Plasmalogens- exciting new evidence

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SusanJ
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Re: Plasmalogens- exciting new evidence

Postby SusanJ » Mon Feb 19, 2018 8:02 am

Orangeblossom wrote:I wonder about possible other sources of Choline. Can it be taken in a supplement?


Other sources besides eggs include beef liver, fish, chicken, red meat, asparagus, beets, broccoli, Brussels sprouts, cauliflower, flax, green peas, lentils, quinoa, shiitake mushrooms and spinach. You'd have to track in Cronometer to see if you're getting enough.

I use sunflower lecithin (not daily though) as a natural source of phosphatidylcholine.

You can also supplement choline, or phosphatidylcholine (or citicoline or alphaGPC, which cross the BBB and helps cognition). Some prefer choline because your body will decide whether it needs to make phosphatidylcholine or acetylcholine (neurotransmitter), or convert to betaine (aka TMG), which acts as an important methyl donor in the methylation cycle. You might need to experiment to see which works best for you.

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Re: Plasmalogens- exciting new evidence

Postby Orangeblossom » Mon Feb 19, 2018 8:47 am

Thanks Susan.

Hmm, it seems other phospholipid changes take place in AD not just plasmalogens.. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565322/

HDL has phospholipids in it I take it, so reduced levels of HDL means reduced phospholipids?

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Re: Plasmalogens- exciting new evidence

Postby Searcher » Mon Feb 19, 2018 9:13 am

Stavia wrote: I was asking specifically if dietary arachidonic acid from eggs has been linked to raised inflammation in vivo.


Stavia,

Cholesterol in eggs seems to be the culprit: increasing inflammatory markers in lean insulin-sensitive subjects but (surprisingly) decreasing them in insulin-resistant subjects. They used 4 eggs per day for 4 weeks.

http://circ.ahajournals.org/content/111/23/3058.long

Eggs up to 7 per week seem neutral with regard to inflammatory markers, according to the Empirical Dietary Inflammation Index.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958288/

I used to eat 3 eggs a day but cut back to 1 per day after reviewing the literature on the dose-response gradient of all-cause mortality and morbidity with egg intake. Unfortunately did not take notes.

Consequently, I usually recommend no more than 7 eggs per week, preferably organic and rich in omega-3.

P.S. Loved NZ, esp Kerosene Creek thermal spring, Wai-o-tapu and the North Island beaches (except for the vicious sandflies). The South Island landscapes are spectacular. Pity about the earthquakes. Great friendly folks. Must be the mussels doing them good.

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Re: Plasmalogens- exciting new evidence

Postby Stavia » Mon Feb 19, 2018 9:34 am

Thanks Searcher. Got it.
Yup, NZ is a fantastic country to live in. We have our problems, but honestly its a great society, and its really easy to get decent unprocessed food.

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Re: Plasmalogens- exciting new evidence

Postby Stavia » Mon Feb 19, 2018 10:01 am

Email from Dayan

I have reviewed the comments on the message board and requested access, but I have not been granted access yet.  There are a lot of interesting comments.  However, sometimes the simplest of questions require a long answer.  Here are three papers from my lab that you can share with your members.  They should answer many of the questions regarding plasmalogens.  One of the issues that is critically important to people trying to self-medicate via supplements is that the biological effect of plasmalogens is dependent upon their structure – not all plasmalogens are the same.  Both the mankidy paper and the wood book chapter describe the structure-activity relationship between different plasmalogens and cholesterol and amyloid regulation.  The Minagawa paper is a bit more technical, but it really exemplifies the functional biological differences between e4 and e3.  I hope that this is helpful.


