Out of the 1 million+ words on research we've written, the following 2000 words may be the most important.
We have deep dives with the research that supports everything below here:
Dozens of NIH studies but… it can get overwhelming.
This review is our attempt to slow-cook this information in an easily accessible format to reach the widest swath of people.
For good reason.
Spending 2-3 hours a day in NIH studies, we keep coming across the same dynamic that secretly guides all things health and mental health.
Outside of pretty significant genetic differences which the body usually finds workarounds for, steroidal hormone loss and early trauma/infection/stress are THE drivers of how we manage stress and the world.
The two are even intertwined!
The most exciting part is that we can actually "overwrite" a great deal of the latter since it's encoded in our immune system and the epigenome (don't worry…we'll explain it all).
Let's get started…here are the topics:
- A quick intro to your steroidal hormones (not just for reproduction)
- The epigenome machine - a changing history that guides how you feel right now
- Early stress and infection leave their mark
- This will go down on your permanent record! Or will it? Tools to unwind the past
Let's get started! Stay with us…this is the biggest key to markedly changing your health trajectory.
A quick intro to your steroidal hormones (not just for reproduction)
Before we get into the really exciting new frontier of editing your past, we have to take a quick detour to steroidal hormones.
After all, they're just for reproduction.
It's probably the greatest failing of our healthcare system bar none. The average doctor has a few hours of instruction on them but mainly around reproduction.
They are so much more!
Estrogen and Testosterone are powerful drivers system-wide of:
One example (of thousands…every cell in your body has receptors).
Looking at the brain, they both drive serotonin…the manager of ALL human behavior.
Serotonin is your new best friend:
- Powerful stress response buffer
- Drives BDNF, our brain's fertilizer
- Supports sleep and mood
- Manages downstream players like dopamine, our "reward circuit"
Serotonin is the target of SSRIs, but they build tolerance (see SSRI review).
- Testosterone drops by 1% each year starting around age 20.
- Estrogen plummets in our late 40's (that's how our journey with CBD began - story here).
Progesterone is fascinating for women. It actually ramps up to protect the amniotic sac from being attacked by the woman's immune system.
Generally, it calms inflammation and pushes back against estrogen. A huge supporter of GABA, our brain's "brake" pedal (target of benzos).
It drops 1% each year and hits 50% by age 40. Hello, autoimmune and anxiety, etc.
That's just a smattering. Gut. Heart. Bone. Muscle. Organs. Brain. You name it…they are intimately involved in supporting every cell!
We did deep dives here:
Here's the rub and why you're probably not on them (if your doctor even tests the levels!).
- A very flawed WHI study came out in 2002 that scared the bejesus out of every woman and doctor (ovarian cancer and blood clots)
- Similar studies came out 2013/2014 for testosterone that did the same for men (cardiovascular)
We looked at the estrogen one specifically in our guide above but the new Bijuva study showed results were actually BETTER with bioidentical oral estradiol/progesterone.
You'll probably have to fight with your doctor (or find a new one) to get Estrace, Prometrium, or bioidentical Testosterone.
Put up your dukes! Check out steroidal hormones and longevity. It really is the first shoe to drop!
That's just a function of aging…we're all on the same boat and it's taking on water. Get your levels tested and supplement as needed. Bioidentical only!
Lots of research in the links above.
Also, Vitamin D is a Steroid! So many people are deficient and it manages around 1000 "transactions" in the body including DNA repair.
Get tested. Support as needed. Check out the review for more guidance.
We needed to dive into steroids because the next exciting piece below is really hard to do if our core replenish/build systems (steroids) are depleted.
Let's now turn to the exciting piece with a focus on mental health (Descarte ruined us…the body and brain are cut from the same stuff).
We need to introduce the most exciting playing field in medicine's future. Your epigenome.
The epigenome machine - a history that guides how you feel right now
In the next few years, you'll see headlines about massive companies (Calico, Altos labs, etc) promising (and probably delivering) on reversing aging. Maybe even back to age 25!
This centers around new understanding of the epigenome.
Stay with us…it's pretty cool!
You have your DNA. Think of it as a hard-coded set of instructions to run every one of your cells.
It doesn't (shouldn't) change much barring mutations.
That's the "nature" side of things. What you're born with.
Then there's the much more exciting "nurture" side. This resides on the epigenome, a set of instructions that determine how those underlying genes are expressed.
Which genes? How long? How much? When?
The difference between your body at age 25 and 50 lies in the epigenome and pretty brilliant scientists may have stumbled on how to remove the "edits" that accumulate as we age.
More on this Yamanaka Factor Research.
That's exciting but our interest in this "setting" is more…practical.
Let's turn there now.
Early stress and infection leave their mark
The brain is essentially a prediction machine. Its immediate goal is to predict situations that will help or harm your chances of survival.
This prediction is based on past experience!
Little "markups" or edits will be made to your settings based on what happens to you.
In fact, the markups can happen in utero or even be passed down from past generations (up to 10 generations in some studies)!
Think of the EQ setting on a stereo. You can boost bass or treble to change the sound (epigenome) for the exact same song (DNA).
The effects are powerful and directly drive health and mental health.
It turns out that infection (viral or other), trauma, and stress early in life can cause life-long shifts.
This trickles down to key pathways we can see (and feel) directly:
- GABA (brain's brake pedal) is downregulated
- Serotonin (stress response and mood manager) is downregulated
- BDNF - brain repair goes down
- Anandamide - backup stress response buffer
- Cortisol - stress hormone increases
- Glutamate - brain's "gas" pedal goes up
- Inflammation goes up
Goodness…what a cluster-you-know-what!
Why would the body put our backs to the wall this way?
