Dietary flaxseed reduces Myocardial Ischemic Lesions, improves cardiac function and lowers cholesterol levels despite the presence of severe obesity in JCR:LA-cp Rats.

Previous work has shown that dietary flaxseed can significantly reduce cardiac damage from a coronary artery ligation-induced myocardial infarction. However, this model uses healthy animals and the ligation creates the infarct in an artificial manner. The purpose of this study was to determine if dietary flaxseed can protect the hearts of JCR:LA-cp rats, a model of genetic obesity and metabolic syndrome, from naturally occurring myocardial ischemic lesions. Male and female obese rats were randomized into four groups (n = 8 each) to receive, for 12 weeks, either a) control diet (Con), b) control diet supplemented with 10% ground flaxseed (CFlax), c) a high-fat, high sucrose (HFHS) diet, or d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. In male obese rats, serum total cholesterol and LDL-C were significantly lower in CFlax compared to Con.  Obese rats on HFHS exhibited increased myocardial ischemic lesions and diastolic dysfunction regardless of sex. HFlax significantly lowered the frequency of cardiac lesions and improved diastolic function in male and female obese rats compared to HFHS. Blood pressures were similar in obese and lean rats. No aortic atherosclerotic lesions were detectable in any group. Collectively, this study shows that a HFHS diet increased myocardial ischemic lesion frequency and abolished the protective effect of female sex on cardiac function. More importantly, the data demonstrates dietary flaxseed protected against the development of small spontaneous cardiac infarcts despite the ingestion of a HFHS diet and the presence of morbid obesity.

Dietary Flaxseed as a Strategy for Improving Human Health.

Flaxseed is a rich source of the omega-3 fatty acid, alpha linolenic acid, the lignan secoisolariciresinol diglucoside and fiber. These compounds provide bioactivity of value to the health of animals and humans through their anti-inflammatory action, anti-oxidative capacity and lipid modulating properties. The characteristics of ingesting flaxseed or its bioactive components are discussed in this article. The benefits of administering flaxseed or the individual bioactive components on health and disease are also discussed in this review. Specifically, the current evidence on the benefits or limitations of dietary flaxseed in a variety of cardiovascular diseases, cancer, gastro-intestinal health and brain development and function, as well as hormonal status in menopausal women, are comprehensive topics for discussion.

Dietary flaxseed independently lowers circulating cholesterol and lowers it beyond the effects of cholesterol-lowering medications alone in patients with peripheral artery disease.

BACKGROUND: Dietary flaxseed lowers cholesterol in healthy subjects with mild biomarkers of cardiovascular disease (CVD). OBJECTIVE: The aim was to investigate the effects of dietary flaxseed on plasma cholesterol in a patient population with clinically significant CVD and in those administered cholesterol-lowering medications (CLMs), primarily statins. METHODS: This double-blind, randomized, placebo-controlled trial examined the effects of a diet supplemented for 12 mo with foods that contained either 30 g of milled flaxseed [milled flaxseed treatment (FX) group; n = 58] or 30 g of whole wheat [placebo (PL) group; n = 52] in a patient population with peripheral artery disease (PAD). Plasma lipids were measured at 0, 1, 6, and 12 mo. RESULTS: Dietary flaxseed in PAD patients resulted in a 15% reduction in circulating LDL cholesterol as early as 1 mo into the trial (P = 0.05). The concentration in the FX group (2.1 ± 0.10 mmol/L) tended to be less than in the PL group (2.5 ± 0.2 mmol/L) at 6 mo (P = 0.12), but not at 12 mo (P = 0.33). Total cholesterol also tended to be lower in the FX group than in the PL group at 1 mo (11%, P = 0.05) and 6 mo (11%, P = 0.07), but not at 12 mo (P = 0.24). In a subgroup of patients taking flaxseed and CLM (n = 36), LDL-cholesterol concentrations were lowered by 8.5% ± 3.0% compared with baseline after 12 mo. This differed from the PL + CLM subgroup (n = 26), which increased by 3.0% ± 4.4% (P = 0.030) to a final concentration of 2.2 ± 0.1 mmol/L. CONCLUSIONS: Milled flaxseed lowers total and LDL cholesterol in patients with PAD and has additional LDL-cholesterol-lowering capabilities when used in conjunction with CLMs. This trial was registered at clinicaltrials.gov as NCT00781950.

Potent antihypertensive action of dietary flaxseed in hypertensive patients.

Flaxseed contains ω-3 fatty acids, lignans, and fiber that together may provide benefits to patients with cardiovascular disease. Animal work identified that patients with peripheral artery disease may particularly benefit from dietary supplementation with flaxseed. Hypertension is commonly associated with peripheral artery disease. The purpose of the study was to examine the effects of daily ingestion of flaxseed on systolic (SBP) and diastolic blood pressure (DBP) in peripheral artery disease patients. In this prospective, double-blinded, placebo-controlled, randomized trial, patients (110 in total) ingested a variety of foods that contained 30 g of milled flaxseed or placebo each day over 6 months. Plasma levels of the ω-3 fatty acid α-linolenic acid and enterolignans increased 2- to 50-fold in the flaxseed-fed group but did not increase significantly in the placebo group. Patient body weights were not significantly different between the 2 groups at any time. SBP was ≈ 10 mm Hg lower, and DBP was ≈ 7 mm Hg lower in the flaxseed group compared with placebo after 6 months. Patients who entered the trial with a SBP ≥ 140 mm Hg at baseline obtained a significant reduction of 15 mm Hg in SBP and 7 mm Hg in DBP from flaxseed ingestion. The antihypertensive effect was achieved selectively in hypertensive patients. Circulating α-linolenic acid levels correlated with SBP and DBP, and lignan levels correlated with changes in DBP. In summary, flaxseed induced one of the most potent antihypertensive effects achieved by a dietary intervention.

