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Cardiovascular Disease and Omega-3
Omega 3 PUFAs and Cardiovascular Disease


As most of us are aware, in today’s society, our human diet is vastly different than that of our ancestors. In earlier times hunting, fishing and gathering of foods was an important part of their lifestyle. This resulted in them acquiring a balance of Omega 6 to Omega 3, a ratio of 1:1. Due to our fast lifestyle and the need for convenience we are now preparing and eating less and less fish and other marine mammals. As a result, our diet is deficient in Omega 3 Long Chain Polyunsaturated Fatty Acids (PUFAs), showing a ratio of 25-35:1. Omega 3 is ‘essential’ for human health and development, meaning that it is necessary for life. This ‘essential’ fatty acid cannot be produced by the body, but must be obtained from another food source such as fish, marine mammals, or Seal Oil capsules.

The Omega 3 Seal Oil (PUFAs), which I have developed, is composed of Eicosapentaenoic Acid (EPA, 20:5n-3), Docosahexaenoic Acid (DHA, 22:6n-3), and Docosapentaenoic Acid (DPA, 22:5n-3). In recent research all three of these components have been proven to be vitally important in human health, growth and development, from infancy to senior years. Omega 3 PUFAs are important for cellular membrane components and the production of eicosanoids, which are hormone like substances that are the body’s cellular check and balance system. The eicosanoids do not last long in the body, so they have to be produced continuously. The production of eicosanoids can be controlled if one is consuming the correct balance of Omega 6 to Omega 3 PUFAs; balance means good health whereas imbalance leads to disease development.

The EPA (Eicosapentaenoic acid) reduces inflammation and blood clots within the cardiovascular system. Also, clinical tests have shown that diet’s rich in EPA are less inclined to develop inflamed joints (Rheumatoid arthritis), inflammation of the intestines (Crohn’s disease), lupus, asthma, multiple sclerosis and skin disease.

The DHA (Docosahexaenoic acid) has been identified as an ‘essential’ building block of the brain, nerve and eye tissue. It is especially important to developing an infant’s visual acuity and motor skills. DHA is supplied naturally through a mother’s breast milk, providing the mother is eating fish and other marine mammals. More recently DHA has been supplemented through Seal Oil Formula Capsules, which is an excellent source of DHA.

With regards to DPA (Docosapentaenoic acid), it is only found in significant amounts in Seal Oil and nursing mother’s breast milk. It is as important as EPA or DHA and is an effective agent in blood vessel walls. Researchers in Japan (2003) found that DPA has a potential inhibitory effect on tumor angiogenesis (new vessel formation). This means that DPA has an anti-cancer effect. 

The composition of these ‘essential’ (dietary elements that the body cannot produce, so they must be acquired through our diet) fatty acids in seal oil are ultimately involved in controlling inflammation, cardiovascular health, myelin sheath development, allergic reactivity, immune response, hormone modulation, IQ, and behavior.

These ‘essential’ fatty acids play a vital role in maintaining the integrity and fluidity of the membranes that surrounds human cells, protecting them from free radical damage (cell attacking molecules which are believed to be one of the main causes of cellular damage and the aging process). Scientific studies have shown that Omega 3 fatty acid deficiency is seen as the leading cause of Westernized Degenerative Diseases such as, Cardiovascular Disease.

The cardiovascular system is composed of the heart and the blood vessels. The heart is a muscle, which is composed of 4 chambers, so when our heart contracts, the blood is pumped out and into the arteries (blood vessels). The arteries (have thick vessel walls), in turn, transport the blood away from the heart, and then the veins transport the blood back into the heart.

Due to our westernized dietary habits, Cardiovascular Disease stops being a remote threat, only to take on a personal relevance. Cardiovascular Disease refers to a class of diseases that involve the heart and/or blood vessels (arteries and veins). It is a result of arterial damage, including such diseases as, Coronary Heart Disease, Atherosclerosis, Hypertension, Arrhythmia, and Stroke.

