Three softgels contain: Fish Oil Concentrate 1. 5 g: Eicosapentaenoic Acid (eicosapentaenoic acid) 210 mg, Docosahexaenoic Acid (docosahexaenoic acid) 125 mg.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
This product has been discontinued by the manufacturer.
This product has been discontinued by the manufacturer.
Below is general information about the effectiveness of the known ingredients contained in the product Pure Dimension. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Pure Dimension. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally and appropriately. DHA has been used safely in studies lasting up to 4 years (1016,1043,6413,10321,10869,11333,90684). Fish oil supplements containing DHA have also been safely used in studies lasting up to 7 years (1016). While doses of DHA up to 4 grams orally daily have been used safely in some clinical research (6143), there is some concern that high intake of omega-3 fatty acids such as DHA might increase the risk of bleeding. For this reason, the US Food and Drug Administration (FDA) recommends that consumers limit intake of DHA plus eicosapentaenoic acid (EPA), another omega-3 fatty acid also found in fish oil, to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739).
POSSIBLY SAFE ...when used intravenously and appropriately, in combination with eicosapentaenoic acid (EPA), short-term. Daily infusions with an omega-3 fatty acid-based lipid emulsion (Omegavenous 10%, Fresenius Aktiengesellschaft) providing 4.2 grams/day of DHA and EPA has been used safely for 14 days (1004).
POSSIBLY UNSAFE ...when used orally in high doses. Doses greater than 3 grams daily might decrease platelet aggregation and increase the risk of bleeding (1313). The US Food and Drug Administration (FDA) recommends that consumers limit intake of DHA plus eicosapentaenoic acid (EPA), another omega-3 fatty acid, to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
DHA is a component of some infant formula (424,1045,5708,5941,7599,14403,15003,15495,17735,48088)(48194,48266,48343,90665,90713,90716,110357). In children 7 years and older, DHA 30 mg/kg daily has been used safely for up to 4 years (90684). Also, DHA 0.4-1 grams daily has been safely used in children ages 4 years and older for up to 1 year (11333,90665,100940,104560).
CHILDREN: POSSIBLY UNSAFE
when used orally in preterm infants born less than 29 weeks gestation.
Although not all findings agree (110356,110359), supplementation with an enteral emulsion containing DHA 40 mg/kg to 60 mg/kg daily might increase the risk of developing or worsening bronchopulmonary dysplasia compared to control emulsion (96523,110359).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
An intake of DHA 650 mg daily from food and/or supplements during pregnancy seems to be required to prevent a reduction in DHA status before delivery (110329). DHA is commonly used during pregnancy and lactation and is a component of some prenatal supplements. DHA is a normal component of breast milk, with higher levels in breast milk following term vs. preterm pregnancies (14393,14394,14396,14400,14403,14397,20000,47977,47994,48095)(90672,90718,110355). When taken as a prenatal supplement, DHA increases DHA levels in breast milk (90685). Doses of DHA ranging from 300-600 mg daily beginning during the first trimester of pregnancy have been used safely in clinical research (90672,90676,90687,90694). When taken during lactation, DHA increases DHA levels in breast milk (109214,110362). When initiated within 72 hours of delivery of a very preterm infant, taking DHA 1.2 grams daily increases DHA levels in breast milk within 14 days (109214). One study found that DHA supplementation during lactation increased the risk of bronchopulmonary dysplasia in breast-feeding infants born less than 29 weeks gestational age (104559); however, it is unclear if this was due to DHA or various confounding factors. The tolerable upper intake level of DHA during pregnancy or lactation has not been established; most experts recommend DHA 200-300 mg daily. While it is typically advised that this need is met by consuming 8-12 ounces of seafood weekly during pregnancy and 4-8 ounces weekly during lactation, those with nutrient deficiency or those following a vegan diet may meet this need with supplementation (95740,95741).
LIKELY SAFE ...when fish oil or prescription EPA is used orally and appropriately as a source of EPA. Fish oil containing EPA has been used safely for up to 7 years (1016,7819,15497). While doses of prescription EPA (Vascepa, formerly ARM101, Amarin) have been used safely at doses up to 4 grams daily (91409,91410,95715,99136), there is some concern that high intake of omega-3 fatty acids such as EPA might increase the risk of bleeding. For this reason, the US Food and Drug Administration (FDA) recommends that consumers limit intake of EPA plus docosahexaenoic acid (DHA), another omega-3 fatty acid also found in fish oil, to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739).
