Nice! The creatine is the one that is interesting. Arguments for it being a top 3 would be its nootropic, muscle building and mTOR activation with exercise.
Background: A bit about myself - I’m a family medicine resident physician (age 30) with a background in computational biochemistry and computer science (for context - before med school got a offer letter for Google after foo.bar secret invite and several rounds of interview. Also, my fiancee is currently a Google engineer in security, feel free to reach out if you’re in tech), planning to go into a geriatrics fellowship.
Not your physician, not medical advice, just what I take personally with my current medical conditions and individual situation. Check with your physician.
None of these are endorsements for any particular products and I don’t have any conflict of interests. I may change products in the future.
Meds:
- Rapamune (branded) 6 mg po qweekly
- Focalin XR (branded) 20 mg po qAM (I have well-compensated ADHD, formally diagnosed by neuropsychological testing)
- Precose (branded acarbose) 25 mg prn with high-carb meals - I use CGM Freestyle Libre 3 to monitor because of dietary nutraceuticals.
- Neurontin 300 mg po prn. Off label anxiety/sleep only, maybe use once a month.
- Psilocybin 25 mg once every 2 months (tea made from psilocybe sourced from a Canadian brick and mortar, added lemon and ginger) + CBT session for GAD. I also have monthly executive coaching with psychiatrist, it bills under my PPO.
Foods/Supplements:
- Natto (equivalent to Vitamin K2 MK-7 100 μg)
- Magnesium L-Threonate (NOW Foods, Magtein) + Vitamin B-6 100 mg USP grade
- Creatine Monohydrate (Alzchem Creapure) 5 g
- Niacin 100mg, USP
- Vitamin D3 1000 IU, USP
- Broccoli sprouts ~4oz, heated & Broccoli ~3 cups, USDA organic (Spermidine & Sulforaphane)
- Collagen Peptides (Vital Proteins) mixed in bone broth (USDA organic)
- Salmon Roe 50g (Vital Choice, wild alaskan)
- KSM-66 Ashwaganda (USDA organic certified)
- 6 cups of green tea, made from USDA organic loose green tea leaves (L-theanine, catechins)
Diet:
16/8 intermittent fasting meals 10am - 6pm, and mostly traditional Okinawa diet (pre-world war II) with some subs from traditional Mediterranean diet if the specific food/herb/spices/tea is not available in the US or deemed a potential safety risk. There’s way too many potential active nutraceuticals that I eat specifically, I’m not going to list them. Note there is likely drug-drug interactions (including those with rapamycin) with my approach which I also carefully account for (at least for known ones listed in databases and current knowledge) and test blood levels for. I’m not going to list them, but I can provide methodology - I used deep neural network with the following databases NIH-Library of Integrated Network-Based Cellular Signatures, Universal Natural Product Database, Kyoto Encyclopedia of Genes and Genomics to look for mTOR, AMPK and SIRT related pathways. I use clinical decision support tools, WGS in CLIA certified, combined with expert consults to avoid interactions and bioavailability issues etc.
Exercise:
Weekend HIIT Saturday morning (Orangetheory for now), sometimes indoor rock climbing on Sundays if I can fit it in. Gym during the week, strength training full body, 1 set, max weight with 5-7 reps, 20 min, circuit. 2-3x/week. On my feet during rounds for 4 hours per day rest of the time. Apple Watch.
Sleep:
Morning blue light therapy, 480 nm, 1000 lux, 15 min. Watch sunrise 5 minutes if possible. Watch sunset 5 minutes. Filter all blue light with polarized night eyeglasses, use red night lights only 3 hours before bed. 7 hrs sleep, custom actigraphy with machine learning algorithm optimization (not as good as PSG).
Skin:
Xeomin injections, 1/4 recommended dose, every 6 months done only by board certified dermatologist
Ketaconazole 2% USP shampoo
Retin-A, topical USP
Salicyclic acid 2% USP face wash
Custom topical prebiotic and probiotic mix (trehalose and many strains of potential probiotics, I make it myself using custom lab equipment)
Custom rapamycin ointment, topical (I make it myself using custom lab equipment)
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I love this post. Congratulations on being so proactive at such a young age. I fully agree with your sleep, diet, and exercise choices.
At this site we’re basically a bunch of informed biohackers, looking at whatever evidence is available, assessing the benefits/ risks, arguing about it some, and then sharing our experience.
I think you’ll enjoy it.
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Welcome, glad to have yet another health professional on board to “try” and keep us hackers within guardrails.
Very extensive stack.
“Spermidine, Sulforaphane, Ashwaganda” I take all of these…can you elaborate your thinking?
Wow, this is high level stuff…hope to learn from this.