Currently there are more than 68 million Americans with one or more cardiovascular diseases such as heart disease, heart attack, and stroke; with many more at risk of developing it. Cardiovascular Disease is the top ranking number one killer, accounting for about one-third of all deaths in industrialized countries.

The risk factors associated with Cardiovascular Disease:


Coronary Heart Disease (Also known as: Coronary Artery Disease) is a narrowing of the small blood vessels that supply blood and oxygen to the heart (coronary arteries). Coronary heart disease usually results from the build up of plaque. Thus, when the coronary arteries narrow, the flow of blood to the heart can slow or stop, which can cause such symptoms as chest pain and shortness of breath.

According to the American heart Association, about every 29 seconds someone in the USA suffers from a Coronary Heart Disease related event, and about every minute someone dies from CHD. For men the risk of having CHD after the age of 40 is 49% and for women it is 32%. However, as women get older the risk of them developing CHD increases almost to that of the men.

The leading cause of Coronary Heart Disease is Atherosclerosis (thickening/hardening of the artery walls), which is characterized by the deposition of atheromatous plaques containing cholesterol and lipids on the innermost layer of the walls of large and medium-sized arteries. These plaques take several years to form (narrowing the arteries and restricting blood flow) and they may eventually fissure, triggering the development of a blood clot (The complete blockage interrupts oxygen supply and results in tissue injury or death), which adheres to the accumulated plaque which in turn leads to myocardial infarction (heart attack). Likewise, the blockage of the arteries to the brain can lead to a stroke. This outcome, activated by irreversible platelet aggregation, is participated by slowing of the blood flow over the plaque.

Atherosclerosis begins early, between the ages 10-20 years. During this time ‘fatty streaks’ are already being deposited on the inner lining of the coronary arteries. Over time these ‘fatty streaks’ grow into larger cholesterol plaques resulting in hard artery walls. Many men and women are unaware that between the ages 20 and 30 they are accumulating cholesterol plaques. Unfortunately, by the time they reach 40 to 50 years of age, many of them already have developed enough atherosclerosis to put them at risk for Coronary Heart Disease.

Attention to these risks factors and common sense about life-style and diet are important strategies for the prevention of Cardiovascular Disease. An over abundance of Omega 6 fatty acids leads to an increase of thromboxane A-2 (TXA-2), a precursor of Arachidonic Acid (AA), is a vasoconstrictor, stimulates platelet aggregation and prostaglandin (PGI-2). PGI-2 derived from arachidonic acid (AA), is vasodilating but has hemostatic and thrombotic properties as well. However, a diet rich in Omega-3 LC-PUFAs lowers the membrane AA content and consequently, the production of the AA-derived eicosanoids TXA-2 and PGI-2. In addition, dietary Omega-3 LC-PUFAs promotes the formation of the 3-series prostanoids TXA-3 (which is less prothrombotic) and PGI-3. Omega-3 LC-PUFAs decrease platelet aggregation and promote vasodilatation. Therefore, a diet rich in Omega-3 LC-PUFAs has antihemostatic and antithrombotic activity. (Omega-3 Long Chain Polyunsaturated Fatty Acids and Health Benefits, Hornstra, G., 1988, p.12). 

In addition, researchers from the Louisiana State University have analyzed the coronary arteries of 23,000 deceased persons, since 1990, from 16 countries and this is one of their findings: “The Inuit who lived on a traditional diet of marine mammals (mainly seal, which is an excellent source of Omega-3 PUFAs) had, at the age of 70, the same coronary artery elasticity as a twenty year old European.” (Okuyama H., Kobayashi T., and Watanabe S., Dietary Fatty Acids: The Omega 6/Omega 3 Balance and Chronic Elderly Diseases. “Program of Lipid Research. 1997, Vol 35, no. 4, pp.409-497).

Atherosclerosis is far less widespread among the Inuit than elsewhere in the world. Though many advertisements for fish oil claim that the Inuit people have a low incidence of cardiovascular disease because they eat a lot of fish, this is not so. In all actuality, Inuit people eat fish only once or twice weekly, while they eat seal or whale twice a day. (Mulvad G M.D. and Pedersen HS M.D., Eat Meat and Blubber from Sea Mammals and Avoid Cardiovascular Disease. Whaling for Food. pp. 45-51).


