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.
Anxiety, the most commonly experienced psychiatric symptom, is a psychological state derived from inappropriate or exaggerated fear leading to distress or impairment. The lifetime prevalence of any anxiety disorder is reported to be approximately 1 in 3.1 Anxiety is often comorbid with depressive disorders2 and is associated with lower health-related quality of life3 and increased risk of all-cause mortality.4 Treatment options include psychological treatments, such as cognitive-behavioral therapy and pharmacological treatments, mainly with selective serotonin reuptake inhibitors.5 Individuals with anxiety and related disorders tend to be more concerned about the potential adverse effects of pharmacological treatments (eg, sedation or drug dependence) and may be reluctant to engage in psychological treatments that can be time-consuming and costly, as well as sometimes limited in availability.6 Thus, evidence-based and safer treatments are required, especially for anxious patients with comorbid medical conditions.
One meta-analysis concluded that omega−3 fatty acid supplementation demonstrated a modest effect for improving ADHD symptoms. A Cochrane review of PUFA (not necessarily omega−3) supplementation found "there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents", while a different review found "insufficient evidence to draw any conclusion about the use of PUFAs for children with specific learning disorders". Another review concluded that the evidence is inconclusive for the use of omega−3 fatty acids in behavior and non-neurodegenerative neuropsychiatric disorders such as ADHD and depression.
Walnuts are chock full of healthy fats — including omega-3s — and also contain a slew of other nutrients like magnesium, biotin, and vitamin E. Some studies even suggest that eating walnuts improves memory, learning ability, and motor development.1 Walnuts are versatile, too — try them with fresh or dried fruit, in salads, or baked into desserts. Get started with these banana walnut waffles — made with coconut sugar and unsweetened almond milk.
Research conducted at the Louisiana State University has shown that fatty acids are effective in treating Alzheimer’s disease. Since fish oil is one of the best sources of essential fatty acids, including EPA and DHA, it helps in the treatment of Alzheimer’s disease. More research conducted at the University of California in Los Angeles (UCLA) validates the usefulness of fish oil as a possible remedy for the disease. The Alzheimer’s Association recommends fish containing a higher content of omega-3 fatty acids to patients since it acts as a defense against Alzheimer’s disease and dementia.
Omega-3 fatty acids have been shown to increase platelet responsiveness to subtherapeutic anticoagulation therapies, including aspirin. Recently, it was noted that patient response to aspirin for anticoagulation therapy is widely variable (45), and, thus, the number of patients with a low response to aspirin or aspirin resistance is estimated to range from <1% to 45%, depending on many variables. However, in patients with stable coronary artery disease taking low-dose aspirin, EPA+DHA supplementation has been proven to be as effective as aspirin dose escalation to 325 mg/d for anticoagulation benefits (45). The antiplatelet drug clopidogrel has also been associated with hyporesponsiveness in some patients. This could be attributed to poor patient compliance, differences in genes and platelet reactivity, variability of drug metabolism, and drug interactions. More importantly, in 1 study, patients receiving standard dual antiplatelet therapy (aspirin 75 mg/d and clopidogrel 600-mg loading dose followed by 75 mg/d) were assigned to either EPA+DHA supplementation or placebo. After 1 mo of treatment, the P2Y12 receptor reactivity index (an indicator of clopidogrel resistance) was significantly lower, by 22%, for patients taking EPA+DHA compared with patients taking placebo (P = 0.020) (46).
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)
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.
Due to the anticipated heterogeneity, a random-effects meta-analysis was chosen rather than a fixed-effects meta-analysis because random-effects modeling is more stringent and incorporates an among-study variance in the calculations. The entire meta-analysis procedure was performed on the platform of Comprehensive Meta-analysis statistical software, version 3 (Biostat). Under the preliminary assumption that the scales for anxiety symptoms are heterogeneous among the recruited studies, we chose Hedges g and 95% confidence intervals to combine the effect sizes, in accordance with the manual of the Comprehensive Meta-analysis statistical software, version 3. Regarding the interpretation of effect sizes, we defined Hedges g values 0 or higher as a better association of treatment with reduced anxiety symptoms of omega-3 PUFAs than in controls. For each analysis, a 2-tailed P value less than .05 was considered to indicate statistical significance. When more than 1 anxiety scale was used in a study, we chose the one with the most informative data (ie, mean and standard deviation [SD] before and after treatment). We entered the primary outcome provided in the included articles or obtained from the original authors. As for the variance imputation, we mainly chose the mean and SD before and after treatment. Later, we entered the mean and SD and calculated the effect sizes based on the software option, standardized by post score SD. In the case of studies with 2 active treatment arms, we merged the 2 active treatment arms into 1 group. If these 2 active treatment arms belonged to different subgroups (ie, different PUFA dosage subgroups), we kept them separate. Regarding the numbers of participants counted, we chose intention-to-treat as our priority. If there were insufficient data in the intention to treat group (ie, some studies only provided the changes in anxiety severity in those participants completing trials), we chose instead the per-protocol numbers of participants.
