Fish Oil and Omega-3 and -7 Supplements Review (Including Krill, Algae, Calamari, and Sea Buckthorn)
Posted: 11/10/2018 Last update: 4/9/2019
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Summary: What You Need to Know About Fish Oil and Other Sources of EPA and DHA
- Does it help? Taking a supplement with EPA and DHA from fish oil (or other source, such as krill oil or algae) offers a wide range of potential benefits for mental health, treating inflammatory disease, maintaining muscle, and even cancer prevention (see What It Does). As far as cardiovascular and cognitive (and memory) benefits, eating fish at least twice a week may do you more good than taking a fish oil supplement, although, if you eat fish, be aware that some types can be high in mercury -- see Getting EPA and DHA from Food).
- How much to take? Different amounts of EPA and DHA have been used for different purposes. A general daily dose is about 300 to 500 mg of EPA and DHA, while some treatments (such as for high triglycerides) involve doses as high as 4,000 mg per day (see What to Consider When Using - Dosage). Focus on the amounts of EPA and DHA in a product rather than the amount of total oil, since the concentration of EPA and DHA in oils ranges from about 33% to 85% (see the comparison chart and second column of the table below for amounts of EPA and DHA and concentration levels). If you need a high daily dose, dividing the dose over the course of the day may reduce any unpleasant aftertaste. Taking fish oil with a meal containing other fats may improve absorption.
- Which form? Fish oil in supplements is generally first processed to purify it. This often involves modifying its chemical form. While all forms can help raise EPA and DHA levels and do so equally well if taken with a high-fat meal, if not taken with a high-fat meal the "re-esterified triglyceride" form may be the best absorbed, with up to 76% greater absorption than from the more common "ethyl ester" form (see ConsumerTips -- Forms of Fish Oil). You can check the form of each product in the second column of the table below.
Which brand? Choose a supplement listed as Approved by ConsumerLab.com in the table below because not all supplements contain their listed ingredients and are properly labeled, and some may be contaminated or rancid. If you need a high dose, it may be more convenient to pick one with a higher concentration (see the second column of the table) so that you can take fewer and/or smaller pills or other units. Compare prices to save money (see last column of the table). To save time, see our Top Picks — these are Approved products that offer exceptional value. You'll see that you can get high-quality supplements for just pennies a day. Be mindful of added ingredients, like vitamins, so you don't unintentionally exceed tolerable intake limits for these. Store oils out of heat and light — refrigeration is a good idea (see Keep It Fresh).
- Compare to prescription omega-3 drugs Some supplements have similarly high amounts and concentrations of EPA and DHA as found in prescription omega-3 drugs like Vascepa and Lovaza, but at lower cost. See how they compare.
- Don't overdo it! Although generally safe, high amounts of EPA and DHA may suppress the immune system. It's best to limit daily intake of EPA and DHA from supplements to no more than 2 grams, unless medically indicated. Fish oil may also thin the blood and slightly lower blood pressure. See Concerns and Cautions for more information.
What It Is:
EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are two principal fatty acids found in fish, krill, calamari, and green-lipped mussel. They belong to a family of nutrients known as omega-3 fatty acids. EPA and DHA can also be obtained from other marine sources, such as algae (algal oil). EPA and DHA are polyunsaturated fats ("good" fats, as opposed to saturated fats which are thought to increase the risk of heart disease). The body can only manufacture limited amounts of EPA and DHA from the essential fatty acid, alpha-linolenic acid (ALA) -- found in flaxseed oil, canola oil, soy oil and walnut oil. For more information about ALA see the separate review covering ALA and GLA products.
What It Does:
Heart Attack and Stroke:
The omega-3 fatty acids EPA and DHA have a number of potentially heart-healthy effects, including reducing triglyceride levels, slightly raising levels of HDL ("good") cholesterol, possibly, "thinning" the blood, reducing levels of homocysteine, and reducing blood pressure.
Furthermore, increased consumption of fish oils from fish and high levels of omega-3s in the blood have been associated with reduced risk of cardiovascular disease and related mortality (Mozaffarian, Ann Int Med 2013). The researchers indicated that the high blood levels could be achieved with average daily intake of a moderate amount of fish providing 250 mg to 400 mg of EPA plus DHA (see Getting EPA and DHA from Food, below) and noted that greater intake would not yield much further benefit. In line with this, the American Heart Association recommends consuming at least 1 to 2 fish servings (3.5 oz per serving), of non-fried, preferably oily fish, per week to reduce the risk of cardiac death, coronary heart disease, and ischemic stroke (the most common type of stroke). It notes that mercury contamination is a concern with some types of fatty fish (i.e. swordfish, tuna, etc.), but the "benefits of 1 to 2 servings a week outweigh the risks, especially if a variety of seafood are consumed." (Rimm, Circulation 2018).
Clinical trials since 2010 cast doubt on the cardiovascular benefits of fish oil supplements (Kwak, Arch Intern Med 2012; Hu, Arch Intern Med 2012; Bosch, NEJM 2012; Rizos, JAMA 2012; Chowdhury, BMJ 2012; Roncaglioni, NEJM 2013; AREDS2 Study, JAMA 2014). This was most recently demonstrated in the VITAL study, a 5-year study among a cross-section of older Americans. The VITAL study showed that supplementing with fish oil (460 mg of EPA and 380 mg of DHA daily) did not result in a lower incidence of major cardiovascular events than placebo. However, among people consuming less than 1.5 servings of fish per week, further analysis showed that the fish oil supplementation resulted in 19% and 40% reductions, respectively, in major cardiovascular events and heart attacks. In addition, African Americans had a 77% reduction in heart attacks with fish oil as compared to placebo (Manson, NEJM 2018). It should be noted, however, that a potential beneficial effect of the fish oil may have been masked in these trials by the fact that participants in most studies continued to take other heart medications and many participants already had significant intake of omega-3 fatty acids from fish in their diets.
There is some evidence that taking high dose fish oil may be beneficial during recovery from heart attack. In a study among 360 men and women who, in addition to standard lifestyle counseling and any required medications -- statins, beta- blockers, etc., began taking high-dose, purified fish oil (four one-gram capsules of Lovaza daily -- providing a total of 1,500 mg DHA and 1,860 mg of EPA) or a placebo within one month of hospitalization for a heart attack, the heart's ability to pump blood modestly improved after six months in those who took fish oil, while it worsened slightly in those who took the placebo (Heydari, Circulation 2016). There were no reports of bleeding (a potential concern with high-dose fish oil).
Among people with high triglyceride levels, high-dose fish oil highly concentrated for EPA rather than DHA demonstrated a 25% reduction in the risk of initial heart attack, stroke or other major cardiac event in a five-year study, and a 30% reduction when subsequent cardiac events were counted (see details for Vascepa.)
Taking into consideration the findings of clinical trials, as well as the American Heart Association's latest recommendations (Rimm, Circulation 2018), the bottom line on fish oil for cardiovascular and cerebrovascular disease is that eating non-fried fatty fish twice per week as part of a healthy diet continues to be recommended and may help to reduce the risk of cardiac death, coronary heart disease, and ischemic stroke. [See ConsumerLab's Canned Tuna and Salmon Review for comparisons of EPA and DHA in canned fish.]
However, regarding fish oil supplements:
Consistent with the recommendations above, an analysis of 10 studies published from 1999 to 2014 involving 78,000 people with or at high risk for cardiovascular disease, found no significant association between supplementation with EPA and/or DHA and the occurrence of any major vascular events such as stroke, coronary heart disease, or death from coronary heart disease. It should be noted, however, that the analysis did not take into account the amounts of omega-3s people were already getting from their diets (Aung, JAMA 2018). Similarly, a much larger review of 79 clinical trials published from 1946 to 2017 involving over 112,000 people with or without cardiovascular disease concluded that taking omega-3 supplements does not reduce heart disease, stroke or death (Abdelhamid, Cochrane Database Syst Rev 2018). In addition, a major, long-term (7.4 year) study of adults with type 1 or type 2 diabetes showed no statistically significant cardiovascular benefit from a daily dose of 1 gram of fish oil (containing 460 mg EPA and 380 mg DHA) compared to a placebo (1 gram of olive oil): 8.9% and 9.2% of each group, respectively, experienced a serious vascular event (e.g., heart attack, stroke, transient ischemic attack) (ASCEND Study, NEJM 2018). In a separate arm of the study, patients were given low-dose aspirin (100 mg) or a matching placebo tablet each day, with 8.5% and 9.6% of each group, respectively, experiencing a serious vascular event, indicating a relative benefit with aspirin if not for the fact that it also caused significantly more major bleeding events (ASCEND Study, NEJM 2018). Although the two arms of the study were not compared, it is interesting to consider that the fish oil might have shown modest benefit if compared to the placebo tablet rather than to olive oil which, itself, may have some cardiovascular benefit, (particularly when substituted for saturated fat in the diet).
- There is no reliable evidence that fish oil supplements prevent heart disease in healthy people who are not at risk for heart disease.
- Research does not support fish oil supplementation for preventing heart attacks in people who have heart disease or who are at risk for heart disease unless they have recently had a heart attack. [High-dose fish oil, however, may provide added benefit to low-dose statin therapy in people with stable coronary artery disease (see Alfaddagh study below)].
