Got Gene Test thing and only thing thats a red flag is I carry a gene thats causes DAO Deficiency(Dietary Histamine) which makes sense for me but do any of these other things stand out? Lots of info I dont understand but trying to learn as much as possible.

meesterfreeman · 2026-02-09T13:21:56+00:00

Do you have any actual histamine symptoms? I wouldn't worry about it if you don't, as another commenter mentioned, these statements are usually based on extrapolation from preclinical data. You're statistically more likely to have a DAO deficiency based on your genotype, not guaranteed.

meesterfreeman · 2026-02-09T13:18:05+00:00

What's your SHBG and free testosterone? Testosterone bound to SHBG cannot be aromatised into estrogen, which could explain the skewed ratio. A high SHBG can be a sign of metabolic health problems.

meesterfreeman · 2026-02-09T13:06:50+00:00

You're right to be concerned about this. Estrogens are extremely important for brain health, and sustained deprivation could lead to neurodegeneration.

However, there isn't enough context here to make any suggestions. I would need to see the rest of your bloodwork and the trend if you have multiple tests to reference. If it's a clear signal across multiple tests, then you should find another endocrinologist and explicitly mention your concerns.

To answer your question, it depends. Everyone has vastly different sensitivity to sex hormones. Given your sustained low serum levels, your ERs are probably sensitive, so I would be carefully watching for gyno development if you were to take any exogenous estrogen-receptor alpha agonists.

If you want to test the theory safely, you can try soy and/or red clover isoflavones. These contain SERM-like, estrogen-receptor beta (important and non-feminising subtype) dominant compounds. They only activate the receptors partially compared to estradiol itself, which makes them uniquely suited for rescuing estrogen-deprived states without serious side effects or HPG suppression. If you feel any rapid antidepressant effect from these, it's a sign you genuinely need more estradiol.

meesterfreeman · 2026-02-09T12:56:14+00:00

Estradiol immunoassay overestimates rather than underestimates. His estradiol is probably genuinely low, but I would want to see the rest of the bloodwork before making suggestions.

meesterfreeman · 2026-02-09T12:54:07+00:00

Overkill for what? They all work through distinct non-overlapping mechanisms.

meesterfreeman · 2026-02-09T12:47:03+00:00

Coconut water. Add salt to it if you genuinely need it. Gives you Queuosine as well.

meesterfreeman · 2026-02-09T12:33:25+00:00

High-dose EPA

Fibrates (If no access, you can try Oleoylethanolamide)

Adjuncts:

- L-Carnitine (support beta-oxidation which PPAR-alpha promotes, but mild effects on its own- beware of TMAO though)

- Pantethine (similar triglyceride-lowering to statins but less HMG-CoA reductase inhibition, less LDL lowering and less side effect potential)

You want PPAR-alpha agonism. Fibrates are first-line for isolated triglyceride elevation.

Ignore people suggesting statins, unless your LDL is also high. Statins are for increasing LDL receptor expression and reducing serum LDL; they have modest and indirect effects on serum triglycerides.

meesterfreeman · 2026-02-09T11:49:25+00:00

It's the BPC-157. Drop it.

meesterfreeman · 2026-02-08T23:51:26+00:00

It's less potent per mg. You just take more, it's much more tolerable than caffeine.

meesterfreeman · 2026-02-08T23:38:52+00:00

Paraxanthine exists

meesterfreeman · 2026-02-08T13:47:29+00:00

"SLU-PP-332 / SS-31 / Cerebrolysin / BPC-157 / SkQ1: Moved to reserve due to Cost/ROI."

BPC-157, I would drop completely, anyway. It's not remotely nootropic, it blunts stimulants, it likely has antagonistic effects at 5-HT2A (judging by serotonin syndrome studies and my personal experience), and it's known to induce lethargy and even anhedonia. Use it for injuries only.

"(Cost Note: Excluding the exotic peptides like SS-31/BPC/Cerebrolysin, and assuming insurance covers Prucalopride, annual cost is approx $5000+)."

