Yes, it’s easy to be certain that what you get has a lot of DNP in it, but hard to be certain of the purity, for the reasons you mentioned.
As for how to measure the results. You could easily measure the results of doses used for weight loss, but for low doses used for longevity I doubt there is anything that you can measure that would give you an indication of whether it’s being of benefit and having the intended effect on uncoupling or not. This is unfortunately the case for a lot of longevity interventions.
Full study:
mito uncoupling.pdf (282.4 KB)
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Here’s a lengthy discussion involving two respected coaches about how to use BAM15 and SLU-PP-332. DNP is still available on the underground, but almost nobody touches it because, like you said, the dosing issues are rather scary.
When I listened to this episode @John_Hemming came to mind.
A rather remarkable claim by Alex is that he can reverse cancer with BAM15 and SLU, and that he has been invited to talk to a group of oncologists about it. Of course, he is also a bit of an LDL-C denier… Still, an interesting podcast episode.
https://www.instagram.com/p/DMr6rmOOOQv/?img_index=1
https://www.instagram.com/alex_kikel/p/DLZpoq2uDYS/
Kikel is an interesting character. I’m not a fan that he put all of his new content behind a $200 a month paywall so I don’t watch him anymore for the most part. I did enjoy some of his lectures.
I don’t know what to make of him. I think Dunning-Kruger is evident, but he also has a lot of success with clients and is at the forefront of experimentation, so I don’t want to discount what he says about peptides and research chems just because he’s wacky on some conventional topics.
Regardless, the podcast was informative regarding dosing for these compounds, and the back and forth between him and Anthony helped to draw out more detail.
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He gets a bit into woo-woo territory at times but the times I fact checked his health theories and claims it has checked out.
I do like his positivity towards longevity.
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Thanks for putting up the study. The median lifespan is much the same, but the mean increases and it looks like it has more of an impact in the mice which manage to survive the median lifespan.
I would think it is reasonable to say that it has a similar effect to caloric restriction, but there is then a question which is if you have the same restriction in energy inputs without the uncoupler is the effect of the uncoupler itself beneficial or harmful.
Personally I am not that bothered to find out as I don’t think this is a sensible intervention.
Here is O3 on the video
Below you’ll find three parts:
- a tidied, abridged transcript (cleaned up, organized by speaker and topic, with repetition and filler removed but the through-line preserved),
- a clear summary of the main positions and practical suggestions, and
- a constructive critique (what’s well-grounded, what’s speculative, and where to be careful).
If you’d like a full, cleaned transcript (timestamps stripped, lightly de-stuttered) as a downloadable text file, say the word and I’ll generate it.
1) Tidied (abridged) transcript — in order of the conversation
Host (DDT Method)
- Frames the episode as a discussion on the “great mitochondrial debate” with Alex and Anthony: how to use newer mitochondrial-targeted compounds (e.g., BAM15, SLU/SLU-PP-332, SS-31) and peptides/small molecules to improve energy, leanness, cognition—without overdoing it.
- Practical questions on dose ranges, stacking vs. separating BAM15 and SLU, and how to monitor benefit vs. harm.
What are people seeing with these compounds?
Alex
- We have stronger tools now (peptides/small molecules) that can override biology if overused.
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“Over-spinning” mitochondria (hyperpolarization) can make you wired/tired, unfocused—similar to taking too many nootropics.
- Dosing is highly individual and changes with your health over time. He gives personal dose examples: e.g., small SLU doses feel strong for him; higher SS-31 doses helped Anthony historically.
- Goal: find the sweet spot, not “more is better.”
Host
- Notes the wide anecdotal spread (micrograms to milligrams) and asks how to navigate it.
Alex
- Use community experience (“pharmaceutical mapping”) to set 80% guidelines, while accepting 20% outliers will differ. Start low, titrate.
How do we know if we’re helping vs. harming?
Anthony
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Use objective markers when possible: hs-CRP, IL-6, oxidized LDL, A1c, 8-OHdG (oxidative DNA damage).
