Dr. Kaeberlein's Optispan Podcast Series - Rapamycin and More

#96

I’m not finding any indication that Cleerly analysis is available outside the US. Cleerly is not selling heavily discounted access to its software in India, which is what the above seems to be trying to imply.

No doubt the CCTA is cheaper.

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#97

Ah… you are correct. At some point I’m sure they will expand there, but it appears not yet.

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#98

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)

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#99

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.

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#100

Introduction to Gene Therapy

  • The discussion begins with an introduction to the guests Ivan Morganov and Anna Vakuseva, who are involved with Unlimited Bio, a company focused on gene therapy.
  • The conversation explores the potential benefits and challenges of gene therapy, particularly in relation to aging and regulatory frameworks.
  • The extracellular matrix is highlighted as a significant yet often overlooked factor in aging, with implications for longevity science.
  • The regulatory landscape for gene therapies is also addressed, emphasizing the need for appropriate models to ensure safety and efficacy.

Personal Backgrounds of the Guests

  • Ivan shares his journey from Russia to Israel, revealing his search for purpose and his desire to combat aging as a significant life challenge.
  • He discusses his early interests in IT and business, leading to his eventual involvement in funding scientific research related to longevity.
  • Anna recounts her academic background in biology and bioengineering, detailing her transition from academia to industry, particularly during the COVID-19 pandemic.
  • Both guests emphasize their commitment to advancing longevity science through innovative therapies.

Concerns About Unregulated Therapies

  • The discussion transitions to concerns regarding unregulated gene therapies, particularly in light of recent conferences and public discourse on the subject.
  • Ivan expresses his belief that overregulation may hinder scientific progress in the field of longevity and gene therapy.
  • The importance of finding a balance between regulation and innovation is emphasized, as well as the need for transparent and effective regulatory models.
  • Anna reflects on the challenges faced in developing therapies and navigating regulatory environments, especially in different countries.

The Role of Extracellular Matrix in Aging

  • Ivan highlights the extracellular matrix as a critical component in aging, suggesting that it has been historically underestimated in longevity research.
  • He argues that the environment surrounding cells is just as important as the cells themselves in determining health outcomes.
  • The conversation touches on the idea that restoring or enhancing the extracellular matrix could be a key strategy in combating age-related decline.
  • Anna adds that understanding the extracellular matrix could lead to breakthroughs in therapies aimed at improving longevity and healthspan.

Unlimited Bio and Its Mission

  • Unlimited Bio was founded with the vision of exploring underappreciated areas of longevity science, particularly focusing on the extracellular matrix.
  • The company aims to develop therapies that address the root causes of aging and improve health outcomes for individuals.
  • Ivan and Anna discuss their goals of creating therapies that are both effective and accessible, emphasizing the importance of scientific validation.
  • They express a commitment to navigating the complexities of regulatory frameworks to bring innovative therapies to market.

Regulatory Challenges and Opportunities

  • The conversation shifts to the regulatory challenges faced by Unlimited Bio, particularly in the context of developing gene therapies.
  • Ivan discusses the bureaucratic hurdles that can impede the progress of promising therapies, highlighting the need for a more streamlined regulatory process.
  • Anna shares insights into how regulatory models can evolve to better support innovation while ensuring patient safety.
  • The importance of international collaboration and knowledge sharing among regulatory bodies is emphasized as a way to improve the landscape for gene therapies.

Current and Future Therapies

  • The discussion delves into the specific therapies being developed by Unlimited Bio, including their VEGF gene therapy for peripheral artery disease.
  • Anna explains the mechanism of action of VEGF, emphasizing its role in promoting new blood vessel formation and improving circulation.
  • The potential applications of VEGF therapy extend beyond peripheral artery disease to include muscle vascularization and hair follicle health.
  • The guests express optimism about the future of gene therapy in the context of aging and longevity, advocating for continued research and development.

Ethical Considerations and Patient Safety

  • The ethical implications of gene therapy, particularly in relation to patient safety and informed consent, are discussed.
  • Ivan stresses the importance of allowing individuals the freedom to choose their therapies while ensuring they are adequately informed of the risks and benefits.
  • The role of insurance companies in regulating access to gene therapies is also highlighted, with an emphasis on the need for transparency and accountability.
  • Both guests agree that as the field of gene therapy evolves, ongoing discussions about ethics and safety will be crucial to its success.

