Fish and Omega-3 Fatty Acids: Sex and Racial Differences in Cardiovascular Outcomes and Cognitive Function.

Both cardiovascular disease (CVD) and cognitive decline are common features of aging. One in 5 deaths is cardiac for both men and women in the United States, and an estimated 50 million are currently living with dementia worldwide. In this review, we summarize sex and racial differences in the role of fish and its very long chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in preventing CVD events and cognitive decline. In prospective studies, women with higher nonfried and fatty fish intake and women and Black individuals with higher plasma levels of EPA and DHA had a lower risk of CVD. In randomized controlled trials of EPA and DHA supplementation in primary CVD prevention, Black subjects benefited in a secondary outcome. In secondary CVD prevention, both men and women benefited, and Asians benefited as a prespecified subgroup. Fish and omega-3 polyunsaturated fatty acids are associated with prevention of cognitive decline in prospective studies. In randomized controlled trials of EPA and DHA supplementation, women have cognitive benefit. DHA seems more beneficial than EPA, and supplementation is more beneficial when started before cognitive decline. Although studies in women and racial groups are limited, life-long intake of nonfried and fatty fish lowers the risk of CVD and cognitive decline, and randomized controlled trials also show the benefit of EPA and DHA supplementation. These findings should be factored into recommendations for future research and clinical recommendations as dietary modalities could be cost-effective for disease prevention.

Dietary Oxidized Linoleic Acids Modulate Fatty Acids in Mice.

Objective: An elevated concentration of oxidized lipids along with the abnormal accumulation of lipids has been linked to the formation of atheromatous plaque and the development of cardiovascular diseases. This study aims to investigate if consumption of different concentrations of dietary oxidized linoleic acid alters the distribution of long chain fatty acids (LCFAs) within the liver relative to plasma in mice. Methods: C57BL/6 male mice (n = 40) were divided into 4 groups: Standard chow as plain control (P group, n =10), Chow supplemented with linoleic acid 9 mg/mouse/day, linoleic control (C group, n=0), oxidized linoleic acid; 9 mg/mouse/day (A group, n=10) and oxidized linoleic acid 18 mg/mouse/day diet (B group, n=10). Liver and plasma samples were extracted, trans-esterified and subsequently analyzed using gas chromatography mass spectrometry (GC-MS) for LCFAs; palmitic acid, stearic acid, oleic acid, linoleic acid and arachidonic acid. Results: LCFA methyl esters were eluted and identified based on their respective physiochemical characteristics of GCMS assay with inter assay coefficient of variation percentage (CV%, 1.81-5.28%), limits of quantification and limit of detection values (2.021-11.402 mg/mL and 1.016-4.430 mg/mL) respectively. Correlation analysis of liver and plasma lipids of the mice groups yielded coefficients (r=0.96, 0.6, 0.8 and 0.33) with fatty acid percentage total of (16%, 10%, 16% and 58%) for the P, C, A and B groups respectively. Conclusion: The sustained consumption of a diet rich in oxidized linoleic acid disrupted fatty acid metabolism. The intake also resulted in elevated concentration of LCFAs that are precursors of bioactive metabolite molecule.

Polyphenolic Compounds and Gut Microbiome in Cardiovascular Diseases.

The onset of Cardiovascular Disease (CVD) is known to be associated with multiple risk factors related to exogenous exposures on predisposed genetic makeup. Diet and lifestyle have a cascade effect on microbiota biodiversity, thus impacting inflammation and heart health. Atherosclerosis is a type of CVD where chronic inflammation contributes to plaque buildup in the arteries resulting in narrowed blood vessels, which obstruct blood flow. Polyphenolic compounds, including flavonoids, most commonly consumed in the form of plants, have been identified to have various mechanisms of action to reduce the inflammatory response in the body. Flavonoids provide a variety of nutraceutical functions including antioxidant, antimicrobial, anti-inflammatory, antiangiogenic, antitumor, and improved pharmacokinetic properties. Therefore, the medicinal use of polyphenolic compounds as an intervention for the inflammatory response, especially relating to the gut microbiome, may significantly reduce the risk of atherosclerotic plaque development and disease onset. This review addresses the role of polyphenolic compounds and gut microbiome in cardiovascular disease. Research studies conducted in cells and animals were reviewed. These studies clearly illustrate that dietary polyphenolic compounds influence resident gut microbiota thus they are associated with the prevention of atherosclerosis progression. Further research in this field is warranted to identify potential gut microbiome mediated therapeutic approaches for CVD.

Anti-atherosclerotic actions of azelaic acid, an end product of linoleic acid peroxidation, in mice.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease associated with the accumulation of oxidized lipids in arterial lesions. Recently we studied the degradation of peroxidized linoleic acid and suggested that oxidation is an essential process that results in the generation of terminal products, namely mono- and dicarboxylic acids that may lack the pro-atherogenic effects of peroxidized lipids. In continuation of that study, we tested the effects of azelaic acid (AzA), one of the end products of linoleic acid peroxidation, on the development of atherosclerosis using low density lipoprotein receptor knockout (LDLr(-/-)) mice. METHODS AND RESULTS: LDLr(-/-) mice were fed with a high fat and high cholesterol Western diet (WD group). Another group of animals were fed the same diet with AzA supplementation (WD+AzA group). After 4 months of feeding, mice were sacrificed and atherosclerotic lesions were measured. The results showed that the average lesion area in WD+AzA group was 38% (p<0.001) less as compared to WD group. The athero-protective effect of AzA was not related to changes in plasma lipid content. AzA supplementation decreased the level of CD68 macrophage marker by 34% (p<0.05). CONCLUSIONS: The finding that AzA exhibits an anti-atherogenic effect suggests that oxidation of lipid peroxidation-derived aldehydes into carboxylic acids could be an important step in the body's defense against oxidative damage.

Dietary oxidized linoleic acid lowers triglycerides via APOA5/APOClll dependent mechanisms.

Previously we have shown that intestinal cells efficiently take up oxidized fatty acids (OxFAs) and that atherosclerosis is increased when animals are fed a high cholesterol diet in the presence of oxidized linoleic acid. Interestingly, we found that in the absence of dietary cholesterol, the oxidized fatty acid fed low-density lipoprotein (LDL) receptor negative mice appeared to have lower plasma triglyceride (TG) levels as compared to animals fed oleic acid. In the present study, we fed C57BL6 mice a normal mice diet supplemented with oleic acid or oxidized linoleic acid (at 18 mg/animal/day) for 2 weeks. After the mice were sacrificed, we measured the plasma lipids and collected livers for the isolation of RNA. The results showed that while there were no significant changes in the levels of total cholesterol and high-density lipoprotein cholesterol (HDLc), there was a significant decrease (41.14%) in the levels of plasma TG in the mice that were fed oxidized fatty acids. The decreases in plasma TG levels were accompanied by significant increases (P<0.001) in the expressions of APOA5 and acetyl-CoA oxidase genes as well as a significant (P<0.04) decrease in APOClll gene expression. Oxidized lipids have been suggested to be ligands for peroxisome proliferator-activated receptor (PPAR*). However, there were no increases in the mRNA or protein levels of PPAR* in the oxidized linoleic acid fed animals. These results suggest that oxidized fatty acids may act through an APOA5/APOClll mechanism that contributes to lowering of TG levels other than PPAR* induction.