Omega-3 supplementation also decreased inflammation as shown by a reduction in lipoprotein -associated phospholipase A2 and platelet activation as shown by a reduction in circulating concentrations of arachidonic acid , However, a residual elevation in triglycerides and triglyceride-rich lipoprotein cholesterol may remain in a substantial fraction of patients treated with statins.
The magnitude of these reductions in triglyceride and non-HDL-cholesterol concentrations was similar to what has been observed in other trials that examined the use of ethyl ester omega-3 supplements as add-ons to statin therapy , A study is underway to assess the benefit of combining omega-3 fatty acids and statins on the risk of major cardiovascular events over a three- to five-year period in patients with hypertriglyceridemia , Often associated with metabolic disorders, nonalcoholic fatty liver disease NAFLD is a condition characterized by an excessive lipid accumulation in the liver i.
Considering that C omega-3 PUFA can reduce fatty acid synthesis and inflammation , a possible therapeutic strategy would be to increase dietary intake of long-chain omega-3 PUFA. A meta-analysis of 18 randomized controlled trials in 1, participants with NAFLD found that omega-3 supplementation showed beneficial effects on liver fat, specific liver enzymatic activities, serum triglycerides , fasting glucose , and insulin resistance However, there was no evidence of an effect on total cholesterol , LDL -cholesterol, HDL -cholesterol, fasting insulin , blood pressure, BMI , and waist circumference Additional studies are needed to examine their efficacy in more severe cases of NASH.
A meta-analysis of 20 randomized controlled trials in 1, participants with rheumatoid arthritis assessed the efficacy of long-chain omega-3 PUFA supplementation on a series of clinical outcomes Omega-3 supplementation 0. Blood concentrations of triglycerides 3 trials and pro-inflammatory leukotriene B4 5 trials were also decreased with supplemental omega-3 PUFA Another meta-analysis of 42 randomized controlled trials examined the effect of omega-3 supplementation mainly as fish oil on arthritic pain in patients diagnosed with different types of arthritis Daily administration of marine-derived EPA 0.
The evidence of an effect of omega-3 supplements in patients with rheumatoid arthritis was deemed of moderate quality In a systematic review of 18 trials, including 1, subjects with rheumatoid arthritis, only 4 of 18 placebo-controlled trials showed a benefit of omega-3 PUFA supplementation 2. Results of a few trials suggested that omega-3 PUFA could spare the need for anti-inflammatory medications in some patients yet failed to show superiority of PUFA in pain management , The limited body of evidence that suggests potential benefits of omega-3 supplementation in rheumatoid arthritis treatment needs strengthening with data from larger studies conducted for longer intervention periods , Crohn's disease: A systematic review evaluated the efficacy of omega-3 supplementation in patients with Crohn's disease , considering the evidence base from both short-term 9 to 24 weeks and long-term 1 year trials Among five trials that evaluated the efficacy of omega-3 supplementation on relapse rates, conflicting outcomes were reported.
Most trials were limited by small sample sizes and short duration — up to three years may be necessary to see an effect on relapse rates given the natural relapsing-remitting course of the disease. The two largest and most recent trials EPIC-1 and EPIC-2 showed no significant effect of omega-3 supplementation on indicators of Crohn's disease remission compared to placebo Other systematic reviews of the literature reached similar conclusions Three short-term trials showed positive effects of omega-3 supplementation on plasma biochemical parameters e.
In spite of its impact on biochemical changes in the short-term, however, the ability of omega-3 supplementation to maintain remission or effect clinically meaningful changes in Crohn's disease is not supported by the current evidence Ulcerative colitis: Seven randomized controlled trials of fish oil supplementation in patients with active ulcerative colitis reported significant improvement in at least one outcome measure, such as decreased corticosteroid use, improved disease activity scores, or improved histology scores In patients with inactive ulcerative colitis, omega-3 supplementation had no effect on relapse rates compared to placebo in four separate trials , While no serious side effects were reported in any trials of fish oil supplementation for the maintenance or remission of inflammatory bowel disease , diarrhea and upper gastrointestinal symptoms occurred more frequently with omega-3 treatment Inflammatory eicosanoids leukotrienes derived from arachidonic acid AA; n-6 are thought to play an important role in the pathology of asthma Because increasing omega-3 fatty acid intake has been found to decrease the formation of AA-derived leukotrienes, a number of clinical trials have examined the effects of long-chain omega-3 fatty acid supplementation on asthma.
