Debating Claims About NR & Rapamycin | 46 - X-Wars

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Our recent episode on the Interventions Testing Program's recent tests on various longevity interventions sparked some interesting debate on X. City of Hope National Medical Center's Alfred E. Mann Family Foundation Chair in Diabetes and Cancer Metabolism Charles Brenner made a remark about the potential negative effects of rapamycin on humans, while Ponce De Leon Health Chief Operating Officer Mike Muldoon plugged the calcium alpha-ketoglutarate supplement Rejuvant (the ITP tests reported no lifespan extension of alpha-ketoglutarate on mice). Matt responded to these comments on X and some interesting back and forth with Charles and Mike ensued.
In this episode, Matt and Nick take a magnifying glass to Charles' and Mike's feedback and examine the published data-and some unpublished data-to consider and respond to their claims. They also discuss the allure of phrases such as "scientifically proven" and "clinically proven" in marketing, and the importance of approaching such phrases with a critical mindset and an eye towards study robustness and methodology as well as the researchers' impartiality.
0:00 Trailer
1:06 Introduction
3:09 Charles Brenner's take on how rapamycin will affect humans
6:05 Matt's response to Charles' take
14:59 Mike Muldoon's take on Rejuvant, a calcium alpha-ketoglutarate supplement
15:30 Matt's response to Mike's take
20:48 A follow-up post from Mike
21:04 Matt's response to Mike's post
39:14 Wrapping up
Producers: Tara Mei, Nicholas Arapis
Video Editor: Jacob Keliikoa
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Hi, I'm Matt Kaeberlein. I spent the first few decades of my career doing scientific research into the biology of aging, trying to understand the finer details of how humans age in order to facilitate translational interventions that promote healthspan and improve quality of life. Now I want to take some of that knowledge out of the lab and into the hands of people who can really use it.
On this podcast I talk about all things aging and healthspan, from supplements and nutrition to the latest discoveries in longevity research. My goal is to lift the veil on the geroscience and longevity world and help you apply what we know to your own personal health trajectory. I care about quality science and will always be honest about what I don't know. I hope you'll find these episodes helpful!

[@erdemy2702]

You are doing great work Dr. Kaeberlein. Unfortunately the world is filled with marketing people trying to make money by being vague. Precise and accurate communication is indeed what we need. I appreciate your communication where you try to base it on facts and reliable information.

[@sticksstonesbuildmybones7837]

I really appreciate Matt's nuance and intolerance of deceptive communication of science. As an older (65yrs) man, who has managed to stay strong and healthy, I still experience age related issues, of course, which I'm excited to challenge and improve where possible. Having some clarity on the science is a time and cost saving advantage when it comes to making choices about what might be worth investing time and $$ in. Thanks for all the useful information!

[@optispan]

We're so glad you find it useful. - Tara

[@MikeVarnco]

This podcast is fantastic, thanks guys!

[@optispan]

Thank you for your support! - Tara

[@MichaelMerritt]

Love that you’re shining a light to all the longevity and lifespan BS out there and a voice of reason. Thank you 😊

[@jaykraft9523]

AKG discussion is fascinating. And discouraging. Have already seen NMN and resveratrol come and go in my daily routine, and CAKG is likely next. Very little left that interests me as a supplement (currently using Glynac and Taurine besides CAKG, but wouldn't be surprised to see them shitcanned as well). I did the methylenation DNA aging test before I started, so will follow up with another test shortly (been on the CAKG+ for over a year). Getting the distinct impression the life extension supplement market is absolutely filled with snakeoil and snakeoil salesmen.

[@RobertNaik]

@@jaykraft9523 I agree strongly. I’m just taking the basic one right now.

[@anirecapped.]

@@RobertNaik Glycine actually worked in the ITP studies.

[@jaykraft9523]

glad to hear it. hoping glynac (glycine with nac) is even better

[@anirecapped.]

@@jaykraft9523 It's almost bound to.

[@radicalveg00]

Matt, I very much appreciate your honesty, especially because I believe you are a longtime friend of Brian Kennedy.

[@newyorkskier]

Charles Brenner is a used-car salesman who did some good science a long time ago

[@RobertNaik]

A few weeks ago I got a full health check. It’s was all good except my kidney function which was just okay. I was doing a lot of running so that probably was why I had some high level. But after doing a bit of research I stopped taking NR to be safe.

[@paveldrobnych]

Kidney fn shouldn’t be affected by aerobic intensity. Mine was fine but I stopped taking those sups anyway

[@RobertNaik]

@@paveldrobnych I’d done some VO2 max work and a race. my eGFR was very good but my creatinine level was very high. I’m not an expert but I think it can be affected by a hard effort like a race. I just google it but My doctor didn’t see any problem at the time. I could be wrong. Have a great day.

[@paulcohen6727]

@@RobertNaikif you supplement with creatine, you will likely get a false high creatinine test result.

[@workingTchr]

I'm in a similar boat and searched around after hearing this. One of the top hits was an article from 2023 in Medical News Today titled, "Scientists identify key pathway underlying kidney disease" that says that NMN is probably GOOD for kidneys. I think we need serious AI to straighten all this out. EDIT: I found the article Kaeberlein was referrng to. It looks like it was the first (and only?) one to address the effect on ELDERLY mice. Being elderly, I'm also going to play it safe and stop taking NMN for now, but I hope this study is proven wrong since there seems to be so much good from NR generally (longevity excepted).

