Bryan Johnson, Is he the New Poster Child for Rapamycin Use?

#27

Yes, none of the supplements have much support for longevity increases as you know.

This is why i think the vast majority of his biological age improvement likely comes from rapamycin and acarbose (the only well-documented, validated longevity drugs in his stack), and why (even though he doesn’t know it) he’s the poster child for rapamycin use :smile:

The supplements are a longer list than most of us here take, but all of them are well known and probably won’t hurt him (though as tongMD mentioned, impact the bioavailability of the drugs).

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#28

Welcome to the forum! It’s great to have a doctor as progressive as yourself here.

Would love to know more about how you go about selecting and testing interventions.

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#29

The truth is, the cost of the rapamycin and acarbose is probably less than $1,000 per year and those alone may (I suspect) give the same level of benefit he’s getting from all the other supplements.

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#30

Welcome Dr. Zolman!

I am a big fan of Mr. Johnson and yourself! I have shared Bryan’s blueprint project with my family and I think what your team has done is amazing. We are all in this longevity journey together and I hope we can make breakthroughs to improve the life and health of everyone. Thank you for your hard work and sharing with the community.

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#31

In the video you guys talk about Bryan taking a non-feminizing estrogen. Is that 17ae2?

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#32

Agreed. Almost all of the list may not matter much.

Here’s a modified far lower cost “blueprint” (not medical advice, talk to your doc) - if ITP ends up translating - and it could well be better than Johnson’s plan:

ITP winning combo:

  1. Rapamycin + acarbose (+ optional canagliflozin intermittently)

Depending on insurance (even low-cost or free ACA HMOs) that can cover generic rapamycin with a low copay - $300/year or buy Indian rapamycin (and canaglifozin) - <$1000/year. (Note - it is marginally better to avoid generics destined for developing countries in the long run)

Old “polypill” concept with example generics (ideally when indicated and individualized therapy with titrated initially low-dose):

  1. Rosuvastatin+ezetimibe (rosuvastatin can be modified to intermittent to minimize potential side effects as needed)
  2. Candesartan cilexetil/telmisartan
  3. Low-dose aspirin (often optional, older adults consider avoiding this)
  4. Sildenafil/tadalafil

Assuming optimally split pills, this can cost <$10/month with insurance and sometimes less if optimal PBM use.

Diet (cost-effective version):

  1. Mixed vegetables + mushrooms (stir-fry blends in grocery can be ~$2, small dash of real EVOO for cooking - general heuristic is 100% Californian or elsewhere in the US)
  2. Lentils/black beans (~$1)
  3. Dark berries (flash-frozen, ~$2)
  4. Steel-cut oats (~$1)
  5. Mixed unsalted nuts/seeds (~$1)
  6. Sardines (includes soft edible bones, water/oil drained, ~$2)
  7. Morning coffee/green tea (~$1)
  8. Salt substitute - 75% NaCl/25% KCl (mostly foolproof and does not impart a bitter taste + metallic aftertaste where NuSalt does) & fresh whole spices ie chopped garlic, ginger, etc (~$1)

Can be ~$11/day or if you’re eating more, <$20/day (wash, scrub, and may soak produce with baking soda)

Can add/swap:
9. Sockeye salmon (astaxanthin) - may swap sardines
10. Collagen peptides (glycine) - may mix in lentil soup cooked in bone broth
11. Natto (spermidine + some MK-7) - may swap beans

Annual preventative generally covered $0 by insurance:
CBC w/ diff
CMP
HbA1c
Lipid panel
TSH/free T4 (optional, indicated if relevant symptoms)

Total cost:

$4,435 per year, but this includes food - it’s roughly around the average American grocery bill. Not surprised - since this would be most likely be mild calorie restriction for a sizable amount of people.

So in actuality this is really close to $0 additional spending.

Don’t see a big reason to spend ~$25k more on food/supplements/testing unless one doesn’t mind diminishing returns and can afford to (it’s the case for me - but I am quite aware most people do not have the same luxuries).

The average American is better off saving themselves scientifically proven extra years based on the laws of Physics by spending that money switching to a used 3-year-old midsize SUV with a 3x lower empirical fatality rate compared to their base model sedan. You’re more likely to get death and disability from a car accident than actually need to pay that much more for marginal items.

