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).

In fact, fish oil is even dipping its way into mainstream medicine. In September 2018, Amarin Corporation, the biopharmaceutical developer of pharmaceutical-grade fish oil Vascepa, released preliminary findings of its double-blind clinical trial. In the study, researchers tracked more than 8,000 adults for a median 4.9 years. The mix of study participants had either established cardiovascular disease or type 2 diabetes and another cardiovascular disease risk factor, along with persistently elevated triglycerides.


This under-the-radar grain is a nutritional powerhouse — and one of the most potent sources of the omega-3 alpha-Linolenic acid (ALA). Sprinkle flaxseeds over your morning oatmeal for a pleasant nutty flavor, or blend them into fruit smoothies to satisfy a picky palate. Need more ideas? Check out The Flaxseed Recipe Book, an easy-to-follow guide for adding flaxseeds to your favorite soups, salads, and main courses.
^ Jump up to: a b Jensen, Craig L.; Voigt, Robert G.; Llorente, Antolin M.; Peters, Sarika U.; Prager, Thomas C.; Zou, Yali L.; Rozelle, Judith C.; Turcich, Marie R.; Fraley, J. Kennard; Anderson, Robert E.; Heird, William C. (2010). "Effects of Early Maternal Docosahexaenoic Acid Intake on Neuropsychological Status and Visual Acuity at Five Years of Age of Breast-Fed Term Infants". The Journal of Pediatrics. 157 (6): 900–05. doi:10.1016/j.jpeds.2010.06.006. PMID 20655543.
Several studies confirmed the benefit of omega-3 supplementation during pregnancy in terms of proper development of the brain and retina. Of the 2 most important long-chain omega-3 fatty acids, EPA and DHA, DHA is the more important for proper cell membrane function and is vital to the development of the fetal brain and retina (17). During the third trimester, vast amounts of DHA accumulate in fetal tissue (20). The 2 most infiltrated fetal areas include the retina and brain, which may correlate with normal eyesight and brain function (19). A study by Judge et al. (20) found that children whose mothers had taken DHA supplementation during pregnancy (n = 29) had significantly better problem-solving skills at 9 mo old (P = 0.017) than those whose mothers had not taken DHA supplementation during pregnancy (n = 15). Another study provided a cognitive assessment of children 2.5 y after maternal EPA+DHA supplementation during pregnancy from 20 wk of gestation until delivery (n = 33) compared with children in a placebo group (n = 39). Children in the EPA + DHA–supplemented group attained significantly higher scores for eye and hand coordination [mean score, 114 (SD 10.2] than those in the placebo group [mean score, 108 (SD 11.3)] (P = 0.021, adjusted P = 0.008) (19).

We’ve written about the dose necessary to achieve measurable benefits before. However, a person’s actual omega-3 intake can be tricky to estimate. Even if you eat at least two servings of fatty fish per week, as the American Heart Association recommends (10), your fish might contain more or less omega-3s depending on the fish species, the time of year, and how you cook it. Even taking fish oil supplements isn’t always straightforward, as dose can be impacted by numerous bioavailability factors, as well as genetics, age, gender, medication-use and lifestyle.
An excessive dosage of fish oil can have adverse allergies and side effects on the body. Furthermore, fish oil can be problematic if you have certain conditions so it is necessary to consume fish oil supplements cautiously. Moreover, it can be consumed in various forms. These include eating the fish directly by baking, roasting, frying, grilling, broiling, or smoking it. It can also be consumed in the form of concentrated dietary supplements like liquid, tablet, capsule, pill, or soft gels. Also, there are various pharmaceutical grades of the oil. It is not necessary to constantly consume pharmaceutical-grade oil or even supplements. You should also consult your doctor to confirm the mode of consuming fish oil and the overall need for it in your diet.

Nielsen, A. A., Jorgensen, L. G., Nielsen, J. N., Eivindson, M., Gronbaek, H., Vind, I., Hougaard, D. M., Skogstrand, K., Jensen, S., Munkholm, P., Brandslund, I., and Hey, H. Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids. Aliment.Pharmacol.Ther. 2005;22(11-12):1121-1128. View abstract.
