Open questions
What we still don't know.
The opposite of every supplier blog. Where the evidence is thin, where experts say they don't have an answer, where long-term safety is unmapped territory.
How we tag uncertainty
- No human RCT
- Animal data only or anecdote. Don't extrapolate.
- Contested
- Experts disagree. Real evidence on both sides.
- Extrapolated
- Conclusions drawn from related compounds or short trials.
- Long-term unknown
- Short-term safety established. Long-term effects unmapped.
- Mechanism unclear
- We see the effect. We don't fully understand why.
No human RCT
· 5Animal data only or anecdote. Don't extrapolate.
SLU-PP-332 human safety + dosing
SLU-PP-332 →What's the actual safe human dose, and what are the long-term effects?
Zero human RCTs exist. Castore (EliteFTS) explicitly says animal-to-human dose conversion is unreliable — people are extrapolating from mouse studies. Brain fog at high doses suggests neuronal glucose depletion but the threshold isn't characterized.
Flagged by · Anthony Castore (EliteFTS)
Survodutide vs Retatrutide
Is Survodutide (GLP-1/glucagon dual) better or worse than Retatrutide for body composition?
No head-to-head trial. Survodutide's MASH (liver disease) approval will likely come before obesity approval. Muscle preservation data is thin compared to tirzepatide. Not yet a real-world option for most.
Flagged by · Industry analysts
CagriSema lean mass preservation
Does adding cagrilintide (amylin analog) to semaglutide protect lean mass better than tirzepatide?
Phase 3 data shows 22.7% weight loss — exceeds either drug alone. But the lean mass partition isn't published. Long-term nausea/GI profile with dual-pathway suppression also unclear.
Flagged by · Jay Campbell, Tyna Moore (implied)
Klotho human supplementation outcomes
Klotho →Does exogenous Klotho actually replicate the longevity benefits seen in observational data?
Strong observational data correlates serum Klotho with healthspan. Jay Campbell reports significant subjective improvement after 4 months. Limited human RCT data on supplementation. The albumin-bound 19-day half-life version is new enough that long-term outcomes don't exist yet.
Flagged by · Jay Campbell (early adopter, optimistic)
KPV vs BPC-157 for inflammation
KPV →Is KPV actually superior to BPC-157 for systemic inflammation, as Hunter Williams claims?
Hunter Williams rates KPV above BPC-157 specifically for inflammation. No head-to-head RCT exists. Most other experts treat them as complements (KPV = fire extinguisher, BPC = construction crew) rather than competitors.
Flagged by · Hunter Williams
Contested
· 5Experts disagree. Real evidence on both sides.
MOTS-c optimal dose range
MOTS-c →Why does the recommended dose range span 40x — from 1mg to 40mg?
Trigili and JD Denham use 1mg 5x/week. Enhanced Man uses 10mg once/week. Some protocols call for 40mg. The variance comes from sourcing, not from any consensus on what works. Plus: cancer risk is theoretical (AMPK/mTOR is the same pathway tumors exploit) and unstudied long-term.
Flagged by · Bachmeyer, Froese, Jones DC, Enhanced Man
IGF-1 LR3 and cancer risk
Retatrutide →Does pharmacologic IGF-1 elevation cause cancer, or is the IGF-1/cancer link from underlying metabolic dysfunction?
Bachmeyer cites a 600,000-person observational study showing no causal IGF-1/cancer link. Other experts (Tatem, Williams) remain cautious — IGF-1 is permissive for cell replication including malignant cells. Distinction between epidemiological correlation and causation is unresolved.
Flagged by · Bachmeyer (skeptical), Tatem (cautious)
LDL on TRT — particle size vs total cholesterol
Is elevated LDL on TRT acceptable if particle size is favorable, or does total LDL still drive plaque?
Jay Campbell and Hunter Williams: only particle size and inflammation matter; standard lipid panels are a distraction. Layne Norton, Talking With Docs: LDL causes plaque even in metabolically healthy lean mass hyperresponders — the LMHR group grew 18mm plaque/year. Get an ApoB and calcium score to settle it for yourself.
Flagged by · Norton, Talking With Docs (skeptical of TRT-only framing)
Russian bioregulators — actual mechanism
Do Russian oral peptides (Epitalon, etc.) actually work, or is it 'mostly marketing hype'?
Dr. Greg Seeds: 'science from a single researcher, never replicated.' Jay Campbell has moved toward US-manufactured versions claiming Russian blister packs are underdosed. The mechanism is plausible but the supply chain and replication failures muddy the evidence.
Flagged by · Greg Seeds (skeptical), Jay Campbell (cautiously optimistic)
MK-677 / Ibutamoren in 35+ users
Is MK-677 ever appropriate, given the insulin resistance and water retention findings?
JD Denham uses ~25mg nightly for 35+ clients not actively cutting. Dr. Tatem ran a personal trial and hit pre-diabetic A1C — banned from compounding 2023. Whether the muscle/sleep benefits ever outweigh the metabolic harm is contested.
Flagged by · Tatem (against), JD Denham (for, narrow use case)
Long-term unknown
· 3Short-term safety established. Long-term effects unmapped.
Retatrutide long-term neurological effects
Retatrutide →Does chronic GLP-1 + GIP + glucagon receptor activation shrink the 'willpower region' of the brain?
Hunter Williams flags this concern publicly. No formal study exists. Off-ramp taper protocols also unestablished — what happens when you stop is unmapped territory.
Flagged by · Hunter Williams
BPC-157 long-term human safety
BPC-157 →What happens after 5+ years of continuous low-dose BPC-157?
All of the human safety data is anecdotal. Bachmeyer treats it as a 'forever peptide' at low continuous dose; others (Trigili, Jay Campbell) recommend cycling. No RCT has tracked >12 months. The dopamine modulation note (skip on antidepressants) suggests CNS effects we haven't fully characterized.
Flagged by · Universal — no expert claims they have long-term safety data
Semax long-term receptor habituation
Semax →If Semax is run continuously, do BDNF receptors permanently down-regulate, or recover with breaks?
Dr. Jones DC calls Semax 'temporary fertilizer' — cyclical only. The 1 month on / 1 week off protocol is empirically derived but not validated by RCT. Whether this rest interval is sufficient for full receptor recovery is unknown.
Flagged by · Jones DC, Bachmeyer
Mechanism unclear
· 2We see the effect. We don't fully understand why.
High-dose chronic GLP-1 mechanism of harm
Is the SIBO/gallbladder/muscle loss damage from GLP-1s dose-dependent, or duration-dependent?
Tyna Moore estimates 45–50% of long-term high-dose users develop SIBO. The pharma dosing protocols 'maximize revenue, not outcomes' (Moore). But whether this is dose, duration, or stack-context driven isn't characterized — and the FDA-approved dose escalation protocol may itself be the problem.
Flagged by · Tyna Moore, Jay Campbell, Jones DC
DSIP — optimal individual dosing
Is DSIP timing morning or evening, and how do you find your personal sweet spot?
Bachmeyer: 10 days on / 5 days off. Enhanced Man: 5 weeks on / 7 weeks off. Tolerance builds quickly above 250 mcg. Both experts explicitly say timing requires individual experimentation — they don't have a protocol that generalizes.
Flagged by · Bachmeyer, Enhanced Man
Why we publish this.
Most peptide content online claims certainty it doesn't have. We'd rather tell you exactly where the evidence ends — so you can decide what risk you're willing to absorb.
When new RCT data lands, we update these entries. When an expert flips position, we update. The list grows; entries get retired only when there's actual data to retire them with.