Omega-3 FA most likely reduce serum triglyceride levels by modulating very-low-density lipoprotein (VLDL) and chylomicron metabolism. There is a consistent finding in the literature that the end effect of fish oil is decreased hepatic secretion of VLDL17—the major endogenous source of triglycerides. This effect occurs most likely through multiple mechanisms, including: (1) decreased synthesis of triglycerides because these omega-3 FA may not be the preferred substrates of the enzyme diacylglycerol O-acyltransferase,18 or they may interact with nuclear transcription factors that control lipogenesis19; cellular metabolism consequently shifts toward a decrease in triglyceride synthesis and an increase in FA oxidation; and (2) the promotion of apolipoprotein B degradation in the liver through the stimulation of an autophagic process.20 This means that fewer VLDL particles can be assembled and secreted. Fish oil may also accelerate VLDL and chylomicron clearance21 by inducing lipoprotein lipase activity.22
The European Journal of Neuroscience published a study in 2013 showing that fish oil reversed all anxiety-like and depression-like behavior changes induced in rats. This is an interesting study because it stresses the importance of supplementing with fish oil at “critical periods of brain development.” (10) This is exactly why I recommend giving fish oil to our kids from early on to help them so they won’t develop anxiety or depression later in life.

We've been taking Omega 3 supplement as recommended anti inflammatory and did helps a lot in keeping our arthritis(RA) at bay. We had been discussing with our doctors on what is the recommended dose of Omega 3 that we can take. We have been taking these gel caps since - http://visiongroupcorp.com/omega3.html. Very informative article most specially the discussions on the effect of both EPA and DHA.

Your body can convert some ALA into EPA and then DHA, but not enough to meet all your body’s needs but the best way to assure you are getting enough heart healthy fats is to eat foods high in the omega 3 fats, and if you can’t or don’t get enough of these necessary fats in your diet, you might consider taking an omega 3 supplement to boost these needed fats. More on this later.


Corresponding Author: Yutaka J. Matsuoka, MD, PhD, Division of Health Care Research, Center for Public Health Sciences, National Cancer Center Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan (yumatsuo@ncc.go.jp); Kuan-Pin Su, MD, PhD, China Medical University Hospital, No. 2, Yude Road, North District, Taichung City, Taiwan 404 (cobolsu@gmail.com).
The ultimate goal of using omega-3 fatty acids is the reduction of cellular inflammation. Since eicosanoids derived from arachidonic acid (AA), an omega-6 fatty acid, are the primary mediators of cellular inflammation, EPA becomes the most important of the omega-3 fatty acids to reduce cellular inflammation for a number of reasons. First, EPA is an inhibitor of the enzyme delta-5-desaturase (D5D) that produces AA (1). The more EPA you have in the diet, the less AA you produce. This essentially chokes off the supply of AA necessary for the production of pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes, etc.). DHA is not an inhibitor of this enzyme because it can’t fit into the active catalytic site of the enzyme due to its larger spatial size. As an additional insurance policy, EPA also competes with AA for the enzyme phospholipase A2 necessary to release AA from the membrane phospholipids (where it is stored). Inhibition of this enzyme is the mechanism of action used by corticosteroids. If you have adequate levels of EPA to compete with AA (i.e. a low AA/EPA ratio), you can realize many of the benefits of corticosteroids but without their side effects. That’s because if you don’t release AA from the cell membrane then you can’t make inflammatory eicosanoids. Because of its increased spatial dimensions, DHA is not a good competitor of phospholipase A2 relative to EPA. On the other hand, EPA and AA are very similar spatially so they are in constant competition for the phospholipase A2 enzyme just as both fatty acids are in constant competition for the delta-5 desaturase enzyme. This is why measuring the AA/EPA ratio is such a powerful predictor of the state of cellular inflammation in your body.

Egert, S., Somoza, V., Kannenberg, F., Fobker, M., Krome, K., Erbersdobler, H. F., and Wahrburg, U. Influence of three rapeseed oil-rich diets, fortified with alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on the composition and oxidizability of low-density lipoproteins: results of a controlled study in healthy volunteers. Eur J Clin Nutr 2007;61(3):314-325. View abstract.

