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. GLA is widely used in Europe to treat diabetic neuropathy and eczema. Both European and U.S. physicians use GLA to treat cyclic mastalgia, a condition marked by breast pain associated with the menstrual cycle. It may also be useful for other PMS symptoms. GLA has also been proposed as a treatment for many other conditions. -------------------------------------------------------------------------------- Requirements/Sources 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 B6, zinc, magnesium, biotin, or calcium.15 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. -------------------------------------------------------------------------------- Therapeutic Dosages The usual dosage of GLA used to treat 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 of 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 rheumatoid arthritis may require as much as 2,000 to 3,000 mg (best obtained from purified GLA). GLA should be taken with food. Don't forget that full benefits may take over 6 months to develop, so be patient. -------------------------------------------------------------------------------- Therapeutic Uses Most commonly in the form of evening primrose oil, GLA has become a standard treatment for cyclic mastalgia, breast pain that cycles with the menstrual period.69 It is widely used for this purpose by conventional physicians in both Europe and North America, and as a mark of its acceptance it is even mentioned in the AMA's official Drug Evaluations textbook.10 Evening primrose oil is also said to be useful for other PMS symptoms, although the evidence is not strong.11 Evening primrose oil also appears to be effective for diabetic neuropathy,12,13 a complication of diabetes. This condition, which develops in many people with diabetes, consists of pain and/or numbness due to progressive nerve damage. Additionally, evening primrose oil is widely used in Europe as a treatment for eczema. Unfortunately, the scientific evidence that it works is mixed at best, and the most recent studies have not found it to be effective.1418 GLA has also been suggested for the treatment of itching due to kidney dialysis.19,20 Very high doses of purified GLA may be of some benefit in treating rheumatoid arthritis, especially when combined with conventional treatments.2124 GLA may also help in Raynaud's phenomenon (a condition in which the fingers and toes react to cold in an exaggerated way).25,26 GLA has also been tried as a treatment for weight loss, with mixed results.27,28 A preliminary study found high doses of GLA may increase the effectiveness of 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. A small double-blind placebo-controlled trial found some symptomatic benefit in ulcerative colitis with evening primrose oil.30 However, another trial found that GLA plus fish oil was not helpful for maintaining remission of this condition.82 GLA is sometimes recommended for kidney stones, however the evidence supporting this use is very preliminary.31,32 Some researchers have suggested that GLA might be beneficial in multiple sclerosis.33 So far, however, little evidence suggests that it helps, and one uncontrolled study failed to find it effective.34,35,36 GLA combined with fish oil may be helpful for treating chronic fatigue syndrome; however, the results of double-blind trials have been mixed.37,38 Although GLA is sometimes suggested as a treatment for tardive dyskinesia, two double-blind studies have found it ineffective for this disorder.39 Some, but not all, studies suggest that GLA and fish oil combined may enhance calcium's benefits in preventing osteoporosis.40,41 A preliminary trial found some evidence that a supplement containing fish oil and evening primrose oil might improve ADHD symptoms.42 Studies involving evening primrose alone, on the other hand, have not found significant positive results.79,80 One promising, but highly preliminary, double-blind, placebo-controlled study suggests that combination therapy with fish oil and GLA may improve symptoms of the severe neurological illness called Huntingtons disease.81 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, prostate enlargement or benign prostatic hyperplasia (BPH), Sjgren's disease, and many more. However, none of these potential uses has as yet