Incomprehensive/ble Notes On Choline

[Frankdee20]

I find it a bit mind bottling when people are concerned with supplementation of choline to complement diet until repletion for fear of potential problems with methylation, but at the same time consume something like 2.5 g of methionine a day through cheese.

This is the quote that often appears:

Protective CO2 and aging
"Methionine and choline are the main dietary sources of methyl donors. Restriction of methionine has many protective effects, including increased average (42%) and maximum (44%) longevity in rats (Richie, et al., 1994). Restriction of methyl donors causes demethylation of DNA (Epner, 2001). The age accelerating effect of methionine might be related to disturbing the methylation balance, inappropriately suppressing cellular activity. Besides its effect on the methyl pool, methionine inhibits thyroid function and damages mitochondria."​

From what I read, methionine restriction can be harmful and producing the counters if there's a choline deficiency.

I'm not disregarding that it can be indeed an issue, especially when you supplement in the adsense of other vitamins or a lot. I also might be missing something, such as choline providing more methyl groups per molecule, or turnover rates of each, but perhaps a greater concern than too much, is too little of it. With excess you're able to control it, niacin is one of the ways. But what can the body do in a deficiency? Chronic insufficieny is quite stressful and you can confirm it through the fast elevation in liver enzyms that happen in choline experiments in a matter of days/weeks. How is this not carcinogenic?

For me, it’s easier to restrict Choline food choices as it’s easily identifiable in eggs, liver, fish, broccoli and milk. I’ve got no idea how to restrict methionine

 

[Terma]

Here's an oddity I haven't been able to explain yet (not enough time - if you already know the answer it would save me some effort):
Methionine restriction prevents the progression of hepatic steatosis in leptin-deficient obese mice - ScienceDirect

MR reversed the severity of steatosis in the ob/ob mouse. This was accompanied by reduced body weight despite similar weight-specific food intake. Compared with the CF group, hepatic TG levels were significantly reduced in response to MR, but adipose tissue weight was not decreased. MR reduced insulin and HOMA ratios but increased total and high-molecular-weight adiponectin levels. Scd1 gene expression was significantly downregulated, while Acadvl, Hadha, and Hadhb were upregulated in MR, corresponding with increased β-hydroxybutyrate levels and a trend toward increased FAO. The VLDL secretion rate was also significantly increased in the MR mice, as were the mRNA levels of ApoB and Mttp. The expression of inflammatory markers, such as Tnf-α and Ccr2, was also downregulated by MR.

Normally methionine/SAMe associates with increased VLDL excretion, but there may be different circumstances, and these obese ******* mice sometimes.

(For the record I lean toward restricting methionine while supplementing adequate choline - alpha gpc - but of course this could be ruined by uncontrolled breakdown to betaine, which is another topic)

 

[Spondive]

I thought related...


In 1937 Dr. Helen Tucker and Dr. H. C. Eckstein determined methionine to be a lipotropic agent. The experiments of Dr. Charles Best and Dr. Jessie Ridout showed that even small doses of methionine have the same effect on fat metabolism as higher doses (Best, 1940; Tucker, 1937). Methionine is an essential amino acid that helps the body take control of excessive serum levels of estrogen for one thing. High estrogen levels reduce bile concentrations that are responsible for fat emulsification and lipid passage through the liver. Methionine helps deactivate estrogens leading to improved fat metabolism and mobilization. It is well noted that elevated estrogen levels, especially in males lead to unsightly adipose depositions and obesity. Overweight men have issues with feminization as their estrogen levels tend to climb. Methionine along with choline detoxifies amines in protein metabolism. It also acts as a catalyst for choline and inositol functions. Methionine has another important function in that it affects the body’s levels of glutathione. Glutathione is a compound in the liver that is crucial in hepatic detoxification and acting as a very potent antioxidant. Glutathione is essential for the defense of the liver against toxic compounds that it metabolizes after oral ingestion. Glutathione is essential for good health and while oral intake of glutathione does nothing to embellish its liver concentrations, it is indispensable for that process to occur with intake of substrates or precursor components. Besides methionine and choline; n-acetylcysteine (NAC) and the amino acids glutamine and glycine are of importance (Shils, 1999).

 

[lvysaur]

Premenopausal women are remarkable in terms of being resistant to depletion (from a link on the previous of the pages):

That shows the opposite of what you're claiming it shows. It shows that men become replete in choline very easily, while women do not, and reproductive women least of all.

