Would You Be Interested In A Choline Supplement?

[SB4]

Depression and other symptoms of high acetylcholine? Not as much alpha-GPC is required. Some take 300-600 mg, though usually with nootropics (eg, 20x noopept oral-equivalent dose).

Acetyl L-carnitine + alpha-GPC + Na-R-ALA is a popular combo. TMA mania.

I think it messed with my Dysautonomia symptoms. I did try nutropics combos and small to large doses. Problem is, if you are looking to get 400mg of choline a day it would equal 1000mg alpha GPC. Too much.

 

[Amazoniac]

"Mitolipin provides less than 30 mg/serving, a bottle would last 5 days to supply that amount." Amazoniac is looking for around 200mg choline per day.

@haidut - The reason for not suggesting 150 mg/serving (which might suffice) is because we start to enter a range that encourages people to double the serving for not finding the recommended amount to be enough.

I forgot to add that an underdeveloped musculature (for various reasons including wasting) will burden the liver further when stored fats are consumed in the body, so it can be one more factor increasing requirements in spite of structural choline being freed up along.

As you know and can tell, its lack around here isn't improbable and some members will inevitably be supplementing (often with shady products due to limited options). So why not offer a reliable choline product?

Are you familiar with short/medium-chain fatty acid esters of phosphatidylcholine such as dioctanoyl mention'd in the article below?

@Amazoniac Thanks. Would guru think that choline chloride would potential skirt that bacterial fermentation issues that phosphatidylcholine could be causing?

I have heard gut bacteria "feed" on choline. Does that mean they feed on the actual molecule or the things attached to it?

Also what would be wrong with buying choline chloride online? Seems fairly cheap.

No guru here, but I think that the opposite is more likely.
It's possible for that effect to be indirect from bile discharge (must be protective to its digestion) or from cholinergic action on nerves.

The scientists have already replied, but here's something interesting..

- Pancreatic and mucosal enzymes in choline phospholipid digestion (!)

"Choline phospholipids (PLs) are major amphiphilic [aquatic/terrestrial] components in cell membranes, plasma lipoproteins, and bile. Their metabolism is central for cell membrane biology, lipid transport, generation of lipid messengers (84, 103, 221, 270, 299, 328), choline homeostasis (164, 296), acetylcholine (ACh) formation (31, 63, 138), and methyl group metabolism (220, 332). The secretion of phosphatidylcholine (PC) in bile is cytoprotective to the biliary and mucosal epithelium (200). It enhances micellar solubilization of biliary cholesterol, the emulgation [imitation] of the dietary triacylglycerols (TAGs), and the micellar solubilization of the lipolysis products (33)."

"Although the dietary supply of choline PLs is a major source of choline, the secretion of PC in bile is much larger (213)."

"Effective digestion and absorption of choline PLs are therefore central for choline homeostasis. The digestion of PC and sphingomyelin (SM) also enhances absorption of other lipids (329) and cholesterol (47). Generated 1-lyso-PC is absorbed and enhances chylomicron PC formation and chylomicron secretion (176, 293), which in turn influences postprandial lipid and glucose metabolism, and fat storage (74, 122). Major metabolites such as lyso-PC, ceramide, sphingosine, and sphingosine-1-phosphate are intracellular and paracrine signals (122, 205), and alternative pathways generate other bioactive compounds as lysophosphatidic acid (LPA) (198) and ACh (31, 282). Hereby, choline PL digestion may affect gut barrier integrity, inflammation and carcinogenesis. Finally, the course of choline PL digestion may influence bacterial metabolism of choline to trimethylamine (TMA) in the gut (274). Absorbed TMA generates trimethylaminoxide (TMAO) that is a pathogenetic factor in arteriosclerosis and cardiovascular disease (27, 286)."


"Whereas the major dietary lipid class, i.e., TAG, is rapidly hydrolyzed by the concerted action of gastric and pancreatic lipases in the stomach and upper small intestine (22, 33, 170, 173, 306), the digestion of choline PLs is more extended and variable (122, 205). The pancreatic secreted phospholipase A2 IB (sPLA2 IB), which hydrolyzes PC to 1-lyso-PC and free fatty acid (FFA) in the proximal small intestine, is well characterized and has an important role in PC digestion, which is, however, not fully defined (121, 152, 194). A role also of other enzymes must be postulated to explain the normal completion of PC absorption and the rather effective absorption of PC fatty acids in sPLA2 IB knockout (KO) mice (241)."

"Intracellular mucosal enzymes effectively degrade lyso-PC to glycerophoshocholine (GPC), and GPC to choline and glycerophosphate, but the identity of these enzymes is uncertain."

