Omega-3 fatty acid#Health effects of omega-3 supplementation

In 1929, George and Mildred Burr discovered that fatty acids were critical to health. If fatty acids were absent from the diet, a life-threatening deficiency syndrome ensued. The Burrs coined the phrase "essential fatty acids".{{cite journal | title = Essential fatty acids: the work of George and Mildred Burr | journal = The Journal of Biological Chemistry | volume = 287 | issue = 42 | pages = 35439–35441 | date = October 2012 | pmid = 23066112 | pmc = 3471758 | doi = 10.1074/jbc.O112.000005 | doi-access = free | vauthors = Mukhopadhyay R }} Since then, researchers have shown a growing interest in unsaturated essential fatty acids as they form the framework for the organism's cell membranes.{{cite journal | vauthors = Caramia G | title = [The essential fatty acids omega-6 and omega-3: from their discovery to their use in therapy] | journal = Minerva Pediatrica | volume = 60 | issue = 2 | pages = 219–233 | date = April 2008 | pmid = 18449139 | url = https://www.minervamedica.it/en/journals/minerva-pediatrics/article.php?cod=R15Y2008N02A0219 | access-date = 8 April 2022 | archive-date = 19 August 2022 | archive-url = https://web.archive.org/web/20220819194627/https://www.minervamedica.it/en/journals/minerva-pediatrics/article.php?cod=R15Y2008N02A0219 | url-status = live }} Subsequently, awareness of the health benefits of essential fatty acids has dramatically increased since the 1980s.{{cite journal | vauthors = Holman RT | title = The slow discovery of the importance of omega 3 essential fatty acids in human health | journal = The Journal of Nutrition | volume = 128 | issue = 2 Suppl | pages = 427S–433S | date = February 1998 | pmid = 9478042 | doi = 10.1093/jn/128.2.427S | doi-access = free }}

On 8 September 2004, the U.S. Food and Drug Administration gave "qualified health claim" status to EPA and DHA omega−3 fatty acids, stating, "supportive but not conclusive research shows that consumption of EPA and DHA [omega−3] fatty acids may reduce the risk of coronary heart disease".{{cite press release |publisher=United States Food and Drug Administration |date=8 September 2004 |url=https://www.fda.gov/SiteIndex/ucm108351.htm |title=FDA announces qualified health claims for omega−3 fatty acids |access-date=10 July 2006}} This updated and modified their health risk advice letter of 2001 (see below).

The Canadian Food Inspection Agency has recognized the importance of DHA omega−3 and permits the following claim for DHA: "DHA, an omega−3 fatty acid, supports the normal physical development of the brain, eyes, and nerves primarily in children under two years of age."Canadian Food Inspection Agency. [http://www.inspection.gc.ca/food/labelling/food-labelling-for-industry/health-claims/eng/1392834838383/1392834887794?chap=8#s16c8 Acceptable nutrient function claims] {{Webarchive|url=https://web.archive.org/web/20181204025251/http://www.inspection.gc.ca/food/labelling/food-labelling-for-industry/health-claims/eng/1392834838383/1392834887794?chap=8#s16c8 |date=4 December 2018 }}. Accessed 30 April 2015

Historically, whole food diets contained sufficient amounts of omega−3, but because omega−3 is readily oxidized, the trend toward shelf-stable processed foods has led to a deficiency in omega−3 in manufactured foods.{{cite journal |vauthors=Simopoulos AP |title=An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity |journal=Nutrients |volume=8 |issue=3 |pages=128 |date=March 2016 |pmc=4808858 |pmid=26950145 |doi=10.3390/nu8030128 |doi-access=free}}

{{main|Fatty acid#Nomenclature}}

File:ALAnumbering.svgs on carbons numbered 9, 12, and 15. The omega (ω) end of the chain is at carbon 18, and the double bond closest to the omega carbon begins at carbon 15 = 18−3. Hence, ALA is a ω−3 fatty acid with ω = 18.]]

The terms ω−3 ("omega−3") fatty acid and n−3 fatty acid are derived from the nomenclature of organic chemistry.{{cite journal | vauthors = Ratnayake WM, Galli C | title = Fat and fatty acid terminology, methods of analysis and fat digestion and metabolism: a background review paper | language = en | journal = Annals of Nutrition & Metabolism | volume = 55 | issue = 1–3 | pages = 8–43 | date = 2009 | pmid = 19752534 | doi = 10.1159/000228994 | doi-access = free }} One way in which an unsaturated fatty acid is named is determined by the location, in its carbon chain, of the double bond which is closest to the methyl end of the molecule. In general terminology, n (or ω) represents the locant of the methyl end of the molecule, while the number n−x (or ω−x) refers to the locant of its nearest double bond. Thus, in omega−3 fatty acids in particular, there is a double bond located at the carbon numbered 3, starting from the methyl end of the fatty acid chain. This classification scheme is useful since most chemical changes occur at the carboxyl end of the molecule, while the methyl group and its nearest double bond are unchanged in most chemical or enzymatic reactions.

In the expressions n−x or ω−x, the symbol is a minus sign rather than a hyphen (or dash), although it is never read as such. Also, the symbol n (or ω) represents the locant of the methyl end, counted from the carboxyl end of the fatty acid carbon chain. For instance, in an omega−3 fatty acid with 18 carbon atoms (see illustration), where the methyl end is at location 18 from the carboxyl end, n (or ω) represents the number 18, and the notation n−3 (or ω−3) represents the subtraction 18−3 = 15, where 15 is the locant of the double bond which is closest to the methyl end, counted from the carboxyl end of the chain.

Although n and ω (omega) are synonymous, the IUPAC recommends that n be used to identify the highest carbon number of a fatty acid. Nevertheless, the more common name – omega−3 fatty acid – is used in both the lay media and scientific literature.

For example, α-linolenic acid (ALA; illustration) is an 18-carbon chain having three double bonds, the first located at the third carbon from the methyl end of the fatty acid chain. Hence, it is an omega−3 fatty acid. Counting from the other end of the chain, that is the carboxyl end, the three double bonds are located at carbons 9, 12, and 15. These three locants are typically indicated as Δ9c, Δ12c, Δ15c, or cisΔ⁹, cisΔ¹², cisΔ¹⁵, or cis-cis-cis-Δ^9,12,15, where c or cis means that the double bonds have a cis configuration.

α-Linolenic acid is polyunsaturated (containing more than one double bond) and is also described by a lipid number, 18:3, meaning that there are 18 carbon atoms and 3 double bonds.

File:EPAnumbering.png (EPA)]]

File:DHAnumbering.png (DHA)]]

An omega−3 fatty acid is a fatty acid with multiple double bonds, where the first double bond is between the third and fourth carbon atoms from the end of the carbon atom chain. "Short-chain" omega−3 fatty acids have a chain of 18 carbon atoms or less, while "long-chain" omega−3 fatty acids have a chain of 20 or more.

Three omega−3 fatty acids are important in human physiology, α-linolenic acid (18:3, n−3; ALA), eicosapentaenoic acid (20:5, n−3; EPA), and docosahexaenoic acid (22:6, n−3; DHA).{{cite web|url=https://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/fats-and-cholesterol/types-of-fat/omega-3-fats/|title=Omega−3 Fatty Acids: An Essential Contribution|publisher=TH Chan School of Public Health, Harvard University, Boston|date=2017|access-date=31 December 2018|archive-date=31 December 2018|archive-url=https://web.archive.org/web/20181231092659/https://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/fats-and-cholesterol/types-of-fat/omega-3-fats/|url-status=live}} These three polyunsaturates have either 3, 5, or 6 double bonds in a carbon chain of 18, 20, or 22 carbon atoms, respectively. As with most naturally-produced fatty acids, all double bonds are in the cis-configuration, in other words, the two hydrogen atoms are on the same side of the double bond; and the double bonds are interrupted by methylene bridges ({{chem2|\sCH2\s}}), so that there are two single bonds between each pair of adjacent double bonds.

The atoms at bis-allylic (between double bonds) sites are prone to oxidation by free radicals. Replacement of hydrogen atoms with deuterium atoms in this location protects the omega−3 fatty acid from lipid peroxidation and ferroptosis.{{cite journal

| last1=Demidov| first1=Vadim V.

| title=Site-specifically deuterated essential lipids as new drugs against neuronal, retinal and vascular degeneration

| journal=Drug Discovery Today| date=1 April 2020| volume=25| issue=8| pages=1469–1476

| doi=10.1016/j.drudis.2020.03.014| pmid=32247036

| s2cid=214794450

}}

This table lists several different names for the most common omega−3 fatty acids found in nature.

Omega−3 fatty acids occur naturally in two forms, triglycerides and phospholipids. In the triglycerides, they, together with other fatty acids, are bonded to glycerol; three fatty acids are attached to glycerol. Phospholipid omega−3 is composed of two fatty acids attached to a phosphate group via glycerol.

The triglycerides can be converted to the free fatty acid or to methyl or ethyl esters, and the individual esters of omega−3 fatty acids are available.{{Clarify | date = January 2018|reason=Commercially or bioavailable? I mean, FDA has approved ethyl esters, so it should be both — but which one is intended here?}}

The 'essential' fatty acids were given their name when researchers found that they are essential to normal growth in young children and animals. The omega−3 fatty acid DHA, also known as docosahexaenoic acid, is found in high abundance in the human brain.{{cite journal | vauthors = van West D, Maes M | title = Polyunsaturated fatty acids in depression | journal = Acta Neuropsychiatrica | volume = 15 | issue = 1 | pages = 15–21 | date = February 2003 | pmid = 26984701 | doi = 10.1034/j.1601-5215.2003.00004.x | s2cid = 5343605 }} It is produced by a desaturation process, but humans lack the desaturase enzyme, which acts to insert double bonds at the ω₆ and ω₃ position. Therefore, the ω₆ and ω₃ polyunsaturated fatty acids cannot be synthesized, are appropriately called essential fatty acids, and must be obtained from the diet.

In 1964, it was discovered that enzymes found in sheep tissues convert omega−6 arachidonic acid into the inflammatory agent, prostaglandin E₂,{{cite journal |last1=Bergström |first1=Sune |last2=Danielsson |first2=Henry |last3=Klenberg |first3=Dorrit |last4=Samuelsson |first4=Bengt |title=The Enzymatic Conversion of Essential Fatty Acids into Prostaglandins |journal=Journal of Biological Chemistry |date=November 1964 |volume=239 |issue=11 |pages=PC4006–PC4008 |doi=10.1016/S0021-9258(18)91234-2 |doi-access=free }} which is involved in the immune response of traumatized and infected tissues.{{cite journal | vauthors = Lands WE | title = Biochemistry and physiology of n-3 fatty acids | journal = FASEB Journal | volume = 6 | issue = 8 | pages = 2530–6 | date = May 1992 | pmid = 1592205 | doi = 10.1096/fasebj.6.8.1592205 | doi-access = free | s2cid = 24182617 | author-link = William E.M. Lands }} By 1979, eicosanoids were further identified, including thromboxanes, prostacyclins, and leukotrienes. The eicosanoids typically have a short period of activity in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. If the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may have deleterious effects. Researchers found that certain omega−3 fatty acids are also converted into eicosanoids and docosanoids,{{cite journal | vauthors = Kuda O | title = Bioactive metabolites of docosahexaenoic acid | journal = Biochimie | volume = 136 | pages = 12–20 | date = May 2017 | pmid = 28087294 | doi = 10.1016/j.biochi.2017.01.002 }} but at a slower rate. If both omega−3 and omega−6 fatty acids are present, they will "compete" to be transformed, so the ratio of long-chain omega−3:omega−6 fatty acids directly affects the type of eicosanoids that are produced.

