I found this microbiome discussion interesting. Fecal transplants from young to old may not be a good idea, actually. Also, Matt throws shade on Pendulum, and it turns out the guest has used Glucose Contol.
Grok made more errors than usual in attribution. I tried to fix them, no warranties.
# The Hidden Side of Health You’re (2)…pdf (432.6 KB)
I like Matt and respect him as a scientist, but I don’t think he’s a very good podcast host. And the bald doctor guy he has on regularly (Kevin?) is really bad at explaining things. I just find myself really frustrated listening to him talk really slowly, saying “you know” a lot of times, and Matt having to like fill in all the blanks.
So I will definitely watch the videos where Matt is talking about a research paper, particularly on Rapamycin, because that’s his expertise. He’s an experienced researcher and peer reviewer and he knows what’s going on. But this stuff like cardiovascular and gut microbiome is too far outside of his field.
GI issues. Back in the day, the protocol was to take 20g per day for a week to “load” your muscles with creatine. A good % of people will get horrible stomach cramps and you’ll be on the toilet for a while. 5g per day is effortless, works well, and likely won’t have any side effects.
Introduction to Gene Therapy
Personal Backgrounds of the Guests
Concerns About Unregulated Therapies
The Role of Extracellular Matrix in Aging
Unlimited Bio and Its Mission
Regulatory Challenges and Opportunities
Current and Future Therapies
Ethical Considerations and Patient Safety
Conclusion and Future Directions
Introduction to Longevity Myths
Myth 1: Measuring Biological Age
Myth 2: Supplements as Core Components of Health
Myth 3: Age and Longevity
Myth 4: FDA Approval and Aging
Myth 5: Resveratrol as a Longevity Molecule
Myth 6: Funding for Aging Research
Myth 7: Genetics and Longevity
Myth 8: Caloric Restriction and Cancer
Myth 9: Rapamycin as a Core Component of Longevity
Myth 10: Peptides as Natural and Safe
Conclusion and Future Discussions
A master of the straw man argument.
I listened to his recent podcast on fighting cognitive decline and thought it was pretty interesting, so I thought I’d link the summary @Jonas posted here.
He and his two guests are starting a brain health program. I’m not so sure I’d be wanting to pay what is probably a lot of money for the two guests to help me, but Matt is obviously very appealing. (Having said that, I’m already doing most of what they listed, so I don’t think I need any of them because I have all of you!).
It was encouraging to see that many of the people here are already doing everything on his list. I’ll mention things that stood out to me.
I was surprised they talked about NAD precursors only because most have seemed dismissive of those of late, but this makes them interesting to me again.
Also, it seems they think low doses of Cialis type drugs might be good for women’s longevity, too. I’ve never heard this mentioned and it never occurred to me, but I guess it makes sense that it would work for both sexes. I know a lot of you do this, so now I might deep dive into the pros and cons for me. I once heard these drugs can increase your risk for a heart attack, but that was when they first came out and I have not read about them again and nor do I know if that was even true.
I didn’t realize rapa might help with brain volume in humans, so this was great news to me. I did the brain MRI and it looked good except for that one area. It was unknown if mine is shrinking or if it’s just where I started.
They mentioned TMG but I was once told only take that if your homocysteine levels need improvement.
They mentioned magnesium theonate, but it seems most people don’t bother with that one. I stopped taking it a while ago.
They made plasma exchange sound really appealing, but alas, it’s very expensive and too rich for my blood (pun intended) to do for a nothing more than a ‘maybe’ for prevention. If it became a sure thing, that would be a different story.
I just watched his podcast with Ryan Ware, one of the founders of https://mitohealth.com/
Matt K and Brian Kennedy are the only two others listed as involved parties.
I have insurance and, by necessity, a concierge doc, so I imagine this would not make financial sense for me, but it looks very appealing for those of you who need to pay for labs and each doc visit.
For people like me, I wish sites like this would let you pay for what you can use and not have to do the whole shebang.
I thought this would have been posted by now but I don’t see it anywhere else. Great discussion but I wish they could’ve spent another hour talking about other topics in addition.
