Does anyone supplement plasmalogens with opencures, or got tested low for them?

[Alex K Chen]

there's a HUGE amount of info on them

https://www.rapamycin.news/t/has-anyone-tried-prodrome-sciences-how-to-increase-choline-plasmalogens-and-gastrointestinal-fatty-acids/735

Supplementation only increased ethanolamine plasmalogens for me, but it seems that this is way more important than choline plasmalogens

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Ethanolamine (Etn)-containing phospholipid is the second most abundant phospholipid, comprising approximately 15–25% of total phospholipids [1], in which phosphatidylethanolamine (PtdEtn), a diacyl glycerophospholipid, and ethanolamine plasmalogen (PlsEtn), an alkenylacylglycerophospholipid, are major constituents [2]. In mammals, PlsEtn is found in several organs, such as the brain, kidney and heart, in which PlsEtn constitutes approximately 50% of Etn-containing phospholipids, whereas, in the liver, plasmalogens are only slightly detectable [2-4]. Choline plasmalogen (PlsCho) is abundant in both the heart and skeletal muscle [2, 3].

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In the ER, acyl/alkyl DHAP reductase (AADHAP-R) catalyzes the reduction of 1-O-alkyl-DHAP to form 1-O-alkyl-2-hydroxyl- sn-glycerol-3-phosphate (1-O-alkyl-G3P) (Hajra, 1997). Then, the acyl/alkyl-G3P-acyltransferase (AAG3P-AT) catalyzes acylation with an acyl-CoA at the sn-2 position of the 1-O-alkyl-G3P to form 1-O-alkyl-2-acyl-G3P. The phosphate group of -O-alkyl-2-acyl-G3P is removed by phosphohydrolase (PH) to form 1-O-alkyl-2-acylglycerol (Wallner and Schmitz, 2011). Next, ethanolamine phosphate head group is added to 1-O-alkyl-2-acylglycerol by the ethanolamine phosphotransferase (E-PT) to generate plasmanylethanolamine (1-O-alkyl-2-acyl-GPE) (Brites et al., 2004). Finally, plasmanylethanolamine is converted into 1-O-alk-1′-enyl 2-acyl phosphatidylethanolamine (PlsEtn) through the action of 1′-alkyl desaturase (TMEM189 homolog) in the presence of molecular oxygen and NADPH. Because there is no plasmenylcholine desaturase found in animals, choline plasmalogens (PlsCho) might be formed only following the hydrolysis of ethanolamine plasmalogens into form 1-O -(1Z-alkenyl)-2-acyl-sn-glycerol, which was then modified by choline phosphotransferase and CDP-choline (Lee, 1998).

 

Edited October 5, 2023 by InquilineKea

[Alex K Chen]

My TMEM189 variants (there is so little info on any of this, and plasmalogen synthesis requires dozens of precursor enzymes, so there are MANY stages where this could go wrong).

 grep "^chr20" alexchennebula.vcf | awk '$2 >= 50118254 && $2 <= 50153723'