Humans can convert short-chain omega−3 fatty acids to long-chain forms (EPA, DHA) with an efficiency below 5%.{{cite journal | vauthors = Gerster H | title = Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? | journal = International Journal for Vitamin and Nutrition Research. Internationale Zeitschrift für Vitamin- und Ernahrungsforschung. Journal International de Vitaminologie et de Nutrition | volume = 68 | issue = 3 | pages = 159–73 | year = 1998 | pmid = 9637947 }}{{cite journal | vauthors = Brenna JT | title = Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in man | journal = Current Opinion in Clinical Nutrition and Metabolic Care | volume = 5 | issue = 2 | pages = 127–32 | date = March 2002 | pmid = 11844977 | doi = 10.1097/00075197-200203000-00002 }} The omega−3 conversion efficiency is greater in women than in men, but less studied.{{cite journal | vauthors = Burdge GC, Calder PC | title = Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults | journal = Reproduction, Nutrition, Development | volume = 45 | issue = 5 | pages = 581–97 | date = September 2005 | pmid = 16188209 | doi = 10.1051/rnd:2005047 | doi-access = free }} Higher ALA and DHA values found in plasma phospholipids of women may be due to the higher activity of desaturases, especially that of delta-6-desaturase.{{cite journal | vauthors = Lohner S, Fekete K, Marosvölgyi T, Decsi T | title = Gender differences in the long-chain polyunsaturated fatty acid status: systematic review of 51 publications | journal = Annals of Nutrition & Metabolism | volume = 62 | issue = 2 | pages = 98–112 | year = 2013 | pmid = 23327902 | doi = 10.1159/000345599 | doi-access = free }}

These conversions occur competitively with omega−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. They both utilize the same desaturase and elongase proteins in order to synthesize inflammatory regulatory proteins.{{cite journal | vauthors = Ruxton CH, Calder PC, Reed SC, Simpson MJ | title = The impact of long-chain n-3 polyunsaturated fatty acids on human health | journal = Nutrition Research Reviews | volume = 18 | issue = 1 | pages = 113–29 | date = June 2005 | pmid = 19079899 | doi = 10.1079/nrr200497 | doi-access = free }} The products of both pathways are vital for growth making a balanced diet of omega−3 and omega−6 important to an individual's health.{{cite journal | vauthors = Simopoulos AP | title = The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases | journal = Experimental Biology and Medicine | volume = 233 | issue = 6 | pages = 674–88 | date = June 2008 | pmid = 18408140 | doi = 10.3181/0711-MR-311 | s2cid = 9044197 }} A balanced intake ratio of 1:1 was believed to be ideal in order for proteins to be able to synthesize both pathways sufficiently, but this has been controversial as of recent research.{{cite journal | vauthors = Griffin BA | title = How relevant is the ratio of dietary n-6 to n-3 polyunsaturated fatty acids to cardiovascular disease risk? Evidence from the OPTILIP study | journal = Current Opinion in Lipidology | volume = 19 | issue = 1 | pages = 57–62 | date = February 2008 | pmid = 18196988 | doi = 10.1097/MOL.0b013e3282f2e2a8 | s2cid = 13058827 }}

The conversion of ALA to EPA and further to DHA in humans has been reported to be limited, but varies with individuals.{{cite web|title= Conversion Efficiency of ALA to DHA in Humans|url=http://www.dhaomega3.org/Overview/Conversion-Efficiency-of-ALA-to-DHA-in-Humans|website=DHA EPA omega−3 Institute|access-date=21 July 2015|archive-date=5 July 2015|archive-url=https://web.archive.org/web/20150705092326/http://www.dhaomega3.org/Overview/Conversion-Efficiency-of-ALA-to-DHA-in-Humans|url-status=live}} Women have higher ALA-to-DHA conversion efficiency than men, which is presumed to be due to the lower rate of use of dietary ALA for beta-oxidation. One preliminary study showed that EPA can be increased by lowering the amount of dietary linoleic acid, and DHA can be increased by elevating intake of dietary ALA.{{cite journal | vauthors = Goyens PL, Spilker ME, Zock PL, Katan MB, Mensink RP | title = Conversion of alpha-linolenic acid in humans is influenced by the absolute amounts of alpha-linolenic acid and linoleic acid in the diet and not by their ratio | journal = The American Journal of Clinical Nutrition | volume = 84 | issue = 1 | pages = 44–53 | date = July 2006 | pmid = 16825680 | doi = 10.1093/ajcn/84.1.44 | doi-access = free }}

{{main|Essential fatty acid interactions}}

Human diet has changed rapidly in recent centuries resulting in a reported increased diet of omega−6 in comparison to omega−3.{{cite journal |last1=DeFilippis |first1=Andrew P. |last2=Sperling |first2=Laurence S. |title=Understanding omega-3's |journal=American Heart Journal |date=March 2006 |volume=151 |issue=3 |pages=564–570 |doi=10.1016/j.ahj.2005.03.051 |pmid=16504616 }} The rapid evolution of human diet away from a 1:1 omega−3 and omega−6 ratio, such as during the Neolithic Agricultural Revolution, has presumably been too fast for humans to have adapted to biological profiles adept at balancing omega−3 and omega−6 ratios of 1:1.{{cite journal | vauthors = Hofmeijer-Sevink MK, Batelaan NM, van Megen HJ, Penninx BW, Cath DC, van den Hout MA, van Balkom AJ | title = Clinical relevance of comorbidity in anxiety disorders: a report from the Netherlands Study of Depression and Anxiety (NESDA) | journal = Journal of Affective Disorders | volume = 137 | issue = 1–3 | pages = 106–12 | date = March 2012 | pmid = 22240085 | doi = 10.1016/j.jad.2011.12.008 | doi-access = free }} This is commonly believed to be the reason why modern diets are correlated with many inflammatory disorders. While omega−3 polyunsaturated fatty acids may be beneficial in preventing heart disease in humans, the level of omega−6 polyunsaturated fatty acids (and, therefore, the ratio) does not matter.{{cite journal | vauthors = Willett WC | title = The role of dietary n-6 fatty acids in the prevention of cardiovascular disease | journal = Journal of Cardiovascular Medicine | volume = 8 | issue = Suppl 1 | pages = S42-45 | date = September 2007 | pmid = 17876199 | doi = 10.2459/01.JCM.0000289275.72556.13 | s2cid = 1420490 }}

Both omega−6 and omega−3 fatty acids are essential: humans must consume them in their diet. Omega−6 and omega−3 eighteen-carbon polyunsaturated fatty acids compete for the same metabolic enzymes, thus the omega−6:omega−3 ratio of ingested fatty acids has significant influence on the ratio and rate of production of eicosanoids, a group of hormones intimately involved in the body's inflammatory and homeostatic processes, which include the prostaglandins, leukotrienes, and thromboxanes, among others. Altering this ratio can change the body's metabolic and inflammatory state.

Metabolites of omega−6 are more inflammatory (esp. arachidonic acid) than those of omega−3. However, in terms of heart health, omega−6 fatty acids are less harmful than they are presumed to be. A meta-analysis of six randomized trials found that replacing saturated fat with omega−6 fats reduced the risk of coronary events by 24%.{{cite web | url=https://www.health.harvard.edu/newsletter_article/no-need-to-avoid-healthy-omega-6-fats | title=No need to avoid healthy omega-6 fats | date=May 2009 | access-date=23 May 2022 | archive-date=23 May 2022 | archive-url=https://web.archive.org/web/20220523190539/https://www.health.harvard.edu/newsletter_article/no-need-to-avoid-healthy-omega-6-fats | url-status=live }}

A healthy ratio of omega−6 to omega−3 is needed; healthy ratios, according to some authors, range from 1:1 to 1:4.{{cite book|author-link= William EM Lands | vauthors = Lands WE |title=Fish, omega−3 and human health |year= 2005 |publisher= American Oil Chemists' Society |isbn=978-1-893997-81-3}} Other authors believe that a ratio of 4:1 (4 times as much omega−6 as omega−3) is already healthy.{{cite journal | vauthors = Simopoulos AP | title = The importance of the ratio of omega-6/omega-3 essential fatty acids | journal = Biomedicine & Pharmacotherapy| volume = 56 | issue = 8 | pages = 365–79 | date = October 2002 | pmid = 12442909 | doi = 10.1016/S0753-3322(02)00253-6 }}{{cite web |vauthors= Daley CA, Abbott A, Doyle P, Nader G, Larson S |title= A literature review of the value-added nutrients found in grass-fed beef products |website= California State University, Chico College of Agriculture |year= 2004 |url= http://www.csuchico.edu/agr/grassfedbeef/health-benefits/index.html |access-date= 23 March 2008 |url-status= dead |archive-url= https://web.archive.org/web/20080706021024/http://www.csuchico.edu/agr/grassfedbeef/health-benefits/index.html |archive-date= 6 July 2008}}

Typical Western diets provide ratios of between 10:1 and 30:1 (i.e., dramatically higher levels of omega−6 than omega−3).{{cite journal | vauthors = Hibbeln JR, Nieminen LR, Blasbalg TL, Riggs JA, Lands WE | title = Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity | journal = The American Journal of Clinical Nutrition | volume = 83 | issue = 6 Suppl | pages = 1483S–1493S | date = June 2006 | pmid = 16841858 | doi = 10.1093/ajcn/83.6.1483S | doi-access = free }} The ratios of omega−6 to omega−3 fatty acids in some common vegetable oils are: canola 2:1, hemp 2–3:1,{{cite book |author1=Martina Bavec |author2=Franc Bavec |title=Organic Production and Use of Alternative Crops |publisher=Taylor & Francis Ltd |location=London |year=2006 |pages = 178 |isbn=978-1-4200-1742-7 |url=https://books.google.com/books?id=70Ey7Kwqf3EC&pg=PA178 |access-date=18 February 2013}} soybean 7:1, olive 3–13:1, sunflower (no omega−3), flax 1:3,Erasmus, Udo, Fats and Oils. 1986. Alive books, Vancouver, {{ISBN|0-920470-16-5}} p. 263 (round-number ratio within ranges given.) cottonseed (almost no omega−3), peanut (no omega−3), grapeseed oil (almost no omega−3) and corn oil 46:1.{{cite web |title=Oil, vegetable, corn, industrial and retail, all purpose salad or cooking; USDA Nutrient Data, SR-21 |url=https://nutritiondata.self.com/facts/fats-and-oils/580/2 |publisher=Conde Nast |access-date=12 April 2014 |archive-date=13 February 2019 |archive-url=https://web.archive.org/web/20190213234946/https://nutritiondata.self.com/facts/fats-and-oils/580/2 |url-status=live }}

DHA in the form of lysophosphatidylcholine is transported into the brain by a membrane transport protein, MFSD2A, which is exclusively expressed in the endothelium of the blood–brain barrier.{{cite web |title=Sodium-dependent lysophosphatidylcholine symporter 1 |url=https://www.uniprot.org/uniprot/Q8NA29 |url-status=live |archive-url=https://web.archive.org/web/20190422170947/https://www.uniprot.org/uniprot/Q8NA29 |archive-date=22 April 2019 |access-date=2 April 2016 |website=UniProt}}{{cite journal |display-authors=6 |vauthors=Nguyen LN, Ma D, Shui G, Wong P, Cazenave-Gassiot A, Zhang X, Wenk MR, Goh EL, Silver DL |date=May 2014 |title=Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid |journal=Nature |volume=509 |issue=7501 |pages=503–6 |bibcode=2014Natur.509..503N |doi=10.1038/nature13241 |pmid=24828044 |s2cid=4462512}}

In the United States, the Institute of Medicine publishes a system of Dietary Reference Intakes, which includes Recommended Dietary Allowances (RDAs) for individual nutrients, and Acceptable Macronutrient Distribution Ranges (AMDRs) for certain groups of nutrients, such as fats. When there is insufficient evidence to determine an RDA, the institute may publish an Adequate Intake (AI) instead, which has a similar meaning but is less certain. The AI for α-linolenic acid is 1.6 grams/day for men and 1.1 grams/day for women, while the AMDR is 0.6% to 1.2% of total energy. Because the physiological potency of EPA and DHA is much greater than that of ALA, it is not possible to estimate one AMDR for all omega−3 fatty acids. Approximately 10 percent of the AMDR can be consumed as EPA and/or DHA.{{cite book | vauthors = ((Food and Nutrition Board)) |publisher= Institute of Medicine of the National Academies |year= 2005 |title= Dietary Reference Intakes For Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids |location= Washington, DC |isbn= 978-0-309-08537-3 |url= https://archive.org/details/isbn_9780309085250/page/423 |pages= [https://archive.org/details/isbn_9780309085250/page/423 423, 770] |access-date= 6 March 2012 }} The Institute of Medicine has not established a RDA or AI for EPA, DHA or the combination, so there is no Daily Value (DVs are derived from RDAs), no labeling of foods or supplements as providing a DV percentage of these fatty acids per serving, and no labeling a food or supplement as an excellent source, or "High in..."{{Citation needed|date=April 2017}} As for safety, there was insufficient evidence as of 2005 to set an upper tolerable limit for omega−3 fatty acids, although the FDA has advised that adults can safely consume up to a total of 3 grams per day of combined DHA and EPA, with no more than 2 g from dietary supplements.

