Your Current Stack and Why, Sept 2023

“The dead only know one thing; it is better to be alive.” - Pvt Joker.

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I’m not really sold on Glynac even though i do it couple times weekly.

Same here. Plus the risk of increasing initiation of certain cancers and their spread with increased glutathione levels is worrying. I have read a lot about this, but have yet to really come to a firm decision as information is still lacking.

It seems like you have a good regiment worked out for yourself. I tend not to skip any meals because I have always been on the thin side and struggle to eat enough at any one meal.

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“I have always been on the thin side and struggle to eat enough at any one meal.” wish I could say that, but have gotten in better shape lately and intend to keep it that way…

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The F1 mice used in the study are B6C3F1. Dr. Miller calls those mice rubbish for experimental purposes because they are not genetically diverse and produce results that are only specific to Black 6 mice. So whenever I see a B6 mouse study, I disregard it’s results. Better to look at the ITP.

This particular strain appears to be larger and very long lived already

https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/b6c3f1-mouse

Thank you for the feedback on the study. I do look at the ITP, but I thought this study was interesting because it focused on supplement combinations that many of us use. It appears they used F1 mice on purpose because they are long lived. This is the reasoning presented in the study:

We used F1 hybrid mice for these studies because they are more disease- and stress-resistant and have larger litters and longer lifespans than their inbred parental lines (Flurkey et al. 2009). Hybrid vigor of this type is thought to arise from the increase in heterozygosity at the loci for which their parents are heteroallelic. B6C3F1 mice have the advantages of being easily produced by a single cross. They are genetically defined and are the longest lived mouse strain of which we are aware (Spindler 2012). It seems likely that compounds which increase the lifespan of healthy, long-lived mice will be more likely to extend the lifespan of other healthy, long-lived mammals, such as humans.

Our results do not support the assumption made in some published studies that screening using enfeebled rodents will expedite the identification of longevity therapeutics (Spindler 2012; Spindler et al. 2013b).

Ideally they would have used heterogeneous wild type mice like the ITP study. I still think there are many interesting results in this study if one reads it through, especially in the discussion section. The fact that one of the supplement was clearly demonstrated to be toxic in otherwise healthy long lived mice is very worrying. They tested the same supplements many of us are taking every day. If the ITP had the time and resources to test all the health supplements on the market I will bet they would find many of them negatively impact longevity, so it seems to me it is just as important to avoid those as to take the ones that are demonstrated to be beneficial by the ITP.

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Interesting. Astaxanthin, taurine, glucosamine did not extend lifespan of B6C3F1 mice. They worked in C57BL/6 or UM-HET3 mice. Is it the dosage problem or other supplements cancel out or they don’t work in long-lived strains?

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BPC-157, normally found in gastric juice, survives digestion. Taken orally it’s useful for healing gut issues (ex gastritis, irritable bowel,etc). But, there’s some evidence that oral BPC can also improve MSK healing (although injectable is probably better for this).
AOD-9604 is also orally bioavailable. It’s a modified growth hormone fragment that is also good for improving musculoskeletal healing. We give patients an oral combination if there two that I formulated (full disclosure) called Rapid Rebound after our stem cell treatments. It’s also great for workout recovery as a daily supplement.

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Here’s my stack…

Rapamycin 6mg/week (for about the last four years)
Acarbose 50 mg before most meals (switched from metformin two years ago)
D+Q twice a year
HGH x 15 mos (just started this)

HOP Box (my company, www.HOPBox.life), twice daily packs with NR, CaAKG, hyaluronic acid, Spermidine, magnesium glycinate, quercetin, Fisetin, apigenin, curcumin, B2, B6, methyl B12, MTHF, TMG, Vitamin D3 (5000iu), Vit K2-mk7, Dihydroberberine, Tributyrin.

Also: Creatine 5g and L-carnosine.
Taurine 1g but increasing that to 3g.

Peptides:
Bpc-157 + AOD9604 oral, as needed (my company, LELabs.co)
Epilation+ thymalin (twice yearly cycle)
GHK-cu twice yearly cycle

Skin:
Tretinoin 3-4 d/week
GHK-cu topical 3-4 d/week
Topical estradiol 0.01% cream daily
Daily antioxidant serum
Love Skinbetter Science and Young Goose
Exosome injections + microneedling twice yearly

I don’t take anything for lipids as I’m Apo E2/E2 and have very low lipids at baseline.

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As far as I know Spindler’s studies are well respected. I think that the feeding procedures are different, which would be a good place to look for explanation of varying results. One criticism of the ITP protocol is that they likely overfeed their animals.

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Look at the doses.

OrthoCore was:

astaxanthin, 2.4 mg

The ITP study with Astaxanthin was, at 4,000ppm, equivalent to something like 3 or 4 Grams per day in humans, and they got around a 12% median lifespan improvement (in male mice).

One of the (many) differences in this type of study is that at the ITP they ask the experts on any given supplement / drug to specify what they think is the dose most likely to show a significant lifespan effect. And that is what they test.

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@AmyK Since it is your company, can you speak to the bioavailability of your spermidine supplement?

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I am always interested in what type of B6 people use and what dosage. Could you please tell us?

Otherwise quite an interesting stack.

Dihydroberberine vs Berberine appears to be one of those debates which is not entirely clear as to which is best (if either is).

Tributyrin is a new one to me.

I have followed the NR vs NMN vs Niacin debate. To be honest I have just stopped supplementing with NMN and although I take a little B3 in a multivitamin I have not increased any other B3. I think one of the reasons for NAD depeltion is a failure of the de novo pathway as result of aging problems generating the de novo enzymes. As I am attacking the aging failures directly I am not so inclined to try to prop up the failures.

