Fish oil as a dietary supplement

DEFINITION: Natural substance essential for health that is promoted as a dietary supplement for specific health benefits.

• PRINCIPAL PROPOSED USES: Heart disease prevention, rheumatoid arthritis
• OTHER PROPOSED USES: Allergies, Alzheimer’s disease, angina, ankylosing spondylitis, asthma, attention deficit hyperactivity disorder, bipolar disorder, borderline personality disorder, cancer-related weight loss, cancer treatment support, chronic fatigue syndrome, congestive heart failure, Crohn’s disease, depression, diabetic neuropathy, dysmenorrhea, eczema prevention, epilepsy, gout, human immunodeficiency virus infection support, hypertension, kidney stones, liver disease, lupus, macular degeneration, male infertility, migraine headaches, multiple sclerosis, osteoporosis, postpartum depression, pregnancy support, prevention of premature birth, prostate cancer prevention, psoriasis, Raynaud’s phenomenon, retinitis pigmentosa, schizophrenia, sickle-cell anemia, stroke prevention, surgery support, ulcerative colitis

Overview

Fish oil contains omega-3 fatty acids, one of the two main classes of essential fatty acids, or EFAs. (The other main type is omega-6.) Essential fatty acids are special fats that the body needs for optimum health.

Interest in the potential therapeutic benefits of omega-3 fatty acids began when studies of the Inuit people found that although their diets contain an enormous amount of fat from fish, seals, and whales, they seldom have heart attacks. This is presumably because those sources of fat are very high in omega-3 fatty acids.

Subsequent investigation found that the omega-3 fatty acids found in fish oil have various effects that tend to reduce the risk of heart disease and strokes. However, research into whether the use of fish oil actually prevents these diseases, while somewhat positive, remains incomplete and somewhat inconsistent. In recognition of this, the U.S. Food and Drug Administration (FDA) has allowed supplements containing fish oil or its constituents to carry a label that acknowledges the potential benefit but must also state, "FDA has concluded that the evidence is inconsistent and inconclusive."

In addition, a slightly modified form of fish oil (omega-3-acid ethyl esters) was approved by the FDA in 2004 as a treatment for hypertriglyceridemia (high triglycerides). This specially processed product, sold under the trade name Lovaza (formerly Omacor), is widely advertised as more effective than ordinary fish oil. However, the prescribing information notes only two small trials to support its effectiveness for this use. This is a far lower level of evidence than usually required for drug approval and also substantially lower than the body of evidence supporting standard fish oil as a treatment for high triglycerides. A similar FDA-approved prescription fish oil, Vascepa (icosapent ethyl), contains eicosapentaenoic acid (EPA) and was approved in 2012.

Fish oil has also shown promise as an anti-inflammatory treatment for conditions such as rheumatoid arthritis, menstrual pain, and lupus. In addition, it might be helpful for various psychiatric conditions.

Requirements and Sources

There is no daily requirement for fish oil. However, a healthy diet should provide at least 5 grams (g) of essential fatty acids daily.

Many grains, fruits, vegetables, sea vegetables, and vegetable oils contain significant amounts of essential omega-6 and omega-3 fatty acids, but oil from cold-water fish is the richest natural source of omega-3 fats. It is commonly stated that people require a certain optimum ratio of omega-3 to omega-6 fatty acids in the diet; however, there is no real evidence that this is true, and there is some evidence that it is false.

Therapeutic Dosages

Typical dosages of fish oil are 3 to 9 g daily, but this is not the upper limit. In one study, participants ingested 60 g daily.

The most important omega-3 fatty acids found in fish oil are called eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To match the dosage used in several major studies, one should take enough fish oil to supply about 2 to 3 g of EPA (2,000-3,500 milligrams [mg]) and about 1 to 2.5 g of DHA daily (1,000-2,500 mg). Far higher doses have been used in some studies; conversely, one study found blood-pressure-lowering effects with a very low daily dosage (0.7 g) of DHA.

DHA and EPA are not identical and might not have identical effects. Some evidence hints that DHA may be more effective than EPA for thinning the blood and for reducing blood pressure. The reverse may be true for reducing triglyceride levels, but study results are conflicting.

