PC choline to stabilize membranes

alfredoolivas

@bio3nergeti The PC breaks down and creates another PC with already circulating fatty acids. Saturated or not.

That's why I suggested that you EAT saturated fat with PC. To supress lypolysis and increase saturated fat that pairs with the lysophosphatidylcholine.

Eating saturated PC will break down and pair with circulating fatty acids anyway. No point paying 40 dollars + shipping for 30 doses of 200mgs of saturated PC, which provides very little free choline.

If you were to inject saturated PC intravenously? Sure, that would be awesome because the PC would stay intact. But in the gut it breaks down and forms different PC based off of blood levels. In the cell it breaks down again, however, the PC delivers fatty acid into the cell and likely the same PC is formed again.

alfredoolivas

@bio3nergetic said in PC choline to stabilize membranes:

High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance

And what has this got to do with supplementing saturated or unsatured PC?

"obese mice fed a HFD or from patients with type II diabetes. HFD altered the lipid composition of exosomes from predominantly phosphatidylethanolamine (PE) in exosomes from lean animals (L-Exo) to phosphatidylcholine (PC) in exosomes from obese animals (H-Exo)"

Nothing was mentioned about saturation, just about what class of molecules compose exosomal space.

bio3nergetic

@alfredoolivas You are looking at it from the perspective of PC count. For myself, the added PUFA is problematic due to the LPCAT3 preference. Eating it with saturated fat doesn't mitigate the lipolytic action. Insulin will, but you are then right back to extra PUFA in circulation. What you're saying still doesn't make sense. It is as if you are saying make an exception for PUFA if taking in PC, and for no apparent reason.

@alfredoolivas said in PC choline to stabilize membranes:

@bio3nergetic said in PC choline to stabilize membranes:

High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance

And what has this got to do with supplementing saturated or unsatured PC?

"obese mice fed a HFD or from patients with type II diabetes. HFD altered the lipid composition of exosomes from predominantly phosphatidylethanolamine (PE) in exosomes from lean animals (L-Exo) to phosphatidylcholine (PC) in exosomes from obese animals (H-Exo)"

Nothing was mentioned about saturation, just about what class of molecules compose exosomal space.

Yes, this is why I mentioned "indirect evidence." You have to pay attention to method and materials to sometimes derive unintended conclusions. Peat often did this as well. I had said: "This was a indirect evidence incidentally, because the researchers were looking at total overall PC from high fat diet as related to disease progression. But guess what, the high fat diet is your typical formula: 25 grams Soybean Oil and almost 300 grams pig lard. This confirming that this enzyme drives PUFA incorporation into membranes. The takeaway being it is doubly important we use saturated PC."

alfredoolivas

@bio3nergetic

@bio3nergetic said in PC choline to stabilize membranes:

Studies show that LPCAT3 knockout mice have reduced PUFA content in PC and are protected from diet-induced fatty liver!

I don't understand - that says nothing about why supplementing unsaturated PC is bad!
Where is the evidence that PUFA preferentially is used for PC synthesis? A
And where is the evidence that saturated fat is just disregarded as a substrate for PC synthesis?
How will using saturated PC combat this? It is broken down in the gut releasing a miniscule amount of saturated fat along with lysophosphatidylcholine.

Study on soybean dervied PC still having beneficial effects on fatty liver:
https://pubmed.ncbi.nlm.nih.gov/25445436/

So far there is two vitro studies on saturated PC, about it being beneficial for PUFA cytotoxcity. Sure if you insert saturated PC into a cell it will act as a carrier for saturated fat, and reverse PUFA effects. But ingesting is incomparable.

LucH

Whatever the fat is [C16-0 (palmitic acid) or C18-n2 (LA, omega-6) or 18:3 n-3 (ALA, omega-3)], the PC will be hydrolyzed before reaching the destination. Need lipoprotein transport.
Excerpt:
Any dietary PC (egg yolk, soy lecithin, sunflower lecithin, krill oil, PC supplements) is broken down into LPC + a fatty acid in the intestine before absorption.
So even if you take PC, your body creates LPC during digestion.