Conclusion and Future Directions

  • The conversation concludes with reflections on the future of gene therapy and its potential to transform the field of longevity science.
  • Ivan and Anna express their commitment to advancing research that addresses the root causes of aging and improves health outcomes for individuals.
  • They emphasize the importance of collaboration between scientists, regulators, and industry to create a sustainable and ethical framework for gene therapies.
  • The guests invite further exploration and dialogue on the promise of gene therapy as a tool for enhancing longevity and healthspan.
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#101

Debunking 10 Longevity Myths You Still Believe

AI Summary:

Introduction to Longevity Myths

  • The podcast episode begins with the hosts discussing a series of longevity myths that have been circulating in popular media and scientific literature.
  • The hosts mention that they have compiled a collection of longevity myths, indicating that this is not a definitive top 10 list but rather a selection of myths that they find important to address.
  • They express confidence that there are many more longevity myths to explore in future episodes, suggesting that this will be an ongoing series.

Myth 1: Measuring Biological Age

  • The first myth discussed is the belief that biological age can be accurately measured, which the hosts clarify is not currently possible.
  • They explain that while chronological age can be measured, biological age remains elusive due to a lack of understanding at the cellular and molecular levels.
  • Instead of measuring biological age directly, scientists use tools to estimate it based on correlations with chronological age and other health metrics.
  • The hosts highlight that tools marketed as biological age clocks, such as epigenetic age clocks, only measure specific DNA methylation changes and not biological age itself.
  • They emphasize that while these tools may provide useful estimates, they do not directly measure biological age, and misrepresentations can lead to misconceptions in the public.
  • The hosts suggest that people should focus on more actionable metrics, such as fitness age or specific health markers, rather than relying solely on biological age estimations.

Myth 2: Supplements as Core Components of Health

  • The second myth tackled is the idea that supplements are essential for improving health and longevity.
  • The hosts clarify that while some supplements can be beneficial, particularly when used to correct deficiencies, they are not a core part of a longevity strategy.
  • They mention specific supplements, such as vitamin D and omega-3 fatty acids, that can be useful when deficiencies are identified through testing.
  • The hosts argue that lifestyle factors, including diet, exercise, sleep, and social relationships, are far more critical for health and longevity than supplements.
  • They conclude that one can have an effective longevity protocol without taking any supplements, emphasizing the importance of lifestyle changes.

Myth 3: Age and Longevity

  • The discussion moves to the myth that one is too old to start worrying about longevity or improving health.
  • The hosts assert that chronological age should not deter anyone from making positive health changes, as everyone can benefit from improved health practices.
  • They reference scientific findings that show interventions to slow biological aging can be effective even when started later in life.
  • The hosts highlight examples from animal studies demonstrating that older subjects can experience improvements in health and function after interventions.
  • They emphasize the idea that it is never too late to take steps toward better health and longevity.

Myth 4: FDA Approval and Aging

  • The next myth is the belief that the FDA will not approve drugs aimed at slowing aging because aging is not classified as a disease.
  • The hosts clarify that the FDA’s focus is on whether a drug improves quality or quantity of life, rather than its classification as a disease.
  • They explain that if a drug can demonstrate safety and efficacy, it can be approved regardless of whether aging is recognized as a disease.
  • The hosts also discuss the potential implications of classifying aging as a disease, particularly regarding insurance reimbursement for aging-targeted therapies.
  • They conclude that the focus should remain on the efficacy of treatments rather than the classification of aging itself.

Myth 5: Resveratrol as a Longevity Molecule

  • The hosts address the myth that resveratrol is a potent longevity molecule, stating that it has been widely debunked in scientific literature.
  • They reference meta-analyses showing that resveratrol does not have a significant positive impact on lifespan, with studies indicating potential negative effects.
  • While acknowledging that some individuals may feel benefits from resveratrol, they stress that it should not be considered a longevity drug.
  • The hosts express surprise at the persistence of this myth, particularly among high-profile influencers who continue to promote resveratrol.

Myth 6: Funding for Aging Research

  • The sixth myth discussed is the notion that aging research is well-funded, which the hosts counter by presenting statistics showing significant underfunding.
  • They highlight that many of the leading causes of death are linked to biological aging yet receive minimal funding from organizations like the NIH.
  • The hosts mention high-profile private funding initiatives but emphasize that these efforts are dwarfed by the overall NIH budget.
  • They argue that a greater allocation of resources toward aging research could lead to significant advancements in health and longevity.
  • The hosts express concern that the current funding landscape does not adequately reflect the potential impact of aging research on public health.