The European Commission sponsored a working group to develop recommendations on dietary fat intake in pregnancy and lactation. In 2008, the working group published consensus recommendations,{{cite journal |author1=Berthold Koletzko |author2=Irene Cetin |author3=J. Thomas Brenna |title=Dietary fat intakes for pregnant and lactating women |journal=British Journal of Nutrition |date=Nov 2007 |volume=98 |issue=5 |pages=873–7 |doi=10.1017/S0007114507764747 |pmid=17688705 |s2cid=3516064 |ref=koletzko2007 |doi-access=free |hdl=11380/610028 |hdl-access=free }} including the following:

• "pregnant and lactating women should aim to achieve an average dietary intake of at least 200 mg DHA/day"
• "women of childbearing age should aim to consume one to two portions of sea fish per week, including oily fish"
• "intake of the DHA precursor, α-linolenic acid, is far less effective with regard to DHA deposition in fetal brain than preformed DHA"

However, the seafood supply to meet these recommendations is currently too low in most European countries and if met would be unsustainable.{{cite journal | vauthors = Lofstedt A, de Roos B, Fernandes PG | title = Less than half of the European dietary recommendations for fish consumption are satisfied by national seafood supplies | journal = European Journal of Nutrition | volume = 60 | issue = 8 | pages = 4219–4228 | date = December 2021 | pmid = 33999272 | pmc = 8572203 | doi = 10.1007/s00394-021-02580-6 }}

In the EU, the EFSA publishes the Dietary Reference Values (DRVs), recommending Adequate Intake values for EPA+DHA and DHA:{{cite journal |author1=European Food Safety Authority (EFSA) |title=Dietary Reference Values for nutrients Summary report |journal=EFSA Supporting Publications |date=2017 |volume=14 |issue=12 |page=23 |doi=10.2903/sp.efsa.2017.e15121 |ref=efsa |doi-access=free }}

:{{note|drv-ai|1}} AI, Adequate Intake

:{{note|drv-months|2}} i.e. the second half of the first year of life (from the beginning of the 7th month to the 1st birthday)

:{{note|drv-preg|3}} in addition to combined intakes of EPA and DHA of 250 mg/day

The American Heart Association (AHA) has made recommendations for EPA and DHA due to their cardiovascular benefits: individuals with no history of coronary heart disease or myocardial infarction should consume oily fish two times per week; and "Treatment is reasonable" for those having been diagnosed with coronary heart disease. For the latter the AHA does not recommend a specific amount of EPA + DHA, although it notes that most trials were at or close to 1000 mg/day. The benefit appears to be on the order of a 9% decrease in relative risk.{{cite journal | vauthors = Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, Costello RB, Kris-Etherton PM, Jacobson TA, Engler MB, Alger HM, Appel LJ, Mozaffarian D | display-authors = 6 | title = Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association | journal = Circulation | volume = 135 | issue = 15 | pages = e867–e884 | date = April 2017 | pmid = 28289069 | doi = 10.1161/CIR.0000000000000482 | pmc = 6903779 }} The European Food Safety Authority (EFSA) approved a claim "EPA and DHA contributes to the normal function of the heart" for products that contain at least 250 mg EPA + DHA. The report did not address the issue of people with pre-existing heart disease. The World Health Organization recommends regular fish consumption (1-2 servings per week, equivalent to 200 to 500 mg/day EPA + DHA) as protective against coronary heart disease and ischaemic stroke.

Heavy metal poisoning from consuming fish oil supplements is highly unlikely, because heavy metals (mercury, lead, nickel, arsenic, and cadmium) selectively bind with protein in the fish flesh rather than accumulate in the oil.A 2005 corporate test by Consumer Labs of 44 fish oils on the US market found all of the products passed safety standards for potential contaminants.{{cite web |title= Product Review: Omega−3 Fatty Acids (EPA and DHA) from Fish/Marine Oils |publisher= ConsumerLab.com |date= 15 March 2005 |url= http://www.consumerlab.com/results/omega3.asp |access-date= 14 August 2007 |archive-date= 31 December 2018 |archive-url= https://web.archive.org/web/20181231194327/https://www.consumerlab.com/reviews/Omega-3_Fatty_Acids_EPA_and_DHA_from_Fish_Marine_Oils/omega3/ |url-status= live }}

However, other contaminants (PCBs, furans, dioxins, and PBDEs) might be found, especially in less-refined fish oil supplements.2005 study by the Food Safety Authority of Ireland: https://www.fsai.ie/uploadedFiles/Dioxins_milk_survey_2005.pdf {{Webarchive|url=https://web.archive.org/web/20200322194215/https://www.fsai.ie/uploadedFiles/Dioxins_milk_survey_2005.pdf |date=22 March 2020 }}

Throughout their history, the Council for Responsible Nutrition and the World Health Organization have published acceptability standards regarding contaminants in fish oil. The most stringent current standard is the International Fish Oils Standard.{{cite web|url=http://www.ifosprogram.com/IFOS/ConsumerReport.aspx|title=IFOS Home – The International Fish Oil Standards Program|access-date=21 August 2011|archive-url=https://web.archive.org/web/20110821051323/http://www.ifosprogram.com/ifos/ConsumerReport.aspx|archive-date=21 August 2011|url-status=dead}}{{primary source inline|date=September 2012}} Fish oils that are molecularly distilled under vacuum typically make this highest-grade; levels of contaminants are stated in parts per billion per trillion.{{citation needed|date=October 2017}}{{cite journal | vauthors = Shahidi F, Wanasundara UN |date=1 June 1998|title=Omega−3 fatty acid concentrates: nutritional aspects and production technologies |journal=Trends in Food Science & Technology |volume=9 |issue=6 |pages=230–40 |doi=10.1016/S0924-2244(98)00044-2}}

A 2022 study found that a number of products on the market used oxidised oils, with the rancidity often masked by flavourings. Another study in 2015 found that an average of 20% of products had excess oxidation. Whether rancid fish oil is harmful remains unclear. Some studies show that highly oxidised fish oil can have a negative impact on cholesterol levels. Animal testing showed that high doses have toxic effects. Furthermore, rancid oil is likely to be less effective than fresh fish oil.{{cite web|date=17 January 2022|title=Revealed: many common omega−3 fish oil supplements are 'rancid'|url=https://www.theguardian.com/environment/2022/jan/17/revealed-many-common-omega-3-fish-oil-supplements-are-rancid|access-date=17 January 2022|website=The Guardian|archive-date=17 January 2022|archive-url=https://web.archive.org/web/20220117070111/https://www.theguardian.com/environment/2022/jan/17/revealed-many-common-omega-3-fish-oil-supplements-are-rancid|url-status=live}}{{cite web|title=Top 10 Fish Oil Supplements|url=https://labdoor.com/rankings/fish-oil|access-date=17 January 2022|website=labdoor|archive-date=17 January 2022|archive-url=https://web.archive.org/web/20220117071028/https://labdoor.com/rankings/fish-oil|url-status=live}}

The most widely available dietary source of EPA and DHA is oily fish, such as salmon, herring, mackerel, anchovies, and sardines. Oils from these fishes have around seven times as much omega−3 as omega−6. Other oily fish, such as tuna, also contain n−3 in somewhat lesser amounts.{{cite journal |vauthors=Mozaffarian, Rimm EB |year=2006 |title=Fish intake, contaminants, and human health: evaluating the risks and the benefits |journal=Journal of the American Medical Association |volume=15 |issue=1 |pages=1885–1899 |issn=0098-7484 |pmid=17047219 |doi=10.1001/jama.296.15.1885|doi-access=free}} Although fish are a dietary source of omega−3 fatty acids, fish do not synthesize omega−3 fatty acids, but rather obtain them via their food supply, including algae or plankton.{{cite journal |vauthors= Falk-Petersen A, Sargent JR, Henderson J, Hegseth EN, Hop H, Okolodkov YB |year=1998|title=Lipids and fatty acids in ice algae and phytoplankton from the Marginal Ice Zone in the Barents Sea|journal=Polar Biology|volume=20|issue=1|pages=41–47|issn=0722-4060|id={{INIST|2356641}}|doi=10.1007/s003000050274|bibcode=1998PoBio..20...41F |s2cid=11027523}}

In order for farmed marine fish to have amounts of EPA and DHA comparable to those of wild-caught fish, their feed must be supplemented with EPA and DHA, most commonly in the form of fish oil. For this reason, 81% of the global fish oil supply in 2009 was consumed by aquaculture. By 2019, two alternative sources of EPA and DHA for fish have been partially commercialized: genetically modified canola oil and Schizochytrium algal oil.{{cite web |title=Nofima has found new sources of omega-3 for fish feed |url=https://thefishsite.com/articles/nofima-has-found-new-sources-of-omega-3-for-fish-feed |website=The Fish Site |language=en |date=31 October 2019}}

{{see also|Fish oil|Cod liver oil}}

File:Lachsölkapsel.jpg

Marine and freshwater fish oil vary in content of arachidonic acid, EPA and DHA.{{cite journal | vauthors = Innis SM, Rioux FM, Auestad N, Ackman RG | title = Marine and freshwater fish oil varying in arachidonic, eicosapentaenoic and docosahexaenoic acids differ in their effects on organ lipids and fatty acids in growing rats | journal = The Journal of Nutrition | volume = 125 | issue = 9 | pages = 2286–93 | date = September 1995 | pmid = 7666244 | doi = 10.1093/jn/125.9.2286 }} They also differ in their effects on organ lipids.

