Peter Attia’s Qualy Podcast (All Episodes)

This is a master post featuring the Key Takeaways from Peter Attia’s (@PeterAttiaMD) short podcast series, The Qualys. The full series is available only to Peter’s paying subscribers, except for periodic episodes that he releases on his main podcast feed. We’ll update this post regularly as new episodes drop.

Evolutionary Reasons for Sleeping | Episode #31

This Qualy comes from Peter’s Part I interview with Dr. Matthew Walker (Podcast Notes)

  • “It took mother nature 3.6 million years to put this 8-hour thing called a night of sleep in place, and within the space of 70 years—if you look at the data—we’ve lopped off almost 20-25% of that”Dr. Matthew Walker
    • Imagine reducing our oxygen saturation by 20-25% over the next 100 years; do you think that’s a good idea??!!
  • Up until 2012, Peter was in the “I’ll sleep when I’m dead camp” 
    • In his medical residency, Peter was working 100+ hours a week—he simply didn’t have time to sleep (Peter estimates, on average, he slept ~28 hours a week)
  • Think about sleep evolutionarily—it HAS to be necessary. If we weren’t sleeping, we could be hunting for food or finding a mate, and during sleep, we’re incredibly vulnerable to attack.
    • “If sleep doesn’t serve an absolutely vital set of functions, it’s the biggest mistake the evolutionary process has ever made” – Dr. Matthew Walker
  • “Sleep is the greatest life support system that you could ever wish for. It’s a remarkable health insurance policy. And what’s great is it’s largely democratic, it’s mostly free, and in terms of a prescription from a doctor, it’s largely painless.”Dr. Matthew Walker
  • Sleep is the foundation on which diet and exercise sit
    • Think about it: If you deprive yourself of food, based on your body fat percentage, you can survive for 30-~380 days
    • Derivation of sleep results in the quickest reduction in health
  • The Guinness Book of World Records now refuses to acknowledge attempts at breaking the world record for the longest period without sleep, which is currently ~24 days

Hierarchies in Healthcare, Physician Burnout, and a Broken System | Episode #30

  • “Certain personality types don’t like to be in the middle or bottom of hierarchies. They either want to be on the top or off the hierarchy. It’s hard for them to feel as if others are controlling them.” – Zubin Damania
  • “In residency, I loved the hierarchy when I could respect the person I was reporting to .. But the problem was, when I encountered someone who I didn’t think was smart enough or knew enough, I wouldn’t hesitate to just steamroll them, and that gets you into a lot of trouble.” – Peter Attia
  • “It speaks to our medical training in general—it’s about kissing the ring of the authority figures so, one day, you’ll be the ring that’s kissed”Zubin Damania
  • No authority figure in the medical field enjoys being questioned by a medical student (and that’s a problem)
  • That said, hierarchies probably serve some good, especially when someone’s life is on the line
  • Very often in his residency, Peter found himself in several predicaments/dilemmas related to breaking “the chain of command” (and thus, dealing with the consequences)

The “Art” of Longevity: The Challenge of Preventative Medicine and Understanding Risk | Episode #29

This Qualy comes from Peter’s interview with Ethan Weiss, M.D.

  • Doctors continuously face the same problem: they don’t know how aggressive to be (or not to be) when treating a patient—especially when it comes to disease prevention
    • The fact is: everything a doctor does to treat a patient has an effect (and sometimes, those effects are adverse)
    • Doctor’s don’t have a tool book—there’s nothing that says, “Given X risk, do Y”
    • “If you’re a hammer and everything’s a nail, even if you’re acting as a hammer and nail in accordance with clinical trials, I suspect you’re still acting in a blunt manner” – Peter Attia
  • “It’s unsettling. You just have to remain humble and hope your patients have some patience that we’re going to be wrong.” – Eric Weiss
    • For example, Eric didn’t pay any attention to Lp(a) until recently (and it’s incredibly predictive of cardiovascular disease risk)
  • Peter plans for the subtitle of his book (due out sometime in 2021) to be “The Science and Art of Longevity”
    • Note the order: “You’re informed by science, but in the end, this still comes down to an art” Peter Attia

What’s the difference between ketone salts and ketone esters? | Episode #28

This audio clip comes from Peter’s interview with Dr. Dom D’Agostinio (Podcast Notes).

  • A salt is an ionic bond between the ketone molecule (most often beta-hydroxybutyrate, AKA BoHB), a monovalent or divalent cation, or an alkaline amino acid
    • The easiest thing to do is bond BoHB with sodium, potassium, calcium, and magnesium
  • A ketone ester contains a covalent bond 
    • With these, “The ketogenic potency is inversely proportional to taste” – Dom D’Agostino
    • Check out this ketone ester from HVMN

Dealing with Anger When You Know it’s Coming | Episode #27

This audio clip comes from Peter’s interview with Sam Harris (Podcast Notes).