Myth 7: Genetics and Longevity

  • The discussion shifts to the myth that longevity is predominantly determined by genetics, which the hosts clarify is not entirely accurate.
  • They explain that while genetics play a role, environmental factors and lifestyle choices have a more substantial impact on longevity.
  • The hosts note that estimates of the genetic contribution to longevity vary but generally suggest it is less than half.
  • They encourage listeners to focus on their lifestyle choices rather than relying solely on family history when considering their longevity.
  • The hosts conclude that individuals have significant control over their health and longevity trajectory through their daily actions.

Myth 8: Caloric Restriction and Cancer

  • The eighth myth tackled is the claim that caloric restriction works solely because it prevents cancer.
  • The hosts argue that caloric restriction is a well-supported intervention for increasing lifespan across various species and does more than just reduce cancer risk.
  • They explain that caloric restriction has been shown to slow aging processes in multiple tissues, not just in relation to cancer.
  • The hosts reference literature that details the various mechanisms through which caloric restriction promotes longevity.
  • They encourage listeners to recognize caloric restriction as a multifaceted approach to health rather than attributing its benefits solely to cancer prevention.

Myth 9: Rapamycin as a Core Component of Longevity

  • The ninth myth is the belief that rapamycin is a core component of improving health and longevity.
  • The hosts clarify that while rapamycin shows promise in animal studies, its effects on human aging are not yet well-established.
  • They caution against assuming that rapamycin should be a foundational aspect of health strategies without clear evidence of its efficacy in humans.
  • The hosts emphasize that lifestyle factors should remain the primary focus for improving health and longevity.
  • They acknowledge that some individuals may benefit from rapamycin, but it should not replace established health practices.

Myth 10: Peptides as Natural and Safe

  • The final myth addressed is the notion that peptides are inherently natural and safe, which the hosts challenge by discussing the complexity of peptide therapies.
  • They explain that while peptides are derived from amino acids, many used in wellness and longevity contexts are not naturally occurring in the body.
  • The hosts caution that the safety and efficacy of many peptides have not been rigorously tested, leading to potential risks.
  • They emphasize the importance of understanding that peptides can have side effects and should be treated with the same caution as pharmaceutical drugs.
  • The hosts advocate for more rigorous testing and regulation of peptide therapies to ensure safety for consumers.

Conclusion and Future Discussions

  • The podcast concludes with an invitation for listeners to submit their suggestions for additional longevity myths to discuss in future episodes.
  • The hosts encourage feedback on the episode and express their hope that the information shared has been educational and engaging.
  • They remind listeners to subscribe to the podcast for future content related to longevity and health.
#102

A master of the straw man argument.

#103

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.

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#104

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.

#105

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.

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#106

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:

Summary

Participants: Brad Stanfield (primary care physician, New Zealand) and interviewer at Longevity Investors Conference

Key Topics Covered:

  1. Brad’s Background

    • Primary care physician in Auckland, NZ
    • Started YouTube channel (end of 2019) focused on evidence-based aging science
    • Initial interest sparked by noticing wrinkles and exploring anti-aging interventions

  2. Rapamycin Clinical Trial

    • Designed 40-person study testing rapamycin (6mg/week) + exercise in older adults
    • Cost ~$500,000 USD
    • Brad mortgaged his house to fund the shortfall (~$150,000)
    • Study completed, results submitted for peer review
    • Planning PhD at University of Auckland to continue this research

  3. Healthcare Philosophy

    • Strong emphasis on clinical guidelines and evidence-based medicine
    • Practices “patient-centered care” rather than paternalistic medicine
    • NZ healthcare system incentivizes prevention over treatment
    • Conservative approach: benefits must “vastly outweigh” risks

  4. Key Medical Opinions

    • Biological age clocks: Shouldn’t guide clinical decisions; lack validation
    • Vitamin D testing: Questions clinical utility; endocrine society doesn’t know optimal levels
    • GLP-1 agonists: Enthusiastic; significant benefits for diabetes prevention and cardiovascular health
    • SGLT2 inhibitors: Uses one personally for blood pressure (off-guideline use)
    • Resveratrol/Metformin: Admits getting these wrong initially

  5. Philosophy on Science Communication

    • Focus on human randomized controlled trials over animal/cell studies
    • Prefers clinical guidelines over individual expert opinions
    • Willing to admit mistakes publicly
    • Critical of high-profile doctors who misrepresent aging biology

  6. Disagreement Areas with Interviewer

    • Trust in medical societies: Brad trusts guidelines more; interviewer skeptical (cites HRT controversy)
    • Vitamin D supplementation: Brad doesn’t test and follows fixed dosing; interviewer believes in personalized approach
    • Risk-benefit calculations: Debate over how much benefit must exceed risk

Critique

Strengths:

  1. Intellectual Honesty: Brad’s willingness to admit past mistakes (resveratrol, sulforaphane, metformin) demonstrates integrity rare in the health influencer space.

