gamma-Linolenic acid

This article is about gamma-Linolenic acid. For α-Linolenic acid, see alpha-Linolenic acid. For linoleic acid (no "n"), see linoleic acid.

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γ-Linolenic acid

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Names
IUPAC name all-cis-6,9,12-octadecatrienoic acid
Other names Gamma-linolenic acid, gamolenic acid, GLA
Identifiers
CAS Number	506-26-3 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:28661 Y
ChEMBL	ChEMBL464982 Y
ChemSpider	4444436 Y
ECHA InfoCard
PubChem CID	5280933
UNII	78YC2MAX4O Y
InChI InChI=1S/C18H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h6-7,9-10,12-13H,2-5,8,11,14-17H2,1H3,(H,19,20)/b7-6-,10-9-,13-12- Y Key: VZCCETWTMQHEPK-QNEBEIHSSA-N Y InChI=1/C18H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h6-7,9-10,12-13H,2-5,8,11,14-17H2,1H3,(H,19,20)/b7-6-,10-9-,13-12- Key: VZCCETWTMQHEPK-QNEBEIHSBP
SMILES O=C(O)CCCC\C=C/C\C=C/C\C=C/CCCCC
Properties
Chemical formula	C18H30O2
Molar mass	278.44 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Y verify (what is YN ?)
Infobox references

Gamma-linolenic acid or GLA (γ-Linolenic acid), (INN and USAN gamolenic acid) is a fatty acid found primarily in vegetable oils. It is sold as a dietary supplement for a variety of human health problems, although there is little or no evidence of its effectiveness. However when acting on GLA, 5-lipoxygenase produces no leukotrienes and the conversion by the enzyme of arachidonic acid to leukotrienes is inhibited.

Chemistry

GLA is categorized as an n−6 (also called ω−6 or omega-6) fatty acid, meaning that the first double bond on the methyl end (designated with n or ω) is the sixth bond. In physiological literature, GLA is designated as 18:3 (n−6). GLA is a carboxylic acid with an 18-carbon chain and three cis double bonds. It is an isomer of α-linolenic acid, which is a polyunsaturated n−3 (omega-3) fatty acid, found in rapeseed canola oil, soy beans, walnuts, flax seed (linseed oil), perilla, chia, and hemp seed.

History

GLA was first isolated from the seed oil of evening primrose. This herbal plant was grown by Native Americans to treat swelling in the body. In the 17th century, it was introduced to Europe and became a popular folk remedy, earning the name king's cure-all. in 1919, Heiduschka and Lüft extracted the oil from evening primrose seeds and described an unusual linolenic acid, which they name γ-. Later, the exact chemical structure was characterized by Riley.

Although there are α- and γ- forms of linolenic acid, there is no β- form. One was once identified, but it turned out to be an artifact of the original analytical process.

Dietary sources

GLA is obtained from vegetable oils such as evening primrose (Oenothera biennis) oil (EPO), blackcurrant seed oil, borage seed oil, and hemp seed oil. GLA is also found in varying amounts in edible hemp seeds, oats, barley, and spirulina. Normal safflower (Carthamus tinctorius) oil does not contain GLA, but a genetically modified GLA safflower oil available in commercial quantities since 2011 contains 40% GLA. Borage oil contains 20% GLA, evening primrose oil ranges from 8% to 10% GLA, and black-currant oil contains 15-20%.

The human body produces GLA from linoleic acid (LA). This reaction is catalyzed by Δ⁶-desaturase (D6D), an enzyme that allows the creation of a double bond on the sixth carbon counting from the carboxyl terminus. LA is consumed sufficiently in most diets, from such abundant sources as cooking oils and meats. However, a lack of GLA can occur when there is a reduction of the efficiency of the D6D conversion (for instance, as people grow older or when there are specific dietary deficiencies) or in disease states wherein there is excessive consumption of GLA metabolites.

Source of eicosanoids

The seed oil of Oenothera biennis (evening primrose) is a source of GLA

From GLA, the body forms dihomo-γ-linolenic acid (DGLA). This is one of the body's three sources of eicosanoids (along with AA and EPA.) DGLA is the precursor of the prostaglandin PGH₁, which in turn forms PGE₁ and the thromboxane TXA₁. Both PGE1₁ and TXA₁ are anti-inflammatory; thromboxane TXA₁, unlike its series-2 variant, induces vasodilation, and inhibits platelet consequently, TXA₁ modulates (reduces) the pro-inflammatory properties of the thromboxane TXA₂. PGE₁ has a role in regulation of immune system function and is used as the medicine alprostadil.

Unlike AA and EPA, DGLA cannot yield leukotrienes. However it can inhibit the formation of pro-inflammatory leukotrienes from AA.

Although GLA is an n−6 fatty acid, a type of acid that is, in general, pro-inflammatory, it has anti-inflammatory properties. (See discussion at Essential fatty acid interactions: The paradox of dietary GLA.)

Health and medicine

GLA has been promoted as medication for a variety of ailments including breast pain and eczema, in particular by David Horrobin (1939 – 2003), whose marketing of evening primrose oil was described by the British Medical Journal (BMJ) as ethically dubious – the substance was likely to be remembered as "a remedy for which there is no disease". In 2002 the UK's Medicines and Healthcare products Regulatory Agency withdrew marketing authorisations for evening primrose oil as an eczema remedy. The BMJ commented in 2003 that it had taken 20 years to demonstrate that the substance was of no use in atopic dermatitis, and called for more transparency in the research on which drug licensing decisions were taken.

GLA is also sometimes promoted as an anti-cancer agent. According to the American Cancer Society there is very little evidence for its effectiveness, and "neither GLA nor other GLA-rich supplements (such as evening primrose oil) have been convincingly shown to be useful in preventing or treating any other health conditions."

Side effects

Meta-analysis by the Cochrane Collaboration reported some evidence of mild and temporary side-effects for trial participants with either product or placebo, including temporary headache and upset stomach or diarrhea. With evening primrose oil (EPO) there was an anticoagulant (blood-thinning) effect. There is a warning with the blood thinner warfarin that taking EPO can increase bleeding. One report warns that if EPO is taken for more than one year there is a potential risk of inflammation, thrombosis, and immunosuppression due to slow accumulation of EPO in the tissues. Another report involves a single case in which EPO was thought to have produced harm, but no clinical evidence of such harm was found in short-term trials.