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Recent Comments


Recent Comments


researchgrounded
Jun 11 2019 10:57 AM
Michael's "Tiered" Supplement

Regarding "the timing of glycine (either for sleep or life extension) and lysine are specific to their use, and are to maintain continuous serum exposure, not to increase bioavailability AUC," possibly for lysine, and certainly for glycine ( which you are not presently taking), I am curious how the pharmacokinetics and pharmacodynamics might be influenced by meals. 

 

That is, while spacing out the glycine regularly may keep the serum exposure more uniform, could some benefits of glycine supplementation be in relative to that of other serum amino acid levels at the time of intake? If so, this would be influenced by intake relative to meals-  

 

To be concrete, if I take all my glycine during a single daily meal, I would certainly would absorb less glycine by competitive inhibition via other dietary amino acids, however I can presumably compensate for this by increasing the glycine dose taken with that daily meal.  On the other hand, the glycine that I do take that meal may have the advantage of contributing to less absorption of methionine and/or the nutrient sensing sequela of said methionine, by maintaining higher hepatic glycine levels.


researchgrounded
Jun 10 2019 11:24 PM
Michael's "Tiered" Supplement

Hi Michael,

 

Your comments were again valuable.

 

Please keep any corrections coming - though I know the difference ( autocorrect at work?), and noticed the systematic error in the posting, I could not edit it out with attempts to edit unsaved.  Hence the two posts back-to-back.  Personally my pet peeve - is loose vs lose!

 

So you type references by hand every time, in full, numbers and all, or is there a part of PubMed or your favorite search engine where the full citation is appropriately formatted in full?  For example if you are citing https://www.ncbi.nlm...les/PMC5715805/ , do you click on "Citation" on the upper right and then select "AMA Format" or do you have another method?  I have published lengthy manuscripts offline using citation managers embedded within my word processor, but have not thus far for web-forum posts which I admittedly type on the fly bypassing the word processor.  Perhaps I should reconsider my practices for quality control considerations.

 

I agree with your comments regarding Attia, and thought the link illustrated it well.  I do enjoy them both, though Patrick admittedly seems at time prone to over-excitement and consequently asymmetric presentation and endorsement of a particular pet subject ( say NRF2 enhancers, broccoli sprouts, and Sauna therapy).  It would be great to have more of a synthesis with contradictory findings or something akin to AUB's "contrary/null findings" https://shockcenter.uab.edu/  To her credit though she does a much better job than 99.9% of the healthspan sphere trying to present data in perspective, and they both also share a higher degree of transparency, minimization of conflict of interest, and interest in scientific integrity which is sadly uncommon in this space.

 

I share many Attia's "obsessions" and philosophy of "strong convictions, loosely held,"  esp. "loosely held," and like Attia I find that as my absolute knowledge in longevity science expands my perception of my relative knowledge diminishes precipitously  :)  This is humbling but motivates me to dig deeper.


Michael
Jun 09 2019 09:41 PM
Michael's "Tiered" Supplement

At this point, my next step is evaluating alternative regiments and possible additions.


You mean "regimen," not "regiment" ;) . I am amazed by how many people make this error: there's a whole regiment of them on Longecity alone.
 

For your glycine ( I know you are not using this one), lysine, and taurine, would you feel comfortable with taking 1000+ mg at a time rather than 500 divided from a safety and tolerance perspective? As you alluded to, you divide primarily for either greater absorption, or to spread out the serum levels so that it can be more biovailable more of the time. In drawing my own health optimization versus convenience regiment I am entertaining taking daily, in the 1000-2000 mg range recognizing this may be less effective than your carefully cultivated regimen; are there liabilities I may be overseeing besides and accepting the efficacy vs convenience tradeoff?


It might be fine with taurine, but the timing of glycine (either for sleep or life extension) and lysine are specific to their use, and are to maintain continuous serum exposure, not to increase bioavailability AUC: see the discussion in the post.
 

On the subject of possible additions, in a non-diabetic without hyperlipidemia, do you see any benefit for berberine.


I've seen far too little long-term human or animal data on either safety or efficacy. I'm not at all convinced by the limited animal evidence that it even is a PCSK9 inhibitor, even in rodents — and if it is, if the effect is durable, since if it happens at all it happens at the transcription regulatory level, which could very well gradually fade due to feedback systems. Moreover, lat time I looked, all the human trials with LDL-C outcomes that have been done in nondiabetics (which is the relevant study design for a PCSK9 inhibitor) have not only been small and short-term, but have used combinations with red yeast rice and often many other ingredients, so one doesn't know what if any contribution the berberine is making — or, again, if it's durable.
 

And would you hesitate to take both a metformin and PCSK9 together or might the double AMPK mechanism of action be beneficially synergistic without too much concern about deleterious synergy?


I focus on empirical outcomes, not mechanisms, and I'm not impressed that AMPK is a good target to focus on even granted that; nor am I convinced that it's a particularly important mediator for either metformin or berberine. And if it were, and we were to wallow in mechanistic speculation on the question: usually when you get an effect of 2 different agents that work through the same mechanism, it's more likely that you get a sub-additive effect than a synergistic or even additive one, unless one of them comes at it both potently and upstream rather than directly: there's only so far one can push these things holding genetics and lifestyle constant.
 

I noticed that you cite your references. What citation manager do you use?


I don't use one.
 

Also, since I mentioned him, would be interested in your take on Dr. Attia. I don't know much about him but he seems to be increasingly positioning himself in the translational longevity space. He and Dr. Rhonda Patrick seem to be brining to the mainstream some ideas formerly restricted more narrowly to Longecity and the broader LE grassroots and research communities.


I'm impressed by Dr. Attia — not so much for his knowledge (which is extensive) or his views (with which I not infrequently disagree), but for his self-enforced intellectual humility (he admits that this is effort for him, his default tendency being toward overzealous confidence in his views), his data-driven approach, and agnosticism. I get thie impression that he has evolved on these issues quite significantly as a result of his experiences at NuSi and the drivers of his departure from same.  He has his frameworks and preferred hypotheses but is decidedly nondogmatic about them, and doesn't try to force the data on an individual patient into them when they clearly don't fit (viz. his arguments with people who insist that they can ignore a sky-high LDL-P so long as it's the result of a ketogenic diet, their CRP is low, and they don't have any coronary calcium). He also has great guests on his podcast, and can glean a lot of value from what would seem to be an unpromising guest.
 
By contrast, while Patrick also often has good guests, she has the unfortunate tendency of stating preliminary hypotheses as facts, and equally of a kind of intellectual passive-aggressiveness; she also fails to take in the key heuristic captured in the Attiaism "That's a fact, but is it a reason?" This last point is well illustrated in the lengthy exchange that Attia and Patrick have in her podcast "Peter Attia, M.D. on Macronutrient Thresholds for Longevity" etc, starting around 25:33 (in the transcript, beginning at "I like to think about it at the level of the gut" etc).


researchgrounded
Jun 09 2019 02:33 PM
Michael's "Tiered" Supplement

Hmmm, I can't seem to edit my post successfully with it saving the changes.  Wanted to add this interesting summary regarding its positioning in nutrient sensing pathways ( see: https://www.ncbi.nlm...les/PMC5839379/ )- I know you are not generally very convinced nor am I  without strong long-term observational data with quality trials at leaset in model organisms if not people..... however, if ( a big if depending on your response) it is deemed low risk as a supplement dosing, might thislower the threshold to supplement with its interesting mechanistic and some albeit not ideal supportive clinical data at this point? 

