I don't think this Federal court Judge has presented any cogent argument that Mori proves or predicts the clinical benefits of Vascepa...Mori was a small clinical trial published in a an Nutrional Journal along side Articles like "Fruit and vegetables: Think Variety: Go ahead Eat",,.."Use of the Term Vegetarian."or "Pomegranate Juice
Consumption reduces oxidative stress"...
Very few to these articles are peer reviewed.
In all likelihood unless this article was identified using a Medlars Study it is very unlikely a medical doctor or researcher was aware of the article. Judge Du makes a very serous error when she assumes that everyone agrees with Mori. Physicians who are interested in the effects of Omega 3s are not only unlikely to be aware of Mori. But there are many other articles scientific or otherwise whose results vary with those of Mori.
Studies on Omega-3s vary widely in their findings and measurements..That very few if any physicians or others have any certainty as to the accuracy of any of them. For example in 2018 the year the R-I trial results were reported a major article in JAMA (Peer Reviewed) stated there was no proof that fish oil or Omega-3s Reduced the risks of Heart disease..
This is a list of references from one study on Krill oil// measurements not much consistency of opinions..
Bioavailability
Among the seven papers, four studies reported data on bioavailability and digestibility of EPA and DHA from KO and FO.26,27,29,31 In one of the studies, the same amounts of FO or KO, but different amounts and structural forms of EPA and DHA (TG versus PL), were used in the experiments,29 while in two studies, different amounts of FO and KO, but similar doses of EPA and DHA were used in the experiments.26,27 Tou et al31 examined the effects of different sources of n-3 PUFAs.
Tillander et al29 used a high-fat diet model and fed the mice with similar doses of KO and FO for 6 weeks. The content of EPA and DHA was lower in KO compared to that in FO, but both groups showed significantly increased plasma and liver PLs of EPA and DHA compared to controls. No difference in increase of EPA and DHA was seen between the FO and the KO groups, which indicates that KO may have a higher bioavailability compared to FO.
Vigerust et al26 used a high-fat-diet transgenic mouse model expressing human tumor necrosis factor (TNF) and fed the mice with similar doses of EPA and DHA from KO and FO for 6 weeks. In the plasma, EPA and DHA significantly increased in both groups compared to controls. The increase in plasma EPA and DHA between the two groups did not differ, suggesting that the bioavailability is not dependent on the structural form of EPA and DHA. Batetta et al27 fed Zucker rats with similar doses of EPA and DHA for 4 weeks, and they reported that plasma EPA and DHA were higher in the FO and KO groups compared to the levels in the corn oil, (CO) group. In the study by Tou et al,31 Sprague Dawley rats were fed a high-fat diet consisting of different marine oils, all containing different amounts of EPA and DHA, for 8 weeks. They measured the digestibility using the formula [(fatty acid intake – fecal fatty acids)/(fatty acid intake)] ×100 and showed no significant difference in EPA digestibility among rats fed the different marine oils. The DHA digestibility was higher in SO- than KO-fed rats. There were no significant differences in DHA digestibility in rats fed MO or tuna oil (TO) compared to SO- or KO-fed rats.
Plasma lipids
Among the seven studies, five studies reported the effects on plasma lipids.25–29 In two of the studies,25,29 the authors used the same amount of FO or KO, containing different amounts and EPA and DHA, in the experiments. Tillander et al29 found no differences in plasma lipids between the FO and the KO groups after 6 weeks. However, within the FO group, total plasma cholesterol, cholesterol ester, free cholesterol, TGs, and PLs were significantly reduced compared to the same in controls. In contrast, Wistar rats fed the same amount of FO and KO for 1–6 weeks showed significantly decreased plasma TG and total cholesterol compared to controls, but these effects seemed to be more pronounced after KO intake compared to FO intake.25 The reason for this discrepancy may be that Tillander et al29 used mice on a high-fat diet and not lean rats, and moreover, the amount of oil differed between the two studies.
