Bones & Central Nervous System

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Omega-3 fatty acids are an essential part of the diet.  Research has proven that a healthy intake of omega-3 acids in the diet is necessary for preventing chronic diseases such as heart disease and arthritis.

In addition, omega-3 acids are present
in the brain where they are required for optimal cognitive function.  The Ameri-can Heart Association recommends a high dietary intake of omega-3 fatty acids to protect the body from serious illnesses.

 

(See Ingredients Listing)

 

(Click here for the enormous range of health benefits from Omega-3 according to the University of Maryland Medical Center

(American Heart Association Report)

 

(National Institutes of Health Report)

Unfortunately, typical diets in developed countries deliver large amounts omega-6 (linoleic and arachidonic) acids and low levels of omega-3 fatty acids.  However, throughout evolution, humans were accustomed to diets providing roughly equal amounts of omega-6 and omega-3 fatty acids. During the last 200 years, the ratio of dietary omega-6: omega-3 fatty acids increased from about 1:1 to 20-25:1. Leading health professionals now recommend ratios between 4:1 and 10:1.

Some researchers link the imbalance of omega-6:omega-3 acids to the rise in heart disease.  Omega-6 is an inflammatory substance while omega-3 is anti-inflammatory.  To prevent buildup of deposits in the arteries and to prevent platelet aggregation which can lead to heart attack or stroke, it is important to maintain a healthy balance of omega-6 to omega-3 fatty acids.  Supplementation may be able to help restore this balance.

 

 

 

 

BACKGROUND:

A healthy balance of dietary omega-6 and omega-3 fatty acids appears to be a prerequisite for normal immune function. Dietary linoleic acid, containing a ratio of 18:2 omega-6 acids, is a precursor to arachidonic acid, which contains 20:4.  Arachidonic acid creates pro-inflammatory substances, while the omega-3 fatty acids EPA and DHA provide a natural counterbalance, because they serve as precursors for the anti-inflammatory substances. Among other factors, sufficient dietary levels of EPA, DHA, and other omega-3 fatty acids are also important in the regulation of normal blood lipoprotein and cholesterol levels.

Some research suggests that people with diets low in omega-3 fatty acids are at increased risk for depression.  Patients with ADHD have seen some decrease in symptoms with ALA supplementation. 

 

Links to important sites:

 

American Heart Association

 

National Institutes of Health

 

 

 

 

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Women & Breast Cancer --

According to the University of Maryland Medical Center:

“Women who regularly consume foods rich in omega-3 fatty acids over many years may be less likely to develop breast cancer and to die from the disease than women who do not follow such a diet. Laboratory and animal studies indicate that omega-3 fatty acids can inhibit the growth of human breast cancer cells and may even prevent the spread of cancer to other parts of the body. Several experts speculate that omega-3 fatty acids in combination with other nutrients (namely, vitamin C, vitamin E, beta-carotene, selenium, and coenzyme Q10) may prove to be of particular value for preventing and treating breast cancer.”

The University of Maryland has produced the following report on omega-3 fatty acids:

Overview
Omega-3 fatty acids are considered essential fatty acids, which means that they are essential to human health but cannot be manufactured by the body. For this reason, omega-3 fatty acids must be obtained from food. Omega-3 fatty acids can be found in fish and certain plant oils. It is important to maintain an appropriate balance of omega-3 and omega-6 (another essential fatty acid) in the diet as these two substances work together to promote health. Also known as polyunsaturated fatty acids (PUFAs), omega-3 and omega-6 fatty acids play a crucial role in brain function as well as normal growth and development.

There are three major types of omega 3 fatty acids that are ingested in foods and used by the body: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Once eaten, the body converts ALA to EPA and DHA, the two types of omega-3 fatty acids more readily used by the body. Extensive research indicates that omega-3 fatty acids reduce inflammation and help prevent certain chronic diseases such as heart disease and arthritis. These essential fatty acids are highly concentrated in the brain and appear to be particularly important for cognitive and behavioral function. In fact, infants who do not get enough omega-3 fatty acids from their mothers during pregnancy are at risk for developing vision and nerve problems.

As mentioned previously, it is very important to maintain a balance between omega-3 and omega-6 fatty acids in the diet. Omega-3 fatty acids help reduce inflammation and most omega-6 fatty acids tend to promote inflammation. An inappropriate balance of these essential fatty acids contributes to the development of disease while a proper balance helps maintain and even improve health. A healthy diet should consist of roughly one omega-3 fatty acid to four omega-6 fatty acids.

The typical American diet tends to contain 11 to 30 times more omega-6 fatty acids than omega-3 fatty acids, and many researchers believe this imbalance is a significant factor in the rising rate of inflammatory disorders in the United States.

In contrast, however, the Mediterranean diet consists of a healthier balance between omega-3 and omega-6 fatty acids and many studies have shown that people who follow this diet are less likely to develop heart disease. The Mediterranean diet does not include much meat (which is high in omega-6 fatty acids) and emphasizes foods rich in omega-3 fatty acids including whole grains, fresh fruits and vegetables, fish, olive oil, garlic, as well as moderate wine consumption.

 

 

 

Uses of Omega-3 from the
University of Maryland Medical Center

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:

High Cholesterol
Those who follow a Mediterranean-style diet tend to have higher HDL ("good") cholesterol levels. Similar to those who follow a Mediterranean diet, Inuit Eskimos, who consume high amounts of omega-3 fatty acids from fatty fish, also tend to have increased HDL cholesterol and decreased triglycerides (fatty material that circulates in the blood). In addition, fish oil supplements containing EPA and DHA have been shown to reduce LDL ("bad") cholesterol and triglycerides. Finally, walnuts (which are rich in ALA) have been shown to lower total cholesterol and triglycerides in people with high cholesterol.