Hypertension or elevated blood pressure indicates that the heart is working harder than normal, putting both the heart and the arteries under a greater strain. Most patients with Hypertension have an increased resistance (stiffness or lack of elasticity) in the peripheral arteries or arterioles. It causes hardening and loss of elasticity of the artery wall so those arteries are no longer able to absorb the systolic pressure waves.

Hypertension, also promotes atherosclerosis by causing micro-injuries that allow low-density lipoproteins (LDLs) to penetrate the artery wall. It is one of the major risk factors in cardiovascular disease, accounting for 34% of deaths in developing countries and increasing the rate of heart failure 5-fold.


Hypertension is associated with:

Studies have shown that supplementation with Omega-3 LC-PUFAs at a relatively high dose (3-9 g/day) markedly lowers systolic and diastolic blood pressure in moderately hypertensive patients. Also, in a Meta analysis, Morris et al, found that a significant reduction in blood pressure in studies with hypertensive subjects who consumed 5.6g/day of Omega-3 Fatty Acids. (Does fish oil lower blood pressure? A Meta analysis of controlled trials. Circulation. 1993; 88: 523-33).

Arrhythmia is an irregular heartbeat. Heart rates can also be irregular. A normal heart rate is 50 to 100 beats per minute. There are two known arrhythmias; the first is bradyarrhythmia (slow), which is less than 60 beats per minute, while the trachyarrhythmia is faster with more than 100 beats per minute. Both Arrhythmias and abnormal heart rates do not necessarily occur together.

Arrhythmia is characterized by:

Arrhythmias may be caused by:


There are various types of arrhythmias such as, those that occur in the heart atria or heart ventricles. Those occurring in the atria are known as Atrial or Supraventricular Arrhythmias because it happens above the ventricles. Whereas, Ventricular Arrhythmias occur in the heart ventricles and are caused by irregular electrical activity of the heart muscle. They are the most serious and are potentially fatal, often resulting in sudden death.

Much of the evidence available today points to the anti-arrhythmia effect of Omega-3 LC-PUFAs on myocardial cells. Animal studies conducted on rats, monkeys and dogs have shown that the severity of arrhythmias experimentally induced by ischemia-reperfusion can be correlated with the type of fatty acids which the animal has previously ingested. Thus, susceptibility to arrhythmias appeared markedly decreased in animals previously fed a fish oil diet. 

In an observational study conducted by Siscovick et al., they found lower cardiac arrest rates in fish consumers, whose cell membranes had a high Omega-3 LC-PUFA content. The results showed effective anti-arrhythmia activity when DHA accounts for approximately 20% of the fatty acids in the cardiomycoyte membranes. This suggests a relationship between the LC-PUFA composition of the mycoyte membrane and death from cardiac arrest. (JAMA, Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. 1995; 274: 1363-7).

Stroke (brain attacks) occurs when the blood flow to a region of the brain is obstructed, which may result in the death of brain tissue causing permanent disability or even death.

With regards to Stroke-There are two known Causes:

The most common risk factors for Stroke are:

Blockage Artery Stroke: Cerebrovascular Accident-CVA is the sudden death of brain cells due to a problem with the blood supply. When the blood supply to the brain is impaired; oxygen and other nutrients cannot be delivered. The cells in the area of the brain in which the blood supply is impaired die. In a stroke the blood vessels narrow due to long-term damaging effects of High Blood Pressure (Hypertension) or Diabetes. Also, inflammation and blood clots may obstruct the cerebral arteries (those which supply the brain).

Statistics show that in the USA, about 400,000 people a year suffer from a stroke, 40% of which are fatal. Also, 75-80% of all strokes are associated with blockages in the carotid arteries, which are preventable.

