Bergmann, R. L., Haschke-Becher, E., Klassen-Wigger, P., Bergmann, K. E., Richter, R., Dudenhausen, J. W., Grathwohl, D., and Haschke, F. Supplementation with 200 mg/day docosahexaenoic acid from mid-pregnancy through lactation improves the docosahexaenoic acid status of mothers with a habitually low fish intake and of their infants. Ann Nutr Metab 2008;52(2):157-166. View abstract.


The three types of omega-3s are APA, EPA and DHA. The first is a medium-chain fatty acid and must be converted into EPA before being synthesized by the body, and only about 1 percent of the APA consumed is able to be converted. EPA and DHA are already in a form ready to be synthesized (and are the subject of most scientific research regarding omega-3s).
In comparison, the omega-3s found in krill appear to be more rapidly incorporated into red blood cell phospholipids.7 This is important, because not only do scientists view the uptake of essential fatty acids in red blood cells as a biomarker for uptake into the brain,8 but additional research suggests that when omega-3 fatty acids such as DHA are bound to phospholipids as they are with krill, it increases their uptake to the brain.9 This is further supported by human clinical research, which suggests ingestion of phospholipid-bound EPA and DHA increase cognitive function scores to a greater degree compared with scores obtained when the fatty acids in the ingested oil were provided in the triglycerides storage form.10

The FDA product label on Lovaza warns of potential bleeding complications with the coadministration of anticoagulants. This warning is based on observational studies that suggested a prolonged bleeding time in populations ingesting high levels of fish oil77 and on in vitro studies that demonstrated an effect on pro-thrombotic mediators such as a reduction in thromboxane A2 production78 and platelet activation factor.79 The same trend, however, has not been clearly demonstrated in measurements of clotting times or in factors of fibrinolysis.80 In addition, in randomized clinical trials of patients undergoing coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, endarterectomy and diagnostic angiography, no adverse bleeding related events have been demonstrated.81 For example, in a trial of 500 patients randomized to pretreatment with 6.9 g of DHA and EPA preparation 2 weeks before balloon percutaneous transluminal coronary angioplasty (where all the patients received 325 mg/d of aspirin and heparin bolus periprocedure), no difference was seen in bleeding complications.82 Similar results were seen in a trial of 610 patients undergoing coronary artery bypass graft surgery, randomized to either placebo or 4 g/d of fish oil and then further randomized to aspirin or warfarin (dosed to an international normalized ratio [INR] goal of 2.5–4.2). At 1 year, the number of bleeding complications was not increased.15 The effect of fish oil on INR values has not been studied extensively, but a small, randomized trial showed that fish oil did not alter the Coumadin dosing regimen.83 There is very little evidence that a lower target INR is necessary in patients receiving chronic warfarin therapy and fish oil.


It can be challenging to get the appropriate intake of EPA and DHA through diet alone, even though EPA and DHA are produced by water plants such as algae and are prevalent in marine animals. A shorter chain omega-3 fatty acid, α-linolenic acid (ALA),6 is a prominent component of our diet as it is found in many land plants that are commonly eaten, but it does not provide the health benefits seen with EPA and DHA. Although it is possible for the body to convert ALA to EPA and DHA by enlongase and desaturase enzymes, research suggests that only a small amount can be synthesized in the body from this process (8). For example, 1 study suggested that only ∼2 to 10% of ALA is converted to EPA or DHA (9), and other studies found even less: Goyens et al. (10) found an ALA conversion of ∼7% for EPA, but only 0.013% for DHA; Hussein et al. (11) found an ALA conversion of only 0.3% for EPA and <0.01% for DHA.
Alpha-linolenic Acid (ALA): This plant-based omega-3 is found in green, leafy vegetables, flaxseeds, chia seeds and canola, walnut and soybean oils (although those rancid oils are not ones I generally recommend). ALA is known as a short-chain omega-3, meaning your body has to convert it into longer-chained EPA and DHA to synthesize it. This process is rather inefficient and only about one percent of the ALA you consume is converted to the long-chain version your body needs (although this percentage is slightly higher for women).
The various enzymes (COX and LOX) that make inflammatory eicosanoids can accommodate both AA and EPA, but again due to the greater spatial size of DHA, these enzymes will have difficulty in converting DHA into eicosanoids. This makes DHA a poor substrate for these key inflammatory enzymes. Thus DHA again has little effect on cellular inflammation whereas EPA can have a powerful impact.
The question is whether the observed cardiovascular benefits often found among fish eaters is due solely to the oils in fish or to some other characteristics of seafood or to still other factors common to those who eat lots of fish, like eating less meat or pursuing a healthier lifestyle over all. Whatever the answer, it does not seem to be fish oil supplements.
When it comes to fat, there's one type you don’t want to cut back on: omega-3 fatty acids. Two crucial ones -- EPA and DHA -- are primarily found in certain fish. ALA (alpha-linolenic acid), another omega-3 fatty acid, is found in plant sources such as nuts and seeds. Not only does your body need these fatty acids to function, but also they deliver some big health benefits.
CHAMPAIGN, Ill. — Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its euphoric effects, but it also has anti-inflammatory benefits. A new study in animal tissue reveals the cascade of chemical reactions that convert omega-3 fatty acids into cannabinoids that have anti-inflammatory benefits – but without the psychotropic high.
Omega AD study, Freund-Levi et al. (47) Double-blind, placebo-controlled, randomized 1741 DHA (1.7 g/d) and EPA (0.6 g/d) Decline in cognitive function did not differ between supplemented group and placebo group at 6 mo. However, patients with very mild cognitive dysfunction (n = 32, MMSE score >27) in the EPA+DHA-supplemented group had a significant reduction in MMSE score decline rate at 6 mo
There is some evidence that omega−3 fatty acids are related to mental health,[47] including that they may tentatively be useful as an add-on for the treatment of depression associated with bipolar disorder.[48] Significant benefits due to EPA supplementation were only seen, however, when treating depressive symptoms and not manic symptoms suggesting a link between omega−3 and depressive mood.[48] There is also preliminary evidence that EPA supplementation is helpful in cases of depression.[49] The link between omega−3 and depression has been attributed to the fact that many of the products of the omega−3 synthesis pathway play key roles in regulating inflammation (such as prostaglandin E3) which have been linked to depression.[50] This link to inflammation regulation has been supported in both in vitro[51] and in vivo studies as well as in meta-analysis studies.[33] The exact mechanism in which omega−3 acts upon the inflammatory system is still controversial as it was commonly believed to have anti-inflammatory effects.[52]
To our knowledge, this is the first systematic review and meta-analysis to examine the anxiolytic effects of omega-3 PUFAs in individuals with anxiety symptoms. The overall findings revealed modest anxiolytic effects of omega-3 PUFAs in individuals with various neuropsychiatric or major physical illnesses. Although participants and diagnoses were heterogeneous, the main finding of this meta-analysis was that omega-3 PUFAs were associated with significant reduction in anxiety symptoms compared with controls; this effect persisted vs placebo controls. Furthermore, the association of treatment with reduced anxiety symptoms of omega-3 PUFA were significantly higher in subgroups with specific clinical diagnoses than in subgroups without clinical conditions.

