Enhancing Your Healthspan to Live Well for 100+ Years with Dr. Peter Attia – The Doctor’s Farmacy with Mark Hyman, MD

Check out The Doctor’s Farmacy Episode Page & Show Notes

Key Takeaways

  • You can’t exercise your way out of a bad diet (it becomes near impossible when your sleep is out of wack)
    • To add – If you sleep 4 hours/night, you’re going to have a BRUTAL time losing weight
  • “I now think the ketogenic diet is a great diet for steady state activity, below threshold”
    • Threshold = the maximum pace you can pace you can sustain for an hour on a bike
    • Anything above this, you need the glycogen and the ketogenic diet just isn’t optimal
  • Normal cholesterol panels from your doctor don’t give you the full picture. Know these two things:
    • 1) The number of LDL particles is much more predictive than LDL cholesterol concentration at predicting your risk of heart disease
    • 2) Measuring LDL cholesterol can under represent the number of LDL particles
  • The 5 Tools of Optimal Health
    • Good nutrition
      • (Or lack of food – “Fasting is the single most important tool we have in our our nutritional toolkit“)
    • Drugs
    • Sleep
    • Exercise
    • Managing distress
      • Our ancestors had more acute stress and less chronic stress. Today, it’s flipped. This is problematic because the long tail effect of high cortisol (the stress hormone) is quite detrimental.
  • The later you consumer food, the worse (all things equal)
    • “If I could be czar of the world for the day and change one thing, on that list would be completely changing the social structure around meals and making breakfast the dominant meal”
  • Instead of trying to live as long as you can, aim to be the most kick ass 100-year-old possible
  • Two easy tools to help escape the pull of the standard American diet
    • Dietary restriction (restricting something like carbs)
      • “Any form of dietary restriction is an improvement over the SAD”
    • Time-restricted eating (restricting when you eat)
    • (the above can also be combined for a potent response)
  • On prolonged fasts:
    • “In my opinion, 3 days is the minimum effective dose, 5 days is the sweet spot, and 7 days is also with benefit and totally doable”
  • Change your nutritional environment so you don’t have to rely on willpower
    • In a moment of weakness, make the worse thing you could possibly eat be a piece of dark chocolate

Books Mentioned

Intro

Peter’s Story

  • Peter used to do some pretty intense swimming
    • He even attempted a swim from Los Angeles to Catalina Island
  • He’d been training his whole life (even up to 4+ hours/day), but a combination of sleep deprivation and a shitty diet actually led him to be pre-diabetic ~10 years or so ago
    • During his med school residency, Peter estimates he was only sleeping ~28 hours/week (~4 hours/night)
    • This kind of goes to show – you can’t exercise your way out of a bad diet (it becomes near impossible when your sleep is out of wack and your cortisol is high)
    • Around this time, Peter remembers drinking 4 1-liter bottles of Gatorade/Powerade per day

The Ketogenic Diet

  • Peter eventually made his way to the ketogenic diet – and boy did he dive in
  • One of the best books on a low-carb diet/ketogneic diet out there – The Art of Low Carbohydrate Living (as well as The Art and Science of Low Carbohydrate Performance)
    • “I still think The Art and Science of Low Carbohydrate Living is one of the best resources on this subject out there”
  • Who is the ketogenic diet good for?
    • “I now think the ketogenic diet is a great diet for steady state activity, below threshold”
      • Threshold = the maximum pace you can pace you can sustain for an hour on a bike
        • Related – “The amount of power I used to be able to put out for an hour [on a bike], I couldn’t put out today for 6 minutes”
        • Anything above this, you need the glycogen and the ketogenic diet just isn’t optimal
  • Peter now does a week of keto prior to, and after, his quarterly 7-day fasts