  2. Financial Commitment: Mortgaging his house for rapamycin research shows remarkable dedication to advancing the field.

  3. Methodological Rigor: Strong emphasis on CONSORT guidelines and proper trial design is commendable.

  4. Patient-Centered Approach: The focus on shared decision-making rather than paternalism is progressive.

Weaknesses & Concerns:

  1. Overly Conservative on Vitamin D:

    • Brad’s position seems paradoxical: he acknowledges people should supplement (because most work indoors/wear sunscreen), but dismisses testing
    • The argument that “we don’t know optimal levels” doesn’t logically lead to “therefore don’t test”
    • Interviewer correctly points out that without measuring, you can’t know if 800 IU is adequate for an individual
    • The retrospective data Brad cites is confounded (institutionalized patients aren’t representative)

  2. Excessive Deference to Guidelines:

    • Brad’s trust in medical societies seems untempered by historical analysis
    • The HRT example is instructive: guidelines were wrong for 20+ years, harming millions of women
    • His counterargument that “medicine needs to be cautious” doesn’t address the harm done by excessive caution
    • Cost-benefit analyses by committees often underweight benefits and overweight rare risks

  3. “Vastly Outweigh” Standard is Problematic:

    • Brad argues benefits must “vastly outweigh” risks, but this is arbitrary
    • Many effective preventive interventions have modest effect sizes at population level but large cumulative benefits
    • This standard would preclude many useful interventions
    • The interviewer’s pushback here is well-founded

  4. Inconsistency on Guidelines:

    • Brad takes an SGLT2 inhibitor off-guideline for blood pressure
    • This reveals that even he recognizes guidelines can be suboptimal
    • Yet he maintains strong deference to them for patients

  5. Limited Engagement with Biological Age Debate:

    • While Brad is correct these tests shouldn’t guide clinical decisions now, he doesn’t engage with their potential future utility
    • Dismissing them entirely seems premature given rapid development in the field

  6. Aging Biology Understanding:

    • Brad doesn’t strongly disagree with interviewer’s pessimistic assessment (10% vs 90% understanding)
    • This suggests his focus on translational medicine may come at expense of deeper mechanistic thinking

Key Philosophical Divide:

The conversation reveals a fundamental tension between:

  • Precautionary principle (Brad): Don’t act without strong evidence; avoid harm
  • Expected value maximization (Interviewer): Calculate probabilities and act when expected benefit exceeds expected harm

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:

  • How to make decisions under uncertainty with asymmetric information
  • The appropriate role of n=1 experimentation
  • How prevention differs from treatment in risk-benefit calculus
  • Whether aging should be treated as a “disease” requiring intervention or “natural process” requiring strong justification for intervention
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#107

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.

Meeting at the Longevity Investors Conference

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’s Background & Starting the YouTube Channel

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.

How to Treat Evidence & Admitting Mistakes

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.

Rapamycin Trial: Motivation, Design & Funding

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.

PhD Plans & Doing High-Quality Trials

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.

Prevention Culture: New Zealand vs US

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.

Vitamin D: Testing vs Population-Level Strategy

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.

Biological Age Tests: Why Brad is Concerned

Host:
Let’s talk about one of your big concerns: biological age scores.

Brad:
Right. I see two main problems:

  1. Lack of clinical validation. We don’t have solid evidence that a given biological age score should drive interventions.
  2. Misuse in decision-making. Some clinicians recommend supplements or treatments based on these scores. That’s premature.

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.

Patient-Centered Care vs Paternalism

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.

How to Judge Clinical Trials (CONSORT)

Brad:
To judge trial quality:

  • Look at the journal as a rough first filter.

  • Then go through the trial using the CONSORT checklist:

    • Randomization
    • Blinding
    • Allocation concealment
    • Power and sample size
    • Pre-specified endpoints
    • Reporting of funding and conflicts

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.

GLP-1s, SGLT2s & Risk–Benefit

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:

  • In type 2 diabetes, GLP-1s and SGLT2s reduce cardiovascular events and slow kidney decline.
  • In obesity, GLP-1s reduce diabetes risk.
  • There’s growing discussion about using them earlier (e.g., prediabetes), potentially instead of metformin, given stronger weight and metabolic effects.

