The chemical structure of eicosapentaenoic acid and docosahexaenoic acid. Eicosapentaenoic acid consists of 20 carbons (C20) with 5 double bonds, and the last unsaturated carbon is located third from the methyl end (n-3). Do-cosahexaenoic acid consists of 22 carbons (C22) with 6 double bonds, and also with the3 last unsaturated carbon located third from the methyl end (n-3). Adapted with permission from Frishman et al, eds. Cardiovascular Pharmacotherapeutics. New York, NY: McGraw Hill; 2003.3
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).
Omega-3 fatty acids, which are found abundantly in fish oil, are increasingly being used in the management of cardiovascular disease. It is clear that fish oil, in clinically used doses (typically 4 g/d of eicosapentaenoic acid and docosahexaenoic acid) reduce high triglycerides. However, the role of omega-3 fatty acids in reducing mortality, sudden death, arrhythmias, myocardial infarction, and heart failure has not yet been established. This review will focus on the current clinical uses of fish oil and provide an update on their effects on triglycerides, coronary artery disease, heart failure, and arrhythmia. We will explore the dietary sources of fish oil as compared with drug therapy, and discuss the use of fish oil products in combination with other commonly used lipid-lowering agents. We will examine the underlying mechanism of fish oil’s action on triglyceride reduction, plaque stability, and effect in diabetes, and review the newly discovered anti-inflammatory effects of fish oil. Finally, we will examine the limitations of current data and suggest recommendations for fish oil use.

Another recent study shows that fatty fish consumption can cut the risk of eye-diabetes complications. The researches tracked the seafood consumption of about 3,600 diabetic men and women between the ages of 55 and 80 for nearly five years. The researchers found that people who regularly consumed 500 milligrams each day of omega-3 fatty acid in their diets (equal to two servings of fatty fish per week) were 48 percent less likely to develop diabetic retinopathy than those who consumed less. (23)

DHA is especially vital for infant and child brain and nervous system development, as well as visual function. In older children, high DHA levels have been shown to improve learning ability, while deficiencies have been linked to learning problems and ADHD. And in adults, some studies have shown that DHA helps protect against cognitive decline and Alzheimer’s disease.
People used to believe that osteoporosis and osteoarthritis were the result of aging and reduced intake of calcium and milk products. Science has now shown that these bone and joint disorders are, in part, due to inflammation. Because of this, bones and joints are prime targets for the anti-inflammatory properties of omega-3 oils from both fish and krill.
Fish oil’s most potent effect on atherosclerosis may be related to its potential to alter plaque inflammation, thereby stabilizing vulnerable plaques. In recent years there has been a growing body of evidence that is shifting the paradigm of how inflammation is contained and dissipated.4 In this new model, inflammation resolution is an active process mediated by lipid-derived compounds. Newly discovered families of chemical mediators, resolvins, and protectins5,6 are directly involved in blocking neutrophil migration, infiltration, and recruitment, as well as in blocking T-cell migration and promoting T-cell apoptosis.7–12 In addition, protectins can reduce tumor necrosis factor and interferon secretion.13 Interestingly, both protectins and resolvins are strictly derived from omega-3 FA. EPA is the substrate of the resolvins family and DHA can be converted to both resolvins and protectins.7 It may be that the effects of fish oil on inflammatory mediators underlie the positive findings demonstrated in several trials assessing fish oil and plaque stability.14–16