[@kylem3356]

I really enjoy your analytical look at these interventions, you taught me that a degree of skepticism is definitely warranted in the longevity field. In which tier would you place Pentadecylic acid aka C15 (An apparently newly discovered essential fatty acid) and Red Light Therapy?

[@bobbobson4030]

Excited to see the results in Marmosets. When are we expecting the paper? Did they observe cataracts and testicular degeneration as in some previous papers?

[@salobaid9652]

Hi Matt I applaud your efforts.I truly enjoy your discussions and rest assured that you are making a difference so please keep up the good work. More than once you eluded to calcium supplementation as if it is something positive to take while you were talking about AKG. As a practicing physician I almost never prescribe calcium supplements for my patients and I try to discontinue it whenever I can.Taking calcium supplements is associated with higher incidence of bone fractures and does not improve bone density,along with the possibility of increasing vascular calcification therefore if any thing comes out of it it is more harm than good. Alpha ketoglutarate should be talked about as possible longevity supplement only and not as a calcium supplements to avoid misleading public who might think AKG is good for more than one purpose where in fact it is not proven for any indication at this point.

[@edgarwilhelm8055]

Thank you so much for familiarizing us non-scientists to the way science works. I remember from my MBA statistical seminars that you cannot prove something but rather disprove an assumption. However, not having used statistics in decades - I forgot about this! Very interesting indeed!!! My only question is - with most of the supplements and interventions not having any effect - will we ever find anything to extend heath-span let alone life-span improvements?

[@optispan]

We certainly hope so. The field is working hard to find interventions that might extend health/lifespan-that includes new drug discovery as well as potentially repurposing existing drugs if they turn out to have a significant effect on health/lifespan. - Tara

[@peterezzell3865]

Yes, niacinamide in modest dose. Plus a few natural substances which address NAMPT in the salvage pathway. Need to good test for NAD+ as it makes no sense to toss in a bolus.

[@scooterboy2284]

I have a question . I have read that high dose niacin (1000mg) can cause hart problems . What dosage do you recommend to increase nad levels ?

[@mitchellgould2053]

The Rejuvant discussion brought up the efficacy of epigenetic testing in regards to lifespan. I wonder if it would be worth running a mouse model rapamycin trial- since the life extending effects are already well documented- and testing its effects on various epigenetic clocks as the mice age. Like, will a mouse that lives 25% longer than average have a 25% younger epigenetic age than average? Or would we see some other effect on the clocks? It’s the clocks themselves that need testing.

[@orion9k]

I do 500mg of b3 niacin / nicotinic acid, almost every day and it's one of my favorite supplements, I especially enjoy the skin flush effect. There is one down side from b3 nicotinic acid, from what I can understand, it increases your blood glucose further if combined with a meal and lowers your blood glucose further if you're fasting, and personally I get extremely sick if I take b3 niacin / nicotinic acid on an empty stomach, but it's cured fast with half a piece of fruit or a meal with some carbs. If you are obese, I would advice you to either stay away from b3 niacin / nicotinic acid or only take it if you plan to be very active for the next hour to few hours 🙏

[@worldtraveler691]

Brenner is a paid consulant for Chromax makers of NR

[@ats89117]

Hmmm. I take AKG because it keeps my hair from graying and even darkened hair that had already turned gray...

[@Dr_b_]

is it working?

[@augurcybernaut4785]

G6PD deficiency has problems reduction

[@bob-ss4wx]

Matt, again gets right to it and communicates IN ENGLISH!

[@notrueflagshere198]

Does Nick have a name? Jikomes?

[@camarosspr]

A better way of extending lifespan Would be to reignite puberty Find the signaling process that starts at 10-12 through 18 Let the body do the job The puberty process is there Just restart it

[@in2caffeine]

reseratrol helped lower my high iron saturation. that may eztend lifespane.

[@Snowymurcia]

That's interesting, is there any more info on this??

[@in2caffeine]

@@Snowymurcia Resveratrol ameliorates iron overload induced liver fibrosis in mice by regulating iron homeostasis.

[@in2caffeine]

@Snowymurcia so I figured why not try since there is no known good way for the body to bring down excess iron effectively. anecdotally, it appeared to improve sleep quality as well.

[@in2caffeine]

@Snowymurcia further improvements with CoQ10 and ground chai seeds is another option, or adjunct. Just try and go to dr to measure iron status...

[@in2caffeine]

@@Snowymurcia Chia seeds and coenzyme Q10 alleviate iron overload induced hepatorenal toxicity in mice via iron chelation and oxidative stress modulation

[@camarosspr]

Not knowing the full mechanism Relying on trials w rats, mamals Is pathetic Its like guessing, like hoping

[@camarosspr]

Restart puberty Find the signaling That's it

[@camarosspr]

3% body fat loss, could be diet 2 pound increase of muscle In 3 months is..... Though you don't look a day older than 60

[@camarosspr]

All these talk bout anti aging and Suplements Theire crude at best Were far from knowing enough body biology, were bout 30% knowledge