If you’re not able to get enough fish oil benefits through your diet, fish oil supplements can be a good option. Fish oil side effects can include belching, bad breath, heartburn, nausea, loose stools, rash and nosebleeds, but in my experience, taking a high-quality fish oil supplement can reduce the likelihood of any unwanted side effects. It’s also a good idea to take fish oil with meals to reduce side effects.
The evidence that fish oil consumption should be used for primary prevention of CAD is based on observational studies. The only randomized trial for primary prevention, the JELIS trial, showed a moderate relative risk reduction and was conducted in a very specific group. Nevertheless, to date, there has been no strong signal suggesting any serious adverse effects of having high DHA and EPA oils in the diet. We agree with the national guidelines that one should consume moderate amounts of fish oil— either in supplement or through the dietary intake of fatty fish with low mercury levels.
Omega-3 fatty acids have been found to play a role in atherosclerosis and peripheral arterial disease (PAD). It is thought that both EPA and DHA improve plaque stability, decrease endothelial activation, and improve vascular permeability, thereby decreasing the chance of experiencing a cardiovascular event (41). It was found that EPA supplementation is associated with significantly higher amounts of EPA in the carotid plaque than placebo (P < 0.0001), which may lead to decreased plaque inflammation and increased stability (42). PAD, a manifestation of atherosclerosis, is characterized by buildup of plaque in the arteries of the leg and can eventually lead to complete blockage of the arteries. EPA+DHA supplementation has been shown to improve endothelial function in patients with PAD by decreasing plasma levels of soluble thrombomodulin from a median value of 33.0 μg/L to 17.0 μg/L (P = 0.04) and improve brachial artery flow–mediated dilation from 6.7% to 10.0% (P = 0.02) (43). Patients who had PAD and were supplemented with EPA experienced a significantly lower major coronary event HR than those who did not take EPA (HR: 0.44; 95% CI: 0.19–0.97; P = 0.041) (44).
It can be challenging to get the appropriate intake of EPA and DHA through diet alone, even though EPA and DHA are produced by water plants such as algae and are prevalent in marine animals. A shorter chain omega-3 fatty acid, α-linolenic acid (ALA),6 is a prominent component of our diet as it is found in many land plants that are commonly eaten, but it does not provide the health benefits seen with EPA and DHA. Although it is possible for the body to convert ALA to EPA and DHA by enlongase and desaturase enzymes, research suggests that only a small amount can be synthesized in the body from this process (8). For example, 1 study suggested that only ∼2 to 10% of ALA is converted to EPA or DHA (9), and other studies found even less: Goyens et al. (10) found an ALA conversion of ∼7% for EPA, but only 0.013% for DHA; Hussein et al. (11) found an ALA conversion of only 0.3% for EPA and <0.01% for DHA.
Not surprising, there are some areas in which both EPA and DHA appear to be equally beneficial. As an example, both are equally effective in reducing triglyceride levels (10). This is probably due to the relatively equivalent activation of the gene transcription factor (PPAR alpha) that causes the enhanced synthesis of the enzymes that oxidize fats in lipoprotein particles. There is also apparently equal activation of the anti-inflammatory gene transcription factor PPAR-gamma (11). Both seem to be equally effective in making powerful anti-inflammatory eicosanoids known as resolvins (12). Finally, although both have no effect on total cholesterol levels, DHA can increase the size of LDL particle to a greater extent than can EPA (10).

EPA is the precursor to DHA in the body and can be converted to DHA with the enzyme delta-6 desaturase, but this process is inefficient in many people (much like the inefficiency of short-chain omega-3s to long-chain). For those individuals taking pure EPA products as well as those taking our EPA-rich products, we still recommend eating oily fish at least once each week to provide a natural source of DHA. Fish provides a unique nutritional package, supplying the diet with important amino acids (the building blocks of proteins) and antioxidants, including vitamins and minerals needed to process fats, so eating fish will also support the natural enzyme-dependent EPA to DHA conversion.

Consumers of oily fish should be aware of the potential presence of heavy metals and fat-soluble pollutants like PCBs and dioxins, which are known to accumulate up the food chain. After extensive review, researchers from Harvard's School of Public Health in the Journal of the American Medical Association (2006) reported that the benefits of fish intake generally far outweigh the potential risks.

The omega-3 index is also important because it is inversely related to one’s omega-6 to omega-3 ratio — another important measurement (3). A lower omega-6/omega-3 ratio (meaning, you consume a balanced amount of these two fatty acid families) is associated with a reduced risk of many chronic diseases, including cardiovascular disease, cancer, and autoimmune disease, to name a few (4). Of course, most people get far too much omega-6 and too little omega-3, thanks to the plethora of highly processed foods in the Western diet.
Irish AB, Viecelli AK, Hawley CM, et al; Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) Study Collaborative Group. Effect of fish oil supplementation and aspirin use on arteriovenous fistula failure in patients requiring hemodialysis: A randomized clinical trial. JAMA Intern Med. 2017;177(2):184-193. View abstract.
A group out of India conducted a study published in Cancer Chemotherapy and Pharmacology based on the premise that “fish oil rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anti-cancer drugs.” The study found that using 5-Fluorouracil (5-FU) to treat colorectal cancer along with fish oil increased the survival rate in carcinogen-treated animals. Researchers also found that the fish oil ameliorated hematologic depression, along with gastrointestinal, hepatic and renal toxicity caused by the 5-FU. (15)
We’ve already seen that fish oil can help with depression-like symptoms in rats, but what about people? A study published in the journal Nutritional Neuroscience evaluated the effects of fish oil supplementation on prefrontal metabolite concentrations in adolescents with major depressive disorder. Researchers found that there was a 40 percent decrease in major depression disorder symptoms in addition to marked improvements in amino acid and nutrition content in the brain, specifically, the right dorsolateral prefrontal cortex. (21)
Brain function and vision rely on dietary intake of DHA to support a broad range of cell membrane properties, particularly in grey matter, which is rich in membranes.[61][62] A major structural component of the mammalian brain, DHA is the most abundant omega−3 fatty acid in the brain.[63] It is under study as a candidate essential nutrient with roles in neurodevelopment, cognition, and neurodegenerative disorders.[61]
Some studies suggest that people who get higher amounts of omega-3s from foods and dietary supplements may have a lower risk of breast cancer and perhaps colorectal cancer. More research is needed to confirm this possible link. Whether omega-3s affect the risk of other cancers is not clear. Clinical trials to examine this possibility are in progress.

