Gamma-Linolenic Acid (GLA)
• Omega-6 Oil(s), Omega-6 Fatty Acids, Sources of GLA Include: Black Currant Seed Oil, Borage Oil, Evening Primrose Oil
• Diabetic Neuropathy
• GLA Alone: Attention Deficit and Hyperactivity Disorder (ADHD), Cyclic Mastalgia, Dry Eyes (in Contact Lens Wearers), Kidney Stones, Premenstrual Syndrome (PMS), Raynaud's Phenomenon, Rheumatoid Arthritis, Ulcerative Colitis, Weight Loss, In Combination with Fish Oil : Attention Deficit and Hyperactivity Disorder (ADHD), Huntington’s Disease, Osteoporosis
GLA (gamma-linolenic acid) is one of the two main types of essential fatty acids . These are "good" fats that are as necessary for your health as vitamins. Specifically, GLA is an omega-6 fatty acid. (For more information on the other major category of essential fatty acids, omega-3, see the article on fish oil .)
The body uses essential fatty acids to make various prostaglandins and leukotrienes. These substances influence inflammation and pain; some of them increase symptoms, while others decrease them. Taking GLA may swing the balance over to the more favorable prostaglandins and leukotrienes, making it helpful for diseases that involve inflammation.
There is some evidence that GLA may be helpful for diabetic neuropathy . The supplement is widely used in the UK and other parts of Europe to treat eczema and cyclic mastalgia (a condition marked by breast pain associated with the menstrual cycle). Current evidence, however, suggests that it may not help. There are many other proposed uses of GLA based on fairly weak evidence.
The body ordinarily makes all the GLA it needs from linoleic acid, an omega-6 essential fatty acid found in many foods. In certain circumstances, however, the body may not be able to convert linoleic acid to GLA efficiently. These include advanced age, diabetes, high alcohol intake, eczema, cyclic mastitis, viral infections, excessive saturated fat intake, elevated cholesterol levels, and deficiencies of vitamin B 6 , zinc, magnesium, biotin, or calcium. 1-5 In such cases, taking GLA supplements may make up for a genuine deficiency.
Very little GLA is found in the diet. Borage oil is the richest supplemental source (17% to 25% GLA), followed by black currant oil (15% to 20%) and evening primrose oil (7% to 10%). Borage and evening primrose are the most common sources used in studies.
It is commonly stated that people require a certain optimum ratio of omega-3 to omega-6 fatty acids in the diet; however, there is no real evidence that this is true, and some evidence that it is false. 91
The typical dosage of GLA when it is used in hopes of alleviating cyclic mastalgia or eczema is about 200 to 400 mg daily (about 2 to 4 g of evening primrose oil or 1 to 2 g borage oil). Diabetic neuropathy is typically treated with about 400 to 600 mg daily (about 4 to 6 g of evening primrose or 2 to 3 g of borage oil), and in rheumatoid arthritis doses as high as 2,000 to 3,000 mg have been tried. (Doses this high can only be obtained from purified GLA, as one would need impractically high doses of evening primrose oil or borage oil to get enough).
GLA should be taken with food. Full benefits (if there are any) may take more than 6 months to develop.
GLA has shown some promise for the treatment of diabetic neuropathy , 12,13 a complication of diabetes . This condition consists of pain and/or numbness due to progressive nerve damage. However, supporting evidence that GLA is effective for this use is quite limited.
Perhaps the most common use of GLA has been as a treatment for eczema . It was once widely dispensed for this purpose by the British healthcare system, but the balance of the evidence indicates that for eczema, GLA is just a placebo treatment. 14-18, 87
GLA is also a popular treatment for cyclic mastalgia (breast pain that cycles with the menstrual period), but the evidence regarding its effectiveness is more negative than positive. 46-49, 83-85 GLA is additionally said to be useful for general premenstrual syndrome (PMS) symptoms, but the supporting evidence for this use is very weak. 11
Despite many positive anecdotes, 42 GLA has failed to prove effective for attention deficit and hyperactivity disorder (ADHD) . 79, 90 One study that used GLA plus fish oil did find weak evidence of benefits. 88 Extremely weak evidence hints that evening primrose oil might be more effective for ADHD if combined with zinc, but this is more of an untested hypothesis than a conclusion. 89
GLA has been studied for numerous other conditions, such as rheumatoid arthritis , 21-24Raynaud's phenomenon (a condition in which the fingers and toes react to cold in an exaggerated way), 25,26weight loss , 27,28ulcerative colitis , 30,82kidney stones , 19,20,31,32multiple sclerosis , 33,36 and increasing the effectiveness of the drug tamoxifen in the treatment of breast cancer . 29Note : Individuals undergoing treatment for cancer should not take GLA (or any other supplement) except under physician supervision.
