Fish Oil Benefits, Side Effects, and Dosage

Fish oil benefits

Early epidemiologic studies found that people who had a high dietary intake of fish had less heart disease (1). This has led to much interest in the health benefits of eating fish and whether fish intake could reduce the risk of coronary heart disease. 

Fish are a source of lean protein, polyunsaturated fats, and vitamin D. Polyunsaturated fatty acids (PUFA) are the key nutrient in fish that provide health benefits. PUFA can be categorized as either omega 3 fatty acids or omega 6 fatty acids. Fatty fish contains mostly the omega 3s (n-3), which have anti-inflammatory properties. 

Research showing the benefits of fish oil have led to the development of n-3 supplements and even prescription fish oil approved by the U.S. `Food and Drug Administration (FDA) to treat high triglycerides.

Fish oil supplements are now one of the most common dietary supplements used in the United States. This article will review fish oil as a source of omega 3 fats covering what it is, the possible benefits and potential risks, and who should take it? 

What is Fish Oil? 

Fish oil is the oil that is extracted from fish tissues. It contains n-3 fatty acids. There are 3 types of n-3 fatty acids: alpha-linolenic acid(ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). 

About 30% of fish oil is n-3 fatty acids and there are several types of omega-3. Fish provide EPA and DHA, whereas, ALA is found in plant oils such as flaxseed oil soybean oil, and canola oil. Omega 3 fish oil is known to have anti-inflammatory effects and offer some health benefits.

Omega fatty acids are used to form eicosanoids in the body. Eicosanoids made from omega 6 fatty acids are mediators of inflammation, vasoconstriction, and platelet aggregation, more so than n-3 fatty acids. Therefore, a higher concentration of n-3 fatty acids compared to omega 6 fatty acids reduce inflammation.

Omega 3 fatty acids are a key component of cell membranes. They have several functions throughout the body including in the heart, blood vessels, immune system, and endocrine system.

Structurally, n-3 fatty acids have a carbon-carbon double bond that is located 3 carbons from the methyl end of the fatty acid chain (4). EPA has 20 carbons and DHA has 22 carbons, making them both long-chain fatty acids.

What Are Good Sources of Fish Oil? 

Eating seafood (both fish and shellfish) is a good way to get fish oil. The Dietary Guidelines for Americans (2) and the American Heart Association (3) recommend about 2 – 4-ounce servings of fish per week.

The types of fish that are good sources include cold-water fish such as salmon, anchovy, mackerel, herring, sardines, tuna (albacore tuna), and lake trout. They are considered oily fish containing rich content of marine omega fatty acids. 

Farmed fish usually have higher amounts of EPA and DHA but it really depends on the feed given to the fish.

Fish accumulate n-3 fatty acids as a result of their food chain. Omega 3 fats are present in microalgae which is eaten by phytoplankton. Fish then eat the phytoplankton providing them with n-3 fatty acids.

If your fish intake is low, there are other ways to get fish oil. Nutrition supplements are available in the form of fish oil, krill oil, cod liver oil, and algal oil.

If you have an allergy to seafood, fish oil supplements are not recommended. Instead, an algal oil, from marine algae, can be used as a source of n-3 fatty acids. The same applies to vegans. 

Other plant-based sources of n-3 fatty acids include flaxseed, flaxseed oil, chia seed, and walnuts but the n-3 fatty acids found in plant sources are a source of alpha-linolenic acid (ALA). ALA is an essential fatty acid that the body can convert to EPA and DHA. An adequate intake (AI) has been established for ALA because it is considered an essential nutrient. The AI ranges from 1.1-1.6 g daily for adult women and men, respectively (4). 

Benefits of Fish Oil

There is a long list of potential benefits of fish oil supplements. Results of several large clinical studies evaluating the effect of supplementation have been published recently. Much of their focus has been on cardiovascular disease (CVD) prevention and heart health. Below are the potential health benefits of fish oil.