  • There are various situations in life where we’re all prone to anger (i.e., getting stuck in traffic, when someone’s late, etc.)
    • Peter gets particularly irked when someone asks an extremely complicated question with the hope of receiving a one-word, definite answer
    • Think of these situations like a video game boss: if you get angry, you lose; if you stay calm , you beat the boss
  • “Getting angry is not the measure of having lost. You can aspire to a time where you never get angry again, or you never get angry in certain circumstances again, but the real practice is to notice, as early as possible, what’s happening and to let go of it.” – Sam Harris
    • The difference between being angry for 10 minutes and 10 seconds and 1 second is enormous! For the most part, the quicker you let go of anger, the better.
      • “But if you can’t be mindful, you have no choice. You’ll be angry as long as you’re angry.”
  • Frame negative situation where you’re prone to anger in a different way
    • Stuck in traffic? Ask yourself, “How can I more so appreciate this as a gift?”
      • Maybe the traffic will allow you to catch up on some podcasts?
    • Bad airline service? Realize that most customer service jobs are quite difficult
      • Have empathy—behind every interaction is a HUMAN BEING

How Does One Select the Best Physician as a Patient? | Episode #26

  • “There’s no one-size-fits-all here. You have to decide what it is you need and want.” – Peter Attia
  • Things to consider:
    • Advocacy: The physician is connected and knows how to help you navigate through a storm
      • For instance, if you need a colonoscopy, they’ll likely the know the best doctor to send you to
    • Ability: The physician has to be skilled (and ideally, they should be up to date on the latest medical research)
    • Affability: You should be able to get along with your physician
    • Availability: Ideally, you should be able to call your physician 24/7
    • Peter adds on the above: “It’s pretty much impossible you’d find all of those in the same physician”
  • Questions you should ask a physician candidate:
    • How busy are you clinically?
    • How much time do you spend reading literature?
    • “It’s mostly just about trying to inquire about the curiosity of the person and their passion for learning. In many ways, if you’re not learning quite a bit as a doctor, you’re probably not practicing great medicine.”Peter Attia
  • “I don’t think people should be afraid of the process of picking a physician taking a while. If you go down the path and you find someone, only to learn six months in you don’t like them, try again.” – Peter Attia
  • In general: You don’t want a doctor who’s intimidated or put off by your interest/obsession in optimal health

Does LDL Cause Heart Disease? | Episode #25

This audio clip comes from Peter’s interview with Dr. Ron Krauss (Podcast Notes)

  • When cholesterol is on an LDL (low-density lipoprotein) particle (AKA LDL-P), we call it “LDL cholesterol” (AKA LDL-C)
    • The amount of cholesterol on an LDL particle can vary
  • People with high LDL cholesterol (LDL-C) are undoubtedly more likely to get heart disease (but the relationship is quite complicated—in many cases, lowering LDL-C doesn’t reduce heart disease risk)
  • Your LDL-P number is more indicative of cardiovascular disease risk than your LDL-C (and your LDL-P count doesn’t always mirror your LDL-C)

Is the food industry still saying that all calories contribute equally to adiposity and insulin resistance? | Episode #24

This audio clip comes from Peter’s interview with Dr. Robert Lustig (Podcast Notes)

  • The food industry preaches: “All calories are the same”
    • Robert has different thoughts: “It’s absolutely not true”
  • Let’s dive in:
    • If you eat 160 calories of almonds, you’ll absorb about ~130 of them; what happened to the other 30 calories?
      • The fiber in the almonds forms a gel on the inside of the intestines (in an area known as the duodenum)—this acts as a secondary barrier preventing absorption 
        • (This lining prevents the liver from getting the whole dose of calories—anything that’s absorbed in the duodenum will go straight to the liver)
      • So, some of the almond calories can’t be absorbed in the duodenum and are forced to travel onwards to the microbiome (aka the jejunum area of the intestine)
    • Take an apple, which is packed with fiber (there are 30 calories in a standard apple, half of which is fructose)
      • So, after eating an apple, some (about half) of its fructose wouldn’t get absorbed in the duodenum and would, instead, make its way to the microbiome where the gut bacteria would then digest it
  • “If you don’t consume fiber, your gut bacteria are not getting the food they need”Dr. Robert Lustig
    • So, to survive, your bacteria will begin autodigesting the mucin layer that sits on the surface of your intestinal epithelial cells; this can cause leaky gut and other GI diseases (i.e., colitis, Chron’s disease, etc.)
    • The take-home message: “Feed your bacteria, or your bacteria will digest you”
  • Do we need more soluble or insoluble fiber?
    • We need both! (Vegetables are an excellent source)
    • The food industry keeps adding soluble fiber, like psyllium husk, to food to make it appear healthier (i.e., fiber bars)
      • But without the insoluble fiber, it doesn’t make a difference

The Steroid Controversy: Mark’s Use and Peter’s Perspective | Episode #23

This clip comes from Peter’s interview with Mark and Chris Bell, two well-known brothers in the fitness/bodybuilding space

  • Mark’s been on and off steroids since age 25 (he gets them prescribed) 
    • “To me, it doesn’t really make a difference whether you grab them from some dude at the gym or whether you get them from a doctor; they’re not going to be all that regulated anyway, no matter how you slice it.” – Mark Bell
  • Steroids DON’T automatically make you stronger—but they do allow you to gain more weight (and thus gain strength)
    • However, once you stop gaining weight, those strength gains start to cease (and the limits of your strength/weight gains are largely limited by genetics)
      • “I don’t think people understand … Take the world’s supply of anabolic steroids and inject it into me, I couldn’t look one-tenth of what Phil Heath looks like”Peter Attia
  • “Once I spent 5 years learning everything there was to learn about anabolic steroids, I came to the conclusion that, while I can’t speak to what happens in bodybuilding—that takes it to a different level, certainly with how they’re used in cycling—more physiologic levels of use, I can’t see any evidence of harm [relating to cardio-metabolic effects].” – PeterAttia

