Identification
- Summary
Gamolenic acid is an ingredient found in a variety of nutritional products.
- Generic Name
- Gamolenic acid
- DrugBank Accession Number
- DB13854
- Background
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.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Gamolenic acid (DB13854)
- Weight
- Average: 278.4296
Monoisotopic: 278.224580204 - Chemical Formula
- C18H30O2
- Synonyms
- (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
Pharmacology
- Indication
Indicated as a dietary supplement for over-the-counter uses.
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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.
- Absorption
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.
- Metabolism
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.
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- Route of elimination
The metabolites of gamolenic acid is expected to undergo renal excretion 8.
- Half-life
No pharmacokinetic data available.
- Clearance
No pharmacokinetic data available.
- Adverse Effects
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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAcetazolamide The therapeutic efficacy of Acetazolamide can be decreased when used in combination with Gamolenic acid. Amifampridine The risk or severity of seizure can be increased when Gamolenic acid is combined with Amifampridine. Amobarbital The therapeutic efficacy of Amobarbital can be decreased when used in combination with Gamolenic acid. Brexanolone The therapeutic efficacy of Brexanolone can be decreased when used in combination with Gamolenic acid. Brivaracetam The therapeutic efficacy of Brivaracetam can be decreased when used in combination with Gamolenic acid. - Food Interactions
- No interactions found.
Products
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Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Beta-carotene 10000I.U. With Borage Oil Cap Gamolenic acid (90 mg / cap) + Beta carotene (10000 unit / cap) Capsule Oral Jamieson Laboratories Ltd 1993-12-31 1997-08-13 Canada 
Bio-efa Borage Gla 240 Cap Gamolenic acid (240 mg) + Linoleic acid (378 mg) + Vitamin E (10 unit) Capsule Oral Pge Canada (86) Inc. 1989-12-31 2006-06-19 Canada Bio-efa Borage Gla 90 Cap Gamolenic acid (90 mg / cap) + Linoleic acid (216 mg / cap) + Vitamin E (10 unit / cap) + alpha-Linolenic acid (1 mg / cap) Capsule Oral Pge Canada (86) Inc. 1989-12-31 2006-06-19 Canada Black Currant Seed Oil Cap Gamolenic acid (41 mg) + Linoleic acid (78 mg) + Vitamin E (10 unit) Capsule Oral Pure Life International Prods Inc. 1993-12-31 2001-08-07 Canada Borage Oil Capsules Gamolenic acid (258 mg) + Linoleic acid (375 mg) + Oleic Acid (148 mg) + Palmitic Acid (96 mg) Capsule Oral General Nutrition Canada Inc. 2001-10-15 2009-08-05 Canada
Categories
- ATC Codes
- D11AX02 — Gamolenic acid
- D11AX — Other dermatologicals
- D11A — OTHER DERMATOLOGICAL PREPARATIONS
- D11 — OTHER DERMATOLOGICAL PREPARATIONS
- D — DERMATOLOGICALS
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- 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.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- 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
- Substituents
- 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
- UNII
- 78YC2MAX4O
- CAS number
- 506-26-3
- InChI Key
- VZCCETWTMQHEPK-QNEBEIHSSA-N
- InChI
- InChI=1S/C18H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h6-7,9-10,12-13H,2-5,8,11,14-17H2,1H3,(H,19,20)/b7-6-,10-9-,13-12-
- IUPAC Name
- (6Z,9Z,12Z)-octadeca-6,9,12-trienoic acid
- SMILES
- CCCCC\C=C/C\C=C/C\C=C/CCCCC(O)=O
References
- General References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Gamma-Linolenic Acid (GLA) Monograph - Semantic Scholar [File]
- External Links
- Human Metabolome Database
- HMDB0003073
- KEGG Drug
- D07213
- KEGG Compound
- C06426
- ChemSpider
- 4444436
- BindingDB
- 50269532
- 25605
- ChEBI
- 28661
- ChEMBL
- CHEMBL464982
- ZINC
- ZINC000003777423
- Wikipedia
- Gamma-Linolenic_acid
- MSDS
- Download (28.3 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count Not Available Completed Treatment Rheumatoid Arthritis, Juvenile 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Liquid Oral Capsule Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.000254 mg/mL ALOGPS logP 6.59 ALOGPS logP 6.06 Chemaxon logS -6 ALOGPS pKa (Strongest Acidic) 4.92 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 37.3 Å2 Chemaxon Rotatable Bond Count 13 Chemaxon Refractivity 89.64 m3·mol-1 Chemaxon Polarizability 33.8 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 208.6940071 predictedDarkChem Lite v0.1.0 [M-H]- 209.0836071 predictedDarkChem Lite v0.1.0 [M-H]- 208.0007071 predictedDarkChem Lite v0.1.0 [M-H]- 208.5141071 predictedDarkChem Lite v0.1.0 [M-H]- 177.04048 predictedDeepCCS 1.0 (2019) [M+H]+ 179.39851 predictedDeepCCS 1.0 (2019) [M+Na]+ 185.49178 predictedDeepCCS 1.0 (2019)
Drug created at June 23, 2017 20:49 / Updated at September 15, 2023 10:38