Omega−3 fatty acids (popularly referred to as ω−3 fatty acids or omega-3 fatty acids) are a family of unsaturated fatty acids that have in common a final carbon–carbon double bond in the n−3 position; that is, the third bond from the methyl end of the fatty acid.
Important nutritionally essential n−3 fatty acids are: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), all of which are polyunsaturated. The human body cannot synthesize n−3 fatty acids de novo, but it can form 20-carbon unsaturated n−3 fatty acids (like EPA) and 22-carbon unsaturated n−3 fatty acids (like DHA) from the eighteen-carbon n−3 fatty acid α-linolenic acid. These conversions occur competitively with n−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. Both the n−3 α-linolenic acid and n−6 linoleic acid are essential nutrients which must be obtained from food. Synthesis of the longer n−3 fatty acids from linolenic acid within the body is competitively slowed by the n−6 analogues. Thus accumulation of long-chain n−3 fatty acids in tissues is more effective when they are obtained directly from food or when competing amounts of n−6 analogs do not greatly exceed the amounts of n−3.
Mainly of benefit for women of a certain age, the 18 carbon α-linolenic acid has not been shown to have the same cardiovascular benefits as DHA or EPA. Currently there are many products on the market which claim to contain health promoting 'omega 3', but contain only α-linolenic acid (ALA), not EPA or DHA. These products contain mainly higher plant oils and must be converted by the body to create DHA and therefore considered less efficient. DHA and EPA are made by microalgae that live in seawater. These are then consumed by fish and accumulate to high levels in their internal organs. If a person has ethical concerns about killing fish, or is concerned about mercury and oceanborne contaminants in fish, DHA can be produced directly from microalgae as a vegetarian source. People with certain circulatory problems, such as varicose veins, benefit from such supplements containing EPA and DHA which stimulate blood circulation, increase the breakdown of fibrin, a compound involved in clot and scar formation, and additionally have been shown to reduce blood pressure. There is strong scientific evidence that n−3 fatty acids reduce blood triglyceride levels and regular intake reduces the risk of secondary and primary heart attack.
Some benefits have been reported in conditions such as rheumatoid arthritis and cardiac arrhythmias.
There is preliminary evidence that n-3 fatty acids supplementation might be helpful in cases of depression and anxiety. Studies report highly significant improvement from n-3 fatty acids supplementation alone and in conjunction with medication.
Some research suggests that fish oil intake may reduce the risk of ischemic and thrombotic stroke. However, very large amounts may actually increase the risk of hemorrhagic stroke (see below). Lower amounts are not related to this risk, 3 grams of total EPA/DHA daily are considered safe with no increased risk of bleeding involved and many studies used substantially higher doses without major side effects (for example: 4.4 grams EPA/2.2 grams DHA in 2003 study).
Several studies report possible anti-cancer effects of n−3 fatty acids (particularly breast, colon and prostate cancer). Omega-3 fatty acids reduced prostate tumor growth, slowed histopathological progression, and increased survival. Among n-3 fatty acids [omega-3], neither long-chain nor short-chain forms were consistently associated with breast cancer risk. High levels of docosahexaenoic acid, however, the most abundant n-3 PUFA [omega-3] in erythrocyte membranes, were associated with a reduced risk of breast cancer.. A 2009 trial found that a supplement of eicosapentaenoic acid helped cancer patients retain muscle mass.
A 2006 report in the Journal of the American Medical Association concluded that their review of literature covering cohorts from many countries with a wide variety of demographic concluded that there was no link between n−3 fatty acids and cancer. This is similar to the findings of a review by the British Medical Journal of studies up to February 2002 that failed to find clear effects of long and shorter chain n−3 fats on total mortality, combined cardiovascular events and cancer.
 Cardiovascular disease
In 1999, the GISSI-Prevenzione Investigators reported in the Lancet, the results of major clinical study in 11,324 patients with a recent myocardial infarction. Treatment 1 gram per day of n−3 fatty acids reduced the occurrence of death, cardiovascular death and sudden cardiac death by 20%, 30% and 45% respectively. These beneficial effects were seen already from three months onwards.
In April 2006, a team led by Lee Hooper at the University of East Anglia in Norwich, UK, published a review of almost 100 separate studies into n−3 fatty acids, found in abundance in oily fish. It concluded that they do not have a significant protective effect against cardiovascular disease. This meta-analysis was controversial and stands in stark contrast with two different reviews also performed in 2006 by the American Journal of Clinical Nutrition and a second JAMA review that both indicated decreases in total mortality and cardiovascular incidents (i.e. myocardial infarctions) associated with the regular consumption of fish and fish oil supplements. In addition n−3 has been shown to reduce symptoms of other mental disorders such as aggression and ADHD.
Several studies published in 2007 have been more positive. In the March 2007 edition of the journal Atherosclerosis, 81 Japanese men with unhealthy blood sugar levels were randomly assigned to receive 1800 mg daily of eicosapentaenoic acid (EPA — an n−3 essential fatty acid from fish oil) with the other half being a control group. The thickness of the carotid arteries and certain measures of blood flow were measured before and after supplementation. This went on for approximately two years. A total of 60 patients (30 in the EPA group and 30 in the control group) completed the study. Those given the EPA had a statistically significant decrease in the thickness of the carotid arteries along with improvement in blood flow. The authors indicated that this was the first demonstration that administration of purified EPA improves the thickness of carotid arteries along with improving blood flow in patients with unhealthy blood sugar levels.
