The Peter Attia Drive – Dr. Rhonda Patrick

Facebooktwitterredditmail

Key Takeaways
  • Data seems to suggest that, maybe the best thing to do is cycle high and low IGF-1 levels
  • Exercise is the single most important thing you can do to preserve brain health
  • Use the sauna
  • A small percentage of people have adverse effects on the ketogenic diet due to high saturated fat intake (raised LDL particle number, more inflammation, markers of cholesterol biosynthesis go up)
    • Be careful, and get your blood tested before deciding if the ketogenic diet is right for you
  • Refeeding after fasting, is just as important as the actual fasting
    • A prolonged fast causes organs to shrink (we don’t know how much of this is due to cells shrinking vs. apoptosis (cell death))
    • During the refeeding phase, the organs regrow with new/healthy cells
Intro
  • This is the first episode of Peter’s new podcast
  • Rhonda Patrick can be found at @foundmyfitness on Twitter
  • “In science, all facts have a half life, and our knowledge is constantly evolving” – Peter
    • “The more we learn, the less we know” – Peter
  • A marker of a thoughtful person – their beliefs are flexible
    • They’re able to acknowledge that what they once believed to be true, might no longer be so
What does Rhonda believe today, that she didn’t believe 4-5 years ago?
  • Rhonda used to believe that the best way to increase health span, was through caloric restriction 
    • When you calorie restrict, you see a major drop in insulin-like growth factor 1 (IGF-1)
      • However, periods of growth (or periods of higher IGF-1 levels) are important – if you’re constantly calorie restricting, you won’t have this
    • A recent study on lemurs, showed caloric restriction increased median and maximum life span, as well as delayed the onset of various degenerative diseases
      • However, there was a massive atrophy (gradual decline/wasting away) of grey brain matter, in regions of the brain that didn’t occur in control animals
        • So sometimes, some of the modalities we think are really good for increasing health span, have other effects
    • Periodic prolonged fasts, are a better way of regulating IGF-1 levels long term
  • Rhonda used to be skeptical of the ketogenic diet being good for long term health
    • More recent, long term studies in animals have changed her mind
    • She’s never done a ketogenic diet herself
The Ketogenic Diet
  • Check out these Podcast Notes for more on the ketogenic diet from Dr. Dom D’Agostino’s appearance on Joe Rogan
  • Peter has a similar story – he was on a ketogenic diet for 3 straight years, but prefers more of a time restricted eating based diet nowadays – he talks about his diet in these Podcast Notes from his appearance on Joe Rogan
    • On a ketogenic diet, he was eating 4500 calories a day
      • He ate 80 grams of carbs a day, and about 100-110 grams of protein, fat made up 90% of his total calories
      • The most efficient way to get that much fat – salad with lots of olive oil
        • The salads contained romaine lettuce, cucumbers, tomatoes, celery, and limited carrots due to their higher carb content
      • Macadamia nuts were also a staple, as well as lots of dairy (cheese, sour cream)
  • The big question remains, why are people losing weight on a ketogenic diet? – Is it because they’re eating less, or is it because they’re increasing fat oxidation (the burning of fat for fuel) which drives up energy expenditure?
