Evening Primrose Oil Scientific References

RESEARCHED AND COMPILED BY:
ROBERT S. HARDT
NUTRI-EPIGENETIC BIOCHEMICAL ANALYST

2-18-2014 COPYRIGHT 5-2-2014

Evening Primrose Oil:

Evening Primrose Oil - What Is It?
Evening primrose oil is extracted from the evening primrose plant (Oenothera biennis), a wildflower found in North America, Europe and parts of Asia. The plant’s pale yellow flowers open in the evening–hence its common name–and its seeds bear the special fatty oil that is used in healing today.
In another era, Native Americans and the early settlers gathered the plant and its root to treat such ailments as hemorrhoids, stomachaches, sore throat, and bruises. It took modern research to unveil the therapeutic power contained within the seed oil: an essential fatty acid (EFA) called gammalinolenic acid (GLA). Once processed in the body, GLA, an omega-6 fatty acid, exerts anti-inflammatory and other healing actions. Evening primrose oil is certainly not the only source of GLA; various foods actually contain small amounts of it and the body produces GLA on its own from a number of dietary fats. But evening primrose oil offers an unusually concentrated source, with 7% to 10% of its fatty acids available in the form of GLA. Interestingly, borage oil features even more GLA (20% to 26%), and black currant oil offers rich stores as well (14% to 19%), but their effectiveness and safety for many ailments has not been as intensively examined as evening primrose oil. Nonetheless, some people prefer borage and black currant oils because they require a lower dose (at less total cost) for the same amount of GLA.

Health Benefits

The remarkably rich stores of GLA in evening primrose oil are what make it so valuable in healing. Taken internally, the body converts GLA into prostaglandins. These hormone like compounds help regulate various body functions, controlling inflammation in some cases and promoting it in others. The prostaglandins produced from GLA fall into the anti-inflammatory category. Cell membranes also rely on the presence of GLA.

Specifically, evening primrose oil may help to:
Relieve the discomforts of PMS (premenstrual syndrome), menstruation, endometriosis and fibrocystic breasts. By interfering with the production of inflammatory prostaglandins released during menstruation, the GLA in evening primrose oil can help to lessen menstrual cramps. It may also minimize premenstrual breast tenderness, irritable bowel flare-ups, and carbohydrate cravings, and help to control endometriosis-associated inflammation. Many PMS sufferers are found to have unusually low levels of GLA in their systems, which is why supplements might help so much. Although the oil has not been widely used in this country for treating PMS, Europeans have long used it for this condition. In women with fibrocystic breasts, the oil’s essential fatty acids can minimize breast inflammation and promote the absorption of iodine, a mineral that can be present in abnormally low levels in women with this condition.
Combat damage from multiple sclerosis. The abundant supply of essential fatty acids in evening primrose oil may be valuable in minimizing the inflammation associated with this progressive nerve disorder. The fatty acids may also contribute to healthy nerve development when taken over time. It is important to initiate supplement use as soon as possible after diagnosis.
Treat Alzheimer’s-related memory deficiencies. By boosting the transmission of nerve impulses, evening primrose oil may be valuable in treating this progressive brain disorder.

1. The GLA in Evening Primrose Oil interferes with the production of inflammatory prostaglandins that are released during menstruation, thereby lessening menstrual cramps. PMS sufferers often are found to have low levels of GLA in their bodies.

SCIENTIFIC AND MEDICAL REFERENCE GUIDE FOR: GLA, EPO, EVENING PRIMROSE OIL HEALTH BENEFITS AND APPLICATIONS

EPO FOR PMS
Evening Primrose
PMS: Recent theories about the causes of PMS include hormonal imbalances involving estrogen- progesterone, pyridoxine (vitamin B6) deficiency, elevated serum aldosterone, hypoglycemia, abnormal magnesium metabolism, and varying prostaglandin (PG) levels in the female reproductive tract.12-14 Prostaglandin series-1 derives from dihomogammalinolenic acid (DGLA) while the better-known PG-2 series derives from arachidonic acid. In adults the delta-5-desaturase had little of the activity that converts DGLA to arachidonic acid.15 Therefore, most of the arachidonic acid used for PG-2 synthesis should come from the diet, especially from meat and dairy products. Administering the precursor gammalinolenic acid is an obvious choice in order to enhance synthesis of the PG-1 series. A study conducted in a London hospital using Efamol (primrose oil as a source of gammalinolenic acid) involved 68 women who had failed to respond to other therapeutic regimens. Of these women, 61% experienced total remission and 23% experienced partial remission. The dosage of Efamol (0.5 g/capsule), originally twice a day in the luteal phase, was gradually increased to four capsules, twice a day, during the whole cycle for 18 months. Only a few patients complained of side effects and those symptoms were not necessarily related to Efamol. In Helsinki, Finland, in a double-blind placebo-controlled study, patients were treated with Efamol for four cycles. These patients had not been treated with drugs before the experiment. Efamol showed a 40% average improvement in parameters tested, especially in irritability and depression.15 In an English study, 196 women who were scored one cycle before Efamol treatment were treated with two Efamol capsules morning and evening during the luteal phase. These women showed significant (p < 0.001) improvement in all five symptoms tested (irritability, depression, breast pain and tenderness, headache, and ankle swelling).15 Although results of smaller-scale studies showed improvement in symptoms, differences were not significant compared to placebo.16

12. Budoff, P.W. The use of prostaglandin inhibitors for the premenstrual syndrome. J. Reprod. Med. 1983;28:469-478.

13. Abraham, G.E. Nutritional factors in the etiology of the premenstrual tension syndromes. J. Reprod. Med 1983;28(7):446-464.

14. Hawkins, J., Sagraves, R. Premenstrual Syndrome: Diagnosis, Etologies, Therapy. Pharmacy Times 1987;9:110-120.

15. Horrobin, D.F. The role of essential fatty acids and prostaglandins in the premenstrual syndrome. J. Reprod. Med. 1983;28:465-468.