High Blood Pressure
Several studies suggest that diets and/or supplements rich in omega-3 fatty acids lower blood pressure significantly in people with hypertension. Fish high in mercury (such as tuna) should be avoided, however, because they may increase blood pressure.

Heart Disease
One of the best ways to help prevent and treat heart disease is to eat a low-fat diet and to replace foods rich in saturated and trans-fat with those that are rich in monounsaturated and polyunsaturated fats (including omega-3 fatty acids). Evidence suggests that EPA and DHA found in fish oil help reduce risk factors for heart disease including high cholesterol and high blood pressure. There is also strong evidence that these substances can help prevent and treat atherosclerosis by inhibiting the development of plaque and blood clots, each of which tends to clog arteries. Studies of heart attack survivors have found that daily omega-3 fatty acid supplements dramatically reduce the risk of death, subsequent heart attacks, and stroke. Similarly, people who eat an ALA-rich diet are less likely to suffer a fatal heart attack.

Stroke
Strong evidence from population-based studies suggests that omega-3 fatty acid intake (primarily from fish), helps protect against stroke caused by plaque buildup and blood clots in the arteries that lead to the brain. In fact, eating at least two servings of fish per week can reduce the risk of stroke by as much as 50%. However, people who eat more than three grams of omega-3 fatty acids per day (equivalent to 3 servings of fish per day) may be at an increased risk for hemorrhagic stroke, a potentially fatal type of stroke in which an artery in the brain leaks or ruptures.

Diabetes
People with diabetes tend to have high triglyceride and low HDL levels. Omega-3 fatty acids from fish oil can help lower triglycerides and raise HDL, so people with diabetes may benefit from eating foods or taking supplements that contain DHA and EPA. ALA (from flaxseed, for example) may not have the same benefit as DHA and EPA because some people with diabetes lack the ability to efficiently convert ALA to a form of omega-3 fatty acids that the body can use readily.

Weight Loss
Many people who are overweight suffer from poor blood sugar control, diabetes, and high cholesterol. Studies suggest that overweight people who follow a weight loss program including exercise tend to achieve better control over their blood sugar and cholesterol levels when fish rich in omega-3 fatty acids (such as salmon, mackerel, and herring) is a staple in their low fat diet.

Arthritis
Most clinical studies investigating the use of omega-3 fatty acid supplements for inflammatory joint conditions have focused almost entirely on rheumatoid arthritis. Several articles reviewing the research in this area conclude that omega-3 fatty acid supplements reduce tenderness in joints, decrease morning stiffness, and allow for a reduction in the amount of medication needed for people with rheumatoid arthritis.

In addition, laboratory studies suggest that diets rich in omega-3 fatty acids (and low in omega-6 fatty acids) may benefit people with other inflammatory disorders, such as osteoarthritis. In fact, several test tube studies of cartilage-containing cells have found that omega-3 fatty acids decrease inflammation and reduce the activity of enzymes that destroy cartilage. Similarly, New Zealand green lipped mussel ( Perna canaliculus ), another potential source of omega-3 fatty acids, has been shown to reduce joint stiffness and pain, increase grip strength, and enhance walking pace in a small group of people with osteoarthritis. In some participants, symptoms worsened before they improved.

Osteoporosis
Studies suggest that omega-3 fatty acids such as EPA help increase levels of calcium in the body, deposit calcium in the bones, and improve bone strength. In addition, studies also suggest that people who are deficient in certain essential fatty acids (particularly EPA and gamma-linolenic acid [GLA], an omega-6 fatty acid) are more likely to suffer from bone loss than those with normal levels of these fatty acids. In a study of women over 65 with osteoporosis, those given EPA and GLA supplements experienced significantly less bone loss over three years than those who were given a placebo. Many of these women also experienced an increase in bone density.

Depression
People who do not get enough omega-3 fatty acids or do not maintain a healthy balance of omega-3 to omega-6 fatty acids in their diet may be at an increased risk for depression. The omega-3 fatty acids are important components of nerve cell membranes. They help nerve cells communicate with each other, which is an essential step in maintaining good mental health.

Levels of omega-3 fatty acids were found to be measurably low and the ratio of omega-6 to omega-3 fatty acids were particularly high in a study of patients hospitalized for depression. In a study of people with depression, those who ate a healthy diet consisting of fatty fish two to three times per week for 5 years experienced a significant reduction in feelings of depression and hostility.

Manic/Depression (Bipolar Disorder)
In a study of 30 people with bipolar disorder, those who were treated with EPA and DHA (in combination with their usual mood stabilizing medications) for four months experienced fewer mood swings and recurrence of either depression or mania than those who received placebo. A similar but larger study is currently underway at the University of California- Los Angeles School of Medicine.

Schizophrenia
Preliminary evidence suggests that people with schizophrenia experience an improvement in symptoms when given omega-3 fatty acids. However, a recent well-designed study concluded that EPA supplements are no better than placebo in improving symptoms of this condition. The conflicting results suggest that more research is needed before conclusions can be drawn about the benefit of omega-3 fatty acids for schizophrenia. Similar to diabetes, people with schizophrenia may not be able to convert ALA to EPA or DHA efficiently.

