In addition to depression, chronic stress leads to loss of volume of the hippocampus—and also causes enlargement of the amygdala, the portion of the brain that regulates anxiety and anger.24 When rats were supplemented with omega-3s during exposure to stress, they showed lower corticosterone levels (a marker of stress), and improved learning on a maze—indicating that the omega-3s helped preserve memory and reduce anxiety.24
For rheumatoid arthritis, one systematic review found consistent, but modest, evidence for the effect of marine n−3 PUFAs on symptoms such as "joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity" as well as the use of non-steroidal anti-inflammatory drugs.[35] The American College of Rheumatology has stated that there may be modest benefit from the use of fish oils, but that it may take months for effects to be seen, and cautions for possible gastrointestinal side effects and the possibility of the supplements containing mercury or vitamin A at toxic levels. The National Center for Complementary and Integrative Health has concluded that "[n]o dietary supplement has shown clear benefits for rheumatoid arthritis", but that there is preliminary evidence that fish oil may be beneficial, but needs further study.[36]
Australian researchers published results of a study examining the effects of fish oil on weight loss in combination with diet and exercise in the May 2007 issue of American Journal of Clinical Nutrition. The results show that a combination of fish oil supplements and regular exercise can reduce body fat while also improving heart and metabolic health. The fish supplementation group had lowered triglycerides, increased HDL cholesterol and improved blood flow. Overall, adding fish oil to a current exercise program (and a overall healthy lifestyle) looks like it can decrease body fat as well as cardiovascular disease risk. (32)
Metagenics offers a wide range of educational opportunities including webinars, group meetings, and seminars as part of our commitment to continuing functional medicine education. Our goal is to give our practitioners further insight to help address their patients’ unique health needs for a higher level of personalized, lifetime wellness care. We have been sharing this ever-growing body of nutritional and lifestyle research for over 25 years.
Luo, J Rizkalla SW Vidal H Oppert JM Colas C Boussairi A Guerre-Millo M Chapuis AS Chevalier A Durand G Slama G. Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study. Diabetes Care. 1998;21(5):717-724. View abstract.
Children: Fish oil is POSSIBLY SAFE when taken by mouth appropriately. Fish oil has been used safely through feeding tubes in infants for up to 9 months. But young children should not eat more than two ounces of fish per week. Fish oil is POSSIBLY UNSAFE when consumed from dietary sources in large amounts. Fatty fish contain toxins such as mercury. Eating contaminated fish frequently can cause brain damage, mental retardation, blindness and seizures in children.
Fatty predatory fish like sharks, swordfish, tilefish, and albacore tuna may be high in omega-3 fatty acids, but due to their position at the top of the food chain, these species may also accumulate toxic substances through biomagnification. For this reason, the United States Environmental Protection Agency recommends limiting consumption (especially for women of childbearing age) of certain (predatory) fish species (e.g. albacore tuna, shark, king mackerel, tilefish and swordfish) due to high levels of the toxic contaminant mercury. Dioxin, PCBs and chlordane are also present.[13] Fish oil is used as a component in aquaculture feed. More than 50 percent of the world's fish oil used in aquaculture feed is fed to farmed salmon.[14]
"All these diseases have a common genesis in inflammation," says Joseph C. Maroon, MD, professor and vice chairman of the department of neurological surgery at the University of Pittsburgh School of Medicine. Co-author of Fish Oil: The Natural Anti-Inflammatory, Maroon says that in large enough amountsomega-3's reduce the inflammatory process that leads to many chronic conditions.
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).
42. Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, Gudmundsen O, Vige R, Payne SP, Ye S, et al. Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis. 2010;212:252–9. [PubMed]
Several other analyses of the evidence have been done in the last few years (2012 or later), and like the 2018 analysis and the AHRQ report, most found little or no evidence for a protective effect of omega-3 supplements against heart disease. However, some earlier analyses suggested that omega-3s could be helpful. The difference between the newer conclusions and the older ones may reflect two changes over time: 
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.
To avoid fish oil supplements containing mercury or other harmful contaminants, purchase supplements from a reputable source that clearly tests for these health-hazardous contaminants in its products. These tests should be ideally conducted by a third-party, and a certificate of analysis should indicate the levels of purity from environmental toxins.
The use of DHA by persons with epilepsy could decrease the frequency of their seizures. Studies have shown that children with epilepsy had a major improvement, i.e. decrease in the frequency of their seizures, but another study showed mixed results with 57 adults taking DHA supplementation. The 57 subjects demonstrated a decreased frequency of seizures for the first six weeks of the study, but for some, it was just a temporary improvement (R).
It’s no surprise that fish — particularly cold-water fatty fish like salmon, mackerel, and anchovies — are rich in omega-3s. It’s called fish oil for a reason, right? Mackerel, for instance, may have more than 3300 mg of omega-3 per serving — that’s more than 6 times the recommended per day dose for healthy adults. Not a huge fish connoisseur? Try some of the quick, simple recipes in Cooking with Fish Like a Pro, an accessible collection of fish recipes to suit every palate.
Krill oil is joining the toolkit for fighting arthritis, thanks to its exceptional anti-inflammatory properties resulting from its phospholipid form of omega-3s. A study in mice with experimental arthritis showed that krill oil supplements reduced arthritis scores and markedly diminished joint swelling. When examined under a microscope, the animals’ joints were remarkably free of inflammatory infiltrates of immune system cells.85
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.