"Choline is supplied in the diet, mainly as choline PLs (20), and is also synthesized in the body by methylation of phosphatidylethanolamine (PE) in the liver (301, 302). In humans the dietary supply of choline PLs is of the order 1–5 g/day (5, 20). The biliary secretion of PC is much larger, on average 11 g/day (213), but the secretion of SM very low (190). The supply of choline PLs from the mucosa is considerable (52) and originates from sloughing of mucosal cells, duodenal secretion of PC-rich surfactant like vesicles (82), ileal PC secretion (81), and generation of vesicles in the enterocyte microvilli (180)."

"The most extensively studied enzyme in PC hydrolysis is sPLA2 IB from pancreas." "The enzyme acts at the interphase of aggregated lipids and is highly influenced by physical form and charge of the aggregates (269). Interfacial activation involves binding, penetration of lipid water interphase, and allosteric effects of detergents (240). Negatively charged substrates are preferred, and bile salts stimulate the activity both by changing physical form and increasing the anionic character of the interphase. The effect of bile salts is, however, biphasic, being stimulatory up to the critical micellar concentration and inhibitory at higher concentrations. A molar-conjugated bile salt/PC ratio of 1.2–2.0:1 was found to be optimal, but at a ratio above 3, activity of sPLA2 IB drastically decreased (197). In human bile, the molar ratio of bile salt/PC is between 3.5 and 6, which is unfavorable for PC hydrolysis (42)." "[..]the average concentration of conjugated bile salts in the upper human ileum was 10 µmol/ml (214), and the PL concentration <2 µmol/ml (11); i.e., the bile salt/PL ratio should be unfavorable for sPLA2 IB action."

"In vivo studies found that human gut lumen contains mostly 1-lyso-PC [?] and unhydrolyzed PC (11)."

"In addition to pancreatic enzymes, mucosal PLs may play a role in PL digestion."

"GPC is formed both in the gut lumen and in the mucosal cells (Fig. 1). Free choline may be generated either by hydrolysis of GPC to choline and glycerophosphate or to glycerol and choline phosphate, succeeded by hydrolysis of the choline phosphate (126)."

"The mucosal cells have a high capacity to hydrolyze GPC generated from absorbed 1-lyso-PC."

"Studies in rats fed PCs radiolabeled in different positions of the molecule indicated that PC is not absorbed intact but is hydrolyzed mainly to 1-lyso-PC, which is effectively absorbed and reacylated into PC or degraded to GPC, glycerophosphate, and free choline (202, 232, 261). Although the proportion of lyso-PC that was reacylated into chyle PC increased with fat feeding, a large proportion was always further degraded. Extending these observations Ikeda et al. (125) fed 14C-choline-labeled PC with soy bean oil to rats and analyzed radioactive metabolites in the lumen and mucosa of different parts of the small intestine. Formation of lyso-PC occurred both proximally and in the jejunum and ileum, but the proportion of water-soluble compounds increased in distal direction. In the ileum, more radioactivity was found in GPC and choline than in PC and lyso-PC in both the lumen and mucosa. There was no evidence for absorption of lyso-PC directly into portal blood (125). Also, studies with luminally perfused mouse intestines and polarized Caco-2 cells indicated that luminal degradation of PC to GPC occurs, without participation of pancreatic enzymes (126)."

"Whether GPC is absorbed intact into the mucosal cells is unknown. In rats the choline part of orally given radiolabeled GPC was effectively assimilated (1). Studies in humans are few. In duodenally intubated volunteers given a mixed test meal containing emulsified fat, i.e., favorable conditions for sPLA2 IB action, there was an effective but variable hydrolysis of PC to 1- but not to 2-lyso-PC or water-soluble choline compounds, but only the proximal part of the small intestine was studied (11, 233)."

"In humans, intake of a breakfast with zero to six eggs per day caused a dose-dependent but moderate increase in TMAO levels (184)."

"A fish meal caused, however, a many fold higher increase in TMAO than in meals with eggs or meat (42). This is due to the high content of TMA and TMAO in fish, where it fills functions related to resistance to cellular stress induced by osmotic or hydrostatic pressure. Fish intake is therefore an important determinant of the inter- and intraindividual variations in TMAO levels in urine (281) and blood (149)." @yerrag - Thankfully.

"TMA is formed by gut bacteria that use choline as an energy and carbon source."

"Early studies found that when 2–8 g of choline salt were fed orally to humans, >60% was recovered in urine as total trimethylamines, i.e., TMA, dimethylamine, or TMAO, within 24 h (58). Less of the choline of PC appeared in these metabolites when 2 g choline was fed as PC (59)."