The Types of Meditation, and Peter’s Favorite Meditation Apps | Episode #22

This clip comes from Peter’s interview with Sam Harris, Ph.D. (Podcast Notes)

  • “Thought is really the obstacle one is overcoming when learning to meditate. Our default mode is to be lost in thought. We’re telling ourselves a story all day long, and we’re not aware of it.” Sam Harris
  • The two main types of meditation:
    • Mantra-based (AKA concentration-based)
      • This involves paying attention to a mantra or repeated phrase, and nothing else
    • Vipassana (AKA insight meditation)
      • This is the type of meditation Sam prefers to practice
      • With this, you just try to be aware of everything (sounds, sensations, moods, thoughts), without reacting – if a thought pops up, you notice it, then come back to center
  • “Mindfulness begins, for most people, as a training of focusing on one object like the breath, but very quickly it becomes something you can apply to the full range of your experience.” Sam Harris
  • The best meditation apps:
    • There’s Sam’s App – Waking Up
      • “I’ve used every one of the apps out there, and I do find yours the best” – Peter Attia
    • 10% Happier, which is probably Peter’s second-favorite
    • Calm
    • Headspace
    • Oak

Cortisol and Healthy Aging | Episode #21

This audio clip comes from Peter’s interview with Dr. Navdeep Chandel, Ph.D.

  • Over-stressing about diet and exercise may be harmful in terms of raising cortisol (the stress hormone)
    • “I pay more attention today to stress than anything else” – Navdeep Chandel
  • Navdeep would absolutely love for a simple blood test to be developed, one you could sell at any pharmacy, which would dictate thyroid hormone, insulin, glucagon, estrogen, testosterone, dopamine, and serotonin, and cortisol levels
    • One problem: Cortisol is mostly bound to albumin in the blood, and it’s free cortisol that exerts the metabolic and physiologic effects (and you can only measure free cortisol in saliva and urine)
  • Stress (excess cortisol) adversely impacts:
    • Blood pressure (and thus the endothelium)
    • Melatonin secretion (and therefore sleep and neuroregeneration)
    • Mitochondrial health
  • “I think for many people, it’s easier to control what they eat, how they exercise, and how they exert discipline around taking medications and supplements, but in many ways, one of the hardest things to control is our response to stress” – Peter Attia
    • The cure for stress?: “Meditation is probably the single most valuable thing I’ve ever found to help regulate this”
  • Sure, overall, alcohol is toxic. But:
    • “The downsides of the ethanol, the hepatic toxicity of the ethanol, can be offset by the emotional benefit that could come from the enjoyment” Peter Attia

What is the most common first presentation of heart disease? | Episode #20

This audio clip comes from Peter’s interview with Dr. Ron Krauss (Podcast Notes)

  • The most common first presentation of heart disease? – Sudden death
    • “One-third of people’s first brush with the knowledge that they have atherosclerosis is death” – Peter Attia
    • For this reason, heart disease can be a silent killer
  • The most significant risk factor for heart disease is age
    • Why? – Like most things in life, atherosclerosis compounds
    • “It’s a cumulative process that can progress at various rates, depending on the condition” – Dr. Ron Krauss
      • If you have genetically elevated cholesterol levels, this process will be accelerated, allowing for a greater risk of heart disease showing up earlier on (it could even be in the teens)
  • Other risk factors for heart disease – smoking, diabetes, hypertension

Changing the Food Industry | Episode #19

This audio clip comes from Peter’s interview with Dr. Robert Lustig (Podcast Notes)

  • “The food system needs to change. They’re not going to change it from the inside because, right now, sugar is their business model. It’s the thing that increases their sales.” Dr. Robert Lustig
    • “They add more sugar, they sell more food, and they know it. That’s why there’s sugar in all the food.”
  • So…. the business model of the food industry needs to change; here are some possible way this could be done:
    • By educating the public – this way, people won’t want sugary food in the first place, and in turn, the food companies won’t sell it
    • Executive branch efforts (from the FDA or USDA)
    • Legislative changes from Congress
    • Judicial impact (there are currently several lawsuits against the food industry)
  • Robert wants to get rid of food subsidies
    • Food subsidies are what enable junk food to be ~half the price of real food
    • “Any subsidy distorts the market. There’s no reason for food subsidies. There’s no economist worth their soul today that believes in food subsidies because they distort the market.”Dr. Robert Lustig
  • Additional Notes
    • Due to the fairness doctrine, it was mandated that anti-tobacco ads follow all tobacco commercials on TV
      • The anti-tobacco ads turned out to be so effective that the tobacco industry withdrew from television 

How to Prevent Metabolic Problems in Your Kids | Episode #18

This audio clip comes from Peter’s interview with Dr. Robert Lustig (Podcast Notes)

  • The median amount of added sugar consumed by a kid is ~90 grams/day
  • “It’s not the added sugar you know, it’s the added sugar you don’t know”Robert Lustig
    • 50% of the added sugar consumed by children comes from candy/cake/ice cream and soda
    • The other half comes from foods you probably didn’t know contain sugar (i.e., pasta, bread, etc.)
      • Sugar is often added to bread to help it last longer without going stale (mostly bread from grocery stores, not bakeries)
  • “Processed food is the problem because processed food is high sugar, low fiber”Robert Lustig
    • Ideally, a child should eat a low sugar, high fiber diet
    • “Every diet that works is real food. Every diet that doesn’t is because it consists of primarily processed food”
    • “If there’s a label on the food, that’s a warning label. That means it’s been processed. Real food doesn’t need a label.”
      • Just think: Is there a nutrition facts label on meat, broccoli, or carrots?

