Appendix C — Your Peptide Evidence Dossier: Blank Workbook

This is the book's deliverable. Everything else in it — forty-four chapters, fourteen appendices, several hundred thousand words — exists to get you to the point where you can fill this in for yourself and keep it current after the book stops being able to help you.

A dossier is not a summary of what this book concluded. It is a record of what you have established, about the compounds you actually care about, in a form you can update when the evidence changes. The book's ratings are in Appendix A and Chapter 37, and you should compare yours against them — but a dossier copied out of Appendix A teaches you nothing and will be stale within two years. One you built yourself will not, because you will know how each entry was made and therefore what would unmake it.

Copy this appendix into whatever you actually use. A notebook, a document, a spreadsheet, a notes app. The format does not matter. The twelve fields do, and so does the discipline of leaving a field blank rather than filling it with something you do not know.

C.1 How to use this workbook

Choose five to ten peptides. Chapter 1 asked you to do this and the instruction has not changed: pick the ones you have actually wondered about, not the ones you think a serious person should pick. The compound your sister started, the one your gym talks about, the one in the serum you already bought. A dossier about compounds you are not curious about will not get maintained, and an unmaintained dossier is worse than none, because it will eventually tell you something that stopped being true.

Fewer than five and you will not see the patterns that only appear across compounds. More than ten and you will not keep it up.

Fill fields as the book teaches them, not all at once. The chapter-by-chapter schedule in this book's continuity plan assigns one field or one skill per chapter, deliberately. A dossier filled in one sitting from memory will be twelve paragraphs of mechanism and no verdicts — mechanism is the easiest field to write and the least informative, and it is where an unstructured effort always drifts.

Leave fields blank. This is the hardest instruction in the appendix and the most important. A blank field is information: it says nobody knows, or you have not looked. A field filled with a plausible sentence you cannot source is worse than empty, because in six months you will not remember which sentences you were sure of. If you write nothing else in the margin, write where you got it.

C.2 The twelve fields

Read the right-hand column carefully. Those twelve failure modes are, between them, most of the bad reasoning about peptides that exists in the world. The fields are not a filing system. They are twelve places where a specific error is easy to make, arranged so that making it is visible.

C.3 The blank template

================================================================
COMPOUND: ______________________________     Last updated: ______
================================================================

1  IDENTITY
   Common name(s):
   Trade name(s), if any:
   Sequence or length:
   Modifications vs. the native molecule:
   Is "the same name" reliably the same molecule?   Y / N / unclear

2  ORIGIN
   Endogenous human / analog of endogenous / found in another
   organism / selected from a library / designed / fragment:
   Notes:
   >> Origin carries no evidentiary weight. Record it; don't lean on it.

3  MECHANISM
   In one plain sentence:
   Receptor / target:
   Direct or indirect (acts on a tissue, or on a gland that acts
   on a tissue)?
   Confidence in the mechanism itself:  established / proposed / unclear

4  PHARMACOLOGY
   Route(s) studied:
   Half-life:
   Oral bioavailability, if relevant:
   What modification made it a drug (if any):
   Does the route it's actually used by match the route studied?

5  EVIDENCE
   Best available human evidence:
     Design (RCT / observational / open-label / case series / none):
     Population — who exactly:
     Endpoint — surrogate or outcome:
     Comparator:
     Size and duration:
     Result:
   Animal / in-vitro only?   Y / N
   Replication:   yes / single trial / none
   What is conspicuously absent:

6  RATING  (one row per claim — add rows freely)
   ┌────────────────────────────────┬────────┬──────────┐
   │ Claim (population + endpoint)  │ Rating │ Dated    │
   ├────────────────────────────────┼────────┼──────────┤
   │                                │        │          │
   │                                │        │          │
   └────────────────────────────────┴────────┴──────────┘
   If ❌ — which kind?   evidence ABSENT / evidence PRESENT and NEGATIVE

7  APPROVED USE
   Approved where, for what indication, in which population:
   Line of therapy / patient selection, if specified:
   Not approved elsewhere because:  never submitted / rejected /
     approved elsewhere only / off-label / not a drug

8  CLAIMED USE
   What it is marketed or discussed as doing:
   Overlap with field 7:   full / partial / none
   >> The gap between 7 and 8 is usually the whole story.

