GLA (Gamma-Linolenic Acid)
GLA is an omega-6 fatty acid produced from linoleic acid by delta-6-desaturase that paradoxically exerts anti-inflammatory effects through its conversion to DGLA and downstream production of anti-inflammatory prostaglandin E1.
Overview
Gamma-linolenic acid (GLA) is an 18-carbon omega-6 polyunsaturated fatty acid (18:3n-6) that occupies a unique position in essential fatty acid metabolism. While most omega-6 fatty acids are associated with pro-inflammatory pathways, GLA is converted to dihomo-gamma-linolenic acid (DGLA), which serves as the precursor to prostaglandin E1 (PGE1) and 15-HETrE—both of which are potent anti-inflammatory mediators. This makes GLA supplementation a strategy for shifting omega-6 metabolism toward anti-inflammatory rather than pro-inflammatory outcomes.
GLA is produced endogenously from dietary linoleic acid by the enzyme delta-6-desaturase, but this conversion step is rate-limiting and can be impaired by aging, diabetes, alcohol consumption, stress, and nutritional deficiencies. Dietary sources of preformed GLA include evening primrose oil (8-10% GLA), borage seed oil (20-24% GLA), and black currant seed oil (15-20% GLA). Direct supplementation bypasses the delta-6-desaturase bottleneck, ensuring adequate DGLA levels for anti-inflammatory prostaglandin production.
Clinical research on GLA has shown benefits in rheumatoid arthritis, where doses of 1.4-2.8 g/day have reduced joint pain, swelling, and morning stiffness in randomized controlled trials. It has been studied for atopic dermatitis (eczema), diabetic neuropathy, and premenstrual syndrome, with varying degrees of evidence. GLA may also support healthy skin barrier function by contributing to ceramide synthesis in the stratum corneum. Its anti-inflammatory effects appear to be enhanced when combined with omega-3 fatty acids (EPA/DHA), which compete with arachidonic acid for the same enzymatic pathways.
Mechanism of Action
Gamma-linolenic acid (GLA) is an omega-6 polyunsaturated fatty acid (18:3n-6) found in borage oil, evening primrose oil, and black currant seed oil. Its primary mechanism of action involves conversion to the elongation product dihomo-gamma-linolenic acid (DGLA), which serves as a precursor for anti-inflammatory eicosanoids. Through the cyclooxygenase (COX) pathway, DGLA is converted to prostaglandin E1 (PGE1), a potent anti-inflammatory and vasodilatory prostaglandin. Through the 15-lipoxygenase (15-LOX) pathway, DGLA produces 15-hydroxyeicosatrienoic acid (15-HETrE), which also has anti-inflammatory properties.
A critical aspect of GLA's mechanism is the competitive inhibition of arachidonic acid (AA) metabolism. DGLA competes with AA for access to COX and LOX enzymes, thereby reducing the production of pro-inflammatory AA-derived eicosanoids including prostaglandin E2 (PGE2), thromboxane A2, and leukotriene B4 (LTB4). This shift in the eicosanoid balance from pro-inflammatory to anti-inflammatory mediators underlies GLA's therapeutic effects in inflammatory conditions.
At the transcriptional level, GLA suppresses activation of NF-κB and AP-1 transcription factors, reducing inflammatory gene expression. GLA and its metabolites also activate peroxisome proliferator-activated receptor gamma (PPAR-γ), a nuclear receptor that regulates inflammation and lipid metabolism. The effects of PGE1 are mediated through specific EP receptors on target cells, particularly immune cells such as macrophages and neutrophils where GLA modulates the production of inflammatory mediators.
Reconstitution Calculator
Reconstitution Calculator
Calculate your peptide dosing
Set up a clean workspace with all supplies ready.