1. Improves lipid levels

Fish oil (specifically EPA) can help address hyperlipidemia, specifically triglyceride levels. They are a type of fat found in your blood. You will get a triglyceride level when you have your cholesterol level checked as part of the lipid profile. High triglyceride levels, as well as, high blood sugar can be a sign of other conditions that raise the risk of heart disease (obesity or metabolic syndrome).

A recent large clinical trial (the REDUCE-IT trial) published in the New England Journal of Medicine evaluated the beneficial effects of 4 grams of icosapent ethyl given daily to people with high levels of triglycerides. icosapent ethyl is made from EPA and is a prescription high dose of fish oil that is FDA approved and marketed under the brand name VASCEPA. The recent study found that icosapent ethyl significantly reduced cardiovascular events compared to placebo (5). One downside to the study was that more patients in the treatment group required hospitalization for atrial fibrillation and flutter

A systematic review in the Cochrane database concurs that EPA reduces serum triglycerides by about 15% (6).

The American Heart Association science advisory suggests that prescription omega 3s, at a dose of 4 grams daily, are an effective and safe option for the treatment of hypertriglyceridemia (7). 

It is important to understand that the REDUCE-IT study was evaluating a pharmacologic high dose and a product that requires a prescription and physician monitoring. If you have high triglyceride levels and other risk factors for heart disease, you should talk with your physician or healthcare provider about your treatment options. It is not recommended to dose over-the-counter fish oil supplements at this amount without medical supervision.

Severe hypertriglyceridemia may also be treated with n-3 fatty acids.

Concern has been raised that some studies found that fish oil supplements compared to placebo increased LDL-cholesterol levels. However, most studies have found no change in LDL levels (7).

In addition to Vascepa, other FDA approved agents include Lovaza, Omtryg, and Epanova.

2. May help lower blood pressure

Hypertension (high blood pressure) is a risk factor for cardiovascular diseases. Studies have looked at the effects of omega 3 fatty acids versus placebo on high blood pressure. 

A 2014 meta-analysis concluded that providing EPA and DHA may help reduce systolic blood pressure (8).

3. Reduce cardiovascular disease risk and cardiovascular (CV) events

Fish oils can reduce CVD by treating the risk factors for the disease. Fish oils may also reduce the risk of cardiovascular events such as sudden cardiac death. This includes myocardial infarction – also known as heart attack, stroke, or the need for percutaneous transluminal coronary angioplasty (a procedure to widen a narrowed arteries).

Several recent trials have been published on this. These large clinical trials include The VITAL study (9) and the ASCEND trial (10), both of which evaluated outcomes of supplementing 1 gram fish oil daily compared to a control group that received a placebo (olive oil). The VITAL study was supported and funded by the National Institutes of Health.

In the VITAL study (9), fish oil did not reduce the primary end point of cardiovascular events when combined. However, when looking at individual events, it showed that there was a significant reduction in myocardial infarction (MI), total coronary heart disease (CHD), and percutaneous transluminal coronary angioplasty in the fish oil group but no reduction in stroke or cardiac death.

Furthermore, there was a greater benefit in the treatment group for people with low fish intake (40% reduction in MI) and for African Americans (77% reduction) with fish oil. Therefore, if you increase your fish consumption in your diet to 2 times per week, it is unlikely you would see additional benefit with supplementation (9).

The ASCEND trial included people with diabetes mellitus that had no evidence of CVD. Over 7 years of follow up, omega 3s did not have a significant effect on the primary end point and reduce the risk of cardiovascular events. However, it did significantly reduce cardiovascular death by 19% (10).

A systematic review published in 2019 included all of the previously mentioned large clinical trials and concluded that omega 3 supplementation reduced the risk of MI, CHD death, total CHD, CVD death, and total CVD (11). 

Yet, a 2020 systematic review concluded that n-3 fatty acids reduced triglyceride levels by 15% but did not affect all-cause mortality, CV events, stroke, or arrhythmias (6). The recent study did find that increasing EPA and DHA may slightly reduce the risk of coronary heart disease and death. 

