Let's just call it the Five Horsemen of the Medical Establishment Apocalypse...
Clippity Clop. Clippity Clop.
You can hear beating hoofs just around the bend.
Our introduction to the current state of medicine - treatment for anxiety as an example, was poor at best. The current status is woefully flawed and reflects 60 years of stagnation.
Actually, the new additions (Xanax and Ativan) are much more addictive and problematic (see benzo review).
Big advances are ahead in how we view and treat health with CRISPR and Yamanaka factor work coming online.
We'll get into those below but till then, there are pretty amazing tools available….right now!
Tools that have powerful effects on every pathway of your body and brain for the better. General longevity and health!
In this case, it's five horsemen!:
- Rapamycin
- CBD Isolate
- Akkermansia
- Psilocybin
- Steroidal Hormones
If I had to choose 5 supplements to take to a desert island (Vitamin D is covered with the sun, right??), it would be these fivw currently.
We'll get into why below along these topics:
- A quick lay of the pathway landscape…what's most important
- Rapamycin - the closest thing we have to a fountain of youth
- CBD Isolate - powerful balancing agent without tolerance/addiction
- Akkermansia - example of powerful gut bacteria that direct metabolism
- Psilocybin - magic mushroom key that's going to revolutionize mental health
- Steroidal hormones - the workhorses of repair/replenishment across the body and brain
- Other players that almost made the list
It's an exciting time to take back your health and this is at the top of the list of tools.
Pharma and traditional medicine's time is coming due! Queue the hooves.
A quick lay of the pathway landscape…what's most important
Okay…these 5 players…why did they make the list?
First, some requirements.
- They can't build tolerance or cause addiction
- They must have far reaching benefits on core pathways
- They must have a strong safety profile
- They need to be revolutionary! Groundbreaking really.
CRISPR promises to revolutionize medicine but Yamanaka factor research is even more exciting.
We have a whole review on Yamanaka for longevity but the quick skinny.
Our DNA is a hard set of instructions to make/run each of our cells. It doesn't change much.
That's nature.
Our epigenome sits right on top (figuratively) and determines how, when, which of those genes get turned on.
Our interaction (and our parents and their parents…etc) directly change this layer.
Little "mark-ups" to this layer also accumulate as we age which drives…aging!
We did a huge review on editing our past's health code.
Yamanaka research (attracting billions of as we speak) aims to strip these mark-ups away which is showing powerful effects to make bodies/brains appear more youthful!
Like we said…exciting stuff. Till that's ready (almost all disease is tied to aging), we need some interim players for longevity and health.
That's this list! We have 1 million+ words of research across many pathways and 1000's of hours buried in NIH research.
These players are the most exciting!
Let's get into it.
Rapamycin - closest thing we have to fountain of youth
Originally billed as an anti-fungal, rap has the best track record for longevity gains.
This is reflected by the ITP (Interventions Testing Program - the gold star of longevity testing) and countless studies across multiple species from yeast to humans!
ITP's result:
Rapamycin – Increased mean and maximal lifespan in both males and females when initiated at 20 months of age (Harrison et al., 2009) and when initiated at 9 months of age (Miller et al., 2011)
https://www.nia.nih.gov/research/dab/interventions-testing-program-itp
So…what is rap?
Essentially, it blocks a pathway called mTOR which functions as a nutrient (protein) sensor in the body.
A quick intro is needed…
All living things (that scientists have looked at) have this system in place in case of hardship.
Famine. Drought. Heat. Cold. Bad times to reproduce essentially.
mTOR runs hot during good times and slows down during bad times which throws the body from growth..to housekeeping.
- Get rid of bad cells (autophagy)
- Run energy more efficiently (mitochondria)
- Conserve metabolism (insulin is its main signal)
The net effect? Huge changes in just about every metric of aging and health.
Too much to go into here but there's a great hub here:
https://www.rapamycin.news/
To the body, it's like a 40% reduction in calories but there are benefits way beyond caloric restriction.
The current approach till we have more guidance is the following:
- 4-6mg 1 time weekly for 6 weeks
- 2 week washout (no rap)
- Rinse - repeat
One note…rap is known as an organ rejection drug but that's at higher levels/daily. Forever!