Attention Deficit/Hyperactivity Disorder (ADHD)
Children with ADHD may have low levels of certain essential fatty acids (including EPA and DHA) in their bodies. In a study of nearly 100 boys, those with lower levels of omega-3 fatty acids demonstrated more learning and behavioral problems (such as temper tantrums and sleep disturbances) than boys with normal omega-3 fatty acid levels. In animal studies, low levels of omega-3 fatty acids have been shown to lower the concentration of certain brain chemicals (such as dopamine and serotonin) related to attention and motivation. Studies that examine the ability of omega-3 supplements to improve symptoms of ADHD are still needed. At this point in time, eating foods high in omega-3 fatty acids is a reasonable approach for someone with ADHD.

Eating Disorders
Studies suggest that men and women with anorexia nervosa have lower than optimal levels of polyunsaturated fatty acids (including ALA and GLA). To prevent the complications associated with essential fatty acid deficiencies, some experts recommend that treatment programs for anorexia nervosa include PUFA-rich foods such as fish and organ meats (which include omega-6 fatty acids).

Burns
Essential fatty acids have been used to reduce inflammation and promote wound healing in burn victims. Animal research indicates that omega-3 fatty acids help promote a healthy balance of proteins in the body -- protein balance is important for recovery after sustaining a burn. Further research is necessary to determine whether omega 3s benefit people in the same way.

Skin Disorders
In one study, 13 people with a particular sensitivity to the sun known as photodermatitis showed significantly less sensitivity to UV rays after taking fish oil supplements. Still, research indicates that topical sunscreens are much better at protecting the skin from damaging effects of the sun than omega-3 fatty acids. In another study of 40 people with psoriasis, those who were treated with medications and EPA supplements did better than those treated with the medications alone. In addition, many clinicians believe that flaxseed (which contains omega-3 fatty acids) is helpful for treating acne.

Inflammatory Bowel Disease (IBD)
When added to medication, such as sulfasalazine (a standard medication for IBD), omega-3 fatty acids may reduce symptoms of Crohn's disease and ulcerative colitis -- the two types of IBD. More studies to investigate this preliminary finding are under way. In animals, it appears that ALA works better at decreasing bowel inflammation than EPA and DHA. Plus, fish oil supplements can cause side effects that are similar to symptoms of IBD (such as flatulence and diarrhea). Time-release preparations may help reduce these unwanted effects.

Asthma
Preliminary research suggests that omega-3 fatty acid supplements (in the form of perilla seed oil, which is rich in ALA) may decrease inflammation and improve lung function in adults with asthma. Omega-6 fatty acids have the opposite effect: they tend to increase inflammation and worsen respiratory function. In a small, well-designed study of 29 children with asthma, those who took fish oil supplements rich in EPA and DHA for 10 months had improvement in their symptoms compared to children who took a placebo pill.

Macular Degeneration
A questionnaire administered to more than 3,000 people over the age of 49 found that those who consumed more fish in their diet were less likely to have macular degeneration (a serious age-related eye condition that can progress to blindness) than those who consumed less fish. Similarly, a study comparing 350 people with macular degeneration to 500 without found that those with a healthy dietary balance of omega-3 and omega-6 fatty acids and higher intake of fish in their diets were less likely to have this particular eye disorder. Another larger study confirms that EPA and DHA from fish, four or more times per week, may reduce the risk of developing macular degeneration. Notably, however, this same study suggests that ALA may actually increase the risk of this eye condition.

Menstrual Pain
In a study of nearly 200 Danish women, those with the highest dietary intake of omega-3 fatty acids had the mildest symptoms during menstruation.

Colon Cancer
Consuming significant amounts of foods rich in omega-3 fatty acids appears to reduce the risk of colorectal cancer. For example, Eskimos, who tend to follow a high fat diet but eat significant amounts of fish rich in omega-3 fatty acids, have a low rate of colorectal cancer. Animal studies and laboratory studies have found that omega-3 fatty acids prevent worsening of colon cancer while omega-6 fatty acids promote the growth of colon tumors. Daily consumption of EPA and DHA also appeared to slow or even reverse the progression of colon cancer in people with early stages of the disease.

However, in an animal study of rats with metastatic colon cancer (in other words, cancer that has spread to other parts of the body such as the liver), omega-3 fatty acids actually promoted the growth of cancer cells in the liver. Until more information is available, it is best for people with advanced stages of colorectal cancer to avoid omega-3 fatty acid supplements and diets rich in this substance.

Breast Cancer
Although not all experts agree, women who regularly consume foods rich in omega-3 fatty acids over many years may be less likely to develop breast cancer. In addition, the risk of dying from breast cancer may be significantly less for those who eat large quantities of omega-3 from fish and brown kelp seaweed (common in Japan). This is particularly true among women who substitute fish for meat. The balance between omega-3 and omega-6 fatty acids appears to play an important role in the development and growth of breast cancer. Further research is still needed to understand the effect that omega-3 fatty acids may have on the prevention or treatment of breast cancer. For example, several researchers speculate that omega-3 fatty acids in combination with other nutrients (namely, vitamin C, vitamin E, beta-carotene, selenium, and coenzyme Q10) may prove to be of particular value for preventing and treating breast cancer.

Prostate Cancer
Laboratory and animal studies indicate that omega-3 fatty acids (specifically, DHA and EPA) may inhibit the growth of prostate cancer. Similarly, population based studies of groups of men suggest that a low-fat diet with the addition of omega-3 fatty acids from fish or fish oil help prevent the development of prostate cancer. Like breast cancer, the balance of omega-3 to omega-6 fatty acids appears to be particularly important for reducing the risk of this condition. ALA, however, may not offer the same benefits as EPA and DHA. In fact, one recent study evaluating 67 men with prostate cancer found that they had higher levels of ALA compared to men without prostate cancer. More research in this area is needed.

