Foodist with Darya Rose, Ph.D. – Dr. Rhonda Patrick on Why Eating Fish, But Not Omega-3 Supplements, Can Help Prevent Alzheimer’s Disease

Check out the Foodist Episode Page and Show Notes

Key Takeaways

  • If you’re having trouble getting pregnant, try tapering down caffeine consumption
  • 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 2-3 fold higher risk of Alzheimer’s Disease
    • People with two alelles have a 10-15 fold higher risk of Alzheimer’s Disease
  • Getting enough sleep, is super important for ApoE4 carriers, to lower their risk of Alzheimer’s Disease…why?
    • There are 2 main ways the body clears amyloid beta plaques from the brain (which are associated with Alzheimer’s Disease)
      • The first way is ApoE mediated – ApoE binds to the plaque and basically gets rid of it
        • ApoE4 binds to amyloid beta plaque 20 fold less efficiently than ApoE3
      • The other way is through the glymphatic system – a series of channels that extend from the spine to the brain, which is activated during deep sleep
        • Cerebral spinal fluid quirts throughout the brain, and literally cleans out debris from dead cells, amyloid plaques, and other things
      • KEY – People with ApoE4 become really dependent on sleep, and the glymphatic system in particular, to reduce their risk of Alzheimer’s Disease
  • Exercise also activates the glymphatic system, as well as improves deep sleep (the stage of sleep in which the glymphatic system is active)
  • There’s been studies that show that DHA supplementation in non-ApoE4 carriers can be useful for protecting against Alzheimer’s Disease, but not in ApoE4 carriers
    • But fish intake, has benefits for everyone…why?
      • Due to some mechanisms described below, it seems to be that ApoE4 carriers need the phospholipid form of DHA to get it into their brains better
      • About 1% of the omega-3 fatty acid DHA is in the phospholipid form in fish
        • In fish oil, usually none of the DHA is in the phospholipid form
        • But fish roe have between 38-70% of DHA in phospholipid form (Rhonda likes to consume salmon roe)
  • DHA (specifically in fish form) has been shown to ameliorate some of the neuro-pathological characteristics in Alzheimer’s patients and also to improve cognitive function
  • You 150% NEED TO EAT MORE LEAFY GREENS

Intro

Children and Pregnancy

  • It seems to be that caffeine consumption is linked to infertility in the scientific literature
    • So if you’re having trouble getting pregnant, try tapering down caffeine consumption
  • A side story – Kevin Rose, Darya’s husband, stopped using the sauna while the couple were trying to get pregnant for the second time
    • Kevin suspected the excess heat from the sauna, was leading to sterility issues (most likely thinking this was the cause, because heat effects sperm motility – but Rhonda hasn’t seen any evidence that it causes sterility)

ApoE4

  • Both Darya and Rhonda are ApoE4 carriers (tested using 23andMe)
    • Darya has 1 allele (she’s type 3,4 – this will make sense after reading the below)
    • Rhonda also has 1 allele
  • What is it?
    • ApoeE is a gene
      • People have different versions of genes for a variety of reasons (aka mutations, which occur randomly)
      • A mutation occurs randomly, but when you start to get >1% of the population coming up with the mutation, it’s called a gene polymorphism (or a SNP – pronounced snip – a single nucleotide polymorphism)
    • There are 4 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 2 copies of the ApoE gene (1 from mom, 1 from dad)
      • Most people have two copies of ApoE3
      • ~25% of the population has at least one ApoE4 allele
  • The ApoE4 allele has been shown to protect against things like malaria
  • BUT there are tradeoffs…
    • People with an ApoE4 allele have an increased risk of Alzheimer’s Disease
      • People with one allele have a 2-3 fold higher risk of Alzheimer’s Disease
      • People with two alelles have a 10-15 fold higher risk of Alzheimer’s Disease
    • There’s also an increased risk of cardiovascular disease
    • Some more facts about ApoE4 carriers:
      • ApoE4 proteins (made from the gene) are made in both the liver and the brain
        • The ApoE4 proteins made in the liver plays an important role in transporting cholesterol and fatty acids (it’s a lipoprotein)
          • It can be found in both low density lipoproteins, and high density lipoproteins (LDL and HDL)
          • Lipoproteins are recycled/used more than once (so once they transport cholesterol to the parts of the bod that need it, they go back to the liver)
          • The problem though, is that ApoE4 based lipoproteins don’t recycle that well back into the liver, and this leads to higher circulating levels of cholesterol
      • ApoE4 proteins made in the brain are made in cells called astrocytes, which act as “supporting” cells for neurons
        • They also transports cholesterol, mainly to neurons

How can you lower your risk of getting Alzheimer’s Disease?

