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Fish oils and atrial fibrillation

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AARHUS, DENMARK. There is impressive evidence that fish oils (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) can materially reduce the risk of sudden cardiac death (cardiac arrest). Researchers at the University of Washington found that men and women who consumed fatty fish just once a week reduced their risk of cardiac arrest by 50%. They believe that fatty fish consumption increases the levels of EPA and DHA in the membranes of red blood cells, which in turn, reduces platelet aggregation and the risk of fatal ventricular arrhythmias. Other researchers have confirmed the protective effect of fish oils against ventricular fibrillation, but very few, if any, studies have investigated the association between fish/fish oil intake and the development of atrial fibrillation.
A group of Danish researchers recently set out to fill in this gap in our knowledge. Their study included 22,528 men and 25,421 women (average age of 56 years) who were free of endocrine and cardiovascular diseases at baseline. All participants completed a detailed semi-quantitative food- and drink-frequency questionnaire and were then followed for an average of 5.7 years. At the end of the follow-up period 374 men (1.7%) and 182 women (0.7%) had been diagnosed with either atrial fibrillation or atrial flutter. About 10% of all participants were being treated for hypertension. Somewhat surprisingly, the researchers found that participants with a high consumption of fatty fish (herring, mackerel, sardines, trout, and salmon) had a significantly higher incidence of new-onset atrial fibrillation than did participants who rarely or never ate oily fish. After adjusting for age, gender, height, BMI, smoking, alcohol consumption, total daily energy intake, systolic blood pressure, treatment for hypertension, cholesterol level, and level of education, the researchers concluded that participants whose daily fish oil intake averaged 1290 mg had a 34% greater risk of developing AF than did those whose intake averaged only 160 mg/day. The difference was statistically significant (p=0.006). The researchers point out that the lack of an observed beneficial effect could have been because the consumption of fish oil was insufficient to prevent arrhythmias. They also say, "We cannot exclude the possibilities that fish oil may prevent the development of atrial fibrillation in patients with symptomatic heart disease or that fish oil may prevent relapses of atrial fibrillation in patients with paroxysmal atrial fibrillation."

Finally, they point out that they did not collect information regarding the use of fish oil supplements and also emphasize that they do not know whether fish oil would have a protective effect against the development of AF in populations with a low intake of fatty fish (such as the United States). Their overall conclusion was that, "Consumption of omega-3 fatty acids from fish is not associated with a reduction in the risk of developing atrial fibrillation or flutter."

Frost, L and Vestergaard, P. n-3 fatty acids consumed from fish and risk of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study. American Journal of Clinical Nutrition, Vol. 81, January 2005, pp. 5-54

Editor's comment: The conclusions of the Danish study are fully in line with the results of the two LAF surveys, which investigated the association between afib severity and fish oil intake. None of our surveys have ever found that a high fish oil intake is associated with fewer or shorter episodes. This, as pointed out by the Danish researchers, could be due to the fact that the fish oil intake was not high enough to provide a benefit. However, this would seem unlikely since the highest intakes were well above those required to provide excellent protection against ventricular fibrillation. The finding that heavy fish consumers have a statistically significant 34% greater risk of developing atrial fibrillation or flutter is worth noting. It is possible that this could be due to the higher mercury intake associated with higher fish consumption. Several studies have shown that people with a high consumption of certain fish have higher mercury levels in their blood and toenails. The lesson here is that the safest way to obtain a high intake of EPA and DHA is through the consumption of a high quality, molecular distilled fish oil supplement. In conclusion then, even though there may be no scientific evidence that fish oils can prevent the development of AF, there are still numerous reasons for ensuring an adequate intake (1-2 grams/day). The evidence that they help prevent cardiac arrest, reduce triglyceride levels, combat inflammation, and help prevent stroke and heart attack makes fish oils a must supplement for all, whether an afibber or not.

