Omega 3 Fatty Acids
Omega-3 fatty acids benefit the heart of healthy people, and those at high risk of — or who have —cardiovascular disease.
Omega-3 Fatty Acids are a dietary supplement found mainly in cold water fish, such as mackerel, herring, halibut, cod, shark and salmon. Lesser amounts of it are found in tuna and shrimp. Another good source of Omega-3 fatty acids can be obtained in flaxseed oil. Arthritis sufferers can experience beneficial results by using a supplement containing omega-3 fatty acids. Due to the effects on the immune response and on cell mediators—such as prostaglandins, cytokines, and leukotrienes--in the body that direct the inflammatory response involved in rheumatoid arthritis, use of supplements containing fish oils or plant oils have been shown to reduce the pain, ,swelling and stiffness of arthritis. Also, arthritis medications can be reduced with its use. Two chemicals contained in omega-3 fatty acids are Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA).
How it Works in Your Body:
Studies suggest that omega-3 fatty acids may be helpful in treating a variety of conditions. The evidence is strongest for heart disease and problems that contribute to heart disease, but the range of possible uses for omega-3 fatty acids include:
Where it is Found:
How to Use:
Consult your doctor if you:
Infants and Children:
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New Findings About Omega-3 Fatty Acids and Depression
Importance of Omega Three Fats in Health and Disease
By Dr. William Connor
Interest in omega-3 fatty acids began some 30 years ago and there are now several thousand papers in the scientific literature supporting their benefits.
There is little doubt that omega-3 fatty acids are important in human nutrition. They are significant structural components of the cell membranes of tissues throughout the body and are especially rich in the retina, brain, and sperm, in which docosahexaenoic acid (DHA) constitutes 36.4% of total fatty acids
Membrane fluidity is essential for proper functioning of these tissues. In the retina, where omega-3 fatty acids are especially important, deficiency can result in decreased vision and abnormal electroretinogram results.
Omega-3 Fatty acids are essential fatty acids, necessary from conception through pregnancy and infancy and, undoubtedly, throughout life.
The ratio of omega-6 to omega-3 fatty acids has increased in industrialized societies because of increased consumption of vegetable oils rich in omega-6 fatty acids, ie, linoleic acid, and reduced consumption of foods rich in omega-3 fatty acids.
Another important feature of omega-3 fatty acids is their role in the prevention and modulation of certain diseases that are common in Western civilization.
The following is a partial list of diseases that may be prevented or ameliorated with omega-3 fatty acids, in descending order of the strength of the available evidence as perceived by this reviewer:
Cardiovascular Benefits Of Omega-3 Fatty Acids
The strongest evidence of a relation between omega-3 fatty acids and disease is the inverse relation between the amount of omega-3 fatty acids in the diet and in blood and tissues and the occurrence of coronary heart disease and its many complications.
Effects of omega-3 fatty acids on coronary heart disease have been shown in hundreds of experiments in animals, humans, tissue culture studies, and clinical trials.
Omega-3 fatty acids from fish have been shown to be protective of heart disease and, by a variety of mechanisms, prevent deaths from coronary disease, particularly cardiac arrest.
The unique properties of these fatty acids in coronary heart disease first became apparent in the investigations of the health status of Greenland Eskimos who consumed diets very high in fat from seals, whales, and fish and yet had a low rate of coronary heart disease.
Further studies clarified this paradox. The fat the Eskimos consumed contained large quantities of the very-long-chain and highly polyunsaturated fatty acids of EPA and DHA, which are abundant in fish, shellfish, and sea mammals and are scarce or absent in land animals and plants. EPA and DHA are synthesized by phytoplankton, which are the plants of the waters and the base of the food chain for marine life.
Dietary omega-3 fatty acids act to prevent heart disease through a variety of actions. They:
EPA and DHA have strong antiarrhythmic action on the heart. In experimental animals and tissue culture systems, EPA and DHA prevent the development of ventricular tachycardia and fibrillation.
Even total mortality has been improved in several studies in which the omega-3 fatty acid intake was increased. In one study, men who consumed salmon 1 time/wk had a 70% less likelihood of cardiac arrest.
In another study overall mortality was decreased by 29% in men with overt cardiovascular disease who consumed omega-3 fatty acids from fish or fish oil, probably because of the reduction in cardiac arrests.
The most recent data on fish consumption and risk of sudden cardiac death were from the Physician's Health Study in the United States in 20551 male physicians. Consumption of 1 fish meal/week was associated with a 52% lower risk of sudden cardiac death compared with consumption of <1 fish meal/month.
Total Death Rate Was Also Lower In Those Who Ate Fish.
