What is krill oil

Krill (Euphausia superba) are small red-colored crustaceans, similar to shrimp, that flourish in the extremely cold waters of the Antarctic Ocean. Krill primarily serve as a food source for other animals in the ocean, for example – whales, seals, penguins, squid and fish. Similar to fish, krill consume a diet rich in omega-3 fatty acids (e.g, algae) and are thereby a natural source of Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) Omega-3 essential fatty acids ¹⁾. Although there are other sources you can get the Omega-3 essential fatty acids from, for example Alpha-linolenic acid (ALA)  from plant oils such as flaxseed, soybean, and canola oils; only krill oil and fish oil is rich in Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) Omega-3 essential fatty acids. Omega-3 Eicosapentaenoic acid (EPA) and Omega-3 Docosahexaenoic acid (DHA) are found in seafood, including fatty fish (e.g., salmon, tuna, and trout) and shellfish (e.g., crab, mussels, and oysters).

• Note the differences between the Omega-3 fatty acids found in flaxseed, soybean, vegetable oils [alpha-linolenic acid (ALA)] from those in fish and seafoods [Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA)].
• Your bodies can convert plant omega-3 fatty acids, Alpha-linolenic acid (ALA), to fish omega-3 fatty acids, Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA), but only a small fraction about 5% of Alpha-linolenic acid (ALA) to eicosapentaenoic acid (EPA), the level of eicosapentaenoic acid (EPA) in blood does not rise when you eat α-linolenic acid (ALA) ²⁾.

Krills survival in such a frigid environment is attributable to krill having a high content of long-chain polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), attached to their cell membranes via phospholipids (primarily phosphatidylcholine). This structure provides optimum membrane fluidity in cold temperatures and an ideal source of omega-3 fatty acids ³⁾. Fish oil contains abundant amounts of Omega-3 PUFAs, most of which is stored as triglycerides. Animal and human studies indicate long-chain polyunsaturated fatty acids bound to phospholipids, like those found in krill oil, have better absorption and delivery to the brain than their methyl ester or triglyceride-formed fish oil counterparts ⁴⁾, ⁵⁾, ⁶⁾.

Seafood vs. Supplements

• For some health conditions, the evidence for benefits from seafood (fish and shellfish) is stronger than the evidence for omega-3 supplements.

How could this happen?

Here are some possibilities:

• Seafood may provide enough omega-3s; more may not be better.
• Other nutrients in seafood besides omega-3s may play a role in its benefits.
• Some of the benefits of seafood may result from people eating it in place of less healthful foods.
• There’s evidence that people who eat seafood have generally healthier lifestyles.

The Federal Government’s Dietary Guidelines for Americans ⁷⁾ recommends that adults eat 8 or more ounces of a variety of seafood (fish or shellfish) per week for the total package of nutrients seafood provides, and that some seafood choices with higher amounts of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) be included. Smaller amounts of seafood are recommended for young children.

The American Heart Association recommends eating fish (particularly fatty fish) at least two times (two servings) a week. Each serving is 3.5 ounce cooked, or about ¾ cup of flaked fish. Fatty fish like salmon, mackerel, herring, lake trout, sardines and albacore tuna are high in omega-3 fatty acids ⁸⁾.

Increasing omega-3 fatty acid consumption through foods is preferable. However, those with coronary artery disease, may not get enough omega-3 by diet alone. These people may want to talk to their doctor about supplements. And for those with high triglycerides, even larger doses could help.

Patients taking more than 3 grams of omega-3 fatty acids from capsules should do so only under a physician’s care. High intakes could cause excessive bleeding in some people.

Eating fish, is there a catch?

Some types of fish may contain high levels of mercury, PCBs (polychlorinated biphenyls), dioxins and other environmental contaminants. Levels of these substances are generally highest in older, larger, predatory fish and marine mammals.

The benefits and risks of eating fish vary depending on a person’s stage of life.

• Children and pregnant women are advised by the U.S. Food and Drug Administration (FDA) to avoid eating those fish with the potential for the highest level of mercury contamination (e.g., shark, swordfish, king mackerel or tilefish); to eat up to 12 ounces (two average meals) per week of a variety of fish and shellfish that are lower in mercury (e.g., canned light tuna, salmon, pollock, catfish); and check local advisories about the safety of fish caught by family and friends in local lakes, rivers and coastal areas.
• For middle-aged and older men and postmenopausal women, the benefits of fish consumption far outweigh the potential risks when the amount of fish are eaten is within the recommendations established by the FDA and Environmental Protection Agency.
• Eating a variety of fish will help minimize any potentially adverse effects due to environmental pollutants.

Five of the most commonly eaten fish or shellfish that are low in mercury are shrimp, canned light tuna, salmon, pollock, and catfish. Avoid eating shark, swordfish, king Mackerel, or tilefish because they contain high levels of mercury.

Avoid large predatory fish (e.g. marlin, pike, swordfish and shark), which are more likely to be contaminated with methylmercury.

[Source ⁹⁾]

What are omega-3 fatty acids?

Omega-3 fatty acids are essential fatty acids, a type of polyunsaturated fatty acid (PUFA) that are vital for brain and nerve function. They are called an “essential fatty acid” because you cannot manufacture them yourself and must get them from food.

Polyunsaturated fatty acids (PUFAs) can be further subdivided on the basis of the location of the first double bond relative to the methyl terminus of the chain. For example, Omega-3 and Omega-6 fatty acids are two of the most biologically significant polyunsaturated fatty acid classes, and have their first double bond on either the third or sixth carbon from the chain terminus, respectively. The final carbon in the fatty acid chain is also known as the omega carbon, hence the common reference to these fatty acids as Omega-3 or Omega-6 PUFAs. The distinction between omega-6 and omega-3 fatty acids is based on the location of the first double bond, counting from the methyl end of the fatty acid molecule (see Figure 2). Omega-6 fatty acids are represented by Linoleic acid (LA) (18:2ω-6) and Arachidonic acid (AA) (20:4ω-6) and omega-3 fatty acids by Alpha-linolenic acid (ALA) (18:3ω-3), Eicosapentaenoic acid (EPA) (20:5ω-3) and Docosahexaenoic acid (DHA) (22:6ω-3).

There are three main types of omega-3 fatty acids:

• Eicosapentaenoic acid (EPA)
• Docosahexaenoic acid (DHA)
• Alpha-linolenic acid (ALA).

The general structures for Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) are shown in Figure 2. Commonly available dietary sources of Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA)are listed in Table 2. Whereas plant foods and vegetable oils lack EPA and DHA, some do contain varying amounts of the Omega-3 PUFA alpha-linolenic acid (ALA), which has 18 carbon atoms and 3 double bonds (Figure 2). Many vegetable oils are greatly enriched in Omega-6 fatty acids (mainly as linoleic acid [LA] in corn, safflower, sunflower and soybean oils), but canola oil (nonhydrogenated), ground flaxseed and walnuts are rich sources of ALA.

The typical North American diet provides about 1–3 g of Omega-3 PUFA alpha-linolenic acid (ALA) per day but only 0.10–0.15 g of EPA (Eicosapentaenoic acid) plus DHA (Docosahexaenoic acid) per day ¹⁰⁾, ¹¹⁾. The very high intake of Omega-6 PUFA, mostly as linoleic acid (LA) (Figure 2) in our diet (12–15 g/day) from common vegetable oils (corn, safflower, soybean) and other sources, yields an overall n-6:n-3 dietary ratio (total omega-6 fatty acids in the diet: total omega-3 fatty acids in the diet) of about 8:1. Health Canada has recommended that this ratio be as low as 4:19 to reduce the competitive influence of high Omega-6 PUFA linoleic acid (LA) intakes on omega-3 PUFA alpha-linolenic acid (ALA) metabolism to its longer chain products (such as EPA and DHA). Although high intakes of Omega-6 PUFA linoleic acid (LA) can provide some modest blood cholesterol lowering, experimental studies in animals have raised concerns regarding the enhancing effect of these high intakes on certain cancers ¹²⁾. This association has not been established in human studies ¹³⁾.

Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) are synthesised by algae and marine plants, particularly in cold water. As a result, most marine-based supplements, including fish oil and krill oil, contain Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA).

Omega-3 fatty acid alpha-linolenic acid (ALA) is made by plants and high amounts of alpha-linolenic acid (ALA) can be found in vegetable oils and nuts. Flax seeds, canola, soy, perilla, and walnuts are all high in ALA. In addition, alpha-linolenic acid (ALA) is also found in the fat of animals that eat grass. Our bodies are able to convert ALA into EPA and DHA; however, research suggests only a small fraction about 5% of Alpha-linolenic acid (ALA) to eicosapentaenoic acid (EPA), the level of eicosapentaenoic acid (EPA) in blood does not rise when we eat α-linolenic acid  (ALA) ¹⁴⁾.

Note the differences between the Omega-3 fatty acids found in flaxseed, soybean, vegetable oils and walnuts [alpha-linolenic acid (ALA)] from those in fish and seafoods [Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA)].

Long-chain Omega-3 and Omega-6 PUFAs are synthesized from the essential fatty acids: alpha-linolenic acid (ALA) and linoleic acid (LA), respectively. Basic structures of these two parent PUFAs are shown in Figure 2. An essential fatty acid cannot be made by the body and must be obtained through dietary sources. Animals and humans have the capacity to metabolize essential fatty acids to long-chain derivatives. Because the Omega-3 and Omega-6 pathways compete with one another for enzyme activity, the ratio of Omega-6 to Omega-3 PUFAs is very important to human health. An overabundance of fatty acids from one family will limit the metabolic production of the longer chain products of the other. The typical Western diet provides Omega-6 and Omega-3 PUFAs in a ratio ranging from 8:1 to 25:1 ¹⁵⁾, values in severe contrast with the recommendations from national health agencies of approximately 4:1 ¹⁶⁾. Lowering the Omega-6/Omega-3 ratio would reduce competition for the enzymes and facilitate the metabolism of more downstream products of alpha-linolenic acid (ALA).

Mammalian cells cannot convert Omega-6 to Omega-3 fatty acids because they lack the converting enzyme, omega-3 desaturase. Omega-6 and Omega-3 fatty acids are not interconvertible, are metabolically and functionally distinct, and often have important opposing physiological effects, therefore their balance in the diet is important ¹⁷⁾.

This study ¹⁸⁾ showed a balanced oOmega-6/Omega-3 ratio 1–2/1 is one of the most important dietary factors in the prevention of obesity, along with physical activity. A lower Omega-6/Omega-3 ratio should be considered in the management of obesity ¹⁹⁾.

Because most diets are already very rich in Omega-6 PUFAs, greater focus needs to be placed on incorporating Omega-3 PUFAs into our diet. Dietary sources of Omega-3 PUFAs are readily available but in limited quantities. Many foods contain alpha-linolenic acid (ALA), including certain vegetable oils, dairy products, flaxseed, walnuts and vegetables ²⁰⁾. Fatty fish, such as mackerel, herring and salmon, provide an excellent source of the long-chain derivatives of ALA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ²¹⁾.

Figure 1. Polyunsaturated Fatty Acids Structure (PUFA)

Figure 2. Omega-3 fatty acids and Omega-6 fatty acids structure

Figure 3. Conversion of dietary ALA to EPA and DHA via Desaturation, elongation and retroconversion of polyunsaturated fatty acids.

[Source ²²⁾]

Recommended Intakes of Omega-3 Fatty Acids

Intake recommendations for fatty acids and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board of the Institute of Medicine. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and sex, include:

• Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals.
• Adequate Intake (AI): established when evidence is insufficient to develop an RDA; intake at this level is assumed to ensure nutritional adequacy.
• Estimated Average Requirement (EAR): average daily level of intake estimated to meet the requirements of 50% of healthy individuals. It is usually used to assess the adequacy of nutrient intakes in populations but not individuals.
• Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects.
• Acceptable Macronutrient Distribution Range (AMDR): range of intake for a particular energy source (macronutrient) that is associated with reduced risk of chronic disease while providing intakes of essential nutrients.

When the Food and Nutrition Board of the Institute of Medicine last reviewed omega-3s, insufficient data were available to establish an Estimated Average Requirement (EAR), so the Food and Nutrition Board of the Institute of Medicine established AIs for all ages based on omega-3 intakes in healthy populations ²³⁾.

Table 1 lists the current Adequate Intake (AIs) for omega-3s in grams per day. Human milk contains omega-3s as ALA, EPA and DHA, so the Institute of Medicine established an AI for infants from birth to 12 months that is equivalent to the mean intake of omega-3s in healthy, breastfed infants.

For infants, the AIs apply to total omega-3s. For ages 1 and older, the AIs apply only to ALA because ALA is the only omega-3 that is essential. The Institute of Medicine did not establish specific intake recommendations for EPA, DHA or other long chain omega-3s.

The Federal Government’s Dietary Guidelines for Americans ²⁴⁾ recommends that adults eat 8 or more ounces of a variety of seafood (fish or shellfish) per week for the total package of nutrients seafood provides, and that some seafood choices with higher amounts of EPA and DHA be included. Smaller amounts of seafood are recommended for young children.

Table 1: Adequate Intakes (AIs) for Omega-3s

Age	Male	Female	Pregnancy	Lactation
Birth to 6 months*	0.5 g	0.5 g
7–12 months*	0.5 g	0.5 g
1–3 years**	0.7 g	0.7 g
4–8 years**	0.9 g	0.9 g
9–13 years**	1.2 g	1.0 g
14–18 years**	1.6 g	1.1 g	1.4 g	1.3 g
19-50 years**	1.6 g	1.1 g	1.4 g	1.3 g
51+ years**	1.6 g	1.1 g

*As total omega-3s
**As ALA

[Source ²⁵⁾]

Table 2. Omega-3 Fatty Acid Foods EPA (Eicosapentaenoic acid) and DHA (Docosahexaenoic acid) – Fish and Seafood Sources

[Source ²⁶⁾]

Table 3. EPA (Eicosapentaenoic acid) and DHA (Docosahexaenoic acid) Content of Fish Species

