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.
Kremer, J. M., Lawrence, D. A., Petrillo, G. F., Litts, L. L., Mullaly, P. M., Rynes, R. I., Stocker, R. P., Parhami, N., Greenstein, N. S., Fuchs, B. R., and . Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune correlates. Arthritis Rheum. 1995;38(8):1107-1114. View abstract.
Bell, J. G., Miller, D., MacDonald, D. J., MacKinlay, E. E., Dick, J. R., Cheseldine, S., Boyle, R. M., Graham, C., and O'Hare, A. E. The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake. Br J Nutr 2010;103(8):1160-1167. View abstract.
So back to fish oil in general. The major fish oil benefits include decreasing the risk of heart disease and stroke while also helping reduce symptoms of depression, hypertension, attention deficit hyperactivity disorder (ADHD), joint pain, arthritis and chronic skin ailments like eczema. (2) Fish oil intake has also been associated with aiding the body in weight loss, fertility, pregnancy and increased energy. Prescription fish oil has even been approved by the FDA to lower unhealthy high triglyceride levels. (3)
First difference is in the area of omega-6 fatty acid metabolism. Whereas EPA is the inhibitor of the enzyme (D5D) that directly produces AA, DHA is an inhibitor of another key enzyme delta-6-desaturase (D6D) that produces the first metabolite from linoleic acid known as gamma linolenic acid or GLA (6). However, this is not exactly an advantage. Even though reduction of GLA will eventually decrease AA production, it also has the more immediate effect of reducing the production of the next metabolite known as dihomo gamma linolenic acid or DGLA. This can be a disaster as a great number of powerful anti-inflammatory eicosanoids are derived from DGLA. This is why if you use high-dose DHA it is essential to add back trace amounts of GLA to maintain sufficient levels of DGLA to continue to produce anti-inflammatory eicosanoids.
Heart disease. Research suggests that eating fish can be effective for keeping people with healthy hearts free of heart disease. People who already have heart disease might also be able to lower their risk of dying from heart disease by eating fish. The picture is less clear for fish oil supplements. For people who already take heart medications such as a "statin" and those who already eat a decent amount of fish, adding on fish oil might not offer any additional benefit.

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]
*Swordfish contains high levels of mercury, as does shark, king mackerel, and tilefish (sometimes called golden bass or golden snapper). Women who are or may become pregnant, nursing mothers, and young children should avoid these high-mercury species of fish, but can eat up to 12 ounces (two average meals) a week of a variety of fish and shellfish that are lower in mercury.

My initial interest in omga-3 was an article by Dr Andrew Stoll in Harvard about May 99, One of my bipolar patients had extreme OCD related to HIV which was not relevant to her. I put her on 9.6g of fish oil and continued her on her regular medication. She was well for the next 3 years with no obvious mental health problem when she was attending here.
Another small study had all volunteers consume the same exact control diet and substituted fish oil for visible fats (things like butter and cream). The volunteers consumed six grams of fish oil each day for three weeks. They found that body fat mass decreased with the intake of fish oil. The researchers conclude that dietary fish oil reduces body fat and stimulates the use of fatty acids for the production of energy in healthy adults. (33a)
Some high-quality omega-3 supplements will have lower amounts than EPA/DHA but accompany them with digestive enzymes. While it looks counterintuitive on a nutrition label, this is often done because there is debate about how much of the omega-3’s you actually absorb from supplements when taken alone. By coupling omega-3’s with a digestive enzyme blend, you are likely able to absorb more of the nutrient without having to consume as many grams.
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]
Omega-3 fatty acids have been found to play a role in atherosclerosis and peripheral arterial disease (PAD). It is thought that both EPA and DHA improve plaque stability, decrease endothelial activation, and improve vascular permeability, thereby decreasing the chance of experiencing a cardiovascular event (41). It was found that EPA supplementation is associated with significantly higher amounts of EPA in the carotid plaque than placebo (P < 0.0001), which may lead to decreased plaque inflammation and increased stability (42). PAD, a manifestation of atherosclerosis, is characterized by buildup of plaque in the arteries of the leg and can eventually lead to complete blockage of the arteries. EPA+DHA supplementation has been shown to improve endothelial function in patients with PAD by decreasing plasma levels of soluble thrombomodulin from a median value of 33.0 μg/L to 17.0 μg/L (P = 0.04) and improve brachial artery flow–mediated dilation from 6.7% to 10.0% (P = 0.02) (43). Patients who had PAD and were supplemented with EPA experienced a significantly lower major coronary event HR than those who did not take EPA (HR: 0.44; 95% CI: 0.19–0.97; P = 0.041) (44).