Statistically speaking, the analyses show that 167 people would need to increase their EPA and DHA intake to prevent one person from having a coronary event. It would take 334 people doing the same to prevent one sudden death from coronary heart disease (6).

4. May help alleviate symptoms of Rheumatoid Arthritis 

Rheumatoid arthritis (RA) is an autoimmune disease that involves inflammation of the joints. Arthritis is associated and stiffness, swelling, and pain. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to treat symptoms of RA. Omega 3 fats are also anti-inflammatory and therefore, suggested as a potential ancillary treatment for people with RA but research has found conflicting results. 

One meta-analysis found a reduced need for drug treatment (NSAIDs) but no improvement in symptoms when taking omega 3s (12). Another meta-analysis found A significant association with omega 3s and reduced RA symptoms (13). A third one found intake of n-3 fatty acids reduced markers of disease activity and inflammation including leukotriene B4 (14). Leukotrienes are eicosanoid inflammatory mediators.

Fish oil may be helpful in relieving inflammation, joint swelling, and joint pain associated with RA but more definitive research studies are needed.

5. Provides DHA for fetal growth and development

DHA is important for fetal growth and development. Observational studies have found a correlation between pregnant women and fish consumption with improved visual-motor skills in their children after birth (15). Additionally, lower seafood consumption during pregnancy had a significant association with their child’s lower verbal IQ scores (16).

However, clinical trials have not shown additional DHA fatty acid consumption during pregnancy to help with child’s cognitive or visual development (17).

Yet, a review of omega 3 intake during pregnancy found increasing intake of omega-3s reduced the incidence of preterm birth and there was less chance of having a baby with low birthweight (18).

The Dietary Guidelines for Americans recommends greater fish intake for pregnant women at 8-12 ounces weekly (2). The benefits of omega 3 from fish consumption appear to outweigh the risk. Mercury content of fish and increase risk of mercury toxicity with high fish intake are a concern during pregnancy.

Fish that contain higher amounts of EPA and DHA but are also low in mercury, such as salmon, herring, sardines, and trout are suggested as the safest options. Examples of fish that tend to have a high potency of mercury include king mackerel, tilefish, swordfish, marlin, orange roughy, and tuna.

If using fish oil capsules, mercury tends to be removed during manufacturing process and purification (4).

Interestingly, most infant formulas and some milk, yogurt and egg products now have added DHA. 

6. May prevent some cancers

Clinical research results on the use of n-3 fatty acids in cancer prevention have been largely inconsistent. While higher doses have been suggested to prevent breast cancer (19), a few studies have suggested increased prostate cancer risk with higher levels of omega 3s (20).

The VITAL study also looked at cancer risk and found that fish oil daily did not cause a significant reduction in the incidence of cancer or cancer mortality rates (9). Specifically, the treatment group did not see lower incidence of breast, colorectal, or prostate cancer compared to the placebo group.

Overall, there is no consistent data to suggest a relationship between omega-3 supplementation and the risk of cancer, and more research is needed.

7. May improve cognitive function in older adults

Research has looked at the effect of omega-3s on dementia and Alzheimer’s disease.

A meta-analysis of cohort data found that 100 mg DHA fatty acid intake daily, reduced risk of dementia by 14%, and Alzheimer’s disease by 37%. (21).

Unfortunately, clinical trials have not yielded similar results and a cochrane review concluded that omega 3 supplementation does not prevent cognitive decline but that it may help in cases where there is already some impairment (22-25). 

More clinical research is needed to determine the role of omega 3 in cognitive function and brain function. 

8. Improve eye health

Age-related macular degeneration can lead to vision loss. Early studies found a correlation between high fish consumption and a lower risk of macular degeneration.

In the AREDS-2 clinical trial, EPA and DHA did not slow the progression to advanced macular degeneration when compared to placebo (26).

