MaxEPA Oil Research Articles

Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis.

ObjectiveTo develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis.DesignSystematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action.ResultsWe identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil) as lead candidates for clinical evaluation.ConclusionsWe demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.

Dietary Fish Oil Enhances Insulin Sensitivity in Miniature Pigs

The effects of dietary fish oil, MaxEPA, and corn oil on insulin sensitivity were examined in male miniature pigs. The pigs (20–35 kg) received 750 g of nonpurified diet per day (160 g/kg protein, 50 g/kg fat) with the addition of either 30 g corn oil or 30 g MaxEPA, resulting in 90 g total fat per kg diet for 4–5 wk. The MaxEPA diet provided 12.6 g (n-3) polyunsaturated fatty acids per kg diet (6.7 g eicosapentaenoic acid, 4.8 g docosahexaenoic acid), 4.7 g (n-3) polyunsaturated fatty acids and 147 mg cholesterol. The corn oil diet provided 22.7 g (n-6) polyunsaturated fatty acids per kg diet and no (n-3) polyunsaturated fatty acids; cholesterol was added to equal the amount in the MaxEPA. After overnight withdrawal of food, intravenous glucose tolerance tests were conducted in conscious pigs by using previously placed jugular vein catheters. Plasma glucose responses and the areas under the plasma glucose curves were similar in seven MaxEPA- and five corn oil-fed pigs. However, the incremental areas under the insulin curves were significantly lower for the pigs fed MaxEPA. Thus values for insulin sensitivity (S1), determined with Bergman's minimal model, were significantly higher for MaxEPA than for corn oil-fed pigs, whereas the rate of glucose disappearance (KG), did not differ between the two groups. Therefore, substitution of (n-3) for (n-6) polyunsaturated fatty acids in dietary lipids is associated with enhanced insulin sensitivity in male pigs.

Diets rich in saturated n-9 and n-3 fatty acids differentially affect the fatty acid composition of phospholipids and function of rat platelets

The aim of the present study was to determine whether dietary intake of monounsaturated or long chain n-3 fatty acids could be effective in lowering platelet responsiveness through modulation of platelet phospholipid composition. Rats were fed diets containing 20% fat with equal cholesterol and 13a-tocopherol contents. These diets were supplemented with saturated, oleic or n-3 fatty acids, n-3 polyunsaturated fatty acids being added either pure, as eicosapentaenoic and docosahexaenoic ethyl esters, or as MaxEPA oil. Dietary n-3 fatty acids did not affect the oxidation status of plasma lipids. Oleic acid- and saturated fatty acid-rich diets led to similar enrichment of platelet phospholipids in arachidonic acid and to comparable thromboxane A(2) generation on stimulation with collagen or thrombin. Platelets of n-3-fed groups were differently enriched in eicosapentaenoic and docosahexaenoic acids at the expense of arachidonic acid. These groups displayed similar thromboxane A(2) production, although levels were lower than those for groups fed with oleic- or saturated fatty acid-rich diets. Only the MaxEPA diet led to a reduction in platelet reactivity, measurable as a small decrease in the aggregation induced by collagen. This diet was also responsible for a high cholesteroUphospholipid ratio and low a-tocopherol content in platelets. Overall results indicated that (i) only MaxEPA reduced platelet reactivity and (ii) this effect was moderate and apparently unrelated to platelet arachidonic acid content, membrane cholesterol to phospholipid ratio or thromboxane A(2) production.

