Davidson, M. H., Stein, E. A., Bays, H. E., Maki, K. C., Doyle, R. T., Shalwitz, R. A., Ballantyne, C. M., and Ginsberg, H. N. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther 2007;29(7):1354-1367. View abstract.
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.
There was a significantly greater association of treatment with reduced anxiety symptoms in participants receiving omega-3 PUFAs than in those not receiving omega-3 PUFAs in the subgroup with an EPA percentage less than 60% (k, 11; Hedges g, 0.485; 95% CI, 0.017-0.954; P = .04; Figure 4)35,49,52,54-61 but 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 subgroup with an EPA percentage of at least 60% (k, 9; Hedges g, 0.092; 95% CI, –0.102 to 0.285; P = .35) (Figure 4).33,34,36,47,48,50,51,53,60 There were no significantly different estimated effect sizes between these 2 subgroups by the interaction test (P = .13).
The Japanese notably have the lowest levels of coronary heart disease mortality and atherosclerosis among developed nations — a phenomena that has been largely subscribed to diet. However, even within Japan, a 10-year study of over 41,000 people found that higher intakes of omega-3s were associated with lower risks of nonfatal coronary events (8). A more recent study also found that Japanese with higher omega-3 index levels (10%) had a lower risk of fatal coronary heart disease than those with a lower omega-3 index levels (8%) (9). The study begs the question of whether maybe even the Japanese have room to improve their omega-3 intake and whether 8% should be considered the lower limit of a desirable range.
The Cochrane researchers found that increasing long-chain omega 3 provides little if any benefit on most outcomes that they looked at. They found high certainty evidence that long-chain omega 3 fats had little or no meaningful effect on the risk of death from any cause. The risk of death from any cause was 8.8% in people who had increased their intake of omega 3 fats, compared with 9% in people in the control groups.
Finally, it is often assumed since there are not high levels of EPA in the brain, that it is not important for neurological function. Actually it is key for reducing neuro-inflammation by competing against AA for access to the same enzymes needed to produce inflammatory eicosanoids. However, once EPA enters into the brain it is rapidly oxidized (2,3). This is not the case with DHA (4). The only way to control cellular inflammation in the brain is to maintain high levels of EPA in the blood. This is why all the work on depression, ADHD, brain trauma, etc. have demonstrated EPA to be superior to DHA (5).
Fish oil combined with fenofibrate has not been studied extensively in randomized controlled trials. Data to date, however, suggest that the combination is safe and effective.63,64 A recent randomized controlled trial of 100 patients with severe hypertriglyceridemia and HIV on highly active antiretroviral therapy showed that a regimen of fenofibrate and 3 g/d of fish oil for 8 weeks was well tolerated. The median baseline triglyceride level of 650 mg/dL was reduced by 65%.63 Another recent randomized, 2 month, double-blind, placebo-controlled trial, which was set up to assess the safety and efficacy of fenofibrate with 4 g of fish oil, showed that in the 81 patients assigned to combination therapy, triglyceride levels were reduced by 61%. Therapy was well-tolerated without significant adverse reactions at 8 weeks or at the end of a 2-year open label extension.64 The combination of fish oil and niacin requires further study.
Studies have also shown that omega-3 fats are anti-arrhythmic (preventing or counteracting cardiac arrhythmia), anti-thrombotic (prevents thrombosis or a blood clot within a blood vessel), anti-atherosclerotic (preventing fatty deposits and fibrosis of the inner layer of your arteries), and anti-inflammatory (counteracting inflammation – the heat, pain, swelling, etc).
This constant sweeping motion of DHA also causes the breakup of lipid rafts in membranes (8). Disruption of these islands of relatively solid lipids makes it more difficult for cancer cells to continue to survive and more difficult for inflammatory cytokines to initiate the signaling responses to turn on inflammatory genes (9). In addition, the greater spatial characteristics of DHA increase the size of LDL particles to a greater extent compared to EPA. As a result, DHA helps reduce the entry of these enlarged LDL particles into the muscle cells that line the artery thus reducing the likelihood of developing atherosclerotic lesions (10). Thus the increased spatial territory swept out by DHA is good news for making certain areas of membranes more fluid or lipoprotein particles larger, even though it reduces the benefits of DHA in competing with AA for key enzymes important in the development of cellular inflammation.
Omega-3 fatty acids are frequently in the news regarding their health benefits (or doubts in some cases). Two types of omega-3s in particular - eicosapentaenoic acid (EPA) and docohexaenoic acid (DHA) – are known to be essential fatty acids. “Essential” refers to the fact that our cells need these fatty acids in order to function normally. But the body cannot make them from other fats, which means it’s “essential” we supply them in our diet or through supplementation.
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).
For those who can’t or choose not to eat fatty fish, or who have certain health issues, supplementation is a way to increase omega-3 levels. “There are some conditions that might respond well to supplementation, such as depression or cardiovascular risk factors, including elevated triglycerides,” explains Kathie Madonna Swift, MS, RDN, LDN.  If you're ooking to increase your omega-3 levels, Click here for six tips to finding the right supplement.
Subgroup meta-analysis of the anxiolytic effects of omega-3 polyunsaturated fatty acids (PUFAs) based on different EPA percentages. The anxiolytic effects of omega-3 PUFAs were significant in the subgroup with an EPA percentage less than 60% (k, 11; Hedges g = 0.485; 95% CI, 0.017 to 0.954; P = .04) but not significant in the subgroups with an EPA percentage of at least 60% (k, 9; Hedges g, 0.092; 95% CI, –0.102 to 0.285; P = .35).
Hernandez, D., Guerra, R., Milena, A., Torres, A., Garcia, S., Garcia, C., Abreu, P., Gonzalez, A., Gomez, M. A., Rufino, M., Gonzalez-Posada, J., Lorenzo, V., and Salido, E. Dietary fish oil does not influence acute rejection rate and graft survival after renal transplantation: a randomized placebo-controlled study. Nephrol.Dial.Transplant. 2002;17(5):897-904. View abstract.
We are now fortunate to understand how these fats work in combination and in isolation, how they are digested, absorbed and utilised in the body, so we are able to tailor different blends of EPA and DHA according to the health benefits we are seeking to achieve. At Igennus, we have long specialised in the role of the omega-3 fatty acid EPA in clinical nutrition, as a powerful tool in the patient’s ‘toolkit’ for helping to regulate inflammation by restoring several biological markers, known as the omega-6 to omega-3 ratio and AA to EPA ratio. Before we discuss the therapeutic role of EPA in nutritional medicine, here’s a very brief summary of the role of both EPA and DHA in health throughout life.
The effect of fish oil on incident atrial fibrillation has not been studied in large randomized trials, and observational population-based trials show mixed results. The Danish Diet, Cancer and Health Study, and the Rotterdam Study followed 47,000 and 5100 middle-aged adults, respectively.45,46 Neither study found that the consumption of fish oil affected the incidence of atrial fibrillation. Similar findings were seen in the Women’s Health Initiative where there was no association between fish and omega-3 FA intake regarding incident atrial fibrillation.47 However, in a 12-year prospective, observational study of 4815 adults over the age of 65, daily fish consumption was associated with a 31% risk reduction in incident atrial fibrillation.48
High triglycerides. Most research shows that fish oil from supplements and food sources can reduce triglyceride levels. The effects of fish oil appear to be the greatest in people who have very high triglyceride levels. Also the amount of fish oil consumed seems to directly affect how much triglyceride levels are reduced. Some fish oil supplements including Lovaza, Omtryg, and Epanova have been approved by the FDA to lower triglycerides.
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