The #1 Law of Medicine | Episode #17

This clip comes from Peter’s interview with Siddhartha Mukherjee, Ph.D. Siddhartha is the author of The Laws of MedicineThe Emperor of All Maladies: A Biography of Cancer, and The Gene: An Intimate History.

  • The first law of medicine: A strong intuition is much more powerful than a weak test
    • “This, to me, is one the great neglected ideas in medicine, perhaps one of the greatest neglected ideas in the world” – Siddhartha Mukherjee
  • Siddhartha presents an example:
    • Say someone flips a coin 20 times, and it comes up tails on each flip
    • Two people, a mathematician and a child, are tasked with predicting the result of the 21st coin flip
      • The mathematician says there’s a 50% chance it will come up tails, and a 50% chance it comes p heads
      • The child, though, realizes that the coin must be rigged
    • Going further:
      • The mathematician thinks of the world as having no history
      • But the child realizes that everything has priors, and you need to understand them before you understand the posteriors 
  • Siddhartha adds:
    • Most of the time, we’re living our lives like the child, always thinking of prior antecedents when pondering life’s questions
    • “You can only interpret a test, in the light of what that test has predicted in the past… The past performance of a test tells you something, but not everything, about the future performance of a test.”Siddhartha Mukherjee
      • “The past is a guide to the future… And this applies to medicine, although it’s a forgotten rule in medicine.”

Rapamycin in Cancer Treatment | Episode #16

This clip is from Peter’s interview with Matt Kaeberlein, Ph.D.

  • If you take a patient with cancer and inhibit mTOR with rapamycin, is it helpful? Or perhaps not help because the tumor has already evolved so much?
    • Rapamycin (a drug) acts on a protein called mTOR (it inhibits its function)
    • “For most cancers, once it’s reached the point of diagnosis, rapamycin is disappointing in its effectiveness” Matt Kaeberlein
      • Why? – As part of the growth progression, most cancers evolve to ignore the signal of decreased mTOR activity
  • The Immune System & Rapamycin
    • “The effects of rapamycin on the immune system could have beneficial effects toward cancer, or detrimental effects”Matt Kaeberlein
      • “We know that immune surveillance is probably THE most important anti-cancer mechanism”
        • Immune function goes down with age, hence why most cancers are age-related
        • If you can boost immune function with rapamycin, and enhance immune surveillance, it’ll have a potent anti-cancer mechanism (this is why in mouse studies, cancers are pushed back during aging with rapamycin supplementation)
      • But… if the dose of rapamycin is high enough, that could inhibit immune function (and thus promote cancer growth)
        • In one study, Matt and his team gave mice a daily high dose of rapamycin (8 mg/kg of body weight) for three months
          • Male mice lived 60% longer post-treatment and got less cancer
          • Female mice showed no difference in lifespan compared to a control group. But, most female mice dosed with high-dose rapamycin ended up dying from aggressive hematopoietic cancers
            • This might indicate female mice are more sensitive to rapamycin than male mice (meaning that they either don’t clear the drug as quickly, or rapamycin has a more significant mTOR inhibitory effect)
            • THAT SAID – in lower dose rapamycin mouse studies, there’s a more significant lifespan benefit in females (compared to males)
  • Give the above:
    • “I think that females, for whatever reason, at a given concentration of rapamycin, are more affected by that amount of the drug”Matt Kaeberlein

A Primer on NAD+/NADH, Its Effect on Lifespan/Healthspan, and a Review of Supplements | Episode #15

This clip comes from Peter’s interview with Dr. Rhonda Patrick. Check out the Podcast Notes.

  • NAD+ is an important co-factor for mitochondria to make energy through the electron transport chain
    • As you age, your NAD+ levels decline (the ratio of NADH to NAD+ shifts)
      • As background: Mitochondria make NADH which is converted to NAD+ to generate energy
  • There are quite a few NAD+ precursor supplements (like NR, which stands for nicotinamide riboside) one can take to boost their NAD+ levels and improve healthspan
    • For us at Podcast Notes, when it comes to a brand of NR, we can’t recommend Elysium Basis enough (use the code “podcast45” at checkout to receive $45 off a semi/annual subscription). We, Matt and Yoni, have been researching the company and trying Basis out for the past 3 months. Basis is a proprietary formulation of crystalline NR and pterostilbene that supports cellular health by increasing and sustaining NAD+
  • PARP, an important enzyme for DNA repair, needs NAD+ for fuel
    • As we get older, we have more DNA damage, and PARP is activated more frequently to repair this DNA, thus using up our free NAD+
  • You can increase NAD+ levels naturally by fasting
    • In the presence of energy (glucose) you convert NAD+ into NADH; in the absence of energy, NAD+ starts to build-up

Screening for Prostate Cancer | Episode #14

This clip is from Peter’s interview with Ted Schaeffer, MD

Setting the Stage

  • “Pretty much every guy is going to die with prostate cancer. But fortunately, most men won’t die from prostate cancer.”Peter Attia

Prostate Anatomy

  • The prostate contains the urethra, the tube through which both semen and urine pass
    • Various tubes pass off from the urethra – think of them as going to different “neighborhoods”
      • Within the neighborhoods, tubes come out at various “houses” (equating to prostate epithelial cells, which make components of the semen)
        • Semen gives nutrients to the sperm while it’s trying to fertilize an egg

What is PSA (Prostate-Specific Antigen)?

