The Joe Rogan Experience: Dr. Rhonda Patrick

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9/10 Microphones: Full Episode

Find Rhonda Patrick at: Foundmyfitness.com, @foundmyfitness

  • Highlights
  • Mixed Martial Arts (MMA) and Brain Injury
  • Genetic Risk Factors for Alzheimer’s Disease
  • Key Chemicals/Supplements for Brain Health
  • Epigenetics
  • Big Picture Recommendations

Highlights

  • People with TBI (traumatic brain injury) can often have Alzheimer’s like symptoms at much younger ages and are much more likely to have Alzheimer’s (e.g. NFL, MMA, etc.)
    • Risk even higher with APOE4 genetic risk factors
  • Learn about your genetic risk factors with 23andme
    • APOE4: Key risk factor for Alzheimer’s disease as you are less able to remove amyloid beta plaques and other things
    • Amyloid beta plaques are one of the key markers of your likelihood of developing Alzheimer’s
    • Sleep: Also helps your body cleanse out amyloid beta plaques
    • Cannabinoids: In addition to benefits for managing nausea in many diseases, recent research shows a benefit in reducing amyloid plaque in the brain and overall survival after TBI
  • Diet: Focus on what you SHOULD eat instead of what you SHOULDN’T
  • Exercise: Does a lot more for you than weight loss
    • Reduced risk of Alzheimer’s, Depression
  • Supplements:
  • Learn more about your blood levels (via your doctor or WellnessFx)
  • Genetic predisposition + bad diet + lack of exercise + stressful environment = Disaster

Mixed Martial Arts (MMA) and Brain Injury

Rhonda recently had her first exposure of MMA with Joe at UFC

  • MMA felt very tribal which was unique/cool vs. other sport events
  • The amount of likely brain damage (e.g. memory issues, Alzheimer’s-like effects) is troubling
  • Choking: May not be as dangerous? (Joe)
    • Rhonda: Choking can cause hypoxia via limited oxygen in the brain which your body can somewhat compensate by increasing blood flow
    • If your brain unable to compensate, then you begin to lose motor control
    • Passing Out is even worse as hypoxic damage (not enough blood to brain) does occur = resulting in
      • Lactate Buildup: Astrocytes (supporting cells in the brain) use glucose via glycolysis and the by product is lactate that goes into the mitochondria to create energy
        • Lactate needs oxygen to be able to be used, and so when you pass out lactate can’t be used and causes damage
        • This is more an issue for larger scale head trauma like in a car crash
      • TBI: Traumatic Brain Injury
        • Anyone playing a sport with blows to the head has a 2-3x increased risk of Alzheimer’s and earlier onset by ~7 years (e.g. NFL, MMA, etc.)
        • Any single blow to head can increase risk, but repeated blows are worse
          • Immediate effects: Tissue damage, diffuse axonal injury

Multiple blow effect lead to a damaging chain reaction

  1. Release of Reactive Oxygen Species in massive amounts that damage the Meninges that form a protective barrier around the brain = cell death
    1. A little of reactive oxygen species can damage DNA that you can usually repair this, but if not it can lead to cancer
    2. But a huge burst of it leads to a defensive mechanism to preemptively kill cells before they mutate and cause cancer (similar to what you do with radiation treatments for cancer)
  2. Astrocytes also start to die and they make up the Blood Brain Barrier which begins to leak potassium, sodium and chloride which enter the brain causing the brain itself to swell
  3. Next microglial cells get activated to try plug in the hole, but that is part of a big immune response = inflammation
  4. Inflammation in the brain leads to accumulation of Amyloid Beta Plagues
    1. Amyloid beta plagues are one of the major pathologies associated with Alzheimer’s
    2. It Generally builds up bit by bit as we age over time, but TBI can trigger them much more quickly
    3. Plaque levels are formed immediately in TBI akin to rapid aging
    4. Amyloid beta forms in between glial cells/neuron forming plaques that disrupt glucose metabolism, create even more reactive oxygen species, immune system/inflammation and have this vicious cycle of more and more damage
      1. Tau proteins (other key sign of developing Alzheimer’s) also don’t function correctly leading to mitochondria dysfunction correctly à synapses start dying
    5. If you can’t build synapses, you can’t learn and brain atrophies
  • In general, cells are already stressed and now they are more susceptible to death (similar to when cells choose to die rather than become cancerous by releasing pro-apoptotic proteins)
    • Note: Some cancers have figured out how to prevent this by expressing these anti-apoptotic proteins
    • Stress plus stress is additive, especially in a short timeframe
    • Joe has seen it during a fight, a guy started off one way and came out different and less able to communicate later
  • One TBI can create damage which can continue for months after the original trauma
  • Energy Triage: Everything in your body requires energy and when there is chronic/major damage due to anything (e.g. head trauma, diabetes, obesity, etc. etc.) your body needs a lot of energy to repair which it needs to conserve elsewhere, essentially Triage for the essential parts which can take away from short term memory, speech etc.
    • Multiple mild injuries can also compound this triage issue