 

Also, since I mentioned him, would be interested in your take on Dr. Attia.  I don't know much about him but he seems to be increasingly positioning himself in the translational longevity space.  He and Dr. Rhonda Patrick seem to be brining to the mainstream some ideas formerly restricted more narrowly to Longecity and the broader LE grassroots and research communities.  


researchgrounded
Jun 09 2019 01:48 PM
Michael's "Tiered" Supplement

That's a great list.  Some are straightforward such as UL / USP / NSF certification.  Others compel investigation, such as sharing third-party certificates, and yet others are have subjective as well as objective information such as responsiveness to inquiries, transparency, etc.  This last category is easiest to assess based on past experiences.  Do you feel comfortable naming the brands you felt passed the last and presumably also other criteria?  Reliability and quality may be a moving target, but starting with those "so far, so good" companies would not be a bad start.

 

I have "graduated" assessing you full list and have incorporated several new supplements thanks to your post with only modest departures.  At this point, my next step is evaluating alternative regiments and possible additions.

 

For your glycine ( I know you are not using this one), lysine, and taurine, would you feel comfortable with taking 1000+ mg at a time rather than 500 divided from a safety and tolerance perspective? As you alluded to, you divide primarily for either greater absorption, or to spread out the serum levels so that it can be more biovailable more of the time.  In drawing my own health optimization versus convenience regiment  I am entertaining taking daily, in the 1000-2000 mg range recognizing this may be less effective than your carefully cultivated regimen; are there liabilities I may be overseeing besides and accepting the efficacy vs convenience tradeoff?

 

On the subject of possible additions, in a non-diabetic without hyperlipidemia, do you see any benefit for berberine.  I read your comments about metformin above and realize it has never as unitherapy yielded good evidence for life-extension ( indeed, quite the oppososite).  However despite the overlap with AMPK mechanism of action with metformin, berberine may also act as a PCSK9 inhibitor.  There is an additional question of bioavailability, though it least some formulations are purported to have greater nonavailability [  https://onlinelibrar...0.1002/ptr.6282  ], and berberine has additional potential albeit theoretical benefits including as Darryl recently pointed out in another thread systemic rather than strictly hepatic circulation as is the case for metformin.  As for the PCSK9 inhibition, anecdotally Peter Attia in an interview recently related his clinical experience that high PCSK9 producers tend to see their LDL go down by about 20% when used for this purpose - Incidentally, what is your take on Attia in the longevity space?  IAC, aside from PCSK9, berberine influences nutrient sensing in other potentially beneficial ways [ https://www.ncbi.nlm...les/PMC5839379/ ], which if low-risk may perhaps justify a lower threshold to supplement despite less-than-convincing outcomes assessments thus far.

 

You have not stated your lipid profile, but even on the last point alone, why not lower your LDL further, the the evidence from PCSK9 inhibitors (e.g., the from the FOURIER trial), with evidence getting the LDL is low as <=30 potentially yielded benefit.  While metformin has its own inconveniences in and intolerances ( lower the anerobic lactic acid threshold with possible fatigue and GI intolerance), it seems at first glance PCSK9 may be a lower risk addition to your regimen.  Or are your concerns over genotoxicity or other matters greater than that expressed by others at a clinical dose of say 1000 mg twice daily - your thoughts? 

 

And would you hesitate to take both a metformin and PCSK9 together or might the double AMPK mechanism of action be beneficially synergistic without too much concern about deleterious synergy?

 

Finally, if applicable, if you did select a berberine supplement at some point, which formulation and brand would you trust most for fidelity and bypassing the first pass effect?.

 

Footnote: off-topic but germane to correspondence, I noticed that you cite your references.  What citation manager do you use?  And how do you cite passages - indented and with a vertical line indicating taken from elsewhere - from paragraphs taken from other parts of the internet outside of the current Longecity thread?  I find the quoting mechanism self-explanatory for Longecity proper, not not so if I am looking to insert a passage from other parts of the internet.  

Feel free to PM me directing me to the best help file, etc, if that helps.  I aim to improve the quality of my posts.


Michael
Jun 01 2019 12:44 AM
Michael's "Tiered" Supplement

From your years experience in the industry, what criteria do you use to vet  "reputable brand?'   Do you have a short list of acceptable sources?

 

Criteria would include having been around for a while; showing scientific literacy and modesty in their marketing materials; have passed some third-party testing (CL, Labdoor, Consumer Reports, occasional media exposés, etc); having their GMPs certified by UL, USP, or NSF; being willing to share third-party certificates of analysis; having easily-found US/Canada/EU address and contact information, and being responsive to inquiries; not having FDA Warning Letters (like this) against them; having non-deceptive Supplement Facts and related info (like not playing fast-and-loose with serving sizes or elemental values); and even having professional-looking  labels and packaging (if they can't even invest in a decent label, how can they run a clean production facility?).

 

I'm not saying they should tick all of these boxes, but those are all things I look at and consider valuable.


researchgrounded
May 20 2019 11:46 PM
Michael's "Tiered" Supplement

Thank you for clarifying on raw material vs brand.  Sound advice on selection. 

 

At a micro-level, I check with ConsumerLabs, but they don't always have an up-to-date listing for any given supplement.  A variety are available from Amazon.com, but presumably this a poor screen!

 

From your years experience in the industry, what criteria do you use to vet  "reputable brand?'   Do you have a short list of acceptable sources?


Michael
May 19 2019 06:25 PM
Michael's "Tiered" Supplement

Lysine timing: yes, it's to keep levels up. Not sure what you're asking about "hedging my bets" on lysine: I don't want it competing with other aminos (currently only Trp) for passage of the BBB.

 

Brands: First, AjiPure is a branded raw material: Thorne and Pure Encapsulations are brands of finished consumer products. I just don't know enough about teh QC of particular retail brands or what they should even be looking for (or whether they'd be looking for it). IT took quite some time for researchers to even identify all the the possible contaminants in Showa Denko's tryptophan that might have been responsible for the EMS crisis, and we still don't know which is the actual culprits decades after the fact. How would one even know where to start on lysine or taurine?

 

Any reputable brand of GLS should be fine, AFAIK.


researchgrounded
May 18 2019 11:18 PM
Michael's "Tiered" Supplement

Also, I see that you understandably prefer Glucosamine sulphate over glucosamine hydrochloride.  What brands do you recommend to source it?


researchgrounded
May 16 2019 05:06 PM
Michael's "Tiered" Supplement
Thanks for the detailed response. I have been making multiple iterations of going through your stack, each with increased granularity. Previously a skeptic, I see value now in evidence-based and personalized supplementation.

Why split up the lysine within and outside of meals? Or was this exclusively to keep levels high ( steady levels pertinent t to lysine supplementation for prevention of encapsulated viruses? Instructions state take on empty stomach to prevent amino acid competition for absorption, is this to hedge your bets?

I can understand the desire for reliable contaminant-free products such as AgiPure lysine and taurine given your experience with creatinine. Do you equally trust any other source? I am contemplating 1000 mg rather than 500 mg capsules of these if possible - and staying away from the powders - and it would be more convenient to take one 1000 mg pill than two 500 mg pills. Woild pure encapsulations, Thorne or other manufacturers ensure fidelity of the product equally if they are NSF verified or do you use other criteria?