- Research does not support fish oil supplementation for preventing stroke or atrial fibrillation.
- Fish oil supplementation may help people with heart failure who have reduced left ventricular function.
- Fish oil supplementation, along with a high intake (3 or more servings per week) of fish may reduce the risk of venous thromboembolism; high-dose fish oil can help lower triglyceride levels in people with severe hypertriglyceridemia [including those whose triglycerides remain high while taking a statin (Kim, Clin Ther 2018)], but any other potential cardiovascular benefit of supplementation may be limited to people who do not regularly consume fish in their diets and who are not taking other medications for heart disease.
Use with statins:
A well-controlled 30-month study, however, found that taking a daily fish oil supplement in addition to low-dose statin therapy provided additional benefit in preventing progression of fibrous coronary plaque in people with stable coronary artery disease and well-controlled LDL levels, although there was not a similar benefit among people taking high-dose statins (at least 40 mg of atorvastatin, 20 mg of rosuvastatin, or 80 mg of simvastatin). Among low-dose statin users, fibrous plaque increased 5% among those not receiving fish oil, but did not increase among those receiving fish oil (1,860 mg of EPA and 1,500 mg DHA, from 4 softgels of Lovaza). It also did not increase among those receiving high-dose statins. Musculoskeletal events, infectious diseases, and joint replacement were also significantly lower among those taking the fish oil (Alfaddagh, J Am Heart Ass 2017). A study in South Korea found that high-dose omega-3 supplementation significantly decreased triglyceride levels in those whose triglyceride levels remained elevated while taking a statin. In the study, men and women with high cholesterol and triglyceride levels received 20 mg of rosuvastatin daily. After one month, those whose triglyceride levels remained high (average 263 mg/dL) continued to take rosuvastatin plus either a high daily dose of omega-3s (1,520 mg DHA + 1,840 EPA) or placebo, for two months. Average triglyceride levels decreased by 26% among those who took the omega-3s and by only 2% among those who took the placebo (Kim, Clin Ther 2018).
Blood Sugar Control:
Although fish oil itself has not been shown to improve blood sugar control (and one study of krill oil suggested a negative effect), a small study of healthy overweight/obese adults in Norway showed that consuming five ounces of fatty fish (salmon: 13% fat) five times per week for dinner for 8 weeks significantly improved blood sugar regulation (i.e., smaller increases in blood sugar) measured two hours after a meal, whereas lean fish (cod: 1% fat) did not. Neither type affected fasting blood sugar levels, and a previous study of healthy, young normal-weight adults showed no effect of either on blood sugar control. (Helland, Br J Nutr 2017)
Arthritis and Other Inflammatory Diseases:
Increased intake of the omega-3 fatty acids in fish oil alter the body's production of substances known as prostaglandins, and, consequently, reduce some forms of inflammation. On the basis of this, EPA and DHA have been tried in the treatment of symptoms of rheumatoid arthritis with considerable success (especially in early stages of the disease). Unlike "disease modifying" drugs, however, fish oil probably doesn't slow the progression of the disease. A study of several thousand women in Sweden found that consistent, long-term term intake averaging more than 210 mg per day of omega-3 fatty acids from eating fish was associated with a 52% lower risk of developing rheumatoid arthritis compared with lower intakes over the period of the study -- about 7.5 years (Di Giuseppe, Ann Rheum Dis 2013). This level of intake is equal to at least one serving per week of a fatty fish, such as salmon, or four servings per week of lean fish, such as cod. The study could not adequately assess the impact of supplement use due to limited use of supplements in the study population. An analysis of twenty-two clinical studies also concluded that marine oils can reduce pain associated with rheumatoid arthritis -- but not joint function and not pain associated with osteoarthritis. [An earlier review of laboratory and clinical studies came to a similar conclusion, noting there was insufficient evidence to support the use of fish oil supplements for osteoarthritis (Boe, Am J Orthop (Belle Mead NJ) 2015)]. The results indicated that it may be best to use a product with at least 50% more EPA than DHA, but an ideal dose could not be determined (Senftleber, Nutrients 2017).
Despite the suggestion, above, regarding the importance of EPA, a more recent study found DHA alone to be somewhat helpful. In the study, 38 men and women with rheumatoid arthritis consumed either DHA-enriched food (providing 2,100 mg of DHA per day from 8 grams of microalgae oil) or food enriched with a placebo (8 grams of sunflower oil providing 4,700 mg of linoleic acid -- an omega-6 fatty acid) for ten weeks. It found that consuming the DHA-enriched food caused a significant decrease in the average number of tender and swollen joints (from about 14 to 10), while consuming sunflower oil-enriched food increased the number of tender and swollen joints (from about 10 to 12). However, neither the DHA nor sunflower oil changed biochemical measures of inflammation (ESR and CRP) or patients' self-assessments of their conditions (Dawczynskia, Clin Nutr 2017).
High doses of omega-3 fatty acids (1,860 mg of EPA and 1,500 mg of DHA daily from 4 softgels of Lovaza) taken for one year by adults with coronary artery disease resulted in no worsening of arthritic pain, stiffness, or physical function while all of these worsened in a similar control group not supplemented with fish oil. In contrast to the control group, the group given Lovaza reported more exercise per week (197 minutes vs. 135 minutes) and less joint replacement surgery (0% vs. 3.1%) (Alfaddagh, J Clin Lipidol 2018 -- additional results from this clinical trial are reported above as Alfaddagh, J Amer Hearth Assoc 2017).
Due to its anti-inflammatory effects, fish oil is sometimes promoted for gout, painful joint inflammation caused by elevated blood levels of uric acid. Preliminary research suggests the omega-3 fatty acids EPA and DHA may inhibit the inflammatory response involved in this form of arthritis (Yan, Immunity 2013), and, in men, having higher blood levels of omega-3 fatty acids (>0.46 mmol/L) has been associated with a lower recurrence of acute gout attacks (Abhishek, Ann Rheum Dis 2016). According to an observational study among men and women who had experienced gout, consuming fish rich in omega-3 fatty acids was associated with a protective effect against recurrent attacks, but taking fish oil supplements (fish oil, cod liver oil or omega-3 fatty acid supplements) did not have this effect (Zhang, American College of Rheumatology Annual Meeting 2015). However, people with gout are advised to limit intake of seafood such as sardines, mackerel and herring (common sources of fish oil in supplements) because these fish contain high levels of purines, compounds known to increase uric acid levels in the blood (American College of Rheumatology 2012; Kaneko, Biol Pharm Bull 2014). Purines are generally thought to be eliminated by purification and distillation during the manufacturing of fish oil; however, one small study found substantial amounts of purine in two fish oil supplements (one cod liver oil supplement and one supplement derived from sardines) (Roy, Food Nutr Sci 2013). In short, eating fish low in purines may be helpful for people with gout, but there is no evidence that taking fish oil supplements is helpful.
The anti-inflammatory effects of EPA and DHA have also caused researchers to investigate possible benefits of fish oil for the treatment of menstrual cramps, inflammatory bowel disease (ulcerative colitis and Crohn's disease), lupus, and IgA nephropathy. For each of these conditions, at least one double-blind study has found positive results. A large European study (Hart 2009) showed that people with the highest consumption of DHA (410 mg to 2,000 mg per day) had a 77% reduction in the risk of developing ulcerative colitis over an average period of four years than those consuming the lowest amount (up to 110 mg per day). Conversely, those consuming the most (15 to 35 grams per day) of linoleic acid (an omega-6 fatty acid) were 2.3 times as likely to develop the disease as those consuming the lowest amount (8 grams - 11 grams per day). In a study in which people with stable ulcerative colitis were given 1,000 mg twice daily of EPA for 6 months, 76.7% remained in remission versus 50% of those given placebo. Levels of fecal calprotectin, a marker of mucosal inflammation, were also significantly reduced in 63.3% of those given EPA versus only 13.3% of those given placebo. The EPA was taken as enteric-coated capsules (in order maximize intact delivery into the small intestine), each containing 500 mg of EPA in the free fatty acid form (ALFA, from SLA Pharma AG — apparently not currently sold in the U.S.) (Scaioli, Clin Gastro Hep 2018).
However, in Crohn's disease, a trial of four grams per day of omega-3 fatty acids (50-60% EPA and 15-25% DHA) was ineffective at preventing relapses.
Supplementing with fish oil may help alleviate symptoms of dry eye (an inflammatory condition also known as keratoconjunctivitis sicca), but so might other fatty acids. The largest and longest study to date, conducted by the University of Pennsylvania and the National Eye Institute, involved giving fish oil or olive oil (intended as a placebo) to several hundred men and women with moderate to severe dry eye for 12 months. Symptoms and signs of dry eye improved among patients receiving fish oil treatment (providing 2,000 mg of EPA and 1,000 mg of DHA in the triglyceride form daily) and among those who received a similar amount of olive oil, with the disease severity score improving by about 13 points out of 100, although there was slightly greater improvement in the fish oil group (Asbell, N Engl J Med 2018).