What happens in the intestine when we get choline form food or a supplement?
Pancreatic phospholipase A2 hydrolyzes PC → lysophosphatidylcholine (LPC) + a free fatty acid.
LPC and free fatty acids are incorporated into mixed micelles with bile salts. These micelles facilitate absorption into enterocytes.
So we need effective bile to optimize things.
I take betaine HCL 1x/day, rather at the evening meal, since pH secretion is top between 11 – 14 o’clock (for proteins) (with ginger and pepsin). (1)
Using forms that enhance cellular uptake
We know choline from food or from supplement are going to be emulsioned. Thus there is a change in the absorption way, no mitochondrial delivery, at the moment. Whatever the form is.
PS: I've tried to understand how the metabolism manage to assimilate PC choline. => 9 pages to summarize "How PC Is Digested, Emulsified, Transported, and Ultimately Reaches Mitochondria".
Livre science-fiction.png

bio3nergetic

@alfredoolivas The knockout LPCAT3 mice have reduced PUFA content in PC AND are protected from diet-induced fatty liver. The correlated fatty liver disease from high fat/high PUFA diet, as it increased (unsaturated) PC, was lacking in these mice. This is rather straight forward in understanding. A mainstreamer perhaps would miss the connection as they don't think of the PUFA component.

Well for starters, from that study there are links to harder evidence for LPCAT3 PUFA preference. Others include:
Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport
Tomomi Hashidate-Yoshida
PNPLA3 is a triglyceride lipase that mobilizes polyunsaturated fatty acids to facilitate hepatic secretion of large-sized very low-density lipoprotein
Liver X receptor agonist upregulates LPCAT3 in human aortic endothelial cells
Delphine Bousquet,
PNPLA3 is a triglyceride lipase that mobilizes polyunsaturated fatty acids to facilitate hepatic secretion of large-sized very low-density lipoprotein
Scott M. Johnson

The PC process is one of incorporation: you incorporate the lipids you ingest. The studies that show benefit from soybean oil PC have to do with contextual facts i.e. no PC is worse than some PUFA PC.

LPCAT3-driven PUFA-PC synthesis in high-fat, high-PUFA diets promotes fatty liver by fueling lipogenesis and VLDL overproduction.
Dietary soybean PC, however, acts as a hepatoprotective agent by improving lipid export, reducing inflammation, and supporting membrane health BUT likely because it bypasses uncontrolled remodeling.

Extra exogenous PC is better than nothing at all in the face of high fat diet. Exogenous PC (especially PUFA-PC like soybean or polyenylphosphatidylcholine/PPC) acts as a functional "rescue" molecule in high-fat diets, even if not ideal. However saturated PC is more stable and less prone to oxidation, making it potentially safer in the context of metabolic stress. Deciphering these studies often takes understanding the context or situation the lab animal is in.

alfredoolivas

@bio3nergetic I am not reffering to how prone saturated PC is to oxidation - I am referring to how pancreatic phospholipase A2 and stomach acid a pH of 1 would break PC bonds. There hasn't been a study on saturated PC in humans, but for other PC (polyethylene Pc)

"this suggests that most oral PC was hydrolyzed to lysolecithin before absorption.”
https://pubmed.ncbi.nlm.nih.gov/7175371/

"PC digestion occurs in the small intestine… Chemical breakdown of PLs is carried out primarily by pancreatic phospholipase A₂ (PLA₂) … It interacts with PLs at the sn-2 position to yield free fatty acid and lysoPC.”
https://pmc.ncbi.nlm.nih.gov/articles/PMC3257636/

bio3nergetic

@alfredoolivas said in PC choline to stabilize membranes:

"PC digestion occurs in the small intestine… Chemical breakdown of PLs is carried out primarily by pancreatic phospholipase A₂ (PLA₂) … It interacts with PLs at the sn-2 position to yield free fatty acid and lysoPC.”

Pancreatic phospholipase A2 and stomach acid a pH of 1 breaking PC bonds does not at all mitigate risk or toxicity of oxidation products, bioactivity of lysoPC, and systemic inflammatory potential of dietary oxidized lipids regarding PUFA. You are conflating these inherent processes with the idea that somehow the physiology is safe from the usual culprit.