    • Peter expects the answer is both – if you do the latter, the former should happen – “You’re eating less, because you’re eating yourself more”
  • Exogenous ketones
    • Rhonda has used exogenous ketones in the past, and has noticed a cognitive boost
      • They raise her focus and lower anxiety
      • She does prefer, however, to enter ketosis through periods of fasting
    • Rhonda has tried HVMN’s ketone ester
      • Her blood ketone levels went from 0.1 mmol to 4.5 mmol in 1 hour – she was eating her normal diet during this time (discussed below)
    • Ketone esters have been found to lower blood glucose levels
      • Peter has also experimented with Acrabose for lowering blood glucose
      • Before a very high carb meal, he’ll often take it to mitigate the negative effects
  • Rhonda finds it hard to go full time ketogenic, due to the many benefits of eating lots of plants/fibrous vegetables
    • Certain micronutrients have a higher density in plants – like folate, magnesium, vitamin k1
    • Fermentable fibers are also good for the gut, which helps regulate immune function
    • It is possible to get all these on a ketogenic diet, it’s just more difficult
  • It’s a question still, how much of the actual health benefits of a ketogenic diet, are due to low protein intake vs. the actual state of being in ketosis
  • IGF-1
    • Peter noticed his lowest IGF-1 levels were the lowest, in the years he was following a ketogenic diet
    • The major dietary regulators of the IGF-1 pathway are protein, essential amino acids, and insulin – on a ketogenic diet, you’re eating little to moderate protein
The Ketogenic diet, Saturated Fat, and Genetics
  • Check out Rhonda’s genetic tool, which pairs with the 23andMe genetic test
  • PPAR-alpha
    • Predominantly found in the liver – involved in fatty acid catabolism and in the production of ketone bodies
  • PPAR-gamma
    • Predominantly found in adipose tissue – involved in taking up free fatty acids into adipose tissue
  • Some people (Peter estimates 10-20% of people), do very badly on a ketogenic diet
    • Negative things that happen:
      • Their LDL particle numbers go up, despite the fact that their triglyceride levels go down
      • Levels of C-reactive protein (CRP) rise – this is a marker of inflammation
      • Markers of cholesterol biosynthesis go up – their bodies are making more cholesterol
      • Their phytosterols go up (which typically go down on a ketogenic diet)
        • Phytosterols are a group of naturally occurring compounds found in plant cell membranes.
        • Cholesterol is the sterol from an animal
        • Phytosterol is the cholesterol equivalent from a plant
        • Note from Podcast NotesThis must mean their body has a harder time clearing phytosterols?
    • Peter had one patient, whom this happened to, here’s what he did:
      • He cut his patient’s saturated fat intake to very low levels (20-25 grams a day)
        • 65% of his fat calories were being consumed from mono unsaturated fat (this is very hard to do, an easy way to get this much mono unsaturated fat is to consume lots of olive oil)
      • After 8-12 weeks, with the same macronutrient distribution (so the same overall levels of protein, carbs, and fat – just with different types of fat – much less saturated fat) – their LDL particle number dropped tremendously, inflammation dropped, and their sterol biomarkers returned to normal
  • People with certain SNPs (pronounced snips – these are basically single gene variants) on PPAR alpha and PPAR gamma, just don’t do well with saturated fat, like Peter’s patient
    • People with these SNPs, should have a higher ratio of poly and mono unsaturated fat to saturated fat inake, in order to lower their type 2 diabetes risk
    • If they consume too much saturated fat, they’ll see effects similar to what was observed with Peter’s patient
  • Why some people have trouble entering ketosis
    • From an evolutionary perspective, you should have been selected out really quickly if you can’t make ketones efficiently 
    • It’s not all about generating ketones, first you have to deplete your glycogen (stored liver glucose) – once our body depletes its stored glucose, then it starts running on ketones
Rhonda’s Diet
  • Rhonda does a time restricted eating based diet
  • She tries to fast for ~15 hours each day
    • Usually, depending on her activity levels, she can obtain a blood ketone level of 0.7-1.0 mmol using a Precision Xtra after 15 hours of fasting
    • Typically she only eats breakfast and an early dinner
  • What does she eat?
