| Formula = C<sub>18</sub>H<sub>30</sub>O<sub>2</sub>
| C=18|H=30|O=2
| MolarMass = [[List of elements by atomic mass|278.43]] g/[[Mole (unit)|mol]]
| Appearance = Colorless oil
| Density =
| MeltingPt =
| BoilingPt =
| Solubility =
}}
}}
}}
}}
__Notoc__
{{SI}}
{{CMG}}
{{CMG}}
==Overview==
==Overview==
'''gamma-Linolenic acid''' (GLA) is an [[essential fatty acid|omega-6 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.
In physiological literature, GLA is designated as 18:3(ω-6). Chemically, GLA is a [[carboxylic acid]] with an 18-carbon chain and three ''[[cis]]'' double bonds; the first double bond is located at the sixth carbon from the omega end. It is also sometimes called '''gamolenic acid'''.<!--especially in articles about evening primrose oil-->
'''Gamma-linolenic acid''' or '''GLA''' ('''γ-Linolenic acid'''), ([[International Nonproprietary Name|INN]] and [[United States Adopted Name|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.<ref name=cochraneepo>[http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004416.pub2/abstract Cochrane Collaboration meta-analysis: Oral evening primrose oil and borage oil for eczema]. Conclusion: lack effect on eczema.</ref><ref>[http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002948.pub2/abstract 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.</ref><ref>[http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001257.pub2/abstract 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.</ref> However when acting on GLA, [[5-lipoxygenase]] produces no [[leukotrienes]] and the conversion by the enzyme of [[arachidonic acid]] to leukotrienes is inhibited.
It is an [[isomer]] of [[alpha-linolenic acid]], which is the [[omega-3 fatty acid]] found in flax seed. Although there are alpha- and gamma- forms of linolenic acid, there is no beta form. One was once identified but it turned out to be an artifact of the original analytical process, (Gunstone).
==Dietary Sources==
==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). GLA is a [[carboxylic acid]] with an 18-carbon chain and three ''[[Cis-trans isomerism|cis]]'' [[double bond]]s. It is an [[isomer]] of [[alpha-linolenic acid|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]], [[Salvia hispanica|chia]], and [[hemp]] seed.
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.
==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
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 6th 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 people grow older and their bodies become unable to produce it in sufficient quantities, or due to specific dietary deficiencies.
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='Eckey1954'>{{cite book | last = Eckey | first = EW | authorlink = | title = Vegetable Fats and Oils (volume 123 of American Chemical Society monograph series) | publisher = Reinhold | year = 1954 | location = | pages = 542 | url = | doi = | id = | isbn = }}</ref>
==A Source of Eicosanoids==
==Dietary sources==
GLA is an [[Omega-6 fatty acid|Omega-6 essential fatty acid]].
GLA is obtained from vegetable oils such as evening primrose (''[[Oenothera biennis]]'') oil (EPO), [[blackcurrant]] seed oil, [[borage seed oil]], and [[hemp oil|hemp seed oil]]. GLA is also found in varying amounts in edible [[hemp]] seeds, oats, barley,<ref>{{cite journal | author = Qureshi AA | journal = Fed. Proc. | volume = 43 | pages = 2626 | year = 1984 | author-separator = , | display-authors = 1 | author2 = <Please add first missing authors to populate metadata.>}}</ref>{{full|date=November 2012}} and [[Spirulina (dietary supplement)|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.<ref>{{cite journal|last=Nykiforuk|first=C.|author2=Shewmaker, C.|title=High level accumulation of gamma linolenic acid in transgenic safflower (Carthamus tinctorius) seeds|journal=Transgenic Research|date=19 August 2011|doi=10.1007/s11248-011-9543-5|volume=21|issue=2|pages=367–81|pmid=21853296}}</ref> Borage oil contains 20% GLA, evening primrose oil ranges from 8% to 10% GLA, and black-currant oil contains 15-20%.<ref>{{cite journal|last=Flider|first=Frank J|title=GLA: Uses and New Sources|journal=INFORM|date=May 2005|volume=16|issue=5|pages=279–282|url=http://www.adoniskish.com/PDF/Super%20Mix/gla.pdf}}</ref>
From GLA, the body forms [[dihomo-gamma-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, (Belch and Hill, 2000).
The human body produces GLA from [[linoleic acid]] (LA). This reaction is catalyzed by Δ<sup>6</sup>-[[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 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 wherein there is excessive consumption of GLA metabolites.<ref name="pmid8386433">{{cite journal |author=Horrobin DF (From the Efamol Research Institute. Kentville. Nova Scotia. Canada) |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>{{dubious|date=September 2013}}
:''Although GLA is an ω-6 fatty acid (which are 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]].''
==Source of eicosanoids==
==Health and Medicine==
[[Image:Middelste teunis bloem R0011876.JPG|thumb|left|The seed oil of ''Oenothera biennis'' (evening primrose) is a source of GLA]]
[[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. Conflicting data are found for GLA in the treatment of [[eczema]]; but the UK's [[Medicines and Healthcare products Regulatory Agency]] has withdrawn GLA's product licence for atopic eczema (Smith, 2003). 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 (Fan and Chapkin, 1998).