In three of the studies, similar amounts of EPA and DHA from KO and FO were used in the experiments, and the dose of EPA and DHA was similar between the experiments.26–28 Vigerust et al26 did not observe any significant difference between the effects of KO and FO on plasma lipids, but KO significantly reduced plasma TG compared to controls, suggesting that KO is more effective than FO in lowering plasma TG. However, LDL cholesterol was significantly reduced in the FO group compared to controls, thus suggesting that FO is more effective than KO in lowering plasma LDL cholesterol. Total plasma cholesterol, free cholesterol, and HDL cholesterol were however significantly reduced in both groups compared to controls, but no differences between KO and FO were observed. These data are in line with the results of Batetta et al,27 who showed that KO and FO significantly reduced LDL cholesterol compared to control. In contrast, Burri et al,28 who fed mice for 12 weeks with similar amounts of EPA and DHA, did not see any changes in plasma lipids in any of the groups. These conflicting results may be due to the longer period of supplementation and probably because the mice were lean and not fed a high fat diet, as was done by Batetta et al27 and Vigerust et al,26 respectively.
Inflammation
Vigerust et al26 did not observe any substantial difference in levels of proinflammatory cytokines between treatment groups. Batetta et al27 compared the effects of KO and FO on ectopic fat and inflammation in obese rats. Lipopolysaccharides significantly increased the release of TNFa from all three groups; however, the increase was higher in the control compared to FO- and KO-treated groups, with no difference between these two groups. In these obese rats, KO also seemed to have a more pronounced inhibitory effect on the endocannabinoid system compared to FO, which is in accordance with the results of the human study by Banni et al.20
Ierna et al30 used an arthritis-induced mouse model to show that clinical arthritis score and hind paw swelling were significantly reduced in the KO group compared to controls. Mice fed the KO also had lower infiltration of inflammatory cells into the joint and synovial layer hyperplasia when compared to control. Thus, in this mouse model, KO seems to be more efficient compared to FO, in the treatment of arthritis. KO did not modulate the levels of serum cytokines, whereas consumption of FO increased the level of interleukin (IL)-1a and IL-13.30 Tou et al31 observed no significant effects on the Series-2 prostaglandins, thromboxane B metabolites, and markers of oxidative stress when rats were fed different marine oils.
Biological effects
In four studies, the aim was to understand biological effects of KO and FO by studying gene expression levels and protein activity in the liver.25,26,28,29 Ferramosca et al25 fed the same amount of FO and KO to rats and both oils significantly reduced the hepatic activity and expression of the mitochondrial tricarboxylate carrier. They also observed that FO and KO significantly reduced the activity of enzymes catalyzing de novo lipogenesis compared to the activity in controls. Tillander et al29 used quantitative polymerase chain reaction (PCR) to study changes in hepatic gene expression after KO and FO supplementation. FO mainly increased the expression of genes involved in fatty acid metabolism, while KO specifically decreased the expression of genes involved in isoprenoid/cholesterol and lipid synthesis.
Vigerust et al26 showed that KO significantly increased the mitochondrial and peroxisomal fatty acid ß-oxidation, as well as the overall carnitine turnover in the liver, which can explain the TG-lowering effect of KO seen in this study. Thus, it seems that KO has a greater potential to promote lipid catabolism. By the use of quantitative PCR, Vigerust et al26 showed that both KO and FO downregulated specific hepatic target genes involved in de novo lipogenesis and genes involved in cholesterol import and synthesis compared to the control-treated groups.
Burri et al28 also fed mice with different amounts of FO and KO to maintain the content of EPA and DHA similar in the two groups to evaluate the efficacy of KO and FO administration on gene expression profiling in liver. Long-chain n-3 PUFAs derived from KO downregulated the activity of pathways involved in hepatic glucose production as well as in lipid and cholesterol synthesis. The data also suggested that KO increases the activity of the mitochondrial respiratory chain. Long-chain n-3 PUFAs derived from FO modulated fewer pathways, even if the content of EPA and DHA was the same as KO, and did not modulate key metabolic pathways regulated by KO. FO also upregulated the cholesterol synthesis pathway, which was the opposite of the effect mediated by KO.