Michael
May 01 2019 11:39 PM
Michael's "Tiered" Supplement

Are you considering resuming glycine , perhaps earlier in the day given your possible somogyi effect, following this recent development @ the ITP: https://onlinelibrar...1111/acel.12953?


The dose used in the ITP study was quite large (8% of diet by weight), was initiated in young adulthood (9 mo), and the effect on lifespan quite modest and uneven (the 6.2% median and 4.5% max figure is averaged over 3 sites, with a much larger effect at UTexas dominating negligible effects in the other two labs); that's not attractive enough for me to consider such a dramatic supplementation program.
 

As for NR, are you considering suspending or adjusting the dose due to potential loss of methyl groups particularly at conventional doses - a hypothetical concern expressed here https://chrismasterj...amide-riboside/ ?
Some of your stack may partially offset this - e.g., creatine, choline - though not necessarily adequately.  That was the short, anecdotal version of a more elaborate version presented in this podcast with Peter Attia: https://peterattiamd...hrismasterjohn/ at around 1:47:15


I'm actually currently taking only 125 mg of NR or NMN 4 d/week, with 250 mg NR 2 d/wk and a one-day weekly holiday, and as you say I have partially offset this potential concern (plus an extremely high dietary intake of folate). I do think it's important to have a decent level of methylating nutrients. I've noted the potential problems of methylnicotinamide, and it's not clear whether/how much that's due to MeNAM being itself toxic vs. it depleting methylating units.
 

Hi Michael, not sure if you are still checking this thread but why not fisetin?

if you have started , what is your protocol ?


I'm not, yet, though I'm certainly considering it and have almost pulled the trigger more than once. Animals on CR per se accumulate fewer senescent cells as they age (PMIDs 26983960, 20844316, 29575469) — including, apparently, CR humans (PMID 29575469 ) — so my risk:benefit is more favorable than for most. Additionally, the results of a senescent cell ablation study by Dmitry Bulavin at Undoing Aging (I hope video will be up soon) scared the snot out of me; I am awaiting to read the paper and understand more before adopting any senolytic protocol (though fisetin, specifically, seems to be less hepatotoxic than other senolytics, and liver damage was the site of the horror in the Bulavin study).

 

As to protocol: most people are defaulting to the Mayo Clinic's study protocol of 20 mg/kg/day, orally for 2 consecutive days (often with some effort to enhance bioavailability). The dose seems about right or a little bit high based on either the HED method or true allometric scaling, but on reflection the time period does not: in the rodents, the acute clearance protocol was 5 days, and if anything the idea of "biological time" might suggest a longer period for a longer-lived mammal.


researchgrounded
Apr 29 2019 07:45 PM
Michael's "Tiered" Supplement
Hi Michael, not sure if you are still checking this thread but why not fisetin?

if you have started , what is your protocol ?
Thanks!

Snozzberry Scientist
Apr 27 2019 04:16 PM
Happy and healthy

Forgot to mention 1 gram EPA, 750 mg DHA daily.


researchgrounded
Apr 02 2019 11:08 PM
Michael's "Tiered" Supplement

Are you considering resuming glycine , perhaps earlier in the day given your possible somogyi effect, following this recent development @ the ITP: https://onlinelibrar...1111/acel.12953?

 

As for NR, are you considering suspending or adjusting the dose due to potential loss of methyl groups particularly at conventional doses - a hypothetical concern expressed here https://chrismasterj...amide-riboside/ ?

Some of your stack may partially offset this - e.g., creatine, choline - though not necessarily adequately.  That was the short, anecdotal version of a more elaborate version presented in this podcast with Peter Attia: https://peterattiamd...hrismasterjohn/ at around 1:47:15


albedo
Mar 13 2019 08:34 PM
A Longevity Promoting Regimen Leveraging the CAP, established and double blind tested by Mother Nature...

HDW, have you tried also to compare other potential biomarkers of aging too, next to the Teloyears, e.g. aging.ai, DNAm, Phenotypic Age etc .. see also the thread on Biological Age. It would be interesting too.


pamojja
Mar 05 2019 10:11 AM
Multi- Vitamin and Mineral stack
If omnivores get enough preformed vitamin A, than the US must be a nation of vegetarians (just joking).

51% of adults there are estimated from their food-intake to remain below their average daily requirement of vitamin A! The nation with the comparatively highest industrial meat production in this world.

But anyway. Michael, do you know how many month after continous supplementation 'serum retinol and RBP don't seen to be reliable indicator of vitamin status'? Couldn't find it. Because for deficiency it seems:

When dietary vitamin A is provided to vitamin A-deficient children, plasma retinol concentration increases rapidly, even before liver stores are restored (Devadas et al., 1978; Jayarajan et al., 1980). Thus, a low concentration of plasma retinol may indicate inadequacy of vitamin A status, although median or mean concentrations for plasma retinol may not be well correlated with valid indicators of vitamin A status.


In my case I supplemented for years, and intake did reflect in serum levels:
(retinol 425-831; RBP 30-60 lab normal ranges)

year vitA  RBP  A/RBC intake(avg. for previous 3 years)
     µg/l  mg/l   ≥7   µg/d

2012  501   44   11.4   1,3
2015  597   53   11.4   5,4
2018  705   47   14.9   6,7
Calculated (though already many years ago) that I got in average about 0.13 µg/d retinol from diet, and in avg. about 4.6 µg/d from supplements. Beta-carotene 1.5 µg/d RE from supplements, and 1.3 µg/d RE from diet.

Now with serum 25(OH)D probably few would doubt the validity of this test, because in 2012 it took me double the intake for reaching half the serum levels, than 5 years later in 2018. Simply to many co-factors posibly affecting absorption and metabolism. While preformed vitamin is still widely seen in something as a mysterious limbo.

Michael
Mar 04 2019 05:21 PM
Multi- Vitamin and Mineral stack

Even without health issues, the study finding up to 50% of the population having difficulty in converting beta-carotene into vitamin A, would at least have me enough concerned, to have serum retinol tested.

 

"Issues" doesn't mean meaningful issues, and omnivores of course get preformed vitamin A already. In any case, as I've pointed out before, serum retinol and RBP don't seem to be reliable indicators of vitamin A status.


pamojja
Mar 04 2019 03:15 PM
Multi- Vitamin and Mineral stack

I really would like to see the peer reviewed study suggesting there is one for rich humans on this planet.


Experimentally supplementing with increasing doses, while monitoring serum retinol levels and thereby experiencing increasing health benefits, convinced me (in my case, with multiple health issues). I didn't have the luxury of having the time to wait for a study probably never done.

Even without health issues, the study finding up to 50% of the population having difficulty in converting beta-carotene into vitamin A, would at least have me enough concerned, to have serum retinol tested.


Benedictus
Mar 04 2019 12:21 PM
Multi- Vitamin and Mineral stack

With all due respect, but Vitamin A for European inhabitants is totally overkill. There's an overdose of dairy-intake and dairy-use in our daily consumption patterns here as it stands. Besides, if not from dairy, we have carrots, pastinaak, not to mention the eggs, liver, fish people eat a lot of here. We don't need Vit A supplemented at all.

Or, better put:

 

If you can pay for regular use of supplements, you probably consume enough foods with vitamin A already. Or you're living a very strange hermit lifestyle or something like that, but a deficiency, I really would like to see the peer reviewed study suggesting there is one for rich humans on this planet.


Seganfredo
Feb 10 2019 10:21 PM
Longevity/Neuroprotection Stack

I'd add some Black Pepper with the Turmeric, as Piperine greatly enhances the absorption of curcumin into the bloodstream.