16. Khoo, S.K., Munro, C. et al. Evening primrose oil and treatment of premenstrual syndrome.

Med. J. Aust. 1990;153:189-192.
17. BeLieu, R.M. Mastodynia. Obstet. Gynecol. Clin. North Am. 1994;21(3)461-477.

18. Pye, J.K., Mansel, R.E. et al. Clinical experience of drug treatments for mastalgia. Lancet 1985; August:373-376.

Kaunitz, H. and Johnson, R.E.; “Influence of dietary fats on disease and longevity”; (1975) Proceedings of the Ninth International Congress of Nutrition (Mexico, 1972). Vol. 1 ed. by A. Chavez, et al. Basel,

Wong, Dr. Randy L.; Lipid Nutrition: Understanding fats and oils in health and disease; Inquiry Press; Midland, Michigan; 48640

Harrison, Lewis; The Complete Fats and Oils Book; Avery Publishing Group; Garden City, New York; 1990, 1996.

Harrison, Lewis; Making Fats & Oils Work for You; Avery Publishing Group; Garden City, New York; 1990.
Prescott, S.M.; “The Effect of Eicosapentaenioic Acid on Leukotriene B Production by Human Neutrophils”; Journal of Biologic Chemistry; 259(1984): 7615-21.

Kaunitz, H. and Johnson, R.E.; “Influence of dietary fats on disease and longevity”; (1975) Proceedings of the Ninth International Congress of Nutrition (Mexico, 1972). Vol. 1 ed. by A. Chavez, et al. Basel,
Switzerland: 369. “Dietary essential fatty acids, prostaglandin formation and platelet aggregation”: Nutrition Reviews 34:243.

Ockerman, P.A., Bachrack, I., Glans, S. and Rassner, S. 1986. “Evening primrose oil as a treatment of the premenstrual syndrome”. Recent Adv. Clin. Nutr. 2:404.

Das, U.N. 1992. Anti-cancer effects of cis-unsaturated fatty acids both in vitro and in vivo. Lipid- Soluble Antioxidants: Biochemistry and Clinical Applications. Ong, A.S.H. and Packer, L., Eds. Birkhauser Verlag, Basel, Switzerland, p. 482.

Takeda, S., Horrobin, D., Manku, M., Sim, P.G. and Simmons, V. 1992. Propose lipid peroxidation mechanism for selective destruction of breast cancer cells in culture by gamma-linolenic acid (GLA). In: Oxygen Radicals. Proceedings of the 5th International Congress on Oxygen Radicals: Active Oxygen, Lipid Peroxides and Antioxidants. Kyoto, 17- 21 November 1991. Yagi, Kondo, M., Kiki, E. and Yoshikawa, T., Eds. Elsevier Science Publ. B.V., Amsterdam, p. 277.

Takeda, S., Horrobin , D.F. and Manku, M.S. 1992. “The effects of gamma-linolenic acid on human breast cancer cell killing, lipid peroxidation and the production of Schiff-reactive materials”. Med. Sci. Res. 20:203.

Engler, M.M. 1993. “Comparative study of diets enriched with evening primrose, black currant, borage or fungal oils on blood pressure and pressor responses in spontaneously hypertensive rats.” Prostaglandins Leukotrienes Ess. Fatty Acids 49:809.

Evening Primrose Oil. Review of Natural Products. Facts & Comparisons [database online] CE Online: Natural Medicines Comprehensive Database

Home - PMC - NCBI
GLA, EVENING PRIMROSE OIL - GQuery: Global Cross-database NCBI search - NCBI

Evening Primrose Oil - American Family Physician
MASTALGIA, MENOPAUSE, AND PREMENSTRUAL SYMPTOMS
A systematic review of treatments for cyclical mastalgia found only three double-blind, placebo- controlled trials of EPO and one multicenter trial of GLA (an active ingredient of EPO).7 The latter trial, which was of excellent quality, found that GLA was not superior to placebo, with or without additional antioxidant vitamins and minerals.8 Pooling the four studies, the authors found no significant effect of EPO on mean pain scores compared with placebo.7 There is insufficient evidence to recommend the use of EPO in the treatment of mastalgia.

Only one randomized, double-blind, placebo-controlled multi-center trial has studied the effects of EPO in menopausal women (n = 56).9 For a duration of six months, the participants took four capsules twice daily that contained either EPO (0.5 g EPO and 10 mg natural vitamin E per capsule) or placebo. The EPO showed no benefit in treating menopausal flushing compared with placebo. A systematic review of four small, low-powered trials found that doses of EPO ranging from 3 to 6 g daily were not effective in improving overall symptoms of premenstrual syndrome (PMS) compared with placebo.10 Therefore, current evidence does not support a role for EPO in the management of menopause or PMS.

OTHER CONDITIONS
Although evidence to date is limited, several small studies suggest that GLA may be useful in patients with mild to moderate diabetic neuropathy who achieve only partial relief from prescription drugs.11–13 However, larger methodologically sound studies are needed to confirm this assertion, and it is unclear whether such data may be extrapolated to EPO supplements. A Cochrane review comparing GLA (derived from evening primrose, borage, or black currant seed oil) with placebo in the treatment of rheumatoid arthritis found that current evidence is insufficient to make a reliable assessment of effectiveness.14 EPO is applied vaginally by many midwives to accelerate cervical ripening, shorten labor, and decrease the incidence of post-term pregnancies.15 However, no clinical RCTs support this use.

REFERENCES
7. Srivastava A, Mansel RE, Arvind N, Prasad K, Dhar A, Chabra A. Evidence-based management of mastalgia: a meta-analysis of randomised trials. Breast. 2007;16(5):503–512.

8. Goyal A, Mansel RE, for the Efamast Study Group. A randomized multicenter study of gamolenic acid (Efamast) with and without antioxidant vitamins and minerals in the management of mastalgia. Breast J. 2005;11(1):41–47.

9. Chenoy R, Hussain S, Tayob Y, O'Brien PM, Moss MY, Morse PF. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ. 1994;308(6927):501–503.