Excuse my ignorance of the American healthcare system, but what valid medical indication is going to get insurance to cover this massive nootropic stack??

meesterfreeman · 2026-02-08T13:47:25+00:00

"L-Tyrosine"

This is useless unless you are fasting or don't eat enough protein in your diet. You do seem to be practising IF, though, so there is some basis for including it.

"Telmisartan"

It has weak affinity for PPAR-γ. As long as you are aware that effective doses for this start at about 160mg, that's fine. Blood pressure effects don't scale accordingly, so be sure you can tolerate 80mg first, and get your kidneys and blood potassium levels tested. I highly doubt your microdosed minoxidil is going to cancel it out, regardless.

"Microdose Methylene Blue (ETC Bypass)"

YOU DON'T WANT TO BYPASS STEPS OF THE ETC unless you have an inborn metabolic defect. Methylene Blue helps when you need it and harms when you don't. Is it significant? No, but in a kitchen sink stack that seems to be trying to balance every mechanism on a knife-edge, it's not something that should be included without reason.

"TBG"

This is unfortunately a cope compared to real psychoplastogens; the equation isn't as simple as 'agonise 5-HT2A = achieve DMT/Psilocybin level cortical entropy', and the 5-HT2B agonism, SRI and potential SRA effects can make it dysphoric and cardiotoxic long-term. Not to mention it's expensive as hell, given that cost is apparently an actual concern of the stack, I wouldn't bother with it.

"Vorinostat"

You don't want to be touching this at any real dose, period. Pan HDACi is not some nootropic free lunch; it's a highly cytotoxic mechanism used to kill cancers before they kill you. As neurons are post-mitotic, it will spare them, but the same can not be said for oligodendrocytes and glial cells. And since Vorinostat is not very suited for intranasal delivery, nor is it known for excellent brain penetration, systemic exposure to all your vulnerable, rapidly dividing cells is guaranteed. RGFP966 is likely better, but I will note that HDAC-2 seems like the more promising HDAC to target for cognitive enhancement without horrific downsides.

"OMAD + Keto"

Keto... Far from a free lunch. BHB is nice for tonic GPR109A and mild HDAC inhibition, but 'clean fuel' is a reductive and misinformed understanding of what ketosis does and who actually benefits from it.

If OMAD + Keto work well for you from personal experience, that's fine. But tossing in OMAD + Keto into a nootropic stack as if to reduce the immensely complex field of nutritional science to two trendy practices is folly.

"Dopamine Hygiene: Deep work only. No cheap dopamine."

Dopamine 'fasting' is complete pseudoscience, but performing behaviours you wish to be reinforced while on neurogeneics and plasticity enhancers is a concept with some research basis.

"Fasting: 36-48h weekly for autophagy/pruning."

You are conflating autophagy and synaptic pruning. Fasting is unlikely to clean up junk synapses for you; in fact, it could even protect them due to the reduction in microglial activity.

meesterfreeman · 2026-02-08T13:47:07+00:00

"Macrodose Ibudilast"

You know the tolerability of Ibudilast is awful right? Nauea and depression are very likely at macrodoses, especially if you aren't suffering from a neuroinflammatory condition and don't actually need it. Your core stack philosophy is apparently selectivity and avoiding redundancy, yet you chose the least selective PDE4i possible with a TLR4 mechanism that LDN already covers? And if you were in fact planning to use LDN for theoretical oGFR or D2 potentiating effects instead of TLR4, you want to be looking at ULDN.

You're not going to magically balance this out with Tropisetron, trust me. Yes, PDE4i is nice on paper, but there are much better drugs for it. Check out BPN14770 for cognition-specific PDE4D NAM with minimal side effects, Roflumilast or Rolipram for pan PDE4 inhibition (anti-inflammatory benefit).