 

[Amazoniac]

That shows the opposite of what you're claiming it shows. It shows that men become replete in choline very easily, while women do not, and reproductive women least of all.

Men in general only became replete with greater intakes in relation to others, so we must be the least resistant (which also reinforces that our requirements must be higher). Then, postmenopausal women, followed by pre. So premenopausal women should be the group that adapts best to low intakes. They claim the synthesis depends on oestrogen, but I don't know about that.

Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by estrogen in human and mouse primary hepatocytes
"When fed a diet low in choline, premenopausal women were much less likely to develop choline-deficiency associated organ dysfunction compared to men or postmenopausal women (19 [the one in question]). This suggests that premenopausal women might have an enhanced capacity for de novo biosynthesis of choline."

 

[Amazoniac]

The right amount of Choline helps my brain a bit, but if I eat 4 eggs, I’m brain dead retartded, completely not in sync with my environment and brutally depressed. I simply don’t eat them.

Guru, even though eggs are nutritious, there's nothing in them (as far as I know) that could exempt them from being also a risky source of methyl donors when eaten in substantial quantities. It's experiences like yours that add to my suspicion that what's wrong with choline supplementation is the form, the quality and the dose. Am I missing something?

 

[Amazoniac]

Choline and its products acetylcholine and phosphatidylcholine

 

[Frankdee20]

Guru, even though eggs are nutritious, there's nothing in them (as far as I know) that could exempt them from being also a risky source of methyl donors when eaten in substantial quantities. It's experiences like yours that add to my suspicion that what's wrong with choline supplementation is the form, the quality and the dose. Am I missing something?

So you mentioned the form, Choline in eggs exists differently than from beef liver. You’re saying the form matters ? How ? Liver has a lot of Choline but effects me differently than eggs. Perhaps because of other things in liver

 

[Terma]

Eggs are not ideal source of choline afaik.

If you eat the yolks only (like paleo guys + Paul Jaminet have advocated for ages now), you get a good choline:methionine ratio. But you still get all that linoleic and arachidonic acid. I never learned if dietary arachidonic acid was really an issue or not (maybe you guys know, but Jaminet and others seemed to think it wasn't; however there were a study or two that clearly showed increased inflammation from egg consumption; but that could easily have been the trimethylamine/gut effect; I prefer to avoid out of simplicity). Regardless, you get a fair chance of being affected by the TMAO issue. In addition the high BCAA/leucine/insulin in eggs probably messes with you. [Also: I forgot if oxidized cholesterol in the yolks was a serious issues, but I always soft-boiled them in case]

As far as I could tell, and what I selected for myself, Alpha-GPC was the best source of choline. If the supplement is produced properly (I saw no research to doubt it from NootropicsDepot, though worth looking into), it should be absorbed well/fast and not contribute any fatty acids of its own.

That said it's probably a good idea to spread it out, both to increase absorption of the ingested amount and to avoid high blood choline levels that would spike acetylcholine too much. However, I haven't figured out if it's best taken with or without food yet, something to do (there are +/- to each).

CDP-choline is not the worst either since it should break down to uridine + choline in human gut, but as far as I saw Alpha-GPC might be absorbed faster than the choline part, while you want to limit consumption of uridine (total/dose as well as only consume it orally with meals).

Both of these avoid the tartaric and citric acids which appear to be gut and kidney burdens, or clearly gut burdens to me personally.

 

[Amazoniac]

I suspect that the same reason for Zeus' Mitolipin being effective can make low-quality eggs a bit concerning since the fat composition along with phosphatidylcholin can perhaps facilitate their incorporation instead of being cleared.

Some days ago I contacted Raj to know his opinion on insufficiency and supplementation. The only reason for not posting his exact replies here is that he didn't answered (and probably won't) if it's fine by him.

Ray, one more thing if you don't mind, regarding your following message to someone:

"I think it's risky to supplement methyl donors in substantial quantity, such as choline, betaine, methionine, and S-adenosylmethionine."​

.
Chris Masterjohn commented that the current estimated requirements for choline were based on depletion and repletion until normalization of liver enzymes, and that these only increase in circulation when there's significant damage already going on from the deficiency; implying that the requirements can be higher than suggested, at least for certain people.

Methionine restriction causes problems in animals that are also limited in choline. You can regulate or dispose a little excess of methyl groups through other means (glycine, niacin, etc), but it can be stressful if you need them but they're not being supplied.