Many people focus on the dosage of fish oil to take, like 1000 mg or 1200 mg, but it is the omega-3s that matter. This is where the benefits of fish oil are found. The two types of omega-3 fatty acids to focus on are EPA and DHA. These omega-3s are naturally found in oily fish like salmon, halibut, sardines and anchovies, and are the very reason why fish oil supplements have received such high praise.
People who eat seafood rich in EPA and DHA at least once a week are less likely to die of heart disease, according to the National Center for Complementary and Alternative Medicine. The fatty acids may also be helpful in relieving symptoms of rheumatoid arthritis. Fish oil has been rated as "Effective" by MedlinePlus for lowering high triglycerides, which can be a major risk factor for heart disease. Fish oil has been rated as "Likely Effective" for keeping healthy hearts free of disease. Although eating baked or broiled fish can reduce the risk of heart disease, fried fish or fish sandwiches not only cancel out any heart-healthy benefits, but may also contribute to heart disease, MedlinePlus notes.
Jump up ^ Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J (July 2006). "n−3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review". The American Journal of Clinical Nutrition. 84 (1): 5–17. doi:10.1093/ajcn/84.1.5. PMID 16825676.

Sorgi, P. J., Hallowell, E. M., Hutchins, H. L. & Sears, B. (2007, January 17). Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder. Nutrition Journal 6(16). Retrieved from http://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-6-16
Omega-3 FA most likely reduce serum triglyceride levels by modulating very-low-density lipoprotein (VLDL) and chylomicron metabolism. There is a consistent finding in the literature that the end effect of fish oil is decreased hepatic secretion of VLDL17—the major endogenous source of triglycerides. This effect occurs most likely through multiple mechanisms, including: (1) decreased synthesis of triglycerides because these omega-3 FA may not be the preferred substrates of the enzyme diacylglycerol O-acyltransferase,18 or they may interact with nuclear transcription factors that control lipogenesis19; cellular metabolism consequently shifts toward a decrease in triglyceride synthesis and an increase in FA oxidation; and (2) the promotion of apolipoprotein B degradation in the liver through the stimulation of an autophagic process.20 This means that fewer VLDL particles can be assembled and secreted. Fish oil may also accelerate VLDL and chylomicron clearance21 by inducing lipoprotein lipase activity.22
Gerber, J. G., Kitch, D. W., Fichtenbaum, C. J., Zackin, R. A., Charles, S., Hogg, E., Acosta, E. P., Connick, E., Wohl, D., Kojic, E. M., Benson, C. A., and Aberg, J. A. Fish oil and fenofibrate for the treatment of hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: results of ACTG A5186. J.Acquir.Immune.Defic.Syndr. 4-1-2008;47(4):459-466. View abstract.

Grigg, L. E., Kay, T. W., Valentine, P. A., Larkins, R., Flower, D. J., Manolas, E. G., O'Dea, K., Sinclair, A. J., Hopper, J. L., and Hunt, D. Determinants of restenosis and lack of effect of dietary supplementation with eicosapentaenoic acid on the incidence of coronary artery restenosis after angioplasty. J Am Coll Cardiol. 3-1-1989;13(3):665-672. View abstract.


