Gamma Linolenic Acid (GLA)

Overview

Gamma linolenic acid (GLA) is derived from linoleic acid, which is the parent omega-6 fatty acid. GLA is the precursor for dihomogamma-linolenic acid (DGLA), which is the precursor to the PGE1 series prostaglandins, and arachidonic acid, which is the precursor to the PGE2 series prostaglandins. Because GLA (and its metabolite DGLA) are the precursors for the synthesis of these prostaglandins, they help to regulate a number of bodily functions (e.g., gamma linolenic acid is essential for adequate skin integrity as well as being an important lubricant for the joints). GLA may also decrease the invasion of several types of cancer. (1) , (2) , (3)

Dosage Info

Dosage Range

Variable depending on the type of oil being used: evening primrose oil, 2 to 6 grams/day; borage oil, 1 to 6 grams/day; black currant seed oil, 2 to 10 grams/day.

Most Common Dosage

500-1,000mg daily.

Dosage Forms

Capsules or bottles of liquid oils.

Adult RDI

None established

Adult ODA

None established

RDA

• : None established

Interactions and Depletions

Interactions

• mineral oil
• Bile acid sequestrants
• orlistat
• chitosan
• olestra
• Lipase inhibitor supplements
• Anticoagulant medications

Active Forms

Gamma linolenic acid, usually coming from oils with high GLA content such as evening primrose, borage, or black currant seed oil.

Absorption

The absorption of fats, including GLA, takes place in the small intestine with the action of lipase enzymes and bile salts, which are excreted.

Toxicities & Precautions

General

Individuals who ingest supplemental GLA are advised to take additional antioxidants, especially vitamin E, to protect against free radical oxidation in the body. (4)

Functions in the Body

Clinical Applications

Elevated Cholesterol

Gamma linolenic acid has been reported to have cholesterol-lowering activity that is approximately 170 times greater than its parent molecule linoleic acid (omega-6), indicating that omega-6 must be converted to GLA in order to exert its beneficial effects on the metabolism and excretion of cholesterol. (5) Therapeutic trials indicate that GLA supplementation provides a significant lowering of LDL-cholesterol levels in hypercholesterolemic patients. (6)

Diabetes

GLA supplementation provides several benefits to individuals with diabetes. It results in improved production of vasodilator prostaglandins, increased nerve blood flow, and nerve conduction velocity. These combined changes greatly reduce the risk of developing diabetes-related neuropathies. (7) , (8)

Alcoholism

GLA supplementation may help alcoholics since alcohol reportedly blocks the enzymatic conversion of omega-6 to GLA. (9) Animal studies indicate that GLA supplementation in the form of evening primrose oil resulted in a substantial reduction of alcohol withdrawal symptoms.

Eczema

Many patients with atopic eczema have adequate or elevated levels of omega-6, but deficiencies in GLA and DGLA, suggesting defective delta-6 desaturase enzyme activity. (10) , (11) Therapeutically, GLA increases the production of anti-inflammatory prostaglandins, which decreases itching. Although some studies report conflicting outcomes, other studies report that patients treated with GLA exhibit less inflammation, dryness, scaling, and overall severity compared to controls. (12) In one study, low dose GLA therapy reduced the severity of skin lesions by 30 percent, whereas higher doses resulted in a 43 percent improvement. (13)

PMS

The results from several double-blind studies indicate that therapy with evening primrose oil, which contains GLA, is an effective treatment for the depression, irritability, breast pain and tenderness, and the fluid retention associated with premenstrual syndrome. (14) However, some other studies have reported no benefit.

Rheumatoid Arthritis

In a randomized, double-blind trial, patients receiving GLA for six months obtained statistically significant and clinically relevant reductions in the signs and symptoms of RA disease activity. (15) Patients in another six-month trial (GLA 1.4 gm/day from borage oil) reported a 36 percent reduction in tender joints; tender joint scores were lowered 45 percent; swollen joint counts decreased 28 percent; and swollen joint scores declined 41 percent, whereas placebo controls made no gains. (16) Other studies report only minor improvements.

Symptoms and Causes of Deficiency

Although most people consume excess quantities of linoleic acid, also known as omega-6, many people are still found to have a deficiency of GLA. Typically, an inefficiency or inhibition of the delta-6 desaturase enzyme, which regulates the conversion of omega-6 to GLA, causes this problem. Some of the major symptoms associated with a deficiency of GLA include problems with skin and hair, arthritis-like conditions, PMS, and cholesterol metabolism.