As we age our arteries become narrower, due to the rough deposit of plague known as stenosis. These diseased arteries can either clog up completely from the accumulated plaque deposits or completely shut down by clotting conditions known as ‘embolism’ and ‘thrombosis’.
When an artery becomes blocked, it can lead to a Transient Cerebral Ischemic (mini-stroke), which is due to the death of brain tissue supplied by the artery. The mini-stroke occurs when there is a temporary impairment in the brain (24 hours), due to a loss of blood supply, which is most often caused by a clot that forms in a blood vessel within the brain (thrombosis). There is a loss of bodily function that is controlled by the portion of the brain, which is affected. This form of stroke comprises 80% of all known strokes. In addition, this can be due to a clot that forms elsewhere in the body, which dislodges and then becomes wedged in an artery of the brain.

Cerebral Hemorrhage Stroke (bleeding in the brain-aneurysm) occurs when the blood vessel(s), which have weakened over time, bursts and bleeds into the surrounding brain tissue. This ultimately leads to blood and oxygen being deprived to parts of the brain.
He K, et al, conducted a study on 43, 671 men aged 40-75 years with no cardiovascular disease. After a 12-year follow-up they documented 608 strokes, including 377 Ischemic, 106 Hemorrhagic, and 125 unclassified strokes. What they found was compared to the men who consumed fish less than once per month, the multivariate Relative Risk (RR) of Ischemic stroke was significantly lower among those who ate fish 1 to 3 times per month (RR, 0.57; 95% confidence interval [CI], 0.35-0.95). (JAMA. Fish consumption and the risk of stroke in men, 2002 Dec 25; 288 (24): 3130-6). Showing that eating fish as least once per month or more can reduce the risk of Ischemic stroke in men.    

Triglyceride (one of the risk factors worth discussing) is a fatty substance, composed of three fatty acids. Triglyceride in the blood comes from either the diet or the liver. It cannot dissolve and circulate in the blood without combining with lipo-protein. Triglyceride levels are influenced by recent fat in our diet. Today, it is recognized that an elevated triglyceride level is often associated with atherosclerosis, including obesity, low levels of HDL-cholesterol, insulin resistance and diabetes mellitus, and small, dense LDL-cholesterol particles. A high post-prandial triglyceride level is increasingly being acknowledged as an independent marker of cardiovascular risk.

Many studies have shown that the Omega-3 LC-PUFAs lower high plasma triglyceride levels. Bonefeld-Jorgensen, EC, et al., conducted two studies on dietary supplementation of Seal Oil on risk factors of atherosclerosis. The first study included ten people taking ten capsules of Seal Oil in their normal Western diet for six weeks. The second study pertained to five people and five Seal Oil capsules per day for six weeks. Blood tests were analyzed for total HDL and LDL-cholesterol and plasma triglyceride, and the ratio of n-6/n-3 fatty acid was determined in the plasma and erythrocyte membranes. An additional test was conducted in the second study on the effect of the pro-inflammatory TNF-alpha cytokine in lymphocytes. What they found was a slight decrease in cholesterol levels; plasma triglyceride and the n-6/n-3 ratio of plasma and erythrocytes were significantly reduced upon Seal Oil intake.  During the intervention period of study two a distinct reduced level of TNF-alpha was observed in isolated lymphocytes. This study suggests that supplementation of 5 or 10 capsules a day may have beneficial effects on factors thought to be associated with cardiovascular disease. (Lipids. 2001 Jan; 36 (1): 7-13). Omega-3 LC-PUFAs are thus of documented nutritional benefit in the prevention of cardiovascular disease. Therefore, all nutritional factors that can help to control high plasma triglyceride levels have a potential role in cardiovascular disease prevention.

While the use of drugs or surgical intervention (i.e. by-passes) is an option for some patients suffering from Cardiovascular Disease, it is important to realize that those interventions do not lessen the importance of dietary factors, such as the use of natural remedies and natural dietary supplements, such as Seal Oil Omega-3 LC-PUFA capsules.

