Lipid abnormalities, enhanced inflammation and oxidative stress seem to represent a vicious circle in atherogenesis, and therapeutic options directed against these processes seems like a reasonable approach in the management of atherosclerotic disorders. Krill oil (RIMFROST Sublime®) is a phospholipid-rich oil with eicosapentaenoic acid (EPA): docosahexaenoic acid (DHA) ratio of 1.8:1. In this pilot study we determined if krill oil could favourable affect plasma lipid parameters and parameters involved in the initiation and progression of atherosclerosis. The study was conducted as a 28 days intervention study examining effect-parameters of dietary supplementation with krill oil (832.5 mg EPA and DHA per day). 17 healthy volunteers in the age group 18–36 (mean age 23 ± 4 years) participated. Plasma lipids, lipoprotein particle sizes, fatty acid composition in plasma and red blood cells (RBCs), plasma cytokines, antioxidant capacity, acylcarntines, carnitine, choline, betaine, and trimethylamine-N-oxide (TMAO) were measured before and after supplementation. Plasma triacylglycerol (TAG) and large very-low density lipoprotein (VLDL) & chylomicron particle concentrations decreased after 28 days of krill oil intake. A significant reduction in the TAG/HDL cholesterol resulted. Krill oil supplementation decreased n-6/n-3 polyunsaturated fatty acids (PUFA) ratio both in plasma and RBCs. This was due to increased EPA, DHA and docosapentaenoic acid (DPA) and reduced amount of arachidonic acid (AA). The increase of n-3 fatty acids and wt % of EPA and DHA in RBC was of smaller magnitude than found in plasma. Krill oil intake increased the antioxidant capacity, double bond index (DBI) and the fatty acid anti-inflammatory index. The plasma atherogenicity index remained constant whereas the thrombogenicity index decreased. Plasma choline, betaine and the carnitine precursor, γ-butyrobetaine were increased after krill oil supplementation whereas the TMAO and carnitine concentrations remained unchanged. Krill oil consumption is considered health beneficial as it decreases cardiovascular disease risk parameters through effects on plasma TAGs, lipoprotein particles, fatty acid profile, redox status and possible inflammation. Noteworthy, no adverse effects on plasma levels of TMAO and carnitine were found.

Dietary intake of marine omega-3 polyunsaturated fatty acids (n-3 PUFAs) can change the plasma profile from atherogenic to cardioprotective. In addition, there is growing evidence that proteins of marine origin may have health benefits. We investigated a phospholipid-protein complex (PPC) from krill that is hypothesized to influence lipid metabolism, inflammation, and redox status. Male Wistar rats were fed a control diet (2% soy oil, 8% lard, 20% casein), or diets where corresponding amounts of casein and lard were replaced with PPC at 3%, 6%, or 11% (wt %), for four weeks. Dietary supplementation with PPC resulted in significantly lower levels of plasma triacylglycerols in the 11% PPC-fed group, probably due to reduced hepatic lipogenesis. Plasma cholesterol levels were also reduced at the highest dose of PPC. In addition, the plasma and liver content of n-3 PUFAs increased while n-6 PUFAs decreased. This was associated with increased total antioxidant capacity in plasma and increased liver gene expression of mitochondrial superoxide dismutase (Sod2). Finally, a reduced plasma level of the inflammatory mediator interleukin-2 (IL-2) was detected in the PPC-fed animals. The present data show that PPC has lipid-lowering effects in rats, and may modulate risk factors related to cardiovascular disease progression.

Hepatic mitochondrial dysfunction plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Methyl donor supplementation has been shown to alleviate NAFLD, connecting the condition to the one-carbon metabolism. Thus, the objective was to investigate regulation of homocysteine (Hcy) and metabolites along the choline oxidation pathway during induction of hepatic steatosis by the fatty acid analogue tetradecylthiopropionic acid (TTP), an inhibitor of mitochondrial fatty acid oxidation. Mice were fed a control diet, or diets containing 0.3 %, 0.6 %, or 0.9 % (w/w) TTP for 14 days. Blood and liver samples were collected, enzyme activities and gene expression were analyzed in liver, lipid and fatty acid composition in liver and plasma, one-carbon metabolites, B-vitamin status, carnitine and acylcarnitines were analyzed in plasma. Liver mitochondrial fatty acid oxidation decreased by 40 % and steatosis was induced in a dose dependent manner; total lipids increased 1.6-fold in animals treated with 0.3 % TTP, 2-fold with 0.6 % TTP and 2.1 fold with 0.9 % TTP compared to control. The higher hepatic concentration of fatty acids was associated with shortening of carbon-length. Furthermore, the inhibited fatty acid oxidation led to a 30-fold decrease in plasma carnitine and 9.3-fold decrease in acetylcarnitine at the highest dose of TTP, whereas an accumulation of palmitoylcarnitine resulted. Compared to the control diet, TTP administration was associated with elevated plasma total Hcy (control: 7.2 ± 0.3 umol/L, 0.9 % TTP: 30.5 ± 5.9 umol/L) and 1.4-1.6 fold increase in the one-carbon metabolites betaine, dimethylglycine, sarcosine and glycine, accompanied by changes in gene expression of the different B-vitamin dependent pathways of Hcy and choline metabolism. A positive correlation between total Hcy and hepatic triacylglycerol resulted. The TTP-induced inhibition of mitochondrial fatty acid oxidation was not associated with increased hepatic oxidative stress or inflammation. Our data suggest a link between mitochondrial dysfunction and the methylation processes within the one-carbon metabolism in mice.