"Studies with small intestinal tissue preparations identified both a saturable high-affinity mechanism for choline uptake and a slower non-saturable process (111, 264). Thus, at low luminal concentration of choline, the uptake is rapid, but with doses that saturate the high-affinity uptake, exposure of choline to TMA forming bacteria may be extended. In the case of PC and SM digestion, release of free choline will occur throughout the jejunum and ileum. Studies in mice and humans show that after PC feeding the time course for the rise in plasma choline and betaine precedes the rise in TMA and TMAO (88, 184). The early rise in plasma choline and betaine may reflect the action of sPLA2 IB, intracellular degradation of absorbed lyso-PC, and the rapid conversion of some choline to betaine in the liver. The later and more extended rise in TMA and TMAO may reflect bacterial access to free choline generated by hydrolysis of GPC formed by PLB and hydrolysis of choline phosphate generated by NPP7 in the jejunum and ileum. Although little choline normally reaches cecum, there must be some TMA formation also in the cecum and colon. It is not known whether gut bacteria also hydrolyze PC and SM in the small intestine. Some bacteria, e.g., some species of Bacteriodetes (267), express PLAs and PLD, and phosphodiesterases. Some express SMase (254), but host NPP7 is the predominant SMase in feces (337). Our view is that bacterial PC and SM digestion in the small intestine is most likely small, but it might be increased in situations with abnormal bacterial overgrowth. The host absorptive pathways for PC and SM choline are effective and designed to complete choline absorption with a limited exposure of free choline to the bacteria."

"Most of the free choline is transferred to the portal vein. The release of free choline from mucosal cells into portal blood and the uptake into liver cells are effective transporter mediated processes (245, 266). Measurements of choline concentration in portal and hepatic veins in sheep indicate an average first pass hepatic clearance of 83% (246). Intraportally injected choline (280) and choline from digested PC (156) and SM (218) are extensively used for hepatic PC synthesis, and newly synthesized PC is preferentially secreted in bile (96, 344). Yet, targeted deletion of CCTα in the liver did not lower PC levels in gallbladder bile in mice (131), indicating that backup mechanisms prioritize bile PC secretion by deriving PC from alternative PC pools. PE methylation is not a preferred source of bile PC (4). However, simultaneous KO of the ABCB4 transporter that mediates secretion of PC into bile prevented death in liver failure of PEMT KO mice on a low-choline diet, which emphasizes the quantitative role of bile PC secretion in overall choline homeostasis (302) and the importance of the integrated regulation of PC and PE metabolism (299)."

"Bile PC secretion and reutilization of absorbed choline for bile PC synthesis are [] dependent on factors that regulate bile acid secretion."

"Although lyso-PC transports choline and fatty acids to most tissues, the liver exhibits the highest uptake per gram tissue (340), but this choline is not preferentially used for bile PC secretion (48)."

"In [summary], the effective first pass uptake of choline by the liver, in combination with the effective hepatic PC synthesis and the preferential secretion of newly synthesized PC into bile, creates an incomplete but quantitatively large enterohepatic circulation of choline. Metabolism of chyle lipoprotein PLs also returns choline to the liver by the uptake of PC, SM, and lyso-PC. This choline is, however, not selectively used for bile PC production, and lyso-PC is also a transporter of choline and fatty acids to most other tissues."


"Choline PLs [in excess] inhibit cholesterol absorption and influence plasma lipoprotein levels (20, 47, 251)."

"An intriguing feature of choline deficiency is the short time needed to develop hepatic biochemical abnormalities in both rats (150) and humans (334)."

"In a baboon model for alcohol liver cirrhosis, soy bean PC (166, 168), but not free choline (167), alleviated the disease."

"Choline deficiency, to which TMA formation may contribute, influences the course of NAFLD (187, 265)."

"A meticulously controlled human study related host genetic polymorphisms and fatty liver development during a choline-deficient diet to the gut microbiome (271)." "Despite this important new information that relates gut microbiome and host genetic variability to metabolic parameters in NAFLD, many important questions remain regarding causality."

"Obese individuals have increased secretion of bile acids (186) and PC in bile (14) and a variable but increased VLDL secretion (185). With a high-fat intake, more of absorbed lyso-PC will be reacylated into chylomicron PC and less choline will be transported by the portal vein. The first pass clearance of free choline by the liver is extensive. Thus a choline concentration gradient throughout the sinusoids may be created, leading to a low uptake in the centrolobular (zone 3) hepatocytes. Like the initial fat accumulation in choline deficiency, liver pathology in NAFLD, NASH, and ALD is most pronounced in this zone (for references see (2)."

"Extension of NAFLD and NASH to zone 1 reflected severity and progression of disease in obese children (2). Choline insufficiency may contribute to this zonality, but there is also a zonal gradient for many other compounds and for oxygen; e.g., periportal zone 1 hepatocytes may take up more bile acids and therefore need more choline for bile PC secretion."

"Without disregarding the role of PE methylation and return of lipoprotein PLs to the liver, we believe that the large amounts of choline transported by the portal vein are crucial to meet the demands for bile and VLDL PC synthesis, in particular when these are increased."