  • It’s a protein made by the prostate to liquefy semen 
    • There are ~100 million PSAs per milliliter of semen
  • A normal PSA level is-age adjusted:
    • For a 40-year old, it’s ~0.5-0.6 ng/ml
    • For a 50-year old, it’s ~1 ng/ml

Screening for Prostate Cancer

  • By checking the levels of PSA in the blood, you can screen for prostate cancer
    • As background:
      • As the prostate increases in size with age, some of the “pipes”/tubes (like the urethra) start leaking PSA into the blood
      • A prostate infection (or cancer) can also cause PSA to leak into the blood
  • No PSA number means you 100% don’t have cancer
    • “But there is a proportional rise in cancer detection with rising PSA numbers” – Ted Schaeffer
      • If you’re young, and your PSA is >2.5 ng/ml, that’s considered to be abnormal

What about ‘percentage of free PSA’ ( %fPSA) measurements?

  • This is a way to measure how much PSA is produced from benign vs. cancer cells
  • Here’s an example to aid in understanding:
    • If two guys have a PSA of 4 ng/ml, and one of them has a free PSA of 1 ng/ml (25% free), while the other guy has a free PSA of 3 ng/ml (75% free) – the former has a higher risk of prostate cancer
  • “A high percent free PSA is associated with a big prostate and less of a chance of prostate cancer. A low percent free PSA is associated with a higher likelihood that the PSA is produced from a gland with prostate cancer in it.”Ted Schaeffer

Insights About Berberine | Episode #13

  • What is berberine?
    • It’s a plant-derived extract
  • What does it do?
    • It’s a “weak” AMPK (AMP-activated protein kinase) activator when taken at a dose of 500-1000 mg 2x a day)
      • In this way, it’s similar to metformin (a drug given to type 2 diabetics to lower their blood glucose levels)
        • “It’s a poor man’s version of metformin” – Peter Attia
        • “I prefer just to use metformin. If we’re going to go down that path, let’s do it with potent drugs that we understand, that are consistent from batch to batch, and that have a much higher oversight of regulation.” – Peter Attia
      • Berberine acts by decreasing hepatic glucose output (upregulating AMPK tells the liver to make less glucose)
  • It’s a “weak” inhibitor of  PCSK9 (a protein that degrades LDL receptors)
    • But… it tends to only work in a subset of people who over-express PCSK9 (and thus have a higher level LDL particle number and LDL cholesterol)
      • So, for these people, supplementing with berberine might lower their LDL cholesterol

Rapamycin’s Effect on Cancer, Cardiovascular Disease, and Neurogenesis | Episode #12

This Qualy episode is from Peter’s interview with Dr. David Sabatini (Podcast Notes)

  • When we think about the life-extending properties of rapamycin, do we believe that it’s a result of delaying the clinical onset of disease and/or delaying the demise of the animal once it has the disease?
    • As an FYI, cancer spends 70-80% of the time undetectable – it becomes detectable only at the end
    • We don’t know if rapamycin is doing anything to prevent the development of cancer
    • In general, rapamycin is not a cytotoxic agent – it won’t kill a cancer cell
    • David’s bet would be that you’re not going to cure cancer if you’ve already got it, but you might slow its growth
  • How does rapamycin affect TOR in the brain with respect to neurodegeneration?
    • Some quick background:
    • Autophagy is really important in the brain (the recycling of damaged cellular components)
    • You need mTORC1 activity to maintain healthy neuron synapses, but you need to be able to modulate (inhibit) mTORC1 to have some level of autophagy to keep the system healthy
      • But we don’t know what modulates mTORC1 in the brain
        • It’s not nutrients like in muscle tissue, because of how much your brain prioritizes nutrients over other tissues in the body
        • The body protects the brain from a nutrient point of view

What are Peter’s thoughts on fasting and ketosis for females? | Episode #11

  • “I can’t make a very compelling case for nutritional ketosis if a female is trying to get pregnant” – Peter Attia
    • Digging deeper, the higher the ketone levels throughout human evolution, the more likely we were separated from food
      • The more likely we were separated from food, the less genetic pressure we would have had to reproduce
    • In a calorie-restricted state, when ketones are elevated, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are suppressed in females
      • Corollary, men’s testosterone levels are unaffected when in a state of ketosis – this makes sense evolutionarily, as it would help them to find food
    • That said, it’s certainly possible for a female to get pregnant while following a ketogenic diet, but it’s probably not optimal
  • “Should a female be in ketosis during pregnancy? The answer is I simply don’t know the answer.” – Peter Attia
  • In a similar light, Peter doesn’t think ketosis is the best nutrition strategy for kids unless they get frequent seizures
    • A far better approach (perhaps across the board) – don’t eat junk food, sugar, or highly-refined carbs
  • But, if a female has gestational diabetes, this question becomes even tougher to answer, as ketosis can be a useful tool for treatment
    • Gestational diabetes isn’t = type 2 diabetes, but they’re similar
  • At the end of the day, context matters
    • If a female’s a type 2 diabetic, perhaps following a ketogenic diet might actually improve her fertility by reducing overall levels of inflammation

