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Recent Comments


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

Why not consume alcohol-free wine?


Florin Clapa
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 Clapa
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.


pamojja
Sep 14 2017 09:37 PM
Multi- Vitamin and Mineral stack

I'm still searching, but I doubt there is any research of A, D3 and K2 in combination with hard health outcomes yet. Only have my own anecdotal case of being plagued with a number of devastating chronic diseases, and without much to loose, therefore was more than willing to experiment while monitoring. I didn't regret.

 

However, you might be absolutely right in that the A:D ratio which worked for me, might turn out completely off in a healthy person. Therefore always worthwhile testing serum retinol and retinol binding protein for confirmation. As an example of a very healthy person, what kind of serum levels you get with A and D?


Michael
Sep 14 2017 09:22 PM
Multi- Vitamin and Mineral stack

In principle, I'd agree that we'd want to be able to evaluate the whole system working together — but I don't know of any proper data on the subject, even in animals. The studies cited in the posts that you and RWhigham link cite are biochemistry, acute toxicity, and rather speculative inductions (eg, that the reason why trials conducted in the 1930s showed that cod liver oil reduced incidence of common colds and respiratory infections but that a 2004 trial yielded mixed results is that the cod liver oils differed in A and D content, and should have had higher D and lower A than the 2004 trial — or that the reason for low 25(OH)D3 in LEF members is excessive vitamin A supplementation from non-LEF multivitamins, even though the article itself says that "Most Foundation members take the Two-Per-Day or Life Extension Mix multi-nutrient formulas," which by their notions of a correct vitamin A dose do not suffer this problem).

 

Are either of you aware of any long-term studies in otherwise-normal, aging mammals testing the effects of different ratios of vitamins A, D3, and K2 against hard health outcomes?


pamojja
Sep 14 2017 08:26 PM
Multi- Vitamin and Mineral stack

Thanks for both comments, only saw them now.

 

I'm thinking more in line with Chris Masterjohn. And got his ideas confirmed through vitamin A and D serum testing, while aiming at the middle of normal ranges. In that I actually need at least a A to D IU ratio of 2 to 1 (the opposite RWhigham suggests). With the higher intake of preformed vitamin A, always slowly titrating and measuring, also infrequent psoriasis outbreaks have ceased (above 24.000 IU/d). But everyone is different, where only individual testing counts.

 

The problem I have with all the references you both provide, is that they look completely unrealistically at one vitamin - A or D in isolation only. That's how I never would even think of them, or further excluding vitamin K2 in all their synergistic effects.


aribadabar
Sep 08 2017 06:37 PM

Michael
Sep 08 2017 04:07 AM
Prevent Early Mortality

To make meaningful comments, we'd have to understand why you were taking these things, and at the dose you're taking them. I see no justification at all for an otherwise-healthy aging person  to be taking Olive Leaf Extract, Ashwangandha, or Curcumin. EGCG, Broccoli Sprout Extract, and Garlic Extract are fine, I suppose, but you'd be better taking the actual foods (and green tea pills have been linked to a fair number of cases of liver toxicity, unlike the tea). Your EPA+DHA dose is probably twice as high as it should be. Your vitamin D is also likely way too high: are you having your 25(OH)D tested, and if so, what level are you targeting? See discussion at my stack (and, indeed, see discussion there on supplementation generally).


Michael
Sep 06 2017 09:30 PM
Michael's "Tiered" Supplement

In response to aribadabar's questions:
 
I quit IP6 because I have persistently high serum phosphorus (which is bad), and because my dietary IP6/phytate and inositol is already likely at the extreme end of the population (legumes and nuts). Additionally, there was little positive reason to take it, either: I don't have any history of kidney stones, I drink plenty of fluids and have a high-intrinsic-water diet, and no one has yet done a study showing it benefits otherwise-healthy aging rodents or humans. And if it's working by mobilizing NK cells, well, who knows what decades of incessant NK stimulation could do?
 
I quit the lactoferrin because I finally admitted to myself that there's never really been any good reason to take the stuff. And my iron stores are still right where I want them to be.
 
Glycine: I decided that I had to stop drinking water just before bed in order to avoid a mid-night trip to the bathroom, which seems like a more sensible way to ensure solid slip than doping myself up with supplements — and I'm reluctant to take it on an empty stomach. Plus, I suspect that it may have been the reason for my occasional bouts of waking up at 3 AM with a pounding heart and a sweat: my hypothesis is that this is due to Somogyi effect, arising from the interaction of glycine-induced insulin secretion with my having CR-associated high insulin sensitivity and low glycogen stores: see here and here. Certainly, I've had none of these episodes in the months since I quit taking it.


Michael
Sep 06 2017 09:19 PM
Michael's "Tiered" Supplement

 

The diff' is that PC raises TMAO less than citicoline.

Do we know whether it raises TMAO less per total mg or per mg of choline supplied? 