The pulsing option (once per week with washout) has actually been shown to improve immune response!
Check out the link above. You can go to pushhealth.com and request it with the reason being "longevity". GoodRx offers discounts if your insurance doesn't cover it.
There's fascinating studies on topical applications as well.
We take one 2mg tablet and dissolve the outer shell. We then place the rap without the coating in a 2000mg CBD bottle and use topically with microneedle device.
A study with rap and ECGC (green tea extract) showed interesting results for regrowing hair and microneedle device (which boosts absorption).
I'm currently in the washout period…and I'm missing how Rap feels! One more week to go. Very exciting tool across just about many metric you want to look at:
- Metabolism
- Cancer
- Gonadal function (looking at it to prolong ovary function for women)
- Immune function
- Cardiovascular (study showed heart enlargement normalized)
Rap is front and center.
A few key notes:
Rap can suppress steroidal hormones and you know how dearly we view them (see steroids and longevity).
For this reason, we're actually switching to 2mg one week and then a week off. Run your labs (metabolic, lipid, steriodal hormones, etc) and adjust accordingly.
Next up, closest to our heart.
CBD Isolate - powerful balancing agent without tolerance/addiction
Sure…we're partial here. After all, CBD isolate helped up navigate a brutal perimenopause.
For good reason. CBD isolate is a gift down here for health.
We have 100's of reviews across almost any category you want to look at but a quick intro into why it's so fascinating.
Every living animal has an endocannabinoid system…it dates back about 600 million years evolutionarily speaking.
This system is tasked with balancing just about every other system after stress including:
- Nervous system - neurotransmitters and more
- Endocrine system - hormones
- Immune system - inflammation and cellular birth/death cycles
We use the word "stress" generally…meaning anything that pushes a key system in one direction or another.
For example…you have a date.
- Cortisol (stress) goes up
- Glutamate (brain's gas pedal) goes up
- Adrenaline goes up
After the date (or hopefully before it ends), this whole "crap, we're on a date" cascade needs to return to normal.
You can't stay in that state forever or you'll burn out.
In fact, constant stress…becomes anxiety! Essentially, our stress response buffers (serotonin, GABA, anandamide) exhaust.
CBD supports this balancing system when it's outgunned!
Unlike its cousin THC, it doesn't push in one direction (hence the side effects and tolerance with THC). It supports when low!
A feedback mechanism. Technically, a positive allosteric modulator.
It's a beautiful thing because very few supplements/medications we have work this way.
They usually push key pathways in one direction and tolerance/side effects result.
In today's world…balance is sorely in need!
To learn more, check out:
The last one is all about the epigenetic markups we discussed above.
The trauma one is even more exciting. Remember the "markups" to our epigenetic layer?
Trauma, infection, and early stress also brings out the red pen! CBD and psilocybin are powerful tools to erase these edits.
We take 300mg daily (this one) which matches research on peak neurogenesis (brain repair/replenishment).
Next up…to the gut!
Akkermansia - example of powerful gut bacteria which direct metabolism
We're slowly learning that metabolism IS health. Especially on the longevity front.
Remember how mTOR's primary signal to ramp up is insulin? Glucose is an Enemy of the State (the state being our body).
We did a deep dive on the problem with glucose.
Akkermansia is an example of a gut bacteria strain that has powerful effects on:
- Gut inflammation
- Metabolism
- Weight
- Mental health
Wait what??? Why mental health?
The gut is our "second" brain with the 2nd biggest number of neurons behind the skull.
They communicate together directly through the vagus nerve (more here - get to know it!).
Akkermansia is partially why metformin and berberine show their powerful effects across the body.
Gut inflammation states directly drive:
- Mental health
- Autoimmune (bacteria escaping into the body)
- Inflammation states (which drive cancer and aging)
Check out our reviews to learn more:
Pendulum has a great akkermansia supplement or their Glucose Control which combines akkermansia and other butyrate forming bacteria.
We lost 10 pounds after starting glucose control. The gut microbiome IS part of the future of better health.
Check out probiotic review to learn more.
Next…to the brain (via the immune system)!
Psilocybin - magic mushroom key ingredient that's going to revolutionize mental health
Big review on Psiloycbyin since it's going to revolutionize mental health shortly.