Several shorter-term studies suggest that fish oil supplementation in combination with other fatty acids and/or vitamins may help. This was shown in a study of postmenopausal women in the U.S. with dry eye who took a formula consisting of fish oil with black currant seed oil and vitamins for six months (Sheppard, Cornea 2013). The daily dose given (4 softgels) provided fish oil (126 mg EPA and 99 mg DHA) and 1,570 mg of black currant seed oil (consisting of 240 mg GLA, 196 mg ALA, 710 mg of LA) in a formula (HydroEye) which also provided vitamins A, B6, C, and E. (Note: The amounts of fatty acids in the product during the study are slightly higher than listed on the HydroEye label, but are within reasonable variation.) A large study of young adults found that taking a fish oil capsule twice daily (each capsule providing 180 mg EPA and 120 mg DHA) improved symptoms of dry eye associated with computer use. The fish oil significantly decreased the rate of tear evaporation. The study was conducted in northern India which has a largely vegetarian diet and low consumption of fish (Bhargava, Contact Lens & Ant Eye 2015). A study among 105 men and women diagnosed with mild to moderate dry eye found those who took 4 softgels containing re-esterified (triglyceride form) fish oil (providing a total daily dose of 1,680 mg of EPA and 560 mg of DHA) (PRN Dry Eye Omega Benefits, Physician Recommended Nutriceuticals) daily for 3 months had modest improvements in symptoms of dry eye, such as soreness, grittiness and sensitivity to light, and decreased dryness (as measured by tear osmolarity), compared to those who took a daily dose of linoleic acid (3,136 mg) (Epitropoulos, Cornea 2016). [Note: The label for this product, which is sold in the U.S., indicates that it also contains 1,000 IU of vitamin D3]. Fish oil supplementation has also been found to be helpful for dry eye associated with wearing contact lenses. A study in Australia among 65 adults who experienced dry eye and discomfort from daily use of soft disposable contact lenses found that fish oil capsules (providing 900 mg of EPA and 600 mg of DHA daily) taken for three months significantly reduced self-reported symptoms of dry eye compared to those who took a placebo (olive oil capsules providing 1,500 mg olive oil per day) or capsules containing a combination of fish oil and flaxseed oil (providing 900 mg of EPA, 600 mg of DHA and 900 mg of ALA per day). Fish oil supplementation also decreased certain markers of eye inflammation just as well as anti-inflammatory corticosteroid eye drops but took much longer to have this effect (three months vs. two weeks). The study also found that fish oil eye drops given four times daily (providing a total of 30 mg of EPA and 3 mg of DHA to each eye per day) for three months decreased certain markers of eye inflammation but did not reduce self-reported symptoms of dry eye compared to taking fish oil capsules (Downie, Invest Ophthalmol Vis Sci 2018).
Although giving fish oil to pregnant women has been shown to decrease the incidence of asthma in their offspring, it does not appear to help people who already have asthma. A study in the U.S. among 98 overweight/obese children and young adults ages 12 to 25 with poorly-controlled asthma found a high daily dose of highly-concentrated fish oil (providing 3,180 mg EPA, 822 mg DHA and 101 mg other omega-3 fatty acids -- from Nordic Naturals) for 24 weeks did not improve measures of lung function or decrease exacerbations requiring urgent medical care and/or systemic corticosteroid medication compared to placebo (Lang, Ann Am Thorac Soc 2019). As noted elsewhere, a green-lipped mussel oil product has shown mixed results for asthma.
Supplementing with fish oil (460 mg of EPA and 380 mg of DHA daily) was not shown to reduce the risk of cancer in a major, 5-year study among a cross-section of older Americans in the VITAL study (Manson, NEJM 2018).
Although some evidence has suggested that fish oil may reduce the risk and/or outcome of cancer of the colon/rectum and breast, while evidence with respect to prostate cancer is mixed.
It has been noted that people diagnosed with colorectal cancer who then consume at least 300 mg per day of omega-3 fatty acids from fish and/or fish oil products have a 41% lower risk of dying from the disease than people consuming less than 100 mg per day (Song, Gut 2016).
Eating fish is associated with a lower risk of recurrence, and risk of death, from breast cancer. In women with early stage breast cancer, higher intakes of DHA and EPA from fish (>73 mg/ day DHA+EPA) have been associated with a 25% lower risk of breast cancer recurrence (Patterson, J Nutr 2011). Another study found that over a 15 year period, women with primary in situ or invasive breast cancer who consumed the most tuna and/or other baked/broiled fish had a 25% to 34% reduction in risk of death from all causes, compared to those who reported eating no fish (Khankari, Cancer 2015). A study among postmenopausal women found that current use (but not past use) of fish oil supplements was associated with a 32% reduction in the risk of breast cancer. Risk was greatly reduced for ductal carcinoma of the breast (the most common form of breast cancer), but not lobular carcinoma (Brasky, Canc Epidemiol Biomarkers Prev 2010). It is speculated that the anti-inflammatory property of fish oil may be responsible for an anti-cancer effect because chronic inflammation is associated with cancer initiation and progression.
There is mixed evidence as to whether fish oil and omega-3 fatty acids help prevent prostate cancer. One study found no association between fish consumption and the development of prostate cancer although it found a large reduction in deaths from prostate cancer (Szymanski, Am J Clin Nutr 2010). A 6-year study of men who self-reported taking fish oil supplements also found no association between fish oil use and the development of prostate cancer (Brasky, Nutr Cancer 2011). However, some studies which did not look directly at the consumption of fish or fish oil but at the ratios of fatty acids in blood serum, have found some unexpected associations with prostate cancer: The most recently reported study of this kind found that men with the highest levels of DHA plus EPA and DPA (another omega-3 fatty acid) were 44% and 71%, respectively, more likely to develop low-grade and high-grade prostate cancers compared to men with the lowest levels (Brasky, JNCI 2013). This report included an additional analysis of several other blood-based studies, most of which, but not all, also showed associations between fatty acids in fish oil (particularly DHA) and development of prostate cancer (particularly high-grade cancer). However, whether or not there is a cause-and-effect relationship between intake of fish oils and prostate cancer is still not known.
Fish oil may prevent weight loss during cancer chemotherapy. Although some trials have not shown a benefit, one study (Murphy, Cancer 2011) showed significant benefit. In this study, patients with non-small cell lung cancer took fish oil throughout initial chemotherapy (approximately 10 weeks). During the course of chemotherapy, patients who did not take fish oil experienced an average weight loss of 5 lbs (of which approximately 2.2 lbs. was muscle). Those taking fish oil had, on average, no change in weight despite having lost, on average, 6.3% of their weight over the previous 6 months. In fact, many of those taking fish oil increased their muscle mass — with the greatest increases corresponding to the greatest increases in plasma EPA concentrations. Cancer response rates to the chemotherapy were similar in the two groups. Patients taking the fish oil were given an option consuming either four 1-gram gelatin capsules per day or 7.5 mL of liquid fish oil per day. Both formulations provided 2.2 grams of EPA per day.
However, more recent research suggests that fish oil (from supplements as well as fish) may interfere with chemotherapy. A fatty acid naturally found in fish oil known as 16:4(n-3) and into which other fatty acids, such as EPA, are converted in the body, has been shown in mice to activate white blood cells leading to resistance to chemotherapy. It is, therefore, advised to temporarily avoid fish oil from the day before chemotherapy until the day thereafter, as well as herring and mackerel (which raise 16:4(n-3) levels more than other fish such as salmon and tuna) in the 48 hours surrounding chemotherapy (Daenen, JAMA Oncology 2015).
As explained below, consuming EPA and DHA from the diet (fish) is associated with lower risk of eye disease. However, as taking EPA and DHA as supplements has not shown benefit.
Analyses of dietary intakes taken as part of the Age-Related Eye Disease Study (AREDS) show that participants who reported the highest intake of EPA and DHA were 30% less likely to develop diseases of the retina -- neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA) -- compared to those with the lowest intake (SanGiovanni, Am J Clin Nutr 2009). Decreased risk of developing AMD was also shown in a study of over 30,000 female health professionals: Those consuming at least one serving per week of fish had a 42% reduction in risk of developing AMD compared to those eating less than one serving per month — and the benefit was greatest with canned tuna or dark-meat fish (e.g., mackerel, salmon, sardines, bluefish, and swordfish) (Christen, Arch Opthamol 2011). Analyzed another way, the risk of developing AMD in this study was reduced by 38% and 36%, respectively, among those with the highest intakes from their diets of DHA (230 mg median intake) and EPA (100 mg median intake) compared to those consuming the least amount (median intakes of 60 mg of DHA and 10 mg of EPA). Based on these observations, EPA and DHA were included in the large AREDS2 (Age-Related Eye Disease Study 2) which evaluated a combination of supplements for preventing the progression of AMD. However, the addition of 350 mg DHA and 650 mg EPA to a combination vitamin A (from beta-carotene), vitamin C, vitamin E, zinc, and copper did not offer any additional benefits for slowing progression of AMD (AREDS2 Res Grp, JAMA 2013). See the Review of Eye Health Supplements for more information about AREDS and AREDS2.
A long-term observational study among 3,482 older men and women (average age 67) with type 2 diabetes found that those who reported consuming = 500 mg EPA+ DHA from foods on a weekly basis were 46% less likely to develop sight-threatening diabetic retinopathy during the six-year study than those who consumed less this amount from their diet (Sala-Vila, JAMA Opthamol 2016). Even greater reductions in risk were observed among those who had advanced diabetes or who also had high blood pressure. The researchers noted that this amount of EPA + DHA can be met by consuming the American Heart Association's recommendation of two serving of fish (preferably oily fish) per week.