POSSIBLY SAFE ...when algal oil is used orally and appropriately as a source of EPA. A specific algal oil supplement (Almega PL) providing EPA 250 mg daily has been used with apparent safety for up to 12 weeks (103314). ...when used intravenously under the guidance of a healthcare professional. Fish oil or omega-3 fatty acid lipid emulsions containing EPA, administered intravenously for 1-4 weeks, have been safely used (1004,66042,66421,89323).
POSSIBLY UNSAFE ...when used orally in high doses. Doses greater than 3 grams daily might decrease blood coagulation and increase the risk of bleeding (1313). The US Food and Drug Administration (FDA) recommends that consumers limit intake of EPA plus DHA, another omega-3 fatty acid, to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. Doses of 3 grams per day and less can be safely used by most people. Fish oil has Generally Recognized As Safe (GRAS) status in the US (1313,1024,2299,2300,2301,2302,2315,2317,4912,5702)(5705,5706,6394,6399,7368,7369,7380,12921,12922,13011)(13766,14382,16733,17408,17991,17992,66454,89325,89336,89346)(89351,89352,89373,89374,101543,103492,103499,103502,104546,105220)(107180,107181,113220). Although higher doses of fish oil, such as 6 grams daily for up to 1 year, have been used safely (89344), there are some safety concerns about using high doses of fish oil. Some older research suggests that doses greater than 3 grams per day can inhibit blood coagulation and potentially increase bleeding risk (8671,8679,8696,66258,21223,21224). However, the most rigorous research to date shows that short-term doses of fish oil 10 grams daily and long-term doses of 1.5 grams daily for up to 52 weeks do not increase the risk of bleeding or affect coagulation parameters in chronically ill and vulnerable patients (97180). Still, doses greater than 3 grams per day might suppress immune response (1313,7384). Patients should only take high-dose fish oil while under medical supervision.
POSSIBLY SAFE ...when parenteral nutrition supplemented with a lipid emulsion enriched in fish oil is used, short-term. Fish oil or omega-3 fatty acid lipid emulsions, administered intravenously for 1-4 weeks, have been safely used (1004,66042,66421,89323,103497).
POSSIBLY UNSAFE ...when fish oil from dietary sources is consumed in large amounts. Fatty fish can contain significant amounts of toxins such as mercury, polychlorinated biphenyls (PCBs), dioxin, and dioxin-related compounds. Very frequent consumption of contaminated fish can cause adverse effects such as tremor, numbness and tingling, difficulty concentrating, and vision problems. Avoid frequent consumption of swordfish, king mackerel, tilefish (also called golden bass or golden snapper), and farm-raised salmon (12964,12965,12966). There is insufficient reliable information available about the safety of fish oil when used topically.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately (5708,5711,65732,66070).
In adolescents 9 years of age and older, fish oil providing doses of up to 2250 mg omega-3 fatty acids daily have been used with apparent safety for up to 12 weeks (101543). Fish oil used in enteral feeds for up to 9 months has been shown to be safe in infants (13745). Young children should limit dietary consumption to no more than two ounces of fish per week (12967,12968). ...when given as part of parenteral nutrition in infants receiving long-term parenteral nutrition (96118,110340,110346,110352).
CHILDREN: POSSIBLY UNSAFE
when fish oil from dietary sources are consumed in large amounts.
Fatty fish can contain significant amounts of toxins such as mercury, polychlorinated biphenyls (PCBs), dioxin, and dioxin-related compounds. Frequent consumption of contaminated fish can cause brain damage, mental retardation, blindness, and seizures in children. Lower levels can cause more subtle problems such as learning disabilities (12964). Young children should limit consumption to no more than 2 ounces per week of fish (12967,12968).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Intake of fish oil during pregnancy does not appear to adversely affect the fetus or nursing infant (1026,1027,1042,8706,12969,12970,12971,12972,12973,14397)(15015,15162,101540,110338,113217,114181). One large clinical trial shows that intake of fish oil from the 24th week of gestation increases the odds of the child having overweight and having metabolic syndrome measurements at age 10 when compared with placebo (114181). More research is needed to confirm these findings. The adequate intake level of omega-3 fatty acids during pregnancy is 1.4 grams daily; the adequate intake level during lactation is 1.3 grams daily (89377). If possible, people who are trying to become pregnant, as well as those who are pregnant or lactating, should avoid swordfish, king mackerel, and tilefish (also called golden bass or golden snapper), as these may contain high levels of methylmercury. Pregnant individuals should also limit consumption of other fatty fish to 12 ounces, or about 3-4 servings, per week.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when fish oil from dietary sources are consumed in large amounts.
