• Anemia
• Anemia, aplastic
• Anemia, general
• Anemia, iron deficiency
• Anemia, sickle cell
• Anemia, vitamin deficiency
• Stroke

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.

• atherosclerosis
• heart attack
• High blood pressure (hypertension)
• osteoarthritis

• overweight

• Stroke
• Weight loss

• 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 - (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. 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). anorexia nervosa
• 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.

• Asthma
• anorexia nervosa
• Breast cancer

• Calcium (Calcium citrate)

• Calcium Gluconate)

• cancer

• Colitis

• Colon cancer
• Crohn's disease
• Diabetes
• Diabetes, gestational
• Diabetic retinopathy
• Emphysema

• Peripheral neuropathy

• Diabetic retinopathy

• Flatulence

• Autonomic neuropathy

• Diarrhea

• Headache

• IBD

• Inflammatory bowel disease

• Lupus

• Lyme disease

• Migraine

• osteoarthritis

• Panic attacks

• Prostate cancer

• Psoriasis

• Rheumatoid arthritis

• overweight

• Schizophrenia

• Weight loss

Where it is Found:

• Mackerel
• Herring
• Halibut
• Cod
• Shark
• Salmon
• Tuna
• Shrimp
• Flaxseed oil

How to Use:
Available as:
Capsules
Oil

Cautions:
Don’t take if you:
Are pregnant, there is a possibility you are pregnant or plan to become pregnant in the future.
Are diabetic, due to the high fat content in supplements
Have a blood clotting problem (omega-3 acids may reduce the ability of the blood to clot)
Will undergo surgery

Consult your doctor if you:
Take any herbs or drugs including aspirin, laxatives, cold and cough remedies, antacids, vitamins, minerals, amino acids, supplements, other prescription or nonprescription drugs.

• Cold

Pregnancy:
Do no use unless advised by your doctor. There are no proven problems in pregnant women taking small or usual amounts, however the chance of problems do exist.

Breastfeeding:
Do no use unless advised by your doctor. There are no proven problems in breast-fed infants of lactating mothers taking small or usual amounts, however the chance of problems do exist.

Infants and Children:
It is hazardous to treat infants and children under 2 with any supplement.

Storage:
Keep in a cool and dry location and away from direct light, but do not freeze.
Keep safely away from children.
Do not keep in bathroom medicine cabinet. Heat and dampness may alter the action of the supplement.

Safe dosage:
To date, there has been no “safe” dosage established.

Toxicity:
Information on the comparative-toxicity rating cannot be found in standard references.

Side Effects:
Signs and symptoms : What to do?
Large amounts may lead to bleeding problems, diminished immunity, predisposition to some malignancies:
Discontinue use. Call your physician immediately

Supporting Research:

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:

• Coronary heart disease and Stroke;
• Essential fatty acid deficiency in infancy (retinal and brain development);
• Autoimmune disorders (e.g., Lupus and nephropathy);
• Crohn's disease;
• Cancers of the breast, colon, and prostate;
• Mild high blood pressure (hypertension) and
• Rheumatoid arthritis.

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:

• Prevent arrhythmias (ventricular tachycardia and fibrillation),
• Prostaglandin and leukotriene precursors,
• Have anti-inflammatory properties,
• Inhibit synthesis of cytokines and mitogens,
• Stimulate endothelial-derived nitric oxide,
• Antithrombotic,
• Have hypolipidemic properties with effects on triglycerides and VLDLs, and
• Inhibit atherosclerosis.

• arrhythmias
• atherosclerosis
• Tachycardia

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.

• atherosclerosis
• Tachycardia

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.

Reduced Atherosclerosis

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.

• atherosclerosis

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.

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.

• 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

• Depression

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

Experimental Studies

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.

• Anxiety
• Depression

Clinical Studies

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

• Anxiety
• Depression

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

Conclusion

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 aclnd@cfs-fm.org.

References:

1. Holub BJ. Clinical Nutrition: 4. Omega-3 fatty acids in cardiovascular care. CMAJ 2002; 166: 608-15.
2. Bourre JM, Dumont O, Piciotti M, Clement M, et al. Essentiality of n-3 fatty acids for brain structure and function. World Rev Nutr Diet 1991; 66: 103-17.
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