Although there is some evidence that omega-3 fatty acid supplementation can decrease the production of inflammatory mediators in asthmatic patients , , evidence that omega-3 fatty acid supplementation decreases the clinical severity of asthma in controlled trials has been inconsistent Three systematic reviews of randomized controlled trials of long-chain omega-3 fatty acid supplementation in asthmatic adults and children found no consistent effects on clinical outcome measures, including pulmonary function tests, asthmatic symptoms, medication use, or bronchial hyperreactivity Immunoglobulin A IgA nephropathy is a kidney disorder that results from the deposition of IgA in the glomeruli of the kidneys.
Since glomerular IgA deposition results in increased production of inflammatory mediators, omega-3 fatty acid supplementation could potentially modulate the inflammatory response and preserve renal function. A meta-analysis assessed the efficacy of omega-3 fatty acid supplementation on adult IgA nephropathy Compared with control groups, omega-3 supplementation had no significant effect on urine protein excretion or glomerular filtration rate.
Only two trials measured changes in serum creatinine a marker of renal function and end-stage renal disease — omega-3 treatment had a beneficial effect on these two parameters in both trials. No adverse events associated with omega-3 supplementation were reported in any of the trials.
A more recent review of the literature identified six trials showing evidence of omega-3 supplementation slowing IgA nephropathy disease progression and three trials reporting no effect Additionally, preliminary data suggested that the potential synergistic actions of aspirin and long-chain omega-3 PUFAs might constitute a promising treatment option Autism spectrum disorders ASD refer to three neurodevelopmental disorders of variable severity, namely autism, Asperger syndrome, and pervasive development disorder.
ASD are characterized by abnormal information processing in the brain due to alterations in the way nerve cells and their synapses connect and organize.
ASD are thought to have a strong genetic basis, yet environmental factors including diet may play an important role. This is supported by observations of PUFA abnormalities in blood of children with ASD, when compared to their peers with no neurodevelopmental disorders A meta-analysis of case-control studies reported lower blood concentrations of DHA and EPA in children with ASD compared to typically developing children; yet, the ratio of total omega-6 to omega-3 fatty acids was similar between children with and without ASD symptoms A systematic review by the same authors identified six randomized controlled trials that examined the effect of primarily long-chain omega-3 PUFA on ASD symptoms Four trials used EPA 0.
A pooled analysis of four of these trials, including a total of participants, showed a small improvement in measures of social interaction and repetitive and restrictive interests and behaviors with long-chain PUFA supplementation for 6 to 16 weeks; however, there was no effect on measures of communication and ASD co-existing conditions, such as hyperactivity, irritability, sensory issues, and gastrointestinal symptoms Two additional systematic reviews and meta-analyses, also published in , identified the same set of trials.
One meta-analysis suggested a benefit of long-chain PUFA on measures of lethargy and stereotypy but found no overall clinical improvement compared to placebo The other meta-analysis suggested an improvement regarding lethargy yet a worsening of externalizing behavior and social skills in children supplemented with omega-3 PUFA The available evidence is based on few trials of small sample sizes and is thus too limited to draw firm conclusions regarding the potential benefit of long-chain PUFA supplementation in ASD management.
Data from ecologic studies across different countries suggested an inverse association between seafood consumption and national rates of major depression and bipolar disorder Several small studies have found omega-3 fatty acid concentrations to be lower in plasma and adipose tissue of individuals suffering from depression compared to controls.