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chr20   50118540        rs12624795      G       A       1078.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=29;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=26.98;SOR=1.255;VQSLOD=5.75;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,29:29:87:1107,87,0
chr20   50118793        rs6012845       C       T       1051.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=28;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=30.36;SOR=0.693;VQSLOD=5.75;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,27:28:81:1080,81,0
chr20   50119435        rs556158758     C       CA      348.73  PASS    AC=2;AF=1.00;AN=2;DB;DP=18;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=29.06;SOR=1.609;VQSLOD=4.55;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,12:13:36:386,36,0
chr20   50120100        rs3092037       TA      T       635.73  PASS    AC=2;AF=1.00;AN=2;DB;DP=21;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=31.79;SOR=1.127;VQSLOD=5.39;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,20:20:60:673,60,0
chr20   50120268        rs143148043     A       AAAACAAAC,AAAACAAACAAAC 674.73  PASS    AC=1,1;AF=0.500,0.500;AN=2;DB;DP=23;ExcessHet=3.0103;FS=0.000;MLEAC=1,1;MLEAF=0.500,0.500;POSITIVE_TRAIN_SITE;QD=19.55;SOR=1.112;VQSLOD=4.70;culprit=FS       GT:AD:DP:GQ:PL  1/2:0,4,11:15:99:712,467,450,174,0,135
chr20   50120856        rs56756656      G       A       1287.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=33;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=38.04;SOR=0.752;VQSLOD=6.06;culprit=QD      GT:AD:DP:GQ:PL  1/1:0,33:33:99:1316,99,0
chr20   50120977        rs6012846       T       C       1130.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=32;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=33.02;SOR=0.756;VQSLOD=6.95;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,31:31:93:1159,93,0
chr20   50122934        rs11416444      T       TA      663.73  PASS    AC=2;AF=1.00;AN=2;DB;DP=24;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;QD=31.61;SOR=0.990;VQSLOD=4.35;culprit=FS  GT:AD:DP:GQ:PL  1/1:0,21:21:63:701,63,0
chr20   50123421        rs6512610       C       A       1473.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=41;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=28.05;SOR=0.693;VQSLOD=5.50;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,40:40:99:1502,119,0
chr20   50125544        rs142890263     TTATCTATCTATC   T       185.73  PASS    AC=1;AF=0.500;AN=2;BaseQRankSum=-4.080e-01;DB;DP=25;ExcessHet=3.0103;FS=5.167;MLEAC=1;MLEAF=0.500;MQRankSum=0.00;QD=11.61;ReadPosRankSum=1.32;SOR=2.584;VQSLOD=-2.443e-01;culprit=FS  GT:AD:DP:GQ:PL  0/1:10,6:17:99:223,0,401
chr20   50125972        rs61656463      G       A       1318.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=36;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=30.34;SOR=0.869;VQSLOD=7.08;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,35:35:99:1347,105,0
chr20   50130287        rs995989613     A       G       478.77  PASS    AC=1;AF=0.500;AN=2;BaseQRankSum=-1.045e+00;DB;DP=30;ExcessHet=3.0103;FS=1.415;MLEAC=1;MLEAF=0.500;MQRankSum=0.00;QD=15.96;ReadPosRankSum=-1.332e+00;SOR=1.022;VQSLOD=2.16;culprit=ReadPosRankSum      GT:AD:DP:GQ:PGT:PID:PL:PS       0|1:16,14:30:99:0|1:50130287_A_G:507,0,605:50130287
chr20   50130294        .       G       C       514.77  PASS    AC=1;AF=0.500;AN=2;BaseQRankSum=2.05;DP=31;ExcessHet=3.0103;FS=0.000;MLEAC=1;MLEAF=0.500;MQRankSum=0.00;QD=16.61;ReadPosRankSum=-4.160e-01;SOR=0.859;VQSLOD=3.89;culprit=FS   GT:AD:DP:GQ:PGT:PID:PL:PS       0|1:16,15:31:99:0|1:50130287_A_G:543,0,604:50130287
chr20   50130418        rs76905385      G       A       545.77  PASS    AC=1;AF=0.500;AN=2;BaseQRankSum=3.23;DB;DP=37;ExcessHet=3.0103;FS=2.884;MLEAC=1;MLEAF=0.500;MQRankSum=0.00;POSITIVE_TRAIN_SITE;QD=14.75;ReadPosRankSum=-5.030e-01;SOR=0.950;VQSLOD=3.53;culprit=FS    GT:AD:DP:GQ:PL  0/1:20,17:37:99:574,0,558
chr20   50131160        rs55894522      T       C       1130.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=39;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=29.76;SOR=0.743;VQSLOD=6.72;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,38:39:99:1159,113,0
chr20   50132011        rs55757919      C       T       1273.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=35;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=33.86;SOR=1.002;VQSLOD=6.67;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,34:35:99:1302,102,0
chr20   50132118        rs6020284       G       T       1522.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=41;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;QD=29.13;SOR=0.793;VQSLOD=5.11;culprit=FS  GT:AD:DP:GQ:PL  1/1:0,39:40:99:1551,117,0
chr20   50132435        rs1980925       A       G       848.77  PASS    AC=2;AF=1.00;AN=2;DB;DP=31;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=29.27;SOR=0.976;VQSLOD=7.32;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,29:30:86:877,86,0
chr20   50133602        rs761213        C       G       748.77  PASS    AC=2;AF=1.00;AN=2;DB;DP=27;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=28.80;SOR=0.846;VQSLOD=5.83;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,26:26:78:777,78,0
