Thanks - took a while to get the files and then get them formatted. Dr. Barzilai and Dr. Zazala were on that panel, and it was a pleasure to meet them.
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I find the “by design” hypothesis compelling. It looks like the original ideal design is gradually eroded by cumulative damage, leading to a final outcome that may likely deviate from the designer’s intended goal. But what was the initial ideal blueprint if there was one at all? We cannot avoid damage unfortunately…
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I agree also that evolution selects for mean lifespan. This is very obvious when you look at different species. If people want I can give a link to one of my posts about this.
My own conclusion is that the aging and development clocks are the same clock. That is in my poster for BSRA again if people want the link to this again just ask.
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Yes, pls post the link.
This is the link which looks at evolution selecting for mean lifespan.
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There is always hope that if we can’t cure Alzheimer’s, at least little by little, we are reducing the per capita incidence.
Nick (PhD, Oxford; MD, Harvard) is one of my favorite YouTube MDs. His videos are a little shorter than most, and he is not always trying to sell anything or get you to upgrade to “Patreon,” ring that bell, etc.
He is personally interested in Alzheimer’s because he possesses two copies of the APOE4 gene variation.
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What oil is it? (20 chars)
lysophosphotydlcholine, probably spelled wrong. Krill oil is a pretty good source.
I take phosphatydlcholine off and on and he never said whether that would help, or if he did I did’t understand it.
Krill oil--------------------------------------------
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So … I think the thing that seems to be clear is that individuals with ApoE4’s (especially homozygous) have real problems getting DHA into their brain (not EPA of which a small % will be converted to DHA).
If the DHA is phospholipid bound then it bypasses the defective receptor … thus an argument for NOT using standard fish oil capsules as they are stripped of their phospholipids. Krill is bound to phospholipids, but also has high risk of being rancid and actually being very hard to determine that it is rancid.
We then see a variety of DHA with phospholipids — and that makes individuals feel like they’ve solve the issue, but when one looks into almost all, they are just DHA/EPA with some mixed phospholipids, but the phospholipids are not actually bound to the DHA.
We know the fatty fish with plenty of Omega 3’s has most of the DHA phospholipid bound … so getting wild caught salmon (biggest fish I’d advise), mackerel, sardines is a good back up. Then I have my backup addition of Krill with the Naturebell product that has a fair bit in it. Amazon.com: Antarctic Krill Oil 2000mg Supplement, 240 Softgels, 3X Strength Natural Source of Omega-3s, EPA 240mg + DHA 160mg + Astaxanthin 800mcg – No Fishy Aftertaste – Mercury Free & Non-GMO : Health & Household
and I take a double dose as I’m trying to get close to 1000 mg of Omega 3’s per day between this and fish.
There are all types of fancy and expensive options out there … this is my current strategy, but it continues to evolve and next month I might change to something different.
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That is true, but:
“Krill are processed quickly on board factory ships in cold Antarctic waters, often within hours of harvest, which reduces pre-extraction spoilage.”
And krill oil contains astaxanthin, an antioxidant, which makes krill oil red and generally gives it a longer shelf life. However, I can’t find any good papers that provide a controlled comparison. i.e., date manufactured, constant temperatures, etc.
But my guess is krill oil has a better shelf life than fish oil, if only because it seems a little more direct to the consumer.
Two brands that were tested; there may be others equally as good:
Kori Pure Antarctic Krill Oil 1200 mg (Labdoor test page): Tested 2025.
Labdoor
Viva Naturals Antarctic Krill Oil (Labdoor test page): PV 1.53 mEq/kg (well below PV 5 limit). Tested Feb 2025.
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So you take 4 softgells correct? Do you worry about increased atrial fibrillation risk?
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The total DHA+EPA is 4 softgels is slightly under 1000 mg and at least in the review I read - it was only in doses significantly over 1 gram of DHA/EPA that we saw excess in AF.
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Are we sure that phospholipid form (Krill Oil) has better absorption/diffusion across the BBB? I only looked at 1 review paper from 2020, but that review basically states that Krill oil has better bioavailability across enterocytes and is broken down into FFA and incorporated into micelles in the GI tract. That’s what I would expect. Doesn’t sound like a phospholipid/fatty acid is absorbed intact into the plasma. The studies they reviewed show either equal plasma/brain levels with KO vs FO, or higher levels with KO which you could easily overcome by taking higher doses of fish oil (cheaper). Just curious because I’ve never looked into it before.
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We know that consuming it in fish does get across the BBB, and standard fish oil tablets strip the phospholipids, whereas krill doesn’t. In individuals without an ApoE4, it gets across either way - however, the understanding we have right now, is that in individuals with an ApoE4 there is a defective DHA transporter … and I’m not clear on how much worse it is to be hetero vs. homozygous - but in that group of individuals, phospholipid bound gets across and bypasses the receptor.
So going up on the dose of standard fish oil will get more EPA in your brain, of which a small % will go to DHA … but really wouldn’t address the issue.
I think the knowledge in this area isn’t complete yet and will likely evolve - but wild caught small fatty fish and krill oil is my current approach.
- Mechanism: APOE4 alters lipidation of apolipoproteins via ABCA1 transporter dysfunction, leading to deficient DHA delivery into the brain 1.
-
Quantitative differences:
- PET tracer studies with ^11C-DHA demonstrated that APOE4 carriers had a ~30% higher uptake of DHA from plasma to brain compared to noncarriers, suggesting increased demand due to baseline DHA deficit 1.
- In cerebrospinal fluid measurements after DHA supplementation, APOE4 carriers showed significantly lower increases in DHA levels compared to noncarriers, consistent with impaired incorporation 1.
- This deficit is dose-dependent on APOE4 allele load: homozygous ε4/ε4 show substantially greater impairment than heterozygous ε3/ε4 or ε2/ε4, although exact quantitative comparisons are limited by small trial sizes 2.
| DHA Form | BBB Transport Mechanism | Effectiveness in Brain Uptake | Clinical Evidence (esp. in APOE4) |
|---|---|---|---|
| Triglyceride DHA (fish oil) | Limited passive diffusion | Poor direct brain accretion | Weak CSF rise; reduced in APOE4 5 |
| Free DHA (NE-DHA) | FATP1, FABP5-mediated transport | Moderate | Suboptimal in APOE4 2 |
| Phospholipid DHA (e.g., PL-DHA) | Esterified sn-2 transport, partially MFSD2A | Better than triglyceride | Higher brain accretion in animal/human studies 4 |
| LysoPC-DHA (phospholipid-bound, especially sn-2) | MFSD2A transporter | Most efficient BBB uptake | Strong experimental support; promising strategy in APOE4 1 |
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