We've repeatedly spoken about the importance of choline in the diet. The recent Georgetown/Federoff paper reveals that phosphatidylcholine appears to be a big player in terms of maintaining proper cell signaling in the brain further underscoring it's neurocognitive enhancing proprieties.
This paper suggests that estrogen, and rs12325817, play a role in converting phosphatidylethanolamine to phosphatidylcholine and MAY help explain the greater incidence of AD in women. From what I understand, choline can EITHER be provided via diet OR via the PEMT pathway. Imagine how a post-menopausal woman, who's not using HRT, and avoiding choline-rich food, could get into trouble
Dietary choline requirements of women: effects of estrogen and genetic variation
http://ajcn.nutrition.org/content/92/5/1113.full
Unfortunately, neither 23 and Me (nor Promethease) report on this SNP. Regardless, this may be a good reason to ensure adequate dietary choline and consider HRT (if post-menopausal) to enhance the catalyzation of phosphatidylethanolamine to phosphatidylcholine. Both E4 men and women may be able to benefit from the supplement SAM-e that also facilitates the PEMT pathway AND promotes serotonin production- another deficiency found in patients that convert to AD according to the Georgetown group.
My interest stems from the fact that I carry two copies of a rare SNP that produces the HIGHEST levels of phosphatidylethanolamine...this COULD be a really good one If you have high levels of HDL; you may also carry it: rs4775041, GG.
Facilitating the PEMT Pathway...
Re: Facilitating the PEMT Pathway...
This is the first time I hit the jackpot with GG! Yes, my HDL has been climbing up from the 60s to 93 now.
Julie, do you recommend taking SAMe and/or choline? Although I am trying to increase my dietary sources of choline (eggs, scallops, shrimp), it is difficult to get the 500mg/day on diet sans red meat.
After having the migraine equivalent on the ultra-low dose estrogen patch, I discontinued estrogen, suspecting that this may have been a side effect.(?) The Stanford neurologist recommended discontinuing estrogen at age 65, so I only had a few years left to be on estrogen anyway. However, my 96 y/o mom insists on remaining on the patch.
Julie, do you recommend taking SAMe and/or choline? Although I am trying to increase my dietary sources of choline (eggs, scallops, shrimp), it is difficult to get the 500mg/day on diet sans red meat.
After having the migraine equivalent on the ultra-low dose estrogen patch, I discontinued estrogen, suspecting that this may have been a side effect.(?) The Stanford neurologist recommended discontinuing estrogen at age 65, so I only had a few years left to be on estrogen anyway. However, my 96 y/o mom insists on remaining on the patch.
Re: Facilitating the PEMT Pathway...
You ask a lot of great questions, Kit! As a non-scientist, I'll do my best to tackle them. Anyone with superior info, please chime it!
Re., choline. the PEMT pathway is a secondary source of choline. Having adequate dietary choline onboard for E4s seems to be really important. IF you were considering supplementation, THAT would be the best place to start. From my understanding, The PE to PC conversion/PEMT pathway is enhanced in women by the presence of estrogen. SAM-e is another way to facilitate that conversion. Because neither 23 and me, nor Promethease report specifically on the one SNP discussed in the article, it's hard to "check" on our conversion status. if you search "PEMT", 23 and Me provides many alleles to search. Promethease provides 3-4. We may have to roll up our sleeves to figure out how to assess our pathways to ensure access to our possible treasure trove- GG- YAY!
I'm really hoping that the ADDF will re-analyze estrogen for the E4 population. This seems like another way in which it would benefit us. When you were using the patch, did you also supplement with progesterone. Perhaps the balancing of both would remedy the headache? My docs have decided as an E4 post-menopausal women, it is advantageous for me to optimize my estrogen, progesterone & testosterone. I'm working on it now.
