Lok CE, Moist L, Hemmelgarn BR, Tonelli M, Vazquez MA, Dorval M, Oliver M, Donnelly S, Allon M, Stanley K; Fish Oil Inhibition of Stenosis in Hemodialysis Grafts (FISH) Study Group. Effect of fish oil supplementation on graft patency and cardiovascular events among patients with new synthetic arteriovenous hemodialysis grafts: a randomized controlled trial. JAMA 2012;307(17):1809-16. View abstract.
Fish oil seems to be a subject of controversy. Some people swear by it, and there are thousands of clinical trials out now trying to study what the latest and greatest thing about the supplement is. The Natural Standard does a really good job collecting and gathering data for those who are interested in delving through what fish oil may or may not be doing to us. Definitive answers, however, may take a little while to get.
A healthy balance of dietary omega 6 and omega 3 fatty acids is a prerequisite for normal immune function, cognitive health, and cardiovascular health. Among other factors, sufficient dietary levels of EPA, DHA or other omega 3 fatty acids are also important in the regulation of normal blood lipoprotein and healthy cholesterol metabolism. Fish oil supplements can also lower elevated triglyceride levels, improving cardiovascular health and reducing the risk of heart disease.†
Hernandez, D., Guerra, R., Milena, A., Torres, A., Garcia, S., Garcia, C., Abreu, P., Gonzalez, A., Gomez, M. A., Rufino, M., Gonzalez-Posada, J., Lorenzo, V., and Salido, E. Dietary fish oil does not influence acute rejection rate and graft survival after renal transplantation: a randomized placebo-controlled study. Nephrol.Dial.Transplant. 2002;17(5):897-904. View abstract.

Fish oils might slow blood clotting. Taking fish oils along with medications that also slow clotting might increase the chances of bruising and bleeding.Some medications that slow blood clotting include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.
Heavy metal poisoning by the body's accumulation of traces of heavy metals, in particular mercury, lead, nickel, arsenic, and cadmium, is a possible risk from consuming fish oil supplements.[medical citation needed] Also, other contaminants (PCBs, furans, dioxins, and PBDEs) might be found, especially in less-refined fish oil supplements.[citation needed] However, heavy metal toxicity from consuming fish oil supplements is highly unlikely, because heavy metals selectively bind with protein in the fish flesh rather than accumulate in the oil. An independent test in 2005 of 44 fish oils on the US market found all of the products passed safety standards for potential contaminants.[107][unreliable source?]
A 2009 metastudy found that patients taking omega-3 supplements with a higher EPA:DHA ratio experienced fewer depressive symptoms. The studies provided evidence that EPA may be more efficacious than DHA in treating depression. However, this metastudy concluded that due to the identified limitations of the included studies, larger, randomized trials are needed to confirm these findings.[40]
In a 2009 letter on a pending revision to the Dietary Guidelines for Americans, the American Heart Association recommended 250–500 mg/day of EPA and DHA.[26] The Guidelines were revised again for 2015-2020; included is a recommendation that adults consume at least eight ounces of a variety of types of fish per week, equating to at least 250 mg/day of EPA + DHA.[citation needed] The Food and Drug Administration recommends not exceeding 3 grams per day of EPA + DHA from all sources, with no more than 2 grams per day from dietary supplements.[27]
The health benefits of fish oil include its ability to aid in weight loss and healthy pregnancy. It also promotes fertility and skin care (particularly for psoriasis and acne). It is beneficial in the treatment of various heart diseases, high cholesterol, depression, anxiety, ADHD, weak immune system, cancer, diabetes, inflammation, arthritis, IBD, AIDS, Alzheimer’s disease, eye disorders, macular degeneration, and ulcers.
