The Physiological Effect of n-3 Polyunsaturated Fatty Acids (n-3 PUFAs) Intake and Exercise on Hemorheology, Microvascular Function, and Physical Performance in Health and Cardiovascular Diseases; Is There an Interaction of Exercise and Dietary n-3 PUFA Intake?

Marko Stupin, Aleksandar Kibel, Ana Stupin, Kristina Selthofer-Relatić, Anita Matić, Martina Mihalj, Zrinka Mihaljević, Ivana Jukić, Ines Drenjančević, Marko Stupin, Aleksandar Kibel, Ana Stupin, Kristina Selthofer-Relatić, Anita Matić, Martina Mihalj, Zrinka Mihaljević, Ivana Jukić, Ines Drenjančević

Abstract

Physical activity has a beneficial effect on systemic hemodynamics, physical strength, and cardiac function in cardiovascular (CV) patients. Potential beneficial effects of dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs), such as α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid on hemorheology, vascular function, inflammation and potential to improve physical performance as well as other CV parameters are currently investigated. Recent meta-analysis suggests no effect of n-3 PUFA supplementation on CV function and outcomes of CV diseases. On the other hand, some studies support beneficial effects of n-3 PUFAs dietary intake on CV and muscular system, as well as on immune responses in healthy and in CV patients. Furthermore, the interaction of exercise and dietary n-3 PUFA intake is understudied. Supplementation of n-3 PUFAs has been shown to have antithrombotic effects (by decreasing blood viscosity, decreasing coagulation factor and PAI-1 levels and platelet aggregation/reactivity, enhancing fibrinolysis, but without effects on erythrocyte deformability). They decrease inflammation by decreasing IL-6, MCP-1, TNFα and hsCRP levels, expression of endothelial cell adhesion molecules and significantly affect blood composition of fatty acids. Treatment with n-3 PUFAs enhances brachial artery blood flow and conductance during exercise and enhances microvascular post-occlusive hyperemic response in healthy humans, however, the effects are unknown in cardiovascular patients. Supplementation of n-3 PUFAs may improve anaerobic endurance and may modulate oxygen consumption during intense exercise, may increase metabolic capacity, enhance endurance capacity delaying the onset of fatigue, and improving muscle hypertrophy and neuromuscular function in humans and animal models. In addition, n-3 PUFAs have anti-inflammatory and anti-nociceptive effects and may attenuate delayed-onset muscle soreness and muscle stiffness, and preserve joint mobility. On the other hand, effects of n-3 PUFAs were variably observed in men and women and they vary depending on dietary protocol, type of supplementation and type of sports activity undertaken, both in healthy and cardiovascular patients. In this review we will discuss the physiological effects of n-3 PUFA intake and exercise on hemorheology, microvascular function, immunomodulation and inflammation and physical performance in healthy persons and in cardiovascular diseases; elucidating if there is an interaction of exercise and diet.

Keywords: cardiovascular; endothelium; exercise; hemorheology; inflammation; microcirculation; muscle; n-3 PUFAs.

Figures

FIGURE 1
FIGURE 1
Algorithms of literature search. From literature search it is evident that a respective number of studies investigated the effect of n-3 PUFA supplementation on hemorheology, vascular/endothelial function/microcirculation, inflammation, and skeletomuscular system in both cardiovascular patients and healthy population (A). However, a significantly smaller number of studies dealt with the effect of n-3 PUFA supplementation in the form of functional food (C), or the potential combined interaction effect of n-3 PUFAs and regular exercise on the mentioned parameters (B). Importantly, there is no available data (a total of 5 search results) on the combined effect of n-3 PUFA supplementation in the form of functional foods and regular aerobic exercise on hemorheology, vascular/endothelial function/microcirculation and inflammation in both healthy population and CV patients (D).
FIGURE 2
FIGURE 2
Metabolism of n-3 and n-6 PUFAs and the most important eicosanoids. The present figure summarizes the metabolism of n-3 PUFAs and n-6 PUFAs by cyclooxygenases (COX), lipoxygenase (LOX), and cytochrome P450.
FIGURE 3
FIGURE 3
Schematic representation of potential antithrombotic effects of n-3 PUFAs and exercise. Potential effects of n-3 PUFAs may include influence on specific coagulation factors of the coagulation cascade (with antithrombotic tendency), effects on arachidonic acid metabolites, blood rheology and (directly and indirectly) platelet aggregation (leading to a decrease in the latter). Other unknown or insufficiently investigated effects might also be involved.
FIGURE 4
FIGURE 4
Functional pathways and molecular mechanisms mediating interaction between n-3 PUFAs and exercise on the one side and endothelial function on the other. The present figure summarizes the results of studies conducted on experimental animals, healthy subjects, and patients (CV, diabetic, obese) on the effect of n-3 PUFA supplementation or regular exercise on endothelial function (NO bioavailability, oxidative stress level and inflammation), vascular function (functional vascular experiments in both macro- and micro-circulation), and traditional cardiovascular risk factors (e.g., blood pressure, serum triglyceride level). It is evident that studies on the effect of regular exercise on the abovementioned parameters provided more uniform results and yielded clear conclusions on the beneficial effect of regular exercise on CV health. On the other hand, studies on the effect on n-3 PUFAs on vascular and endothelial function, especially studies in patients and healthy subjects, provided very divergent and inconclusive results, evidently due to the heterogeneity in experimental design with the emphasis on different form, dose and duration of n-3 PUFA supplementation used in these studies. There is a paucity of data on the combined effect of n-3 PUFAs and regular exercise on CV function in general.
FIGURE 5
FIGURE 5
Schematic representation of potential immune mechanisms affected by n-3 PUFAs and exercise in CV patients (outcomes). The effect of exercise and n-3 PUFAs on NF-κB transcriptional activity. Effect of exercise is dependent on the type and intensity level of physical activity. An acute bout of exercise activates myocardial NF-κB and increases toll-like receptor 4 signaling leading to inflammation while moderate exercise reduces NF-κB signaling and activates the SIRT1-AMPK-PGC1α axis, resulting in decreased inflammation and reduced muscle loss.

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