9  RISKS
   Known adverse effects at studied use:
   Risks specific to unstudied use:
   Risks specific to preparation quality:
   Interactions and contraindications:
   What is unknown because nobody has looked:

10 STATUS
   Regulatory:
   Sport / anti-doping:
   How it is actually being sold:
   Access, cost, supply:
   Preparation quality — what could be established, and what can't:

11 VERDICT
   In one sentence, for my situation:
   Confidence:   high / moderate / low
   As a question I could ask a clinician:

12 WHAT WOULD CHANGE MY MIND
   To move this UP:
   To move this DOWN:
   The study that would settle it — population, endpoint,
   comparator, duration, rough size:
   Is such a study underway or planned?   yes / no / unknown

================================================================
SOURCES:
================================================================

C.4 Field notes: what actually goes in each

Field 1 — Identity. A name is not a specification. Chapter 32 established that two vials labeled identically may differ in impurity profile, counterion, water content, and actual peptide mass; Chapter 34 established that a certificate describes a sample rather than a vial. Record the sequence or length if you can find it, and record the modifications relative to the native molecule, because those are usually where the drug is. The last line of this field — "is the same name reliably the same molecule?" — is the one to think hardest about. For semaglutide from a pharmacy the answer is yes. For a research-labeled vial of a five-residue fragment it is no, and that is a fact about your knowledge rather than about the compound.

Field 2 — Origin. Fill it in, then discount it. Exenatide was found in the venom of a lizard and is well supported. Several compounds this book rates ❌ are exact fragments of human proteins. Chapter 31 made the same argument about veterinary use and Chapter 35 about discovery: an origin story is the most common substitute for evidence in peptide marketing and one of the least informative facts about a molecule. The field exists so you have somewhere to put the origin story where it cannot contaminate field 6.

Field 3 — Mechanism. One plain sentence first, then the detail. If you cannot write the plain sentence, you do not understand the mechanism yet and should say so rather than transcribing a paragraph you half-follow. Note whether the action is direct or indirect — Chapter 15's secretagogues act on a gland that acts on a tissue, which adds a whole layer of variability. Then observe the rule the book repeats more than any other: mechanism never upgrades a rating. A beautiful mechanism with no outcome evidence is a hypothesis. Chapter 22's substance P antagonists bound their target exactly as designed and did not treat pain.

Field 4 — Pharmacology. The field readers skip and should not. Chapter 4 established that delivery is the central problem of the entire class. The line that does the most work here is the last one: does the route it is actually used by match the route it was studied by? A compound with oral human data being injected, or an injectable compound being sold as a capsule or a cream, is a compound whose evidence base does not apply to the way it is being taken — and that gap is invisible unless you have written both down.

Field 5 — Evidence. The core field, and the one with the most structure for a reason. Do not record how many studies exist. Record the best one, described by its design. Chapter 5's method is entirely contained in the sub-lines: population, endpoint, comparator, size, duration, result. The two lines at the bottom matter as much as the ones above: replication, because a single positive trial is a weaker thing than most coverage implies, and what is conspicuously absent, because the shape of a missing literature is informative. Sixty animal studies and no human trial is not a partial answer to a human question. It is an answer to a different question.

Field 6 — Rating. One row per claim, and expect several rows. This is rating rule 6 — one molecule, many ratings — and it is the field where the book's whole method either takes hold or does not. Semaglutide is ✅ for weight loss in obesity, ✅ for cardiovascular risk reduction in a specific population, and 🔬 for Alzheimer's disease, all at once and all correctly.

Date every row. A rating is a statement about the evidence at a moment, and an undated rating is a claim about the eternal, which is not the kind of claim anyone is in a position to make.

And mark which kind of ❌ you mean. The book distinguishes two: evidence absent — nobody has run the trial, so the claim is unsupported and also untested — and evidence present and negative — the trial was run properly and the answer was no. The second is a much stronger state of knowledge. The field knows far more about nesiritide, which failed a large outcome trial, than about BPC-157, which has never had one. Readers consistently get this backwards.

Field 7 — Approved use. Copy the indication precisely, including the population and any line-of- therapy restriction. Chapter 38 established that approval is a judgment about a specific claim rather than a certificate about a molecule, and that "not approved" has five distinct meanings — the sub-line asks which one applies, because "never submitted" and "submitted and rejected" are opposite signals wearing the same words.

Field 8 — Claimed use. Record what it is sold as doing, in the seller's own terms, without editing it into something more reasonable. Then compare with field 7. The gap between fields 7 and 8 is, for most compounds in this book, the entire story — and it is only visible because the two are recorded separately. A single "what it's for" field would hide it, which is why there isn't one.