Finding Meaning in Struggle and Why We Are Less Happy Than Ever (David Foster Wallace) | Episode #10

  • Peter is a massive fan of David Foster Wallace, particularly his famous commencement speech (which he tries to relisten to every month or so)
    • “I’ve been asked before, ‘If you could bring anyone back from the dead, who would it be?’ I think it’d be him. If I could go back in time and spend a day with anybody, it’d probably be with David Foster Wallace.” Peter Attia
  • In the commencement speech, David discusses how we all worship something: whether money, power, your body/physical allure, etc.
    • “He almost makes the case that at least if you pick a God to worship, the harm to you might be less. If it’s money you worship, you’ll never have enough. If it’s power you worship, you’ll never feel strong enough. If it’s intellect you worship, you’ll always feel like a fraud.” – Peter Attia
      • People who place their self-worth in their intellect continuously have feelings of self-doubt
    • Sadly, David ended up taking his own life by suicide 3 years after he gave the talk
  • Related – check out David Foster Wallace’s interview with Terry Gross in 1997
    • David is asked about his novel, Infinite Jest, and how he thinks about pleasure:
      • “A lot of the impetus for writing Infinite Jest was just the fact that I was about 30, and I had a lot of friends who were about 30, and we’d all been grotesquely over-educated our whole lives, had better healthcare and more money than our parents did, and we were all extraordinarily sad. I think it has something to do with being raised in an era where a successful life is making a lot of money, having an attractive spouse, or getting famous in some way, allowing you to experience as much pleasure as possible. This ends up being empty and low-calorie… Believe it or not, this came as an epiphany at age 30, sitting around talking about why on earth we were so miserable when we’d been so lucky.” 
      • “I have a very weird and amateur sense than an enormous part of my generation, and the generation right after mine is an extremely sad and lost generation. When you think about the material comforts and political freedoms we enjoy, it’s just strange.”

How silent bravado and incessant striving can lead to a functional (and actual) death, and why Paul is critical of the current state of psychiatry | Episode #9

  • Hard times:
    • Paul’s brother died by suicide
    • A year later, one of Paul’s close friends also died in a “reckless” manner
  • Paul adds – “I saw this common root in those two deaths. They confused me and made me feel very helpless, vulnerable, wanting to be able to understand better, and wanting to fight against this thing that made it so hard for people to get help.”
    • Paul’s brother and his friend had struggles, but there just wasn’t an accessible venue for getting adequate help
      • “That silent struggle became very real to me. That leads to death, not all the time, but way more often than even is remotely acceptable.”
  • “The deaths that we see in front of us are viscerally moving hallmarks of what is so pervasive in our society. The way our society is structured really beckons us to death in life… to lose touch with the basics of our own value system. This incessant striving, not incessant striving to achieve, although we may see it that way, but incessant striving to not pause and not feel our vulnerabilities.” 
  • On the field of psychiatry:
    • “I’m not a very positive or hopeful person about the state of the field I’m in which doesn’t broadly enough train people in brain biology – not just in the use of medicines, but in what those medicines actually do.”
      • Specifically: the actual effect of those medicines in the brain and their cascade of effects – this part of the field often gets ignored
    • There’s been a debate on whether or not psychiatrists should still be trained in psychotherapy – YES
      • “I think it’s crazy to consider having people that are giving medicines to other people that aren’t thinking about what it’s like to really understand someone”
  • It’s so important to lend light to the things that influence and motivate us that are in the unconscious
    • Paul terms this – “The gigantic part of the iceberg that’s underneath the water but is most deterministic of our behaviors, choices, and feelings”

Fasting as a Powerful Drug in the Toolbox of Medicine | Episode #8

  • Does Peter find protein catabolism (muscle breakdown) is effected during a prolonged fast?
    • It’s not something he specifically measures (besides taking a picture of himself in the mirror)
      • “I’d love to do a 7-day fast in an environment where I could have a muscle biopsy and a fat biopsy every single day”
  • “I think that fasting is such a powerful tool; I think of it as one of the most powerful drugs we have in the entire toolbox of medicine.”
    • “But I’m frustrated I don’t know the dose of the drug to give” 
      • Why? – We can’t measure autophagy so we’re completely guessing at the best fasting protocol
      • Imagine you’re some doctor walking around, someone hands you a bottle of pills and says, “This is the single most valuable drug we have.”
        • You ask him, “How much do I give?” and he has no idea!
      • “Right in the middle of our face is this awesome thing we really don’t understand enough about”
  • Peter identifies eating one-meal-a-day as time-restricted feeding, not intermittent fasting
  • “I always feel like the inflammation dissipates from my body when I’m fasting”
  • During his fasts, Peter will occasionally measure urinary cortisol levels (he hasn’t seen much of a change)
  • “If there’s one thing about fasting that sucks, it’s that my body odor becomes unbearable… It’s perspiration; it’s not that I’m perspiring much, it just stinks.”