been scientifically evaluated to any significant extent. -------------------------------------------------------------------------------- What Is the Scientific Evidence for GLA (Gamma-Linolenic Acid)? Cyclic Mastalgia 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 researchers have found that it seems to be associated with an imbalance of fatty acids in the body.43 Evidence suggests that GLA relieves cyclic mastalgia, perhaps by restoring the balance of essential fatty acids.44 One report published in 1985 compared the effectiveness of four different therapies in women with severe, painful mastalgia: GLA from evening primrose oil and the pharmaceuticals danazol, bromocriptine, and progestins (often, but not quite accurately, called progesterone).45 The results suggest that evening primrose oil was effective in just under 50% of participants. However, this was not actually a study in the usual sense; it was more a collation of records from the Cardiff Clinic, a medical center that specializes in the treatment of breast pain. Contrary to how this study is sometimes reported, it did not have a placebo group. To really know whether a treatment is effective, you need double-blind placebo-controlled studies to eliminate the power of suggestion. One such study was reported in 1981. This trial followed 73 women suffering from cyclic mastalgia.46 The results were consistent with the Cardiff Clinic's results, finding that evening primrose oil reduced pain in almost 50% of the women taking it, while only 19% of the women improved in the placebo group. However, this study was reported only in a very brief form, and many details are missing. We really need better-designed and better-reported studies to know for sure how effective evening primrose oil really is for cyclic mastalgia. If you have a severe form of cyclic mastalgia with actual breast cysts, there is some evidence that evening primrose oil will not be completely effective. In a double-blind study of 200 women treated for 1 year, evening primrose oil had no effect on recurrent breast cysts.47 The conclusion appears to be that evening primrose oil relieves breast pain but cannot make breast cysts go away.48 Negative results were also seen in a small placebo-controlled study of 23 women with established breast lumps.49 Participants who took evening primrose oil for 6 months showed no more improvement than individuals who received no treatment. Other PMS Symptoms Although several small studies suggest that GLA as evening primrose oil is helpful in reducing overall PMS symptoms, all of them suffer from serious flaws.50 Diabetic Neuropathy 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 In addition, numerous studies in animals have found that evening primrose oil can protect nerves from diabetes-induced nerve injury.53,54 There is some preliminary evidence that GLA may be more effective for this condition when it is combined with lipoic acid.55,56 Eczema Despite the fact that GLA (evening primrose oil) is widely used in Europe to treat eczema, the evidence that it works is mixed at best. A 1989 review of the literature found significant benefit in the nine double-blind controlled studies performed to that date.57 Evening primrose oil seemed especially effective in relieving itching. However, this review has been sharply criticized for including poorly designed studies and possibly misinterpreting study results.58 Improvements in symptoms other than itching were seen in a double-blind study of 48 children with eczema.59 However, other 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.60 A 24-week double-blind study of 160 adults with eczema, who were given either placebo or GLA from borage oil, also found no benefit.61 In addition, negative results were seen in a 16-week double-blind placebo-controlled study of 102 individuals with eczema.62 Another double-blind trial followed 39 people with hand dermatitis for 24 weeks. Evening primrose oil at a dosage of 6 g daily produced no significant improvement as compared to the placebo.63 Itching Due to Kidney Dialysis GLA has been tried for improving itching in individuals undergoing kidney dialysis. However, one small double-blind placebo-controlled trial failed to find benefit.64 Another trial compared GLA-rich evening primrose oil to linoleic acid and found itching