It is also believed that women who do not have a sufficient intake of EPA and DHA in their diet suffer from depression after childbirth, as there is a transfer of some amount of brain mass from the mother to the child in the last stages of pregnancy. Thus, it is very beneficial to consume fish oil either by eating fish or taking fish oil supplements, tablets, capsules, or pills during pregnancy for the overall development of the child and the well-being of the mother. However, it should be noted that fish oil obtained from the liver of the fish, example – cod liver oil, should not be consumed during pregnancy as cod liver oil is high in retinol and vitamin A, which are usually known to cause birth defects.
It’s no surprise that fish — particularly cold-water fatty fish like salmon, mackerel, and anchovies — are rich in omega-3s. It’s called fish oil for a reason, right? Mackerel, for instance, may have more than 3300 mg of omega-3 per serving — that’s more than 6 times the recommended per day dose for healthy adults. Not a huge fish connoisseur? Try some of the quick, simple recipes in Cooking with Fish Like a Pro, an accessible collection of fish recipes to suit every palate.
Various scales were used in these studies to evaluate the target outcome of anxiety symptoms: the Yale-Brown Obsessive-Compulsive Scale, Profile of Mood States, State-Trait Anxiety Inventory, Hamilton Anxiety Rating Scale, Generalized Anxiety Disorder questionnaire, Depression, Anxiety, and Stress Scales, Clinician-Administered Posttraumatic Stress Disorder Scale, Beck Anxiety Inventory, visual analog scale of anxiety, Impact of Event Scale–Revised, Conners score anxiety subscale, Neuropsychiatric Inventory, test anxiety severity, Hospital Anxiety and Depression Scale anxiety subscale, and Child Behavior Checklist anxiety subscale. The psychiatric and physical health conditions of the recruited participants also varied widely: general population without specific clinical conditions,36,47,51,55,60 participants with acute myocardial infarction,35 borderline personality disorder,2 mild to severe depression,59 obsessive-compulsive disorder,33 severe accidental injury,49 participants who were traumatized by disaster,54 participants with substance abuse disorder,34 women with premenstrual syndrome,56 children with attention-deficit/hyperactivity disorder,48,53 Alzheimer disease,58 generally healthy undergraduate college students but with test anxiety,61 Parkinson disease,52 and participants with Tourette syndrome.57 Sixteen studies compared the effect of omega-3 PUFA treatment with that of the placebo33,34,36,47-49,51-53,55-61; the other 3 studies were non–placebo controlled trials.35,50,54 The mean (SD) Jadad score of the recruited studies was 3.8 (1.0) (eTable in the Supplement).
There have been conflicting results reported about EPA and DHA and their use with regard to major coronary events and their use after myocardial infarction. EPA+DHA has been associated with a reduced risk of recurrent coronary artery events and sudden cardiac death after an acute myocardial infarction (RR, 0.47; 95% CI: 0.219–0.995) and a reduction in heart failure events (adjusted HR: 0.92; 99% CI: 0.849–0.999) (34–36). A study using EPA supplementation in combination with a statin, compared with statin therapy alone, found that, after 5 y, the patients in the EPA group (n = 262) who had a history of coronary artery disease had a 19% relative reduction in major coronary events (P = 0.011). However, in patients with no history of coronary artery disease (n = 104), major coronary events were reduced by 18%, but this finding was not significant (37). This Japanese population already has a high relative intake of fish compared with other nations, and, thus, these data suggest that supplementation has cardiovascular benefits in those who already have sufficient baseline EPA+DHA levels. Another study compared patients with impaired glucose metabolism (n = 4565) with normoglycemic patients (n = 14,080). Impaired glucose metabolism patients had a significantly higher coronary artery disease HR (1.71 in the non-EPA group and 1.63 in the EPA group). The primary endpoint was any major coronary event including sudden cardiac death, myocardial infarction, and other nonfatal events. Treatment of impaired glucose metabolism patients with EPA showed a significantly lower major coronary event HR of 0.78 compared with the non–EPA-treated impaired glucose metabolism patients (95% CI: 0.60–0.998; P = 0.048), which demonstrates that EPA significantly suppresses major coronary events (38). When looking at the use of EPA+DHA and cardiovascular events after myocardial infarction, of 4837 patients, a major cardiovascular event occurred in 671 patients (13.9%) (39). A post hoc analysis of the data from these diabetic patients showed that rates of fatal coronary heart disease and arrhythmia-related events were lower among patients in the EPA+DHA group than among the placebo group (HR for fatal coronary heart disease: 0.51; 95% CI: 0.27–0.97; HR for arrhythmia-related events: 0.51; 95% CI: 0.24–1.11, not statistically significant) (39). Another study found that there was no significant difference in sudden cardiac death or total mortality between an EPA+DHA supplementation group and a control group in those patients treated after myocardial infarction (40). Although these last 2 studies appear to be negative in their results, it is possible that the more aggressive treatment with medications in these more recent studies could attribute to this.