Although it is not known how omega-3 fatty acid intake affects the incidence of depression, modulation of neuronal signaling pathways and eicosanoid production have been proposed as possible mechanisms There may be some benefit of omega-3 PUFA supplementation on depressive disorders, but it is difficult to compare studies and draw conclusions due to great heterogeneity among the trials , Small sample sizes, lack of standardization of therapeutic doses, type of omega-3 PUFA administered, co-treatment with pharmacological agents, and diagnostic criteria vary among the trials.
A systematic review of all published randomized controlled trials investigated the effect of omega-3 PUFA supplementation on the prevention and treatment of several types of depression and other neuropsychiatric disorders With respect to major depression, most studies reported a positive effect of omega-3 supplements on depressive symptoms, though efficacy is still considered inconclusive given the great variability among trials. A meta-analysis grouped trials by type of diagnosis of depression A positive effect of omega-3 supplementation was found in 11 trials in participants with a diagnosis of major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders [DSM] criteria.
Omega-3 supplementation also appeared to be effective in the pooled analysis of eight trials in participants not formally diagnosed with major depressive disorder, i. There was no mood improvement with omega-3 supplements in generally healthy adults experiencing depressive symptoms, as suggested by the pooled analysis of six trials Finally, a Cochrane systematic review and meta-analysis of 20 randomized controlled trials reported a small benefit of omega-3 supplementation on depressive symptoms when compared to placebo , yet the evidence was deemed of very low quality and the positive effect was judged likely to be biased and not clinically significant Unipolar depression and bipolar disorder are considered distinct psychiatric conditions, although major depression occurs in both.
A meta-analysis of eight case-control studies that compared the PUFA composition of red blood cell membranes between patients with bipolar disorder and healthy subjects showed abnormally low red blood cell DHA concentrations with bipolar disorder As with major depression, reviews of trials indicated that omega-3 supplementation may have a positive effect as an adjunct to therapy in patients with bipolar disorder , Additionally, a randomized , placebo-controlled trial in participants with bipolar disorder reported a reduction in the severity of manic episodes with daily supplementation of 1, mg omega-3 PUFA for three months While there is some promising evidence for the use of omega-3 fatty acids for major depression and bipolar disorder, additional trials that account for dietary omega-3 intake, changes in red blood cell PUFA concentrations, the ratio of EPA:DHA provided, and co-treatment with medications are necessary.
A meta-analysis of 18 studies compared the PUFA composition of red blood cell membranes in patients with schizophrenia to individuals without the disorder Several mechanisms may account for PUFA abnormalities in schizophrenia, such as altered lipid metabolism , increased oxidative stress , or changes in diet consequent to disease-related behavior.
The use of long-chain omega-3 fatty acid supplements to alleviate symptoms of schizophrenia or to mitigate adverse effects of antipsychotic medications has been investigated in a number of clinical trials , In a recent randomized , placebo -controlled trial in 50 subjects with recent onset of schizophrenia who were medicated, daily supplementation with EPA mg and DHA mg reduced psychotic symptoms assessed with the Brief Psychiatric Rating Scale only in those who were not taking the anxiolytic , lorazepam Ativan Overall, however, there was no effect of long-chain PUFA supplements on schizophrenia symptoms.
Yet, given the high safety profile of fish oil supplements and some evidence of a positive effect of EPA supplementation in a subset of trials, some clinicians may consider EPA a useful adjunct to antipsychotic therapy in patients with schizophrenia.
Several mechanisms suggest that omega-3 PUFA supplementation may improve the cognitive performance of individuals with Alzheimer's disease and other types of dementia. In particular, the antioxidative and anti- inflammatory properties of these PUFA may help protect neurons , promote synaptic plasticity , and limit cellular death. The PUFA composition of the diet appears to influence blood cholesterol , which may play a role in the pathology of Alzheimer's disease.
A Cochrane review identified three randomized , placebo -controlled trials in patients with Alzheimer's disease of mild-to-moderate severity These trials compared daily supplementation with DHA between mg and 1, mg and EPA between mg and mg to a placebo for 12 months , or 18 months Of note, the study by Quinn et al.
