Jeppe Hagstrup Christensen

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.

Marine n-3 Fatty Acids, Wine Intake, and Heart Rate Variability in Patients Referred for Coronary Angiography

Background —Dietary n-3 polyunsaturated fatty acids (PUFAs) derived from fish may reduce the incidence of sudden cardiac death (SCD). In addition, wine drinking is suggested to have a protective effect against cardiovascular death. Methods and Results —We included 291 patients referred for coronary angiography in whom ischemic heart disease was suspected and all of whom completed a food questionnaire regarding fish and wine intake. The n-3 PUFA composition of granulocyte membranes and of adipose tissue was measured. In addition, 24-hour heart rate variability (HRV) was analyzed. Fish intake was positively associated with the level of n-3 PUFAs in adipose tissue. Significant positive correlation coefficients were found between HRV indices and the levels of n-3 PUFAs in granulocytes. Wine intake was also significantly positively related to HRV, but the patients with the highest wine intake also had the highest intake of fish, as documented by a high n-3 PUFA content in adipose tissue. Multiple linear regression analysis revealed that traditional factors such as treatment with &bgr;-blockers, smoking, age, and previous myocardial infarction were independently related to HRV, and furthermore that n-3 PUFAs (but not wine intake) were significantly independently associated with HRV. Conclusions —The close positive association between n-3 PUFAs and HRV in patients suspected of having ischemic heart disease may indicate a protective effect of n-3 PUFAs against SCD. This may partly explain the reduction in SCD observed in humans with a modest intake of n-3 PUFA. Wine intake was also positively correlated with HRV, but this correlation was no longer significant after controlling for the cellular level of n-3 PUFA.

C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease

The acute-phase reactant C-reactive protein (CRP) has emerged as an independent risk factor for coronary artery disease. Experimental and clinical studies provide evidence of anti-inflammatory effects of n-3 polyunsaturated fatty acids (PUFA) derived from fish. We have studied the effect of marine n-3 PUFA on CRP levels in 269 patients referred for coronary angiography because of clinical suspicion of coronary artery disease. All patients filled out a food questionnaire regarding fish intake. The n-3 PUFA content of granulocyte membranes was determined and the concentration of CRP in serum was measured using a highly sensitive assay. The results were related to angiographic findings. CRP was significantly higher in patients with significant coronary stenoses than in those with no significant angiographic changes (p <0.001), but the CRP levels were not associated with the number of diseased vessels. Subjects with CRP levels in the lower quartile had a significantly higher content of docosahexaenoic acid (DHA) in granulocytes than subjects with CRP levels in the upper quartile (p = 0.02), and in a multivariate linear regression analysis, DHA was independently correlated to CRP (R(2) = 0.179; p = 0.003). The inverse correlation between CRP and DHA may reflect an anti-inflammatory effect of DHA in patients with stable coronary artery disease and suggest a novel mechanism by which fish consumption may decrease the risk of coronary artery disease.

N-3 Fatty Acids as Secondary Prevention against Cardiovascular Events in Patients Who Undergo Chronic Hemodialysis: A Randomized, Placebo-Controlled Intervention Trial

Patients who are treated with chronic hemodialysis (HD) experience premature cardiovascular disease and an increased mortality. N-3 polyunsaturated fatty acids (PUFA) may be effective in the secondary prevention of cardiovascular disease, but the effects of n-3 PUFA has not previously been examined in HD patients. It was hypothesized that secondary prevention with n-3 PUFA would reduce the number of cardiovascular events and death in patients who are treated with chronic HD. A randomized, double-blind, placebo-controlled intervention trial compared the effect of n-3 PUFA and a control treatment as secondary prevention of cardiovascular events in HD patients. The primary outcome was a composite of total cardiovascular events and death. A total of 206 patients were randomly assigned to treatment with n-3 PUFA or control treatment and followed for 2 yr or until reaching a predefined end point. During the trial, 121 (59%) of 206 patients reached a primary end point. N-3 PUFA had no significant effect on the primary composite end point of cardiovascular events and death (62 versus 59; NS). In the n-3 PUFA group, a significant reduction was seen in the number of myocardial infarctions (four versus 13; P = 0.036). This trial was limited by a relatively small number of patients and a large number of withdrawals. However, it is concluded that treatment with n-3 PUFA did not reduce the total number of cardiovascular events and death in this high-risk population. N-3 PUFA significantly reduced the number of myocardial infarctions as a secondary outcome, a finding that might be of clinical interest.