Restoration of cardiomyocyte function in streptozotocin-induced diabetic rats after treatment with vanadate in a tea decoction.

Diabetes mellitus is associated with abnormal cardiomyocyte Ca(2+) transients and contractile performance. We investigated the possibility that an alteration in inositol trisphosphate/phospholipase C (IP3/PLC) signalling may be involved in this dysfunction. Phosphatidic acid stimulates cardiomyocyte contraction through an IP3/PLC signaling cascade. We also tested a novel therapeutic intervention to assess its efficacy in reversing any potential defects. Diabetes was induced in Sprague-Dawley rats by streptozotocin treatment and maintained for an 8 week experimental period. Active cell shortening was significantly depressed in cardiomyocytes obtained from diabetic and insulin-treated diabetic rats in comparison to normal control animals. Perfusion of the cells with phosphatidic acid induced an increase in contraction of control rat cardiomyocytes whereas its effect was inhibitory in cells from streptozotocin-induced diabetic rats. Diabetic rats were also treated orally with vanadate administered in a black tea extract (T/V) for the 8 week period. T/V treatment resulted in a contractile response that was not different from cells of control animals. Furthermore, cardiomyocytes from T/V-treated animals exhibited significantly improved Ca(2+) transients in comparison to diabetic animals and exhibited a normalized response to phosphatidic acid perfusion. It is concluded that a T/V glycemic therapy is capable of preventing the defect in IP3/PLC signaling that occurs in diabetes and can restore normal cardiac contractile function.

Trans-fatty acids in the diet stimulate atherosclerosis.

Epidemiological evidence has associated dietary trans-fatty acids (TFAs) with coronary heart disease. It is assumed that TFAs stimulate atherosclerosis, but this has not been proven. The purpose of this study was to determine the effects of consuming 2 concentrations of TFAs obtained from commercially hydrogenated vegetable shortening on atherosclerotic development in the presence or absence of elevated dietary cholesterol. Low-density lipoprotein receptor-deficient mice were fed 1 of 7 experimental diets for 14 weeks: low regular fat (LR), low trans-fat (LT), regular high fat, high trans-fat (HT), or a diet containing 2% cholesterol with low regular fat (C + LR), low trans-fat (C + LT), or high trans-fat (C + HT). The extent of lesion development was quantified by en face examination of the dissected aortae. Dietary cholesterol supplementation significantly elevated serum cholesterol levels. Surprisingly, this rise was partially attenuated by the addition of TFAs (C + LT and C + HT) in the diet. Serum triglyceride levels were elevated with the higher-fat diets and with the combination of trans-fat and cholesterol. Animals consuming TFAs in the absence of dietary cholesterol developed a significantly greater extent of aortic atherosclerotic lesions as compared with control animals (LT > LR and HT > regular high fat). Atherosclerotic lesions were more extensive after cholesterol feeding, but the addition of TFAs to this atherogenic diet did not advance atherosclerotic development further. In summary, TFAs are atherogenic on their own; but they do not stimulate further effects beyond the strongly atherogenic effects of dietary cholesterol.

Effects of omega-3 polyunsaturated fatty acids on cardiac sarcolemmal Na(+)/H(+) exchange.

Myocardial ischemia-reperfusion activates the Na(+)/H(+) exchanger, which induces arrhythmias, cell damage, and eventually cell death. Inhibition of the exchanger reduces cell damage and lowers the incidence of arrhythmias after ischemia-reperfusion. The omega-3 polyunsaturated fatty acids (PUFAs) are also known to be cardioprotective and antiarrhythmic during ischemia-reperfusion challenge. Some of the action of PUFAs may occur via inhibition of the Na(+)/H(+) exchanger. The purpose of our study was to determine the capacity for selected PUFAs to alter cardiac sarcolemmal (SL) Na(+)/H(+) exchange. Cardiac membranes highly enriched in SL vesicles were exposed to 10-100 microM eicosapentanoic acid (EPA) or docosahexanoic acid (DHA). H(+)-dependent (22)Na(+) uptake was inhibited by 30-50% after treatment with > or =50 microM EPA or > or =25 microM DHA. This was a specific effect of these PUFAs, because 50 microM linoleic acid or linolenic acid had no significant effect on Na(+)/H(+) exchange. The SL vesicles did not exhibit an increase in passive Na(+) efflux after PUFA treatment. In conclusion, EPA and DHA can potently inhibit cardiac SL Na(+)/H(+) exchange at physiologically relevant concentrations. This may explain, in part, their known cardioprotective effects and antiarrhythmic actions during ischemia-reperfusion.