Fish Oil

Omega-3s are polyunsaturated fatty acids (a type of so-called “healthy fat”) that is essential for the healthy maintenance of lipids, one of the four major types of macromolecules in the human body. Omega-3 fatty acids are very important for proper brain function, disease prevention, and optimal health.

There are three types of omega-3 fatty acids: alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). ALA comes from plants and nuts (such as hemp, walnuts, soybeans, flaxseed, and canola oil), whereas DHA and EPA are found in marine organisms such as fatty fish, krill, and algae. The human body can only metabolize about 10% of plant-based ALA molecules into the other forms of omega-3, meaning that DHA and EPA need to be obtained by eating fatty fish or consuming omega-3 supplements.^{[11, 12, 13, 14]}

The DHA and EPA that are present in fish, fish oil, and krill oil, are originally synthesized by microalgae, not by the fish. When fish consume phytoplankton that consumed the microalgae, they accumulate the omega-3s in their tissues.^[15]

Fish oil contains both EPA and DHA. EPA is a fatty acid essential for the whole body, whereas DHA is mostly used by the eyes and the brain for visual and neurological benefits.^[13] The human brain consists of about 60% fat, half of which is in the form of the essential fatty acid DHA. DHA is also found in the retina of the eyeball and regular consumption is important to prevent age-related eye diseases like macular degeneration.^[3] However, since EPA and DHA have similar molecular structures (DHA is two carbon atoms longer than EPA), EPA can be converted into DHA through a biological pathway called Sprecher’s shunt when more DHA is needed.

Omega-3 fatty acids DHA and EPA perform a variety of crucial roles throughout the human body such as breaking down triglycerides, regulating muscle activity, secreting hormones, clotting blood, and facilitating cell division and growth.^[5] One of the best-publicized benefits of omega-3 is its potential for reducing inflammation and keeping the heart healthy, and there has been significant research to support this claim.^[8] Although there is still some debate about what specific role omega-3 plays in combating heart disease, many studies have shown that omega-3 (specifically EPA) can help to decrease the levels of triglycerides in the blood and lower the risk of atherosclerosis, among other positive cardiovascular benefits.^{[14, 16, 17]} Many studies strongly support the claim that regular consumption of fish decreases the risk of cardiovascular diseases and some have even indicated that by ingesting the recommended amount of omega-3, individuals can substantially reduce their risk of sudden death from a heart attack.^{[7, 18, 19]}

Likewise, DHA fulfills many important functions in the brain, ranging from helping to combat depression and preventing neurological disorders to maintaining and improving cognitive function.^{[3, 8, 15]} The synapses between neurons contain DHA, indicating that having a sufficient amount of this type of omega-3 is crucial for neurotransmission. Conversely, low levels of DHA have been cited as a factor that can contribute to the onset of Alzheimer’s disease and development of dementia.^{[6, 7, 13]} DHA is also contained in the retinas and helps to develop and maintain healthy vision.

Further research has indicated that omega-3 fatty acids perform other beneficial functions throughout the body, such as strengthening joints to prevent rheumatoid arthritis.^{[5, 8, 20]}

Omega-3 also plays a role in “turning on” gene expression. The amounts of EPA and DHA in the body can help determine the speed of gene regulation.^[21] Omega-3 fatty acids also support the internal production of energy by undergoing β-oxidation, which splits the carbon chain and releases CO2, thus contributing to the ATP production process.^[22]

Overall, the primary function of omega-3 fatty acids is to regulate levels of various forms of lipids throughout vital parts of the body, including the brain and the heart. Omega-3 can increase levels of HDL (“good cholesterol”), decrease triglyceride levels, and help maintain a healthy blood pressure.^[23] Essentially, omega-3 provides the good fat that is needed to eliminate harmful fats from the body.