Other
Although further research is needed, preliminary evidence suggests that omega-3 fatty acids may also prove helpful in protecting against certain infections and treating a variety of conditions including ulcers, migraine headaches, preterm labor, emphysema, psoriasis, glaucoma, Lyme disease, lupus, and panic attacks.

Dietary Sources
Fish oils and plant oils are the primary dietary source of omega-3 fatty acids. Another potential source of omega-3 fatty acids is New Zealand green lipped mussels ( Perna canaliculus),used for centuries by the Maories to promote good health. EPA and DHA are found in cold-water fish such as salmon, mackerel, halibut, sardines, and herring. ALA is found in flaxseeds, flaxseed oil, canola (rapeseed) oil, soybeans, soybean oil, pumpkin seeds, pumpkin seed oil, purslane, perilla seed oil, walnuts, and walnut oil.

Available Forms
In addition to the dietary sources described, EPA and DHA can be taken in the form of fish oil capsules. Flaxseed, flaxseed oil, and fish oil should be kept refrigerated. Whole flaxseeds must be ground within 24 hours of use, otherwise the ingredients lose their activity. Flaxseeds are also available in ground form in a special mylar package so that the components in the flaxseeds stay active.

Be sure to buy omega-3 fatty acid supplements made by established companies who certify that their products are free of heavy metals such as mercury.

Precautions
Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable healthcare provider.

Omega-3 fatty acids should be used cautiously by people who bruise easily, have a bleeding disorder, or take blood-thinning medications because excessive amounts of omega-3 fatty acids may lead to bleeding. In fact, people who eat more than three grams of omega-3 fatty acids per day (equivalent to 3 servings of fish per day) may be at an increased risk for hemorrhagic stroke, a potentially fatal condition in which an artery in the brain leaks or ruptures.

Fish oil can cause flatulence and diarrhea. Time-release preparations may reduce these side effects, however.

People with either diabetes or schizophrenia may lack the ability to convert ALA to EPA and DHA, the forms more readily used in the body. Therefore, people with these conditions should obtain their omega-3 fatty acids from dietary sources rich in EPA and DHA.

Although studies have found that regular consumption of fish (which includes the omega-3 fatty acids EPA and DHA) may reduce the risk of macular degeneration, a recent study including two large groups of men and women found that diets rich in ALA may substantially increase the risk of this disease. More research is needed in this area. Until this information becomes available, it is best for people with macular degeneration to obtain omega-3 fatty acids from sources of EPA and DHA, rather than ALA.

Similar to macular degeneration, fish and fish oil may protect against prostate cancer, but ALA may be associated with increased risk of prostate cancer in men. More research in this area is needed.

It is best to use lipid extracts rather than the powder form of New Zealand green lipped mussels because there is less chance of an allergic reaction. People who are allergic to seafood should avoid New Zealand green lipped mussels. In some individuals who take New Zealand green lipped mussels, arthritis symptoms may worsen before they improve.

Possible Interactions
If you are currently being treated with any of the following medications, you should not use omega-3 fatty acid supplements without first talking to your healthcare provider.

Blood-thinning Medications
Omega-3 fatty acids may increase the blood-thinning effects of aspirin or warfarin. While the combination of aspirin and omega-3 fatty acids may actually be helpful under certain circumstances (such as heart disease), they should only be taken together under the guidance and supervision of your healthcare provider.

Cyclosporine
Taking omega-3 fatty acids during cyclosporine therapy may reduce toxic side effects (such as high blood pressure and kidney damage) associated with this medication in transplant patients.

Etretinate and Topical Steroids
The addition of omega-3 fatty acids (specifically EPA) to a drug regimen of etretinate and topical corticosteroids may improve symptoms of psoriasis.

Cholesterol-lowering Medications
Following certain nutritional guidelines, including increasing the amount of omega-3 fatty acids in your diet and reducing the omega-6 to omega-3 ratio, may allow a group of cholesterol lowering medications known as "statins" (such as atorvastatin, lovastatin, and simvastatin) to work more effectively.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
In an animal study, treatment with omega-3 fatty acids reduced the risk of ulcers from nonsteroidal anti-inflammatory drugs (NSAIDs). More research is needed to evaluate whether omega-3 fatty acids would have the same effects in people.

 

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Sanders TA, Hinds A. The influence of a fish oil high in docosahexaenoic acid on plasma lipoprotein and vitamin E concentrations and haemostatic function in healthy male volunteers. Br J Nutr . 1992;68(1):163-173.
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American Heart Association
Fish and Omega-3 Fatty Acids

AHA Recommendation

Omega-3 fatty acids benefit the heart of healthy people, and those at high risk of — or who have — cardiovascular disease.

 We recommend eating fish (particularly fatty fish) at least two times a week.  Fish is a good source of protein and doesn’t have the high saturated fat that fatty meat products do.  Fatty fish like mackerel, lake trout, herring, sardines, albacore tuna and salmon are high in two kinds of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
To learn about omega-3 levels for different types of fish — as well as mercury levels, which can be a concern — see our Encyclopedia entry on Fish, Levels of Mercury and Omega-3 Fatty Acids.

We also recommend eating tofu and other forms of soybeans, canola, walnut and flaxseed, and their oils. These contain alpha-linolenic acid (LNA),  which can become omega-3 fatty acid in the body. The extent of this modification is modest and controversial, however. More studies are needed to show a cause-and-effect relationship between alpha-linolenic acid and heart disease.

