Jørn Munkhof Møller

Effect of fish oil on heart rate variability in survivors of myocardial infarction: a double blind randomised controlled trial

Marine n-3 polyunsaturated fatty acids may protect against ischaemic heart disease.1 In the diet and reinfarction trial patients with an acute myocardial infarction advised to eat fish rich in n-3 polyunsaturated fatty acids had a 29% reduction in two year all cause mortality compared with controls.2 The authors hypothesised that dietary n-3 polyunsaturated fatty acids might reduce malignant ventricular arrhythmias and sudden cardiac death, as reported in animals.3 We investigated a possible antiarrhythmic effect of dietary n-3 polyunsaturated fatty acids in survivors of myocardial infarction. Patients were eligible for study if they had been discharged from the department of cardiology at Aalborg Hospital between November 1991 and August 1993 after a myocardial infarction and had a ventricular ejection fraction below 0.40. We excluded patients aged over 75, patients with pacemakers or permanent tachyarrhythmias, and those with serious non-cardiac disease. Eighty one patients fulfilled the inclusion criteria and 55 gave informed consent to a double blind placebo controlled trial. Patients were randomly …

Fish Consumption, n-3 Fatty Acids in Cell Membranes, and Heart Rate Variability in Survivors of Myocardial Infarction With Left Ventricular Dysfunction

To elucidate a possible antiarrhythmic effect of long-chained n-3 polyunsaturated fatty acids, heart rate variability was assessed in 52 patients with a previous myocardial infarction and left ventricular dysfunction. The content of n-3 polyunsaturated fatty acids in platelets was closely associated with the patients fish-consuming habits, and a significant positive correlation was observed between the n-3 fatty acid docosahexaenoic acid and heart rate variability.

Bioavailability of marine n-3 fatty acid formulations.

The use of marine n-3 polyunsaturated fatty acids (n-3 PUFA) as supplements has prompted the development of concentrated formulations to overcome compliance problems. The present study compares three concentrated preparations - ethyl esters, free fatty acids and re-esterified triglycerides - with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. Seventy-two volunteers were given approximately 3.3g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks. Increases in absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA.

The effect of n-3 fatty acids on neutrophil chemiluminescence

The effect of dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) on the production of free oxygen radicals from activated neutrophils was investigated in healthy subjects, using chemiluminescence. In the first study 22 persons were give 4 g n-3 PUFAs daily for 6 weeks. There was a median reduction of chemiluminescence from neutrophils stimulated with opsonized zymosan of 37% (p < 0.001). The median content of eicosapentaenoic acid in platelets, used as an indicator for cellular fatty acid profile, increased from 0.70 to 2.80% (p < 0.001), and there was a significant negative correlation between the chemiluminescence signal and the content of eicosapentaenoic acid in platelets (p < 0.001). In a second, low-dose study 24 persons were allocated to daily supplementation with either 0.65 g n-3 PUFAs or with a control oil for 6 weeks. Compared to the control group there was a median reduction of 38 and 44% in chemiluminescence from neutrophils stimulated with opsonized zymosan and phorbol,12-myristate,13-acetate (PMA), respectively. Neither of these differences, however, was statistically significant. These findings lend support for a possible role of n-3 PUFAs in the management of inflammatory disorders.

The acute effect of a single very high dose of n-3 fatty acids on coagulation and fibrinolysis

The objective of the study was to investigate the acute effect of a single very high dose of n-3 PUFA on coagulation and fibrinolysis. Forty healthy volunteers were randomized into two groups to receive either 20 grams of n-3 PUFA or 20 grams of n-6 PUFA as a single dose at 6 p.m. with their evening meal. Coagulation and fibrinolysis were evaluated in the fasting state at 8 a.m. the next morning and compared to values obtained at 8 a.m. the day before, when the participants were on their habitual diets. PAI-1 activity in plasma increased by a mean of 62% in subjects randomized to receive n-3 PUFA despite that no changes could be demonstrated in t-PA antigen levels. PAI-1 activity was unaltered in the 20 controls receiving n-6 PUFA. Plasma fibrinogen, coagulation factor VII, thrombin-antithrombin complexes and D-dimer did not significantly change after either supplement. The substantial increase in levels of PAI-1 activity in plasma after a single very high dose of n-3 PUFA may limit the usefulness of single very high doses of n-3 PUFA in acute clinical conditions.

The acute effects of a single very high dose of n−3 fatty acids on plasma lipids and lipoproteins in healthy subjects

Forty healthy volunteers were allocated in a double blind, randomized study to receive either 20 g of n−3 polyunsaturated fatty acids (PUFA) or 20 g of n−6 PUFA at their evening meal. The effect on plasma lipids and lipoproteins of this single dose of fish oilvs. corn oil was studied the next morning, 14 h after ingestion. Plasma triglycerides and very low density lipoprotein-cholesterol significantly decreased (33%) after n−3 PUFA (P<0.001), and significantly (P<0.01) more than after intake of n−6 PUFA. The decrease in plasma triglycerides after n−3 PUFA ingestion was more pronounced in subjects with higher baseline levels of triglycerides (P<0.001). Total cholesterol decreased after both supplements, but did not differ between the supplements. Low density lipoprotein-cholesterol did not change, and high density lipoprotein-cholesterol significantly decreased in subjects given n−3 PUFA compared to baseline, but not when compared to subjects receiving n−6 PUFA. In conclusion, we have shown that a single very high dose of n−3 PUFA has a pronounced hypotriglyceridemic effect, which is directly related to the initial plasma level.