What is Peter looking to achieve with his blood glucose monitor? | Episode #7

  • Peter wears a Dexcom G6 continuous glucose monitor (CGM)
    • Check out the Podcast Notes Dexcoms CEO Kevin Sayer’s appearance on Peter’s podcast
    • “The G6, along with the Oura Ring, and I’ve worn every wearable that there is… they’re the only two that seem sticky enough that I can’t stop wearing them”
  • A CGM allows you to see your blood glucose levels in real-time
  • “It’s a great way for me to control my behavior… There is no more powerful behavioral tool for me than my CGM.”
    • How so? – It makes Peter WAY less likely to eat something like a cookie because he’ll have to stare his CGM data in the face afterward
  • “It’s allowed me to very eloquently calibrate how to tether activity levels, nutrient deprivation, the consumption of treats, and minimize the damage”
    • For example – Fasting all day and also getting a workout in will drastically reduce the blood glucose spike Peter experiences after consuming some form of carbohydrate
  • CGMs are a medical device, typically reserved for diabetics – they allow them to accurately dose their insulin
    • It’s not openly available for consumers – you need a doctor’s prescription
      • That being said – “Doctors write prescriptions for way crazier things than CGMs. You got doc’s writing prescriptions for pain meds and every hormone under the sun. I don’t think it’s a big stretch to say, ‘Doc, I need a CGM.’”
  • A good proxy for having a low level of insulin = having a low level of glucose AND a low level of glucose variability
    • A CGM will let you see both

The ABCs of Alzheimer’s Prevention | Episode #6

  • The ABC’s of Alzheimer’s Prevention
    • A: Anthropometrics – This includes body fat, lean mass, and visceral fat
    • B: Biomarkers – Specifically cholesterol markers
      • The basics –  LDL, HDL, triglycerides
      • The extensive – ApoB, particle subtype, LDL-p
      • Other biomarkers Richard focuses on – markers of inflammation (hsCRP, fibrinogen, lplA-2, myeloperoxidase)
        • “HsCRP is probably;y the most informative”
      • Peter adds – “You do more detailed lipid profiling than most cardiologists do”
    • C: Cognitive Function
      • As mentioned in these Podcast Notes, cognitive activity wards off cognitive decline
      • Exercise is the most important thing you can do to perverse brain health
      • Supplementing with EPA and DHA is thought to reduce risk of Alzheimer’s
  • Alzheimer’s Research
    • “Alzheimer’s prevention is so underfunded. It is an embarrassment to this disease state.”
    • The success rate of pharmacology for Alzheimer’s disease is 0.4%
      • 99.6% of drugs brought forth to treat Alzheimer’s disease are failures
      • For this reason, it’s much more effective to fund Alzheimer’s prevention research rather than Alzheimer’s disease treatment research
        • At this time, of every $100 allotted to Alzheimer’s disease research, $99.90 are going to Alzheimer’s disease treatment

A Unifying Theory of Aging | Episode #5

  • The Central Tenants of Aging (AKA what goes bonkers when you get older)
    • Epigenetic changes
    • Changes in cell communication
    • Inflammation
    • The build-up of senescent cells
    • Protein misfolding
    • Telomere loss
    • Genomic instability
    • Metabolic changes
    • Adverse responses to amino acids and other nutrient inputs
  • The Unifying Theory of Aging
    • Although the above doesn’t seem all that related, David believes he’s discovered an underlying factor. He explains:
      • The genome is digital information (it can easily be stored and read)
      • As it turns out, the genome is very much intact within older people/animals
      • People inherent epigenetic information from their parents (AKA the pattern of gene expression AKA the pattern to which certain genes are turned on/off)
        • This information acts in multiple dimensions: it adapts to what we eat/drink, if we exercise, and how much sleep we get (genes are being turned on/off ALL the time)
          • David refers to the above as “analog information”
    • “That’s the problem with aging: we don’t lose the digital information… the compact disc of our lives is still intact when we’re old, but it’s as if we have a scratched CD and cells don’t read the right genes at the right time.” 
      • In simple terms – Genes are being turned on/off when they shouldn’t be
        • Because of this, cells start losing their functionality and basically their identity (so you’d get a liver cell behaving as a neural cell)
  • How confident is David that he’ll see a step function change in human longevity during his lifetime?
    • “There really hasn’t been a step function change in human longevity since the introduction of sanitation” – Peter
      • Perhaps there was also one with the introduction of antibiotics and vaccinations
    • “I’m getting more and more confident” – David

How much does cognitive activity ward off cognitive decline? | Episode #4

  • Early-life risk factors for Alzheimer’s disease are different than those of mid-life and late-life
    • “Early-life risk can be mitigated most by long-term educational attainment”
      • In simple terms – people who go on to obtain secondary and tertiary education have a lower risk of Alzheimer’s disease 
  • Early- and mid-life musical experience can allow one to build up greater cognitive reserves so that if they do get Alzheimer’s, they’re much more resilient 
    • “I think music is a great way to recruit different parts of the brain to work together and the stronger those pathways get, the better the person does”
  • Cognitive activity allows one to build up “backup pathways” which help slow the speed of cognitive decline if they go on to get Alzheimer’s disease
    • “People with high cognitive reserves (cognitive backup systems) are more resistant to the effects of amyloid beta”
      • The build-up of amyloid beta is thought to be one of the contributing factors of Alzheimer’s disease