Regarding eggs (for being one of the best sources of choline), I'm not aware of anything in them that could prevent issues of provision of methyl groups in substantial quantities for example. Or in other words, they can be just as bad as a supplement in terms of being a source of excess substrate for methylation. This seems to me an issue of improper amount, rather than the source.

What do you think?
Are saturated phosphatidylcholines acceptable?

.
He commented that eggs are nutritious whereas supplements can be just a source of methyl groups.
I replied:

Some people are allergic to eggs, don't enjoy them or just can't source reliable ones. It can be quite tough to get enough choline without them, especially if the needs are higher. Liver is a great source, but I guess not for daily consumption. Most foods provide some, but not enough for such cases.

Do you think that supplementation to compensate for a suboptimal choline intake in an overall good diet still poses the risk of excess methyl groups?
If you were to supplement, which form would you choose?

I don't sell products, I'm just gathering enough opinions until they can finally deactivate my internal guidance system.

He then sent me this:
Diet, Methyl Donors and DNA Methylation: Interactions between Dietary Folate, Methionine and Choline | The Journal of Nutrition | Oxford Academic

This part is interesting:

For humans, the major sources of methyl groups in foods come from methionine (∼10 mmol of methyl/d), one-carbon metabolism via methylfolate (∼5–10 mmol of methyl/d), and from choline [∼ 30 mmoles methyl/d (11)]

Steven Zeisel has many articles on choline, some of them were already posted here.​

I then replied:

I've read some of Steven Zeisel's publications before. Was there anything specific in that article? Because it reinforces that a choline insufficiency can compromise other nutrients, that a lack of choline along with methionine isn't a good idea, and that there is such thing as hypomethylation and cancer (at least for onset).

One quart of milch provides about 150 mg of choline (involving him again).

..and again:

Sex and menopausal status influence human dietary requirements for the nutrient choline
"We identified a group of rapid depleters who developed organ dysfunction when fed the AI of choline (550 mg choline · 70 kg−1 · d−1). We presume that these men, when free-living, consumed diets that had a higher choline content; this would explain the decreased mean plasma phosphatidylcholine concentrations that we observed after 10 d of the 550-mg choline diet. Similarly, our experimental diet was likely higher in betaine than was the subjects’ ad libitum diets, perhaps explaining the increased mean plasma betaine concentration observed. These rapid depleters developed fatty liver, muscle damage, or both that reversed when they consumed a high-choline diet (825 mg · 70 kg−1 · d−1 diet) or an ad libitum diet."​

.
For such cases it would be very difficult to achieve that without eggs. I'm open to the idea that choline supplementation isn't safe, but (as mentioned before) it seems to me that any issue appears to be from improper amount or other nutrients being missed as well. As far as I know, there isn't anything in eggs that could balance excess methyl groups (in spite of being nutritious).

Many people report improvement from betaine supplementation and I interpret it as a sign of lack of methyl donors from stress. Should the person back off to prevent potential complications or meet the increased demand? Because if those are indeed missing, the alternative way to obtain them would be through tissue breakdown to release choline and aminoacids.

Am I missing something?

.
He commented something about eggs and milk providing so much methionid that lowering choline isn't an issue.
..included this:
https://www.liebertpub.com/doi/abs/10.1089/rej.2009.0902

--
Random links:
- 19x Increase in Growth Hormone 60min After Ingestion of 1g of Glycerophosphocholine (GPC) in Young Male Subjects - SuppVersity (..the common bean in question is soy)
- WO2000048986A2 - Low odor choline salts - Google Patents (choline acetate is mentioned, but worth reading regardless)
- Table 1 from Comparative in vitro study of cholinium-based ionic liquids and deep eutectic solvents toward fish cell line. - Semantic Scholar

 

[Amazoniac]

So you mentioned the form, Choline in eggs exists differently than from beef liver. You’re saying the form matters ? How ? Liver has a lot of Choline but effects me differently than eggs. Perhaps because of other things in liver

Examples:

Choline - Linus Pauling Institute

"Taking large doses of choline in the form of phosphatidylcholine (lecithin) does not generally result in fishy body odor, because its metabolism results in little trimethylamine."

