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.

Abstract-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.

Myocardial ischemia/reperfusion (I/R) injury increases the generation of oxidized phosphatidylcholines (OxPCs) which results in cell death. However, the mechanism by which OxPCs mediate cell death is largely unknown. The aim of this study was to determine the mechanisms by which OxPC triggers cardiomyocyte cell death during reperfusion injury. Cardiomyocyte viability, bioenergetic response and calcium transients were determined in the presence of OxPCs. Fragmented OxPCs resulted in a decrease in cell viability with POVPC and PONPC having the most potent cardiotoxic effect in both a concentration and time dependent manner (P<0.05). POVPC and PONPC also caused a significant decrease in Ca2+ transients and net contraction in isolated cardiomyocytes compared to vehicle treated control cells (P<0.05). PONPC depressed maximal respiration rate (p<0.01; 54%) and spare respiratory capacity (p<0.01; 54.5%). Notably, neither caspase 3 activation or TUNEL staining was observed in cells treated with either POVPC or PONPC. Further, cardiac myocytes treated with OxPCs were indistinguishable from vehicle treated control cells with respect to nuclear HMGB1 activity. Glutathione peroxidase 4 activity was markedly suppressed in cardiomyocytes treated with POVPC and PONPC. Importantly, cell death induced by OxPCs could be suppressed E06 Ab, directed against OxPCs or by ferrostatin. The findings of the present study suggest that OxPCs disrupt mitochondrial bioenergetics, calcium transients and provoke wide spread cell death through ferroptosis during I/R. Neutralization of OxPC with E06 or with ferrostatin-1 prevents cell death during reperfusion. Our study demonstrates a novel signaling pathway that operationally links generation of OxPC during cardiac I/R to ferroptosis.