Additionally, omega 3 supplements in a randomized, double-blind, clinical trial led to an improvement in symptoms associated with dry eye disease but the control group also experienced similar improvements. There was no significant difference between the omega 3 group and the control group (27).

There are numerous studies already published on the possible benefits of n-3 fatty acid intake. Additional areas of research include the effects of omega-3s on clinical outcomes for major depressive disorder, anxiety, bipolar disorder, inflammatory bowel disease, fatty liver, ADHD, allergies, asthma, cystic fibrosis, and more. At this time, there is insufficient evidence to recommend fish oil for these conditions (4). Further stud is needed and large clinical trials such as VITAL and ASCEND will provide the most useful data. 

Also, there is insufficient evidence that omega 3 supplementation has any significant effect on glycemic control or fasting insulin levels in people with diabetes mellitus (28). Nor does omega-3 appear to aid with weight loss (29, 30).

Who Should Take Fish Oil? 

Anyone who is unable to consume much fish, let alone the recommended amount of seafood in their diet, may benefit from DHA and EPA supplementation. If you are in good health and eat fish at least twice per week, it is unlikely supplements will provide greater benefit.

For the most part, taking a daily supplement is considered safe.

However, a few people may need to avoid fish oil. The supplements are not recommended for anyone with a fish or shellfish allergy. In this case, plant-based omega 3 supplements such as flaxseed oil are available.

Additionally, fish oil may slow blood clotting. Therefore, it is not recommended for anyone with a bleeding disorder and should be used cautiously in people who have prescribed anticoagulants (for example, blood thinner known as warfarin which is sold under the brand name Coumadin). 

This is because fish oil has anti-platelet effects but doesn’t appear to be any more potent than aspirin (4). No serious adverse events or increaseed risk of bleeding were reported in the VITAL or ASCEND clinical trials (9, 10). For this same reason, it should not be taken for 2 weeks prior to surgery.

Amounts greater than 3 grams daily may also reduce immune system activity. Taking additional n-3 fatty acid supplements may not be recommended for people on immune-suppressing medications.

If you are considering taking a fish oil supplement, be sure to discuss this with your doctor.

How Much Fish Oil Do I Need? 

The only formal recommendations in the United States on fish oil are to consume 2 – 4-ounce servings per week.

Linoleic acid (LA) and ALA are the only two essential fatty acids meaning they can only be obtained through diet. The body can not make them. LA is an omega 6 and ALA is an omega 3. Since fish oil is not 100%Z EPA and DHA, it is possible some of these other fatty acids will be provided. Symptoms of essential fatty acid deficiency include dermatitis, hair loss, and increased risk of infection butdeficiency is rare in the United States.

In the United States, an adequate intake (AI) has been established for omega 3 fatty acids but it is specific to alpha-linolenic acid (ALA) because it is an essential fatty acid. For adults, the AI for ALA ranges from 1.1-1.6 grams daily. No AI has been established for EPA or DHA as they are not considered essential. 

The World Health Organization (WHO) recommends 200-500 mg daily of combined EPA and DHA.

How to Supplement 

Dosage

Believe it or not, there are omega 3 supplements on the market that have little to no EPA and DHA. Be sure to check that the supplement does contain the needed EPA and DHA.

Generally, 250-500 mg EPA and DHA combined is a good goal. The World Health Organization (WHO) recommends 200-500 mg of EPA and DHA combined daily. 

Some of the clinical studies discussed above used a 1 gram fish oil capsules but not all of that consisted of EPA and DHA. For example, in the ASCEND trial, a 1 gram capsule provided 460 mg EPA and 380 mg DHA (10).

The Institute of Medicine suggests that doses in excess of 900 mg of EPA or 600 mg of DHA daily, may reduce immune function.

Although no formal upper limit has been established, the FDA has suggested not to exceed 3 grams daily of combined EPA and DHA. There are prescription dose supplements available but they must be used under the direction of a medical doctor.