"Choline supplementation may be given in the form of PC, not as choline salt, to minimize metabolism to TMA in the gut."

"PC in the mucous layer has protective functions related to its amphiphilic properties. Choline deficiency may hamper barrier integrity, and choline and GPC levels were low in large bowel biopsies from ulcerative colitis (UC) patients (18). Furthermore, decreased levels of choline compounds in serum of patients with UC were reported (54, 317). A therapeutic effect in UC of a slow release formulation of PC has been demonstrated (137, 273), but it is unknown whether this is due to addition of PC to the mucous layer, a restoration of mucosal levels of choline compounds, or other mechanisms (80)."

"PC inhibited the TNF-α-activated inflammatory response in Caco-2 cells and decreased macrophage actin assembly that is part of the activation during phagocytosis (291), indicating that it may influence bacteria/mucosa interactions by several mechanisms. In experimental colitis in rats, dietary PC alleviated the disease (147). In other animal experiments, a diet low in choline and folate aggravated experimental intestinal inflammation and hampered small intestinal differentiation and barrier function (26, 181). On the other hand, choline deficiency alleviated colitis induced by dextran sulfate sodium (DSS) via elimination of NK cells (250). Overexpression of sPLA2 X (255) exhibited an immunosuppressed phenotype and resistance to induction of colitis with DSS (195). It is not known whether this effect is related to the role of sPLA2 X in PC digestion or to other mechanisms such as the role of sPLA2 X in mucosal stem cell differentiation, Wnt signaling, and eicosanoid formation (257)."

"ACh is not only a neuronal transmitter of fundamental importance in the gut. As review'd in Refs. 12, 316, it is formed in numerous extraneuronal tissues, including gut epithelium, and may have trophic effects, which are essential for mucosal functions; e.g., studies of crypt-villus organoids from small intestine showed an effect of ACh formation on stem cell stimulation and epithelial integrity (283); ACh may have trophic effects, which are essential for mucosal functions; and ACh signaling is expressed in lymphocyte subpopulations in the gut and exerts immunoregulatory functions (321). The cholinergic effects of nicotine have been implicated in the protective effects of smoking in UC (17)."

"Many tumors, including colorectal cancer (CRC), exhibit upregulation of choline kinase-α and CCT and increased PC synthesis (10). Feeding choline PLs might either enhance tumorigenesis by increasing choline access or counteract CRC by an anti-inflammatory effect in the colon. Two case control studies (174, 209) related a high-plasma level of choline to reduced risk of CRC, but a study on male smokers with CRC found the opposite (99). Animal experiments are also contradictory. In Min−/+ mice, a methyl-deficient diet suppressed tumor formation (102), but another study found that betaine inhibited formation of inflammation-associated experimental CRC (141). We find no experimental studies that specifically examine effect of dietary PC in CRC models."

"Cystic fibrosis (CF) is characterized by lowered plasma choline PLs with a decrease in several molecular species of PC. Lyso-PC levels are low (227). Increased loss of PL in feces and lowered ACh in leukocytes and lung tissue were observed (127, 128). Since CF affects both pancreatic secretion and intestinal secretory and absorptive functions, both pancreatic insufficiency and intestinal dysfunction may contribute to these findings. Studies of sPLA2 IB and PLB function in CF are lacking. In a transgenic CF mouse model, alk-SMase, N-CDase, and IALP were normal (224). A structured PC formulation improved choline and PC levels, and muscular function, in CF patients (256). Studies on PC and SM absorption in CF are needed."​

 

[SB4]

@Amazoniac Very interesting, thanks. I would have to guess I was over saturating lumenal transporters with too much Lecithin at anyone time causing gut bacteria to get there hands on it.

 

[Amazoniac]

@Amazoniac Very interesting, thanks. I would have to guess I was over saturating lumenal transporters with too much Lecithin at anyone time causing gut bacteria to get there hands on it.

A few days prior to creating this thread I contacted Pedro Cásner and he seemed open to the idea, Jorge Dincó has been bugged for a while now. There appears to be enough demand for such product.

The intention in considering 'personal computer' with shorter-chain fats attach'd is because you could reap the benefits of its digestion without risking making cells incorporate the specific fatty acid and assume an odd composition over time; the body would would have no choice but to replace all of the fatty acids if it's going to use it for structure.

However! These materials are expensive*, and I wouldn't be counting on a released supplement soon; it can take time for vendors to source it (or find alternatives). There's phosphatidylcholine derived from eggs, but given what @whit's friends are fed, I'm not sure if they end up with a desirable profile, yet still better than seeds.
*Because of this, 150 mg/serving must make it more feasible.

An advantage of water-soluble forms is if the person has issues with fat digestion (but there can be with its metabolism as well later on as well). A disadvantage is that these tend to be delivered faster, which might be undesirable if a lot is taken at the once.

