Gamma-Linolenic Acid (GLA)

James Meschino DC, MS, ROHP

General Features
Evening primrose oil, black currant oil and borage oil contain Gamma-Linolenic Acid, which is an omega-6 fatty acid.  Gamma-Linolenic Acid is a precursor in the synthesis of prostaglandin E1 (PGE1), which is known to have anti-inflammatory properties.¹  Thus, Gamma-Linolenic supplementation has used in the treatment of rheumatoid arthritis and other inflammatory conditions.²

The body can synthesize Gamma-Linolenic Acid from linolenic acid (found in many vegetable oils), however people with certain conditions appear to have a defect in the delta-6 desaturase enzyme that converts linolenic acid (LA) to Gamma-Linolenic Acid (GLA).  Patients with premenstrual syndrome, diabetes, scleroderma, Sjogren’s Syndrome, Tardive Dyskinesia, eczema, and other skin conditions tend to have this metabolic block and research demonstrates that supplementation with a medicinal oil, rich in GLA, has helped people with these conditions.

Furthermore, the delta-6 desaturase enzyme requires vitamin B₆, magnesium and zinc as cofactors to convert LA to GLA.

Suboptimal status of these micronutrients also impairs the conversion of LA to GLA, as does the presence of trans-fatty acids and alcohol in the diet.^3-15

There is also evidence that an excess intake of LA stimulates conversion of GLA to arachidonic acid via the delta-5 desaturase enzyme.  Arachidonic acid is proinflammatory and contributes to cardiovascular risk and other health problems.¹⁶

Nevertheless, supplementation with oils that contain Gamma-Linolenic Acid have shown them to be of benefit for certain conditions.^11-15

As a general reference, evening primrose oil contains 9 percent Gamma-Linolenic Acid, borage seed oil is 22 percent GLA and black currant seed oil is 22 percent GLA and also contains 13 percent omega-3 fatty acids as alpha-linolenic acid.¹

Supplementation Studies and Clinical Application

1. Diabetic Neuropathy

Supplementation with Gamma-Linolenic acid-containing oil has been shown to help repair diabetic neuropathy and prevent nerve damage in diabetics as evidenced by placebo-controlled studies.

Objective parameters, including nerve conduction studies, sensation and reflex testing were used to verify the neurological improvement.  Diabetics have a decreased ability to convert LA to GLA, which is important for nerve cell membrane structure and impulse conduction.  Supplementation of oils yielding as little as 240 to 480 mg of GLA have shown proven benefit in the prevention and treatment of diabetic neuropathy.¹⁷

2. Arthritis and Joint Inflammatory Diseases

Some studies have demonstrated that supplementation with evening primrose oil or black currant oil can significantly reduce symptoms and signs of rheumatoid arthritis in double-blind, placebo-controlled, randomized trials.

Other studies have failed to show improvement and researchers attribute this failure to the ability of GLA to raise tissue levels of arachidonic acid, while reducing cell membrane concentrations of omega-3 fatty acids.  In these cases fish, fish oil or flaxseed oil may be more beneficial.  The dosage of GLA used in the successful studies reported here used an oil yielding 2.8gm per day of GLA.^18,19,20

3. Skin Inflammatory Conditions (Eczema, Psoriasis)

Supplementation with oils that yield GLA have demonstrated improvement in patients suffering from eczema (atopic dermatitis) and psoriasis (GLA content of 274 mg, twice a day). – Studies using increased fish consumption or fish oil supplementation have also shown benefit in patients with psoriasis.^21-24

Dosage Ranges
For most conditions mentioned in this review supplementation of 270-540 mg GLA per day is typically used.  This implies that 3,000-6,000 mg of evening primrose oil would be required to yield this amount of pure GLA, as evening primrose oil is 9 percent GLA content.

Side Effects and Toxicity
GLA is very non-toxic.  Evening primrose oil has been reported to exacerbate symptoms of temporal lobe epilepsy, which can sometimes be mistaken for schizophrenia.^25,26

Drug-Nutrient Interactions
GLA-containing oils may increase seizure activity in patients taking anti-seizure medications.²⁷

N.B.  Concurrent supplementation of GLA, EPA, or LNA with a B-50 complex, vitamin E, vitamin C, zinc and magnesium helps to encourage the synthesis of anti-inflammatory prostaglandins (series 1 and 3).  These vitamins and minerals act as cofactors to help catalyze enzymatic conversion of essential fatty acids to the more desirable prostaglandins of the one and three series.¹