The pooled analysis of these trials showed no beneficial effect of omega-3 supplementation on measures of global and specific cognitive functions, measures of functional outcomes, and measures of dementia severity There was no difference between intervention and placebo arms regarding the occurrence of adverse effects Linoleic acid LA : Food sources of LA include vegetable oils, such as soybean, safflower, and corn oil; nuts ; seeds; and some vegetables.
Some foods that are rich in LA are listed in Table 2. Therefore, AA is absent in vegetable oils and fats and present in small amounts in meat, poultry, and eggs. Canola oil is also an excellent source of ALA. Some foods that are rich in ALA are listed in Table 3.
Flaxseed oil also known as flax oil or linseed oil is available as an ALA supplement. A number of fish oils are marketed as omega-3 fatty acid supplements. Cod liver oil is also a rich source of EPA and DHA, but some cod liver oil preparations may contain excessive amounts of preformed vitamin A retinol and vitamin D DHA supplements derived from algal and fungal sources are also available.
All omega-3 fatty acid supplements are absorbed more efficiently with meals. Dividing one's daily dose into two or three smaller doses throughout the day will decrease the risk of gastrointestinal side effects see Safety. Presently, manufacturers are not required to list the amounts of DHA and AA added to infant formula on the label.
However, most infant formula manufacturers provide this information. High doses of borage seed oil, evening primrose oil, or black currant seed oil may cause gastrointestinal upset, loose stools, or diarrhea Although flaxseed oil is generally well tolerated, high doses may cause loose stools or diarrhea Allergic and anaphylactic reactions have been reported with flaxseed and flaxseed oil ingestion Belching and heartburn have also been reported.
Additionally, high doses may cause nausea and loose stools. Potential for excessive bleeding: The potential for high omega-3 fatty acid intakes, especially EPA and DHA, to prolong bleeding times has been well studied and may play a role in the cardioprotective effects of omega-3 fatty acids. Although the US Institute of Medicine did not establish a tolerable upper intake level UL for omega-3 fatty acids, caution was advised with the use of supplemental EPA and DHA, especially in those who are at increased risk of excessive bleeding see Drug interactions and Nutrient interactions 1 , Potential for immune system suppression: Although the suppression of inflammatory responses resulting from increased omega-3 fatty acid intakes may benefit individuals with inflammatory or autoimmune diseases , anti-inflammatory doses of omega-3 fatty acids could decrease the potential of the immune system to destroy pathogens Studies comparing measures of immune cell function outside the body ex vivo at baseline and after supplementing people with omega-3 fatty acids, mainly EPA and DHA, have demonstrated immunosuppressive effects at doses as low as 0.
Although it is not clear if these findings translate to impaired immune responses in vivo , caution should be observed when considering omega-3 fatty acid supplementation in individuals with compromised immune systems.
Potential other effects: Although fish oil supplements are unlikely to affect glucose homeostasis , people with diabetes mellitus who are considering fish oil supplements should inform their physician and be monitored if they choose to take them However, some preterm infants receiving fish oil-enriched formula had decreased plasma AA concentrations, which were associated with decreased weight but not length and head circumference , This effect was attributed to the potential for high concentrations of EPA to interfere with the synthesis of AA, which is essential for normal growth.
Randomized controlled trials have not found any adverse effects on growth in infants fed formulas enriched with AA and DHA for up to one year The safety of supplemental omega-3 and omega-6 fatty acids , including borage seed oil, evening primrose oil, black currant seed oil, and flaxseed oil, has not been established in pregnant or lactating breast-feeding women Some species of fish may contain significant levels of methylmercury, polychlorinated biphenyls PCBs , or other environmental contaminants In general, larger predatory fish, such as swordfish, tend to contain the highest levels of these contaminants.