Many studies have evaluated fish oil for depression. Most have shown a benefit, but some have not. Those that have shown a benefit have tended to use large doses (about 1,500 mg to 3,500 mg per day of omega-3 fatty acids) containing more EPA than DHA and often in populations not already getting much fish oil from their diets.
A study of depressed older women in a nursing home setting showed that after taking high-dose omega-3 fatty acids for eight weeks (2,500 mg once daily consisting of 1,670 mg EPA and 830 mg DHA), 40.9% had a remission of depression compared to 16.7% of those taking placebo (Rondanelli, J Am Col Nutr 2010). This study also found a statistically significant improvement in the self-assessed quality of life and that the fish oil treatment was well tolerated. In another study, the combination of EPA plus the prescription antidepressant fluoxetine (Prozac) was better than either EPA or fluoxetine alone for treating major depression in a short-term (8-week) study of 60 people. However, a study of people with congestive heart failure and depression failed to show any additional benefit from EPA (930 mg) and DHA (750 mg) daily when added to treatment with the prescription antidepressant sertraline (Zoloft) (Carney, JAMA 2009).
The best evidence for omega-3's has been in cases of major and moderate depression, but not mild depression, and one group of researchers has concluded that the antidepressant benefit is strongly dependent upon the EPA content of the supplement. After pooling and reviewing studies using a total of 1,000 mg to 6,000 mg of EPA and DHA, those in which EPA was 60% or more of the total showed a highly significant improvement, whereas those that were less than 60% EPA did not (Martins, Molec Psy 2012). An analysis of eight clinical studies which investigated the effects of taking EPA and/or DHA from fish oil with various anti-depressants (including SSRI drugs such as fluoxetine and sertraline and tricyclic drugs such as amitriptyline) found that, overall, there appeared to be additive benefit, especially from EPA in doses of about 1,000 mg — 2,000 mg per day, concluding, "EPA-rich omega-3 fish oil may be recommended for the adjunctive treatment of major depressive disorder." (Sarris, Am J Psychiatry 2016). Other researchers, however, believe that any benefit is, at best, small to negligible (Bloch, Molec Psy 2012). Nevertheless, further analysis of blood samples from the study by Rondanelli (above) found that elderly depression is characterized by very low levels of omega-3s, in particular EPA, in red blood cell membranes compared to those in healthy individuals and that EPA-rich supplementation restored EPA concentrations to normal values (Rizzo, Nutr J 2012). Interestingly, an earlier study using 1,000 mg, 2,000 mg, or 4,000 mg of EPA found that only the group receiving 1,000 mg had a significantly better outcome than a group receiving placebo (Peet, Arch Gen Psychiatry 2002).
A small study among young adults (average age 20) with mild to moderate depression but not taking antidepressant medication, found that those who took two fish oil capsules (providing a total of 1000 mg EPA and 400 mg of DHA ) daily for 21 days had significantly improved self-reported depression scores compared to those who took a placebo. At the end of the study, 67% of those who took EPA and DHA were no longer clinically depressed, compared to 20% in the placebo group (Ginty, Psychiatry Res 2015). It's worth noting that the amount of EPA given and ratio to DHA are consistent with those suggested by earlier research for treating depression.
A possible explanation for moderate improvements in depression among those who respond to fish oil, is that fish oil increases white matter (myelinated fibers that connect brain cells) in areas of the brain which can be compromised in depression. A small study of 16 acutely depressed adults with major depression found that among the 5 whose depression improved over the 6-week period of taking 4 grams of fish oil daily (OmegaLife-3, Unicity International, Inc., providing 1,600 mg of EPA and 800 mg DHA), 80% had increases in white matter in key brain regions, compared to only 45% of those whose depression did not improve (Chhetry, J Psychiatr Res 2016).
In adolescents and children:
A benefit with fish oil was found in a small study in Slovakia among children and adolescents (average age 15) with depression. The children took fish oil (providing 1,000 mg EPA and 750 mg DHA) or a placebo (linoleic acid from sunflower oil) daily for three months. Most of the children in both groups were continued on SSRI antidepressants (sertraline, fluvoxamine or fluoxetine) throughout the study. Severity of depression symptoms was reduced by an average of 25% in those who took fish oil, compared to only 9% among those who took the placebo. However, the fish oil was not effective in those with mixed depression and anxiety (Trebaticka, Child Adolesc Psych Ment Hlth 2017). It's interesting to note that the fish oil used in this study is roughly in-line with what has been most likely to work in other studies: It provided 1,000 mg of EPA, which was nearly 60% the omega-3 content.
A 10-week study in New York of adolescents (aged 12 to 19 years) with moderate to severe major depressive disorder and not taking antidepressants found that both fish oil and a placebo (soybean and corn oil providing mainly omega-6 fatty acids) were equally effective at decreasing depression severity (about 40% to 50% of the participants in each group improved), although fish oil was not superior to placebo. However, participants reported consuming 8 servings per week of foods high in omega-3 fatty acids, such as fish, i.e., they were generally not lacking intake of omega-3 fatty acids. The daily dose of omega-3s from fish oil (which was 67% EPA and 33% DHA) began at 1,200 mg but, if not effective, was increased during the study, such that ending doses averaged 3,200 to 3,400 mg of omega-3's or placebo (Gabbay, J Clin Psychiatry 2018).
An analysis of blood samples from 1,600 military personnel showed those who committed suicide had, prior to suicide, significantly lower blood levels of DHA than personnel who did not commit suicide (Lewis, J Clin Psychiatry 2011). The population studied was predominantly male and the risk of suicide was found to be 62% greater among men with levels of serum DHA below 1.75% (% of total serum fatty acids) compared to those with higher levels. There was no such relationship with EPA levels. The researchers note that omega-3 fatty acid levels were generally low across the military personnel in the study, much lower than in the general population, and suggested that even greater risk reductions could be possible with higher serum levels of DHA.
Fish oil supplementation was associated with a modest improvement in anxiety symptoms among people with a clinically diagnosed neuropsychiatric or major physical illness, according to an analysis of 19 controlled clinical trials. The association was weaker in people without a diagnosed disease and it was greater when the dose was 2,000 mg or more of EPA and DHA per day and the ratio of EPA/DHA was less than 60% (Su, JAMA Network Open 2018). Among the studies analyzed was one of U.S. medical students that showed, over 12 weeks, that those who received high-dose omega-3 fatty acids (2,496 mg once daily providing 2,085 mg EPA and 348 mg DHA) had a 20% reduction in anxiety symptoms compared to those receiving placebo treatment. Treated students also had a 14% decrease in a marker of inflammation (stimulated IL-6 production) (Kiecolt-Glaser, Brain Behav Immun 2011). The study intentionally used an extremely concentrated fish oil (supplied by OmegaBrite) high in EPA due to earlier evidence that EPA has relatively stronger anti-inflammatory and antidepressant effects than DHA.
Fish oil may slightly blunt some responses to mental stress, according to a study of young men and women given a large amount of fish oil (9 grams daily providing 1,600 mg EPA and 1,100 mg DHA) for eight weeks. When the participants were asked perform math calculations as quickly as possible for 5 minutes (a mental stress test), the mean heart rate increased by 3 beats less per minute after fish oil therapy than when the test had been taken at the beginning of the study, before therapy. The increase in total nervous activity (measured by nerve activity in the leg) was also significantly less after fish oil therapy. A control group, given olive oil instead of fish oil, did not have these reductions in heart rate and nervous activity (Carter, Am J Physiol 2013). However, in another study, fish oil was not found to be helpful. In the study, 90 men and women in Australia with self-reported chronic moderate to high levels of work stress took four capsules daily of predominately EPA fish oil (4 grams daily providing 2,200 mg of EPA and 440 mg of DHA) for three months. Those taking the fish oil did not experience reductions in psychological stress compared to those taking placebo (olive oil) (Bradbury, Front Pharmacol 2017). There was also no improvement in other measures of stress, such as the ratio of cortisol to DHEA and levels of inflammatory cytokines.
Fish oil may help reduce the frequency of migraine headaches, although the evidence is mixed. Based on positive findings of some small, early studies, a placebo-controlled study involving 183 migraine patients was conducted in France in which roughly half the patients received 6 grams of fish oil daily for 16 weeks and the other half received a placebo. During this period, 55% and 45% reductions in migraine attacks occurred, respectively, in the fish oil and placebo groups, indicating a strong placebo effect and a modest fish oil effect. However, the primary end-point of the study was the effect during only the last 4 weeks of treatment and, during that time, there was no statistically significant difference in the number of attacks between the two groups (Pradalier, Cephalalgia 2001). A placebo-controlled study of 60 migraine patients in Brazil found a significant benefit from giving fish oil containing 400 mg EPA plus 350 mg DHA twice-a-day before meals. For ethical reasons, the fish oil and placebo groups also received a low daily dose (10 mg) of amitriptyline (an antidepressant helpful for migraine). During 8 weeks of treatment, 66.7% of those given fish oil achieved an 80% reduction in the number of days of headache while only 33.3% of those given placebo achieved this level of reduction — a statistically significant difference (Soares, Nutr Neurosci, 2017).