Some manufacturers add vitamin E to fish oil capsules to keep the oil from becoming rancid. Another method is to remove all the oxygen from the capsule. The fatty acid content of fish oil supplement capsules tend to oxidize, meaning they can degrade, and may contain lower amounts of fatty acids than advertised.

One should purchase fish oil products certified as free of significant levels of mercury, toxic organochlorines, and polychlorobiphenyls (PCBs). Also, if possible, seek out supplements made from sustainably harvested fish to minimize the negative environmental impacts associated with industrial fishing operations.

Flaxseed oil also contains omega-3 fatty acids, although of a different kind. Flaxseed oil has been suggested as a less smelly substitute for fish oil. However, it is far from clear whether flaxseed oil is therapeutically equivalent to fish oil.

Therapeutic Uses

Consumption of fish oil alters the body’s production of certain substances in the class of chemicals called prostaglandins. Some prostaglandins increase inflammation, while others decrease it. The prostaglandins whose production is enhanced by fish oil fall into the anti-inflammatory category. Based on this, fish oil has been tried as a treatment for early stages of rheumatoid arthritis, with positive results. It is thought to significantly reduce symptoms without causing side effects and may magnify the benefits of standard arthritis drugs. However, while some standard medications can slow the progression of the disease, there is no evidence that fish oil can do this. Much weaker evidence hints that fish oil might be helpful for the related disease ankylosing spondylitis.

Fish oil’s apparent anti-inflammatory properties are the likely explanation for its apparent benefit in dysmenorrhea (menstrual pain), as seen in two studies. Similarly, fish oil may be helpful for the autoimmune disease lupus. (However, two studies failed to find fish oil helpful for kidney disease caused by lupus.) Evidence has been mixed regarding whether fish oil is beneficial for Crohn’s disease or ulcerative colitis, conditions in which parts of the digestive tract are highly inflamed. However, two well-designed trials enrolling a total of 738 persons convincingly failed to find any benefit for omega-3 fatty acid supplementation in the prevention of Crohn’s disease relapse.

Incomplete evidence hints but does not prove that fish or fish oil might help prevent death caused by heart disease. This effect seems to result from several separate actions. The best documented involves reducing high triglyceride levels; studies enrolling more than two thousand people have substantiated this use. In addition, fish oil might raise HDL (good) cholesterol levels, thin the blood, lower levels of homocysteine, prevent dangerous heart arrhythmias, slow heart rate, improve blood vessel tone, and decrease blood pressure. These effects also support findings that fish oil may help prevent strokes. However, results are conflicting on whether people with angina should take fish oil or increase their intake of fatty fish. One large study found that fish oil increased risk of sudden death.

For a number of theoretical reasons, it has been suggested that fish oil and its constituents (especially a slightly modified form of EPA called ethyl-EPA) might have positive effects on various psychiatric disorders, most notably depression. However, there is no convincing evidence that low levels of omega-3 fatty acids in the bloodstream lead to even mild depression. Moreover, larger trials have generally failed to demonstrate a beneficial effect of fish oil-related products in those experiencing depression. Preliminary, and not altogether consistent, evidence hints that high doses of fish oil may produce benefits in bipolar disorder, reducing risk of relapse and improving emotional state.

Other preliminary, and again not altogether consistent, evidence hints that fish oil might enhance the effectiveness of standard drugs (such as phenothiazines) for schizophrenia. One trial of eighty-one adolescents and young adults (considered at very high risk) found that daily omega-3 fatty acid supplements for twelve weeks delayed transition to a first full psychotic episode (such as schizophrenia) within one year.

Fish oil has also shown a bit of promise for other mental and cognitive disorders, including borderline personality disorder. In one study, DHA failed to augment the effectiveness of standard therapy for attention deficit hyperactivity disorder (ADHD). However, two studies that evaluated the potential benefits of fish oil combined with omega-6 fatty acids found some evidence of benefit for this condition. Finally, one small trial found evidence that the use of fish oil might decrease anger and aggressiveness in people with a history of aggressive behaviors, substance abuse, and problems with the law.

Small studies also suggest that fish oil may be helpful in Raynaud’s phenomenon (a condition in which a person’s hands and feet show abnormal sensitivity to cold temperatures), sickle cell anemia, and a form of kidney disease called IgA nephropathy.