Low-fat diets reduce consumption of omega-6, GLA, and other important fatty acids.

Consuming large quantities of trans fatty acids from foods containing partially hydrogenated fats and oils inhibits the enzyme delta-6-desaturase, which is responsible for the conversion of omega-6 to GLA and also the conversion of omega-3 to EPA and DHA. (17)

Diabetic individuals frequently have inadequate delta-6 desaturase enzyme activity, which causes them to be deficient in production of gamma linolenic acid. (18)

Alcohol also appears to be able to inhibit delta-6 desaturase enzyme activity, which can result in decreased production of GLA.

Hypothyroidism decreases production of GLA.

Dietary Sources

The primary dietary sources of GLA are borage oil (20%), black currant seed oil (15%), and evening primrose oil (9%).

References

1. View Abstract: Das UN. Occlusion of infusion vessels on gamma-linolenic acid infusion. Prostaglandins Leukot Essent Fatty Acids. Jan2004;70(1):23-32.
2. View Abstract: Agombar A, Cooper AJ, Johnson CD. An aqueous formulation of gamma-linolenic acid with anti-proliferative action on human pancreatic cancer cell lines. Anticancer Drugs. Feb2004;15(2):157-60.
3. View Abstract: Karia C, Harwood JL, Morris AP, Heard CM. Simultaneous permeation of tamoxifen and gamma linolenic acid across excised human skin. Further evidence of the permeation of solvated complexes. Int J Pharm. Mar2004;271(1-2):305-9.
4. View Abstract: Mainou-Fowler T, et al. Gamma-linolenic acid induces apoptosis in B-chronic lymphocytic leukaemia cells in vitro. Leuk Lymphoma. Jan2001;40(3-4):393-403.
5. View Abstract: Horrobin DF, Manku MS. How do polyunsaturated fatty acids lower plasma cholesterol levels? Lipids. Aug1983;18(8):558-62.
6. View Abstract: Ishikawa T, et al. Effects of gammalinolenic acid on plasma lipoproteins and apolipoproteins. Atherosclerosis. Feb1989;75(2-3):95-104.
7. Jamal GA, et al. Gamma-linolenic acid in diabetic neuropathy. Lancet. 1986;Vol 1:1098.
8. View Abstract: Cameron NE, Cotter MA. Metabolic and vascular factors in the pathogenesis of diabetic neuropathy. Diabetes. Sep1997;46(Suppl 2):S31-7.
9. View Abstract: Horrobin DF. A biochemical basis for alcoholism and alcohol-induced damage including the fetal alcohol syndrome and cirrhosis: interference with essential fatty acid and prostaglandin metabolism. Med Hypotheses. Sep1980;6(9):929-42.
10. View Abstract: Manku MS, et al. Reduced levels of prostaglandin precursors in the blood of atopic patients: defective delta-6-desaturase function as a biochemical basis for atopy. Prostaglandins Leukot Med. Dec1982;9(6):615-28.
11. View Abstract: Horrobin DF. Essential fatty acid metabolism and its modification in atopic eczema. Am J Clin Nutr. Jan2000;71(1 Suppl):367S-72S.
12. View Abstract: Kerscher MJ, Korting HC. Treatment of atopic eczema with evening primrose oil: rationale and clinical results. Clin Investig. Feb1992;70(2):167-71.
13. Wright S, Burton JL. Oral evening-primrose-seed oil improves atopic eczema. Lancet. Nov1982;2(8308):1120-2.
14. View Abstract: Horrobin DF. The role of essential fatty acids and prostaglandins in the premenstrual syndrome. J Reprod Med. Jul1983;28(7):465-8.
15. View Abstract: Zurier RB, et al. Gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum. Nov1996;39(11):1808-17.
16. View Abstract: Leventhal, et al. Treatment of rheumatoid arthritis with gammalinolenic acid. Ann Intern Med. Nov1993;119(9):867-73.
17. View Abstract: Booyens J, et al. The role of unnatural dietary trans and cis unsaturated fatty acids in the epidemiology of coronary artery disease. Med Hypotheses. Mar1988;25(3):175-82.
18. View Abstract: Horrobin DF. Fatty acid metabolism in health and disease: the role of delta-6-desaturase. Am J Clin Nutr. May1993;57(5 Suppl):732S-736S.