Not all forms of fish oil may be equally digestible. Of four studies that compare bioavailability of the glyceryl ester form of fish oil vs. the ethyl ester form, two have concluded the natural glyceryl ester form is better, and the other two studies did not find a significant difference. No studies have shown the ethyl ester form to be superior, although it is cheaper to manufacture.{{cite journal | vauthors = Lawson LD, Hughes BG | title = Absorption of eicosapentaenoic acid and docosahexaenoic acid from fish oil triacylglycerols or fish oil ethyl esters co-ingested with a high-fat meal | journal = Biochemical and Biophysical Research Communications | volume = 156 | issue = 2 | pages = 960–3 | date = October 1988 | pmid = 2847723 | doi = 10.1016/S0006-291X(88)80937-9 }}{{cite journal | vauthors = Beckermann B, Beneke M, Seitz I | title = [Comparative bioavailability of eicosapentaenoic acid and docosahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers] | language = de | journal = Arzneimittel-Forschung | volume = 40 | issue = 6 | pages = 700–4 | date = June 1990 | pmid = 2144420 }}

File:Krill oil capsules cropped.png

Krill oil is a source of omega−3 fatty acids.{{cite journal | vauthors = Tur JA, Bibiloni MM, Sureda A, Pons A | title = Dietary sources of omega 3 fatty acids: public health risks and benefits | journal = The British Journal of Nutrition | volume = 107 | issue = Suppl 2 | pages = S23-52 | date = June 2012 | pmid = 22591897 | doi = 10.1017/S0007114512001456 | doi-access = free }} The effect of krill oil, at a lower dose of EPA + DHA (62.8%), was demonstrated to be similar to that of fish oil on blood lipid levels and markers of inflammation in healthy humans.{{cite journal | vauthors = Ulven SM, Kirkhus B, Lamglait A, Basu S, Elind E, Haider T, Berge K, Vik H, Pedersen JI | display-authors = 6 | title = Metabolic effects of krill oil are essentially similar to those of fish oil but at lower dose of EPA and DHA, in healthy volunteers | journal = Lipids | volume = 46 | issue = 1 | pages = 37–46 | date = January 2011 | pmid = 21042875 | pmc = 3024511 | doi = 10.1007/s11745-010-3490-4 }} While not an endangered species, krill are a mainstay of the diets of many ocean-based species including whales, causing environmental and scientific concerns about their sustainability.{{cite journal | vauthors = Atkinson A, Siegel V, Pakhomov E, Rothery P | title = Long-term decline in krill stock and increase in salps within the Southern Ocean | journal = Nature | volume = 432 | issue = 7013 | pages = 100–3 | date = November 2004 | pmid = 15525989 | doi = 10.1038/nature02996 | bibcode = 2004Natur.432..100A | s2cid = 4397262 }}{{cite web|url=http://www.stuff.co.nz/science/10093611/Malnutrition-behind-whale-strandings|title=Malnutrition behind whale strandings|vauthors=Orr A|publisher=Stuff, Fairfax New Zealand Limited|date=2014|access-date=8 August 2015|archive-date=5 April 2019|archive-url=https://web.archive.org/web/20190405113935/http://www.stuff.co.nz/science/10093611/Malnutrition-behind-whale-strandings|url-status=live}}{{cite web|url=https://www.ccamlr.org/en/fisheries/krill-fisheries-and-sustainability|publisher=Commission for the Conservation of Antarctic Marine Living Resources, Tasmania, Australia|title=Krill fisheries and sustainability|date=2015|access-date=8 August 2015|archive-date=14 April 2019|archive-url=https://web.archive.org/web/20190414211636/https://www.ccamlr.org/en/fisheries/krill-fisheries-and-sustainability|url-status=live}}

Preliminary studies indicate that the DHA and EPA omega−3 fatty acids found in krill oil are more bio-available than in fish oil.{{cite journal | vauthors = Köhler A, Sarkkinen E, Tapola N, Niskanen T, Bruheim I | title = Bioavailability of fatty acids from krill oil, krill meal and fish oil in healthy subjects--a randomized, single-dose, cross-over trial | journal = Lipids in Health and Disease | volume = 14 | pages = 19 | date = March 2015 | pmid = 25884846 | pmc = 4374210 | doi = 10.1186/s12944-015-0015-4 | doi-access = free }} Additionally, krill oil contains astaxanthin, a marine-source keto-carotenoid antioxidant that may act synergistically with EPA and DHA.{{cite journal | vauthors = Saw CL, Yang AY, Guo Y, Kong AN | title = Astaxanthin and omega-3 fatty acids individually and in combination protect against oxidative stress via the Nrf2-ARE pathway | journal = Food and Chemical Toxicology | volume = 62 | pages = 869–875 | date = December 2013 | pmid = 24157545 | doi = 10.1016/j.fct.2013.10.023 }}{{cite journal | vauthors = Barros MP, Poppe SC, Bondan EF | title = Neuroprotective properties of the marine carotenoid astaxanthin and omega-3 fatty acids, and perspectives for the natural combination of both in krill oil | journal = Nutrients | volume = 6 | issue = 3 | pages = 1293–1317 | date = March 2014 | pmid = 24667135 | pmc = 3967194 | doi = 10.3390/nu6031293 | doi-access = free }}{{cite news |vauthors=Zimmer C |author-link=Carl Zimmer |title=Inuit Study Adds Twist to Omega-3 Fatty Acids' Health Story |url=https://www.nytimes.com/2015/09/22/science/inuit-study-adds-twist-to-omega-3-fatty-acids-health-story.html |date=17 September 2015 |work=The New York Times |access-date=11 October 2015 |archive-date=9 January 2019 |archive-url=https://web.archive.org/web/20190109042557/https://www.nytimes.com/2015/09/22/science/inuit-study-adds-twist-to-omega-3-fatty-acids-health-story.html |url-status=live }}{{cite news |vauthors=O'Connor A |title=Fish Oil Claims Not Supported by Research |url=http://well.blogs.nytimes.com/2015/03/30/fish-oil-claims-not-supported-by-research/ |date=30 March 2015 |work=The New York Times |access-date=11 October 2015 |archive-date=28 May 2018 |archive-url=https://web.archive.org/web/20180528110348/https://well.blogs.nytimes.com/2015/03/30/fish-oil-claims-not-supported-by-research/ |url-status=live }}

{{See also|Algal oil}}

File:Semillas de Chía.jpg is grown commercially for its seeds rich in ALA]]

File:Flax seeds.jpg seeds contain linseed oil which has high ALA content]]

File:Vegan omega-3 supplements.jpg sp.), 96.3% of total content]]

Linseed (or flaxseed) (Linum usitatissimum) and its oil are perhaps the most widely available botanical source of the omega−3 fatty acid ALA. Flaxseed oil consists of approximately 55% ALA, which makes it six times richer than most fish oils in omega−3 fatty acids.{{cite book| vauthors = Bartram T |title=Bartram's Encyclopedia of Herbal Medicine: The Definitive Guide to the Herbal Treatments of Diseases|date=September 2002|publisher=Da Capo Press|isbn=978-1-56924-550-7 |pages = 271}} A portion of this is converted by the body to EPA and DHA, though the actual converted percentage may differ between men and women.{{cite journal | vauthors = Decsi T, Kennedy K | title = Sex-specific differences in essential fatty acid metabolism | journal = The American Journal of Clinical Nutrition | volume = 94 | issue = 6 Suppl | pages = 1914S–1919S | date = December 2011 | pmid = 22089435 | doi = 10.3945/ajcn.110.000893 | doi-access = free }}

The longer-chain EPA and DHA are only naturally made by marine algae and phytoplankton. The microalgae Crypthecodinium cohnii and Schizochytrium are rich sources of DHA, but not EPA, and can be produced commercially in bioreactors for use as food additives. Oil from brown algae (kelp) is a source of EPA.{{cite journal | vauthors = van Ginneken VJ, Helsper JP, de Visser W, van Keulen H, Brandenburg WA | title = Polyunsaturated fatty acids in various macroalgal species from North Atlantic and tropical seas | journal = Lipids in Health and Disease | volume = 10 | issue = 104 | pages = 104 | date = June 2011 | pmid = 21696609 | pmc = 3131239 | doi = 10.1186/1476-511X-10-104 | doi-access = free }} The alga Nannochloropsis also has high levels of EPA.{{cite journal | vauthors = Collins ML, Lynch B, Barfield W, Bull A, Ryan AS, Astwood JD | title = Genetic and acute toxicological evaluation of an algal oil containing eicosapentaenoic acid (EPA) and palmitoleic acid | journal = Food and Chemical Toxicology | volume = 72 | pages = 162–8 | date = October 2014 | pmid = 25057807 | doi = 10.1016/j.fct.2014.07.021 }}

Some transgenic initiatives have transferred the ability to make EPA and DHA into existing high-yielding crop species of land plants:{{cite journal |last1=West |first1=AL |last2=Miles |first2=EA |last3=Lillycrop |first3=KA |last4=Napier |first4=JA |last5=Calder |first5=PC |last6=Burdge |first6=GC |title=Genetically modified plants are an alternative to oily fish for providing n-3 polyunsaturated fatty acids in the human diet: A summary of the findings of a Biotechnology and Biological Sciences Research Council funded project. |journal=Nutrition Bulletin |date=March 2021 |volume=46 |issue=1 |pages=60–68 |doi=10.1111/nbu.12478 |pmid=33776584 |pmc=7986926}}

• Camelina sativa: In 2013, Rothamsted Research reported two genetically modified forms of this plant. Oil from the seeds of this plant contained on average 15% ALA, 11% EPA, and 8% DHA in one development and 11% ALA and 24% EPA in another.{{cite journal | vauthors = Ruiz-Lopez N, Haslam RP, Napier JA, Sayanova O | title = Successful high-level accumulation of fish oil omega-3 long-chain polyunsaturated fatty acids in a transgenic oilseed crop | journal = The Plant Journal | volume = 77 | issue = 2 | pages = 198–208 | date = January 2014 | pmid = 24308505 | pmc = 4253037 | doi = 10.1111/tpj.12378 }}{{cite news |last1=Coghlan |first1=Andy |title=Designer plants have vital fish oils in their seeds |url=https://www.newscientist.com/article/mg22129503-000-designer-plants-have-vital-fish-oils-in-their-seeds/ |work=New Scientist |date=31 December 2013 }}
• Canola: In 2011, CSIRO, GRDC, and Nufarm developed a version of canola that produces DHA in seeds; the oil contains 10% DHA and almost no EPA. In 2018, it was approved as an animal feed additive in Australia.{{cite web |title=Omega-3 canola |url=https://www.csiro.au/en/research/production/biotechnology/Omega-3-canola |website=www.csiro.au |language=en}} In 2021, the US FDA acknowledged it as a New Dietary Ingredient for humans.{{cite press release |last1=Nutritional |first1=Nuseed |title=FDA Acknowledges Nutriterra® Total Omega-3 Canola Oil is a Safe New Dietary Ingredient |url=https://www.prnewswire.com/news-releases/fda-acknowledges-nutriterra-total-omega-3-canola-oil-is-a-safe-new-dietary-ingredient-301354794.html |website=www.prnewswire.com |language=en}} Separately, Cargill has commercialized a different strain of canola that produces EPA and DHA for fish feed. The oil contains 8.1% EPA and 0.8% DHA.

