Not all Omega 3's are the same...?

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
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Not all Omega 3's are the same...?

Postby broiler_x » Mon Oct 08, 2018 8:11 am

An interesting new paper was just published last week which proposed a theory to explain why dietary supplementation of omega 3 is not as beneficial as diet-derived omega 3 for ApoE4 carriers (specifically the omega 3 called DHA).

FASEB J. 2018 Oct 5:fj201801412R. doi: 10.1096/fj.201801412R. [Epub ahead of print]
Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.
Patrick RP1.


Dietary and supplemental intake of the ω-3 fatty acid docosahexaenoic acid (DHA) reduces risk of Alzheimer's disease (AD) and ameliorates symptoms. The apolipoprotein E ( APOE) 4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. The mechanisms behind this varied response remain unknown. I posit that the difference is that fish contain DHA in phospholipid form, whereas fish oil supplements do not. This influences whether DHA is metabolized to nonesterified DHA (free DHA) or a phospholipid form called lysophosphatidylcholine DHA (DHA-lysoPC). Free DHA is transported across the outer membrane leaflet of the blood-brain barrier (BBB) via passive diffusion, and DHA-lysoPC is transported across the inner membrane leaflet of the BBB via the major facilitator superfamily domain-containing protein 2A. I propose that APOE4 carriers have impaired brain transport of free DHA but not of DHA-lysoPC, as a consequence of a breakdown in the outer membrane leaflet of the BBB, putting them at increased risk for AD. Dietary sources of DHA in phospholipid form may provide a means to increase plasma levels of DHA-lysoPC, thereby decreasing the risk of AD.-Patrick, R. P. Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.

Her conclusion is that the diet-derived DHA is in a phospholipid form which is able to cross the blood brain barrier much better than free DHA (as found in most supplements) in ApoE4 people.

Does this mean we should just be eating fish and dumping our omega 3 supplements? Actually I found that you can find supplements that contain DHA in the phospholipid form (at least that's what is claimed), and it appears that any omega 3 that comes from Krill oil should be high in phospholipid form DHA. The author even hints at that in the final sentence of her paper:

"There is a pressing need for clinical trials evaluating the effects of omega-3 in phospholipid form, either from fish roe oil or krill oil, on cognitive function in APOE4 carriers with AD."

Personally I just bought some krill oil based supplements. I will not post a link to any products, as I don't want to appear to be promoting anything. They're pretty easy to find.

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Re: Not all Omega 3's are the same...?

Postby circular » Mon Oct 08, 2018 9:25 am

Thanks for posting this broiler, many of us have been waiting a good while to see this paper. Rhonda Patrick is one of my favorite podcasters to listen to and learn from. I have some questions about this I hope will become clearer as time goes on:

1) Last night I listened to Peter Attia's interview with Dr. Richard Isaacson. The latter made an unequivocal statement, presumably arising from some published or unpublished research, that apoe4's benefit from DHA but that it takes them longer to achieve the results. I think he said due to our faster cycling of it. Julie has mentioned a number of times here that we may just need more of it since we cycle it fast, where Dr. Isaacson was suggesting we just need to be taking it for longer, I guess to let it build up. This is all very vague, but I wonder whether Dr. Patrick has parsed it all out already.

2) Dr. Patrick used to take Nordic Naturals 'Omega-3 Phospholipids', 'the potent alternative to krill'. When I learned that I started using them too. This, theoretically, has dovetailed nicely with my need to address my very hampered choline SNPs (three SNPs all homozygous). Then I learned that Dr. Patrick had switched to salmon roe but I stayed with the NN product. Some time later I began dipping into what may be inflammatory affects of neu5gc that are high in some animal products. Interestingly while neu5gc levels are low in fish, they are very high in roe.

Since I'm not inclined to eat roe, I'm hoping maybe supplementing with the NN O-3 phospholipids for long enough will work just fine.

Just found the link to PDF here.
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Not all Omega 3's are the same...?

Postby Julie G » Wed Oct 10, 2018 3:12 pm

Thanks for sharing. This feels significant for us and could explain the inconsistencies that we’ve seen in research. I could be wrong, but isn’t the phospholipid form of DHA a component of the plasmalogen precursor that Dr. Goodenowe is trialing to raise plasmalogen levels outlined in this thread? If so, this represents a convergence of several moving pieces for us. BTW, I love that Dr. Patrick, a fellow E4 carrier is working on this :D.

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Re: Not all Omega 3's are the same...?

Postby LG1 » Sat Jan 12, 2019 8:28 pm

Fascinating topic. I immediately purchased salmon roe online. Very expensive. I’m embarrassed to say I can’t stomach it at all. It is revolting. It looks so pretty in the picture :). I’m not sure what to do with it! If anyone has any ideas on how to hide the taste let me know I’ve tried several things already and they don’t work. Right now it’s in my freezer.

Clearly I will be taking the krill supplement for now.

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Re: Not all Omega 3's are the same...?

Postby SoCalGuy » Sat Jan 12, 2019 10:06 pm

It tends to work best in sushi. I agree it is very difficult to eat on it's own. I get some periodically from a local health store and I take it like medicine, a spoonful that I down as quickly as possible.

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