This meta-analysis investigates the effects of dietary and nondietary (i.e. supplemental) intake of n-3 polyunsaturated fatty acids on coronary heart disease.

Bottom line
This paper finds that n-3 polyunsaturated fatty acids reduce the risk of mortality due to myocardial reinfarction, sudden death and overall mortality in patients with coronary heart disease.

Reference
HC Bucher et al. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. American Journal of Medicine 2002 112: 298-304.
Search
The literature was searched using several databases (e.g. MEDLINE, Embase) for randomised controlled trials, published in all languages from 1966 to 1999. The Cochrane Library and references of identified papers were also examined. To be included, trials had to have compared dietary or supplemental intake of n-3 polyunsaturated fatty acids with a control diet or placebo in patients with coronary heart disease and followed them for at least six months.

Eleven trials met these criteria: two using dietary intervention and nine using supplementation. There were a total of 7,951 patients in the intervention groups (range 31 to 5,666) and 7,855 patients in the control groups (range 28 to 5,658). The mean age was 49 to 66 years; between 33% and 100% had a previous myocardial infarction; and the average follow-up lasted 20 months (range 6 to 46 months). 

Results
In patients with coronary heart disease, diets enriched with n-3 polyunsaturated fatty acids:

had no effect on nonfatal myocardial infarction (risk ratio 0.8, 95% confidence interval 0.5 to 1.2); 

reduced the risk of fatal myocardial infarction (risk ratio 0.7, 95% confidence interval 0.6 to 0.8); 

reduced the risk of sudden death (risk ratio 0.7, 95% confidence interval 0.6 to 0.9; 5 trials); 

reduced the risk of overall mortality (risk ratio 0.8, 95% confidence interval 0.7 to 0.9; 9 trials). 
Comment
The strength of this meta-analysis is that it only included randomised controlled trials, but unfortunately it has the usual limitations, e.g. small sample sizes (there were 300 or fewer participants in nine of the trials) and the amount and type of n-3 polyunsaturated fatty acid varied considerably. It is therefore difficult to infer anything beyond the observed associations, e.g. the size of the risk reductions; the amount of n-3 fatty acids required to achieve them; or the differences (if any) between dietary and supplemental n-3 polyunsaturated fatty acids.

However, the current UK recommendation is to eat one to two portions of oil-rich fish per week. A separate recommendation of a weekly intake of 1.5 g (i.e. one small serving) of eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) has also been made. (The trials in this analysis used supplements of EPA and DHA, with doses varying from 0.3 to 6.0 g and 0.6 to 3.7 g respectively.)

The protective effect of n-3 polyunsaturated fatty acids has been attributed to EPA and DHA, which are present in fish oil and the flesh of oil-rich fish (e.g. mackerel, salmon, kippers, herring), and alpha-linolenic acid, the richest sources of which are seed oils (e.g. rapeseed and soya) and nuts (e.g. walnuts). For those who do not like or do not eat fish, supplements containing n-3 fatty acids are an option, although it is better to obtain them through dietary sources.
Healthy Hearts 
According to an article in the November 1, 1995, issue of The Journal of the American Medical Association (Vol. 274, No. 17), one serving of fatty-fish per week, such as salmon, can reduce the risk of cardiac arrest by 50-70 percent.

David S. Siscovick, M.D., M.P.H., from the University of Washington in Seattle, and colleagues assessed the cardiac benefits of a type of polyunsaturated fatty acid (long-chain n-3) found primarily in seafood. The study involved a total of 827 subjects aged 24-74 years: 334 case patients with primary cardiac arrest attended by paramedics from 1988-1994; and 493 population-based controls matched for age and sex.

Based on a survey of food intake, the researchers found: "An intake of 5.5 grams of n-3 fatty acids per month was associated with 50 percent reduction in the risk of primary cardiac arrest."

An 84 gram (three ounce) serving of cooked fresh salmon (a fatty fish) contains 1.49 grams of n-3 fatty acids. Four servings of salmon per month would provide 5.96 grams of n-3 fatty acids, enough to reap the cardiac benefits, according to the study. One serving of albacore tuna contains 0.74 grams of n-3 fatty acids and cod contains 0.23 grams of n-3 fatty acids.

