Digestion, absorption, and metabolism characteristics of EPA-enriched phosphoethanolamine plasmalogens based on gastrointestinal functions in healthy mice

Wang T, Cong P, Cui J, Jiang S, Xu J, Xue C, Huang Q, Zhang T, and Wang Y. (2019) Digestion, absorption, and metabolism characteristics of EPA-enriched phosphoethanolamine plasmalogens based on gastrointestinal functions in healthy mice. Journal of Agricultural and Food Chemistry, 67.

Plasmalogens are a class of phospholipids that contain a vinyl-ether bond at the sn-1 position, giving these lipids roles in protecting against oxidative stress, aiding vesicular fusion, and in membrane organization. Eicosapentaenoic acid (EPA) is a ubiquitous omega-3, long-chain polyunsaturated fatty acid commonly found in marine animals. It has been shown to promote healthy brain function and regulate glycolipid metabolism. EPA-enriched plasmalogens (EPA-PlsEtns) consist of an EPA moiety attached at sn-2 with an ester bond, and an ethanolamine group at sn-3. This class of lipids are commonly found in shellfish and other marine animals. EPA-PlsEtn treatment has proven to be effective for memory and learning in a beta-amyloid-induced Alzheimer’s disease rat model (1) and EPA-PlsEtn has been shown to have greater efficacy compared to EPA-enriched phosphatidylethanolamine (EPA-PtdEtn) at preventing the formation of beta-amyloid (2) suggesting an important role for the vinyl-ether bond in EPA-PlsEtn. Although the metabolism and absorption of plasmalogens has been well characterized, this has not been completed on EPA-PlsEtn. Wang et al focused their work on the digestion, absorption, and metabolism of EPA-PlsEtn by analyzing fatty acids found in serum and feces after treatment, as well as what was found within the intestinal wall and contents of the small intestine.

To determine the digestion and absorption of EPA-PlsEtn, the time course of EPA available in the serum was investigated in the 16 hours following treatment. It was found that EPA increased over time, with peaks at 5 hours and 10 hours, then began to decline after 10 hours. Even at the end of 16 hours however serum levels were elevated compared to pre-treatment. It has been previously shown that free EPA absorbs quickly and peaks around 3 hours. Wang et al suggest that EPA may have entered the liver and been secreted into the serum as very low density lipoprotein (VLDL), explaining the longer duration required for levels to peak. As stated, the peak for lipid digestion is within the first 5 hours of treatment, thus fatty acid levels in the serum were also studied at this earlier timepoint. PtdEtns and PlsEtns were found to increase by 4-fold from 0 hours to the 5 hours. As well, EPA-PlsEtn and EPA-PtdEtn showed a 40-fold increase over time, but docosahexaenoic acid (DHA) enriched PlsEtn (DHA-PlsEtn) and DHA-PtdEtn did not. It was shown that the amount of EPA-PlsEtn within total PlsEtn increased from 0.71% to 6.44%, further indicating that the treatment was able to be absorbed and enter the serum.

To examine whether EPA-PlsEtn was absorbed in its entirety, feces was collected three days after treatment to measure the total fatty acid levels. No EPA was found in the feces, indicating that EPA-PlsEtn was uptaken and incorporated by the body. C16:0 and C18:0 were found at higher levels, consistent with previous reports that long-chain saturated fatty acids are predominantly released in feces. Lipids are absorbed primarily in the intestine and enter the blood, therefore Wang et al determined the fatty acid composition of the intestinal wall within 5 hours of EPA-PlsEtn treatment. At 0.5 hours after treatment, the intestinal wall showed its greatest EPA level at ~1.5 mg, which decreased to 0.9 mg by 1 hour, followed by no significant difference in EPA level from 1-5 hours after treatment. In addition to analyzing the feces and the intestinal wall, the total fatty acid level of the small intestine contents was measured. It was found that the total fatty acid levels increased sharply by 1 hour after treatment, and this trend was also in the main fatty acids (C16:0, C18:0, C18:1, and EPA).

Wang et al demonstrated that treatment with EPA-PlsEtn can be incorporated into serum, feces, intestinal wall, and intestinal contents confirming the body’s ability to digest, metabolize, and absorb these lipids. Importantly, this work also suggests that the vinyl bond, found within the ethanolamine plasmalogen, can be taken up by the intestine and circulated. These findings by Wang et al support work done by MLD. Using a carbon-13 labeled synthetic DHA-containing plasmalogen, we demonstrated uptake into the serum within 1-6 hours post-treatment. Our work also showed that the vinyl-ether bond remained intact during digestion and absorption following oral administration. Together these studies confirm that oral administration of plasmalogens is feasible and that the critical vinyl bond remains intact. As more information is learned about plasmalogens and their value in different disorders, optimizing their structure will be crucial. The findings that enriching plasmalogens with EPA improves levels and is able to be utilized, indicates that plasmalogens with other polyunsaturated fatty acids, including DHA, could show similar efficacy.

1.     Yamashita, S.; Hashimoto, M.; Haque, A. M.; Nakagawa, K.; Kinoshita, M.; Shido, O.; Miyazawa, T. Oral Administration of Ethanolamine Glycerophospholipid Containing a High Level of Plasmalogen Improves Memory Impairment in Amyloid beta-Infused Rats. Lipids 2017, 52 (7), 575−585

2.     Che, H.; Zhou, M.; Zhang, T.; Zhang, L.; Ding, L.; Yanagita, T.; Xu, J.; Xue, C.; Wang, Y. EPA enriched ethanolamine plasmalogens significantly improve cognition of Alzheimer’s disease mouse model by suppressing β-amyloid generation. J. Funct. Foods 2018, 41, 9−18