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.
1 Like
Krill oil--------------------------------------------
1 Like
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.
8 Likes
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.
6 Likes
So you take 4 softgells correct? Do you worry about increased atrial fibrillation risk?
2 Likes
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.
2 Likes
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.
2 Likes
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 |
6 Likes
It looks like most of the phospholipid-O3 in Krill oil is bound at sn-2. When cleaved by PLA2 in the intestinal tract you get FFA similar to standard TAG-O3. In order for Krill oil to yield LPC-O3 you need to cleave at sn-1 which doesn’t happen in the body to my knowledge.
2 Likes
What about Plasmalogen bound DHA ? Plasmalogen is a special type of phospholipid that is present predominantly in the human brain and heart.
DHA bound Plasmalogen is available under product name Prodrome Neuro, but is quite pricy : I pay $335 for a 90 day supply of 900mg of Plasmalogen bound to DHA (not clear how much of that is DHA vs Plasmalogen precursor). The primary benefit is supposed to be the Plasmalogen precursor, but the DHA bound version is supposed to be particularly beneficial for the brain. There is another version called Prodrome Glia where the Plasmalogen is bound to Omega-9, that is supposed to be optimal for the nerves outside the brain : This one is around $185 for a 90 day supply of 900mg of Plasmalogen precursor bound to Omega-9.
Hi, I never really know what to target. Do you have a specific research rationale for this level? And do you aim for a specific DHA EPA ratio?
I’m at 3 portions of sardines/salmon a week. So roughly 5000 mg per week. Just wondering whether to go an extra portion of sushi…
We target to Omega 3 index, for most people taking a bit of fish plus ~1 gram EPA+DHA gets a reasonable % to our goal of 8%. The issue remains – what gets to the brain in ApoE4 individuals.
The argument for the plasmalogen which is expensive is something I’ve reviewed - and given that we have adequate research showing eating fish gets to the brain in those with ApoE4’s I’m not inclined to purchase that product.
The discussion with @Shady is interesting as by that approach, we’d think omega 3’s consumed in fish would not be transported across the BBB - yet they are (in those with ApoE4’s). I think there is more to the story … and I suspect my recommendations will likely have to evolve as new information comes available.
3 Likes
@DrFraser as you know not all O-3 in fish is TAG bound. Depending on the fish diet there are papers showing up to 40% of O-3 are phospholipid form. The lowest I found was ~3%. A lesser percentage being LPC-O3. I think if you want to increase dietary LPC-O3 you either need more fatty fish, fish roe (best source), or the Accentrate product which is LPC form. The metabolism pathway I described above for Krill Oil was described in a paper from the Alzheimer’s Drug Discovery Foundation.
1 Like
Thought this was interesting, in terms of target levels. The mouse study suggests quite a high dose of the best “lysophosphatidylcholine” form of DHA: 452mg. Or double that for the next best phospholipid form (phosphatidylserine) and 7 to 17x for the non-phospholipid form - triacylglycerol DHA (TAG).
If eating sardines that would require at least 2 tins a day?
“Using the allometric scaling [50], we calculate that the human equivalent daily dose of LPC-DHA for efficient brain enrichment is about 452 mg DHA for a 70 kg person, whereas the dosage using TAG-DHA, based on the previous studies, is about 3.4 g to 8.9 g of DHA per day.”
This metabolic pathway diagram is quite neat. But it suggests that the phospholipid-bound dha in Krill oil, containing being sn2 form won’t help DHA brain levels.
“Based on the results presented here, we conclude that the most commonly used carriers of DHA, namely TAG-DHA (as in fish oil), sn-2 DHA PC (as in krill oil) or ethyl esters (as in Lovaza®, Omacor®) do not enrich brain DHA, because they are absorbed as TAG, which is not efficiently converted to LPC-DHA in the liver”
1 Like
My apology in advance if this was posted before. These short trials – 8 weeks in this case – irritate me but the findings are modestly positive.
1 Like
A new paper (pointed to by @nicknorwitzMDPhD).
Lithium orotate, not galantamine hydrochloride, memantine, or rivastigmine, is the only medication that I know of that addresses prevention, symptoms, and possible reversal of dementia progression.
“https://www.youtube.com/watch?v=Hcz0Eyp1LE4”
Lithium deficiency and the onset of Alzheimer’s disease | Nature
3 Likes
back on my hobby horse topic : “how much phospholipid-bound DHA is enough?”… this association (only) study I posted elsewhere suggests 4 portions of fish a week is better than 3 (the % relates to vascular brain disease in 75 year olds and is rather terrifyingly high!)
“Researchers found that among people who ate no fish, 31% had markers of severe underlying vascular brain disease, compared to 23% of those who ate three servings a week, and 18% of those who ate four or more servings of fish per week. This association between lower fish consumption and greater severity of markers of vascular brain disease was independent of any differences in brain volumes and other variables like age and sex.”
3 Likes
Another interesting one…
https://www.medscape.com/viewarticle/experimental-med-tied-slowed-alzheimers-biomarker-2025a1000lo8
1 Like