Field 9 — Risks. Three separate categories, deliberately. Risks at studied use, which are the ones on a label. Risks specific to unstudied use, which no label covers. And risks specific to preparation quality — Chapter 19's territory, entirely independent of whether the molecule works. Then the line most people leave blank and shouldn't: what is unknown because nobody has looked. For a compound with no human trials, the honest risk entry is not "no known side effects." It is "unknown, and 'no reports' is not the same as 'no harms' when there is no reporting pathway."

Field 10 — Status. Five questions that get collapsed into one and should not be. This field took five chapters to fill — Chapter 12 opened it with access and cost, Chapter 19 added the quality-risk line, Chapter 34 added what a certificate can establish, and Chapter 38 closed it with regulatory and sport-doping status. Keep it in a column entirely separate from field 6, and never let one adjust the other. A compound can be approved somewhere and thinly evidenced. A compound can be unapproved everywhere and simply untested.

Field 11 — Verdict. One sentence, for your situation, with a confidence level. Then the line Chapter 39 added: the same verdict, rephrased as a question you could ask a clinician. That conversion is a test as much as a courtesy — a verdict that cannot be turned into an answerable question was probably a feeling. "There's not enough evidence for this" becomes "what would you want to see before considering this?" and the second version can actually get answered.

Field 12 — What would change my mind. Chapter 6 asked you to write this before you needed it, and the ordering is the point: it is nearly impossible to write honestly once you are invested. Chapter 35 sharpened it from a sentiment into a specification — not "better evidence" but the study, with its population, endpoint, comparator, duration, and rough size.

An entry with an empty field 12 is not a conclusion. It is a belief. A claim you cannot imagine disconfirming is not being held as a claim, and this is as true of a confident ❌ as of a hopeful ⚠️.

C.5 A completed entry, for calibration

Filled to the standard the rest should aim at. Numbers are as stated in this book, dated to 2026.

================================================================
COMPOUND: Semaglutide                        Last updated: 2026
================================================================

1  IDENTITY   GLP-1 receptor agonist. Trade names differ by
   indication and dose. 31-residue backbone based on human GLP-1,
   with three modifications: position 8 Ala->Aib; position 34
   Lys->Arg; C18 diacid attached via a spacer at position 26.
   Same name = same molecule? YES from a pharmacy. NOT reliably
   so for compounded or gray-market material (different salt
   forms and concentrations have been documented).

2  ORIGIN   Analog of an endogenous human hormone. Note the
   class's deeper origin: the first drug in it, exenatide, was
   found in Gila monster venom. Carries no evidentiary weight.

3  MECHANISM   Activates the GLP-1 receptor, producing
   glucose-dependent insulin secretion, reduced glucagon, slowed
   gastric emptying, and reduced appetite via central and vagal
   signaling. Direct agonist. Mechanism: established.

4  PHARMACOLOGY   Subcutaneous weekly; also an oral formulation
   co-formulated with the absorption enhancer SNAC, at roughly
   1% bioavailability. Half-life ~1 week, vs. ~1-2 minutes for
   native GLP-1. The C18 diacid drives albumin binding, which
   defeats renal filtration; Aib at position 8 defeats DPP-4.
   Route used matches route studied: YES.

5  EVIDENCE
   STEP 1 — RCT. Adults with overweight/obesity WITHOUT diabetes.
     2.4 mg weekly, 68 weeks, vs. placebo. ~-15% body weight from
     baseline vs. ~-2.4% placebo. Endpoint: weight (a surrogate).
   STEP 2 — same dose, adults WITH type 2 diabetes: ~-10%.
     >> Same drug, same dose, different population, materially
        different result. This is why field 6 is per-claim.
   SELECT — RCT, ~17,000 participants, ~3 years. Established CVD
     plus overweight/obesity, without diabetes. MACE reduced ~20%
     RELATIVE (HR ~0.80); ABSOLUTE ~8% -> ~6.5%, i.e. ~1.5
     percentage points; NNT ~65-70. Endpoint: a hard outcome.
   Replication: extensive across the STEP program.
   Conspicuously absent: very long-term (decade-plus) data;
     head-to-head outcome trials against tirzepatide.

6  RATING
   Weight loss, adults w/ overweight or obesity, no diabetes  ✅ 2026
   Glycemic control, type 2 diabetes                          ✅ 2026
   MACE reduction, established CVD + overweight/obesity,
     without diabetes                                         ✅ 2026
   Alzheimer's disease                                        🔬 2026
   Addiction / substance use                                  🔬 2026
   "Anti-aging" or longevity in healthy adults                ❌ 2026
     (kind: evidence ABSENT — not tested, not refuted)

7  APPROVED USE   Approved in many jurisdictions; indications
   and populations differ by product and by country. Not a single
   global approval — check the label that applies.