Also, according to some studies, but not all, fish oil may help treat the undesired weight loss often experienced by people with cancer. In addition, highly preliminary evidence hints that DHA might enhance the effects of the cancer chemotherapy drug doxorubicin and decrease side effects of the chemotherapy drug irinotecan.

Use of fish oil by pregnant women may help lengthen pregnancies and increase birth weight somewhat but does not appear to prevent premature birth or low birth weight. In addition, the use of fish oil by pregnant women may support healthy brain function and help prevent eczema and allergies in offspring.

Intriguing, but unreliable, evidence hints that fish oil, or its constituents, might be helpful for treating kidney stones or alleviating the symptoms of chronic fatigue syndrome.

Results are inconsistent regarding whether the use of fish oil can decrease seizure frequency in people with epilepsy.

One study found that insulin metabolism in 278 young, overweight persons improved on a calorie-restricted diet rich in fish oil from seafood or supplements compared with those on a diet low in fish oil, suggesting that fish oil may help delay the onset of diabetes in susceptible persons. Fish oil has also been proposed as a treatment for many other conditions, including diabetic neuropathy, allergies, and gout, but there has been little real scientific investigation of these uses.

Some studies suggest that fish oil combined with omega-6 essential fatty acids may augment the effectiveness of calcium in the treatment of osteoporosis.

One promising, but highly preliminary, double-blind, placebo-controlled study suggests that the same combination therapy may improve symptoms of the severe, degenerative neurological condition called Huntington’s disease.

Use of a fish oil product as part of a total parenteral (intravenous feeding) nutrition regimen may help speed recovery after major abdominal surgery.

For several other conditions, the balance of the evidence suggests that fish oil is not effective. For example, despite widely publicized claims that fish oil helps asthma, most preliminary studies have failed to provide evidence that it is effective, and one study found that fish oil can actually worsen aspirin-related asthma. However, there is some evidence that the use of fish oil could help prevent exercise-induced asthma in athletes. In a randomized controlled trial with long-term follow-up, women who took fish oil during late pregnancy reduced the risk of asthma in their children up to sixteen years later. One study found that fish oil did not benefit the lung function of persons with cystic fibrosis.

Similarly, a sixteen-week, double-blind, placebo-controlled study of 167 persons with recurrent migraine headaches found that fish oil did not significantly reduce headache frequency or severity. Conflicting results have been seen in other, much smaller trials of fish oil for migraines.

One study found weak evidence that the use of fish oil might decrease aggressive behavior in young girls (but, in this study, not in young boys). Another study found benefit in developmental coordination disorder (a condition in which children display a lack of physical coordination and problems with learning and behavior).

Fish oil is also sometimes recommended for enhancing immunity in human immunodeficiency virus (HIV) infection. However, one six-month, double-blind study found that a combination of the omega-3 fatty acids in fish oil plus the amino acid arginine was no more effective than placebo in improving immune function in people with HIV. Fish oil, however, might help persons with HIV gain weight.

In one large, randomized controlled trial, diets rich in fish and omega-3 fatty acids from fish were associated with a significant reduction in the risk of developing colorectal cancer among men in a twenty-two-year period. Another study provides preliminary evidence for the benefits of fish oil in reducing the risk of prostate cancer. Another study, by contrast, found that men who consumed fish oil supplements actually experienced a slight increase in the risk of prostate cancer. On balance, there is still relatively little evidence that the consumption of fish oil reduces cancer risk.

Studies have shown that fish oil could help symptoms of multiple sclerosis, improving the quality of life and preventing relapses.

Although one study found fish oil somewhat helpful in psoriasis, a much larger study found no benefit.

DHA has been evaluated as a possible treatment for male infertility, but a double-blind trial of twenty-eight men with impaired sperm activity found no benefit. In 2020, an observational study with over 1,600 young men found participants who took fish oil supplements had larger testes, produced semen, and had a higher sperm count than those who did not.

Combination therapy with gamma-linolenic acid (GLA) and fish oil failed to prove effective for cyclic breast pain.

One study failed to find fish oil more effective than placebo for treating stress.

