Gamolenic acid



Gamolenic acid is an ingredient found in a variety of nutritional products.

Generic Name
Gamolenic acid
DrugBank Accession Number

Gamolenic acid, or gamma-linolenic acid (γ-Linolenic acid) or GLA, is an essential fatty acid (EFA) comprised of 18 carbon atoms with three double bonds 8 that is most commonly found in human milk and other botanical sources 1. It is an omega-6 polyunsaturated fatty acid (PUFA) also referred to as 18:3n-6; 6,9,12-octadecatrienoic acid; and cis-6, cis-9, cis-12- octadecatrienoic acid 8. Gamolenic acid is produced minimally in the body as the delta 6-desaturase metabolite of Linolenic acid. It is converted to Dihomo-gamma-linolenic acid, a biosynthetic precursor of monoenoic prostaglandins such as PGE1. While Gamolenic acid is found naturally in the fatty acid fractions of some plant seed oils 8, Evening primrose oil and Borage oil are rich sources of gamolenic acid. Evening primrose oil has been investigated for clinical use in menopausal syndrome, diabetic neuropathy, and breast pain, where gamolenic acid is present at concentrations of 7-14% 8. Gamolenic acid may be found in over-the-counter dietary supplements. Gamolenic acid is also found in some fungal sources and also present naturally in the form of triglycerides 8. Various clinical indications of gamolenic acid have been studied, including rheumatoid arthritis, atopic eczema, acute respiratory distress syndrome, asthma, premenstrual syndrome, cardiovascular disease, ulcerative colitis, ADHD, cancer, osteoporosis, diabetic neuropathy, and insomnia.

Small Molecule
Approved, Investigational
Average: 278.4296
Monoisotopic: 278.224580204
Chemical Formula
  • (6,9,12)-linolenic acid
  • (6Z,9Z,12Z)-Octadecatrienoic acid
  • (Z,Z,Z)-6,9,12-octadecatrienoic acid
  • 18:3 (n-6)
  • 6-cis,9-cis,12-cis-octadecatrienoic acid
  • 6,9,12-Octadecatrienoic acid
  • all-cis-6,9,12-octadecatrienoic acid
  • gamma-Linolenic acid
  • Gammalinolenic acid
  • gamoleic acid
  • Gamolenic acid
  • GLA
  • Octadeca-6,9,12-triensäure
  • γ-linolenic acid
  • γ-Linolensäure
External IDs
  • NDI 609



Indicated as a dietary supplement for over-the-counter uses.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more

Gamolenic acid is converted to PGE1, which exhibits anti-inflammatory, antithrombotic, antiproliferative, and lipid-lowering effects 8. PGE1 also induces smooth muscle relaxation and vasodilation. Gamolenic acid is an essential component of membrane phospholipids, including the mitochondrial membrane, where it enhances the the integrity and the fluidity of the membrane 8.

Bone and joint health: In a pilot study of women with a mean age of 79.5 years and senile osteoporosis, the use of gamolenic acid in combination with calcium and eicosapentaenoic acid was associated with an increase in femoral bone density and lumbar spine density in comparison to placebo, where there were no observable changes 6. In clinical studies of patients with rheumatoid arthritis, treatment with gamolenic acid-containing oils resulted in an improvement in symptoms, measured by joint tenderness counts and scores, joint swelling scores, physician global assessment, and pain 8.

Inflammation: A study demonstrated that oral administration of gamolenic acid suppressed human T-cell proliferation and activation by interfering with early events in the TcR/CD3-receptor–mediated signal transduction cascade 2.

Atherosclerosis: In ApoE genetic knock-out mice, dietary gamolenic acid was shown to reduce the average medial layer thickness of the vessel wall and reduces the size of atherosclerotic lesions 2.

Diabetic complications: In a clinical trial of patients with mild diabetic neuropathy or distal diabetic neuropathy, treatment with gamolenic acid was associated with improved symptoms in hot and cold threshold, sensation, tendon reflexes, and muscle strength 8. GLA ameliorated the inflammatory profile in diabetic nephropathy in rat studies 3.

Cancer: In three human tumor cell lines (the neuroblastoma CHP-212, the tubal carcinoma TG, and the colon carcinoma SW-620), gamolenic acid elicited cytotoxic effects in tumours by blocking cell proliferation following incorporation into malignant cells 5. In both clinical and animal studies of breast cancer, gamolenic acid, in combination with tamoxifen, down-regulated the expression of estrogen receptors 8.