References

1. Murray M. Encyclopedia of Nutritional Supplements.  Rocklin, CA: Prima Publishing; 1996.  252-68.
2. Joe LA, Hart LL. Evening primrose oil in rheumatoid arthritis.  Ann Pharmacother 1993;27:1475-7[review].
3. Horrobin DF. The importance of gamma-linolenic acid and prostaglandin E1 in human nutrition and medicine.  J Holistic Med 1981;3:118-39.
4. Horrobin DF, Manku M, Brush M, et al. Abnormalities in plasma essential fatty acid levels in women with pre-menstrual syndrome and with non-malignant breast disease.  J Nutr Med 1991;2:259-64.
5. Keen H, Payan J, Allawi J, et al. Treatment of diabetic neuropathy with gamma-linolenic acid.  Diabetes Care 1993;16:8-15[reviews].
6. Horrobin DF. Essential fatty acid metabolism in diseases of connective tissue with special reference to scleroderma and to Sjogren’s syndrome.  Med Hypoth 1984;14:233-47.
7. Horrobin DF, Campbell A. Sjogren’s syndrome and the sicca syndrome: the role of prostaglandin E1 deficiency.  Treatment with essential fatty acids and vitamin C.  Med Hypoth 1980;6:225-32.
8. Vaddadi KS, Gilleard CJ. Essential fatty acids, tardive dyskinesia, and schizophrenia.  In: Horrobin DF, editor.  Omega-6 Essential Fatty Acids: Pathophysiology and Roles in Clinical Medicine.  New York, NY: Alan R Liss; 1990.  333–43.
9. Manku MS, Horrobin, DF, Morse NL, et al. Essential fatty acids in the plasma phospholipids of patients with atopic eczema.  Br J Derm 1984;110:643.
10. Horrobin DF. Essential fatty acids in clinical dermatology.  J Am Acad Dermatol 1989;20:1045-53.
11. Mansel RE, Pye JK, Hughes LE. Effects of essential fatty acids on cyclical mastalgia and noncyclical breast disorders.  In:  Omega-6 Essential Fatty Acids: Pathophysiology and Roles in Clinical Medicine.  Horrobin DF, editor.  New York, NY: Alan R Liss, 1990.  557-66.
12. Keen H, Payan J, Allawi J, Walker J, Jamal GA, Weir AI, et al. Treatment of diabetic neuropathy with gamma-linolenic acid.  Diabetes Care 1993;16:8-15.
13. Horribin DF. Essential fatty acid metabolism in diseases of connective tissue with special reference to scleroderma and to Sjogren’s syndrome.  Med Hypoth 1984;14:233-47.
14. Vaddadi KS, Gilleard CJ. Essential fatty acids, tardive dyskinesia, and schizophrenia.  In: Horrobin DF, editor.  Omega-6 Essential Fatty Acids: Pathophysiology and Roles in Clinical Medicine.  New York, NY: Alan R Liss; 1990.  333-43.
15. Schalin-Karrila M, Mattila L, Jansen CT, Uotila P. Evening primrose oil in the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins.  Brit J Dermatol 1987;117:11-9.
16. Janti J. Evening primrose oil in rheumatoid arthritis: changes in serum lipids and fatty acids.  Annals Rheumatol Dis 1989;48:124-7.
17. Keen H, Payan J, Allawi J, Walker J, Jamal GA, Weir AI, et al. Treatment of diabetic neuropathy with gamma-linolenic acid.  The Gamma-Linolenic Acid Multicenter Trial Group.  Diabetic Care 1993;16:8-15.
18. Zurier RB, Rossetti RG, Jacobson EW, et al. Gamma-linolenic acid treatment of rheumatoid arthritis.  A randomized, placebo-controlled trial.  Arthritis Rheum 1996;11:1808-17.
19. Leventhal LJ, Boyce EG, Zurier Rb. Treatment of rheumatoid arthritis with black currant seed oil.  Br J Rheumatol 1994;9:847-52.
20. Jantti J, Nikkari T, Solakivi T, Vapaatalo H, et al. Evening primrose oil in rheumatoid arthritis.  Changes in serum lipids and fatty acids.  Annals Rheum Dis 1989;48:124-7.
21. Andreassi M, Forleo P, Di Lorio Z, Masci S, Abate G, Amerio P. Efficacy of gamma-linolenic acid in the treatment of patients with atopic dermatitis.  J Int Med Res 1997;5:266-74.
22. Borrek S, Hildebrandt A, Forster J. Gamma-linolenic acid-rich borage seed oil capsules in children with atopic dermatitis. A placebo-controlled double-blind study.  Klin Padiatr 1997;3:100-4.
23. Hederos C, Berg, A. Epogam evening primrose oil treatment on atopic dermatitis and asthma.  Arch Dis Child 1996;6:494-7.
24. Collier PM, Ursell A, Zaremba K, Payne CM, Staughton RC, Sanders T. Effect of regular consumption of oily fish compared with white fish on chronic plaque psoriasis.  Ew J Clin Nutr 1993;4:251-4.
25. Vaddadl KS. The use of gamma-linolenic acid and linolenic acid to differentiate between temporal lobe epilepsy and schizophrenia.  Prostaglandins Med 1981;6:375-9.
26. Holman CP, Bell AFJ. A trial of evening primrose oil in the treatment of chronic schizophrenia.  J Orthomol Psychiatr 1983;12:302-4.
27. Miller LG. Selected clinical considerations focusing on known or potential drug-herb interactions.  Arch Intern Med 1998;158:2200-11.