Sent from my SM-G930F using Tapatalk

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Re: Plasmalogens- exciting new evidence

Postby Stavia » Mon Feb 19, 2018 10:04 am

Abstract
We determined the molecular mechanisms underlying apolipoprotein E (ApoE)-isoformdependent
lipid efflux from neurons and ApoE-deficient astrocytes in culture. The ability of
ApoE3 to induce lipid efflux was 2.5- to 3.9-fold greater than ApoE4. To explore the contributions
of the amino- and carboxyl-terminal tertiary structure domains of ApoE to cellular lipid efflux,
each domain was studied separately. The amino-terminal fragment of ApoE3 (22-kDa-ApoE3)
induced lipid efflux greater than 22-kDa-ApoE4, whereas the common carboxyl-terminal fragment
of ApoE induced very low levels of lipid efflux. Addition of segments of the carboxyl-terminal
domain to 22-kDa-ApoE3 additively induced lipid efflux in a length-dependent manner; in
contrast, this effect did not occur with ApoE4. This observation, coupled with the fact that
introduction of the E255A mutation (which disrupts domain–domain interaction) into ApoE4
increases lipid efflux, indicates that interaction between the amino- and carboxyl-terminal domains
in ApoE4 reduces the ability of this isoform to mediate lipid efflux from neural cells. Dimeric 22-
kDa or intact ApoE3 induced higher lipid efflux than monomeric 22-kDa or intact ApoE3,
respectively, indicating that dimerization of ApoE3 enhances the ability to release lipids. The
adenosine triphosphate–binding cassette protein A1 (ABCA1) is involved in ApoE-induced lipid
efflux. In conclusion, there are two major factors, intramolecular domain interaction and
intermolecular dimerization, that cause ApoE-isoform-dependent lipid efflux from neural cells in
culture.


minagawa_2009 APOE isoform lipid efflux.pdf
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Re: Plasmalogens- exciting new evidence

Postby Stavia » Mon Feb 19, 2018 10:04 am

Abstract Although dementia of the Alzheimer’s type (DAT)
is the most common form of dementia, the severity of dementia
is only weakly correlated with DAT pathology. In contrast,
postmortem measurements of cholinergic function
and membrane ethanolamine plasmalogen (PlsEtn) content
in the cortex and hippocampus correlate with the severity of
dementia in DAT. Currently, the largest risk factor for DAT
is age. Because the synthesis of PlsEtn occurs via a single
nonredundant peroxisomal pathway that has been shown
to decrease with age and PlsEtn is decreased in the DAT
brain, we investigated potential relationships between
serum PlsEtn levels, dementia severity, and DAT pathology.
In total, serum PlsEtn levels were measured in five independent
population collections comprising .400 clinically
demented and .350 nondemented subjects. Circulating
PlsEtn levels were observed to be significantly decreased in
serum from clinically and pathologically diagnosed DAT
subjects at all stages of dementia, and the severity of this
decrease correlated with the severity of dementia. Furthermore,
a linear regression model predicted that serum PlsEtn
levels decrease years before clinical symptoms. The putative
roles that PlsEtn biochemistry play in the etiology of
cholinergic degeneration, amyloid accumulation, and dementia
are discussed.—Goodenowe, D. B., L. L. Cook, J. Liu,
Y. Lu, D. A. Jayasinghe, P. W. K. Ahiahonu, D. Heath, Y.
Yamazaki, J. Flax, K. F. Krenitsky, D. L. Sparks, A. Lerner,
R. P. Friedland, T. Kudo, K. Kamino, T. Morihara, M.
Takeda, and P. L. Wood. Peripheral ethanolamine plasmalogen
deficiency: a logical causative factor in Alzheimer’s
disease and dementia. J. Lipid Res. 2007. 48: 2485–2498.




Goodenowe_2007_Plasmalogens and AD.PDF
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Re: Plasmalogens- exciting new evidence

Postby Stavia » Mon Feb 19, 2018 10:04 am

Plasmalogen Deficit: A New and Testable
Hypothesis for the Etiology of
Alzheimer’s Disease
Paul L. Wood, M. Amin Khan, Rishikesh Mankidy,
Tara Smith and Dayan B. Goodenowe
Phenomenome Discoveries,
Canada
1. Introduction
Alzheimer’s disease (AD) is a complex cognitive disorder for which the single greatest risk
factor is age. The pathophysiological basis for AD is still a matter of debate with no current
hypothesis explaining all of the complex pathological changes observed. These include
neurofibrillary tangles, amyloid plaques, neuroinflammation, hypomyelination, neuronal
shrinkage (eg. N- basalis cholinergic neurons, resulting in a dramatic cholinergic deficit),
ocular pathology, microvascular pathology and liver peroxisomal dysfunction. The
hypothesis that we are presenting, namely peroxisomal dysfunction resulting in decreased
supply of critical ethanolamine plasmalogens to the brain, eye and vascular endothelium, is
the first hypothesis that can potentially explain all of these complex pathologies in AD. The
value of this hypothesis is that it is imminently testable via resupply of critical ether lipid
precursors of plasmalogens. PPI-1011