Skin disorders: In an open study of patients with atopic dermatitis, which is a disorder related to a deficiency of delta-6-desaturase and inefficient conversion of linoleic acid to gamolenic acid, daily administration of gamolenic acid was associated with a significant increase in plasma GLA and DGLA levels in combination with an improvement of clinical signs of atopic dermatitis 7.

Respiratory disorders: In patients with acute lung injury or acute respiratory distress syndrome, gamolenic acid was shown to reduce cytokine production and neutrophil recruitment into the lung 1. In patients with atopic asthma, gamolenic acid blocked ex vivo synthesis of leukotrienes from whole blood and isolated neutrophils compared to the placebo group 1.

Mechanism of action

Once gamolenic acid (GLA) is absorbed and converted to dihomo-gamolenic acid (DGLA), circulating DGLA fatty acids are converted to several lipid mediators with predominantly anti-inflammatory properties, such as prostaglandin-E1 (PGE1) and 15-HETrE. The anti-inflammatory effects of DGLA are attributed to both the anti-inflammatory properties of DGLA-derived metabolites and the ability of DGLA and its products to compete with arachidonic acid (AA) in the synthesis of pro-inflammatory potent eicosanoid products, such as prostaglandins, thromboxane and leukotrienes 1. Both PGE1 and 15-HETrE are known to suppress inflammation, promote vasodilation, lower blood pressure, inhibit smooth muscle cell proliferation, inhibit platelet aggregation, and exert anti-neoplastic activities 1. PGE1 is a potent vasodilator that binds to surface receptors on smooth muscle cells, increasing intracellular cAMP 8. PGE1 is binds to G protein coupled surface PGE (EP) receptors and prostacyclin (IP) receptors as a natural ligand 2.

GLA is proposed to enhance calcium absorption, reduce excretion and increase calcium deposition in bone 6. It is proposed that GLA may suppress tumor growth in vivo by increasing the expression of E-cadherin, a cell-to-cell adhesion molecule that acts as a suppressor of metastasis. Another possible mechanism of tumour suppression is that GLA also reduces tumor-endothelium adhesion, which is a key factor in the establishment of distant metastases, partly by improving gap junction communication within the endothelium 2. By targeting the inflammatory process involved in the pathogenesis of diabetic nephropathy, GLA inhibits the expression of inflammatory mediators that tend be elevated in diabetes, intracellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), thereby attenuates the recruitment and infiltration of monocytes or macrophages 3.


The findings from a pharmacokinetic study suggest that therapeutic levels of GLA can be achieved within a week. The fasting plasma GLA levels plateaued within seven days of beginning treatment, regardless of dose 8.

Volume of distribution

No pharmacokinetic data available.

Protein binding

No pharmacokinetic data available.


Via elongation mediated by elongase (ELOVL5), gamolenic acid is rapidly converted to dihomo-gamma-linolenic acid (DGLA), which is further cyclooxygenated to prostaglandin E1 (PGE1) via COX-1 or COX-2 enzymatic activity depending on the cell type 1. PGE1 may be metabolized to smaller prostaglandin remnants, primarily dicarboxylic acids, which undergo renal excretion 8. DGLA may be converted to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid (15-HETrE) by 15-lipoxygenase enzyme 1.

Although the enzymatic pathway is less predominant relative to ELOVL5 in most cells, DGLA may also be converted to arachidonic acid (AA) via delta-5-desaturate activity 4, where hydrogen atoms are selectively removed to create new double bonds F27]. Arachidonic acid is a precursor in the biosynthesis of prostaglandin E2, thromboxanes, and leukotrienes, which are potent inflammatory mediators and play an important role in inflammatory pathways.

Hover over products below to view reaction partners

Route of elimination

The metabolites of gamolenic acid is expected to undergo renal excretion 8.


No pharmacokinetic data available.


No pharmacokinetic data available.

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample

Oral TDLO reported in man is 3.14 mg/kg/42D (intermittent) MSDS. While limited cases of soft stool, belching, and abdominal bloating have been reported from dietary supplements containing gamolenic acid, daily doses up to 2.8 g were well tolerated 8.

Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
AcetazolamideThe therapeutic efficacy of Acetazolamide can be decreased when used in combination with Gamolenic acid.
AmifampridineThe risk or severity of seizure can be increased when Gamolenic acid is combined with Amifampridine.
AmobarbitalThe therapeutic efficacy of Amobarbital can be decreased when used in combination with Gamolenic acid.
BrexanoloneThe therapeutic efficacy of Brexanolone can be decreased when used in combination with Gamolenic acid.
BrivaracetamThe therapeutic efficacy of Brivaracetam can be decreased when used in combination with Gamolenic acid.
Food Interactions
No interactions found.


Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Beta-carotene 10000I.U. With Borage Oil CapGamolenic acid (90 mg / cap) + Beta carotene (10000 unit / cap)CapsuleOralJamieson Laboratories Ltd1993-12-311997-08-13Canada flag
Bio-efa Borage Gla 240 CapGamolenic acid (240 mg) + Linoleic acid (378 mg) + Vitamin E (10 unit)CapsuleOralPge Canada (86) Inc.1989-12-312006-06-19Canada flag
Bio-efa Borage Gla 90 CapGamolenic acid (90 mg / cap) + Linoleic acid (216 mg / cap) + Vitamin E (10 unit / cap) + alpha-Linolenic acid (1 mg / cap)CapsuleOralPge Canada (86) Inc.1989-12-312006-06-19Canada flag
Black Currant Seed Oil CapGamolenic acid (41 mg) + Linoleic acid (78 mg) + Vitamin E (10 unit)CapsuleOralPure Life International Prods Inc.1993-12-312001-08-07Canada flag
Borage Oil CapsulesGamolenic acid (258 mg) + Linoleic acid (375 mg) + Oleic Acid (148 mg) + Palmitic Acid (96 mg)CapsuleOralGeneral Nutrition Canada Inc.2001-10-152009-08-05Canada flag


ATC Codes
D11AX02 — Gamolenic acidD11AX52 — Gamolenic acid, combinations
Drug Categories
Chemical TaxonomyProvided by Classyfire
This compound belongs to the class of organic compounds known as lineolic acids and derivatives. These are derivatives of lineolic acid. Lineolic acid is a polyunsaturated omega-6 18 carbon long fatty acid, with two CC double bonds at the 9- and 12-positions.
Organic compounds
Super Class
Lipids and lipid-like molecules
Fatty Acyls
Sub Class
Lineolic acids and derivatives
Direct Parent
Lineolic acids and derivatives
Alternative Parents
Long-chain fatty acids / Unsaturated fatty acids / Straight chain fatty acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Aliphatic acyclic compound / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Fatty acid / Hydrocarbon derivative / Long-chain fatty acid / Monocarboxylic acid or derivatives / Octadecanoid / Organic oxide
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
omega-6 fatty acid, linolenic acid (CHEBI:28661) / Unsaturated fatty acids, Polyunsaturated fatty acids (C06426) / Unsaturated fatty acids (LMFA01030141)
Affected organisms
Not Available

Chemical Identifiers

CAS number
InChI Key
(6Z,9Z,12Z)-octadeca-6,9,12-trienoic acid


General References
  1. Sergeant S, Rahbar E, Chilton FH: Gamma-linolenic acid, Dihommo-gamma linolenic, Eicosanoids and Inflammatory Processes. Eur J Pharmacol. 2016 Aug 15;785:77-86. doi: 10.1016/j.ejphar.2016.04.020. Epub 2016 Apr 12. [Article]
  2. Fan YY, Chapkin RS: Importance of dietary gamma-linolenic acid in human health and nutrition. J Nutr. 1998 Sep;128(9):1411-4. doi: 10.1093/jn/128.9.1411. [Article]
  3. Kim DH, Yoo TH, Lee SH, Kang HY, Nam BY, Kwak SJ, Kim JK, Park JT, Han SH, Kang SW: Gamma linolenic acid exerts anti-inflammatory and anti-fibrotic effects in diabetic nephropathy. Yonsei Med J. 2012 Nov 1;53(6):1165-75. doi: 10.3349/ymj.2012.53.6.1165. [Article]
  4. Chamberlin AJ, Bauer JE: Dietary gamma-linolenic acid supports arachidonic acid accretion and associated Delta-5 desaturase activity in feline uterine but not ovarian tissues. J Nutr Sci. 2014 Oct 13;3:e43. doi: 10.1017/jns.2014.41. eCollection 2014. [Article]
  5. Hrelia S, Bordoni A, Biagi P, Rossi CA, Bernardi L, Horrobin DF, Pession A: gamma-Linolenic acid supplementation can affect cancer cell proliferation via modification of fatty acid composition. Biochem Biophys Res Commun. 1996 Aug 14;225(2):441-7. doi: 10.1006/bbrc.1996.1192. [Article]
  6. Kruger MC, Coetzer H, de Winter R, Gericke G, van Papendorp DH: Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano). 1998 Oct;10(5):385-94. [Article]
  7. Simon D, Eng PA, Borelli S, Kagi R, Zimmermann C, Zahner C, Drewe J, Hess L, Ferrari G, Lautenschlager S, Wuthrich B, Schmid-Grendelmeier P: Gamma-linolenic acid levels correlate with clinical efficacy of evening primrose oil in patients with atopic dermatitis. Adv Ther. 2014 Feb;31(2):180-8. doi: 10.1007/s12325-014-0093-0. Epub 2014 Jan 17. [Article]
  8. Gamma-Linolenic Acid (GLA) Monograph - Semantic Scholar [File]
Human Metabolome Database
KEGG Compound
Download (28.3 KB)

