Alzheimers: Omega-3 Fish Oil Protects The Brain
CategoriesThere is hope for Alzheimer's patients and those who are at risk. A new study by Louisiana State University scientists shows that docosahexaenoic acid (DHA), an omega-3 fatty acid found in coldwater fish such as mackerel, sardines and salmon, reduces levels of a protein known to cause damaging plaques in the brains of Alzheimer's patients.
With a fairly simple type of intervention - a change of diet or just adding some of the fish oil readily available in your local health food store - we now have a valid preventive tool against a disease that has been on the rise, resisting pharmaceutical intervention.
See Scientists Discover How Fish Oil Protects the Brain
As the article mentions, much of the research into omega-3 fatty acids is centered on the prevention of heart disease, one of the major killer diseases in the developed countries. Perhaps a general increase of the proper fatty acids and dietary antioxidants in what we eat could go a long way towards reducing the incidence of not only Alzheimer's but also cardiovascular disease. The damaging rush to control cholesterol levels by the way of lipid-lowering statin drugs (see articles on the inherent dangers of lipitor here and here) could easily come to an early end if these connections were widely recognized by health professionals.
The following somewhat technical overview by Beldeu Singh suggests as much.
- - -
Date: Thu, 29 Sep 2005
From: beldeu singh
Subject: WHY OMEGA-3 FISH OIL PROTECTS YOUR HEART AND BRAIN
The interest in omega-3 fish oil comes from studies in omega-3 polyunsaturated fatty acids which have been observed to help reduce the risk of heart disease. Several studies have indicated that increasing omega-3 essential fatty acids in the diet and reducing saturated fats and omega-6 polyunsaturated fatty acids can significantly reduce the risk of mortality from cardiovascular disease and that includes patients with previous cardiac events. There is strong experimental evidence that omega 3 fatty acids may prevent sudden cardiac death in humans.
There are studies that continue to assess the role of omega-3 fatty acids in cardiovascular disease. One of the most recent fish oil study reported in the Annals of Internal Medicine concluded that omega-3 fatty acids can slow the course of atherosclerosis and may reduce the risk of further heart disease. The Diet and Reinfarction Trial (DART) showed a 29% reduction in overall mortality rates in survivors of a first myocardial infarction who ingested as little as two fish meals per week for two years.
Some experiments suggest fatty acids in fish oils have a potent antiarrythmic effects. In the laboratory, these omega-3 fatty acids prevent myocardial cells from losing calcium, which is essential for normal contractility.
The importance of eating fish may be that it acts at such an early stage to inhibit plaque formation in the process of atherosclerosis. The impact of omega 3 fatty acids on blood cholesterol level is due to the saturated fat reduction, not from the specific effect of the fish oils. Marine omega-3 fatty acids have been shown to effectively lower blood triglyceride levels. The proposed mechanism of action is related to the production of potent eicosanoids.
"Rat diets high in fish oil have been shown to be protective against ischemia-induced fatal ventricular arrhythmias. Increasing evidence suggests that this may also apply to humans. To confirm the evidence in animals, researchers tested a concentrate of the free fish-oil fatty acids and found them to be antiarrhythmic. In this study, the researchers tested
the pure free fatty acids of the 2 major dietary -3 polyunsaturated fatty acids in fish oil: cis-5,8,11,14,17-eicosapentaenoic acid (C20:5-3) and cis- 4,7,10,13,16,19-docosahexaenoic acid (C22:6-3), and the parent omega-3 fatty acid in some vegetable oils, cis-9,12,15--linolenic acid (C18:3-3), administered intravenously on albumin or a phospholipid emulsion.The tests were performed in a dog model of cardiac sudden death. Dogs were prepared with a large anterior wall myocardial infarction produced surgically and an inflatable cuff placed around the left circumflex coronary artery. With the dogs running on a treadmill 1 month after the surgery, occlusion of the left circumflex artery regularly produced ventricular fibrillation in the control tests done 1 week before and after the test, with the -3 fatty acids administered intravenously as their pure free fatty acid. With infusion of the eicosapentaenoic acid, 5 of 7 dogs were protected from fatal ventricular arrhythmias (P smaller than 0.02). With docosahexaenoic acid, 6 of 8 dogs were protected, and with -linolenic acid, 6 of 8 dogs were also protected (P smaller than 0.004 for each). The before and after control studies performed on the same animal all resulted in fatal ventricular arrhythmias, from which they were defibrillated" (George et al, (Circulation. 1999;99:2452-2457: American Heart Association, Inc.)