Genetic Risk Factors

  • Genetic Predisposition (e.g. gene polymorphisms) can make the effects of TBI even worse for some people (these tend to be the same genetic risk factors for Alzheimer’s)
  • APOE is a risk for AD with 3 variants (APOE 2, 3, 4)
    • In the brain, cholesterol is made by astrocytes and the APOE transports this to neurons
    • Most people have 2 APOE3 alleles (1 from each parent)
    • 25% of people have 1 allele that is APOE4
      • APOE4 increases risk of Alzheimer’s 2-3x , TBI alone also increases risk of AD 2-3x, stroke and other neurodegenerative diseases
      • People with TBI and APOE4 have 10X risk of AD (25% of people)
    • 2% of people have both alleles as APOE4 (from both parents)
      • 2 APOE4 alleles increases your risk of Alzheimer’s by 10X
    • 65-80% of all Alzheimer’s disease have at least 1 allele of APOE4
      • APOE4 limits your ability to repair damage in the brain such as cleaning up amyloid beta plaque by bringing cholesterol and fatty acids to the neuron s and
      • In addition, APOE4 actually causes other damages itself
      • After damage, the brain usually increase APOE, but if you end up with more APOE4 this actually leads to even more damage
    • Find out if you have APOE with 23andme for ($99)
      • FDA recently stopped them from informing you about specific risk factors (but you can use other services to review your raw data – including on Foundmyfitness)
        • The technology has a small chance of error, so you may get a false positive
      • Rhonda does have 1 allele for APOE4… via her father (she is obviously very interested in finding out ways to reduce her risk, but we wish this wasn’t the case)
      • Fighters would be smart to get checked for risk (Joe- fighters will resist this and still want to fight, but waiting until you feel the impact, it is way too late –sadly)
    • BUT, sleep also helps you get rid of amyloid beta
    • Nutrition is also a huge factor: People who are obese, diabetics, etc. are also at risk for Alzheimer’s/Parkinson’s
      • This may be related to inflammation leading to the release of pro-inflammatory cytokines that cross the Blood Brain Barrier causing neural inflammation and thus aggregation of amyloid plaques
      • Brain inflammation in the brain also trigger Prostaglandins E2inhibits your brain’s ability to release Serotonin (can cause depressive symptoms and other problems beyond mood)
    • Children with autism also tend to have problems with their microbiome and inflammation in your gut which also leads to inflammation in the brain
  • Sense of Smell is a good predictor of Alzheimer’s and even all-cause mortality
    • The Olfactory Bulb requires a constant supply of neural stem cells coming from the subventricular zone
    • When you can’t supply this, you can’t smell anymore = you lack neural stems cells which means you can no longer make new connections in the brain
    • Joe knows people (Gary Goodrich) who were knocked out and lost their sense of smell
    • Study giving young blood from mice to old mice: Can stimulate stem cells in mice and making them younger (NOT translatable to humans – sorry Twilight/Dracula fans)
      • Found they could isolate a specific growth factor, just inject that and get same results in mice
      • A new study in Stanford trying this in humans – people with mild AD
  • Chris Henry (football player): Autopsy of his brain looked like a 70 year old AD patients – he was 26 (likely due to chronic brain damage)
    • 76/79 NFL players who’s brains were evaluated after death has significant amyloid plaque build-up
    • Impulsive behavior is related to neuro-degenerative diseases (but many fighters are impulsive to begin with – so might already have issues here…)
      • Self-directed (suicide) or towards others
      • Lack of long term planning
    • Serotonin plays a big role in regulating impulsivity
    • If you acutely flood the brain with serotonin, you can acutely decrease impulsive behavior (2010 study) – unclear this can be done for long term

