AD is a devastating disease for which there are limited treatment options and no cure. Memory loss is an early indicator of the disease, which is progressive, and leads to the inability of the patient to care for him- or herself and eventually to death (47). Currently, the number of individuals with AD is estimated to be 26.6 million and is expected to increase to 106.2 million by 2050 (48). There have been many studies conducted regarding the use of omega-3 fatty acid supplementation and AD (Table 2). DHA is present in large amounts in neuron membrane phospholipids, where it is involved in proper function of the nervous system, which is why it is thought to play a role in AD (49). A case-control study consisting of 148 patients with cognitive impairment [Mini-Mental State Examination (MMSE) score <24] and 45 control patients (MMSE score ≥24) showed that serum cholesteryl ester-EPA and -DHA levels were significantly lower (P < 0.05 and P < 0.001, respectively) in all MMSE score quartiles of patients with AD compared with control values (49). Another study found that a diet characterized by higher intakes of foods high in omega-3 fatty acids (salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, dark and green leafy vegetables), and a lower intake of foods low in omega-3 fatty acids (high-fat dairy products, red meat, organ meat, butter) was strongly associated with a lower AD risk (50). Image analysis of brain sections of an aged AD mouse model showed that overall plaque burden was significantly reduced by 40.3% in mice with a diet enriched with DHA (P < 0.05) compared with placebo. The largest reductions (40–50%) were seen in brain regions that are thought to be involved with AD, the hippocampus and parietal cortex (51). A central event in AD is thought to be the activation of multiple inflammatory cells in the brain. Release of IL-1B, IL-6, and TNF α from microglia cells may lead to dysfunction of the neurons in the brain (52). In 1 study, AD patients treated with EPA+DHA supplementation increased their plasma concentrations of EPA and DHA, which were associated with reduced release of inflammatory factors IL-1B, IL-6, and granulocyte colony–stimulating factor from peripheral blood mononuclear cells (53).
ODS seeks to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, supporting research, sharing research results, and educating the public. Its resources include publications (such as Dietary Supplements: What You Need to Know), fact sheets on a variety of specific supplement ingredients and products (such as vitamin D and multivitamin/mineral supplements), and the PubMed Dietary Supplement Subset
Additional side effects of fish oil supplements which have been reported include headache, short-term memory loss, depression, somatic disorders, and increased risk of colon cancer, nasopharyngitis, worsening of asthma symptoms, hemolytic anemia, decreased physical activity, increased appetite, a general uncomfortable feeling or increased blood pressure. The percentage of users that develop these side effects is not known. If these side effects become severe it is recommended that you stop using fish oil supplements.
Warfarin (Coumadin) is used to slow blood clotting. Fish oil also might slow blood clotting. Taking fish oil with warfarin might slow blood clotting too much and increase the risk of bleeding. However, conflicting results suggests that fish oil does not increase the effects of warfarin. Until more is known, use cautiously in combination with warfarin. Have your blood checked regularly, as your dose of warfarin (Coumadin) might need to be changed.
A study in 2013, (Stafford, Jackson, Mayo-Wilson, Morrison, Kendall), stated the following in its conclusion: "Although evidence of benefits for any specific intervention is not conclusive, these findings suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the potential for benefit of psychological interventions in the treatment of people at high risk of psychosis."`[56]
Oe, H., Hozumi, T., Murata, E., Matsuura, H., Negishi, K., Matsumura, Y., Iwata, S., Ogawa, K., Sugioka, K., Takemoto, Y., Shimada, K., Yoshiyama, M., Ishikura, Y., Kiso, Y., and Yoshikawa, J. Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals. Heart 2008;94(3):316-321. View abstract.
High levels of the oils in blood samples were linked with a 71 per cent increased risk of developing an aggressive and dangerous form of prostate cancer, according to the research. That study, if I recall correctly, mentioned concern about men eating fish more than a certain number of times a week having a 54% increased risk of developing prostate cancer.
Yamagishi, K., Iso, H., Date, C., Fukui, M., Wakai, K., Kikuchi, S., Inaba, Y., Tanabe, N., and Tamakoshi, A. Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study. J.Am.Coll.Cardiol. 9-16-2008;52(12):988-996. View abstract.