In fact, peppers, in genral, are known as overall "enhancers" to any primary drug/supplement they may be coadministered with. Without piperine from the BP, turmeric is very poorly absorbed and, as a result, you could be missing out on many of its advantages.

 

Great stack. *thumbs up*


Michael
Jan 28 2019 06:02 PM
Michael's "Tiered" Supplement

Full'a sugar, and several of the mechanisms for CVD protection from wine involve the alcohol.

 

IAC, I actually quit wine last October, after reconsideration of the epidemiology, particularly the nature of the observed stable low-level drinkers. Not going to detail that now ;) .


Florin
Jan 28 2019 07:27 AM
Michael's "Tiered" Supplement

Why not consume alcohol-free wine?


Florin
Aug 09 2018 05:35 PM
Michael's "Tiered" Supplement

Here's some more bad news about glucosamine: it has bad effects in both the normal and injured intervertebral discs of animal models, and at least in vitro, there are other problems associated with glucosamine.

 

Effects of Oral Glucosamine on Intervertebral Disc Matrix in an Animal Model
https://www.thespine...0776-0/abstract

 

Glucosamine supplementation demonstrates a negative effect on intervertebral disc matrix in an animal model of disc degeneration.
https://www.ncbi.nlm...pubmed/23324939

 

Glucosamine promotes longevity by mimicking a low-carb diet
https://www.longecit...-low-carb-diet/


Michael
Jul 27 2018 05:21 PM
Michael's "Tiered" Supplement

Michael, do you have any concerns about the long-term safety of glucosamine? Some say that there's a theoretical potential for kidney and eye damage.

 

Oral glucosamine increases expression of transforming growth factor β1 (TGFβ1) and connective tissue growth factor (CTGF) mRNA in rat cartilage and kidney: implications for human efficacy and toxicity.
https://www.ncbi.nlm...pubmed/21466783

 

Hm. Your citation seems far too preliminary to raise concern (they don't even have protein levels in the kidney, and nothing in the eye); however, you triggered me to dig, and I see these two studies finding a rise in IOP with glucosamine. The second study, which is more robust in design, only finds a rise because of a mixture of a lower baseline (reversion to the mean?) and some post hoc fiddling, and "Although mean rise of IOP was statistically significant in the glucosamine group, more than 2 mm Hg rise in IOP was also more in the treatment group (34% of those receiving treatment vs 12.5% of patients on placebo)." And it was done in Iran.

 

However, even a suggestion of a risk may not be worth it to some people, especially if their inflammation is already low or they have reason to think they're at risk of glaucoma.

 

It'd sure be nice to have this done more robustly, and also to see some epidemiology on glucosamine supplement users.


Florin
Jul 27 2018 05:40 AM
Michael's "Tiered" Supplement

Michael, do you have any concerns about the long-term safety of glucosamine? Some say that there's a theoretical potential for kidney and eye damage.

 

Oral glucosamine increases expression of transforming growth factor β1 (TGFβ1) and connective tissue growth factor (CTGF) mRNA in rat cartilage and kidney: implications for human efficacy and toxicity.
https://www.ncbi.nlm...pubmed/21466783


Gayle63
Jun 13 2018 02:12 AM
Longevity/Neuroprotection Stack

Thank you for your suggestions, both of you! I will drop a few based on your recommendations and look into the rosmarinic acid. Never heard of that one! I feel great on this stack, but then I've never had any health issues or complaints. I'm thinking long game here. I very much appreciate the input!


steenblock
May 25 2018 04:45 AM
ʘ˩ʘ FOCUS stack for JOINT HEALTH

might think about calcium carbonate/magnesium/potassium bicarb three times a day or at least at the end of a workout or during and in the late afternoon 

In general, these might be good for preventive but when you are really suffering or have autoimmune problems you will have to change these around.Like increase them all or selectively.


revenant
Apr 02 2018 02:56 AM
Longevity/Neuroprotection Stack

Maybe consider leaving out the ALC, it probably contributes to inflammation by nourishing  gut microbes that are best kept in check. Add egcg, reshi and, carnosine. The nicotinamide riboside and pterostelbene are super awesome. I would drop the resveretrol if you are taking pterostelbene. I have reservation about taking PQQ and nicotinamide riboside together. The B complex should be liquid and sublingual. Oh yes.. also a rosmarinic acid polyphenol supplement may be something to look into. It is likely gonna be very good for your skin by preventing AGE crosslinks.


QuestforLife
Mar 06 2018 03:14 PM
A Longevity Promoting Regimen Leveraging the CAP, established and double blind tested by Mother Nature...

It looks like one of the key drivers of inflammation rising in the aging human might be the release of mitochondrial DNA into the bloodstream, which is then recognized as bacterial DNA and attacked by leucocytes. See the following papers:

 

'The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore'; and

 

'BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis'.

 

Apologies, I am new to Longecity and am not allowed to post hyperlinks.

 

Personally I think it is a lack of replicative ability in aging proliferative cells that is the source of the problem, and that a blockade on the inflammatory cascade can only delay the inevitable rather than fully rejuvenate - but this might be the best we have until we manage to restore cells' proliferative ability.


Leon93
Jan 10 2018 10:31 AM
Michael's "Tiered" Supplement

Michael, I have yet a few more questions: on k2, is there really a need to supplement it when one gets sufficient amounts of it (or k1) on a diet? Whether it´s mk7 or mk4? If so, what is the minimal required dosage? Especially for someone my age?

And regarding CR; is it also really making one live longer? So far I have read different evidence upon it on this site. Some say it has been shown to increase lifespan in animals, but not in humans. Perhaps it will only increase the quality of one´s phenotype?
But constantly CR´ing can´t be healthy right? If one does so he/she will continue to lose weight until he/she practically dies of starvation. My BMI is already most of the time in between 17.5-19.5, as of now it is about 17.5. I think I´m already CR´ing without me knowing it as I have lost some weight. You can´t encourage people to keep continue CR´ing until they become hospitalized?

 

And have you ever looked into coleus forskohlin for increasing BMD? It seems to be completely safe. DNA damage, cytotoxicity, general toxicity, liver damage and case studies all gave negative results. The only caveats I could fine is a study which noticed genotoxicity in Allium cepa (onions). It also raised heart rate 16% in a human study. But I´m not sure it´s a negative thing per se, as coffee also seems to raise heart rate, which you also take (though I´m not sure if decaf coffee raises heart rate). It might be a little bit undesirable when looking at it from a longevity perspective. But I´m not qualified enough to make this definitive conclusion. One study even noticed it being promising for cancer: http://onlinelibrary...320622/abstract  


Leon93
Jan 04 2018 05:56 AM
Michael's "Tiered" Supplement

Greger is not a reliable source of health information.

We will see in a short moment. Even though we started with CoQ10, let me first address vit D.

His argument here is based on a mixture of (a) older meta-analyses of studies on single outcomes and not individual patient-level data, and (b) the paleo-adaptationist fallacy that "natural" levels are better.

No, Greger actually said the opposite at 3:05; that the natural level actually is not the optimal level per se. So no ´paleo-adaptionist´ fallacy here.
 

"something, dont quite remember was a long time ago" is not a good citation. IAC, this is a painstaking individual patient-data meta-analysis of eight independent prospective cohort studies from Norway, Germany, Iceland, Denmark, and the Netherlands, not some single study of "Scandinavians."

