A new review1 published in the journal Nutrients examined whether the combination of omega-3 polyunsaturated fatty acids and a statin drug has a beneficial or negative interaction for cardiovascular health. While both statins and omega-3 polyunsaturated fatty acids possess heart-health benefits, including decreasing LDL cholesterol and triglycerides, respectively, the effects of concomitant use of statins and omega-3s are not well understood. Ultimately, the review found that the combination of omega-3s and statins for heart health can sometimes be complementary, but can also be antagonistic. The authors note that further intervention studies are needed to explore the interaction.
Statins, which are classified as anti-dyslipidemic drugs, have been shown to potentially reduce the instances of cardiovascular disease and mortality by reducing LDL cholesterol. Dyslipidemia is an abnormal amount of lipids, including triglycerides, cholesterol, and fat phospholipids in the blood.
Omega-3 polyunsaturated fatty acids, meanwhile, may help to reduce triglycerides, although the authors note that “the mechanisms of action are not completely understood; however, it is thought that a combination of reduced triglyceride synthesis and increased oxidation of triglycerides induced by [omega-3 long-chain polyunsaturated fatty acids] act to lower circulating triglyceride concentrations.”
The authors also note that omega-3 and statins have a few overlapping commonalities. These include their ability to enhance endothelial nitric oxide synthesis, inhibit the production of pro-inflammatory cytokines, and lower of LDL cholesterol by repressing active and mRNA expression of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA) enzyme. Thus, in this review, the authors sought to examine the complementary or competing effects of combined use of statins and omega-3s.
The authors cite clinical studies which investigated the effect of various statins with omega-3 long-chain polyunsaturated fatty acids on cardiovascular risk factors in patients with elevated cholesterol and triglycerides. In those studies, the combination of omega-3s and statins decreased patients’ triglycerides, total cholesterol, and thrombotic potential compared to statin-only. The authors concluded that, in general, concomitant therapy with statin medication and omega-3 polyunsaturated fatty acids is complementary. In addition to the combination’s potential for lowering triglycerides and LDL cholesterol, it may also lower LDL cholesterol particle size, which results in a more favorable lipoprotein distribution.
On the other hand, existing data also indicates that there may be antagonistic effects of concomitant use of statins and omega-3s. First, statins and omega-3 fatty acids interact to modulate fatty acid synthesis and metabolism. However, “pleiotropic effects of statins and [omega-3 long-chain polyunsaturated fatty acids] overlap,” the authors write. “For example, cytochrome P450 enzymes that metabolize statins may affect omega-3 long chain polyunsaturated fatty acid metabolism and vice versa.” Statins may also alter the balance of omega-3 and omega-6 fatty acids, which could increase pro-inflammatory eicosanoids and contribute to atherosclerosis.
Further, statins may cause a mitochondrial ubiquinone deficiency, which blocks the ability of omega-3 fatty acids to precondition myocytes, or muscle cells. This reduces their effectiveness in reducing cardiac arrhythmias.
Finally, while both statins and omega-3 fatty acids block HMG-CoA reductase, omega-3 fatty acids block HMG-CoA reductase albeit less effectively, which results in a smaller effect size for the combination.
Both omega-3 polyunsaturated fatty acids and statins are recommended for prevention of cardiovascular diseases, the authors conclude, although each nutrient has a distinct mode of action. And, while there are overlapping characteristics in the heart-health effects of omega-3 fatty acids and statins, “prospective intervention studies that stratify for statin use are warranted to explore the interaction further.”
1. Bird JK et al., “The role of n-3 long chain polyunsaturated fatty acids in cardiovascular disease prevention, and interactions with statins,” Nutrients, vol. 10, no. 6 (June 15, 2018): 775