chr20   50134440        rs232747        A       G       847.77  PASS    AC=2;AF=1.00;AN=2;DB;DP=31;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=28.26;SOR=0.976;VQSLOD=6.31;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,30:30:89:876,89,0
chr20   50136722        rs768151281     C       CA      218.75  PASS    AC=2;AF=1.00;AN=2;DB;DP=9;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;QD=27.34;SOR=1.179;VQSLOD=2.86;culprit=FS   GT:AD:DP:GQ:PL  1/1:0,8:8:24:256,24,0
chr20   50138474        rs232739        A       G       1002.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=37;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=27.10;SOR=1.270;VQSLOD=6.46;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,37:37:99:1031,110,0
chr20   50139019        rs232738        A       G       1498.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=44;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=26.17;SOR=1.259;VQSLOD=5.90;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,42:42:99:1527,126,0
chr20   50139679        rs558811955     CT      C       555.73  PASS    AC=2;AF=1.00;AN=2;DB;DP=22;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=30.87;SOR=0.914;VQSLOD=6.14;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,18:18:54:593,54,0
chr20   50140226        rs2869958       C       T       1291.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=35;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=25.96;SOR=1.244;VQSLOD=5.79;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,34:34:99:1320,102,0
chr20   50142461        rs7270617       G       A       1044.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=31;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=24.87;SOR=1.382;VQSLOD=4.76;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,28:28:84:1073,84,0
chr20   50142682        rs1370395130    G       GC      33.73   PASS    AC=1;AF=0.500;AN=2;BaseQRankSum=-1.465e+00;DB;DP=12;ExcessHet=3.0103;FS=4.260;MLEAC=1;MLEAF=0.500;MQRankSum=0.00;NEGATIVE_TRAIN_SITE;POSITIVE_TRAIN_SITE;QD=4.22;ReadPosRankSum=-1.350e-01;SOR=0.061;VQSLOD=-5.840e-02;culprit=QD     GT:AD:DP:GQ:PL  0/1:5,3:8:71:71,0,146
chr20   50143701        rs10574784      CTT     C       1110.73 PASS    AC=2;AF=1.00;AN=2;DB;DP=29;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=21.34;SOR=0.693;VQSLOD=5.43;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,26:26:78:1148,78,0
chr20   50145849        rs1053928251    T       C       409.77  PASS    AC=1;AF=0.500;AN=2;BaseQRankSum=-3.157e+00;DB;DP=25;ExcessHet=3.0103;FS=3.755;MLEAC=1;MLEAF=0.500;MQRankSum=0.00;QD=17.07;ReadPosRankSum=0.615;SOR=0.223;VQSLOD=1.98;culprit=ReadPosRankSum   GT:AD:DP:GQ:PL  0/1:10,14:24:99:438,0,330
chr20   50146840        rs893791908     T       C       646.77  PASS    AC=1;AF=0.500;AN=2;BaseQRankSum=-2.291e+00;DB;DP=44;ExcessHet=3.0103;FS=8.433;MLEAC=1;MLEAF=0.500;MQRankSum=0.00;QD=14.70;ReadPosRankSum=0.354;SOR=0.782;VQSLOD=0.879;culprit=FS      GT:AD:DP:GQ:PL  0/1:20,24:44:99:675,0,618
chr20   50147496        rs232737        G       C       1863.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=50;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=28.19;SOR=0.859;VQSLOD=6.11;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,50:50:99:1892,150,0
chr20   50147758        rs232736        G       A       2056.77 PASS    AC=2;AF=1.00;AN=2;BaseQRankSum=1.54;DB;DP=55;ExcessHet=3.0103;FS=4.102;MLEAC=2;MLEAF=1.00;MQRankSum=0.00;NEGATIVE_TRAIN_SITE;POSITIVE_TRAIN_SITE;QD=32.04;ReadPosRankSum=0.706;SOR=1.055;VQSLOD=0.244;culprit=DP      GT:AD:DP:GQ:PL  1/1:1,53:54:99:2085,124,0
chr20   50147850        rs232735        C       G       1644.77 PASS    AC=2;AF=1.00;AN=2;BaseQRankSum=1.80;DB;DP=47;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQRankSum=0.00;POSITIVE_TRAIN_SITE;QD=30.90;ReadPosRankSum=0.655;SOR=0.352;VQSLOD=3.60;culprit=FS   GT:AD:DP:GQ:PL  1/1:1,44:45:99:1673,125,0
chr20   50147891        rs3091898       T       TCTA    2026.73 PASS    AC=2;AF=1.00;AN=2;DB;DP=48;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=30.60;SOR=1.085;VQSLOD=5.83;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,46:46:99:2064,138,0
chr20   50148358        rs1410533328    A       G       639.77  PASS    AC=1;AF=0.500;AN=2;BaseQRankSum=-1.979e+00;DB;DP=44;ExcessHet=3.0103;FS=0.000;MLEAC=1;MLEAF=0.500;MQRankSum=0.00;QD=14.88;ReadPosRankSum=0.073;SOR=0.892;VQSLOD=3.32;culprit=FS       GT:AD:DP:GQ:PL  0/1:19,24:43:99:668,0,582
chr20   50150314        rs232734        T       C       1111.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=41;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=27.79;SOR=1.981;VQSLOD=5.72;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,40:40:99:1140,120,0
chr20   50152518        rs6020298       G       A       1441.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=41;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;POSITIVE_TRAIN_SITE;QD=32.03;SOR=1.040;VQSLOD=7.15;culprit=FS      GT:AD:DP:GQ:PL  1/1:0,38:38:99:1470,114,0
chr20   50153622        rs232733        T       C       1139.77 PASS    AC=2;AF=1.00;AN=2;DB;DP=34;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;QD=26.64;SOR=1.284;VQSLOD=4.01;culprit=FS  GT:AD:DP:GQ:PL  1/1:0,32:32:96:1168,96,0