- Scientific Opinion on Dietary Reference Values for choline | ESFA

"Dietary free choline is quickly taken up by the enterocytes, mediated by the saturable organic cation transporters (OCTs) (choline transporter-like protein 1 (CTL1) or solute carrier 44A1 (SLC44A1)) (Section 2.3.3.), which rely on facilitated diffusion governed by the choline concentration gradient and the electrical potential across the membrane, then free choline is cleared from the plasma within about three hours (Zeisel et al., 1980; Jope et al., 1982). Dietary PC increases plasma choline concentration for 8–12 hours, without a significant rise in PC concentration in plasma (Zeisel et al., 1980; Jope et al., 1982). PChol and GPC are rapidly absorbed and appear in plasma predominantly as free choline.

PC and GPC from the diet or secreted in the bile are hydrolysed by phospholipases (PLs) to liberate choline (Zeisel and Blusztajn, 1994). Water-soluble choline compounds (PChol and GPC) can also enter the portal circulation of the liver intact. Lipid-soluble compounds (PC and SPM) are either hydrolysed by PLs or enter the lymph incorporated into chylomicrons."

"Choline is stored in tissues either as membrane-bound phospholipids or as intracellular PC or GPC (Zeisel and Blusztajn, 1994). Choline is stored in the brain as membrane-bound phospholipids, which are hydrolysed by choline acetyltransferase to provide choline for acetylcholine synthesis (Section 2.2.1.). In most animal tissues, PC accounts for 95% of the total choline content, the remaining 5% are choline, PChol, GPC, CDP-choline and acetylcholine (Li and Vance, 2008)."

"Excretion of choline in the urine is low in relation to usual dietary intakes. De la Huerga and Popper (1951) (Section 2.3.5.2.2.) determined the excretion of choline and TMA in the urine in four healthy adult subjects after single oral doses of 2–8 g of choline (as choline bicarbonate). The authors detected no or negligible choline in urine at baseline and not more than 0.3% of the administered dose thereafter. Within 24 hours, two thirds of the administered dose were excreted as TMA and TMAO, which suggests that unabsorbed choline was metabolised by the intestinal microbiota."​

- Comparative effects of choline chloride and phosphatidylcholine on plasma and liver lipid levels in rats fed a choline-deficient high cholesterol diet

As commented on the other thread, I don't know much about choline chloride, but there are human experiments with it. Is the one that people have been using pure? Because choline dosing is substantial.

 

[Amazoniac]

Glycerophosphocholine is the form is would favor for now until these gurus offer something better.

It's not synthetic, usually derived from soy or sunflower lecithin but the fatty acids are removed. Sold as 99% pure and hopefully this means that a great deal of the impure portion is not industrial contaminants.

Even though we don't know how much of it is adsorbed intact, we do know that these water-soluble forms tend to be broken down during digestion, reach the liver and then are released to other tissues, which is what we want.

Its absorption is far better compared to the cheap forms.

Another positive point is that it's the major form in milch (about 60%), and when you include free choline and phosphocholine (since they might all be broken down to some extent), that's 90%. Therefore I doubt it's unsafe.

- Incomprehensive/ble Notes On Choline

Spoiler: Choline forms in milch

Fat content is approximate, otherwise when it's 0% they wouldn't be able to detect any fat-soluble form.

Two cups of milch provide about 50 mg of choline as glycerophosphocholine, 15 mg as free choline and 10 mg as phosphocholine, totaling 75 mg.

As SB4 commented, the glycerophosphocholine molecule is 40% choline (which is also nice for not having to deal with a lot of undesirable stuff to get what you want), so you'd need 125 mg of GPC to get 50 mg of choline (or 200 mg to get 80 mg).

It's possible to obtain more of it through foods in a sitting, but for regular use, I would stick to lower doses more frequently (ex.: 3x 150 mg of GPC for 180 mg of choline), try to aim for the least possible amount for the desired effect, and would avoid taking it without the other B-vitamins (or when magnesium is lacking).

 

[Amazoniac]

- To TCA300 : What Is Your Daily Regimen (diet And Supplements)?

La-da-da-da-dahh
It's the motherfuckin' t-c-single-a (tca!)

 

[SB4]

@Amazoniac So if we took some aGPC and mixed it with say Caprylic acid we could create a phosphatidylcholine molecule with the 2 fatty acids being C8.

If we mixed aGPC with palmitic acid would the same happen? I suspect it is not that easy. Perhaps enzymes are needed to connect the fats to glycerol.

If aGPC is mixed in water would it loose its emulsion properties? Would the H2O occupy the 2 remaining spaces on the glycerol molecule?

 

[Amazoniac]

@Amazoniac So if we took some aGPC and mixed it with say Caprylic acid we could create a phosphatidylcholine molecule with the 2 fatty acids being C8.

