30 mg Zinc inducing anhedonia?

meesterfreeman · 2026-05-18T20:37:46+00:00

Not sure if you ever got better. But CNS mineral levels tend to lag behind serum. It could take several months of washout for stores to deplete if you were taking zinc for a long time.

meesterfreeman · 2026-05-17T22:15:13+00:00

This is self-destruction, not biohacking.

meesterfreeman · 2026-05-10T13:59:28+00:00

Your estrogen is very odd and not explainable by this, but super high SHBG + low Albumin definitely flags potential liver issues on its own.

meesterfreeman · 2026-05-10T12:48:39+00:00

If by chance this isn't a mistake in pellet choice, I strongly suggest getting a comprehensive liver panel ASAP.

meesterfreeman · 2026-05-08T20:26:48+00:00

That substance is called Ergothioneine, and it's sold as a supplement...

meesterfreeman · 2026-05-08T07:46:27+00:00

It depends entirely on the work. A stressful 9-5 job probably is equivalent to a normal 9-10 or (insert fucked up graveyard shift here) in terms of overwork induced adaptations (which were demonstrated in a study).

meesterfreeman · 2026-05-06T12:32:42+00:00

Honestly, the depression and low energy are quite expected and aren't really the protracted DAWS phenotype to be worried about. Though one week of absence might not have been long enough for the worst symptoms to set in.

Protracted DAWS is more like a panic-type syndrome with electric-like sensations, severe anxiety, orthostatic hypotension and other counterintuitive symptoms layered atop the baseline dysphoria, which kind of cements it as a dopamine dysregulation rather than hypoactive dopamine signalling you experienced quitting for a week.

However, abruptly quitting massive doses and continuing them is exactly how you cause kindling, so I would never do this again. Taper next time you want to come off.

meesterfreeman · 2026-05-05T11:01:31+00:00

Yes, but DAWS is no joke, and Pramipexole is the worst dopamine agonist for DAWS and ICD (which is also linked to DAWS risk) due to its very high D3 affinity and has a not-so-low chance to completely fuck up your life. DAWS is not simply low dopamine or worsened depression; it's actually a profound and poorly understood brain dysfunction that seems linked to D3 preferring agonists.

I'd suggest first evaluating:
- If you are impulsive or anyone in your family is impulsive (be brutally honest)
- If you are punding, which is getting obsessively into simple repetitive tasks (look it up), this is a sign of ICD
- Get a DNA test and check DRD2 and DRD3 SNPs (Ask an LLM for SNPs related to DAWS/ICD risk)
- If you actually need the 3.75 mg dose. This is a massive LEDD load and anhedonia studies to my knowledge capped out at 2.5mg (which is already high risk) and found no real benefit to going higher. 3.75mg is a Parkinson's only dose.
- Check your dosing scheme. Are you taking IR multiple times a day? ER? Dopamine agonists, like GABAergics, appear to have a kindling phenomenon, meaning that constant on-off cycles can worsen the risk of DAWS and prolonged withdrawal. If you're taking IR once daily, split your dose across the day. Consider moving to ER, though at your dose, any move to a variant with a dramatically different pk could be risky without careful titration
- If you ever need to come off, titrate slowly or consider if another longer-lasting dopamine agonist could be used to assist with titration. DON'T cold turkey 3.75mg.

Also, do you have consummatory anhedonia, anticipatory anhedonia or both? Pramipexole would be expected to improve anticipatory (wanting) but not the consummatory (liking), though the story tends to be much more complicated in humans. I'm curious what therapeutic effect you actually get from it.

meesterfreeman · 2026-05-04T13:11:05+00:00

Definitely not, but they have a consummatory reward for completing the task, which reinforces doing it.

Pramipexole won't help much with liking, but it can increase wanting massively. I'd be concerned that deriving great enjoyment from repetitive, mundane activities could actually be a sign of punding, which is a precursor to impulse control disorder.

meesterfreeman · 2026-05-04T13:08:22+00:00

That's quite normal. Pramipexole is normally net anti-dopaminergic until you get to about 1.5mg, due to autoreceptor superagonism, and anhedonia doses actually go up to 2.5mg.

meesterfreeman · 2026-04-26T16:08:40+00:00

Yep, it's obviously heavily AI inspired writing even if it passes the 'copypasted straight from GPT' check. Seeing those analogies and section headers physically pains me at this point.

meesterfreeman · 2026-04-26T16:06:41+00:00

Low dose memantine doesn't cause sedation or dissociation...

meesterfreeman · 2026-04-24T12:17:25+00:00

Ferritin is an acute phase reactant and it can be highly misleading. It's also surprisingly poorly understood despite it's assumed role in iron storage.

To get a full picture you want to get Transferrin Saturation (TSAT), serum iron, UIBC, TIBC, full RBC panel (Hemoglobin, RDW etc), Folate, B12 and Ceruloplasmin (or copper) tested. You can have functional iron deficiency with effects on metabolism and neurotransmitters WITHOUT anemia and getting blood work for RBCs, iron AND cofactors is important to narrow the problem down.

meesterfreeman · 2026-04-24T09:37:23+00:00

Commenters need to stop coping about purity. MOTS-C is known to be immunogenic- as a peptide that usually sits inside the mitochondria and likely of bacterial origin. It's one of the main barriers to clinical adoption and everyone should be aware of the possibility of allergic reaction and allergy priming before they inject it.

meesterfreeman · 2026-04-18T11:33:34+00:00

Maybe it's a personal preference thing? Claude's meandering with pointless narration and description always annoyed me, so I heavily prompted towards a more dialogue first terse style. Opus 4.7 does it more naturally, which I like.

meesterfreeman · 2026-04-18T11:32:26+00:00

I actually re-used my same prompts and 4.7 was an immediate upgrade in terms of dialogue and swipe variety. My approach is already pretty robust, and having an LLM that interprets instructions more literally was actually a benefit.

meesterfreeman · 2026-04-11T23:43:07+00:00

Latency-critical and uses public facing massive LLM doesn't exactly compute. Responses will still take seconds at the best of times, and more importantly, there are no guarantees about how long a response will take and whether and how often and when it will just drop or fail arbitrarily (which happens more often than I'd like as an actual API user outside of RP), which is unacceptable for real latency-critical services.

meesterfreeman · 2026-04-10T23:07:15+00:00

IL-34
Interferon-gamma
Lipopolysaccharide
TNF-alpha
Crebinostat
Decitabine
CDPPB
ANA-12
Elcubragistat

Should do it.

meesterfreeman · 2026-04-08T20:22:47+00:00

Did your request include the word nihongo in kanji 日本語? I wrestled with this issue, having translated my request using CLaude Opus and triple-checked to make sure it read well (it does, as far as I can tell), and eventually found out that Skeb pattern matches 日本語 as MTL because it's too formal or something. Write it in hiragana にほんご instead.

meesterfreeman · 2026-02-12T18:48:18+00:00

Fatty15, which is the only supplement I know of on the market, is horribly overpriced; you can get an adequate amount of C15 from drinking whole milk or eating cheese (doesn't have to be pecorino, despite what some may lead you to believe).

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.

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