"CDP-choline (citicoline) and choline salts, such as choline chloride and choline bitartrate, are available as supplements. Phosphatidylcholine supplements also provide choline; however, choline comprises only about 13% of the weight of phosphatidylcholine (79). Therefore, a supplement containing 4,230 mg (4.23 grams) of phosphatidylcholine would provide 550 mg of choline. Although the term "lecithin" is synonymous with phosphatidylcholine when used in chemistry, commercial lecithins are usually prepared from soybean, sunflower, and rapeseed, and may contain anywhere from 20%-90% of phosphatidylcholine. Egg yolk lecithin is a more unlikely source of lecithin in dietary supplements. Moreover, the nature of phosphatidylcholine-containing fatty acids depends on whether lecithin is produced from vegetable, animal, or microbial sources. In particular, soybean lecithin is richer in polyunsaturated fatty acids than egg yolk lecithin (80)."

 

[Amazoniac]

Male Rats Fed Methyl- and Folate-Deficient Diets with or without Niacin Develop Hepatic Carcinomas Associated with Decreased Tissue NAD Concentrations and Altered Poly(ADP-ribose) Polymerase Activity

"All rats fed the methyl-deficient diets in both experiments showed typical effects of a methyl donor deficiency, such as fatty livers, decreased hepatic SAM concentration and either increased or unaltered hepatic SAH levels (data not shown). In Experiment 1, decreasing the methionine in the diet by decreasing the casein content increased the severity of the effects. In both experiments, however, hepatocellular carcinomas developed only in rats fed the '6% gelatin, 6% casein' diet with or without niacin. Rats fed either the 12 or 8% casein diet did not develop carcinomas, although the methionine contents of the 8% casein (2.5 g/kg diet) and 6% casein and gelatin diet (2.3 g/kg diet) were similar. One striking difference in the amino acid composition of casein and gelatin is that gelatin contains more glycine than does casein (MCFD-B, 14.9 g/kg diet; 8% MCFD, 1.6 g/kg diet). In an experiment by Krumdieck et al. (1992), a severe shift in the folylpolyglutamate distribution towards shorter forms was observed in livers of rats receiving supplemental glycine (25 g/kg diet). More than a 10-fold increase in monoglutamate and a reduction of hexa- and pentaglutamates were observed. Although these rats had a normal folic acid intake, the total liver folates in these rats dropped to about one third of control levels. It is possible that also in the case of the MCFD-B diet the high glycine content caused a further decrease in liver folate levels and therefore rendered rats more methyl deficient."​

.
That's even worse if you consider that animals eating 6% of caseid were eating half the amount of PUFA. However their sucrose consumption increased a lot and the combination isn't good.

Spoiler

The initials are for: Methionine, Choline, Folate, Niacin, Deficient.

Thanks to Travo for schooling me about varying colors of highlights.

.

"In Experiment 2, 100% of rats fed the casein-gelatin diets (MCFD-B and MCFND-B) developed tumors, whereas in the first experiment only one out of four rats fed the MCFND-A diet showed hepatocarcinomas. The MCFD-B and MCFND-B diets contained 2.3 g of methionine, no choline, no folate and 10 μg of vitamin B-12 per kilogram of diet. In experiments in which Fischer 344 rats were fed the Lombardi diet, 20–50% of the rats were reported to develop hepatocellular carcinoma after 11–24 mo (Ghoshal and Farber 1984, Mikol et al. 1983, Nakae et al. 1992). The Lombardi diet contained 2 g of methionine, traces of choline, 10 μg of vitamin B-12 and 2 mg of folate per kilogram of diet. The diet composition in regard to the methionine, choline, cysteine and oil content of the Lombardi diet is very similar to the diet used in our laboratory except for the absence of folate and increase in glycine. We hypothesize that the folate deficiency, enhanced by the increased glycine content, leads to a more severe methyl donor deficiency and an increased carcinogenic effect. This is not surprising because the endogenous formation of methionine from homocysteine depends on folate as a cofactor (Krumdieck 1990). If the folic acid supply is compromised, less methionine is formed and less S-adenosylmethionine is available for methylation."​

The PUFA content tripled as vvcll. I avoid blaming on it, but in this case it seemed to be a major contributor. The diet went from 50 g of soybean oil/kg to 150 g. On the other thread about PUFA and cancer, the animals became more vulnerable with as little as 0.5% of linoleic acid (weight of diet, not calories). Here they were getting about 9%.

But what's important is that a diet deficient in methyl donors brutalized the NAD concentration in tissues of animals regardless if they were also deficient in niacin or not:

"No differences were found in either number and size of tumors in rats fed the MCFD-B or MCFND-B diet. In rats fed the MCFND-B diet, tissue and plasma NAD levels were not significantly different from those of rats fed the diet containing niacin (MCFD-B). Rats apparently had enough NAD through the conversion of tryptophan to maintain niacin levels as in those fed MCFD-B. To produce a more severe niacin deficiency, it may be necessary to reduce the amount of tryptophan in the diet."