Background
In 1996 the American Heart Association released its Science Advisory, “Fish Consumption, Fish Oil, Lipids and Coronary Heart Disease.” Since then important new findings have been reported about the benefits of omega-3 fatty acids on cardiovascular disease.  These include evidence from randomized, controlled clinical trials.  New information has emerged about how omega-3 fatty acids affect heart function (including antiarrhythmic effects), hemodynamics (cardiac mechanics) and arterial endothelial function.  These findings are outlined in our November 2002 Scientific Statement, “Fish Consumption, Fish Oil, Omega-3 Fatty Acids and Cardiovascular Disease.”

The ways that omega-3 fatty acids reduce CVD risk are still being studied. 
However, research has shown that they:
•  decrease risk of arrhythmias, which can lead to sudden cardiac death
•  decrease triglyceride levels
•  decrease growth rate of atherosclerotic plaque
•  lower blood pressure (slightly)

What do epidemiological and observational studies show?

Epidemiologic and clinical trials have shown that omega-3 fatty acids reduce CVD incidence.  Large-scale epidemiologic studies suggest that people at risk for coronary heart disease benefit from consuming omega-3 fatty acids from plants and marine sources.

The ideal amount to take isn’t clear.  Evidence from prospective secondary prevention studies suggests that taking EPA+DHA ranging from 0.5 to 1.8 grams per day (either as fatty fish or supplements) significantly reduces deaths from heart disease and all causes.  For alpha-linolenic acid, a total intake of 1.5–3 grams per day seems beneficial.

Randomized clinical trials have shown that omega-3 fatty acid supplements can reduce cardiovascular events (death, non-fatal heart attacks, non-fatal strokes).  They can also slow the progression of atherosclerosis in coronary patients.  However, more studies are needed to confirm and further define the health benefits of omega-3 fatty acid supplements for preventing a first or subsequent cardiovascular event.  For example, placebo-controlled, double-blind, randomized clinical trials are needed to document the safety and efficacy of omega-3 fatty acid supplements in high-risk patients (those with type 2 diabetes, dyslipidemia, hypertension and smokers) and coronary patients on drug therapy.  Mechanistic studies on their apparent effects on sudden death also are needed.

Increasing omega-3 fatty acid intake through foods is preferable.  However, coronary artery disease patients may not be able to get enough omega-3 by diet alone.  These people may want to talk to their doctor about taking a supplement.  Supplements also could help people with high triglycerides, who need even larger doses.  The availability of high-quality omega-3 fatty acid supplements, free of contaminants, is an important prerequisite to their use.

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Medline Plus, from the National Institutes of Health:
Dietary sources of omega-3 fatty acids include fish oil and certain plant/nut oils. Fish oil contains both docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), while some nuts (English walnuts) and vegetable oils (canola, soybean, flaxseed/linseed, olive) contain alpha-linolenic acid (ALA).

There is evidence from multiple studies supporting intake of recommended amounts of DHA and EPA in the form of dietary fish or fish oil supplements lowers triglycerides, reduces the risk of death, heart attack, dangerous abnormal heart rhythms, and strokes in people with known cardiovascular disease, slows the buildup of atherosclerotic plaques ("hardening of the arteries"), and lowers blood pressure slightly. However, high doses may have harmful effects, such as an increased risk of bleeding. Although similar benefits are proposed for alpha-linolenic acid, scientific evidence is less compelling, and beneficial effects may be less pronounced.

Some species of fish carry a higher risk of environmental contamination, such as with methylmercury.

Synonyms
α-linolenic acid (ALA, C18:3n-3), alpha-linolenic acid, cod liver oil, coldwater fish, docosahexaenoic acid (DHA, C22:6n-3), eicosapentaenoic acid (EPA, C20:5n-3), fish oil fatty acids, fish body oil, fish extract, fish liver oil, halibut oil, long chain polyunsaturated fatty acids, mackerel oil, marine oil, menhaden oil, n-3 fatty acids, n-3 polyunsaturated fatty acids, omega fatty acids, omega-3 oils, polyunsaturated fatty acids (PUFA), salmon oil, shark liver oil, w-3 fatty acids.

Note: Should not be confused with omega-6 fatty acids.

Evidence
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Angina pectoris
Preliminary studies report reductions in angina associated with fish oil intake. Better research is necessary before a firm conclusion can be drawn.  C

Asthma
Several studies in this area do not provide enough reliable evidence to form a clear conclusion, with some studies reporting no effects, and others finding benefits. Because most studies have been small without clear descriptions of design or results, the results cannot be considered conclusive.  C

Atherosclerosis
Some research reports that regular intake of fish or fish oil supplements reduces the risk of developing atherosclerotic plaques in the arteries of the heart, while other research reports no effects. Additional evidence is necessary before a firm conclusion can be drawn in this area.  C
Bipolar disorder
Several studies in this area do not provide enough reliable evidence to form a clear conclusion.  C

Cancer prevention
Several population (epidemiologic) studies report that dietary omega-3 fatty acids or fish oil may reduce the risk of developing breast, colon, or prostate cancer. Randomized controlled trials are necessary before a clear conclusion can be drawn.  C

Cardiac arrhythmias (abnormal heart rhythms)
There is promising evidence that omega-3 fatty acids may decrease the risk of cardiac arrhythmias. This is one proposed mechanism behind the reduced number of heart attacks in people who regularly ingest fish oil or EPA + DHA. Additional research is needed in this area specifically before a firm conclusion can be reached.  C

Colon cancer
Omega-3 fatty acids are commonly taken by cancer patients. Although preliminary studies report that growth of colon cancer cells may be reduced by taking fish oil, effects on survival or remission have not been measured adequately.  C

Crohn's disease
It has been suggested that effects of omega-3 fatty acids on inflammation may be beneficial in patients with Crohn's disease when added to standard therapy, and several studies have been conducted in this area. Results are conflicting, and no clear conclusion can be drawn at this time.  C