Fish oil has been studied for its potential effects on eye health as well. DHA has been tried for slowing the progression of retinitis pigmentosa (a condition in which the retina gradually degenerates), but without much success. In observational studies, people who happen to consume a diet rich in omega-3 fatty acids seem to lower their risk of age-related macular degeneration (the most common cause of blindness in older adults). However, in the absence of randomized controlled trials, it is not possible to say whether or not it is omega-3 that produces this benefit.

Studies of fish oil have failed to find it helpful for Alzheimer’s disease, whether for slowing its progression or improving symptoms. Also, one well-designed study failed to find any benefit of fish oil for enhancing memory and mental function in older adults without dementia in a twenty-six-week period.

Use of essential fatty acids in the omega-3 family has also shown some promise for the treatment of nonalcoholic fatty liver.

Scientific Evidence

Heart disease prevention. Studies on fish or fish oil for preventing cardiovascular disease, slowing the progression of cardiovascular disease, and preventing heart-related death have returned somewhat contradictory results. A 2021 systematic review found that fish oil supplements were associated with modestly reduced cardiac mortality, sudden cardiac death, and cardiovascular events. Researchers noted that while this was evident in past studies, studies in the 2010s and 2020s indicated otherwise. However, the researchers believe that this is because of incorrect and incomplete interpretations of the results.

As noted, fish oil is hypothesized to exert several separate effects that act together to help protect the heart. The most important action of fish oil may be its apparent ability to reduce high triglyceride levels. Like cholesterol, triglycerides are a type of fat in the blood that tends to damage the arteries, leading to heart disease. According to most studies, fish oil supplements can reduce triglycerides by as much as 25 to 30 percent. In a detailed review of forty-seven randomized trials, researchers concluded that fish oil can significantly reduce triglyceride levels with no change in total cholesterol levels and only slight increases in HDL (good) cholesterol and LDL (bad) cholesterol.

A slightly modified form of fish oil (omega-3-acid ethyl esters) has been approved by the FDA as a treatment for elevated triglycerides. However, in some studies, the use of fish oil has markedly raised LDL cholesterol, which might offset some of the benefit. A 2009 review of thirty trials involving about fifteen hundred persons with type 2 diabetes demonstrated that marine-derived omega-3 polyunsaturated fatty acids (mean dose 2.4 g per day) lowered triglyceride levels but increased LDL cholesterol after an average twenty-four weeks of treatment. However, later studies have generated conflicting results, with some citing that fish oil does not benefit people with type 2 diabetes in any way.

Stanols and sterols (or phytosterols) are naturally occurring substances found in various plants that can help to lower cholesterol in persons with normal or mildly to moderately elevated levels. A study investigating the possible benefit of combining a phytosterol with fish oil found that together they significantly lowered total cholesterol, LDL cholesterol, and triglycerides, and raised HDL (good) cholesterol in persons with undesirable cholesterol profiles.

Fish oil has been specifically studied for reducing triglyceride levels in people with diabetes, and it appears to do so safely and effectively. It also seems to remain effective in persons who are already using statin drugs to control lipid levels (people both with and without diabetes). However, one study found that the standard drug gemfibrozil (Lopid) is more effective than fish oil for reducing triglycerides.

Some but not all studies suggest that fish, fish oil, or EPA or DHA separately may also raise the level of HDL (good) cholesterol and possibly improve other aspects of cholesterol profile. This too should help prevent heart disease. Additionally, fish oil may help the heart by thinning the blood and by reducing blood levels of homocysteine, though not all studies have found a positive effect.

Studies contradict one another on whether fish oil can lower blood pressure, but on balance the supplement does seem to exert a modest positive effect. A six-week, double-blind, placebo-controlled study of fifty-nine overweight men suggests that the DHA in fish oil, not the EPA, is responsible for this benefit.

Evidence is conflicting on whether fish oil helps prevent heart arrhythmias. A large Italian trial involving almost seven thousand participants found that fish oil may modestly reduce the risk of death or admission to the hospital for cardiovascular reasons in persons with congestive heart failure. Finally, fish oil may slightly reduce heart rate. This effect could contribute to preventing heart attacks and other heart problems.