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Simple proxies:
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Glucose curves: faster return to ~75–95 mg/dL and lower post-meal spikes suggest improved insulin sensitivity.
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VO₂max/RER or Lumen-type RER proxies: more metabolic flexibility (ability to oxidize fat at rest).
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Subjective flags that suggest overdoing it: brain fog, “can’t get air in” despite normal pulse ox, anxiety—can arise from ATP shortfalls and chemoreceptor dysregulation.
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Quality/purity caveat: many are research compounds; contaminants (e.g., LPS, metals) can outweigh benefits.
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Structure dictates function: SS-31 stabilizes cardiolipin, but you still need raw materials (phospholipids, fatty acids) to build healthy membranes.
Mitochondrial basics and “spinning”
Alex
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Recaps structure: outer/inner membranes; cristae surface area; matrix; electron transport → proton pumping → ATP synthase.
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Healthy inner-membrane potential often cited around ~150–200 mV (literature varies).
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Too low (hypopolarization): trends to apoptosis.
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Too high (hyperpolarization): excess ROS from electron/proton leak (his “over-spinning”).
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JC-1 dye can index polarization (red = higher Δψm; green = lower).
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Compound effects (high-level):
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SLU/SLU-PP-332 tends to increase mitochondrial activity/biogenesis signaling.
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BAM15 is an uncoupler that slightly lowers membrane potential (he cites a few mV) and increases oxygen consumption/heat.
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Hormones matter: insulin and testosterone can influence gradients/flux; stacks can potentiate effects → go low and slow.
Host
- Re-emphasizes: foundations and “little things” (e.g., SOD support via spirulina; antioxidant strategies) can be “game-changers.”
Biogenesis, fission/fusion, refeeds & diet cycling
Anthony
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Low energy → AMPK → ↑ lipolysis/glycolysis and signals PGC-1α → biogenesis. mTOR supports growth/repair (muscle, myelination, memory).
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Fission–mitophagy–fusion cycle: divide → remove bad parts → fuse good parts into more efficient super-complexes.
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Dieting plateaus often reflect excess fission without adequate fusion; planned refeeds help drive fusion and restore efficiency.
- Practical calorie cycling template (from Dr. Seeds): 3-day blocks at 50%, 100%, 75%, 100%, 50%, 110%—with macros tailored to training stimulus (N1 style: neuro / hypertrophy / metabolic).
Alex
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Refeed physiology: phosphate repletion spikes membrane potential and promotes better fusion/fission cycling.
- You can amplify fasts or mimic fasting benefits with tools (exogenous ketones, polyamines, carnitine, etc.), but match to the person.
“If I fast then refeed, what would you add?”
Alex (sample fast → refeed scaffolding)
- During the fast (duration individualized): exogenous ketones, GH/peptide axis (context-dependent), polyamines (e.g., spermidine/spermine), autophagy supports, MCTs, mild oxygen/CO₂ techniques; possibly yohimbine; conclude with insulin-sensitizing agents (berberine/metformin or insulin in advanced/clinical contexts) to transition into refeed.
- During refeed: aim for glycogen restoration and anabolism while keeping fat oxidation efficient; consider carnitine to “shuttle” fuels.
Anthony
- Prefers modulated intake rather than full 24-h fasts for most athletes; keep detox and recovery substrate coming.
- Macros by training day type (more carbs post-lift; more fats on off-days for neural/plasmalogen rebuilding).
The BAM15 + SLU question
Alex (pro-combo, with strict dosing)
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BAM15 uses: fat loss via uncoupling; potential neurological benefits; nutrient partitioning at micro-doses; oncology interest.
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SLU-PP-332 (“SLU”) uses: signals PGC-1α and related pathways; supports biogenesis and mitochondrial function; claims tissue-repair effects.
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Together: sees them as complementary (one “bleeds” energy, the other “fortifies/activates”), but they potentiate each other → start very low (e.g., on the order of ~tens of mg BAM15 with ~100 μg SLU in his examples) and titrate only if well-tolerated. If intolerant, separate them by day.