Clinical Trials

Clinical Trials
Not AvailableCompletedTreatmentRheumatoid Arthritis, Juvenile1


Not Available
Not Available
Dosage Forms
Not Available
Not Available


Experimental Properties
Not Available
Predicted Properties
Water Solubility0.000254 mg/mLALOGPS
pKa (Strongest Acidic)4.92Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area37.3 Å2Chemaxon
Rotatable Bond Count13Chemaxon
Refractivity89.64 m3·mol-1Chemaxon
Polarizability33.8 Å3Chemaxon
Number of Rings0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available


Mass Spec (NIST)
Not Available
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MS (1 TMS)GC-MSsplash10-005c-9800000000-7b6e7a36b048f5ed69bd
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0006-9650000000-eec5566c0f0f90bf0049
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-00b9-9300000000-254ecb989081fdc719d2
GC-MS Spectrum - GC-MSGC-MSsplash10-005c-9800000000-7b6e7a36b048f5ed69bd
Mass Spectrum (Electron Ionization)MSsplash10-00nf-9200000000-cf911df79059a750cb2a
MS/MS Spectrum - ESI-TOF 20V, NegativeLC-MS/MSsplash10-005l-0902100000-6fc8730bd28daa779b66
MS/MS Spectrum - ESI-TOF 30V, NegativeLC-MS/MSsplash10-005l-0902100000-6fc8730bd28daa779b66
MS/MS Spectrum - ESI-TOF 10V, NegativeLC-MS/MSsplash10-005l-0902100000-6fc8730bd28daa779b66
MS/MS Spectrum - ESI-TOF , NegativeLC-MS/MSsplash10-005l-0902100000-6fc8730bd28daa779b66
MS/MS Spectrum - ESI-TOF 20V, NegativeLC-MS/MSsplash10-004i-0090000000-143e6ddfa05656a4c4da
MS/MS Spectrum - ESI-TOF 30V, NegativeLC-MS/MSsplash10-004i-0090000000-0b9ba563ad074fe141e8
MS/MS Spectrum - ESI-TOF 10V, NegativeLC-MS/MSsplash10-004i-0090000000-63bf7d731625d5577978
MS/MS Spectrum - ESI-TOF 10V, NegativeLC-MS/MSsplash10-004i-0090000000-fbc4e202a8b26c91dc9e
MS/MS Spectrum - ESI-TOF , NegativeLC-MS/MSsplash10-004i-0090000000-b56d00321ab0921fe7b7
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-004i-0090000000-dcae4273443fd52bbb03
LC-MS/MS Spectrum - LC-ESI-TOF , negativeLC-MS/MSsplash10-004i-0090000000-143e6ddfa05656a4c4da
LC-MS/MS Spectrum - LC-ESI-TOF , negativeLC-MS/MSsplash10-004i-0090000000-0b9ba563ad074fe141e8
LC-MS/MS Spectrum - LC-ESI-TOF , negativeLC-MS/MSsplash10-004i-0090000000-63bf7d731625d5577978
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-01r6-5690000000-de47bbd83d61796fb726
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0090000000-817c92837eff26b2b7f8
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0290000000-88f5d47ccc2e6323f783
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00lr-9700000000-2a5e2c83c40c13667cc2
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-052f-3690000000-85669b539916423af7ab
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-05pp-9100000000-b7229aa685c2c1b863b3
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
DarkChem Lite v0.1.0
DarkChem Lite v0.1.0
DarkChem Lite v0.1.0
DarkChem Lite v0.1.0
DeepCCS 1.0 (2019)
DeepCCS 1.0 (2019)
DeepCCS 1.0 (2019)

Drug created at June 23, 2017 20:49 / Updated at September 15, 2023 10:38