Other studies have investigated the potential benefits of combination treatment using GLA and fish oil. Conditions studied include osteoporosis , 40,41chronic fatigue syndrome , 37,38periodontitis (gum disease), 90 and Huntington’s disease. In these trials, some promising (but far from definitive) results have been seen. However, this combination therapy has failed to prove effective for cyclic mastalgia . 85
GLA is sometimes suggested as a treatment for tardive dyskinesia , but two double-blind studies have failed to find it helpful for this disorder. 39 GLA has also failed to prove effective for the itching caused by kidney dialysis. 64
There is some evidence that GLA may benefit patients with eye problems. One randomized trial indicated that orally administered evening primrose oil was more effective than olive oil (placebo) at reducing dry eye symptoms and improving comfort in users of soft contact lens.93 In addition, Sjogren's syndrome, an autoimmune condition in which the immune system destroys moisture-producing glands, often causes dry eyes due to lack of tears. One small double-blind study found that a combination of GLA and the omega-6 fatty acid linoleic acid (found in many vegetable oils) may improve dry eye symptoms in Sjogren's.94 Finally, patients who undergo laser surgery for vision correction (photorefractive keratectomy) are sometimes left with a hazy appearance to their cornea. Another small randomized trial found some potential benefit of a supplement containing omega-6 fatty acids in preventing this complication.95
Thus far, we've mentioned only a fraction of the conditions for which GLA has been proposed as a treatment. Others include: asthma , allergies , bursitis , endometriosis , heart disease , irritable bowel syndrome , prostate cancer , benign prostatic hyperplasia (BPH) , and Sjogren's disease . However, none of these potential uses has as yet been scientifically evaluated to any significant extent.
What Is the Scientific Evidence for Gamma-Linolenic Acid?
Diabetic neuropathy is a gradual degeneration of nerves caused by diabetes. There is some evidence that GLA can be helpful, if you give it long enough to work. In one double-blind, placebo-controlled study, 111 people with mild diabetic neuropathy received either 480 mg daily of GLA or placebo. 51 After 12 months, the group taking GLA was doing significantly better than the placebo group. Good results were seen in a smaller study as well. 52 However, these promising findings lack further research validation.
Despite the fact that GLA (usually as evening primrose oil) is widely used in Europe to treat eczema , it appears most likely that the treatment is not truly effective. The anecdotes of cure that abound are, most likely, simply testimonials to the placebo effect (as well as a strong marketing campaign by one evening primrose oil supplier).
A 1989 review of the literature found significant benefit in the 9 double-blind controlled studies performed to that date, all involving evening primrose oil. 57 This study led to widespread sales of one evening primrose oil product. However, this review has been sharply criticized for including poorly designed studies and possibly misinterpreting study results. 58
Improvements in symptoms were also seen in a later double-blind study of 48 children with eczema. 59
However, more recent and better conducted research has failed to find any benefit. For example, a 16-week, double-blind study involving 58 children with eczema found no difference between the effects of evening primrose oil and placebo (substantial improvements were seen, but to the same extent for placebo and evening primrose oil). 60 Lack of specific benefit was also seen with evening primrose oil or evening primrose oil plus fish oil in a 16-week, double-blind, placebo-controlled study of 102 individuals with eczema. 62 Finally, a double-blind trial followed 39 people with hand dermatitis for 24 weeks, and again found no greater benefits than those produced by placebo. 63
GLA taken orally from borage oil has also failed to prove effective. In a 24-week, double-blind study of 160 adults with eczema, the treatment provided no greater benefits than placebo. 61 The same was seen in a 12-week, double-blind, placebo-controlled study of 151 adults and children with eczema. 87
Finally, in a double-blind, placebo-controlled study of 118 infants at high risk for developing eczema in the future, a GLA supplement made from borage oil failed to provided a significant protective effect. 86
However, an interesting double-blind study tested the use of undershirts coated with borage oil for treatment of eczema.92 In this 2-week study of 32 children aged 1-10 years old, use of these coated undershirts appeared to reduce eczema symptoms. However, additional higher quality research studies need to be undertaken to establish whether or not this method of delivery really works.
Cyclic mastalgia , also known as fibrocystic breast disease, cyclic mastitis, and mastodynia, is a condition in which a woman's breasts become painful during the week or two before her menstrual period. The discomfort is accompanied by swelling, inflammation, and sometimes actual cysts that form in the breasts. It is often associated with other symptoms of premenstrual syndrome (PMS) .
