Rolf Wallin

Effects of a new fluid fish oil concentrate, ESKIMO-3, on triglycerides, cholesterol, fibrinogen and blood pressure

Abstract. Eskimos have a very low incidence of cardiovascular disease, at least in part due to a high intake of n‐3 fatty acids. ESKIMO‐3 is a new stabilized (insensitive to oxidation) fluid fish oil concentrate, 30 ml of which contains an amount of eicosapentaenoic acid and total n‐3 fatty acids equivalent to the daily intake among Eskimos.

Effect of bread containing stable fish oil on plasma phospholipid fatty acids, triglycerides, HDL-cholesterol, and malondialdehyde in subjects with hyperlipidemia

To investigate the effects of daily intake of a small amount of fish oil in bread, 36 subjects with hyperlipidemia were randomly divided into three groups: stable fish oil with oat fibre, control with oat fibre and control with wheat fibre. Phospholipid fatty acids, triglycerides, cholesterol and malondialdehyde (MDA) were measured. Plasma levels of eicosapentaenoic and docosahexaenoic acid and total omega-3 fatty acids were increased after 2 and 4 weeks of daily intake of 93 g bread containing 1.3 g stable fish oil. Triglycerides were decreased and HDL- cholesterol increased after intake of the bread containing stable fish oil. No significant changes occurred in the control groups. Intake of the bread containing stable fish oil did not induce any signs of lipid peroxidation; on the contrary, plasma MDA values were slightly decreased after intake of all types of bread. This study showed that in subjects with hyperlipidemia intake of bread containing a small amount of fish oil results in a significant increase in omega-3 fatty acids, an increase in HDL-cholesterol, and a decrease in triglycerides and MDA, which may reduce the risk of ischemic heart disease.

Effects of fish oil alone and combined with long chain (n-6) fatty acids on some coronary risk factors in male subjects

The effects of fish oil alone were compared with those of fish oil combined 1:1 with evening primrose oil rich in long chain (n-6) fatty acids in a double-blind cross-over study. After administration of fish oil there was a highly significant increase in 20:5 (n-3) (eicosapentaenoic acid) and 22:6 (n-3) (docosahexaenoic acid) and a significant decrease in (n-6) fatty acids in plasma phospholipids. After consumption of the fish oil/evening primrose oil mixture, the increase in (n-3) and the decrease in (n-6) fatty acids were considerably smaller. Triglycerides in serum decreased by 36% (P < 0.01) after the fish oil and by 29% (P < 0.05) after the fish oil/evening primrose oil mixture. Atherogenic index decreased by 12% (P < 0.05) after fish oil/evening primrose oil and by 6% (P = ns) after fish oil alone. This difference was statistically significant (P < 0.05). Plasma homocysteine was reduced by 10% (P < 0.05) after the fish oil/evening primrose oil mixture and decreased 4% (P = ns) after the fish oil alone. Plasma fibrinogen decreased after both oils. The combined oils did not raise plasminogen activator inhibitor-1 (PAI-1) antigen at all, whereas after fish oil there was a 49% (P < 0.05) increase. Fish oil increased the ratio C20:4 to C20:3, an index of delta-5-desaturase, by 96% (P < 0.001) and reduced the ratio of C20:3 to C18:2, an index of delta-6-desaturase, by 38% (P < 0.001), whereas the fish oil/evening primrose oil mixture left these indexes unchanged. A high index of delta-5-desaturase has been found to be correlated to increased insulin sensitivity. In conclusion, combination of fish oil and evening primrose oil had a more favorable effect on the atherogenic index and caused no increase in PAI-1 antigen. The effects on triglycerides and PAI-1 of the fish oil and the mixture appears to be a result of their (n-3) fatty acid content.

