Discerning Whether and How Long-Chain, n -3 Fatty Acids Lower Blood Pressure: A Comment on Skulas-Ray et al.
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INVITED COMMENTARY
Discerning Whether and How Long-Chain, n-3 Fatty Acids Lower Blood Pressure: A Comment on Skulas-Ray et al. Matthew F. Muldoon, M.D, M.P.H
Published online: 24 August 2012 # The Society of Behavioral Medicine 2012
A plethora of epidemiologic evidence links consumption of fish and n-3 fatty acids with reduced morbidity and mortality from atherosclerotic cardiovascular disease [1]. What is not at all clear is how such benefits accrue, how long diet must be changed, and what quantity of n-3 fatty acids confers disease protection. An important, randomized clinical trial recently found no reduction in major cardiovascular events from a margarine providing the relatively low dose of 400 mg daily of n-3 fatty acids for 40 months [2]. In the current issue, Skulas-Ray and colleagues report a clinical experiment examining the dose–response relationship between n-3 fatty acid supplementation and BP at rest and during acute mental stress [3]. BP was reduced comparably at rest and during stress by 3,400 mg/day for 8 weeks, whereas the lower dose of 850 mg had no effect. BP reduction was proportional to the increase in circulating n-3 fatty acids, corroborating the existence of a presumably linear, dose–response relationship. The authors further report a robust reduction in stroke volume, which in conjunction with a reduced heart rate (found in prior studies), yields a notable decline in resting cardiac output. Several caveats about the study design warrant mention. Subjects were normotensive, and the BP reduction of about 2 mmHg from high-dose supplementation may be larger in persons with high-normal or hypertensive BP. The duration of 8 weeks may be insufficient to fully characterize the effects of a diet change since tissue levels may require more than 4 months to plateau [4]. Finally, the use of a cross-over design has efficiencies at the cost of susceptibility to carry-over effects. The latter two issues could have conspired to produce null findings for the low dose but would not have biased the findings. M. F. Muldoon (*) Heart and Vascular Institute, University of Pittsburgh School Medicine, Pittsburgh, PA, USA e-mail: [email protected]
In the context of extant literatures, Skulas-Ray's study indicates that BP declines with n-3 consumption in normotensives, extending the relatively robust evidence for such effects in persons with hypertension [5]. This suggests a role for fish and n-3 intake in hypertension prevention [6]. The manner in which BP falls could involve cardiovascular autonomic control or direct effects on the heart and vasculature. Research on n-3 fatty acids and heart rate variability, an index of cardiac autonomic control, is rather mixed, perhaps due to effect modification by concurrent health behaviors, such as exercise [7]. The current findings of reduced heart rate, stroke volume, and cardiac output, and lengthened pre-ejection period, all point to modulation of cardiac autonomic control. This collection of alterations in cardiovascular function at rest begs the question of how n-3 fat
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