Determination of omega-3 fatty acids in heart tissue
KANSAS CITY, MISSOURI. There is overwhelming evidence that omega-3 fatty acids or, more specifically, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main components of fish oils, are highly effective in preventing sudden cardiac death, death from heart disease, and certain arrhythmias. Investigations involving individual heart cells have shown that EPA + DHA prolong the refractory state of the cells by interacting with fast-acting sodium channels and L-type calcium channels. It is thus clear that the cardioprotective effect of EPA + DHA is intimately associated with the degree to which these two fatty acids are actually incorporated into the heart tissue (myocardium). The ultimate test of the extent of incorporation is, of course, analysis of the heart tissue itself; however this, for obvious reasons, is not terribly practical.
Researchers at the Mid America Heart Institute now report that the EPA + DHA content of red blood cells (RBCs) almost exactly mirrors the concentration in the myocardium. Their study involved 20 heart transplant patients whose EPA + DHA level was measured in heart tissue and red blood cells. The researchers found an almost perfect correlation (r = 0.82) between the content in cardiac tissue and the content of RBCs.

In a subsequent experiment involving 25 heart transplant patients, the researchers measured EPA + DHA in biopsied myocardial tissue, plasma lipids, cells scraped from the cheek (buccal tissue), and red blood cells before and after 6 months of supplementation with 300 mg EPA + 200 mg DHA. The supplementation resulted in a 272% increase in EPA and a 94% increase in DHA in the heart tissue itself. The corresponding increases in plasma lipids, buccal tissue, and RBCs were 365% and 104%, 124% and 95%, and 279% and 84% respectively. The best correlation was between myocardial tissue and RBCs followed by myocardial tissue and buccal tissue. The researchers conclude that EPA and DHA levels in RBCs give an accurate indication of the content in heart cells. Buccal tissue is also a good indicator, but more cumbersome and exacting to obtain than a blood sample. The researchers also point out that RBC content is a good indicator of long-term intake, whereas plasma lipids vary depending on the food consumed on the day immediately preceding the test.

Harris, WS, et al. Omega-3 fatty acids in cardiac biopsies from heart transplantation patients: correlation with erythrocytes and response to supplementation. Circulation, Vol. 110, September 21, 2004, pp. 1645- 49

Fish oils benefit patients with lupus
BELFAST, NORTHERN IRELAND. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease. It can manifest itself via a photosensitive facial rash, fatigue, anorexia, weight loss, and night sweats and can progress to life-threatening involvement of the heart, lungs, kidneys or central nervous system. Flare-ups of SLE are typically followed by periods of clinical remission. Fish oils and copper have both been found useful in the treatment of other inflammatory diseases, so researchers at the University of Ulster decided to see if supplementation with one or both of these would help alleviate SLE symptoms.

Their clinical trial involved 52 SLE patients who were randomly assigned to receive 3 grams/day of fish oil providing 540 mg/day of EPA (eicosapentaenoic acid) and 360 mg/day of DHA (docosahexaenoic acid), 3 mg/day of copper in the form of a copper di-glycinate amino acid complex, both fish oil and copper, or a placebo. The study lasted 24 weeks and participants were assessed at baseline, 6, 12 and 24 weeks.

The researchers found that disease activity at 24 weeks, as measured by the SLAM-R score, was significantly less in the groups that had supplemented with fish oil than in the placebo and copper only groups. They conclude that supplementation with fish oil may be effective in favourably modifying the symptomatic disease activity in SLE.

Duffy, EM, et al. The clinical effect of dietary supplementation with omega-3 fish oils and/or copper in systemic lupus erythematosus. Journal of Rheumatology, Vol. 31, August 2004, pp. 1551-56
Fish oils help prevent prostate cancer

BETHESDA, MARYLAND. Alpha-linolenic acid (ALA) is a major component of flax seed oil and has been associated with significant cardiovascular benefits. Some studies, however, have shown that a high intake of ALA is associated with an increased risk of prostate cancer. A prestigious team of researchers from the National Cancer Institute, the Harvard Medical School, the Harvard School of Public Health, and the Karolinska Institutet in Stockholm has just released the results of a study aimed at settling the controversy as to whether or not ALA is detrimental when it comes to prostate cancer. The researchers also determined the effect of other fatty acids, including fish oils, on prostate cancer risk.

