Effects of a purified krill oil phospholipid rich in long-chain omega-3 fatty acids on cardiovascular disease risk factors in non-human primates with naturally occurring diabetes type-2 and dyslipidemia

Abstract

BackgroundHigh serum levels of cholesterol, in particular low-density lipoprotein cholesterol, are considered a significant risk factor for development of cardiovascular disease. Therefore, rigorous treatment regimens with statins and other pharmaceuticals have been used extensively to reduce elevated cholesterol levels. Literature data have not clearly concluded whether long-chain omega-3 fatty acids reduce, increase or leave circulating cholesterol unaffected. In the present study a novel krill-oil derived preparation of omega-3 rich phospholipids, mainly phosphatidylcholine, was administered orally at increasing doses for 12 weeks to dyslipidemic non-human primates, and cholesterols and several other risk factors for cardiovascular disease were measured before, during and after treatment.MethodsSix dyslipidemic non-human primates suffering from naturally occurring diabetes type-2 were included, three in a vehicle control group and three being treated with the omega-3 rich phospholipid preparation. The control and test items were given daily by gavage and the doses of the test item were 50, 150 and 450 mg phospholipids/kg/day. Each dose level was given for 4 weeks. Plasma concentrations of the omega-3 fatty acids were measured in connection with change in dose and the omega-3 index in erythrocytes was determined bi-weekly. Blood lipids, apolipoproteins and diabetes, inflammatory and safety biomarkers were determined either weekly, biweekly or every 4 weeks. For the blood lipids and apolipoproteins, control-adjusted mean values are presented while absolute values are presented for the other parameters. Due to the low number of animals in each group, no statistical analyses were done.ResultsThe only detectable effects measured during dosing with the lowest dose were an increase in HDL-cholesterol and apolipoprotein A1. The intermediate and high doses decreased total cholesterol, LDL-cholesterol, apolipoprotein B100 and triglycerides and increased HDL-cholesterol and apolipoprotein A1. No effects were seen on the diabetes and inflammatory markers and on safety biomarkers.ConclusionsThe results indicate that the omega-3 rich phospholipid preparation had a positive impact on cardiovascular disease risk factors by reducing total cholesterol, LDL-cholesterol and triglycerides and increasing HDL-cholesterol. These findings justify further investigations of this preparation in animal models of dyslipidemia and, provided the current findings are confirmed, in human trials.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0411-z) contains supplementary material, which is available to authorized users.

Antarctic Krill (Euphausia superba) Oil: A Comprehensive Review of Chemical Composition, Extraction Technologies, Health Benefits, and Current Applications

“…Similar results were also reported in a different animal model of cynomolgus monkeys by Hals et al. (). They suggested that krill oil was effective in improving CVD risk factors including TC, LDL‐C, HDL‐C, TAG, apolipoprotein B100, and apolipoprotein A1 in dyslipidemic nonhuman primates suffering from naturally occurring diabetes type‐2.…”

“…Abnormal levels of TAG, total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), and low‐density lipoprotein cholesterol (LDL‐C) potentially increase the risks of CVD, and they have often been regarded as CVD risk factors (Papakonstantinou, Lambadiari, Dimitriadis, & Zampelas, ). Some studies were conducted in animal models to evaluate the effects of krill oil on these CVD risk factors in blood and tissues (Batetta et al., ; Hals, Wang, & Xiao, ; Sun et al., ; Tandy et al., ; Zhu, Shi, Qian, Cai, & Li, ). An 8‐week feeding trial supplemented with 1.25%, 2.50%, or 5.00% krill oil in diet showed that the krill oil‐containing diet significantly reduced hepatic TG and TC levels, as well as decreased the serum TG in high‐fat‐fed mice (Tandy et al., ).…”

The time course of erythrocyte membrane fatty acid concentrations during and after treatment of non-human primates with increasing doses of an omega-3 rich phospholipid preparation derived from krill-oil

“…Due to the various physiological effects of the endocannabinoids, in particular their regulatory effects on appetite, food intake, adipose tissue and ectopic fat accumulation and insulin sensitivity [16], a reduction of the relative abundance of their precursors and, subsequently, of their biosynthesized amounts, may have significant biological implications. Thus, the trend for the reduction in arachidonoylethanolamide (anandamide) and 2-AG levels may explain in part some of the beneficial metabolic effects observed with the krill oil preparation [11]. However, also EPA and DHA-derived ethanolamides are emerging as bona fide non-endocannabinoid mediators with potential anti-inflammatory actions [17] and we found here that EPA-ethanolamide, which is ultimately derived from the long chain omega-3 FA whose levels increased the most and most consistently in our study, i.e.…”

“…Inclusion criteria were predefined and were related to diabetes parameters (HbA1c, glucose and insulin) and blood lipid levels (triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c)). The results from the screening as well as details of housing conditions and care are described in [11]. Vital data of the monkeys included in the study are given in Table 3.…”

“…Selected safety parameters were also analyzed. The results from this part of the study are reported separately [11]. …”