Jumat, 03 April 2009

DEFINITION, MECHANISMS, FUNCTIONAL OF OMEGA-3 FATTY ACID

1. INTRODUCTION

Omega-3 fatty acids are being increasingly promoted as important dietary components for health and disease prevention. These fatty acids are naturally enriched in fatty fish like salmon and tuna and in fish-oil supplements. An increasing number of foods that are not traditional sources of omega-3 fatty acids, such as dairy and bakery products, are now being fortified with small amounts of these fatty acids. Fatty acids have many fates in the body, including β-oxidation for energy, storage in depot fat or incorporation into phospholipids, which form the major structural components of all cellular membranes Because humans do not have the enzymatic machinery required to synthesize omega-3 fatty acids, they must be obtained from the diet (termed “essential fatty acids”) (Suretter, 2008).


Omega-3 fatty acids are a family of fatty acids that contain two or more double bonds (“polyunsaturated”). One of which is located three carbon positions from the methyl terminus (“omega-3” or “n-3”) because the body is unable to synthesize in appreciable amounts omega-3 fatty acids that are longer than 14 carbons they are obtained primarily from dietary sources (Friedman & Moe, 2006).

Fish such as tuna, trout and salmon are especially rich sources of these fatty acids. Fish oil supplements are also a rich source as they typically contain 30%–50% omega-3 fatty acids by weight. Small quantities of omega-3 fatty acids are naturally present in meats like beef, pork and poultry. But also is plant sources such as flax and canola oil. The marine omega-3 fatty acids preparation we used contains a small amount of antioxidant vitamin E (equal to approximately 16 IU vitaminE/day), which theoretically may be expected to have an effect. (Surette, 2008 ; Goodfellow et al., 2009).

The phospholipid polyunsaturated fatty acids (PUFAs) hypothesis of depression is enlightening a promising path to discover the unsolved of depression. There are two main types of PUFAs in the human body. The omega–6 (n–6) series derived from cis-linoleic acid (LA, 18: 2) and the omega–3 (n–3) series derived from α-linolenic acid (ALA, 18: 3), n–3 and n–6 PUFAs are important constituents of all cell membranes. They are essential for survival of humans and other mammals, and cannot be synthesized in the body. The inability of vertebrates to synthesis linoleic acid (18:2ω6) and α-linolenic acid (18:3ω3) leads to essential requirement for these fatty acids (FAs) in diet (Pinsu, 2009 ; Dennis et al., 1993). There are three major types of omega 3 fatty acids including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and also docosahexaenoic acid (DHA) (Alshatwi & Alrefai, 2007). Omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are highly polyunsaturated and readily undergo oxidation (Sethi et al., 2002).

Omega-3 polyunsaturated fatty acids (PUFAs) are one of dietary substrates that have reported cardioprotective benefits. Omega-3 PUFAs generally exert their cardioprotective effects through changes in lipids and lipoproteins (Alshatwi & Alrefai, 2007). The structural role of long chain polyunsaturated fatty acids (LCPUFAs) and the functional correlates of specific Fas are being increasingly recognized. The LCPUFAs arachidonic acid (20:4w6) is an important membrane component and precursor to prostaglandins, leucotrienes, and epoxides (Dennis et al., 1993).

The aim of this study was to determine the effects of omega-3 fatty acid in human health. And known mechanisme from work omega-3 fatty acid.


2. MEKANISME OF OMEGA-3


The biological mechanisms to explain the role of n–3 fatty acids in depression are the regulation of neurotransmitters and signal transduction by PUFAs. The change in fatty acid concentration in the brain, induced by chronic deficiency in dietary n–3 fatty acids, could lead to an increase in serotonin 2 (5-HT2) and decrease in dopamine 2 receptor density in the frontal cortex. The upregulation of 5-HT2A/C receptors and down regulation of dopamine receptor are thought to play a role in the pathophysiology of depression. Furthermore, high cerebrospinal fluid concentration of 5-hydroxy-indoleacetic acid (5-HIAA), a metabolite of serotonin and an indicator of brain serotonin turnover, has been shown to be associated with high plasma concentration of n–3 PUFAs among healthy human.