Fatty fish can contain significant amounts of toxins such as mercury, polychlorinated biphenyls (PCBs), dioxin, and dioxin-related compounds. If possible, people who are trying to become pregnant, as well as those who are pregnant or lactating, should avoid swordfish, king mackerel, and tilefish (also called golden bass or golden snapper), as these may contain high levels of methylmercury. Pregnant individuals should also limit consumption of other fatty fish to 12 ounces, or about 3-4 servings, per week (12967,12968).
Below is general information about the interactions of the known ingredients contained in the product Pure Dimension. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, DHA may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
 Details
Although some clinical evidence suggests that DHA might reduce collagen-stimulated platelet aggregation and thromboxane release, most clinical evidence suggests that DHA alone does not affect blood clotting (11112,11113,48020). However, theoretically, when given in combination with EPA as fish oil, concomitant use with anticoagulant or antiplatelet drugs (including aspirin) might increase risk of bleeding.
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Theoretically, taking DHA with antidiabetes drugs might reduce the effects of these medications.
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In people with type 2 diabetes, including those taking oral hypoglycemic medications, DHA seems to increase fasting blood glucose levels (10321).
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Theoretically, taking DHA with antihypertensive drugs might increase the risk of hypotension.
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Theoretically, EPA may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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In human research, taking EPA has been shown to inhibit platelet aggregation (9930).
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Theoretically, taking EPA with antihypertensive drugs might increase the risk of hypotension.
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Fish oil may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, evidence is conflicting.
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While fish oil may not be a potent inhibitor of platelet function, high doses of fish oil might have antiplatelet effects. Theoretically, concomitant use of fish oil with anticoagulant or antiplatelet drugs may increase the risk of bleeding (8671,8679,8696,13769,21223,21224,66258). However, the most rigorous research shows that short-term doses of fish oil 10 grams daily or long-term doses of 1.5 grams daily for up to 52 weeks does not increase the risk of bleeding or affect coagulation parameters in chronically ill and vulnerable patients (97180). Other controlled research shows that fish oil does not affect platelet function or increase the risk of bleeding (17990,17996,66105,66267,89374,107180). Some research even suggests that perioperative fish oil use decreases bleeding risk (89352). Some research suggests fish oil does not have additive antiplatelet effects when combined with aspirin (13769), but other clinical evidence suggests that adding fish oil to low-dose aspirin treatment increases antiplatelet effects in patients who are aspirin-resistant (21226). Also, some clinical research seems to show that fish oil has additive antiplatelet effects when used with aspirin and clopidogrel compared to aspirin and clopidogrel alone (21225).
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Theoretically, taking fish oil with antihypertensive drugs might increase the risk of hypotension.
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Theoretically, taking fish oil with contraceptive drugs might decrease the triglyceride-lowering effects of fish oil.
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There is some evidence that contraceptive drugs might interfere with the triglyceride lowering effects of fish oils (8694).
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Taking fish oil with cyclosporine might increase levels and adverse effects of cyclosporine.
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In kidney transplant recipients on a general immunosuppressive regimen, taking omega-3 fatty acids daily seems to increase peak blood levels of cyclosporine when compared with placebo. This increase was as much as 20% after one month. However, the area under the curve was not significantly affected (66472).
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Theoretically, taking fish oil with orlistat might decrease the absorption of fish oil fatty acids.
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Orlistat binds lipase in the gastrointestinal tract and reduces fat absorption. Theoretically, taking fish oil with orlistat might decrease absorption of fish oil fatty acids. To avoid this potential interaction, recommend separating administration of orlistat and fish oil by at least 2 hours.
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Theoretically, taking fish oil with platinum agents can cause resistance to platinum agents, potentially decreasing their effectiveness.