We do not know the cause of cyclic mastalgia, but some researchers believe that it is associated with an imbalance of fatty acids in the body. 43 On this basis, evening primrose oil became a popular treatment for cyclic mastalgia. However, there are considerable doubts regarding whether it is actually effective.
The main supporting evidence comes from three controlled studies that appeared to find benefit. 46,83,84 Unfortunately, all of these suffered from significant limitations in study design and reporting, and cannot be taken as reliable. A much better quality study found that evening primrose oil, by itself or with fish oil , is not more effective than placebo for cyclic breast pain. 85 (As with eczema, placebo treatment itself was found to be quite effective.) Other studies have found evening primrose oil ineffective for established breast cysts. 47-49
Other Premenstrual Symptoms
Although several small studies suggest that GLA as evening primrose oil is helpful in reducing overall PMS symptoms, all of these studies suffer from serious flaws that make the results difficult to trust. 50
According to many studies, fish oil, a source of omega-3 essential fatty acids, improves symptoms of rheumatoid arthritis . A few studies suggest that GLA may also help. One double-blind study followed 56 people with rheumatoid arthritis for 6 months. 66 Participants received either 2.8 g daily of purified GLA or placebo. The group taking GLA experienced significantly fewer symptoms than the placebo group, and the improvements grew over time.
Other small studies have found similar results. 67,68 The overall conclusion appears to be that purified GLA might offer some benefit for rheumatoid arthritis, especially when used along with standard treatment for rheumatoid arthritis, 69 but the evidence is weak.
High dosages of evening primrose oil may be useful for Raynaud's phenomenon , a condition in which a person's hands and feet show abnormal sensitivity to cold temperature. A small double-blind study found that GLA produced significantly better results than placebo. 70,71 Similar results have been obtained with the omega-3 fatty acids found in fish oil. However, larger studies would be necessary to actually establish effectiveness.
There is some evidence that essential fatty acids may enhance the effectiveness of calcium for the treatment or prevention of osteoporosis . In one study, 65 postmenopausal women were given calcium along with either placebo or a combination of omega-6 fatty acids (from evening primrose oil) and omega-3 fatty acids (from fish oil ) for a period of 18 months. At the end of the study period, the group receiving essential fatty acids had higher bone density and fewer fractures than the placebo group. 72
However, a 12-month, double-blind trial of 42 postmenopausal women found no benefit. 73
The explanation for the discrepancy may lie in the differences between the women studied. The first study involved women living in nursing homes, while the second studied healthier women living on their own. The latter group of women may have been better nourished and already received enough essential fatty acids in their diet.
Attention Deficit and Hyperactivity Syndrome
Based on evidence that essential fatty acids are necessary for the proper development of brain function in growing children, essential fatty acids have been tried for the treatment of ADHD and related conditions. A preliminary double-blind, placebo-controlled trial found some evidence that a supplement containing fish oil and evening primrose oil might improve ADHD symptoms. 74 However, a high rate of dropouts makes the results of this study less than reliable. A repeat study found this combination no better than placebo. 88
Evening primrose oil by itself was found no better than placebo in a double-blind, placebo-controlled trial. 79 In another small placebo-controlled, comparative trial, evening primrose oil proved less effective than standard medical treatment. 80
A 12-week, double-blind study that enrolled 100 significantly overweight women compared the effectiveness of evening primrose oil to placebo. 75 No difference was seen between the groups. However, there was a high dropout rate in this trial (over 25%), which somewhat decreases the meaningfulness of the results. In addition, many participants were known to have "refractory obesity," meaning that they had already failed to respond to other forms of treatment.
Another double-blind trial, involving 47 people, tested the unusual hypothesis that evening primrose might only work in individuals with a family history of obesity. 76 The results showed that use of evening primrose oil produced a small but significant loss of weight. Interestingly, participants whose parents were both obese showed even better response.
Considering the contradictory nature of this evidence, more research is necessary to determine whether evening primrose oil is really useful for weight loss.
Most of the safety information we have regarding GLA comes from experience with evening primrose oil.
Animal studies suggest that evening primrose oil is completely nontoxic and noncarcinogenic. 77 More than 4,000 people have taken GLA or evening primrose oil in scientific studies, and no significant adverse effects have ever been noted.
Early reports suggested the possibility that GLA might worsen temporal lobe epilepsy, but there has been no later confirmation. 78
The maximum safe dosage of GLA for young children, pregnant or nursing women, or those with severe liver or kidney disease has not been established.
8. Mansel RE, Gateley CA, Harrison BJ, et al. Effects and tolerability of n-6 essential fatty acid supplementation in patients with recurrent breast cysts—a randomized double-blind placebo-controlled trial. J Nutr Med. 1990;1:195-200.