The research was conducted by researchers at the Department of Physiology, The Ohio State University, Columbus, Ohio (G.E.B.) and Departments of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Mass (J.X.K., A.L.). The results from these experiments indicate that purified -3 fatty acids can prevent ischemia-induced ventricular fibrillation in this dog model of sudden cardiac death.
One key study on diet found an association between dietary intake of omega-3 fatty acids from fish and a reduced risk for sudden cardiac death. Eating as little as one to two fish servings a week may reduce the risk of occurrence of cardiac arrest. The first clinical cardiovascular trial was reported in 1989 by Burr and associates. They performed a randomized controlled trial with a factorial design in 2033 men to determine whether dietary advice on fat, fish, or fiber is beneficial in the secondary prevention of myocardial infarction (MI). No benefits accrued from the fat and fiber advice. At the end of 2 years, however, there was a 29% reduction in mortality in the 1015 men who had received advice to eat oily fish, at least 200- to 400-g portions twice weekly, compared with the 1018 men who had not received such advice. (Burr et al, Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989; 334: 757-61.) Such anthropological studies often provide important information for further research.
Protective effects not linked to levels of total cholesterol
Fortunately there were follow-up studies, and the follow-up findings of the Lyon Diet Heart Study were reported. This study showed a dramatic 70% reduction in all-cause mortality due to reduction in CHD mortality. The reduction in risk was not associated with differences in total cholesterol (De Lorgeril M et al, Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 1994; 143: 1454-1459.)
This finding is of critical importance as it shows that the cardioprotective effect of a Mediterranean style diet is not linked to total cholesterol.
A subsequent study examined traditional risk factors and the rate of cardiovascular complications after myocardial infarction. This classic secondary prevention study that showed a significant reduction (29%) in all-cause mortality over a two-year period in subjects eating as little as two to three fish portions per week (De Lorgeril M et al, Final report of the Lyon Diet Heart Study. Circulation 1999;99:779-785.)
More recently, the data in the Physicians‚ Health Study have been examined to test whether n-3 fatty acid consumption would reduce the risk of sudden death in subjects without a history of preexisting cardiovascular disease. A prospective, nested, case-control analysis among apparently healthy men who were followed up for 17 years in the Physicians‚ Health Study was conducted retrospectively (Albert CM, et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med. 2002; 346: 1113-1118). Ninety-four men were identified in whom sudden cardiac death occurred as the first manifestation of cardiovascular disease. The fatty acid composition of blood, which had been collected at baseline on all subjects, was determined. Baseline blood levels of long-chain n-3 fatty acids were very significantly inversely related to the risk of sudden death. Compared with the men whose blood levels of the n-3 fish oil fatty acids were in the lowest quartile, the relative risk of sudden death was significantly lower among men in the third quartile (relative risk ratio, 0.28) and in the fourth quartile (0.19). The 72% and 81% relative risk reductions are the largest beneficial cardiac effects of the n-3 PUFAs reported thus far in humans.
The alpha-linolenic acid-rich Mediterranean diet which has been shown to have cardioprotective effects indicates several important nutritional implications of the Lyon Diet Heart Study. Dr. Leaf stresses the importance of nutrition and its key role in reducing heart disease risk (Leaf A. Dietary prevention of coronary heart disease. The Lyon Diet Heart Study. Circulation 1999; 99:733-735.)
The absence of a link between the cardioprotective effect of omega-3 oil and its ability to reduce the risk of sudden death in subjects without a history of preexisting cardiovascular disease have a very special significance in understanding the role of omega-3 oil in heart health.