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-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential nutrients that have potential preventive and therapeutic effects on psychiatric disorders, such as anxiety and depression,7-15 as well as comorbid depression and anxiety in physically ill patients,16-19 patients with coronary heart disease,20,21 and pregnant women.22,23 Preclinical data support the effectiveness of omega-3 PUFAs as treatment for anxiety disorders. Song et al24,25 found that an EPA-rich diet could reduce the development of anxiety-like behaviors in rats as well as normalize dopamine levels in the ventral striatum. In addition, Yamada et al26 showed that a high dietary omega-3 to omega-6 PUFA ratio reduced contextual fear behaviors in mice and that these effects were abolished by a cannabinoid CB1 receptor antagonist.
Most brands of fish oil have been proven safe, free of detectable traces of mercury, and do not contain unsafe levels of PCBs (polychlorinated biphenyls), a toxin and pollutant believed to pose various health threats. To avoid contaminants in an unrefined supplement, it's best to choose a fish-oil supplement made from small, oily fish like anchovy, sardines or menhaden.
Fish oil is a concentrated source of omega-3 fats, which are also called ω-3 fatty acids or n-3 fatty acids. To get more scientific, omega-3s are long-chain polyunsaturated fatty acids, or PUFAs. Our bodies are able to make most of the fats we need need, but that’s not true for omega-3 fatty acids. When it comes to these essential fats, we need to get them from omega-3 foods or supplements.
Samsonov, M. A., Vasil'ev, A. V., Pogozheva, A. V., Pokrovskaia, G. R., Mal'tsev, G. I., Biiasheva, I. R., and Orlova, L. A. [The effect of a soy protein isolate and sources of polyunsaturated omega-3 fatty acids in an anti-atherosclerotic diet on the lipid spectrum of blood serum and immunological indicators in patients with ischemic heart disease and hypertension]. Vopr.Med Khim. 1992;38(5):47-50. View abstract.
Jump up ^ Abdelhamid, Asmaa S; Brown, Tracey J; Brainard, Julii S; Biswas, Priti; Thorpe, Gabrielle C; Moore, Helen J; Deane, Katherine HO; AlAbdulghafoor, Fai K; Summerbell, Carolyn D; Worthington, Helen V; Song, Fujian; Hooper, Lee (18 July 2018). "Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD003177.pub3.
Interestingly, the results are also consistent with our recent findings that somatic anxiety is associated with omega-3 PUFA deficits and the genetic risks of PUFA metabolic enzyme cytosolic phospholipase A2 in major depressive disorder62,63 and interferon α–induced neuropsychiatric syndrome.63,64 Brain membranes contain a high proportion of omega-3 PUFAs and their derivatives and most animal and human studies suggest that a lack of omega-3 PUFAs in the brain might induce various behavioral and neuropsychiatric disorders,16,65-70 including anxiety-related behaviors.12,18,19,32,49,71 Emerging evidence suggests that omega-3 PUFAs interfere with and possibly control several neurobiological processes, such as neurotransmitter systems, neuroplasticity, and inflammation,12,72 which is postulated to be the mechanism underlying anxiety and depression.
Thanks to fatdog11 for that informative post about PCB’s in fish-oil supplements. Are these same toxicity levels found in fish themselves, or possibly are these levels so high only in highly concentrated fish-oil products? Also, can fatdog11 please inform us more about algae-derived omega-3. What are the DHA and EPA levels in these capsules? What is the cost, and where can they be purchased?

Results  In total, 1203 participants with omega-3 PUFA treatment (mean age, 43.7 years; mean female proportion, 55.0%; mean omega-3 PUFA dosage, 1605.7 mg/d) and 1037 participants without omega-3 PUFA treatment (mean age, 40.6 years; mean female proportion, 55.0%) showed an association between clinical anxiety symptoms among participants with omega-3 PUFA treatment compared with control arms (Hedges g, 0.374; 95% CI, 0.081-0.666; P = .01). Subgroup analysis showed that the association of treatment with reduced anxiety symptoms was significantly greater in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. The anxiolytic effect of omega-3 PUFAs was significantly better than that of controls only in subgroups with a higher dosage (at least 2000 mg/d) and not in subgroups with a lower dosage (<2000 mg/d).
