This question comes up all the time and it's an interesting one:
why are neutral lipids (NL) less active than polar lipids (PL) when it comes down to CVDs and Inflammation?
In order to answer this, let's see the structures of PL vs NL.
The polar lipids have a phospho-head (polar head) on C-3 of the glycerol backbone whereas the NL are just esters (acid +EtOH --> ester + H20).
PL being polar are water soluble and more mobile in the water environment of our body.
NL are not.
So, imagine now, when you swallow a supplement that has ethyl esters of EPA and DHA. It needs to go through the stomach, where it hydrolyzes and the free EPA and DHA are then in a very hostile environment (low pH, many oxidative agents around etc); will they ever reach the blood stream? Yes, at very tiny amounts.
So, even when they reach the blood stream... can they stop PAF (Platelet Activating Factor)?
What the hell is PAF now?
Here is PAF.
PAF, 1-O-alkyl-2-sn-acetyl-glycero-3-phosphocholine, is a potent phospholipid mediator, which is characterized by an alkyl ether linkage at the sn-1 position, an acetyl group at the sn-2 position, and a phosphocholine group at the sn-3 position. These are important structurally distinguishing features that are critical to the biological activity of PAF, which is mediated by stereospecific binding to its specific receptor (PAF-R). PAF plays a role in several chronic diseases, in particular CVD.
So, PL with omega-3 fatty acids in positions 1 and 2 are more agile and more bioefficient because they mimic betten than neutral omega-3s the structure of PAF.
Competing for PAF receptor site, PL "inactivate" PAF and hence inhibit PAF-induced platelet aggregation, as shown here.
Therefore, when scientists talk about levels of omega-3 in red blood cells (RBC), these are not neutral omega-3s since NL are not water soluble.
Everything comes down to two fundamental Chemistry concepts:
1. Polarity
and
2. Solubility.
or as Chemists say, we say...
"Like dissolves like" is an expression used by chemists to remember how some solvents work. It refers to "polar" and "nonpolar" solvents and solutes. Basic example: Water is polar. Oil is non polar. Water will not dissolve oil.
Fish contains polar lipids.
Fish supplements (most of them!) contain NL.
Therefore...
Inflammation and cardiovascular disease: are marine phospholipids the answer?
why are neutral lipids (NL) less active than polar lipids (PL) when it comes down to CVDs and Inflammation?
In order to answer this, let's see the structures of PL vs NL.
 | |
| Transesterification reaction of a triglyceride of PUFA and ethanol.This process makes it easier to purify, refine, and concentrate the PUFAs. However, the derivatives obtained are less bioavailable because they have to be changed again to the triglyceride form in vivo. From https://www.azom.com/article.aspx?ArticleID=12419 |
 |
| The most common structures of phospholipids are depicted: phospholipids with a glycerol backbone (GPLs); sphingomyelin as a representative of a sphingosine-backbone phospholipid (SPLs); and alkyl-phospholipids (Alkyl-GPLs) that have a fatty chain linked with an ether-bond at the sn-1 position of the glycerol backbone. From https://www.mdpi.com/1420-3049/22/11/1964 |
The polar lipids have a phospho-head (polar head) on C-3 of the glycerol backbone whereas the NL are just esters (acid +EtOH --> ester + H20).
PL being polar are water soluble and more mobile in the water environment of our body.
NL are not.
So, imagine now, when you swallow a supplement that has ethyl esters of EPA and DHA. It needs to go through the stomach, where it hydrolyzes and the free EPA and DHA are then in a very hostile environment (low pH, many oxidative agents around etc); will they ever reach the blood stream? Yes, at very tiny amounts.
So, even when they reach the blood stream... can they stop PAF (Platelet Activating Factor)?
What the hell is PAF now?
Here is PAF.
 |
| The structure of the classic platelet-activating factor molecule https://link.springer.com/referenceworkentry/10.1007%2F978-3-319-54528-8_95-1 |
PAF, 1-O-alkyl-2-sn-acetyl-glycero-3-phosphocholine, is a potent phospholipid mediator, which is characterized by an alkyl ether linkage at the sn-1 position, an acetyl group at the sn-2 position, and a phosphocholine group at the sn-3 position. These are important structurally distinguishing features that are critical to the biological activity of PAF, which is mediated by stereospecific binding to its specific receptor (PAF-R). PAF plays a role in several chronic diseases, in particular CVD.
So, PL with omega-3 fatty acids in positions 1 and 2 are more agile and more bioefficient because they mimic betten than neutral omega-3s the structure of PAF.
Competing for PAF receptor site, PL "inactivate" PAF and hence inhibit PAF-induced platelet aggregation, as shown here.
Therefore, when scientists talk about levels of omega-3 in red blood cells (RBC), these are not neutral omega-3s since NL are not water soluble.
Everything comes down to two fundamental Chemistry concepts:
1. Polarity
and
2. Solubility.
or as Chemists say, we say...
"Like dissolves like" is an expression used by chemists to remember how some solvents work. It refers to "polar" and "nonpolar" solvents and solutes. Basic example: Water is polar. Oil is non polar. Water will not dissolve oil.
Fish contains polar lipids.
Fish supplements (most of them!) contain NL.
Therefore...
Inflammation and cardiovascular disease: are marine phospholipids the answer?
 | |
| Fig. 2 A schematic demonstrating the differences between the structures, digestion, and absorption of (A) triacylglycerols and (B) polar lipids such as phospholipids. (C) Highlights the putative bioavailability and bioactivity differences between n-3 PUFA bound to either TAG or PL. This figure has been adapted from Lordan et al.4 and Burri et al.86 with permission from MDPI, copyright 2017 and 2012 respectively. https://pubmed.ncbi.nlm.nih.gov/32270798/ |