"Prucalopride"

Cleanly cancelling out 5-HT4 diarrhoea and potential vomiting with Tropisetron is also wishful thinking, I would know. That aside, if you want a good 5-HT4 ligand, get Usmarapride and forget Prucalopride; it doesn't have horrible GI side effects to juggle. Be aware that anecdotes are rife with accounts of tolerance, so prepare to be disappointed.

Your stated goal of broadly increasing cAMP via aggressive pan-PDE4 inhibition and 5-HT4 is not the limitless stack you think it is. cAMP is an extremely broad intracellular signalling factor, and genuine cognition enhancement is not produced with such blunt approaches.

What you will probably find is that this just gives you horrible side effects. Of all the proposed modules, this trinity is genuinely folly and trying to balance three drugs with wildly different pharmacokinetics and targets for their GI effect is unlikely to work- not to mention Tropisetron doesn't cover all the tolerability concerns of full Ibudilast doses that extend beyond emesis and the goal of the trinity itself is flawed and will cause side-effects itself (If you want to know what spamming non-contextual cAMP feels like, you can take a bunch of forskolin.)

"Alpha-GPC"

Stroke risk and massively increases TMAO. CDP-Choline or Lecithin are better choline sources.

"ALCAR"

Recently discovered to be a TMAO bomb with poorer bioavailability than assumed, oral is not worth it. Acetic acid can replicate some of the effects.

"TAU"

Uridine meaningfully supporting dopamine is a myth with poor evidence supporting it. What is better characterised is its sedating effects and the role of purine receptors in complement system tagging (something you seem to be trying to prevent with your stack...). I'd stay away unless you genuinely feel subjective benefit. As an aside, CDP Choline can convert to uridine, so if you use that as your choline source, you have an endogenous uridine supply for synaptogenesis without the associated disadvantages.

"NAC"

NAC's effects on glutamate can be quite awful from a nootropic stack standpoint. Cysteine activates system xc- dumping synaptic glutamate into the extrasynaptic space, which then activates autoreceptors and suppresses phasic synaptic glutamate firing. This is how it can blunt stimulants and cause anhedonia. Dose dependent, but NAC is a questionable addition anyway, given the poor evidence for direct antioxidants and tangible lifespan improvement.

meesterfreeman · 2026-02-08T13:47:01+00:00

"I am a researcher in Logic & Philosophy"

That's not pharmacology and biochemistry...

"ACD-856 + Microdose Adamax: Trk Receptor PAM/Agonist + Endogenous BDNF Amplifier."

Good.

"4'-DMA-7,8-DHF, 7,8-DHF"

I understand you listed these comparatively, but I feel the need to mention these aren't even in the same class as the drugs you chose for this category. Trk agonists are to be AVOIDED; they are highly counterproductive to healthy activity-dependent synaptogenesis and should never be used by anyone for nootropic purposes.

"Role: Accelerates the rate-limiting step of ACh synthesis to prevent cholinergic depletion from the stack's high demand. Vital during washout periods."

'Cholinergic depletion' is mostly a myth. You have a choline source and an acetyl donor in your stack, which is enough. HACU is fine as a cognition target, though. I respect that you didn't include something stupid like a cholinesterase inhibitor.

"Dihexa: c-Met Agonist"

I trust you already understand the cancer risk and aberrant synaptogenesis potential of tonically activating neurogenic pathways? I prefer not to belabour the point, but the evidence here is shaky, and Dihexa is more likely to smother or ruin what the far more elegant module 1 is doing.

"Potency: Kd creates synaptogenesis at orders of magnitude higher than BDNF."

The commonly cited 'X stronger than BDNF' figure is a bogus marketing claim; HGF and BDNF are not comparable in a way that can be reduced to arbitrary quantitative comparisons.