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@tongMD Wow! You are on it! Amazing detailed and thoughtful. I love the fusion of multiple layers of approaches and philosophies. My favorites are Psilocybin, Natto, Salmon Roe, Okinawa diet (pre-world war II), clinical decision support tools, skin regime and my favorite watching sunset / sunrise for 5 min. Thank you!
Quick questions? Why 6mg Rapamycin at your age? I know the mice study show improvement at younger ages of starting, but most of the younger people that use Rapamycin lean towards the 3mg. Any physical and or symptom change you can note since starting Rapamycin? Do you freeze your broccoli sprouts to enhance your sulforaphane dose?
I really appreciate everyone that takes the time to share their own approach. I love the contrast from @tongMD to @Maveric78 ( Rapa / Vit D/ Creatine).
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It’s an open question when is best, how much, or if rapamycin is even going to slow “aging” in humans. The current evidence is considered weak but the potential benefits and implied number needed to treat make sense in my situation, with careful monitoring.
So to be frank - dosing is a wild guess based on in silico, mammalian studies across multiple species, my labs over time, and titrated dose over the past few months (1 mg increase every 2 weeks) - I may increase or decrease over time as new information comes out.
As for age to start, from multiple clues as a pure guess - humans get “pre-atherosclerosis” in their teenage years and 20s already - I suspect it starts getting harder to reverse in 30s with “no risk factor” erectile dysfunction (an easy way to correlate with subclinical atherosclerosis) seen in a significant amount of men in age 30s (including athletes who presumably are very healthy), hence early intervention is worth a shot if it appears to reduce the incidence of any easy non-interventional tests that can cumulatively have some predictive value. We already know the poor NNT of high-dose statins/PCSK9 inhibitors.
Women have exponentially increasing risks of Down syndrome babies roughly starting at the maternal age of 30. Paternal age of 30-40 starts affecting babies too, it’s no surprise sperm donations only want around age <35. Peak bone mass is at age 25-30. Athletic performance peaks around 30. And a bit less than 40 is the “implied lifespan” for humans. I was only worried about brain development in my 20s (one of the many clues is schizophrenia incidence drops at the 30s, memory peaks right at 30), so I started at 30, because younger men are just more likely to get a heart attack in 30s, albeit lower risk than older men. I figured getting the tradeoff point potentially just a few years early (instead of 35-40) makes sense to me when heart disease is still a top 5 cause of sudden death for 30-year-old males (even when adjusted for pure congenital problems like hocm).
At some point even if you’re a healthy 35 year old master athlete - you have a good chance of having CAD that becomes more difficult to reverse over time, and what’s considered a low risk of <10% heart attack over next 10 years that could end up in high dose statin use (there is a decent NNH) and a plethora of tests and polypharmacy is enough to reconsider exploring any options that might result in insurance.
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There are some negative findings in Rapamycin/mice treated early.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1474-9726.2012.00832.x
“We also note, however, that mice treated with rapamycin starting at 9 months of age have significantly higher incidence of testicular degeneration and cataracts; harmful effects”
But completely agree, a very much open question.
Welcome to the dart board club.
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I have semen frozen, monitor sex drive, and other clinical symptoms on top of labs. I might end up stopping rapamycin, increasing time in between doses to 10-14 days, or taking a holiday until later, but the idea is catching things early by follow-up. It’s probably reversible at least in part. The most important part is my brain and anything related to the nervous system not dying or getting damaged - the rest could possibly be replaced in say 2-5 decades.
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All good reasoning.
Rapamycin may help prolong ovarian function for longer oocyte production in women, but this may also carry a higher Downs Syndrome rate that is seen with advancing maternal age ( 1/2500 in 25 y/o vs. 1/250 in 35 y/o vs 1/40 in a 40 y/o).
Risk level has so much to do with the risk of NOT doing something vs. just the risk of doing something:)
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My feeling is that the more compounds you introduce, the more difficult it becomes to parse out the specific benefits (and side effects) of each. We are already taking a calculated risk by taking a drug with limited human testing. Introducing another untested drug like Acarbose could have an additive effect, no additional effect… or it could actually negate the benefit of Rapamycin.
I strongly suspect, when it comes to longevity drugs, the benefits will not be (fully) additive. Two drugs that increase lifespan by 15% individually may only increase it 18 or 20% when taken together (we’ve already seen evidence of this in the ITP). I’m simply not willing to multiply risk for a potential extra 3%. But underlying this decision is also my personal motivation. I’m not primarily aiming to live longer, I’m hoping to reduce the physical decline such that I become increasingly competitive as I progress down the Masters’ age categories.