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Platinum-induced fatty acids (PIFAs) are fatty acids secreted from human and mouse stem cells when exposed to platinum-based chemotherapy. Animal research suggests that PIFAs cause resistance to chemotherapy by stimulating lysophospholipid production in the spleen, which interferes with the DNA damage caused by certain chemotherapy drugs (92076). One PIFA, known as 16:4(n-3), has been found in both raw fish and some commercially available fish oil products. Mackerel and herring have high PIFA concentrations, while salmon and tuna have low PIFA concentrations. Levels of PIFA in commercial fish oil products ranged from 0.2- 5.7 microMol. Animal research shows that PIFA-containing fish oil products cause resistance to cisplatin, fluorouracil, irinotecan, and oxaliplatin (91250,92075). It is unclear if all commercially available fish oil products contain PIFAs. Additionally, it is argued that levels of PIFA found in some fish oil products are too low to be of clinical concern. Furthermore, a lack of chemotherapy resistance in countries with high fish intake, such as Greenland, Japan, and Norway, suggest that this interaction may not be clinically significant (91288,91289).
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Taking fish oil with sirolimus might increase levels and adverse effects of sirolimus.
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Pharmacokinetic research shows that omega-3 fatty acids increase exposure to sirolimus in kidney transplant patients on a calcineurin inhibitor-free immunosuppressive regimen. A 25% dose reduction in sirolimus was required to keep patients within the expected trough-concentration window (105232). Researchers hypothesize that this may be due to inhibition of cytochrome P450 3A4 (CYP3A4) by fish oil, although this has not been confirmed in clinical research.
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Taking fish oil with tacrolimus might increase levels and adverse effects of tacrolimus.
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In a small group of patients, taking fish oil 2.6 grams (Omacor) daily for 4 weeks increased the 8-hour area under the curve of tacrolimus by 25% when compared with baseline. Peak levels were increased by approximately 22% (105212). Researchers hypothesize that this may be due either to an increase in bioavailability or to inhibition of cytochrome P450 3A4 (CYP3A4) by fish oil, although this has not been confirmed in clinical research.
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Fish oil may have antiplatelet effects and might increase the risk of bleeding if used with warfarin.
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Below is general information about the adverse effects of the known ingredients contained in the product Pure Dimension. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, DHA is generally well-tolerated when used in doses up to 3 grams daily.
Intravenously, DHA seems to be well tolerated.
Most Common Adverse Effects:
Orally: Belching, fishy aftertaste, loose stools, and nausea.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about increased risk of bleeding with high doses of fish oil containing DHA.
Cardiovascular ...Orally, DHA might increase low-density lipoprotein (LDL) cholesterol levels. However, this appears to be primarily due to increases in the large buoyant type of LDL particles. The small, dense type of LDL particles are reduced (6143,48013,48078,48083,48174,48338).
Dermatologic ...Orally, DHA has been associated with one report of rash and one report of warmth on hands in one clinical study (48217). In another clinical study, two patients taking DHA 400 mg daily reported acne (11333). In another clinical study, one parent of a pediatric patient treated with DHA 600 mg daily reported increased hair loss beginning 6 weeks after completion of supplementation (90699). It is unclear if this adverse effect is specifically related to DHA intake.
Gastrointestinal
...Orally, DHA may cause gastrointestinal upset, fishy aftertaste, belching, flatulence, heartburn, loose stools, anorexia, and dry mouth (10869,11333,48217,109218).
There is also some evidence that increased serum levels of DHA might be associated with an increased risk for atrophic gastritis associated with Helicobacter pylori infection, but further research is needed to clarify this finding (8709).
For fish oils containing EPA and DHA, side effects can include fishy taste, belching, nausea, and loose stools (1009,1313,8699,10007). Three people with pre-existing familial adenomatous polyposis were diagnosed with malignant lesions during the course of long-term fish oil use (999).
Genitourinary ...Orally, one patient in one clinical study who was taking DHA 1, 2, or 4 grams daily (specific dose unclear) reported decreased libido (48217).