Key Chemicals/Supplements for Brain Health

  • Glutathione: Major brain antioxidant
    • Key for brain aging, more tends decrease AD/damage/etc.
    • Made of 3 amino acids: glutatemic acid, glycine and cysteine
      • Our body bonds them by using an enzyme called glutathione synthase
    • Other enzymes use glutathione as an antioxidant
    • With age we decrease the amount of glutathione we make
    • Because it’s made in our cells, there is no way to transport those three things into our cells by taking it orally – pointless… UNLESS Liposomal
    • Liposomal Glutathione – Only one with a chance of potentially valuable
      • Can bypass transport rules and get into cells
      • Not many studies, some animals have shown some get into the brain, but at a dose wayyyy higher than you can take/afford
      • Usually available at 100-400mg/dose and very expensive
      • You may get some in your brain, but not sure how much you get…
      • Only tries to solve half the problem as the enzymes that use glutathione also decrease with age, so just getting more glutathione in your body, doesn’t mean you can use it…
    • 2014 study on TBI with mice and found that if they directly added glutathione to a mouse brain within 3 hours, they prevented like 70% of the damage (not human study)
    • Ongoing studies to see what can be done with humans
    • Other ways to increase glutathione:
      • Tumeric: Common in curries (a spice)
        • Circumin: gets into brain, antioxidant alone and turns on glutathione genes and the entire glutathione system
          • Rapidly metabolized which activates a pathway in a liver to metabolize asap… – so not very usable
          • Piperine in black pepper can slow this metabolism down and increase bioavailability of circumin (and lots of other things) in the body by 2000x
            • There would be a concern that this could impact the half-life of other medications/supplements you are taking… be cautious
          • Tumerone, also in turmeric that does a lot of similar things to circumin and repairs brain damage by proliferation of neural stem cells in the subventricular zone (mouse study in 2014)
            • Still unclear at what dose and if could work at all in humans (trials ongoing )
          • DHA/EPA are key for the brain health and people look to Fish/Krill oil for supplementation
          • Krill Oil vs. Fish Oil?
            • Fish oil- molecular distilled to get rid of mercury and other things, and to concentrate the EPA/DHA, usually including an ethanol backbone which we can’t well absorb it later (can be put back into a triglyceride form, but rarely done – Nordic Naturals does this)
            • Krill Oil: Phospholipid form, can be easily absorbed and transported to good parts of body – better bioavailability
              • Can get DHA into your brain via use a transporter called lisophotatital choline
              • That reason alone is a reason to use Krill Oil
              • Fish oil concentrates higher levels of DHA, but your brain doesn’t need that much of DHA, but when it does it likes the Krill oil
              • Also contain astraxanthin that helps protect eyes with aging (rods/cones), other benefits too
            • Brain does need lots of EPA which Fish Oil does have
              • So Rhonda takes both Fish oil (2000mg) and Krill oil
            • Arnica: potential inhibitor of aerobic bacteria
            • Alpha Lipoic Acid: Given to old rats, it makes their brain’s young in Rhonda’s mentor’s study
              • Absorbed better without protein
            • Eyes: What to take for vision?
            • Bullshit/Unproven: Echinacea, Golden Seal, Homeopathy

Probiotics

  • Probiotics are important, can help create an acidic environment in your bug which can kill off bad bacteria in your gut, can also add good bacteria such as Acidophilus
    • Kombucha: Good source of probiotics
    • Lactate: Which is a source of energy from your mitochondria which helps you maintain your gut immune cells
    • (SEE CROSS Post from RHONDA’s Podcast with the Sonnenburgs – Gut Bacteria Experts from Stanford)
    • Gut inflammation also is a triage problem where your body devotes tons of energy from other places that need it, which creates chronic/long term damage (similar to what is happening with inflammation in the brain)
      • Obese/Diabetes are constantly in this state…
    • Rhonda’s Lab at Children’s Hospital in Oakland: Works with lots of children with diabetes, obesity, etc. and have developed the CHORI-Bar which is filled with great micro-nutrients (see Rhonda’ podcast about it)
      • Instead of vitamins, this combined with fiber/other things
      • Giving these to obese people with no other changes in the diet vs. lean people
        • Good things straight away in lean people
        • Takes many weeks to start showing up in obese patients as they first need to fix some things
      • Cannabinoids:
        • Recent study has shown that THC can reduce the accumulation of amyloid beta (move up)
        • Patients at hospital after TBI (moderate to severe) with highest levels of THC were least likely to die (dose dependent effect)
        • In mice: given low THC dose 48-hours before TBI or 1-7 days after
          • Dramatic neuro-inflammatory pathway
        • 2 types of Cannabinoids receptors in the brain, CB1 andCB2
          • CB1: Found on neurons
            • Recent study showed agonizing CB1 lead to long term potentiation
            • Learning something new enhances a neuronal signal – help learn long term
            • CB1 gets ride of the inhibitory, unless antagonized by amyloid beta
            • May be some acute effect on short term memory and might be a tradeoff benefit for long term potentiation
          • CB2: On microglia- immune cells in the brain
            • Cannabinoids in CB2 prevent the immune cells from activates and creating neuro-inflammation
            • Unclear how
          • More research now as $$$$ is involved in Colorado, etc. – hundreds of millions of tax dollars – More states will follow the money
          • Reduction of intraocular pressure for glaucoma, nausea with AIDS/Cancer, etc. etc. etc.
          • Decrease in violent crime, DUI risk drunk driving…
            • Incredible how few DUI we have giving how every CVS, restaurant, bar you drive by is selling drugs (alcohol)
            • People with APOE4 who drink alcohol are at even more risk as the alcohol adds more stress on top of stress and cells are now more likely to die
            • Exercise is very important to reduce risk for APOE4 people
              • I’m not trying to just lose weight, I’m trying to avoid having my brain atrophy when I’m older
              • Mouse study: Exercise causes your muscle cells to de-toxify kynurenine which is a byproduct of tryptophan metabolism (precursor to serotonin in the brain)
                • Form kynurenine under stress, helps make T-cells
                • Make too much kynurenine (don’t get tryptophan) it can cross blood-brain barrier and create quinaloic acid, a neurotoxin, that actual kills cells in the brain, activates microglia/inflammation
                • Also can cause depression by reducing amount of serotonin (exercise took the depression away)
                • Exercises during the kynurenine into something else so it can’t get in the brain
              • Exercise is awesome of TONS of reasons, just do it!!!
            • Unclear if you can split out the psychotropic effects from other effects and still get the benefits

