Incomprehensive/ble Notes On Choline

Terma

Member
Joined
May 8, 2017
Messages
1,063
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."
Yeah I'd be curious how true that is in practice. I always buy the 99% and put the jar in a ziplock and it only clumps a little (the 50% doesn't clump at all, but gave gut issues - do not buy). Some commenters complained theirs melted, but mine's been fine in 40-55% humidity air. Seattle maybe?

Btw the Suppversity guy has a vendetta against GPC, to him it's a ripoff compared to choline bitartrate. But his fanbase takes 1-1.5g choline/day for gainz and GH and sure at that rate it'll make you poor. This forum is the polar opposite, people feed their livers 100g+ fructose/day and high protein (which always comes out to high methionine in practice -> PEMT) while scaring themselves away from various nutrients.
 

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
OP
Amazoniac

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
- Fair enough with selenium. I guess it's possible for its content to be higher in conventional chickens' due to ration.
- Zinc and B6, I'm not sure. It's not something likely to be missing in those amounts in people's meals unless they're part of an experiment by Kawamura and team that decide that it is a good a idea to give 400 mg of choline on empty stomach after the owanight fast.
- I was thinking about riboflavin and biotin. Maybe also vitamin A.
 

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
- Fair enough with selenium. I guess it's possible for its content to be higher in conventional chickens' due to ration.
- Zinc and B6, I'm not sure. It's not something likely to be missing in those amounts in people's meals unless they're part of an experiment by Kawamura and team that decide that it is a good a idea to give 400 mg of choline on empty stomach after the owanight fast.
- I was thinking about riboflavin and biotin. Maybe also vitamin A.

I meant that zinc, B6 and selenium are known to be able to antagonize choline in certain tissues/organs. B6 is a cofactor for the synthesis of GABA, which is the main antagonist to choline in the CNS.
 
OP
Amazoniac

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
I meant that zinc, B6 and selenium are known to be able to antagonize choline in certain tissues/organs. B6 is a cofactor for the synthesis of GABA, which is the main antagonist to choline in the CNS.
Thanks, Zeus. It's difficult to find a satisfactory explanation for the safety of choline from eggs. At this point I assume that I'm missing something.
people feed their livers 100g+ fructose/day and high protein (which always comes out to high methionine in practice -> PEMT) while scaring themselves away from various nutrients
Terma, what does you means by that? How can a high-methionine diet worsen the effects of a lack of choline?
 

Terma

Member
Joined
May 8, 2017
Messages
1,063
PEMT is known for producing especially unsaturated phospholipids, see post on other thread. So in choline-deficient diet, PEMT pushes out more PUFA phospholipids to the rest of the body, instead of dealing with them itself (glucuronidation according to RP) or worst case including them as triglycerides instead when it can't. Which makes a lot of sense since it's the "stress"-induced emergency pathway and estrogen-promoted pathway during pregnancy, and falls in line with general impressions of MET (note some side effects of lowering estrogen albeit rodents again: 1 2). Then consider how people seem to be fighting estrogen a lot on this forum... but then get scared off from choline because of the positive estrogen<->choline association RP has created. Those people are also consuming tons of MET. Only problem is... in the liver, you want the exact opposite since choline contributes more to Kennedy than PEMT through methylation.
 
Last edited:

Terma

Member
Joined
May 8, 2017
Messages
1,063
There were words missing there, you get why I can't do this more than 1x/week:
PEMT is known for producing especially unsaturated phospholipids, see post on other thread. So in choline-deficient diet, liver PEMT pushes out more PUFA phospholipids to the rest of the body, instead of the liver dealing with them itself (glucuronidation according to RP) or worst case including them as triglycerides instead when it can't.
 

Frankdee20

Member
Joined
Jul 13, 2017
Messages
3,772
Location
Sun Coast, USA
Magnesium is a decent anticholinergic, I’m not sure the mechanism though. Perhaps NMDA inhibition, or 5ht1a interaction.
 