Fish Species and Description	DHA per 100 g	EPA per 100 g	DHA+EPA per 100 g	DHA+EPA per 85 g (3 oz.)
Crustaceans, crab, Alaska king, cooked, moist heat	0.118	0.295	0.413	0.351
Crustaceans, crab, blue, cooked, moist heat	0.231	0.243	0.474	0.403
Crustaceans, crab, Dungeness, cooked, moist heat	0.113	0.281	0.394	0.335
Crustaceans, crab, queen, cooked, moist heat	0.145	0.332	0.477	0.405
Crustaceans, crayfish, mixed species, farmed, cooked, moist heat	0.038	0.124	0.162	0.138
Crustaceans, crayfish, mixed species, wild, cooked, moist heat	0.047	0.119	0.166	0.141
Crustaceans, lobster, northern, cooked, moist heat	0.031	0.053	0.084	0.071
Crustaceans, shrimp, mixed species, cooked, moist heat	0.144	0.171	0.315	0.268
Crustaceans, spiny lobster, mixed species, cooked, moist heat	0.139	0.341	0.480	0.408
Fish, anchovy, European, raw	0.911	0.538	1.449	1.232
Fish, anchovy, European, canned in oil, drained solids	1.292	0.763	2.055	1.747
Fish, bass, freshwater, mixed species, cooked, dry heat	0.458	0.305	0.763	0.649
Fish, bass, striped, cooked, dry heat	0.750	0.217	0.967	0.822
Fish, bluefish, cooked, dry heat	0.665	0.323	0.988	0.840
Fish, turbot, cooked, dry heat	0.123	0.09	0.213	0.181
Fish, carp, cooked, dry heat	0.146	0.305	0.451	0.383
Fish, catfish, channel, farmed, cooked, dry heat	0.128	0.049	0.177	0.150
Fish, catfish, channel, wild, cooked, dry heat	0.137	0.100	0.237	0.201
Fish, caviar, black and red, granular	3.800	2.741	6.541	5.560
Fish, cod, Atlantic, cooked, dry heat	0.154	0.004	0.158	0.134
Fish, cod, Pacific, cooked, dry heat	0.173	0.103	0.276	0.235
Fish, croaker, Atlantic, raw	0.097	0.123	0.22	0.187
Fish, dolphin fish, cooked, dry heat	0.113	0.026	0.139	0.118
Fish, drum, freshwater, cooked, dry heat	0.368	0.295	0.663	0.564
Fish, eel, mixed species, cooked, dry heat	0.081	0.108	0.189	0.161
Fish, fish portions and sticks, frozen, preheated	0.128	0.086	0.214	0.182
Fish, flatfish (flounder and sole species), cooked, dry heat	0.258	0.243	0.501	0.426
Fish, grouper, mixed species, cooked, dry heat	0.213	0.035	0.248	0.211
Fish, haddock, cooked, dry heat	0.162	0.076	0.238	0.202
Fish, halibut, Atlantic and Pacific, cooked, dry heat	0.374	0.091	0.465	0.395
Fish, halibut, Greenland, cooked, dry heat	0.504	0.674	1.178	1.001
Fish, herring, Atlantic, cooked, dry heat	1.105	0.909	2.014	1.712
Fish, herring, Atlantic, kippered	1.179	0.97	2.149	1.827
Fish, herring, Pacific, cooked, dry heat	0.883	1.242	2.125	1.806
Fish, lingcod, cooked, dry heat	0.130	0.133	0.263	0.224
Fish, mackerel, Atlantic, cooked, dry heat	0.699	0.504	1.203	1.023
Fish, mackerel, king, cooked, dry heat	0.227	0.174	0.401	0.341
Fish, mackerel, Pacific and jack, mixed species, cooked, dry heat	1.195	0.653	1.848	1.571
Fish, mackerel, Spanish, cooked, dry heat	0.952	0.294	1.246	1.059
Fish, mullet, striped, cooked, dry heat	0.148	0.18	0.328	0.279
Fish, ocean perch, Atlantic, cooked, dry heat	0.271	0.103	0.374	0.318
Fish, perch, mixed species, cooked, dry heat	0.223	0.101	0.324	0.275
Fish, pike, northern, cooked, dry heat	0.095	0.042	0.137	0.116
Fish, pike, walleye, cooked, dry heat	0.288	0.11	0.398	0.338
Fish, pollock, Atlantic, cooked, dry heat	0.451	0.091	0.542	0.461
Fish, pompano, Florida, cooked, dry heat	??	??	??	0.620 est
Fish, rockfish, Pacific, mixed species, cooked, dry heat	0.262	0.181	0.443	0.377
Fish, roe, mixed species, cooked, dry heat	1.747	1.26	3.007	2.556
Fish, roe, mixed species, raw	1.363	0.983	2.346	1.994
Fish, roughy, orange, raw	0	0.001	0.001	0.001
Fish, sablefish, cooked, dry heat	0.920	0.867	1.787	1.519
Fish, sablefish, smoked	0.945	0.891	1.836	1.561
Fish, salmon, Atlantic, farmed, cooked, dry heat	1.457	0.69	2.147	1.825
Fish, salmon, Atlantic, wild, cooked, dry heat	1.429	0.411	1.84	1.564
Fish, salmon, Chinook, cooked, dry heat	0.727	1.01	1.737	1.476
Fish, salmon, chum, cooked, dry heat	0.505	0.299	0.804	0.683
Fish, salmon, chum, drained solids with bone	0.702	0.473	1.175	0.999
Fish, salmon, coho, farmed, cooked, dry heat	0.871	0.408	1.279	1.087
Fish, salmon, coho, wild, cooked, dry heat	0.658	0.401	1.059	0.900
Fish, salmon, pink, cooked, dry heat	0.751	0.537	1.288	1.095
Fish, salmon, sockeye, cooked, dry heat	0.700	0.53	1.23	1.046
Fish, sardine, Atlantic, canned in oil, drained solids with bone	0.509	0.473	0.982	0.835
Fish, scup, raw (Porgy—assigned to low omega-3 group)	no data	no data	no data	no data
Fish, sea bass, mixed species, cooked, dry heat	0.556	0.206	0.762	0.648
Fish, sea trout, mixed species, cooked, dry heat	0.265	0.211	0.476	0.405
Fish, shad, American, raw	1.321	1.086	2.407	2.046
Fish, shark, mixed species, raw	0.527	0.316	0.843	0.717
Fish, sheepshead, cooked, dry heat	0.107	0.083	0.19	0.162
Fish, smelt, rainbow, cooked, dry heat	0.536	0.353	0.889	0.756
Fish, snapper, mixed species, cooked, dry heat	0.273	0.048	0.321	0.273
Fish, spot, cooked, dry heat	0.526	0.282	0.808	0.687
Fish, sturgeon, mixed species, cooked, dry heat	0.119	0.249	0.368	0.313
Fish, sucker, white, cooked, dry heat	0.371	0.244	0.615	0.523
Fish, sunfish, pumpkin seed, cooked, dry heat	0.092	0.047	0.139	0.118
Fish, swordfish, cooked, dry heat	0.681	0.138	0.819	0.696
Fish, tilefish, cooked, dry heat	0.733	0.172	0.905	0.769
Fish, trout, mixed species, cooked, dry heat	0.677	0.259	0.936	0.796
Fish, trout, rainbow, farmed, cooked, dry heat	0.820	0.334	1.154	0.981
Fish, trout, rainbow, wild, cooked, dry heat	0.520	0.468	0.988	0.840
Fish, tuna, fresh, bluefin, cooked, dry heat	1.141	0.363	1.504	1.278
Fish, tuna, light, canned in oil, drained solids	0.101	0.027	0.128	0.109
Fish, tuna, light, canned in water, drained solids	0.223	0.047	0.27	0.230
Fish, tuna, skipjack, fresh, cooked, dry heat	0.237	0.091	0.328	0.279
Fish, tuna, white, canned in water, drained solids	0.629	0.233	0.862	0.733
Fish, tuna, yellowfin, fresh, cooked, dry heat	0.232	0.047	0.279	0.237
Fish, whitefish, mixed species, cooked, dry heat	1.206	0.406	1.612	1.370
Fish, whiting, mixed species, cooked, dry heat	0.235	0.283	0.518	0.440
Fish, wolffish, Atlantic, cooked, dry heat	0.405	0.393	0.798	0.678
Frog legs, raw			0.034	0.020
Mollusks, abalone, mixed species, raw	0	0.049	0.049	0.042
Mollusks, clam, mixed species, cooked, moist heat	0.146	0.138	0.284	0.241
Mollusks, conch, baked or broiled	0.072	0.048	0.12	0.102
Mollusks, cuttlefish, mixed species, cooked, moist heat	0.132	0.078	0.21	0.179
Mollusks, mussel, blue, cooked, moist heat	0.506	0.276	0.782	0.665
Mollusks, octopus, common, cooked, moist heat	0.162	0.152	0.314	0.267
Mollusks, oyster, eastern, farmed, cooked, dry heat	0.211	0.229	0.44	0.374
Mollusks, oyster, eastern, wild, cooked, dry heat	0.291	0.26	0.551	0.468
Mollusks, oyster, Pacific, cooked, moist heat	0.500	0.876	1.376	1.170
Mollusks, scallop, mixed species, cooked, breaded and fried	0.103	0.086	0.18	0.161
Mollusks, whelk, unspecified, cooked, moist heat	0.012	0.008	0.02	0.017

[Source ²⁷⁾]

Table 4. Other sources of Omega-3 Alpha-Linolenic Acid (ALA) – Non-Seafood Sources

[Source ²⁸⁾]

Supplements that contain Omega-3s

• Several types of dietary supplements contain omega-3s.
• Fish oil supplements contain EPA and DHA.
• Fish liver oil supplements, such as cod liver oil, contain EPA and DHA, and they also contain vitamins A and D, in amounts that vary from product to product. Vitamins A and D can be harmful in excessive amounts.
• Krill oil contains EPA and DHA.
• Algal oils are a vegetarian source of DHA; some also contain EPA.
• Flaxseed oil contains ALA.