Even $5-8k more is already pushing the boundaries of returns, if one wanted to go organic - marginal for most foods on this list after processing and cooking, besides berries and some nuts.

Throw in a few marginal tests (apoB can be ~$3 cash pay, hs-CRP ~$18, one-time Lp(a) test around ~$12 is generally worthwhile) and targeted micronutrient interventions ie USP grade Vitamin D 1,000-2,000 IU, magnesium taurate, and creatine (Creapure) - it might be <$300/year.

If you really want to gamble a little further out with high safety profile interventions, assuming higher quality source:

High-dose EPA fish oil (EPA/DHA/mixed tocopherols), nutritional yeast (B-complex), unsalted bone broth (glycine/HA/glucosamine), deep orange egg yolk (lutein/zeaxanthin/phosphatidylcholine), 100% cacao nibs (cocoa flavanols), etc with microdose lithium, if not already available from the local water supply.

Not particularly difficult to add several “functional foods” with some animal-derived products, compared to the impractical “unicorn vegan excel spreadsheet diet” with a “kitchen sink” of pills that can have so many possible combined quality assurance and cost-effectiveness issues - often impossible to get USP grade or close to equivalent.

If you want a valid CLIA-certified whole genome sequencing test (ie useful for avoiding side effects in statins under pharmacogenetic standards or if you have clinically meaningful CYP variants etc), some clinical trials pay you to get one and you may meet the best physician-scientists involved (some may include multi-omics testing).

So, if one plays all the cards skillfully, one can come out way ahead of Johnson with an even better healthcare team and more quality data when considering the possible harms of “VIP medicine” and overtesting issues and getting paid for it.

Ultimately, may cost less than $0 additional with better results if skill is applied.

Then, add in some luck and one may get to “longevity escape velocity” - if it ends up being plausible. Spending $2M is really no match for average Joe and massive luck factor.

What isn’t usually mentioned is how much luck factor is involved. This “blueprint” concept appears to be aimed at media exposure and makes it seem as if engineering can currently bypass luck using some form of Big Data hyperbole. As much as the engineering side of me wanted to believe that we can currently do that, it’s just not true yet. Probably not anytime soon.

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#33

Great post. Where do you get the low cost lab work? I pay ~$35 for an ApoB test

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#34

Below is Zolman’s profile from his website.

  1. I have created the 500+ Zolman Clocks to measure biological age in all 78 organ types across both genders, comprised of over 500 sub-clocks (multiple clocks per organ) to prove reversal of aging and prove n=1 LEV (longevity escape velocity) using my N=1 LEV equation.

  2. I have written the Zolman Biological Age Marker (Z-BAM) criteria, with evergreen peer-review, 15 statistical criteria that markers must meet a minimum set of to be statistically and clinically valid, with no close comparison of such objective criteria made before to critically appraise biological age markers of any type (imaging, device or biosample based)

  3. I created the Longevity Level 123 protocol to measure and reverse aging in all 78 organs using the most statistically rationale evidence based medicine (EBM) approach. This involves writing hundreds of novel experimental clinical guidelines covering every experimental longevity test and therapy, built on international gold-standard EBM principles such as AGREE2, IPDAS, N=1 CONSORT, GRADE, Cochrane Handbook of systematic reviews, NICE manual, etc. I have also extended beyond these gold-standards with my own standards for informed consent.

Level 123 protocol is designed using systems thinking to be unsurpassably systematic in every possible evidence based factor that can contribute to unwanted clinical or biomarker (imaging, device, biosample) outcomes

Level 1 = Proven to raise mean lifespan by 2+ years in 50%+ of people and stack their effects: 6 components: CRON, AHEI-2010 diet, Exercise, BMI, Alcohol, Smoking

Level 2 = Non-age related: 13 categories of non-age related causes of unwanted clinical outcomes

Level 3 = Measure 500+ Zolman Clocks, other clocks, 78 organ ages, Level 3 tests and therapies experimental clinical guidelines

  1. I created Longevity School to teach Longevity 123 protocol and how to measure the 78 organ clocks at research grade standard. This allows clinicians and innovators to become their own rejuvenation research groups by using gold-standard markers with gold-standard methodology, and see which organs or markers they can rejuvenate with on label, off label or unlicensed therapies.