LucH

Talk with AI
Context:
Title: PC choline to stabilize membranes.
I put in excerpt:
You aren’t talking the same language:

- One is speaking about altered PUFA as carrier (fueling lipogenesis and VLDL overproduction, upregulating LPCAT3 in human aortic endothelial cells), making saturated PC more stable and less prone to oxidation. The added PUFA (in the supplement) is problematic due to the LPCAT3 preference.
- The other one excerpting that most oral PC has been hydrolyzed to lysolecithin before absorption / incorporate in tissues (breakdown of PLs is carried out primarily by pancreatic phospholipase A₂.
  https://bioenergetic.forum/topic/9164/pc-choline-to-stabilize-membranes/8?_=1770916434026

My comment (LucH):
Whatever the fat is [C16-0 (palmitic acid) or C18-n2 (LA, omega-6) or 18:3 n-3 (ALA, omega-3)], the PC will be hydrolyzed before reaching the destination. Need lipoprotein transport.
Excerpt:
Any dietary PC (egg yolk, soy lecithin, sunflower lecithin, krill oil, PC supplements) is broken down into LPC + a fatty acid in the intestine before absorption.
So even if you take PC, your body creates LPC during digestion.

*) Request to AI
A comment to set things clear, though they don’t seem to speak the same language, trying to argue sth different.
Analyze, please, with an advice to set the eyes again in front of the holes!

Answer from AI (gemini3)
It looks like you've stepped into a classic "forest for the trees" debate. Both sides are technically correct about specific mechanisms, but they are arguing from different stages of the metabolic pipeline.
To "set the eyes back in front of the holes," we need to look at the transition from ingestion to integration. Here is a breakdown of the two positions and the reality of the biochemistry.

The Disconnect: Mechanism vs. Metabolism
The two sides are talking past each other because one is focused on downstream signaling (what the molecule does once it's in the cell) and the other is focused on upstream processing (what happens in the gut).
The Digestive Reality (The "Hydrolysis" Filter)
Your comment (LucH) hits the nail on the head regarding the "gatekeeper." When you ingest Phosphatidylcholine (PC), it doesn't travel through your blood like a whole Lego set.
 The Breakdown: Pancreatic phospholipase A₂ cleaves the fatty acid at the sn−2 position.
 The Result: You are left with Lysolecithin (LPC) and a Free Fatty Acid (FFA).
 The Absorption: These components are absorbed into the enterocytes (intestinal cells).
 The Re-assembly: Inside the enterocyte, they are often re-esterified into new phospholipids or triglycerides to be packed into chylomicrons.
The Bottom Line: You cannot "target" a specific membrane with a specific oral PC molecule because the body deconstructs it and puts it into the general fatty acid pool or re-assembles it based on current metabolic needs.
Where Side A Has a Point (The LPCAT3 Factor)
While Side B is right about the breakdown, Side A is right about the preference. Even if the PC is broken down into LPC, the enzyme LPCAT3 is the "re-builder."
LPCAT3 has a high affinity for polyunsaturated fatty acids (PUFAs). So, if your diet (or supplement) is flooded with PUFAs, LPCAT3 will preferentially grab those to rebuild the membrane. This is where the "fueling lipogenesis" and "VLDL overproduction" concerns come in. It’s not that the PC stayed intact; it’s that the raw materials provided by the supplement gave LPCAT3 the tools to build the "wrong" kind of membrane.