    • Salmon, salad, a sauteed vegetable in olive oil
    • Smoothies with blueberries, avacado, and kale
    • Some watermelon in the summer time
    • Nuts as a snack – usually walnuts, almonds, macadamia nuts, cashews, and pistachios
IGF-1
  • Humans that have gene polymorphisms, that raise  IGF-1 levels, have a higher incidence of cancer, and vice versa
  • Check out the images below (image credit) relating all cause mortality, cancer mortality, and cardiovascular disease mortality with serum IGF-1 levels
    •  
    • It seems like only very high levels of IGF-1 are problematic
    • Most of the uptick in mortality above the 70th percentile of serum IGF-1 levels, is driven by cancer
    • Maybe the best thing to do is cycle high and low IGF-1 levels
  • The older you get, the better IGF-1 seems to be, due to it’s ability to help preserve lean tissue
  • The benefits of IGF-1
    • IGF-1 plays an important role in the repair/growth of muscle
    • It plays an important role in neurogenesis, and allowing existing neurons to survive
  • Exercise and IGF-1
    • The boost in neurogenesis (the creation of new neurons), via brain-derived neurotophic factor (BDNF), after exercise requires IGF-1
    • People who are exercising, are putting IGF-1 to the places it’s supposed to go (muscle and brain tissue)
      • If you’re going to eat a high protein diet (and refined carbs), you should be active and exercise often
  • Fasting
    • Fasting has tremendous potential for the treatment of autoimmune disease and cancer 
    • A prolonged fast (and sometimes a fasting mimicking diet(FMD)) causes organs to shrink (we don’t know how much this is due to cells shrinking vs. apoptosis (cell death)) – for more on the FMD, check out these Podcast Notes from Dr. Valter Longo on Rich Roll
      • During the refeeding phase, the organs regrow 
      • Stem cells are activated by low IGF-1, and then IGF-1 is needed to proliferate those stem cells into that new tissue/organ -so the refeeding is just as important as the actual fasting
    • Dr. Valter Lono has done some studies showing that in people with Multiple Sclerosis (MS) on a fasting mimicking diet, during the refeeding phase, the stem cells are formed into normal non-autoimmune cells – effectively treating the MS
    • Dr. Longo has also shown that in cancer patients, a 48 hour water fast sensitized cancer cells to death, and prevented death among healthy cells
      • “The results are so phenomenal, that I would not be surprised if in the next 10 years, some form of fasting is required as a standard of cancer care” – Peter
      • Patients need a better insight of nutrition going into cancer therapy – it’s a tough spot because physicians care more about patients maintaining their weight
    • Fasting prior to surgery (1-2 days) has been shown to help with the response to, and recovery from, invasive operations
More on Exercise
  • It seems to be that exercise is the single most important thing you can do to preserve brain health
  • Rhonda finds exercise very much improves anxiety levels and improves her decision making ability
    • She loves to go on a very long run if she’s struggling with a decision
  • Strength training has been shown to prevent muscle atrophy (the wasting away of muscle), and lower the incidence of cancer
  • VO2 Max – the ability of the body to transport oxygen during exercise, improved with high intensity interval training
    • This declines about 10% per decade – muscle mass declines at the same rate
    • 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
The Many Benefits of Sauna Use
  • Sauna use (~20 minutes at 170-180 °F) has been shown to lower cardiovascular related mortality
    • 2-3 times a week has been shown to lower risk 27%
    • 4-7 times a week, 50%
    • All cause mortality is also lowered
  • Sauna use has been shown to aid sleep
    • The more negative the derivative of temperature – so d(Temp.)/d(time) – when you sleep, the faster you’ll go to sleep, and the longer you’ll stay asleep
    • So… sauna before bed, then take a cold shower, then go right to bed, you’ll sleep like a rock- Rhonda swears by it
    • Heat stress has been shown to elongate the REM stages of sleep in piglets
  • Sauna use is very similar to cardiovascular exercise
  • Rhonda has noticed a huge boost in mood after using a dry sauna
    • Infrared saunas don’t get hot enough (140 °F)
  • Sweating allows you to excrete BPAs, mercury, phalates, and heavy metals
  • Sauna use has a positive effect on the immune system and mood
    • When you get sick, two primary pro-inflammatory cytokines are activated – Interlukin one beta (IL-1B) and Tumor necrosis factor alpha (TNFa)
      • IL-1 activates another cytokine called interleukin 6, or IL-6
        • IL-6 is a “bad guy” – it’s most consistently elevated in depressed people