Spoiler

.
"In previous publications it has been shown that the PARP activity was increased in livers of methyl-deficient rats after 3 wk (Henning et al. 1989b). In the present study, the hepatic PARP activity was enhanced during a mild reduction in hepatic NAD concentrations (about 80% of controls), and the activity was lower than that of controls following a further reduction in NAD concentration (<60% of control) (Table 3). Because DNA strand breaks have been reported in the choline-folate–deficient rat model (James et al. 1989), we hypothesize that PARP activity was stimulated by DNA strand breaks to facilitate DNA repair. Stimulation of PARP activity may lead to a reduction of NAD below 60% of the control value leading to an inhibition of PARP activity, as observed in livers of rats fed the MCFND-A diet. The NAD concentrations were decreased in liver and blood at 6 mo, and at 17 mo other tissues showed alterations in NAD levels, suggesting a general change in niacin metabolism, possibly secondary to alterations in PARP activity. These alterations in PARP activity and NAD may slow DNA repair processes and increase DNA damage."​

.
I don't think decreased food intake could explain it alone because at the beginning of the experiment the animals were eating almost as much as the control group and there was already a marked drop in NAD concentrations.

 

[Amazoniac]

I think I'll also look into which mushrooms are a good source of it.

But the more encouraging amounts are usually when they're dried. Shiiiiitake mushrooms seem to concentrate choline in this form:

Spoiler

Choline Deficiency, Its Consequences and How You Fix It - SuppVersity

 

[Jennifer]

But the more encouraging amounts are usually when they're dried. Shiiiiitake mushrooms seem to concentrate choline in this form:

LOL You confuse me when you do that. I checked and white buttons are supposedly a source of B12 so I'll try to find them dried. I have dried shiitakes — not as potent as the penti shiitake, but they should suffice. Thanks! :)

 

[Amazoniac]

@haidut,

If you go through the various studies linked on the Mitolipin thread, they're supporting phosphatidylcholine in general. If you note, those are usually classic choline experiments (fatty liver, cognitive dysfunction, etc) that have been run with different forms of choline before.

It is an advantage that your supplement can provide it fully saturated, but the main component missing and being replenished must be choline.

As you know, eggs have plenty of phosphatidylcholine and no one considers it a vehicle for fats, it's considered a source of choline.
Should you now be thinking: "So what?"

VVc11, since the links that you shared have good outcomes for forms that aren't providing saturated fats, the benefit can't be explained by replacing unsaturated fats alone. If you accept that it's choline that's making most of the difference (since the other components of phosphatidylcholine aren't difficult to obtain as far as I know), it might be a choline supplement in essence.

Having enough choline is more important than supplying it already saturated. If the diet is deficient in it, it isn't unlikely to disfavor intact absorption and cleave it for other purposes. If the diet provides enough and safe fats are around, they should eventually combine for cell structure.

Analytical approaches to determination of total choline in foods and dietary supplements

Spoiler: Chaemical structures of choline and major choline-related compounds

The glycerophosphocholine supplements on the market are usually derived from soy and sometimes flowers of the suns. They're purified having the fatty acids removed, becoming wasser-soluble:

GlyceroPhosphoCholine (GPC), Mind-Body Nutrient for Active Living And Healthy Aging

"Quantitatively, the main phospholipid of membranes is phosphatidylcholine (PC). Cells grow or renew themselves by making new membrane mass, and this creates demand for PC, which in its turn is most efficiently synthesized from GPC.35"

"GPC is unique in being a water-phase phospholipid. Technically it is a “deacylated” PC—the PC molecule without its usual fatty acid tails (see Fig. 2). The GPC molecule is readily transformed to PC by simply adding back the fatty acid tails,35 and enzymes exist to do this trick with very little energy cost. Therefore GPC has special value for our cells: in its native form it is a unique protectant that can attain high levels in the cytoplasm without doing damage. Then, this reservoir can be drawn upon to make PC for membrane mass, notably without the major energy expenditure of energy needed to make PC from simpler precursors such as CDP-choline.35"

Spoiler: Main difference between GPC and PC

From a conversation with the same pimp of the other thread:

there's 10 mg of Diokine-GPC in every 100 g of skim milk. Ray commented somewhere that he sometimes consumed up to 3 quarts of milch in a day, which alone provides about 280 mg of choline as Dio-GPC

Frank of the Dees often mentions issues with extra choline (such as depressa), and this experience seems recurrent whenever people consume a lot of eggs or supplement more choline than needed. However! He also mentioned that this doesn't occur (or at least not as bad) with liver. So it reinforces two things:
- that eggs are nutritious but there's nothing in them that make them safe in terms of providing imbalanced amounts of choline
- that choline is problematic or even risky (mostly?) in the absence of other B-vitamins or beyond needs; which is probably one of the reasons for B12 being potentially harmful alone.