Hematologic ...Orally, DHA might cause nose bleeds, but this is uncommon. Onset of severe nose bleeds has been reported in one clinical study in one child who took DHA 600 mg daily (98542). Although most clinical research shows that DHA does not affect blood clotting when taken alone (11112,11113,48020), there is some concern that taking high doses of oils providing DHA along with eicosapentaenoic acid (EPA) might decrease blood coagulation and increase the risk of bleeding (1313). The US Food and Drug Administration (FDA) recommends that consumers limit intake of EPA plus DHA to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739).
Neurologic/CNS ...Orally, DHA may cause dizziness, headache, insomnia, fatigue, and anxiety (10869,11333,48217). In one clinical study, one parent of a pediatric patient treated with DHA 600 mg daily reported increased disruptive behavior in the child (90699).
Ocular/Otic ...Orally, DHA may cause watery eyes but results are inconsistent. In one clinical study, five of 167 infants fed formula containing 0.32% or 0.64% DHA experienced watery eyes. However, none of the infants fed formula containing 0.96% DHA experienced watery eyes (90670). In one clinical study, one patient taking DHA 400 mg daily experienced an ear infection. It is unclear if this event was related to DHA supplementation.
Oncologic ...Orally, DHA may increase the risk of prostate cancer, but additional research is needed to clarify this finding. A meta-analysis of data from observational studies found that higher dietary intake of DHA is associated with a non-linear increased risk of prostate cancer (90677). It is unclear if supplemental DHA intake is associated with increased risk of prostate cancer.
Pulmonary/Respiratory ...Orally, worsened asthma symptoms were reported by one parent of one patient with asthma taking DHA 600 mg daily (90699).
General
...Orally, prescription EPA or EPA derived from fish oil is generally well tolerated in doses of up to 3 grams daily.
Agal oil providing EPA seems to be well tolerated. Doses of EPA greater than 3 grams daily are possibly unsafe.
Intravenously, fish oil or omega-3 fatty acid lipid emulsions containing EPA seem to be well tolerated.
Most Common Adverse Effects:
Orally: Belching, diarrhea, epigastric discomfort, fishy aftertaste, and nausea.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about increased risk of bleeding with high doses.
Cardiovascular ...Orally, taking the prescription ethyl-EPA product (Vascepa, Amarin) 4 grams daily has been linked to a 1% greater risk of atrial fibrillation or atrial flutter that required hospitalization when compared with placebo (101286).
Dermatologic ...Orally, reported side effects of EPA have included skin rash and itching (15497).
Gastrointestinal ...Orally, reported side effects of EPA have included nausea, diarrhea, and epigastric discomfort (15497,103314,110365,110366). For fish oils containing EPA and docosahexaenoic acid, side effects can include fishy taste, belching, nausea, and loose stools (10007).
Hematologic ...Orally, reported side effects of EPA, as well as fish oils containing EPA and docosahexaenoic acid (DHA), have included nosebleed (10007,15497). There is some concern that taking high doses of oils providing EPA along with DHA might decrease blood coagulation and increase the risk of bleeding (1313). To reduce this risk, the US Food and Drug Administration (FDA) recommends that consumers limit intake of EPA plus DHA to 3 grams daily, with no more than 2 grams daily from a dietary supplement (95739). The prescription ethyl-EPA product (Vascepa, Amarin) 4 grams daily has been linked to bleeding in 12% of patients, compared with 10% in the placebo group. Serious bleeding occurred in 3% of the Vascepa group compared to 2% in the placebo group (101286).
Immunologic ...There is preliminary evidence that the EPA in fish oil decreases natural killer (NK) cell activity. Due to this effect, there is concern that increased intake of EPA might have some adverse immunologic effects and possibly increase the risk for viral infections and some cancers (8718).
Musculoskeletal ...Orally, EPA may cause musculoskeletal pain in some patients, although results from clinical research are conflicting. In one clinical study, a higher percentage of patients treated with ethyl-EPA 2 or 4 grams daily experienced joint pain compared to placebo (3.4% and 1.7% vs 0.4%, respectively) (91409). However, in another study, slightly fewer patients taking ethyl-EPA 1.8 grams daily experienced joint, lumbar, or muscle pain compared to placebo (1.6% vs 2.0%, respectively) (15497).
Oncologic ...Three people with pre-existing familial adenomatous polyposis have been diagnosed with malignant lesions during the course of long-term high-docosahexaenoic acid fish oil use (999); however, it is unclear if fish oil, or more specifically EPA, was the cause.
