rhonda patrick

ApoE4, Fish Oil, DHA, Metformin, Sulforaphane, Magnesium, and Using the Sauna – Dr. Rhonda Patrick on The Kevin Rose Show

Check out Kevin Rose’s Podcast Page

Key Takeaways

  • To increase absorption into the brain, it’s best to consume the phospholipid form of DHA (found in fish, fish roe, krill oil, and fish eggs) rather than the other, less-absorbed, forms of DHA found in fish oil supplements 
  • Exercise is probably superior to metformin in terms of delaying aging and preventing/treating type 2 diabetes
  • Metformin blunts the beneficial effects of exercise
  • Sulforaphane is a compound formed from the glucoraphanin found in cruciferous vegetables
    • It increases glutathione (the body’s master antioxidant) levels in the plasma and brain, as well as facilitates the excretion of harmful carcinogens
    • The best way to get your sulforaphane: Broccoli sprouts
  • Magnesium is critical for repairing DNA damage
  • There’s tons of benefit overlap when it comes to using the sauna and exercising

Supplements Mentioned

Intro

ApoE4 Predicts Alzheimer’s Disease Risk

  • ApoE is a gene
  • There are four different isoforms (AKA alleles) of ApoE – they’re referred to as 1, 2, 3, and 4 (but most of the time you’ll find 2, 3 and 4)
  • Everybody has two copies of the ApoE gene (one from mom and one from dad)
    • Most people have two copies of ApoE3
  • People with an ApoE4 allele have an increased risk of Alzheimer’s disease (you can use 23andMe to see your ApoE phenotype)
    • People with one allele have a 2-fold higher risk of Alzheimer’s disease, while those two alleles have a 10-15-fold higher risk
      • Around 25% of the population has at least one copy of ApoE4
      • 65-85% of the people diagnosed with Alzheimer disease have at least one copy of ApoE4

DHA Transport Across the Blood-Brain Barrier

  • The blood-brain barrier (BBB) is lined with endothelial cells, separated by tight junctions
    • As we age, these tight junctions become compromised – this becomes even more of an issue in people with an ApoE4 allele
  • DHA is one of the predominant omega-3s, primarily found in marine sources
    • The only type of DHA that crosses the blood-brain barrier is DHA bound to albumin (a protein found in the bloodstream which transports a variety of molecules to tissue throughout the body)
      • There are two forms of DHA bound to albumin:
        • Free DHA, DHA that’s not esterified (it’s not attached to anything besides albumin)
          • This complex gets transported across the BBB via passive diffusion, but because normal aging and ApoE4 both disrupt these tight junctions, this diffusion process can be compromised
        • The phospholipid form of DHA, known as lysophosphatidylcholine DHA (AKA lysoPC DHA)
          • This complex is transported across the BBB using a specific transporter. allowing it to bypass any tight junction defects
  • What does this all mean?
    • The phospholipid form of DHA bypasses the BBB tight junction defects associated with age and ApoE4

DHA is Essential for Brain Health

  • DHA plays a vital role in the brain
    • 🎧 Most importantly, it prevents and improves several of the hallmark’s associated with Alzheimer’s disease (like the build-up of tau tangles and amyloid-beta plaques)
    • It’s also crucial for transporting glucose across the BBB (and a lack of glucose getting into the brain is a hallmark of Alzheimer’s disease)
      • More specifically, DHA increases glucose transporter levels on the BBB
      • Why does this matter?
        • “Brain glucose levels are important for preventing a lot of the hallmarks associated with Alzheimer’s disease… Not being able to get glucose into the brain can play a causal role in Alzheimer’s disease.” – Dr. Rhonda Patrick
      • Related: Insulin insensitivity can also reduce glucose getting into the brain