Reasons why Omega-3 LC-PUFAs should compliment those afflicted with Cardiovascular Disease:
1. Omega-3 LC-PUFAs lowers serum triglyceride levels. (Some patients who suffer from non-insulin dependent diabetes (NIDDM) have elevated triglyceride levels).
2. Omega-3 LC-PUFAs increases HDL cholesterol levels. (Those with low levels of HDL cholesterol have a high level of correlation with increased risk of Coronary Artery Disease, more so in those with elevated triglyceride and LDL levels).
3. Omega-3 LC-PUFAs reduces blood pressure. (It has been shown that Omega-3 can reduce blood pressure by 5-10% in patients with hypertension).
4. Omega-3 LC-PUFAs helps to maintain artery wall elasticity. (One of the reasons why it helps to reduce blood pressure. Also reduces the risk of further mechanical damage to vessel walls, which can lead to extended Atherosclerosis).
5. Omega-3 LC-PUFAs reduce the adhesiveness (stickiness) of platelet and blood cells. (Cells that adhere to blood vessel walls cause localized inflammation. Omega-3 reduces the ability of both the platelets and white blood cells to adhere to the vessel walls and each other. A thrombus formation starts out as a mass of blood cells and platelets, but the Omega-3 helps to reduce this risk).
6. Omega-3 LC-PUFAs stabilizes heart rhythm. (Research has shown that Omega-3 fatty acids do improve the heart rhythm stability in both healthy people and those who suffered from a myocardial infraction, heart attack).
7. Omega-3 LC-PUFAs protects against immunological over-reaction. (Clinically Omega-3 is known for the positive results from patients inflicted with Rheumatoid Arthritis (inflammatory condition). However, it is also important for its protection against atherosclerosis. Atherosclerosis is seen as developing as an inflammation response to injuries to the artery walls. Recent research has shown that atherosclerosis can be reduced with supplementation of Omega-3 LC-PUFAs.).  

This being said, while Omega-3 LC-PUFAs has been shown to have anti-inflammatory, antithrombotic, anti-arrhythmic actions, and immune-modulating properties, it cannot save or treat the Cardiovascular System on its own. In order for Omega-3 LC-PUFAs to do its part we have to do ours by attaining and maintaining a well-balanced diet, one that is rich in fruits, vegetables, exercise, fish/marine mammals, and/or Seal Oil Capsules.      




