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.

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”
      • Purchase an Oura Ring using the above link for a $40 discount
  • 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

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  • 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

  • With the Oura Ring(purchase a ring using this link for a $40 discount), 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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