I agree that the B-vitamins that are directly involved in methylation are riskier, but they must still be present.

Terma, a tip hat.

 

[haidut]

@haidut,

If you go through the various studies linked on the Mitolipin thread, they're supporting phosphatidylcholine in general. If you note, those are usually classic choline experiments (fatty liver, cognitive dysfunction, etc) that have been run with different forms of choline before.

It is an advantage that your supplement can provide it fully saturated, but the main component missing and being replenished must be choline.

As you know, eggs have plenty of phosphatidylcholine and no one considers it a vehicle for fats, it's considered a source of choline.
Should you now be thinking: "So what?"

VVc11, since the links that you shared have good outcomes for forms that aren't providing saturated fats, the benefit can't be explained by replacing unsaturated fats alone. If you accept that it's choline that's making most of the difference (since the other components of phosphatidylcholine aren't difficult to obtain as far as I know), it might be a choline supplement in essence.

Having enough choline is more important than supplying it already saturated. If the diet is deficient in it, it isn't unlikely to disfavor intact absorption and cleave it for other purposes. If the diet provides enough and safe fats are around, they should eventually combine for cell structure.

Analytical approaches to determination of total choline in foods and dietary supplements

Spoiler: Chaemical structures of choline and major choline-related compounds

View attachment 10491

The glycerophosphocholine supplements on the market are usually derived from soy and sometimes flowers of the suns. They're purified having the fatty acids removed, becoming wasser-soluble:

GlyceroPhosphoCholine (GPC), Mind-Body Nutrient for Active Living And Healthy Aging

"Quantitatively, the main phospholipid of membranes is phosphatidylcholine (PC). Cells grow or renew themselves by making new membrane mass, and this creates demand for PC, which in its turn is most efficiently synthesized from GPC.35"

"GPC is unique in being a water-phase phospholipid. Technically it is a “deacylated” PC—the PC molecule without its usual fatty acid tails (see Fig. 2). The GPC molecule is readily transformed to PC by simply adding back the fatty acid tails,35 and enzymes exist to do this trick with very little energy cost. Therefore GPC has special value for our cells: in its native form it is a unique protectant that can attain high levels in the cytoplasm without doing damage. Then, this reservoir can be drawn upon to make PC for membrane mass, notably without the major energy expenditure of energy needed to make PC from simpler precursors such as CDP-choline.35"

Spoiler: Main difference between GPC and PC

View attachment 10492

From a conversation with the same pimp of the other thread:

​

Frank of the Dees often mentions issues with extra choline (such as depressa), and this experience seems recurrent whenever people consume a lot of eggs or supplement more choline than needed. However! He also mentioned that this doesn't occur (or at least not as bad) with liver. So it reinforces two things:
- that eggs are nutritious but there's nothing in them that make them safe in terms of providing imbalanced amounts of choline
- that choline is problematic or even risky (mostly?) in the absence of other B-vitamins or beyond needs; which is probably one of the reasons for B12 being potentially harmful alone.

I agree that the B-vitamins that are directly involved in methylation are riskier, but they must still be present.

Terma, a tip hat.

Some choline is indeed required for proper health but I think the needed amounts are a lot less than what most people consume. Similar to methionine, which has an optimal daily dose of 0.2mg/kg for humans, I think choline is probably best around the same doses. So, milk and eggs could be good source, as would liver, and they seem to provide the balancing nutrients. A single dose of MitoLipin also provide 200mg of SFA PC, but the amount of choline is actually less, so up to 2-3 doses of MitoLipin would probably be needed to reach the 150mg-200mg daily choline intake.

 

[Terma]

@haidut,

If you go through the various studies linked on the Mitolipin thread, they're supporting phosphatidylcholine in general. If you note, those are usually classic choline experiments (fatty liver, cognitive dysfunction, etc) that have been run with different forms of choline before.

It is an advantage that your supplement can provide it fully saturated, but the main component missing and being replenished must be choline.