What do scientists know about the effectiveness of omega-3 supplements?

• Research indicates that omega-3 supplements don’t reduce the risk of heart disease. However, people who eat seafood one to four times a week are less likely to die of heart disease.
• High doses of omega-3s can reduce levels of triglycerides.
• Omega-3 supplements may help relieve symptoms of rheumatoid arthritis.
• Omega-3 supplements have not been convincingly shown to slow the progression of the eye disease age-related macular degeneration.
• For most other conditions for which omega-3 supplements have been studied, the evidence is inconclusive or doesn’t indicate that omega-3s are beneficial.

Conditions Affecting the Circulatory System

Heart Disease

• A 2011 evaluation of 17 studies indicated that people who eat seafood (fish and shellfish) one to four times a week are less likely to die of heart disease than those who rarely or never eat seafood.
• A 2018 analysis of 10 major omega-3 supplementation studies (77,917 total participants, all at high risk of heart disease), each of which involved at least 500 participants and a treatment duration of at least a year, found no evidence that omega-3s could reduce the risk of fatal or nonfatal coronary heart disease.
• In 2016, the U.S. Government’s Agency for Healthcare Research and Quality ²⁹⁾ did a comprehensive evaluation of 98 studies of omega-3s and heart disease, including both diet and supplementation studies. They did not find evidence that omega-3s can reduce the risk of heart attacks or death from heart disease.
• Several other analyses of the evidence have been done in the last few years (2012 or later), and like the 2018 analysis and the AHRQ report ³⁰⁾, most found little or no evidence for a protective effect of omega-3 supplements against heart disease. However, some earlier analyses suggested that omega-3s could be helpful. The difference between the newer conclusions and the older ones may reflect two changes over time:
  • Public health messages that urge people to eat more seafood may have led to greater consumption of omega-3s from food. Additional omega-3s, beyond the amounts consumed by people who eat seafood, may not have extra benefits.
  • More people are taking medicines that reduce the risk of heart attacks, such as statin drugs to treat high cholesterol. Omega-3s may not offer extra benefits beyond those of modern drug treatment.

Stroke

• Eating seafood (fish and shellfish) has been linked to a moderate reduction in the risk of stroke.
• According to the Agency for Healthcare Research and Quality ³¹⁾ report, there is some evidence that omega-3s from marine sources (such as fish oil) may reduce the risk of one type of stroke (ischemic stroke—the type caused by narrowing or blockage of a blood vessel in the brain), but omega-3s have not been shown to reduce total strokes or death from stroke.

Triglycerides

• Triglycerides are a type of fat found in people’s blood. Excessive levels of triglycerides may raise the risk of heart disease. Dietary changes, weight control, and exercise are used to lower triglyceride levels. Some people also need to take medicine to lower their triglyceride levels.
• High doses of omega-3 fatty acids can reduce triglyceride levels.
  • Several products containing omega-3s have been approved as prescription drugs to be used in combination with diet to reduce triglyceride levels in patients whose triglyceride levels are very high.
  • The composition of these products is not the same as that of typical omega-3 supplements, and the testing and regulation of prescription drugs differ from those for dietary supplements. Therefore, the effects of these prescription products may not be the same as those of omega-3 dietary supplements.

Conditions Affecting the Brain, Nervous System, or Mental Health

Depression

• It’s uncertain whether omega-3 fatty acid supplements are helpful for depression. Although some studies have had promising results, a 2015 evaluation of 26 studies that included more than 1,400 people concluded that if there is an effect, it may be too small to be meaningful. Other analyses have suggested that if omega-3s do have an effect, EPA may be more beneficial than DHA and that omega-3s may best be used in addition to antidepressant medication rather than in place of it.
• Omega-3s have not been shown to relieve symptoms of depression that occur during pregnancy or after childbirth.
• Depression can be a serious illness. If you or someone in your family may have depression, consult a health care provider.

Attention-Deficit Hyperactivity Disorder (ADHD)

• Research on omega-3s for ADHD has had conflicting results. It’s uncertain whether omega-3s have any benefit for symptoms of this condition.

Alzheimer’s Disease/Cognitive Impairment

• Some research indicates that people who eat more seafood may have a reduced risk of cognitive decline. However, omega-3 supplements haven’t been shown to help prevent cognitive impairment or Alzheimer’s disease or to improve symptoms of these conditions. For example, a large NIH-sponsored study completed in 2015 indicated that taking EPA and DHA supplements did not slow cognitive decline in older adults. The people studied were participants in a larger eye disease study, and all of them had age-related macular degeneration (AMD).
• It’s possible that omega-3s might have different effects in people with different genetic backgrounds. A 2017 research review suggested that people who carry a gene called APOE4, which is associated with an increased risk of Alzheimer’s disease, might benefit from taking DHA before developing signs of Alzheimer’s.

Other Conditions Affecting the Brain, Nervous System, or Mental Health

• Omega-3s have also been studied for autism spectrum disorders, borderline personality disorder, multiple sclerosis, and schizophrenia, but the evidence regarding their effects on these conditions is inconclusive.

Eye Diseases

Age-Related Macular Degeneration

• Age-related macular degeneration (AMD) is an eye disease that can cause vision loss in older people. Two major National Institutes of Health (NIH)-sponsored studies, called Age-Related Eye Disease Study (AREDS) and Age-Related Eye Disease Study 2 (AREDS2), showed that dietary supplements containing specific combinations of vitamins, antioxidants, and zinc helped slow the progression of AMD in people who were at high risk of developing the advanced stage of this disease. AREDS2, which had more than 4,000 participants and was completed in 2013, also tested EPA and DHA. The results showed that adding these omega-3s to the supplement formulation didn’t provide any additional benefits. Other, smaller studies of omega-3 supplements also haven’t shown them to have a beneficial effect on the progression of AMD.

Dry Eye Disease

• The results of several small studies had suggested that taking omega-3 supplements might help relieve symptoms of dry eye disease. However, a 2018 NIH-sponsored study that tested omega-3 supplements for a full year in a larger group (535 study participants) with moderate-to-severe dry eye disease found that the supplements were no more helpful than a placebo (an inactive substance).

Retinitis Pigmentosa

• Only a few studies have been conducted on omega-3s for retinitis pigmentosa, and these studies have not shown any clear evidence of beneficial effects.

Other Conditions

Rheumatoid Arthritis

• The types of omega-3s found in seafood and fish oil may be modestly helpful in relieving symptoms of rheumatoid arthritis and decreasing patients’ need for nonsteroidal anti-inflammatory drugs.
• Conventional medical treatment for rheumatoid arthritis can slow joint damage. If you have rheumatoid arthritis, don’t change your use of prescribed medications without consulting your health care provider.

Infant Development

• The nutritional value of seafood is important during early development. The Dietary Guidelines for Americans 2015–2020 and guidance from the U.S. Food and Drug Administration and Environmental Protection Agency recommend that women who are pregnant or breastfeeding eat at least 8 ounces but no more than 12 ounces of a variety of seafood each week, from choices that are lower in methyl mercury. Methyl mercury can be harmful to the brain and nervous system if a person is exposed to too much of it.
• In 2016, Agency for Healthcare Research and Quality ³²⁾ reviewed 143 studies that evaluated the effects of giving omega-3 supplements to pregnant or breastfeeding women or giving formulas with added DHA to infants. They found that when women took omega-3 supplements during pregnancy, their babies’ birth weight was slightly higher, but the risk of an undesirably low birth weight did not change. Also, when women took omega-3 supplements during pregnancy, their pregnancies lasted a little longer, but there was no effect on the risk of premature birth. Omega-3s were not found to have effects on any other aspects of the mothers’ or infants’ health or the infants’ long-term development. Aspects of the infants’ health that were not shown to be affected by omega-3s include growth after birth, visual acuity, long-term neurological and cognitive development, and the risks of autism, ADHD, learning disorders, and allergies.
• In a study published after the Agency for Healthcare Research and Quality report ³³⁾, scientists in Denmark gave high-dose fish oil supplements or placebos to 736 pregnant women during the third trimester of pregnancy. Children born to mothers who had taken fish oil were less likely to develop asthma or persistent wheezing in early childhood, and this was most noticeable in children whose mothers had low blood levels of EPA and DHA before they started to take the supplements. However, other studies that evaluated the effects of omega-3 supplementation during pregnancy on childhood asthma risk have had inconsistent results.