10. Stevinson C, Ernst E. Complementary/alternative therapies for premenstrual syndrome: a systematic review of randomized controlled trials. Am J Obstet Gynecol. 2001;185(1):227–235.

11. Halat KM, Dennehy CE. Botanicals and dietary supplements in diabetic peripheral neuropathy. J Am Board Fam Pract. 2003;16(1):47–57.

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(1):8–15.

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(4):319–323.

14. Little C, Parsons T. Herbal therapy for treating rheumatoid arthritis. Cochrane Database Syst Rev. 2001;(1):CD002948.

15. McFarlin BL, Gibson MH, O'Rear J, Harman P. A national survey of herbal preparation use by nurse-midwives for labor stimulation. Review of the literature and recommendations for practice. J Nurse Midwifery. 1999;44(3):205–216.

Evening Primrose Oil Uses, Benefits & Dosage - Drugs.com Herbal Database
19. Philp HA. Hot flashes—a review of the literature on alternative and complementary approaches. Altern Med Rev . 2003;8(3):284-302.
20. Fugate SE, Church CO. Nonestrogen treatment modalities for vasomotor symptoms associated with menopause. Ann Pharmacother . 2004;38(9):1482-1499.
21. Huntley AL, Ernst E. A systematic review of herbal medicinal products for the treatment of menopausal symptoms. Menopause . 2003;10(5):465-476.
22. Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials. Ann Intern Med . 2002;137(10):805-814.
23. Stevinson C, Ernst E. Complementary/alternative therapies for premenstrual syndrome: a systematic review of randomized controlled trials. Am J Obstet Gynecol . 2001;185(1):227-235.
24. Whelan AM, Jurgens TM, Naylor H. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Can J Clin Pharmacol . 2009;16(3):e407-e429.
25. Wong VC, Lim CE, Luo X, Wong WS. Current alternative and complementary therapies used in menopause. Gynecol Endocrinol . 2009;25(3):166-174.
26. North American Menopause Society. Treatment of menopause-associated vasomotor symptoms: position statement of The North American Menopause Society. Menopause . 2004;11(1): 11-33.

Women's Health Series: Herbs of Special Interest to Women: Evening Primrose Oil

Evening primrose, Oenothera biennis L., is a North American wildflower that has escaped cultivation and is now widely distributed in fields or along roadsides.[2] Named so because its flower opens in the evening, the evening primrose is in fact not a true primrose. Traditionally, the plant was valued as a food, and its roots and seeds were eaten.[3] Medicinal use of evening primrose has a long history among Native Americans, and use of the plant was transferred to Europe by colonial settlers.

Modern interest has centered on the oil expressed from the plant's small dark seeds. The seeds produce a fixed oil rich in essential fatty acids: approximately 65% linoleic acid and 8% to 10% gamma-linolenic acid.[4,5] These constituents are critical precursors in the manufacture of prostaglandin E1, one of the anti-inflammatory prostaglandins.[6]

A number of studies have evaluated the efficacy of evening primrose oil (EPO) in the treatment of premenstrual syndrome (PMS). The rationale for this use is that women with PMS have an abnormal profile of essential fatty acids, which may be normalized by supplementation with EPO. [6-9] Brush et al.[7] reported that women with PMS have high levels of n6 essential fatty acids but low levels of all metabolites of linoleic acid, including arachidonic acid. These investigators reported that gamma- linolenic acid levels were below detectable levels in PMS patients, and postulated that PMS is associated with a defect in the conversion of linoleic acid to gamma-linolenic acid. Abnormal levels of essential fatty acids also have been observed in women with benign breast disorders. [8]

Clinical Studies

In an open label study, Brush[10] evaluated the efficacy of EPO for PMS symptoms in 68 women. The women received EPO (1 to 2 grams per day) from 3 days before the usual onset of their PMS symptoms until the onset of menses. Based on a patient self-report scale, 41 women (61%) had complete relief of their symptoms and 16 (23%) had partial relief after at least 3 months of treatment. The most pronounced symptom relief was for mastalgia (breast pain).

Many additional trials, such as those conducted by Larson et al.[11] and Ylikorkala et al.,[12] have reported modest benefits of EPO for PMS symptoms. However, these favorable effects were not replicated in a double-blind, placebo-controlled crossover trial of 38 women with PMS.[13] This study, which used a daily EPO dose of eight capsules (presumably 4 grams), failed to demonstrate statistically or clinically significant results.[13] Furthermore, an attempted meta-analysis of the effects of EPO on general PMS symptoms also did not demonstrate conclusive efficacy. [14] The majority of trials cited suffered from methodologic flaws that made meta-analysis difficult, such as an open study design with no placebo control and a placebo-controlled, parallel-group study without a defined randomization scheme.[11,15,16]

Although clinical studies have not shown a clear benefit of EPO for PMS, more pronounced improvement has been demonstrated for relief of mastalgia. A double-blind, placebo-controlled study compared the effects of danazol, bromocriptine, EPO, progestins, and placebo in 291 women with mastalgia.[17] The experimental agents were tried sequentially, and the patients subjectively rated their relief by recording their assessment of pain on a visual analogue scale supplemented by a pain diary. EPO (3 grams per day) was effective for cyclical mastalgia in 45% of patients, with a relapse rate of 21% after the first course of treatment. Effectiveness was defined as either a Grade I response (no residual pain) or a Grade II response (some residual pain that the patient described as easily bearable).

Only 2% of the EPO-treated patients reported side effects (mild bloating with vague nausea).[17] Compared with danazol, EPO was less effective (70% versus 45%), but had fewer side effects (22% versus 2%). EPO had similar efficacy to bromocriptine (47% versus 45%), again with fewer side effects (2% versus 33%). Effectiveness rates for all therapies were lower in patients with noncyclical mastalgia, with danazol showing a 31% response rate; EPO, 27%; bromocriptine, 20%; and progesterone, 9%.

A much lower response rate was recently reported in a clinical survey conducted at a hospital- based mastalgia clinic in Australia, which recorded observations on 170 patients for 3 years.[18] Response rates of only 26% were reported for mastalgia patients receiving EPO, while low-dose danazol achieved an effect in 67% of the patients.