They had a nice little debate as well, where I am fully on Matt’s side. If there is any criticism I have about Dr. Stanfield, it’s that he is slightly too conservative when it comes to prevention. I have a ton of respect for him though.
Claude:
I’ll fetch and analyze that YouTube video for you.I’m unable to directly access YouTube videos through my tools. However, I can see from your document that you’ve already provided a transcript of what appears to be an interview between Brad Stanfield and someone at a Longevity Investors Conference in Gstaad, Switzerland.
Let me create a tidy summary and critique based on the transcript you’ve provided:
Participants: Brad Stanfield (primary care physician, New Zealand) and interviewer at Longevity Investors Conference
Key Topics Covered:
Brad’s Background
Rapamycin Clinical Trial
Healthcare Philosophy
Key Medical Opinions
Philosophy on Science Communication
Disagreement Areas with Interviewer
Strengths:
Intellectual Honesty: Brad’s willingness to admit past mistakes (resveratrol, sulforaphane, metformin) demonstrates integrity rare in the health influencer space.
Financial Commitment: Mortgaging his house for rapamycin research shows remarkable dedication to advancing the field.
Methodological Rigor: Strong emphasis on CONSORT guidelines and proper trial design is commendable.
Patient-Centered Approach: The focus on shared decision-making rather than paternalism is progressive.
Weaknesses & Concerns:
Overly Conservative on Vitamin D:
Excessive Deference to Guidelines:
“Vastly Outweigh” Standard is Problematic:
Inconsistency on Guidelines:
Limited Engagement with Biological Age Debate:
Aging Biology Understanding:
Key Philosophical Divide:
The conversation reveals a fundamental tension between:
Both approaches have merit, but Brad’s position seems more suited to resource-constrained public health systems than to personalized/precision medicine for motivated individuals.
Overall Assessment:
Brad Stanfield is clearly a thoughtful, ethical physician doing important work (especially the rapamycin trial). However, his framework may be overly conservative for the longevity optimization context. His strength in clinical medicine and guideline adherence becomes a limitation when applied to preventive/enhancement medicine where guidelines lag evidence and individual variation matters more.
The interview would have benefited from deeper exploration of:
Claude failed to do the transcript, but I have the transcript from chatGPT
Introduction
Host:
The very high-profile medical doctor continues to get the fundamental biology of aging literature wrong and presents it incorrectly. I can’t help but ask myself: is it that they don’t know better, or that they do know better and choose to keep presenting bad information?
My wife once said, “This is a draft idea. No one will ever listen to you.” And here we are now. She’s since said, “Yeah, I was wrong.”
We were still left with about a $150,000 shortfall for the study, and that’s where my wife let us remortgage our house.
How we understood the surface of the Earth in 500 BC—I feel like that’s how we understand the biology of aging today. There’s a lot we don’t understand. If we were really getting closer to solving aging, we ought to be able to increase the lifespan of a mouse by more than what Rick and Roy did 50 years ago. We aren’t doing it.
One of my biggest concerns is that no doctor should be recommending these tests.
Host:
Hey guys, look who I ran into at the Longevity Investors Conference in Gstaad, Switzerland: Brad Stanfield. This is the first time we’ve met in person. I’ve been on your podcast a couple of times and we’ve done some other things together, which I’m sure we’ll talk about. Great to connect in person. We’ll just talk about whatever comes to mind and see where it goes.
Brad:
Absolutely. A lot of people watching will know of you or have seen your podcast, but may not know much about you or how you got interested in this space. I’ll say “longevity,” but you can choose a different word if you like. Maybe talk about your background, what you’re doing now, and how you got into your YouTube channel and day job.
Brad:
My day job is as a primary care physician in Auckland, New Zealand. Getting there was a bit of a journey.
As a junior doctor working in hospitals, I noticed some wrinkles around my eyes. That kicked off my interest in aging—are we closer to slowing the aging process, what can we do about wrinkles, are there breakthroughs underway? That led me into things like metformin and IGF-1, and that really started my journey.
Originally, I had the idea of becoming an orthopedic surgeon. I spent about a year fixing broken bones and hips but realized that lifestyle wasn’t for me. I took a year out and worked in the emergency department. During that time I kept thinking: I’m really interested in the aging process, but I want to bring science into this field—especially because there’s so much misinformation online.