Fatal cardiac arrythmias
The clinical importance of omega-3 studies lie in the fact that 50-60% of deaths in the heart disease cases are sudden cardiac deaths - i.e. deaths that occur within one hour of the symptoms of a heart attack. These deaths are attributed to sustained ventricular arrhythmias or irregular heart beat. Animal studies experiments had shown that fatty acids from n-3 fish oils are stored in cell membranes of heart cells suggesting their peculiar role in preventing sudden heart death caused by fatal arrhythmias. But what initiates fatal arrhythmia? The answer to this lies in biochemistry and physiology. So, Leaf and other researchers cultured neonatal heart cells from rats. Under the microscope, these cells clumped together which as a clump of heart cells beat spontaneously and rhythmically just like the heart as an organ. Toxic agents known to produce fatal arrhythmias in humans were added to the medium bathing the cultured cells, and the effects of adding the n-3 fatty acids were observed. Increased extracellular Ca2+, the cardiac glycoside ouabain, isoproterenol, lysophosphatidylcholine and acylcarnitine, thromboxane, and even the Ca2+ ionophore A23187 were tested. All of these agents induced tachyarrhythmias in the isolated myocytes (Leaf A Circulation. 2003;107:2646, 2003 American Heart Association, Inc.)
Of particular interest are the effects of elevated perfusate Ca2+ and ouabain on the myoctes. Both agents induced rapid contractions, contractures and fibrillation of the myocytes. When EPA was added to the superfusate, the beating rate slowed, and when the high Ca2+ or ouabain was added in the presence of the EPA, no arrhythmia was induced. Furthermore, after a violent fibrillation was induced in the cells by both elevated calcium and ouabain, addition of EPA stopped the arrhythmias, and the cells resumed their fairly regular contractions. The addition of the dilipidated BSA to remove the free fatty acid from the myocytes resulted in recurrence of the arrhythmia. This indicated two important facts as outlined by Dr. Leaf. First, the EPA could be extracted from the cells in the continued presence of the toxins, and the arrhythmia would return, which indicated that the fatty acids were acting without strong ionic or covalent binding to any constituent in the cell membrane. If they had such binding, we would not have been able to extract the EPA from the cells with the albumin. It appears the free fatty acids act directly on the heart cells and need only partition (dissolve) into the hospitable hydrophobic interior of phospholipids of the plasma membranes of myocytes to elicit their antiarrhythmic actions. Second, when we tested the ethyl ester of the EPA, it had no prompt antiarrhythmic action; only the free fatty acid with its negative carboxyl charge was antiarrhythmic. Herein lies the key in understanding the role of omega-3 oil - its role as an antioxidant.
Protection from oxidative stress
My conclusion is that when the neonatal heart cells were subject to toxic chemicals which were either free radicals or generated free radicals in the heart they attached to the cell wall and subjected it to oxidative stress. Under this condition ions flowed in one direction across the cell membrane out of the heart especially magnesium ions, sodium ions, potassium ions and calcium ions thereby severely disrupting metabolic activity in the heart cells resulting in arrhythmia and when this metabolic activity stopped under continued severe oxidative stress, the heart cells die. The carbonyl with the negative charge readily gives its electrons to the free radicals and they become neutral and stable which renders them harmless because in the neutral state they cannot cause oxidative stress. Naturally, when the free fatty with its negative carboxyl was removed, excess free radicals moved in to continue their oxidative stress on the cell membrane of heart cells.
This mechanism clearly suggests that omega-3 oil molecules reside in the cell membrane of cell and it not only protects the heart but also protects other cells in the body including brain cells and cells in the ovarian follicles and testes from free radical oxidative stress as well as lipid peroxidation of the cell wall. Its free radical scavenging activity in brain cells may explain why intake of omega-3 fish oil may reduce depression or delay or prevent brain impairment caused by free radicals or heavy metal ions. In this regard, it may also protect T4 cells from oxidative damage and prevent entry of the HIV virus into the cell.