If we mixed aGPC with palmitic acid would the same happen? I suspect it is not that easy. Perhaps enzymes are needed to connect the fats to glycerol.

If aGPC is mixed in water would it loose its emulsion properties? Would the H2O occupy the 2 remaining spaces on the glycerol molecule?

As you can tell from the image above, glycerophosphocholine is a result of phosphatidylcholine catabolism, and you'll find various charts on choline metabolism representing it as such, suggesting also that it has to be completely broken down for the body to be able to synthesize from scratch the desired form. Terma for whatever reason prefers CDP-choline, maybe it's related to this.

But I always thought it was suspicious that the process can't simply be reversed (as you described, yet in the body).

- Identification of a novel GPCAT activity and a new pathway for phosphatidylcholine biosynthesis in S. cerevisiae

"In the present [yeasty] paper we show [] that GPC can be acylated by yeast microsomal membranes in an acyl-CoA dependent reaction to form lysophosphatidylcholine (LPC), which is then further efficiently acylated to form PC. We call this novel enzymatic activity GPC acyltransferase (GPCAT). Accordingly, a direct recycling pathway for PC exists in eukaryotes, which involves deacylation of PC followed by reacylation of the resulting GPC."​

However there's the chance that these forms are not adsorbed intact, so synthesis from scratch will be required anyway.
The meal composition might affect to some extent the fatty acids that are incorporated, but they won't combine outside of the body.

GPC seems to me a decent alternative.

 

[Terma]

I love your topic so I'm going to bump it, but I won't have physical ability to post more in it until many nows from this now.

 

[Amazoniac]

- Absorption, tissue distribution and excretion of radiolabelled compounds in rats after administration of [14C]-l-α-glycerylphosphorylcholine

"The absorption, distribution and excretion of a-GPC were studied in rats after i.v. and oral doses of the compound labelled with [14C]-choline or with [14C]-glycerol. Kinetics were different for the two labelled compounds and for i.v., and oral dosing. Intact a-GPC, glycerol phosphate, choline and/or choline phosphate and at least two unidentified metabolites for each labelling position could be detected in blood after i.v. injection. After oral administration, the main circulating metabolite was choline (after [14C]-GPC); intact a-GPC was not present after either labelled compound although there were the same unknown metabolites as after i.v. injection."​

The problem with choline experiments is that they use high doses, in this one the lowest ingested dose was 100 mg/kg, grossly equivalent to a human dose of 16 mg/kg, so more than 1000 mg of GPC in a shot, providing 400 mg of choline.

Baseline values to compare weren't available, but check out tissue distribution after a while:

Spoiler

The graph from the other thread was modified to classify them by GPC (Gpcho) content/serving due to supplements in mind:

- Incomprehensive/ble Notes On Choline

Spoiler

Liver is the food that provides the most GPC in a serving: 175 mg of it, which gives you 70 mg of choline. Therefore a dose of more than 1000 mg is quite high.
From the graph you can tell why 150 mg of GPC is reasonable (especially if you also consider the 'Total watery cho').


There are two further measures to make it safer:

• Using it in meals that contain plenty of glycine. A concern with choline supplementation is regarding methylation, but if glycine is capable of protecting the person from excess methionine, the same has to apply to choline since both enter the same cycle.
• Taking it after a meal to be sure that tissues are already charged and that (in Raj's terms) it's going to be put to good use. It's nice that it has a sweet taste.

I love your topic so I'm going to bump it, but I won't have physical ability to post more in it until many nows from this now.

Don't worry, take your time, you have a reserved place in our hall of gurus, just like Such or Trabis. In spite of being lumped into this group, each of you that get there is one of a kind, or what they refer to as sui genesis.

 

[Amazoniac]

As always, I would start by grasping the average of a week on your favorite nutrition app (which happens to be Cron-o-meter). From there, you'll know how probable it is that you're lacking.

I forgot to comment that there's a considerable decrease in choline content when milk is process'd to other products such as cheese or strain'd yogurt, and even regular yogurt can be affected (I was going to prolactinize this word as well, but 3 in a sentence is too much):

Yogurt: Nutritive and Therapeutic Aspects

Spoiler

I believes that the following is illustrative:

- Incomprehensive/ble Notes On Choline (first link)

Spoiler: Pay attention to your scroll thumb and how it will shorten by expanding this

But requirements vary depending on the conditions, so what's low depends..

A High-carb Diet May Explain Why Okinawans Live So Long​

..but these are almost opposites of what was list'd on the original post.

Given that meals will be providing some and that it's prudent to avoid an excess of supplemental choline, it's worth starting with only 100 mg of GPC 3x a day, providing 120 mg of choline, and work from there if needed. In case you sense that more is desirable, consider adding another instance, increase the amount to 150 mg in one of them, or a combination of these, trying to avoid taking more than 150 mg at a time before you familiarize with it enough to judge what's safe and adequate for you.

