Gamma-linolenic acid (GLA) is a polyunsaturated fatty acid (PUFA) in the omega-6 series. It is derived from linoleic acid, and it is the precursor of arachidonic acid and the prostaglandin E₁ series.

Direct supplementation of GLA is ordinarily in the form of evening primrose oil, black currant seed oil, and borage oil. These sources also provide linoleic acid. For example, evening primrose oil is 72% linoleic acid.

People who have diabetes are less able to convert linoleic acid to GLA than healthy individuals. Other conditions that appear to reduce the capacity to convert linoleic acid to GLA include aging, alcoholism, atopic dermatitis, premenstrual syndrome, rheumatoid arthritis, cancer, and cardiovascular disease.

GLA is of benefit to diabetics by improving nerve conduction and preventing diabetic neuropathy. One animal study suggests that the combination of GLA and ascorbate is particularly advantageous.

Upon ingestion, GLA is elongated rapidly to dihomogamma-linolenic acid (DGLA). DGLA is efficacious in vasodilation, lowering of blood pressure, and the prevention of atherosclerosis.

GLA has an anti-inflammatory effect in humans. The mechanism is not completely understood, but oral administration of GLA can help suppress T-cell proliferation; GLA and DGLA suppress T-cell activation. In at least one study, rheumatoid arthritis patients taking GLA for a year improved over time, suggesting that GLA can function as a slow-acting, disease-modifying antirheumatic drug. The hope is to establish a therapeutic GLA dose that will reduce the need for other medication in persons with rheumatoid arthritis. This would help reduce the gastrointestinal problems associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Research results are, however, somewhat controversial. There is some evidence that the effect of long-term supplementation actually may be contrary to the desired results of reducing inflammation. Nevertheless, GLA supplementation is particularly popular with persons with rheumatoid arthritis.

Corroborated studies suggest that GLA is unique among the omega-6 PUFA series in suppressing tumor growth and metastasis. It inhibits both motility and invasiveness of human colon cancer, breast cancer, and melanoma cells. Whether DGLA and prostaglandin E are involved in the process remains to be determined.

Recent animal research has suggested that GLA, in combination with eicosapentaenoic acid (EPA), can be beneficial in senile osteoporosis because it enhances absorption and retention of calcium. In addition, a pilot study done on elderly women suggested that GLA and EPA reduce bone turnover rates and have beneficial effects on bone density and calcium absorbtion.

A recent Japanese study showed that evening primrose oil may be beneficial for hemodialysis patients with uremic skin symptoms. Patients given evening primrose oil showed significant improvement in skin dryness, pruritis, and erythema; and an increase in plasma concentration of a wide variety of essential fatty acids, more than patients who were given linoleic acid.

The ratio of omega-6 oils to omega-3 oils should be 4:1. However, the American diet provides more than 10 times the needed amount of omega-6 oils in the form of linoleic acid. This is because they comprise the primary oil ingredient added to most processed foods and are found in commonly used cooking oils. The total intake of linoleic acid is approximately 100 times the GLA intake. Because GLA is not found in abundance in common foods, supplementation may be necessary to mimic clinical dosages.

In addition to the plant seed oils of evening primrose, black currant, borage, and fungal oils, GLA is found in human milk and, in small amounts, in a wide variety of common foods, particularly organ meats.

Gamma-linolenic acid is a long-chain polyunsaturated fatty acid with 18 carbon atoms. It is derived from linoleic acid; it is elongated to dihomo-gamma-linolenic acid (DGLA), then desaturated to arachidonic acid, and then is converted to the prostaglandin E1 series (PGE1).

GLA is available directly from evening primrose oil (7% to 10% GLA), black current seed oil (15% to 20% GLA), borage oil (18% to 26% GLA), and fungal oil (23% to 26% GLA). GLA bioavailability may be related to the precise triacylglycerol composition. Although the GLA concentration in borage oil appears to be twice as high as in evening primrose oil, research has shown that the GLA effects, such as formation of prostaglandin E1, are comparable for both on a gram-for-gram basis.