The other possible biological mechanisms of the beneficial effects of n–3 PUFAs on mood and physical illness are regulation of the corticotropin-releasing factor, inhibition of protein kinase C, suppression of phosphatidylinositol-associated second messenger activity, modulation of heart rate variability via parasympathetic nervous system, increased dendritic arborization and synapse formation, promotion of neuroprotection and prevention of neuronal apoptosis, and synthesis of neuroprotectin D1 inhibit angiotensin-converting enzyme and 3-hydroxy-3-methylglutaryl coenzyme A reductase activities, and their competition with AA for enzymatic action and the resultant reduction in the inflammatory response (Pinsu, 2008).

Although we are able to convert dietary α-linolenic acid into eicosapentaenoic, docosapentaenoic and docosahexaenoic acids (which are found in fish and fish oils). this conversion is not efficient in people who consume a typical Western diet. Consequently, following the consumption of foods containing α-linolenic acid, our tissues are exposed to very little of the types of omega-3 fatty acids found in fish and fish oil (Surette, 2008).

The fundamental mechanism by which omega-3 FA appear to mitigate risk for CHD begins with the enrichment of membrane phospholipids with EPA and DHA. Once these long chain n-3 FA are resident in cell membranes, they may have at least four separate effects. First, because of their highly unsaturated nature, they may alter membrane properties. This can have the secondary effect of changing the microenvironment of transmembrane proteins (e.g., receptors) altering the manner in which they interact with their ligands. Altering membrane FA composition can also affect the ability of membrane-associated proteins to actually associate with the membrane and consequently to interact with other multi-protein complexes involved with cell signaling systems.

In addition, a variety of cell stressors (e.g., inflammatory mediators) interact with transmembrane receptors and subsequently initiate intracellular G-protein linked responses, one of which is the activation of phospholipase A2 (PLA2). This enzyme hydrolyzes long-chain omega-6 and omega-3 FA esterified to inner leaflet phospholipids, liberating them and making them available for conversion to a wide variety of eicosanoids via cyclo-oxygenase, lipoxygenase, and cytochrome P-450 monooxygenases.

These molecules powerfully influence cellular metabolism. PLA2-liberated omega-3 FA may directly modify the activity of ion channel themselves, resulting in altered resting membrane potentials. Finally, intracellular omega-3 FA are also able to serve as ligands for a variety of nuclear receptors (e.g., peroxisome proliferation activated receptors (PPARs), sterol receptor element binding protein (SREBP)-1c, retinoid X receptor, farnesol X receptor, and hepatocyte nuclear factor-α which impact inflammatory responses and lipid metabolism.

3. FUNCTIONAL OF OMEGA-3

Feeding humans fish oils has been shown to reduce oxygen-derived free radical formation in neutrophils and monocytes, and to enhance NO (Nitric Oxide) production by cultured human endothelial cells. Speculatively, it is also possible that a reduction in the formation of oxygen derived free radicals by endothelial cells and thus increased bioavailability of NO (Goodfellow et al., 2000). In addition, omega-3 FAs especially EPA and DHA contribute benefits through their antiarrhythmic, anti-inflammatory, antithrombotic effects. Moreover, EPA and DHA also improve vascular endothelial function and help lower blood pressure, platelet sensitivity, brain and retina (Alshatwi & Alrefai, 2007 ; Dennis et al., 1993).

Omega-3 fatty acids affect health and disease has led to a large body of evidence which suggests that these dietary lipids modulate numerous processes, including brain and visual development, inflammatory reactions, thrombosis, carcinogenesis. And also reduce mortality in non-transplanted patients. Omega-3 can reduce hypertension early after heart transplantation. Omega-3 in some reports also improve renal function in chronic progressive renal disease and kidney graft recipients (Holm et al., 2001).

This positive affect of omega-3 fatty acids was primarily associated with higher DHA levels. Previous work on omega-3 fatty acids has suggested that DHA has greater benefit than EPA for lowering blood pressure. The positive effect of higher omega-3 fatty acid levels on endothelial function raises the possibility that increased consumption of omega-3 fatty acids beginning early in life may favorably alter the risk of cardiovascular disease. Omega-3 is possible is possible improvements in endothelial function may be responsible for this reduced risk of heart disease in diabetic patients (Mori et al., 1999 ; Hu et al., 2003).