Let’s get some definitions out of the way…

  • Cholesterol – cargo carried by lipoproteins
  • Lipoproteins – spherical macro molecules, composed of cholesterol and other lipids (like triglyceride and phospholipids), and most importantly a variety of different proteins which form a capsule around the lipid cargo
    • Cholesterol is hydrophobic, so it repels water
    • To move cholesterol through the blood stream, you need to package it in something hydrophilic (the lipoprotein)
  • When cholesterol is on an HDL (high density lipoprotein – a form of lipoprotein) particle – we call it HDL cholesterol (HDL-C)
  • When cholesterol is on an LDL (low density lipoprotein – another form of lipoprotein) particle – we call it LDL cholesterol (LDL-C)
    • So the LDL cholesterol number in your blood is the amount of cholesterol you have on all of your circulating LDL particles
      • LDL particles (LDL-P) are most strongly correlated to cardiovascular disease risk
        • LDL cholesterol is just cargo on an LDL particle – the amount of cholesterol on an LDL particle can vary
          • The LDL particles that have less cholesterol are smaller and more dense, the ones that have more cholesterol are larger and less dense
        • The LDL particle causes the plaque to develop within the arteries, not the cholesterol
  • Your LDL particle number is more indicative of cardiovascular disease risk than your LDL cholesterol number
  • The key protein that holds a lipoprotein particle together – ApoB 100
    • ApoB 100 is  often used as a surrogate to measuring LDL particle number
      • There is only one ApoB per LDL particle
      • ApoB is found on other particles, but primarily on LDL
      • Measuring LDL cholesterol can under represent the number of LDL particles, compared with the measurement of ApoB

Cholesterol – Part 1

  • Check out Peter’s blog series on cholesterol – it’s quite eye-opening
  • One of Peter’s earliest podcasts was an interview with Dr. Ron Krauss, an expert on cholesterol – check out the Podcast Notes
    • Peter also recorded a 5-part series with Dr. Tom Dayspring, which you might also find helpful for understanding cholesterol
  • “I think it’s safe to say I don’t even pay attention to HDL anymore”
    • “Everyone talks about HDL as the ‘good cholesterol’ – a term that makes me want to kill kittens”
      • The truth – a high HDL cholesterol is relative (it’s more of an “association that’s along for the ride”)
    • What really matters – the function of the HDL (which we can’t measure)
      • AKA the ability of an HDL particle to delipidate
    • For example – many people have high HDL cholesterol, yet have cardiovascular disease because their high HDL is the result of their HDL not being able to correctly delipidate
  • The action item:
    • Find a doctor who can order some advance cholesterol tests (particle sizes/numbers etc.)

The 4 Drivers of Cardiovascular Disease

  • Realize it’s very hard to gauge, from a blood test alone, your risk for cardiovascular disease, of which there are 4 drivers (outside of smoking and hypertension)
    • Lipoproteins
      • As mentioned above, these particles carry the sterol into the sub-endothelial space (AKA it’s the carrier for the cholesterol particle that gets into your arteries)
        • And if the cholesterol stays present, over time it oxides which kicks off an inflammatory pathway…. leading to heart disease
      • Smaller LDL particles (with less cholesterol) are more dangerous 
        • People with smaller LDL particles are at a greater risk for heart disease
    • Metabolism
      • AKA your insulin sensitivity, average blood glucose level, triglyceride count, etc.
      • Remember – “Type 2 diabetes is a disorder of carbohydrate intolerance”
        • Thus, you’re not able to metabolize whatever carbohydrate load you have, leading to high average blood glucose levels (HA1C is the blood marker for long-term average blood glucose)
          • Once your HA1C reaches 6.5% (which corresponds to an approximate blood glucose average of 130-140 mg/dL), you have type 2 diabetes
        • Metformin is a type 2 diabetes drug which can lower both glucose and insulin
          • The best way to mimic metformin – good nutrition
    • Inflammation
      • Not discussed
    • Endothelial function
      • Not discussed

Why do smoking and high blood pressure raise your risk of cardiovascular disease?