Fish oil has only a small benefit on the risk of premature birth. A 2015 meta-analysis of the effect of omega−3 supplementation during pregnancy did not demonstrate a decrease in the rate of preterm birth or improve outcomes in women with singleton pregnancies with no prior preterm births. A systematic review and meta-analysis published the same year reached the opposite conclusion, specifically, that omega−3 fatty acids were effective in "preventing early and any preterm delivery".
To evaluate the potential placebo effect, we made further subgrouping analyses. In the subgroups of studies using placebo controls, the omega-3 PUFAs still revealed a consistent positive anxiolytic association with anxiety symptoms. These phenomena meant that the anxiolytic effect of omega-3 PUFAs is probably not entirely owing to the placebo effect.
Your retina contains quite a bit of DHA, making it necessary for that fatty acid to function. (90) The National Eye Institute, part of the National Institutes of Health, concludes that there is “consistent evidence” suggesting long-chain polyunsaturated fatty acids DHA and EPA are necessary for retinal health and may help protect the eyes from disease. (91)
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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.
According to the National Psoriasis Foundation, fish oil can aid in preventing or slowing heart disease, which is especially great for psoriasis and psoriatic arthritis sufferers who are at a higher risk of developing heart disease. (27) When it comes to using fish oil supplements for the alleviation of psoriasis symptoms, studies have been mixed with some showing improvement but others showing no effect. If you suffer from psoriasis, you may want to try a fish oil supplement, or else I highly recommend that you make sure to have fish rich in omega-3s regularly.
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).
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.
The omega-3 PUFA EPA and DHA are important throughout life and are a dietary necessity found predominantly in fish and fish-oil supplements. The omega-3 fatty acids EPA and DHA are essential for proper fetal development, and supplementation during pregnancy has also been linked to decreased immune responses in infants including decreased incidence of allergies in infants. Omega-3 fatty acid consumption has been associated with improved cardiovascular function in terms of antiinflammatory properties, PAD, reduced major coronary events, and improved antiplatelet effects in the face of aspirin resistance or clopidogrel hyporesponsiveness. Patients with AD have been shown to be deficient in DHA, and supplementing them with EPA+DHA not only reverses this deficiency, but may also improve cognitive functioning in patients with very mild AD. With increasing rates of pediatric allergies, cardiovascular disease, and AD in the United States, EPA and DHA may be a safe and inexpensive link to a healthier life. Further research should be conducted in humans to assess a variety of clinical outcomes including quality of life and mental status. In addition, because potent lipid mediator metabolites of EPA and DHA are of great interest currently, their influence on these important outcomes should be assessed because current evidence suggests that their antiinflammatory and tissue-protective effects are nearly 1000 times greater than those of EPA and DHA (7).
If you get your omega-3 index measured, you’ll know if your current efforts are sufficient. And this knowledge is especially important given that even health-conscious people are not always self-aware. One survey found that in a group of people with omega-3 index levels in the intermediate risk range, some 30% believed they were consuming enough omega-3s (11). One registered dietitian wrote a compelling story about exactly this experience. She discovered she was in the intermediate range, in spite of her intentions to eat enough fish.
Fish oil is effective in reducing inflammation in the blood and tissues. Regular consumption of fish oil supplements, tablets, pills, and capsules is helpful to those who suffer from chronic inflammatory diseases. Fish oil is effective in treating gastrointestinal disorders, Celiac disease, short bowel syndrome and inflammatory bowel disease (IBD) including Crohn’s Disease and ulcerative colitis, which are both typical disorders of the intestine. Patients suffering from Crohn’s disease often find it difficult to absorb vitamins, fats, and essential supplements. Fish oil supplements are an effective diet for such patients.
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.
Nine studies with 10 data sets used omega-3 PUFA dosages of less than 2000 mg/d.35,47,48,51,53,55,56,60,61 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, 9; Hedges g, 0.457; 95% CI, –0.077 to 0.991; P = .09) (Figure 3B). Ten studies with 10 data sets used omega-3 PUFA dosages of at least 2000 mg/d.33,34,36,49,50,52,54,55,57-59 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, 11; Hedges g, 0.213; 95% CI, 0.031-0.395; P = .02) (Figure 3B). Furthermore, there was no significantly different estimated effect sizes between these 2 subgroups by the interaction test (P = .40).