 
Dr. Cosmas Ho M.D., C.C.F.P.
October 2005
Recent Research:
1.Greenland Eskimos have very few cardiac deaths. Bang and Dyberg found that their marine based diet was very rich in Omega-3 Polyunsaturated Fatty Acids (n-3 LC-PUFAs). These have antiarrhythmic, endothelial protective, antiatherogenic, antithrombotic and antiplatelet effects in many observational studies, which have pointed to their potential role in secondary prevention post myocardial infarction (MI). (Harrison, N. and Abhyankar B., Current Medical Research and Opinion. Vol.21, No. 1, 2005, pp.95-100).
2.Supplementation with Omega-3 fatty acids was preformed on 33 subjects. The results showed that Arachidonic acid/Eicosapentaenoic Acid ratio (AA/EPA) was strongly reduced by theOmega-3 supplementation. This AA/EPA reduction was correlated with a concomitant decrease of insulin and homocysteine levels. (European Journal of Clinical Investigation. 2005 Aug; 35 (8): 499-507).
3.A rich source of Omega-3 PUFA is found in fish and marine mammals (seal, walrus, whale), which are a large part of the traditional diet of the Alaskan Natives (Eskimos, American Indians, Aleuts), a group that has been reported to have a lower mortality rate from cardiovascular disease than non-Natives. An autopsy study (extent of atherosclerosis and its risk factors and analysis of stored triglyceride fatty acids) was conducted on both Alaskan Natives and non-Native subjects living in Alaska. Findings indicated that the Alaska Natives had less advanced atherosclerosis in coronary arteries, along with higher proportions of Omega-3 and lower proportions of omega-6 PUFA in adipose tissue, than did non-Natives. Concluding that the higher dietary intake of  Omega-3 PUFA may account for the lower heart disease mortality among Alaska Natives. (Atherosclerosis. 2005, Aug; 181 92: 353-62).
4.11 hemodialysis (HD) patients ages 59 +/- 17 years were treated with Omega-3 fatty acids 91.2g/day combined with 11.2g/day pectin) for 12 weeks. Serum concentrations of c-reactive protein, homocysteine (HcY), lipids, complement factors, blood gas analysis, shunt blood flow, and re-circulation, as well as peripheral oxygen saturation at the hand and foot, were measured at the start (t0w), and after 12-weeks (t12w) of therapy. The results showed that several cardiovascular risk factors were significantly influenced. Levels of very-low density lipoproteins (t0w, 77+/-26; t12w, 63+/-32 mg/dL; P<.05) and triglycerides (t0w, 261+/-157; t12w, 228+/-131 mg/dL; P=0.68) were decreased. Limited positive effects on metabolic parameters were elevated by short-term administration of Omega-3 fatty acids in HD patients. Based on previous studies and on suspicion of atherosclerotic disorder in examined HD patients, we suppose that only high doses of omega-3 fatty acids given for a longer time influence inflammation and atherosclerosis. (J Ren Nutr. 2005 Apr; 15 (2): 253-6).
5.Calo L, et al, studied 160 prospective coronary bypass patients (average age 66 yrs) to see what impact dietary PUFAs have on the development of post-surgery atrial fibrillation and recovery. One group received 2 g/day n-3 LC-PUFAs with usual care for at least 5 days prior to surgery. The control group received usual care without supplementation. The authors found that there was a 54% reduction in the occurrence of atrial fibrillation with n-3 LC-PUFAs, which compares favorably with reductions achieved with conventional drug therapies such as beta-blockers or sotalol. N-3 LC-PUFAs have the advantage of virtually no adverse side effects in low to moderate doses. Simple and effective, they are just what the doctor should order. (N-3 Fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized controlled trial. J Am Coll Cardiol 2005; 45: 1723-1728).
6.Chairman, A, et al, studied fish oil effects on heart muscle damage after cardiac surgery, with 40 patients undergoing coronary artery bypass surgery, who were randomly assigned to consume fish oil (8 g/day) or placebo (short-chain fatty acids) for 5 to 7 weeks prior to surgery. They found that the release of troponin 1 significantly increased in all patients immediately following surgery and values were highly variable among patients. At 24 hours post surgery, troponin 1 fell significantly in the fish oil group (46 +_ 23% of post operative values, p=0.0002), but remained elevated in the placebo group (107+_ 72% of post operative values, p=0.013) until 120 hours following surgery. (Fish oil before cardiac surgery: neutrophil activation is unaffected but myocardial damage is moderated. Prostaglandins Leukot Essent Fatty Acids 2005; 72: 257-265).