Of great clinical importance, EPA and DHA supplementation during pregnancy has been associated with longer gestation and increased concentrations of EPA and DHA in fetal tissues (21). In 2005, preterm births accounted for 12.7% of all births in the United States, increasing the likelihood of health complications (22). Carrying a baby to term is very important because prematurity is the cause of various infant diseases and can lead to death; preterm delivery is an underlying factor for 85% of the deaths of normally formed infants (23). One mechanism by which EPA and DHA may decrease the incidence of preterm birth is by decreasing prostaglandin E2 and prostaglandin F2α production, therefore reducing inflammation within the uterus, which could be associated with preterm labor (21, 24). Several studies investigated EPA and DHA intake during pregnancy and its correlation with longer gestation. Conclusions were that EPA+DHA supplementation during pregnancy delayed the onset of delivery to term or closer to term; however, supplementation did not delay delivery to the point of being post-term (20, 23, 25). This supports the evidence that EPA+DHA ingestion leads to optimal pregnancy length. EPA+DHA supplementation reduced the HR of preterm delivery by 44% (95% CI: 14–64%) in those who consumed relatively low amounts of fish and 39% (95% CI: 16–56%) in those who consumed medium amounts of fish; however, a level of statistical significance was not met (P = 0.10) (23). The Judge et al. (20) study found that women who had DHA supplementation from gestation week 24 until full-term delivery carried their infants significantly (P = 0.019) longer than did the women in the placebo group. One study found that DHA supplementation after gestation week 21 led to fewer preterm births (<34 wk of gestation) in the DHA group compared with the control group (1.09% vs. 2.25%; adjusted RR, 0.49; 95% CI: 0.25–0.94; P = 0.03). Also, mean birth weight was 68 g heavier (95% CI: 23–114 g; P = 0.003) and fewer infants were of low birth weight in the DHA group compared with the control group (3.41% vs. 5.27%; adjusted RR, 0.65; 95% CI: 0.44–0.96; P = 0.03) (25).
Various scales were used in these studies to evaluate the target outcome of anxiety symptoms: the Yale-Brown Obsessive-Compulsive Scale, Profile of Mood States, State-Trait Anxiety Inventory, Hamilton Anxiety Rating Scale, Generalized Anxiety Disorder questionnaire, Depression, Anxiety, and Stress Scales, Clinician-Administered Posttraumatic Stress Disorder Scale, Beck Anxiety Inventory, visual analog scale of anxiety, Impact of Event Scale–Revised, Conners score anxiety subscale, Neuropsychiatric Inventory, test anxiety severity, Hospital Anxiety and Depression Scale anxiety subscale, and Child Behavior Checklist anxiety subscale. The psychiatric and physical health conditions of the recruited participants also varied widely: general population without specific clinical conditions,36,47,51,55,60 participants with acute myocardial infarction,35 borderline personality disorder,2 mild to severe depression,59 obsessive-compulsive disorder,33 severe accidental injury,49 participants who were traumatized by disaster,54 participants with substance abuse disorder,34 women with premenstrual syndrome,56 children with attention-deficit/hyperactivity disorder,48,53 Alzheimer disease,58 generally healthy undergraduate college students but with test anxiety,61 Parkinson disease,52 and participants with Tourette syndrome.57 Sixteen studies compared the effect of omega-3 PUFA treatment with that of the placebo33,34,36,47-49,51-53,55-61; the other 3 studies were non–placebo controlled trials.35,50,54 The mean (SD) Jadad score of the recruited studies was 3.8 (1.0) (eTable in the Supplement).

One meta-analysis concluded that omega−3 fatty acid supplementation demonstrated a modest effect for improving ADHD symptoms.[39] 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",[40] while a different review found "insufficient evidence to draw any conclusion about the use of PUFAs for children with specific learning disorders".[41] 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.[42]

Heterogeneity was examined using the Q statistic and the corresponding P values,41 and the I2 statistic was used to evaluate the proportion of variation resulting from among-study differences. Any possible publication bias was detected with both funnel plots and Egger regression in the main part of the meta-analysis.42 By using Duval and Tweedie’s trim-and-fill test, we adjusted the effect sizes for potential publication bias if there was evidence of publication bias detected by this test in the Comprehensive Meta-analysis statistical software, version 3.43 To investigate the potential confounding effects of any outliers within the recruited studies, sensitivity testing was conducted with the 1-study removal method to detect the potential outliers.44