Arsenault, L. N., Matthan, N., Scott, T. M., Dallal, G., Lichtenstein, A. H., Folstein, M. F., Rosenberg, I., and Tucker, K. L. Validity of estimated dietary eicosapentaenoic acid and docosahexaenoic acid intakes determined by interviewer-administered food frequency questionnaire among older adults with mild-to-moderate cognitive impairment or dementia. Am J Epidemiol 7-1-2009;170(1):95-103. View abstract.

For example, large predatory fish like shark, swordfish, king mackerel, tilefish and albacore tuna can contain high levels of methyl mercury, a toxin that would override any health benefit, especially for the developing brains of fetuses and young children as well as for adults, Dr. Nesheim and Marion Nestle, professor emerita of nutrition, food studies and public health at New York University, noted in 2014 in an editorial in the American Journal of Clinical Nutrition. (Levels of mercury and other contaminants in fish have since declined somewhat but are not negligible.)
The supplements contain omega-3 fatty acids, the polyunsaturated oils prominent in fatty cold water fish like salmon, sardines and mackerel. In many observational studies, people who regularly consumed fish two or more times a week were less likely to suffer heart attacks, strokes and cardiovascular deaths than those who ate fish infrequently or not at all.

The evidence linking the consumption of marine omega−3 fats to a lower risk of cancer is poor.[8][13] With the possible exception of breast cancer,[8][14][15] there is insufficient evidence that supplementation with omega−3 fatty acids has an effect on different cancers.[5][16] The effect of consumption on prostate cancer is not conclusive.[8][15] There is a decreased risk with higher blood levels of DPA, but an increased risk of more aggressive prostate cancer was shown with higher blood levels of combined EPA and DHA.[17] In people with advanced cancer and cachexia, omega−3 fatty acids supplements may be of benefit, improving appetite, weight, and quality of life.[18]


However, since the dosage of fish oil required for an ideal effect in the improvement of a patient is unknown, the Arthritis Center in the Department of Rheumatology at John Hopkins University considers including omega-3 fatty acids and fish oil in the treatment of arthritis as controversial. The University also cautions that arthritis patients must be wary of all the other side effects that can come from using fish oil. You can read more about arthritis on the web page of the Arthritis Foundation and the Arthritis Center.
Humans are unable to place double bonds beyond position 9 on long chain polyunsaturated fatty acids (FA), making the omega-3 FA synthesized in plants and in marine microalgae essential elements to the human diet.1 Fish contain high levels of 2 omega-3 FA, eicosapentaenoic acid (EPA; C20:5 n-3), and docosahexaenoic acid [DHA]; C22:6 n-3)2,3 (Fig. 1). Many claims about the role of these omega-3 FA have been made in the prevention and treatment of cardiovascular disease. For instance, fish oil is seen as having a therapeutic role in coronary artery disease (CAD), heart failure, fatal and nonfatal arrhythmias, as well as offering an alternative or adjunct to the standard therapy for hypertriglyceridemia and diabetes. This review will highlight the potential mechanisms of fish oil on cardiovascular disease and provide an update of clinical trial results. The established uses in the treatment of hypertriglyceridemia and sources of omega-3 FA—both dietary and drug therapy—will be iterated, along with its potential application in combination with standard hypolipidemic agents. Finally, the limitations of current data will be addressed, as well as suggested recommendations for clinical use.
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?]
Human growth and intellectual development – DHA plays a very important role during fetal development, early infancy and old age. High concentrations of DHA are found in the brain and increase 300 to 500 percent in an infant’s brain during the last trimester of pregnancy. Adding DHA to a pregnant mother’s diet may be beneficial for the fetus’s brain development. Elderly people should also take EPA DHA, because as we get older, our bodies form less EPA and DHA, which may cause less mental focus and cognitive function. Taking EPA DHA also may help with mental abnormalities, such as Alzheimer’s disease and dementia.