A 2012 study involved children from 6 to 12 years of age with ADHD who were being treated with methylphenidate and standard behavior therapy for more than six months. The parents of these children reported no improvement in behavior and academic learning using these standard treatments. The researchers randomly gave some of the children an omega-3 and omega-6 acid supplementation or a placebo. They found “statistically significant improvement” for the omega group in the following categories: restlessness, aggressiveness, completing work and academic performance. (5)
A 2009 metastudy found that patients taking omega-3 supplements with a higher EPA:DHA ratio experienced fewer depressive symptoms. The studies provided evidence that EPA may be more efficacious than DHA in treating depression. However, this metastudy concluded that due to the identified limitations of the included studies, larger, randomized trials are needed to confirm these findings.[40]
Increased EPA levels in the blood and cell membranes effectively regulates inflammatory pathways and reduces total inflammatory ‘load’, so for any inflammatory conditions or concerns, we recommend a phase of pure EPA supplementation for at least 3-6 months. Pre-loading the body with pure EPA (without the opposing actions of DHA for uptake and utilisation) ensures constant replenishment of EPA ’supplies’ to support its high rate of turnover. Since DHA levels remain fairly stable and much lower daily amounts are required, DHA levels can be supported continually through dietary intake, or increased to 250 mg daily in later stages of treatment through supplementation.

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).


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.
Human growth and intellectual development – DHA plays a very important role during fetal development, early infancy and old age. High concentrations of DHA are found in the brain and increase 300 to 500 percent in an infant’s brain during the last trimester of pregnancy. Adding DHA to a pregnant mother’s diet may be beneficial for the fetus’s brain development. Elderly people should also take EPA DHA, because as we get older, our bodies form less EPA and DHA, which may cause less mental focus and cognitive function. Taking EPA DHA also may help with mental abnormalities, such as Alzheimer’s disease and dementia.
Omega−3 fatty acids are important for normal metabolism.[8] Mammals are unable to synthesize omega−3 fatty acids, but can obtain the shorter-chain omega−3 fatty acid ALA (18 carbons and 3 double bonds) through diet and use it to form the more important long-chain omega−3 fatty acids, EPA (20 carbons and 5 double bonds) and then from EPA, the most crucial, DHA (22 carbons and 6 double bonds).[8] The ability to make the longer-chain omega−3 fatty acids from ALA may be impaired in aging.[9][10] In foods exposed to air, unsaturated fatty acids are vulnerable to oxidation and rancidity.[11]

After just seven days, those supplementing with krill had their CRP levels reduced by 19.3%, while in the placebo group, CRP levels rose by 15.7%. Even more impressive, the krill benefit was long-lasting. The krill group’s CRP levels continued to fall by 29.7% at 14 days, and 30.9% at 30 days. More importantly from the patients’ points of view, the krill oil supplement reduced pain scores by 28.9%, reduced stiffness by 20.3%, and reduced functional impairment by 22.8%.