A second approach was used to confirm the findings, the researchers reported. In addition to direct dietary intake of n-3 fatty acids, the researchers also assessed the benefits of n-3 fatty acids by using a biomarker (measuring the level of fatty acids in the blood). Other research cited in the study shows that consumption of n-3 fatty acids increases the levels of these fatty acids in blood cell membranes and may reduce the clumping of blood platlets and also coronary spasm.

The researchers found that small increases in the percentage of n-3 fatty acids in the total fatty-acid level could substantially lower the risk of heart attack. They write: "Compared with a red blood cell membrane n-3 polyunsaturated fatty acid level of 3.3 percent of total fatty acids, a red blood cell n-3 polyunsaturated fatty acid level of 4.3 percent of total fatty acids was associated with a 50 percent reduction in the risk of primary cardiac arrest, and a level of 5.0 percent of total fatty acids was associated with a 70 percent reduction."

The authors write: "Our findings suggest an inverse relation of both dietary intake and red blood cell membrane levels of n-3 polyunsaturated fatty acids with the risk of primary cardiac arrest. . . The consistency of the findings using two different approaches to the measurement of n-3 polyunsaturated fatty acid intake from seafood -- a food frequency questionaire and a biomarker -- enhances considerably the validity of our findings."

They conclude: "Taken together, the data suggest that when compared to no seafood intake, dietary intake of modest amounts of n-3 fatty acids from seafood may reduce vulnerability to ventricular fibrillation and, thereby, reduce the risk of coronary heart disease mortality. Additional clinical trials to assess the effectiveness of efforts to enhance dietary intake of n-3 polyunsaturated fatty acids for the prevention of primary cardiac arrest should be considered."

Abstract:
Moderate physical training induced a decrease in arterial blood pressure in fish oil-fed rats as compared to sunflower seed oil-fed rats [14]. The purpose of this study was to determine if these changes were due to modifications of the left ventricular function of the heart. Forty rats were fed a semi-purified diet containing either 10% sunflower seed oil or 10% fish oil (EPAX 3000TG, Pronova). Each dietary group was assigned to two sub-groups, one being constituted by sedentary animals and the other by trained animals. Training was achieved by daily running for 60 minutes at moderate intensity for three weeks. At the end of the training period, the animals were sacrificed and their hearts were immediately perfused according to the working mode. The phospholipid fatty acid composition and parameters of the left ventricular function were determined. Feeding fish oil markedly reduced the proportion of n-6 polyunsaturated fatty acids (PUFA, 18:2 n-6, 20:4 n-6, 22:4 n-6 and 22:5 n-6) in cardiac phospholipids. The n-6 PUFA were replaced by n-3 PUFA (mainly docosahexaenoic acid). In sedentary animals, the fluid dynamic (aortic and coronary flow, cardiac output) was not modified by the diet. The heart rate was reduced (-10%) in n-3 PUFA-rich hearts. Physical training did not markedly alter the polyunsaturated fatty acid profile of cardiac phospholipids. Conversely, it reduced the heart rate, aortic flow and cardiac output (-11, -21 and , respectively) at a similar extent in the two dietary groups. In a second set of experiments, the training period was repeated in animals fed a commercially available diet (A103, UAR) which simultaneously provided n-6 and n-3 fatty acids. In these dietary conditions, neither the aortic flow nor the heart rate was decreased by physical exercise. These results suggest that both n-6 and n-3 PUFA in the diet are necessary to ensure a good cardiac adaptation to moderate physical training. Furthermore, the fish oil-induced decrease in arterial blood pressure in trained animals was not related to changes in cardiac contractility, but to a decrease in vascular resistances. Moderate physical training + dietary n-3 PUFA might be used to prevent hypertension and cardiovascular diseases. 


Keywords: dietary polyunsaturated fatty acids / moderate physical training / cardiac function