Psychosis and Schizophrenia
A year-long study in adolescents and young adults (ages 13 to 25) identified as at risk for developing psychosis or schizophrenia found those who took 700 mg EPA plus 480 DHA from fish oil daily for 3 months were much less likely to develop a psychotic disorder in the nine months following treatment compared to those who had taken a placebo: Among those who took the EPA and DHA, 4.9% developed psychosis compared to 27.5% of those in the placebo group (Amminger, Arch Gen Psychiatry 2010). In a follow-up study approximately 7 years after the original treatment with EPA and DHA, only 10% had developed psychosis, compared to 40% among the placebo group. Those who took the fish oil had significantly higher measures of psychosocial functioning and required less medication than those who took the placebo. The researchers speculated that omega-3 supplementation may be especially effective during adolescence, when the brain is still undergoing significant development (Amminger, Nature Communications 2015).
A study in Poland among first-episode schizophrenia patients (ages 16 to 35) found a small to moderate benefit from taking fish oil in addition to regular medication. During 26 weeks of taking 4 capsules daily of concentrated fish oil (providing a daily total of 1,320 mg of EPA and 880 mg of DHA) rather than a placebo containing olive oil, 69.4% experienced at least a 50% improvement in symptom severity while only 40% of those given the placebo experienced this level of improvement. The greatest improvements were in depressive symptoms. The researchers noted that studies of fish oil in people with chronic (long-term) schizophrenia have shown mixed results, suggesting that fish oil may be more effective at early stages of the disease (Pawelczyk, J Psych Res 2016).
While fish oil supplementation may provide the benefits noted above, an international, placebo-controlled study found no benefit when adding it to cognitive behavioral case management (CBCM) for adolescents and young adults at high risk for psychotic disorders. During the first six months of the study, subjects were given up to 20 sessions of CBCM and, each day, took four capsules of highly concentrated fish oil providing a total of 840 mg of EPA and 560 mg of DHA. Antipsychotic medication was not given, but antidepressant and anti-anxiety medication was permitted. Although a lower than expected percentage of subjects developed psychosis during the study, the percentage was not significantly different between those given the fish oil and those given placebo (paraffin oil). Over a full year (including six months after fish oil and regular CBCM treatment ended), about 11% of both the fish oil and placebo groups had progressed to psychosis. (McGorry, JAMA Psychiatry 2016)
Omega-3 fatty acids inhibit neuronal excitability and reduce seizures in animal models, but, at high doses (1,700 mg to 2,200 mg of EPA + DHA daily), have failed to reduce seizures in people with drug-resistant epilepsy. However, a small, but well-controlled study using a lower dose (1,080 mg of EPA plus DHA per day) for 10 weeks found a 33.6% reduction in seizure frequency compared to placebo. A higher dose (twice the dose) was also tested but was not effective. The fish oil used in the study, which was funded by the National Institutes of Health, was Nature Made Fish Oil 360 mg OMEGA-3. The lower dose consisted of 3 gel capsules per day (each capsule containing 216 mg of EPA and 144 mg of DHA), while the higher dose was 6 capsules per day. During treatment with low-dose, patients had an average of 12.18 seizures per month, compared to 17.67 and 18.34 seizures per month, respectively, with the high-dose and placebo (DeGiorgio, J Neurol Neurosurg Psychiatry, 2014). The study authors note that a potential reason why the lower dose was more beneficial than higher dose is that high-doses of fish oil may cause excessive reductions in non-esterified fatty acids (e.g., arachidonic acid), and that a study of fish oil in depression found a similar benefit using low-dose, but not higher-dose fish oil (Peet, Arch Gen Psychiatry 2002).
Attention Deficit/Hyperactivity Disorder (ADHD)and Executive Functioning In Children/Adolescents:
Studies using fish oil supplements in treating ADHD have yielded conflicting results. Evidence seems to suggest supplements may improve symptoms of inattention specifically, and not symptoms of ADHD more generally. A double-blind, placebo-controlled 16-week study giving boys aged 8 to 14 years fish oil (in a margarine spread containing 650 mg of EPA and 650 mg of DHA daily) found it to modestly improve parent-rated attention in boys with ADHD and in typically developing boys. Most of the boys with ADHD were also taking prescription medication. No effect, however, was seen in brain activity or on performance of cognitive control tasks (Bos, Neuropsychopharm 2015).
In contrast, an improvement in executive functioning was found in a study among 95 girls and boys (average age 11) with mood disorders (depression, bipolar disorder or unspecified) who took two capsules of fish oil providing a daily total of 700 mg EPA, 100 mg DHA and 134 mg other omega-3 fatty acids (OmegaBrite -- who provided the capsules) in addition to twice-weekly therapy sessions for three months. Significant improvements in parent-reported executive functioning (working memory and cognitive skills such as attention, planning, organizing, switching between tasks) were found in comparison to those who had the same therapy but took a placebo. The same dose of fish oil also significantly improved parent-reported executive functioning compared to placebo in children who did not receive therapy sessions (Vesco, J Child Psychol Psychiatry 2017). It is difficult to say, however, to what extent the improvements may have been due to improvements in depressive symptoms, which also occurred (Fristad, J Child Adolesc Psychopharmacol 2015; Fristad, J Clin Child Adolesc Psychol 2016).
Reading Skills in Children
A double-blind, placebo-controlled study in boys and girls (ages 9 and 10) in Sweden found that a dose of 558 mg EPA, 174 mg DHA and 60 mg gamma-linolenic acid (GLA -- an omega-6 fatty acid) taken daily for three months modestly improved reading ability, including the ability to read and pronounce unfamiliar words and the ability to read a series of letters quickly, as well as reading comprehension, compared to placebo. Although none of the children had a reading disability or ADHD, the researchers noted that the greatest improvements were found in children who had attention problems (as reported by parents) (Johnson, J Child Psychol Psychiatry 2016).
During Pregnancy: Effects on Children
DHA is important for normal development and functioning of the brain and retina in the fetus and in infants. For this reason, it is thought that pregnant or nursing mothers may benefit from supplementation. DHA is also often added to formula for premature infants and some regular infant formulas and foods. As discussed below, the benefits of such supplementation during pregnancy have not been established with regard to brain function, but the use of fish oil during pregnancy may reduce the risk of premature birth as well as colds in infants and asthma and allergy in children.
In an Australian study, pregnant women were given 800 mg of DHA and 100 mg of EPA daily (from 1,500 mg of fish oil in capsules) until birth. Compared to women given placebo (vegetable oil capsules), there was no statistically significant increase in cognitive or language development in offspring during early childhood (Makrides, JAMA 2010), nor when the children were evaluated again at 4 years of age (Makrides, JAMA 2014), nor when the children were tested for IQ at age 7 -- at which age they were reported to have slightly more behavioral and executive functioning problems than children in the placebo group (Gould, JAMA 2017). Somewhat fewer of the treated women had postpartum depression (9.67%) than those who received placebo (11.19%), but this was not statistically significant. However, there was a significant decrease in very premature births (1.09% in the treated group vs. 2.25% in the placebo group) as well as fewer low birth weight infants and fewer admissions to neonatal intensive care units. There were also fewer fetal/infant deaths among those taking fish oil, although not by a statistically significant margin. At the same time, more of the treated women were induced or had cesarean sections because they were post term. Babies born to treated women in the study were nearly 40% less likely to have egg allergies in their first year of life in comparison to babies of untreated women. They were also less likely to have eczema, although this association did not hold after the results were adjusted for factors such as maternal history of allergies (Palmer, BMJ 2012). A related editorial recommended that pregnant women should get 200 mg of DHA per day either from a supplement or low-mercury fish and that the benefit of higher intakes remains unclear (Oken, JAMA 2010).
A major study in Denmark found that fish oil supplementation during pregnancy decreased the occurrence of persistent wheeze and asthma in offspring. Starting at 24 weeks of pregnancy, women took 4 capsules daily, each containing 1 gram of concentrated fish oil providing 330 mg of EPA and 220 mg of DHA in the triglyceride form. By age 5, wheeze/asthma had developed in 23.7% of children whose mothers received a placebo (olive oil), compared to only 16.9% of those whose mothers received the fish oil supplement. Fish oil was particularly important for children of women who started with lower blood levels of fish oil (one-third of the women) -- 35.1% in the placebo group developed asthma/wheeze compared to 17.5% in the supplemented group. Women in the U.S. tend to consume only half the amount of omega-3 fatty acids from their diets as those in Denmark, suggesting even greater potential benefit in the U.S. population (Bisgaard, NEJM 2016).
An analysis which weighed the potential cognitive benefits with the risks (from exposure to mercury) of consuming fish during pregnancy suggested that consuming two seafood meals (8 to 12 oz) per week during pregnancy could increase a child's IQ an additional 3.3 IQ points by age 9. Consuming this recommended amount as tuna provided increases between 2.8 and 3.1 IQ points, while salmon (which generally has a higher concentration of EPA and DHA) provides 3.2 IQ points; however, as noted by the researchers, the benefit may be due, in part, to nutrients from fish other than EPA and DHA, such as vitamin D, selenium, and amino acids. No adverse cognitive effects from mercury were expected from consuming this amount of fish per week, and depending on the type of fish, you would have to consume many times this amount before getting the minimum amount of mercury known to cause adverse cognitive effects (for example, 120 light tuna sandwiches per week) (McGuire, Nutr J 2016).