relieved equally; but due to the lack of a placebo control, these results are difficult to interpret.65 Rheumatoid Arthritis According to many studies, fish oil, a source of omega-3 essential fatty acids, definitely improves symptoms of rheumatoid arthritis.A few studies suggest that GLA may also work. One double-blind study followed 56 people with rheumatoid arthritis for 6 months.66 Participants received either 2.8 g daily of 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.67,68The overall conclusion appears to be that purified GLA may offer some benefit for rheumatoid arthritis, especially when used along with standard treatment for rheumatoid arthritis.69 Raynaud's Phenomenon 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. Osteoporosis There is some evidence that essential fatty acids may enhance the effectiveness of calcium. 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 (ADHD) 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. Evening primrose oil by itself was found ineffective for attention deficit disorder 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 Weight Loss 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 tested the unusual hypothesis that evening primrose might only work in individuals with a family history of obesity.76 A total of 47 people with a family history of obesity were enrolled in this study. 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. -------------------------------------------------------------------------------- Safety Issues 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 Over 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. -------------------------------------------------------------------------------- References 1. Horrobin DF. Nutritional and medical importance of gamma-linolenic acid. Prog Lipid Res. 1992;31:163194. 2. Horrobin DF. The use of gamma-linolenic acid in diabetic neuropathy. Agents Actions Suppl. 1992;37:120144. 3. Horrobin DF, Stewart C. Evening primrose oil in atopic eczema. Lancet. 1990;335:864865. 4. Horrobin DF, Manku MS, Brush M, et al. Abnormalities in plasma essential fatty acid levels in women with premenstrual syndrome and with nonmalignant breast disease. J Nutr Med. 1991;2:259264. 5. Manku MS, Horrobin DF, Morse NL, et al. Essential fatty acids in the plasma phospholipids of patients with atopic eczema. Br J Dermatol. 1984;110:643648. 6. Pye JK, Mansel RE, Hughes LE. Clinical experience of drug treatments for mastalgia. Lancet. 1985;2:373377. 7. Pashby NL, Mansel RE, Hughes LE, et al. A clinical trial of evening primrose oil in mastalgia [abstract]. Br J Surg. 1981;68:801. 8. Mansel RE, Gateley CA, Harrison BJ, et al. Effects and tolerability of n-6 essential fatty acid supplementation in patients with recurrent breast cystsa randomized double-blind placebo-controlled trial. J Nutr Med. 1990;1:195200. 9. Mansel RE, Harrison BJ, Melhuish J, et al. A randomized trial of dietary intervention with essential fatty acids in patients with categorized cysts. Ann N Y Acad Sci. 1990;586:288294. 10. Drug Evaluations Annual. Vol 2. Milwaukee, Wis.: American Medical Association; 1991. 11. Budeiri D, Li Wan Po A, Dornan JC. Is evening primrose oil of value in the treatment of premenstrual syndrome? Control Clin Trials. 1996;17:6068. 12. Keen H, Payan J, Allawi J, et al. Treatment of diabetic neuropathy with gamma-linolenic acid. The gamma-Linolenic Acid Multicenter Trial Group. Diabetes Care. 1993;16:815. 13. Jamal GA, Carmichael H. The effect of gamma-linolenic acid on human diabetic peripheral neuropathy: a double-blind placebo-controlled trial. Diabet Med. 1990;7:319323. 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;121:7590. 15. Berth-Jones J, Graham-Brown RA. Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis. Lancet. 1993;341:15571560. 16. Hederos CA, Berg A. Epogam evening primrose oil treatment in atopic dermatitis and asthma. Arch Dis Child. 1996;75:494497. 17. Henz BM, Jablonska S, van de Kerkhof PC, et al. Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema. Br J Dermatol. 1999;140:685688. 18. Whitaker DK, Cilliers J, de Beer C. Evening primrose oil (Epogam) in the treatment of chronic hand dermatitis: disappointing therapeutic results. Dermatology. 1996;193:115120. 19. Tamimi NA, Mikhail AI, and Stevens PE. Role of gamma-linolenic acid in uraemic pruritus [letter]. Nephron. 