Advice to Re-Center the Debate
To clear the air, the conversation needs to move away from "What does this supplement molecule do?" to "What does this supplement do to the Intracellular Pool?"
The "Eyes in Front of the Holes" Perspective: Stop arguing about whether the PC stays intact (it doesn't). Start focusing on the ratio of fatty acids being introduced. If you flood the system with a PUFA-based PC supplement, you are providing the specific substrate that LPCAT3 uses to drive the exact metabolic pathways Side A is worried about.
The takeaway: The specific fatty acid "tail" on your PC supplement matters not because it survives digestion, but because it dictates the "parts list" available to your cells for reconstruction.
Would you like me to draft a concise "rebuttal" or summary you can post back to that forum thread to bridge these two points?
LucH says:
No need. Fine so. Just find a bullet end image. Analogy if pertinent. Material brought to VLD particles.
AI says
Think of the liver as a factory floor. The oral PC supplement isn't a "finished machine" arriving at the loading dock; it is a delivery of raw scrap metal.
 The Gut (The Shredder): Digestion is the shredder that breaks the PC into individual components (LPC and Fatty Acids).
 The Cell (The Assembly Line): Inside the cell, enzymes like LPCAT3 are the workers on the line. They don't care where the scrap came from; they just grab what is closest to them.
 The VLDL (The Shipping Crate): If you deliver a pile of PUFA-heavy scrap, the workers (LPCAT3) will build PUFA-rich membranes and pack them into the VLDL shipping crates.
The Point: If the parts you supplied are "oxidizable" or "pro-lipogenic" (PUFAs), it doesn't matter how expensive the original "Ferrari" was. Your body is now built out of those specific parts.
Bottom Line: Stop looking at the "PC" label on the bottle and start looking at the Fatty Acid profile on the back. That is the only material that actually makes it into the VLDL shipping crate.
Would you like me to generate an image of this "Biological Assembly Line" packing those VLDL crates?
LucH says:
Yes, but only with a two-side direction lines (==>). PNG.
PC choline. PUFA vehicle problem.png
The specific fatty acid "tail" on your PC supplement matters not because it survives digestion, but because it dictates the message available to your cells for reconstruction. Raw material available at the end will serve as a cargo. It’s not about the form the fat takes at the start; it’s about the raw material available at the finish line.
LucH says :
End. Thanks.
AI says:
It sounds like you've got a solid handle on the "cargo vs. vehicle" distinction now—the perfect way to bridge that gap in the forum debate.

alfredoolivas

@bio3nergetic said in PC choline to stabilize membranes:

and systemic inflammatory potential of dietary oxidized lipids regarding PUFA.

0.65g of soy / sunflower fatty acids in a gram of PC? I wouldn't worry about that at all.

bio3nergetic

@alfredoolivas Right, and as the understanding now settles into a different argument i.e. amount, it simply makes no sense to add in more PUFA regardless of amount when addressing PC exogenously. Where I allow my daily PUFA comes from whole food, eggs, etc. IF I consider exogenous use I'd look at something like mitolipin..

alfredoolivas

@bio3nergetic Every single study apart from two in vitro studies on the thread of Mitolipin, that showed it's beneficial effects were done using unsaturated phosphatidyl choline.

It's the end result that matters, not the theoretical effects of less than 1g of PUFA. To me.

Topical Administration:
The skin-permeation-enhancing effect of phosphatidylcholine: caffeine as a model active ingredient. - PubMed - NCBI
The hypocholesterolemic and antiatherogenic effects of topically applied phosphatidylcholine in rabbits with heritable hypercholesterolemia. - PubMed - NCBI
Effects of phosphatidylcholine on the topical bioavailability of corticosteroids assessed by the human skin blanching assay. - PubMed - NCBI

General/Miscellaneous:
Cell membranes and apoptosis: role of cardiolipin, phosphatidylcholine, and anticancer lipid analogues. - PubMed - NCBI
Biochemical effects of phosphatidylcholine treatment in rats. - PubMed - NCBI
Rapid stopping of A23187 action by phosphatidylcholine. - PubMed - NCBI
Blockade of alpha-adrenergic receptors by analogues of phosphatidylcholine. - PubMed - NCBI
The effect of mixed phosphatidylcholine liposomes on beef heart cytochrome c oxidase [proceedings]. - PubMed - NCBI
Cytochrome c Interaction with Cardiolipin/Phosphatidylcholine Model Membranes: Effect of Cardiolipin Protonation - ScienceDirect
Inhibition of mammalian cytotoxic cells by phosphatidylcholine and its analogue
Studies on cytochrome oxidase. Interactions of the cytochrome oxidase protein with phospholipids and cytochrome c. - PubMed - NCBI

Inflammation:
Anti-inflammatory action of a phosphatidylcholine, phosphatidylethanolamine and N-acylphosphatidylethanolamine-enriched diet in carrageenan-induced... - PubMed - NCBI
Anti-inflammatory effects of phosphatidylcholine. - PubMed - NCBI
Protective effect of phosphatidylcholine on lipopolysaccharide-induced acute inflammation in multiple organ injury. - PubMed - NCBI
Soy phosphatidylcholine inhibited TLR4-mediated MCP-1 expression in vascular cells. - PubMed - NCBI