After being ingested, omega-3 is digested in the small intestine and then absorbed into the blood. Depending on the type of omega-3 consumed, the molecules may undergo a series of desaturation and elongation processes known as Sprecher’s pathway (or Sprecher’s shunt). For example, ALA molecules can be converted into molecules of EPA and DHA. EPA molecules can be converted into DHA molecules through Sprecher’s shunt, as well.^[22] ALA, EPA, and DHA can also desaturate or elongate in order to become other types of fatty acids, if and when they are required in the body.^[3]

Over the last century, the American diet has changed so that people now consume significantly less fish, which is heavy in the fatty acid omega-3, and significantly more products containing corn oil, which is heavy in the fatty acid omega-6.^[5] It it theorized, that omega-6 fatty acids compete with omega-3 fats in the body, causing complications such as increasing inflammation and cardiovascular disease.^[3] And unlike omega-3s, which provide “good fats” for the body, corn oil contains trans fatty acids, which are known to contribute to high levels of low-density lipoproteins (LDL cholesterol) and triglycerides in the blood.^{[3, 6]}

Furthermore, the recent move towards farmed sources of fish vs. wild ones also contributes to a wide-scale underconsumption of omega-3s. Farmed fish has been shown to have significantly less DHA and EPA than wild fish due to suboptimal feed used in aqua-farms.^[24]

Symptoms of clinical omega 3 deficiency include general fatigue, brain fog and memory problems, dry skin, heart problems, trouble regulating mood and depression, inflammation, and poor circulation.^[10] Someone with low levels of omega 3, but not quite at the clinical deficiency level, can experience nonspecific symptoms or be asymptomatic.
It is especially important for pregnant and lactating women to make sure they are not deficient in omega-3 as this essential fatty acid contributes to healthy fetal development.^{[3, 8]}

Fatty fish such as salmon, tuna, and mackerel are primary natural sources of the omega-3 fatty acids EPA and DHA, and it is recommended to eat fatty fish twice a week.^[18] Opt for wild fish over farmed whenever possible, however. A recent fatty acid composition analysis of Scottish farmed Atlantic salmon concluded a significant decrease in the fish EPA and DHA content due to feed replacement.^[15] In wild salmon, the ratio of omega-3s to omega-6s is 14.5. Due to the use of vegetable oils in feed for farmed salmon, their ratio can be as low as 1.5 as well as decreased overall omega-3 levels per serving.^[24]

When adding fatty fish to your diet, it is important to be aware of its potential for contamination with heavy metals and other toxins, which can be especially hazardous for pregnant and lactating women and young children.^[10] Fish caught from the open water, as well as farmed fish, often contain some amounts of methyl mercury due to pollution and other environmental factors.^{[8, 18]} Certain types of fish should generally be avoided due to their high mercury content, including shark, swordfish, tilefish, and king mackerel.^[20]

Because most Americans are not consuming enough omega-3 from fatty fish, daily supplementation with fish oil is a viable option to make up for the lack of suggested intake. Fish oil contains sufficient amounts of DHA and EPA to complement a diet that is low in fatty fish.^[25] Although different fish oil supplements on the market contain varying amounts amounts of EPA and DHA, they always contain a higher proportion of EPA than DHA.

When choosing an omega 3 supplement, you should be concerned about the source, the processing it’s been through, the reputation of the manufacturer, and the molecular form it is in.

There are 3 main forms of omega-3s available on the market today: phospholipids, triglycerides, and ethyl esters. When fish oil is consumed in the form of eating fatty fish like wild salmon, the fish oil is mostly in the triglyceride form, whereas most supplements on the market are in ethyl ester form. Natural triglyceride fish oil is converted to ethyl ester form to purify it and concentrate it for supplement purposes. This is done by replacing glycerol molecules in the triglyceride with ethanol.^[26]

Phospholipids and triglycerides have been proven to be much more readily absorbed by the body than ethyl esters. One study found that fish oil free acids were absorbed at a rate of at least 95 percent. Two forms of triglycerides (eicosapentaenoic acid and docosahexaenoic acid) were absorbed 68 percent and 57 percent as well as the free acids, while ethyl esters were absorbed only about 20 percent as well as the free acids.^[27] Phospholipids, found in krill oil, also have been determined to have greater bioavailability than ethyl esters.^[28] In addition to not being absorbed as readily, ethyl esters also oxidize (go rancid) much faster than triglycerides. That said, consuming a high-fat meal along with ethyl esters has been shown to increase their rate of absorption to about 60 percent.^[29]

Because of the relatively low bioavailability of ethyl esters, some supplement manufacturers have taken on the extra process of turning the purified and concentrated ethyl ester form of fish oil to triglyceride form — otherwise known as re-esterified triglycerides. This is currently the best form to consume. Unfortunately, most of the supplements on the market are ethyl esters because they are the cheapest to produce.