Eggs produced by hens fed a diet of greens and insects contain higher levels of omega−3 fatty acids than those produced by chickens fed corn or soybeans.{{cite web|url=https://www.medicalnewstoday.com/releases/51575|title=How Omega-6s Usurped Omega-3s In US Diet|website=Medical News Today|access-date=28 April 2020|archive-date=28 July 2020|archive-url=https://web.archive.org/web/20200728031737/https://www.medicalnewstoday.com/releases/51575|url-status=live}} In addition to feeding chickens insects and greens, fish oils may be added to their diets to increase the omega−3 fatty acid concentrations in eggs.{{cite journal | vauthors = Trebunová A, Vasko L, Svedová M, Kastel' R, Tucková M, Mach P | title = The influence of omega-3 polyunsaturated fatty acids feeding on the composition of fatty acids in fatty tissues and eggs of laying hens | journal = DTW. Deutsche Tierarztliche Wochenschrift | volume = 114 | issue = 7 | pages = 275–279 | date = July 2007 | pmid = 17724936 }}

The addition of flax and canola seeds, both good sources of alpha-linolenic acid, to the diets of laying chickens, increases the omega−3 content of the eggs, predominantly DHA.{{cite journal | vauthors = Cherian G, Sim JS | title = Effect of feeding full fat flax and canola seeds to laying hens on the fatty acid composition of eggs, embryos, and newly hatched chicks. | journal = Poultry Science | date = April 1991 | volume = 70 | issue = 4 | pages = 917–22 | doi = 10.3382/ps.0700917 | doi-access = free }} However, this enrichment could lead to an increment of lipid oxidation in the eggs if the seeds are used in higher doses, without using an appropriate antioxidant.{{cite journal | vauthors = Vlaicu PA, Panaite TD, Turcu RP | title = Enriching laying hens eggs by feeding diets with different fatty acid composition and antioxidants | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 20707 | date = October 2021 | pmid = 34667227 | pmc = 8526598 | doi = 10.1038/s41598-021-00343-1 | bibcode = 2021NatSR..1120707V }}

The addition of green algae or seaweed to the diets boosts the content of DHA and EPA, which are the forms of omega−3 approved by the FDA for medical claims. A common consumer complaint is "Omega−3 eggs can sometimes have a fishy taste if the hens are fed marine oils".{{cite news |vauthors=Colin S |url=https://www.huffingtonpost.com/2010/06/03/egg-taste-test-says-no-di_n_599286.html |title=Washington Post's Egg Taste Test Says Homegrown And Factory Eggs Taste The Same [UPDATED, POLL] |publisher=Huffingtonpost.com |date=3 June 2010 |access-date=3 January 2011 |archive-date=10 June 2010 |archive-url=https://web.archive.org/web/20100610015751/http://www.huffingtonpost.com/2010/06/03/egg-taste-test-says-no-di_n_599286.html |url-status=live }}

Omega−3 fatty acids are formed in the chloroplasts of green leaves and algae. While seaweeds and algae are the sources of omega−3 fatty acids present in fish, grass is the source of omega−3 fatty acids present in grass-fed animals.{{cite journal | vauthors = Garton GA | title = Fatty acid composition of the lipids of pasture grasses | journal = Nature | volume = 187 | issue = 4736 | pages = 511–2 | date = August 1960 | pmid = 13826699 | doi = 10.1038/187511b0 | bibcode = 1960Natur.187..511G | s2cid = 4296061 }} When cattle are taken off omega−3 fatty acid-rich grass and shipped to a feedlot to be fattened on omega−3 fatty acid deficient grain, they begin losing their store of this beneficial fat. Each day that an animal spends in the feedlot, the amount of omega−3 fatty acids in its meat is diminished.{{cite journal | vauthors = Duckett SK, Wagner DG, Yates LD, Dolezal HG, May SG | title = Effects of time on feed on beef nutrient composition | journal = Journal of Animal Science | volume = 71 | issue = 8 | pages = 2079–88 | date = August 1993 | pmid = 8376232 | doi = 10.2527/1993.7182079x }}

The omega−6:omega−3 ratio of grass-fed beef is about 2:1, making it a more useful source of omega−3 than grain-fed beef, which usually has a ratio of 4:1.

In a 2009 joint study by the USDA and researchers at Clemson University in South Carolina, grass-fed beef was compared with grain-finished beef. The researchers found that grass-finished beef is higher in moisture content, 42.5% lower total lipid content, 54% lower in total fatty acids, 54% higher in beta-carotene, 288% higher in vitamin E (alpha-tocopherol), higher in the B-vitamins thiamin and riboflavin, higher in the minerals calcium, magnesium, and potassium, 193% higher in total omega−3s, 117% higher in CLA (cis-9, trans-11 octadecenoic acid, a conjugated linoleic acid, which is a potential cancer fighter), 90% higher in vaccenic acid (which can be transformed into CLA), lower in the saturated fats, and has a healthier ratio of omega−6 to omega−3 fatty acids (1.65 vs 4.84). Protein and cholesterol content were equal.{{cite journal | vauthors = Duckett SK, Neel JP, Fontenot JP, Clapham WM | title = Effects of winter stocker growth rate and finishing system on: III. Tissue proximate, fatty acid, vitamin, and cholesterol content | journal = Journal of Animal Science | volume = 87 | issue = 9 | pages = 2961–70 | date = September 2009 | pmid = 19502506 | doi = 10.2527/jas.2009-1850 }}

The omega−3 content of chicken meat may be enhanced by increasing the animals' dietary intake of grains high in omega−3, such as flax, chia, and canola.{{cite journal | vauthors = Azcona JO, Schang MJ, Garcia PT, Gallinger C, Ayerza Jr R, Coates W |year= 2008 |title= Omega−3 enriched broiler meat: The influence of dietary alpha-linolenic omega−3 fatty acid sources on growth, performance and meat fatty acid composition |journal= Canadian Journal of Animal Science |volume= 88 |pages= 257–69 |doi= 10.4141/CJAS07081 |issue= 2|doi-access= free}}

Kangaroo meat is also a source of omega−3, with fillet and steak containing 74 mg per 100 g of raw meat.{{cite web|title=Gourmet Game – Amazing Nutrition Facts|url=http://www.macromeats-gourmetgame.com.au/Nutrition/AmazingNutritionFacts.aspx|archive-url=https://web.archive.org/web/20090301215435/http://www.macromeats-gourmetgame.com.au/Nutrition/AmazingNutritionFacts.aspx|url-status=dead|archive-date=1 March 2009|date=31 May 2019}}

Seal oil is a source of EPA, DPA, and DHA, and is commonly used in Arctic regions. According to Health Canada, it helps to support the development of the brain, eyes, and nerves in children up to 12 years of age.{{cite web |url=http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/monograph/mono_seal_oil_huile_phoque-eng.php |title=Natural Health Product Monograph – Seal Oil |publisher=Health Canada |date=22 June 2009 |access-date=20 June 2012 |archive-url=https://web.archive.org/web/20120319162030/http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/monograph/mono_seal_oil_huile_phoque-eng.php |archive-date=19 March 2012 |url-status=dead }} Like all seal products, it is not allowed to be imported into the European Union.{{cite web |last= European Parliament |author-link= European Parliament |title= MEPs adopt strict conditions for the placing on the market of seal products in the European Union |work= Hearings |publisher= European Parliament |date= 9 November 2009 |url= http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//TEXT+IM-PRESS+20090504IPR54952+0+DOC+XML+V0//EN |access-date= 12 March 2010 |archive-date= 14 October 2012 |archive-url= https://web.archive.org/web/20121014122132/http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//TEXT+IM-PRESS+20090504IPR54952+0+DOC+XML+V0//EN |url-status= live }}

A Canadian company, FeelGood Natural Health, pleaded guilty in 2023 to illegally selling seal oil capsules to American consumers. The company sold over 900 bottles of the capsules, worth over $10,000. Seal oil is made from the blubber of dead seals, and is illegal to sell in the United States under the Marine Mammal Protection Act. The global population of harp seals stands at around 7 million, and they have been hunted in Canada for thousands of years. FeelGood was sentenced to pay a fine of $20,000 and three years of probation.{{cite news |vauthors=Whittle P |url=https://apnews.com/article/canadian-seal-oil-importer-pleads-guilty-65a9e1387f9fea441bd2e9d595e2d451 |title=Canadian company pleads guilty to shipping banned seal oil to US |publisher=Associated Press |date=6 June 2023 |access-date=8 June 2023 |archive-date=8 June 2023 |archive-url=https://web.archive.org/web/20230608013018/https://apnews.com/article/canadian-seal-oil-importer-pleads-guilty-65a9e1387f9fea441bd2e9d595e2d451 |url-status=live }}

A trend in the early 21st century was to fortify food with omega−3 fatty acids.{{cite journal |vauthors=Ganesan B, Brothersen C, McMahon DJ |title=Fortification of foods with omega-3 polyunsaturated fatty acids |journal=Critical Reviews in Food Science and Nutrition |volume=54 |issue=1 |pages=98–114 |date=2014 |pmid=24188235 |s2cid=44629122 |doi=10.1080/10408398.2011.578221}}{{cite news|url=https://www.theglobeandmail.com/life/health-and-fitness/ask-a-health-expert/omega-3-eggs-healthier-choice-or-marketing-gimmick/article4574714/|title=Omega-3 eggs: healthier choice or marketing gimmick?|newspaper=The Toronto Globe and Mail|vauthors=Beck L|date=9 May 2018|access-date=7 March 2019|archive-date=10 August 2020|archive-url=https://web.archive.org/web/20200810054317/https://www.theglobeandmail.com/life/health-and-fitness/ask-a-health-expert/omega-3-eggs-healthier-choice-or-marketing-gimmick/article4574714/|url-status=live}}

{{See also|Fish oil#Health effects}}

The association between supplementation and a lower risk of all-cause mortality is inconclusive.{{cite journal | vauthors = Rizos EC, Elisaf MS | title = Does Supplementation with Omega-3 PUFAs Add to the Prevention of Cardiovascular Disease? | journal = Current Cardiology Reports | volume = 19 | issue = 6 | pages = 47 | date = June 2017 | pmid = 28432658 | doi = 10.1007/s11886-017-0856-8 | s2cid = 23585060 }}

There is insufficient evidence that supplementation with omega−3 fatty acids has an effect on different cancers.{{cite journal | vauthors = Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins JP, Capps NE, Riemersma RA, Ebrahim SB, Davey Smith G | display-authors = 6 | title = Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review | journal = BMJ | volume = 332 | issue = 7544 | pages = 752–760 | date = April 2006 | pmid = 16565093 | pmc = 1420708 | doi = 10.1136/bmj.38755.366331.2F }}{{cite journal | vauthors = MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, Lim YW, Traina SB, Hilton L, Garland R, Morton SC | display-authors = 6 | title = Effects of omega-3 fatty acids on cancer risk: a systematic review | journal = JAMA | volume = 295 | issue = 4 | pages = 403–415 | date = January 2006 | pmid = 16434631 | doi = 10.1001/jama.295.4.403 | hdl-access = free | hdl = 10919/79706 }} Omega−3 supplements do not improve body weight, muscle maintenance or quality of life in cancer patients.{{cite journal |last1=Lam |first1=Chung Nga |last2=Watt |first2=Amanda E. |last3=Isenring |first3=Elizabeth A. |last4=de van der Schueren |first4=Marian A.E. |last5=van der Meij |first5=Barbara S. |title=The effect of oral omega-3 polyunsaturated fatty acid supplementation on muscle maintenance and quality of life in patients with cancer: A systematic review and meta-analysis |journal=Clinical Nutrition |date=June 2021 |volume=40 |issue=6 |pages=3815–3826 |doi=10.1016/j.clnu.2021.04.031 |pmid=34130028 |url=https://pure.bond.edu.au/ws/files/46881350/ESPEN20_LB_2108_Final_version.pdf }}

Moderate and high quality evidence from a 2020 review showed that EPA and DHA, such as that found in omega−3 polyunsaturated fatty acid supplements, does not appear to improve mortality or cardiovascular health.{{cite journal | vauthors = Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KH, Summerbell CD, Worthington HV, Song F, Hooper L | display-authors = 6 | title = Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 3 | pages = CD003177 | date = February 2020 | pmid = 32114706 | pmc = 7049091 | doi = 10.1002/14651858.CD003177.pub5 }} There is weak evidence indicating that α-linolenic acid may be associated with a small reduction in the risk of a cardiovascular event or the risk of arrhythmia.