 

Per mole (properly) of choline  supplied. We don't have actual quantification on citicoline, but it's been demonstrated that it raises it, and since citicoline is hydrolyzed in the intestine prior to absorption, the relative amount should be similar to that of choline salts; clean PC barely raises TMA(O) at all, whereas choline salts raise it ninefold.


Gordo
Sep 06 2017 05:01 PM
Life Extension and Great Health Regimen Stack

Decent holistic reasoning, but while Jiaogulan has ben shown to improve insulin sensitivity and reduce HbA1c, it doesn't have any evidence for it's longevity effects. You could pick something like rapamycin, selegiline, metformin, or aspirin for more assured increases in lifespan. I'd even pick reishi, another 'immortality herb' over jiaogulan, but ideally both need to be studied more... I hope we can secure some funding for such research in the near future!

Turmeric + Black Pepper is probably not doing much for you, considering you have a plant-based diet already. The clinically meaninful effects are seen with high doses of mixed curcuminoids, not plain turmeric.

Otherwise... good approach!

 

OK, let me take these one at a time.  First with regard to mushrooms, I agree, which is why I specifically mentioned them in my write up, although I could have gone into more detail.  Shiitake and Reishi are fine choices, I recommend a wide variety, and even the plain old cheap white button mushroom is very good for you.  Oyster mushrooms contain natural LDL lowering compounds.

 

With regard to jiaogulan - there are a large number of published studies from reputable sources demonstrating its health benefits, if you take that alone, its pretty logical to assume it would help with longevity, anecdotally, the people groups that consume it daily are known for their comparative longevity (admittedly, that alone is not great evidence).  Its very hard to scientifically prove ANYTHING is good for human longevity, we just know what improves biomarkers of health.  Mouse studies are interesting but not always relevant.  

 

"You could pick something like rapamycin, selegiline, metformin, or aspirin for more assured increases in lifespan"

 

I consider these myths, mostly debunked, although still under active scientific scrutiny. There is even less evidence that these will result in longevity than exists for jiaogulan, in fact taking these drugs is more likely to harm an otherwise healthy person. Rapamycin is well known for compromising the immune system and promoting cancer, metformin has an enormous list of negative side effects and has never been shown to increase max lifespans (more on this below).  Aspirin is a terrible idea for healthy people (primarily due to increased chance of gastrointestinal bleeding):Aspirin Bleeding Risks Outweigh Benefits - ABC News

 

 

"The following critique was authored by a Professor of Applied Statistics at the Open University in the UK ("Professor" is a much more senior position in the UK than the USA, denoting something like a department head), and seems cogent and consistent with a slightly cryptic phrase in the abstract, in which case teh study is likely not worth paying much attention to:
 

Quote

Expert reaction to study looking at type 2 diabetes, metformin and lifespan

 

The title of this paper itself is not helpful in that anyone reading it might get the wrong idea – this study cannot actually answer the question it poses (“Can people with type 2 diabetes live longer than those without?”) for reasons discussed below, and it sounds almost as if there are grounds to advise people without diabetes to take metformin. But in fact the study isn’t saying that at all.

In the press release, Craig Currie says “People lose on average around eight years from their life expectancy after developing diabetes” and goes on to explain why. So if the life expectancy of people with type 2 diabetes is so much shorter, how on earth can they “live longer than people without the disease”, as the title of the release and the paper both say?

The answer is that the comparison in the paper runs only over the time period when the patients with diabetes were on first-line treatment with metformin, on its own (and there’s a similar comparison involving patients whose first-line treatment is with sulphonylureas). At some point after this first-line treatment starts, many of the patients with diabetes would be switched from metformin alone onto a second-line treatment, and this switch is (or should be) necessary because the diabetes or its effects have got worse. But at that point the comparison in this study simply stops.

So the quote in the press release about an eight year reduction in life expectancy, in people who develop type 2 diabetes, is talking about the entire rest of a person’s life after the diagnosis, including the time when they might be on a more aggressive second-line treatment. But the comparison in the paper is looking only at the time before the treatment changes. ...

[MR: This is evidently what the abstract means by using a "censored followup:" they ONLY looked at deaths occurring WHILE the person was on metformin or sulfonylureas: if your disease progressed, and they added on a secnd drug to bring your glucose back under control, you were simply "censored" out of further followup. This would obviously greatly bias the resulting mortality rates (and note: it is for sure from the abstract that they did not actually look at life expectancy, despite the press release AND the title of the abstract: explicitly , they ONLY looked at mortality rates of people while they were only on one drug (or, during the matched number of years of the nondiabetic controls). This means, by definition, that people who were put on the drug most usually used for the mildest diabetes (metformin) and who remained stable and healthy on it, were being compared to more severe patients at outset (on sulfonylureas), and as soon as they got sick they vanished from the analysis! Comparing even average nondiabetic people to unusually successful diabetics is, from the get-go, comparing elite diabetics to merely average aging people. Returning to the critique:]

The researchers did match the controls with patients with diabetes in certain ways, and in their statistical analysis they try to allow statistically for other differences between the people with diabetes and the controls. But the paper itself points out some issues. The researchers could not take into account certain possible confounders (other variables that might affect the comparison) because they did not have data on them for enough of the controls. Even without that important issue, statistical adjustment for confounders is never perfect. The difference in survival between people with diabetes on metformin, and controls without diabetes, was statistically significant but in fact rather small, and probably within the range where it could be explained by residual confounding ...

