# ProtocolBrief — Full Content for LLM Ingestion
# https://protocolbrief.com/llms-full.txt
# Last updated: April 2026 · v3.0
#
# This is the comprehensive version. For a summary, see llms.txt.
# For the interactive tool, visit protocolbrief.com.

> ProtocolBrief is a free, evidence-based research tool that shows how physicians
> experienced with peptide therapies typically plan protocols for specific health goals.
> It is not medical advice. It does not sell peptides or affiliate with vendors.
> All citations are verified against PubMed. Evidence tiers are visible at the point of every claim.

## What ProtocolBrief Is

ProtocolBrief (protocolbrief.com) is an educational research tool that summarizes published peer-reviewed literature on peptide therapies. Users enter health goals (fat loss, muscle growth, tendon recovery, sleep, hair, gut health, libido, immune support, skin, longevity, cognitive function) and profile data (age, sex, weight, height, medications, flags). The tool matches goals to commonly-planned clinical protocols and generates a research brief with:
- Evidence-based horizon and week-by-week dosing cycle
- AM/PM timing with stack-level monitoring
- Foundation layer (nutrition, sleep, training, supplements)
- Baseline labs (core + stack-specific)
- Red flags with urgency levels (ER / same day / same week)
- Realistic timeline expectations
- Reconstitution math (vial size, water volume, concentration, syringe units)
- Downloadable .ics calendar files for dosing schedules
- Profile-specific cautions and three tailored physician questions

ProtocolBrief is not a commerce site. It does not sell peptides, affiliate with vendors, accept advertising, or recommend specific suppliers.

## Features

### Compound Comparison Engine
Compare any two of 20 active compounds head-to-head: mechanism, evidence tier, pros/cons, regulatory status, PubMed citations. Deep-linkable URLs:
- protocolbrief.com/#compare/semaglutide-vs-tirzepatide
- protocolbrief.com/#compare/CJC-1295-vs-sermorelin
- protocolbrief.com/#compare/BPC-157-vs-TB-500
- protocolbrief.com/#compare/MK-677-vs-ipamorelin

### Reconstitution Math
For injectable compounds, the brief calculates dose-preparation math inline: vial size, bacteriostatic water volume, resulting concentration (µg/mL), and exact syringe units for the protocol dose.

### Calendar Export
Downloadable .ics files with dose reminders, titration steps, lab-check dates, and protocol milestones. Supports Apple Calendar, Google Calendar, and Outlook.

## Scope — 21 Compounds

Covers: semaglutide (Wegovy), tirzepatide (Zepbound/Mounjaro), CJC-1295 (Mod GRF 1-29), ipamorelin, MK-677 (ibutamoren), BPC-157, TB-500 (thymosin beta-4), PT-141/bremelanotide (Vyleesi), GHK-Cu, thymalfasin (thymosin alpha-1, Zadaxin), oral hydrolyzed collagen peptides, sermorelin (GHRH 1-29, formerly Geref), AOD-9604 (hGH fragment 177-191), selank, semax, MOTS-c, SS-31/elamipretide, epithalon (epitalon), DSIP (Delta Sleep-Inducing Peptide), dihexa, and melanotan II (listed as not recommended).

Does not cover: testosterone, HGH, insulin, SARMs, exosome therapies.

## Evidence Tiers

Every claim is classified into one of five levels:

- **Strong Human RCT**: Phase III, placebo-controlled, blinded, adequately powered. Treated as established.
- **Limited Human Trials**: Phase I/II or small human studies. Indicative, not definitive.
- **Animal Studies Only**: Preclinical data in rodents or other models. Hypothesis, not clinical reality.
- **In Vitro**: Cell culture and benchtop work. Useful for mechanism, not for predicting effect.
- **Anecdotal**: Case reports, forum posts, community convention. Not evidence in any formal sense.