I looked it up again, and let me summarize by giving a short chronogical history on vit D:
https://nutritionfac...recommendation/

First this video (from 2011) at about 1:01 shows about >80-90nmol/L is where your body will not be putting more vit D in circulation, about right in the middle where your conclusion of 75-100nmol/L is.

https://nutritionfac...vitamin-d-bate/. Then his conclusion here is 2000IU seems to be best for people in general. Off course, like you pointed out in your ´patient-level data´, the 2000IU is just an average. Some need more or less. You yourself take in about 500-1000IU, but you could be getting more sunlight than the people in Greger´s cited study did. Or you might be taking it in with your meals, which contributes to higher absorption.

However, this is a very old video of doctor Greger from December 2011. The same link also states an ideal of 80nmol/L at 1:27, which is what your study also cites.
 

Now is a more recent video from 2016. One of the statistics in this video looks remarkably similiar to the one you cited: https://nutritionfacts.org/video/how-much-vitamin-d-should-you-take/. However, this one is outdated. New data in this video shows about >135nmol/L is better than 80nmol/L. Why? Because some of these vit D studies are based on Scandinavian cod liver supplements, which contributed to increased mortality risk due to their vitamin A content, which was beyond the upper dosage. So the U-shaped curve is outdated.
Note the meta-analysis study you stated on vit D cites: ´European consortium of eight prospective studies, including seven general population cohorts´ So this study probably was from these cod liver studies were mostly from Scandinavian countries.

From here on I will just advise you to watch the entire video. After you´re done, we arrive at the video I linked earlier. Please watch this one again, and what I said earlier will make more sense now:

https://nutritionfacts.org/video/the-optimal-dose-of-vitamin-d-based-on-natural-levels/

I said 3:12 before, but I meant to say the study at 3:18. 5000IU pills make more sense now. Perhaps even 10000IU might be better on days without any sun. But it depends on several variables. For some 5000IU might be more than enough, or even 10000IU, just like Greger cited in some of his videos on vit D.

Now on CoQ10.

 

Does he provide direct evidence of this happening in vivo in aging mammals, or is this the usual mechanistic speculation based on in vitro nonsense? And if so, does he provide direct evidence that this happens in CR animals (as noted, that's why I'm taking it), or alternatively that it is sufficient to counteract the "normal" age-related decline?

Did you watch the video (entirely)? At 2:30 he shows a study which shows mammals can produce ATP themselves after consuming chlorophyll compounds. Or you can read the study yourself: https://www.ncbi.nlm.nih.gov/pubmed/24198392
And at 3:47 he shows a study which states our bodies can produce CoQ10 after sunlight exposure. Or view this study here yourself: https://www.ncbi.nlm.nih.gov/pubmed/22928808

Whether you´re doing CR or not, as long as you eat chlorophyll containing foods and expose your body to the sun, your body will produce CoQ10. I agree sun exposure is carcinogenic, that´s why I take vit D mself, but I guess some sun exposure is unavoidable right? Why not make good use of it? I couldnt figure out though how much was produced, but perhaps you could figure it out?

 

They're only moderately difficult to obtain. Get a prescription or order from reliable online pharmacies.
Also in the Netherlands? I looked online for any website but couldn´t find any.

 

Then on the carninutrients: I actually agreed with you. To be honest, I was pushing you a bit in order to get a response. I myself supplement with carninutrients as well for a few months now: beta-alanine, taurine, carnitine and creatine.
However, I did some research some time ago and found out carnitine, taurine and carnosine aren´t a problem in those who take in high amounts of protein every day (~.7g-.8g< protein per pound). Then our bodies would synthesize all we need. There are also some sources claiming our bodies can only synthesize up to 1g of creatine per day, when we need 2g total each day. But I am a bit sceptical of this, considering sites make very distinct claims about creatine and there being no site which accurately lists all creatine sources. It´s also pretty weird no amino acid except creatine would be a problem. I think it´s obvious why I think this is weird.

 

You do seems to be aware of the relationship between choline and TMAO. I haven´t looked into the choline studies you told about, will look into it. However, there is some evidence vegetarians aren´t getting enought carnitine either (when they take in only moderate amounts of protein, like 70-80 grams a day):
https://www.ncbi.nlm.nih.gov/pubmed/2756917; https://www.ncbi.nlm.nih.gov/pubmed/21753065;
Would you consider supplementing it now as well just like choline, even though there is a TMAO connection?:
https://nutritionfac...mao-connection/. I mean, carnitine should be as essential, just as choline after all.

 

I also have a little bit extra info about it in the following video, please read my comments: https://nutritionfac...in-supplements/
 

Loaded with omega-6: no, thanks.
Is there a specific reason you avoid omega 6? Omega 6 is only a problem if you eat it with omega 3, in which case the omega 3 gets ´behind in the line´ of what your body will use fas DHA/EPA. Just consume your omega 3´s first every day, then only omega 6 later. Or simply supplement with a sufficient DHA/EPA omega algae pill.

The bioavailability of Zn in wheat bran is extremely low. 2 T of wheat germ contains 1.8 mg Zn, 0.8 mg omega-6, and 121 mg of phosphorus, plus

Wheat Germ Agglutinin: no, thanks.

I said bran/germ as I was quick in my response, but the following links shows 100g wheat germ contains about 14-12mg, which is pretty significant: https://www.healthal...icles/zinc.php; http://nutritiondata...0000000-w.html. Toasted wheat germ even has 17mg.
And I don´t seed what´s wrong with lectins like WGA. They even have many benefits for our bodies:
http://www.sciencedirect.com/science/article/pii/S0733521014000228. As far as I know, when lectins show negative effects, they either use high dosages or use unhealthy populations. Soy isovlavones don´t scare me for this reason, as gynaecomastia only was perceived in case studies involving at least a kilo of soy products daily.
The only one who seems to worry about agglutinin is Mercola, who is nothing more than a witch doctor in my eyes. He only wants to sell his products, unlike Greger who established a non-profit site where procedures goes towards charities.

Although a long-term prospective epidemiological study did find an association between Ginkgo use and slow cognitive decline, its power is limted by only requiring one reported intake at any of ten follwups assessments over the course of 20 yearas (1), whereas two well-done clinical trials (2,3) found no benefit. That's not a good reason for putting a concentrated phytochemical into your body for decades.

Well, never mind the ginkgo now. I just found out ginkgo should be avoided, read about what I typed here:
http://www.longecity.org/forum/topic/98805-known-negative-side-effects-on-certain-supplementsherbsspices/page-2#entry837103
But if a certain supplement is safe, I see no reason why long-term supplementation should be harmful. Whether it is a certain tea, herb, spice or regular food.

Antioxidants, shmantioxidants: that canard should have died in 1992. I'm not aware of any actual health benefits of any of these listed substances in normal, otherwise-healthy aging mammals after oral administration. Can you cite any (with primary scientific citations)?

Don´t have one at hand. But it´s handy for anti-aging and stress as far as I know. Here´s a handy startpage on it:
https://nutritionfacts.org/topics/antioxidants/

 

Never mind c60, PQQ and NMN, I decided I have no interest in them anymore. However, I do have a couple of questions for you I wandered about:
1) any reason why you´re vegetarian and not omnivorous or whole-food plant-based/vegan? When I looked at your diet I couldn´t spot any animal products though.
2) Are you aware of more people who list their diet and supplement regimen on this or another site in detail like yourself?