According to the American Heart Association (AHA), clinical trials have shown that omega-3 is effective in reducing the incidence of cardiovascular diseases (CVD). Fish oil is a great source of omega-3 and therefore, reduces the risk of heart diseases and heart arrhythmias. It also lowers the level of bad cholesterol (LDL) and increases the level of good cholesterol (HDL). Fish oil prevents the accumulation of triglycerides and also reduces the level of excess triglycerides. Preliminary research has shown that fish oil can be used to prevent atherosclerosis in coronary patients. Thus, fish oil is effective in preventing strokes and regular usage of fish oil can help avoid sudden cardiac death. As per the American Heart Association, these preliminary findings still need to be confirmed by a further detailed research.
Omega 3 fatty acids are monounsaturated fats that come from food sources—primarily cold water fish (eg, salmon, trout, tuna, mackerel, and herring)—that contain EPA (eicosapentaenoic acid) and docosahexaenoic acid (DHA). Other fatty acids are derived from plant-derived sources of food—including nuts (especially walnuts) and seeds (eg, flax, chia, sunflower)—that have primarily ALA (alpha-linolenic acid).
To reap all the omega-3 benefits, it may be difficult for some people to eat the required amounts of oily fish, particularly with the well-known dangers of farmed fish, which are more readily available to most Americans. That’s why some people consider a high-quality omega-3 supplement in addition to a well-rounded diet. I’ll discuss supplements in a moment, though.

In addition, there was no significant difference in the association of treatment with reduced anxiety symptoms between participants receiving omega-3 PUFAs and those not receiving omega-3 PUFAs in the adolescent subgroup (aged <18 years) (k, 3; Hedges g, 0.020; 95% CI, –0.209 to 0.250; P = .86),48,53,57 in the adult subgroup (aged ≥18 years but <60 years) (k, 11; Hedges g, 0.388; 95% CI, –0.012 to 0.788; P = .06),33,35,36,47,49-51,54-56,59 or in the elderly subgroup (aged ≥60 years) (k, 3; Hedges g, –0.112; 95% CI, –0.406 to 0.181; P = .45).52,58,60 These insignificant results might be due to the smaller sample sizes in each subgroup.
Only fish and breast milk contain all the members of the omega-3 family, including its two main stars, EPA and DHA. Because Americans as a rule consume far too few omega-3s from fish or fish oil, it’s no surprise that the majority of Americans have low omega-3 index levels as well. A recent study of global omega-3 index levels found that an estimated 95% of Americans (with the exception of folks from Alaska) had an omega-3 index of 4 or below, putting them in the high risk category (5, 6, 7).
Soy can get a bad rap — and may indeed cause problems for people with certain food sensitivities — but this delicious bean is one of the most powerful (and versatile) ways to add omega-3 to your diet. Whole soybeans (known as edamame) are a favorite protein-packed snack for vegetarians; more processed forms (including tofu, soy milk, and soybean-based cooking oil) make soy infinitely more accessible. For some ideas, check out the 1998 classic, The Whole Soy Cookbook, which outlines how to cook with soy-based products ranging from miso to tempeh and beyond.
The Department of Ecology of the State of Washington has ranked various seafood based on its EPA and DHA concentrations. The highest-ranking seafood is mackerel, excluding King mackerel, that has a concentration of 1,790 milligrams of combined EPA and DHA per 100 grams, followed by salmon at 1,590; bluefin tuna has between 1173 and 1504 milligrams; sardines contain 980 milligrams; albacore tuna has 862 milligrams; bass has 640 milligrams; tuna has 630 milligrams; trout and swordfish have 580 milligrams; and walleye has 530 milligrams. Other seafood, which includes sea bass, clams, lobster, scallops, catfish, cod, pollock, crayfish and scallops contains between 200 and 500 milligrams of EPA and DHA per 100 grams. Breaded fish products rank lowest on the list with only 0.26 milligram per 100 grams.
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.
Arsenault, L. N., Matthan, N., Scott, T. M., Dallal, G., Lichtenstein, A. H., Folstein, M. F., Rosenberg, I., and Tucker, K. L. Validity of estimated dietary eicosapentaenoic acid and docosahexaenoic acid intakes determined by interviewer-administered food frequency questionnaire among older adults with mild-to-moderate cognitive impairment or dementia. Am J Epidemiol 7-1-2009;170(1):95-103. View abstract.