As you know, eggs have plenty of phosphatidylcholine and no one considers it a vehicle for fats, it's considered a source of choline.
Should you now be thinking: "So what?"

VVc11, since the links that you shared have good outcomes for forms that aren't providing saturated fats, the benefit can't be explained by replacing unsaturated fats alone. If you accept that it's choline that's making most of the difference (since the other components of phosphatidylcholine aren't difficult to obtain as far as I know), it might be a choline supplement in essence.

Having enough choline is more important than supplying it already saturated. If the diet is deficient in it, it isn't unlikely to disfavor intact absorption and cleave it for other purposes. If the diet provides enough and safe fats are around, they should eventually combine for cell structure.

Analytical approaches to determination of total choline in foods and dietary supplements

Spoiler: Chaemical structures of choline and major choline-related compounds

View attachment 10491

The glycerophosphocholine supplements on the market are usually derived from soy and sometimes flowers of the suns. They're purified having the fatty acids removed, becoming wasser-soluble:

GlyceroPhosphoCholine (GPC), Mind-Body Nutrient for Active Living And Healthy Aging

"Quantitatively, the main phospholipid of membranes is phosphatidylcholine (PC). Cells grow or renew themselves by making new membrane mass, and this creates demand for PC, which in its turn is most efficiently synthesized from GPC.35"

"GPC is unique in being a water-phase phospholipid. Technically it is a “deacylated” PC—the PC molecule without its usual fatty acid tails (see Fig. 2). The GPC molecule is readily transformed to PC by simply adding back the fatty acid tails,35 and enzymes exist to do this trick with very little energy cost. Therefore GPC has special value for our cells: in its native form it is a unique protectant that can attain high levels in the cytoplasm without doing damage. Then, this reservoir can be drawn upon to make PC for membrane mass, notably without the major energy expenditure of energy needed to make PC from simpler precursors such as CDP-choline.35"

Spoiler: Main difference between GPC and PC

View attachment 10492

From a conversation with the same pimp of the other thread:

​

Frank of the Dees often mentions issues with extra choline (such as depressa), and this experience seems recurrent whenever people consume a lot of eggs or supplement more choline than needed. However! He also mentioned that this doesn't occur (or at least not as bad) with liver. So it reinforces two things:
- that eggs are nutritious but there's nothing in them that make them safe in terms of providing imbalanced amounts of choline
- that choline is problematic or even risky (mostly?) in the absence of other B-vitamins or beyond needs; which is probably one of the reasons for B12 being potentially harmful alone.

I agree that the B-vitamins that are directly involved in methylation are riskier, but they must still be present.

Terma, a tip hat.

That's about right (and yeah it's from soy - that usually bothers someone - but no fatty acids, so idc...)

Unfortunately the Alpha-GPC is not thought to be absorbed across the gut barrier intact either, so the claims about intracellular form are probably moot. It still works mainly as a prodrug for blood choline. There's confusion about Alpha-GPC absorption in the online articles due to people reading only abstracts (also for one of them the full paper is missing) [where they inject through i.v. vs oral]. But in this one it's quite clear the oral form did not pass the gut barrier of rats as GPC: Absorption, tissue distribution and excretion of radio labe l led compounds in rats after administration of [14C]- l-α-g lycery lphosphory lcho line [see discussion for i.v. vs oral]

The advantage is it should be absorbed faster in gut compared to other cholines and food (helping avoid gut bacteria, TMAO, certainly the organic acids). Or in other words you can probably get away with less total choline ingestion since less is wasted.

 

[Amazoniac]

Some choline is indeed required for proper health but I think the needed amounts are a lot less than what most people consume. Similar to methionine, which has an optimal daily dose of 0.2mg/kg for humans, I think choline is probably best around the same doses. So, milk and eggs could be good source, as would liver, and they seem to provide the balancing nutrients. A single dose of MitoLipin also provide 200mg of SFA PC, but the amount of choline is actually less, so up to 2-3 doses of MitoLipin would probably be needed to reach the 150mg-200mg daily choline intake.

Thanks to you for being open and minded.

What makes you think that choline is needed in similar amounts? You must be right, but some people might have elevated needs imposed maybe by high doses of niacin, plenty of fructose, saturated fats (?), other nutrient deficiencies, predisposition to its insufficiency, etc.

