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📝 Everything Good Is Correlated With High IQ? The Peptide Hype Test, Why You WON’T Lose Weight & How to Beat Procrastination (Premium)
Published 6 days ago • 10 min read
​Creatine:One of the most well-researched and effective supplements for enhancing muscle strength, cognitive function, and overall energy production, with benefits extending beyond athletes to general health and aging.
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This wide-spanning conversation — with some compelling back and forth debate on ethics — covers many existential topics on humanity, society, and politics. Is GDP still a good metric? Where is embryo selection technology heading and what are ethical dilemmas associated with it? Is there an argument for gene editing being a moral necessity? Can we live forever and is that something noble to strive for? Does our meritocracy need critical maintenance? Is space travel going to require a change to the human anatomy? And more, if you can believe it
Peptides are everywhere right now, but how much of the hype is actually backed by evidence? In this episode, Peter Attia breaks down what peptides really are, how to evaluate the science behind them, and why a powerful story, a doctor’s prescription or an impressive testimonial does not automatically mean a peptide works​
Got a crazy idea? “Just do it!” While this iconic slogan was formulated in Nike’s marketing department, it perfectly captures how Phil Knight started running toward his crazy idea at full speed, as he explains in Shoe Dog: A Memoir by the Creator of Nike. His story is an entrepreneurial masterclass in what can happen when you lace up your shoes and never stop until you reach the finish line
“Health positive manifold” = the smarter you are the more physically and mentally healthy you are
“Not always to a huge degree, but to at least some degree”
Smarter = better job = more money = more resources for health?
“Gene editing is a moral necessity”
Gene editing and gene therapy are just the next tier of medical technology
Medicine protects us from bad outcomes, so why is this any different?
Especially if the cost to do so approaches zero
Targeted edits to a gene can mimic taking a pharmaceutical for life
Gene therapies are permanent one-time solutions
“We can save so many lives without having to worry about adherence”
“We’re very close to just eradicating tons of diseases with gene therapies”
Example: Lipoprotein(a) or Lp(a) deposits on the walls of your arteries and causes heart disease at very high rates. There are currently no drugs for it, but there are five gene therapies in trials right now.
There’s no reason to worry about side effects when editing genes for specific function
Example: A healthy person has a genetic predisposition to low cholesterol. Because of this, they have better overall health and a lower risk of heart attack. So, given the evidence, why would we assume editing a dysfunctional cholesterol gene to be lower could have any effect other than living a healthier life? The gene simply does what it’s coded to do.
The USA and China are both failing at this…
The Guokao test in China accurately identifies the smartest people, but China misallocates them
The smart people end up working on corrupt bureaucratic things rather than innovation in the private markets
America, alternatively, doesn’t send any smart people to work in government
The government doesn’t pay well and has eternally growing regulations that deter innovators
Use this same framework for any drug (BPC 157 fails every part of the framework):
(1) Is there a viable mechanism of action?
What is the molecular target
What changes downstream
Why would that produce the clinical effect being claimed
“Without that chain, a claim like it boosts energy or supports immunity or reduces inflammation can mean almost anything and almost certainly nothing”
A real mechanism also shows you how a product could fail
It may not reach the relevant tissue
It may require an unsafe dose
It may move a biomarker without changing health outcomes
If a compound has no plausible mechanism, that should be an early red flag
(2) Does it improve meaningful outcomes in humans, not just in animals or lab studies
(3) Do we understand dosing, pharmacokinetics, short term risk, long term risk and what you need to monitor?
(4) Judge risk in context
A serious risk can be reasonable for a lethal disease
The same risk may make no sense for a small improvement in wellness or recovery
(5) Is there a better characterized way to get the same result?
Peptides create a perfect setting for expectation to influence results…
Social media testimonials make them feel validated
A clinician or peptide clinic adds authority
Paying a lot of money raises expectations
Injections feel advanced and serious
“Controlled human trials are how you separate the drug from the drama that surrounds it”
The biggest wellness claims often sit in the hardest areas to prove
Brain boosting is difficult because of the blood brain barrier
Tissue repair is biologically complex
Broad promises of regeneration and optimisation are harder to test than treating a specific disease
Not wanting to lose can be more powerful than wanting to win
Phil attended undergrad at the University of Oregon, graduated with a master’s degree from Stanford, and spent a year in the Army. But then, he found himself back at home in his childhood bedroom…
Phil didn’t know what success would look like for him — like his friends with budding careers — but all he knew was that he needed to be successful to live a meaningful life
“Like it or not, life is a game. Whoever refuses to play, gets left on the sidelines. And I didn’t want that.”