Cystic fibrosis
A small amount of research in this area does not provide enough reliable evidence to form a clear conclusion.  C

Dementia
Well-designed clinical trials are needed before omega-3 fatty acids can be recommended for the prevention of cognitive impairment or dementia.  C

Depression
Several studies on the use of omega 3 fatty acids in depression, including positive results in postpartum depression, do not provide enough reliable evidence to form a clear conclusion or replace standard treatments. However, based on one recent study, omega-3 fatty acids may have therapeutic benefits in childhood depression. Promising initial evidence requires confirmation with larger, well-designed trials.  C

Dysmenorrhea (painful menstruation)
There is preliminary evidence suggesting possible benefits of fish oil/omega-3 fatty acids in patients with dysmenorrhea. Additional research is necessary before a firm conclusion can be reached.  C

Eczema
Several studies of EPA for eczema do not provide enough reliable evidence to form a clear conclusion.  C

IgA nephropathy
There are conflicting results from several trials in this area.  C

Infant eye / brain development
Well-designed research is necessary before a clear conclusion can be reached.  C

Lupus erythematosus
There is not enough reliable evidence to form a clear conclusion in this area.  C

Nephrotic syndrome
There is not enough reliable evidence to form a clear conclusion in this area.  C

Preeclampsia
Several studies of fish oil do not provide enough reliable evidence to form a clear conclusion in this area.  C

Prevention of graft failure after heart bypass surgery
There is limited study of the use of fish oils in patients after undergoing coronary artery bypass grafting (CABG). Additional evidence is necessary before a firm conclusion can be drawn in this area.  C

Prevention of restenosis after coronary angioplasty (PTCA)
Several randomized controlled trials have evaluated whether omega-3 fatty acid intake reduces blockage of arteries in the heart following balloon angioplasty (percutaneous transluminal coronary angioplasty/PTCA). The evidence in this area remains inconclusive.  C

Primary cardiovascular disease prevention (α-linolenic acid [ALA])
Additional research is necessary before a conclusion can be drawn in this area.  C

Psoriasis
Several studies in this area do not provide enough reliable evidence to form a clear conclusion.  C

Schizophrenia
There is promising preliminary evidence from several randomized controlled trials in this area. Additional research is necessary before a firm conclusion can be reached.  C

Secondary cardiovascular disease prevention (α-linolenic acid [ALA])
Several randomized controlled trials have examined the effects of alpha-linolenic acid in people with a history of heart attack. Although some studies suggest benefits, others do not. Additional research is necessary before a conclusion can be drawn in this area.  C

Stroke prevention
Several large studies of populations ("epidemiologic" studies) have examined the effects of omega-3 fatty acid intake on stroke risk. Some studies suggest benefits, while others do not. Effects are likely on ischemic or thrombotic stroke risk, and very large intakes of omega-3 fatty acids ("Eskimo" amounts) may actually increase the risk of hemorrhagic (bleeding) stroke. At this time, it is unclear if there are benefits in people with or without a history of stroke, or if effects of fish oil are comparable to other treatment strategies.  C

Ulcerative colitis
It has been suggested that effects of omega-3 fatty acids on inflammation may be beneficial in patients with ulcerative colitis when added to standard therapy, and several studies have been conducted in this area. Better research is necessary before a clear conclusion can be drawn.  C

*Key to grades

A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use;
F: Strong scientific evidence against this use.

Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Acute myocardial infarction (heart attack), acute respiratory distress syndrome (ARDS), age related macular degeneration, aggressive behavior, agoraphobia, AIDS, allergies, Alzheimer's disease, anticoagulation, antiphospholipid syndrome, attention deficit hyperactivity disorder (ADHD), anthracycline-induced cardiac toxicity, bacterial infections, breast cysts, breast tenderness, chronic fatigue syndrome (postviral fatigue syndrome), chronic obstructive pulmonary disease, cirrhosis, common cold, congestive heart failure, critical illness, deficiency (omega-3 fatty acid), dermatomyositis, diabetic nephropathy, diabetic neuropathy, dyslexia, dyspraxia, endocrine disorders (glycogen storage diseases), exercise performance enhancement, fibromyalgia, gallstones, gingivitis, glaucoma, glomerulonephritis, gout, hay fever, headache, hepatorenal syndrome, hypoxia, ichthyosis (skin disorder), immunosuppression, inflammatory conditions (Behcet's syndrome), joint problems (cartilage repair), kidney disease prevention, kidney stones, leprosy, leukemia, malaria, male infertility, mastalgia (breast pain), memory enhancement, menopausal symptoms, menstrual cramps, methotrexate toxicity, multiple sclerosis, myopathy, nephritis (autoimmune), neuropathy, night vision enhancement, obesity, osteoarthritis, osteoporosis, otitis media (ear infection), panic disorder, peripheral vascular disease, pregnancy nutritional supplement, premature birth prevention, premenstrual syndrome, prostate cancer prevention, protection from isotretinoin drug toxicity, psychological disorders (borderline personality disorder), Raynaud's phenomenon, Refsum's syndrome, retinitis pigmentosa, Reye's syndrome, seizure disorder, Sjogren's syndrome, suicide prevention, systemic lupus erythematosus, tardive dyskinesia, tennis elbow, ulcerative colitis, urolithiasis (bladder stones), vision enhancement, weight loss.RETURN TO TOP

Dosing
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older):
Average dietary intake of omega-3/omega-6 fatty acids: Average Americans consume approximately 1.6 grams of omega-3 fatty acids each day, of which about 1.4 grams (~90%) comes from α-linolenic acid, and only 0.1-0.2 grams (~10%) from EPA and DHA. In Western diets, people consume roughly 10 times more omega-6 fatty acids than omega-3 fatty acids. These large amounts of omega-6 fatty acids come from the common use of vegetable oils containing linoleic acid (for example: corn oil, evening primrose oil, pumpkin oil, safflower oil, sesame oil, soybean oil, sunflower oil, walnut oil, wheatgerm oil). Because omega-6 and omega-3 fatty acids compete with each other to be converted to active metabolites in the body, benefits can be reached either by decreasing intake of omega-6 fatty acids, or by increasing omega-3 fatty acids.