The essential fatty acids are known as vitamin F. The Food and Drug Administration prohibits the term "vitamin F" for advertising purposes, because of problems with foods such as french fries being advertised as "vitamin enriched" because they were fried in oil.

• Evening primrose oil
• Black currant seed oil
• Borage oil
• Borage oil capsules

• Rheumatoid arthritis: GLA may reduce inflammation by suppressing T-cell proliferation and activation.
• Diabetes: GLA supplementation assists nerve function and helps prevent nerve disease in diabetics.
• Cancer: GLA may suppress tumor growth and metastasis, particularly in colon cancer, breast cancer, and melanoma.
• Heart disease: GLA may prevent heart disease by inhibiting plaque formation, increasing vasodilation, and lowering blood pressure.
• Eyes: GLA is beneficial in Sjogren's syndrome and may be useful in other dry eye conditions.
• Supplementation may alleviate the symptoms of aging, alcoholism, atopic dermatitis, osteoporosis, and premenstrual syndrome.
• Menstrual problems (amenorrhea, dysmenorrhea): Essential fatty acids such as those found in flaxseed, evening primrose, and borage oils reduce inflammation and support hormone production. Dosage is 1,000 to 1,500 mg daily or bid.

There is no recommended dietary allowance (RDA) for GLA.

A recommended dosage for rheumatoid arthritis is 1.4 g/day. As the cost of oils can be prohibitive, and lower doses are usually effective, an acceptable clinical dosage of evening primrose, black currant, or borage oil would be 1,500 mg daily or bid.

Studies have shown that up to 2.8 g of GLA/day is well tolerated.

Dietary sources of GLA appear to be completely nontoxic. A healthy person eating a normal diet should consume fewer saturated fats and more polyunsaturated essential fatty acids.

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The activity of ceftazidime against Pseudomonas aeruginosa appears to be potentiated by fatty acids, including GLA (Giamarellos-Bourboulis et al. 1999). In vitro, GLA exerts bacteriostatic effects on Escherichia coli and, in combination with arachidonic acid, is bacteriocidal to P aeruginosa.

In ovarian cancer cells, pre-incorporation of either gamma-linolenic acid (GLA) or eicosapentaenoic acid (EPA) increased sensitivity to doxorubicin and cisplatin; however, it was difficult to distinguish the cytotoxicity of the drug from the fatty acid (Plumb et al. 1993). The cytotoxicity of the fatty acids was additive with that of the drugs. Another study investigating the effectiveness of this combination therapy on human neuroblastoma cell lines found that addition of GLA to the growth medium reduced the cytotoxic effects of cisplatin and carboplatin (Ikushima et al. 1990).

Preclinical data suggest a possible enhancement of cellular uptake of idarubicin when cells are enriched with GLA (Davies et al. 1999). In multidrug resistant human breast cancer and bladder cancer cells, pre-incorporation of GLA at non-cytotoxic levels increased the cellular uptake of idarubicin. In addition, GLA changed the intracellular distribution of mitoxantrone.

GLA may interact with the estrogen receptor antagonist tamoxifen. In one short-term phase II clinical trial, high-dose GLA therapy (8 capsules/day po supplying 2.8 g GLA) potentiated the effects of tamoxifen (20 mg od) in 38 stage I-II breast cancer patients, 90% of whom were estrogen receptor-positive (Kenny et al. 2000). Patients given GLA exhibited a faster treatment response that was evident by 6 weeks.

In human neuroblastoma cell lines, addition of GLA to the growth medium enhanced the cytotoxic effects of the vinca alkaloids, vincristine, vinblastine, and vindesine (Ikushima et al. 1990). In both vincristine-sensitive and -resistant human cervical cancer cells, GLA was cytotoxic (Madhavi and Das 1994).

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