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Discussion
Studies on the bioavailability of EPA and DHA from KO and FO in humans and animals are limited and their interpretation is difficult, as different amounts of EPA and DHA have been used, duration of intervention differs among the studies, and different study groups have been included. Two human studies that are included in this review – one postprandial study and one intervention study – used the same amount of EPA and DHA from KO or FO, and they both show that the bioavailability of EPA and DHA from KO seems to be higher than from that from FO.19,21 This strengthens the hypothesis that there is a difference between the bioavailability of PUFAs from KO and FO. In contrast, Laidlaw et al24 showed that similar amounts of EPA from PL KO and TG SO resulted in the same increase in whole-blood EPA, suggesting that there is no difference in bioavailability of DHA from FO and KO. The problem in comparing these studies is that one study analyzed whole-blood fatty acids, while the two other studies used plasma PLs and plasma RBCs. In future studies, the same amount of EPA and DHA from KO and FO should be compared in plasma PLs, RBCs, and whole blood. If possible, adipose tissue biopsies should also be taken to study whether the fatty acids from KO and FO are differently incorporated into adipose tissue, as shown in the animal study by Tou et al.31 In animals, one study29 also indicates that KO may have a higher bioavailability compared to FO; however, another study indicates that bioavailability is not dependent on the structural form of EPA and DHA.26
The doses of KO and FO, type of study subjects, and duration of the studies showed very limited effects on lipids and inflammatory markers in human studies. Most of the studies did not see any effects between the groups. In one study,19 total cholesterol and LDL cholesterol increased following intake of KO and FO compared to controls, while Bunea et al23 showed reduction in concentration of total cholesterol and LDL cholesterol by KO and FO, as well as reduction in TG by KO. KO (at most doses) was more efficient than FO in reducing glucose and LDL cholesterol, whereas high-dose KO was more efficient in reducing plasma TG than FO.23
In the future, better-designed clinical studies are warranted to gain insight into the beneficial health effects of KO compared to FO. The animal studies show that there is a very small difference between KO and FO when it comes to health effects. KO seems to be more efficient in reducing the concentration of plasma TG, liver TG, and endocannabinoids, compared to FO, in animal studies. No adverse effects were reported.
Because KO and FO differ in their structural form, this may influence the incorporation of EPA and DHA into cells, resulting in different biological effects. KO also contains the antioxidant astaxanthin that protects the unsaturated bonds in the fatty acid from oxidative damage, which may influence the biological effects of KO. The possible biological difference between FO and KO was studied in animal models using gene expression analysis.25,26,28,29 EPA and DHA possibly regulate the activity of transcription factors by acting as ligands for the peroxisome-proliferator-activated receptor alpha (PPARa) or influence the activity of sterol regulator element-binding protein 1-c (SREBP1c).32,33 Consequently, these fatty acids have the ability to control transcription factor activity, which in turn regulates gene expression. Many of the beneficial health effects of EPA and DHA may be linked to their role of regulating expression of genes encoding proteins involved in transport, uptake, and storage of lipids, as well as enzymes involved in metabolic pathways and processes. The results from the studies included here show that FO upregulated the cholesterol synthesis pathway, which was opposite of the effect mediated by KO. KO also regulated more metabolic pathways than FO because glucose, fatty acid, and lipid metabolism pathways were affected by KO in some studies, and the same biological response was not seen with FO. This difference in biological effect may be caused by the different structure of PLs in KO and TG in FO.
In humans, it is also possible to perform biological studies using peripheral blood mononuclear cells (PBMCs), which are readily available, and FO has previously been shown to be able to modulate gene expression in these cells in human trials.34 PBMC gene expression analysis in human dietary intervention studies with FO and KO can be a powerful tool to understand the underlying molecular mechanisms of the effect mediated by these oils on lipid metabolism and inflammation in humans.
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Conclusion
Studies suggest that there may be a difference in the bioavailability of EPA and DHA after intake of KO and FO. However, more human studies designed to compare the effect of KO and FO are needed to conclude if the bioavailability of EPA and DHA differs between KO and FO. Furthermore, it is also necessary to document beneficial health effects of KO with high-quality human studies and to investigate whether these effects differ compared to the effects observed after regular fish and FO intake.
":>) JL