The Best Sources of DHA

  • Fish oil supplements mostly contain free DHA
    • Note, there are quite a few forms of free DHA (i.e., triglyceride form DHA, ethyl ester form DHA, free fatty acid form DHA, etc.)
      • The higher-quality fish oils contain mostly triglyceride form DHA, while the cheaper ones contain ethyl ester form DHA
  • Fish, fish roe, fish eggs (like caviar) and krill oil predominantly contain phospholipid form DHA
    • Fish contain ~1-1.5% of their DHA in the phospholipid form (the remaining is in the triglyceride form)
    • Fish roe (salmon roe, herring roe, flying fish roe, etc.) contain 38-75% of their DHA in the phospholipid form
    • 35% of the DHA found in krill oil is in the phospholipid form
      • That said, krill oil supplements tend not to be too high in their DHA concentration (they only contain 60-80 mg per serving) – you’d probably be better off taking a higher dose of fish oil (~1 gram), even if it’s not in the phospholipid form
  • Long story short: “The bottom line here is that, for the dietary phospholipid form of DHA, you’re going get more bang for your buck” Dr. Rhonda Patrick

DHA for the Developing Brain

  • The phospholipid form of DHA has been shown to be the preferred form of DHA taken up into the developing brain
    • It’s taken up ~10x better than DHA found in the free fatty acid form

Rhoda’s Fish Oil Supplement Regimen

  • Rhonda supplements with 3 grams of high-DHA Norwegian PURE-3 fish oil daily (6 pills), high-EPA Norwegian PURE-3 fish oil, and tries to consume both salmon and fish roe regularly
    • She prefers to consume her salmon roe on a slice of avocado topped with lemon juice (she’ll even give it to her son, but adds a little Boursin cheese on top)
    • Rhonda also gives her son high-DHA Norwegian PURE-3 fish oil, mixed in with oatmeal

EPA

  • EPA is a potent anti-inflammatory agent and is also good for brain health
  • Recent studies show that highly purified EPA, supplemented in high doses (up to 3 grams per day), lowers triglyceride levels and reduces risk of cardiovascular disease
  • Other evidence suggests EPA may be useful for mitigating depressive symptoms

If You’re Healthy, Think Twice About Metformin

  • What is it?
    • It’s a drug given to type 2 diabetics to lower their blood glucose levels, but it’s gotten quite popular among the biohacking scene
      • More specifically, it decreases the production of glucose in the liver, decreases glucose uptake in the gut, and increases overall glucose utilization by improving insulin sensitivity in skeletal muscle
    • Rhonda, personally, has never taken it
  • Many claim metformin supplementation improves lifespan, but…
    • Findings have been skeptical in rodent models, with many variations among dose, gender, and dose timing (specifically, the age of the mouse when given the first treatment)
      • Certain combinations of the above actually decrease lifespan, particularly in male mice
    • Indeed, among type 2 diabetics, taking metformin improves lifespan, but if you’re healthy, think twice
  • Doesn’t metformin reduce the risk of cancer?
    • Yes, among type 2 diabetics, but it;’s yet to be determined if that’s the case for healthy people taking the drug

Metformin Blunts the Beneficial Effects of Exercise

  • It’s been shown that 150 minutes of moderate-intensity exercise per week prevented the progression of pre-diabetes to type 2 diabetes by 60%
    • Comparatively, metformin prevented this progression by 30% in pre-diabetics
  • You might think metformin and exercise have a synergistic effect, but multiple randomized control trials have shown the opposite seems to be true
    • “Taking metformin in the context of either aerobic exercise or strength training seems to blunt many of the positive effects of exercise.”Dr. Rhonda Patrick
  • Rhonda recalls a study in which metformin, dosed at 500-1,000 mg, depending on body weight, was given to individuals who were at risk for type 2 diabetes. Participants were prescribed 45 minutes of aerobic exercise 3x a week.
    • The results?
      • Metformin prevented the exercise-induced improvements in cardio-respiratory fitness by 50% 
        • (Cardio-respiratory fitness is one of the most significant predictors of disease and mortality)
      • Metformin inhibited improvements in mitochondrial respiration
        • Metformin activates AMP-kinase, which is beneficial (AMP-kinase is also activated through exercise and fasting). But, metformin does so by mildly disrupting a particular part of the mitochondria that generate energy, which is harmful.
      • Metformin diminished whole-body insulin sensitivity after aerobic exercise
  • Can’t you just time your metformin to not interfere with exercise?
    • Probably not – the effects of metformin last ~36 hours after your last dose
  • Rhonda recalls another study which showed that taking ~1700 mg of metformin for 14 weeks inhibited muscle mass gain from resistance training
    • Why? – AMP-kinase activation inhibits mTOR