        • IL-1 also activates IL-10, which is anti-inflammatory
    • Exercise (and sauna use) activates IL-6 (also IL-10) like crazy, but doesn’t activate IL-1 or TNFa
      • IL-6 plays a key role in exercise’s ability to induce insulin sensitivity
      • If you block IL-6, you block the beneficial metabolic effects of exercise
        • So by exercising, and taking a nonsteroidal anti-inflammatory agent afterwards, you block the effects of IL-6
        • There’s been studies showing taking high dose antioxidants (like vitamin C) suppressed the insulin sensitivity effects of exercise, possibly by suppressing IL-6
    • The higher the IL-6 levels rise after sauna use, the more potent the antidepressant effect
  • One animal study showed that heat stress increased levels of glucose transporters – it improved insulin sensitivity, and lowered blood glucose (the glucose was being taken into muscle better
  • Heat stress increases heat shock protein (HSP) levels which play an important role in preventing neurodegenerative diseases like dementia
  • While using a sauna, dynorphin is upregulated to help your body cool down
    • Heat stress causes the release of beta-endorphins in the brain (same with exercise)
    • Dynorphin is responsible for what one might call, a dizziness feeling, at the tail end of a sauna session – that feeling of “oh god, I have to get out”
    • Dynorphin binds to kapa opioid receptors in the brain
      • This causes a feedback response in other opioid receptors in the brain (mu opioid receptors) which bind to beta endorphins
      • Once your are past the dizziness/dysphoric feeling from dynorphin release, you feel really good
        • Why? – More mu opioid receptors are binding to beta endorphins
        • This explains the lasting “feel good” effects from sauna use throughout the day, and allows you to feel the effects of beta endorphins even more
Cold Stress
  • In the past, Peter has used ice baths to help recover from difficult workouts
  • Rhonda will sometimes take a cold shower before a big talk
  • Norepinepherine is released in the brain after some form of cold exposure
    • Plasma norepinepherine levels correlate with the levels in the brain
    • Norepinepherine increases mood
  • If Rhonda stacks a sauna session with a cold shower afterwards, she sleeps amazing
  • Cold exposure has been shown to effectively boost biomarkers of mitochondrial biogenesis
    • Exercise does this more efficiently
  • Cold exposure within an hour after strength training seems to blunt some of the hypertrophy effects
    • This is the same reason people don’t take any form of anti inflammatory agents after working out – it impairs the rebuild, as mentioned above
    • The anti-inflammatory response starts to peak about an hour after exercise
NAD+
  • Many supplements out there claim to boost NAD+ levels, and increase longevity
  • As you age, the ratio of NADH to NAD+ goes down
  • NAD+ is an important co-factor for mitochondria to make energy through the electron transport chain
    • 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+ for fuel
  • NAD+ supplementation (or taking precursors that then turn into NAD+) has been shown in animal studies (rodents) to improve health span
  • NAD+ precursor supplementation in humans has been found to increase plasma NAD+ levels, but the questions still remains of whether or not it’s getting to the mitochondira
  • You can increase NAD+ levels with fasting
    • By fasting you convert NAD+ into NADH
      • In the presence of carbohydrate abundance the NADH ratio increases. Nutrient depletion allows for NADH to get metabolized allowing NAD+ to build up, thus casing a shift in the ratio in favor of NAD+
What is the most interesting question that Rhonda doesn’t yet know the answer to, but she feels like is knowable?
  • For someone like herself, would doing a prolonged fast a few times a year truly have an effect at increasing stem cell production, and help get rid of dysfunctional immune, liver, and muscle cells?,
    • Would those dysfunctional cells then be repopulated with healthy new cells?
    • Would this healthy rejuvenation improve health span and delay the onset of age related diseases?
    • How often and how long would you need to fast?
The Next Frontier of Medicine
  • Being able to target certain tissues/cells and leave other tissues/cells alone
    • It’s not hard to kill a cancer cell with chemotherapy – it IS hard to kill a cancer cell and not a normal cell
Other
  • Peter checks his blood every 6-8 weeks
Facebooktwitterredditmail
Liked it? Take a second to support Podcast Notes on Patreon!
2 Comments

Don't Miss Out!

The Only Place To Get a Weekly Summary of Our Favorite Podcast Notes, Free!

Before You Go, Don't Miss Out!

The Only Place To Get a Weekly Summary of Our Favorite Podcast Notes, Free!