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.
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.
Research conducted by Professor Peter Howe at the University of South Australia has shown that fish oil improves the efficacy of exercise in attempts to reduce weight. Volunteers who were given fish oil in their diet showed greater weight loss as compared to those who did not regularly consume it. Fish oil contains omega-3 fatty acids, which help to promote the weight loss, so a combination of physical workout and intake of this oil helps in reducing body fat significantly faster.
Australian researchers published results of a study examining the effects of fish oil on weight loss in combination with diet and exercise in the May 2007 issue of American Journal of Clinical Nutrition. The results show that a combination of fish oil supplements and regular exercise can reduce body fat while also improving heart and metabolic health. The fish supplementation group had lowered triglycerides, increased HDL cholesterol and improved blood flow. Overall, adding fish oil to a current exercise program (and a overall healthy lifestyle) looks like it can decrease body fat as well as cardiovascular disease risk. (32)
A group out of India conducted a study published in Cancer Chemotherapy and Pharmacology based on the premise that “fish oil rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anti-cancer drugs.” The study found that using 5-Fluorouracil (5-FU) to treat colorectal cancer along with fish oil increased the survival rate in carcinogen-treated animals. Researchers also found that the fish oil ameliorated hematologic depression, along with gastrointestinal, hepatic and renal toxicity caused by the 5-FU. (15)
What's more, ALA is just a precursor to EPA and DHA. You need certain enzymes to elongate and desaturate ALA so it can become long-chained omega-3s. Unfortunately, this does not work in some people, particularly those who are deficient in certain vitamins and minerals, leading to very low conversion rates – only 1 percent of ALA is converted to EPA/DHA. In some, the conversion can even dip as low as 0.1 to 0.5 percent!
Typical Western diets provide ratios of between 10:1 and 30:1 (i.e., dramatically higher levels of omega−6 than omega−3). The ratios of omega−6 to omega−3 fatty acids in some common vegetable oils are: canola 2:1, hemp 2–3:1, soybean 7:1, olive 3–13:1, sunflower (no omega−3), flax 1:3, cottonseed (almost no omega−3), peanut (no omega−3), grapeseed oil (almost no omega−3) and corn oil 46:1.
Belalcazar, L. M., Reboussin, D. M., Haffner, S. M., Reeves, R. S., Schwenke, D. C., Hoogeveen, R. C., Pi-Sunyer, F. X., and Ballantyne, C. M. Marine omega-3 fatty acid intake: associations with cardiometabolic risk and response to weight loss intervention in the Look AHEAD (Action for Health in Diabetes) study. Diabetes Care 2010;33(1):197-199. View abstract.
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
Cochrane lead author, Dr. Lee Hooper from the University of East Anglia, UK said: “We can be confident in the findings of this review which go against the popular belief that long-chain omega 3 supplements protect the heart. This large systematic review included information from many thousands of people over long periods. Despite all this information, we don’t see protective effects.
Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential nutrients that have potential preventive and therapeutic effects on psychiatric disorders, such as anxiety and depression,7-15 as well as comorbid depression and anxiety in physically ill patients,16-19 patients with coronary heart disease,20,21 and pregnant women.22,23 Preclinical data support the effectiveness of omega-3 PUFAs as treatment for anxiety disorders. Song et al24,25 found that an EPA-rich diet could reduce the development of anxiety-like behaviors in rats as well as normalize dopamine levels in the ventral striatum. In addition, Yamada et al26 showed that a high dietary omega-3 to omega-6 PUFA ratio reduced contextual fear behaviors in mice and that these effects were abolished by a cannabinoid CB1 receptor antagonist.
To improve the health of your heart, brain, skin, hair, body and much, much more, consider adding fish oil to your daily supplement regime or consume wild-caught fish daily. If you’re adverse to fish oil pills, make sure to get at least two servings of fatty fish each week to fulfill your omega-3 needs and provide your body with fish oil benefits. This is a recommendation also encouraged by the American Heart Association. (38)
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.
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.
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.
