#5

Hello Beth, thx for pointing this link out it’s really rich! - These are the supplements I take with regard to APOE4,

Spermidine 5.5 mg
Selenium (200 ųg) (every 3 days)
omega 3 1126mg/ epa 670/ dha 330
Noopeptide 20 mg
Alpha gpc 200 mg (every 3 days)
phosphatidylserine (150mg)
Bacopa 20:1 400 mg
L-theanine 500 mg

but I might need to increase omega 3 and spermidine and possibly vitamin D? although I’m also starting to think I’m already taking a lot of supplements and I might be triggering the immune system too much and hence psoriasis? I’m not sure…I might need some testing to figure it out… I’m also wondering if taking Rapa Acarbose and Metformin needs a reduction in my supplement regimen or not…

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#6

I probably know less about all this than everyone else here, so I can’t offer anything too useful, but I’ll say that the overwhelming majority of people on here are on rapa and acarbose (fewer on metformin) and 1,555,883,999 supplements :). You’ll soon discover this.

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#7

I recommend you read this thread: Predicting Alzheimers & Dementia (and minimizing risk)

Also - I would work to simplify your supplement protocol. For example - Fisetin has no strong data behind it. You can watch this video to learn more about senolytics and fisetin specifically:

NMN and NAD precursors, also highly questionable, see this part of the video:

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#8

thx a lot! Incredible resources, I’m digging them…

on another note, I saw that recently Rapa seemed to perform badly on several clocks and I probably missed a thread about that on this forum? It seems that it didn’t concern anybody here so I’m sure there’s some flaw in the assessment of the drug’s effects on those trials…?

#9

Right, no concern about clocks. Also: the value of the clocks themselves hovers around zero. If you listen to that yt video RapAdmin posted above, this is extensively discussed. It really pays to explore the resources provided, because they answer many questions one might have. Good questions, though!

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#10

Yes - see this discussion: The Effect of longevity interventions on epigenetic clocks (BioRxiv) - #9 by Neo

also this one: Bryan Johnson stops rapamycin

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#11

One thing I would be concerned about is your cardiovascular disease risk. Your cholesterol seems towards the high end and you may want to consider something like Bempedoic Acid and Ezetemibe (1 pill). They can be cheaply and easily ordered from India.

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#12

Hi, to boost your immunity to combat the inverse psoriasis, you could consider injectable gluthatione,
it costs 44 euro in Italy and my pharmacy in Belgium can sell it to me at the same price;

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#13

With your inverse psoriasis and increased cardiovascular risk with that diagnosis alone, combined with elevated LDL and HTN, I would think about adding a statin.

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#14

This looks really interesting especially as my supplementation didn’t seem to replenish enough my gluthatione levels - I didn’t proceed with that idea yet cause I need a nurse to inject it for me and probably a prescription to get it…but your input revived the idea and I think it’s one of the right thing to do so thx for bringing that up!

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#15

Thx for this - I’m reading about statin and ezetimibe and it feels that the latter might have less side effects and achieve the same results…? In anycase I’m
seriously considering adding metformin and ezetimibe now to my protocol, I’m going for some blood test next week and track my glucose levels with a glucometer starting tmw and figure the next steps in terms of ordering those meds from India if I can’t get them prescribed here in Italy…

All your replies have been really helpful and motivating and I’m grateful for all of them :pray:

#16

You could also consider this if you what to avoid getting a prescription / nurse for the injection;

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#17

You can overdose on glutathione, so I prefer to take the precursors, glycine and NAC, and let my body produce as much glutathione as it needs.

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#18

After supplementing with 500 mg-1g of liposomal glutathione, 600 mg NAC, and 3 g glycine daily, beside everything else listed above, my GPX levels came back low at 21.2 (reference range: 76-904). Meanwhile, my GR was 100 (range: 12.7-487), suggesting my system has an hard time to both absorb GR and convert to GPX (expected) despite supplementation.

Given this, I’ve switched to 100 mg of S-acetyl glutathione to replace my questionable-quality liposomal glutathione, though I’m pretty sure this dosage may be too low for my needs. I’m testing my levels again at the end of the week and considering IV or suppositories to boost levels before figuring out long-term maintenance.

Meanwhile testing my glucose levels to probably move forward with Metformin…

Thx a lot for your input! Will keep updating…

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#19

Like everything, it needs to be balanced accordingly. A doctor told me that before the “no needles policy” in cycling, cyclists in the Tour de France, used 600mg every day ( so 22 days in a row) with great succes

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#20

I use a brand called Bempetol-EZ that combines the two (Bempedoic Acid 180mg + Ezetimibe 10mg). Generic version of NEXLIZET

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#21

You’re taking quite a big stack of supplements. I would carefully add additional drugs/supplements one-by-one and test them if they meet your target goals

  • LDL 115 mg/dL would be considered on a higher side (if you consider PESA study where the safer levels appears to be under 60 mg/dL). Many people on this forum (including myself) take Rosovastatin 5mg, and to get additional lipid lowering effect (without needing to bump up statin dose), you could add Ezetimibe 10mg, and if necessary Bempedoic acid 180mg as well. You could add one or two of these, take them for a couple of weeks, and test your LDL-c or Apo(B) levels (which are cheap tests to do) and see what sort of lipid lowering effect you get, and then titrate accordingly. Psyllium husk (if you can tolerate fibre) can also offer a small lipid loweing effect

  • Note that Berberine that you’re taking also has a small lipid lowering effect. I would suggest dihydroberberine (instead of regular berberine) due to better absorption, and smaller 1/5th dosage will do the same job, and much less chances of developing liver toxicity (in theory, I haven’t tested that).