The study involved 47,866 male American health professionals who were followed over a 14-year period beginning in 1986. The participants completed detailed food frequency questionnaires in 1986, 1990 and 1994. By the year 2000, 2965 new cases of prostate cancer had been reported with 448 of these being advanced (metastasized) or fatal. The overall incidence of new prostate cancer detected over the 14-year period was 0.5% per year.

The researchers found no correlation between ALA intake and overall prostate cancer risk, but did observe a strong association between a high ALA intake and the risk of advanced prostate cancer. Men with a high ALA intake (greater than 0.58% of energy or about 1.3 grams/day) were twice as likely to develop advanced prostate cancer as were men with a lower intake (less than 0.37% of energy or about 0.8 grams/day) even after adjusting for all other known variables that could affect the risk. The risk was slightly higher for ALA from non-animal sources than for ALA from meat and dairy sources. There was a trend for red meat, mayonnaise and salad dressings to be associated with a higher risk. The intake of two other abundant fatty acids, linoleic acid and arachidonic acid, was not related to prostate cancer risk.

The team of researchers found a protective effect associated with a high intake of fish oils - eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Men with a daily intake of more than 0.214% of daily energy (about 470 mg/day) were 11% less likely to develop prostate cancer than were men with an intake less than 0.057% of energy (about 125 mg/day). The beneficial effect of EPA plus DHA was particularly pronounced in regard to the incidence of advanced prostate cancer. Fish oil supplements were slightly less effective than fish oils from fatty fish perhaps indicating that vitamin D and vitamin A are necessary to obtain the maximum benefit.

Leitzmann, MF, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. American Journal of Clinical Nutrition, Vol. 80, July 2004, pp. 204-16

Fish oils in cancer prevention
STOCKHOLM, SWEDEN. Several test tube (in vitro) and animal experiments have clearly shown that the long-chain omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main components of fish oil, help inhibit the promotion and progression of cancer. Their beneficial effect is particularly pronounced in hormone-dependent cancers such as breast and prostate cancer. Some, but not all, epidemiologic studies have also found a beneficial effect.

Researchers at Sweden’s famous Karolinska Institutet have just published a comprehensive review of the current knowledge regarding the role of PUFAs in carcinogenesis. They conclude that omega-3 PUFAs are protective against cancer progression, while omega-6 PUFAs, notably arachidonic acid and its derivatives, help promote the growth of cancer. They believe the n-3 PUFAs exert their beneficial effects in several different ways:

They suppress the synthesis of pro-inflammatory eicosanoids from arachidonic acid and thus produce an overall anti-inflammatory effect.
They positively affect gene expression or the activities of signal transduction molecules involved in the control of cell growth, differentiation apoptosis, angiogenesis and metastasis.
They suppress excessive production of nitrogen oxide (NO) during chronic inflammation and thereby help prevent DNA damage and impaired DNA repair.
They decrease estrogen production and thus reduce the estrogen-stimulated growth of hormone-dependent cancer cells.
Fish oils improve insulin sensitivity and cell membrane fluidity and may help prevent metastasis through these effects.
Free radicals and reactive oxygen species produced in cells may attack PUFAs resulting in the formation of more free radicals, specifically hydroperoxides. The hydroperoxides, in turn, may damage DNA ultimately leading to cancer. These effects have indeed been observed in some in vitro experiments, but not in actual human beings. Many studies have shown that fish oils actually retard aging and suppress so-called free radical diseases such as atherosclerosis and cancer. Other studies have shown that a daily EPA + DHA intake in excess of 2.3 grams decreases the production of superoxide, a potent cancer promoter. At least one in vitro and one animal experiment have observed that EPA + DHA kill human breast cancer cells via the formation of hydroperoxides, but that this effect is strongly inhibited by vitamin E. Thus, at this point, it is not entirely clear whether EPA + DHA exert part of their beneficial effect through an increase or a decrease in the production of free radicals and reactive oxygen species. The researchers recommend more work in this area, but emphasize that the major benefits of fish oils probably are associated with their ability to inhibit the synthesis of arachidonic acid-derived, pro-inflammatory eicosanoids. The Swedish researchers also confirm that fatty, cold-water fish are the best sources of EPA and DHA and that the conversion rate of alpha- linolenic acid (flaxseed oil) to EPA is very low, even in healthy humans – probably in the order of 2-5%.