People were extrapolating single-cell research straight to human supplements: “Look what happened in a single cell, therefore you should take this.” You still see that all the time. That motivated me to start my YouTube channel.
I had no idea it would grow or that people would listen. My wife told me, “This is a daft idea, no one will ever listen to you, you shouldn’t do this.” But here we are now. She admits she was wrong—and that’s the only time I’ve heard her say that. She’s been very supportive.
I started the channel at the end of 2019, while working in the emergency department. My early videos—now deleted—were filmed on a couch in a hospital residence after night shifts. One thing led to another.
Host:
Your channel has done great. What do you think led to its success?
Brad:
I think people were craving clear communication of human, clinical trial data. There’s so much misinformation and people genuinely want to be healthy, not misled.
People seem to appreciate that I’m guideline-driven. Primary care guidelines are fantastic, but most of the public don’t know about them. I try to democratize that information in a way that isn’t too dreary. I think that approach resonated.
Host:
When I first saw your videos, I had to get past the “YouTube style” to get to the content. But your work is very data-driven and stays scientific. In my view, you’re more conservative in presenting science than I am. I really like how rigorous you are.
Brad:
I appreciate that. Honestly, I’m scared when I publish a video in case I’ve got something wrong. With the channel size I have, if I make mistakes and people follow that advice, that’s a real problem—especially as a practicing physician. The advice I give on YouTube needs to match what I give to patients in clinic.
If I’m wrong on YouTube, I’m potentially wrong with patients too. So I double-check guidelines, make sure I haven’t missed key clinical trials, and focus on randomized controlled trials. A lot of people quote observational data—vitamin D, magnesium—huge associative datasets suggesting benefits, but randomized human trials often show mixed or null results. Vitamin D and cancer is a classic; the VITAL trial is one I often cite.
Host:
All evidence is imperfect—even clinical trials. You have to synthesize everything and form a probabilistic understanding of what’s most likely to be true, recognizing it can change.
I also care deeply about accuracy, but we’re going to make mistakes. The key is being willing to say, “I got this wrong, here’s what the evidence actually says.” That separates people trying to do their best from those chasing clicks.
Brad:
Exactly. I’ve publicly corrected myself on resveratrol, sulforaphane supplements, metformin, and more. I went wrong when I deviated from my clinical training and got pulled along by charismatic individuals in the aging space. I trusted “elders” in the field instead of applying my usual standards.
I think people appreciate that I say, “I got it wrong, here’s why, and here’s what I’m changing.”
Host:
Many people got fooled by the resveratrol story. It’s frustrating that some big, well-credentialed names still misrepresent aging biology and sirtuin data, especially when they should know better by now.
There’s a very high-profile medical doctor who consistently misstates basic aging biology and sirtuin/resveratrol literature. It’s unfortunate.
Brad:
I don’t really watch that person’s content.
Host:
Let’s switch topics to rapamycin. You became very interested in testing rapamycin in the context of exercise response in healthy older adults. You raised funds with philanthropic support, viewer donations, and your own resources—which is uncommon. Talk about that trial: what it tested, how it worked, and where it’s at.
Brad:
My interest in rapamycin came from the Interventions Testing Program, where rapamycin repeatedly extended lifespan in male and female mice.
Clinically, rapamycin has a bad reputation as an immunosuppressant for transplant patients, so there’s concern that if we get the dose wrong in healthy people, we might increase infections or cancer. Fortunately, some human trials show that if mTOR inhibitors are dosed correctly, those risks can be managed. But we still lack robust data in healthy individuals.
A lifespan study in humans would take decades, so we needed a functional outcome. I focused on muscle performance, which declines with age and is linked to overactive mTOR in older muscle. Overactive mTOR may limit autophagy. The idea: dose rapamycin intermittently to turn mTOR down, allow autophagy and cellular cleanup, then use exercise to reactivate mTOR to rebuild healthier tissue.