7.Studies in animals and some in patients with various heart diseases have reported a reduction in ventricular fibrillation with the administration of long chain Omega-3 polyunsaturated fatty acids (n-3 LC-PUFAs). Many reports have described reduced atrial fibrillation with the consumption of n-3 LC-PUFAs and a mechanism of action involving changes in the flow of ions has been described. (Raitt MH, et al, JAMA 2005; 293:2884-2891).
8.Christensen JH, et al, conducted an observational study with 98 patients who had both ischemic heart disease and an ICD. They were monitored over the course of one year to determine if there was a relationship between the concentration of n-3 LC-PUFAs in their serum phospholipids and ventricular events. During this period, 22 patients (25%) incurred a total of 71 ventricular events (39 ventricular tachycardia and 32 fibrillation events). Patients who had more than one episode of ventricular arrhythmias had significantly lower total and individual n-3 LC-PUFAs compared with patients who had no ventricular arrhythmias. The observation of reduced ventricular arrhythmias in high-risk patients who had greater levels of phospholipid n-3 LC-PUFAs supports epidemiological and clinical evidence for the anti-arrhythmic properties of these fatty acids. (n-3 fatty acids and ventricular arrhythmias in patients with ischemic heart disease and implantable cardioverter defibrillators. Europace 2005; 7: 338-344).
9.According to a study conducted by Ness AR, et al, Atherosclerosis starts early, with fatty streaks occurring by age 5 and fibrosis plaques by age 20. (Diet in childhood and adult cardiovascular and all cause mortality: the Boyd Orr Cohort. Heart 2005; 91: 894-898).
10.In the Meta-Analysis of randomized, double blind, placebo-controlled clinical trials, fish oil reduced HR, particularly with higher baseline HR or longer duration of treatment. Showing that fish oil consumption directly or indirectly influences cardiac electro-physiology in humans. This effect may directly account for part of the observed benefits of fish intake on cardiovascular risk, particularly risk of arrhythmic events, and may indicate favorable effects on physiological systems such as on automic-tone, vascular resistance, or ventricular efficiency that improve cardiovascular health. (Mozaffarian D, et al. Effect of Fish Oil on Heart Rate in Humans: A Meta-Analysis of Randomized Controlled Trials. Circulation. 2005; 112: &NA; -.).
11.Doses of less than 1 g/d appear to reduce risk for fatal coronary heart disease events, perhaps by stabilizing the myocardium and reducing risk for fatal arrhythmias. New evidence points to a possible benefit on atrial fibrillation, particularly in the immediate post-cardiac surgery setting. Studies in women with coronary heart disease now suggest that plaque progression may be slowed by increased intakes of oily fish, even in women with diabetes. If intakes of the latter are adequate (perhaps over 250 mg/d), then there appears to be little need to consume more ALA or less LA. (Extending the Cardiovascular Benefits of Omega-3 Fatty Acids. Curr Atherosclerosis Rep. 2005 Sep; 7 (5): 375-380).
12.Long chain n-3 PUFAs have been shown to decrease blood triacylglycerol (triglyceride) concentrations, to decrease production of chemoattractants, growth factors, adhesion molecules, inflammatory eicosanoids, and inflammatory cytokines, to lower blood pressure, to increase nitric oxide production, endothelial relaxation and vascular compliance, to decrease thrombosis, and cardiac arrhythmias, and to increase heart rate variability. A recent study suggests that long chain n-3 PUFAs might also act to stabilize advanced atherosclerotic plaques, perhaps through their anti-inflammatory effects. (Calder P, n-3 Fatty acids and cardiovascular disease: evidence explained and mechanisms explored. Clinical Science, 2004, 107, p.1-11). 
13.Another potential antiatherogenic mechanism of Omega-3 fatty acids is their interference with the arachidonic acid cascade that generates a wide variety of eicosanoids. EPA not only can replace arachidonic acid in the phospholipid bilayers, but it is also a competitive inhibitor of the cyclooxygenase, reducing the production of the 2-series prostaglandins, thromboxins, and prostacyclins and the 4-series leukotriens. The 3- and 5- series (respectively) produced from EPA are generally less biologically active. DHA, although not a direct inhibitor or arachidonic acid metabolism, nevertheless can inhibit platelet aggregation by reducing the affinity of platelet TxA2/PGH2 receptor for its ligand. The net effects of Omega-3 fatty acids are thus known to reduce inflammatory processes, vasoconstriction, and platelet aggregation, all known to be antiatherogenic. (Penny M, et al, Fish Consumption, Fish Oil, Omega-3 fatty Acids, and cardiovascular Disease. Circulation. 2002; 106: 2747).