All people need to consume omega-3 fats regularly. The recommended daily intake for adults is 1.6 grams for males and 1.1 grams for females, according to the National Institutes of Health. The omega-3 family encompasses numerous fatty acids, but three primary forms are eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid. The first two forms primarily occur in fish, such as salmon, mackerel, and tuna. The third can be found in plant oils, including flaxseed, soybean, walnut, and canola oils.
56. Davidson MH, Stein EA, Bays HE, et al. COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. 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;29:1354–1367. [PubMed]
Agency for Healthcare Research and Quality. Effects of Omega-3 Fatty Acids on Lipids and Glycemic Control in Type II Diabetes and the Metabolic Syndrome and on Inflammatory Bowel Disease, Rheumatoid Arthritis, Renal Disease, Systemic Lupus Erythematosus, and Osteoporosis. AHRQ Publication No. 04-E012-1; 2004. Available at: https://archive.ahrq.gov/downloads/pub/evidence/pdf/o3lipid/o3lipid.pdf. (Accessed February 7, 2017).
Studies have also found that omega-3 fatty acids from fish oil are associated with improved survival rates for heart attack victims. A study published in the medical journal Circulation found that people who took a high dose of fish oil each for six months following the occurrence of a heart attack actually improved their hearts’ overall functioning and also reduced biomarkers of systemic inflammation. (20)
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.
Interestingly, the results are also consistent with our recent findings that somatic anxiety is associated with omega-3 PUFA deficits and the genetic risks of PUFA metabolic enzyme cytosolic phospholipase A2 in major depressive disorder62,63 and interferon α–induced neuropsychiatric syndrome.63,64 Brain membranes contain a high proportion of omega-3 PUFAs and their derivatives and most animal and human studies suggest that a lack of omega-3 PUFAs in the brain might induce various behavioral and neuropsychiatric disorders,16,65-70 including anxiety-related behaviors.12,18,19,32,49,71 Emerging evidence suggests that omega-3 PUFAs interfere with and possibly control several neurobiological processes, such as neurotransmitter systems, neuroplasticity, and inflammation,12,72 which is postulated to be the mechanism underlying anxiety and depression.
Two psychiatrists (P.-T.T. and T.-Y.C.) separately performed a systematic literature search of the PubMed, Embase, ProQuest, ScienceDirect, Cochrane Library, ClinicalKey, Web of Science, and ClinicalTrials.gov databases to March 4, 2018. Because we presumed some clinical trials would use investigating scales for some other mood symptoms but also contain symptoms of anxiety, we tried to use some nonspecific medical subject heading terms to include those clinical trials. Therefore, we used the following keywords: omega-3, eicosapentaenoic acid, EPA, DHA, or docosahexaenoic acid; and anxiety, anxiety disorder, generalized anxiety disorder, agoraphobia, panic disorder, or posttraumatic stress disorder. After removing duplicate studies, the same 2 authors screened the search results according to the title and abstract to evaluate eligibility. List of potentially relevant studies were generated for a full-text review. Any inconsistencies were discussed with a third author to achieve final consensus. To expand the list of potentially eligible articles, we performed a manual search of the reference lists of review articles in this area.12,38,39
Under these conditions, it may make sense to try fish oil even at higher doses than what I recommended. There is some evidence that krill oil will get the omega-3 fatty acids better into the brain in the psychiatric conditions that I listed. And there is some evidence that EPA-rich fish oils are better than DHA-rich fish oils for some of those psychiatric conditions as well. So there’s room to play around with the different possibilities if those things apply to you. But for the average case, limit the fish oil to 250 milligrams of EPA and DHA combined when you take it, but in all cases, go for food first, and go for fish oil only after you have exhausted those possibilities.
Maximizing the benefits you get from omega-3s is highly dependent on how they are absorbed and transported throughout your body. Although these fatty acids are water soluble, they cannot be easily transported into your blood in their free form. Therefore, they need to be packaged in lipoprotein vehicles for them to be better absorbed into your bloodstream.