Larsson, SC, et al. Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. American Journal of Clinical Nutrition, Vol. 79, June 2004, pp. 935-45

Editor’s comment: There would appear to be a growing body of evidence to the effect that long-chain omega-3 fatty acids, in particular EPA and DHA, help prevent the promotion and progression of certain cancers, notably hormone-dependent ones. Some of the mechanisms involved in this protective effect are well understood. While others, notably the role of free-radical formation, clearly need more work. Of some concern is the uncertainty surrounding vitamin E. Both vitamin E and fish oils have been found to help prevent hormone- dependent cancers, so taking both for cancer prevention is probably desirable. The situation is much less clear when it comes to slowing down an existing cancer and preventing it from spreading. Should one just rely on vitamin E (particularly the succinate form) or place one’s faith in fish oils, or is the combination of the two the best way to go? Clearly more research in this area is urgently required.

Lifespan and fatty acids
Australian researchers have just released the results of a fascinating study which links longevity with the fatty acid composition of cell membranes. They discovered animals that have a preponderance of saturated fatty acids in their membranes have a slower metabolism and live far longer than animals that have lots of polyunsaturated fats in their membranes. The key fatty acid would seem to be the highly polyunsaturated docosahexaenoic acid (DHA), a major component of fish oils. It turns out that cell membranes rich in DHA are a lot more fluid than membranes rich in saturated fatty acids. This results in a faster metabolism and quicker reaction times all around, especially in the brain and eyes. Unfortunately, DHA is also an easy target for free radicals that leak out of mitochondria as they produce energy. The end result is that fluid, unsaturated membranes deteriorate and age faster than more viscous, saturated ones. Free radical attacks can also damage proteins and DNA. On the other hand, a shortage of DHA in cell membranes can lead to serious problems like high blood pressure, heart disease, diabetes, and depression. So you guessed it – you can't win! About the only proven way of increasing longevity is by restricting calorie intake which apparently removes some DHA from membranes.

Fox, Douglas. The speed of life. New Scientist, November 1, 2003, pp. 42-45

Antiarrhythmic properties of fish oils
CHIETI, ITALY. Several large clinical trials have confirmed the ability of fish oils to prevent sudden cardiac death in both presumably healthy subjects as well as in patients having suffered a heart attack (myocardial infarction). Considering that sudden cardiac death, largely caused by ventricular fibrillation, accounts for somewhere between 250,000 and 300,000 deaths every year in the US alone, it is clearly highly significant that a diet rich in oily fish or fish oil supplements may reduce the incidence of sudden cardiac death by up to 45%.

Researchers at the universities of Chieti and Pisa recently published a review of the current "state-of-the-art" in regard to fish oils and arrhythmias. Highlights are:

Supplementation with fish oils shows its beneficial effect within a few weeks.
It is unlikely that the biological effects of fish oils would vary depending on source (oily fish or fish oil supplement).
Animal experiments have shown that fish oils act on individual myocytes (heart cells) to inhibit the excitatory Na+ current, stabilize the inactivated state of the Na channel, and prolong the effective refractory period of the cardiac cycle. The L-type Ca++ current is also inhibited by fish oils and the outward flow of K+ is reduced. All effects which would reduce the tendency to arrhythmia either by decreasing automaticity or by interfering with re-entry circuits.
Two small trials have shown a reduction in PVCs (premature ventricular complexes) with fish oil supplementation. In one of these trials 34 participants with frequent PVCs, but no life- threatening arrhythmias were given 2.4 grams/day of fish oils while the control group was given sunflower seed oil which is rich in linoleic acid (an omega-6 fatty acid). PVCs decreased by 48% in the fish oil group as compared to 25% in the sunflower seed group.
Fish oils have been shown to decrease heart rate variability and there is some suggestion that they may also reduce sympathetic and increase parasympathetic (vagal) activity in the autonomic nervous system.
Prostaglandins and thromboxane A2, produced from arachidonic acid, are mostly proarrhythmic so a high intake of omega-6 fatty acids may be detrimental.
Although most research, so far, has focused on the effect of fish oil on life-threatening ventricular arrhythmias it is likely than many of the findings may also be applicable to atrial fibrillation.
De Caterina, Raffaele, et al. Antiarrhythmic effects of omega-3 fatty acids: from epidemiology to bedside. American Heart Journal, Vol. 146, September 2003, pp. 420-30