Effects of ??-3 and ??-6 Fatty Acid???Rich Oils on the Cardiovascular System of Thermally Injured Rabbits: Changes in Plasma Triglycerides, Plasma Cholesterol, Relative Blood Viscosity, Platelet Count, and Bleeding Time

New Zealand white male rabbits were studied to determine how supplements of soybean oil, soybean + MaxEPA oil, or MaxEPA oil affected their cardiovascular status when they were burned. Plasma triglyceride concentrations increased at 2 hours after burn injury (28 days after supplement administration) and declined by the end of the study in all three experimental groups of rabbits. These same animals showed no noticeable differences in the plasma concentrations of total cholesterol or in the high-density lipoprotein cholesterol subfractions. Plasma low-density/very-low-density lipoprotein cholesterol levels remained unchanged at 2 hours after burn injury/sham treatment but increased by the end of the study in all three experimental groups of rabbits. The mean platelet number was significantly higher in burned/sham treated rabbits given soybean oil supplement as compared with numbers in those given either soybean oil + MaxEPA oil or MaxEPA oil supplement. Plasma relative viscosity was highest in the soybean oil-supplemented rabbits, decreased in animals fed soybean oil + MaxEPA, and lowest in MaxEPA oil-supplemented rabbits. Mean bleeding time was lowest in soybean oil-fed rabbits. The bleeding time was higher in rabbits fed soybean oil+MaxEPA oil and highest in MaxEPA oil-supplemented animals. Platelet number and plasma viscosity were highest in the soybean oil-supplemented rabbits and lowest in the MaxEPA oil-supplemented group. The reverse pattern occurred when bleeding time was established. Overall results obtained suggest that supplementation with oils rich in omega-3 and omega-6 fatty acids may have significant effects on the cardiovascular health of burned male New Zealand white rabbits.

Effects of supplemented omega-3 and omega-6 fatty acid rich oils on the cardiovascular system of thermally injured rabbits: changes in plasma and platelet fatty acids.

The effects of omega-3 fatty acid rich oil (MaxEPA oil), omega-6 fatty acid rich oil (soybean oil), and a combination of omega-3 and omega-6 oils (MaxEPA oil + soybean oil) on cardiovascular health-related parameters of thermally injured and control (sham) rabbits were determined. Plasma and platelet analyses of burned rabbits fed with MaxEPA oil revealed significantly higher concentrations of eicosapentaenoic acid and docosahexaenoic acid + myristic acid. Linolenic acid concentrations declined in animals supplemented with soybean oil + MaxEPA oil. At the end of this study the lowest concentrations of linoleic acid and arachidonic acid were found in the sham and burned groups supplemented with soybean oil + MaxEPA oil. Overall, favorable significant differences in plasma and platelet fatty acids concentrations were found in burned or sham groups supplemented with MaxEPA when compared with those of groups supplemented with soybean oil. These favorable changes in plasma and platelet lipids may have an impact on the risk of cardiovascular disease in thermally injured patients.

The type of dietary polyunsaturated fatty acids influences high density lipoprotein-mediated cholesterol efflux

We have examined the effects of dietary n−3 and n−6 polyunsaturated fatty acids on the composition of high density lipoproteins (HDL) in rabbits and on the ability of the HDL to promote cholesterol efflux from rabbit fibroblasts. We observed that HDL from rabbits fed MaxEPA oil contained significantly more unesterified cholesterol and cholesteryl ester than HDL from rabbits fed chow or chow plus safflower oil. The rate of net efflux of cholesterol from rabbit skin fibroblasts to medium containing HDL from animals fed chow plus MaxEPA oil was substantially greater than was seen when the medium contained HDL from rabbits fed chow alone or chow plus safflower oil. We suggest that the faster cholesterol efflux seen with HDL from animals fed MaxEPA oil supplements may account for some of the protection against coronary artery disease that has been reported for individuals consuming diets rich in marine mammals, fish or fish oils.

Comparison of diets supplemented with fish oil or olive oil on plasma lipoproteins in insulin-dependent diabetics