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>. Both PGE1<sub>1</sub> and TXA<sub>1</sub> are anti-inflammatory; [[thromboxane]] TXA<sub>1</sub>, unlike its series-2 variant, induces vasodilation, and inhibits platelet<ref>{{cite web|last=King|first=Michael W|title=Introduction to the Eicosanoids|url=http://themedicalbiochemistrypage.org/eicosanoids.php|work=The Medical Biochemistry Page|publisher=1996–2013 themedicalbiochemistrypage.org, LLC|accessdate=23 July 2013}}</ref> consequently, TXA<sub>1</sub> modulates (reduces) the pro-inflammatory properties of the thromboxane TXA<sub>2</sub>. PGE<sub>1</sub> has a role in regulation of [[immune system]] function and is used as the medicine [[alprostadil]].
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]]. But it cautions that large well-designed studies are still needed (NIH Medline Plus).
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.
==History==
In the [[Middle Ages]], a [[folk remedy]] would be to take [[borage]] for any problems from [[rheumatism]] to [[heart disease]].
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]]; (e.g. Horrobin, 2000). He also founded Scotia Pharmaceuticals, which sold this oil as a pharmaceutical, which led to controversy even after his death (Williams 2003).
==References==
<references />
* {{cite web| author= Belch, Jill JF and Hill, Alexander| title=Evening primrose oil and borage oil in rheumatologic conditions|year=January 2000| url= http://www.ajcn.org/cgi/content/full/71/1/352S|accessmonthday=February 12 |accessyear=2006}} PubMed cite.
** "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."
*{{cite journal
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
|author=Williams, Hywel C
|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>
|journal=BMJ |year=13 Dec 2003|volume=327|pages=1358-1359|
|title=Editorial: Evening primrose oil for atopic dermatitis—Time to say goodnight |url=http://bmj.bmjjournals.com/cgi/content/full/327/7428/1358?maxtoshow=&HITS=40&hits=40&RESULTFORMAT=1&andorexacttitle=and&andorexacttitleabs=and&fulltext=evening+primrose+oil&andorexactfulltext=and&searchid=1075237688900_20317&stored_search=&FIRSTINDEX=0&sortspec=relevance&fdate=10/1/2003&resourcetype=1,2,3,4}} British Medical Journal summary editorial on evening primrose oil in the treatment of eczema
*[http://bmj.bmjjournals.com/cgi/content/full/327/7428/1385?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=eczema&andorexactfulltext=and&searchid=1122926769658_2505&stored_search=&FIRSTINDEX=0&sortspec=relevance&resourcetype=1 British Medical Journal: Efficacy and tolerability of borage oil in adults and children with atopic eczema].
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|Essential fatty acid interactions: The paradox of dietary GLA]].)''
* {{cite journal | author=Fan, Yang-Yi and Robert S. Chapkin
==Health and medicine==
| title=''Importance of Dietary gamma -Linolenic Acid in Human Health and Nutrition''
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".<ref name=dh-obit>{{cite journal|doi=10.1136/bmj.326.7394.885|title=David Horrobin|year=2003|last1=Richmond|first1=C.|journal=BMJ|volume=326|issue=7394|pages=885}}</ref>
In 2002 the UK's [[Medicines and Healthcare products Regulatory Agency]] withdrew marketing authorisations for evening primrose oil as an eczema remedy.<ref name=goodnight>{{cite journal|jstor=25457999|doi=10.1136/bmj.327.7428.1358|title=Evening primrose oil for atopic dermatitis: Time To Say Goodnight|year=2003|last1=Williams|first1=H. C|journal=BMJ|volume=327|issue=7428|pages=1358–9|pmid=14670851|pmc=292973}}</ref> 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.<ref name=Smith2003>{{cite journal|doi = 10.1136/bmj.327.7428.0-h|title = The drugs don't work|year = 2003|last1 = Smith|first1 = R.|journal = BMJ|volume = 327|issue = 7428|pages = 0–h}}</ref>
* Gunstone, Frank, [http://www.lapinskas.com/publications/3918.html Personal Communication] at Peter Lapinskas' pages; URL Retrieved [[3 February]] [[2006]]
*{{cite journal| author = Horrobin, David
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."<ref name=acs>{{cite web
| title=MedlinePlus Herbs and Supplements: Evening primrose oil
| accessdate= January 19|accessyear=2007}}
==See also==
[[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 [[Oenothera biennis|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{{cn|date=July 2014}} 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 [[Tissue (biology)|tissues]]. Another report{{cn|date=July 2014}} 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.<ref name=cochraneepo/>
Gamma-linolenic acid or GLA (γ-Linolenic acid), (INN and USANgamolenic 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.[1][2][3] 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 cisdouble bonds. It is an isomer of α-linolenic acid, which is a polyunsaturated n−3 (omega-3) fatty acid, found in rapeseedcanola 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.[4]
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.[5]
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,[6][full citation needed] 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.[7] Borage oil contains 20% GLA, evening primrose oil ranges from 8% to 10% GLA, and black-currant oil contains 15-20%.[8]
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.[9][dubious – discuss]
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[10] 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.[11]
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".[12]
In 2002 the UK's Medicines and Healthcare products Regulatory Agency withdrew marketing authorisations for evening primrose oil as an eczema remedy.[13] 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.[14]
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."[15]
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[citation needed] 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[citation needed] 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.[1]
↑King, Michael W. "Introduction to the Eicosanoids". The Medical Biochemistry Page. 1996–2013 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): 352S–6S. PMID10617996. 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.
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