Health problems such as those induced by toxic chemicals in the experiment conducted by Dr. Leaf and associates on neonatal heart cells must also be noted in other chemicals. Vioxx is a good example. Vioxx had known severe and serious side effects. Its label had warned as follows; "If you experience an allergic reaction, intestinal bleeding, or kidney problems while taking Vioxx stop treatment and seek medical help immediately". Less severe and more common side effects of Vioxx that do not require you to stop treatment include the following:
» Headache » Dizziness » Diarrhea » Nausea and/or vomiting » Heartburn, stomach pain and upset » Swelling of the legs and/or feet » High blood pressure » Back pain » Tiredness » Urinary tract infectionIn one study, there was an increased relative risk for confirmed cardiovascular events, such as heart attack and stroke, beginning after 18 months of treatment in the patients taking Vioxx compared to those taking placebo. The results for the first 18 months of the approved study did not show any increased risk of confirmed cardiovascular events on Vioxx, and in this respect, are similar to the results of two placebo-controlled studies described in the current U.S. labeling for Vioxx. So, prolonged oxidative stress from toxic medication can initiate cardiovascular disease in humans through free radical chain generating reactions in the body.
Particulate air pollution
Studies on free radical induced heart problems must consider one very interesting study on humans at a hospital in the US. At Boston's Beth Israel Deaconess Medical Center, studies of hospital admissions and emergency department visits have linked exposure to particulate air pollution with increased risk of cardiovascular diseases. This study is the first to examine short-term transient effects of air pollution on the risk of heart attack. This study focused on levels of the smaller pollutants. These tiny particles are known as PM2.5 because they measure less than 2.5 micrometers in diameter. They are so small that they can get past the normal defense mechanisms in the lungs and penetrate deeply into the air exchange regions or alveoli and may pass into the blood stream.
The risk of heart attack was higher among those with elevated PM2.5 in the two hours before the onset of symptoms. In addition, researchers observed a higher heart attack risk when 24-hour average exposure to PM2.5 was considered, indicating a delayed response to the particles. Data analysis considering both time windows jointly revealed a 48 percent higher risk of heart attack when PM2.5 concentration increased by 25 micrograms per cubic meter of air (µg/m3) in the two-hours before symptoms began. Fine particulate air pollution is produced primarily by combustion processes in automobile engines, power plants, refineries, smelters and other industry and this explains why sudden cardiac death is a common occurrence in industrialized nations and in people caught in traffic jams. Larger pollutant particles of airborne dust and debris from farming, construction work and mining are far less likely to trigger heart attack but they generate free radicals in the body.
The fairly rapid effect of very fine pollutants suggests that these free radicals may stick onto the cell walls of cells of the heart muscle and cause a one-way transport of magnesium ions across the cell membranes out of the cells, triggering a magnesium deficiency in the heart cells. It may be case of rapid direct free radical action on cell walls causing sudden heart failure. Excess magnesium in circulating blood may end up in the brain where it may cause complications while it selectively impairs the release of nitric oxide from the coronary endothelium and stimulate vasoconstriction.
It may be concluded that very fine pollutants and even heavy metals such as lead, cadmium and mercury pose a threat very similar to free radicals on the cell membranes and have the potential to induce arrhythmia if they are present in sufficient amounts or if the antioxidant level is low in the blood or in the cell walls. Older people, especially those above 40 years of age may be at a higher risk and to this group we can include people with a low antioxidant diet.
In older people there is a reduction in enzyme and vitamin activity. The absorption of vitamins and minerals drops after the age of 40. With increase in age the production of enzymes in the body also drops and the antioxidant defense mechanism naturally becomes less efficient. By the age 40, the enzyme levels drop by 50%. At 50 it drops to 10% and by 70, the enzyme level is only at 5% of the peak levels during prime of youth. Thus, with advancing age, the repair mechanisms at the molecular level are slow while excess free radical scavenging activity is extremely low. At this stage there is accumulation of free radicals in the body which can lead to abnormal functions in cells including mutagenesis and cancers while the aging process sets in and the body may suffer a host of degenerative illnesses.
Oxidative stress in the body leading to such problems may begin much earlier due to exposure to free radicals or free radical generating chemicals such as cigarette smoke, alcohol and drug abuse or toxicity from drugs or heavy metals or exposure to radiation for which conditions there is no specific cure. One of nature's way may lie in increasing blood antioxidant levels with antioxidants that activate enzymes involved in the Krebs cycle that are sensitive to peroxide inactivation or sensitive to inactivation by free radicals. This process will enhance the production of antioxidant enzymes while increasing the absorption of minerals and boost vitamin activity in the body and have a restorative effect on the hormonal system.
