Omega-3 fatty acids, fish oil, alpha-linolenic acid
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| Omega-3
fatty acids, fish oil, alpha-linolenic acid |
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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).
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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.
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Some species of fish carry a higher risk of environmental contamination, such
as with methylmercury.
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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.
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Note: Should not be confused with omega-6 fatty acids.
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.
| Uses based on scientific evidence |
Grade* |
| High blood pressure
Multiple human trials report small reductions in blood pressure with
intake of omega-3 fatty acid. DHA may have greater benefits than EPA.
However, high intakes of omega-3 fatty acids per day may be necessary to
obtain clinically relevant effects, and at this dose level, there is an
increased risk of bleeding. Therefore, a qualified healthcare provider
should be consulted prior to starting treatment with supplements.
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A |
| Hypertriglyceridemia (fish oil / EPA plus DHA)
There is strong scientific evidence from human trials that omega-3 fatty
acids from fish or fish oil supplements (EPA + DHA) significantly reduce
blood triglyceride levels. Benefits appear to be dose-dependent. Fish
oil supplements also appear to cause small improvements in high-density
lipoprotein ("good cholesterol"); however, increases
(worsening) in low-density lipoprotein levels (LDL/"bad
cholesterol") are also observed.It is not clear if alpha-linolenic
acid significantly affects triglyceride levels, and there is conflicting
evidence in this area.The American Heart Association has published
recommendations for EPA + DHA. Because of the risk of bleeding from
omega-3 fatty acids, a qualified healthcare provider should be consulted
prior to starting treatment with supplements.There is growing evidence
that reducing C-Reactive Protein (CRP) is beneficial towards favorable
cardiovascular outcomes, although additional research is pending in this
area. The data on fish oils and CRP levels is mixed.
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A |
| Secondary cardiovascular disease prevention (fish
oil / EPA plus DHA)
Several well-conducted randomized controlled trials report that in
people with a history of heart attack, regular consumption of oily fish
or fish oil/omega-3 supplements reduces the risk of non-fatal heart
attack, fatal heart attack, sudden death, and all-cause mortality (death
due to any cause). Most patients in these studies were also using
conventional heart drugs, suggesting that the benefits of fish oils may
add to the effects of other therapies.
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A |
| Primary cardiovascular disease prevention (fish
intake)
Several large studies of populations ("epidemiologic" studies)
report a significantly lower rate of death from heart disease in men and
women who regularly eat fish. Other epidemiologic research reports no
such benefits. It is not clear if reported benefits only occur in
certain groups of people, such as those at risk of developing heart
disease. Overall, the evidence suggests benefits of regular consumption
of fish oil. However, well-designed randomized controlled trials which
classify people by their risk of developing heart disease are necessary
before a firm conclusion can be drawn.
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B |
| Protection from cyclosporine toxicity in organ
transplant patients
There are multiple studies of heart transplant and kidney transplant
patients taking cyclosporine (Neoral®), who were administered fish oil
supplements. The majority of trials report improvements in kidney
function, and less high blood pressure compared to patients not taking
fish oil. Although several recent studies report no benefits on kidney
function, the weight of scientific evidence favors the beneficial
effects of fish oil.
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B |
| Rheumatoid arthritis (fish oil)
Multiple randomized controlled trials report improvements in morning
stiffness and joint tenderness with the regular intake of fish oil
supplements for up to three months. Benefits have been reported as
additive with anti-inflammatory medications such as NSAIDs (like
ibuprofen or aspirin). However, because of weaknesses in study designs
and reporting, better research is necessary before a strong favorable
recommendation can be made. Effects beyond three months of treatment
have not been well evaluated.
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B |
| Angina pectoris
Preliminary studies report reductions in angina associated with fish oil
intake. Better research is necessary before a firm conclusion can be
drawn.
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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.
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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.
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C |
| Bipolar disorder
Several studies in this area do not provide enough reliable evidence to
form a clear conclusion.
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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.
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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.
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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.
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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.
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C |
| Cystic fibrosis
A small amount of research in this area does not provide enough reliable
evidence to form a clear conclusion.
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C |
| Dementia
Well-designed clinical trials are needed before omega-3 fatty acids can
be recommended for the prevention of cognitive impairment or dementia.
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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.
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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.
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C |
| Eczema
Several studies of EPA for eczema do not provide enough reliable
evidence to form a clear conclusion.
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C |
| IgA nephropathy
There are conflicting results from several trials in this area.
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C |
| Infant eye / brain development
Well-designed research is necessary before a clear conclusion can be
reached.
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C |
| Lupus erythematosus
There is not enough reliable evidence to form a clear conclusion in this
area.
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C |
| Nephrotic syndrome
There is not enough reliable evidence to form a clear conclusion in this
area.
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C |
| Preeclampsia
Several studies of fish oil do not provide enough reliable evidence to
form a clear conclusion in this area.
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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.
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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.
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C |
| Primary cardiovascular disease prevention (α-linolenic
acid [ALA])
Additional research is necessary before a conclusion can be drawn in
this area.
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C |
| Psoriasis
Several studies in this area do not provide enough reliable evidence to
form a clear conclusion.
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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.
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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.
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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.
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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.
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C |
| Appetite / weight loss in cancer patients
There is preliminary evidence that fish oil supplementation does not
improve appetite or prevent weight loss in cancer patients. Further
study is warranted.
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D |
| Diabetes
The available scientific evidence suggests that there are no significant
long-term effects of fish oil in patients with diabetes. Most studies in
this area are not well designed.
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D |
| Hypercholesterolemia
Although fish oil is able to reduce triglycerides, beneficial effects on
blood cholesterol levels have not been demonstrated. Fish oil
supplements appear to cause small improvements in high-density
lipoprotein ("good cholesterol"); however, increases
(worsening) in low-density lipoprotein levels ("bad
cholesterol") are also observed. Fish oil does not appear to affect
C-reactive protein (CRP) levels.
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D |
| Transplant rejection prevention (kidney and heart)
There are multiple studies of heart transplant and kidney transplant
patients taking cyclosporine (Neoral®), who were administered fish oil
supplements. The majority of trials report improvements in kidney
function (glomerular filtration rate, serum creatinine), and less
hypertension (high blood pressure) compared to patients not taking fish
oil. However, several recent studies report no benefits on kidney
function, and no changes have been found in rates of rejection or graft
survival.
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D |
*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.
Grading rationale
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.
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):
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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.
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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):
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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.
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
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Mild elevations in liver function tests (alanine aminotransferase) have been
reported rarely.
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Skin rashes have been reported rarely.
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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
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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.
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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.
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
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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®).
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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.
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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.
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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
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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.
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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.
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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.
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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.
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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.