“This idea has since been pretty discredited; we really don’t know if the Eskimos got heart disease or not,” said Malden C. Nesheim, emeritus professor of nutrition at Cornell University, who chaired an Institute of Medicine committee assessing the risks and benefits of seafood in the early 2000s. “I’ve been an omega-3 skeptic since doing this study.”
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The hypotriglyceridemic effect of fish oil is well established and is related to both dose and baseline triglyceride level. Patients with triglycerides <90 mg/dL will be negligibly affected unless very high doses of omega-3 FA are used.67,68 However, in patients with triglycerides >200 mg/dL, who are treated with 4 g/d of fish oil, a 30% reduction in triglycerides is expected.17,69 For patients with triglycerides >500 mg/dL who are at risk for pancreatitis, the National Cholesterol Education Program Adult Treatment Panel III guidelines recommend using fish oil supplements as an adjunctive therapy to fibrates and nicotinic acid.70 Lovaza capsules have been shown to be effective, safe, and comparable to gemfibrozil in treating triglycerides at this range.71,72 The official label recommendation for Lovaza is for patients with triglycerides >500 mg/dL.73
Special attention should also be given to the fact that most women have major deficiencies of omega-3. A 1991 study at the Mayo Clinic focused on 19 "normal" pregnant women consuming "normal diets," and it showed that all were deficient in omega-3 fats. Another study compared Inuit (Eskimo) women to Canadian women, and it revealed omega-3 deficiency in the milk of the Canadian nursing moms.
Science is dynamic, not static, and as scientific understanding advances scientists sometimes have to modify their positions. Dr. Kidd’s position on EPA and DHA has now changed due to advances in the clinical and basic scientific research. Though the brain carries predominantly DHA and very little EPA, clinical trial results clearly indicate EPA has benefit for mood and probably other higher brain functions. At the basic science level, it has become clear that both EPA and DHA, not DHA alone, are required for the brain to make new nerve cells. Dr. Kidd very closely monitors the research on EPA and… Read more »
Omega-3 [(n-3)] long-chain PUFA, including EPA and DHA, are dietary fats with an array of health benefits (1). They are incorporated in many parts of the body including cell membranes (2) and play a role in antiinflammatory processes and in the viscosity of cell membranes (3, 4). EPA and DHA are essential for proper fetal development and healthy aging (5). DHA is a key component of all cell membranes and is found in abundance in the brain and retina (6). EPA and DHA are also the precursors of several metabolites that are potent lipid mediators, considered by many investigators to be beneficial in the prevention or treatment of several diseases (7).
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.
Jump up ^ Naliwaiko, K.; Araújo, R.L.F.; Da Fonseca, R.V.; Castilho, J.C.; Andreatini, R.; Bellissimo, M.I.; Oliveira, B.H.; Martins, E.F.; Curi, R.; Fernandes, L.C.; Ferraz, A.C. (2004). "Effects of Fish Oil on the Central Nervous System: A New Potential Antidepressant?". Nutritional Neuroscience. 7 (2): 91–99. doi:10.1080/10284150410001704525. PMID 15279495.
The bottom line of all that is that there was no clear health benefit from consuming omega-3 fatty acids in food or supplements. There was a suggestion of a possible benefit from LCn3 on cardiac events, but this did not hold up when they took into consideration the quality of the evidence. The better trials, with less risk of bias, tended to be negative.
Keck, P. E., Jr., Mintz, J., McElroy, S. L., Freeman, M. P., Suppes, T., Frye, M. A., Altshuler, L. L., Kupka, R., Nolen, W. A., Leverich, G. S., Denicoff, K. D., Grunze, H., Duan, N., and Post, R. M. Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol.Psychiatry 11-1-2006;60(9):1020-1022. View abstract.
McNamara, R. K., Able, J., Jandacek, R., Rider, T., Tso, P., Eliassen, J. C., Alfieri, D., Weber, W., Jarvis, K., DelBello, M. P., Strakowski, S. M., and Adler, C. M. Docosahexaenoic acid supplementation increases prefrontal cortex activation during sustained attention in healthy boys: a placebo-controlled, dose-ranging, functional magnetic resonance imaging study. Am J Clin Nutr 2010;91(4):1060-1067. View abstract.
Nakamura, N., Hamazaki, T., Ohta, M., Okuda, K., Urakaze, M., Sawazaki, S., Yamazaki, K., Satoh, A., Temaru, R., Ishikura, Y., Takata, M., Kishida, M., and Kobayashi, M. Joint effects of HMG-CoA reductase inhibitors and eicosapentaenoic acids on serum lipid profile and plasma fatty acid concentrations in patients with hyperlipidemia. Int J Clin Lab Res 1999;29(1):22-25. View abstract.