To evaluate the potential placebo effect, we made further subgrouping analyses. In the subgroups of studies using placebo controls, the omega-3 PUFAs still revealed a consistent positive anxiolytic association with anxiety symptoms. These phenomena meant that the anxiolytic effect of omega-3 PUFAs is probably not entirely owing to the placebo effect.
The GISSI-Heart Failure trial was the first blinded, randomized trial to assess the efficacy of fish oil supplements in patients with heart failure.51 The trial enrolled 7046 subjects with heart failure; 60% with New York Heart Association class II symptoms and 40% with a history of MI. The majority of patients were on a standard heart failure regimen, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, and spironolactone, but only 22% were on a statin. At an average of 3.9 years, the coprimary end points of death and death or hospital admission for cardiovascular reasons were reduced by approximately 9% with fish oil supplementation. Sudden cardiac death, a secondary end-point, showed a statistically nonsignificant relative risk reduction of 7% with fish oil. There was also a reduction in 2 other arrhythmia-related secondary end-points: first hospitalization for ventricular arrhythmia and presumed arrhythmic death.
Due to the anticipated heterogeneity, a random-effects meta-analysis was chosen rather than a fixed-effects meta-analysis because random-effects modeling is more stringent and incorporates an among-study variance in the calculations. The entire meta-analysis procedure was performed on the platform of Comprehensive Meta-analysis statistical software, version 3 (Biostat). Under the preliminary assumption that the scales for anxiety symptoms are heterogeneous among the recruited studies, we chose Hedges g and 95% confidence intervals to combine the effect sizes, in accordance with the manual of the Comprehensive Meta-analysis statistical software, version 3. Regarding the interpretation of effect sizes, we defined Hedges g values 0 or higher as a better association of treatment with reduced anxiety symptoms of omega-3 PUFAs than in controls. For each analysis, a 2-tailed P value less than .05 was considered to indicate statistical significance. When more than 1 anxiety scale was used in a study, we chose the one with the most informative data (ie, mean and standard deviation [SD] before and after treatment). We entered the primary outcome provided in the included articles or obtained from the original authors. As for the variance imputation, we mainly chose the mean and SD before and after treatment. Later, we entered the mean and SD and calculated the effect sizes based on the software option, standardized by post score SD. In the case of studies with 2 active treatment arms, we merged the 2 active treatment arms into 1 group. If these 2 active treatment arms belonged to different subgroups (ie, different PUFA dosage subgroups), we kept them separate. Regarding the numbers of participants counted, we chose intention-to-treat as our priority. If there were insufficient data in the intention to treat group (ie, some studies only provided the changes in anxiety severity in those participants completing trials), we chose instead the per-protocol numbers of participants.
The studies examining the possible benefits of omega-3s continue. Researchers are looking at a range of health outcomes and the impact of a heart healthy diet rich in omega 3 fatty acids on a range of chronic disease. For instance, Dr. Hooper's team is beginning to evaluate the effects that omega-3 fats may have on diabetes, dementia, and some cancers.
"All these diseases have a common genesis in inflammation," says Joseph C. Maroon, MD, professor and vice chairman of the department of neurological surgery at the University of Pittsburgh School of Medicine. Co-author of Fish Oil: The Natural Anti-Inflammatory, Maroon says that in large enough amountsomega-3's reduce the inflammatory process that leads to many chronic conditions.
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)
Many studies documenting the benefits of omega-3s have been conducted with supplemental daily dosages between 2 and 5 grams of EPA and DHA, more than you could get in 2 servings of fish a week. But that doesn't mean eating fish is an exercise in futility. Many studies document its benefits. For example, a 2003 National Eye Institute study showed that 60- to 80-year-olds eating fish more than twice a week were half as likely to develop macular degeneration as those who ate no fish at all.
Fish or seafood allergy: Some people who are allergic to seafood such as fish might also be allergic to fish oil supplements. There is no reliable information showing how likely people with seafood allergy are to have an allergic reaction to fish oil. Until more is known, advise patients allergic to seafood to avoid or use fish oil supplements cautiously.