Dayan Goodenowe wrote:Hi everyone,
Excellent questions. The metabolic precursor to the blood and membrane plasmalogens (the vinyl ether phospholipid form) is the 1-O-alkyl, 2-acyl glycerol (free hydroxy at sn-3). Detailed structure activity of modulating specific plasmalogen species using specific alkyl-acyl glycerols is published here https://www.ncbi.nlm.nih.gov/pubmed/20546600. Of particular interest to the APOE e4 community is figure 8 which shows that only highly unsaturated fatty acid containing plasmalogens (C1, C9, C10) are effective at lowering cholesterol and that they do this by increasing cholesterol esterification (i.e. clearance). It is these same species that also lower amyloid levels. It is decreased levels of these species of vinyl ether phospholipids that have the strongest association with reduced cognition and increased mortality and it is these same species that we recently showed that high blood levels neutralize the e4 effect on cognition https://www.ncbi.nlm.nih.gov/pubmed/31022959. PPI-1011 is a non-natural precursor to the DHA 1-O-alkylglycerol (C1 in the above paper) that I invented in my drug development days to be orally bioavailable. The detailed bioavailability is published here https://www.ncbi.nlm.nih.gov/pubmed/22142382. My new plasmalogen oils are a natural version of PPI-1011 that in addition to DHA also contains EPA. The only difference is that instead of lipoic acid at sn-3 (which does not naturally occur), my new oils contain a fatty acid at sn-3 (which does naturally occur). I use DHA and EPA at sn-3 - so, as an added benefit, the new oils completely replace your current omega-3 supplements. In regards to PPI-1011 the neuroprotection was afforded from 10-50 mg/kg - which in a 75kg (~170lb) person is 750-3750mg/day, which is pretty reasonable. 1ml of the plasmalogen oil contains 900mg of the 1-O-alkyl-2,3-diacylglycerol. In regards to the bioavailability question, it is getting the DHA fatty acid from the dietary source, through the gut and then on to the blood phospholipids - specifically the sn-2 position of blood phospholipids that has to happen. 1-O-alkyl-2-DHA-3-OH is very good at this. Regular dietary phospholipids and triacylglycerols are digested to create free fatty acids in the gut - phospholipase A2 for phospholipids and lipases for triacylglycerols. These dietary components cannot transfer their sn-2 fatty acids directly to phospholipids in the blood. The free fatty acids have to find their way onto phospholipids. The plasmalogen oils deliver the DHA 1-O-alkylglycerol, which directly enters the biosynthetic pathway and retains the DHA as described in the linked papers.
Julie G wrote:Our proposed biomarker study will enable us to monitor all of the biomarkers utilized in this paper, plus give us access to a plasmalogen precursor supplement that raises levels. I’m hopeful that the NIH will see value in approving a grant that will help us move forward…
Julie -- I'm also very interested in this proposed biomarker study you've mentioned. I searched the forum here but didn't see it anywhere. Is there a link you could post? I just did another round of tests for myself and am always up for adding to this sort of citizen-science.
My wife and I did purchase a year's supply, each off the indiegogo campaign.
docmaas wrote:Thinking seriously of the current Indiegogo offer and a new Tesla Cybertruck.
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