Recommended daily intake of omega-3 fatty acids (healthy adults): For healthy adults with no history of heart disease, the American Heart Association recommends eating fish at least two times per week. In particular, fatty fish are recommended, such as anchovies, bluefish, carp, catfish, halibut, herring, lake trout, mackerel, pompano, salmon, striped sea bass, tuna (albacore), and whitefish. It is also recommended to consume plant-derived sources of α-linolenic acid, such as tofu/soybeans, walnuts, flaxseed oil, and canola oil. The World Health Organization and governmental health agencies of several countries recommend consuming 0.3-0.5 grams of daily EPA + DHA and 0.8-1.1 grams of daily α-linolenic acid. A doctor and pharmacist should be consulted for dosing for other conditions.

Children (younger than 18 years):
Omega-3 fatty acids are used in some infant formulas, although effective doses are not clearly established. Ingestion of fresh fish should be limited in young children due to the presence of potentially harmful environmental contaminants. Fish oil capsules should not be used in children except under the direction of a physician.

Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies
People with allergy or hypersensitivity to fish should avoid fish oil or omega-3 fatty acid products derived from fish. Skin rash has been reported rarely. People with allergy or hypersensitivity to nuts should avoid alpha linolenic acid or omega-3 fatty acid products that are derived from the types of nuts to which they react.

Side Effects and Warnings
The U.S. Food and Drug Administration classifies low intake of omega-3 fatty acids from fish as GRAS (Generally Regarded as Safe). Caution may be warranted, however, in diabetic patients due to potential (albeit unlikely) increases in blood sugar levels, patients at risk of bleeding, or in those with high levels of low-density lipoprotein (LDL). Fish meat may contain methylmercury and caution is warranted in young children and pregnant/breastfeeding women.

Omega-3 fatty acids may increase the risk of bleeding, although there is little evidence of significant bleeding risk at lower doses. Very large intakes of fish oil/omega-3 fatty acids ("Eskimo" amounts) may increase the risk of hemorrhagic (bleeding) stroke. High doses have also been associated with nosebleed and blood in the urine. Fish oils appear to decrease platelet aggregation and prolong bleeding time, increase fibrinolysis (breaking down of blood clots), and may reduce von Willebrand factor.

Potentially harmful contaminants such as dioxins, methylmercury, and polychlorinated biphenyls (PCBs) are found in some species of fish. Methylmercury accumulates in fish meat more than in fish oil, and fish oil supplements appear to contain almost no mercury. Therefore, safety concerns apply to eating fish but likely not to ingesting fish oil supplements. Heavy metals are most harmful in young children and pregnant/nursing women.

Gastrointestinal upset is common with the use of fish oil supplements. Diarrhea may also occur, with potentially severe diarrhea at very high doses. There are also reports of increased burping, acid reflux/heartburn/indigestion, abdominal bloating, and abdominal pain. Fishy aftertaste is a common effect. Gastrointestinal side effects can be minimized if fish oils are taken with meals and if doses are started low and gradually increased.

Multiple human trials report small reductions in blood pressure with intake of omega-3 fatty acids. Reductions of 2-5 mmHg have been observed, and effects appear to be dose-responsive (higher doses have greater effects). DHA may have greater effects than EPA. Caution is warranted in patients with low blood pressure or in those taking blood-pressure lowering medications.

Although slight increases in fasting blood glucose levels have been noted in patients with type 2 ("adult onset") diabetes, the available scientific evidence suggests that there are no significant long-term effects of fish oil in patients with diabetes, including no changes in hemoglobin A1c levels. Limited reports in the 1980s of increased insulin needs in diabetic patients taking long-term fish oils may be related to other dietary changes or weight gain.
Fish oil taken for many months may cause a deficiency of vitamin E, and therefore vitamin E is added to many commercial fish oil products. As a result, regular use of vitamin E-enriched products may lead to elevated levels of this fat-soluble vitamin. Fish liver oil contains the fat-soluble vitamins A and D, and therefore fish liver oil products (such as cod liver oil) may increase the risk of vitamin A or D toxicity.

Increases (worsening) in low-density lipoprotein levels ("bad cholesterol") by 5-10% are observed with intake of omega-3 fatty acids. Effects are dose-dependent.

Mild elevations in liver function tests (alanine aminotransferase) have been reported rarely. Skin rashes have been reported rarely.

There are rare reports of mania in patients with bipolar disorder or major depression. Restlessness and formication (the sensation of ants crawling on the skin) have also been reported.

Pregnancy and Breastfeeding
Potentially harmful contaminants such as dioxins, methylmercury, and polychlorinated biphenyls (PCBs) are found in some species of fish, and may be harmful in pregnant/nursing women. Methylmercury accumulates in fish meat more than in fish oil, and fish oil supplements appear to contain almost no mercury. Therefore, these safety concerns apply to eating fish but likely not to ingesting fish oil supplements. However, unrefined fish oil preparations may contain pesticides.

