Plasmalogens Week #4 – Nutrition

Continuing Plasmalogens Week with two 2025 papers, starting with a simulated in vitro model of how humans digest mussel plasmalogens:

“Plasmalogens (Pls) have promising therapeutic potential in the treatment of neurological disorders, but their distribution, compositional intricacies, and structural alterations during the digestive process are unclear. This study aimed to address this gap by isolating Pls-enriched fractions from mussel (Mytilus edulis) and simulating their digestion in vitro across the mouth, stomach, and intestine phases.

Comparison between Pls and normal phospholipids, sharing identical fatty acyl compositions, illuminated a heightened susceptibility of Pls to catabolism during stomach digestion, which is mainly attributed to the hydrolysis reaction of Pls sensitive to acidic conditions. Phospholipid digestion commenced during the gastric phase and continued with notable catabolism in the intestinal phase, resulting in the release of substantial amounts of free fatty acids (FFAs) and lysophospholipids (LPs), which subsequently formed lipid droplets of larger sizes. Larger droplets delay intestinal absorption, extending the window period for Pls hydrolysis by pancreatic lipase.

The digestive behaviour of Pls with different polar head groups indicated that pancreatic lipase appears to digest phosphatidylethanolamine plasmalogen (PlsPE) to a greater extent than phosphatidylcholine plasmalogen (PlsPC). 41 PlsPE and 14 PlsPC were observed, suggesting that Pls may be more readily digested in the gastrointestinal tract compared to conventional phospholipids.

Generally, lipids are first absorbed by intestinal epithelial cells and undergo lipid remodeling before being transported into lymphatic fluid and then entering the bloodstream. During lipid absorption, PE can be partially converted into PC for lipid remodeling. Since in vitro digestion models cannot fully simulate the intestinal microenvironment (such as microbial metabolism and intestinal epithelial absorption), animal experiments are required to verify the actual bioavailability of PlsPE and PlsPC.”

https://www.sciencedirect.com/science/article/pii/S2666154325006799 “Characterization of plasmalogen properties and metabolic behavior during the simulated multi-stage digestion of Mytilus edulis phospholipids based on untargeted lipidomics”


A review highlighted nutritional implications of changes in plasmalogen chemistry:

“Plasmalogens vary quantitatively in biological systems due to biosynthesis, degradation, remodeling, and certain external stressors. Not only concentrations, but also the composition of molecular species within the plasmalogen pool changes. These shifts often involve the shortening of sn-2 fatty acyl chains, the loss of PUFAs such as DHA and EPA, and the accumulation of oxidized, truncated, or degraded species, as a result of radical-mediated oxidation and/or enzymatic degradation.

The possible increase in lysophospholipids (typically LPE and LPC, corresponding to PlsEtn and PlsCho, respectively) may be attributed to the loss of intact plasmalogens during degradation, especially in the sn-1 position. Lysoplasmalogens can be re-acylated to regenerate the original plasmalogens or create new plasmalogen species with different sn-2 fatty acyl compositions.

These molecular-level transitions highlight the complexity of plasmalogen dynamics and emphasize the need for quantitative, species-specific analysis. Variations are influenced by physiological conditions, pathological states, and nutritional supplementation.

Plasmalogens are primarily those derived from animal products, such as fish, meat, and dairy products, as well as certain marine foods. Microorganism-derived plasmalogens are attracting researchers’ attention, representing a new way of effectively utilizing bacterial resources as a ‘food’ source. Compounds provided can be plasmalogens (either PlsCho and PlsEtn, extracted from natural sources or synthesized) or plasmalogen precursors (e.g., alkylglycerols).”

https://www.mdpi.com/2072-6643/17/22/3497 “The Changes in Plasmalogens: Chemical Diversity and Nutritional Implications—A Narrative Review”

A challenge researchers haven’t satisfactorily addressed yet is the question of whether beneficial oral intake of plasmalogens can be mechanistically attributed to specific plasmalogen breakdown products or to intact plasmalogens. This review introduced two other mechanistic uncertainties in that 1) absorbed and digested breakdown products can be recycled back into plasmalogens, and 2) gut microbiota can also produce plasmalogens. I’ve read papers that speculated but didn’t demonstrate that either of these factors contributed to their results.

This review cited Dr. Goodenowe’s plasmalogen precursor clinical trial mentioned in Plasmalogens Parts 1, 2, and 3. The first paper above, and most of the papers in Plasmalogen Week cited his other research.


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