Miscellaneous Conditions

• Omega-3s have been studied for other conditions, with either inconclusive or negative results. These conditions include allergies, atopic eczema (an allergic skin condition), cystic fibrosis, diabetes, inflammatory bowel diseases (Crohn’s disease or ulcerative colitis), intermittent claudication (a circulatory problem), nonalcoholic fatty liver disease, and osteoporosis.

What do scientists know about the safety of omega-3 supplements?

• Omega-3s usually produce only mild side effects, if any. Side effects of omega-3 supplements are usually mild. They include unpleasant taste, bad breath, bad-smelling sweat, headache, and gastrointestinal symptoms such as heartburn, nausea, and diarrhea.
• Several large studies have linked higher blood levels of long-chain omega-3s with higher risks of prostate cancer. However, other research has shown that men who frequently eat seafood have lower prostate cancer death rates and that dietary intakes of long-chain omega-3s aren’t associated with prostate cancer risk. The reason for these apparently conflicting findings is unclear.
• Omega-3 supplements may interact with drugs that affect blood clotting.
• It’s uncertain whether people with seafood allergies can safely take fish oil supplements. If you’re taking medicine that affects blood clotting or if you’re allergic to fish or shellfish, consult your health care provider before taking omega-3 supplements.

In general taking fish oil supplement is quite safe. Commonly reported side effects of omega-3 supplements are usually mild. These include unpleasant taste, bad breath, heartburn, nausea, gastrointestinal discomfort, diarrhea, headache, and odoriferous sweat ³⁴⁾, ³⁵⁾.

Common gastrointestinal symptoms like nausea occurred at rates of ≈4% at dosages <3 g/d and increased to ≈20% at a dosage of 4 g/d.

The Institute of Medicine did not establish a UL for any omega-3s, although it noted that high doses of DHA and/or EPA (900 mg/day of EPA plus 600 mg/day DHA or more for several weeks) might reduce immune function due to suppression of inflammatory responses. Doses of 2–15 g/day EPA and/or DHA might also increase bleeding time by reducing platelet aggregation ³⁶⁾. However, according to the European Food Safety Authority, long-term consumption of EPA and DHA supplements at combined doses of up to about 5 g/day appears to be safe ³⁷⁾. It noted that these doses have not been shown to cause bleeding problems or affect immune function, glucose homeostasis, or lipid peroxidation. The FDA recommends not exceeding 3 g/day EPA and DHA combined, with up to 2 g/day from dietary supplements. Some doses used in clinical trials exceed these levels.

Omega-3 supplements may extend bleeding time (the time it takes for a cut to stop bleeding). People who take drugs that affect bleeding time, such as anticoagulants (“blood thinners”) or nonsteroidal anti-inflammatory drugs (NSAIDs), should discuss the use of omega-3 fatty acid supplements with a health care provider.

Krill oil benefits

Most of krill oil’s health benefits are attributed to its high Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) content. Numerous studies have identified the antithrombotic, antiarrhythmic, antiatherosclerotic, and anti-inflammatory mechanisms associated with an increased consumption of these omega-3 fatty acids ³⁸⁾, ³⁹⁾, ⁴⁰⁾.

More studies are needed to determine whether phosphatidylcholine and astaxanthin provide an additive effect.

Phosphatidylcholine by itself has shown promise as a dietary supplement to improve homocysteine status, liver disorders, and respiratory distress ⁴¹⁾.

Astaxanthin may have independent positive effects due to its antioxidant capabilities. When oxygen radical absorptive capacity values of various antioxidants were compared, astaxanthin was found to be 34-times more effective than CoQ10 and 48-times more effective than fish oil ⁴²⁾.

Preliminary human studies indicate krill oil may be superior to fish oil in the reduction of premenstrual syndrome (PMS) complications ⁴³⁾ and biomarkers of dyslipidemia ⁴⁴⁾.

Krill oil consumption has also shown a positive effect on markers of inflammation ⁴⁵⁾.

Is krill oil better than fish oil?

Although there are similarities, numerous differences exist between krill oil and fish oil. Krill oil is only available as a supplement, primarily in softgel formulation ⁴⁶⁾. The size of krill oil softgels is markedly smaller and may be more suitable for individuals with swallowing difficulties. On the other hand, fish oil is available in both prescription and supplement formulations including softgels and liquid ⁴⁷⁾. More important, however, are the differences in omega-3 content and delivery ⁴⁸⁾. The EPA+DHA content of krill oil is markedly less per softgel (and serving) compared to fish oil. For example, the dose of EPA+DHA of pure krill oil products may range from ~45 to 200 mg/softgel compared to ~300 to 2,250 mg/softgel or teaspoon among the various fish oil formulations ⁴⁹⁾, ⁵⁰⁾, ⁵¹⁾.

Fish oil is a type of polyunsaturated fatty acids that is derived from fish and contain a rich source of Omega-3 essential fatty acids that are important for a number of functions in your body. Fish oil is commonly found in fatty fish such as salmon, tuna, and trout—and shellfish—such as crab, mussels, and oysters. Omega-3 fatty acids are called essential fatty acids because your body cannot make them and you need it them in your diet.

Both fish oil and krill oil are a source of omega-3 fatty acids, predominantly Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA). Harvesting of both fish and krill for their respective oils has an impact on our environment, and most human studies have failed to show significant health benefits. Krill oil is inherently more stable than fish oil, and lacks a fishy smell and taste. Krill oil appears to be better absorbed than fish oil, but more studies are needed to determine whether this translates into any further health benefits. The best way to improve your omega-3 intake is to eat fish at least twice a week, as recommended by the American Heart Association (who notably prefer increasing dietary intake of fish over supplements) ⁵²⁾.

The fatty acid form is also a key factor differentiating these agents. The Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA) found in krill oil is primarily incorporated in phospholipids, whereas omega-3 fatty acids in fish oil are generally present as triglycerides or ethyl esters ⁵³⁾. Some data have suggested that phospholipids are more efficient at delivering EPA+DHA ⁵⁴⁾. This difference in chemical form may therefore impact the absorption and bioavailability of the Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA) and the dose required to achieve the various cardiovascular effects.

Although a limited number of studies comparing the effects of krill oil and fish oil on the omega-3 index have suggested greater increases with krill oil ⁵⁵⁾, ⁵⁶⁾ newer data do not support these findings ⁵⁷⁾.

Unlike fish oil, krill oil also contain a potent antioxidant carotenoid, astaxanthin, that helps prevent long-chain polyunsaturated fatty acids oxidation ⁵⁸⁾. This colorful carotenoid antioxidant, astaxanthin is responsible for the red color observed in salmon meat, cooked shellfish, and certain krill oil supplements. Although this powerful antioxidant has previously demonstrated HDL “good” cholesterol increasing properties, clinical benefits and therapeutic use of astaxanthin remain unclear ⁵⁹⁾.

Cost may also be an important consideration for patients choosing omega-3 products. Typically, supplemental fish oil is considerably less expensive compared to krill oil. A cost analysis of common products indicated that fish oil supplements range from 1 to 15 cents while krill oil is approximately 30 cents per 100 mg of EPA+DHA ⁶⁰⁾.

Krill Oil vs Fish Oil on Cholesterol

Very few randomized studies have examined the effects of krill oil on cardiovascular health or hyperlipidemia. Researchers in Quebec compared Neptune Krill Oil (NKO®) with high EPA and DHA fish oil (3:2 ratio) or placebo in a 12-week, prospective, randomized, double-blind clinical trial ⁶¹⁾. 120 participants ages 25-75, with moderate-to-high cholesterol (193.9-347.9 mg/dL) and triglycerides (203.8-354.4 mg/dL) for a minimum of six months, were divided into four groups.