The effect of dietary n-3 fatty acids on serum concentrations of C-reactive protein: a dose-response study.

C-reactive protein (CRP) is a sensitive marker for low-grade inflammation. Long-chain n-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects. The objective of the present study was to investigate the effect on serum levels of CRP of n-3 PUFA at two different doses. We also investigated correlations between CRP and the cellular contents of PUFA. Sixty healthy volunteers (twenty-five women and thirty-five men) were randomly assigned to three treatment groups in a double-blind design. The subjects received a supplement of either 6.6 g n-3 PUFA/d, 2.0 g n-3 PUFA/d or placebo (olive oil) for 12 weeks. CRP was measured using a highly sensitive assay. The median serum CRP concentration was 0.78 mg/l. No significant correlations were found between CRP and the content of n-3 PUFA in granulocytes or platelets. Subjects receiving n-3 PUFA had a significant (P<0.01) increase in the cellular contents of 20 : 5n-3, 22 : 5n-3 and 22 : 6n-3, with the largest increase occurring in the group receiving 6.6 g PUFA/d. A significant (P<0.01) decrease in cellular content of 18 : 2n-6 and 20 : 4n-6 was observed simultaneously. Serum CRP concentrations, however, were unaffected by the PUFA-containing supplements. The present study shows that dietary supplementation with PUFA-containing supplements has no effect on serum concentrations of CRP, measured with a highly sensitive assay, in healthy subjects.

Effects of trans- and n-3 unsaturated fatty acids on cardiovascular risk markers in healthy males. An 8 weeks dietary intervention study.

Background: Studies of long-term intake of industrially produced trans fatty acids (TFA) and n-3 polyunsaturated fatty acids (PUFA) suggest opposite effects on cardiovascular disease risk. Common mechanisms of action are probable.Objective: To examine the effects on cardiovascular risk markers of dietary enrichment with TFA or n-3 PUFA.Design: Randomized, double-blind, parallel intervention trial.Setting: Department of Human Nutrition, The Royal Veterinary and Agricultural University.Subjects: In all, 87 healthy males included, 79 completed.Intervention: Subjects were randomly assigned to 8 weeks of a daily intake of 33 g of experimental fats from either partially hydrogenated soy oil containing 20 g of TFA, 12 g of fish oil with approximately 4 g of n-3 PUFA and 21 g of control fat, or 33 g of control fat. The experimental fats were incorporated into bakery products. Plasma lipids, blood pressure, heart rate variability (HRV), arterial dilatory capacity, compliance, and distensibility were recorded before and after intervention and at follow-up 12 weeks after the intervention.Results: High-density lipoprotein cholesterol (HDL-C) decreased in the TFA group and triglycerides and mean arterial blood pressure decreased in the n-3 PUFA group compared to the control group. HRV, arterial dilatory capacity, compliance, and distensibility were unchanged.Conclusion: The results indicate that the association between coronary heart disease risk and intake of TFA and n-3 PUFA relates only modestly to changes in traditional risk markers.Sponsorship: Danish Medical Research Council (Grant no. 22-01-0390), Center of Advanced Food Research (Copenhagen, Denmark) (Grant no. KVL-R-2001-107), the Danish Heart Association (Grant no. 99-2-3-45-22748), Novozymes (Bagsvaerd, Denmark), Aarhus Olie (Aarhus, Denmark), and from private sources. The experimental fats were provided by Pronova Biocare (Aalesund, Norway) and Aarhus Olie (Aarhus, Denmark).

