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Gamma-Linolenic
Acid (GLA) |
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Overview |
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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. |

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Dietary Sources |
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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. |

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Constituents/Composition |
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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. |

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Commercial
Preparations |
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- Evening primrose oil
- Black currant seed oil
- Borage oil
- Borage oil capsules
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Therapeutic Uses |
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- 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.
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Dosage Ranges and Duration of
Administration |
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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. |

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Side
Effects/Toxicology |
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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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Warnings/Contraindications/Precautions |
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N/A |

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Interactions |
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Ceftazidime
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. Cisplatin;
Doxorubicin
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).
Idarubicin;
Mitoxantrone
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. Tamoxifen
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.
Vincristine;
Vinblastine
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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References |
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Davies CL, Loizidou M, Cooper AJ, et al. Effect of gamma-linolenic acid on
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Copyright © 2000 Integrative Medicine
Communications This publication contains
information relating to general principles
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