3) I need some help with niacin. RWhigham commented in this post something about niacin/niacinamide perhaps decreasing lifespan:
http://www.longecity.org/forum/topic/79920-nicotinamide-without-the-riboside-nicotinamide-by-itself-any-good/. Is this a typo?

And you yourself once said it Increases chance for diabetes. However, another post mentioned blood sugar is only raised temporarily. After same use this blood sugar rise will eventually disappear.
Is 500mg a sufficient dose or is 1g a lot better? I cant find any good info on it. Do take I´m only 24 years old, so I need less than someone older.

4) Ever thought about taking heart rate lowering supplements like valerian or adaptogens at moments of stress? Sure beats lavender, which has been associated with gynaecomastia (see my link about negative side effects linked earlier).
5) Any reason why you dont take spices like dill, chervil or cardamom?

6) Do you know anything about supplementing bromelain? Anything good or bad?

 

Final, are you one of the ´makers´ of this site? I gotta say I like the site and I thank you for it! :D

EDIT: here is your link about choline: 
https://www.crsociet...or-vegetarians/. And this is the one of veganhealth.org I was talking about: http://www.veganhealth.org/articles/choline. The article of veganhealth.org contains 5 of the 7 sources your link cites. It has 27 total sources however, also on a few other subjects. The two sources it doesn´t contain are xciv and xcv. I haven´t looked properly at it yet, but you might want to check it out yourself. It´s interesting to see however how they both arrive at different conclusions. Veganhealth.org doesn´t hold any bias, Jack Norris is more than happy to supplement when there is enought evidence to the contrary. He already supplements some nutrients.

I also just noticed you sometimes take 750mcg of melatonin. You can also eat an ounce of goji berries for about 15mcg of melatonin: https://nutritionfac...s-for-insomnia/. Because melatonin is potent it can increase blood levels 50-fold in the body, so one can get about 750mcg of melatonin per 1 ounce of goji berries.

I noticed Darryl has some info on phosphatidylcholine you might be interested in to read: 
https://nutritionfac...omething-fishy/


Michael
Dec 27 2017 04:11 PM
Michael's "Tiered" Supplement

Michael, there is a video on nutritionfacts.org which tells how our bodies can produce CoQ10 on our own (hint, you would have to eat green leafy vegetables and get some sun afterwards): https://nutritionfac...oq10-naturally/


Greger is not a reliable source of health information. Does he provide direct evidence of this happening in vivo in aging mammals, or is this the usual mechanistic speculation based on in vitro nonsense? And if so, does he provide direct evidence that this happens in CR animals (as noted, that's why I'm taking it), or alternatively that it is sufficient to counteract the "normal" age-related decline?
 
IAC, sun exposure is a carcinogen. I'll take the pill. Ditto on vitamin D.
 

Too bad metformin, rapamycin and acarbose seem impossible to obtain.


They're only moderately difficult to obtain. Get a prescription or order from reliable online pharmacies.
 

And why no n-acetyl glucosamine but sulphate/sulfate?


The cited studies used GLS, not NAG.
 

On the Vit D, I looked into it a long time ago but the conclusion was that the study you reference was not legit (based on people taking in fish in Scandinavia or something, dont quite remember was a long time ago).


"something, dont quite remember was a long time ago" is not a good citation. IAC, this is a painstaking individual patient-data meta-analysis of eight independent prospective cohort studies from Norway, Germany, Iceland, Denmark, and the Netherlands, not some single study of "Scandinavians."
 

The video had a different conclusion on that (3:12): https://nutritionfac...atural-levels/This is why I personally take 10000IU on days without sun and 5000 IU on days with some sun in winter of few in summer.


Greger is not a reliable source of health information. His argument here is based on a mixture of (a) older meta-analyses of studies on single outcomes and not individual patient-level data, and (b) the paleo-adaptationist fallacy that "natural" levels are better.
 

Carninutrients: why do you take taurine and beta-alanine in such high doses? Taurine barely offers any benefits for as far as I´ve read and omnivores have an average intake of 100-400mg as I have read and about 50-300mg for beta alanine + 36,5% of b-alanine is carnosine so up to 822mg should be sufficient (sorry, no direct sources to back this up as I haven´t safed them but you can probably find the sources yourself).


Taurine: see my paragraph on this, beginning "AjiPure Taurine: Absent in vegetarian diet;" and references (32) and (33) on benefits and dose. Beta-alanine: because those are the doses used in clinical trials.

No references, no argument.
 

Carnitine has been shown to not raise TMAO levels in vegans though: https://nutritionfac...ao-connection/


That's what's reported, yes — but (a) it's based on a single "carnitine challenge consisting of co-administration of 250 mg d3-(methyl)-carnitine and an 8-ounce sirloin steak" in a small sample size (n=23), and (b) presuming it's real, the reason why is presumably because carnitine is so low in the veg(etar)ian diet that bacteria that avidly metabolize it don't get the fuel they need to grow to substantial numbers in the gut. If you obviate that situation by taking a supplement every day, you'll be feeding those bugs and their numbers will expand accordingly, leading to omnivore-level TMAO production.
 

Plus, carnitine probably raises sperm quality (see the comments I made in the link; user: Leon)


Bonus! By not taking it, I get a little background birth control ;) .
 

Veganhealth.org has a page on choline and says the 450/550mg per day is based on a single old study.


If it says that (link, don't claim), it's wrong: the DRI is supported by multiple studies, including those I cited in my linked "supplements for vegetarians" post.
 

As user Darryl also pointed out, 170-300mg might be sufficient supplemented with betaine (easily obtained from wheat bran).


Betaine raises TMAO. Wheat bran is not remotely a high enough source of betaine, and betaine not an adequate substitute for choline, to make up the gap.
 

Zinc: wheat bran/germ offer insane high amounts of zinc.

 
The bioavailability of Zn in wheat bran is extremely low. 2 T of wheat germ contains 1.8 mg Zn, 0.8 mg omega-6, and 121 mg of phosphorus, plus
Wheat Germ Agglutinin: no, thanks.
 

Pumpkin seeds and sesame seeds as well, but lower. Tryptophan can also be easily obtained from diet: http://nutritiondata...0000000000.html


Loaded with omega-6: no, thanks.
 

Is there a specific reason you haven´t looked into spices and herbs? Ginkgo biloba might hold some promising effects for cognition and turmeric, sumac and cloves f.e. are very high in antioxidants. Amla (powder or berry/dried berry) and astaxanthin are also extremely high in antioxidants.


Although a long-term prospective epidemiological study did find an association between Ginkgo use and slow cognitive decline, its power is limted by only requiring one reported intake at any of ten follwups assessments over the course of 20 yearas (1), whereas two well-done clinical trials (2,3) found no benefit. That's not a good reason for putting a concentrated phytochemical into your body for decades.

Antioxidants, shmantioxidants: that canard should have died in 1992. I'm not aware of any actual health benefits of any of these listed substances in normal, otherwise-healthy aging mammals after oral administration. Can you cite any (with primary scientific citations)?
 

Any reason for not supplementing PQQ, NMN or c60?


PQQ: I'm aware of no evidence of benefits in normal, otherwise-healthy aging mammals in vivo after oral administration. Can you cite any (with primary scientific citations)?

NMN: I'm taking NR; I don't think we know enough to think that either is better at this point, or that taking both is better than taking one at the same total molar dose. NR's supply chain is clearer, it has a monographed analytical method, and it's cheaper.

c60: a lot of hype over a badly-done, retracted animal study that doesn't pass the laugh test. There is at present no evidence of benefits in normal, otherwise-healthy aging mammals in vivo after oral administration — or can you cite any (with primary scientific citations)?
 