14. Marchioli R, et al, studied 11,323 patients, who recently survived a recent (<3 months) myocardial infarction, were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment 9control) on top of optimal pharmacological treatment and lifestyle advice. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths. This shows that the early effect of low-dose (1 g/d) n-3 PUFAs on total morality and sudden death supports the hypothesis of an antiarrhythmic effect. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies. (Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time course analysis of the results of the GISSI-Prevenzione. Circulation. 2002 Apr 23; 105 (16): 1897-903).
15.Bucher HC, et al, meta-analysis suggests that dietary and no-dietary intake of n-3 Polyunsaturated Fatty Acids reduces overall mortality, mortality due to myocardial infarction, and sudden death in patients with coronary heart disease. (N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2002 Mar; 12 (4): 298-304).
16.Compared with women who ate fish less than once per month, those with higher intake of fish had a lower risk of total stroke: the multivariate relative risks (RRs), adjusted for age, smoking, and other cardiovascular risk factors, were 0.93 (95% CI, 0.55-1.12) for once per week, 0.73 (95% CI, 0.47-1.14) for 2 to 4 times per week, and 0.48 (95% CI, 0.21-1.06) for 5 or more times per week (P for trend=. 06). Among stroke subtypes, a significantly reduced risk of thrombotic infarction was found among women who ate fish 2 or more times per week (multivariate RR, 0.49; 95% CI, 0.26-0.93). Women in the highest quintile of intake of long chain Omega-3 polyunsaturated fatty acid intakes had reduced their risk of total stroke and thrombotic infarction, with the multivariate RRs of 0.72 (95% CI, 0.53-0.99) and 0.67 (95% CI, 0.42-1.07), respectively. Concluding that the higher consumption of fish and Omega-3 Polyunsaturated Fatty Acids is associated with a reduced risk of thrombotic infarction, primarily among women who do not take aspirin regularly. (Iso H, et al, Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA. 2001 Jan 17; 285 (3): 304-12).
17.An epidemiological study (1960, 1965, 1970, 1985) conducted by Keli SO, et al, showed that the mean fish consumption in 1970 was 17.9 g/d. Men who consumed more than 20 g/d in 1970 had a reduced risk of stroke compared with those who consumed less fish. The hazard ratio (HR) amounted to 0.49% 995% confidence interval [CI], 0.24 to 0.99), and did not change after adjustments for potential cofounders. Fewer strokes occurred among the 301 men who always reported fish consumption between 1960-1970 than among the men who changed fish consumption habits between 1960-1970 or did not consume fish at all (HR, 0.63; 95% CI, 0.34 to 1.16). These findings suggest that consumption of at least one portion of fish per week may be associated with a reduced stroke incidence. (Fish consumption and risk of stroke. The Zutphen Study. Stroke. 1994 Feb; 25 (2): 328-32).   
18.A recent study has been published in which adipose tissue biopsies and segments of coronary arteries were sampled from 40 autopsies. The degree of coronary artery disease was estimated quantitatively by morophometry, and the fatty acid composition of adipose-tissue was analyzed. In this study an inverse relationship between adipose-tissue docosahexaenoic acid concentration and the degree of coronary artery disease was demonstrated. This supports the hypothesis of an antiatherosclerotic effect of fish oils. (Dyerberg J, et al, The Effect of Fish-Oil on Cardiovascular Risk Markers. Omega-3 Fatty Acids: Metabolism and Biological Effects. 1993, p.165).
19.Patients who suffered a myocardial infarction (MI) often have dyslipidaemia, with raised triglycerides and lowered HDL-cholesterol. Fifty-three patients (42 men and 11 woman) all with a history of documented MI and a triglyceride (TG) value >- 2.0 mmol/L were randomly assigned to 12 weeks treatment with 4 g K85 daily or placebo (corn oil), after an initial 8 weeks dietary run-in period. We found a decrease of the plasma TG concentration, reflecting lower VLDL-levels, upon treatment with 4 g omega-3 ethyl ester concentrate K85 daily for 3 months in patients that had sustained a myocardial infarction and were resistant to dietary advice. Minor changes were noted in the plasma LDL and HDL fractions. (Swahn E, Olsson AG, Omega-3-Ethyl Ester Concentrate. Fish Oil for Secondary prevention in Myocardial Infarction. Omega-3 fatty Acids: Metabolism and Biological Effects. 1993, pp. 217-222).
20. According to Burr ML, et al, state that a substantial difference has been achieved between the diets of subjects advised to eat fish and those of the subjects not given this advice. This was confirmed by a significant difference in the EPA content in the plasma fatty acids. (Fish in the Secondary prevention of Myocardial Infarction: A Randomized Control Trial. Health Effects of Fish and Fish Oils. 1989, p.325).
21.www.omega3-drho.com