Thrombosis, or the tendency to form blood clots, is a major complication of coronary atherosclerosis that can lead to heart attacks.
The omega-3 fatty acids from fish oil have powerful antithrombotic actions. EPA inhibits the synthesis of thromboxane A2 from arachidonic acid in platelets. This prostaglandin causes platelet aggregation and vasoconstriction.
As a result, fish oil ingestion by humans increases the bleeding time and decreases the stickiness of the platelets for aggregation to glass beads. In addition, the administration of fish oil enhances the production of prostacyclin, a prostaglandin that produces vasodilation and less sticky platelets.
The EPA and DHA contained in fish oil fed to experimental animals actually inhibited development of atherosclerosis. There is evidence in both pigs and monkeys that dietary fish oil prevents atherosclerosis by actions other than reducing plasma cholesterol concentrations.
Atherosclerotic plaque formation may also be lessened by the reduction in growth factors after fish-oil consumption. Not only is platelet-derived growth factor diminished by fish oil consumption, but its messenger RNA is reduced. Because atherosclerosis begins with cellular proliferation in response to the influx of cholesterol-rich lipoproteins, the inhibition of this proliferation would greatly reduce the growth of the atherosclerotic plaque.
Reduced Cholesterol Levels
The pronounced effect of fish oil on high blood fats or elevated cholesterol levels is especially well documented and is supported by results of precise dietary studies in which the effects of a diet rich in salmon oil were compared with those of a vegetable oil and a diet high in saturated fat.
Fish oil in particular was shown to lower plasma cholesterol and triglyceride concentrations. Apolipoprotein B production is reduced by consumption of fish oil in comparison with vegetable oils such as safflower or olive oil.
Omega-3 Fatty Acids Essential Components Of Cell Membranes In Infancy
There are 2 critical periods for the acquisition of these essential omega-3 fatty acids: during fetal development and after birth until the biochemical development in the brain and retina is completed.
As already noted, the omega-3 fatty acid DHA is an important constituent of the cell membrane of these neural structures.
Omega-3 fatty acid deficiency is manifested in both the blood and in tissue biochemistry. Of note is a strikingly low concentration of DHA, which may fall to as much as one-fifth of the normal amount.
In addition, the body attempts to replace the deficient DHA with another highly polyunsaturated fatty acid of the omega-6 series. In rhesus monkeys, omega-3 fatty acid -- deficient diets fed to pregnant animals and then continued after birth induce profound functional changes such as reduced vision, abnormal electroretinograms, impaired visual evoked potential, more stereotypic behavior (e.g., pacing), and, perhaps, disturbances of cognition.
Some of these findings have been replicated in infants fed formulas deficient in omega-3 fatty acids. Most studies of premature infants have shown visual impairment and abnormal electroretinograms.
A recent study in full-term infants, in which a standard infant formula was compared with human milk and with formulas enriched with DHA, provided unequivocal evidence of considerable differences in visual evoked potential.
In all of the human studies, the biochemical evidence in plasma, red blood cells, and, occasionally, in tissues from autopsied infants has substantiated the omega-3 fatty acid deficiency state. The lower concentrations of DHA in plasma and erythrocytes are mirrored by lower concentrations in the brain and retina. Formula-fed infants have lower concentrations of brain DHA than do infants fed human milk. They also have lower intelligence quotients.
During pregnancy, both maternal stores and dietary intake of omega-3 fatty acids are of importance in insuring that the baby has adequate amounts of omega-3 fatty acids at the time of birth.
All the polyunsaturated fatty acids, including DHA, are transferred across the placenta into fetal blood. In addition, EPA and DHA in maternal adipose tissue can be mobilized as free fatty acids bound to albumin and be made available to the developing fetus via placenta transport.
Several studies in monkeys have indicated that when the maternal diet is deficient in omega-3 fatty acids, the infant at birth is likewise deficient as evidenced by low DHA concentrations in their plasma and red blood cells.
In humans, it was shown that the administration of fish oil or sardines to pregnant women led to higher DHA concentrations in both maternal plasma and red blood cells and in cord blood plasma and red blood cells at the time of birth.