References
1: Amieva H, Meillon C, Helmer C, Barberger-Gateau P, Dartigues JF. Ginkgo biloba extract and long-term cognitive decline: a 20-year follow-up population-based study. PLoS One. 2013;8(1):e52755. doi: 10.1371/journal.pone.0052755. Epub 2013 Jan 11. PubMed PMID: 23326356; PubMed Central PMCID: PMC3543404.

2: van Dongen M, van Rossum E, Kessels A, Sielhorst H, Knipschild P. Ginkgo for elderly people with dementia and age-associated memory impairment: a randomized clinical trial. J Clin Epidemiol. 2003 Apr;56(4):367-76. PubMed PMID: 12767414.

3: Snitz BE, O'Meara ES, Carlson MC, Arnold AM, Ives DG, Rapp SR, Saxton J, Lopez OL, Dunn LO, Sink KM, DeKosky ST; Ginkgo Evaluation of Memory (GEM) Study Investigators. Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. JAMA. 2009 Dec 23;302(24):2663-70. doi: 10.1001/jama.2009.1913. PubMed PMID: 20040554; PubMed Central PMCID: PMC2832285.


Leon93
Dec 23 2017 11:42 AM
Michael's "Tiered" Supplement

Michael, there is a video on nutritionfacts.org which tells how our bodies can produce CoQ10 on our own (hint, you would have to eat green leafy vegetables and get some sun afterwards): https://nutritionfac...oq10-naturally/
On the Vit D, I looked into it a long time ago but the conclusion was that the study you reference was not legit (based on people taking in fish in Scandinavia or something, dont quite remember was a long time ago). The video had a different conclusion on that (3:12): https://nutritionfac...atural-levels/ This is why I personally take 10000IU on days without sun and 5000 IU on days with some sun in winter of few in summer.
This link states humans get in an average of a bit lower than 1mg of lithium a day up to about 3mg: https://getfit.jilli...thium-1831.html Vegetables and grains seem to be high in it.

Carninutrients: why do you take taurine and beta-alanine in such high doses? Taurine barely offers any benefits for as far as I´ve read and omnivores have an average intake of 100-400mg as I have read and about 50-300mg for beta alanine + 36,5% of b-alanine is carnosine so up to 822mg should be sufficient (sorry, no direct sources to back this up as I haven´t safed them but you can probably find the sources yourself).  
Carnitine has been shown to not raise TMAO levels in vegans though: https://nutritionfac...ao-connection/ 
Plus, carnitine probably raises sperm quality (see the comments I made in the link; user: Leon)

B12 might be better in cyanocobalamin form as Michael Greger often suggests as there is more research to support it and the other forms don´t work for every person. It´s also the cheapest and safest form. Greger suggests 2500mg a week but if you look at this video, 3750 should be closer to the ideal dosage: https://nutritionfac...of-vitamin-b12/

Veganhealth.org has a page on choline and says the 450/550mg per day is based on a single old study. As user Darryl also pointed out, 170-300mg might be sufficient supplemented with betaine (easily obtained from wheat bran).

 

Zinc: wheat bran/germ offer insane high amounts of zinc. Pumpkin seeds and sesame seeds as well, but lower. Tryptophan can also be easily obtained from diet: http://nutritiondata...0000000000.html

Is there a specific reason you haven´t looked into spices and herbs? Ginkgo biloba might hold some promising effects for cognition and turmeric, sumac and cloves f.e. are very high in antioxidants. Amla (powder or berry/dried berry) and astaxanthin are also extremely high in antioxidants.

Too bad metformin, rapamycin and acarbose seem impossible to obtain. Any reason for not supplementing PQQ, NMN or c60?  And why no n-acetyl glucosamine but sulphate/sulfate?


pamojja
Dec 18 2017 09:46 PM
A Longevity Promoting Regimen Leveraging the CAP, established and double blind tested by Mother Nature...

I hadn't run across the Vitamin A info. Might you suggest a link?

 

If there's a way to take more Vitamin D3 and keep the dosing risk low, I'm in to do it.

 

For example the point of view by Chris Masterjohn.

 

If you remember slimjohn, he also has given it lot of thought on his forum, for example here. (needs signing up, but is for free)

 

Personally on Pauling's therapy for many years, reached his recommendation of 25.000 IU preformed vitamin A only recently. Since which my infrequent psoriasis outbreaks have completely ceased.

 

Then there is Dr. Coimbra from Brasilia, which uses REALLY large doses of vitamin D against MS, and describes all precautions he recommends. A selection of texts for example here.

 

Enjoy.


HighDesertWizard
Dec 18 2017 06:35 PM
A Longevity Promoting Regimen Leveraging the CAP, established and double blind tested by Mother Nature...

 

Various NF-kB Herbal Inhibitors -- Daily Fisetin, Feverfew, Berberine, Bitter Melon, Propoulis

Fisetin, Feverfew, Berberine, Bitter Melon, are all strong P450 3A inhibitors. Propoulis inhibits P450 1A2 only.  3A is the most important

While stacking NF-kB inhibitors it might be wise to avoid stacking a lot of P450 inhibitors. P450 is one of the ways the liver detoxes the things we  eat.

 Everyone who can should check their P450 genetics. Defects are common.

 

No effect on P450  3A

   Ashwagandha
   Astragalus
   Curcumin
   Eleuthero senticosus - Siberian Eleuthero
   Icariin/Horny Goat Weed
   Metformin
   Nettle Root
   PQQ

 

P450 enhancers

  Aspirin

  Astragalus
  Eleuthero senticosus
  Nettle Root  (some other not 3A)
 
P450 inhibitors  - some of these (at the top) are very strong, some are not.  This list shows how easy an herbal stack could inhibit P450
  Grapefruit juice
  Berberine
  Naringen
  Schizandra
  Quercetin
  Bergamot
  Bitter Melon
  Andrographis
  Resveratrol
  Pterostilbene
  Fisetin
  EGCG extract - a fairly weak 0-20% effect at 800 mg/d
  Magnolia/Honokiol
  Ginkgo
  Bacopa
  Wild Yam
  Bilberry  - and most berries
  Milk Thistle
  Grape seed extract
  Ginger
  Aloe Vera
  Pomegranate
  Propoulis- inhibits 1A2 only

 

 

Thank you very much RWhigham for the info... I will look into this and be back with comments when I have them.


HighDesertWizard
Dec 18 2017 06:31 PM
A Longevity Promoting Regimen Leveraging the CAP, established and double blind tested by Mother Nature...

20.000 IU D3 ongoing is quite a dose. What 25(OH)D3 levels to you get with that? Or aim at?

Do you take any retinol? Since vitamin A and D3 and K2 all seem to support each other, and prevent toxicity of each taken at high doses. Did you ever test your serum retinol and retinol binding protein?

 

Thanks.

 

 

Hi pamojja...  I remember you from years ago at Dr Davis' Track Your Plaque forum. I posted there as wccaguy.

 

I understand it's a large dose. I supplement with Vitamin K.

 

I get my Vitamin D3 blood tested regularly. I've only tested Vitamin D3 over a hundred once.

 

I hadn't run across the Vitamin A info. Might you suggest a link?

 

If there's a way to take more Vitamin D3 and keep the dosing risk low, I'm in to do it.

 

Thank you for the information.