 

[Vesi]

I forgot to comment that there's a considerable decrease in choline content when milk is process'd to other products such as cheese or strain'd yogurt, and even regular yogurt can be affected (I was going to prolactinize this word as well, but 3 in a sentence is too much):

Spoiler

View attachment 13632

Thank you, i was wondering how much choline is lost in fat free milk vs whole. According to this chart, and Nutritiondata info ( Milk, whole, 3.25% milkfat Nutrition Facts & Calories ), whole milk has more choline per calorie than fat free milk.

Skim 4.8mg / 100g, calories 35, 0.14mg per calorie
Whole 14.3mg / 100g, calories 60, 0.24mg per calorie

( also for comparison:
Egg, whole 225mg / 100g, calories 155, 1.45mg per calorie
Egg, yolk 628mg / 100g, calories 317, 2.15mg per calorie
Beef liver 418mg / 100g, calories 175, 2.4mg per calorie
Potato, boiled 13.2mg / 100g, calories 86, 0.15mg per calorie
Beef, sirloin 88.8mg / 100g, calories 142, 0.63mg per calorie
Broccoli, boiled 40.1mg / 100g
Spinach, boiled 19.7mg / 100g
)

 

[Amazoniac]

Thank you, i was wondering how much choline is lost in fat free milk vs whole. According to this chart, and Nutritiondata info ( Milk, whole, 3.25% milkfat Nutrition Facts & Calories ), whole milk has more choline per calorie than fat free milk.

Skim 4.8mg / 100g, calories 35, 0.14mg per calorie
Whole 14.3mg / 100g, calories 60, 0.24mg per calorie

( also for comparison:
Egg, whole 225mg / 100g, calories 155, 1.45mg per calorie
Egg, yolk 628mg / 100g, calories 317, 2.15mg per calorie
Beef liver 418mg / 100g, calories 175, 2.4mg per calorie
Potato, boiled 13.2mg / 100g, calories 86, 0.15mg per calorie
Beef, sirloin 88.8mg / 100g, calories 142, 0.63mg per calorie
Broccoli, boiled 40.1mg / 100g
Spinach, boiled 19.7mg / 100g
)

It has to be a comparison per serving to be fair because of fat calories in whole milch.

 

[redsun]

Many people don't consume dairy and eggs (which are great sources of choline) due to intolerance/allergy, for not being able to find reliables ones, and/or for not finding them appealing. Some meats provide a considerable amount, but they're not eaten in sufficient quantities. Organ meats can be good sources but aren't consumed frequently enough, so we can disconsider them.

So a low choline intake isn't unlikely. To add to the problem:

• Plenty of fructose
• Saturated fat in generous amounts
• Methionine restriction
  
• Low creatine (muscle meats)
• Not enough vegetables
• High-dose B-vitamins supplementation
• Impair'd liver and metabolism in general
  
• Estrogen artificially lowered
• Extraordinary needs

There's nothing inherently wrong with most of these, but it's a synergistic program to increase the choline requirement.

And then you'll find subset of people avoiding even leafy greens due to the poison/"vitamin" A issue, so sources become scarce.

- Incomprehensive/ble Notes On Choline
- Meeting the Choline Requirement — Eggs, Organs, and the Wheat Paradox | Mito
- Consuming Creatine in Foods and Supplements | Mito

Therefore I suspect that having a decent choline supplement available for the community is something reasonable.


As far as I know, phosphatidylcholine is the least problematic form, but the choline supplements available are sourced from seeds and are often of poor quality.

The fatty acids attached to phosphatidylcholine are changed when metabolized, so it's possible for the fatty acid profile of a meal to be reflected in the phosphatidylcholine molecule to some extent when incorporated. This is an argument in favor of using any phosphatidylcholine ester, but if it's polyunsaturated, there would be an unecessary exposure to these fats in a weight ratio of about 1:8. As an example, for every 0.2 g of choline, it's an obtention of 1.6 g of PUFAs with the risk of these being incorporated where they shouldn't (hence Zeus using phosphatidylcholine as a carrier for fatty acids) and also adding up over time.

Zeus' Mitolipin would be ideal if it wasn't for the price and volume: it's clearly not intended to be a choline supplement.

200 mg/serving lasting 2 months or so is what I had in mind; it's a moderate dose that was found to be the average missing from people's diet. This is physically possible since the serving of lecithin products is 2.5 g, whereas such product would be less than 2 g.
Mitolipin provides less than 30 mg/serving, a bottle would last 5 days to supply that amount.


- Storage & Handling of Lipids | Avanti Lipids

"Lipids composed of fatty acids that are completely saturated (e.g., dimyristoyl or dipalmitoyl phosphatidylcholine) are stable as powders."