More than 30 clinical trials have tested different omega-3 preparations in people with depression. Most studies have used omega-3s as add-on therapy for people who are taking prescription antidepressants with limited or no benefit. Fewer studies have examined omega-3 therapy alone. Clinical trials typically use EPA alone or a combination of EPA plus DHA, at doses from 0.5 to 1 gram per day to 6 to 10 grams per day. To give some perspective, 1 gram per day would correspond to eating three salmon meals per week.
As always with such trials, you can never prove zero benefit (or zero risk), but an essentially negative trial or meta-analysis sets statistical limits on the size of any remaining plausible effect. What we can now say with a fairly high degree of confidence is that any health benefit from consuming omega-3 fatty acids is tiny, probably too small to warrant supplementing (or adding it to pasta).
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.
Three randomized trials assessing more than 600 patients with known malignant ventricular arrhythmia were carried out under the protection of implanted cardioverter defibrillator (ICD) therapy.41–43 In all 3 of the trials, 75% of the patients had ischemic heart disease, survived ventricular tachycardia or ventricular fibrillation and were randomized to 1 to 3 g/d of fish oil. In the first trial of its kind, 402 patients with ICDs were randomized to either a fish oil or an olive oil supplement.41 Although statistical significance was not reached, after approximately 1 year the primary end-point of time to first ICD cardioversion for ventricular tachycardia or fibrillation or death from any cause was longer in the fish oil group. This finding was not replicated in a trial of 200 patients who were randomized to either fish oil or a placebo and followed for a median of approximately 2 years.42 In fact, time to first ICD cardioversion was not changed and the incidence of recurrent ventricular tachycardia and fibrillation was more common in the group assigned to fish oil. In the largest trial, 546 patients were randomized to supplemental fish oil or a placebo and were followed for a mean period of 1 year.43 The primary outcome of the rate of ICD cardioversion or all-cause mortality was not reduced. It was concluded in a recent meta-analysis of these trials that fish oil did not have a protective effect.44
I now suspect that those thousands of gel-covered capsules I’ve swallowed over the years may have done little more than enrich the pockets of supplement producers and sellers. A number of extensive analyses have been conducted, some supporting and others refuting the value of fish oils to the cardiovascular system, along with studies of other purported health benefits that also have had mixed results.
Several large studies have linked higher blood levels of long-chain omega-3s with higher risks of prostate cancer. However, other research has shown that men who frequently eat seafood have lower prostate cancer death rates and that dietary intakes of long-chain omega-3s aren’t associated with prostate cancer risk. The reason for these apparently conflicting findings is unclear. 
Docosahexaenoic acid (DHA) found primarily in fish oil, this is the ultimate form of fatty acid in humans. Most people get far too little of this all-important fatty acid, especially since the conversion of ALA to DHA is slow and minimally yielding. Getting a daily dose of of DHA (600 to 1000 mg) from supplements is preferable to reap the health benefits. You have a choice of taking a fish oil supplement or one derived from algae or krill, a shrimp-like crustacean.
DHA is vital for early brain development and maintenance, while EPA seems to be closely related to behavior and mood. Together, both molecules provide critical neuroprotective benefits.11 These neuroprotective effects are important for the prevention of age-related brain shrinkage (cortical atrophy). Aging adults with brain shrinkage often experience memory loss, cognitive decline, and an increase in depression.12-14
Although there was significant heterogeneity among the included studies (Cochran Q, 178.820; df, 18; I2, 89.934%; P < .001), the sensitivity test suggested that the main significant results of the meta-analysis would not change after removal of any of the included studies. However, through direct inspection of the forest plot, we detected the potential influence of some outliers, such as the studies by Sohrabi et al56 and Yehuda et al.61 These 2 studies evaluated anxiety symptoms with a visual analog scale of anxiety and test anxiety severity, which are seldom used in psychiatric research and lack a definite report to prove their equivalent sensitivity and specificity to some other frequently used anxiety rating scales, such as depression, anxiety, and stress scales or the Hamilton anxiety rating scale. Therefore, these studies might have affected the interpretation of the current meta-analysis.
After just seven days, those supplementing with krill had their CRP levels reduced by 19.3%, while in the placebo group, CRP levels rose by 15.7%. Even more impressive, the krill benefit was long-lasting. The krill group’s CRP levels continued to fall by 29.7% at 14 days, and 30.9% at 30 days. More importantly from the patients’ points of view, the krill oil supplement reduced pain scores by 28.9%, reduced stiffness by 20.3%, and reduced functional impairment by 22.8%.
Omega-3s are generally safe and well tolerated. Stomach upset and “fishy taste” have been the most common complaints, but they are less frequent now thanks to manufacturing methods that reduce impurities. Past concerns about omega-3s increasing the risk of bleeding have been largely disproven, but caution is still advised in people taking blood thinners or who are about to undergo surgery. As mentioned, caution is needed in people with bipolar disorder to prevent cycling to mania. Because omega-3s are important to brain development, and pregnancy depletes omega-3 in expectant mothers, supplementation should theoretically benefit pregnant women and their children. Fish consumption in pregnancy is supported by the FDA, but because we do not have long-term data on safety or optimal dosing of omega-3s in pregnancy, expectant mothers should consider omega-3 supplements judiciously.
What makes omega-3 fats special? They are an integral part of cell membranes throughout the body and affect the function of the cell receptors in these membranes. They provide the starting point for making hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They also bind to receptors in cells that regulate genetic function. Likely due to these effects, omega-3 fats have been shown to help prevent heart disease and stroke, may help control lupus, eczema, and rheumatoid arthritis, and may play protective roles in cancer and other conditions.
Meta‐analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all‐cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high‐quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high‐quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses – LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.
Fish oil is also used for diabetes, prediabetes, asthma, a movement and coordination disorder called dyspraxia, dyslexia, eczema, autism, obesity, weak bones (osteoporosis), rheumatoid arthritis (RA), osteoarthritis, psoriasis, an autoimmune disease called systemic lupus erythematosus (SLE), multiple sclerosis, HIV/AIDS, cystic fibrosis, gum disease, Lyme disease, sickle cell disease, and preventing weight loss caused by some cancer drugs.
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