🗺️ MOCs (Maps of Content)

MOCScope
Peptides MOCAll peptide hub notes + mechanism notes + stacks
Cannabis MOCCannabis hub + mechanisms + biometrics + risks + detection
Alcohol MOCAlcohol hub + mechanisms + biometrics + risks + detection
Cocaine MOCCocaine hub + mechanisms + risks
Adaptogens MOCAshwagandha + Bacopa + shared mechanisms
Ancient Medicine MOCAyurveda, TCM, Thai Traditional Medicine systems
Body Systems MOCBody-system condition notes + safety triage

Vault Policy Notes (Internal)

Last updated: 2026-04-26 (Ozempic FDA Warning Letter 2026 — Batch 181)

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