Longevity School is an online platform with native mobile apps, desktop apps, video content that adheres to Medical Education gold-standards, evergreen peer-review and conflict of interest statements. Longevity School provides certification and revalidation in Longevity Escape Velocity Medicine (LEVMED) Speciality Training, first published in the peer-reviewed PubMed listed journal Rejuvenation Research February edition in 2018 and presented at the 2018 the Undoing Aging Conference.

  1. I created the field of competitive longevity, publishing the first Rejuvenation Leaderboards and using a rationale and evidence based points system based on the 500+ Zolman Component Clocks to rank individuals. I further expanded this concept to sub-leaderboards for specific organ rejuvenation.

  2. I have also created many multi-organ clocks that provide a systemic view of aging processes that will affect many organs, these also need to be reversed.

  3. I have created the first organ age heatmaps which show biological age heatmaps within organs, showing which parts of one’s individual organs are aging fastest and causing the overall organ to be older.

  4. I actively call out pseudomedicine, pseudo-aging tests, pseudo aging therapies, sub-par practice and objectively irrational thinking using evidence based medicine principles and peer-reviewed references to back up my claims. This includes the concept of ‘no guideline → no experimental test or therapy’.

  5. I have written the first experimental clinical guidelines and pharmacokinetic pharmacodynamic translational models for all wild type mouse lifespan studies interventions, e.g. Rapamycin, Alfatradiol, NGDA, AAV/CMV HTERT/Follistatin/klotho etc (50+). I have ranked every wild type mouse lifespan study by effect size on maximal lifespan and this is a core part of longevity school and level 3 therapy strategy.

His clientele include Bryan Johnson, founder of Braintree-Venmo (sold to Paypal for $800M), Kernel and OS Fund, and with Oliver created Project Blueprint, documenting his work with Oliver to maximally reverse the quantified biological age of all of his organs using the 500+ Zolman Clocks and Level 123 protocol. Bryan and Oliver’s parents are the first people to go through the Longevity Level 123 protocol, quantify the biological age of all 78 organs using Zolman Clocks and maximally reverse them using Level 123 therapies experimental clinical guidelines.

Qualifications

Oliver earned his M.B.B.S. from King’s College London, England (equivalent to the US M.D.)

First Class Honours BSc in Regenerative Medicine, Innovation Technology & Biology of Aging.

Visiting Fellowship in Evidence Based Medicine, at the University of Sydney

Cambridge University Judge Business School Accelerator Program

Cambridge University Medical Education Masters to be started in 2023

Young guy (29), in school most of the time. Wonder how many patients he has treated. There is no stated hospital experience, nor research lab experience.

Website offers software, longevity school training, red wine polyphenols for $800 [12 bottle lot ($66 per bottle of 60, but not sold individually)], and testing ( The Zolman 78 organ panel).

Hmmm.

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#35

Bryan looks great for a calorie restricted vegan man. He definitely wouldn’t look that way without the testosterone.

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#36

There is no claimed new approach to anti-aging; only a claimed new approach to measuring. I fail to see the value of another method of measuring. What needs to be discovered is the measured (improvements to aging) and the means to achieved that which is measured.

Time to move on.

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#37

Ray Kurzweil would almost be jealous.

Pascalian Medicine in action:

Pascalian medicine is a theory that suggests taking a “betting” approach to medical treatment. The idea is to take a variety of medications, even those that may only have a small chance of working, in order to increase the chances of finding something that will be effective. The theory is named after philosopher Blaise Pascal, who proposed the idea of “Pascal’s Wager” in which he argued that it is better to believe in God, even if there is only a small chance of it being true, because the potential benefits outweigh the potential harm. In a similar way, Pascalian medicine argues that it is better to try a variety of medications, even if they may have a small chance of working, because the potential benefits outweigh the potential harm. It’s important to note that this theory is still in the early stages of development, and it’s not currently widely accepted in the medical community.
-ChatGPT

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#39

Well would seem like rapamycin and maybe acarbose drove his improment based on what we know from ITP.
If you look at percentage drop 5/45 it is about 11% reduction
By comparison my reduction is 9/69 or 13%
and I’m not eating that vegan crap

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#40

Home institution cash pay

But here is an option that can save one a bit for routine labs - works pretty much anywhere in US: https://ownyourlabs.com

Not medical advice, not your doc, beware risks of overtesting.