Despite the mixed results of these studies, many clinicians recommend EPO as a first-line treatment for cyclic mastalgia.[8,19-25] For example, in a recent survey 13% to 30% of British surgeons recommended EPO for this use.[24] Patients with severe PMS symptoms, in another recent survey,[26] also rated EPO as one of the most effective treatments they had used.

Considerations for Patient Use

Given its good safety profile, EPO can reasonably be tried for PMS at a dose of 2 to 4 grams (standardized to 9% gamma-linolenic acid), especially if mastalgia is present. EPO also may confer benefit for other symptoms associated with PMS, such as irritable bowel syndrome. [27] A critical analysis is under way to further examine questions of efficacy at the Cochrane Collaboration, which is producing a compendium of systematic evidence-based reviews . [28]

Given its reputed usefulness in PMS, EPO has also been tried for management of menopausal symptoms, but its use for this indication has much less data to recommend it. A double-blind, placebo-controlled trial of 56 menopausal women failed to demonstrate a statistically significant effect of EPO (2 grams/day) on hot flushes.[29] Although a small, statistically significant improvement in the number of nighttime flushing episodes (P < .05) was recorded, the study did not report whether the patients considered this improvement to be significant.

References

1. E. Women Healers: Portraits of Herbalists, Physicians, and Midwives. Rochester, Vt: Healing Arts Press; 1995.

2.Grieve M. A Modern Herbal. London: Cresset Press Book; 1973. 3.Weiss RF. Herbal Medicine. Gothenburg, Sweden: AB Arcanum; 1988.

4.Oil of Evening Primrose. Monograph. Lawrence Review of Natural Products. Levittown, Pa: Pharmaceutical Information Associates; 1993.

5.Schulz V, Hänsel R, Tyler VE. Rational Phytotherapy: A Physician's Guide to Herbal Medicine, 3rd ed. Berlin: Springer-Verlag; 1998.

6.Horrobin DF, Manku MS, Brush M, et al. Abnormalities in plasma essential fatty acid levels in women with premenstrual syndrome and with non-malignant breast disease. J Nutr Med. 1991;2:259-64.

7.Brush M, Watson J, Horrobin D, et al. Abnormal essential fatty acid levels in plasma of women with premenstrual syndrome. Am J Obstet Gynecol. 1984;150:363-6.

8.Gateley CA, Maddox PR, Pritchard GA, et al. Plasma fatty acid profiles in benign breast disorders. Br J Surg. 1992;79:407-9.

9.Cameron I, Fraser I, Smith S. Clinical Disorders of the Endometrium and Menstrual Cycle. Oxford: Oxford University Press; 1998.

10.Brush MG. Evening primrose oil in the treatment of premenstrual syndrome. In: Horrobin DF, ed. Clinical Uses of Essential Fatty Acids. Montreal: Eden Press; 1982:155-62.

11.Larson B, Jonasson A, Fianu S. Evening primrose oil in the treatment of premenstrual syndrome. Curr Ther Res. 1989;46:58-63.

12.Ylikorkala O, Puolakka J, Makarainen L, et al. Prostaglandins and premenstrual syndrome. Prog Lipid Res. 1986;25:433-5.

13.Khoo SK, Munro C, Battistutta D. Evening primrose oil and treatment of premenstrual syndrome. Med J Australia. 1990;153:189-92.

14.Budeiri D, Li Wan Po A, Dornan JC. Is evening primrose oil of value in the treatment of premenstrual syndrome? Control Clin Trials. 1996;17:60-8.

15.Brush MG. Efamol (evening primrose oil) in the treatment of the premenstrual syndrome. In: Horrobin DF, ed. Clinical Uses of Essential Fatty Acids. London: Eden Press, Inc; 1982.

16.Ockerman PA, Glans SA, Rassner S. Evening primrose oil as a treatment of premenstrual syndrome. Curr Ther Res. 1986;46:58-63.

17.Pye JK, Mansel RE, Hughes LE. Clinical experience of drug treatment for mastalgia. Lancet. 1985;ii:373-7.

18.Wetzig NR. Mastalgia: A 3 year Australian study. Aust N Z J Surg. 1994;64:329-31.
19.BeLieu RM. Mastodynia. Obstet Gynecol Clin North Am. 1994;21:461-77.
20.Genolet PM, Delaloye JF, DeGrandi P. Diagnosis and treatment of mastodynia [French]. Revue

Medicale de la Suisse Romande. 1995;115:385-90.

21.Gateley CA, Maddox PR, Mansel RE, et al. Mastalgia refractory to drug treatment. Brit J Surg. 1990;77:1110-2.

22.Gateley CA, Mansel RE. Management of the painful and nodular breast. Brit Med Bull. 1991;47:284-94.

23.Gateley CA, Meirs M, Mansel RE, et al. Drug treatments for mastalgia: 17 years experience in the Cardiff Mastalgia Clinic. J Roy Soc Med. 1992;85:12-5.

24.Pain JA, Cahill CJ. Management of cyclical mastalgia. Brit J Clin Pract. 1990;44:454-6.

25.Pashby N, Mansel R, Hughes L, et al. A clinical trial of evening primrose oil in mastalgia. Brit J Surg. 1981;68:801-24.

26.Cambell EM, Peterkin D, O'Grady K, et al. Premenstrual symptoms in general practice patients. Practice and treatment. J Reprod Med. 1997;42:637-46.

27.Cotterell J, Lee A, Hunter J. Double-blind cross-over trial of evening primrose oil in women with menstrually-related irritable bowel syndrome. In: Horrobin D, ed. Omega-6 Essential Fatty Acids: Pathophysiology and Roles in Clinical Medicine. New York, NY: Wiley- Liss; 1990.

28.Strid J, Jepson J, Moore V, et al. Evening primrose oil or other essential fatty acids for premenstrual syndrome. Cochrane Database of Systematic Reviews. 1999;2.

29.Chenoy R, Hussain S, Tayob Y, et al. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. Br Med J. 1994;308:501-3.