OP
Amazoniac

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
PEMT is known for producing especially unsaturated phospholipids, see post on other thread. So in choline-deficient diet, PEMT pushes out more PUFA phospholipids to the rest of the body, instead of dealing with them itself (glucuronidation according to RP) or worst case including them as triglycerides instead when it can't. Which makes a lot of sense since it's the "stress"-induced emergency pathway and estrogen-promoted pathway during pregnancy, and falls in line with general impressions of MET (note some side effects of lowering estrogen albeit rodents again: 1 2). Then consider how people seem to be fighting estrogen a lot on this forum... but then get scared off from choline because of the positive estrogen<->choline association RP has created. Those people are also consuming tons of MET. Only problem is... in the liver, you want the exact opposite since choline contributes more to Kennedy than PEMT through methylation.
Thank you.
For those that missed:
Skeletal Muscle Phosphatidylcholine And Phosphatidylethanolamine Are Related To Insulin Sensitivity

I'm really puzzled at the choline resistance encountered here, especially given that methionine is absolved. I've been trying to search with prejudicia maxima (Travo, 2018) for the possibility of choline intake increasing the risk of cancer without much success, usually finding the opposite. Even the publication that Raj mentioned acknowledges that it's stressful:

Can Dietary Methionine Restriction Increase the Effectiveness of Chemotherapy in Treatment of Advanced Cancer?
"Animal studies have demonstrated that severe, prolonged methyl deficiency induced by dietary restriction of methionine, choline, homocysteine, and folate leads to global demethylation of normal liver DNA and resultant increased susceptibility to DNA strand breaks [44]. Inhibition of DNA methylation by methionine restriction may therefore make cancer cell DNA susceptible to damage."​

And the main foci wasn't on choline, but on methionine (as expected).

Methyl Groups in Carcinogenesis: Effects on the NA Methylata and Gene Expressa

For the 20th time: what am I missing? :banghead: (tyw, 2017)
 
Last edited:

Terma

Member
Joined
May 8, 2017
Messages
1,063
Thank you.
For those that missed:
Skeletal Muscle Phosphatidylcholine And Phosphatidylethanolamine Are Related To Insulin Sensitivity

I'm really puzzled at the choline resistance encountered here, especially given that methionine is absolved. I've been trying to search with prejudicia maxima (Travo, 2018) for the possibility of choline intake increasing the risk of cancer without much success, usually finding the opposite. Even the publication that Raj mentioned acknowledges that it's stressful:

Can Dietary Methionine Restriction Increase the Effectiveness of Chemotherapy in Treatment of Advanced Cancer?
"Animal studies have demonstrated that severe, prolonged methyl deficiency induced by dietary restriction of methionine, choline, homocysteine, and folate leads to global demethylation of normal liver DNA and resultant increased susceptibility to DNA strand breaks [44]. Inhibition of DNA methylation by methionine restriction may therefore make cancer cell DNA susceptible to damage."​

And the main foci wasn't on choline, but on methionine (as expected).

Methyl Groups in Carcinogenesis: Effects on the NA Methylata and Gene Expressa

For the 20th time: what am I missing? :banghead: (tyw, 2017)
Yeah, I could never find anything too alarming about low dose choline except TMAO issue. In disease states you do get the issue of inflammation/stress increasing phospholipase chronically breaking down phosphatidylcholine leaving free choline (thus acetylcholine). But if you take that as a reason to stop consuming choline the liver will just make it up with PEMT anyway, leaving you worse off. It's loosely sort of like blaming glucose for diabetes.

Again everything I take is low-dose, low-dose GPC, low-dose uridine (oral with food only), low-/medium-dose fructose, low-dose niacin, only exception is Mg (which someone pointed out is necessary for the PC synthesis, but you need Mg and ATP for just about everything).
 

Terma

Member
Joined
May 8, 2017
Messages
1,063
I guess from what I just wrote you can also gleam the extreme importance of phospholipid synthesis in disease states, since if it's being broken down at an increased rate and not replaced, well that's your cellular integrity out the window and you're ****88.
 
OP
Amazoniac

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
- Choline and betaine consumption lowers cancer risk: a meta-analysis of epidemiologic studies

"So far, there have been a number of epidemiologic studies exploring whether dietary consumption of choline and betaine is associated with the risk of cancer but the results are conflicting. Also, to our knowledge, no article has been found to attempt to make a summary of the results. Hence, it will be of interest to evaluate whether the consumption of choline and betaine is one of the dietary factors that are related with cancer incidence, on the basis of present epidemiologic evidence."