Although krill oil is more expensive than fish oil, it generally contains smaller doses of omega-3 fatty acids. Krill oil supplements contain smaller amounts of EPA and DHA per serving because the fatty acids in krill oil cannot be concentrated, but their phospholipid form is also better absorbed than ethyl ester fish oil. Krill oil comes from the Antarctic krill, a shrimp-like crustacean. The health benefits of krill oil are not yet thoroughly understood, but existing research is promising. As a result, for people who want to increase their DHA and EPA consumption, triglyceride-form fish oil is a better choice.

Krill oil might be metabolized more easily than fish oil because the EPA and DHA molecules in krill oil are bonded to phospholipids, whereas those in fish oil are bonded to triglycerides.^{[1, 14, 16]} Phospholipids are thought to be more absorbable because they are both hydrophobic and hydrophilic, whereas triglycerides are only hydrophobic. Essentially, the fatty acids in krill oil are dissolvable in water but those in fish oil are not. It follows that the EPA and DHA molecules in krill oil may be more bioavailable than those contained in fish oil, if fish oil is not consumed with a meal containing fat.^{[2, 15, 22]} However, although some studies have found that the Omega-3s in krill oil are more bioavailable than those in fish oil, other studies have found no differences in bioavailability.^[30] For example, one study found that when the same doses and Omega-3 concentrations were used, fish oil and krill oil products had comparable oral bioavailability.^[31] The bottom line is that the research is mixed, at best, on whether you can absorb more Omega-3s from krill oil than from fish oil.

Krill oil also contains the antioxidant astaxanthin, which helps to preserve the omega-3s in the oil. In addition, although research on astaxanthin is limited, some studies show that it helps to keep omega-3s from breaking down or going rancid. By itself, astaxanthin has been shown to reduce oxidative stress and inflammation which makes it a very valuable supplement for long-term health.^{[1, 8]}

On a more global level, the production of krill oil is thought to be more sustainable than the production of fish oil. Krill are easier to harvest than many fish species.^[15] Furthermore, obtaining omega-3 directly from fish is becoming more expensive and potentially more detrimental to the environment, as commercial fishing has led to the decline of certain fish populations. An alternative source of omega-3 such as krill oil may be a plausible and sustainable option.^[8] However, krill oil is still a relatively new focus for health research. Further studies are needed to fully understand how the omega-3 in krill oil is absorbed by the body, as well as its potential health benefits.^[16] As krill oil consumption increases, researchers theorize that lower quality products with higher levels of pollution will enter the market. Watch out for krill oil purity and manufacturing quality when choosing a supplement.^[32]

It is difficult to get enough Omega 3s if you’re a vegan, since EPA and DHA are primarily available in fish, krill, and algal oil. Alpha-linolenic acid (ALA) is a precursor to EPA and DHA that is found in the oils of flaxseed, soybean, canola, and other plants. However, ALA must be converted by the body into EPA and DHA, and the conversion rate is less than 15 percent. As a result, consuming ALA is not a practical way to increase levels of EPA and DHA.^[33]

Algal oil, which contains significant amounts of DHA (and small amounts of EPA), is a good option for vegetarians who choose not to consume fish oil or krill oil, and people who have seafood allergies. Due to low content of EPA however, it is not the best overall choice for omega-3 supplementation.

The National Heart Association recommends eating fatty fish and consuming plant-based omega-3 fatty acids at least twice a week. This level of consumption provides approximately 400-500 mg per week of EPA and DHA.^{[3, 7, 8]} The Mayo Clinic estimates that Americans consume only 10 to 20 mg of EPA and DHA each day, or approximately 70-140 mg per week, which is well under half of the recommended amount.^[6]

Fish oil supplements vary in their EPA and DHA content, and also vary widely in absorption and purity. The most common supplements on the market are in the not well absorbed ethyl ester form (assume the supplement you are looking at is ethyl ester unless otherwise stated). These commonly contain about 180 mg of EPA and 120 mg of DHA, although this will vary among different brands, and some contain significantly more (highly concentrated) and some less. Some omega 3 supplements are also in phospholipid form but sourced from fish roe.

The re-esterified triglyceride form of fish oil has the best of both worlds as it is well absorbed, is highly filtered and concentrated, and does not go rancid (oxidize) as quickly as the ethyl ester form. However, this form also tends to be more expensive as manufacturers need to put the purified and concentrated ethyl ester form through a glycerolysis process to convert it back to the well-absorbed triglyceride formulation.