Effects of a small dose of stable fish oil substituted for margarine in bread on plasma phospholipid fatty acids and serum triglycerides

Fish oil concentrates, fluid or in capsules, have shown beneficial effects on several risk factors for cardiovasular disease, but their use implies addition of fat to the diet. In order to overcome this, substitution of fish oil for other fat in a food product was tried in the present investigation. The effects of a small dose of fish oil substituted for margarine in bread on plasma phospholipid fatty acids and serum triglycerides were determined in a parallel, single-blinded, randomized study in 17 healthy subjects. Daily intake of 1 g stable fish oil containing 38 percent n-3 fatty acids (Eskimo-3®) for 4 weeks increased long-chain n-3 fatty acids in plasma phospholipids by almost 50 percent (p<0.05) and decreased serum triglycerides by 17 percent (p<0.005). Plasma α-tocopherol and TBARS (thiobarbituric acid reactive substances), measured as malondialdehyde, a marker of lipid peroxidation, and blood glucose, were unchanged. In a blinded consumer sensory test only 2 out of 195 subjects perceived any taste of fish aroma in the bread containing fish oil. This study showed that by use of a stable fish oil preparation it is possible to substitute fish oil for margarine in bread, a food product consumed in large amounts, and that a small amount of this fish oil has significant effects on blood lipids, without any signs of lipid peroxidation.

Differences in coagulation and fibrinolysis after traumatic and septic shock in man

In a prospective investigation of 19 patients with traumatic (n = 11) and septic (n = 8) shock admitted to the Intensive Care Unit of the University Hospital of Uppsala, differences in coagulation and fibrinolysis between the two conditions were evaluated. It was found that plasma coagulation variables such as thrombotest, normotest and antithrombin III were significantly lower in the septic patients, thus indicating a more intense and/or altered intravascular coagulation. Significantly higher levels of the von Willerbrand factor were found in septic patients, indicating a greater release from endothelial cells and platelets. The plasminogen activator inhibitor and the plasminogen-binding form of alpha 2-antiplasmin showed significantly higher values in septic patients, indicating a greater fibrinolysis inhibition in these patients. The greater disturbance in the protease-inhibitor balance in septicaemia was also verified by significantly lower levels of plasminogen and alpha 2-macroglobulin than after traumatic shock. Two out of 11 patients in traumatic shock developed the adult respiratory distress syndrome with a slow onset and benign course, whereas six out of eight septic shock patients developed a similar syndrome with a rapid onset and malignant course. These laboratory and clinical results lend further support to the hypothesis that the differences in coagulation and fibrinolysis systems reflect partly different pathogenic mechanisms underlying septic- and traumatic-induced adult respiratory distress syndrome.

Mixed Tocopherols Have a Stronger Inhibitory Effect on Lipid Peroxidation Than α-Tocopherol Alone

Intake of vitamin E with food (mixed tocopherols) has been found to counteract the development of atherosclerotic cardiovascular disease, whereas intake of large amounts of pure &agr;-tocopherol has shown only a slight or no effect in clinical studies. This study was designed to investigate the effects of &agr;-tocopherol alone and a mixed tocopherol preparation (&ggr;-, &dgr;-, and &agr;-tocopherol) on hydrogen peroxide–induced lipid peroxidation in human erythrocytes. Erythrocytes were incubated with different concentrations of &agr;-tocopherol or mixed tocopherols and then exposed to hydrogen peroxide. Tocopherol levels and malondialdehyde-thiobarbituric acid–reactive substances were determined by high-performance liquid chromatography and fatty acids by gas chromatography. Incubation of erythrocytes with tocopherols (30–120 &mgr;M) increased the tocopherol level in a concentration-dependent manner. The uptake of &ggr;- and &dgr;-tocopherols was much higher than that of &agr;-tocopherol. Hydrogen peroxide strongly increased lipid peroxidation and decreased polyunsaturated fatty acids in erythrocytes. Both &agr;-tocopherol and the tocopherol mixture protected the cells from lipid peroxidation, the mixture being much more potent than &agr;-tocopherol alone. This study indicates that a mixture of tocopherols has a stronger inhibitory effect on lipid peroxidation induced in human erythrocytes than &agr;-tocopherol alone, due to higher uptake of &ggr;- and &dgr;-tocopherol in the cells.