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With the elucidation of plasmalogen biosynthesis genes and pathway for aerobic organisms, especially the recent identification of 1′-alkyl desaturase responsible for the conversion of plasmanylphospholipid into plasmalogens (Gallego-García et al., 2019), designing and efficient expression of plasmalogen biosynthetic modules in engineering host cells such as yeast cells become possible. The production and composition of plasmalogens is controlled by synthetic genes and certain rate-limiting steps in biosynthesis such as Far1/2 and 1-alkyl-DHAP (Paul et al., 2019). It was found that supplementation with alkyl glycerol can increase plasmalogen levels in cultured cells (Marigny et al., 2002), animals (Brites et al., 2011), and humans (Das et al., 1992). The most commonly used alkyl glycerols to increase plasmalogen levels in mammalian research are chimyl (O-16:0), batyl (O-18:0), and selachyl (O-18:1) alcohols (Brites et al., 2011; Rasmiena et al., 2015; Tham et al., 2018). Therefore, expression of plasmalogen products can be regulated under specific conditions through the genetic circuit designing and integration of gene modules composed of plasmalogen-related genes and rate-limiting elements. Standard and modularized biological elements can be used to reconstruct the metabolic network in host cells to efficiently synthesize or improve plasmalogen products that meet needs. For anaerobic biosynthesis of plasmalogen, it is necessary for us to identify the key gene(s) responsible for the formation of the vinyl ether bond of plasmalogens in anaerobic bacteria before its synthetic biological study and application.

 

Edited October 6, 2023 by InquilineKea

[Alex K Chen]

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The original scientific studies indicated doses of 900mg (10mg/kg) were effective for protection but that doses of up to 4500mg (50mg/kg) were best for repair*. In our clinical work now with leaders in Clinical Neurology, we are confirming exactly that – our most recent results observe benefits with doses ranging from 900mg to 3600mg. That is why we formulated our plasmalogen product to have a daily serving of 900mg. 

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Data from the Rush University Memory and Aging Project. Final dataset: 1262 participants, participants still living since last clinical visit = 896, participants deceased since last visit = 862. The average age at enrollment = 81. Low plasmalogens = 5th percentile +/- 95% CI. High plasmalogens = 95th percentile +/- 95% CI.

Data from the Rush University Memory and Aging Project showed that a 95-year-old with high plasmalogen levels had the same chance of dying in five years as a 65-year-old with low plasmalogen levels. A 95-year-old with high levels had an almost 70 percent chance of living to their 100th birthday whereas a person the same age with low plasmalogen levels had a less than 20 percent chance of living to their 100th birthday. These results were shocking.

 

 

Edited March 3 by InquilineKea