Prostaglandins Other Lipid Mediat., 2017, pii: S1098-8823(17)30048-5. doi: 10.1016/j.prostaglandins.2017.07.005.

Omega-3 polyunsaturated fatty acids improve endothelial function in humans at risk for atherosclerosis: A review.

Zehr, KR. Walker, MK.

Key Findings

Endothelial dysfunction is one of the earliest events in the pathological development of atherosclerotic diseases, and flow-mediated dilation (FMD) is the non-invasive, gold standard for measuring endothelial dysfunction in the clinic.  Evidence from multiple epidemiological, experimental and clinical studies suggests that n-3 PUFAs can decrease the risk of CV disease, in part, by improving vascular function. Three n-3 PUFAs have vasoprotective benefits include decreased arterial plaque buildup, increased anti-inflammatory properties, improved endothelial dependent vasodilation as measured by FMD, decreased blood pressure, and increased antioxidant capacity. The review of published studies reveals that n-3 PUFA supplementation can successfully improve endothelial dysfunction in individuals with risk factors for atherosclerotic CV disease, including hyperlipidemia, cigarette smoking, elevated BMI, and metabolic syndrome. Of the 22 studies, n-3 PUFA supplementation improved endothelial dysfunction in 18 of them. In two studies, diets were enriched in ALA and suggested a low cumulative dose (100–200 g) improved endothelial dysfunction, but did not reduce triglycerides, while a much higher cumulative dose (630 g) improved both outcomes. The mechanisms underlying the improvement of endothelial dysfunction by n-3 PUFA supplementation in human subjects have not been fully elucidated. Studies show that n-3 PUFAs can inhibit endothelial activation, and are anti-inflammatory and antihypertensive. Based on this review of the literature, individuals with traditional risk factors for atherosclerotic CV disease could derive vasoprotective benefits from n-3 PUFA supplementation, particularly from an EPA+DHA formulation resulting in cumulative dose95 g over a minimum of 4 weeks. While results from ALA-enriched diets appear promising, currently the evidence is inadequate to conclude whether formulations containing only ALA, EPA, or DHA have similar benefit as formulations of EPA+DHA.

ABSTRACT:

Epidemiology studies and clinical trials show that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can prevent atherosclerotic morbidity and evidence suggests this may be mediated by improving endothelial dysfunction. Endothelial dysfunction is characterized by reduced vasodilation and a pro-inflammatory, pro-thrombotic state, and is an early pathological event in the development of atherosclerosis. Flow-mediated dilation (FMD), a gold standard for assessing endothelial dysfunction, is a predictor of future cardiovascular events and coronary heart disease risk. Notably, risk factors for endothelial dysfunction include classic risk factors for atherosclerosis: Elevated lipids, diabetes, hypertension, elevated BMI, cigarette smoking, and metabolic syndrome. In this paper, we review the ability of n-3 PUFAs to improve endothelial dysfunction in individuals with classic risk factors for atherosclerosis, but lacking diagnosed atherosclerotic disease, with the goal of identifying those individuals that might gain the most vasoprotection from n-3 PUFA supplements. We include trials using eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or alpha-linolenic acid (ALA) alone, or EPA+DHA; and assessing endothelial function by FMD, forearm blood flow, or peripheral arterial tonometry. We found that n-3 PUFAs improved endothelial dysfunction in 16 of 17 studies in individuals with hyperlipidemia, elevated BMI, metabolic syndrome, or that smoked cigarettes, but only in 2 of 5 studies in diabetics. Further, these trials showed that use of EPA+DHA consistently improve endothelial dysfunction; ALA-enriched diets appear promising; but use of EPA or DHA alone requires further study. We conclude that individuals with hyperlipidemia, elevated BMI, metabolic syndrome, or that smoke could derive vasoprotective benefits from EPA+DHA supplementation.

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