• Group 1 received 2 or 3 gram Neptune Krill Oil daily, depending on body mass index (BMI).
• Group 2 received 1 or 1.5 g Neptune Krill Oil daily(depending on BMI) during the 12 weeks of the study and an additional 500 mg Neptune Krill Oil as a maintenance dose for a 90 day follow-up period. In bothgroups a BMI >30 justified the higher of the two doses.
• Group 3 received 3 g Fish Oil (180 mg EPA, 120 mg DHA per g) daily, while
• Group 4 received aplacebo.

Parameters examined at baseline, 30, and 90 days (180 days for the follow-up in group 2) included HDL (good cholesterol), LDL (bad cholesterol) and total cholesterol, blood glucose, and triglycerides. At the end of 90 days those taking krill oil at a daily dose of 1 g, 1.5 g, 2 g, or 3 g achieved significant reductions of LDL of 32 %, 36 %, 37% and 39 percent, respectively. Reductions in total cholesterol were 13.4%, 13.7%, 18.1% and 18 percent, respectively, while triglyceride reductions were 11.03%, 11.89%, 27.62%, and 26.51 percent respectively. Blood glucose was reduced 6.3 percent in the 1-g and 1.5-g krill group, and 5.6 percent in those taking 2 or 3 g krill daily.

In comparison, the fish oil group had an average 5.9% reduction in cholesterol and the placebo group had a 9.1-percent increase. Subjects taking the fish oil also had a non-significant 4.6-percent decrease in LDL cholesterol.

Those receiving the placebo had a significant 13% increase in LDL cholesterol. There was a non-significant decrease in glucose and triglycerides for both the 3 g fish oil and placebo groups.

The largest changes in serum lipids occurred for HDL cholesterol. After 90 days, the 1, 1.5, 2, and 3 g krill oil groups had significant HDL “good” increases of 44%, 43%, 55% and 59 percent, while the fish oil group had only a 4.2% increase; the placebo group had a non-significant decrease of HDL.

During the 12-week follow-up, when subjects in the 1- and 1.5-g krill group were maintained on 500 mg krill oil daily, all markers maintained statistical significance except glucose ⁶²⁾.

While the findings for krill oil were impressive, the magnitude of the changes in lipid measures was considerably higher than what one might expect. Additionally, comparison is limited by the fact that the EPA and DHA content of the krill oil supplements was not provided. Thus these findings require further validation.

Another open-label randomized parallel study ⁶³⁾ examined the comparative effects of krill oil and fish oil in 122 participants documented to have no other routine sources of omega-3s. Participants were randomized to 1 of 3 groups: krill oil 3 g daily, fish oil 1.8 g daily, or no supplementation for 7 weeks. A total of 115 participants finished the study. The krill oil used in this study was extracted from Antarctic krill. The daily dose was 6 capsules, each containing 500 mg of oil providing 90.5 mg EPA + DHA and 103.5 mg of omega-3 polyunsaturated fatty acids (PUFAs). The omega-3 fish oil source was a Norway product given in a daily dose of 3 capsules containing 600 mg each of fish oil with 288 mg EPA + DHA and 330 mg of omega-3 PUFAs. In total, the daily amount of krill oil was approximately 63% of the dosage contained in the fish oil ⁶⁴⁾.

Blood samples were taken after an overnight fast of at least 12 hours at baseline and at the final visit. Plasma levels of EPA, DHA, and docosapentaenoic acid (DPA) increased significantly during the intervention in both the krill oil and fish oil groups compared to control. During the intervention phase, small changes were seen in levels of HDL “good” cholesterol, LDL “bad” cholesterol, and triglycerides. However, the only significant change was the increase in LDL-Cholesterol within the fish oil group. No differences were seen in the HDL-C / triglyceride ratio within the fish oil or control groups. Conversely, the ratio was significantly increased in the krill oil group. Changes in apolipoprotein B (Apo B-100) were minor and nonsignificant for all study groups. Only the within change in Apo B-100 levels for the krill oil group was significant. In addition, no significant increases were seen among the 3 groups in markers for inflammation, hemostasis, or oxidative stress. Withdrawal rates were similar among the 3 groups. The comparable increases in EPA and DHA among the krill oil users despite a lower dose of omega-3 PUFAs compared to the fish oil group are consistent with earlier studies suggesting that krill oil is a more bioavailable source of omega-3 PUFAs ⁶⁵⁾.

Another study specifically addressed the impact of krill oil on serum triglycerides and the omega-3 index ⁶⁶⁾. In a double-blind, randomized, placebo-controlled trial, 300 patients with triglyceride levels of 150 to 499 mg/dL were given varying doses of krill oil (0.5, 1, 2, or 4 g per day) or olive oil (placebo) for 12 weeks. These amounts of krill oil corresponded to 100, 200, 400, or 800 mg of EPA+DHA per day. Participants reported low consumption of fatty fish defined as less than twice per month. Fasting triglyceride levels were measured at baseline, 6, and 12 weeks. Compared to placebo, patients on krill oil demonstrated a 10.2% reduction in triglyceride levels ⁶⁷⁾. No differences in LDL-C levels were observed. Perhaps the most important finding from this study was the significant increase in the omega-3 index in all krill oil groups seen at both 6 and 12 weeks. The corresponding changes were 8%, 18%, 29%, and 73% for the 0.5, 1, 2, and 4 g krill oil dose compared to -3% (minus 3 percent) with placebo. A major limitation of this study is the high intra-individual variability that occurred in the fasting triglyceride measurements. Overall, the average daily dose of krill oil was 1.875 g providing 385 mg of EPA+DHA. This resulted in approximately a 6% reduction in triglyceride levels compared to baseline ⁶⁸⁾. This daily dose is lower than that used in earlier studies evaluating triglycerides. Additional studies with multiple measurements of triglyceride levels for each individual will be needed to confirm these findings.

The minimal number of clinical studies and substantial heterogeneity of designs preclude any definitive conclusions. Taken as a whole, however, these randomized trials provide preliminary evidence that krill oil is at least equivalent to and perhaps better than fish oil at increasing blood levels of EPA and DHA ⁶⁹⁾. However, it is not known whether these changes would translate into improved cardiovascular outcomes. Additional studies are needed to further explore the effects of krill oil on the lipid panel and, in particular, the potential impact on triglyceride reduction.

The American Heart Association position statement, published in 2002 ⁷⁰⁾, does not recognize krill oil as an omega-3 supplement. This is understandable considering that the emergence of krill oil began after the American Heart Association recommendations. However, no other major position statements regarding cholesterol or cardiovascular risk prevention that have been published more recently address the appropriate use of krill oil, including the 2013 American College of Cardiology and the American Heart Association cholesterol guidelines ⁷¹⁾. As such, krill oil should not be considered first-line therapy for omega-3 intake and cardioprotection. Additionally, krill oil does not appear to be effective for clinically relevant triglyceride lowering, because randomized controlled trials indicate only modest reductions ⁷²⁾. Therefore, krill oil cannot be recommended for hypertriglyceridemia at this time.

Because of these factors, krill oil currently has a limited role in cardiovascular risk prevention, with the potential to expand as more research is completed. Most studies evaluating the impact of krill oil on the omega-3 index indicate efficient absorption of EPA+DHA. The omega-3 index is reflective of the EPA+DHA consumption recommended by the American Heart Association and the potential for cardioprotection ⁷³⁾. Thus, it is reasonable to consider krill oil as an alternative for achieving cardiovascular benefits in patients who are unable to increase fish consumption or utilize fish oil. Specific patient groups that may be candidates for krill oil include those with an aversion to dietary fish and individuals unable to swallow the large fish oil softgels or who have a dislike for the liquid. If the efficient uptake of EPA+DHA from krill oil that has been observed in smaller studies is replicated in larger randomized controlled trials, patients may be able to obtain cardioprotection at a lower EPA+DHA intake than what is currently recommended by the American Heart Association. Additionally, krill is sensitive to degradation and the process for obtaining the key components is more complex than that of fish oil. In view of these issues, we emphasize the importance of getting your krill oil products only from reliable manufacturers.