This study was designed to compare changes in high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol in normolipidaemic male insulin-dependent diabetics (IDD) following dietary supplementation with either the fish oil concentrate Max EPA or olive oil. The contribution of the small quantity of cholesterol in Max EPA to these changes was also examined. Twenty-seven subjects were matched in groups of three and randomly allocated to one of three treatment groups of nine subjects each. Subjects were given 15 1-g capsules of oil daily for 3 weeks, consisting of either Max EPA, olive oil, or olive oil to which was added the same amount of cholesterol as contained in Max EPA, respectively. There was a significant increase in eicosapentaenoic acid, and a decrease in arachidonic acid, in the platelet membrane phospholipids of subjects taking Max EPA. In this group, there was an approximately 30% increase in serum HDL 2-cholesterol (0.59 ± 0.07 to 0.77 ± 0.11 mmol/L, mean ± SEM; P < .01) and a corresponding decrease in HDL 3-cholesterol (0.79 ± 0.03 to 0.71 ± 0.03 mmol/L; P < .05). Although total and LDL-cholesterol concentrations were also higher after Max EPA, the changes were not significant. Triglycerides were significantly decreased by Max EPA. There were no significant changes in lipids in the groups given olive oil. These results show that compared with olive oil, dietary supplementation with Max EPA substantially increases HDL 2-cholesterol in insulin-dependent diabetics. This is most likely due to a selective effect of ω3 fatty acids. An increase of this proportion in the cardioprotective HDL 2-cholesterol, if sustained over time, could have a major impact on vascular health in diabetics.

Effects of Fish Oil Supplements in NIDDM Subjects: Controlled Study

The aim of this study was to evaluate the effects of a fish oil preparation (MaxEPA) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic (NIDDM) subjects. Eighty NIDDM outpatients aged 55.9 yr (mean SD 11.5 yr) participated in a prospective double-blind placebo-controlled study of MaxEPA capsules (10 g/day) or olive oil (control) treatment over 6 wk. Patients received either MaxEPA or olive oil in addition to preexisting therapy. Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk. Platelet membrane eicosapentaenoic acid (EPA) content increased in the treatment group (P less than 0.001). MaxEPA supplementation was associated with a significant fall in total triglycerides (P less than 0.001) but did not affect total cholesterol (P = 0.7) compared with control treatment. Fasting plasma glucose increased after 3 wk (P = 0.01) but not after 6 wk (P = 0.17) treatment with MaxEPA. Spontaneous platelet aggregation in whole blood fell in the MaxEPA group (P less than 0.02) after 6 wk, but there were no changes in agonist-induced platelet aggregation, thromboxane generation in platelet-rich plasma, or plasma beta-thromboglobulin and platelet factor IV levels. An increase in clotting factor VII (P = 0.02), without changes in fibrinogen or factor X levels, occurred in the MaxEPA group. Similar reductions in blood pressure were observed in both groups. Dietary supplementation with MaxEPA capsules (10 g/day) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels. Most indices of platelet function are unaffected by this therapy.

Fish oil attenuates the cholesterol induced rise in lipoprotein cholesterol

Fish oils rich in n-3 fatty acids lower plasma triglyceride profoundly but the effect on plasma cholesterol is not clear. This study tested the capacity of MaxEPA oil to modify the rise in lipoprotein cholesterol during cholesterol-rich diets. Six subjects were tested with three diets: 1) habitual (P/S 0.47, cholesterol 710 mg/d); 2) fish oil (40 g/d MaxEPA, P/S 1.62, cholesterol 190 mg/d); 3) fish oil + egg yolk (P/S 1.62, cholesterol 940 mg/d). Changing from habitual to fish oil significantly lowered cholesterol and triglyceride levels in plasma, VLDL, LDL, and HDL and in plasma apo-A1 and apo-B. However the addition of 750 mg/d cholesterol to the fish oil failed to raise lipoprotein cholesterol or apoprotein levels significantly, although plasma cholesterol rose slightly; n-3 fatty acids are therefore capable of lowering lipoprotein cholesterol even when the intake of cholesterol is high.

Enhancing effect of dietary supplementation with ω-3 fatty acids on plasma fibrinolysis in normal subjects

A supplement of MaxEPA oil containing 5 g of ω-3 polyunsaturated fatty acids was given for two weeks to nine normal volunteers. The vascular plasminogen activator (VPA) level increased and there was a fall in the levels of inhibitors of vascular plasminogen activator (IPA) and of plasmin, α 2-antiplasmin ( α 2-AP). No significant changes occur in serum cholesterol, triglycerides, HDL or LDL levels.