Metformin and Brain Health

  • As glucose dysregulation is tied to adverse brain health, improving it will definitely improve overall brain function
    • There’s data showing type 2 diabetics taking metformin have improved cognitive function

Rhonda’s Final Thoughts on Metformin

  • 🎧 “I think exercise is better than metformin for preventing type 2 diabetes, treating type 2 diabetes, and I also think it’s better than metformin at delaying aging… You’re better off exercising than taking a metformin pill.” Dr. Rhonda Patrick
  • “I’m not convinced that taking metformin in addition to exercise is good. In fact, I think it’s actually not beneficial for people who are exercising.”

Get Your Sulforaphane

  • What is it?
    • It’s a beneficial molecule formed from the glucoraphanin found in cruciferous vegetables (i.e., broccoli, Brussel sprouts, cabbage, cauliflower, etc.)
      • When the plant tissue is crushed/chewed, an enzyme called myrosinase is activated which turns glucoraphanin into sulforaphane
  • The best way to get your sulforaphane: Broccoli sprouts
    • Sprouts have 10x more glucoraphanin than the mature broccoli plant
    • To grow your own broccoli sprouts use this kit with these seeds
    • 100 grams of sprouts contain ~40 mg of sulforaphane

Are there any good sulforaphane supplements?

  • Avmacol, which has ~3.5 mg in each tablet (their recommended dose is 2 tablets)
    • This is Kevin’s sulforaphane supplement of choice – he cycles it monthly (1 month on, 1 month off)
  • Prostaphane (each tablet has ~10 mg of sulforaphane)
    • Rhonda takes 1 tablet per day, rather than taking the time to make her own sprouts

What are the benefits of sulforaphane?

  • Increased glutathione (the body’s master antioxidant) in the plasma and brain (proven at a dose of 18 mg of sulforaphane/day)
    • Increased brain glutathione levels have been shown to be beneficial for treating neurological disorders and reducing symptoms of autism through the reduction of oxidative stress
  • Other studies in which participants were dosed with 10 grams of broccoli sprout extract per day found that:
    • Oxidized LDL, thought to play a causal role in cardiovascular disease, was reduced
    • Serum triglycerides were reduced by 18-19%
    • Atherogenic index was decreased by 50%
  • 🎧 Sulforaphane increases the excretion of harmful carcinogens like benzyne and acrolein, both of which are found in cigarette smoke and air pollution, by up to 60%
    • How so? – Through its activation of a critical pathway involved in longevity, the Nrf2 pathway, which increases a variety of detoxification enzymes

Magnesium Helps Repair DNA Damage

  • L-threonate, a specific form of magnesium, is thought to cross the blood-brain barrier more efficiently than non-L-threonate forms of magnesium
    • Some animal studies show it improves cognitive function, reverses memory deficits, and prevents the loss of synapses, but Rhonda is still skeptical
  • In 2014, 45% of the population was deficient in their magnesium consumption
    • Just how much magnesium should you get on a daily basis? – 300-400 mg
    • Because magnesium is stored in muscle tissue and bone, anytime your body has low amounts, it pulls from there. Therefore, unless you’re incredibly deficient, your plasma magnesium levels won’t indicate a deficiency.
    • Magnesium deficiency MATTERS – magnesium is critical for repairing DNA damage
      • Thus, over time, damage compounds and leads to age-related diseases
  • The best source of magnesium: Dark/leafy greens
  • In the past, Rhonda has supplemented with magnesium glycinate, but she tries her best to get her magnesium from food