7x / week for weeks
Research
Reported Effects
Combination Therapy:: Most effective when combined with fish oil/omega-3s rather than used alone, as the two types of fatty acids work synergistically. Individual Variation:: Delta-6-desaturase activity varies among individuals, making GLA more beneficial for those with reduced enzyme activity due to aging, nutrient deficiency, or other factors. Timeline:: Effects on inflammation and skin health typically require consistent use over several weeks to months. Dose-Response:: Clinical studies suggest 125-500mg daily as effective doses, with higher amounts not necessarily providing additional benefits
- Most effective when combined with fish oil/omega-3s rather than used alone, as the two types of fatty acids work synergistically
- Delta-6-desaturase activity varies among individuals, making GLA more beneficial for those with reduced enzyme activity due to aging, nutrient deficiency, or other factors
- Effects on inflammation and skin health typically require consistent use over several weeks to months
- Clinical studies suggest 125-500mg daily as effective doses, with higher amounts not necessarily providing additional benefits
Safety Profile
Safety Profile: GLA (Gamma-Linolenic Acid)
Common Side Effects
- Mild gastrointestinal discomfort (bloating, nausea, soft stools)
- Belching or fishy aftertaste (especially with evening primrose or borage oil sources)
- Headache (occasionally reported at higher doses)
- Mild skin reactions in sensitive individuals
Serious Adverse Effects
- Bleeding risk: GLA has mild antiplatelet activity; at high doses may increase bleeding tendency
- Seizure threshold reduction: Borage oil (a common GLA source) contains pyrrolizidine alkaloids (PAs) in unrefined forms, which are hepatotoxic; always use PA-free certified products
- Rare hepatotoxicity with long-term use of PA-containing borage oil preparations
- Allergic reactions (rare) including rash, swelling, or difficulty breathing
Contraindications
- Known allergy to evening primrose, borage, or blackcurrant seed oils
- Seizure disorders (evening primrose oil may lower seizure threshold)
- Bleeding disorders or upcoming surgery (discontinue 2 weeks prior)
- Pregnancy (may induce labor; evening primrose oil has uterotonic properties)
- Severe liver disease (particularly with borage-sourced GLA)
Drug Interactions
- Anticoagulants/antiplatelets (warfarin, aspirin, clopidogrel): Increased bleeding risk
- Anticonvulsants (phenothiazines, phenobarbital): May lower seizure threshold
- NSAIDs: Additive bleeding risk
- Anesthetics: Discontinue prior to surgery due to bleeding and seizure concerns
- Cyclosporine: May enhance anti-inflammatory effects but requires monitoring
Population-Specific Considerations
- Pregnancy/Lactation: Generally not recommended; limited safety data; potential uterotonic effects
- Children: Limited clinical data; use only under medical supervision at reduced doses
- Elderly: Monitor for bleeding, especially if on anticoagulant therapy
- Hepatic impairment: Use PA-free sources only; monitor liver function
- Surgical patients: Discontinue at least 14 days before elective procedures
Pharmacokinetic Profile
Quick Start
- Typical Dose
- 125-500mg daily appears to be the most commonly recommended range based on user reports and clinical data
Safety Profile
Common Side Effects
- Generally Well-Tolerated:: Most users report minimal to no side effects when used at recommended doses
- Digestive Issues:: Rare reports of mild gastrointestinal discomfort, particularly at higher doses or when first starting supplementation
- Interaction Concerns:: May interact with blood thinners or medications affecting prostaglandin pathways
- Quality Considerations:: Supplement quality and source matter; evening primrose, borage, and black currant oils have different GLA concentrations and additional medicinal properties
References (3)
- [3]Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipids and fatty acid profiles in women
→ GLA supplementation combined with fish oil demonstrates lipid-modifying and anti-inflammatory properties in women, with synergistic effects when used together.
- [2]Co-supplementation of healthy women with fish oil and evening primrose oil increases plasma docosahexaenoic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid levels without reducing arachidonic acid concentrations
→ Combined fish oil and evening primrose oil supplementation effectively increases GLA and DGLA levels in healthy women without negatively impacting arachidonic acid concentrations.
- [1]Gamma-linolenic acid, Dihommo-gamma linolenic, Eicosanoids and Inflammatory Processes
→ GLA supplementation bypasses the rate-limiting delta-6-desaturase step and is quickly elongated to DGLA, which can be converted to anti-inflammatory prostaglandins, making it useful for managing inflammatory processes.
GIP (Glucose-Dependent Insulinotropic Polypeptide)
GIP (Glucose-Dependent Insulinotropic Polypeptide, formerly known as Gastric Inhibitory Polypeptide) is an endogenous incretin hormone produced by enteroendocri
Glow Blend (TB-500 / BPC-157 / GHK-Cu)
The **Glow Blend** combines three of the most well-researched regenerative peptides — TB-500, BPC-157, and GHK-Cu — into a single formulation targeting skin hea