Anthony (contra-combo, pro-separation)
- Mechanistically opposed commands: uncoupling (BAM15) reduces ATP efficiency while SLU increases ATP production and demand; running both simultaneously risks excess ROS, depletion of glutathione/NADPH/SOD/catalase, and maladaptive mitochondrial remodeling.
- Recommends separating usage: SLU on training days; BAM15 on off days (≤ ~2×/wk), citing half-life differences (BAM15 ~1 h; SLU longer).
- Before any of it, build the structure (membranes, phospholipids, fatty acids), hydrate (osmolytes), and ensure fuel availability (beta-oxidation competence).
- Supportive stack ideas: morning low-dose leucine + fasted walk (AMPK); injectable carnitine; 5-amino-1MQ (↑ NAD availability; “shrinks adipocytes” claim); ketone esters (optimize NAD+/NADH; activate NRF2 antioxidant program); telmisartan (PPAR signaling & BP lowering; brain-penetrant); idebenone/CoQ10, PQQ, urolithin A, evening melatonin.
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Overuse signatures: brain fog, unexplained fatigue despite sleep/intake adjustments; sometimes worsened A1c or 8-OHdG.
Host (clarifies risk)
- Are we talking “you’ll get cancer” vs. “you’ll feel awful”?
Anthony: Not instant cancer; think progressive metabolic/structural harm if chronically overdone.
Alex (rebuttal)
- Emphasizes dose and context; cites cases with good results (including serious conditions) but agrees foundations and careful titration matter.
- If combining creates issues, don’t, or alternate by day.
If someone insists on combining, how to be safer?
Anthony
- Wouldn’t recommend it. If someone is going to anyway: lean heavily on ketone esters (K4/Kinetic Pro), structural lipids (phosphatidylcholine, plasmalogens, omega-rich oils), hydration/osmolytes, melatonin, urolithin A, PQQ, CoQ10/idebenone, carnitine, consider telmisartan/5-amino-1MQ, and monitor labs (oxidative stress panels, mitochondrial function kits), plus glucose and symptoms.
Alex (if separating)
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Rest days: BAM15 + ketones; thyroid support (if appropriate), carnitine, brain support (e.g., J147 in his practice).
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Training days: SLU; possibly GH/peptides (context-dependent). Mentions advanced bodybuilding add-ons (IGF-1 DES targeted, HA injections)—not for general use.
Closing
- All agree on respectful disagreement, individual response, and foundations first.
- Brief plugs: Anthony’s new products (including SLU + urolithin A formula; structural/hydration/sleep lines); Alex’s members forum and work with teams; both working on mitochondrial research angles.
2) Summary — what you should take away
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Core disagreement:
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Alex: BAM15 + SLU can be synergistic at very low doses in the right context; if not tolerated, split them.
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Anthony: Because mechanisms are opposed, co-administration increases ROS risk and impairs remodeling; separate them (SLU on training days, BAM15 on rest days ≤2×/wk).
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Everyone agrees on:
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Start low, go slow. Dosing is individual and state-dependent.
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Foundations first: sleep, light, training that matches the goal, hydration, electrolytes/osmolytes, membrane builders (phospholipids/plasmalogens/PUFAs), micronutrients.
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Measure something: glucose dynamics; VO₂max/RER (or a proxy); subjective signs (focus vs. fog, energy vs. wired/tired).
- Most of these compounds are research chemicals; purity matters.
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Mechanistic frame: Mitochondria require healthy structure (membranes/cristae) and balanced fission–mitophagy–fusion to get more efficient. Over- or under-polarizing hurts.
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Diet/training tactics:
- Calorie cycling (e.g., 3-day 50/100/75/100/50/110% blocks) to encourage proper fission–fusion balance.
- Refeeds replete phosphate and help drive fusion. Align macros with training stimulus (neuro vs. hypertrophy vs. metabolic).
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Practical stacks highlighted (illustrative, not endorsements):
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Support biogenesis and antioxidant tone: urolithin A, PQQ, CoQ10/idebenone, melatonin.
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Fuel delivery/oxidation: carnitine, exogenous ketones (specific ester blends), low-dose leucine + fasted walk for AMPK.