A 2018 meta-analysis found no support that daily intake of one gram of omega−3 fatty acid in individuals with a history of coronary heart disease prevents fatal coronary heart disease, nonfatal myocardial infarction or any other vascular event.{{cite journal | vauthors = Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse JM, Rauch B, Ness A, Galan P, Chew EY, Bosch J, Collins R, Lewington S, Armitage J, Clarke R | display-authors = 6 | title = Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals | journal = JAMA Cardiology | volume = 3 | issue = 3 | pages = 225–234 | date = March 2018 | pmid = 29387889 | pmc = 5885893 | doi = 10.1001/jamacardio.2017.5205 }} However, omega−3 fatty acid supplementation greater than one gram daily for at least a year may be protective against cardiac death, sudden death, and myocardial infarction in people who have a history of cardiovascular disease.{{cite journal | vauthors = Casula M, Soranna D, Catapano AL, Corrao G | title = Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo controlled trials [corrected] | journal = Atherosclerosis. Supplements | volume = 14 | issue = 2 | pages = 243–51 | date = August 2013 | pmid = 23958480 | doi = 10.1016/S1567-5688(13)70005-9 }} No protective effect against the development of stroke or all-cause mortality was seen in this population. A 2021 meta-analysis found that supplementation was associated with a reduced risk of myocardial infarction and coronary heart disease.{{cite journal |vauthors=Bernasconi AA, Wiest MM, Lavie CJ, Milani RV, Laukkanen JA |title=Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials |journal=Mayo Clinic Proceedings |volume=96 |issue=2 |pages=304–313 |date=February 2021 |pmid=32951855 |doi=10.1016/j.mayocp.2020.08.034 |url=https://www.mayoclinicproceedings.org/article/S0025-6196(20)30985-X/fulltext|doi-access=free }}

Fish oil supplementation has not been shown to benefit revascularization or abnormal heart rhythms and has no effect on heart failure hospital admission rates.{{cite journal | vauthors = Kotwal S, Jun M, Sullivan D, Perkovic V, Neal B | title = Omega 3 Fatty acids and cardiovascular outcomes: systematic review and meta-analysis | journal = Circulation: Cardiovascular Quality and Outcomes | volume = 5 | issue = 6 | pages = 808–18 | date = November 2012 | pmid = 23110790 | doi = 10.1161/CIRCOUTCOMES.112.966168 | doi-access = free }} Furthermore, fish oil supplement studies have failed to support claims of preventing heart attacks or strokes.{{cite journal | vauthors = Grey A, Bolland M | title = Clinical trial evidence and use of fish oil supplements | journal = JAMA Internal Medicine | volume = 174 | issue = 3 | pages = 460–2 | date = March 2014 | pmid = 24352849 | doi = 10.1001/jamainternmed.2013.12765 | doi-access = free }} In the EU, a review by the European Medicines Agency of omega−3 fatty acid medicines containing a combination of an ethyl ester of eicosapentaenoic acid and docosahexaenoic acid at a dose of 1 g per day concluded that these medicines are not effective in secondary prevention of heart problems in people who have had a myocardial infarction.{{Cite web|url=https://www.ema.europa.eu/en/medicines/human/referrals/omega-3-acid-ethyl-esters-containing-medicinal-products-oral-use-secondary-prevention-after|title=Omega-3-acid ethyl esters - containing medicinal products for oral in use in secondary prevention after myocardial infarction|date=6 June 2019|website=European Medicines Agency|access-date=4 October 2019|archive-date=13 April 2019|archive-url=https://web.archive.org/web/20190413160818/https://www.ema.europa.eu/en/medicines/human/referrals/omega-3-fatty-acid-medicines|url-status=live}}

Evidence suggests that omega−3 fatty acids modestly lower blood pressure (systolic and diastolic) in people with hypertension and in people with normal blood pressure.{{cite journal | vauthors = Miller PE, Van Elswyk M, Alexander DD | title = Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials | journal = American Journal of Hypertension | volume = 27 | issue = 7 | pages = 885–96 | date = July 2014 | pmid = 24610882 | pmc = 4054797 | doi = 10.1093/ajh/hpu024 }}{{cite journal | vauthors = Morris MC, Sacks F, Rosner B | title = Does fish oil lower blood pressure? A meta-analysis of controlled trials | journal = Circulation | volume = 88 | issue = 2 | pages = 523–33 | date = August 1993 | pmid = 8339414 | doi = 10.1161/01.CIR.88.2.523 | doi-access = free }} Omega−3 fatty acids can also reduce heart rate,{{cite journal | vauthors = Mori TA, Bao DQ, Burke V, Puddey IB, Beilin LJ | title = Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans | journal = Hypertension | volume = 34 | issue = 2 | pages = 253–60 | date = August 1999 | pmid = 10454450 | doi = 10.1161/01.HYP.34.2.253 | doi-access = free }} an emerging risk factor. Some evidence suggests that people with certain circulatory problems, such as varicose veins, may benefit from the consumption of EPA and DHA, which may stimulate blood circulation and increase the breakdown of fibrin, a protein involved in blood clotting and scar formation.

Omega−3 fatty acids reduce blood triglyceride levels, but do not significantly change the level of LDL cholesterol or HDL cholesterol.{{cite journal | vauthors = Weintraub HS | title = Overview of prescription omega-3 fatty acid products for hypertriglyceridemia | journal = Postgraduate Medicine | volume = 126 | issue = 7 | pages = 7–18 | date = November 2014 | pmid = 25387209 | doi = 10.3810/pgm.2014.11.2828 | s2cid = 12524547 }}{{cite journal | vauthors = Wu L, Parhofer KG | title = Diabetic dyslipidemia | journal = Metabolism | volume = 63 | issue = 12 | pages = 1469–79 | date = December 2014 | pmid = 25242435 | doi = 10.1016/j.metabol.2014.08.010 }} The American Heart Association position (2011) is that borderline elevated triglycerides, defined as 150–199 mg/dL, can be lowered by 0.5–1.0 grams of EPA and DHA per day; high triglycerides 200–499 mg/dL benefit from 1–2 g/day; and >500 mg/dL be treated under a physician's supervision with 2–4 g/day using a prescription product.{{cite journal | vauthors = Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S | display-authors = 6 | title = Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association | journal = Circulation | volume = 123 | issue = 20 | pages = 2292–333 | date = May 2011 | pmid = 21502576 | doi = 10.1161/CIR.0b013e3182160726 | doi-access = free }} In this population, omega−3 fatty acid supplementation decreases the risk of heart disease by about 25%.{{cite journal | vauthors = Skulas-Ray AC, Wilson PW, Harris WS, Brinton EA, Kris-Etherton PM, Richter CK, Jacobson TA, Engler MB, Miller M, Robinson JG, Blum CB, Rodriguez-Leyva D, de Ferranti SD, Welty FK | display-authors = 6 | title = Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association | journal = Circulation | volume = 140 | issue = 12 | pages = e673–e691 | date = September 2019 | pmid = 31422671 | doi = 10.1161/CIR.0000000000000709 | doi-access = free }}

A 2019 review found that omega−3 fatty acid supplements make little or no difference to cardiovascular mortality and that people with myocardial infarction have no benefit in taking the supplements.{{cite journal | vauthors = Popoff F, Balaciano G, Bardach A, Comandé D, Irazola V, Catalano HN, Izcovich A | title = Omega 3 fatty acid supplementation after myocardial infarction: a systematic review and meta-analysis | journal = BMC Cardiovascular Disorders | volume = 19 | issue = 1 | pages = 136 | date = June 2019 | pmid = 31164089 | pmc = 6549284 | doi = 10.1186/s12872-019-1086-3 | doi-access = free }} A 2021 review found that omega−3 supplementation did not affect cardiovascular disease outcomes.

A 2021 review concluded that use of omega−3 supplements was associated with an increased risk of atrial fibrillation in people having high blood triglycerides.{{cite journal |vauthors=Lombardi M, Carbone S, Del Buono MG, Chiabrando JG, Vescovo GM, Camilli M, Montone RA, Vergallo R, Abbate A, Biondi-Zoccai G, Dixon DL, Crea F|display-authors=3 |title=Omega-3 fatty acids supplementation and risk of atrial fibrillation: an updated meta-analysis of randomized controlled trials |journal=European Heart Journal - Cardiovascular Pharmacotherapy |volume=7 |issue=4 |pages=e69–e70 |date=July 2021 |pmid=33910233 |pmc=8302253 |doi=10.1093/ehjcvp/pvab008}} A meta-analysis showed that use of marine omega−3 supplementation was associated with an increased risk of atrial fibrillation, with the risk appearing to increase for doses greater than one gram per day.{{cite journal | vauthors = Gencer B, Djousse L, Al-Ramady OT, Cook NR, Manson JE, Albert CM|display-authors=3 | title = Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis | journal = Circulation | volume = 144 | issue = 25 | pages = 1981–1990 | date = December 2021 | pmid = 34612056 | pmc = 9109217 | doi = 10.1161/CIRCULATIONAHA.121.055654 }}

In people with chronic kidney disease (CKD) who require hemodialysis, vascular blockage due to clotting may prevent dialysis therapy. Omega−3 fatty acids contribute to the production of eicosanoid molecules that reduce clotting. However, a Cochrane review in 2018 did not find clear evidence that omega−3 supplementation has any impact on the prevention of vascular blockage in people with CKD.{{cite journal | vauthors = Tam KW, Wu MY, Siddiqui FJ, Chan ES, Zhu Y, Jafar TH | title = Omega-3 fatty acids for dialysis vascular access outcomes in patients with chronic kidney disease | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 11 | pages = CD011353 | date = November 2018 | pmid = 30480758 | pmc = 6517057 | doi = 10.1002/14651858.CD011353.pub2 | collaboration = Cochrane Kidney and Transplant Group }} There was also moderate certainty that supplementation did not prevent hospitalisation or death within a 12-month period.

A 2022 Cochrane review of controlled trials did not find clear evidence that marine-derived omega−3 supplementation improves cognitive and physical recovery or social, and emotional wellbeing following stroke diagnosis, nor prevents stroke recurrence and mortality.{{cite journal | vauthors = Alvarez Campano CG, Macleod MJ, Aucott L, Thies F | title = Marine-derived n-3 fatty acids therapy for stroke | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 6 | pages = CD012815 | date = June 2022 | pmid = 35766825 | pmc = 9241930 | doi = 10.1002/14651858.CD012815.pub3 }} In this review, mood appeared to worsen slightly among those receiving 3g fish oil supplementation for 12 weeks; psychometric scores changed by 1.41 (0.07 to 2.75) points less than those receiving palm and soy oil. However, this represented only a single small study and was not observed in a study lasting more than 3 months. Overall, the review was limited by the small amount of high-quality evidence available.

A 2013 systematic review found tentative evidence of benefit for lowering inflammation levels in healthy adults and in people with one or more biomarkers of metabolic syndrome.{{cite journal | vauthors = Robinson LE, Mazurak VC | title = N-3 polyunsaturated fatty acids: relationship to inflammation in healthy adults and adults exhibiting features of metabolic syndrome | journal = Lipids | volume = 48 | issue = 4 | pages = 319–332 | date = April 2013 | pmid = 23456976 | doi = 10.1007/s11745-013-3774-6 | s2cid = 4005634 }} Consumption of omega−3 fatty acids from marine sources lowers blood markers of inflammation such as C-reactive protein, interleukin 6, and TNF alpha.{{cite journal | vauthors = Li K, Huang T, Zheng J, Wu K, Li D | title = Effect of marine-derived n-3 polyunsaturated fatty acids on C-reactive protein, interleukin 6 and tumor necrosis factor α: a meta-analysis | journal = PLOS ONE | volume = 9 | issue = 2 | pages = e88103 | date = February 2014 | pmid = 24505395 | pmc = 3914936 | doi = 10.1371/journal.pone.0088103 | doi-access = free | bibcode = 2014PLoSO...988103L }}{{cite journal | vauthors = Artiach G, Sarajlic P, Bäck M | title = Inflammation and its resolution in coronary artery disease: a tightrope walk between omega-6 and omega-3 polyunsaturated fatty acids | journal = Kardiologia Polska | volume = 78 | issue = 2 | pages = 93–95 | date = February 2020 | pmid = 32108752 | doi = 10.33963/KP.15202 | doi-access = free }}{{cite journal | vauthors = Kavyani Z, Musazadeh V, Fathi S, Hossein Faghfouri A, Dehghan P, Sarmadi B | title = Efficacy of the omega-3 fatty acids supplementation on inflammatory biomarkers: An umbrella meta-analysis | journal = International Immunopharmacology | volume = 111 | pages = 109104 | date = October 2022 | pmid = 35914448 | doi = 10.1016/j.intimp.2022.109104 | s2cid = 251209023 }}