1999;83:170171. 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;81:151159. 21. Zurier RB, Rossetti RG, Jacobson EW, et al. gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum. 1996;39:18081817. 22. Leventhal LJ, Boyce EG, Zurier RB. Treatment of rheumatoid arthritis with blackcurrant seed oil. Br J Rheumatol. 1994;33:847852. 23. Leventhal LJ, Boyce EG, Zurier RB. Treatment of rheumatoid arthritis with gammalinolenic acid. Ann Intern Med. 1993;119:867873. 24. Rothman D, DeLuca P, Zurier RB. Botanical lipids: Effects on inflammation, immune responses, and rheumatoid arthritis. Semin Arthritis Rheum. 1995;25:8796. 25. Belch JJ, Shaw B, O'Dowd A, et al. Evening primrose oil (Efamol) as a treatment for cold-induced vasospasm (Raynaud's phenomenon). Prog Lipid Res. 1986;25:335340. 26. Belch JJ, Shaw B, O'Dowd A, et al. Evening primrose oil (Efamol) in the treatment of Raynaud's phenomenon: a double-blind study. Thromb Haemost. 1985;54:490494. 27. Haslett C, Douglas JG, Chalmers SR, et al. A double-blind evaluation of evening primrose oil as an antiobesity agent. IntJObes. 1983;7:549553. 28. Garcia CM, Carter J, Chou A. Gamma linolenic acid causes weight loss and lower blood pressure in overweight patients with family history of obesity. SwedJBiolMed. 1986;4:811. 29. Kenny FS, Pinder SE, Ellis IO, et al. Gamma linolenic acid with tamoxifen as primary therapy in breast cancer. Int J Cancer. 2000;85:643648. 30. Greenfield SM, Green AT, Teare JP, et al. A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis. Aliment Pharmacol Ther. 1993;7:159166. 31. Buck AC, Jenkins A, Lingam K, et al. The treatment of idiopathic recurrent urolithiasis with fish oil (EPA) and evening primrose oil (GLA)a double blind study. J Urol. 1993;149:253A. 32. Tulloch I, Smellie WS, Buck AC. Evening primrose oil reduces urinary calcium excretion in both normal and hypercalciuric rats. Urol Res. 1994;22:227230. 33. Horrobin DF. Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil. Med Hypotheses. 1979;5:365378. 34. Field EJ, Joyce G. Effect of prolonged ingestion of gamma-linolenate by MS patients. Eur Neurol. 1978;17:6776. 35. Bates D. Dietary lipids and multiple sclerosis. Ups J Med Sci Suppl. 1990;48:173187. 36. Horrobin DF. Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil. Med Hypotheses. 1979;5:365378. 37. Behan PO, Behan WM, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand. 1990;82:209216. 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;99:112116. 39. Vaddadi K. Dyskinesias and their treatment with essential fatty acids: a review. Prostaglandins Leukot Essent Fatty Acids. 1996;55:8994. 40. Kruger MC, Coetzer H, de Winter R, et al. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano). 1998;10:385394. 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 EfacalW v. calcium alone. Br J Nutr. 2000;83:629635. 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 2428, 2000; Brighton, United Kingdom. 43. Horrobin DF, Manku MS, Brush M, et al. Abnormalities in plasma essential fatty acid levels in women with premenstrual syndrome and with nonmalignant breast disease. J Nutr Med. 1991;2:259264. 44. Horrobin DF, Manku MS, Brush M, et al. Abnormalities in plasma essential fatty acid levels in women with premenstrual syndrome and with nonmalignant breast disease. J Nutr Med. 1991;2:259264. 45. Pye JK, Mansel RE, Hughes LE. Clinical experience of drug treatments for mastalgia. Lancet. 1985;2:373377. 46. Pashby NL, Mansel RE, Hughes LE, et al. A clinical trial of evening primrose oil in mastalgia [abstract]. Br J Surg. 1981;68:801. 47. Mansel RE, Gateley CA, Harrison BJ, et al. Effects and tolerability of n-6 essential fatty acid supplementation in patients with recurrent breast cystsa randomized double-blind placebo-controlled trial. J Nutr Med. 1990;1:195200. 48. Mansel RE, Harrison BJ, Melhuish J, et al. A randomized trial of dietary intervention with essential fatty acids in patients with categorized cysts. Ann N Y Acad Sci. 1990;586:288294. 49. Kollias J, Macmillan RD, Sibbering DM, et al. Effect of evening primrose oil on clinically diagnosed fibroadenomas. Breast. 2000;9:3536. 50. Budeiri D, Li Wan Po A, Dornan JC. Is evening primrose oil of value in the treatment of premenstrual syndrome? Control Clin Trials. 1996;17:6068. 