The Food and Drug Administration (FDA) advises that without the permission of a doctor, you should not consume more than 3 grams of omega-3 fatty acids per day (of which no more than 2 grams should come from supplements).^[9] However, it is common for medical professionals to recommend that individuals with high cholesterol, high triglycerides, or a history of coronary heart disease consume significantly higher doses of omega-3 fatty acids, and they may even recommend a prescription-strength formulation.^{[10, 11]}

You can safely consume up to 2,000 mg of DHA + EPA daily from a high-quality, highly absorbed fish oil. People consuming closer to the upper side of the range are bound to see more benefits. Studies show that eating a high-fat meal with fish oil consumption increases its absorption.^[34]

As with all supplements, always follow the recommended dosage guidelines on the packaging, and if you have been advised to take fish oil or krill oil by a doctor, closely follow his or her instructions. The FDA has advised that without a doctor’s consent, people should not consume more than 3 grams per day of omega-3 fatty acids, as a combination of food and supplementation, and no more than 2 grams of omega-3 fatty acids per day should come from supplementation.^[6]

There are a few omega-3 formulations that have been approved by the FDA for prescription use. Lovaza, Vascepa, and Epanova are high-dosage omega-3 formulations that can be prescribed by a doctor for individuals with high cholesterol, high triglycerides, or heart disease. For comparison, there are 840 mg of EPA and DHA in each Lovaza capsule of fish oil; about 465 mg of that is EPA and 375 mg is DHA. The suggested dose is 4 capsules daily, which is twice the FDA recommended amount for those supplementing with a non-prescription fish oil.

Indications of consuming too much omega-3 include nausea, diarrhea, and other gastrointestinal complications. Although this can be caused by taking an excessively high dose, these side effects can also result from the specific ingredients in the supplement. Trying a smaller dose or a different formulation may help, but you should consult with a doctor of side effects persist or if serious side effects such as changes in blood pressure, blood sugar, or bleeding occur. Cod liver oil supplements contain omega-3 fatty acids as well as substantial amounts of vitamin A and vitamin D. When supplementing with cod liver oil, it is important to monitor not only your omega-3 intake but also your vitamin A and vitamin D intake to ensure that you are only ingesting the recommended amounts of those compounds (as too much vitamin A is toxic to the body and that level is reached sooner than most anticipate).

Caution should be taken when combining omega-3 supplements with anything that affects blood pressure or blood sugar levels, or any medication that increases the risk of bleeding.^[6] There are specific medications that can have interactions with omega-3 fatty acid supplements. You should always talk to your doctor before beginning an omega-3 supplement if you are taking a blood-thinning medication (including aspirin, warfarin, or clopidogrel).^[35] Omega-3 supplements can also have interactions with cholesterol-lowering medications, diabetes medications, and nonsteroidal anti-inflammatory drugs. Individuals taking these medications should always consult with a doctor before beginning omega-3 supplementation, as the medication dosages may need to be adjusted accordingly.

When choosing a fish oil supplement, always select a high-quality brand in order to avoid sources of fish oil that have been contaminated by heavy metals or other toxins. Manufacturers should always certify that their products are free from mercury, lead, and cadmium, and do third party independent testing to prove it.

All of our recommended fish oil products pass the following standards, and we recommend this is what you look for in your fish oil product:

• Highly absorbable phospholipid or triglyceride form
• Oil is sourced from wild cold-water, small, fatty fish or fish roe
• Fish oil is purified using an oxygen-free process (to prevent rancidity)
• Final product is independently tested for purity (to ensure no contaminants such as mercury, lead, or cadmium)
• Final product is independently tested for dosage
• Final product is highly concentrated and has high bioavailability
• Manufacturer has excellent reputation for high-quality products
• Manufacturer has been inspected and certified by watch-dog fish oil and supplement agencies such as the NSF, TGA, CRN, USP, EP, and IFOS

Time-release preparations can diminish some of the unpleasant side effects of fish oil such as nausea, diarrhea, bloating, burping, and gas. Certain fish oil supplements have a “fishy” aftertaste that can be somewhat off-putting, so choose a formulation with an enteric coating, which prevents the supplement from being digested until it reaches the small intestines.^[36] Look for a “burpless” option – all of our recommended products have been screened for this. Fish oil (but not krill oil) supplements should always be refrigerated to prevent the oil from going rancid.^[10]

References:
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