  • Sleep!
    • “Sleep is really important, particularly for ApoE4 carriers”
      • There are 2 main ways the body clears amyloid beta plaques from the brain (which are associated with Alzheimer’s Disease)
        • The first way is ApoE mediated – ApoE binds to the plaque and basically gets rid of it
          • ApoE4 binds to amyloid beta plaque 20 fold less efficiently than ApoE3
        • The other way is through the glymphatic system – a series of channels that extend from the spine to the brain, which is activated during deep sleep
          • Cerebral spinal fluid quirts throughout the brain, and literally cleans out debris from dead cells, amyloid plaques, and other things
      • KEY – People with ApoE4 become really dependent on sleep, and the glymphatic system in particular, to reduce their risk of Alzheimer’s Disease
    • Rhonda uses an Oura Ring
      • Use the code “podcastnotes” for $50 off your own ring at checkout
    • As a side not – The amount of REM sleep you get is linked to how creative you are in the scientific literature 
  • Exercise
    • Exercise has been shown to increase the growth of new neurons particularly in the hippocampus region of the brain (this is where a lot of neuronal loss occurs in Alzheimer’s Disease)
    • It also activates the glymphatic system
    • Exercise also improves deep sleep (the stage important for glymphatic activation)
      • As we age, the amount of deep sleep we get drops

Rhonda’s New Paper

  • What was it about? – How the omega-3 fatty acid DHA (in supplemental form) is transported into the brain differently in ApoE4 carriers
    • DHA is one of the omega-3 fatty acids in fish oil
    • It plays an important structural role in neurons, as well as their receptors 
    • It’s also very important for taking glucose up into the brain
      • DHA is important for regulating the function of glucose transporters at the blood brain barrier
      • Your brain needs glucose – low brain glucose is one of the defining characteristics of Alzheimer’s Disease
        • Glucose in the brain is also important for preventing the formation of  “tau tangles”, which is also tied to Alzheimer’s Fisease
    • DHA has also been shown to reduce amyloid plaques
    • In short – “DHA is really important, you want to get it into your brain”

Fish Oil vs. Fish

  • There’s been studies that show that DHA supplementation in non-ApoE4 carriers can be useful for protecting against Alzheimer’s Disease, but not in ApoE4 carriers
    • But fish intake, has benefits for everyone
  • Why this difference?
    • DHA gets into the brain 2 ways:
      • The first way is essentially just by being in the free fatty acid form (it’s small and lipophilic), passing between the endothelial cells/tight junctions of the blood brain barrier (also know as the “free fatty acid floating way”)
      • The second way is in a phospholipid form (so it’s not in the free fatty acid form), and in this form it binds to a transporter that’s at the blood brain barrier
        • The transporter flips the phospholipid DHA across the blood brain barrier
    • It seems though, in the phospholipid form, DHA gets into the brain quicker 
      • In the free fatty acid form, it takes a little longer
      • (This doesn’t really matter all that much, except when you’re dealing with something like a traumatic brain injury (TBI) – DHA has been shown to be really important for improving outcomes from TBI)
    • ApoE4 disrupts the tight junctions of the blood brain barrier, leading to a leaky blood brain barrier that gets progressively worse with age
      • This led Rhonda to the hypothesis that ApoE4 carriers need the phospholipid form of DHA to get it into their brains better
  • So why is this relevant?
    • About 1% of the omega-3 fatty acid DHA is in the phospholipid form in fish 
      • In fish oil, usually none of the DHA is in the phospholipid form
        • NOTE – If you take non-phospholipid DHA fish oil, you do eventually form the phospholipid DHA, just not as much as you do if you consume in phospholipid form
  • But only 1%?
    • Yes, but fish roe have between 38-70% of DHA in phospholipid form
      • So eat more caviar!!
  • What about krill oil?
    • The DHA is in the phospholipid form, but the problem is it’s not very concentrated
  • Why doesn’t fish oil have any DHA in the phospholipid form?
    • It has to do with the molecular distillation process used to purify the fish oil away from potential contaminants (PBC, mercury etc.)
      • The DHA is removed (which makes it “free DHA” or an “ethyl ester”) and companies just leave it in this form when it’s all put back together into fish oil
  • Rhonda eats salmon roe (and did so during her pregnancy as well)
    • It’s a low mercury fish
    • It also has something called astazanthin in it
    • You can buy flying fish roe at Japanese markets

DHA and Pregnancy

  • DHA in the phospholipid form gets taken up into the developing fetal brain quicker than DHA in the non-phospholipid form

DHA and Alzheimer’s Disease

  • DHA (specifically in fish form) has been shown to ameliorate some of the neuro-pathological characteristics in Alzheimer’s patients (most of which carry ApoE4) and also to improve cognitive function
    • What dose? – The more fish, the more the benefit
      • Eating it 3-4x a week, is better than 1x a wek
    • BUT this hasn’t been shown yet with supplemental DHA in the phospholipid form (for ApoE4 carriers) (Rhonda hopes research will be done in this area soon) (final note – it seems like you can’t purchase supplemental DHA in the phospholipid for, it’s only available for research purposes)
  • Studies have shown, however, that in non-ApoE4 carriers (it’s assumed without Alzheimer’s Disease?), benefits were seen at 2g of DHA per day (in the non-phospholipid form – aka normal fish oil)
    • So the question becomes, do ApoE4 carriers need 4g/day+ of non-phospholipid DGA (normal fish oil), and/or DHA in the phospholipid form)

What about vegans?