8  CLAIMED USE   Marketed and discussed for weight loss and
   diabetes (matches 7) and, informally, for a long list of
   effects from inflammation to addiction to aging (does not).
   Overlap with field 7: PARTIAL.

9  RISKS   At studied use: gastrointestinal effects are common;
   labeled warnings apply and should be read. Unstudied use:
   long-term use in populations not represented in the trials.
   Preparation quality: substantial for compounded and
   gray-market material — different concentrations, different
   salt forms, different delivery devices.
   Peri-operative: slowed gastric emptying is an anesthetic
   consideration; disclose before any procedure.
   Unknown because nobody has looked: decade-scale outcomes.

10 STATUS   Regulatory: approved, varies by jurisdiction.
   Sport: GLP-1 agonists are not a classical doping class, but
   check the current WADA List rather than this book.
   Sold as: prescription product; also compounded (restricted
   as shortages resolved) and gray-market.
   Access/cost: a live policy fight — see Chapter 12.
   Quality: establishable for pharmacy product; not for
   unverifiable sources.

11 VERDICT   Among the best-evidenced drugs in this book for
   two specific claims, one of them a hard outcome. Everything
   beyond those claims is a separate question with its own,
   mostly weaker, evidence. Confidence: HIGH — for those claims.
   As a question: "The cardiovascular result was in people with
   established heart disease and no diabetes — does that
   population include me?"

12 WHAT WOULD CHANGE MY MIND
   DOWN: a long-term safety signal in post-marketing
     surveillance; failed replication of SELECT.
   UP (for an unrated indication): a powered RCT with a hard
     outcome in that population — not a mechanism paper, not a
     subgroup, not a press release.
   Study that would settle Alzheimer's: RCT in early Alzheimer's
     disease, cognitive and functional endpoints, placebo
     comparator, multi-year, several thousand participants.
   Underway or planned? Yes — trials in this area are running.
================================================================

Notice what the completed entry does that a summary would not. It carries five ratings for one molecule without contradiction. It separates a relative risk reduction from an absolute one, which is the single most common way trial results are oversold. It records that the same drug at the same dose produced ~−15% in one population and ~−10% in another, which is field 6's entire justification sitting in plain sight. And field 12 names the trial that would settle an open question rather than saying "more research is needed."

C.6 Maintaining it

Re-read your 🔬 and ⚠️ entries against your own field 12, not against the latest headline. Ratings drift upward over time and almost never downward, because every piece of news that reaches you about a compound you are watching is, by selection, news someone thought worth publicizing. Chapter 6's testimonial dynamic operates on your own attention. The defense is mechanical: you wrote down what would move the rating, so check whether that happened.

Nothing upgrades a rating except the readout named in field 12. Not a press release, not a conference abstract, not a funding round, not a new mechanism paper, not a clinician's enthusiasm, not a friend's result. This is rating rule 3 applied to your own file, and it is the rule you will be most tempted to break.

Date every change and keep the old version. A dossier with a history tells you something a current snapshot cannot: how you were wrong before, and in which direction. Almost everyone drifts consistently — some readers are systematically too generous with compounds they want to work, others systematically too harsh with anything that sounds like marketing. You cannot correct a bias you have never measured.

Review it when something happens, not on a schedule. A trial reads out, a drug is approved or withdrawn, a shortage resolves, someone asks you a question you cannot answer. Those are the moments the dossier earns its keep.

Expect to remove entries. A compound you stop caring about should come out. A dossier is a working file, not an archive.

C.7 The point of the exercise

You will not remember most of this book. That is normal, and the book was built expecting it.

What should survive is the shape of the twelve fields — the reflex that makes you ask, when somebody tells you a peptide does something, for whom, measured how, compared to what, and how would we know if it were false. That reflex is not about peptides. It transfers to supplements, to medical claims generally, to nutrition, to any field where confident people make specific claims about complicated systems and the specificity is doing more persuasive work than the evidence.

The dossier is the training apparatus. The reflex is the thing you keep.

Related: Chapter 5 (the method) · Chapter 6 (field 12, written early) · Chapter 37 (the master table, for comparison) · Chapter 39 (verdicts as questions) · Chapter 40 (full assembly) · Appendix A (the book's ratings) · Appendix F (red flags) · Appendix H (worked evaluations)