Krill Oil and Osteoarthritis

A double-blind, placebo-controlled, randomized, prospective study examined the effect of 300 mg Neptune Krill Oil daily on C-reactive protein (CRP) and
functional testing scores for arthritis ⁷⁴⁾.

Ninety participants had a diagnosis of cardiovascular disease and/or rheumatoid arthritis and/or osteoarthritis, and an elevated CRP (>1.0 mg/dL) for three consecutive weeks. Western Ontario and McMaster Universities (WOMAC) osteoarthritis score and CRP were measured at baseline and at days 7, 14, and 30.

After seven days of krill supplementation, CRP decreased by 19.3 percent in the experimental group, while it increased by 15.7 percent in the control group. By day 14 and day 30, CRP decreased by 29.7 and 30.9 percent, respectively, in the krill oil group, while the placebo group experienced an increase of 32.1 percent by day 14 and a lowering to a total increase of 25.1 percent by day 30. When comparing krill supplementation to placebo, differences at day 7, day 14 and day 30  were all statistically significant. When compared to placebo, WOMAC osteoarthritis score results showed krill significantly reduced pain scores and stiffness scores and functional⁷⁵⁾.

Krill Oil vs Fish Oil on Premenstrual Syndrome

In a 90-day study, Sampalis et al. ⁷⁶⁾ compared the effects of Neptune Krill Oil to fish oil on multiple parameters of function in Premenstrual Syndrome (PMS) via an assessment questionnaire and the total consumption of analgesics for pain and discomfort associated with PMS.

Seventy subjects of child-bearing age were assigned to ingest 2 grams krill oil daily (800 mg phospholipids, 600 mg EPA and DHA) (n=36) or 2 grams fish oil daily (600 mg EPA and DHA at an 3:2 ratio) (n=34) for the first 30 days of the trial. In the final 60 days both groups were instructed to take the assigned supplements eight days prior to and two days during menstruation.

Questionnaires were completed and analgesic medication intakes were measured at baseline, 45, and 90 days.

After the first 45 days the krill oil group showed significant for all parameters improvements in breast tenderness, joint pain, weight gain, abdominal pain, swelling, and bloating, as well as feelings of being overwhelmed, stressed, irritable, and depressed. The fish oil group demonstrated significant improvements in weight gain and abdominal pain at day 45, and improvements in weight gain, abdominal pain, and swelling at day 90. When consumption of analgesic medication during menstruation by the krill oil group was compared to the fish oil group, it was found that the average consumption of 1.2 g ibuprofen or 2.5 g
acetaminophen taken at baseline changed in both groups. The krill oil group had reduced consumption to 0.9 g ibuprofen and 1.5 g acetaminophen at day 45, and 0.6 g ibuprofen and 1.0 g acetaminophen at day 9) – a total decrease in analgesics of 50 percent after 90 days. The fish oil group decreased intake to 0.9 g ibuprofen and 1.65 g acetaminophen by day 45, and 0.8 g ibuprofen and 1.48 g acetaminophen by day 90 – a total reduction of 33% and 41 percent, respectively.
Interestingly, the authors noted, “Patients taking NKO did not experience any gastrointestinal difficulties such as regurgitation, while 64 percent of the women in the fish oil group complained of unpleasant reflux” ⁷⁷⁾.

Krill Oil vs Fish Oil on Human Brain Function in Healthy Elderly Volunteers

Aging reduces regional cerebral blood flow, which causes deterioration of cerebral function ⁷⁸⁾. Aging has also been shown to reduce the level of dorsolateral prefrontal cortex activity during execution of working memory tasks ⁷⁹⁾.

In a study involving 45 healthy male subjects in their 60s and 70s who had retired from employment in the Japanese business sector ⁸⁰⁾. Eligibility for participation was as follows: right-handedness, not requiring prescription medication, no history of mental disorders or cerebrovascular disease, absence of serious liver, kidney, heart, respiratory, endocrine, or metabolic diseases, and absence of food allergies to fish or crustaceans. The participants were clinically confirmed by a psychiatrist to have no cognitive impairment.

Three types of experimental supplement were used: krill oil as a typical oil rich in PUFAs incorporated in phosphatidylcholine, sardine oil as a typical fish oil, and medium-chain triglycerides as placebo. Subjects were asked to take four capsules twice a day after breakfast and dinner for 12 weeks (eight capsules daily), from the day following the initial measurements to the day of the final measurements.

The results of this study suggest that long-term ingestion of krill oil and sardine oil promotes working memory function by activating the dorsolateral prefrontal cortex in elderly people, and thus prevents deterioration in cognitive activity ⁸¹⁾. However, sardine oil, which contains the largest amounts of EPA and DHA fatty acids, was not shown to possess any activation effects regarding the calculation task, and only krill oil, containing lesser amounts of these fatty acids, was shown to have an effect, possibly due to its higher percentage of phospholipids, in particular phosphatidylcholine ⁸²⁾. This finding indicates that n-3 PUFAs incorporated in phosphatidylcholine act on brain function more efficiently than those incorporated in triglycerides ⁸³⁾.

Krill oil dosage

Therapeutic doses range from 1-3 grams krill oil per day, with maintenance dosing of 500 mg daily ⁸⁴⁾.

Always talk to your doctor before taking supplements of any kind, including omega-3’s, and particularly if you have a medical condition such as asthma, inflammatory bowel disease, liver disease or a heart rhythm disorder. Take a supplement from a reputable manufacturer with good quality control measures to ensure the supplement is as free from contaminants, including heavy metal toxins (such as mercury), as possible. Pregnant women and young children should be especially cautious about taking fish oil supplements.

A study specifically addressed the impact of krill oil on serum triglycerides and the omega-3 index ⁸⁵⁾. In a double-blind, randomized, placebo-controlled trial, 300 patients with triglyceride levels of 150 to 499 mg/dL were given varying doses of krill oil (0.5, 1, 2, or 4 g per day) or olive oil (placebo) for 12 weeks. These amounts of krill oil corresponded to 100, 200, 400, or 800 mg of EPA+DHA per day. Participants reported low consumption of fatty fish defined as less than twice per month. Fasting triglyceride levels were measured at baseline, 6, and 12 weeks. In an effort to increase statistical power, the final analyses pooled all krill oil patients regardless of dose. Compared to placebo, patients on krill oil demonstrated a 10.2% reduction in triglyceride levels. No differences in LDL-C “bad” cholesterol levels were observed. Perhaps the most important finding from this study was the significant increase in the omega-3 index in all krill oil groups seen at both 6 and 12 weeks. The corresponding changes were 8%, 18%, 29%, and 73% for the 0.5, 1, 2, and 4 g krill oil dose compared to -3% with placebo. A major limitation of this study is the high intra-individual variability that occurred in the fasting triglyceride measurements. Because this had not been taken into account in the power calculations, the investigators were forced to pool all of the krill oil users into one group despite varying doses. Overall, the average daily dose of krill oil was 1.875 g providing 385 mg of EPA+DHA ⁸⁶⁾. This resulted in approximately a 6% reduction in triglyceride levels compared to baseline. This daily dose is lower than that used in earlier studies evaluating triglycerides. Additional studies with multiple measurements of triglyceride levels for each individual will be needed to confirm these findings.

Usual Adult Dose for Hypertriglyceridemia

• 1 gram prescription only products:
• 4 grams orally daily; may be given as a single dose or 2 divided doses.

Comments:

• Assess triglyceride levels carefully before starting therapy and identify other possible causes (e.g. diabetes, hypothyroidism, medications) and manage appropriately.
• Patients should be on a lipid lowering diet prior to using this medication, and continue the diet during use of this medication.
• Capsules should be swallowed whole; do not break, crush, chew or dissolve capsules.
• In clinical trials, the medication was administered with meals.

Renal Dose Adjustments

• Data not available

Liver Dose Adjustments

• Data not available

Hemodialysis

• Data not available

Pregnancy

Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. It is unknown whether Omega-3-Acid Ethyl Esters capsules can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Omega-3-Acid Ethyl Esters capsules should be used during pregnancy only if the potential benefit to the patient justifies the potential risk to the fetus.