It is not known if omega-3 fatty acid supplementation of women during pregnancy or breastfeeding is beneficial to infants. It has been suggested that high intake of omega-3 fatty acids during pregnancy, particularly DHA, may increase birth weight and gestational length (254). However, higher doses may not be advisable due to the potential risk of bleeding. Fatty acids are added to some infant formulas.

Interactions
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs
In theory, omega-3 fatty acids may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

Based on human studies, omega-3 fatty acids may lower blood pressure and add to the effects of drugs that may also affect blood pressure.

Fish oil supplements may lower blood sugar levels a small amount. Caution is advised when using medications that may also lower blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare provider. Medication adjustments may be necessary.

Omega-3 fatty acids lower triglyceride levels, but can actually increase (worsen) low-density lipoprotein (LDL/"bad cholesterol") levels by a small amount. Therefore, omega-3 fatty acids may add to the triglyceride-lowering effects of agents like niacin/nicotinic acid, fibrates such as gemfibrozil (Lopid®), or resins such as cholestyramine (Questran®). However, omega-3 fatty acids may work against the LDL-lowering properties of "statin" drugs like atorvastatin (Lipitor®) and lovastatin (Mevacor®).

Interactions with Herbs and Dietary Supplements
In theory, omega-3 fatty acids may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of  Ginkgo biloba , and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

Based on human studies, omega-3 fatty acids may lower blood pressure, and theoretically may add to the effects of agents that may also affect blood pressure.

Fish oil supplements may lower blood sugar levels a small amount. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

Omega-3 fatty acids lower triglyceride levels, but can actually increase (worsen) low-density lipoprotein (LDL/"bad cholesterol") levels by a small amount. Therefore, omega-3 fatty acids may add to the triglyceride-lowering effects of agents like niacin/nicotinic acid, but may work against the potential LDL-lowering properties of agents like barley, garlic, guggul, psyllium, soy, or sweet almond.

Fish oil taken for many months may cause a deficiency of vitamin E, and therefore vitamin E is added to many commercial fish oil products. As a result, regular use of vitamin E-enriched products may lead to elevated levels of this fat-soluble vitamin. Fish liver oil contains the fat-soluble vitamins A and D, and therefore fish liver oil products (such as cod liver oil) may increase the risk of vitamin A or D toxicity. Since fat-soluble vitamins can build up in the body and cause toxicity, patients taking multiple vitamins regularly or in high doses should discuss this risk with their healthcare practitioners.
Methodology
This information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): Serguei Axentsev, MD, PhD, D.Sci. (Natural Standard Research Collaboration); Rawan Barakat, PharmD (Massachusetts College of Pharmacy); Ethan Basch, MD (Memorial Sloan-Kettering Cancer Center); Steve Bent, MD (University of California San Francisco); Cynthia Dacey, PharmD (Natural Standard Research Collaboration); Cathi Dennehey, PharmD (University of California San Francisco); Paul Hammerness, MD (Harvard Medical School); Paul Knaus, PharmD (Northeastern University); Mojisola Sekoni, PharmD (Massachusetts College of Pharmacy); Elizabeth Sheehan, PharmD (Northeastern University); Michael Smith, MScPharm, ND (Canadian College of Naturopathic Medicine); Philippe Szapary, MD (University of Pennsylvania); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Wendy Weissner, BA (Natural Standard Research Collaboration).

Selected references
Berbert AA, Kondo CR, Almendra CL, et al. Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition 2005;21(2):131-136.
Bittiner SB, Tucker WF, Cartwright I, et al. A double-blind, randomised, placebo-controlled trial of fish oil in psoriasis. Lancet 2-20-1988;1(8582):378-380.
Bjorneboe A, Smith AK, Bjorneboe GE, et al. Effect of dietary supplementation with n-3 fatty acids on clinical manifestations of psoriasis. Br J Dermatol 1988;118(1):77-83.
Brouwer IA, Zock PL, Camm AJ, et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA. 2006 Jun 14;295(22):2613-9.
Burns CP, Halabi S, Clamon G, et al. Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia. Cancer 7-15-2004;101(2):370-378.
Chan JK, McDonald BE, Gerrard JM, et al. Effect of dietary alpha-linolenic acid and its ratio to linoleic acid on platelet and plasma fatty acids and thrombogenesis. Lipids 1993;28(9):811-817.
Dry J, Vincent D. Effect of a fish oil diet on asthma: results of a 1-year double-blind study. Int Arch Allergy Appl Immunol. 1991;95(2-3):156-157.
Duffy EM, Meenagh GK, McMillan SA, et al. The clinical effect of dietary supplementation with omega-3 fish oils and/or copper in systemic lupus erythematosus. J Rheumatol. 2004;31(8):1551-1556.
Erkkila AT, Lichtenstein AH, Mozaffarian D, et al. Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. Am J Clin Nutr. 2004;80(3):626-632.
Fenton WS, Dickerson F, Boronow J, et al. A placebo-controlled trial of omega-3 Fatty Acid (ethyl eicosapentaenoic Acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry 2001;158(12):2071-2074.
Lim WS, Gammack JK, Van Niekerk J, et al. Omega 3 fatty acid for the prevention of dementia. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005379.
Mostad IL, Bjerve KS, Bjorgaas MR, et al. Effects of n-3 fatty acids in subjects with type 2 diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation. Am J Clin Nutr. 2006 Sep;84(3):540-50.
Olsen SF, Secher NJ, Tabor A, et al. Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team. BJOG. 2000;107(3):382-395.
Stoll AL, Severus WE, Freeman MP, et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen.Psychiatry 1999;56(5):407-412.
Su KP, Huang SY, Chiu CC, et al. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur.Neuropsychopharmacol. 2003;13(4):267-271. November 01, 2006.


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