Personally, I take:

  • An ARB for genetically driven hypertension.
  • An SGLT2 inhibitor as an add-on for blood pressure and diuretic effect, after consulting a nephrologist.

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.

Are We Close to “Solving” Aging?

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:

  1. Our current framework is useful. We know enough to improve healthspan and probably lifespan in humans and companion animals.
  2. We underfund discovery. The hallmarks framework has narrowed focus. It’s now hard to fund work that doesn’t fit those boxes, so we get deep dives into known pathways but too little true discovery.

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.

3 Likes
#108

Thank you @John_Hemming

#109

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.

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#110

One of the reasons why I buy his supplements.

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#111

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.

9 Likes
#112

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.

4 Likes
#113

The healthy disagreement between these two doctors makes for an incredibly good interview. It is certainly worth watching in its entirety.

3 Likes
#114

AI Summary:

Introduction to Longevity and Aging

  • The discussion opens with the idea of achieving longevity escape velocity, which refers to a point where advancements in medicine and technology allow individuals to live significantly longer and healthier lives.
  • The speakers emphasize that modern medicine often fails to keep people healthy, focusing instead on prolonging life without addressing overall health quality.
  • Concerns are raised about the potential for charlatans to exploit the growing interest in longevity, leading to misinformation and ineffective treatments in the field.

Measuring Biological Age

  • The conversation shifts to the complexities of measuring biological age, with experts suggesting that current methods are not fully reliable or accurate.
  • It is highlighted that while biological age can be estimated through various metrics, these do not provide a definitive measure of an individual’s health or aging process.
  • The importance of focusing on current health status and quality of life is emphasized over the pursuit of an exact biological age measurement.
  • Experts agree that existing biological age clocks measure correlated factors rather than biological age itself, which can lead to misconceptions about their utility.

The Role of Glycans in Aging

  • The discussion introduces glycans as significant biological molecules that play a crucial role in cellular functions and inflammation regulation.
  • Glycans are described as modifications of proteins that evolved to manage the complexity of multicellular life, influencing various physiological processes.
  • Research on glycans aims to understand their role in inflammation, which is linked to many modern diseases, and how they can be utilized in clinical diagnostics.
  • The concept of glycan age is proposed as a potential clinical measure that could provide insights into an individual’s ability to regulate inflammation and overall health.

Biological Age Testing and Its Limitations

  • The speakers share personal experiences with various biological age tests, noting inconsistencies in results that raise questions about their reliability.
  • It is highlighted that many tests claim to measure biological age but are actually estimating it based on correlated biological markers, leading to potential misunderstandings.
  • Concerns are raised regarding the lack of transparency in testing companies about error rates and the implications for consumers and healthcare providers.
  • The necessity for accurate and clinically validated tests is emphasized to ensure that individuals can make informed decisions about their health based on reliable data.

The Future of Longevity Research

  • Looking ahead, the experts express optimism about the potential advancements in longevity research and the possibility of achieving significant breakthroughs within the next decade.
  • The panel agrees that a shift towards more proactive health measures and resource allocation in aging research could lead to substantial improvements in healthspan and lifespan.
  • They anticipate that AI-driven tools will emerge to help individuals make better health decisions based on comprehensive data analysis.
  • The importance of public and institutional support for longevity research is underscored, with a call for a cultural shift in how aging and health are perceived and addressed.

Challenges and Concerns in the Longevity Space

  • The speakers express concerns about the potential for misinformation and the rise of unproven treatments as the longevity movement gains popularity.
  • They caution against the influence of charlatans who may exploit public interest in longevity for profit without providing scientifically validated solutions.
  • The need for a rigorous scientific approach to aging research is emphasized to ensure that advancements lead to genuine improvements in health and longevity.
  • The conversation reflects a desire for a balanced approach that combines optimism about scientific advancements with caution regarding the commercialization of longevity.

Conclusion and Call to Action

  • The discussion concludes with a call for individuals to take charge of their health and explore avenues for improving their quality of life through informed choices.
  • The experts encourage a proactive mindset towards health, emphasizing that understanding and utilizing available data can empower individuals to make better lifestyle decisions.
  • They express hope that the longevity movement will continue to evolve in a way that prioritizes scientific integrity and public health.
2 Likes
#115

See research study using Rapamycin at 1 mg per day and blood testing of subjects.

What a Pilot Study on Rapamycin and Cardiomyopathy Tells Us About Reversing the Biology of the Aging Heart

4 Likes