For rheumatoid arthritis, one systematic review found consistent but modest evidence for the effect of marine n−3 PUFAs on symptoms such as "joint swelling and pain, duration of morning stiffness, global assessments of pain and disease activity" as well as the use of non-steroidal anti-inflammatory drugs.{{cite journal | vauthors = Miles EA, Calder PC | title = Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis | journal = The British Journal of Nutrition | volume = 107 | issue = Suppl 2 | pages = S171-84 | date = June 2012 | pmid = 22591891 | doi = 10.1017/S0007114512001560 | doi-access = free }} The American College of Rheumatology has stated that there may be modest benefit from the use of fish oils, but that it may take months for effects to be seen, and cautions for possible gastrointestinal side effects and the possibility of the supplements containing mercury or vitamin A at toxic levels.{{cite web |url=https://www.rheumatology.org/i-am-a/patient-caregiver/treatments/herbal-remedies-supplements-acupuncture-for-arthritis |title=Herbal Remedies, Supplements & Acupuncture for Arthritis - Supplements for arthritis |publisher=American College of Rheumatology |date=June 2018 |access-date=6 April 2019 |archive-date=20 March 2022 |archive-url=https://web.archive.org/web/20220320115559/https://www.rheumatology.org/i-am-a/patient-caregiver/treatments/herbal-remedies-supplements-acupuncture-for-arthritis |url-status=live }} The National Center for Complementary and Integrative Health has concluded that "supplements containing omega−3 fatty acids{{nbsp}}... may help relieve rheumatoid arthritis symptoms" but warns that such supplements "may interact with drugs that affect blood clotting".{{cite web|title=Rheumatoid Arthritis: In-Depth|url=https://nccih.nih.gov/health/RA/getthefacts.htm|publisher=National Center for Complementary and Alternative Medicine|date=January 2019|access-date=6 April 2019|archive-date=28 July 2020|archive-url=https://web.archive.org/web/20200728123010/https://www.nccih.nih.gov/health/RA/getthefacts.htm|url-status=live}}

One meta-analysis concluded that omega−3 fatty acid supplementation demonstrated a modest effect for improving ADHD symptoms.{{cite journal | vauthors = Bloch MH, Qawasmi A | title = Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 50 | issue = 10 | pages = 991–1000 | date = October 2011 | pmid = 21961774 | pmc = 3625948 | doi = 10.1016/j.jaac.2011.06.008 }} A Cochrane review of PUFA (not necessarily omega−3) supplementation found "there is little evidence that PUFA supplementation provides any benefit for the symptoms of ADHD in children and adolescents",{{cite journal | vauthors = Gillies D, Leach MJ, Perez Algorta G | title = Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 4 | pages = CD007986 | date = April 2023 | pmid = 37058600 | pmc = 10103546 | doi = 10.1002/14651858.CD007986.pub3 }} while a different review found "insufficient evidence to draw any conclusion about the use of PUFAs for children with specific learning disorders".{{cite journal | vauthors = Tan ML, Ho JJ, Teh KH | title = Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders | journal = The Cochrane Database of Systematic Reviews | volume = 12 | pages = CD009398 | date = December 2012 | pmid = 23235675 | doi = 10.1002/14651858.CD009398.pub2 | veditors = Tan ML }} Another review concluded that the evidence is inconclusive for the use of omega−3 fatty acids in behavior and non-neurodegenerative neuropsychiatric disorders such as ADHD and depression.{{cite journal | vauthors = Ortega RM, Rodríguez-Rodríguez E, López-Sobaler AM | title = Effects of omega 3 fatty acids supplementation in behavior and non-neurodegenerative neuropsychiatric disorders | journal = The British Journal of Nutrition | volume = 107 | issue = Suppl 2 | pages = S261–S270 | date = June 2012 | pmid = 22591900 | doi = 10.1017/S000711451200164X | doi-access = free }}

A 2015 meta-analysis of the effect of omega−3 supplementation during pregnancy did not demonstrate a decrease in the rate of preterm birth or improve outcomes in women with singleton pregnancies with no prior preterm births.{{cite web |url= http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014013752 |title= Omega−3 long chain polyunsaturated fatty acids to prevent preterm birth: a meta-analysis of randomized controlled trials |website= www.crd.york.ac.uk |access-date= 1 March 2016 |archive-date= 18 July 2018 |archive-url= https://web.archive.org/web/20180718001340/http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42014013752 |url-status= live }} A 2018 Cochrane systematic review with moderate to high quality of evidence suggested that omega−3 fatty acids may reduce risk of perinatal death, risk of low body weight babies; and possibly mildly increased LGA babies.{{cite journal | vauthors = Middleton P, Gomersall JC, Gould JF, Shepherd E, Olsen SF, Makrides M | title = Omega-3 fatty acid addition during pregnancy | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | pages = CD003402 | date = November 2018 | issue = 11 | pmid = 30480773 | pmc = 6516961 | doi = 10.1002/14651858.cd003402.pub3 }}

A 2021 umbrella review with moderate to high quality of evidence suggested that "omega-3 supplementation during pregnancy can exert favorable effects against pre-eclampsia, low-birth weight, pre-term delivery, and post-partum depression, and can improve anthropometric measures, immune system, and visual activity in infants and cardiometabolic risk factors in pregnant mothers."{{cite journal | vauthors = Firouzabadi FD, Shab-Bidar S, Jayedi A | title = The effects of omega-3 polyunsaturated fatty acids supplementation in pregnancy, lactation, and infancy: An umbrella review of meta-analyses of randomized trials | journal = Pharmacological Research | volume = 177 | issue = | pages = 106100 | date = March 2022 | pmid = 35104631 | doi = 10.1016/j.phrs.2022.106100 | s2cid = 246419684 }}

Omega−3 supplementation has not been shown to significantly affect symptoms of anxiety, major depressive disorder or schizophrenia.{{cite journal |last1=Deane |first1=Katherine H. O. |last2=Jimoh |first2=Oluseyi F. |last3=Biswas |first3=Priti |last4=O'Brien |first4=Alex |last5=Hanson |first5=Sarah |last6=Abdelhamid |first6=Asmaa S. |last7=Fox |first7=Chris |last8=Hooper |first8=Lee |title=Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials |journal=The British Journal of Psychiatry |date=March 2021 |volume=218 |issue=3 |pages=135–142 |doi=10.1192/bjp.2019.234 |pmid=31647041 |url=https://ueaeprints.uea.ac.uk/id/eprint/72390/1/Accepted_Manuscript.pdf }}{{cite journal | vauthors = Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, Veronese N, Schuch F, Smith L, Solmi M, Carvalho AF, Vancampfort D, Berk M, Stubbs B, Sarris J | display-authors = 6 | title = The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials | journal = World Psychiatry | volume = 18 | issue = 3 | pages = 308–324 | date = October 2019 | pmid = 31496103 | pmc = 6732706 | doi = 10.1002/wps.20672 | doi-access = free }} A 2021 Cochrane review concluded that there is not "sufficient high‐certainty evidence to determine the effects of n‐3PUFAs as a treatment for MDD".{{cite journal | vauthors = Appleton KM, Voyias PD, Sallis HM, Dawson S, Ness AR, Churchill R, Perry R | title = Omega-3 fatty acids for depression in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 11 | pages = CD004692 | date = November 2021 | pmid = 34817851 | pmc = 8612309 | doi = 10.1002/14651858.CD004692.pub5 }} Omega−3 fatty acids have also been investigated as an add-on for the treatment of depression associated with bipolar disorder although there is limited data available.{{cite journal | vauthors = Montgomery P, Richardson AJ | title = Omega-3 fatty acids for bipolar disorder | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD005169 | date = April 2008 | pmid = 18425912 | doi = 10.1002/14651858.CD005169.pub2 }} Two reviews have suggested that omega−3 fatty acid supplementation significantly improves depressive symptoms in perinatal women.{{cite journal | vauthors = Zhang MM, Zou Y, Li SM, Wang L, Sun YH, Shi L, Lu L, Bao YP, Li SX | display-authors = 6 | title = The efficacy and safety of omega-3 fatty acids on depressive symptoms in perinatal women: a meta-analysis of randomized placebo-controlled trials | journal = Translational Psychiatry | volume = 10 | issue = 1 | pages = 193 | date = June 2020 | pmid = 32555188 | pmc = 7299975 | doi = 10.1038/s41398-020-00886-3 }} A 2021 systematic review indicated that omega-3 fatty acid supplements may potentially offer varying degrees of symptom relief for schizophrenia. The review found the most significant benefits in early stages of the illness, particularly in individuals experiencing their first episode or those in the prodromal phase, with less pronounced benefits in chronic cases. The effectiveness of omega-3 supplementation can be influenced by factors like age and the duration of untreated illness.{{cite journal |vauthors=Hsu MC, Ouyang WC |title=A Systematic Review of Effectiveness of Omega-3 Fatty Acid Supplementation on Symptoms, Social Functions, and Neurobiological Variables in Schizophrenia |journal=Biological Research for Nursing |volume=23 |issue=4 |pages=723–737 |date=October 2021 |pmid=34281415 |doi=10.1177/10998004211020121}}

A 2015 study concluded that there are multiple factors responsible for depression and deficiency of omega−3 fatty acids can be one of them. It further stated that only those patients who have depression due to insufficient omega−3 fatty acids can respond well to the omega−3 supplements while others are unlikely to get any positive effects.{{cite journal |last1=Wani |first1=Ab Latif |last2=Bhat |first2=Sajad Ahmad |last3=Ara |first3=Anjum |title=Omega-3 fatty acids and the treatment of depression: a review of scientific evidence |journal=Integrative Medicine Research |date=September 2015 |volume=4 |issue=3 |pages=132–141 |doi=10.1016/j.imr.2015.07.003 |pmid=28664119 |pmc=5481805 }} Meta-analysis suggest that supplements with higher concentration of EPA than DHA are more likely to act as anti-depressants.{{cite journal|title=Brain eicosapentaenoic acid metabolism as a lead for novel therapeutics in major depression|url=https://www.sciencedirect.com/science/article/abs/pii/S0889159119303022|year=2020|author=Richard P. Bazinet|journal=Brain, Behavior, and Immunity |volume=85 |pages=21–28 |doi=10.1016/j.bbi.2019.07.001 |pmid=31278982 }}{{cite web|title=Omega-3 fatty acids for mood disorders|url=https://www.health.harvard.edu/blog/omega-3-fatty-acids-for-mood-disorders-2018080314414|date=27 October 2020|author=David Mischoulon|publisher=Harvard Health Publishing}}

In contrast to dietary supplementation studies, there is significant difficulty in interpreting the literature regarding dietary intake of omega−3 fatty acids (e.g. from fish) due to participant recall and systematic differences in diets.{{cite journal | vauthors = Sanhueza C, Ryan L, Foxcroft DR | title = Diet and the risk of unipolar depression in adults: systematic review of cohort studies | journal = Journal of Human Nutrition and Dietetics | volume = 26 | issue = 1 | pages = 56–70 | date = February 2013 | pmid = 23078460 | doi = 10.1111/j.1365-277X.2012.01283.x }} There is also controversy as to the efficacy of omega−3, with many meta-analysis papers finding heterogeneity among results which can be explained mostly by publication bias.{{cite journal | vauthors = Appleton KM, Rogers PJ, Ness AR | title = Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood | journal = The American Journal of Clinical Nutrition | volume = 91 | issue = 3 | pages = 757–70 | date = March 2010 | pmid = 20130098 | doi = 10.3945/ajcn.2009.28313 | doi-access = free }}{{cite journal | vauthors = Bloch MH, Hannestad J | title = Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis | journal = Molecular Psychiatry | volume = 17 | issue = 12 | pages = 1272–82 | date = December 2012 | pmid = 21931319 | pmc = 3625950 | doi = 10.1038/mp.2011.100 }} A significant correlation between shorter treatment trials was associated with increased omega−3 efficacy for treating depressed symptoms further implicating bias in publication.