"Lipids composed of fatty acids containing one or more double bonds (e.g., dioleoyl phosphatidylcholine or egg phosphatidylcholine) are not stable as powders. These lipids are extremely hygroscopic as powders and will quickly absorb moisture and become gummy upon opening the container. This could result in hydrolysis or oxidation of the material."​

How could conservative doses of it used as part of a complex be more problematic than a prolonged insufficiency? We can't ignore that its lack isn't something rare in this community.

If you have an object, please post.
By the way, I don't know why a 'No' alternative was included since it's about having enough people interested, and too many 'nitric oxide synthases' give an impression that it's not worth it.

--
@haidut @healthnatura @LifeGivingStore @Terma

Can you elaborate on how B-vitamins increase the choline requirement? Thanks.

 

[Amazoniac]

Can you elaborate on how B-vitamins increase the choline requirement? Thanks.

Excess niacin will drain methyl groups, hence the recommendation to pair with betaine (each molecule of them providing 3 groups compared to 1 from methionine) and preventing disturbances. You can recycle and obtain indirectly, but 3 grams of niacin is not symbolic.

- Interactions Of Thiamine, Riboflavin, And Other B-vitamins (I don't remember the mechanism, but there are publications on it)

 

[Terma]

Never got back... Well, another source wouldn't hurt, but honestly in all late circumstances I've been content with low-dose 99% alpha-GPC (ND) as a choline prodrug, and recently have done well re-trying CDP-choline as a choline/uridine source (alpha-GPC more toward morning, CDP-choline at dinner though only in limited doses - I am going to try triacetyluridine/UMP oral again for nearer to bedtime, since no choline - did several times in the last 5 years but not with this arsenal - uridine works better with a crowd, much like (methyl)folate, which happen to require each other). The rest I get from shrimp (and liver). You could always make better-tested offers - whether an alternative form or one of those reduxed, I might gopher it. I don't bother with pre-formed phospholipids much unless they were intended for gut health (as you posted about) as an interesting topic or to help absorption of other compounds. You could have predicted this post. [I'm comfortable with my choices on this topic, so attention shifted to specific contexts and uses (timing) for them such as astrocyte, gut health, sleep... Otherwise I seriously appreciate someone soldiered this cause so minutely]

 

[Momentum]

Alpha-GPC hasn't yet been broken down. Also, bioavailability is higher. Another (linked) study suggested excess choline is what makes it to be consumed by gut bacteria (which then give off bad metabolites).

Higher levels of TMA results in a fishy odor and is typically caused by choline and acetyl L-carnitine. Riboflavin helps metabolise TMA, as it's part of the chain that creates the metabolizing enzymes.

@baccheion This thread is mainly above my knowledge, but I'm wondering if it can give me insight into some of deficiencies or abundances. Years ago, I took one drop of DMSO orally. Kids came home from school and were just about gagging from the horrible rotten fish smell in the house. It turned out to be me.....and I couldn't smell it. Terrifying. (I take a lot of MSM oral, but have never had a problem.)
I'm just about to order several of @haidut 's supps and I'm worried about too much DMSO topical and becoming odorous (this happened with my DD's dog's soft tissue application after several days, also severe gut distress). Mainly, hoping for insight in something to correct in me. (BTW - high doses of L-carnitine make me very short tempered.) Thanks for any insights.

 

[baccheion]

@baccheion This thread is mainly above my knowledge, but I'm wondering if it can give me insight into some of deficiencies or abundances. Years ago, I took one drop of DMSO orally. Kids came home from school and were just about gagging from the horrible rotten fish smell in the house. It turned out to be me.....and I couldn't smell it. Terrifying. (I take a lot of MSM oral, but have never had a problem.)
I'm just about to order several of @haidut 's supps and I'm worried about too much DMSO topical and becoming odorous (this happened with my DD's dog's soft tissue application after several days, also severe gut distress). Mainly, hoping for insight in something to correct in me. (BTW - high doses of L-carnitine make me very short tempered.) Thanks for any insights.

Unsure about remedying DMSO (except not applying). I was referring to internal choline and L-carnitine metabolites.

Acetyl L-carnitine increases acetylcholine and norepinephrine. Eventually, it also increases serotonin. Higher norepinephrine can result in irritability.

 

[Momentum]

Unsure about remedying DMSO (except not applying). I was referring to internal choline and L-carnitine metabolites.

Acetyl L-carnitine increases acetylcholine and norepinephrine. Eventually, it also increases serotonin. Higher norepinephrine can result in irritability.

Thank you.

 

[Adrienlcrx]

@Amazoniac La CHOLINE L-BITARTRATE Nutrimuscle est un nutriment essentiel pour la cognition et la fonction nerveuse, lié aux vitamines du groupe B. I think it can be interesting if you ive in Europe...