Plasmalogens- exciting new evidence

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Julie G
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Re: Plasmalogens- exciting new evidence

Postby Julie G » Sat May 25, 2019 1:51 pm

I wonder if Dr. Goodenowe would share his thoughts on the lipophilic stain question?

Lol, chrissyr. I'm one step ahead of you and already got his response:
Hi Julie,
The issue of cholesterol gets contentious because people confuse biomarkers of cholesterol with the function of cholesterol. Circulating cholesterol biomarkers (total, ldl, hdl) are crude biomarkers that we can use to infer the relative status of biological functions that are influenced by cholesterol levels. Cholesterol exerts its biological function in membranes, which is where 80% of your body’s cholesterol resides. This cholesterol cannot be detected by blood tests. However, it can be inferred from biological processes known to be heavily influenced by membrane cholesterol levels – like APP processing. The Crum paper indirectly shows that statin use does not affect membrane cholesterol levels in the brain (i.e. no change in amyloid). For example, high levels of HDL cholesterol is good because it infers that membrane levels will be lower. If you translate the Michikawa figure to the human brain, then e2 carriers would have high brain HDL-cholesterol (good) and e4 carriers would have low HDL-cholesterol (bad), however, this translates into the exact opposite effect in the membrane where the e2 membrane will have low cholesterol (good) and the e4 membrane will have high cholesterol (bad).

One of the possible pleiotropic effects of statins is as a ppar agonist. This would explain the data in the barter paper that shows that the increase in HDL is associated with a decrease in triglycerides (a ppar effect). The subtle nature of the effect means that the most likely ppar subtype is gamma (but it could be a bit of alpha too – I do not know the relative specificities of the different statins on the different ppar types at different doses). Ppar-gamma induction is neuroprotective and increases plasmalogens and may explain the association between statin use and reduced AD in some studies – may also explain negative muscle symptoms in some statin users. Discussing this further requires a lot of detail digging, and I am not totally up to speed on all the research in this area.

When we start talking about off-target drug effects, things get really complicated and it become very difficult to determine what is affecting what.

I hope that this is helpful.

Best wishes,
Dayan

Clear as mud, eh? Later today, I'll try to refer back to the Crum paper to assess the size of the dataset, etc. If anyone else can make any inferences, I'm all ears.

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MarcR
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Re: Plasmalogens- exciting new evidence

Postby MarcR » Sat May 25, 2019 4:07 pm

The evidence that high plasmalogen levels (PBV) protect against dementia is compelling. Unfortunately, there are no commercially available PBV tests. What's the best practical way to estimate PBV?

In Table 4, I see that the strongest relationship in the entire matrix connects plasmalogens (PBV) with triglycerides with a coefficient of -0.043. (The negative coefficient relates high PBV with low trigs.) Looking further on the PBV row, I see that the relationship with HDL-C, while only two-thirds as strong (abs(0.029) / abs(-0.043) = 67%), offers another angle. In contrast, the PBV-predictive value of the composite HDL-R ratio (0.020) suffers considerably from the relative irrelevance of TC (0.009) and is less than half as strong as triglycerides.

So from the data presented in this new paper, I conclude that the popular trigs/HDL-C ratio, already well established as a marker of insulin resistance, offers the best readily available hint regarding one's PBV levels. In the absence of something more definitive, I'm going to use this as my personal rule of thumb:

trigs/HDL-C < 1 --> high PBV
trigs/HDL-C >1 and <2 --> middling PBV
trigs/HDL-C >2 --> low PBV

I wonder why HDL-R was featured in this paper rather than trigs/HDL-C. I would love to see trigs/HDL-C rows in Tables 1 and 3 and columns in Figure 1 and Table 4.

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Re: Plasmalogens- exciting new evidence

Postby chrissyr » Sat May 25, 2019 5:25 pm

Julie G wrote:Lol, chrissyr. I'm one step ahead of you and already got his response:


Oh you are many many many steps ahead of me, my friend, and I thank you for that!

Yes, clear as mud, to be expected!

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Re: Plasmalogens- exciting new evidence

Postby chrissyr » Sun May 26, 2019 4:53 am

Lipidomic analyses revealed that statin treatment i) reduced the content of oxidizable polyunsaturated phosphatidylcholine (PUPC) species containing DHA and linoleic acid in LDL; ii) preferentially increased the content of PUPC species containing arachidonic acid (AA) in small, dense HDL3; iii) induced significant elevation in the content of phosphatidylcholine and phosphatidylethanolamine (PE) plasmalogens containing AA and DHA in HDL3; and iv) induced formation of HDL3 particles with increased capacity to inactivate PCOOH with formation of redox-inactive phospholipid hydroxide. Statin action attenuated LDL oxidability Concomitantly, the capacity of HDL3 to inactivate redox-active PCOOH was enhanced relative to HDL2, consistent with preferential enrichment of PE plasmalogens and PUPC in HDL3.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087874/

I didn't see study posted, apologies if it was. The study was on men with metabolic syndrome.

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Stavia
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Re: Plasmalogens- exciting new evidence

Postby Stavia » Tue May 28, 2019 3:06 am

Brand new Plasmalogen supplement. Ethanolamine- plasmalogen 14mg per capsule with DHA at sn-2.
Made here in New Zealand from local marine sources. I have been trying it for almost 2 weeks, I was very kindly given a bottle to trial.
Dunno if its placebo but I feel sharper and sleeping better. More energy.
Its very expensive to make which is consistent with Dr Goodenowe's reports on manufacturing costs.
I will probably add it to my stack on an ongoing basis. I do eat our green lipped mussels often but I'd like to hedge my bets. There is enough evidence to support me paying for it. My trig/hdl ratio is good, but I'm not convinced its a specific enough surrogate marker for plasmalogen status. ImageImageImage

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Re: Plasmalogens- exciting new evidence

Postby mike » Tue May 28, 2019 12:43 pm

$130 US / month on Biomer's international website - is it cheaper in-country?
Sonoma Mike
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Stavia
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Re: Plasmalogens- exciting new evidence

Postby Stavia » Tue May 28, 2019 1:02 pm

Its not on his local website currently. I emailed him last night to ask. Ill let you know

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Rainbow
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Re: Plasmalogens- exciting new evidence

Postby Rainbow » Sat Jun 08, 2019 11:08 am

Stavia wrote:Its not on his local website currently. I emailed him last night to ask. Ill let you know
Stavia, did you manage to find out about this? I'd also be curious to know.
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Stavia
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Re: Plasmalogens- exciting new evidence

Postby Stavia » Sat Jun 08, 2019 12:17 pm

Sorry Rainbow, yes I did.
Its not available here in New Zealand from a local website yet.
I've been taking it for 3 weeks now - sleeping really well which is unexpected.
We are travelling overseas currently and I normally have to take sleeping pills for jetlag but not this time. Correlation. Very difficult to tease out causation.

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Rainbow
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Re: Plasmalogens- exciting new evidence

Postby Rainbow » Sat Jun 08, 2019 3:39 pm

Stavia wrote:Sorry Rainbow, yes I did.
Its not available here in New Zealand from a local website yet.
I've been taking it for 3 weeks now - sleeping really well which is unexpected.
We are travelling overseas currently and I normally have to take sleeping pills for jetlag but not this time. Correlation. Very difficult to tease out causation.
Thanks for letting me know! That's great that you've been sleeping well. Fingers crossed that it's more than correlation (but no assumptions made).

My parents and I might take the plunge and give this supplement a go too. If only for a month or two to see whether it noticeably affects our sleep or energy levels.
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