Α-Linolenic acid

α-Linolenic acid, also known as alpha-linolenic acid (ALA) (from Greek alpha meaning "first" and linon meaning flax), is an n−3, or omega-3, essential fatty acid. ALA is found in many seeds and oils, including flaxseed, walnuts, chia, hemp, and many common vegetable oils.

In terms of its structure, it is named all-cis-9,12,15-octadecatrienoic acid. In physiological literature, it is listed by its lipid number, 18:3 (n−3). It is a carboxylic acid with an 18-carbon chain and three cis double bonds. The first double bond is located at the third carbon from the methyl end of the fatty acid chain, known as the n end. Thus, α-linolenic acid is a polyunsaturated n−3 (omega-3) fatty acid. It is a regioisomer of gamma-linolenic acid (GLA), an 18:3 (n−6) fatty acid (i.e., a polyunsaturated omega-6 fatty acid with three double bonds).

Etymology
The word linolenic is an irregular derivation from linoleic, which itself is derived from the Greek word linon (flax). Oleic means "of or relating to oleic acid" because saturating an omega-6 double bond of linoleic acid produces oleic acid. Similarly saturating one of linolenic acid's double bonds produces linoleic acid.

Dietary sources
Seed oils are the richest sources of α-linolenic acid, notably those of hempseed, chia, perilla, flaxseed (linseed oil), rapeseed (canola), and soybeans. α-Linolenic acid is also obtained from the thylakoid membranes in the leaves of Pisum sativum (pea leaves). Plant chloroplasts consisting of more than 95 percent of photosynthetic thylakoid membranes are highly fluid due to the large abundance of ALA, evident as sharp resonances in high-resolution carbon-13 NMR spectra. Some studies state that ALA remains stable during processing and cooking. However, other studies state that ALA might not be suitable for baking as it will polymerize with itself, a feature exploited in paint with transition metal catalysts. Some ALA may also oxidize at baking temperatures. ALA percentages in the table below refer to the oils extracted from each item.

Metabolism


α-Linolenic acid can be obtained by humans only through their diets. Humans lack the desaturase enzymes required for processing stearic acid into A-linoleic acid or other unsaturated fatty acids.

Dietary α-linolenic acid is metabolized to stearidonic acid, a precursor to a collection of polyunsaturated 20-, 22-, 24-, etc fatty acids (eicosatetraenoic acid, eicosapentaenoic acid, docosapentaenoic acid, tetracosapentaenoic acid, 6,9,12,15,18,21-tetracosahexaenoic acid, docosahexaenoic acid). Because the efficacy of n−3 long-chain polyunsaturated fatty acid (LC-PUFA) synthesis decreases down the cascade of α-linolenic acid conversion, DHA synthesis from α-linolenic acid is even more restricted than that of EPA. Conversion of ALA to DHA is higher in women than in men.

Stability and hydrogenation
Compared to many other oils, α-linolenic acid is more susceptible to oxidation. It becomes rancid more quickly in air. Oxidative instability of α-linolenic acid is one reason why producers choose to partially hydrogenate oils containing α-linolenic acid, such as soybean oil. Soybeans are the largest source of edible oils in the U.S., and, as of a 2007 study, 40% of soy oil production was partially hydrogenated.

Hydrogenation of ALA-containing fats can introduce trans fats. Consumers are increasingly avoiding products that contain trans fats, and governments have begun to ban trans fats in food products. These regulations and market pressures have spurred the development of soybeans low in α-linolenic acid. These new soybean varieties yield a more stable oil that often do not require hydrogenation for many applications.

Health
ALA consumption is associated with a lower risk of cardiovascular disease and a reduced risk of fatal coronary heart disease. Dietary ALA intake can improve lipid profiles by decreasing triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein. A 2021 review found that ALA intake is associated with a reduced risk of mortality from all causes, cardiovascular disease, and coronary heart disease but a slightly higher risk of cancer mortality.

History
In 1887, linolenic acid was discovered and named by the Austrian chemist Karl Hazura of the Imperial Technical Institute at Vienna (although he did not separate its isomers). α-Linolenic acid was first isolated in pure form in 1909 by Ernst Erdmann and F. Bedford of the University of Halle an der Saale, Germany, and by Adolf Rollett of the Universität Berlin, Germany, working independently, as cited in J. W. McCutcheon's synthesis in 1942, and referred to in Green and Hilditch's 1930s survey. It was first artificially synthesized in 1995 from C6 homologating agents. A Wittig reaction of the phosphonium salt of [(Z-Z)-nona-3,6-dien-1-yl]triphenylphosphonium bromide with methyl 9-oxononanoate, followed by saponification, completed the synthesis.