General
...Orally and parenterally, fish oil is generally well-tolerated.
Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Abdominal pain, bad breath, fishy aftertaste, heartburn, increased low-density lipoprotein (LDL) cholesterol levels, loose stools, nausea, and rash.
Serious Adverse Effects (Rare):
Orally: Atrial fibrillation. When taken in doses of 3 grams or more daily, there are rare reports of increased risk of bleeding and stroke, as well as immune suppression.
Cardiovascular
...Orally, fish oil supplements in doses of 3-10 grams daily can cause a dose-dependent increase in low-density lipoprotein (LDL) cholesterol levels in some people (2299,2318,8678,8698,15734,15735,48120,65729) by increasing the size of LDL particles (9771).
Therefore, LDL levels should be monitored in people who take fish oil supplements (15734). But fish oil doesn't seem to cause development of atherosclerosis, despite earlier concerns that polyunsaturated fatty acids, such as omega-3 fatty acids, might increase the oxidation of LDL (1011,2323,7165,7366,8695,8700,9771).
There is concern that fish oil supplements may be associated with an increased risk for atrial fibrillation (AF). In one large clinical study (the STRENGTH trial), taking a prescription fish oil product (Epanova) 4 grams daily for up to 5 years was associated with an increased risk for AF, with a number needed to harm of 114 when compared with a corn oil control. The patients in this study were considered to be at high risk for future cardiovascular disease (CVD) (103491). Also, one large population study in adults without CVD suggests that regular use of fish oil supplements is associated with a modestly higher risk of both atrial fibrillation and stroke when compared with non-use of fish oil supplements (114182).
In a secondary analysis of the Omega-3 fatty acids in Elderly patients with Myocardial Infarction (OMEMI) trial, adults aged 70-82 years with recent myocardial infarction supplementing with 1.8 grams daily of n-3 PUFA (EPA/DHA) for 24 months had a 90% increased risk of developing AF or micro-AF, which is characterized by short, AF-like activity lasting less than 30 seconds. Changes in serum EPA levels seem to mediate this risk, with higher serum EPA levels predictive of an increased risk of AF and intermediate serum EPA levels predictive of an increased risk of micro-AF (112469).
Meta-analyses of randomized controlled trials show that taking omega-3 fatty acid supplements increases the incidence rate ratio for AF by up to 37% when compared with placebo, with an increased incidence rate associated with doses of more than 1 gram daily. One study in these analyses used eicosapentaenoic acid (EPA) alone as purified icosapent ethyl (106075,107171,107181).
In 2023, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency issued a public statement on the use of omega-3-acid ethyl esters, concluding that exposure to omega-3-acid ethyl esters for the treatment of hypertriglyceridemia is associated with a dose-dependent increased risk of AF in patients with established cardiovascular disease or risk factors for cardiovascular disease when compared with placebo. The highest risk of AF is associated with a dose of 4 grams daily. If AF occurs, treatment should be permanently discontinued (112467).
Dermatologic
...Orally, skin rashes, itching, and skin irritation have been reported (66498,66492,66488,89369,104551).
A case of severe tissue inflammation and breast tissue necrosis has been reported for a female who injected fish oil from capsules subcutaneously for breast augmentation (89371).
Gastrointestinal
...Orally, most adverse effects of omega-3 fatty acids are gastrointestinal in nature (12915,65599,65728,65770,65780,65904,66061,66104,66164,66488)(89347,89357,103491,103551,107172,114184).
Gastrointestinal upset is common with the use of fish oil supplements, occurring in up to 5% of patients in clinical trials, with nausea in up to 1.5% of patients (2307,16733,65599,65732,65762,65830,65886,65925,65974)(66020,66042,66083,66104,66130,66164,66169,66358,66370,66488)(66494,66498,89347,103491,104551,110353,114184). Diarrhea and loose stools may also occur (6257,10871,65599,65648,65830,65935,66042,66061,66104,66119)(66130,66173,66492,89347,89359,103491,104551,107172,110353), with potentially severe diarrhea at very high doses (12986,16901,66093,66356). There have also been reports of increased burping (17963,65648,65729,65770,65830,66020,66042,66077,66164,66169)(66492,66494,104551,114184), acid reflux, heartburn (104551,110338), indigestion (65566,65830,66061,66104,66173,89359,114184), abdominal bloating (66083,66104), abdominal or gastrointestinal pain or discomfort (8680,17996,66119,66492,103491), anorexia (62390,89359), flatulence (66492), constipation (16901), nausea and vomiting (65728,65830,66104,66130,66488,103491,104551), steatorrhea (66119,66354,66356), fishy hiccups (66488), metallic taste (66488), and a fishy breath odor and aftertaste (16901,65648,65729,65762,66020,66042,66061,66077,66083,66104)(66130,66164,66172,66173,66424,66488,66494,89369,104551,107172). Also, some preliminary evidence suggests that increased serum levels of omega-3 fatty acids, especially DHA, might increase the risk for atrophic gastritis (8709).