Re., choline. the PEMT pathway is a secondary source of choline. Having adequate dietary choline onboard for E4s seems to be really important. IF you were considering supplementation, THAT would be the best place to start. From my understanding, The PE to PC conversion/PEMT pathway is enhanced in women by the presence of estrogen. SAM-e is another way to facilitate that conversion. Because neither 23 and me, nor Promethease report specifically on the one SNP discussed in the article, it's hard to "check" on our conversion status. if you search "PEMT", 23 and Me provides many alleles to search. Promethease provides 3-4. We may have to roll up our sleeves to figure out how to assess our pathways to ensure access to our possible treasure trove- GG- YAY!
I'm really hoping that the ADDF will re-analyze estrogen for the E4 population. This seems like another way in which it would benefit us. When you were using the patch, did you also supplement with progesterone. Perhaps the balancing of both would remedy the headache? My docs have decided as an E4 post-menopausal women, it is advantageous for me to optimize my estrogen, progesterone & testosterone. I'm working on it now.
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Re: Facilitating the PEMT Pathway...
Oh girls, I don't think we hit the jackpot (I'm GG too). According to dbsnp "C" is the minor allele. Let me know if you think that is incorrect....it would be good news for us.
Re: Facilitating the PEMT Pathway...
Snpedia says:
I'm also GG, so we're looking to be a "rare" bunch here.
http://snpedia.com/index.php/Rs4775041The rarer rs4775041(G) allele was associated with increased phosphatidylethanolamine values.
I'm also GG, so we're looking to be a "rare" bunch here.
Re: Facilitating the PEMT Pathway...
What are the chances
Yes, Susan, that's my understanding that we have very high level of PE. Since it's the precursor to PC, and since the Georgetown group found high levels of PC to be protective...I'm SPECULATING it could be a very good thing; only IF our PEMT pathway is working well.
Is my logic flawed? I'm waaaaay past due for a lottery win
Yes, Susan, that's my understanding that we have very high level of PE. Since it's the precursor to PC, and since the Georgetown group found high levels of PC to be protective...I'm SPECULATING it could be a very good thing; only IF our PEMT pathway is working well.
Is my logic flawed? I'm waaaaay past due for a lottery win
Re: Facilitating the PEMT Pathway...
Well, I am also GG on this SNP. Looks like it is common among APOE4 women. Will any of the gents chime in on their status?
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Re: Facilitating the PEMT Pathway...
I still think the rare allele is C, not G. I think snpedia is wrong. If you go to the study, it states the minor allele is the advantageous one and according to dbsnp, the minor allele is C, the major allele is G. I would like to be wrong so we could all be winners here, but either dbsnp is wrong, or snpedia is wrong. Help please....
From the study cited:
"One example is SNP , which is also in the list of our top ranking associations. This SNP is located in a linkage disequilibrium block containing the gene coding for LIPC, a key enzyme of the long-chain fatty acid metabolism. This polymorphism associates with the concentrations of numerous glycerophosphatidylcholines, glycerophosphatidylethanolamines and sphingomyelins (up to p = 9.66×10−8; Figure 3 and Table S2). For instance, homozygotes carrying the minor allele have on average 70% higher concentrations of the phosphatidylethanolamine diacyl C38:6 (PE aa C38:6) than homozygotes for the major allele."
From the study cited:
"One example is SNP , which is also in the list of our top ranking associations. This SNP is located in a linkage disequilibrium block containing the gene coding for LIPC, a key enzyme of the long-chain fatty acid metabolism. This polymorphism associates with the concentrations of numerous glycerophosphatidylcholines, glycerophosphatidylethanolamines and sphingomyelins (up to p = 9.66×10−8; Figure 3 and Table S2). For instance, homozygotes carrying the minor allele have on average 70% higher concentrations of the phosphatidylethanolamine diacyl C38:6 (PE aa C38:6) than homozygotes for the major allele."
Re: Facilitating the PEMT Pathway...
I'm not genotyped on this but my brother is GG and has a very low HDL. That made me wonder so I checked 1000 Genes and they say "C" is the minor allele at 21%. Sorry....
http://browser.1000genomes.org/Homo_sap ... vf=3665232
http://browser.1000genomes.org/Homo_sap ... vf=3665232
Re: Facilitating the PEMT Pathway...
...so is SNPedia and Promethease also WRONG when they say we have the highest levels of phoshatidylethanolamine?