Infants born to women in Mexico given 400 mg DHA daily (from algal oil from Martek Biosciences) during pregnancy (starting at about 20 weeks) had a lower occurrence of colds during the first three month of life than those whose mothers received placebo treatment (37.6% vs. 44.6%, respectively) (Imhoff-Kunsch, Pediatrics 2011). However, median daily intake of DHA among pregnant women in Mexico is much lower than in the U.S. (80 mg vs. 100 to 200 mg, respectively), so the findings may not apply to groups already consuming higher amounts of DHA.
During Early Childhood:
A large study in which 1-year-olds in Ohio who were born preterm and had been weaned off breast milk and formula were given DHA (200 mg) and arachidonic acid (200 mg) daily for 6 months showed no improvement in cognitive development and early measures of executive function versus placebo, and possible negative effects on language development (Keim, JAMA Ped 2018). (Arachidonic acid (AA) is an omega-6 fatty acid believed to be important for infant growth and brain development. It is present in human milk and is commonly added to infant formula along with DHA (Hadley, Nutrients 2016). The lack of effect on cognitive development is generally consistent with previous studies on infants and pre-term neonates, calling into question the benefit of DHA and AA supplementation in these groups.
Population studies suggest that consumption of DHA is associated with reduced incidence of Alzheimer disease and animal studies demonstrate that DHA intake reduces Alzheimer-like brain disease. However, a study showed that supplementation with DHA from algae did not slow cognitive and functional decline in individuals with mild to moderate Alzheimer disease (Quinn, JAMA 2010). There was also no apparent reduction in the decline in brain volume. In the study, patients received 2 grams of DHA from algal oil daily or placebo for 18 months. All of the patients had previously consumed less than 200 mg of DHA per day and had not taken supplements with DHA or EPA. Among those given DHA in the study, plasma levels of DHA tripled and the amount of DHA in cerebrospinal fluid increased by 38%, with no significant change in those taking placebo. It should be noted that the study did not assess whether DHA could play a preventative role in Alzheimer's disease, nor did it assess the effect of DHA in conjunction with EPA.
A placebo-controlled, 1-year pilot study of 34 adults with mild to moderate impairment from Alzheimer's disease found that alpha-lipoic acid and fish oil slowed the decline in subjects' cognitive functioning. The combination also slowed the decline in subjects' abilities to perform daily activities, as did fish oil alone, but not alpha-lipoic acid alone. The participants normally ate fish no more than once per week and most continued to take Alzheimer's medications. A capsule of alpha-lipoic acid (600 mg) was taken each morning along with 2 fish oil capsules (each containing 1 gram of fish oil, providing 325 mg EPA and 225 mg DHA in the triglyceride form). Another fish oil capsule was taken with lunch (Shinto, J Alzheimers Dis 2014). Although earlier studies, such as that above, have not shown a benefit with omega-3 fatty acids in Alzheimer's disease, this study differed in that the fish oil had a high ratio of EPA to DHA.
A small study involving daily intake of a drink (Smartfish, Norway) providing 1,000 mg of EPA and 1,000 mg of DHA along with a modest amount of vitamin D (400 IU) and an undisclosed amount of antioxidants (pomegranate, chokeberry and resveratrol) found that the drink -- consumed daily for 4 to 17 months -- had no effect on cognition in people with Alzheimer's disease, nor in people with mild cognitive impairment. The study also evaluated the drink's effect on the ability of immune system cells in the subjects to remove amyloid beta - a neurotoxic molecule associated with Alzheimer's disease. No improvement in this immune function was found in Alzheimer's patients, although this did improve in people with mild cognitive impairment and normal cognitive function (Fiala, FASEB J 2015).
A study in Sweden among people with mild to moderate Alzheimer's disease found that daily supplementation with 1,700 mg of DHA and 600 mg of EPA for six months benefitted only those with adequate B vitamin status (determined by blood levels of homocysteine). In comparison to those with higher homocysteine levels, people with levels below 11.7 mmol/L experienced a 7.1% improvement in cognitive performance and a 22.3% reduction in a rating scale of dementia. This was consistent with an earlier study by the same researchers which showed B vitamins were most helpful in reducing brain shrinkage in Alzheimer's patients with higher blood levels of EPA and DHA. The researchers explained that the two types of nutrients work together: B vitamins are necessary to form phosphatidylcholine which is necessary to carry DHA and EPA over the blood-brain barrier (Jerneren, J Alz Dis 2019).
Age-related Cognitive Decline:
Many studies have explored the use of DHA-rich fish oil for people with age-related cognitive decline (ARCD). Unlike Alzheimer's disease, ARCD is not considered a disease and is a more gradual and, perhaps, normal consequence of aging. The benefit has generally been modest at best and may depend on stage of cognitive decline, age of the person, and whether or not they are already consuming fish in their diet, as described below.
A 6-month study of people over age 65 with mild cognitive impairment showed that those receiving daily fish oil containing a large amount of DHA (1,550 mg) with EPA (400 mg) improved scores on verbal fluency (although not on any other memory or cognition test) compared to those in a control group receiving safflower oil (containing the omega-6 fatty acid, linoleic acid). An EPA/DHA combination (1,670 mg EPA with 160 mg DHA) did not affect any aspect of cognition or memory. However, both the EPA/DHA combination and, to a slightly greater extent, the DHA/EPA combination reduced depressive symptoms in these mildly cognitively impaired individuals (Sinn, Br J Nutr 2011). The researchers note that depression is a potential risk factor for progression to dementia, so the reduction of depressive symptoms may reduce the risk of dementia. In another study (Yurko-Mauro, Alzheimer's & Dementia 2010), participants with ARCD were given 900 mg per day of DHA from algal oil or placebo for 24 weeks. Those taking DHA showed significant improvements in verbal recognition memory, but no improvement in working memory or on executive function tests. Plasma DHA levels doubled in the group receiving the supplementation.
A multi-year study of several hundred older individuals (approximately 70 to 80 years of age) found that cognitive function and brain volume (size) were better preserved among those who reported using fish oil supplements than those who did not (the types and dosage of fish oil used were not identified). The effect, however, was only seen among those who started with normal cognitive function, not those who already had mild cognitive impairment or Alzheimer's disease. In addition, the benefit was only found among people who did not have a specific gene (APOE e4) associated with increased risk of Alzheimer's disease. The researchers note that these apparent effects are consistent with other research. Similarly, other studies have shown a positive association between consumption of fatty fish and better cognitive health, and indicate that middle age may be a particularly significant period for the potential role of omega-3 fatty acids in better cognitive aging. (Daiello, Alzheimer's & Dementia 2015). Analyses of two studies which showed reduced cognitive decline and reduced brain shrinkage with a B vitamin combination concluded that the benefits were only found among people who began the studies with blood plasma levels of omega-3 fatty acids in the upper range of normal (see B Vitamin Review).
Neither daily fish oil (650 mg of EPA and 350 mg of DHA) nor lutein and zeaxanthin (10 mg and 2 mg, respectively) were found to reduce cognitive decline in a large, well-controlled, 5-year study of older individuals in the U.S. (average age of 73) who were part of a larger study of supplements to slow age-related macular degeneration, an eye disease (see the AREDS2 study). Yearly decline in cognitive function was essentially the same for those taking these supplements as for those taking placebo (Chew, JAMA 2015). However, the study population was described as "well-nourished" and may have already been regularly consuming fish.
A placebo-controlled study of healthy older individuals in China with mild cognitive impairment found that taking 2 grams of DHA from algal oil daily for one year improved aspects of short- and long-term memory, although not other measures of cognition (e.g., arithmetic, vocabulary). MRI scans of those given algal oil (from Martek Biosciences, whose parent company, DSM, funded the study) showed a 4% increase in the volume of the hippocampus (a key area for memory formation), while those given a similar amount of corn oil did not have this improvement, nor improvements in cognitive function (Zhang, J Alz Disease 2016). Another study among older men and women (average age 71) in China with mild cognitive impairment found that 480 mg DHA and 720 mg EPA per day from fish oil slightly improved overall measures of cognitive function, perceptual speed and working memory, but not mental arithmetic efficiency or recognition memory, compared to placebo (olive oil) (Bo, Nutrients 2017). Blood levels of DHA and EPA in participants were somewhat low at the beginning of the study, which may help explain why supplementation was helpful.
A large study in France among older adults (average age 75) with self-reported cognitive difficulties found that supplementing with 800 mg of DHA and 225 mg of EPA from fish oil daily did not reduce cognitive decline compared to placebo. There was also no benefit from a lifestyle intervention (physical activity, cognitive training, and nutritional advice) by itself or in combination with omega-3 supplementation (Andrieu, Lancet Neurol 2017). Similarly, an 18-month study in Australia among older adults (average age 73) found that daily supplementation with 1,720 mg of DHA and 600 mg of EPA did not help maintain or improve cognitive performance relative to results with placebo (an olive oil low in polyphenols). However, those in the study were consuming fish twice per week on average (Danthiir, Am J Clin Nutr 2018).