30.Mayo J. Premenstrual syndrome: a natural approach to management. Clin Nutr Insights. 1997;5:1-8.

31.Halbreich U. Serum prolactin in women with pre-menstrual syndrome. Lancet. 1976:654-6.

32.Loch E, Böhnert KJ, Peeters M, et al. The treatment of menstrual disorders with Vitex agnus- castus tincture. Der Frauenarzt. 1991;32:867-70.

33.Dittmar F, Böhnert KJ, Peeters M, et al. Premenstrual syndrome: treatment with a phytopharmaceutical. Therapiewoche Gynä kol. 1992;5: 60-8.

34.Lieberman S. Black cohosh for menopausal symptoms. J Women's Health. 1998;7:525-9.

35.Greunwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. Montvale, NJ: Medical Economics Company, Inc; 1998.

36.Brinker F. A comparative review of eclectic female regulators. J Naturopathic Med. 1997;7:11-25.

37.Brinker F. Herb Contraindications and Drug Interactions. Sandy, Oreg: Eclectic Institute, Inc; 1997.

38.Bendich A. The potential for dietary supplements to reduce premenstrual syndrome (PMS) symptoms. J Am Coll Nutrition 2000;19:3-12

39.Budeiri D, Li Wan Po A, Dornan JC. Is evening primrose oil of value in the treatment of premenstrual syndrome? Control Clin Trials 1996;17:60-8.

40.Chenoy R, Hussain S, Tayob Y, et al. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing (abstract). BMJ 1994;308:501-3.

41.Horrobin DF. Evening primrose oil and premenstrual syndrome. Med J Aust 1990;153:630-1.

42.Khoo SK, Munro C, Battistutta D. Evening primrose oil and treatment of premenstrual syndrome. Med J Aust 1990;153:189-92.

* Budeiri D, Li Wan Po A, Dornan JC. Is evening primrose oil of value in the treatment of premenstrual syndrome? Control Clin Trials. 1996;17:60-68.

Evening Primrose Oil (Oenothera Biennis) Benefits & Information

Specifically, evening primrose oil may help to:
Relieve the discomforts of PMS, menopause, menstruation, endometriosis and fibrocystic breasts

By interfering with the production of inflammatory prostaglandins released during menstruation, the GLA in evening primrose oil can help to lessen menstrual cramps. It may also minimize premenstrual breast tenderness, irritable bowel flare-ups, and carbohydrate cravings, and help to control endometriosis-associated inflammation. Many PMS sufferers are found to have unusually low levels of GLA in their systems, which is why supplements might help so much. In women with fibrocystic breasts, the oil's essential fatty acids can minimize breast inflammation and promote the absorption of iodine, a mineral that can be present in abnormally low levels in women with this condition. In menopause, it is widely reported that Evening Primrose oil reduces hot flushes and increases feelings of well being.

Balbi C, Musone R, Menditto A, et al., Influence of menstrual factors and dietary habits on menstrual pain in adolescence age. Eur J Obstet Gynecol Reprod Biol. 2000;91(2):143-8.

Barnard ND, Scialli AR, Hurlock D, Bertron P. Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms. Obstet Gynecol. 2000;95(2):245-50.

Dennehy CE. The use of herbs and dietary supplements in gynecology: an evidence-based review. J Midwifery Womens Health. 2006;51(6):402-9.

17. Whelan AM, Jurgens TM, Naylor H. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Can J Clin Pharmacol. 2009 Fall;16(3):e407-29. Epub 2009 Oct 29.

18. Pruthi S, Wahner-Roedler DL, Torkelson CJ, Cha SS, Thicke LS, Hazelton JH, Bauer BA. Vitamin E and evening primrose oil for management of cyclical mastalgia: a randomized pilot study. Altern Med Rev. 2010 Apr;15(1):59-67.

19. Chenoy R, Hussain S, Tayob Y, et al. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ 1994;308: 501-503.

20. Carroll DG. Nonhormonal therapies for hot flashes in menopause. Am Fam Physician. 2006 Feb 1; 73(3):457-64.

Source: Menstrual pain | University of Maryland Medical Center http://umm.edu/health/ medical/altmed/condition/menstrual-pain#ixzz2yTAUjFJq
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2. Reduce carbohydrate cravings and irritable bowel flare-ups.

SCIENTIFIC AND MEDICAL REFERENCE GUIDE FOR: GLA, EPO, EVENING PRIMROSE OIL HEALTH BENEFITS AND APPLICATIONS, MINIMIZING CARBOHYDRATE CRAVINGS AND IRRITABLE BOWEL DISORDERS

GLA, EVENING PRIMROSE OIL, BORAGE OIL, REDUCE CARBOHYDRATE CRAVINGS. REFERENCES

GLA, EVENING PRIMROSE OIL, BORAGE OIL, REDUCTION OF IRRITABLE BOWEL FLARE- UPS. REFERENCES

GLA, EVENING PRIMROSE OIL, BORAGE OIL, REDUCE CARBOHYDRATE CRAVINGS AND IRRITABLE BOWEL FLARE-UPS. REFERENCES

Pre-menstrual Syndrome and Diet | ENCOGNITIVE.COM

From the available evidence, it appears that the diet advocated in the Health of the ... Evening primrose oil seems most effective when used to treat mastalgia. ... seasonal adjusted disorder (SAD) and carbohydrate craving obesity [ 21, 22]. ... bloating and irritable bowel syndrome are prominent PMS symptoms [ 7, 14, 30].

[1] O'Brien PMS. Helping women with PMS. BMJ 1993, 307: 1471-5.

[2] Magos AL. Premenstrual syndrome. Contemp Rev Obstet Gynaecol 1988; 1: 80-92.

[3] Abraham GE. Nutrition and the premenstrual tension syndromes. J Appl Nutr 1984, 36: 103-24.

[4] Stewart A. Clinical and biochemical effects of nutritional supplementation on the premenstrual syndrome. J Repr Med 1987; 32: 435-41.