With your input, we designed a trial: exercise three days a week (Mon/Wed/Fri) plus 6 mg rapamycin once weekly on Saturday. The primary endpoint was the 30-second chair stand test—sensitive to lower-body power in older adults.
It was only a 40-person study, but took about two years to fund. Viewers donated; Vadell contributed; the total cost was about USD $500,000. After two years we were only a quarter funded. To close the remaining gap we created a supplement line, with the idea that profits could fund clinical trials like this. Another funder came on board, but we still had a ~$150,000 shortfall.
That’s when my wife agreed we could remortgage our house to get the trial done.
We’ve completed the study, written it up, and submitted it for peer review. Once that’s done, we can share the results. I think they’re exciting and informative for how to dose rapamycin in healthy individuals to affect muscle performance.
Host:
Your wife sounds extremely supportive.
Brad:
I’m very lucky. Still paying off that mortgage though.
Host:
Why 6 mg once a week?
Brad:
We lack definitive human data—that’s exactly why we did the study. We chose intermittent dosing to create windows of mTOR inhibition (to boost autophagy) followed by drug washout so that exercise could reactivate mTOR for muscle building. The hope is that this “on/off” pattern optimizes the balance.
Host:
You need mTOR to build muscle, so chronic suppression is a concern. Animals on rapamycin show better muscle function with age, but human data are sparse.
Brad:
Exactly. It’s a major gap we wanted to help fill. Big pharma has little incentive to fund these trials, so it required unconventional funding.
We’ve submitted the paper; it hasn’t been rejected and has been under review for a while, which is a good sign.
Host:
You’re also starting a PhD. Why, given you’re an MD with a successful channel and a supplement brand?
Brad:
Presenting other people’s data is one thing. I want to generate high-quality data myself—especially because many studies in this space aren’t robust.
I want our trials to be rock-solid and CONSORT-compliant: proper randomization, blinding, powering, reporting, minimizing bias. A PhD at the University of Auckland gives me supervision, structure, and better access to funding pathways. Our rapamycin work is fully non-profit, and the university is happy to sponsor it; 100% of donations go to the studies.
If people want to donate, they can contact me via my website, drstanfield.com, or through my YouTube channel, and I’ll connect them with the correct people at the university.
Host:
We’ve talked offline about prevention. My view is that US primary care is reactive, not focused on keeping people healthy. You’ve said New Zealand is different.
Brad:
New Zealand has a predominantly public system. A key goal is to prevent hospitalizations because they’re expensive. Preventing heart attacks and strokes in primary care is more cost-effective than treating them.
The government incentivizes prevention, and training reflects that. There’s a strong prevention culture. It’s jarring to hear how different it is in the US, where incentives favor procedures and hospital care.
Host:
Insurers in the US don’t reliably value prevention, and many patients won’t do something if insurance doesn’t pay. That culture plus misaligned incentives makes change hard.
Brad:
Because funding is constrained in New Zealand, there are clear guard rails on what tests I can order. I spend a lot of time on my channel discussing which tests are worthwhile and which are not. People often think “more data is better,” but unnecessary testing can be wasteful or harmful.
Brad:
Vitamin D is a good example. There was (and is) a big push to test vitamin D levels. Recent Endocrine Society guidelines essentially say we don’t know how to interpret vitamin D levels in a way that meaningfully changes outcomes for most people.
Trials using ~800 IU daily seem to “lock in” bone and immune benefits for the general population. Higher doses have shown potential harm. Vitamin D blood levels often track frailty or indoor living rather than cause outcomes. Retrospective data haven’t strongly supported routine testing as a driver of better outcomes.
Given cost constraints and limited benefit, broadly testing everyone isn’t a great use of resources in my setting. People can still self-pay if they wish, but at the population level we prioritize interventions with clearer impact.
Host:
I’m skeptical of guideline committees because of past failures like hormone replacement therapy (HRT) after the Women’s Health Initiative. I worry they overweight small safety signals and underweight quality-of-life and broader benefits.
Brad:
I see guidelines as our “least bad” option. They’re produced by domain experts reviewing the evidence. Not perfect, but better than individual “cowboy” interpretations. Medicine should move cautiously; reversing widespread recommendations is difficult.