Is krill oil better than fish oil for omega-3? Krill oil and fish oil are popular dietary supplements containing omega-3. Krill oil comes from a small crustacean while fish oil comes from oily fish, such as salmon. Both are shown to increase blood levels of omega-3 and have benefits for health. Learn more about the differences between krill oil and fish oil here. Read now
Omega−3 fatty acids are formed in the chloroplasts of green leaves and algae. While seaweeds and algae are the source of omega−3 fatty acids present in fish, grass is the source of omega−3 fatty acids present in grass fed animals.[134] When cattle are taken off omega−3 fatty acid rich grass and shipped to a feedlot to be fattened on omega−3 fatty acid deficient grain, they begin losing their store of this beneficial fat. Each day that an animal spends in the feedlot, the amount of omega−3 fatty acids in its meat is diminished.[135]
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 review provides good evidence that taking long-chain omega 3 (fish oil, EPA or DHA) supplements does not benefit heart health or reduce our risk of stroke or death from any cause.  The most trustworthy studies consistently showed little or no effect of long-chain omega 3 fats on cardiovascular health. On the other hand, while oily fish is a healthy food, it is unclear from the small number of trials whether eating more oily fish is protective of our hearts. 
CONDITIONS OF USE AND IMPORTANT INFORMATION: This information is meant to supplement, not replace advice from your doctor or healthcare provider and is not meant to cover all possible uses, precautions, interactions or adverse effects. This information may not fit your specific health circumstances. Never delay or disregard seeking professional medical advice from your doctor or other qualified health care provider because of something you have read on WebMD. You should always speak with your doctor or health care professional before you start, stop, or change any prescribed part of your health care plan or treatment and to determine what course of therapy is right for you.
• Fish oil – Fish oil is among the primary ways that people enhance their intake of omega-3 fats. High-quality fish oils can certainly provide many health benefits. However, this oil is weak in antioxidants. This means that as you increase your omega-3 intake through fish oil consumption, you actually increase your need for added antioxidant protection.
“This systematic review did find moderate evidence that ALA, found in plant oils (such as rapeseed or canola oil) and nuts (particularly walnuts) may be slightly protective of some diseases of the heart and circulation. However, the effect is very small, 143 people would need to increase their ALA intake to prevent one person developing arrhythmia. One thousand people would need to increase their ALA intake to prevent one person dying of coronary heart disease or experiencing a cardiovascular event.  ALA is an essential fatty acid, an important part of a balanced diet, and increasing intakes may be slightly beneficial for prevention or treatment of cardiovascular disease."

Of great clinical importance, EPA and DHA supplementation during pregnancy has been associated with longer gestation and increased concentrations of EPA and DHA in fetal tissues (21). In 2005, preterm births accounted for 12.7% of all births in the United States, increasing the likelihood of health complications (22). Carrying a baby to term is very important because prematurity is the cause of various infant diseases and can lead to death; preterm delivery is an underlying factor for 85% of the deaths of normally formed infants (23). One mechanism by which EPA and DHA may decrease the incidence of preterm birth is by decreasing prostaglandin E2 and prostaglandin F2α production, therefore reducing inflammation within the uterus, which could be associated with preterm labor (21, 24). Several studies investigated EPA and DHA intake during pregnancy and its correlation with longer gestation. Conclusions were that EPA+DHA supplementation during pregnancy delayed the onset of delivery to term or closer to term; however, supplementation did not delay delivery to the point of being post-term (20, 23, 25). This supports the evidence that EPA+DHA ingestion leads to optimal pregnancy length. EPA+DHA supplementation reduced the HR of preterm delivery by 44% (95% CI: 14–64%) in those who consumed relatively low amounts of fish and 39% (95% CI: 16–56%) in those who consumed medium amounts of fish; however, a level of statistical significance was not met (P = 0.10) (23). The Judge et al. (20) study found that women who had DHA supplementation from gestation week 24 until full-term delivery carried their infants significantly (P = 0.019) longer than did the women in the placebo group. One study found that DHA supplementation after gestation week 21 led to fewer preterm births (<34 wk of gestation) in the DHA group compared with the control group (1.09% vs. 2.25%; adjusted RR, 0.49; 95% CI: 0.25–0.94; P = 0.03). Also, mean birth weight was 68 g heavier (95% CI: 23–114 g; P = 0.003) and fewer infants were of low birth weight in the DHA group compared with the control group (3.41% vs. 5.27%; adjusted RR, 0.65; 95% CI: 0.44–0.96; P = 0.03) (25).