Doses in excess of 2-15 grams daily have been suggested to increase your bleeding risk.

Frequency

Fish oil is typically taken as a daily dose. Whether you take it once or twice daily depends on the dosage and potency of the nutrition supplements.

Quality

Dietary supplements are not regulated in the same manner as medications in the United States. 

Generally speaking, you should look for ones that have been tested and verified by the third party organization. By looking for a seal from the U.S. Pharmacopeia (USP), NSF, or Consumer Lab, you are assured that the supplement is providing what the label says. Specific to the quality of omega 3 products, there are international fish oil standards known as the GOED standard for purity.

For processed fish oils, you will want to be sure they went through a purification process with gets rid of harmful levels of contaminants and heavy metals, like mercury and PCBs. In addition, you could look for the source of the oil to make sure it comes from a fish that is known to have low contaminant and mercury levels.

Try to avoid supplements that contain fillers or artificial ingredients.

Fish oil supplements are prone to oxidation and can go rancid. Capsuls and liquids can be stored in the refrigerator to maintain freshness and slow oxidation. Be sure to check the expiration date. Oxidation will cause a bad odor so you will know if they have gone rancid. Products that also contain vitamin E have been suggested to last longer.

Form

Fish oils are available in different supplement form including natural triglycerides, free fatty acids, ethyl esters, re-esterified triglycerides, and phospholipids. Natural triglycerides are the form that occurs naturally in fish oil. It is most common that they are in the triglyceride form but some come in the form of omega-3 acid ethyl esters or reformed triglycerides. Krill oil is primarily phospholipids.

Some have suggested that omega 3 in the form of ethyl esters have a lower bioavailability (absorption is more efficient) compared to triglycerides or phospholipids but research on this has provided mixed results. All forms have been shown to increase blood levels of omega-3.

The fish oil preparations are also available as capsules, soft gels, liquid or gummy forms. Which fish oil product form you decide on may be a matter of personal choice. Some find the capsules rather large and difficult to swallow. In this case, the liquid form or gummy form is an option.

Concentration

Natural FO is only 30% EPA and DHA. Likewise, most fish oil capsules will partially be made up of the omega 3s and partially other fats.

It is important to look at the product label for ingredients and the Supplement Facts label to check that the EPA and DHA content provides an appropriate amount.

Side Effects

The most common side effects have to do with a fishy taste, a lingering fishy aftertaste, belching, and bad breath. Some have mentioned heartburn, nausea or upset stomach, and diarrhea as side effects of omega 3.

Fish oil supplements may help to reduce blood pressure. Blood pressure should be monitored closely if fish oil capsules are introduced. Should your blood pressure drop too low, you may need adjustments to your medications.

Bottom Line

A healthy diet is one that includes adequate amounts of omega 3 fatty acids. This is best done by including cold-water fish in the diet in place of meat. A Mediterranean diet that is low in total dietary fat and includes mostly unsaturated fats is recommended. Most healthy adults should be able to meet their omega-3 intake goals by consuming fish. 

For those who can not eat seafood, there are alternative ways of getting omega 3s. Several types of fatty acid supplements are available on the market. 

Additionally, fish oil supplements can be used in conjunction with statins to treat hypertriglyceridemia. They also provide some cardiovascular benefits and prevent major cardiovascular events associated with coronary artery disease. 

A high dose of fish oil is available by prescription as a treatment option for high triglyceride levels. If you have high triglycerides and additional cardiovascular risk factors, discuss with your health care provider whether the effect of fish oil could play in an important role in your health.

Omega 3s may also help alleviate rheumatoid arthritis symptoms. Research continues on the benefits of fish oil and the efficacy of its use with regard to brain health, eye health, and disease prevention.

While there are no serious side effects, the use of fish oil should be discussed with your medical doctor and/or Registered Dietitian to find out if supplementing is right for you. 

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