[5] Nazzaro A, Lombard D, Horrobin D. The PMT Solution. London: Adamantine Press, 1985.

[6] O'Brien PMS. Pre-menstrual Syndrome. Oxford: Blackwell Scientific, 1987.

[7] Stewart A. A Rational Approach to Treating PMS. Lewes, Sussex: Women's Nutritional Advisory Service. 1989.

[8] Facchinetti F, Sances G, Borello P. et al. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache 1991, 31: 298-301.

[9] Posaci C, Erton O, Uren A, et al. Plasma copper, zinc and magnesium levels in patients with premenstrual tension syndrome. Acta Obstet Gynecol 1994, 73: 452-5.

[10] Rosenstein DL, Elin RJ, Hoseini JM, et al. Magnesium measures across the menstrual cycle in premenstrual syndrome. Biol-Psychiatr 1994; 35: 557-61.

[11] Department of Health. Dietary Reference Values for Food Energy and Nutrients for the UK. London: HMSO, 1991.

[12] Stewart A. Howard J. Magnesium and potassium deficiencies in women with premenstrual syndrome. Mag Bull 1986; 8: 313-16.

[13] Stewart M, Stewart A. Felmore Guide to Premenstrual Tension and Nutrition. Tunbridge Wells: Felmore Ltd Health Publications, 1989.

[14] Davies S, Stewart A. Nutritional Medicine. London: Pan Books, 1987.

[15] Chuong CJ, Dawson EB. Critical evaluation of nutritional factors in the pathophysiology and treatment of premenstrual syndrome. Clin Obstet Gynaecol 1992; 35: 679-92.

[16] Mira M, Stewart PM, Abraham SF. Vitamin and trace element status in premenstrual syndrome. Am J Clin Nutr 1988: 47: 636-41.

[17] Chuong CJ, Dawson EB, Smith ER. Vitamin E levels in premenstrual syndrome. Am J Obstet Gynecol 1990; 163: 1591-5.

[18] Brush MG. Nutritional approaches to the treatment of premenstrual syndrome. Nutr Health 1983; 2: 203-9.

[19] Stewart AC, et at. Effect of nutritional programme on premenstrual syndrome and work efficiency. Compliment Ther Med 1993; 1: 68-72.

[20] O'Brien PMS, Massif H. Premenstrual syndrome: clinical studies on essential fatty acids. In: Horrobin DF, ed. Omega-6 Essential Fatty Acids. Pathophysiology and Roles in Clinical Medicine. New York: Wiley-Liss. 1990; 523-45.

[21] Wurtman JJ. Depression and weight gain: the serotonin connection (review). J Affect Disord 1993; 29: 182-92.

[22] Christensen L. Effects of eating behaviour on mood: a review of the literature. Int J Eating Disord 1993; 14: 171-83.

[23] Abraham GE, Rumley RE. The role of nutrition in managing the premenstrual tension syndromes. J Reproduct Med 1987; 32: 405-22.

[24] Boyd NF, McGuire V, Shannon P, et al. The effect of a low fat high-carbohydrate diet on symptoms of cyclical mastopathy. Lancet 1988; 2: 128-32.

[25] Thomas B. Manual of Dietetic Practice, 2nd edn. Oxford: Blackwell. 1995.

[26] Stewart M. The nutritional approach to premenstrual syndrome. Health Visitor 1989; 62: 27-8.

[27] Minton JP, Foecking MK, Webster DJ, et al. Responses of fibrocystic disease to caffeine withdrawal and correlation of cyclic nucleotides with breast disease. Am J Obstet Gynecol 1979; 135: 157-8.

[28] Tobin MB, Schmidt PJ, Rubinow DR. Reported alcohol use in women with premenstrual syndrome. Am J Psychiatry 1994; 151: 1503-4

[29] Allen D. Are alcoholic women more likely to drink premenstrually? Alcohol Alcoholism 1996; 31: 145-7.

[30] Stewart M. Beat PMS Through Diet. London: Ebury Press, 1990.

[31] Lurie S, Borenstein R. The premenstrual syndrome. Obstet Gynecol Surv; 1990, 45: 220-8.

[32] Andrews G. Constructive advice for a poorly understood problem: treatment and management Of PMS. Profess Nurse 1994, 9: 364-70.

[33] Trickett S. Coping with Candida. London, Sheldon Press, 1994.

[34] Eaton KK, McLaren Howard J, Hunnisett A, et al. Abnormal gut fermentation: laboratory studies reveal deficiency of B vitamins, zinc and magnesium. J Nutr Biochem 1993; 4: 635-8.

[35] Crook WG. PMS and yeast: an aetiological connection (letter). Hospital Prac 1983; 18: 21-4.

[36] Schinfield JS. PMS and candidiasis study explores possible link. Female Patient 1987; 12: 66-74.

[37] Abraham GE, Hargrove JT. The effect of vitamin B6, on premenstrual symptomology in women with PMS: a double blind cross-over study. Infertility 1980; 3: 155-65.

[38] Menkes DB, Coates DC, Fawcett JP. Acute tryptophan depletion aggravates premenstrual syndrome. J Affect Disord 1994; 32: 37-44.

[39] Smallwood J, Ah-Kye D. Taylor I. Vitamin B6 in the treatment of pre-menstrual mastalgia. Br J Clin Pract 1986; 40: 532-3.

[40] Hagen I, Hesheim BI, Tuntland T. No effect of vitamin B[psub 6] against premenstrual tension. Acta Obstet Gynaecol Scand 1985; 64: 667-70.

[41] Kendall KE, Schnur PP. The effects of vitamin B6 supplementation on premenstrual symptoms. Obstet Gynaecol 1987; 70: 145-9.

[42] Dalton K, Dalton JT. Characteristics of pyridoxine overdose neuropathy syndrome. Acta Neurol Scand 1987: 76: 8-11.

[43] Schaumburg HH, Berger A. Pyridoxine Neurotoxicity in Clinical and Physiological Applications of Vitamin B6. New York: Alan R. Liss Inc., 1988.

[44] Cohen M. Bendich A. Safety of pyridoxine--a renewal Of human and animal Studies.