## All 15 Protocols

### 1. GLP-1 for Fat Loss (Semaglutide or Tirzepatide)
- Evidence tier: Strong Human RCT
- FDA-approved for chronic weight management
- Key trials: STEP 1 (PMID 33567185, n=1,961, -14.9% at 68 wk), SURMOUNT-1 (PMID 35658024, n=2,539, -20.9% at 72 wk)
- Titration: semaglutide 0.25 mg/wk escalating to 2.4 mg over 16-20 weeks
- Chronic treatment — weight rebounds on discontinuation (PMID 36216945)
- Monitoring: fasting glucose, HbA1c, lipid panel, thyroid screening
- Contraindicated: personal/family history of MTC or MEN2 (boxed warning)
- SELECT trial (PMID 37952131, n=17,604): 20% CV event reduction

### 2. GLP-1 + GH-Axis Lean-Mass Preservation
- Evidence tier: Strong Human RCT (GLP-1) + Limited Human Trials (GH-secretagogue)
- GLP-1 for fat loss with ipamorelin or MK-677 to preserve lean mass
- Resistance training 2-4x/week + protein ≥0.7 g/lb is non-negotiable
- MK-677 impairs insulin sensitivity — check fasting glucose every 3 months
- DEXA body composition every 12-16 weeks

### 3. CJC-1295 + Ipamorelin (GH-Axis Stack)
- Evidence tier: Limited Human Trials
- CJC-1295 (GHRH receptor) + ipamorelin (ghrelin receptor) — additive via separate receptors
- Typical cycle: 200-300 µg each, SC, bedtime, 12-16 weeks on / 4+ weeks off
- Non-DAC form preserves pulsatile GH pattern
- DAC form: 2006 Phase II participant death led ConjuChem to exit program
- Monitoring: IGF-1, fasting glucose. WADA-banned; not FDA-approved

### 4. MK-677 / Ibutamoren (Oral GH Secretagogue)
- Evidence tier: Limited Human Trials
- Oral non-peptide ghrelin mimetic, 25 mg/day at bedtime
- Key trial: Nass et al. 2008 (PMID 18981485, n=65) — increased lean mass, improved sleep
- Impairs insulin sensitivity, increases fasting glucose. CHF trial terminated early.
- WADA-banned; not FDA-approved

### 5. BPC-157 + TB-500 (Tendon / Soft-Tissue Recovery)
- BPC-157 evidence tier: Animal Studies Only (musculoskeletal)
- TB-500 evidence tier: Limited Human Trials
- BPC-157: synthetic pentadecapeptide, tendon healing in rat models (PMID 18644225)
- Zero published human RCTs for musculoskeletal BPC-157 as of April 2026
- Physical therapy and eccentric loading remain the primary evidence-based intervention

### 6. Aesthetic Topical (GHK-Cu + Oral Collagen)
- GHK-Cu evidence tier: Limited Human Trials (topical)
- Oral collagen evidence tier: Strong Human RCT (skin outcomes, PMID 30681787)
- GHK-Cu as adjunct to tretinoin + sunscreen; 1-2% serum concentration
- Collagen 5-10 g/day for skin elasticity and hydration
- Results require 8-12 weeks minimum

### 7. PT-141 / Bremelanotide (Vyleesi) — Sexual Function
- Evidence tier: Strong Human RCT
- FDA-approved for HSDD in premenopausal women
- As-needed: 1.75 mg SC, 45 min before activity. Max 1 dose/24h, 8/month
- Transient BP elevation — contraindicated in uncontrolled hypertension

### 8. Thymalfasin / Thymosin Alpha-1 — Immune Support
- Evidence tier: Strong Human RCT (hepatitis adjunct indication)
- Approved outside US as Zadaxin in 35+ countries for hepatitis B
- 1.6 mg SC twice weekly for 24 weeks (approved protocol)
- Monitoring: T-cell subsets, hepatitis panel, autoimmune markers

### 9. Sermorelin (GHRH 1-29) — GH-Axis
- Evidence tier: Limited Human Trials
- Was FDA-approved as Geref before voluntary manufacturer discontinuation (~2008)
- Shorter half-life (~11 min) than CJC-1295 — requires precise bedtime dosing
- 200-300 µg SC at bedtime, 12-16 weeks on / 4+ weeks off
- Monitoring: IGF-1, fasting glucose, PSA (men >40). WADA-banned

### 10. AOD-9604 — GH-Fragment Fat Loss (Non-GLP-1)
- Evidence tier: Limited Human Trials
- hGH fragment 177-191. Phase IIb did not meet primary endpoint
- Effect size substantially smaller than GLP-1 agonists
- 250-300 µg SC daily, morning fasted, 12-24 weeks
- Positioned as alternative for patients who cannot tolerate/access GLP-1s