Michael
Nov 24 2017 05:00 AM
Michael's "Tiered" Supplement

Because (a) rapamycin is really a pretty risky drug to take experimentally (at least at levels likely to be effective, assuming the rodent data does indeed translate — see discussion here and this followup) and (b) there seems to be surprisingly little advantage to starting rapa earlier in life vs. later, perhaps because its beneficial effects become more relevant in opposition to secondary aging processes or because the mixture of deleterious to beneficial effects shifts with the changing aging milieu — or perhaps simply because of changing pharmacokinetics, since in the mice at least plasma levels at a given dose are much higher in aged vs. young animals.

 

So I feel I've got some time, and we'll certainly know a lot more in a few years.

 

The stupidest thing in the universe is a life extensionist dead of the long-term toxic effects of his experimental fountain-of-youth pill.


Chris Pollyanna
Nov 24 2017 04:23 AM
Michael's "Tiered" Supplement

Hi Michael,

 

I'm curious as to why you don't take Rapamycin considering that at top of your post you state "whereas we now have extremely convincing evidence for rapamycin" as regards to supplements.

 

I'm thinking of getting my parents, who are in their seventies, on rapamycin (once weekly 5mg) + metformin as a stepping stone to the availability of senolytic treatments.

 

Thanks,

 

Chris


Michael
Oct 23 2017 07:09 PM
Michael's "Tiered" Supplement

Michael,
 
"my iron stores are still right where I want them to be."[/size]
 
What levels e.g. of ferritin do you consider optimal for most people? 

I like the entire suite of functional iron markers to be very low-normal. Absent such "full-spectrum" testing, low-normal ferritin.

Benko
Oct 23 2017 06:40 PM
Michael's "Tiered" Supplement

Michael,

 

"my iron stores are still right where I want them to be."

 

What levels e.g. of ferritin do you consider optimal for most people? 


RWhigham
Oct 14 2017 05:35 PM
A Longevity Promoting Regimen Leveraging the CAP, established and double blind tested by Mother Nature...

Various NF-kB Herbal Inhibitors -- Daily Fisetin, Feverfew, Berberine, Bitter Melon, Propoulis

Fisetin, Feverfew, Berberine, Bitter Melon, are all strong P450 3A inhibitors. Propoulis inhibits P450 1A2 only.  3A is the most important

While stacking NF-kB inhibitors it might be wise to avoid stacking a lot of P450 inhibitors. P450 is one of the ways the liver detoxes the things we  eat.

 Everyone who can should check their P450 genetics. Defects are common.

 

No effect on P450  3A

   Ashwagandha
   Astragalus
   Curcumin
   Eleuthero senticosus - Siberian Eleuthero
   Icariin/Horny Goat Weed
   Metformin
   Nettle Root
   PQQ

 

P450 enhancers

  Aspirin

  Astragalus
  Eleuthero senticosus
  Nettle Root  (some other not 3A)
 
P450 inhibitors  - some of these (at the top) are very strong, some are not.  This list shows how easy an herbal stack could inhibit P450
  Grapefruit juice
  Berberine
  Naringen
  Schizandra
  Quercetin
  Bergamot
  Bitter Melon
  Andrographis
  Resveratrol
  Pterostilbene
  Fisetin
  EGCG extract - a fairly weak 0-20% effect at 800 mg/d
  Magnolia/Honokiol
  Ginkgo
  Bacopa
  Wild Yam
  Bilberry  - and most berries
  Milk Thistle
  Grape seed extract
  Ginger
  Aloe Vera
  Pomegranate
  Propoulis- inhibits 1A2 only

Adam Karlovsky
Oct 11 2017 03:04 AM
Longevity/Neuroprotection Stack

Be careful with your vitamin C and E dosages, too. If you are taking AREDS2 Preservision twice a day you could cut back to once a day, reduce any risks of chronic vitamin C, E and zinc overdose, and likely reap most of the benefits of the lutein/zeaxanthin


Adam Karlovsky
Oct 11 2017 03:01 AM
Longevity/Neuroprotection Stack

Looks like a killer stack! How do you feel on it? Have you tried going a month without it and making a comparison?

My recommendations: 

- Resveratrol results have been disappointing, and it can be expensive. You could consider dropping it unless you think it makes you feel noticeably better.
- Alpha Lipoic Acid doesn't have to be a daily supplement, maybe just take it when you are particularly stressed or doing something stressful.

- Acetyl-L Carnitine could be dropped back to 100-500 mg per day.
- Schisandra could be dropped, unless you think it makes you feel noticeably better.

- Ubiquinol could be dropped back to once a week. It seems to be useful as a "top up" but likely not worth a daily supplement unless you're on statins.

- Vinpocetine could be dropped, unless you think it makes you feel noticeably better.
- Turmeric can be switched to a cheap curcumin + piperine supplement. e.g. Doctor's Best

+ Methylene Blue, a low dose (1-10 mg diluted in water, drunk over the day) seems to be a very cheap, safe and medically promising supplement.
+ Sodium Oxybate, if you can get a prescription or join a trial, is a very promising preventative for dementia. Improving sleep depth is vital for mental health.


Michael
Sep 18 2017 03:01 AM
Michael's "Tiered" Supplement

But serum retinol and RBP don't seem to be reliable indicators of vitamin A status, and I have great night vision, no hyperkeratosis, and my immune system seems highly functional despite all the weirdness around CR immune function studies.


pamojja
Sep 17 2017 10:52 PM
Michael's "Tiered" Supplement

It's just that I trust a cheap retinol and RBP test in my serum more than research in any other. Had these (fat-diet and BMI) also covered, but needed ridiculous high amounts just to normalize my levels.


Michael
Sep 17 2017 10:04 PM
Michael's "Tiered" Supplement

Nope! I get ≈1/9 of the DRI RDA from retinol, and 5.68 times the DRI RDA for vitamin A as carotenoids from beta-carotene alone, plus lots of alpha-carotene: that more than coveres a genetic variation of up to -69% from the canonical SNP (and we don't know the percentage of slow-converters have been included in the studies used to set the DRI RDA: unless every single one of them had the reference SNP, -69% is a worst-case scenario). Plus, human and animal evidence shows that bioconversion is increased in the face of a high-fat diet (check), and is negatively correlated with BMI (covered).


pamojja
Sep 17 2017 09:55 PM
Michael's "Tiered" Supplement

Thanks. so this study: http://www.fasebj.or...23/4/1041.fulldoesn't concerns you?


Michael
Sep 15 2017 08:30 PM
Michael's "Tiered" Supplement

I've never seen any compelling case for RBP testing, granted my very large beta-carotene intake and small but nonzero retinol intake. My 25(OH)D3, as I mentioned, is now in the low end of the 30-40 ng/dL range.


pamojja
Sep 15 2017 07:42 PM
A Longevity Promoting Regimen Leveraging the CAP, established and double blind tested by Mother Nature...

20.000 IU D3 ongoing is quite a dose. What 25(OH)D3 levels to you get with that? Or aim at?

Do you take any retinol? Since vitamin A and D3 and K2 all seem to support each other, and prevent toxicity of each taken at high doses. Did you ever test your serum retinol and retinol binding protein?

 

Thanks.


pamojja
Sep 15 2017 07:34 PM
Michael's "Tiered" Supplement

Michael, as followup on a discussion elsewhere, did you ever test serum retinol and RBP? Also would be interested in you 25(OH)D3, if you would be willing to share.