A study in 2013, (Stafford, Jackson, Mayo-Wilson, Morrison, Kendall), stated the following in its conclusion: "Although evidence of benefits for any specific intervention is not conclusive, these findings suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the potential for benefit of psychological interventions in the treatment of people at high risk of psychosis."`[56]
Under these conditions, it may make sense to try fish oil even at higher doses than what I recommended. There is some evidence that krill oil will get the omega-3 fatty acids better into the brain in the psychiatric conditions that I listed. And there is some evidence that EPA-rich fish oils are better than DHA-rich fish oils for some of those psychiatric conditions as well. So there’s room to play around with the different possibilities if those things apply to you. But for the average case, limit the fish oil to 250 milligrams of EPA and DHA combined when you take it, but in all cases, go for food first, and go for fish oil only after you have exhausted those possibilities.
In 1964 it was discovered that enzymes found in sheep tissues convert omega−6 arachidonic acid into the inflammatory agent called prostaglandin E2[71] which both causes the sensation of pain and expedites healing and immune response in traumatized and infected tissues.[72] By 1979 more of what are now known as eicosanoids were discovered: thromboxanes, prostacyclins, and the leukotrienes.[72] The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. If the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may, however, have deleterious effects.[72] Researchers found that certain omega−3 fatty acids are also converted into eicosanoids, but at a much slower rate. Eicosanoids made from omega−3 fatty acids are often referred to as anti-inflammatory, but in fact they are just less inflammatory than those made from omega−6 fats. If both omega−3 and omega−6 fatty acids are present, they will "compete" to be transformed,[72] so the ratio of long-chain omega−3:omega−6 fatty acids directly affects the type of eicosanoids that are produced.[72]
Animal studies show potent reduction of liver fat stores, glucose levels, and cholesterol levels in mice supplemented with krill oil while being fed a high fat diet.64,65 While many of these effects are seen with fish oil as well, studies show that krill oil, with its unique phospholipid structure, had the added benefit of increasing fat-burning in mitochondria while reducing new glucose production in the liver.66,67 As with so many other complex disease processes, utilizing multiple pathways to reduce disease is a highly effective strategy.67
Human studies also confirm cognition and memory improvement with omega-3 supplementation. For example, a study showed that both fish oil and krill oil enhanced cognitive function in a group of older men by increasing oxygen delivery to their brains. Interestingly, for those taking krill oil this effect was more prominent than those taking fish oil, though both groups were significantly better than placebo.30 As we pointed out earlier, because the omega-3 DHA is bound to phospholipids in krill it may be more effectively incorporated into the critical cell membrane in brain cells.
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.

There’s more good news when it comes to fish oil and eye health, and it’s just not just for diabetic this time. Fish oil has been shown to reverse age-related eye disorders. In March 2014, French researchers evaluated 290 patients with age-related macular degeneration (AMD), and they discovered that dietary oil fish and seafood intake were significantly lower in AMD patients. Due to the high EPA and DHA levels in fish oil, it was concluded that this kind of nutritional intervention could especially benefit those at high risk for neovascular age-related macular degeneration. (24)
Human growth and intellectual development – DHA plays a very important role during fetal development, early infancy and old age. High concentrations of DHA are found in the brain and increase 300 to 500 percent in an infant’s brain during the last trimester of pregnancy. Adding DHA to a pregnant mother’s diet may be beneficial for the fetus’s brain development. Elderly people should also take EPA DHA, because as we get older, our bodies form less EPA and DHA, which may cause less mental focus and cognitive function. Taking EPA DHA also may help with mental abnormalities, such as Alzheimer’s disease and dementia.
In some cases, fish oil pills may cause loose stools, nausea, diarrhea, and decreased appetite, fat in the stools, vomiting or constipation. These side effects can be minimized by taking a fish oil capsule that is coated, which is designed to help eliminate the "fish burps" many users complain about. Starting with low doses of the supplement and working up to a full dose can also help minimize side effects. You can also pair fish oil supplements with meals so that they enter your body more slowly, minimizing the risk of side effects occurring.
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.
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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