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I am aware of polypharmacy - in fact, being surrounded by pharmacists and researchers in geriatrics, along with access to patient charts taking rapamycin with other drugs is probably the best possible field to get to “appropriate polypharmacy” the quickest - I suspect over 5-10 years I’ll have a better answer since I’m in contact with a physician who routine prescribes rapamycin to older people on 20 different other drugs. Geriatrics has a lot to do with managing medications. And they aren’t easy physicians to find since few want to study an extra year or two just to get paid much less than a general practitioner.
As for your specific concern - acarbose has very, very low systemic absorption. Acarbose acts locally. I’m not taking it continuously - just high carb meals prn at a low dose. In my situation, the odds seem fair that the interaction is probably near zero but I can’t say for sure of course.
The biggest concern to me is how you reliably measure “aging” and track what is actually happening in the body when there are no or few noninvasive ways to tell accurately. My guess is I can probably reliably tell in 5-10 years whether my stack is likely “working” (not just changing biomarkers that may not actually change disease course) for me personally and narrow down from there once more data is available. When you have a reliable test, you can do crossovers, use an elimination method, trial of medication elimination/tapers, and vary change timing/combination of meds based on the mechanism of action to demonstrate interaction. If there is some interaction and the main MoA is known - it can probably be measured and adjusted to appropriate levels in the individual. I see this all the time with geriatric patients that have psychiatric disorders on a highly variable polygenetic basis while we play medication roulette. You are forced to play with the dials with mostly blinds. The problem is actually getting someone trustworthy and competent to play with the dials while knowing what clinical signs to look out for, let alone knowing that you need someone to do that in the first place.
I found the few physicians available to prescribe rapamycin are either really great at what they do or not much experience in playing with dials.
By the same token, you could end up having no or negative effect on lifespan and healthspan for rapamycin monotherapy. It’s happened to people with calorie restriction before. But there is also a risk of under-prescribing and too little tracking when you get too worried about polypharmacy off the bat. We’ve tried monotherapies for so many decades for Alzheimer’s and failed so often that there is a surge of interest in combination therapies. I think “aging” as a disease also fits this polytherapy category very squarely. Rapamycin appears to be the best monotherapy to start experimenting with after I looked at recent unpublished dog study results, human trials, ancedotes, and giving my dogs some over >5 years was enough for me to try, but eventually polytherapy is probably going to be needed, barring highly expensive and experimental gene therapy.
The opposite also occurs - some people are heavy smokers, heavy drinkers, and eat junk food with no meds - yet live 100+ healthy years. But it would probably become clear that his lifestyle was not harming this person over 5-10 years if you did accurate enough tests.
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I tend to agree that more interventions won’t necessarily be additive but will certainly increase risk, especially if we’re talking meds.
And regarding biomarkers, it’s far from clear. When I was in my 20’s I was 140 pounds at 6 feet 1 , exercising for hours a day, and had a HbA1C of 5.9. I’ve ranged 5.7 to 5.9 for close to 40 years of so called “ pre diabetes “.
Am I diabetic? Nope. CAD nope.
Retinopathy? My ophthalmologist says I have the eyes of a 40 year old.
Nephropathy? Not at all.
Pre diabetes has certainly helped the drug companies sell a lot of metformin. I’ll give them credit for that.
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Indeed, we have a lot of associational studies, but everything boils down to n=1 actual documented health status.
Start them early, then upsell them when they cross into full on 911 diabetes with newer and more expensive glucose lowering meds.
FWIW
Metformin Hcl
120 Tablet, 500mg
The cost{pay cash, no insurance] is less than $4.00 retail in North NJ area. {As of 07/04/2022]
They would have to sell large amount of metformin.
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Haha, yeah.
I remember reading this from several years ago
It’s interesting that 12.5 % of centenarians were found to be diabetic, and that was when HbA1C cutoff of 6.5 was used. I guess it’s 20% at 6.0. And can you imagine the number of prediabetics? It’s a downright epidemic!
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Here’s the centenarians study
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Wasn’t always generic I’d guess
Yep, the specificity is actually pretty low for specifically the prediabetes cutoff on HbA1c in the US. I think the idea was to get more people alarmed earlier at the risk of false positives.
You could also be an “exercise nonresponder” btw.
Take a look at the sales of metformin in the millions
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Seems to fit well with increasing t2dm/prediabetes incidence. If anything I remember some Indian metformin getting recalled due to carcinogens and these people are generally running relatively slim profit margins. A geri psych fellow once told me 1 in 10 times the cause of poor response to psych meds is actually because the medication is generic and made outside of the US despite FDA “bioequivalence”. Yet the insurance companies will often deny paying for branded to test that theory.
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