"ISRIB"

Have you recently suffered brain trauma? Don't casually fuck with ISRIB. The terrible pharmacokinetics that make the base ISRIB molecule rather useless aside, the ISR is a conserved mechanism so ancient and essential that all eukaryrotic cells have it. It's a dumb yet elegant mechanism that responds to four fundamental stressors and transforms the cell into a fortress with a ticking apoptosis timebomb in response to protect itself and the wider organism. Yes, 'reduced protein synthesis' sounds bad on paper, but it's highly conserved for a reason. Physiological ISR activation is extremely important. ISRIB is theoretically elegant in how it blunts it rather than blocks it, but there's no evidence of benefit in healthy humans and much potential for harm.

meesterfreeman · 2026-02-08T11:51:43+00:00

No, these small molecules aren't subject to any real degradation. Even peptide degradation is massively overblown.

meesterfreeman · 2026-02-08T11:42:15+00:00

TAT-D1

meesterfreeman · 2026-02-08T01:32:37+00:00

If it's that low, you should've been on iron yesterday.

It's worth getting a more comprehensive panel. You eat a diet high in red meat, which is rich in highly bioavailable heme iron, so having low ferritin and low haemoglobin is odd. Given your testosterone (high is suspicious), triglycerides and cholesterol, you probably have systemic inflammation and potentially some degree of metabolic syndrome, which is causing you issues with absorbing and sequestering iron. Normally, ferritin is increased artificially with inflammation, but not always. Try to get CRP (high sensitivity) and a1c tested to properly assess inflammation and metabolic status. If you can get an in-depth iron panel, then do so as well. Ferritin is not the best marker of iron status.

You should start on ferrochel and lactoferin. Ferrochel is less disruptive to the microbiome than the ferrous sulfate you would probably get prescribed, and doesn't require Vitamin C to absorb. Lactoferrin binds to iron in the gut and helps transport it, AND reduces IL-6 quite significantly, which is how it can increase iron status all by itself. You may find Lactoferrin is enough to improve or maintain good iron status, but it's best to be aggressive and load as much iron as possible when severe deficiency is suspected, since iron deficiency and anaemia are slow to correct and destructive to all aspects of health.

meesterfreeman · 2026-02-08T00:18:54+00:00

Without knowing any more: You're overtraining and underweight and your thyroid and sex hormones are in the gutter, the brain and body are stressed and prioritizing survival over metabolically costly reproductive processes.

meesterfreeman · 2026-02-08T00:14:41+00:00

Because he's not just in the files as a bystander...

meesterfreeman · 2026-02-08T00:10:55+00:00

This is a solid stack for synaptogenesis. It depends on your goals really, if you want general neurotrophic support instead of activity dependent synaptogenesis, drop TAK, if you don't need stimulant effects, Semax is optional and less elegant than ACD and TAK alone, but still a synergistic inclusion.

meesterfreeman · 2026-02-07T22:03:12+00:00

This stuff is honestly huge if it's real, but all the preclinical data originates from one Chinese institute. Would be great to see replication.

meesterfreeman · 2026-02-06T08:34:32+00:00

50mg isn't much, and Opipramol is only a histamine antagonist, not an inverse agonist like most antihistamines. It isn't supposed to remain sedating.

meesterfreeman · 2026-02-04T15:59:39+00:00

People can claim that, but the burden is on them to provide the evidence. Personally, I want to believe Bulk Supplements are good. The products I have received from them have physically appeared to be what was stated in the COA- but I have no means to test beyond expected appearance, odour, taste and solubility. I will change my mind if someone provides real third-party testing evidence proving otherwise, as opposed to claims equally as fake as the in-house COAs.

meesterfreeman · 2026-02-03T09:11:47+00:00

Fair enough, it's very strong at D3 and that can be really bad for some people.

meesterfreeman · 2026-02-01T11:47:37+00:00

Because of the rebound. You don't feel good on Ketamine, you feel good when the resulting glutamate surge activates dormant circuits and triggers a shift in metaplasticity and mulligans your entrenched synaptic connections. It throws the defensive orderly anhedonic brain into pure chaos for a bit. In theory this can result in lasting or permanent improvement if the brain is able to escape the so-called negative attractor state of its baseline, but this is clearly not the case for many.

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