Scavenging free radicals
There is considerable epidemiological evidence indicating an association between diets rich in fresh fruits and vegetables and a decreased risk of cardiovascular disease and certain forms of cancer (Qian et al. Journal of Zhejiang University SCIENCE 2004 5 (6): 6767-683). The active dietary constituents identified as antioxidants (such as vitamins, carotenoids, polyphenols, sterols etc) are known to provide protective effect by scavenging free radicals and can be expected to prevent chronic illnesses due to free radical damage to cells in the body. While the human body is endowed with endogenous free radical scavenging antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase/reductase, it requires exogenous antioxidants such as vitamins and B-carotene: yet the antioxidant defense system may prove to be insufficient in critical situations such as contamination by heavy metals or in oxidative stress wherein the production or presence of free radicals increases significantly as when Dr. Leaf subjected the clump of neonatal heart cells to toxic chemicals. That very same experiment also proves that when antioxidants (in his experiment was the free fatty acid with its negative carboxyl charge) are made available to the point of oxidative stress in sufficient quantities the oxidative stress is removed and the disease condition (in his case was arrhythmia) was reversed (and the cells resumed their fairly regular contractions) making a strong case for naturopathy.
Protecting the brain
Brain cells have a layer of fat called myelin. Myelin is manufactured by Schwann's cells, and consists of 70-80% lipids (fat) and 20-30% protein. Myelin coats and insulates the axon (except for periodic breaks called nodes of Ranvier), increasing the speed of transmission along the axon. Hence omega-3 fish oil ought to protect brain cells in the same way it protects heart cells as shpown in the Leaf experiment.
The four important facts from studies that omega-3 fatty acids-; (1) act to inhibit plaque formation in
artieries; (2) can slow the course of atheroscelerosis; (3) protect the heart from ventricular arrythmias when considered with the fact that it is the oxidation of LDL (bad cholesterol) that promotes plaque formation and the progress of atheroscelerosis, leads to the conclusion that the carbonyl group in omega-3 fish oil acts as an antioxidant, readily donating its electron to free radicals to neutralize them and render then harmless. Excess free radicals and reactive oxygen species in the blood especially when the antioxidant levels in the blood drop with advancing years or when antioxidants in the blood are depleted by cigarette smoke or prolonged used of toxic medication, there is an increase in the chance of oxidation of increasing amounts of LDL and that naturally increases the chances of oxidized LDL attaching to the arterial walls as plaque thereby reducing the blood flow in heart vessels and resulting in an impairment in heart function and a threat to health.There are many studies in this direction or approach which point to the development of an antioxidant pharmacopoeia in the near future in the practice of medicine. One good study involved a research on the effects of cruciferous vegetable extracts on female patients with abnormal cervical cells. The extract indole-3-carbonyl was given and after 12 weeks the abnormal cells had disappeared in half the treated patients whereas the placebo patients showed no improvement (Bell MC et al, Gynecol Oncol 2000:78:123-9). Similar studies must be conducted in which free fatty acid with its negative carboxyl is given together with indole-3-carbonyl extract to patients with certain patients to achieve better results than the Bell study.
It becomes advisable to consume a broad range of antioxidants through our diets and that must include a variety of fruits, vegetables, nuts and oils such as omega-3 fish oil without heavy metal contamination. That notion goes along with evolutionary, which means taking into account the environment in which primate and hominid evolution and later homo sapiens took place, spanning a time period 15-20 million years. That also simultaneously seems to suggest a low carbohydrate diet and if rice is to be consumed, it would be better to take small quantities of unpolished rice. Similarly, it dictates ingesting raw sugar rather than white sugar. With regard to how much of these essential n-3 fatty acids we should be ingesting, the recent advice of the American Heart Association that everyone should have at least 2 meals of oily fish per week appears to be a prudent general recommendation.
Beldeu Singh can be reached at
beldeu@yahoo.com
posted by Sepp Hasslberger on Thursday September 29 2005
updated on Wednesday October 5 2005URL of this article:
http://www.newmediaexplorer.org/sepp/2005/09/29/alzheimers_omega3_fish_oil_protects_the_brain.htm