  • They reduce the efficacy of the endothellium (a single cell layer that lines your arteries), thus making it easier for something to cross the barrier
    • Note that many particles cross this barrier, but they come right back out – it’s not the crossing of the barrier that’s problematic, it’s the retention of a particle getting stuck in there (and subsequent oxidation over time which creates the inflammatory response)

Cholesterol & Cardiovascular Disease – Part 2

  • Cardiovascular disease is the leading cause of death in the U.S.
  • Atherosclerosis is another name for the inflammatory process kicked off within the arteries after a LDL particle carrying cholesterol enters the sub-endothelial space, gets stuck, and oxidizes 
    • 8-12% of people have a genetic disposition to atherosclerosis because they have elevated Lp(a) levels (a Lp(a) particle is just a LDL particle with an Apo(a) particle attached to it)
  • The most reliable data shows the number of LDL particles is much more predictive than LDL cholesterol concentration at predicting your risk of heart disease
  • EVERY cell in the body makes cholesterol
    • If you don’t have cholesterol within a cell – the cell dies
  • “If you’re playing the long game, and the long game is delaying atherosclerosis as long a possible, I’m just not sure on what planet you want to walk around with an LDL particle number through the roof”
    • Atherosclerosis is INEVITABLE if you live long enough
  • If you’re a non-smoker in the developed world, it’s very likely you’ll die from atherosclerosis, cancer, or an accident

The 5 Health Tools

  • Good Nutrition
    • “If there was a drug that could cure high blood pressure, cure diabetes, cure heart failure, cure kidney failure, and cure liver failure I’d buy stock right away. But there is. It’s called food. But it’s not patentable.” – Mark
    • OR a lack of food
      • “Fasting is the single most important tool we have in our our nutritional toolkit”
    • When you eat a diet high in processed carbohydrates, your insulin levels will always be high
      • Insulin does 2 things:
        • Promote lipogenesis (making a fat cell fatter)
        • Prevents your fat cell from releasing fat for fuel (lipolysis)
      • In general – a low-carb diet will always make it easier to lose weight
  • Drugs
    • Ex. metfomin, a common drug used to treat type 2 diabetes
  • Sleep
  • Exercise
  • Managing distress
    • For more on this topic, check out the Podcast Notes from Peter’s interview with Dr. Robert Sapolsky    
    • Our ancestors had more acute stress and less chronic stress
      • Today, it’s flipped 
      • This is problematic because the long tail effect of high cortisol (the stress hormone) is quite detrimental       
    • Cortisol does 2 things
      • It liberates fat from fat cells and enhances lipolysis (think – if you’re being attacked by a tiger, you need a ton of fatty acids around for energy)       
        • (so in this sense it’s catabolic to a fat cell – it breaks it down)
      • BUT, cortisol is also anabolic to a fat cell (it puts fat in)
        • People with disordered high levels of cortisol accumulate large levels of fat

Is saturated fat bad?

  • It depends 
    • Mark had noticed that if he eats more saturated fat his lipid profile gets worse
  • It comes down to the question – “Are lipoproteins necessary, but not sufficient, for atherosclerosis?”
    • (This is a similar question to – “Is an ApoE gene necessary but not sufficient, necessary and sufficient, or neither necessary nor sufficient for somebody to get Alzheimer’s disease?”)
    • “I think the evidence with atherosclerosis and lipoproteins is as close to unambiguous as you can get in medicine and biology”
      • This means the lipoprotein is necessary but not a sufficient condition for atherosclerosis (you can’t get atherosclerosis if you don’t have the lipoprotein, but just because you have the lipoprotein doesn’t mean you’ll get atherosclerosis)
    • Similarly – smoking is neither necessary nor sufficient to get heart disease (but it’s still causal)
      • Also – Just because you smoke doesn’t mean you’ll get heart disease
  • So….
    • Many people who eat tons of saturated fat have high LDL cholesterol levels which is necessary, but not sufficient, for atherosclerosis

Methods of Treating High LDL Cholesterol

  • Every LDL particle is driven by the burden of transportation it needs to carry (the more triglyceride you have, the more LDL particles you need to carry them)
    • “If the LDL particle count is high and they also have higher triglyceride levels, those patients will respond well to nutritional therapy”
  • Statins reduce cholesterol synthesis (which as a side effect, cause the liver to upregulate LDL receptors, thus pulling more LDL particles out of circulation)
    • Statins inhibit an enzyme in the early part of the pathway necessary for making cholesterol
    • Note – ~10% of people report muscle pain when taking a statin
      • But there are so many statins out there one might try (CRESTOR, LIPITOR, LIVALO – which is less potent)
      • Peter’s go-to for his patients Pravastatin – it’s not very strong at all
  • Or you can attack cholesterol absorption (certain drugs block the absorption of cholesterol – like Zetia)
  • If someone has normal triglycerides, normal cholesterol synthesis, and normal cholesterol absorption, and they still have sky high cholesterol levels – it’s possible they have defective LDL receptors (which is largely genetic)
    • These patients might be a perfect candidate for a PCSK9 inhibitor (which also lowers Lp(a))

