Plasmalogens- exciting new evidence

[Dayan Goodenowe]

I made detailed videos for the scientifically adventurous - both regarding how the APOE alleles and plasmalogens contribute to cognition, cholesterol regulation, and amyloid as well as the research supporting plasmalogens and neurodegeneration here: https://www.prodromesciences.com/science

[apod]

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.

Super interesting. My concern here would be that the Kickstarter campaign claims that the plasmalogen oil is "proven to prevent neurodegeneration", yet, the reference listed is a different compound with lipoid acid (which the product for sale does not include). Lipoic acid itself, for instance, has been showed to offer "profound" dopaminergic protection in mouse-models of neurodegeneration https://www.ncbi.nlm.nih.gov/pubmed/26084861

[Dayan Goodenowe]

Trying not to go too far down the rabbit hole. My primary interest is in the elevation of blood plasmalogens to maintain protective levels, which is what the plasmalogen oils are designed to do. The human blood and brain data linking low plasmalogen levels with an increased risk of dementia is well documented. In parkinsonian monkeys treated with PPI-1011, it is the blood levels of the target plasmalogen that correlate with improved function - see figure 5 in https://www.ncbi.nlm.nih.gov/pubmed/25771209. Lipoic acid is a very interesting and well studied molecule, however it only makes up 25% of PPI-1011, which makes its dose only 2.5-12.5 mg/kg in the PPI-1011 studies. I have been taking the supplement for over a month now - I felt that it was important to take it myself before giving it to others. After about 2 weeks I started noticing a change in my vision - at first, I was concerned because my vision was blurred when reading, but then I realized it was because of my glasses - when I took them off, I could see clearly. Now, I cannot use my glasses for reading anything within 3-4 feet. This was totally unexpected. On a more personal note, my dad is 82 and e4 positive. I have been able to keep his blood plasmalogen levels high for the last 6-7 years by using a supplement cocktail to prevent degradation of and moderate resistance training to stimulate the synthesis of plasmalogens. He actually has levels better than me and is currently healthier than most 60 year-olds. I know that it is selfish, but I am just glad that I was able to get this product made in time for when he needs it most. But hey - he is my dad. Ultimately, it is a decision that everyone must make for themselves. For me, low plasmalogens is just something I am not willing to (or see any reason to) risk.

[babl]

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…

Learning so much here! So exciting! I'm very tempted to pick up some of the plasmalogen oil from the Indiegogo campaign, but would much prefer to try it in a more (or less! ) 'scientific' way. Meaning, I'd like to do some before and after biomarker tests to see if the plasmalogen actually affects some real numbers. I'm a big tracker of my own biomarkers as I like to know what's going on in my body, and what the various things I try do to them.

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.

One last question for folks on this thread -- being a Rhonda Patrick junkie, I've added salmon roe to my diet as a way of increasing phospholipids. I wonder if it might also contain plasmalogen? Didn't see salmon roe mentioned in any of the comments here, though. Does anyone know?

[Tincup]

Hi friends, I see that Dr. Goodenowe's plasmalogen supplement is available for pre-order through an Indiegogo campaign. I'm tempted to bite. Anyone else?

My wife and I did purchase a year's supply, each off the indiegogo campaign.

[Julie G]

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.

babl, I'm happy you asked about this. It's a great opportunity to update the whole community. For anyone unfamiliar with the proposed project, you can read about it here. One of our collaborators, OpenCures, accidentally missed a deadline for an NIH grant they were trying to secure to lower costs for our members. They've since reapplied and the grant is currently under review by NIH. We did spend some time exploring the price of participating in the project without financial assistance and our BOD found the cost to be prohibitive. Once we hear anything, we will pass the information along to you.

My wife and I did purchase a year's supply, each off the indiegogo campaign.

FWIW, I did the same. I'm excited to give this a try.

[babl]

I signed up for the Indiegogo campaign, also. Are there specific biomarkers I can be tracking to check for plasmalogen levels, other than a lipid panel?

[docmaas]

https://www.cambridge.org/core/journals ... ore-reader#

I'm guessing there is a tight connection between inositol and plasmalogens and suspect addition of either can enhance the other. As noted in my experience I saw significant insulin resistance reduction after 30 days on neuro-plas and also saw less but still positive impact on ir on 2g of myo-inositol/day over 30 days. I think I also rested better and my memory seemed better as well on neuro-plas, maybe because of resting better.

There are reports that the statin pitavastatin also positively impacts plasmalogens and remant cholesterol more that other statins and is also reputed to be lower in nod (new onset diabetes) though the whole diabetes question appears to be unsettled as regards any of the statins.

Personally after a 2 week washout of berberine I now tolerate pitavastatin very well. Berberine is a powerful cp-450 impacter particulary for the 2c9 transporter which is used by pitavastatin.

Thinking seriously of the current Indiegogo offer and a new Tesla Cybertruck.

Mike

[mike]

Thinking seriously of the current Indiegogo offer and a new Tesla Cybertruck.
Mike

If you ask me. It looks like a stealth bomber...
This from another Mike whose license plate reads: MODELT3

[docmaas]

Yes it does a bit. Hadn't really noticed it till you mentioned it.

Mike