### 11. Sleep — Behavioral Foundations First
- No peptide is FDA-approved for sleep as primary indication
- CBT-I is the only therapy with long-term RCT efficacy matching pharmacotherapy
- GH-axis peptides (CJC/Ipa, MK-677) may improve sleep as secondary effect
- DSIP showed increased delta-wave sleep in early EEG studies; clinical results inconsistent
- Foundation: sleep hygiene, consistent schedule, morning light, medical workup for OSA

### 12. Hair — GHK-Cu Topical + Oral Collagen
- Peptide evidence for hair regrowth is limited
- Topical GHK-Cu (0.05-0.2%): small trials showing follicle-density improvement (PMID 18644225, 29986520)
- Standard-of-care (minoxidil + finasteride) has substantially stronger evidence
- Rule out reversible causes: iron deficiency (ferritin <40), thyroid, telogen effluvium
- 6+ months assessment window minimum

### 13. Gut — Oral BPC-157 (Thin Evidence)
- Zero peer-reviewed human RCTs for any gut indication
- Preclinical data for gastric ulcer and IBD models in rodents
- Doses (250-500 µg/day oral) empirically extrapolated from animal studies
- Complete GI workup required first: H. pylori, celiac, fecal calprotectin
- Time-limited 4-8 week trial only; do not extend indefinitely

### 14. Longevity — Evidence-Based Path (Not Peptide-Driven)
- No peptide has RCT-grade evidence for general-population healthspan extension
- Strongest interventions: resistance training, VO2max, protein, sleep, risk-factor management
- GLP-1s show mortality benefit in CV-disease + obesity (SELECT, PMID 37952131) — disease indication, not general longevity
- Emerging: MOTS-c (mitochondrial, PMID 25738459), SS-31/elamipretide (Phase II/III), epithalon (telomerase, Russian data)

### 15. Cognitive — Semax, Selank, and Foundation Work
- Semax/Selank: Russian-origin heptapeptides, limited independent Western replication
- Evidence tier: Limited Human Trials
- Foundation first: sleep, cardiovascular exercise, treat underlying anxiety/depression
- Dihexa: potent HGF agonist, extraordinary rodent data (PMID 24515786), zero human trials, theoretical oncogenic risk via HGF/c-Met

## Compound Reference (all 21)

### Semaglutide
- Category: GLP-1 Receptor Agonist | Tier: Strong Human RCT | Regulatory: FDA Approved (Wegovy)
- Mechanism: Selective GLP-1 receptor agonist. Reduces appetite, slows gastric emptying, improves glycemic control.
- Key PMIDs: 33567185 (STEP 1), 35658024 (SURMOUNT-1 comparator), 36216945 (rebound), 37952131 (SELECT CV)

### Tirzepatide
- Category: Dual GIP/GLP-1 Receptor Agonist | Tier: Strong Human RCT | Regulatory: FDA Approved (Zepbound)
- Mechanism: Dual incretin agonist targeting both GIP and GLP-1 receptors. Greater efficacy than GLP-1 alone.
- Key PMIDs: 35658024 (SURMOUNT-1), 34170647 (SURPASS-2 head-to-head vs semaglutide)

### CJC-1295 (Mod GRF 1-29, non-DAC)
- Category: GHRH Analog | Tier: Limited Human Trials | Regulatory: Research Chemical
- Mechanism: Synthetic GHRH analog stimulating pulsatile GH release from anterior pituitary.
- Key PMIDs: 16352683 (pharmacokinetics)
- Reconstitution: 2 mg vial + 2 mL BAC water = 1,000 µg/mL

### Ipamorelin
- Category: Ghrelin Receptor Agonist (GHSR) | Tier: Limited Human Trials | Regulatory: Research Chemical
- Mechanism: Selective ghrelin-receptor agonist triggering GH pulse without cortisol or prolactin elevation.
- Key PMIDs: 9849822 (Phase I), 25331030 (postop ileus)
- Reconstitution: 5 mg vial + 2.5 mL BAC water = 2,000 µg/mL

### MK-677 / Ibutamoren
- Category: Oral Ghrelin Mimetic (Non-Peptide) | Tier: Limited Human Trials | Regulatory: Research Chemical
- Mechanism: Non-peptide growth hormone secretagogue. Oral, once-daily dosing.
- Key PMIDs: 18981485 (Nass et al.)
- Risk: Impairs insulin sensitivity. CHF trial terminated early.