14. Morse PF, Horrobin DF, Manku MS, et al. Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema. Relationship between plasma essential fatty acid changes and clinical response. Br J Dermatol. 1989;121:75-90.
20. Yoshimoto-Furuie K, Yoshimoto K, Tanaka T, et al. Effects of oral supplementation with evening primrose oil for six weeks on plasma essential fatty acids and uremic skin symptoms in hemodialysis patients. Nephron. 1999;81:151-159.
38. Warren G, McKendrick M, Peet M. The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA. Acta Neurol Scand. 1999;99:112-116.
41. Bassey EJ, Littlewood JJ, Rothwell MC, et al. Lack of effect of supplementation with essential fatty acids on bone mineral density in healthy pre- and postmenopausal women: two randomized controlled trials of EfacalŴ v. calcium alone. Br J Nutr. 2000;83:629-635.
42. Richardson AJ, McDaid AM, Calvin CM, et al. Reduced behavioural and learning problems in children with specific learning difficulties after supplementation with highly unsaturated fatty acids: a randomized double-blind placebo-controlled trial. Presented at: 2nd Forum of European Neuroscience Societies; July 24-28, 2000; Brighton, United Kingdom.
47. Mansel RE, Gateley CA, Harrison BJ, et al. Effects and tolerability of n-6 essential fatty acid supplementation in patients with recurrent breast cysts—a randomized double-blind placebo-controlled trial. J Nutr Med. 1990;1:195-200.
53. Stevens EJ, Lockett MJ, Carrington AL, et al. Essential fatty acid treatment prevents nerve ischaemia and associated conduction anomalies in rats with experimental diabetes mellitus. Diabetologia. 1993;36:397-401.
57. Morse PF, Horrobin DF, Manku MS, et al. Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema. Relationship between plasma essential fatty acid changes and clinical response. Br J Dermatol. 1989;121:75-90.
59. Biagi PL, Bordoni A, Hrelia S, et al. The effect of gamma-linolenic acid on clinical status, red cell fatty acid composition and membrane microviscosity in infants with atopic dermatitis. Drugs Exp Clin Res. 1994;20:77-84.
65. Yoshimoto-Furuie K, Yoshimoto K, Tanaka T, et al. Effects of oral supplementation with evening primrose oil for six weeks on plasma essential fatty acids and uremic skin symptoms in hemodialysis patients. Nephron. 1999;81:151-159.
73. Bassey EJ, Littlewood JJ, Rothwell MC, et al. Lack of effect of supplementation with essential fatty acids on bone mineral density in healthy pre- and postmenopausal women: two randomized controlled trials of EfacalŴ v. calcium alone. Br J Nutr. 2000;83:629-635.
74. Richardson AJ, McDaid AM, Calvin CM, et al. Reduced behavioural and learning problems in children with specific learning difficulties after supplementation with highly unsaturated fatty acids: a randomized double-blind placebo-controlled trial. Presented at: 2nd Forum of European Neuroscience Societies; July 24-28, 2000; Brighton, United Kingdom.
82. Middleton SJ, Naylor S, Woolner J, et al. A double-blind, randomized, placebo-controlled trial of essential fatty acid supplementation in the maintenance of remission of ulcerative colitis. Aliment Pharmacol Ther. 2002;16:1131-1135.
83. Mansel RE, Pye KJ, Hughes LE. A controlled trial of evening primrose oil (Efamol) in cyclic premenstrual matalgia. Abstract 47. Proceedings of the 2nd International Symposium on Premenstrual, Postpartum, and Meonopausal Mood Disorders; 1987; Kiawah Island, SC.
85. Blommers J, De Lange-De Klerk ES, Kuik DJ, et al. Evening primrose oil and fish oil for severe chronic mastalgia: A randomized, double-blind, controlled trial. Am J Obstet Gynecol. 2002;187:1389-1394.
86. Van Gool CJ, Thijs C, Henquet CJ, et al. Gamma-Linolenic acid supplementation for prophylaxis of atopic dermatitis—a randomized controlled trial in infants at high familial risk. Am J Clin Nutr. 2003;77:943-951.
87. Takwale A, Tan E, Agarwal S, et al. Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial. BMJ. 2003;327:1385.
89. Arnold LE, Pinkham SM, Votolato N. Does zinc moderate essential fatty acid and amphetamine treatment of attention-deficit/hyperactivifty disorder? J Child Adolesc Psychopharmacol. 2000;10:111-117.
92. Kanehara S, Ohtani T, Uede K, et al. Clinical effects of undershirts coated with borage oil on children with atopic dermatitis: A double-blind, placebo-controlled clinical trial. J Dermatol. 2007;34:811-815.
Last reviewed April 2008 by EBSCO CAM Review Board
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