The peptides are also an interesting area, but again that is propping up the system rather than fixing it. However, there is a role for that although that is not my personal focus at the moment.

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This is my daily routine.

Rapamycin 5 mg once a week.

Senolytic protocols, 3–4 times a year: Fisetin 30 mg per kg body weight, 2-3 hours after fisetin, I take quercetin (Thornes) , theaflavines (LE) and Piperlongumine

Mornings:
5 gr Creatine, Tripple espresso.
Quercetin (Thornes) + green tea extract,after an hour or so I take curcumin, Always the BCM 95 from LE (The life extension product).
Based on my personal experience, the green tea + Quercetin + Curcumine BCM 95 is favourite combination. It improves my wellbeing, reduces brain fog, and increases my mood.
I also take activated vitamin b-complex from Life Extension and psyllium husk.

Before Lunch: Pine bark extract, pomegranate extract, Gotu kola (Centella asiatica), amla

Late afternoon: 2 gr NAC + A combination product containing collagen peptides, Chondroitin sulfate, MSM, Vitamine C

Before Dinner: Amla + 5 mg Lithium orotate (Taken every other day)

Before sleep: Magnesium threonate 1,5–2 gr (or 200 mg magnesium citrate) and 3–4 gr taurine. When I wake up during the night I also take 1,5-3 gr taurine( but not after 3 AM).

I am struggling with, how to incorporate effective CD38 inhibition and Sirt6 activation.

I am considering how/If to use. Panthetine, Pyridoxamine. Astaxanthine, I have used Astaxanthine but having doubts since ITP used quite large daily dose.

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Great question. Short answer - it’s unclear how bioavailable any of the polyamines truly are or why they (apparently) have benefits. We use a concentrated, pure form of spermidine from NNB called Puremidine. As you likely know, there’s epidemiological data in humans as well as animal data indicating oral spermidine may be beneficial in improving lifespan, reducing inflammation, improving skin and hair, etc.
But, recent studies testing spermidine blood levels after oral administration have called its bioavailability into question. So, we don’t know for sure. It could be that spermidine and other polyamines work primarily on the gut epithelium by improving barrier function and renewal instead of getting absorbed intact. Some studies support this such as this one ,
Other studies seem to indicate polyamines are easily transported via passive diffusion through the intestinal walls, so one definitely wonders where they are going if not into the blood. We included spermidine in our formulation because the potential benefits seem to outweigh the risks but we evaluate our formulation for HOP Box every 6 months and will always be iterating on it as the science evolves. Thanks for the question. :slight_smile:

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We have the following for B vitamins (per day): B2 (riboflavin) 25 mg, B6 pyridoxal-5-phosphate) 5 mg, B12 (methylcobalamin) 500 mcg, 5-MTHF (quatrefolic 5-methyltetrahydrofolate) 500 mg.

I like berberine but it’s sometimes not well tolerated. Dihydroberberine seems to have better bioavailability and is very well tolerated (minimal gI effects)

And I agree that the whole NAD- activation thing is tough. I’d love to just include niacin instead of a different precursor but the side effects are too rough for some people.

Tributyrin is a great postbiotic (it contains three butyrate molecules). Interestingly, acarbose seems to offer some of the same benefits by also increasing colonic butyrate. So, maybe I don’t need both but most people aren’t taking acarbose.

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Thanks for a thorough answer. And for the paper. I have been trying to get spermadine from chlorella and wheat germ using volume to make up for small amounts in food. I’ve stopped the wheat germ until I can better understand the gut heal effect of raw wheat. Perhaps gut health is what I should focus on anyway.

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Your well made point is exactly the message I got from this study i.e. it may be pointless to take these types of broad multi-combination longevity supplements because they do not work (in mice). Either the dose is wrong or the combinations are ineffective for what ever reason.

I did not find the study to necessarily be anti-supplement as the researchers did recognize that many of the individual supplements have well proven track records and specific effects to help a specific condition.

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do you take these with any fat so as to be more soluble?

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My top supplements and drugs, and these are of course what an old man takes. Why only the top? Because I have cupboards full of supplements that I take now and then. There are just so many supplements that I can take on a given day. The supplements/drugs below are ones I take daily or regularly.

Supplements: How long?
Creatine, decades
Melatonin, decades
Lithium, decades
Ginko Biloba, decades
B vitamins, decades
L-theanine, decades
Boswellia serratta, ~four years
Glycine, ~two years
Vitamin D3/K2 , ~two years
Taurine, ~one year
Pantethine, ~six months
Sildenafil, ~four months

Drugs:
Tamsulosin, decades
Metoprolol, ~ six years
Rapamycin, ~ two years
Acarbose, ~nine months
Telmisartan, ~three months
Ezetimibe, ~three months

Most often used other supplements/drugs used occasionally:
L-serine
Multi-mineral supplement
Zinc
B-6
Lion’s many mushrooms
Chlorella
Spirulina
Fisetin
PEA
EGCG
Astaxanthin

And a plethora of other supplements that catch my eye from time to time.

Adjunct anti-aging protocols:
Exercise
Steam room and/or sauna 3-6 times/week
Whole-body red light therapy 4 -6 times/week

See how easy it is to have a supplement list that is unwieldy.
Problems with a list as long as this one includes timing and interactions.

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I’m not trying to be funny… This is a serious question… Is the sildenafil taken daily or as needed. I ask because some people take it daily because they believe the nitric oxide boost is healthful. Others take it for pulmonary hypertension. And some take it just for fun.

Also, I was just reading in another thread your use of pantethine. I think you were going to quit Lipitor and try that alone. Did you try it alone for your cholesterol before moving on to other drugs in combination?