A 2018 Cochrane systematic review assessed the heart outcomes in seventy-nine randomized clinical trials involving omega-3 fatty acids and over 112,000 participants, most of whom had existing heart conditions. Although EPA and DHA consumption likely lowered blood fat levels, triglycerides, and HDL cholesterol, there was little or no significant impact on all-cause mortality or the risks of heart attacks, stroke, heart disease–related deaths, or other heart problems and events. There was also very modest improvement in arrhythmias with higher ALA consumption but no change in deaths. Raising EPA, DHA, and ALA intake did not appear to influence body weight or composition.

According to multiyear Harvard Medical School study findings published in 2018, the greatest heart health benefits from fish oil supplementation were found in those who do not consume fish or eat little of it; those with known risk factors for heart disease, stroke, or cardiac arrest; and African Americans.

A meta-analysis in 2021 suggested that fish oil may be helpful in preventing fatal heart events, such as sudden cardiac death or coronary heart disease death. Fish oil was noted to be particularly effective in preventing heart-related deaths in patients who had experienced a previous cardiovascular event.

Rheumatoid arthritis. The results of numerous small, double-blind trials indicate that omega-3 fatty acids in fish oil can help reduce the symptoms of rheumatoid arthritis. One small study suggests that it may help persons with rheumatoid arthritis to lower their dose of nonsteroidal anti-inflammatory medication (such as ibuprofen). The benefits of the fish oil effect may be enhanced by a vegetarian diet. Simultaneous supplementation with olive oil (about two teaspoons daily) may further increase the benefits. However, unlike some conventional treatments, fish oil probably does not slow the progression of rheumatoid arthritis.

Menstrual pain. The regular use of fish oil may reduce the pain of menstrual cramps. In a four-month study of forty-two young women age fifteen to eighteen years, one-half the participants received a daily dose of 6 g of fish oil, providing 1,080 mg of EPA and 720 mg of DHA daily. After two months, they were switched to placebo for another two months. The other group received the same treatments in reverse order. The results showed that these young women experienced significantly less menstrual pain while they were taking fish oil.

Another double-blind study followed seventy-eight women, who received either fish oil, seal oil, fish oil with vitamin B₁₂ (7.5 mcg [micrograms] daily), or placebo for three full menstrual periods. Significant improvements were seen in all treatment groups, but the combination of fish oil and vitamin B₁₂ proved most effective, and its benefits continued for the longest time after treatment was stopped (three months). The researchers offered no explanation why vitamin B12 should be helpful.

Bipolar disorder. A four-month, double-blind, placebo-controlled study of thirty people suggests that fish oil can enhance the effects of standard treatments for bipolar disorder, reducing risk of relapse and improving emotional state. Eleven of the fourteen persons who took fish oil improved or remained well during the course of the study, while only six of the sixteen given placebo responded similarly. Another small study found that ethyl-EPA (a modified form of EPA) is helpful for the depressive phase of bipolar disease.

Depression. A four-week, double-blind, placebo-controlled trial evaluated the potential benefits of fish oil in twenty persons with depression. All but one participant were also taking standard antidepressants and had been taking them for at least three months. By week three, the level of depression had improved to a significantly greater extent in the fish oil group than in the placebo group. Six of ten participants given fish oil, but only one of ten given placebo, showed at least a 50 percent reduction in depression scores by the end of the trial. (A reduction of this magnitude is considered a cure.)

A double-blind, placebo-controlled study of seventy people who were still depressed despite standard drug therapy (such as selective serotonin reuptake inhibitors) found that additional treatment with ethyl-EPA improved symptoms. Similar add-on benefits were seen in other double-blind studies of ethyl-EPA or mixed essential fatty acids. However, one study failed to find benefit with fish oil as an add-on treatment. Another double-blind study failed to find DHA alone helpful for depression. A third, relatively large placebo-controlled study found no benefit for fish oil in improving mental well-being among 320 older adults without a diagnosis of depression.

In 2019, a British Journal of Psychiatry systematic review of thirty-one randomized clinical trials reported that increased intake of long-chain omega-3 fatty acids did little to nothing to prevent or treat depression and anxiety.