51. Keen H, Payan J, Allawi J, et al. Treatment of diabetic neuropathy with gamma-linolenic acid. The gamma-Linolenic Acid Multicenter Trial Group. Diabetes Care. 1993;16:815. 52. Jamal GA, Carmichael H. The effect of gamma-linolenic acid on human diabetic peripheral neuropathy: a double-blind placebo-controlled trial. Diabet Med. 1990;7:319323. 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;36:397401. 54. Reichert R. Evening primrose oil and diabetic neuropathy. Q Rev Natr Med. 1995;129133. 55. Hounsom L, Horrobin DF, Tritschler H, et al. A lipoic acid-gamma linolenic acid conjugate is effective against multiple indices of experimental diabetic neuropathy. Diabetologia. 1998;41:839843. 56. Cameron NE, Cotter MA, Horrobin DH, et al. Effects of alpha-lipoic acid on neurovascular function in diabetic rats: Interaction with essential fatty acids. Diabetologia. 1998;41:390399. 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;121:7590. 58. Berth-Jones J, Graham-Brown RA. Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis. Lancet. 1993;341:15571560. 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;20:7784. 60. Hederos CA, Berg A. Epogam evening primrose oil treatment in atopic dermatitis and asthma. Arch Dis Child. 1996;75:494497. 61. Henz BM, Jablonska S, van de Kerkhof PC, et al. Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema. Br J Dermatol. 1999;140:685688. 62. Berth-Jones J, Graham-Brown RA. Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis. Lancet. 1993;341:15571560. 63. Whitaker DK, Cilliers J, de Beer C. Evening primrose oil (Epogam) in the treatment of chronic hand dermatitis: disappointing therapeutic results. Dermatology. 1996;193:115120. 64. Tamimi NA, Mikhail AI, Stevens PE. Role of gamma-linolenic acid in uraemic pruritus [letter]. Nephron. 1999;83:170171. 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;81:151159. 66. Zurier RB, Rossetti RG, Jacobson EW, et al. gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum. 1996;39:18081817. 67. Leventhal LJ, Boyce EG, Zurier RB. Treatment of rheumatoid arthritis with blackcurrant seed oil. Br J Rheumatol. 1994;33:847852. 68. Leventhal LJ, Boyce EG, Zurier RB. Treatment of rheumatoid arthritis with gammalinolenic acid. Ann Intern Med. 1993;119:867873. 69. Rothman D, DeLuca P, Zurier RB. Botanical lipids: Effects on inflammation, immune responses, and rheumatoid arthritis. Semin Arthritis Rheum. 1995;25:8796. 70. Belch JJ, Shaw B, O'Dowd A, et al. Evening primrose oil (Efamol) as a treatment for cold-induced vasospasm (Raynaud's phenomenon). Prog Lipid Res. 1986;25:335340. 71. Belch JJ, Shaw B, O'Dowd A, et al. Evening primrose oil (Efamol) in the treatment of Raynaud's phenomenon: a double-blind study. Thromb Haemost. 1985;54:490494. 72. Kruger MC, Coetzer H, de Winter R, et al. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano). 1998;10:385394. 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 EfacalW v. calcium alone. Br J Nutr. 2000;83:629635. 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 2428, 2000; Brighton, United Kingdom. 75. Haslett C, Douglas JG, Chalmers SR, et al. A double-blind evaluation of evening primrose oil as an antiobesity agent. Int J Obes. 1983;7:549553. 76. Garcia CM, Carter J, Chou A. Gamma linolenic acid causes weight loss and lower blood pressure in overweight patients with family history of obesity. Swed J Biol Med. 1986;4:811. 77. Horrobin DF. Nutritional and medical importance of gamma-linolenic acid. Prog Lipid Res. 1992;31:163194. 78. Vaddadi KS. The use of gamma-linolenic acid and linoleic acid to differentiate between temporal lobe epilepsy and schizophrenia. Prostaglandins Med. 1981;6:375379. 79. Aman MG, Mitchell EA, Turbott SH. The effects of essential fatty acid supplementation by Efamol in hyperactive children. J Abnorm Child Psychol. 1987;15:7590. 80. Arnold LE, Kleykamp D, Votolato NA, et al. Gamma-linolenic acid for attention-deficit hyperactivity disorder: placebo-controlled comparison to D-amphetamine. Biol Psychiatry. 1989;25:222228. 81. Vaddadi KS, Soosai E, Chiu E, et al. A randomised, placebo-controlled, double blind study of treatment of Huntington's disease with unsaturated fatty acids. Neuroreport. 2002;13:29-33. 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. |
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