n-3 fatty acids from fish and coronary artery disease: implications for public health

OBJECTIVE To review and discuss the effect of n-3 polyunsaturated fatty acids (PUFA) from fish in the prevention and, primarily, in the treatment of coronary artery disease (CAD). DESIGN Overview of the literature. SETTING Denmark. RESULTS There is good evidence that fish consumption may reduce the risk of CAD. CONCLUSIONS Fish can be recommended to reduce the risk of CAD both in healthy subjects and in patients with a high risk of CAD or with documented CAD. The use of fish oil concentrates can not be recommended in general, but may be considered in patients after a myocardial infarction or in patients with hypertriglyceridaemia. An increased intake of n-3 polyunsaturated fatty acids from fish may have substantial implications for public health and health economy by decreasing the risk of coronary events and sudden cardiac death.

Soluble adhesion molecules in healthy subjects: a dose-response study using n-3 fatty acids.

BACKGROUND AND AIM Long-chain n-3 polyunsaturated fatty acids (PUFA) may protect against atherosclerotic disease, and serum levels of soluble cellular adhesion molecules (sCAMs) possibly reflect the inflammatory process underlying atherosclerosis. We studied the effect of n-3 PUFA dietary supplementation on the serum levels of sP-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), and the correlation between sCAMs and the fatty acid composition of granulocyte membranes. METHODS AND RESULTS Sixty healthy volunteers were randomly assigned to receive a daily supplement of n-3 PUFA 6.6 g, n-3 PUFA 2.0 g, or olive oil for 12 weeks in a double blind design. A significant negative correlation was found between serum sICAM-1 levels and the DHA content of granulocyte membranes at entry. After supplementation with 6.6 g of n-3 PUFA, there was a significant decrease only in sP-selectin, which a gender subanalysis showed to be more marked in men. Among the women, there was a significant decrease in sICAM-1 in the PUFA 2.0 g group and a significant increase in sVCAM-1 in the PUFA 6.6 g group. CONCLUSIONS The results indicate that high-dose supplementation with n-3 PUFA decreases sP-selectin levels in healthy subjects, thus suggesting a decrease in platelet reactivity or endothelial activation. However, the effect of n-3 PUFA on sCAMs is complex and may depend on gender and n-3 PUFA dose.

The effect of n-3 fatty acids on lipids and lipoproteins in patients treated with chronic haemodialysis: a randomized placebo-controlled intervention study

BACKGROUND Patients with end-stage renal disease (ESRD) have an increased mortality, mainly due to cardiovascular disease (CVD). ESRD is accompanied by several lipid abnormalities, which may be responsible for part of the increased risk of CVD in this population. n-3 polyunsaturated fatty acids (PUFA) lower plasma triglycerides in patients with normal renal function. The aim of the present study was to examine the effect of n-3 PUFA on serum lipid and lipoproteins in patients treated with chronic haemodialysis (HD). METHODS In a double-blind randomized placebo-controlled design, patients with documented CVD, treated with HD for a minimum of 6 months, were randomized to treatment with n-3 PUFA or a control treatment (olive oil). A dietary intake of n-3 PUFA was assessed with a dietary questionnaire. Plasma lipids and lipoproteins and the content of n-3 PUFA in serum phospholipids were measured at baseline and after 3 months. RESULTS Two hundred and six patients were included. Serum phospholipid levels of n-3 PUFA were significantly higher in patients reporting a high fish intake compared to patients reporting a low fish intake. After 3 months, a significant decrease was seen in serum triglycerides in the n-3 PUFA group compared to the control group (P = 0.01). No significant effect was seen on total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, Lp(a) or apoB. CONCLUSION In patients treated with HD, consumption of fish increases levels of n-3 PUFA. Additional supplementation with n-3 PUFA for 3 months further increases levels of n-3 PUFA and lowers serum triglycerides, but does not significantly affect other plasma lipids or lipoproteins.