Postpartum depression. The effectiveness of fish oil supplementation in treating or preventing perinatal (including postpartum) depression is unclear. A small preliminary study of women found that fish oil was significantly more effective than placebo at alleviating postpartum depression. However, another small, placebo-controlled study was unable to show a benefit in women with depression, whether before or after delivery. In addition, a 2009 trial of 182 pregnant women with suspected low intake of DHA found that daily DHA supplementation (with or without arachidonic acid) did not reduce risk of postpartum depression, compared with placebo. Also, in another, much larger study involving 2,399 women, researchers found that fish oil capsules (a combination of DHA 800 mg per day and EPA 100 mg per day) did not prevent postpartum depression. It also did not improve the cognitive and language development in their children up to four years after their birth.

Raynaud’s phenomenon. In small, double-blind studies, fish oil has been found to reduce the severe finger and toe responses to cold temperatures that occur in Raynaud’s phenomenon. However, these studies suggest that a higher-than-usual dosage must be used to get results, perhaps 12 g daily.

Osteoporosis. There is some evidence that essential fatty acids may enhance the effectiveness of calcium in osteoporosis. In one study, sixty-five postmenopausal women were given calcium with either placebo or a combination of omega-6 fatty acids (from evening primrose oil) and omega-3 fatty acids (from fish oil) for eighteen months. At the end of the study period, the group receiving essential fatty acids had higher bone density and fewer fractures than the placebo group. However, a twelve-month, double-blind trial of forty-two postmenopausal women found no benefit.

The explanation for the discrepancy may lie in the differences between the women studied. The first study involved women living in nursing homes, while the second study looked at healthier women living on their own. The latter group of women may have been better nourished and already receiving enough essential fatty acids in their diet.

Lupus. Lupus is a serious autoimmune disease that can cause numerous problems, including fatigue, joint pain, and kidney disease. One small, thirty-four-week, double-blind, placebo-controlled crossover study compared placebo with daily doses of EPA (20 g) from fish oil. Seventeen persons completed the trial. Of these, fourteen showed improvement when taking EPA, while only four did so when treated with placebo. Another small study found similar benefits with fish oil in a twenty-four-week period. However, two small studies failed to find fish oil helpful for lupus nephritis (kidney damage caused by lupus).

Attention deficit hyperactivity disorder (ADHD). Based on evidence that essential fatty acids are necessary for the proper development of brain function in growing children, essential fatty acids have been tried for the treatment of ADHD and related conditions. A preliminary double-blind, placebo-controlled trial found some evidence that a supplement containing fish oil and evening primrose oil might improve ADHD symptoms. However, a high dropout rate makes the results of this trial somewhat unreliable. Another small study examined fish oil in children with ADHD who had thirst and skin problems. Benefits were seen with fish oil, but the benefits also occurred with placebo and did so to about the same extent.

Safety Issues

Fish oil appears to be generally safe. The most common problem is fishy burps. Other digestive effects include flatulence, pain, nausea, diarrhea, and acid reflux. However, there are some safety concerns to consider.

For example, it has been suggested that some fish oil products contain excessive levels of toxic substances such as organochlorines and PCBs. If possible, one should try to purchase fish oil products certified not to contain significant levels of these contaminants. Various types of fish contain mercury, but this has not been a problem with fish oil supplements, according to some reports.

Fish oil has a mild blood-thinning effect; in one case report, it increased the effect of the blood-thinning medication warfarin (Coumadin). People who are at risk of bleeding complications for any reason should consult a physician before taking fish oil, and those about to undergo surgery should stop or wait to start taking fish oil supplements.

High doses of fish oil may raise blood sugar levels. Nonetheless, persons with diabetes should take supplements only on the advice of a physician.

Fish oil may modestly increase weight and lower total cholesterol and HDL (good) cholesterol levels. It may also raise the level of LDL (bad) cholesterol; however, this effect may be short-lived.

Avoid exceeding the safe maximum intake of vitamins A and D. These vitamins are fat soluble, which means that excess amounts tend to build up in the body, possibly reaching toxic levels. The official maximum daily intake of vitamin A is 3,000 mcg for pregnant women and other adults. The bottle label will help one determine how much vitamin A one is receiving. (It is less likely that a person will get enough vitamin D to produce toxic effects.) Meanwhile, fish oil consumption can also inhibit vitamin E.

Other potential side effects include low blood pressure and insomnia; the link between fish oil intake and stroke in humans remains inconclusive.

It can also interact with prescription medications or dietary supplements taken for blood pressure or weight loss. Contraceptives may reduce fish oil's effectiveness on triglycerides.

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