Good points, Miroslav. Focusing on your 4th point, with so many different formulations on the market that contain various preservatives, only looking at the blood levels of omega-3’s as the flag for increased risk for prostate cancer tends to ignore the fact that certain populations in coastal regions maintain a diet high in omega fish oils and don’t have a marked increase level of prostate cancer, pointing to the fact that another agent may be to blame here.
Gorjao, R., Verlengia, R., Lima, T. M., Soriano, F. G., Boaventura, M. F., Kanunfre, C. C., Peres, C. M., Sampaio, S. C., Otton, R., Folador, A., Martins, E. F., Curi, T. C., Portiolli, E. P., Newsholme, P., and Curi, R. Effect of docosahexaenoic acid-rich fish oil supplementation on human leukocyte function. Clin Nutr 2006;25(6):923-938. View abstract.
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.

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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.
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
It exists in nature in three forms, one derived from land plants and two derived from marine sources. In the body, omega-3 is highly concentrated in the brain; it is critical to the formation and maintenance of nerve cell membranes. Research shows that in the nervous system, omega-3s foster the development of brain circuitry and the processing of information. They also play important roles in stabilizing mood and staving off cognitive decline. Low levels of omega-3s are linked to poor memory and depression. Omega-3 fats are also critical for the formation of anti-inflammatory molecules in the body.
Several recent clinical studies, especially those focusing on the benefits of omega-3 in inflammatory conditions, have investigated the actions of pure-EPA in protecting against excess inflammation in the body. EPA works in several different ways. Firstly, it is the precursor to a number of immune messengers, collectively called ‘eicosanoids’ (series-3 prostaglandins, series-3 thromboxanes and series-5 leukotrienes,) all of which have anti-inflammatory roles.
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
This under-the-radar grain is a nutritional powerhouse — and one of the most potent sources of the omega-3 alpha-Linolenic acid (ALA). Sprinkle flaxseeds over your morning oatmeal for a pleasant nutty flavor, or blend them into fruit smoothies to satisfy a picky palate. Need more ideas? Check out The Flaxseed Recipe Book, an easy-to-follow guide for adding flaxseeds to your favorite soups, salads, and main courses.
In my opinion, the key benefit of DHA lies in its unique spatial characteristics. As mentioned earlier, the extra double bond (six in DHA vs. five in EPA) and increased carbon length (22 carbons in DHA vs. 20 in EPA) means that DHA takes up takes up a lot more space than does EPA in the membrane. Although this increase in spatial volume makes DHA a poor substrate for phospholipase A2 as well as the COX and LOX enzymes, it does a great job of making membranes (especially those in the brain) a lot more fluid as the DHA sweeps out a much greater volume in the membrane than does EPA. This increase in membrane fluidity is critical for synaptic vesicles and the retina of the eye as it allows receptors to rotate more effectively thus increasing the transmission of signals from the surface of the membrane to the interior of the nerve cells. This is why DHA is a critical component of these highly fluid portions of the nerves (7). On the other hand, the myelin membrane is essentially an insulator so that relatively little DHA is found in that part of the membrane.