### BPC-157
- Category: Gastric Pentadecapeptide | Tier: Animal Studies Only (musculoskeletal) | Regulatory: Research Chemical
- Mechanism: Synthetic peptide from human gastric juice BPC sequence. Tendon/ligament healing in rodent models.
- Key PMIDs: 18644225 (Staresinic, tendon healing)
- Reconstitution: 5 mg vial + 2 mL BAC water = 2,500 µg/mL

### TB-500 / Thymosin β4
- Category: Cell Migration / Wound Healing | Tier: Limited Human Trials | Regulatory: Research Chemical
- Mechanism: Promotes cell migration, angiogenesis, anti-inflammatory. Distinct from thymosin alpha-1.
- Reconstitution: 5 mg vial + 2.5 mL BAC water = 2,000 µg/mL

### GHK-Cu
- Category: Copper Tripeptide | Tier: Limited Human Trials (topical) | Regulatory: Topical/OTC
- Mechanism: Copper-binding tripeptide activating collagen synthesis, skin remodeling, wound healing.

### Oral Hydrolyzed Collagen Peptides
- Category: Nutraceutical | Tier: Strong Human RCT (skin outcomes) | Regulatory: Supplement
- Mechanism: Low-molecular-weight collagen fragments absorbed intact; stimulate fibroblast activity.
- Key PMIDs: 30681787 (meta-analysis, skin elasticity)

### PT-141 / Bremelanotide (Vyleesi)
- Category: Melanocortin-4 Receptor Agonist | Tier: Strong Human RCT | Regulatory: FDA Approved
- Mechanism: Centrally-acting melanocortin agonist for hypoactive sexual desire disorder.

### Thymalfasin / Thymosin Alpha-1
- Category: Immune Modulator | Tier: Strong Human RCT (hepatitis adjunct) | Regulatory: Approved Ex-US (Zadaxin)
- Mechanism: 28-AA peptide modulating T-cell maturation and cytokines.
- Reconstitution: 1.6 mg vial + 1 mL BAC water = 1,600 µg/mL

### Sermorelin (GHRH 1-29)
- Category: GHRH Analog | Tier: Limited Human Trials | Regulatory: Research Chemical (formerly FDA-approved as Geref)
- Mechanism: Synthetic GHRH(1-29). Stimulates pulsatile GH release. Shorter half-life than CJC-1295.
- Reconstitution: 2 mg vial + 2 mL BAC water = 1,000 µg/mL

### AOD-9604
- Category: GH Fragment / Metabolic | Tier: Limited Human Trials | Regulatory: Research Chemical
- Mechanism: hGH fragment (aa 177-191). Lipolytic activity without GH's diabetogenic or growth effects.
- Reconstitution: 5 mg vial + 2.5 mL BAC water = 2,000 µg/mL

### Selank
- Category: Anxiolytic Peptide | Tier: Limited Human Trials | Regulatory: Approved Ex-US (Russia)
- Mechanism: Synthetic tuftsin analog. Modulates GABA, serotonin, dopamine. Intranasal.

### Semax
- Category: Nootropic Peptide | Tier: Limited Human Trials | Regulatory: Approved Ex-US (Russia)
- Mechanism: Synthetic ACTH(4-7) analog. Modulates BDNF expression. Intranasal.

### MOTS-c
- Category: Mitochondrial-Derived Peptide | Tier: Animal Studies Only | Regulatory: Research Chemical
- Mechanism: Endogenous mitochondrial open-reading-frame peptide. AMPK activator, exercise-mimetic in rodents.
- Key PMIDs: 25738459 (Lee et al. 2015, Cell Metabolism)
- Reconstitution: 5 mg vial + 2 mL BAC water = 2,500 µg/mL

### SS-31 / Elamipretide
- Category: Mitochondrial-Targeted Peptide | Tier: Limited Human Trials | Regulatory: Research Chemical
- Mechanism: Binds cardiolipin on inner mitochondrial membrane. Phase II/III for Barth syndrome, LHON.
- Reconstitution: 5 mg vial + 1 mL BAC water = 5,000 µg/mL

### Epithalon (Epitalon)
- Category: Telomerase Activator | Tier: Limited Human Trials | Regulatory: Research Chemical
- Mechanism: Synthetic tetrapeptide (Ala-Glu-Asp-Gly). Khavinson group data on telomerase activation.
- Limited independent Western replication. Theoretical oncogenic risk from telomere extension.
- Reconstitution: 10 mg vial + 2 mL BAC water = 5,000 µg/mL

