Omega-3 fatty acid supplementation and cardiovascular disease

Abstract

Epidemiological studies on Greenland Inuits in the 1970s and subsequent human studies have established an inverse relationship between the ingestion of omega-3 fatty acids [C(20-22) ω 3 polyunsaturated fatty acids (PUFA)], blood levels of C(20-22) ω 3 PUFA, and mortality associated with cardiovascular disease (CVD). C(20-22) ω 3 PUFA have pleiotropic effects on cell function and regulate multiple pathways controlling blood lipids, inflammatory factors, and cellular events in cardiomyocytes and vascular endothelial cells. The hypolipemic, anti-inflammatory, anti-arrhythmic properties of these fatty acids confer cardioprotection. Accordingly, national heart associations and government agencies have recommended increased consumption of fatty fish or ω 3 PUFA supplements to prevent CVD. In addition to fatty fish, sources of ω 3 PUFA are available from plants, algae, and yeast. A key question examined in this review is whether nonfish sources of ω 3 PUFA are as effective as fatty fish-derived C(20-22) ω 3 PUFA at managing risk factors linked to CVD. We focused on ω 3 PUFA metabolism and the capacity of ω 3 PUFA supplements to regulate key cellular events linked to CVD. The outcome of our analysis reveals that nonfish sources of ω 3 PUFA vary in their capacity to regulate blood levels of C(20-22) ω 3 PUFA and CVD risk factors.

Fig. 1.

Structures of dietary ω 3 and ω 6 polyunsaturated fatty acids. A: C₁₈ ω 3 and ω 6 PUFA. B: C_20–22 ω 3 and ω 6 PUFA.

Fig. 2.

Pathways for C₁₈ PUFA conversion to C_20–22 PUFA synthesis. The pathway illustrates the conversion of the essential fatty acid ALA (18:3, ω 3) to the end product DHA (22:6, ω 3). The enzymes involved in this pathway include two fatty acid desaturases (FADS1 and FADS2), two fatty acid elongases (Elovl2 and Elovl5), and peroxisomal β -oxidation (p- β Ox). Nonesterified fatty acids are converted to fatty acyl-CoAs by fatty acyl CoA synthetases; the fatty acids progress through the pathway as fatty acyl CoAs. Humans and rodents ingesting essential fatty acid-sufficient diets accumulate DHA in blood and tissues. Sources of dietary ω 3 PUFA [ALA, SDA (18:4, ω 3), EPA (20:5, ω 3), and DHA] include plants, fish, yeast, and algae. Details of the pathway are presented in the text.

Fig. 3.

Overview of C_20–22 ω 3 PUFA regulation of cell function.

Fig. 4.

Overview of dietary C_18-22 ω 3 PUFA effects on cardiovascular disease.