Naturally Occurring Compounds That Do Remarkable Things with Low Toxicity

  • “I don’t think it’s an accident that the 3 most impressive drugs in the toolkit of longevity are all natural occurring”
    • Statins
  • The toxicity of the above are all very low (and there’s probably a reason for this, as they all occur in nature)
  • Antibiotics also fit in this category

The Centenarian Olympics

  • How long does Peter hope to live?
    • “I just want to exceed what my genetic potential is.”
      • Peter estimated, genetically, he’s probably wired to make it to his 80s
  • Peter’s main health goal – be the most kick ass 100-year-old (Peter, 46 now, calls this “being in the Centenarian Olympics”)
    • Peter estimates, to do so, he needs to be able to:
      • Carry 4 bags of groceries up multiple flights of stairs
      • Get up off the floor using a single point of support (so many 100-year-olds can’t do this… or even get out of a chair)
      • Put a large (~30 lb.) bag in the overhead compartment of an airplane
      • Pull himself out of a swimming pool without stairs
  • What is Peter focusing on to do the above?
    • Stability (in addition to mobility)
      • “Stability is the thing that most of us have lost generally by the time we’re 5”
        • Once humans begin sitting, they lose the connection to their pelvic floor muscles – this causes all sorts of things to start going south
      • Peter is in the process of taking exercises from yoga, Pilates, dynamic neuromuscular stabilization and building a protocol for helping people regain their stability all over the body
    • Strength
    • Aerobic (mitochondrial efficiency)
    • Anaerobic (hard, short-term bursts)

Diet and Nutrition – Part 2

  • Peter does a 7-day water-only fast once per quarter, sandwiched by a week of the ketogenic diet on each side
  • “I think we can all agree, no matter what your dietary bent is, the standard American diet (SAD) is not a good diet”
  • There are two tools to help people escape the pull of the SAD:
    • Dietary restriction (restricting something like carbs)
      • “Any form of dietary restriction is an improvement over the SAD”
    • Time-restricted eating (restricting when you eat)
    • (the above can also be combined for a more potent response)
  • But on top of the above, you can also add in intermittent fasting (periodic prolonged fasts)
    • (Peter reserves the term “intermittent fasting” for fasts of 3 days or longer)
    • “In my opinion, 3 days is the minimum effective dose, 5 days is the sweet spot, and 7 days is also with benefit and totally doable”
    • You can either do a water-only fast or just restrict calories to very low levels (AKA a fasting mimicking diet)
  • At the time of this recording (7 PM), Peter hadn’t eaten yet
    • He’s noticed that when he time-restricts his eating late into the evening, his sleep suffers – he prefers to have a much earlier eating window

Peter’s Daily Routine

  • He *attempts* to wake up and meditates before doing anything else
  • Peter adds – “Whether it’s exercise, nutrition, meditation, or sleep – you HAVE to prioritize them”
    • “Everyone’s an asset allocator when it comes to a resource even more precious than money… time”
  • Peter aims for 8 hours in bed, every single night… no matter what (this usually translates to 7.5 hours of sleep)
  • “I actually really struggle with food. Left to my own vices, I could just eat nonstop junk food all day every day”
    • “The reason I don’t is not because I have some great discipline, it’s because I surround myself with good food choices. The worst thing I could eat in a moment of weakness is dark chocolate.”
    • The takeaway – change your environment so you don’t have to rely on willpower
  • “My whole life is basically one big hack that tries to make eating, sleeping, meditating, and doing all the other things that matter to me as frictionless as possible”
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