Capanni, M., Calella, F., Biagini, M. R., Genise, S., Raimondi, L., Bedogni, G., Svegliati-Baroni, G., Sofi, F., Milani, S., Abbate, R., Surrenti, C., and Casini, A. Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment.Pharmacol.Ther. 4-15-2006;23(8):1143-1151. View abstract.
After a large number of lab studies found that omega-3 fatty acids may be effective in slowing or reversing the growth of hormonal cancers, namely prostate and breast cancer cells, animal and human epidemiological studies have been conducted to see whether this effect occurred in real-life scenarios. The evidence is somewhat conflicting in some reports, but there is some evidence to suggest breast and prostate cancers may be potentially slowed (or the risk reduced) in people who eat a lot of oily fish and possibly those who supplement with omega-3. (66, 67, 68)
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.
Omega AD study, Irving et al. (54) Double-blind, placebo-controlled, randomized 1741 DHA (1.7 g/d) and EPA (0.6 g/d) for 6 mo, then for all subjects (supplementation group and placebo group) Supplementation was associated with positive weight gain and appetite in supplementation group at 6 mo, but not in the placebo group, and for both groups at 12 mo
From the time of your pregnancy through your child's later life, omega-3 fats DHA and EPA have a radically important role in her brain health and other functions. I recommend supplementing with krill oil before and during pregnancy, and while you breastfeed. Babies receive DHA through your breast milk, so continuing breastfeeding through the first year will give your child a great headstart for health and success.
EPA, which is eicosapentaenoic acid, and DHA, which is docosahexaenoic acid, are two types of omega-3 fatty acids that are most commonly found in seafood. These polyunsaturated fats are known to have preventative health benefits and have been studied for their role in treating certain chronic conditions. In addition to dietary sources, certain supplements such as fish oil, are also rich in EPA and DHA.
Metagenics offers a wide range of educational opportunities including webinars, group meetings, and seminars as part of our commitment to continuing functional medicine education. Our goal is to give our practitioners further insight to help address their patients’ unique health needs for a higher level of personalized, lifetime wellness care. We have been sharing this ever-growing body of nutritional and lifestyle research for over 25 years.
Although results from studies regarding the disease processes of AD seem to be promising, there are conflicting data regarding the use of omega-3 fatty acids in terms of cognitive function. Neuropsychiatric symptoms accompany AD from early stages and tend to increase with the progression of the disease (55). An analysis of 174 patients randomized to a placebo group or to a group with mild to moderate AD (MMSE score ≥15) treated with daily DHA (1.7 g) and EPA (0.6 g) found that at 6 mo, the decline in cognitive function did not differ between the groups. Yet, in a subgroup with very mild cognitive dysfunction (n = 32, MMSE score >27), they observed a significant reduction in the MMSE decline rate in the DHA+EPA-supplemented group compared with the placebo group (47). Another study that looked at DHA supplementation in individuals with mild to moderate AD used the Alzheimer's Disease Assessment Scale–Cognitive subscale, which evaluates cognitive function on a 70-point scale in terms of memory, attention, language, orientation, and praxis. This study found that DHA supplementation had no beneficial effect on cognition during the 18-mo trial period for the DHA group vs. placebo (56).
While fish oil has plenty of beneficial qualities, there is a lot of hype around its possible applications, and not all of them are accurate, so be wary when reading literature on this useful oil. Fish oil manufacturers have attempted to market it as a remedy for almost anything. We suggest that readers educate themselves fully before making an informed decision, rather than getting affected by both negative and positive propaganda about the beneficial applications of fish oil.
A 2008 meta-study by the Canadian Medical Association Journal found fish oil supplementation did not demonstrate any preventative benefit to cardiac patients with ventricular arrhythmias.[36] A 2012 meta-analysis published in the Journal of the American Medical Association, covering 20 studies and 68,680 patients, found that Omega-3 Fatty Acid supplementation did not reduce the chance of death, cardiac death, heart attack or stroke.[37]

3. DHA affects your child's learning and behavior. Do you want to maximize your child's intellectual potential? A study published in Plos One in June 20138 linked low levels of DHA with poorer reading, and memory and behavioral problems in healthy school-age children. In another study published in the American Journal of Clinical Nutrition in August 2013,9 children who consumed an omega-3 fat supplement as infants scored higher on rule learning, vocabulary, and intelligent testing at ages 3 to 5.
Like I mentioned earlier, there are no official guidelines for the proper amount of omega-3s you should consume each day. However, most organization agree that at least 2 servings of a 3.5 ounce serving of fish (preferably oily) each week is a good start. That equals about 500 milligrams of EPA/DHA each day. For treating disease, up to 4,000 milligrams per day is recommended by various studies, although values do vary. (96) It’s why a pescatarian diet can have such health protective effects.
Most brands of fish oil have been proven safe, free of detectable traces of mercury, and do not contain unsafe levels of PCBs (polychlorinated biphenyls), a toxin and pollutant believed to pose various health threats. To avoid contaminants in an unrefined supplement, it's best to choose a fish-oil supplement made from small, oily fish like anchovy, sardines or menhaden.
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Studies don’t seem to mention blood content of omega 6, or saturated fats–the overall balnce of triglycerides, so they seem to have been done in a “vacuum”. At least, the data is so presented. Also, high protein may be an issue not being tested, but hovering in the background of the participants’ diets. Many “miracle cures”, and I wish it wasnt so, are being not only “debunked”, but “proven” outright dangerous.


Damage to the kidneys caused the drug cyclosporine. Cyclosporine is a medication that reduces the chance of organ rejection after an organ transplant. Taking fish oil seems to prevent kidney damage in people taking this drug. Fish oil also seems to improve kidney function during the recovery phase following the rejection of a transplanted organ in people taking cyclosporine.
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