"Findings from our meta-analysis manifested that high choline and betaine consumption contributed to cancer prevention. Moreover, the dose-response analysis further demonstrated the protective effect from choline and betaine consumption towards cancer occurrence: an increase in choline plus betaine consumption of 100 mg/day significantly lowered the chance of developing cancer by 11%."

"A few studies on animals and humans have shown that dietary choline and folate are supplementary to each other if either of them gets in a state of deprivation[21,22,23]."

"[..]in animals studies, choline deficiency causes cancer via inducing dysfunction in mitochondria and excessive production of reactive oxygen species (ROS)[24,25], which has long been considered to be one of mechanisms in promoting cancer[26,27]. In addition, Ghoshal et al. have reported that in experimental animals, a 0.8% supplemented dietary consumption of choline aids in the action of cancer prevention in complete[28]."

"[..]if the recommended dietary adequate intake (550 mg/day for men and 425 mg/day for women) for choline[32] is took as a standard, there are only a minority of people meeting it."

"To conclude, our meta-analysis manifests that choline and betaine consumption possesses the ability to lower cancer risk. However, these results should be considered with caution on account of the considerable heterogeneity, the potential biases and confounding factors."​

:confused2

--
- Association of choline and betaine levels with cancer incidence and survival: A meta-analysis - ScienceDirect
- Can tetracycline-induced fatty liver in pregnancy be attributed to choline deficiency? - ScienceDirect
 
OP
Amazoniac

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
The more I think about this, the less it makes sense to allow an insufficiency to develop out of fear of some supplementation (provided that other B-vitamins are adequate).


Andro (Suppversity) pointed out the following:
According to Coates et al. plasma choline concentrations can double after a 2-egg meal (~225mg choline) by up to two-fold (Coates. 2005). That would effectively be more than what we see as peak increase in the study at hand. And certainly puts the "need" for supplemental choline into perspective.
Steven Zeisel again:

Choline: Needed for Normal Development of Memory
Plasma choline concentration varies in response to diet [28] and can rise as much as two-fold after a two-egg meal.
.
Keep in mind that he's after the effects that can concern forum members. He's implying that 1 g of GPC (~400 mg of choline) given on empty stomach after overnight fast does not boost choline levels as effectively as 2 eggs (~300 mg of choline?) eaten as part of a meal.


Also, every possible detrimental effect of choline in terms of undesirable methylation is mediated through methionine anyway. It has to recycle homocysteine to methionine and only then exert its effects. This means that as long as you have enough glycine, the body should have control over reactions:
So you can have this influx of methionine that comes in, and you can be predisposed to at least transient overmethylation in the sense that if you don’t have the glycine buffer to mop up the extra methyl groups, then you have less control over the level of methylation that’s happening in that moment in the postprandial state.

Glycine is going to take up a methyl group and become sarcosine, or it’s gonna take up two methyl groups and become dimethylglycine, and you may pee that out in your urine, or you may salvage it through various pathways where you can eventually get those methyl groups back into the regular system where they could actually recycle homocysteine.

But in general, I think it’s helpful to think of glycine as mainly getting peed out in the urine because if you have some problem of overmethylation, then that’s essentially what it’s gonna do. It’s gonna waste your glycine, and if you don’t have that glycine there, it’s gonna predispose you to rampant overmethylation.

Niacinamide Or Just Plain Niacin?


But there's more: you should also be able to feel the detrimental effects, it must not be silent (I guess the same applies to B12 and most nutrients). As long as your awareness is fine, it should give you clues when something is off. Maybe it's just a matter of adjustment (form, dose, timing, meal combination, purity, and so on), but if the adverse effect doesn't improve, then any benefit might not be worth it.
 
Last edited:
OP
Amazoniac

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
Laboratory Evaluations for Integrative and Functional Medicine (0967394945, 9780967394947) - Richard S. Lord, J. Alexander Bralley

upload_2018-9-24_12-13-22.png


upload_2018-9-24_12-23-9.png


upload_2018-9-24_12-17-30.png


upload_2018-9-24_12-17-38.png
 
OP
Amazoniac

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
- Vitamin B12 , Folic Acid, and Choline Interrelations | Nutrition Reviews | Oxford Academic

"In recent years it has become increasingly common to discover instances where a change in the amount of one dietary component profoundly changes the dietary requirement for another. Elucidation of these relations has generally led to important advances in knowledge of fundamental biochemistry and improvements in applied nutrition as well. The niacin-tryptophan and the methionine-cystine-choline relations are well-known examples."