A 2016 Cochrane review found no convincing evidence for the use of omega‐3 PUFA supplements in treatment of Alzheimer's disease or dementia.{{cite journal | vauthors = Burckhardt M, Herke M, Wustmann T, Watzke S, Langer G, Fink A | title = Omega-3 fatty acids for the treatment of dementia | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 4 | pages = CD009002 | date = April 2016 | pmid = 27063583 | pmc = 7117565 | doi = 10.1002/14651858.CD009002.pub3 }} There is preliminary evidence of effect on mild cognitive problems, but none supporting an effect in healthy people or those with dementia.{{cite journal | vauthors = Mazereeuw G, Lanctôt KL, Chau SA, Swardfager W, Herrmann N | title = Effects of ω-3 fatty acids on cognitive performance: a meta-analysis | journal = Neurobiology of Aging | volume = 33 | issue = 7 | pages = 1482.e17–1482.e29 | date = July 2012 | pmid = 22305186 | doi = 10.1016/j.neurobiolaging.2011.12.014 | s2cid = 2603173 }}{{cite journal | vauthors = Forbes SC, Holroyd-Leduc JM, Poulin MJ, Hogan DB | title = Effect of Nutrients, Dietary Supplements and Vitamins on Cognition: a Systematic Review and Meta-Analysis of Randomized Controlled Trials | journal = Canadian Geriatrics Journal | volume = 18 | issue = 4 | pages = 231–245 | date = December 2015 | pmid = 26740832 | pmc = 4696451 | doi = 10.5770/cgj.18.189 }} A 2020 review suggested that omega−3 supplementation has no effect on global cognitive function but has a mild benefit in improving memory in non-demented adults.{{cite journal | vauthors = Alex A, Abbott KA, McEvoy M, Schofield PW, Garg ML | title = Long-chain omega-3 polyunsaturated fatty acids and cognitive decline in non-demented adults: a systematic review and meta-analysis | journal = Nutrition Reviews | volume = 78 | issue = 7 | pages = 563–578 | date = July 2020 | pmid = 31841161 | doi = 10.1093/nutrit/nuz073 | doi-access = free }}

A 2022 review found promising evidence for prevention of cognitive decline in people who regularly eat long-chain omega−3 rich foods. Conversely, clinical trials with participants already diagnosed with Alzheimer's show no effect.{{cite journal | vauthors = Wood AH, Chappell HF, Zulyniak MA | title = Dietary and supplemental long-chain omega-3 fatty acids as moderators of cognitive impairment and Alzheimer's disease | journal = European Journal of Nutrition | volume = 61 | issue = 2 | pages = 589–604 | date = March 2022 | pmid = 34392394 | pmc = 8854294 | doi = 10.1007/s00394-021-02655-4 }} A 2020 review concluded that long-chain omega−3 supplements do not deter cognitive decline in older adults.{{cite journal |vauthors=Brainard JS, Jimoh OF, Deane KH, Biswas P, Donaldson D, Maas K, Abdelhamid AS, Hooper L |title=Omega-3, Omega-6, and Polyunsaturated Fat for Cognition: Systematic Review and Meta-analysis of Randomized Trials |journal=Journal of the American Medical Directors Association |volume=21 |issue=10 |pages=1439–1450.e21 |date=October 2020 |pmid=32305302 |doi=10.1016/j.jamda.2020.02.022 |url=https://ueaeprints.uea.ac.uk/id/eprint/74328/4/Accepted_Manuscript.pdf }}

Brain function and vision rely on dietary intake of DHA to support a broad range of cell membrane properties, particularly in grey matter, which is rich in membranes.{{cite journal | vauthors = Bradbury J | title = Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain | journal = Nutrients | volume = 3 | issue = 5 | pages = 529–554 | date = May 2011 | pmid = 22254110 | pmc = 3257695 | doi = 10.3390/nu3050529 | doi-access = free }}{{cite journal | vauthors = Harris WS, Baack ML | title = Beyond building better brains: bridging the docosahexaenoic acid (DHA) gap of prematurity | journal = Journal of Perinatology | volume = 35 | issue = 1 | pages = 1–7 | date = January 2015 | pmid = 25357095 | pmc = 4281288 | doi = 10.1038/jp.2014.195 }} A major structural component of the mammalian brain, DHA is the most abundant omega−3 fatty acid in the brain.{{cite journal | vauthors = Hüppi PS | title = Nutrition for the brain: commentary on the article by Isaacs et al. on page 308 | journal = Pediatric Research | volume = 63 | issue = 3 | pages = 229–231 | date = March 2008 | pmid = 18287959 | doi = 10.1203/pdr.0b013e318168c6d1 | s2cid = 6564743 | doi-access = free }}{{cite journal | vauthors = Horrocks LA, Yeo YK | title = Health benefits of docosahexaenoic acid (DHA) | journal = Pharmacological Research | volume = 40 | issue = 3 | pages = 211–225 | date = September 1999 | pmid = 10479465 | doi = 10.1006/phrs.1999.0495 }} Omega−3 PUFA supplementation has no effect on macular degeneration or development of visual loss.{{cite journal | vauthors = Lawrenson JG, Evans JR | title = Omega 3 fatty acids for preventing or slowing the progression of age-related macular degeneration | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 4 | pages = CD010015 | date = April 2015 | pmid = 25856365 | pmc = 7087473 | doi = 10.1002/14651858.CD010015.pub3 }}

Results of studies investigating the role of LCPUFA supplementation and LCPUFA status in the prevention and therapy of atopic diseases (allergic rhinoconjunctivitis, atopic dermatitis, and allergic asthma) are controversial; therefore, {{As of|2013|lc=y}} it could not be stated either that the nutritional intake of n−3 fatty acids has a clear preventive or therapeutic role, or that the intake of n-6 fatty acids has a promoting role in the context of atopic diseases.Lohner S, Decsi T. Role of Long-Chain Polyunsaturated Fatty Acids in the Prevention and Treatment of Atopic Diseases. In: Polyunsaturated Fatty Acids: Sources, Antioxidant Properties, and Health Benefits (edited by: Angel Catalá). NOVA Publishers. 2013. Chapter 11, pp. 1–24. ({{ISBN|978-1-62948-151-7}})

People with PKU often have low intake of omega−3 fatty acids, because nutrients rich in omega−3 fatty acids are excluded from their diet due to high protein content.{{cite journal | vauthors = Lohner S, Fekete K, Decsi T | title = Lower n-3 long-chain polyunsaturated fatty acid values in patients with phenylketonuria: a systematic review and meta-analysis | journal = Nutrition Research | volume = 33 | issue = 7 | pages = 513–20 | date = July 2013 | pmid = 23827125 | doi = 10.1016/j.nutres.2013.05.003 }}

As of 2015, there was no evidence that taking omega−3 supplements can prevent asthma attacks in children.{{cite journal | vauthors = Muley P, Shah M, Muley A | title = Omega-3 Fatty Acids Supplementation in Children to Prevent Asthma: Is It Worthy?-A Systematic Review and Meta-Analysis | journal = Journal of Allergy | volume = 2015 | pages = 312052 | date = 2015 | pmid = 26357518 | pmc = 4556859 | doi = 10.1155/2015/312052 | doi-access = free }}

A 2019 review found that omega−3 supplements have no effect on prevention and treatment of type 2 diabetes.{{cite journal |last1=Brown |first1=Tracey J |last2=Brainard |first2=Julii |last3=Song |first3=Fujian |last4=Wang |first4=Xia |last5=Abdelhamid |first5=Asmaa |last6=Hooper |first6=Lee |title=Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials |journal=BMJ |date=21 August 2019 |volume=366 |pages=l4697 |doi=10.1136/bmj.l4697 |pmid=31434641 |pmc=6699594 }}{{cite report |type=Preprint |title=Boosting omega-3 fatty acid intake is unlikely to prevent type 2 diabetes |date=12 November 2019 |doi=10.3310/signal-000833 }} A 2021 meta-analysis found that supplementation with omega−3 had positive effects on diabetes biomarkers, such as fasting blood glucose and insulin resistance.{{cite journal |display-authors=3|vauthors=Delpino FM, Figueiredo LM, da Silva BG, da Silva TG, Mintem GC, Bielemann RM, Gigante DP |title=Omega-3 supplementation and diabetes: A systematic review and meta-analysis |journal=Critical Reviews in Food Science and Nutrition |volume=62 |issue=16 |pages=4435–4448 |date=2022 |pmid=33480268 |doi=10.1080/10408398.2021.1875977|s2cid=231677714 }}

A 2017 animal study examined the effects of omega−3 supplement on BPF-induced erectile dysfunction. Rats in the treatment group were found to have significantly improved erection quality.{{cite web|author=Adeyemi Fatai Odetayo, Luqman Aribidesi Olayaki|title=Omega 3 fatty acid improves sexual and erectile function in BPF-treated rats by upregulating NO/cGMP signaling and steroidogenic enzymes activities|date=23 October 2023|website=Nature.com|url=https://www.nature.com/articles/s41598-023-45344-4}}

{{portal |Biology|Medicine}}

{{div col|colwidth=20em|small=yes}}

• {{Annotated link |Omega-3-acid ethyl esters|Omega−3 acid ethyl esters}}
• {{Annotated link |Essential fatty acid interactions}}
• {{Annotated link |Essential nutrients}}
• {{Annotated link |Inflammation}}
• {{Annotated link |Olive oil regulation and adulteration}}
• {{Annotated link |Omega-6 fatty acid|Omega−6 fatty acid}}
• {{Annotated link |Omega-7 fatty acid|Omega−7 fatty acid}}
• {{Annotated link |Omega-9 fatty acid|Omega−9 fatty acid}}
• {{Annotated link |Ratio of fatty acids in different foods}}
• {{Annotated link |Reinforced lipids}}

{{div col end}}

{{reflist}}

{{refbegin}}

• {{cite book | vauthors = Allport S | title = The Queen of Fats: Why Omega−3s Were Removed from the Western Diet and What We Can Do to Replace Them | url = https://archive.org/details/queenoffatswhyo00allp | url-access = registration | publisher = University of California Press | date = September 2006 | isbn = 978-0-520-24282-1 | oclc = 801139991 }}
• {{cite book | vauthors = Chow CK | title = Fatty Acids in Foods and Their Health Implications | publisher = Routledge Publishing | location = New York | date = 2001 | oclc = 25508943 }}
• {{cite book | vauthors = Clover C | title = The End of the Line: How overfishing is changing the world and what we eat | publisher = Ebury Press | location = London | isbn = 0-09-189780-7 | oclc = 67383509 | year = 2004 }}
• {{cite book |vauthors=Greenberg P |year=2018 |title=The Omega Principle: Seafood and the Quest for a Long Life and a Healthier Planet |url=https://books.google.com/books?id=9Ok6DwAAQBAJ |location=New York |publisher=Penguin Press |isbn=9781594206344 |oclc=1007552654 |access-date=13 July 2018 |archive-date=18 September 2023 |archive-url=https://web.archive.org/web/20230918053635/https://books.google.com/books?id=9Ok6DwAAQBAJ |url-status=live }}
• {{cite book | vauthors = Stoll AL | title = The Omega−3 Connection: how you can restore your body's natural balance and treat depression | publisher = Simon & Schuster | date = 2001 | isbn = 0-684-87138-6 | oclc = 670441405 }}

{{Refend}}

{{Commons category|Omega-3 fatty acids|position=left}}

{{Lipids}}

{{DEFAULTSORT:Omega-3 Fatty Acid}}

Category:Alkenoic acids

Category:Anti-inflammatory agents

Category:Biologically based therapies

Category:Fatty acids