Removing the skin, fat, and internal organs of the fish prior to cooking and allowing the fat to drain from the fish while it cooks will decrease exposure to a number of fat-soluble pollutants, such as PCBs However, methylmercury is found throughout the muscle of fish, so these cooking precautions will not reduce exposure to methylmercury.
Organic mercury compounds are toxic and excessive exposure can cause brain and kidney damage. The developing fetus, infants, and young children are especially vulnerable to the toxic effects of mercury on the brain. In order to limit their exposure to methylmercury, the US Food and Drug Administration FDA and Environmental Protection Agency have formulated joint recommendations for women who may become pregnant, pregnant women, breast-feeding women, and parents.
These recommendations are presented in Table 5. More information about mercury levels in commercial fish and shellfish is available from the FDA.
Of note, the Dietary Guidelines for Americans recommend the consumption of salmon, anchovies, herring, shad, sardines, Pacific oysters, trout, and Atlantic and Pacific mackerel not king mackerel , which are higher in EPA and DHA and lower in methylmercury Although concerns have been raised regarding the potential for omega-3 fatty acid supplements derived from fish oil to contain methylmercury, PCBs, and dioxins, several independent laboratory analyses in the US have found commercially available omega-3 fatty acid supplements to be free of methylmercury, PCBs, and dioxins The absence of methylmercury in omega-3 fatty acid supplements can be explained by the fact that mercury accumulates in the muscle, rather than the fat of fish In general, fish body oils contain lower concentrations of PCBs and other fat-soluble contaminants than fish liver oils.
Additionally, fish oils that have been more highly refined and deodorized contain lower concentrations of PCBs Pyrrolizidine alkaloids, potentially hepatotoxic and carcinogenic compounds, are found in various parts of the borage plant. People who take borage oil supplements should use products that are certified free of unsaturated pyrrolizidine alkaloids High doses of black currant seed oil, borage seed oil, evening primrose oil, flaxseed oil, and fish oil may inhibit platelet aggregation; therefore, these supplements should be used with caution in people on anticoagulant medications In particular, people taking fish oil or long-chain omega-3 fatty acid EPA and DHA supplements in combination with anticoagulant drugs, including aspirin, clopidogrel Plavix , dalteparin Fragmin , dipyridamole Persantine , enoxaparin Lovenox , heparin, ticlopidine Ticlid , and warfarin Coumadin , should have their coagulation status monitored using a standardized prothrombin time assay international normalized ratio [INR].
Outside the body, PUFA become rancid oxidized more easily than saturated fatty acids. Inside the body, results of animal studies and limited data in humans suggest that the amount of vitamin E required to prevent lipid peroxidation increases with the amount of PUFA consumed One widely used recommendation for vitamin E intake is 0. Although EPA and DHA are easily oxidized outside the body, it is presently unclear whether they are more susceptible to oxidative damage within the body High vitamin E intakes have not been found to decrease biomarkers of oxidative damage when EPA and DHA intakes are increased , , but some experts believe that an increase in PUFA intake, particularly omega-3 PUFA intake, should be accompanied by an increase in vitamin E intake 1.
The potential benefits associated with obtaining long-chain omega-3 fatty acids through moderate consumption of fish e. For information about contaminants in fish and guidelines for fish consumption by women of childbearing age, see Contaminants in fish. Seafood, nuts , seeds, and oils, which are all part of healthy dietary patterns, provide essential fatty acids. The Dietary Guidelines provide dietary recommendations regarding the amounts of these foods for those who choose to follow a healthy US-style eating pattern, a healthy Mediterranean-style eating pattern, or a healthy vegetarian eating pattern Table 8.
The American Heart Association recommends that people without documented coronary heart disease CHD eat a variety of fish preferably oily at least twice weekly Pregnant women and children should avoid fish that typically have higher levels of methylmercury see Contaminants in fish. For adults, the World Health Organization recommends an acceptable macronutrient distribution range AMDR for omega-6 fatty acid intake of 2.