Since EPA and DHA are both essential for health and appear together in nature, many studies have attempted to treat clinical conditions with combined EPA and DHA oils, but the outcomes have been varied, contradictory and disappointing. Consequently, researchers have started to investigate the individual actions of EPA and DHA in isolation, in numerous health conditions where an omega-3 deficiency is related to symptoms or known to play a causative role. The emerging evidence shows marked differences between how these two fatty acids affect us – not just at the cellular level but also the body as a whole.
Excessive amounts of chemicals. Using excessive amounts of fish products such as shark, farm raised salmon or mackerel can be dangerous. These products may be exposed to excessive amounts of chemicals such as mercury which can build up in the body and cause negative effects. While it is healthy to consume fish, it is important to seek out quality sources to avoid exposure to these chemicals. Using a supplement to get high levels of omega-3s into your system is also recommended because these products are produced in such a way that they will not expose you to unsafe chemicals.
Guallar, E., Aro, A., Jimenez, F. J., Martin-Moreno, J. M., Salminen, I., van't Veer, P., Kardinaal, A. F., Gomez-Aracena, J., Martin, B. C., Kohlmeier, L., Kark, J. D., Mazaev, V. P., Ringstad, J., Guillen, J., Riemersma, R. A., Huttunen, J. K., Thamm, M., and Kok, F. J. Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study. Arterioscler.Thromb.Vasc.Biol 1999;19(4):1111-1118. View abstract.
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]
If a chicken eats a diet heavy in omega-3s — such as flaxseed and other nutrient-dense grains — its eggs will be fortified with higher levels of those healthy fatty acids. If you can afford a little extra expense, look for omega-3-enriched eggs from humanely raised chickens that roam free and forage for insects and plants, which give the eggs even further nutrients and health benefits.
Fish oil has been shown to have a direct electrophysiological effect on the myocardium. Initial experience with animal ischemia models demonstrated that the ventricular fibrillation threshold was increased in both animals fed or infused with omega-3 FA.23,24 This progressed to a demonstration, on a cellular and ion channel level, that omega-3 FA reduce both sodium currents and L-type calcium currents.25–29 It is hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current reduces arrhythmogenic depolarizing currents.30

The absence of DHA in many pure EPA trials, and therefore lack of competition between EPA and DHA during digestion and consequently for uptake, is considered to be partly responsible for the positive outcomes. Simply put, pure EPA delivers more EPA into cells where it is needed than combined EPA & DHA blends. Consequently, oils containing DHA may not be suitable for a variety of conditions when treatment relies on increasing levels of EPA and its end products.
Fish oil supplements are available as liquids or capsules. Some capsules are enteric-coated to pass through the stomach before dissolving in the small intestine, thus helping prevent indigestion and "fish burps". Poorly manufactured enteric-coated products have the potential to release ingredients too early. ConsumerLab.com, a for-profit supplement testing company, reported that 1 of the 24 enteric-coated fish oil supplements it evaluated released ingredients prematurely.[48]
Three omega−3 fatty acids are important in human physiology, α-linolenic acid (18:3, n-3; ALA), eicosapentaenoic acid (20:5, n-3; EPA), and docosahexaenoic acid (22:6, n-3; DHA).[67] These three polyunsaturates have either 3, 5, or 6 double bonds in a carbon chain of 18, 20, or 22 carbon atoms, respectively. As with most naturally-produced fatty acids, all double bonds are in the cis-configuration, in other words, the two hydrogen atoms are on the same side of the double bond; and the double bonds are interrupted by methylene bridges (-CH
One day I was cooking pasta when the kitchen started to fill with the odor of fish. I happen to hate fish, so this was not a pleasant experience. It was also a mystery, since I never cook fish. A little detective work discovered that the offensive odor was coming from the pasta. Apparently I didn’t notice the “Now with Omega 3” label on the box when I purchased it. My daughter and I still refer to this as the “fish pasta incident”.
When it comes to omega-3 benefits, there are rarely nutrients that pack this many positive health outcomes into one compound. The most commonly known benefit of omega-3s is a reduced risk of heart disease, but that’s not the only studied plus of getting lots of omega-3s in your diet — from fetal development to retinal function to weight management (and a lot more in between), these acids support and promote optimal health for anyone. (1)

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People with metabolic syndrome (the combination of central obesity, high blood pressure, disturbed lipid profile, and impaired glucose tolerance) are at increased risk of death from cardiovascular disease, diabetes, cancer, and other apparently “age-related” disorders. Because metabolic syndrome is closely associated with chronic low-grade inflammation, the powerful anti-inflammatory effects of omega-3 fats are especially important as a means of slowing or stopping the progression of this deadly disorder.
Cancer. Research on the effects of fish oil in preventing cancer has produced conflicting results. Some population research suggests that eating fish or having higher blood levels of omega-3 fatty acids from fish oil is linked to a lower risk of different cancers, including oral cancer, pharyngeal cancer, esophageal cancer, colon cancer, rectal cancer, breast cancer, ovarian cancer, and prostate cancer. But other research suggests that eating fish does not reduce the risk of cancer.
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