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#41

That’s a big leap of logic there in that hypothesis and frankly, some magical thinking in that blog. The common trap of believing that more numbers/“data” must be the better one. There was a meta-analysis that showed Ivermectin is a treatment for COVID once. But the problem was one couldn’t trust the numbers for bias. Turns out numbers were made up. Garbage in, garbage out.

Most people are horrendous at predicting success rates or potential for harm. Small studies often have spurious results. Almost always overestimates. The base rate of deep experts in the field is 5-10% or so.

But maybe one is a special prediction superstar. In that case, I suggest making millions on biotech stocks with one’s amazing talent and beating the team of PhDs involved in hedge funds - it’ll translate to higher life expectancy and one can empirically prove skill. One doesn’t need to be right all the time - just some level of accuracy about the confidence level and then calculate corresponding position sizing.

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#42

Vegans can look that way without steroids with a deeply impractical unicorn Excel spreadsheet diet. Plant protein is simply not the same, so one has to spend way more on effort, time, and costs (plant protein is more costly and more intake). Then there’s the additional time, risk and costs with a ton of supplements. Some sports supplements are spiked with anything from desginer SARMs/steroids to meth. Why risk it? Makes no practical sense to me - so I strongly suspect ideological veganism beneath a veneer of “data-driven ethical veganism” - reminds me of “EA veganism” Sam Bankman-Fried.

But frankly, 4% body fat is cutting it close with a weaker immune system - steroids aren’t helping either. Hardly the bastion of health he is claiming.

I’ve been down to 6% wayyy back just once to see how far it’ll go. It sucks. I suspect I’d have felt better if I had chose the steroids route.

10-12% is probably healthier if you care about healthspan and if you care about attracting the opposite sex - most women (ex-female bodybuilders) seem to find right around 12% more physically attractive than 4-6%.

Meanwhile, getting an infection could knock you out for a few weeks. Some people I’ve seen knocked out longer.

Seems like the tradeoffs for what Johnson is claiming aren’t worthwhile for most people with similar goals. It seems more geared towards media exposure by spending 2M instead of directly publishable clinical trials. Again, reminds me of Sam Bankman-Fried. I can’t prove anything particularly malevolent nor am I asserting that - but I’d simply be wary with the hyperbole types.

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#43

I’m not sure what more numbers/data has anything do with the “hypothesis” nor why it proves it is magical thinking.

#44

Your cited blog’s hypothesis relies on numbers and data to drive what to add to a kitchen sink. But biased numbers and wild overestimates are common.

#45

The point is that supplements that are pretty safe or harmless have a big potential upside, and if you combine many - like Ray Kurzweil with 100 pills, maybe a few have a big effect. Not something I advocate for, just I don’t see where the magical thinking part is.

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#46

Patient safety isn’t one-dimensional. As an example, combination therapies in kitchen sink approaches are not tested and purported “high safety” additions can cause interactions or a cascade of effects, which could turn out net negative. It can also change with time as physiology changes in older age. I’m not against combination therapies inherently btw - but at least one should consider doing some well-designed experiments ie mice or dogs, etc.

My apologies for the unclear articulation - part of the magical thinking is attributing good outcomes (whatever that is originally claimed) to supplements and “tons of data”, rather than often more likely placebo effects and proven interventions.

This is partly why I suggest well-designed crossover N-of-1 studies if you take this approach at the very least if you don’t mind additional patient safety risks, preferably after doing some testing even if one has a high risk tolerance. How many people (particularly those seeking attention from media/social media) actually do rigorous empirical testing, rather than veering towards hyperbole and/or spurious claims?

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#47

The purpose of Pascalian medicine isn’t that supplements are chosen in the first place based on their potential benefit, mostly that they are safe. If they are, all you are hoping for is that they will have a benefit. So you just take 100 supplements like Kurzweil, they don’t seem to do any harm, and maybe one or two have a beneficial effect in the end. You don’t measure outcomes at all nor do I see how the placebo effect plays into this. Not something I recommend, just an interesting thought experiment.

Interactions and cascade of effects is one of the reasons I’m not so interested in 100 supplements like kurzweil. Or at least now. And the complexity of taking so many supplements, costs, etc. I’m not a strong believer in the hypothesis either, it’s just a kind of fun article IMO.