In short, there is no single optimal EPA:DHA ratio. If we are really healthy, with an optimal omega-6 to omega-3 ratio (from a diet rich in omega-3 fatty acids and low in grains and vegetable oils) and have an active, stress-free lifestyle, relying on standard fish oil in the natural 1.5:1 EPA:DHA ratio or simply consuming oily fish is completely adequate.
Evidence in the population generally does not support a beneficial role for omega−3 fatty acid supplementation in preventing cardiovascular disease (including myocardial infarction and sudden cardiac death) or stroke.[4][19][20][21] A 2018 meta-analysis found no support that daily intake of one gram of omega-3 fatty acid in individuals with a history of coronary heart disease prevents fatal coronary heart disease, nonfatal myocardial infarction or any other vascular event.[6] However, omega−3 fatty acid supplementation greater than one gram daily for at least a year may be protective against cardiac death, sudden death, and myocardial infarction in people who have a history of cardiovascular disease.[22] No protective effect against the development of stroke or all-cause mortality was seen in this population.[22] Eating a diet high in fish that contain long chain omega−3 fatty acids does appear to decrease the risk of stroke.[23] Fish oil supplementation has not been shown to benefit revascularization or abnormal heart rhythms and has no effect on heart failure hospital admission rates.[24] Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes.[7]
The Lyon Diet Heart Study, performed shortly after the DART study, was a prospective trial of 607 survivors of MI who were randomized to either a Mediterranean diet or a regular Western diet.49 At a mean follow-up of 27 months, the primary end point of death from cardiovascular causes and nonfatal deaths had a 73% relative risk reduction—a positive effect that continued at follow up assessment at a mean of 46 months.50 FA analysis of plasma lipids showed that in the patients randomized to a Mediterranean diet, there was a higher concentration of alpha-linolenic acid as well as EPA. Fish, however, was consumed in similar amounts by both the Western and Mediterranean diet groups. The higher blood level of EPA in the Mediterranean diet arm was attributed to its synthesis from alpha-linolenic acid, which was 60-times higher than the plasma concentration of EPA. In addition, the risk reduction that occurred in this trial could not be attributed to one particular diet intervention because as the consumption of fruits and vegetables increased, the consumption of monounsaturated fat increased, while saturated fat and cholesterol were decreased.
Omega-3 FA most likely reduce serum triglyceride levels by modulating very-low-density lipoprotein (VLDL) and chylomicron metabolism. There is a consistent finding in the literature that the end effect of fish oil is decreased hepatic secretion of VLDL17—the major endogenous source of triglycerides. This effect occurs most likely through multiple mechanisms, including: (1) decreased synthesis of triglycerides because these omega-3 FA may not be the preferred substrates of the enzyme diacylglycerol O-acyltransferase,18 or they may interact with nuclear transcription factors that control lipogenesis19; cellular metabolism consequently shifts toward a decrease in triglyceride synthesis and an increase in FA oxidation; and (2) the promotion of apolipoprotein B degradation in the liver through the stimulation of an autophagic process.20 This means that fewer VLDL particles can be assembled and secreted. Fish oil may also accelerate VLDL and chylomicron clearance21 by inducing lipoprotein lipase activity.22
There is, however, significant difficulty in interpreting the literature due to participant recall and systematic differences in diets.[53] There is also controversy as to the efficacy of omega−3, with many meta-analysis papers finding heterogeneity among results which can be explained mostly by publication bias.[54][55] A significant correlation between shorter treatment trials was associated with increased omega−3 efficacy for treating depressed symptoms further implicating bias in publication.[55]

Fish oil is FDA approved to lower triglycerides levels, but it is also used for many other conditions. It is most often used for conditions related to the heart and blood system. Some people use fish oil to lower blood pressure, triglycerides and cholesterol levels. Fish oil has also been used for preventing heart disease or stroke, as well as for clogged arteries, chest pain, irregular heartbeat, bypass surgery, heart failure, rapid heartbeat, preventing blood clots, and high blood pressure after a heart transplant.
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