Once membrane phospholipids have adequate concentrations of DHA, there is an avid retention of these fatty acids in the brain and the retina, even though the diet may subsequently be deficient. Several studies illustrate clearly the effects of omega-3 deficiency in both animals and humans.American Journal of Clinical Nutrition, Vol. 71, No. 1, 171S-175S, January 2000
New Findings About Omega-3 Fatty Acids and Depression
By Alan C. Logan, ND, FRSH
Omega-3 fatty acids are polyunsaturated fatty acids that are considered essential because they cannot be synthesized by the human body. Dietary sources of omega-3 fatty acids include plants (particularly flax, canola, walnuts and hemp) and fish (particularly ocean fish such as sardines, anchovies, salmon and mackerel). Plants contain the parent omega-3, alpha-linolenic acid (ALA), which can be converted into eicosapentanoic acid (EPA) and docosahexanoic acid (DHA).1
Dietary fish and fish oil supplements are a direct source of EPA and DHA. The influence of ALA, EPA and DHA in human health has been the subject of intense research over the last three decades. Although best known for cardiovascular benefits, new findings indicate that the influence of omega-3 fatty acids in mental health, particularly EPA, may currently be underestimated. Epidemiological, experimental and new clinical studies have all shown a strong connection between omega-3 fatty acids, or a lack thereof, and major depression.
These exciting new findings are not entirely surprising when one considers that the brain itself is 60 percent fat and that one-third of all fatty acids are of the polyunsaturated variety.2,3 As discussed below, the current research highlights the critical role of these fatty acids in the central nervous system (CNS).
Omega-3 Intake Declines, Depression Rates Climb
There has been a significant drop-off in omega-3 fatty acid intake within Western countries over the last century. The opposite can be said of omega-6 intake. Although essential, omega-6-rich oils are found in abundance in the North American food supply. Currently these omega-6 oils (corn, safflower, sunflower, cottonseed, sesame) are outnumbering omega-3 fatty acids by a ratio of up to 20:1.4,5
This ratio is a long way off the close to 1:1 omega-6 to omega-3 ratio as recommended by the international panel of essential fatty acid experts in the Journal of the American College of Nutrition.6 The average daily intake of EPA/DHA combined is 130mg in North America, 520mg short of published recommendations and 870mg short of the 1000mg recommended by the American Heart Association in cases of heart disease.1
In direct contrast to the depletion of omega-3 fatty acids from the Western food supply, the rates of depression have dramatically increased in Western countries. In addition, depression is now occurring more commonly in younger persons. The average age of onset of depression has continued to dip over the last 100 years. Scientists investigating the change in rates of depression have made it clear that these findings cannot be explained away by changes in attitudes of health professionals or society, diagnostic criteria, reporting bias, institutional or other artifacts.7,8 Perhaps the inadequate omega-3 intake, the major deviations in fatty acids ratios and the quarter-century-old message that all fat is unhealthy has had an untold influence on rates of depression.
Fish Consumption and Depression
There have been a number of studies that have examined national and international fish consumption data and compared them to rates of depression. Dr. Joseph Hibbeln of the National Institutes of Health is a pioneer in this area. He, and his group, have shown that higher national consumption of fish for a nation equals lower rates of depression versus countries consuming the least amount of fish.9 He has also shown that higher fish consumption is correlated with lower risk of postpartum depression10 and seasonal affective disorder.11
Other researchers have shown that even within a nation, fish consumption is associated with lower risk of depression and higher mental health status.12,13 Finally, researches are now observing increasing rates of depression in regions of the world that are moving away from traditional omega-3-rich diets to typical Western foods.14
Laboratory Tests in Depression
The epidemiological studies clearly suggest that adequate omega-3 fatty acids may be an important protective factor in depression. Correlation, however, does not prove causation. To add to the strength of the epidemiological studies, scientists have examined the levels of omega-3 fatty acids in the blood cells and fat storage cells of those with major depression.