Wood_2011_Plasmalogen deficit in AD Book Chapter.pdf
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Re: Plasmalogens- exciting new evidence

Postby Stavia » Mon Feb 19, 2018 10:04 am

Abstract
Background: Disrupted cholesterol regulation leading to increased circulating and membrane cholesterol levels is
implicated in many age-related chronic diseases such as cardiovascular disease (CVD), Alzheimer's disease (AD), and
cancer. In vitro and ex vivo cellular plasmalogen deficiency models have been shown to exhibit impaired intra- and
extra-cellular processing of cholesterol. Furthermore, depleted brain plasmalogens have been implicated in AD and
serum plasmalogen deficiencies have been linked to AD, CVD, and cancer.
Results: Using plasmalogen deficient (NRel-4) and plasmalogen sufficient (HEK293) cells we investigated the effect of
species-dependent plasmalogen restoration/augmentation on membrane cholesterol processing. The results of these
studies indicate that the esterification of cholesterol is dependent upon the amount of polyunsaturated fatty acid
(PUFA)-containing ethanolamine plasmalogen (PlsEtn) present in the membrane. We further elucidate that the
concentration-dependent increase in esterified cholesterol observed with PUFA-PlsEtn was due to a concentrationdependent
increase in sterol-O-acyltransferase-1 (SOAT1) levels, an observation not reproduced by 3-hydroxy-3-
methyl-glutaryl-CoA (HMG-CoA) reductase inhibition.
Conclusion: The present study describes a novel mechanism of cholesterol regulation that is consistent with clinical
and epidemiological studies of cholesterol, aging and disease. Specifically, the present study describes how selective
membrane PUFA-PlsEtn enhancement can be achieved using 1-alkyl-2-PUFA glycerols and through this action reduce
levels of total and free cholesterol in cells.




Mankidy_2010_Membrane Plasmalogen and Cholesterol Regulation2.pdf
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Re: Plasmalogens- exciting new evidence

Postby Stavia » Mon Feb 19, 2018 4:49 pm

bit of background biochemistry for the uninitiated and perplexed.
Remember my primer? page 2 I discuss the 4 main types of lipids - sterols including cholesterol; fatty acids including saturated, monounsaturated and polyunsaturated; triglycerides; and phospholipids.

A phospholipid has a glycerol backbone just like a triglyceride, but one of the 3 fatty acids in a triglyceride is replaced by a phosphate group. This makes the molecule "aliphatic" ie can dissolve in fat and water and the naturally form a bilayer which is the cell membrane.
The simplest phosophlipid is phosphatidic acid. It is just a glycerol backbone, one phosphate group, and two fatty acids,. These latter are attached in a way called an "ester" link to the backbone. Other molecules can attach to the phosphate group making more complex phospholipids. Examples are choline which gives phosphatidylcholine; ethanolamine giving phosphatidylethanolamine; serine giving phosphatidyserine; and others.

The three carbons of the glycerol are numbered 1, 2, 3 (the one where the phosphate joins). In a plasmalogen, the fatty acid joined to the first carbon is joined in a way called an "ether" link. this changes the shape of the molecule, and remember, in biochemistry, shape often determines function of a molecule.
the 1st carbon of the glycerol chain is also called the sn-1 position and the second, the sn-2 position.
Now remember that fatty acids can be of many different forms? saturated, unsaturated, monounsaturated - so the plasmalogen will be different depending on what fatty acid is joined to the sn1 and sn2 positions. Typically the sn-2 position in a plasmalogen will be a polyunsaturated one - and we would much prefer this to be an omega 3 such as DHA rather than an omega 6 such as arachidonic acid.
Plasmalogens have another molecule joined to the phosphate group just like ordinary phosophlipids - usually ethanolamine or choline.

I will attempt to draw this for you all and will post my scribbling in a few minutes.


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