From what I calculated (not sure if it's correct), your supplement provides about 25-30 mg of cholin per serving. So to reach those 200 mg with it alone would require about 5-7 servings. Have you read the message on the other thread with Terma? I wonder how much is absorbed intact, because depending on this it might be preferable to simplify the process and lower the price by selling only the stearic acid form (since you mentioned it's cheaper), which is just as reliable and can make it feasible for those that want it as a choline supplement.

Do you have an opinion on glycerophosphocholine?

--
Out of curiosity and unrelated, this is what a company claims to justify impurities:
"Why don’t we sell an Alpha-GPC 100% Powder? Alpha-GPC with a purity of greater than 99% will undergo hygroscopy very quickly as soon as it meets the air."

 

[haidut]

Thanks to you for being open and minded.

What makes you think that choline is needed in similar amounts? You must be right, but some people might have elevated needs imposed maybe by high doses of niacin, plenty of fructose, saturated fats (?), other nutrient deficiencies, predisposition to its insufficiency, etc.

From what I calculated (not sure if it's correct), your supplement provides about 25-30 mg of cholin per serving. So to reach those 200 mg with it alone would require about 5-7 servings. Have you read the message on the other thread with Terma? I wonder how much is absorbed intact, because depending on this it might be preferable to simplify the process and lower the price by selling only the stearic acid form (since you mentioned it's cheaper), which is just as reliable and can make it feasible for those that want it as a choline supplement.

Do you have an opinion on glycerophosphocholine?

--
Out of curiosity and unrelated, this is what a company claims to justify impurities:
"Why don’t we sell an Alpha-GPC 100% Powder? Alpha-GPC with a purity of greater than 99% will undergo hygroscopy very quickly as soon as it meets the air."

Older studies showed that the minimum amount is about 50mg daily to prevent liver issues and optimal amounts to be in the 200mg-300mg range. I can't find the studies right now but here is one blog that also talks about it and is probably based on the same studies I saw. So, 2-3 servings of MitoLipin would probably be enough, since there would also be additional choline from dietary sources. These days lecithin is added to pretty much any prepared food, so it is hard to avoid it.
Choline – Vegan Health
"...The Dietary Reference Intake (DRI) for choline is 550 mg/day for men and 425 mg/day for women. It is based on only one study comparing those amounts to 50 mg/day, with no intermediary amounts examined. Eating less than 50 mg/day can result in liver damage, but it is very unlikely that a vegan would have such a low intake. Some people have genetic mutations that increase the need for choline; it is not clear how much choline such people need but the DRI is probably adequate for almost everyone. If you suspect any sort of liver dysfunction, it might be worth talking to your physician about boosting your choline intake or supplementing with it in moderate amounts. The data on choline and chronic disease (cardiovascular disease, dementia, and cancer) is somewhat mixed. Ideal amounts appear to be about 300 mg per day. Most vegans probably get about that much from the foods they eat."

 

[Amazoniac]

Older studies showed that the minimum amount is about 50mg daily to prevent liver issues and optimal amounts to be in the 200mg-300mg range. I can't find the studies right now but here is one blog that also talks about it and is probably based on the same studies I saw. So, 2-3 servings of MitoLipin would probably be enough, since there would also be additional choline from dietary sources. These days lecithin is added to pretty much any prepared food, so it is hard to avoid it.
Choline – Vegan Health
"...The Dietary Reference Intake (DRI) for choline is 550 mg/day for men and 425 mg/day for women. It is based on only one study comparing those amounts to 50 mg/day, with no intermediary amounts examined. Eating less than 50 mg/day can result in liver damage, but it is very unlikely that a vegan would have such a low intake. Some people have genetic mutations that increase the need for choline; it is not clear how much choline such people need but the DRI is probably adequate for almost everyone. If you suspect any sort of liver dysfunction, it might be worth talking to your physician about boosting your choline intake or supplementing with it in moderate amounts. The data on choline and chronic disease (cardiovascular disease, dementia, and cancer) is somewhat mixed. Ideal amounts appear to be about 300 mg per day. Most vegans probably get about that much from the foods they eat."

Incomprehensive/ble Notes On Choline

They estimated 350 mg to be the average consumption for men that don't eat eggs (Table 3 in the first link). On the last link, it's difficult to tell because the graded consumption goes from 412.5 to 275.00, so we don't know how many of them normalized their blood markers with 350 mg or so, but there's a considerable number of men and postmenopausal women that didn't meet their requirements with less than that. Some people seem to require very high amounts.

60-80 mg from 2-3 servings of Mitolipin wouldn't make a lot of difference for them.