Gamma-Linolenic acid

# Overview
Gamma-linolenic acid or GLA (-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 n6 (also called 6 or omega-6) fatty acid, meaning that the first double bond on the methyl end (designated with n or ) is the sixth bond. In physiological literature, GLA is designated as 18:3 (n6). GLA is a carboxylic acid with an 18-carbon chain and three cis double bonds. It is an isomer of -linolenic acid, which is a polyunsaturated n3 (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 Luft extracted the oil from evening primrose seeds and described an unusual linolenic acid, which they name -.
Later, the exact chemical structure was characterized by Riley.
Although there are - and - forms of linolenic acid, there is no - 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 6-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
From GLA, the body forms dihomo--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 n6 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.

# Notes and references
-  Jump up to: 1.0 1.1 Cochrane Collaboration meta-analysis: Oral evening primrose oil and borage oil for eczema. Conclusion: lack effect on eczema.
-  Cochrane Collaboration meta-analysis: Herbal therapy for treating rheumatoid arthritis. Conclusion: moderate evidence that oils containing GLA afford some benefit in relieving symptoms for RA. Many trials of herbal therapies are hampered by research design flaws and inadequate reporting.
-  Cochrane Collaboration meta-analysis: Polyunsaturated fatty acid supplementation for schizophrenia. Conclusion: Some studies show some improvement, but not statistically significant. Trials were small and short, most of the data they reported were not usable, and half of the trials were funded by the group supplying the trial medication.
-  Yung-Sheng Huang, Vincent A. Ziboh (2001). Gamma-Linolenic Acid: Recent Advances in Biotechnology and Clinical Applications. AOCS Press. p. 259. ISBN 1-893997-17-0. Retrieved 2007-12-07..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
-  Eckey, EW (1954). Vegetable Fats and Oils (volume 123 of American Chemical Society monograph series). Reinhold. p. 542.
-  Qureshi AA;  et al. (1984). Fed. Proc. 43: 2626. Unknown parameter |author-separator= ignored (help); Missing or empty |title= (help)
-  Nykiforuk, C.; Shewmaker, C. (19 August 2011). "High level accumulation of gamma linolenic acid in transgenic safflower (Carthamus tinctorius) seeds". Transgenic Research. 21 (2): 36781. doi:10.1007/s11248-011-9543-5. PMID 21853296.
-  Flider, Frank J (May 2005). "GLA: Uses and New Sources" (PDF). INFORM. 16 (5): 279282.
-  Horrobin DF (From the Efamol Research Institute. Kentville. Nova Scotia. Canada) (1993). "Fatty acid metabolism in health and disease: the role of delta-6-desaturase" (pdf). Am. J. Clin. Nutr. 57 (5 Suppl): 732S736S, discussion 736S737S. PMID 8386433.
-  King, Michael W. "Introduction to the Eicosanoids". The Medical Biochemistry Page. 19962013 themedicalbiochemistrypage.org, LLC. Retrieved 23 July 2013.
-  Belch JJ, Hill A (2000). "Evening primrose oil and borage oil in rheumatologic conditions". Am. J. Clin. Nutr. 71 (1 Suppl): 352S6S. PMID 10617996. Retrieved 2007-12-07. DGLA itself cannot be converted to LTs but can form a 15-hydroxyl derivative that blocks the transformation of arachidonic acid to LTs. Increasing DGLA intake may allow DGLA to act as a competitive inhibitor of 2-series PGs and 4-series LTs and, thus, suppress inflammation.
-  Richmond, C. (2003). "David Horrobin". BMJ. 326 (7394): 885. doi:10.1136/bmj.326.7394.885.
-  Williams, H. C (2003). "Evening primrose oil for atopic dermatitis: Time To Say Goodnight". BMJ. 327 (7428): 13589. doi:10.1136/bmj.327.7428.1358. JSTOR 25457999. PMC 292973. PMID 14670851.
-  Smith, R. (2003). "The drugs don't work". BMJ. 327 (7428): 0h. doi:10.1136/bmj.327.7428.0-h.
-  "Gamma Linolenic Acid". American Cancer Society. 13 May 2010. Retrieved August 2013. Check date values in: |accessdate= (help)