Epigenetics

  • Behavioral Epigenetics: Relationship between what is happening in your environment and your genetics
  • Examples
    • Nurturing: Mice offspring who are not nurtured have less oxytocin, then they grow up and are less nurturing to their offspring and it perpetuates
      • Females tend to have more estrogen without nurturing and more likely to have sex with anyone… (Correlation with humans?)
    • Monogamy: Similar effect seen vasopressin important to males during mating
      • Prairie Voles are monogamous and have higher level of vasopressin receptors in their brains vs. other species of voles (who knew there were so many Voles!)
        • They also grow more receptors while mating which makes them more monogamous
        • But if you remove these receptors they are no longer monogamous
      • Similar effect seen in non-human primates who are normally monogamous
      • Human study: men with failed marriages had less vasopressin receptors
    • Early life stress events can impact serotonin (e.g. MICE- lack of care from mother when a baby which releases serotonin and helps you better manage stress, oxytocin is also released with nurturing)
      • Mice without this grow up very fearful/stressed
      • Seems similar to children with tough childhoods
      • Likely worse in people who already have polymorphisms for serotonin issues – genetically vulnerable
      • Diet is also connected, Vitamin D is important, Omega 3s as sell
    • Bonobos: Have so much sex that they can’t keep in zoos without upsetting people (NOT monogamous)
      • They did a currency experiment with bonobos where money = food
      • First thing they did was start trading the coins for sex with females…
        • The oldest profession for multiple species it seems…
      • Bonobos are also the least violent type of Ape, maybe because they have the most sex?

(I wonder if @Bonobos knew this when naming their company?)


Big Picture Recommendations

  • A human is the collection all these genetic, environmental, hormones, etc.
    • Some we can’t control like where you are born, genetics, etc. and some we can
  • Start with your diet to get most of these good micro-nutrients like vitamins and minerals
  • Avoid sugar, refined crap, nitrites (nitrates are good and in all plants)
    • Nitrites can form nitrosamines which are potent carcinogens during cell replications (often used to cure meats)
    • Cooking nitrites can be dangerous as they can form into Nitrosamines
    • Buy bacon without Nitrites
  • It takes a lot of continuous effort/time to keep up with everything, calculate and execute on
  • It’s a lot easier to focus on what you SHOULD eat instead of what you SHOULDN’T
    • Too easy to be caught up in the minutia and distracted from what matters
    • If you feed your body what it needs it can fight off the bad things
  • Disinformation among even Medical Experts
    • They even misunderstand things like the variety in types of Vitamin E
    • It’s just so complex and we keep learning new things and that is hard to keep up with, especially when you’re a full time Dr.
    • Many Dr.’s haven’t been trained in nutrition science, genes, etc. – we need to fix this
    • Even a degree in nutrition has flaws as a lot of the dogma has changed and they are not often very hardcore science in their focus
  • Rhonda keeps switching her fields from chemistry, aging, cancer, nutrition and the brain
    • This helps you have new perspectives that people who only do one thing don’t see
  • Learn more about your blood levels and genetic data:
    • WellnessFX: Rhonda has done a couple guest blog posts
      • Consumer focused blood tests on all blood markers (e.g. EPA, DHA, cholesterol, etc.)
      • Include a panel of nutritionists, etc. to help you interpret your results
      • Then you can make changes in your diet and try make an impact
      • Part of the “Quantified Self” movement
    • Genetic data is the other component via 23andme (see above)
      • Rhonda would like to see APOE testing adopted by the NFL, boxing, MMA, etc.
      • “Like being a hemophiliac who wants to sword-fight” – Joe

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All notes are intended to reflect the podcast and have not been independently verified.

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