Gamma-Linolenic acid

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 = CCCCCC=C/CC=C/CC=C/CCCCC(=O)O
PubChem = 5280933
Section2 = Chembox Properties
Formula = C₁₈H₃₀O₂
MolarMass = 278.43 g/mol

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 "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 bonds. It is an isomer of α-linolenic acid, which is the "n"−3 fatty acid found in flax 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.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] 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.cite web| author=Gunstone, Frank
url=http://www.lapinskas.com/publications/3918.html
title=Personal Communication at Peter Lapinskas' pages
accessdate= 2006-02-03]

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, 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 pharmacies, health food stores, or online shops.

The human body produces GLA from linoleic acid (LA). This reaction is catalized by Δ⁶-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 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 where there is excessive consumption of GLA metabolites.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=]

A Source of Eicosanoids

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. PGE₁ has a role in regulation of immune system function and is used as the medicine alprostadil. TXA₁ modulates the pro-inflammatory properties of the thromboxane TXA₂.

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

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 .)"

Health and Medicine

GLA is sometimes prescribed in the belief that it has anti-inflammatory properties lacking some of the common side effects of other anti-inflammatory drugs. Herbal medicine advocates recommend GLA for autoimmune disorders, arthritis, eczema and PMS with noticeable results not expected for months. Research is ongoing, investigating GLA as a potential anticancer agent. [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").] GLA is unique among the omega-6 polyunsaturated fatty acids (linoleic acid, GLA and arachidonic acid) in its potential to suppress tumor growth and metastasis.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]

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 cells 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.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] 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 eczemaand skin irritation.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] 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.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 ]

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.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|month= January | year= 2000
accessdate= 2007-01-05
volume= 71
pmid= 10617999] He also founded Scotia Pharmaceuticals, which sold this oil as a pharmaceutical, which led to controversy even after his death.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]

References

ee also

*Linolenic acid