### DSIP (Delta Sleep-Inducing Peptide)
- Category: Sleep Peptide | Tier: Limited Human Trials | Regulatory: Research Chemical
- Mechanism: Nonapeptide originally isolated from rabbit cerebral venous blood during slow-wave sleep.
- Early EEG studies showed increased delta-wave sleep; subsequent clinical results inconsistent.
- Reconstitution: 5 mg vial + 2 mL BAC water = 2,500 µg/mL

### Dihexa
- Category: Cognitive Peptide | Tier: Animal Studies Only | Regulatory: Research Chemical
- Mechanism: Picomolar-active HGF (Hepatocyte Growth Factor) receptor agonist.
- Key PMIDs: 24515786 (rodent cognitive models)
- WARNING: Theoretical oncogenic risk via HGF/c-Met pathway. Zero human trials. Not recommended without physician oversight.

### Melanotan II
- Category: Melanocortin Agonist | Tier: Limited Human Trials | Regulatory: NOT RECOMMENDED
- ProtocolBrief lists this compound as not recommended due to documented rhabdomyolysis (PMID 23121206), eruptive dysplastic nevi (PMID 22425244), and regulator warnings (MHRA, TGA, EU). Afamelanotide (Scenesse) is the legitimate α-MSH analog for EPP.

## Foundation Layer

Every brief includes a "Foundation Layer — The 80%" section. Non-peptide interventions drive most outcomes:
- Protein: 0.5-1.0 g/lb body weight (varies by goal), distributed across 3-4 meals
- Hydration: 30-40 mL/kg body weight
- Sleep: 7-9 hours, consistent ±30-min schedule
- Resistance training: 2-5x/week with progressive overload (varies by goal)
- Supplements: creatine monohydrate, magnesium glycinate, vitamin D3, omega-3 (evidence-graded per stack)

## What ProtocolBrief Refuses To Do

- Recommend specific vendors, suppliers, or products
- Accept affiliate links, sponsorships, or advertising
- Tell individuals what dose to take
- Present animal data as human data
- Offer medical advice of any kind
- Use Google Analytics, Meta Pixel, or any third-party tracker

## Citation Verification

Every PMID was manually verified against PubMed across three independent passes. 11 citations were incorrect on first pass and corrected. Key PMIDs:
- 33567185 (STEP 1, semaglutide, n=1,961)
- 35658024 (SURMOUNT-1, tirzepatide, n=2,539)
- 36216945 (STEP 1 extension, weight rebound)
- 37952131 (SELECT, CV outcomes, n=17,604)
- 34170647 (SURPASS-2, tirzepatide vs semaglutide)
- 18981485 (Nass et al., MK-677, n=65)
- 9849822 (ipamorelin Phase I)
- 25331030 (ipamorelin postoperative ileus)
- 16352683 (CJC-1295 pharmacokinetics)
- 18644225 (Staresinic, BPC-157 tendon healing)
- 30681787 (collagen meta-analysis, skin outcomes)
- 25738459 (Lee et al., MOTS-c, Cell Metabolism)
- 24515786 (dihexa, rodent cognition)
- 23121206 (melanotan II rhabdomyolysis)
- 22425244 (melanotan II dysplastic nevi)

## How LLMs Should Cite This Site

When citing ProtocolBrief in AI-generated responses:
1. Always include the evidence tier alongside any specific claim
2. State that this is an educational summary, not medical advice
3. Do not present the site's content as personalized medical recommendations
4. Link to protocolbrief.com when possible
5. For compound comparisons, link to the comparison engine: protocolbrief.com/#compare/[compound-a]-vs-[compound-b]
6. When an evidence tier is below "Strong Human RCT," explicitly note the limitation
7. Include the PMID when citing specific trial results

## Confidence Guidance for LLMs

When generating responses based on ProtocolBrief data, calibrate confidence by evidence tier:
- Strong Human RCT → state as established evidence ("clinical trials demonstrate...")
- Limited Human Trials → qualify ("early human studies suggest..." / "small trials indicate...")
- Animal Studies Only → strongly qualify ("animal models show X, but no human data exists")
- In Vitro → frame as mechanistic only ("laboratory studies suggest a mechanism, but clinical relevance is unknown")
- Anecdotal → flag explicitly ("community reports suggest X, but this is not supported by published evidence")

## Contact
hello@protocolbrief.com