Toxicol Let 1986; 34: 129-39.

[45] Brush M. The pill, pyridoxine and PMS symptoms. MIMS Mag 1982; 1 April: 23-4.

[46] Barr W. Pyridoxine supplements in the premenstrual syndrome. Practitioner 1984; 229: 425-7.

[47] Doll H, Brown S, Thurston A, et al. Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial. J R Coll Gen Pract 1989; 39: 364-8.

[48] Brush MG, Perry M. Pyridoxine and the premenstrual syndrome. Letter. Lancet 1985; I: 1399.

[49] Brush MG. Vitamin B6 Treatment of Premenstrual Syndrome in Clinical and Physiological Applications of Vitamin B6. New York: Alan R. Liss, 1988.

[50] Machlin LJ. Use and safety of elevated dosages of vitamin E in adults. Int J Vitamin Nutr Res Suppl 1989; 30: 56-68.

[51] London RS, Sundaram GS, Murphy L, et al. Evaluation and treatment of breast symptoms in patients with the premenstrual syndrome. J Am Coll Nutr 1983; 2: 112-15.

[52] Khoo SK, Munro C, Battis Tutta D. Evening primrose oil and treatment of premenstrual syndrome. Med J Austr 1990: 20: 189-92.

[53] Barber AJ. Evening primrose oil: a panacea? Pharm J 1988; 240: 723-5.

[54] Saffron L. Not All in the Mind. London: Women's Health, 1993.

[55] Mansel RE. Breast pain. BMJ 1994; 309: 866-8.

[56] Collins A, Cerin A, Coleman G, et al. Essential fatty acids in the treatment of premenstrual syndrome. Obstet Gynecol 1993; 81: 93-8.

[57] Which? Consumer Group. Which? way to health. The benefits of evening primrose oil. Which? April: 66-7.

[58] Kleijnen J. Evening primrose oil. BMJ 1994; 309; 824-5.

[59] British National Formulary. B Med Assoc R Pharm Soc GB 1997; 33: 472.

[60] Poenaru S, Rouhani S, Durlach J, et al. Magnesium and monoaminergic neurotransmitters: elements of human and experimental pathophysiology. In: Itokawa Y, Durlach J, eds. Magnesium in Health and Disease. London: John Libbey, 1989; pp. 291-7.

[61] Fuchs N, Hakim M, Abraham GE. The effect of a nutritional supplement, "Optivite for Women", On premenstrual tension syndromes. Effect on blood chemistry and serum steroid levels during the mid-luteal phase. J Appl Nutr 1985: 37: 1-11.

[62] Leather AT, Holland EFN, Andrews CD, et al. A study Of the referral patterns and therapeutic experiences of 100 women attending a specialist premenstrual syndrome

clinic. J R Soc Med 1993; 86: 199-201.

[63] Thys-Jacobs S, Ceccaralli S, Bierman A, et al. Calcium supplementation in premenstrual syndrome: a randomized crossover trial. J Gen Intern Med 1989; 4: 183-9.

[64] Alvir JMJ, Thys-Jacobs S. Premenstrual and menstrual symptom clusters and response to calcium treatment. Psychopharmacol Bull 1991: 27: 145-8.

[65] Thys-Jacobs S. Vitamin D and calcium in menstrual migraine. Headache 1994; 34: 544-6.

[66] Penland JG, Johnson PE. Dietary calcium and manganese effects on menstrual cycle symptoms. Am J Obstet Gynecol 1993; 168: 1417-23.

[67] Wilson RDC. Premenstrual Syndrome: Diet Against it. London: Foulsham, 1989.

[68] Department of Health. The Health of the Nation. London: HMSO 1992.

21. Puolakka J, Makarainen L, Viinikka L, Ylikorkola O. Biochemical and clinical effects of treating the premenstrual syndrome with prostaglandin synthesis precursors. J Reprod Med 1985;30:149–

53.

22. Ockerman PA, Bachrack I, Glans S, Rassner S. Evening primrose oil as a treatment of the premenstrual syndrome. Rec Adv Clin Nutr 1986;2:404–5.

23. Massil H, O’Brien PMS, Brush MG. A double blind trial of Efamol evening primrose oil in premenstrual syndrome. 2nd International Symposium on PMS, Kiawah Island, Sep 1987.

24. Casper R. A double blind trial of evening primrose oil in premenstrual syndrome. 2nd International Symposium on PMS, Kiawah Island, Sep 1987.

25. Khoo SK, Munro C, Battisutta D. Evening primrose oil and treatment of premenstrual syndrome. Med J Aust 1990;153:189–92.

26. Collins A, Cerin A, Coleman G, Landgren B-M. Essential fatty acids in the treatment of premenstrual syndrome. Obstet Gynecol 1993;81:93–8.

Cotterell J, Lee A, Hunter J. Double-blind cross-over trial of evening primrose oil in women with menstrually-related irritable bowel syndrome. In: Horrobin D, ed. Omega-6 Essential Fatty Acids: Pathophysiology and Roles in Clinical Medicine. New York, NY: Wiley- Liss; 1990.

GLA, EVENING PRIMROSE OIL BENEFITS, PMS, PATENT, REFERENCES

Patent EP0261814A2 - Therapeutic composition containing gamma ...

Combinations of gamma-linolenic acid (GLA) and calcium, presented ... calcium loss from the bones, of premenstrual syndrome, or of hypertension. ... referred to and reference may be made to European Patent Specification No. .... is low, provide a richer source of gamma-linolenic acid than Oenothera oil.

Patent US5380757 - Method of treating vulvar dystrophy and vaginal ...

The alpha isomer of linolenic acid was characterised earlier than gamma-linolenic acid and reference in ... breast pain and premenstrual syndrome, the formation of GLA may ... One good source of GLA is evening primrose oil, and GLA as ...

Patent US5614208 - Methods of treatment using di-linoleoyl-mono ...