Gastrointestinal side effects may be minimized if fish oils are taken with meals and if doses are started low and gradually increased. Taking supplements with meals or freezing them seems to help decrease these side effects for some patients (12975). Enteric coated fish products might also help reduce side effects (6258).
Hematologic
...Orally, 3 grams or greater of omega-3 fatty acids daily may inhibit platelet aggregation and increase the risk of bleeding; however, there is little evidence of statistically significant bleeding risk at lower doses (1313,8699,66500,66501,66334,101543).
Very large intakes of fish oil or omega-3 fatty acids (more than 46 grams per day) may increase the risk of ischemic or hemorrhagic (bleeding) stroke (7603,66502).
A case of hemolytic anemia has been reported for an infant with short bowel syndrome who developed liver disease from total parenteral nutrition (TPN) and was switched to a specific TPN with fish oil (Omegaven, Fresenius-Kabi, Graz, Austria) instead. After stopping the fish oil-TPN, the anemia was reversed suggesting that parenteral fish oil might cause hemolytic anemia (66022).
Hepatic ...Orally, mild elevations in liver function tests, such as alanine aminotransferase and aspartate aminotransferase, have been reported rarely (66353,113218).
Immunologic
...A case of anaphylaxis following ingestion of a fish oil capsule has been reported for a female patient with a history of allergy to crab.
The patient was treated successfully with epinephrine, but had several recurrences of stridor over the next 2 days (89378).
There is also some evidence that fish oil in doses greater than 3 grams per day might adversely affect immune function. Fish oil appears to suppress T- and B-cell function and to reduce the production of cytokines, which might be detrimental to elderly people and people with suppressed immune function such as patients with human immunodeficiency virus (HIV) infection (1313,7383,7384).
Neurologic/CNS ...Orally, fish oil may cause headache, dizziness, and inability to sleep (65599,65648,89359,103491,104551). Also, restlessness and formication have been reported in less than 1% of studied cases of patients taking fish oil (66498).
Oncologic ...There is some concern that high fish intake may increase the risk for certain types of cancer. One large epidemiological study has found that dietary intake of fish oil from fatty fish twice a week or more is associated with a 16% increased risk of breast cancer when compared with eating fatty fish less than twice weekly (107175). Additionally, an analysis of the NIH-AARP Diet and Health Study, a prospective cohort study in over 491,000 older adults, has found that total intake of fish is associated with increased melanoma risk over a median follow-up of 15.5 years. When the lowest and highest quintiles of intake are compared, there is a 22% increase in the risk for malignant melanoma and a 28% increase in the risk for melanoma in situ. In sub-group analyses, all melanoma incidence is positively associated with tuna intake or non-fried fish intake, but malignant melanoma incidence is inversely associated with fried fish intake (108509). It was suggested that the positive associations could be due to contaminants in fish such as polychlorinated biphenyls, dioxins, arsenic, and mercury.
Pulmonary/Respiratory ...Orally, fish oil has been reported to cause nasopharyngitis and upper respiratory tract infections in 3. 3% of patients in one clinical trial (65798). Exacerbation of asthma and apnea have been reported for patients using fish oil (1040,66061,66119,66354).
Other ...Fish oil can contribute to caloric intake and may cause weight gain if used long-term. One gram of fat or oil provides 9 kcal (6871). Fish oil capsules containing 500 mg omega-3 fatty acids in 1 gram of oil would supply about 13.5 kcal per capsule (6871,6874). Fish oil supplements also contain cholesterol in amounts from 1-6 mg per gram of fish oil (3022,6871).