Fish consumption lowers heart rate
LILLE, FRANCE. There is increasing evidence that an elevated heart rate is associated with an increased risk of sudden cardiac death. In the Paris Prospective Study, which included more than 7700 men followed up for 23 years, the mean difference between controls and patients who died suddenly from cardiac arrest was 4.1 beats per minute.

A group of European researchers now reports that regular fish consumption can lower heart rate by as much as 2 bpm. Their study included 9758 men aged 50 to 59 years from four European cities (Belfast, Lille, Strasbourg, and Toulouse). Twenty-seven per cent of the men consumed fish less than once per week, 47% consumed fish once a week, 20% twice a week, and the remaining 6% more than twice a week. The average heart rate (adjusted for age, physical activity, smoking, alcohol consumption, etc) was 67.5 bpm in men consuming fish less than once per week and 65.6 bpm in men consuming fish more than twice per week.

Fish consumers also had lower triglyceride levels, lower blood pressure (both systolic and diastolic), and higher levels of beneficial HDL cholesterol than did non-consumers. The erythrocyte content of DHA (docosahexaenoic acid) in the blood was found to be inversely correlated with heart rate.

The researchers point out that there is considerable evidence that omega-3 fatty acids such as those found in fish and fish oils stabilize the electrical activity of heart cells by elevating the action potential threshold and prolonging the relative refractory time. There is also evidence that a high omega-3 content of blood cells and serum cholesterol esters is associated with increased heart rate variability. A higher heart rate variability has been associated with a decreased risk of cardiac disease and a longer lifespan.

Dallongeville, Jean, et al. Fish consumption is associated with lower heart rates. Circulation, Vol. 108, August 19, 2003, pp. 820-25

Fish oil protects against Alzheimer's disease
CHICAGO, ILLINOIS. High levels of the omega-3 fatty acid docosahexaenoic acid (DHA) are found in the more active areas of the brain including the cerebral cortex, mitochondria, synaptosomes, and synaptic vesicles. At least one epidemiologic study has shown that patients with Alzheimer's disease (AD) have significantly lower levels of omega-3 fatty acids in their plasma phospholipids than do age-matched controls. Researchers at the Rush-Presbyterian-St. Luke's Medical Center now report that older people can reduce their risk of developing AD by increasing their intake of fish and fish oil (DHA). Their study included 815 men and women over the age of 65 years who had showed no sign of AD during a thorough baseline examination. About 2 years after the examination all participants completed a 154-item food frequency questionnaire and provided information about their current use of supplements. After another 2 years all participants were again subjected to a thorough, structured neurologic clinical evaluation to establish the presence or absence of AD. A total of 131 study participants were found to have developed AD over the 3.9-year follow-up period.
The researchers found that participants who consumed fish just once a week had a 60% lower risk of developing AD than did those who rarely or never ate fish. They also observed that participants whose daily intake of DHA was about 100 mg/day had an incidence of AD which was 70% lower than those with an intake of 30 mg/day or less.

Eicosapentaenoic acid (EPA), another component of fish oil, showed no appreciable effect; however, the maximum intake was only 30 mg/day. A high total intake of omega-3 fatty acids was also strongly correlated with a reduced risk for AD. Participants with an intake of 1.6 – 4.1 grams/day had a 70% lower risk than those with an intake below 1.05 grams/day. Alpha-linolenic acid (flaxseed oil) intake was not associated with AD risk except in the case of people with the APOE-epsilon 4 allele where a high intake was strongly protective. The researchers conclude that an increased intake of fish or omega-3 fatty acids, especially DHA, can substantially reduce the risk of developing Alzheimer's disease.

