Gamma-Linolenic acid
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{{Chembox new
| Name = '''γ-linolenic acid'''
| OtherNames= Gamma-linolenic acid, GLA
| ImageFile = GLAnumbering.png
| ImageSize = 400px
| IUPACName = all-''cis''-6,9,12-octadecatrienoic acid
| Section1 = {{Chembox Identifiers
| SMILES = CCCCC\C=C/C\C=C/C\C=C/CCCCC(=O)O
| PubChem = 5280933
}}
| Section2 = {{Chembox Properties
| Formula = C<sub>18</sub>H<sub>30</sub>O<sub>2</sub>
| MolarMass = [[List of elements by atomic mass|278.43]] g/[[Mole (unit)|mol]]
}}
}}
{{For2|an explanation of ''n'' and numerical nomenclature (such as ''n''−6 or 18:3)|[[Fatty acid#Nomenclature|Nomenclature of fatty acids]]}}
'''[[Gamma|γ]]-Linolenic acid''' ('''gamma-linolenic acid''' or '''GLA''', sometimes called '''gamolenic acid''') is an [[essential fatty acid]] found primarily in vegetable oils. It is sold as a dietary supplement for treating problems with [[inflammation]] and auto-immune diseases. The efficacy of such use is disputed.
==Chemistry==
GLA is categorized as an [[omega-6 fatty acid|''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). Chemically, GLA is a [[carboxylic acid]] with an 18-carbon chain and three ''[[cis]]'' [[double bond]]s. It is an [[isomer]] of [[alpha-linolenic acid|α-linolenic acid]], which is the [[omega-3 fatty acid|''n''−3 fatty acid]] found in flax seed.
==History==
GLA was first isolated from the seed oil of [[Oenothera|evening primrose]]. This herbal plant was grown by [[Indigenous peoples of the Americas|Native American]]s 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.<ref name=Huang>{{cite book
|title=Gamma-Linolenic Acid: Recent Advances in Biotechnology and Clinical Applications
|author= Yung-Sheng Huang, Vincent A. Ziboh
|url=http://books.google.com/books?hl=en&lr=&c2coff=1&id=vU5KdI_FXZwC&oi=fnd&pg=PR7&dq=++%22gamma+linolenic+acid%22&ots=9XpUTzP3N7&sig=gSqqGX5E_z-3qqzbs8E47pGoDJE#PPR6,M1
|year= 2001 |publisher=AOCS Press|pages=259 |isbn= 1893997170
|accessdate=2007-12-07}}</ref>
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.<ref name=gunstone>{{cite web| author=Gunstone, Frank
|url=http://www.lapinskas.com/publications/3918.html
|title=Personal Communication at Peter Lapinskas' pages
|accessdate= 2006-02-03}}
</ref>
==Dietary Sources==
GLA is obtained from vegetable oils, such as evening primrose (''[[Oenothera biennis]]'') oil, [[blackcurrant]] seed oil, [[borage]] oil and [[hemp]] seed oil, and from [[Spirulina (dietary supplement)|spirulina]], a [[cyanobacterium]]. Each contains varying amounts of the fatty acid, with borage oil usually being the most heavily concentrated form. All are widely available in [[pharmacy|pharmacies]], [[health food store]]s, or [[online shop]]s.
The human body produces GLA from [[linoleic acid]] (LA). This reaction is catalized by Δ<sup>6</sup>-[[desaturase]] (D6D), an enzyme which 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 oil]]s and [[meat]]s. 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 where there is excessive consumption of GLA metabolites.<ref name="pmid8386433">{{cite journal |author=Horrobin DF |title=Fatty acid metabolism in health and disease: the role of delta-6-desaturase |journal=Am. J. Clin. Nutr. |volume=57 |issue=5 Suppl |pages=732S–736S; discussion 736S–737S |year=1993 |url=http://www.ajcn.org/cgi/reprint/57/5/732S.pdf|format=pdf|pmid=8386433 |doi=}}</ref>
==A Source of Eicosanoids==
From GLA, the body forms [[dihomo-gamma-linolenic acid|dihomo-γ-linolenic acid]] (DGLA). This is one of the body's three sources of [[eicosanoid]]s (along with [[Arachidonic acid|AA]] and [[Eicosapentaenoic acid|EPA]].) DGLA is the precursor of the [[prostaglandin]] PGH<sub>1</sub>, which in turn forms PGE<sub>1</sub> and the [[thromboxane]] TXA<sub>1</sub>. PGE<sub>1</sub> has a role in regulation of [[immune system]] function and is used as the medicine [[alprostadil]]. TXA<sub>1</sub> modulates the pro-inflammatory properties of the thromboxane TXA<sub>2</sub>.
Unlike AA and EPA, DGLA cannot yield [[leukotrienes]]. However it can inhibit the formation of pro-inflammatory leukotrienes from AA.<ref name="Belch">{{cite journal |author=Belch JJ, Hill A |title=Evening primrose oil and borage oil in rheumatologic conditions |journal=Am. J. Clin. Nutr. |volume=71 |issue=1 Suppl |pages=352S–6S |year=2000 |pmid=10617996 |doi= | url= http://www.ajcn.org/cgi/content/full/71/1/352S
|quote=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. |accessdate=2007-12-07}}</ref>
Although GLA is an ''n''−6 fatty acid, a type of acid which is generally pro-inflammatory, it has anti-inflammatory properties. ''(See discussion at [[Essential fatty acid interactions#The paradox of dietary GLA|Essential fatty acid interactions: The paradox of dietary GLA]].)''
