Shark liver oil supplementation enriches endogenous plasmalogens and reduces markers of dyslipidaemia and inflammation

Paul S, Smith AAT, Culham K, Gunawan KA, Weir JM, Cinel MA, Jayawardana KS, Mellett NA, Lee MKS, Murphy AJ, Lancaster GI, Nestel PJ, Kingwell MA, and Meikle PJ. (2021) Shark liver oil supplementation enriches endogenous plasmalogens and reduces markers of dyslipidaemia and inflammation. Journal of Lipid Research

Plasmalogens are a class of lipids that contain a vinyl-ether bond at sn-1, an ester bond at sn-2 and often an ethanolamine polar headgroup at sn-3 on a glycerol backbone. The vinyl-ether bond causes these lipids to play an important role in various cellular functions including vesicular fusion, membrane organization and fluidity, and provide protection against oxidative stress. The wide variety of roles they play means that when plasmalogens are reduced, it can be associated with many diseases, including metabolic disease. Metabolic disease is a group of chronic conditions, such as obesity, type 2 diabetes, and cardiovascular disease, all of which have altered lipid metabolism and can lead to lipid accumulation. Lipid accumulation can negatively affect cell and tissue function through oxidative stress and inflammation. Shark liver oil (SLO) is a dietary supplement containing alkylglycerols and is known to increase plasmalogen levels. However, the mechanisms behind how SLO alters lipid levels are not well understood. Paul et al investigated the effects of SLO supplementation on lipid levels and clinical measures.

Ten overweight or obese men with at least two features of metabolic syndrome were administered 4 g of purified SLO (Alkyrol®) daily for 3 weeks. The SLO contained many monoalkyl-diacylglycerol species (TG(O)) where the 1-O-alkyl portion was predominantly the O-18:1 alkyl chain. The fatty acyl chain was more diverse. When analyzing the plasma from the participants after SLO supplementation, 293 different lipid species were found to have significant changes. A significant decrease was seen in 139 lipid species and an increase in 154 lipid species. Total TG(O) levels was increased in the treatment group compared to the control group, as expected, however the TG(O) species with medium chain fatty acids (16-18 carbons) were higher, but those with longer chain fatty acids (20-24 carbons) were lower after SLO supplementation relative to levels in SLO. In addition, plasmalogens increased significantly in the SLO-treated group and the greatest increase was in the O-18:1 species. Contrasting this increase, there were decreases in classes of other lipids including phosphatidylethanolamines, phosphatidylcholines, sphingomyelin, and phosphatidylglycerol, to name a few, as well as reductions in cholesterol, diacylglycerol, and triacylglycerol with the SLO supplementation. Similar to plasma, white blood cells also showed significant changes in lipid species after SLO administration, and species with O-18:1 showed the greatest increases.

To determine if the changes in lipid levels had any effect on clinical measures, inflammatory markers, blood cell counts, and monocyte (white blood cell) populations were studied. SLO supplementation was found to decrease total cholesterol, non-high density lipoprotein (non-HDL) cholesterol, and triglycerides but had no effect on fasting glucose, insulin, low density lipoprotein (LDL) cholesterol, HDL cholesterol, or inflammatory cytokines. There was a reduction of red blood cells and hemoglobin with SLO supplementation, but no difference was seen in whole blood count, or monocyte count.

Paul et al demonstrated that SLO supplementation elicits changes in the lipidome and provides some alteration of clinical measures, however, the effects seen were varied and the levels of numerous non-target lipid classes were also altered. Although it was suspected that TG(O) levels would increase since they are much higher in SLO than found in humans, the different species seen in SLO compared to the SLO-supplemented individuals indicates that there was significant remodeling of the acyl chain in the body. There was an increase in many O-18:1 alkyl chain species, but phosphatidylcholines, which are the most abundant phospholipid in circulating lipoproteins, was decreased. The duration that the participants were treated was only 3 weeks and therefore does not provide evidence for the effect of long-term supplementation, nor does it demonstrate how lipid and lipoprotein classes would be impacted over time. Paul et al also state that although there seemed to be some benefits from the SLO, non-purified SLO contains a lot of unwanted substances including heavy metals, squalene, excessive amounts of vitamin A and D which could negatively affect the liver and other major organs as the substance is metabolized. If the goal of SLO treatment is to increase plasmalogen levels, the authors indicate that this oil is not a good option. These findings provide further support for the necessity in regulating plasmalogen supplements and they suggest that most shark liver oil products on the market should not be used since the substance is not pure. Synthetic plasmalogens would be a safer option through having stronger regulations on the contents of the supplement and would be easier to produce in larger quantities.