Abnormal rapid heart rhythms (ventricular arrhythmias). Population research suggests that eating a lot of fish has no effect on the risk for abnormal rapid heart rhythms. Clinical research is inconsistent. Some research shows that taking fish oil daily does not affect the risk for abnormal heart rhythms. But other research shows that taking fish oil for 11 months delays the development of the condition. However, overall, taking fish oil does not seem to reduce the risk of death in people with abnormal rapid heart rhythms.
These conversions occur competitively with omega−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. They both utilize the same desaturase and elongase proteins in order to synthesize inflammatory regulatory proteins.[50] The products of both pathways are vital for growth making a balanced diet of omega−3 and omega−6 important to an individual's health.[77] A balanced intake ratio of 1:1 was believed to be ideal in order for proteins to be able to synthesize both pathways sufficiently, but this has been controversial as of recent research.[78]
Reduce Metabolic Syndrome Symptoms: The cluster of risk factors known as metabolic syndrome includes abdominal obesity, high blood sugar, high triglycerides, high blood pressure and low HDL cholesterol. These risk factors are indicative of a high chance you might develop heart disease, stroke or diabetes. Multiple studies have found omega-3 supplementation improve the symptoms of metabolic syndrome and may help to protect you from the related diseases. (22, 23, 24, 25)

However, the researchers do have some good news. They concluded that omega 3 fatty acids do appear to reduce the type of blood cholesterol known as triglycerides, but that supplements probably are not useful for preventing or improving heart and circulatory problems. And, upping your intake of plant-based omega 3s high in ALA (ie, walnuts, flaxseed and flax oil, chia seeds) may help your heart somewhat.2
In a study published after the AHRQ report, scientists in Denmark gave high-dose fish oil supplements or placebos to 736 pregnant women during the third trimester of pregnancy. Children born to mothers who had taken fish oil were less likely to develop asthma or persistent wheezing in early childhood, and this was most noticeable in children whose mothers had low blood levels of EPA and DHA before they started to take the supplements. However, other studies that evaluated the effects of omega-3 supplementation during pregnancy on childhood asthma risk have had inconsistent results.

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.

Full citation: Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, AlAbdulghafoor FK, Summerbell CD, Worthington HV, Song F, Hooper L. Omega 3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2018, Issue 7. Art. No.: CD003177. DOI: 10.1002/14651858.CD003177.pub3.


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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.
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).

If you’ve been paying attention to health headlines over the last few decades, you’ve likely heard about essential fatty acids (EFAs) — specifically omega-3s and omega-6s. These nutrients play many vital roles in supporting our overall health, including increasing nutrient absorption, ensuring proper growth and development of the brain and nervous system, and reducing the risk of chronic illnesses, such as heart disease.  Click here for a guide to understanding omega-3 and omega-6 fatty acids and how they influence your health.


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)
The most extensive data of the effect of fish oil on lipoprotein subfractions are based on trials performed before the widespread use of statins. This data were aggregated over a decade ago in a meta-analysis of 16 randomized trials including over 1500 patients.17 In this analysis, low-density lipoprotein (LDL) was increased by an average of 5% and high-density lipoprotein was marginally changed. Although a shift toward less atherogenic, larger and more buoyant LDL particle composition has been shown,74 this has been offset by the observation that the number of apolipoprotein B 100 particles increases and may be more susceptible to oxidation.75 Increased conversion of remnant particles (intermediate density lipoprotein) to LDL has also been observed.76
Marchioli, R., Barzi, F., Bomba, E., Chieffo, C., Di, Gregorio D., Di, Mascio R., Franzosi, M. G., Geraci, E., Levantesi, G., Maggioni, A. P., Mantini, L., Marfisi, R. M., Mastrogiuseppe, G., Mininni, N., Nicolosi, G. L., Santini, M., Schweiger, C., Tavazzi, L., Tognoni, G., Tucci, C., and Valagussa, F. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 4-23-2002;105(16):1897-1903. View abstract.
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
Fish oils seem to decrease blood pressure. Taking fish oils along with medications for high blood pressure might cause your blood pressure to go too low.Some medications for high blood pressure include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.
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.
Higher visual acuity after DHA supplementation is a consistent finding in infants born preterm. For infants born at term, the results are less consistent and are better explained by differences in sensitivity of the visual acuity test (electrophysiologic tests being more sensitive than subjective tests) or by differences in the amount of DHA included in the experimental formula.
Cardiovascular disease is the cause of 38% of all deaths in the United States, many of which are preventable (28). Chronic inflammation is thought to be the cause of many chronic diseases, including cardiovascular disease (29). EPA and DHA are thought to have antiinflammatory effects and a role in oxidative stress (30) and to improve cellular function through changes in gene expression (31). In a study that used human blood samples, EPA+DHA intake changed the expression of 1040 genes and resulted in a decreased expression of genes involved in inflammatory and atherogenesis-related pathways, such as nuclear transcription factor κB signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling (31). Circulating markers of inflammation, such as C-reactive protein (CRP), TNF α, and some ILs (IL-6, IL-1), correlate with an increased probability of experiencing a cardiovascular event (32). Inflammatory markers such as IL-6 trigger CRP to be synthesized by the liver, and elevated levels of CRP are associated with an increased risk of the development of cardiovascular disease (33). A study of 89 patients showed that those treated with EPA+DHA had a significant reduction in high-sensitivity CRP (66.7%, P < 0.01) (33). The same study also showed a significant reduction in heat shock protein 27 antibody titers (57.69%, P < 0.05), which have been shown to be overexpressed in heart muscle cells after a return of blood flow after a period of ischemia (ischemia-reperfusion injury) and may potentially have a cardioprotective effect (33).