Fish oil combined with fenofibrate has not been studied extensively in randomized controlled trials. Data to date, however, suggest that the combination is safe and effective.63,64 A recent randomized controlled trial of 100 patients with severe hypertriglyceridemia and HIV on highly active antiretroviral therapy showed that a regimen of fenofibrate and 3 g/d of fish oil for 8 weeks was well tolerated. The median baseline triglyceride level of 650 mg/dL was reduced by 65%.63 Another recent randomized, 2 month, double-blind, placebo-controlled trial, which was set up to assess the safety and efficacy of fenofibrate with 4 g of fish oil, showed that in the 81 patients assigned to combination therapy, triglyceride levels were reduced by 61%. Therapy was well-tolerated without significant adverse reactions at 8 weeks or at the end of a 2-year open label extension.64 The combination of fish oil and niacin requires further study.
Omega-3 is a group of long-chain polyunsaturated fatty acids, perhaps most notably found in fatty fish. As science parses the biological actions of nutrients, it turns out that omega-3 fats do many good things for the body and the brain. Known as an "essential" fatty acid, meaning the body must take it in from food sources, omega-3 is important to human metabolism.
The current American diet has changed over time to be high in SFA and low in omega-3 fatty acids (12). This change in eating habits is centered on fast food containing high amounts of saturated fat, which has small amounts of essential omega-3 PUFA compared with food prepared in the home (13). Seafood sources such as fish and fish-oil supplements are the primary contributors of the 2 biologically important dietary omega-3 fatty acids, EPA and DHA (14–16). This low intake of dietary EPA and DHA is thought to be associated with increased inflammatory processes as well as poor fetal development, general cardiovascular health, and risk of the development of Alzheimer's disease (AD).
From the time of your pregnancy through your child's later life, omega-3 fats DHA and EPA have a radically important role in her brain health and other functions. I recommend supplementing with krill oil before and during pregnancy, and while you breastfeed. Babies receive DHA through your breast milk, so continuing breastfeeding through the first year will give your child a great headstart for health and success.
Like I mentioned earlier, there are no official guidelines for the proper amount of omega-3s you should consume each day. However, most organization agree that at least 2 servings of a 3.5 ounce serving of fish (preferably oily) each week is a good start. That equals about 500 milligrams of EPA/DHA each day. For treating disease, up to 4,000 milligrams per day is recommended by various studies, although values do vary. (96) It’s why a pescatarian diet can have such health protective effects.

Omega-3s are generally safe and well tolerated. Stomach upset and “fishy taste” have been the most common complaints, but they are less frequent now thanks to manufacturing methods that reduce impurities. Past concerns about omega-3s increasing the risk of bleeding have been largely disproven, but caution is still advised in people taking blood thinners or who are about to undergo surgery. As mentioned, caution is needed in people with bipolar disorder to prevent cycling to mania. Because omega-3s are important to brain development, and pregnancy depletes omega-3 in expectant mothers, supplementation should theoretically benefit pregnant women and their children. Fish consumption in pregnancy is supported by the FDA, but because we do not have long-term data on safety or optimal dosing of omega-3s in pregnancy, expectant mothers should consider omega-3 supplements judiciously.
Five studies with 7 data sets recruited participants without specific clinical conditions.36,47,51,55,60 The main results revealed that there was no significant difference in the association of treatment with reduced anxiety symptoms between patients receiving omega-3 PUFA treatment and those not receiving it (k, 5; Hedges g, –0.008; 95% CI, –0.266 to 0.250; P = .95) (Figure 3A). Fourteen studies with 14 data sets recruited participants with specific clinical diagnoses.33-35,48-50,52-54,56-59,61 The main results revealed a significantly greater association of treatment with reduced anxiety symptoms in patients receiving omega-3 PUFA treatment than in those not receiving it (k, 14; Hedges g, 0.512; 95% CI, 0.119-0.906; P = .01) (Figure 3A). Furthermore, according to the interaction test, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions (P = .03).