In summary, the omega-3 fatty acid DHA (900 to 2,000 mg daily), such as from fish or algal oil, may slow some aspects of age-related cognitive decline in people without advanced dementia, but the benefit seems limited to use during middle age and/or among those who are not getting significant omega-3 fatty acids in their diets.
Memory-enhancement in Healthy Individuals:
In a small study of healthy, young adults, better working memory performance has been found to correlate with higher levels of DHA (as measured in red blood cell membranes), but not EPA (Narendran, PLoS One 2012). Working memory performance was tested by showing a series of letters and numbers and asking what appeared one, two, and three times prior. Those who had higher DHA levels performed better on the "3-back" question than those with lower levels. The subjects were then asked to take 2 grams of highly-concentrated fish oil (Lovaza, 930 mg EPA and 750 mg DHA) daily for six months and tested again: Scores improved on the "3-back" question and those who previously had the lowest DHA levels improved the most. Similarly, another 6-month study in healthy young adults with diets low in omega-3 fatty acids found those given a DHA-rich fish oil supplement daily (2,250 mg of fish oil providing 1,160 mg of DHA and 170 mg EPA) had improved memory performance compared to those who received placebo (Stonehouse, Am J Clin Nutr 2013). Specifically, women had greater improvements in episodic memory -- correctly remembering one more word or picture, while men experienced greater improvements in reaction times of working memory -- completing tasks 20% faster than men in the placebo group. The report notes that 6 months was chosen as the study period as this is required for DHA levels in tissue to plateau.
A placebo-controlled study in 65 healthy adults ages 50 to 75 years, found that taking fish oil for 6 months resulted in a 26% increase in executive functioning (e.g., verbal fluency, visual tasks, reading ability). There was no overall improvement in memory, although there was an improvement in memory consolidation -- the recall of words after a 30-minute delay. Those who took the fish oil also had significant gains in the structure and volume of tissue in several areas of the brain, improvements in the lining of the carotid artery, and a mean 3.4% reduction in diastolic blood pressure. The participants took 4 fish oil capsules daily, each containing 1,000 mg of fish oil (300 mg EPA and 220 mg DHA) which included 15 mg of vitamin E as preservative, and continued eating their normal diet, with most consuming fish one time per week (Witte, Cereb Cortex 2013).
A study is underway in Holland (Food2Learn) to evaluate the effects of krill oil on the cognitive functioning of adolescents with lower educational performance. Baseline testing (before starting krill) of the students has shown a positive association between levels of EPA + DHA in their blood and performance on two cognitive measures: processing speed and impulsivity control. However, no association was found with short-term memory or six other cognitive measures (van der Wurff, Nutrients 2016).
Strength and Muscle:
Omega-3 fatty acids can help maintain and build muscle tissue. Evidence from several studies suggests that fish oil can help maintain muscle mass and modestly improve muscular strength and/or endurance and enhance the effects of training.
A study among 20 recreationally active young women who had one leg experimentally immobilized with a knee brace for two weeks found that those who started taking daily high-dose fish oil four weeks before immobilization had less decline in muscle volume than those given sunflower oil (8% vs. 14% decline, respectively). In fact, two weeks after the brace was removed, muscle volume was back to normal for those who had taken fish oil but it remained reduced in the control group. Biopsies revealed that muscle synthesis was higher with the fish oil group throughout the study. Following immobilization, leg strength decreased more in the control group than in the fish oil group, but the difference was not statistically significant. The fish oil was taken as a liquid providing 2,970 mg of EPA and 2,030 mg of DHA daily (McGlory, FASEB J 2019).
A 6-month, placebo-controlled study in healthy older men and women (60 to 85 years of age) found that high-dose, extremely concentrated fish oil increased muscle mass and function, while these declined in the control group receiving corn oil. The fish oil was Lovaza, taken as 2 pills with both breakfast and dinner, providing 1,860 mg of EPA and 1,500 mg of DHA daily (similar to amounts in about 3 servings of fatty fish). Compared to the control group, those getting the fish oil had about a 3.5% increase in muscle mass and a 6% increase in strength. The researchers noted that the therapy made up for 2 to 3 years of losses associated with normal aging and these changes were the same or greater than those which have been reported with testosterone, growth hormone, or DHEA, but less than what has been reported with exercise (Smith, AJCN 2015). Similarly, a study among healthy older adults (average age 70) who performed resistance exercise (twice per week) found that 3 grams of fish oil daily, providing a daily total of 2,100 mg of EPA and 600 mg of DHA (Barlean's) increased muscle strength by 34% in women. This was significantly greater than the 16% increase among women given placebo. In men, however, fish oil did not result in significant improvement compared to placebo. The researchers speculated that older women may have a greater capacity for improvement from resistance exercise than older men. Unlike the study discussed further above, there were no increases in muscle mass in either women or men (Da Boit, Am J Clin Nutr 2016).
A small study in Brazil looked at the potential benefit of fish oil on strength training in older individuals, based on the fact that omega-3's play a role in the plasma membrane and cell function of muscles (Rodacki, Am J Clin Nutr 2012). Forty-five mostly sedentary women in their mid-60s were given two doses a day of a gram of fish oil containing 180 mg of EPA and 120 mg of DHA. After twelve weeks of supervised lower-body resistance-training (3 times per week), the strength of those taking the fish oil had improved more than those who did not supplement. Functional capacity (e.g., the speed of rising from a chair) also increased more among those who took fish oil. There was no improvement in the strength of women who took fish oil without strength training, and taking fish oil for two months before training started did not confer added benefit.
A small study among male and female European competitive soccer players (average age 22) found that a high daily dose of fish oil (100 mg/kg of bodyweight; average dose 7 grams of fish oil providing 4,900 mg of EPA and 1,400 mg DHA daily) taken for one month modestly improved exercise endurance compared to placebo. After one month, those who took the fish oil were able to run an average of 203 meters further than before supplementation began, while those who took the placebo ran an average of 63 meters further; however, there were no improvements in running speed, or muscle strength or power (Gravina, Int J Sport Nutr Exerc Metab 2017).
A study among young resistance-trained men and women found that taking 3 grams of krill oil (providing 240 mg DHA, 393 mg EPA, and 0.54 mg astaxanthin) daily for two months while participating in regular resistance exercise did not increase strength, lean body mass, nor cognition, significantly more than an equivalent amount of olive oil given as a placebo (Georges, J Nutr Metab 2018).
Muscle Pain and Inflammation After Exercise (Omega XL)
A small study found that daily supplementation with a combination of green-lipped mussel oil, olive oil and vitamin E (Omega XL/PCSO-524, Pharmalink International) significantly reduced muscle damage, pain and inflammation after exercise in young men (average age 22) (Mickleborough, J Int Soc Sports Nutr 2015). In the study, the men took 8 Omega XL capsules per day (providing a total daily dose of 800 mg olive oil, 400 mg green lipped mussel oil extract (58 mg EPA + 44 mg DHA) and 1.8 mg vitamin E) or 8 placebo capsules (containing 1,200 mg olive oil) daily for one month. On the 26th day of supplementation, the men performed a downhill running exercise designed to induce muscle damage. Those who took the green-lipped mussel oil combination had significantly less delayed-onset muscle soreness (DOMS) on the third and fourth day after exercise, as well as lower levels of certain blood markers for muscle damage and inflammation, compared to those who took a placebo. The study was funded by Pharmalink International. [Note: this product was tested by ConsumerLab.com in 2014 and 2016 and was neither "Approved" or "Not Approved" because the label did not claim to contain a specific amount of omega-3 fatty acids — it was found each time to contain only about 6 mg of EPA and 5 mg of DHA per softgel, very low amounts compared to other omega-3 fatty acid supplements, although consistent with the amounts per pill in the above study].
There is mixed evidence that Omega XL/PCSO-524 may also be helpful for other conditions, and many of the clinical studies on this product were not properly designed (i.e. not double-blinded, placebo-controlled, etc.). For example, one study found it significantly reduced pain and improved physical function in men and women with osteoarthritis of the knee and/or hip when compared to fish oil (Zawadzki, Mar Drugs 2013), but another study found no such benefit when compared to a placebo (Lau,Progress in Nutrition 2004). In addition, a study found Omega XL/PCSO-524 to reduce the occurrence of wheezing in adults with asthma (Emelyanov, Eur Respir J 2002), while a study in children with asthma found no benefit compared to placebo (Lello, Inter J of Asthma, Allergy and Immunol 2012). Any promotion of the product for heart health appears to be based on the fact that it contains omega-3 fatty acids, not published clinical studies, although, as noted, it contains a scant amount of omega-3s. (See Cautions and Concerns for safety concerns about green-lipped mussel extract).
A small study found that daily supplementation with either omega-3 fatty acids (EPA and DHA) or the omega-6 fatty acid GLA significantly reduced the number and severity of acne lesions in men and women ages 18 to 33 years old with mild to moderate acne (Jung Acta Derm Venereol 2014). Participants received 2 capsules daily containing either omega-3 fatty acids (providing a total of 1,000 mg EPA and 1,000 mg DHA) or GLA (providing a total of 400 mg GLA from 2,000 mg borage oil) for 10 weeks. A third group, serving as the control, did not receive supplementation or any other treatment. At the end of the study, both treatment groups experienced a significant reduction in the number of inflammatory acne lesions (42.6% and 32.7%, respectively) and non-inflammatory acne lesions (19.6% and 15.8%, respectively). There was also a significant reduction in the severity of acne lesions in both groups (29% and 22%, respectively). No significant changes were seen in the control group.