Use the Sauna

  • For more on the benefits of using a sauna, check out these Podcast Notes
  • Sauna use (4-7x per week at a temperature of 175 °F for 20 minutes):
    • Reduces the risk of cardiovascular disease
    • Reduces the risk of stroke
    • Reduces the risk of sudden cardiac death
    • Improves arterial compliance
    • Reduces the risk of Alzheimer’s disease
    • Enhances mood
  • 🎧 Using the sauna mimics the effects of moderate-intensity aerobic exercise
    • Think about it: Both increase core body temperature and heart rate, facilitate sweating, increase blood flow, etc.
      • Kevin has noticed a 20-minute sauna session at 175 °F increases his heart rate to 105 BPM
      • Rhonda estimates her heart rate gets to ~120 BMP after 30 minutes in a 168 °F sauna
    • In general, a 25-minute sauna session is comparable to 25 minutes doing 100 Watts on a stationary bike
  • Using the sauna after a workout reduces delayed-onset muscle soreness and increases strength gains
  • Using the sauna is the best way to increase the body’s production of heat shock proteins
    • Sitting in a 163 °F sauna for 30 minutes increases heat shock protein levels by ~50%
    • The most essential thing heat shock proteins do: help maintain the proper 3-dimensional structure of cellular proteins
      • When a protein’s 3-dimensional structure gets altered, it tends to sit around much longer than it’s supposed to (instead of being degraded) – this causes it to start forming protein aggregates with other proteins. Protein aggregation has been shown to play a causal role in many neurodegenerative diseases.
    • Heat shock proteins also slow muscular atrophy (the wasting away of muscle)
  • In addition to exercise, Rhonda has noticed her 4x weekly sauna sessions significantly improve her mood
    • “Exercise and sauna, I need them for my brain. Period.” – Dr. Rhonda Patrick

The FoundMyFitness Mission

  • The best way to help Rhonda’s efforts – support her with a premium membership ($15/month). Extra perks include:
    • A private podcast feed with Q&As and early releases
    • Exclusive show notes for each podcast
    • Podcast slides
    • A 2x monthly research round-up
    • FoundMyFitness swag
  • Rhonda currently has a few contractors on her team, but she’s looking for more full-time scientists

Continuous Glucose Monitor (CGM) Insights

  • Both Rhonda and Kevin wear one
  • 🎧 “One of the things I’ve noticed is that I absolutely need exercise in order to have a good glucose regulation… If I don’t exercise for 3 days, it’s like boom; I’ll wake up with significantly higher fasting blood glucose levels.”Dr. Rhonda Patrick
  • Wither her CGM, Rhonda has also noticed:
    • Eating a decent amount of protein before consuming any carbs will mitigate her post-meal blood glucose spikes
    • Regular exercise decreases her postprandial blood sugar spikes 

Additional Notes

  • “The average doctor is many years behind what the science is actually telling us to do, so if you want to know the latest and greatest, it’s best to go to scientists.” – Kevin Rose
  • Kevin plans to eat mostly a pescatarian diet during the first part of 2020
    • He also plans to limit his drinking
  • Kevin gives his dog an omega-3 supplement (specific brand not mentioned)
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One thought on “ApoE4, Fish Oil, DHA, Metformin, Sulforaphane, Magnesium, and Using the Sauna – Dr. Rhonda Patrick on The Kevin Rose Show

  1. Your summary on the fish oil thing is a little bit off. It’s too absolute. One of the other take-homes is that with a sufficient dose of fish oil, it may be possible that you’re getting a substantial form of the DHA-lysoPC metabolite by making it up with sheer volume of DHA. Rhonda’s whole omega-3 story amounts to this:
    • DHA lysoPC utilizes active transport in the brain
    • Phospholipid form of DHA tends to produce more DHA lysoPC
    • However, other forms produce it (though potentially dramatically less), as well… thus, if you’re not getting DHA-lysoPC via phospholipid form, taking very large doses of fish oil triglyceride form may still successfully saturate the active transport mechanism.

    While salmon roe is almost 40% phospholipid DHA (nice!), fish meat is only 1-2%, which is mostly inconsequential since a supplement is at least going to give you more omega-3 overall to metabolize.

    Krill oil on the other hand is mostly dead on arrival because of its low overall dose, even if it’s phospholipid.

    Here’s some useful resources…
    Original press release for Rhonda’s story
    https://www.prnewswire.com/news-releases/omega-3-dha-in-phospholipid-form-may-bypass-faulty-brain-transport-in-alzheimers-disease-300737564.html

    Also, here is Dr. Patrick’s version of this same episode where she’s attached her own intro that clarifies some of those points on omega-3…
    https://soundcloud.com/foundmyfitness/rhonda-krs-2

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