The effect of fish oil on incident atrial fibrillation has not been studied in large randomized trials, and observational population-based trials show mixed results. The Danish Diet, Cancer and Health Study, and the Rotterdam Study followed 47,000 and 5100 middle-aged adults, respectively.45,46 Neither study found that the consumption of fish oil affected the incidence of atrial fibrillation. Similar findings were seen in the Women’s Health Initiative where there was no association between fish and omega-3 FA intake regarding incident atrial fibrillation.47 However, in a 12-year prospective, observational study of 4815 adults over the age of 65, daily fish consumption was associated with a 31% risk reduction in incident atrial fibrillation.48
Because patients with depression experience rapid shrinking of their hippocampus, many strategies for relieving depression focus on increasing new brain cell growth in that specific area of the brain.23 There’s now evidence that increasing omega-3 intake, especially DHA, may be an effective way of treating or preventing depression, partly by protecting the hippocampus from further shrinkage.23
Fish oil supplements vary in the amounts and ratios of DHA and EPA they contain. For example, salmon oil naturally contains more DHA than EPA; a supplement derived from algae may only contain DHA. Krill oil contains significant amounts of both EPA and DHA. Read the labels and remember whatever supplement you buy, it must have at least 600 mg of DHA.
Despite this one study, you should still consider eating fish and other seafood as a healthy strategy. If we could absolutely, positively say that the benefits of eating seafood comes entirely from omega-3 fats, then downing fish oil pills would be an alternative to eating fish. But it’s more than likely that you need the entire orchestra of fish fats, vitamins, minerals, and supporting molecules, rather than the lone notes of EPA and DHA.
An animal study involving the omega-3 ETA discovered that subjects experienced a drop in overall inflammation similar to that caused by NSAIDs (non-steroidal anti-inflammatory drugs), but without the dangerous gastrointestinal side effects. The study authors also pointed out that eicosapentaenoic acid seems to be even more potent than the conventional omega-3s found in fish oil supplements (EPA/DHA). (56)
The chemical structures of EPA and DHA are very similar and they compete for uptake and processing resources. During digestion, the triglyceride molecules in standard fish oil are broken down into a mono glycerol and two free fatty acids, small enough to be absorbed into cells of the gut lining. More often than not, DHA is the fatty acid that remains attached to the glycerol backbone, meaning in essence that DHA gets a ‘free pass’ into the gut, while the remaining free fatty acids (more often EPA) must reattach onto a glycerol molecule or risk being oxidised and used as fuel. The implication of this is that DHA levels in our cells are often concentrated at the expense of EPA after absorption when taking EPA and DHA in the standard ratio of 1.5 to 1.

Fish oil supplements in our study averaged 473.3mg EPA + 243.1mg DHA in a single serving. These average values were stretched by outliers on both extremes of the spectrum. Nature Made Cod Liver Oil (50mg EPA/serving) and Schiff MegaRed Krill Oil (29mg DHA/serving) recorded category lows for the two omega-3 fatty acids. Ocean Blue Professional Omega-3 (1260mg EPA/serving) and Dr. Tobias Optimum Omega-3 Fish Oil (600mg DHA/serving), on the other hand, recorded category highs for EPA and DHA content.
The number, location, and orientation of the double bonds determine the health effects of fatty acids on the body. One aspect of this is their effect on triglycerides and LDL and HDL types of cholesterol, which in turn affect how much cholesterol gets deposited on the inside of blood vessels. There are also subtypes of LDL and HDL which are also likely important to their health effects.
Nonetheless, large population studies with solid data both on the participants’ diets and causes of disease and death bolstered the beliefs that eating fish often was a heart-healthy practice linked to reduced rates of cardiovascular disease. For example, a comprehensive analysis conducted by Dr. Dariush Mozaffarian and Eric Rimm of the Harvard T.H. Chan School of Public Health found that eating two servings of fatty fish a week — equal to about two grams of omega-3 fatty acids — lowered the risk of death from heart disease by more than a third and total deaths by 17 percent.
Fish or seafood allergy: Some people who are allergic to seafood such as fish might also be allergic to fish oil supplements. There is no reliable information showing how likely people with seafood allergy are to have an allergic reaction to fish oil. Until more is known, advise patients allergic to seafood to avoid or use fish oil supplements cautiously.
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