Haemophilic patients with hepatitis C have higher viral load compared to other well-defined patient groups.

Comparison of hepatitis C viral load between different patient populations has been hampered by the use of different technology in individual studies. We had the impression that haemophilic (HAEM) patients had a higher serum load of hepatitis C virus (HCV) compared to other HCV‐infected patients. We therefore studied viral load and genotypes in active illicit drug users (IDU), HAEM patients and patients with post‐transfusion hepatitis (PTH). The study comprises 225 HCV‐RNA positive patients, 117 IDU, 60 HAEM patients and 48 PTH patients. All patients were anti‐HIV negative. HCV‐RNA was measured with a quantitative reverse transcription polymerase chain reaction (RT–PCR) method, HCV‐genotypes were determined with genotype specific primers in RT–PCR in 221 patients. Four patients could not be genotyped with our assay and were excluded. Overall viral load was higher in genotypes 1 and 2 compared to genotype 3, median values of HCV‐RNA were 1400 × 103 geq ml−1, 2700 × 103 geq ml−1 and 270 × 103 geq ml−1, respectively. HAEM patients had significantly higher viral load for both genotypes 1 and 3 compared to the IDU and PTH patients. In a multiple linear regression model HCV‐RNA viral load was independently associated with HAEM and genotype, but not to age, gender or disease duration. In conclusion, HAEM patients have higher viral load than IDU and PTH patients. The reason for this is unknown, but it may be due to host factors or mode of transmission with multiple inoculations.

HBeAg and not genotypes predicts viral load in patients with hepatitis B in Denmark: A nationwide cohort study

Abstract Objective. To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe). Materials. We investigated 1025 patients with hepatitis B virus infection in a nationwide study in Denmark. Results. Prevalence of genotypes were: 10.5% A, 17.3% B, 20.5% C, 45.7% D, 3.2% E, 0.6% F, 1.1% G and 1% had more than one genotype. Nearly 60% of patients with genotype A were from Africa, 82% and 93% with genotypes B or C were from East Asia, 62% with genotype D came from the Middle East and 91% with genotype E came from Africa. More women had genotypes B (p = 0.006) or C (p < 0.001) while more men had genotypes A (p = 0.015) or D (p < 0.001). Women with genotypes B and D were younger than men (p < 0.001, p = 0.026). Viral load differed in genotype A and D compared with B and C (p < 0.001), and between anti-HBe and hepatitis B e antigen (HBeAg) positive patients (median values 5.4 × 103 IU/ml and 7.4 × 107 IU/ml, respectively, p < 0.001). Viral load depended on the presence of HBeAg (p < 0.001; OR, 95% CI: 0.05, 0.03–0.07) in the adjusted analysis and was not affected by origin (p = 0.65), age (p = 0.12), gender (p = 0.06) or genotype (p = 0.10). Conclusion. HBeAg status and not HBV genotype influenced viral load in this nationwide study. HBeAg positive patients had median HBV-DNA levels 10,000 times higher than those anti-HBe positive across genotypes.

The effect of low-dose supplementation with n-3 polyunsaturated fatty acids on some risk markers of coronary heart disease

Epidemiological data have suggested that a low dose of dietary n-3 polyunsaturated fatty acids from seafood may protect against coronary heart disease. We studied the effect of supplementation with a low dose of very long-chain n-3 fatty acids (0.65 g day-1) on plasma lipids, haemostasis, and neutrophil aggregation. Twenty-four healthy subjects were randomized to supplementation with very long-chain n-3 fatty acids or a control oil for 8 weeks. Laboratory analyses were done twice before and twice at the end of the supplementation period. The supplement with n-3 polyunsaturated fatty acid did not significantly affect plasma lipids or plasma levels of fibrinogen, factor VII, plasminogen activator inhibitor, whole blood aggregation or aggregability of neutrophil leukocytes. Therefore, the potential beneficial effect of very long-chain n-3 fatty acids in coronary heart disease is likely to be mediated through other mechanisms.

HOMOCYSTEINE IN GREENLAND INUITS

Patients with homozygous homocystinuria are at greatly increased risk for development of atherosclerosis and thrombosis (1). Elevated plasma levels of homocysteine (HCY) are caused by reduced enzymatic catabolism or reduced enzymatic remethylation of HCY, due to either hereditary enzyme defects or to nutritional deficiencies of vitamins functioning as cofactors. However, several recent studies have suggested that persons with mildly elevated plasma levels of HCY also are at increased risk for coronary heart disease. (2-4). There are some indications that dietary n-3 polyunsaturated fatty acids (PUFAs) may offer protection against coronary heart disease (5-6). Several mechanisms may be involved, including beneficial effects of n-3 PUFAs on plasma lipids, platelet and leukocyte reactivity, blood pressure and vasoreactivity (7). Interestingly, Olszewski el al. recently found HCY-levels to be lowered 36% in 15 type IIa or IIb hyperlipemic men by n-3 PUFA supplementation. A possible beneficial effect of n-3 PUFA on the incidence of coronary heart disease was initially suggested from studies in Greenland Inuits by our group (8). We therefore investigated plasma levels of homocysteine in a group of traditionally living Greenland Inuits with a diet consisting mainly of marine food and with a very high content of n-3 PUFAs.