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Signals: telmisartan (PPAR & BP), 5-amino-1MQ (investigational), GH/peptides in specific athletic contexts (specialist supervision).
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When to stop/taper: brain fog, persistent wired-tired, worsened glucose control, rising oxidative stress markers—back off and re-establish foundations.
3) Critique — strengths, gaps, and cautions
What’s strong/helpful
- The “structure before function” message is sound. Membrane lipids and mitochondrial quality control underpin any benefit from signaling drugs.
- Emphasis on monitoring (glucose/RER, subjective cognition/energy) is practical and safer than blind dosing.
- Framing fission–mitophagy–fusion and refeeds to sustain mitochondrial efficiency aligns with current physiological thinking.
- The separation strategy (SLU on work days, BAM15 on rest days) is a conservative, mechanistically coherent way to avoid forcing competing commands.
What’s speculative / needs stronger evidence
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SLU-PP-332 and BAM15: promising preclinical tools, but human safety/efficacy data are limited. Discussions of multi-organ or long-term benefits are largely extrapolations.
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Combining BAM15 + SLU: there are no rigorous human data on the combo. Alex’s positive cases are encouraging but anecdotal and often amid heavy polypharmacy. Anthony’s caution is mechanistically grounded.
- Several add-ons mentioned (5-amino-1MQ, J147, high-dose melatonin, IGF-1 DES targeting) are research-stage/off-label with uncertain long-term risk.
Points that could confuse a general audience (worth clarifying)
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Telmisartan acts primarily as an angiotensin II receptor blocker with PPAR-γ partial agonism; benefits on metabolic tone are plausible, but it remains a prescription antihypertensive—not a casual supplement.
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Leucine → AMPK: leucine is classically mTOR-activating at customary doses; the “low-dose leucine for AMPK” point is interesting but dose- and context-specific and not a general rule.
- Devices like Lumen provide RER-like signals but are proxies; they can trend directionally but aren’t equivalent to lab gas-exchange testing.
- Claims about “new genetics every ~10 years” and some epigenetic simplifications were discussed informally; treat as speculative.
Safety & sourcing
- The warning about contaminants in gray-market peptides/small molecules is important. If one chooses to experiment, analytical reports and medical oversight matter.
- Stacking stimulatory mitochondrial agents can backfire: if you notice brain fog, anxiety, palpitations, or exercise intolerance, stop/taper and re-establish sleep, nutrition, hydration, and training balance.
Pragmatic alternative for most people
- Prioritize: sleep regularity, morning light, periodized training matched to macros, omega-3s/phospholipids, creatine, carnitine (if low), protein adequacy, and perhaps urolithin A/CoQ10/PQQ/melatonin under guidance.
- If experimenting with either BAM15-like uncoupling or SLU-like signaling, trial them separately, log dose/response (energy, focus, glucose curve), and cycle off if benefits fade or side effects emerge.
Want the full cleaned transcript?
I can produce a downloadable text file that strips the timestamps and tidies the prose (no content removed). Just say “yes—generate the full tidy transcript,” and I’ll share a link.
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Thomas Seyfried has a hypothesis that a lot of cancer is mitochondrial.
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The ITP tested DNP in the 2020 cohort and found no increase in lifespan.
I’ve taken it before, I wouldn’t recommend it, especially with GLP-1’s available
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If someone really wants DNP sources I can suggest a couple, but you’d have to send at least 3 capsules out for testing. 200mg is the standard size.
SS-31 repairs the DNA, not sure if it was meant to be lumped with uncouplers. (I do 40mg daily for two weeks, 4x a year and certainly isn’t an uncoupler)
Most of these ‘Influencers’ are sellouts. They pump stupid, mostly abandoned (for the purpose they want you to take them) chemicals and usually own research peptide sites that build the exact chemicals into products for profit.
I have lab tested 20mg SLU-PP-332 and 100MG does nothing. Tried a few other mcg versions and nothing. So maybe it’s just me, but total snake oil.
BAM15 might be real, but all the RAW’s I have found are out of this world priced for the dosage a human would need.
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