If things were bad (or dangerous or without food or abusive, etc) in the past, the brain wants to be ready. Settings adjusted. Be vigilant. Be on guard. Be…anxious!!
Here's where it gets even more interesting!
A big part of this historical record resides…in your immune system!
How would stress for Holocaust survivors be passed down to later generations and drive increased risk for mental health issues and changes in metabolism??
The DNA isn't changing. There must be a way for this information to pass down from generation to generation.
Very similar to a recording of past interactions with different viruses. Hmmmm. The immune system!
New clues are teasing this out.
For example, new research on psilocybin (which will revolutionize addiction and mental health) shows that the long-term effects were due to epigenetic changes to genes….in the immune system!
Insult to injury…early trauma, stress, and infection can also reduce…steroidal hormone function!
One note…the immune system is super complex but it responds to infection or psychological stress about the same!
Childhood abandonment ramps up inflammation just like strep throat!
Understanding this is very important.
That all sounds pretty depressing but it's so so exciting!
Why??? Because we can calm the storm!
Tools to unwind on our semi-permanent record
There are ways to re-tool the immune system and "forget" the past edits that drive physical and mental health issues.
One important warning!
We MUST avoid tolerance and addiction.
Tolerance is what happens when a substance (drug, med, or supplement) pushes a key pathway in one direction.
The body strikes back! It will actually reduce receptor activity and numbers for that given pathway which means we end up worse off than when we started.
You see this everywhere:
- SSRIs - serotonin
- Benzos - GABA
- Alcohol - serotonin and GABA
- THC/cannabis - anandamide
- Nicotine - acetylcholine
- NSAIDs - COX2
- Stimulants - adrenaline and glutamate
- Opioids - Opioid system!
Some of these also spike dopamine which drives addiction but tolerance is enough to make you miserable.
So…our toolkit to rebalance our immune system and also support key pathways:
- Magnesium glycinate
- CBD isolate
- Medicinal mushrooms
- Vitamin D
- Steroidal hormone support
A quick intro since we have deep dives for each.
Magnesium glycinate and mental health
Mag is our mineral stress response buffer. A metallic wet blanket for inflammation, stress, and glutamate!
Many people are deficient because mono-crop farming and pesticides kill the conveyor belt (bacteria and fungi) that move it from soil to food.
Glycinate gets across the blood-brain barrier best.
It directly supports GABA, calms glutamate (which just leaks out from hyperactive immune response), and calms inflammation.
Mag works fast and slow. 3 x 100mg daily is great support.
Sure, this is close to our heart but only because the research is ridiculous.
CBD is a feedback player in our system that balances other key systems including:
Again, this occurs since the endocannabinoid system is tasked with balancing the immune, endocrine, and nervous system.
No small task and CBD doesn't build tolerance like THC does. It supports when low!
Its support of BDNF may be the biggest coup since BDNF is THE key to mental health and addiction!
Research shows that peak neurogenesis is at 300mg daily.
Our distant cousins are so fascinating for retooling our immune response and supporting repair/replenishment.
They support BDNF, calm inflammation, and affect so many different pathways.
There's a great blend which we use here.
Lion's mane, Reishi, Turkey Tail, and more all in one capsule.
Learn all about medicinal mushrooms and mental health medicinal mushrooms and health.
Vitamin D is actually a steroid…one we get from the sun!
But we're not in the sun like our ancestors and our D reflects this.
D is a massive manager of the immune response, sleep, and mental health.
1000s of chemical processes and a slew of DNA repair pathways require D to work.
Get your levels tested and aim for 50-60 ng/ml.
Then question why your doctor never tested you before!
D is also critical for your steroidal hormones to function correctly. Go figure.
Learn about D here.
So much exciting research is further South…to the gut!
Berberine is a powerful player to calm inflammation there.
The gut works like a thermostat…setting the inflammation setting for the rest of the body and the brain via the Vagus Nerve.
Gut inflammation and breaks in the gut barrier cause a host of different issues to the…host!
This is the one we use.
NAC is a powerful supporter of our entire detox pathway which centers around glutathione.
More importantly, NAC acts like a sink for excess glutamate (the brain's gas pedal).
When the immune system is ramped up, its sentinels called microglia just leak out glutamate which is toxic to our neurons when excessive.
There's interesting research on NAC and mental health reflecting this calming effect.
Steroidal hormone support
We covered this!
- Estradiol - Estrace
- Progesterone - Prometrium
- Testosterone - oral sublingual from compound formulary
It must be bioidentical. You can get your levels tested (the Dutch test is the best option) and adjust accordingly.
Don't go for the "your levels are fine for your age" if older. Do you feel the same at 50 that you do at 25? No!
Find a better doctor. Better yet…a naturopath who actually learns about hormones.
Finally…we can dream…
The key ingredient in magic mushrooms is a total game-changer for everything we discussed above.
It's as close to an epigenetic "eraser" that we have till Yamanaka factors just scrub it clean.
We even looked at whether psilocybin is a form of Yamanaka factor effect we can have now.
It's not legal yet but that's coming and the question will then be…why did they suppress the research and access for 60 years with a tally of suffering and loss that's unrivaled?
Yes…it's that powerful. A new study on heavy alcohol use saw an 88% reduction!
If you're not comfortable with psilocybin when it comes online, CBD does the same thing…just at a slower pace (BDNF is the big "editing" player).
We looked at CBD and epigenetic remodeling but its effect on "fear extinction"...essentially "forgetting" traumatic experience write-up is a great example.
That's a wrap!
You are now at the cutting edge of mental health and health generally. Not just masking the symptoms while making the underlying storm worse.
If you want to read the deep dive with dozens of NIH studies, enjoy here.
Welcome to the future. Take it back from the past!
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.