"There are many reasons to suspect that a relation might exist between folic acid, vitamin B12, and choline. The partial interchangeability of vitamin B12 and methionine or choline in the diet of chicks and rats (H. R. Bird, M. Rubin, and A. C. Groschke, J . Nutrition 33, 319 (1947); A. E. Schaefer, K. D. Salmon, and D. R. Strength, Proc. SOC. Exp. Biol. Ned. 71, 193, 202 (1949)) and the similar action of folic acid, vitamin B12, and choline in the treatment of certain macrocytic anemias in man (Nutrition Reviews 6, 89, 90, 245 (1948); 7, 255 (1949)) are but a few of the many observations which might be offered in support of this idea."

"A. E. Schaefer, W. D. Salmon, D. R. Strength, and D. H. Copeland (J. Nutrition 40, 95 (1950)) have been able to show that the nutritional requirements for folic acid, vitamin B12, and choline are mutually interdependent in both rats and chicks under certain experimental conditions. Their experiments were conducted using a basal diet composed of extracted peanut meal, casein, cystine, sucrose, cod liver oil, lard, salts, and the usual vitamins except B12 and folic acid. This diet provided 0.3 per cent methionine and only 0.007 per cent choline. When the basal diet was supplemented with 0.04 per cent choline chloride or 0.128 per cent methionine and fed to weanling rats, 100 per cent of the animals developed renal hemorrhage within two weeks. Addition of 2, 10, or 100 mg. of folic acid per kilogram of the choline-supplemented diet reduced the incidence of renal hemorrhage to 75, 42, and 50 per cent, respectively, while 30 to 150 micrograms of vitamin B12 per kilogram of ration reduced the incidence 50 per cent. However, 10 mg. of folic acid with 30 micrograms of vitamin B12 completely prevented the renal lesions. Vitamin B12 and folic acid were without effect unless choline or methionine (presumably) were added to the ration. Both folic acid and B12 were effective in preventing death, in lessening the severity of renal hemorrhage, when it occurred, and in promoting growth. Vitamin B12 and folic acid together promoted slightly better growth than either alone."

"When day-old chicks were fed the basal diet supplemented with 0.6 per cent choline chloride, rather poor growth occurred. Thirty micrograms of vitamin B12 or 2 mg. of folic acid per kilogram of ration caused growth increments of 67 to 70 g. per chick in four weeks. Increasing the B12 to 150 micrograms or the folic acid to 100 mg. produced but little better growth. However, 30 micrograms of B12 plus 2 mg. of folic acid caused a growth increase of 126 g. per chick."

"When chicks were fed the basal diet supplemented with only 0.10 per cent choline chloride, similar growth responses to folic acid and B12 were observed except that 2 mg. of folic acid were but slightly effective whereas 100 mg. of this vitamin had a marked effect. Again B12 and folic acid together produced the best growth. As little as 5 micrograms of B12 per kilogram of ration produced a marked effect when 100 mg. of folic acid were in the ration. On the other hand, only 0.2 mg. of folic acid was required to produce marked growth improvement when optimal B12 was present."

"Hemoglobin concentration was about 25 per cent below normal in chicks maintained on the basal choline-supplemented ration. Addition of either folic acid or B12 produced nearly normal hemoglobin values, while B12 and folic acid together produced slightly superior results."​

- Folate and Choline Interrelationships
 

Jackrabbit

Member
Joined
Jun 29, 2018
Messages
172
@Amazoniac would you please be kind enough to explain to my simple brain why there would be a benefit to taking choline and cyproheptadine simultaneously?

It was my (feeble minded) understanding that and anticholinergic would somehow counteract choline.
 
OP
Amazoniac

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
@Amazoniac would you please be kind enough to explain to my simple brain why there would be a benefit to taking choline and cyproheptadine simultaneously?

It was my (feeble minded) understanding that and anticholinergic would somehow counteract choline.
Guru, I think @Terma might give you a better reply.
 

Similar threads

Back
Top Bottom