Animal Data: Omega-3-Acid Ethyl Esters have been shown to have an embryocidal effect in pregnant rats when given in doses resulting in exposures 7 times the recommended human dose of 4 grams/day based on a body surface area comparison.

In female rats given oral gavage doses of 100, 600, and 2,000 mg/kg/day beginning 2 weeks prior to mating and continuing through gestation and lactation, no adverse effects were observed in the high dose group (5 times human systemic exposure following an oral dose of 4 grams/day based on body surface area comparison).

In pregnant rats given oral gavage doses of 1,000, 3,000, and 6,000 mg/kg/day from gestation day 6 through 15, no adverse effects were observed (14 times human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison).

In pregnant rats given oral gavage doses of 100, 600, and 2,000 mg/kg/day from gestation day 14 through lactation day 21, no adverse effects were seen at 2,000 mg/kg/day (5 times the human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison). However, decreased live births (20% reduction) and decreased survival to postnatal day 4 (40% reduction) were observed in a dose-ranging study using higher doses of 3,000 mg/kg/day (7 times the human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison).

In pregnant rabbits given oral gavage doses of 375, 750, and 1,500 mg/kg/day from gestation day 7 through 19, no findings were observed in the fetuses in groups given 375 mg/kg/day (2 times human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison). However, at higher doses, evidence of maternal toxicity was observed (4 times human systemic exposure following an oral dose of 4 grams/day based on a body surface area comparison).

Breastfeeding

Studies with Omega-3-Acid Ethyl Esters have demonstrated excretion in human milk. The effect of this excretion on the infant of a nursing mother is unknown; caution should be exercised when Omega-3-Acid Ethyl Esters capsules are administered to a nursing mother. An animal study in lactating rats given oral gavage 14C-ethyl EPA demonstrated that drug levels were 6 to 14 times higher in milk than in plasma.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

A limited number of subjects older than 65 years were enrolled in the clinical trials of Omega-3-Acid Ethyl Esters capsules. Safety and efficacy findings in subjects older than 60 years did not appear to differ from those of subjects younger than 60 years.

Krill oil side effects

There are currently no known toxicity levels for krill oil. Side effects associated with the consumption of krill oil may include an increase in gastrointestinal
complaints such as flatulence, gas, bloating, and/or diarrhea ⁸⁷⁾.

Commonly reported side effects of omega-3 supplements are usually mild. These include unpleasant taste, bad breath, heartburn, nausea, gastrointestinal discomfort, diarrhea, headache, and odoriferous sweat ⁸⁸⁾, ⁸⁹⁾.

Along with its needed effects, omega-3 polyunsaturated fatty acids may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Fish Allergy

Omega-3 capsules contains ethyl esters of omega-3 fatty acids (EPA and DHA) obtained from the oil of several fish sources. It is not known whether patients with allergies to fish and/or shellfish, are at increased risk of an allergic reaction to Omega-3-Acid Ethyl Esters capsules. Omega-3-Acid Ethyl Esters capsules should be used with caution in patients with known hypersensitivity to fish and/or shellfish.

Theoretically, people who are allergic to fish or shellfish should avoid fish oil or krill oil supplements. However, there has only been one documented case of an anaphylactic reaction to fish oil and none to krill oil, indicating that an allergy to supplements is extremely rare. Always speak to your doctor before taking supplements if you have a fish or shellfish allergy ⁹⁰⁾.

In general, omega-3 supplements (includes both fish and krill oil) may affect blood sugar levels, lower blood pressure, and increase the risk of bleeding, particularly at higher dosages or in those with bleeding disorders or already taking medications that increase the risk of bleeding (such as warfarin or aspirin). Higher dosages of fish oil may also lead to vitamin A or D toxicity. Cough, diarrhoea, nausea, and flatulence are common side effects associated with their use.

Recurrent Atrial Fibrillation (AF) or Flutter

In a double-blind, placebo-controlled trial of 663 subjects with symptomatic paroxysmal AF (n = 542) or persistent AF (n = 121), recurrent AF or flutter was observed in subjects randomized to Omega-3-Acid Ethyl Esters who received 8 grams/day for 7 days and 4 grams/day thereafter for 23 weeks at a higher rate relative to placebo. Subjects in this trial had median baseline triglycerides of 127 mg/dL, had no substantial structural heart disease, were taking no anti-arrhythmic therapy (rate control permitted), and were in normal sinus rhythm at baseline.

At 24 weeks, in the paroxysmal AF stratum, there were 129 (47%) first recurrent symptomatic AF or flutter events on placebo and 141 (53%) on Omega-3-Acid Ethyl Esters [primary endpoint, HR 1.19; 95% CI: 0.93, 1.35]. In the persistent AF stratum, there were 19 (35%) events on placebo and 34 (52%) events on Omega-3-Acid Ethyl Esters. Although the clinical significance of these results is uncertain, there is a possible association between Omega-3-Acid Ethyl Esters and more frequent recurrences of symptomatic atrial fibrillation or flutter in patients with paroxysmal or persistent atrial fibrillation, particularly within the first 2 to 3 months of initiating therapy.

Omega-3-Acid Ethyl Esters capsules are not indicated for the treatment of AF or flutter.

Check with your doctor immediately if any of the following side effects occur while taking omega-3 polyunsaturated fatty acids:

Incidence Not Known

• bleeding gums
• cough
• coughing up blood
• difficulty with breathing or swallowing
• dizziness
• fast or irregular heartbeat
• headache
• hives, itching, or skin rash
• increased menstrual flow or vaginal bleeding
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red or black, tarry stools
• red or dark brown urine
• sweating
• tightness in the chest
• unusual tiredness or weakness

Some side effects of omega-3 polyunsaturated fatty acids may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less Common

• acid or sour stomach
• bad, unusual, or unpleasant (after) taste
• belching
• bloated or full feeling
• change in taste
• excess air or gas in the stomach
• heartburn
• indigestion
• stomach discomfort, upset, or pain

Incidence Not Known

• diarrhea
• difficulty having a bowel movement (stool)
• loss of appetite
• nausea or vomiting
• passing of gas
• stomach fullness

Gastrointestinal

Common (1% to 10%): Eructation, dyspepsia, nausea, gastrointestinal disorders (including abdominal distension, abdominal pain, constipation, diarrhea, flatulence, gastroesophageal reflux disease, vomiting)

Uncommon (0.1% to 1%): Gastrointestinal hemorrhage, gastroenteritis

Rare (less than 0.1%): Gastrointestinal pain

Very rare (less than 0.01%): Lower gastrointestinal hemorrhage

General

The most common adverse events were eructation, dyspepsia, and taste perversion

Other

Common (1% to 10%): Infection, pain

Uncommon (0.1% to 1%): Death

Dermatologic

Common (1% to 10%): Rash

Uncommon (0.1% to 1%): Atopic dermatitis

Rare (less than 0.1%): Urticaria, acne, rash pruritic

Frequency not reported: Pruritus

Cardiovascular

Uncommon (0.1% to 1%): Hypotension

Musculoskeletal

Common (1% to 10%): Back pain

Metabolic

Uncommon (0.1% to 1%): Hyperglycemia, gout, high triglycerides

Very rare (less than 0.01%): Blood lactate dehydrogenase increased

Nervous system

Common (1% to 10%): Taste perversion

Uncommon (0.1% to 1%): Dizziness, dysgeusia, headache, hyperactivity

Respiratory

Uncommon (0.1% to 1%): Epistaxis

Very rare (less than 0.01%): Nasal dryness

Frequency not reported: Influenza

Hypersensitivity

Rare (less than 0.1%): Hypersensitivity

Postmarketing reports: Anaphylactic reaction

Hematologic

Very rare (less than 0.01%): White blood count increased,

Frequency not reported: Slight prolongation of bleeding time

Postmarketing reports: Hemorrhagic diathesis

Psychiatric

Uncommon (0.1% to 1%): Tics, tantrum, insomnia

Hepatic

Rare (less than 0.1%): Liver disorders (including increased ALT, increased AST, and transaminases increased).