Pregnancy and breast-feeding: Fish oil is LIKELY SAFE when taken by mouth appropriately. Taking fish oil during pregnancy does not seem to affect the fetus or baby while breast-feeding. Women who are pregnant or who may become pregnant, and nursing mothers should avoid shark, swordfish, king mackerel, and tilefish (also called golden bass or golden snapper), as these may contain high levels of mercury. Limit consumption of other fish to 12 ounces/week (about 3 to 4 servings/week). Fish oil is POSSIBLY UNSAFE when dietary sources are consumed in large amounts. Fatty fish contain toxins such as mercury.
A March 2010 lawsuit filed by a California environmental group claimed that eight brands of fish oil supplements contained excessive levels of PCB's, including CVS/pharmacy, Nature Made, Rite Aid, GNC, Solgar, Twinlab, Now Health, Omega Protein and Pharmavite. The majority of these products were either cod liver or shark liver oils. Those participating in the lawsuit claim that because the liver is the major filtering and detoxifying organ, PCB content may be higher in liver-based oils than in fish oil produced from the processing of whole fish.[63][64]

To improve the health of your heart, brain, skin, hair, body and much, much more, consider adding fish oil to your daily supplement regime or consume wild-caught fish daily. If you’re adverse to fish oil pills, make sure to get at least two servings of fatty fish each week to fulfill your omega-3 needs and provide your body with fish oil benefits. This is a recommendation also encouraged by the American Heart Association. (38)

In later life, cognitive function and brain deterioration may become a concern. Once again, maintaining high levels of EPA has been shown to lower the risk of developing and worsening cognitive decline and dementia. If, however, you know someone who already has a diagnosis of dementia or Alzheimer’s, their brain has already been damaged and needs structural support. At this point, DHA becomes important again and taking a high-EPA product that contains 250mg of DHA also is important to prevent further loss of brain tissue.
There was no significant association between the Hedges g and mean age (k, 17; P = .51), female proportion (k, 18; P = .32), mean omega-3 PUFA dosage (k, 19; P = .307), EPA to DHA ratio (k, 17; P = .86), dropout rate in the omega-3 PUFA group (k, 18; P = .71), duration of omega-3 PUFA treatment (k, 19; P = .14), Jadad score of randomization (k, 19; P = .10), Jadad score of blindness (k, 19; P = .57), or total Jadad score (k, 19; P = .18).

Cast about for healthy canned tuna. Think all tuna is created equal? Think again. Choose canned light tuna instead of tuna steaks or albacore tuna. It tends to have less mercury. Albacore may contain three times the mercury of chunk light tuna. Check fish guides for the latest information about foods low in toxins but high in omega-3. Two good online sources are:
Peroxides can be produced when fish oil spoils. A study commissioned by the government of Norway concluded there would be some health concern related to the regular consumption of oxidized (rancid) fish/marine oils, particularly in regards to the gastrointestinal tract, but there is not enough data to determine the risk. The amount of spoilage and contamination in a supplement depends on the raw materials and processes of extraction, refining, concentration, encapsulation, storage and transportation.[51] ConsumerLab.com reports in its review that it found spoilage in test reports it ordered on some fish oil supplement products.[52]
For several years now, the fish oil and Alzheimer’s disease connection has been studied with consistent results. The essential fatty acids vital for brain function that are found in fish oil can not only slow cognitive decline, but can help prevent brain atrophy in older adults. A study published in the FASEB Journal looked at the health effects of four- to 17-month dietary supplementation with omega-3 fatty acids and antioxidants. The findings once again confirm the potential for fish oil to be used as a weapon to fend off the onset of cognitive decline and Alzheimer’s disease. (8)
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).

De Truchis, P., Kirstetter, M., Perier, A., Meunier, C., Zucman, D., Force, G., Doll, J., Katlama, C., Rozenbaum, W., Masson, H., Gardette, J., and Melchior, J. C. Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV-infected patients taking potent antiretroviral therapy: a randomized prospective study. J.Acquir.Immune.Defic.Syndr. 3-1-2007;44(3):278-285. View abstract.
Higdon JV, Liu J, Du S, et al. Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic acid and docosahexaenoic acid is not associated with greater in vivo lipid peroxidation compared with oils rich in oleate and linoleate as assessed by plasma malondialdehyde and F(2)- isoprostanes. Am J Clin Nutr 2000;72:714-22. View abstract.
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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.