Further, the paper itself also points out that people with diabetes are more likely be monitored for, and receive interventions for, problems with the heart and circulation. This extra intervention and monitoring, and the possibility of residual confounding, between them cast huge doubt on the possibility that the better survival in the patients taking metformin, compared to controls without diabetes, was simply because they were taking metformin. ...

http://www.scienceme...n-and-lifespan/

 

And, as a reminder: metformin has been tested now at high and low doses in normal, healthy mice, and also in a somewhat flawed study in rats, and in no case has metformin increased maximum lifespan;there was a very mild increase in average LS in the mouse studies, which might well be due to residual effects of a diet of lab chow and no exercise." [Credit to Michael Rae on that metformin info].

 

"Turmeric + Black Pepper is probably not doing much for you"

Like Jiogulan, there is a mountain of scientific evidence for the benefits of small amounts of turmeric in one's diet, among many other things, its a very powerful anti-inflamatory.  Slightly off topic, but its also a phenomenal tool for recovery improving postoperative pain and fatigue.

 

-Gordo


aribadabar
Sep 06 2017 04:42 AM
Michael's "Tiered" Supplement

Why did you remove Lactoferrin, Inositol /IP-6 and Glycine from your regimen as per its previous version?


Adam Karlovsky
Sep 06 2017 03:25 AM
Life Extension and Great Health Regimen Stack

Decent holistic reasoning, but while Jiaogulan has ben shown to improve insulin sensitivity and reduce HbA1c, it doesn't have any evidence for it's longevity effects. You could pick something like rapamycin, selegiline, metformin, or aspirin for more assured increases in lifespan. I'd even pick reishi, another 'immortality herb' over jiaogulan, but ideally both need to be studied more... I hope we can secure some funding for such research in the near future!

Turmeric + Black Pepper is probably not doing much for you, considering you have a plant-based diet already. The clinically meaninful effects are seen with high doses of mixed curcuminoids, not plain turmeric.

Otherwise... good approach!


Michael
Sep 04 2017 08:02 PM

jwilcox25
Sep 04 2017 02:52 AM
Michael's "Tiered" Supplement

The diff' is that PC raises TMAO less than citicoline. I don't know which would raise serum choline more, but I prefer PC because it's both safer based on TMAO and I think consuming it this way is more conservative: my far-from-expert understanding is that CDP-choline is quite rare in the diet, being only present as an intermediate in PC synthesis in the CDP-choline pathway.

Do we know whether it raises TMAO less per total mg or per mg of choline supplied?  


RWhigham
Sep 03 2017 10:29 PM
Multi- Vitamin and Mineral stack
high intake of preformed vitamin A increases fracture risk.

Ref: Excess Vitamin A Can Thwart Vitamin D

Osteoporosis is caused by a mismatch between vitamin A, D, and K2.  The ideal A/D ratio wt/wt is about 5 to 1 which corresponds to an iu/iu ratio of 1 to 2.4 since 1 mg of vitamin A is 3,333 iu and 1 mg of  vitamin D3 is 40,000 iu  so  5 g to 1 g  = (5)(3,333 iu)/40,000 iu =  1 to 2.4  iu/iu

 

Example:  vitamin A retinol at 1,000 iu per day needs 2,400 iu per day of D3.

 

The "more is better" supplements are ridiculous--a quick look a Amazon show "vitamin A" in 5,000 to 25,000 iu capsules (likely mostly beta-carotene).  A 25,000 iu dose of retinol would need to be balanced with 2.4 x 25,000 = 60,000 iu of D3.  Perhaps you could take one 25,000 iu vitamin A (as retinol) per month and balance it with 2,000 iu of vitamin D3 daily.


Michael
Sep 01 2017 06:14 PM
Multi- Vitamin and Mineral stack

A note of caution on preformed vitamin A. You're right that the acute toxicity of very high levels of retinol has possibly been overestimated, but there is significant evidence that high intake of preformed vitamin A increases fracture risk. The studies aren't totally consistent; notably, studies based on serum levels are far less likely to find an association, but that may be because serum retinyl esters poorly track high dietary intake. Even so, a meta-analysis of prospective studies concluded that both high dietary and high blood retinol are associated with elevated fracture risk.