Vitamin E supplementation counteracts the fish oil-induced increase of blood glucose in humans

The objective of the study was to examine the effect of extra vitamin E in fish oil on some variables of glucose and lipid metabolism and on fibrinolysis in mildly hypertriglyceridemic men. Twelve subjects were given 30 mL/d of an ordinary fish oil (5.4 g eicosapentaenoic acid and 3.2 g docosahexaenoic acid) stabilized with vitamin E (1.5 IU/g, FO) and the same fish oil supplemented with extra vitamin E (4.5 IU/g, FO+E) for 4 wk in a randomized double-blind cross-over study. Fasting blood glucose concentration was increased after the period on FO (by 10%, P 270 mg/L) also decreased (by 22%, P < 0.05, and 16%, NS, respectively), with no significant differences between treatments. Plasminogen activator inhibitor-1 activity and antigen were significantly increased after both treatments. It is concluded that extra vitamin E counteracts the blood glucose increase that is often seen after fish oil intake.

Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double‐blind placebo‐controlled study

Karlberg K‐E, Saldeen T, Wallin R, Henriksson P, Nyquist O, Sylvén C (Huddinge Hospital, Huddinge; University of Uppsala, Uppsala; and Södertälje; Sweden). Intravenous nitroglycerin reduces ischaemia in unstable angina pectoris: a double‐blind placebo‐controlled study. J Intern Med 1998; 243: 25–31

DIETARY (n-3) FATTY ACIDS INCREASE SUPEROXIDE DISMUTASE ACTIVITY AND DECREASE THROMBOXANE PRODUCTION IN THE RAT HEART

The aims of the present studies were to examine the effects of fish oil (containing (n-3) polyunsaturated fatty acids) on myocardial thromboxane and prostacyclin production, superoxide dismutase (SOD) activity and malondialdehyde (MDA) production in the rat. Male rats were fed standard pellet diets and the same diets enriched with 7% (w/w) stabilized fish oil or 7% butter (saturated fat) for 2–6 wk. Myocardial production of thromboxane was lower in rats given fish oil than in those fed standard pellets (P < 0.01) or saturated fat (P < 0.05) and the prostacyclin/thromboxane ratio was higher than in rats fed standard pellets (P < 0.05). Myocardial SOD activity was higher in rats fed stabilized fish oil than in those given saturated fat (P < 0.05). Supplementation of the stabilized fish oil with extra vitamin E did not have any major effect on thromboxane and prostacyclin production or SOD activity. The percentage of arachidonic acid in the myocardial phospholipids was lower (P < 0.001) during fish oil than during saturated fat feeding, with no modifying effect of vitamin E supplementation. Feeding with the stabilized fish oil did not alter the myocardial α-tocopherol concentration, but the myocardial MDA concentration in vitro was higher (P < 0.01) than after feeding with saturated fat. Supplementation of the stabilized fish oil with extra vitamin E resulted in a higher α-tocopherol (P < 0.05) and lower MDA concentration (P < 0.05) in the myocardium compared to the unsupplemented fish oil. Plasma MDA concentration was not changed by fish oil feeding. In conclusion, fish oil feeding resulted in higher myocardial SOD activity and lower thromboxane production. These changes may be contributory mechanisms underlying the antiarrhythmic effect of fish oil. Copyright

Effects of stable fish oil and simvastatin on plasma lipoproteins in patients with hyperlipidemia

The aim of this study was to investigate the effect of a stable fish oil and simvastatin on plasma lipoproteins and erythrocyte fatty acids in patients with hyperlipidemia. Eighty-eight patients with hyperlipidemia were randomized into four groups to receive: fish oil, simvastatin, fish oil + simvastatin, or low fat diet (controls) for 12 weeks. Plasma total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL), and high density lipoprotein cholesterol (HDL) were measured before and after treatment. Intake of 9.2 g daily of stable fish oil for 12 weeks reduced plasma TG (P < 0.0001), TC (P = 0.003), LDL (P = 0.03), the LDL/HDL ratio (P = 0.003), and the TG/HDL ratio (p < 0.0001) and increased HDL (P =0.036). Eicosapentaenoic acid (P = 0.001) and docosahexaenoic acid (P = 0.009) levels in erythrocytes increased. Intake of simvastatin 10 mg daily resulted in decreased TC, LDL, and LDL/HDL ratio (P < 0.0001). Fish oil markedly potentiated the triglyceride lowering effect of simvastatin, whereas simvastatin markedly potentiated the cholesterol reducing effect of fish oil. This study showed that simvastatin therapy with addition of stable fish oil may be more beneficial in lowering plasma lipoproteins than simvastatin or fish oil alone.