In another study published in the American Journal of Health System Pharmacy March 2007, patients with high triglycerides and poor coronary artery health were given 4 grams a day of a combination of EPA and DHA along with some monounsaturated fatty acids. Those patients with very unhealthy triglyceride levels (above 500 mg/dl) reduced their triglycerides on average 45% and their VLDL cholesterol by more than 50%. VLDL is a bad type of cholesterol and elevated triglycerides can also be deleterious for cardiovascular health.
Another study on the benefits of EPA was published in The Lancet in March 2007. This study involved over 18,000 patients with unhealthy cholesterol levels. The patients were randomly assigned to receive either 1,800 mg a day of EPA with a statin drug or a statin drug alone. The trial went on for a total of five years. It was found at the end of the study those patients in the EPA group had superior cardiovascular function. Non-fatal coronary events were also significantly reduced in the EPA group. The authors concluded that EPA is a promising treatment for prevention of major coronary events, especially non-fatal coronary events.
Similar to those who follow a Mediterranean diet, Arctic-dwelling Inuit - who consume high amounts of n−3 fatty acids from fatty fish - also tend to have higher proportions of n−3, increased HDL cholesterol and decreased triglycerides (fatty material that circulates in the blood) and less heart disease. Eating walnuts (the ratio of n−3 to n−6 is circa 1:4 respectively) was reported to lower total cholesterol by 4% relative to controls when people also ate 27% less cholesterol.
A study carried out involving 465 women showed serum levels of eicosapentaenoic acid is inversely related to the levels of anti-oxidized-LDL antibodies. Oxidative modification of LDL is thought to play an important role in the development of atherosclerosis.
 Immune function
Another study regarding fish oil was published in the Journal of Nutrition in April 2007. Sixty four healthy Danish infants from nine to twelve months of age received either cow's milk or infant formula alone or with fish oil. It was found that those infants supplemented with fish oil had improvement in immune function maturation with no apparent reduction in immune activation.
 Brain health
There was yet another study on n−3 fatty acids published in the April 2007 Journal of Neuroscience. A group of mice were genetically modified to develop accumulation of amyloid and tau proteins in the brain similar to that seen in people with poor memory. The mice were divided into four groups with one group receiving a typical American diet (with high ratio of n−6 to n−3 fatty acids being 10 to 1). The other three groups were given food with a balanced 1 to 1 n−6 to n−3 ratio and two additional groups supplemented with DHA plus long chain n−6 fatty acids. After three months of feeding, all the DHA supplemented groups were noted to have a lower accumulation of beta amyloid and tau protein. Some research suggests that these abnormal proteins may contribute to the development of memory loss in later years.
There is also a study published regarding n−3 supplementation in children with learning and behavioral problems. This study was published in the April 2007 edition of the Journal of the Developmental and Behavioral Pediatrics (5), where 132 children, between the ages of seven to twelve years old, with poor learning, participated in a randomized, placebo-controlled, double-blinded interventional trial. A total of 104 children completed the trial. For the first fifteen weeks of this study, the children were given polyunsaturated fatty acids (n−3 and n−6, 3000 mg a day), polyunsaturated fatty acids plus multi-vitamins and minerals or placebo. After fifteen weeks, all groups crossed over to the polyunsaturated fatty acids (PUFA) plus vitamins and mineral supplement. Parents were asked to rate their children's condition after fifteen and thirty weeks. After thirty weeks, parental ratings of behavior improved significantly in nine out of fourteen scales. The lead author of the study, Dr. Sinn, indicated the present study is the largest PUFA trial to date with children falling in the poor learning and focus range. The results support those of other studies that have found improvement in poor developmental health with essential fatty acid supplementation.
A study examining whether omega-3 exerts neuroprotective action in Parkinson's disease found that it did, using an experimental model, exhibit a protective effect (much like it did for Alzheimer's disease as well). The scientists exposed mice to either a control or a high omega-3 diet from two to twelve months of age and then treated them with a neurotoxin commonly used as an experimental model for Parkinson's. The scientists found that high doses of omega-3 given to the experimental group completely prevented the neurotoxin-induced decrease of dopamine that ordinarily occurs. Since Parkinson's is a disease caused by disruption of the dopamine system, this protective effect exhibited could show promise for future research in the prevention of Parkinson's disease.
 Rheumatoid arthritis
Research in 2005 and 2006 has suggested that the in-vitro anti-inflammatory activity of n−3 acids translates into clinical benefits. Cohorts of neck pain patients and of rheumatoid arthritis sufferers have demonstrated benefits comparable to those receiving standard NSAIDs. Those who follow a Mediterranean-style diet tend to have less heart disease, higher HDL ("good") cholesterol levels and higher proportions of n−3 in tissue highly unsaturated fatty acids.
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