The American Heart Association recommends that people without documented CHD eat a variety of fish preferably oily at least twice weekly The Linus Pauling Institute recommends that generally healthy adults increase their intake of long-chain omega-3 fatty acids by eating fish twice weekly and consuming foods rich in ALA, such as walnuts, flaxseeds, and flaxseed or canola oil.
If you don't regularly consume fish, consider taking a two-gram fish oil supplement several times a week. If you are prone to bleeding or take anticoagulant drugs, consult your physician.
Originally written in by: Jane Higdon, Ph. Updated in December by: Jane Higdon, Ph. Updated in April by: Victoria J. Drake, Ph. Updated in April by: Giana Angelo, Ph. Updated in May by: Barbara Delage, Ph. Reviewed in June by: Donald B. Jump, Ph. Food and Nutrition Board, Institute of Medicine. Washington, D. The National Academies Press. Lichtenstein A, Jones PJ. Lipids: Absorption and Transport.
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Essential fatty acid deficiency and home total parenteral nutrition patients. Absence of the biochemical symptoms of essential fatty acid deficiency in surgical patients undergoing protein sparing therapy. Deficiencies of essential fatty acids, vitamin A and E and changes in plasma lipoproteins in patients with reduced fat absorption or intestinal failure. Eur J Clin Nutr. Direct transesterification of plasma fatty acids for the diagnosis of essential fatty acid deficiency in cystic fibrosis.
A case of human linolenic acid deficiency involving neurological abnormalities. An n-3 fatty acid deficiency impairs rat spatial learning in the Barnes maze. Behav Neurosci. Fedorova I, Salem N, Jr. Omega-3 fatty acids and rodent behavior. The omega-3 index: a new risk factor for death from coronary heart disease? Prev Med. Effects of fish-oil supplementation on myocardial fatty acids in humans. Willett WC. The role of dietary n-6 fatty acids in the prevention of cardiovascular disease.
Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer.
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Prostaglandins Leukot Essent Fatty Acids. Decline in fish consumption among pregnant women after a national mercury advisory. Obstet Gynecol. The contents of this website are for educational purposes and are not intended to offer personal medical advice. You should seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
The Nutrition Source does not recommend or endorse any products. Skip to content The Nutrition Source. Harvard T. The Nutrition Source Menu. Vegetarians and vegans often lack DHA and should take microalgae supplements to make sure they get enough of this omega-3 8 , 9. While the latter two are primarily found in animal foods, ALA occurs in many plant foods.
Both are used to produce signaling molecules called eicosanoids, which have various roles related to inflammation and blood clotting Yet, omega-3s are anti-inflammatory , and scientists hypothesize that eating too much omega-6 counteracts these beneficial effects. In the Western diet, omega-6 intake is very high compared to that of omega-3s, so the ratio is currently skewed far towards the omega-6 side Maintaining a balance between these two fats — often termed the omega-6 to omega-3 ratio — may be important for optimal health.
Although insufficient evidence exists to show that omega-6 is harmful, most health professionals agree that getting enough omega-3 is important for health Omega-3 and -6 fats are used to produce important signaling molecules called eicosanoids. Balancing your intake of these fatty acids is considered important for optimal health.
Omega-3 fatty acids, particularly DHA, are vital for your brain and retinas 7. It is particularly important for pregnant and breastfeeding women to get enough DHA, as it can affect the health and intelligence of the baby Additionally, sufficient omega-3 intake can have powerful health benefits for adults.
Although evidence is mixed, studies indicate that omega-3 fatty acids can protect against all sorts of illnesses, including breast cancer, depression, ADHD, and various inflammatory diseases 14 , 15 , 16 , These are both cheap and effective. Omega-3 fatty acids play several important roles in your body. They have anti-inflammatory effects and are an essential component of your brain and eyes.
Omega-3 fatty acids are a family of polyunsaturated fats associated with several health benefits. High intake is linked to a reduced risk of inflammatory diseases and depression. Rich natural sources of omega-3, although few, include fish oil , fatty fish, flaxseed oil, and walnuts.
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