The competition between EPA and DHA during digestion and absorption and the fact that DHA appears to ‘block’ the therapeutic actions of EPA can therefore be an issue if we are looking to optimise the benefits associated with EPA (Martins 2009; Bloch & Qawasmi et al, 2011; Sublette et al, 2011). High dose, high concentration and high ratio EPA supplements increase the effectiveness in depression studies, and pure EPA-only is optimal. Depression is also a condition with an inflammatory basis, so this is likely another significant reason for EPA being the key player – its antagonistic relationship with the inflammatory omega-3 AA (arachidonic acid) is very effective at reducing inflammation.

The DART study, published in 1989, was the first randomized trial to show the efficacy of fish oil on CAD.37 In the trial, 2033 post-MI patients were randomized to receive 3 types of diets: a diet that was either high in cereal fiber, polyunsaturated fat, or fish oil. The fish oil group consumed 200 to 400 g/wk of fatty fish (2 portions of fish per week) or 0.5 g/d of Maxepa fish oil supplement. At 2 years, the primary end point of all-cause mortality was reduced by 29% in the fish oil group, whereas no improvement was seen in the other dietary advice groups.


The three types of omega-3s are APA, EPA and DHA. The first is a medium-chain fatty acid and must be converted into EPA before being synthesized by the body, and only about 1 percent of the APA consumed is able to be converted. EPA and DHA are already in a form ready to be synthesized (and are the subject of most scientific research regarding omega-3s).
For dry eye: Fish oil supplements providing EPA 360-1680 mg and DHA 240-560 mg have been used for 4-12 weeks. Some people used the specific product (PRN Dry Eye Omega Benefits softgels). A specific combination product containing EPA 450 mg, DHA 300 mg, and flaxseed oil 1000 mg (TheraTears Nutrition, Advanced Nutrition Research; Caruso’s Natural Health UltraMAX fish oil, Sydney, New South Wales, Australia) has been used once daily for 90 days.
For dry eye: Fish oil supplements providing EPA 360-1680 mg and DHA 240-560 mg have been used for 4-12 weeks. Some people used the specific product (PRN Dry Eye Omega Benefits softgels). A specific combination product containing EPA 450 mg, DHA 300 mg, and flaxseed oil 1000 mg (TheraTears Nutrition, Advanced Nutrition Research) has been used once daily for 90 days.
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)
Further, according to subgroup results based on the presence of specific clinical diagnoses or not, the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly higher in subgroups with specific clinical diagnoses than in subgroups without clinical conditions. Among 6 studies included in a meta-analysis of the effect of omega-3 PUFAs on depressive symptoms, the analysis showed a nearly null effect of omega-3 PUFAs on depressive symptoms in healthy participants.73 Although the reason for the null effect of omega-3 PUFAs on anxiety and depressive symptoms remains unclear, certain pathophysiological conditions might be required for omega-3 PUFAs to exert an association of treatment with reduced anxiety symptoms.
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.
Omega-3s have been studied in various mood disorders, such as postpartum depression, with some promising results. In bipolar disorder (manic depression), the omega-3s may be most effective for the depressed phase rather than the manic phase of the illness. The omega-3s have also been proposed to alleviate or prevent other psychiatric conditions including schizophrenia, borderline personality disorder, obsessive compulsive disorder, and attention deficit disorder. However, there is still not enough evidence to recommend the omega-3s in these conditions.
They also found that taking more long-chain omega 3 fats (including EPA and DHA), primarily through supplements probably makes little or no difference to risk of cardiovascular events, coronary heart deaths, coronary heart disease events, stroke or heart irregularities. Long-chain omega 3 fats probably did reduce some blood fats, triglycerides and HDL cholesterol. Reducing triglycerides is likely to be protective of heart diseases, but reducing HDL has the opposite effect. The researchers collected information on harms from the studies, but information on bleeding and blood clots was very limited. 
Heart disease. 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.
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