Yurico Adkins, Darshan S. Kelley
Western Human Nutrition Center, ARS, USDA, University of California Davis, CA 95616, USA Department of Nutrition, University of California Davis, CA 95616, USA Journal of Nutrition Biochemistry 21 (2010) 781-792
BASED ON THE RESULTS OF CELLULAR AND MOLECULAR STUDIES, THE CARDIOPROTECTIVE EFFECTS OF POLYUNSATURATED FATTY ACIDS OMEGA 3 DOES NOT SEEM ATTRIBUTABLE TO A SINGLE SYSTEM, BUT TO A TRUE INTEGRATED ACTION WHICH, IN ADDITION TO THE “SIMPLE” GOOD FUNCTIONING OF THE HEART PUMP, EXTENDS TO THE INTEGRITY OF VASCULAR COMPONENT AND THE OPTIMIZATION OF THE PRECIOUS FLUID THAT FLOWS.
PREAMBLE
Regarding what is stated in the international literature, there is an aspect of the research dedicated to cardiovascular disease (CVD) which investigates aspects of cardio-protective Omega-3 polyunsaturated fatty acids and, in particular, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Several studies, conducted on a large scale, have concluded that the consumption of “fish oil” or specific Omega-3 fats is an effective strategy in reducing morbidity and mortality from CVD, and to reduce the dangerousness of the above risk factors.
In addition to this, it was shown that the Omega-3 fats improve a high number of hemodynamic characteristics such as:
- Blood pressure
- Left ventricular diastolic filling
- Heart rate
- Endothelial function
to which are associated with other cardio-protective effects of extreme interest:
- Arrhythmia Prevention
- Reduction in plasma triglycerides
- Increase in vascular relaxation
- Anti-inflammatory activity
- Inhibition of platelet aggregation
- increased plaque stability
- Anti-atherosclerotic action
All it associated with an almost complete absence of side effects that made these nutraceuticals among the safest substances (GRAS – Generally Recognized as Safe) by the Food and Drug Administration.
STRUCTURE AND BIOCHEMISTRY OF ESSENTIAL FATTY ACIDS (EFA)
Within the animals that take fatty acids, the concentration of these in the plasma, cell and tissue is proportional to the introduced quantity. In particular, the integration of the diet with DHA produces an increase of its content in red blood cells, while the administration of EPA determines an increase of its content in the plasma; the incorporation of EPA and DHA in immune cells (neutrophils, monocytes, T lymphocytes and B lymphocytes) increases proportionally with the consumption of fish oil.
In erythrocytes, the phospholipids of the cell membrane are enriched with ω-3 fatty acids during maturation of the reticulocyte within the bone marrow and, subsequently, by direct exchange in the plasma, thanks to albumin serum (containing lysophosphatidylcholine) associated with EPA and DHA.
In the human heart the concentration of DHA is 10 times that of the EPA (5.1% against 0.5%.)
ACTION OF AGE n-3 ON THE PROPERTIES OF CELL MEMBRANES
A physical-chemical mechanism, through which the ω-3 AGE prevents CVD, begins with the variation of the properties of cell membranes, following the incorporation of the omega-3. The type and amount of fatty acids employed directly influence some membrane properties such as fluidity. The number and location of double bonds, as well as the length of the carbon chain, change the properties of the fatty acids, the enzymatic kits involved and the membrane proteins that modulate intracellular signaling pathways.
Subject of the study were also the forces exerted by AGE ω-3 on the cell membrane, about the conductance of ion channels. The intravenous administration or with the omega-3 diet showed antiarrhythmic effects through multiple mechanisms: a direct mechanism is to reduce the electrical excitability of the membrane and the activity of voltage-dependent Na + channels of cardiomyocytes; the result is obtained through an increase in the threshold of depolarization normally required to initiate a contraction and prolong the subsequent refractory period. The fatal arrhythmias are caused not only by a dysfunction of Na + channels but also by the variability of the free Ca ++ in the cytosol. EPA and DHA exert a modulation on L-type Ca ++ channels, which results in a lowering of free Ca ++ and its flow velocity.
ACTION OF AGE ω-3 ON VASCULAR ENDOTHELIAL CELLS AND THE MUSCLE LAYER
AGEs ω-3 shows a beneficial action on the vascular endothelial cells by decreasing endothelial activation and inhibiting the production of inflammatory cytokines which, instead, have a reverse effect.
The treatment with AGE ω-3 also decreases the operation of the active adhesion molecules on human monocytes or of macrophages of rat; this effect reduces the adhesion and the migration of monocytes to the endothelium and, consequently, the development of atherosclerosis and the inflammatory process. The vasorelaxing effect of DHA has been attributed to the decrease of the Ca++ flux.
As mentioned before, the AGE ω-3 are able to modify the production of pro-inflammatory eicosanoids in favor of the vasodilator and antithrombotic results. It was also suggested that omega-3 increase an endothelium-dependent relaxation thanks to an increase in the release of NO which, in turn, inhibits platelet aggregation, leukocyte adhesion and proliferation of smooth muscle cells.
ACTION OF AGE-3 ON TRIGLYCERIDES (TG) IN BLOOD
Elevated plasma levels of TG, both during fasting and in the postprandial phase, determine an increase in inflammation and constitute independent risk factors for CVD.
The integration of the diet with AGE ω-3 reduces the concentration of TG and inflammatory markers. Again, the administration of DHA exerts a positive effect by reducing by 25% the concentration of TG, both fasting and after a meal, and lowers the amount of atherogenic substances, such as LDL particles, the total LDL and the remaining chylomicrons.
CONCLUSIONS
Based on the results of cellular and molecular studies, the cardio-protective effects of AGEs seem not attributable to a single system, but to a synergy of multiple mechanisms of action, an intricate system that contemplates lowering TG, the fight against the inflammation, the regulation of transcription factors and gene expression, membrane fluidity, antithrombotic and antiarrhythmic effects: a true integrated action which widens the concept of cardio-protection in addition to the “simple” good operation of the cardiac pump, extending to the integrity of the vascular component and optimizing the characteristics of the precious fluid that flows.
