Abstract
Dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been associated with a lower incidence of cardiovascular events and sudden cardiac death. Flaxseed is a rich plant source of n-3 PUFAs and can retard the progression and accelerate the regression of atherosclerotic plaques. The aim of the study was to examine the preventive and therapeutic effects of dietary flaxseed on arrhythmias and heart dysfunction that develops after a myocardial infarction (MI). The left anterior descending coronary artery was ligated in rats to induce the MI. Rats were randomized into five groups: sham MI with normal chow, MI with normal chow, MI with 10% milled flaxseed supplementation (flax), MI with 4.4% supplemented flax oil enriched in alpha-linolenic acid (ALA) and MI with flax lignan secoisolariciresinol diglucoside (SDG) supplementation (0.44%). Animals were fed with their respective diets for 2 weeks before and for 8 weeks after the surgery. Echocardiography and continuous electrocardiographic recordings were obtained after ligation to confirm the induction of the MI, to check for arrhythmias and to assess cardiac function. Histological examination was also performed to evaluate cardiac fibrosis. Dietary supplementation with flaxseed, ALA or SDG before and after the induction of the MI significantly reduced the incidence of arrhythmias and resulted in significantly smaller infarct size, less left ventricle dilation, and decreased myocardial fibrosis and tumor necrosis factor-α levels compared to the control MI group. Together, this study supports a beneficial effect of dietary flaxseed in patients for the prevention and treatment of arrhythmias and ventricular remodeling post-MI.
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Key Points
This study extends the role of flaxseed and its beneficial cardiovascular effects. The FLAX-PAD trial, a 1-year randomized controlled trial, demonstrated a significant reduction of 10mm Hg systolic blood pressure and 7 mmHg diastolic blood pressure in peripheral artery disease patients with elevated blood pressure. In LDL receptor knockout mice, flaxseed suppressed atherosclerotic plaque formation and was found to be effective in regression of established plaques. Flaxseed supplementation has also reduced the incidence of ventricular arrhythmias in hearts challenged by ischemia–reperfusion (I/R) ex vivo. ALA found within flaxseed reduces apoptosis in cardiomyocytes during I/R insult. Flaxseed also regulates glucose levels, thereby exerting a hypoglycemic effect in diabetes. In this study, the authors hypothesized that in an animal model of myocardial infarction (MI) induced by coronary artery ligation (CAL), supplementation of the diet with flaxseed or its components before and after an MI may reduce the incidence of cardiac arrhythmias, prevent extensive fibrosis after the infarction, and improve cardiac structure and function post-MI.
The data demonstrated that dietary flaxseed given to animals before and after an MI (a) reduced the incidence of arrhythmias, (b) limited the size of the chamber, (d) exerted an anti-inflammatory effect and (e) reduced cardiac fibrosis. Dietary flaxseed and, in particular, flax oil demonstrated a significant antiarrhythmic action in vivo. The mechanism responsible for the effects of dietary flaxseed on the heart post-MI, therefore, likely involves, directly or indirectly, ALA. Dietary supplementation of flaxseed and flax oil enriched in ALA in this study increased the plasma levels of both ALA and EPA, clear evidence that ALA is metabolized in rats to the longer-chain polyunsaturated fatty acid EPA but not to DHA.
The process by which the dietary flaxseed decreased the size of the infarct in the present study may involve a multifactorial mechanism. ALA has been shown to decrease the production of reactive oxygen species, up-regulate the expression of antiapoptotic proteins in the myocardium and inhibit the activity of angiotensin-converting enzyme. SDG has also been reported to reduce infarct size and improve cardiac contractility. Taken together, the present results support dietary flaxseed as a prophylaxis for cardiovascular disease. Dietary flaxseed and/or its bioactive ingredients reduce the occurrence of arrhythmias, limit infarct size, attenuate left ventricular dilation and decrease cardiac fibrosis after an MI. These data further support the consumption of omega-3 fatty acids from marine and plant sources as an approach to reduce the risk of coronary artery disease and sudden cardiac death. It is important to recognize that the present results demonstrate the impact of this dietary intervention which was carried out before and after the induction of the MI. The effects of a dietary treatment induced solely after an MI will need further investigation. The results presented here represent a template to further investigate the efficacy of using flaxseed as a dietary supplement in patients who have already had an MI as well as to encourage the use of flaxseed as a preventative measure before an MI occurs.