Periodontitis (Inflammation Around Teeth)
A small, controlled, 3-month study found that giving 2,000 mg per day of DHA (from four capsules of algal oil which was 53.6% DHA) along with low-dose aspirin (81 mg per day) improved outcomes in people with periodontitis (inflammation around teeth causing pocketing) in comparison to aspirin plus placebo (soy/corn oil). Those receiving the DHA had greater reductions in local inflammation and pocketing around teeth (Naqvi, J Dent Res 2014). The researchers speculate that, in the presence of aspirin, DHA is converted to a compound used by certain white blood cells to produce other compounds (e.g. resolvins and protectins) which help resolve inflammation. Aspirin alone does not have this effect and it is not known whether DHA alone would have this effect. An earlier pilot study of EPA alone did not affect periodontitis, although positive results were seen with 2,000 mg per day of GLA (an omega-6 fatty acid) (Rosenstein, Prosta Leukot Essent Fatty Acids 2003).
Protection from Effects of Air Pollution
A small study by scientists at the U.S. Environmental Protection Agency (EPA) in middle-aged people found that fish oil supplementation protected against adverse cardiac and lipid effects associated with air pollution exposure (Tong, Env Health Perp 2012). Participants in the study were given daily capsules of fish oil (3 grams, providing 1230 mg EPA and 822 mg DHA) or olive oil for four weeks and then exposed to air containing particles for two hours. This caused the group taking olive oil to experience undesirable changes in blood lipids (increased LDL and triglyceride levels), but this did not occur in the fish oil group. The fish oil group also experienced less negative effects on heart functioning than the olive oil group.
However, a second small study found that supplementation with olive oil provided protection against other vascular effects of air pollution that fish oil supplementation did not. In the study, middle-aged men and women who took 3 grams of olive oil daily for four weeks experienced significantly better endothelial function after being exposed to air conditioning particles for two hours compared to those who took 3 grams of fish oil or placebo (Tong AJRCCM 2014). This suggests that olive oil and fish oil may each offer different cardio-protective benefits when it comes to air pollution exposure.
Other proposed uses of fish oils with some support include Raynaud's phenomenon (abnormal sensitivity of hands and feet to cold), chronic fatigue syndrome, cystic fibrosis, and osteoporosis.
The balance of current evidence suggests that fish oil is not effective for psoriasis, male infertility and enhancing immunity in people with HIV. Although some research has indicated that omega-3 fatty acid supplements might have anti-inflammatory effects that could benefit patients with multiple sclerosis (MS), a placebo-controlled study of 92 MS patients found no beneficial effect with daily fish oil (1,350 mg EPA and 850 mg DHA) for 2 years whether taken alone (for 6 months) or in combination with interferon (for 18 months) (Torkildsen, Arch Neurol 2012).
Fish oil supplements are commonly given to pets to help maintain their coats and skin. [Reviews of other pet supplements by ConsumerLab.com include ALA and GLA, Joint Supplements and Multivitamins/Multiminerals.]
For information on dosages see What to Consider When Using.
Quality Concerns and What CL Tested For:
Because omega-3 fatty acids are obtained from natural sources, levels of fatty acids in supplements can vary, depending on the source and method of processing.
Contamination has also been an issue, because fish can accumulate toxins such as mercury, dioxins, and polychlorinated biphenyls (PCBs). Mercury can damage the nervous system -- particularly in a fetus. Dioxins and PCBs may be carcinogenic at low levels of exposure over time and may have other deleterious effects.
The freshness of the oil is also an important consideration because rancid fish oils can have an extremely unpleasant odor and taste, and oxidized fish oil may be less safe and effective. A 7-week study in Norway, for example, found that high-quality (non-oxidized) fish oil taken daily by healthy adults resulted in a 6% decrease in LDL ("bad") cholesterol, while oxidized fish oil resulted in a 19% increase in LDL. Total cholesterol also decreased with high-quality fish oil compared to oxidized fish oil. Each fish oil contained the same amount of omega-3 fatty acids (700 mg EPA and 900 mg DHA). The researchers speculated that oxidized fish oil might enhance the solubility of cholesterol in the gut and increase its absorption, thus raising cholesterol levels (Rundblad, Br J Nutr 2017). Similarly, an earlier study found that highly oxidized (spoiled) omega-3 fatty acids from capsules had a negative effect on cholesterol levels in contrast to less oxidized omega-3 fatty acids which reduced triglyceride and cholesterol levels (Garcia-Hernandez, Int J Food Sci Nutr 2013).
While you can sometimes tell that a fish oil is rancid when you take it directly as a liquid, this can be masked by added flavors and not readily detected if you use a softgel and other encapsulated product. There may be safety considerations with oxidized fish oils due to a variety of compounds produced, some of which are odorless, such as peroxides. A study commissioned by the government of Norway (where fish oil supplement use is extremely high) concluded there would be some health concern related to the regular consumption of oxidized fish/marine oils, particularly in regards to the gastrointestinal tract, but there is not enough data to determine the risk (The Norwegian Scientific Committee for Food Safety, 2011). The study explained that the amount of spoilage and contamination in a supplement depends on the raw materials and processes of extraction, refining, concentration, encapsulation, storage and transportation. However, it saw no significant risk of contamination by microorganisms, proteins, lysophospholipids, cholesterol, and trans-fats. (ConsumerLab.com's tests of fish oil also indicate only insignificant amounts (less than 1%) of trans-fats, meaning that a capsule with 1,000 mg of fish oil contains less than 10 mg, or 0.01 grams, of trans-fat.)
Some studies of the freshness of supplements have suggested that a large percentage may be oxidized. For example, a study in Canada of mostly fish oil supplements (Jackowski, J Nutr Sci 2015) found that 50% exceeded voluntary oxidation limits. However, this study did not necessarily exclude products containing flavors which can interfere with testing, and this may have led to misleading findings and the conclusion that children's products (80% of which included flavorings) were more likely to be oxidized. The study also concluded that encapsulated, unflavored fish oil appears to be the safest and most readily testable type of product. It should be noted, however, that several of the researchers were employees of Pivotal Therapeutics, Inc., which exclusively sells encapsulated, unflavored fish oil. A private research group in Boston reported that three "top-selling" fish oil dietary supplements "exceeded maximum international industry standards" with regard to oxidization, but an extremely concentrated prescription fish oil did not (product identities were not disclosed). It also reported that each supplement contained "significant levels of saturated fat in addition to desirable omega-3 fatty acids." The report, however, is somewhat misleading in that 1) the oxidation values for the supplements were inflated by the researchers to "normalize" them to one gram of omega-3 fatty acids, rather than to one gram of fish oil -- which is the true industry standard, and 2) fish oil naturally contains saturated fats as well as unsaturated fats, so finding some saturated fats is expected and is not surprising. Amarin Pharma, the maker of a prescription fish oil (VASCEPA) funded the writing of the report. (Mason, Biochem and Biophy Res Comm 2016). A study of 33 fish and marine oil supplements purchased on the internet and in retail stores in Norway found peroxide levels (one measure of oxidation) to vary almost 10-fold, from 1.04—10.83 meq/kg, but the average level among products was 3.61 meq/kg, which is well below the GOED limit of 5 meq/kg which ConsumerLab.com applies in its reviews (Halvorsen, Food Nutr Res 2011).
ConsumerLab.com's tests for spoilage were conducted on newly opened products, maintained out of heat and moisture. However, be aware that spoilage may occur after products are opened and exposed to air and/or excessive heat (see Keep It Fresh for storage tips). Lemon and other citrus flavorings, which are common in marine oil supplements, as well as vanillin, can interfere with spoilage testing, giving a falsely high reading. In addition, deeply colored oils, such as krill, cannot be evaluated in this test. Consequently, ConsumerLab.com was not able to determine spoilage in such products, as indicated with "N/A" (not applicable) in the "Freshness" column of the results table below). To be sure a product was not spoiled and passed oxidation tests, look for a check mark in that column.
Capsules that are enteric-coated and are expected to release the oil after the stomach to theoretically reduce fishy aftertaste or burp. If they release too soon they lose that potential benefit. If they release too late, the oil may not get absorbed. ConsumerLab.com tested enteric-coated fish oil products according to the specifications set forth by the United States Pharmacopeia (USP).
Neither the FDA nor any other federal or state agency routinely tests fish or marine oil supplements for quality prior to sale. ConsumerLab.com, as part of its mission to independently evaluate products that affect health, wellness, and nutrition, purchased many dietary supplements sold in the U.S. claiming to contain EPA and/or DHA and tested them for their levels of omega-3 fatty acids (EPA, DHA and, if listed, ALA), lead, cadmium, arsenic, mercury, PCBs, and signs of spoilage (unless containing flavorings or deeply colored -- issues which prevent accurate testing for spoilage, as noted above). Enteric-coated capsules were tested to see if they properly released their ingredients. Among the products purchased and tested, the majority was for use by people and a few were for use by pets. Most of the supplements were softgel capsules or liquids.
For more information about the testing, see How Products Were Evaluated.