Morris, MC, et al. Consumption of fish and n-3 fatty acids and risk of incident of Alzheimer's disease. Archives of Neurology, Vol. 60, July 2003, pp. 940-46

Friedland, RP. Fish consumption and the risk of Alzheimer disease. Archives of Neurology, Vol. 60, July 2003, pp. 940-46

Editor's comment: High doses of fish oils should always be accompanied by vitamins E and C in order to prevent oxidation of the oil.

Fish oils benefit the heart
SOUTHAMPTON, UNITED KINGDOM. It is well established that populations with a high consumption of oily fish have a lower incidence of heart disease and several studies have confirmed that fish oils (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) are the protective components. There is also impressive evidence that they help prevent atherosclerosis, lower blood pressure, reduce triglyceride levels, and are highly protective against both fatal and non-fatal heart attacks. Fish oils also have antiarrhythmic effects and help prevent blood clotting.

Recent research concludes that perhaps the most important effect of fish oils, when it comes to preventing cardiovascular disease, is their ability to stabilize atherosclerotic plaque by reducing the infiltration of inflammatory and immune cells (lymphocytes and macrophages) into the plaque. Heart attacks are now believed to involve the rupture of an atherosclerotic plaque. These plaques come in two main varieties, those with a thin, unstable fibrous cap and those with a thick, stable fibrous cap. A recent study showed that supplementation with 1.4 grams/day of fish oil significantly reduced macrophage infiltration and resulted in a substantial shift towards a preponderance of stable, thick-capped plaques. At least two studies have shown that the beneficial effects of fish oils on heart health become clear after about 2 months.

Calder, Philip C. New evidence in support of the cardiovascular benefit of long-chain n-3 fatty acids. Italian Heart Journal, Vol. 4, July 2003, pp. 427-29

Fish oils benefit women with diabetes
BOSTON, MASSACHUSETTS. Several studies have found a clear inverse association between the consumption of fish and fish oils and the risk of coronary heart disease (CHD) and sudden cardiac death. However, it is not known whether this protective effect extends to diabetes patients. Researchers at the Harvard Medical School have just concluded a study to examine this. Their study included 5103 female nurses with diabetes, but free of cardiovascular disease and cancer at entry. Between 1980 and 1996 there were 362 cases of CHD (7.1%) and 468 deaths from all causes in the study group (9.2%). The causes of death were CHD or stroke – 161, cancer – 172, and other causes – 135.

Study participants completed detailed food frequency questionnaires in 1980, 1984, 1986, 1990 and 1994. The researchers noted a strong correlation between the risk of CHD and fish intake. Women who consumed fish once a week had a 40% lower risk of CHD than did women who consumed fish less than once per month. Eating fish 5 times per week reduced CHD risk by 64% and overall mortality by 52%. Only dark-meat fish (mackerel, salmon, sardines, bluefish, and swordfish) and shrimp, lobster and scallops showed a beneficial effect. The researchers also calculated the amount of fish oils (eicosapentaenoic acid and docosahexaenoic acid) obtained from the diet and found that study participants with an average intake of just 250 mg/day had a 31% reduction in CHD and a 37% reduction in death from all causes compared to participants with a low (40 mg or less) daily intake. The researchers note that fish oil supplementation does not impair glycemic control and suggest that regular fish consumption should be considered as an integral part of a healthy diet for the management of diabetes.

Hu, Frank B., et al. Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. Circulation, Vol. 107, April 15, 2003, pp. 1852-57
Grundy, Scott M. N-3 fatty acids: priority for post-myocardial infarction clinical trials. Circulation, Vol. 107, April 15, 2003, pp. 1834-36 (editorial)

Editor's comment: Swordfish, bluefish and king mackerel have high levels of mercury or methyl mercury and should not be eaten regularly, if at all.

Cognitive function and fat intake
PARIS, FRANCE. Several epidemiological studies have shown that a high dietary intake of linoleic acid and a low intake of fish oils (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) are associated with cognitive impairment and an increased risk of dementia. French researchers now report that the fatty acid composition in erythrocytes (red blood cells) is an indicator of the risk of cognitive function decline (ability to learn, think and remember).