In 2016, AHRQ reviewed 143 studies that evaluated the effects of giving omega-3 supplements to pregnant or breastfeeding women or giving formulas with added DHA to infants. They found that when women took omega-3 supplements during pregnancy, their babies’ birth weight was slightly higher, but the risk of an undesirably low birth weight did not change. Also, when women took omega-3 supplements during pregnancy, their pregnancies lasted a little longer, but there was no effect on the risk of premature birth. Omega-3s were not found to have effects on any other aspects of the mothers’ or infants’ health or the infants’ long-term development. Aspects of the infants’ health that were not shown to be affected by omega-3s include growth after birth, visual acuity, long-term neurological and cognitive development, and the risks of autism, ADHD, learning disorders, and allergies.
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.
To exclude the possible confounding effects of clinical variables on the Hedges g, metaregression analysis was conducted with an unrestricted maximum likelihood random-effects model of single variables when there were more than 10 data sets available. Specifically, the clinical variables of interest included mean age, female proportion, sample size, mean body mass index, daily omega-3 PUFA dosage, EPA to DHA ratio, treatment duration, dropout rate, and others. In addition, a subgroup meta-analysis was conducted to investigate potential sources of heterogeneity, specifically, a further subgroup meta-analysis focused on those trials that were placebo controlled or non–placebo controlled. To more clearly uncover the differences in the meta-analysis results among the recruited studies, a further subgroup meta-analysis was performed according to the presence of a specific clinical diagnosis or no specific clinical condition, mean omega-3 PUFA daily dosage, and mean age. In addition, in a previous study, the EPA percentage (ie, ≥60%) in the PUFA regimens had different effects on depression treatment.9 Therefore, we also arranged the subgroup meta-analysis based on the EPA percentage. Furthermore, we arranged subgroup meta-analysis procedures only when there were at least 3 data sets included.45 To investigate the potentially different estimated effect sizes between subgroups, we performed an interaction test and calculated the corresponding P values.46

Foods such as meat, eggs, fish and nuts contain omega-3 and omega-6 fatty acids, which the body converts into endocannabinoids – cannabinoids that the body produces naturally, said Aditi Das, a University of Illinois professor of comparative biosciences and biochemistry, who led the study. Cannabinoids in marijuana and endocannabinoids produced in the body can support the body’s immune system and therefore are attractive targets for the development of anti-inflammatory therapeutics, she said.
Infant development. There is some evidence that mothers who eat fish or take fish oil supplements during pregnancy may improve some aspects of their baby's mental development. Taking fish oil during breast-feeding does not have this effect. However, feeding infants formula fortified with fish oil appears to improve some aspect of the baby's vision by the age of 2 months.
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