Omega−3 fatty acid

Omega−3 oils, ω−3 fatty acids or n−3 fatty acids, are polyunsaturated fatty acids characterized by the presence of a double bond three atoms away from the terminal methyl group in their chemical structure. They are widely distributed in nature, are important constituents of animal lipid metabolism, and play an important role in the human diet and in human physiology. The three types of omega−3 fatty acids involved in human physiology are α-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid. ALA can be found in plants, while DHA and EPA are found in algae and fish. Marine algae and phytoplankton are primary sources of omega−3 fatty acids. DHA and EPA accumulate in fish that eat these algae. Common sources of plant oils containing ALA include walnuts, edible seeds and flaxseeds as well as hempseed oil, while sources of EPA and DHA include fish and fish oils, and algae oil.
Almost without exception, animals are unable to synthesize the essential omega−3 fatty acid ALA and can only obtain it through diet. However, they can use ALA, when available, to form EPA and DHA, by creating additional double bonds along its carbon chain and extending it. ALA is used to make EPA, which is then used to make DHA. The ability to make the longer-chain omega−3 fatty acids from ALA may be impaired in aging. In foods exposed to air, unsaturated fatty acids are vulnerable to oxidation and rancidity.
Omega−3 fatty acid supplementation has limited evidence of benefit in preventing cancer, all-cause mortality and most cardiovascular outcomes, although it modestly lowers blood pressure and reduces triglycerides. Since 2002, the United States Food and Drug Administration has approved four fish oil-based prescription drugs for the management of hypertriglyceridemia, namely Lovaza, Omtryg, Vascepa and Epanova.

History

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". Since then, researchers have shown a growing interest in unsaturated essential fatty acids as they form the framework for the organism's cell membranes. Subsequently, awareness of the health benefits of essential fatty acids has dramatically increased since the 1980s.
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 fatty acids may reduce the risk of coronary heart disease". This updated and modified their health risk advice letter of 2001.
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."
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.

Nomenclature

The terms ω−3 fatty acid and n−3 fatty acid are derived from the nomenclature of organic chemistry. 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 represents the locant of the methyl end of the molecule, while the number n−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, although it is never read as such. Also, the symbol n 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, where the methyl end is at location 18 from the carboxyl end, n represents the number 18, and the notation n−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 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.

Example

For example, α-linolenic acid 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 and is also described by a lipid number, 18:3, meaning that there are 18 carbon atoms and 3 double bonds.

Chemistry

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, eicosapentaenoic acid, and docosahexaenoic acid. 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, so that there are two single bonds between each pair of adjacent double bonds.
The atoms at bis-allylic 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.

List of omega−3 fatty acids

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

Common name	Lipid number	Chemical name
Hexadecatrienoic acid	16:3	all-''cis-7,10,13-hexadecatrienoic acid
α-Linolenic acid	18:3	all-cis-9,12,15-octadecatrienoic acid
Stearidonic acid	18:4	all-cis-6,9,12,15-octadecatetraenoic acid
Eicosatrienoic acid	20:3	all-cis-11,14,17-eicosatrienoic acid
Eicosatetraenoic acid	20:4	all-cis-8,11,14,17-eicosatetraenoic acid
Eicosapentaenoic acid	20:5	all-cis-5,8,11,14,17-eicosapentaenoic acid
Heneicosapentaenoic acid	21:5	all-cis-6,9,12,15,18-heneicosapentaenoic acid
Docosapentaenoic acid, Clupanodonic acid	22:5	all-cis-7,10,13,16,19-docosapentaenoic acid
Docosahexaenoic acid	22:6	all-cis-4,7,10,13,16,19-docosahexaenoic acid
Tetracosapentaenoic acid	24:5	all-cis-9,12,15,18,21-tetracosapentaenoic acid
Tetracosahexaenoic acid	24:6	all-cis''-6,9,12,15,18,21-tetracosahexaenoic acid

Forms

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.

Mechanism of action

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. 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, which is involved in the immune response of traumatized and infected tissues. 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, 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.