Their study involved 246 men and women (aged 63 to 74 years) who had the lipid (fatty acid) composition of their erythrocytes analyzed in 1995. All participants also underwent tests to determine their cognitive function at baseline and after a 4-year follow-up period. The researchers found that study participants with high erythrocyte levels of stearic acid (a saturated fatty acid) had a 91% higher risk of having experienced a significant decline in cognitive function over the 4 years than did participants with average levels. Participants with high levels of linoleic acid (an unsaturated omega-6 acid) had a 59% increased risk of decline while those with high levels of EPA and DHA had a 41% lower risk of experiencing cognitive decline than did those with normal levels.

The researchers suggest that the omega-3 fatty acids EPA and especially DHA help keep the membranes of brain cells more fluid while saturated and omega-6 fatty acids tend to "harden" them. They believe this and the anti-inflammatory effects of EPA and DHA are what help preserve cognitive function.

Heude, Barbara, et al. Cognitive decline and fatty acid composition of erythrocyte membranes – The EVA Study. American Journal of Clinical Nutrition, Vol. 77, April 2003, pp. 803-08

Editor's comment: Stearic acid is found in high quantities in beef, mutton, and pork while omega-6 fatty acids are abundant in vegetables oils such as safflower, sunflower, and soybean oil. The long-chain omega-3 fatty acids (EPA and DHA) are found in fatty fish and fish oils.

Fish oils help prevent stroke and heart attacks
SOUTHAMPTON, UNITED KINGDOM. Atherosclerosis increases the risk of stroke and heart attack because part of the atherosclerotic buildup (plaque) on the inner wall of arteries may dislodge and block smaller arteries in the brain and heart respectively and thus cut off the vital supply of oxygenated blood. Depending on its tendency to break loose from the artery wall plaque is classified as either stable or unstable with the stable form being the least likely to cause problems.
Researchers at the University of Southampton have just completed a clinical trial to see if fish oil supplementation would improve plaque stability and thus help prevent heart attack and stroke. Their study involved 162 patients who were awaiting carotid endarterectomy (an operation involving the removal of atherosclerotic deposits from the carotid artery feeding the brain). The patients were randomly allocated to receive a placebo, fish oil (omega-3 polyunsaturated fatty acid) or sunflower oil (omega-6 polyunsaturated fatty acid) daily from the time they entered the study until the endarterectomy during which atherosclerotic plaque was removed for analysis. The placebo capsules contained an 80:20 blend of palm and soybean oils (a composition which closely matches that of the average UK diet); the sunflower oil capsules contained 1 gram of sunflower oil plus 1 mg of vitamin E (alpha-tocopherol); the fish oil capsules contained 1 gram of fish oil and 1 mg of vitamin E. The participants took 6 capsules daily providing a total to 3.6 grams linoleic acid (in the sunflower oil capsules) or 850 mg EPA (eicosapentaenoic acid) + 500 mg of DHA (docosahexaenoic acid) in the fish oil capsules.

The duration of supplementation varied between 7 and 189 days with the median being 42 days. Upon analysis of the removed plaque the researchers found that the supplemented fish oil (EPA and DHA) had been readily incorporated into the plaques and had resulted in favourable changes. Plaque from fish oil treated patients tended to have thick fibrous caps and no signs of inflammation indicating more stability. Plaques from the control and sunflower oil groups, on the other hand, tended to have thin fibrous caps and signs of inflammation indicating less stability. The number of macrophages (large scavenger cells) in the plaque of fish oil treated patients was also significantly less than the number observed in the control and sunflower oil groups.

The researchers conclude that the increased plaque stability observed in the fish oil treated patients could explain the reduction in fatal and non-fatal heart attacks and strokes associated with an increased intake of fish oils.

Thies, Frank, et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. The Lancet, Vol. 361, February 8, 2003, pp. 477- 85

Older people benefit from fish oils
SEATTLE, WASHINGTON. There is abundant evidence that a diet rich in fatty fish is highly protective against death from heart disease in people 65 years of age and younger. Now researchers at the University of Washington and the Fred Hutchinson Cancer Research Center have extended the evidence to include people with an average age of 78 years. Their study included 54 men and women who had suffered a fatal heart attack or other fatal ischemic heart disease event, 125 people who had suffered a non-fatal heart attack, and 179 matched controls. All study subjects had blood samples drawn about 2 years prior to the cardiovascular event. The phospholipid phase of the blood plasma was isolated and analyzed for its contents of the fatty acids eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), and linoleic acid (LA). EPA and DHA are the main constituents of fish oil, ALA is found in canola, flax and soybean oils, and LA is a main constituent of safflower and cottonseed oils.