==Health and Medicine==
[[Image:Middelste teunis bloem R0011876.JPG|thumb|left|The seed oil of ''Oenothera biennis'' (evening primrose) is a source of GLA]]
GLA is sometimes prescribed in the belief that it has anti-[[inflammation|inflammatory]] properties lacking some of the common [[Adverse drug reaction|side effects]] of other [[anti-inflammatory drug]]s. [[Herbal medicine]] advocates recommend GLA for [[autoimmune disorder]]s, [[arthritis]], [[eczema]] and [[premenstrual stress syndrome|PMS]] with noticeable results not expected for months. Research is ongoing, investigating GLA as a potential [[cancer|anticancer]] agent.<ref>{{cite web | url=http://news.bbc.co.uk/2/hi/health/4395826.stm | title=Plant oil 'acts like cancer drug' | date=[[2005-11-02]]}} (describing work by Dr Javier Menendez and colleagues at Northwestern University and published in ''Journal of the National Cancer Institute'').</ref> GLA is unique among the omega-6 [[polyunsaturated fatty acid]]s (linoleic acid, GLA and [[arachidonic acid]]) in its potential to suppress tumor growth and metastasis.<ref name=fan>
{{cite journal | author=Fan, Yang-Yi and Robert S. Chapkin
| title=''Importance of Dietary γ-Linolenic Acid in Human Health and Nutrition''
| url=http://jn.nutrition.org/cgi/content/full/128/9/1411
| date= [[9 September]] [[1998]] | accessdate= 2007-01-05
| journal =Journal of Nutrition
| volume = 128 |issue = 9 |pages = 1411–1414
| pmid=9732298}}</ref>
GLA can also form a [[lithium salt]], increasing its solubility in water. The resulting compound is Li-GLA, also called lithium gammalinolenate. Li-GLA is currently in phase II [[clinical trials]] to determine whether it is useful in the treatment of [[HIV]] infections, since it has the ability to destroy HIV-infected [[T cell]]s [[in vitro]]. It has a number of side-effects, including a reduction in [[hemoglobin]], [[hematuria]], [[gastrointestinal]] disturbance, fatigue and headache.[http://www.hivnet.ubc.ca/e/clinicaltrials/R083.html CTN#083,LiGLA]
===Atopic Eczema===
Conflicting data are found for GLA in the treatment of [[eczema]]. The UK's [[Medicines and Healthcare products Regulatory Agency]] has withdrawn GLA's product licence for atopic eczema.<ref name=Smith2003>{{cite journal| author = Smith, Richard
| url = http://www.bmj.com/cgi/content/full/327/7428/0-h
| journal = British Medical Journal | doi = 10.1136/bmj.327.7428.0-h
| title = The drugs don't work
| accessdate = 2007-01-05
| date = [[13 December]], [[2003]]
| volume = 327
| pages = 0-h}}</ref> Still, the US [[National Institute of Health]]'s MedlinePlus states that there is 'B' grade evidence ('good scientific evidence') for the efficacy of [[evening primrose oil]] in the treatment of [[eczema]]
and skin [[irritation]].<ref name=medline1>{{cite web|
| author = NIH Medline Plus
| url=http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-primrose.html
| title=MedlinePlus Herbs and Supplements: Evening primrose oil
| accessdate= January 19|accessyear=2007}}</ref> But it cautions that large well-designed studies are still needed.
A controlled study of borage oil for eczema found no benefit to GLA; it underperformed placebo.<ref name=ec>{{cite journal |author=Takwale A, Tan E, Agarwal S, ''et al'' |title=Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial |journal=BMJ |volume=327 |issue=7428 |pages=1385 |year=2003 |pmid=14670885 |doi=10.1136/bmj.327.7428.1385|
url=http://bmj.bmjjournals.com/cgi/content/full/327/7428/1385 }}</ref>
==History==
The medical use of GLA has been controversial. [[David Horrobin]] published much research on the use of GLA (as evening primrose oil) as a dietary supplement for treating [[atopic eczema]].<ref name=horribin>{{cite journal| author = Horrobin, David
| url = http://www.ajcn.org/cgi/content/full/71/1/367S
| title= Essential fatty acid metabolism and its modification in atopic eczema
| journal= American Journal of Clinical Nutrition| issue= 1 |pages= 367S–372s|year= January 2000
| accessdate= 2007-01-05
| volume= 71
| pmid= 10617999}}</ref>
He also founded Scotia Pharmaceuticals, which sold this oil as a pharmaceutical, which led to controversy even after his death.<ref name=williams1>{{cite journal
|author=Williams, Hywel C
|journal=BMJ |year=13 Dec 2003|volume=327|pages=1358–1359
|doi= 10.1136/bmj.327.7428.1358 |accessdate=2007-01-19
|title=Editorial: Evening primrose oil for atopic dermatitis—Time to say goodnight |url=http://bmj.bmjjournals.com/cgi/content/full/327/7428/1358
|pmid=14670851
}} British Medical Journal summary editorial on evening primrose oil in the treatment of eczema
</ref>
==References==
{{reflist|2}}
==See also==
*[[Alpha-linolenic acid|Linolenic acid]]
{{Fatty acids}}
{{Other dermatological preparations}}
[[Category:Fatty acids|γ]]
[[Category:Lipids|Linolenic acid, gamma-]]
[[de:Gamma-Linolensäure]]
[[es:Ácido gamma-linolénico]]
[[fr:Acide γ-linolénique]]
[[nl:Gamma-linoleenzuur]]
[[ja:γ-リノレン酸]]
[[pl:Kwas gammalinolenowy]]
[[pt:Ácido gama-linolênico]]