Brain/Memory/Mood/Cognition/Nervous system:
Protective effects of phosphatidylcholine on oxaliplatin-induced neuropathy in rats. - PubMed - NCBI
Dietary phosphatidylcholine improves maze-learning performance in adult mice. - PubMed - NCBI
Impairment of brain mitochondrial functions by β-hemolytic Group B Streptococcus. Effect of cardiolipin and phosphatidylcholine. - PubMed - NCBI
Protective effects of a phosphatidylcholine-enriched diet in lipopolysaccharide-induced experimental neuroinflammation in the rat. - PubMed - NCBI
Effect of phosphatidylcholine on explicit memory. - PubMed - NCBI
A report on phosphatidylcholine therapy in a Down syndrome child. - PubMed - NCBI
http://www.amsciepub.com/doi/abs/10.2466/pr0.1986.58.1.207?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed&
http://www.sciencedirect.com/science/article/pii/S0140673683921086
[Combination of phosphatidylcholine and pentoxifylline in the therapy of progressive obstructive stroke]. - PubMed - NCBI

Liver/Gallbladder:
Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: in vitro and in vivo experiments. - PubMed - NCBI
Accumulation of lipid in rat liver was induced by vitamin B₆ deficiency and was ameliorated by supplemental phosphatidylcholine in the diet. - PubMed - NCBI
Hepatoprotective effect of phosphatidylcholine against carbon tetrachloride liver damage in mice. - PubMed - NCBI
Hyperreactivity of Blood Leukocytes in Patients with NAFLD to Ex Vivo Lipopolysaccharide Treatment Is Modulated by Metformin and Phosphatidylcholin... - PubMed - NCBI
[Effects of phosphatidylcholine pretreatment during acute experimental biliary reflux]. - PubMed - NCBI
Dietary phosphatidylcholine alleviates fatty liver induced by orotic acid. - PubMed - NCBI
Phosphatidylcholine-enriched diet prevents gallstone formation in mice susceptible to cholelithiasis. - PubMed - NCBI
http://www.ncbi.nlm.nih.gov/pubmed/7539565
http://www.ncbi.nlm.nih.gov/pubmed/24292666
http://www.ncbi.nlm.nih.gov/pubmed/21745592
http://www.ncbi.nlm.nih.gov/pubmed/20832797
http://www.ncbi.nlm.nih.gov/pubmed/8276192
http://www.ncbi.nlm.nih.gov/pubmed/8276177

Heart/Kidney:
http://www.ncbi.nlm.nih.gov/pubmed/23684996
http://www.ncbi.nlm.nih.gov/pubmed/1420493

Cancer:
http://www.ncbi.nlm.nih.gov/pubmed/17399847
http://www.ncbi.nlm.nih.gov/pubmed/24772432
http://www.ncbi.nlm.nih.gov/pubmed/19579625

Obesity/Diabetes/Metabolism:
http://www.ncbi.nlm.nih.gov/pubmed/25445436
http://www.ncbi.nlm.nih.gov/pubmed/22468042
http://www.ncbi.nlm.nih.gov/pubmed/22145579
http://www.ncbi.nlm.nih.gov/pubmed/21614002

Bones:
http://www.ncbi.nlm.nih.gov/pubmed/19766625
http://www.ncbi.nlm.nih.gov/pubmed/19296835

Anti-viral/anti-bacterial:
http://www.ncbi.nlm.nih.gov/pubmed/9708184
http://www.ncbi.nlm.nih.gov/pubmed/8516563
http://www.ncbi.nlm.nih.gov/pubmed/1570416
http://www.ncbi.nlm.nih.gov/pubmed/1530351

bio3nergetic

@alfredoolivas For myself, and PUFA sensitivity as well as past IBD experience, it is not theoretical it is practical. My exception of PC , again is primarily through food first. That is my threshold of tolerance. Outside of that I have no interest in adding more PUFA. There is no reasonable or convincing argument to do otherwise if one's diet is sorted. The understanding of PC and its benefits are again, as a necessarily evil not as a point of putting PUFA on a pedestal. The effects mentioned have been demonstrated without the PUFA risk with saturated lipids. The understanding that far is sufficient to deduce that IF one is to use PC exogenously opt for saturated. If you don't want to for personal reasons, by all means go ahead.