The primary substance of magic mushrooms, psilocybin is showing impressive results across almost every facet of mental health and addiction (intimately tied).
It's an explosion of BDNF, our brain's repair/growth factor plus a reset of the connectome…how our brain is integrated system wide.
Both can be impacted by early trauma, infection, and stress!
When you dig down into any substance that is used for mental health (CBD, SSRIs, Exercise, Mindful Meditation, etc), you find this pathway!
It doesn't have to be a full trip. The future for people over a certain age will be about maintenance doses (.1-.5 grams) to keep the brain more "plastic".
This is basically a cheat code to function in a more youthful state when BDNF is flowing (the reason you can learn a language so much earlier when young).
Then there's the baggage...
- Trauma
- Infection
- Stress
- Inflammation
- Parents??
Yes…we all have it and it may go back to in utero or even past generations (up to 10 in studies).
Do we have a clear explanation of how our past affects our present and the key pathway?
The immune system records the damage.
Here's the fascinating part with psilocybin or medicinal mushrooms in general.
A study found that the long term effects of psilocybin were due to genes being turned on and off…related to the brain's immune system!
Yes…rebalancing immune function drove the positive benefits long term.
Learn why the immune system is the future of mental health or better yet, read our simple summary review.
Finally….the workhorses of the body and brain.
Steroidal hormones - the workhorses of repair/replenishment across the body and brain
We need a whole rethink on estrogen, progesterone, and testosterone.
So much misinformation.
This has nothing to do with reproduction, libido, or muscles (even though they directly benefit).
We're talking brain, heart, bone, organs, immune function, etc.
Every cell in your body has receptors!
So how to view them?
- Estrogen and testosterone are the primary repair/replenishment pathways
- Progesterone is a calming, opposing force to estrogen
Let's take one example (of thousands)
Serotonin. Our master regulator of ALL human behavior. It's not the "feel good" neurotransmitter.
More like feel "right". Right in your own skin player.
It also drives BDNF, the brain's fertilizer from above with psilocybin.
Here's the rub:
- Progesterone drops about 1% from age 20; down 50% by age 40
- Testosterone drops 1% from age 20…straight line down
- Estrogen plummets late 40's during perimenopause (see our story here)
The research on supplementation is just ridiculous. Dr. Attia's rewind podcast gives a good review.
You can almost pick any issue and find a positive impact.
So why aren't we all on it? Why hasn't you're doctor been prescribing instead of drugs to address the symptoms of its loss (SSRIs, benzos, sleep aids, blood pressure, statins, etc)?
A bogus WHI study in 2001-2002 scared everyone off of estradiol (big review here)
Similar hit pieces in 2013-2014 did the same for testosterone.
It gets worse. These were primarily based on synthetics which do not function the same as bioidentical (just look at NIH studies).
For example, the new Bijuva (bioidentical oral estradiol and progesterone) actually showed BETTER profiles for ovarian cancer and blood clots (the two boogeymen from 2001 study).
Read the research!
Make sure it's bioidentical.
Estrace for estradiol and prometrium for progesterone.
We had to get a sublingual testosterone from a compounding formulary since the creams don't absorb well.
The Dutch test is a great way to see your results and don't take the "your numbers are fine for your age" nonsense.
Does 50 feel like 25?
Related Research:
- Steroidal hormones and longevity
- Estradiol guide
- Progesterone guide
- Testosterone health guide
- Vitamin D (it's a steroid from the sun but many are deficient)
Okay…some honorable mentions.
Other players that almost made the list
If we were allowed a bigger bag on the desert island, we'd bring the following:
- Magnesium glycinate - calming agent in the nervous system and immune system
- Berberine - powerful gut balancing agent
- NAC - sink for excess glutamate and supports detox system
- Medicinal mushrooms - balances the immune system and supports repair
Big reviews for each of those.
Finally, we have a giant guide on cold exposure and mental health in the works. Goodness...it's a monster hack down here!
Otherwise, the big 5 are as close today as we have to bridge over to Yamanaka factor options and CRISPR…the next revolution of health care.
And they're available RIGHT NOW!
Related Research:
Is psilocybin a mini Yamanaka factor
CBD and SIRT for longevity
Pterostilbene and longevity
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.