The Importance of Exercise for Brain Health | Episode #3

  • “That’s another change in my belief system today vs. 5 or 6 years ago… 5 or 6 I didn’t think exercise was that important for longevity” – Peter
  • It seems to be that exercise is the single most important thing you can do to preserve brain health
    • “If you’re not active every day, we have to change that”
  • Rhonda finds exercise very much improves her anxiety levels and as well as her decision-making ability
    • “If I have something that’s bothering me or giving me anxiety or I have to make a really important decision, going for a long run really helps me”
  • There have been multiple studies showing aerobic exercise helps with executive function and long-term planning
  • Strength training has been shown to prevent muscle atrophy (the wasting away of muscle), and lower the incidence of cancer
  • VO2 max is the ability of the body to transport oxygen during exercise – this improves with high-intensity interval training (HIIT
    • VO2 max declines about 10% per decade (muscle mass declines at the same rate)
      • Rhonda recalls a study showing that 24 sessions of high-intensity interval training (45 minutes total including both a 5-minute warm up and cool down, going at 70% max capacity with 1-minute breaks) improved VO2 max by 12%
    • PVO2 max is important for cyclist – this is the power output at VO2 max
    • VVO2 max is important for runners – this is the velocity you carry at VO2 max
    • The VO2 max of a professional cyclist is 80-90 mg/ml/kg
  • To sum up – “If you can maintain muscle mass and you can maintain peak aerobic performance, it doesn’t even matter at that point if you’re living longer, you’re clearly living better”

What are the best lab tests to request specifically for longevity? | Episode #2


  • With a blood test, Peter looks for the following in regards to longevity:
    • What is this person’s risk of atherosclerotic disease or stroke? (this is largely driven by – lipoprotiens, inflammation, and endothelial dysfunction)
      • With a blood test, in the lipoprotein department, you can measure – Lp(a), LDL, LDL particle number, cholesterol, and vLDL
        • Note – The higher your Lp(a) – the greater your chance of cardiovascular mortality
      • On the inflammation side, you can measure specific and non-specific markers of inflammation (specific in regards to where the inflammation is coming from)
        • Non-specific – Fibrinogen, C-reactive protein (CRP)
        • Specific – Oxidized LDL (Ox-LDL), Lp-PLA2, Oxidized Phospholipid (Ox-PL)
      • For endothelial health, a blood test allows one to measure – insulin, homocysteine, ADMA and SDMA (both inhibitors of nitric oxide synthase)
      • In general – the younger you are, the more a blood tells you about your risk of cardiovascular diseaser 
    • What is this person’s risk of cancer?
      • “This is where blood gives us the least insight”
      • Cancer really comes down to understanding inflammation and metabolic health
        • One key factor here – minimizing hyperinsulinemia 
    • What is this person’s risk of neurodegenerative disease?
      • Alzheimer’s Disease is closely related to cardiovascular disease in terms of risk stratification 
        • Your ApoE genotype (measured with a DNA analysis) immediately qualifies you as low, medium, or high risk
  • What about fasting blood glucose?
    • If you’re fasting blood glucose level is 150 mg/dL – there’s clearly a problem
    • “Now that I wear a continuous glucose monitor and I know my glucose 24/7, the difference between a fasting glucose of 90 and 105 in the morning is much more a function of my cortisol level than it is anything to do with insulin sensitivity”
      • In simple terms – stress and a lack of sleep can raise your fasting blood glucose

What are Peter’s thoughts on alcohol consumption and health? | Episode #1

Key Takeaways

  • “I’m not convinced there’s a single benefit to ethanol in the human body”
  • “I’m not trying to say a glass of red wine a day is harmful. I’m saying it’s not benefiting your health.”
  • The effect of alcohol on sleep:
    • Resting heart rate is increased
    • It takes longer to reach your lowest resting heart rate during the night
    • Heart rate variability drops
    • REM cycles are compressed

Peter’s Thoughts on the Consumption of Alcohol

  • Alcohol is a toxin, but the dose makes the poison
    • There’s a probability distribution that drives the impact of any toxin on a population – some will be largely unimpacted, others will be the opposite
  • “I’m not convinced there’s a single benefit to ethanol in the human body”
    • An oz. of distilled spirit, a 4 oz. glass of wine, and a beer are all about 15 grams of ethanol
  • Alcohol (ethanol) affects both the liver and brain
    • The effect on the brain = the buzz (the central nervous system depression with some euphoria)
    • The effect on the liver is highly similar to that of sugar/fructose
  • Peter has noticed that when he drinks, he loosens the reigns on what he eats

Peter’s Drinking Rules

  • As a general rule, don’t drink
    • Never drink on airplanes
  • If you do drink, drink good alcohol

Peter’s Favorites

  • Wine – Clio
  • Tequila – Clase Azul Reposado (neat)
    • 1942 is also pretty good
  • Beer – he’s not willing to say because it’s too hard to find

Isn’t red wine associated with longevity?

  • “I’m not trying to say a glass of red wine a day is harmful. I’m saying it’s not benefiting your health.”
  • Red wine does have small amounts of resveratrol and a while back, David Sinclair‘s lab showed that resveratrol (in high concentrations) enhances longevity
    • There are two issues with this:
      • Peter doesn’t necessarily believe the data – it hasn’t been reproduced
      • The amount of resveratrol in red wine is too minute
  • But you have to consider, if a little red wine helps you unwind perhaps there’s a net benefit
    • It might lower your cortisol/distress

The Effect of Alcohol on Sleep

  • Peter has noticed:
    • 1 drink in the evening doesn’t impact his sleep
    • 2 or more drinks absolutely does “and does so in a profound way”
      • His resting heart rate will increase by 10+ beats
      • It’ll take longer for him to reach his resting heart rate (you ideally want your resting heart rate to be achieved within the first third of the night)
      • His heart rate variability drops
      • His REM cycles are compressed
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