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Information from National Library of Medicine and the National Institutes of Health (NIH)
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.
SynonymsReturn
to top
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.
EvidenceReturn
to top
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.
*Key to
grades
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. DosingReturn
to top
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.
SafetyReturn
to top
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.
InteractionsReturn
to top
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
Return to top
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
Return to top
1.
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.
2.
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.
3.
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.
4.
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.
5.
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.
6.
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.
7.
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.
8.
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.
9.
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.
10.
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.
11.
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.
12.
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.
13.
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.
14.
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.
15.
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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