Four studies have shown that those with depression do indeed have lower levels of omega-3 fatty acids in the blood.15-18 One of the studies showed that the lower the level of EPA, the more severe the clinical depression.15 In addition, a recent study showed that the patients with depression have 35 percent less DHA in fat storage cells versus healthy controls.19
Over the last decade, neuroscientists have been examining the consequences of omega-3 deficiencies in the central nervous system. Alterations in serotonin and dopamine levels, as well as the functioning of these two important neurotransmitters is evident in an omega-3 deficiency. The changes observed in omega-3 deficiency in animals is strikingly similar to that found in autopsy studies of human depression.20
In addition to changing serotonin and dopamine levels and functioning, omega-3 deficiencies are known to compromise the blood-brain barrier, which normally protects the brain from unwanted matter gaining access.21 Omega-3 deficiency can also decrease normal blood flow to the brain,22,23 an interesting finding given the studies which show that patients with depression have compromised blood flow to a number of brain regions.24,25 Finally, omega-3 deficiency also causes a 35 percent reduction in brain phosphatidylserine (PS) levels.26 This is also of relevance when considering that PS has documented antidepressant activity in humans.27,28
Mechanisms of EPA/DHA Regulation of Mood
DHA is found in high levels in the cells of the central nervous system (neurons); here it acts as a form of scaffolding for structural support.29 When omega-3 intake is inadequate, the nerve cell becomes stiff as cholesterol and omega-6 fatty acids are substituted for omega-3.30 When a nerve cell becomes rigid, proper neurotransmission from cell to cell and within cells will be compromised.31
While DHA provides structure and helps to ensure normal neurotransmission, EPA may be more important in the signaling within nerve cells.32 Normalizing communications within nerve cells has been suggested to be an important factor in alleviating depressive symptoms.33 In addition, EPA can lower the levels of two important immune chemicals, tumour necrosis factor alpha (TNFa) and interleukin 1 beta (IL-1ß), as well as prostaglandin E2.34
All three of these chemicals are elevated in depression.35-38 In fact, higher levels of TNFa and IL-1ß are associated with severity of depression.39 Finally, EPA has been hypothesized to increase brain-derived neurotropic factor (BDNF), which is known to be lower in depressed patients.20 BDNF is neuroprotective, enhances neurotransmission, has antidepressant activity and supports normal brain structure. BDNF may prevent the death of nerve cells in depression.
There have been some published case reports indicating that flaxseed oil may be helpful in cases of bipolar depression and the anxiety disorder agoraphobia.40 The first controlled clinical trial indicating that omega-3 fatty acids may be of benefit in depression was published in 1999. In this case, 9:6 g of EPA/DHA versus placebo led to longer periods of remission and improvement in depressive symptoms in those with bipolar depression.41
Some researchers theorize that such high doses of EPA/DHA may not be necessary and that low levels of pure EPA may be of benefit.32 In a study published in the American Journal of Psychiatry, researchers showed that just 2g of pure EPA could improve the symptoms of treatment-resistant depression. The researchers found that the EPA (versus placebo), when added to an ineffective antidepressant for one month, significantly improved depressive symptoms.42
A larger study published in Archives of General Psychiatry replicated these findings, however, this time various doses of EPA were examined. Those on ineffective antidepressants were given 1g, 2g or 4g of pure EPA or a placebo in addition to the medication. Interestingly, the 1g daily dose of EPA led to the most significant improvements over the three-month study; it appeared that less was more. There were significant improvements in depressive symptoms, sleep, anxiety, lassitude, libido and thoughts of suicide.43
Researchers from Taiwan Medical University published a recent study in which they found that a 4.4g EPA and 2.2g DHA mix could alleviate depression versus placebo in those with treatment-resistant depression. This was a two-month study involving patients who were on antidepressants that were not working. As with the other omega-3 studies discussed, the fish oil was well tolerated and no adverse events were reported.44
There is also evidence that omega-3 oils may be of benefit in treating depressive symptoms outside of major depressive disorder. Canadian researchers showed that Antarctic krill oil (400mg EPA, 240mg DHA) could improve depressive symptoms associated with premenstrual syndrome.45 Harvard researchers have also shown that just 1g of pure EPA is beneficial in the treatment of borderline personality disorder. This personality disorder, which is particularly difficult to treat, is characterized by both depressive and aggressive symptoms. This was a two-month placebo-controlled study and the results showed that EPA has a mood-regulating effect, improving both depression and aggression versus placebo.46
To date, with one exception, all studies conducted on omega-3 fatty acids and mood have had a positive outcome. The singular negative study examined pure DHA in patients with depression. The results in the case showed that DHA alone was no better than placebo in alleviating depressive symptoms.47
Although an influence of EPA and DHA on brain physiology and structure is apparent, the precise mechanisms whereby omega-3 fatty acids may alleviate depression remain unknown. The results of the clinical trials reinforce the epidemiological and experimental studies, underscoring the importance of adequate omega-3 intake in those with depression.
The long-term studies of fish oil supplements in the area of cardiovascular health, some spanning three-plus years, have shown that they are safe and well tolerated.48,49 Patients with depression or depressive symptoms should discuss omega-3 fatty acids with their health care providers. While scientists continue to unravel the neuropsychological influences of omega-3 fatty acids, it should be recognized that they are not a substitute for appropriate mental health evaluation and care.
Alan C. Logan is a naturopathic physician licensed in Connecticut. Valedictorian of the Canadian College of Naturopathic Medicine, class of 2001, his recent medline-indexed article "Neurobehavioral Aspects of Omega-3 Fatty Acids: Possible Mechanisms and Therapeutic Value in Major Depression" is available to medical professionals by writing to Dr. Logan at firstname.lastname@example.org.