Host:
But that caution can cause harm too, as many women lost access to HRT benefits for decades.
Brad:
We can debate that specific history, but my broader point is: following well-constructed guidelines usually reduces errors at the population level, while allowing for justified individual deviations.
Host:
Let’s talk about one of your big concerns: biological age scores.
Brad:
Right. I see two main problems:
I see biological age tests as interesting research tools, but they shouldn’t guide routine clinical decisions on preventing heart disease, stroke, or cancer.
Host:
I agree. No doctor should recommend a test they don’t understand, can’t quantify in terms of accuracy/precision, or that doesn’t clearly inform care. That describes most biological age tests today.
Brad:
If patients want to pay for them and they find them motivating, fine. But I explain that our management plan for real risks won’t change based on that number.
Brad:
In my training there was a strong shift away from paternalism and toward patient-centered care. It’s not my job to dictate; it’s my job to present benefits, risks, and options, and support informed decisions.
If patients ask what I’d recommend, I’ll say, “Based on this evidence and these guidelines, I suggest X,” but it’s their decision.
Host:
Many US doctors are still more paternalistic. I like your approach, though it can be hard when the “true” information is uncertain and evolving.
Brad:
To judge trial quality:
Look at the journal as a rough first filter.
Then go through the trial using the CONSORT checklist:
If a trial doesn’t meet these standards, I’m cautious about its conclusions. Many non-replicating early results come from underpowered or poorly designed studies.
Host:
On risk–benefit, you often say benefits should “vastly” outweigh risks. Why “vastly”?
Brad:
Because harms can be large for a minority of patients. With GLP-1 agonists, most people benefit, but some experience severe GI issues or very rare serious complications. Medications always carry risks; I want to be confident that for almost everyone, net benefit is clearly positive.
I explain risks and benefits and let patients decide. Fear is a real driver, so they need honest numbers.
Host:
How do you see GLP-1s and SGLT2 inhibitors?
Brad:
They’re effective preventative tools in the right context:
Personally, I take:
That’s outside strict guideline indications but is a fully informed, patient-centered decision—where in this case I’m the patient.
If a patient similarly informed wanted SGLT2s as second-line with an ARB, I’d consider it, making clear it’s not yet guideline standard.
Host:
You wanted to discuss whether treating the “hallmarks of aging” is enough and how close we are to understanding aging biology.
I often use the Hecataeus map analogy: our current view of aging is like a 500 BC world map—useful but crude, with huge unknowns. I’d say we’re closer to 10% than 90% understanding.
Two implications if that’s true:
A telling point: the largest lifespan extension in a mammal (discounting extreme developmental manipulations) is still classic caloric restriction work by Walford and others ~50 years ago. If we were close to “curing aging,” we’d expect to beat that routinely in mice. We haven’t.
So: lots of good progress, but we need more resources for exploring the unknown alongside targeted, mechanistic work. We should walk and chew gum at the same time.
Brad:
Agreed—there’s a lot to be done. This has been great; let’s continue the discussion another time.
Host:
Absolutely. Thanks for sitting down.
If you’d like, next step I can: (a) turn this into a clean article-style piece, or (b) strip it down to a bullet-point summary + key themes for rapid reference.
Generally Brad Stanfield is a little too conservative for my taste, but I have to admire his dedication to the study. How many researchers mortgage their house to do a study? Wow.
One of the reasons why I buy his supplements.
And again, I just need to point out what an absolute failure this is. People throw around millions or billions of dollars on sheer vanity projects, but people like Brad, Matt K have to scrabble around for pennies to answer super important questions.
There must be plenty of people with 9 or 10 figure net worths at those investor conferences. If you could fund a study that eventually extends life expectancy by 1 year, the accompanying economic gains are MASSIVE. It’s so short sighted to keep doing these tiny, short studies which hint at something promising, and never just asking the big question. If I ever become wealthy enough, it’s one of the first things I’d do with my money.
The question with studies, however, is what the answer is that they might obtain.
I am an investor so I look at things from an investor’s perspective. Investing is different to philanthropy. Too many spending proposals are really philanthropy rather than investment.