Presumably as a consequence of these cell membrane effects, omega-3 FA can diminish the activity of inflammatory cells and reduce levels of certain inflammatory mediators, which may ultimately result in reduced arterial plaque fragility. The decrease in serum triglycerides that is produced by intakes of 3-4 g/d of EPA+DHA appears to be secondary to increased hepatic beta-oxidation and decreased lipogenesis, which themselves are the result of modulation of the nuclear receptor actions (Calder et al., 2006).

4. CONCLUSION

- Highest content omega-3 be at fish and fish oil, flax and canola oil, and marine alga.
- The precise mechanisms by which omega-3 FA reduce risk for cardiac event.
- The clinical benefits related to consumption of fish and fish oil, such as antiarrhythmic, anti-inflammatory, antithrombotic effects, etc.

5. REFERENCES

Alshatwi, A. A & Alrefai. N. A. (2007). A Comparison of Serum Omega - 3 Fatty Acid Concentrations Between Patients with Coronary Heart Disease and Healthy Subjects. Pakistan Journal of Nutrition 6 (1): Pp. 72-74.

Calder, P. C. (2006). n-3 Polyunsaturated Fatty Acids, Inflammation, and Inflammatory Diseases. Journal of American Clinical Nutrition. 83. Pp. 1505S-1519S.

Dennis, R. H., Eileen. E. B., David.G. B., & Ricardo. D. U. (1993). Effects of Suplementation With ω3 Long-Chain Polyunsaturated Fatty Acids on Retinal and Cortical Development in Premature Infants1-3. Journal of The American Clinical Nutrition. 57. Pp. 807S-812S.

Friedman, A & Moe. S. (2006). Review of the Effects of Omega-3 Supplementation in Dialysis Patients. Journal Clinical American Society of Nephrology 1. Pp. 182-192.

Goodfellow, J., M. F. Bellamy., M.W.Ramsey., C. J. H. Jones & M. J. Lewis. (2000). Dietary Supplementation With Marine Omega-3 Fatty Acids Improve Systemic Large Artery Endothelial Function in Subjects With Hypercholesterolemia. Journal of The American College of Cardiology. Vol. 35., No. 2. Pp. 265-270.

Harris, W. S. (2007). Omega-3 Fatty Acids and Cardiovascular Disease: A Case for Omega-3 Index as a New Risk Factor. Journal Pharmacol Res, 55(3). Pp. 217-223.

Holm, T., Andreassen. A. K., Aukrust. P., Andersen. K., Geiran. O. R., Kjekshus. J., Simonsen. S., & Gullestad. L. (2001). Omega-3 Fatty Acids Improve Blood Pressure Control and Preserve Renal Function in Hypertensive Heart Transplant Recipients. Journal of European Heart, 22. Pp. 428-436.

Hu, F. B., Cho. E., Rexrode. K. M., Albert C. M., & Manson. J. E. (2003). Fish and Long-Chain Omega-3 Fatty Acid Intake and Risk of Coronary Heart Disease and Total Mortality in Diabetic Women. Circulation, 107. Pp. 1852-1857.

Mori, T. A., Bao. D.Q., Burke. V., Puddey. I. B & Beilin. L. J. (1999). Docosahexaenoic Acid But Not Eicosapentaenoic Acid Lowers Ambulatory Blood Pressure And Heart Rate In Humans. Journal Hypertension. 34. Pp.253-260.

Pinsu, K. (2008). Biological Mechanism of Antidepressant Effect of Omega–3 Fatty Acids: How Does Fish Oil Act as a ‘Mind-Body Interface’?. Neurosignals. Taiwan.

Sethi, S., Ziouzenkova. O., Ni. H., Wagner. D. D., Plutzky. J., & Mayadas. N.T. (2002). Oxidized Omega-3 Fatty Acids in Fish Oil Inhibit Leukocyte-Endothelial Interactions through Activation of PPARalpha. Journal Blood. Vol. 100. Number. 4. Pp. 1340-1346.

Surette, M. E. (2008). The Science Behind Dietary Omega-3 Fatty Acid. CMAJ. Canada.