  • For rapamycin, I suggest starting with a very low dose (1mg or 2mg per week) and gradually work your way up to your target dose (the popular range for people this forum is roughly 5mg-8mg). Look out for any side effects. There are many blogs on this forum to get started.

  • You haven’t shared any info on your metabolic parameters (like fasting insulin and HBA1C). I assume you want to include metformin and acarbose for generally longevity effects. For some people, these drugs can mitigate the potential hyperglycaemic response (which may be a benovalent response) to taking rapamycin. But in my case, rapa doesn’t seem to affect my glucose parameters. In your case, as a very active individual following a good diet, you may want to decide if you really need these drugs

  • Given your methylation is impaired (which is the case with me as well, heterozygous for MTHFR A1298C), some of the methylation support supplements you’re taking makes sense. E.g. L-methylfolate, TMG, Alpha-GPC

  • I agree with the comment already mentioned on this page that Glycine + NAC as precursors to glutathione (indirect effect), may be a better option compared to taking glutathione (direct effect), so that the body can regulate and produce enough glutathione on a supply-demand basis. In addition, oral gluathione brands are generally poorly absorbed

  • Urolithin-A: The science for this doesn’t appear to be very strong. Some people anecdotally claim benefits, but it is hard to tell. Also very expensive

  • In terms of some of the other supplements you’re taking (such as plant phenols and antioxidants), there is mixed opinion as to whether they are needed / move the needle. E.g. CoQ10, Vitamin C, Bacopa, probiotics, etc. But if they’re helping with your conditions, then well and good.

In general, keep an eye on liver enzymes and kidney function tests (both cheap tests) when you’re taking a lot of drugs and supplements.

Just my 2 cents

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#22

@snax444 You took the words right out of my mouth. Excellent post! :slight_smile:

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#23

Hello, and thanks for your generous insights—I really appreciate it!

  • LDL: I’m not doing too well—my levels have been hovering between 115 and 121 in my last two tests, despite berberine (I didn’t know about the dihydro form, I will look into that!), omega-3, exercise, and a solid diet. I’ve been discussing pharmacological options with my doctor, but so far, I’ve only managed to get prescribed ezetimibe, which I doubt will be enough to reach ~70. He proposed a statin, but I’ve read here that they affect desmosterol and are not recommended for APOE4 carriers. I’d much rather follow your suggestion of BA + ezetimibe (NEXLIZET) - thanks a lot for that! Now I just need to convince him…

  • HbA1c: Currently at 5.5%. Fasting glucose ranges from 84 on a good day to 100 on a bad one. I hit 199 after a 200g carb meal, which pushed me to start metformin 4x/week based on the info I found here. I’m happy with the results and think I can optimize my A1c at ~5% or lower. I’ll test again soon. It also seems beneficial for improving leaky gut, and I kind of feel it.

  • Methylation: This is an ongoing battle. A few months ago, my homocysteine was at 14 (range 4-15.40), and I managed to bring it down to 11.8 by increasing TMG to 1g. Now I’m upping it to 2g, hoping to get below 10 and closer to 9. My folate was at 14.9 (range: 4.6–18.7) and B12 at 357 (range: 191–663). I think I could increase B12 a bit and want to switch to hydroxocobalamin, which seems optimal for MTHFR and COMT. How are you managing your homocysteine and related markers with MTHFR?

  • Rapamycin: I’ve been tempted for a while but I am unsure how I’ll handle my lipids—especially given my genetic predisposition to diabetes, and also my glucose…

  • Glutathione: My GPX levels came back low (21.2, reference range: 76–904). Poor oral absorption is a real issue, and I can’t get the recommended suppository shipped to Italy. I might move to Tationil injections for a quicker boost, though they require some prep. Waiting on my latest test results - I’ve recently switched from liposomal glutathione to S-acetyl-glutathione. I take glycine and NAC daily, but they don’t seem to be enough on their own.

  • Antioxidants: I’m now looking for a more structured cycle for some of them. My NRF2 is at 301, suggesting solid antioxidant activity, but I’m still unsure how to balance oxidative stress without interfering with necessary redox processes. The doctor who suggested the NRF2 test was happy with the result.

  • Brain: I feel the effects of my brain stack strongly, which benefits my work as a scholar, and I hope it helps keep APOE4 risks at bay. (I don’t use all the brain stack compounds daily, btw). My psilocybin microdosing protocol has been particularly enjoyable and efficient, I think I forgot to mention it in my OP.

  • Urolithin: It works really well for me - I feel the effects quite potently and take it every other day (500mg–1g). It also benefits my gut. It’s a bit pricey, but I get it from Aeternum, so it’s not too crazy in the end.

  • Liver enzymes: They’re right in optimal range atm - so, looks like I’m ready to abuse some more drugs now :laughing:

Thanks again for your time and insights—I always appreciate the collective brainpower circulating in this community! Looking forward to sharing more :heart:

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#24

What do you feel “potently”? I have been wondering about urolithin A. Even if it works the subjective feeling from it would be hard to predict: increased mitophagy might feel like tiredness but then post recovery with healthier mitochondria might feel like the opposite. But if you take it every day, I couldn’t begin to guess at how it works or how you might feel. I would think it should be used in pulses to let the body recover. Or maybe the effect is so small that it doesn’t require a separate recovery phase. But you feel it “potently” so I’m intrigued.