I have positive views about Brad Stanfield even though I don’t agree with him on everything. In fact I have some quite serious disagreements. As I see it raising funds via the supplements for the study is not a bad idea. However, there remains a question as to what additional useable knowledge we might get from the study.
The healthy disagreement between these two doctors makes for an incredibly good interview. It is certainly worth watching in its entirety.
Introduction to Longevity and Aging
Measuring Biological Age
The Role of Glycans in Aging
Biological Age Testing and Its Limitations
The Future of Longevity Research
Challenges and Concerns in the Longevity Space
Conclusion and Call to Action
See research study using Rapamycin at 1 mg per day and blood testing of subjects.
This is an AMA episode where Dr Matt answers the pressing questions audience had. In this episode, Matt shares candid updates on his TRT journey and physique, debates rapamycin protocols vs. extreme fasting, and separates the scary headlines from the science on microplastics and “magic” mushrooms. Plus: why he wakes up at 4:30 AM, the truth about HBOT, and a surprising update on his books.
Here is the high-resolution summary and analysis of the “Ask Matt Anything” transcript.
In this AMA session, Matt Kaeberlein addresses audience questions regarding longevity interventions, emphasizing a data-driven, pragmatic approach over “shiny object” syndrome. A significant portion of the discussion focuses on his personal transition to Testosterone Replacement Therapy (TRT) for primary hypogonadism. He details the psychological hurdles of accepting a lifelong therapy, the failure of natural supplements (boron, diet), and the clinical outcomes: improved physique and energy, but notably altered blood biomarkers including elevated hematocrit and suppressed HDL. He notes that while fear of injections delayed his start, the benefits have outweighed the risks, and he is now experimenting with daily micro-dosing to manage side effects.
Regarding Rapamycin, Kaeberlein maintains his protocol despite rumors of peers (e.g., Peter Attia) cycling off. He argues that new data continues to support Rapamycin’s efficacy for cognitive and inflammatory decline, rejecting the notion of stopping based on anecdotes or “mouth sores” without personal adverse effects. He distinguishes between Rapamycin and 48-hour water fasts: while both inhibit mTOR, fasting induces broader physiological stress responses and caloric restriction benefits that Rapamycin does not replicate entirely.
The session also covers skepticism toward Hyperbaric Oxygen Therapy (HBOT) for general longevity (citing a lack of animal lifespan data compared to hypoxia), a dismissal of epigenetic clocks in favor of functional and clinical chemistry biomarkers (e.g., lipids, insulin), and a pragmatic stance on microplastics—acknowledging their ubiquity (specifically from car tires) while advising against anxiety-induced avoidance.
| Claim Made | Evidence Provided | Assessment |
|---|---|---|
| Rapamycin causes sleep disruption. | Speaker notes this is anecdotal; animal data suggests it attenuates age-related circadian decline. | Weak / Anecdotal |
| 48-hour fasting equals weekly Rapamycin. | Both inhibit mTOR. Speaker notes fasting has broader effects; Rapamycin is more specific. | Speculative / Plausible |
| TRT causes hair loss. | Speaker noted initial thinning but no acceleration; admits age is a confounder. | Confounded / Subjective |
| TRT lowers HDL and raises Hematocrit. | Speaker’s n=1 blood work confirmed suppressed HDL and elevated hematocrit post-TRT. | Strong / Consensus |
| Car tires are a major source of microplastics. | Speaker cites external data suggesting tires contribute more than food packaging. | Strong (Supported by environmental research) |
| Epigenetic clocks are superior to clinical markers. | Speaker refutes this, arguing clinical markers (lipids, insulin) + functional tests are more actionable. | Strong (Clinically valid) |
| HBOT extends lifespan. | Speaker notes absence of mouse lifespan data; cites data that hypoxia (low oxygen) extends lifespan. | Unsupported (for HBOT longevity) |
Kaeberlein distinguishes between Rapamycin (an allosteric inhibitor of mTORC1) and Fasting (a physiological stressors).
Claim: Car tires are a major source of microplastics.
Claim: Hypoxia (low oxygen) increases lifespan in mice, not Hyperbaria.
Claim: Rapamycin improves age-related sleep fragmentation.