The researchers found that subjects with a high phospholipid content of EPA + DHA had a 70% lower incidence of fatal heart disease than did those with a lower level (4.1% versus 3.3% of total fatty acids). Participants with a high level of ALA had a 50% reduced risk of fatal heart disease. Subjects with a high level of LA, on the other hand, had a 2.4 times higher incidence of fatal heart disease than did those with a lower level. There was no association between the levels of the fatty acids and the incidence of non-fatal heart attacks. The researchers ascribe this to the fact that EPA and DHA (and perhaps ALA) are known to prevent ventricular arrhythmias – the main factor in sudden cardiac death. Ventricular arrhythmias are not involved in non-fatal heart attacks.

The researchers conclude that their findings lend further support to the recommendation from the American Heart Association to consume 2 fish meals (preferably fatty fish) per week. Dr. William Harris of the University of Missouri, in commenting on the results, suggests that a combined daily intake of 1 gram of EPA + DHA is both safe and prudent, but that supplementation with fish oil capsules may be required to achieve this goal.

Lemaitre, RN, et al. n-3 polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. American Journal of Clinical Nutrition, Vol. 77, February 2003, pp. 319-25

Harris, WS. n-3 long-chain polyunsaturated fatty acids reduce risk of coronary heart disease death: extending the evidence to the elderly. American Journal of Clinical Nutrition, Vol. 77, February 2003, pp. 279-80 (editorial)

Fish oils for heart health
The American Heart Association has acknowledged that the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential for heart health. They now recommend that people without heart disease eat fish 2 or more times per week and consume a diet rich in alpha-linolenic acid. Heart disease patients should consume about 1 gram of EPA and DHA daily. Patients with high triglyceride levels may benefit from supplementing with 2 to 4 grams of EPA plus DHA per day in capsule form. EPA and DHA are the main components of fish oils.

Arteriosclerosis, Thrombosis and Vascular Biology, Vol. 23, February 2003, pp. e23-e31, 151- 52
Omega-3 fatty acids and cholesterol

GUELPH, CANADA. Supplementation with fish oils (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) is highly effective in lowering the blood level of triglycerides. High triglyceride levels are a major risk factor for heart disease particularly in women. Some studies have shown that fish oil supplementation may increase the level of LDL-cholesterol (the "bad" kind), but that the ratio of HDL-cholesterol (the "good" kind) to LDL remains unchanged.
Researchers at the University of Guelph have just completed a study aimed at determining if taking gamma-linolenic acid (GLA) along with the fish oil would maintain the benefits of lowering triglyceride levels without the possible commensurate disadvantage of increasing LDL levels. Their study involved 32 women between the ages of 36 and 68 years who were assigned to one of four supplementation protocols for 28 days.

Group A: 4 grams of EPA + DHA daily (control group)
Group B: 4 grams of EPA + DHA + 1 gram of GLA
Group C: 4 grams of EPA + DHA + 2 grams of GLA
Group D: 4 grams of EPA + DHA + 4 grams of GLA
At the end of the trial period LDL concentrations were about 12% lower than at baseline in groups C and D and within plus or minus 2% of baseline values in groups A and B. Triglyceride concentrations were 40% lower at day 28 in group A, 39% lower in group B, and 35% lower in group C. There was no difference in triglyceride level in group D between day 0 and day 28 indicating that the GLA overpowered the effect of EPA and DHA on triglyceride reduction. The important LDL/HDL ratio was reduced by 6% in group B, 15% in group C, and 20% in group D. The researchers conclude that a supplementation protocol involving 4 grams of EPA + DHA plus 2 grams of GLA per day is optimum for achieving desirable cholesterol and triglyceride levels in women. They estimate that this protocol reduces the risk of having a heart attack within the next 10 years by 43%.

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