  • If you want to slow brain aging, or you’re an ApoE4 carrier, and you want to follow a vegetarian/vegan diet, what can you do?
    • ALA (alpha-linolenic acid), which is found in plants like flax seeds and walnuts, is a source of omega-3s, which does get converted to EPA and DHA (the two other omega-3s predominantly found in marine organisms)
      • But it doesn’t get converted all that well
      • Estrogen can improve this conversion
      • Gene SNPs also play a role – some people convert better than others
    • Micro algae is also a good supplement to think – it has more DHA, so it bypasses this conversion
    • “Honestly though, I think it’s best if you just eat some fish roe or fish”

How can people figure out if they are an ApoE4 carrier?

  • 23andMe and AncestoryDNA
  • BUT keep in mind – “There are errors in the methods that they use to sequence the variety of these genes that they’re looking at. You may be told that you’re an ApoE4 carrier, but the testing wasn’t actually accurate, or vice versa.”
    • In particular, ApoE is a difficult one to test, as well – “It’s one of the gene’s that’s most likely to not be accurate”
  • Rhonda has a cool tool on her site that allows you to upload your 23andMe data to get some pretty interesting data

What does Rhonda’s diet look like?

  • For the most part, she just tries to make sure she’s getting all her micronutrients (there are about 30-40 essential ones)
    • These are vitamins, minerals, essential fatty acids, and amino acids that we can’t produce, so we have to get them from our diet
    • They’re not only important for short-term survival, but also for aging
  • Some examples – folate, vitamin k1/k2, magnesium, calcium, carotenoids 
    • Leafy greens are really high in folate, magnesium, vitamin k1, calcium, lutein and zeaxanthin (both carotenoids important for preventing degeneration of the retina, as well as for brain health), and vitamin C
      • “If I don’t have greens with a meal, including breakfast, it’s totally mental, but I feel deprived, like I’m aging my cells”
  • More of what she eats:
    • Healthy fats (avacado, nuts) as a snack
    • She’ll commonly have suateed kale with eggs for breakfast (eggs are high in choline)
    • For protein, she eats mainly the omega-3 fatty acid proteins (wild Alaskan salmon – this is very low in mercury)
    • In the winter, she’ll make more stews with grass fed beef and sometimes good quality chicken
  • Most people are deficient in the micronutrients you find in leafy greens 
    • Folate is very important for making new cells in the body – it’s a precursor to make a DNA nucleotide called thymine (if you don’t have enough folate, you end up putting another nucleotide called uracil, which is from RNA, which sort of damages the DNA strand) 
      • We’re CONSTANTLY making new cells
    • Folate is also important for providing precursors for epigenetics (being able to turn on/off genes at different times)
      • You need certain molecules to do this, and folate helps provide those molecules
    • Vitamin k1 is also very high in leafy greens
      • It’s important for blood clotting
      • But when you get enough k1, it actually serves the function of what k2 does 
      • Both k1 and k2 play important roles in calcium homeostasis, and specifically removing calcium from the blood stream to prevent calcium plaques from forming

What else did Rhonda do, nutrition wise, while pregnant?

  • She mainly just focused on getting all her micronutrients
  • She did eat a lot of wild Alaskan salmon
    • Why? – Studies show that the omega-3 fatty acids in the salmon protect against mercury toxicity (specifically in developing fetal brains) – this goes against common pediatrician recommendations 
    • “Not eating fish might actually be worse than eating fish low in mercury”
  • She ate a lot of fruits, and whole grains
    • Sometimes oatmeal with nuts and berriers
  • Anything she avoided?
    • Sugar for the most part, as well as anything processed
    • Rice due to its high arsenic content (shrimp are really high in arsenic)
    • She was cautious of dark chocolate, which can be high in cadmium and arsenic
    • She didn’t drink out of ANY plastic bottles (even the BPA free bottles because the BPS has been showing to have similar effects) 
      • Phthalates in the plastic were also a concern
        • Several studies have shown phthalates are linked to developmental delays 
        • (Phthalates are also found in nail polish, hair sprays, plastic packaging, and vinal flooring)
        • Phthaletes also effect testosterone levels in pregnant women
      • Also metal cans as well, to avoid any trace metals
    • Broccoli sprouts (which are normally VERY good for you because they’re high in sulforaphane) because of the potential for ecoli contamination

Random

  • Rhonda says she used to have high LDL cholesterol, which she thinks was a result of cooking a lot of coconut oil (which is high in saturated fat)
    • Saturated fat can raise LDL cholesterol
    • She says after cutting it out, her levels dropped significantly 
  • Arsenic and cadmium are excreteted 15x more in sweat than urine
    • Mercury is mostly excreted through urine
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