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Epidemiological evidence has associated dietary trans fatty acids (TFA) with heart disease. TFA are primarily from hydrogenated fats rich in elaidic acid, but dairy products also contain naturally occurring TFA such as vaccenic acid. Our purpose in this study was to compare the effects of consuming a commercially hydrogenated vegetable shortening rich in elaidic TFA (18:1t9) or a butter rich in vaccenic TFA (18:1t11) in the absence and presence of dietary cholesterol on atherosclerosis. LDL receptor deficient (LDLr(-/-)) mice were fed 1 of 8 experimental diets for 14 wk with the fat content replaced by: regular (pork/soy) fat (RG), elaidic shortening (ES), regular butter (RB), vaccenic butter (VB), or an atherogenic diet containing 2% cholesterol with RG (CH+RG), ES (CH+ES), RB (CH+RB), or VB (CH+VB). Serum cholesterol levels were elevated with cholesterol feeding (P < 0.001), whereas serum triglyceride levels were higher only in the CH+RB (P < 0.001) and CH+VB (P < 0.001) groups compared with the other 6 groups. Serum cholesterol and triglyceride levels were significantly lower in the CH+VB group than in the CH+RB group (P < 0.001). Atherosclerosis was stimulated by dietary ES compared with RG (P = 0.021), but CH+ES did not stimulate atherosclerosis beyond CH+RG alone. In contrast, VB did not induce an increase in atherosclerotic plaque formation compared with the RG and RB diets and the CH+VB diet reduced atherosclerosis compared with the other diets containing cholesterol (P < 0.01). In summary, consuming a hydrogenated elaidic acid-rich diet stimulates atherosclerosis, whereas a vaccenic acid-rich butter protects against atherosclerosis in this animal model. [ABSTRACT FROM AUTHOR]

Background: Although the combination of doxorubicin (DOX) and trastuzumab (TRZ) reduces the progression and recurrence of breast cancer, these anticancer drugs are associated with significant cardiotoxic side effects., Objective: We investigated whether prophylactic administration of flaxseed (FLX) and its bioactive components, α-linolenic acid (ALA) and secoisolariciresinol diglucoside (SDG), would be cardioprotective against DOX + TRZ-mediated cardiotoxicity in a chronic in vivo female murine model., Methods: Wild-type C57BL/6 female mice (10-12 wk old) received daily prophylactic treatment with one of the following diets: 1) regular control (RC) semi-purified diet; 2) 10% FLX diet; 3) 4.4% ALA diet; or 4) 0.44% SDG diet for a total of 6 wks. Within each arm, mice received 3 weekly injections of 0.9% saline or a combination of DOX [8 mg/(kg.wk)] and TRZ [3 mg/(kg.wk)] starting at the end of week 3. The main outcome was to evaluate the effects of FLX, ALA, and SDG on cardiovascular remodeling and markers of apoptosis, inflammation, and mitochondrial dysfunction. Significance between measurements was determined using a 4 (diet) × 2 (chemotherapy) × 2 (time) mixed factorial design with repeated measures., Results: In the RC + DOX + TRZ-treated mice at week 6 of the study, the left ventricular ejection fraction (LVEF) decreased by 50% compared with the baseline LVEF (P < 0.05). However, the prophylactic administration of the FLX, ALA, or SDG diet was partially cardioprotective, with mice in these treatment groups showing an ∼68% increase in LVEF compared with the RC + DOX + TRZ-treated group at week 6 (P < 0.05). Although markers of inflammation (nuclear transcription factor κB), apoptosis [poly (ADP-ribose) polymerase-1 and the ratio of BCL2-associated X protein to B-cell lymphoma-extra large], and mitochondrial dysfunction (BCL2-interacting protein 3) were significantly elevated by approximately 2-fold following treatment with RC + DOX + TRZ compared with treatment with RC + saline at week 6, prophylactic administration of FLX, ALA, or SDG partially downregulated these signaling pathways., Conclusion: In a chronic in vivo female C57BL/6 mouse model of DOX + TRZ-mediated cardiotoxicity, FLX, ALA, and SDG were partially cardioprotective., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

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., (© 2015 American Society for Nutrition.)

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the (n-3) PUFA found in fish oils, exert antiarrhythmic effects during ischemia. Flaxseed is the richest plant source of another (n-3) PUFA, alpha-linolenic acid (ALA), yet its effects remain largely unknown. Our objective was to determine whether a flaxseed-rich diet is antiarrhythmic in normal and hypercholesterolemic rabbits. Male New Zealand White (NZW) rabbits (n = 14-16) were fed as follows: regular diet (REG group); diet containing 10% flaxseed (FLX group); 0.5% cholesterol (CHL group); or 0.5% cholesterol + 10% flaxseed (CHL/FLX group) for up to 16 wk. Plasma cholesterol was significantly elevated in the CHL and CHL/FLX groups. Plasma triglycerides were unchanged. ALA levels increased significantly in plasma and hearts of the FLX and CHL/FLX groups. After the feeding period, rabbit hearts were isolated and subjected to global ischemia (30 min) and reperfusion (45 min). Ventricular fibrillation (VF) occurred during ischemia in 33% of REG but in none of FLX hearts, and 28% of CHL but only 6% of CHL/FLX hearts. VF incidence during reperfusion was 28% and 26% in REG and FLX hearts, respectively. The incidence significantly increased to 64% in CHL hearts, and was significantly attenuated (18%) in CHL/FLX hearts. CHL markedly prolonged the QT interval, whereas FLX significantly shortened the QT interval and reduced arrhythmias in the FLX and CHL/FLX hearts. In vitro application of (n-3) PUFA shortened the action potential duration, an effect consistent with the QT data. This study demonstrates that dietary flaxseed exerts antiarrhythmic effects during ischemia-reperfusion in rabbit hearts, possibly through shortening of the action potential.