Your first employees need to be as mission driven as you are
Jeff Johnson didn’t only help Phil sell shoes, but he wanted to expand his market, he wanted to try new marketing strategies, and he craved feedback — he wrote to Phil from California unanswered almost every day
Jeff believed that “running, done right in the correct spirit and with the proper form is a mystical exercise, no less than meditation or prayer”
Jeff had many people throw soda cans at him and mock him while he was out for runs, so he was personally invested in changing the narrative around running
Jeff saw the potential of Blue Ribbon and asked for a full time job even when the company was $11,000 in debt and losing more money by the day
Jeff became the first full-time employee
Reinvest to become the best
Phil did not believe in having any cash in his bank account, he put every dollar back into the business
Phil put every dollar he earned from his full-time job into the business
Phil had to go from bank to bank to get new and bigger loans for inventory
Build the market first and sales will follow
Phil, Bill, and Jeff focused on celebrating the activity of running rather than trying to sell shoes
Bill wrote a book titled Jogging, which introduced people to the idea that “everyone is an athlete”
The book sold millions of copies and created thousands of new shoe customers
“Business is war without bullets”
Phil was an avid reader, taking lessons from generals and samurai to apply to business
Phil’s three main heroes were Churchill, Kennedy, and Tolstoy
“I had no love of violence, but I was fascinated by leadership under extreme conditions”
Don’t tell people how to do things, tell them what to do instead — you’ll often be surprised by the results
Jeff’s only command from Phil was to go sell shoes, how he did it was all his own
Jeff went above and beyond in everything, even sending customers congratulation cards after they finished races
Jeff was the one that convinced Phil to open a store, or rather, a “mecca for runners”
This store was a place for runners to commune and learn more about running
“Johnson, the aspiring cult leader of runners, finally had his church”
Best evidence based sleep supplements: tart cherry juice, chamomile or apigenin, kiwis, magnesium bisglycinate, omega-3, and melatonin
Use melatonin mainly to reset your sleep timing for travel, jet lag, or another circadian-rhythm problemFor those situations, he typically uses a low dose: around 0.3–0.5 mg, not the common 5–10 mg dose
People generally sleep less well when they share a bed… Reduce movement and noise before jumping straight to separate rooms. Try these
Separate sheets
A setup with less motion transfer
A pillow between you
Earplugs
Copy parts of your home setup when you travel
Bring your pillow
Use a familiar smell, such as lavender
Keep the room cool and dark
The 54321 method for fat loss
5: Be active 5 days a week
Walking, exercise, work, or other movement all count
Rest days are fine
4: Do structured exercise 4 days a week
Not every session needs to be intense
Yoga can count
3: Train hard enough to sweat on at least 3 days a week
2: Strength train 2 days a week
1: Have at least 1 day where your heart rate gets very high
Separate the goal from the tactic
“I want to lose fat” is a goal
“I need to exercise more and diet” is a tactic
All psych drugs historically work by messing with the 3 big monoamines: serotonin, dopamine, and norepinephrine
SSRIs specifically boost serotonin by blocking its reuptake, so more of it hangs around in the synapse
Raising serotonin can actually lower dopamine
That’s why some people on SSRIs feel emotionally flat or blunted even while their anxiety or depression gets better
Calling SSRIs antidepressants is bad marketing… they actually work better for anxiety than for depression in a lot of cases
Prozac was one of the first and purest SSRIs
Zoloft has a bonus effect of mildly blocking dopamine reuptake too
Lexapro gets used a ton for dysthymia (chronic low grade depressive mood, not just full blown depression)
Changes in the modern world triggering mental health problems
Social media and constant device use are huge contributors
People get isolated and end up with a distorted view of reality shaped by algorithms built for commerce
Some pretty stark trends: less sex, fewer real relationships, more reliance on online porn instead… dropping fertility rates
The socioeconomic divide is a big deal too
It’s driving a ton of anxiety and demoralization, especially in people who already have lower adaptive capacity
A lot of people are actively pushing back by moving toward nature, getting off the grid, and things like that
Stuff that used to be automatic, like being outside, being social, being disconnected from constant information, is no longer the default
You now have to make a deliberate effort to get those things back
Linus lays out his personal framework for thinking about mental health
Hormones and the endocrine system
Inflammation
Metabolism
Stress circuitry
Circadian biology and sleep architecture
​
Chronic pain taps into your stress circuitry and raises cortisol
That cortisol is actually toxic to the hippocampus and lowers BDNF, which your brain needs for neuroplasticity
The brain never operates in isolation! It’s part of a much bigger system with constant back and forth feedback between neurotransmitters and these foundational biological systems
Psychotic disorders and bipolar target: above 1.5 mmol
Benefits of the ketogenic diet: influences neurotransmitter levels (particularly glutamate, GABA, adenosine), changes calcium channel regulation, changes gene expression, reduces brain inflammation, improves the health of the gut microbiome, improves insulin resistance and signaling
A ketogenic diet has two critical benefits for mitochondrial health: (1) stimulates mitophagy (like autophagy for mitochondria); (2) stimulates mitochondrial biogenesis (increases the number and health of mitochondrial cells)
Mitophagy: gobbling up dead cells in mitochondria to replace them with newer, healthier cells
Autophagy is stimulated by fasting or fasting-mimicking states
Mitochondrial dysfunction is associated with nearly every physical and mental health disorder and disorder of aging
On mitophagy: “The most powerful signal and tool we have right now is related to diet – it’s calorie restriction…fasting and intermittent fasting…and fasting mimicking diets” – Dr. Chris Palmer
Glucose doesn’t tell the full story – high glucose levels are often a symptom, maybe of mitochondrial dysfunction somewhere in the brain and body
It is true that consuming large amounts of junk food and processed foods can lead to dysregulation of glucose levels, but this isn’t true of everyone
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