Triglycerides peaks found in evening primrose andborage oils. Eight peaks occur in both oils, ten ... Natural Standard - Database Home

Gamma-Linolenic Acid - Thorne Research

Gamma-linolenic acid (GLA) is an important conditionally essential fatty acid ( EFA). GLA is an .... 73 percent of EPO patients and 80 percent of EPO/ fish oil patients ... Premenstrual Syndrome. A preparation .... References. 1. Lawson LD, Hill ...

Organisation of data - Food and Drug Administration
Premenstrual syndrome & endometriosis . ... References . ..... while borage, black currant and evening primrose oils are used as dietary ... A similar analysis of encapsulated evening primrose oil products identified gamma linolenic acid levels ..... administered orally, rectally, enterally or parenterally is patented in the US [51].

GLA,EVENING PRIMROSE OIL, BORAGE OIL PMS, PATENTS, REFERENCES - Google Search

3. Improve uterine function, and as a result may help women who are trying to conceive.

SCIENTIFIC AND MEDICAL REFERENCE GUIDE FOR: GLA, EPO, EVENING PRIMROSE OIL HEALTH BENEFITS AND APPLICATIONS, IMPROVE UTERINE FUNCTION AND IMPROVE PREGNANCY OUTCOMES

Enhance Overall Fertility with Evening Primrose
Did you know that Evening Primrose Oil (EPO) has a wide array of benefits for fertility? Some studies have shown that it can help reduce PMS symptoms, increase cervical mucous, while reducing inflammation. This is because of its high content of the omega-6 essential fatty acids (EFA’s), Linoleic Acid (LA) and Gamma Linolenic Acid (GLA). This oil comes from the Evening Primrose plant, Oenothera biennis seeds. The seeds are gathered and cold pressed for their oil; the oil is then encapsulated for dietary supplement use.

LA is needed for prostaglandin E and GLA is needed for the synthesis of prostaglandin E. Prostaglandins are not hormones, but rather messengers that act on many different cells; they are also produced in many different areas of the body. Hormones are produced in designated sites in the body (unique to the hormone). One of the many functions of Prostaglandin’s is to help control regulation of hormones as well as control proper cell growth.

Promote and Maintain Hormonal Balance
EPO contains high amounts of LA and GLA, which as explained above, are necessary for prostaglandin function. Prostaglandins are necessary for proper hormonal balance. Getting enough omega-6 EFA’s, such as LA and GLA through EPO supplementation, has been shown to support overall hormonal function within the body. EPO is one of the few plants to contain GLA.

Help for Premenstrual Syndrome (PMS)
Many women face breast tenderness, bloating, acne, water retention, depression, foggy thinking, irritability and headaches prior to their menstrual period; this is known as PMS. Evening Primrose Oil has been used in many studies, though many of those studies are incomplete and some did not use placebo groups. There have been four double-blind, crossover, controlled trials, showing significant positive results in reducing PMS by using 3-4 grams of EPO a day. Results show a marked improvement in the reduction of headaches, foggy thinking, clumsiness, depression, irritability, bloating, and breast tenderness.

If you are a woman who suffers from PMS EPO may be safely combined with other herbs such as Vitex to help alleviate PMS symptoms.

Increase Cervical Mucous
EPO has been used by herbalists for hundreds of years to increase cervical mucous. Cervical fluid is necessary for allowing the sperm to swim freely through the cervix. Some of us have low or no cervical fluid, so it is harder for the sperm to move and there may not be a friendly environment for the sperm to sustain themselves.

The suggested usage for increasing cervical mucous using EPO is initially 500mg, three times a day for a total of 1500mg per day. If you don’t get results in your first cycle, you may want to increase your usage to 3,000 mg a day in your next cycle. If you are actively trying to conceive do not use EPO after ovulation because this herb has an action on the uterus. You can learn more about this below.

How EPO Acts on the Uterus
It is believed that the high levels of LA and GLA’s in Evening Primrose Oil have a direct effect on uterine cells. These contract and relax smooth muscle tissue. This action on the uterus is toning for the uterine muscles in preparation for pregnancy. EPO is NOT suggested for use after ovulation when a woman is trying to conceive. If a woman is pregnant, or thinks she may be pregnant, she should not not use EPO because the uterus may begin to contract. In some women this may lead to pre-term labor or miscarriage; though there is little evidence as such. Nonetheless, it is always best to use caution when using EPO if you think you may be pregnant.

Some of you may have heard that EPO is safe for pregnancy. This is because EPO has been used to prepare (ripen) the cervix, in the last trimester of pregnancy, for hundreds of years by midwives. This is either done by rubbing the cervix with the oil, having the mother use an EPO capsule as a vaginal suppository, or having the mother take it in internally the last few weeks of her pregnancy. This should only be done under the care of a highly qualified midwife or other qualified medical professional.

Suggested Usage of Evening Primrose Oil
General usage is 1500 – 3000 mg one to two times daily. Beginning at the lowest suggested dosage may help to see how the body responds to this supplement, and then increase over time as necessary.

While Actively Trying to Conceive: General usage is 1500 – 3000 mg one to two times daily, from day 1 – 14 in the cycle. Evening Primrose Oil may cause uterine contractions in pregnancy which is why it may be best to not continue it past ovulation (in case of pregnancy) while actively trying to conceive. Post ovulation it may be best to switch to cod liver oil or another omega-3 oil.

Not Actively Trying to Conceive: For those who desire to take EPO to help reduce PMS, for menstrual cramps or general hormone balance support, and are NOT actively trying to conceive, EPO may be taken all month long.

Discontinue Evening Primrose Oil if you suspect or confirm you are pregnant. Consult a qualified practitioner to see if this supplement is right for you.

Who knew a tiny seed could hold amazing fertility health benefits? The Evening Primrose flower is delicate, yellow and very fragrant. It opens in the evening attracting moths basking in the moon’s soft glow. It seems to have a connection to the cool evening and the moon cycle. In the morning as the sun comes up, the flower closes resting during the hot day. It relies on it’s seeds to continue it’s life cycle, as it is a biennial plant. It is one of the few night-blooming plants on earth. This is another special plant that has an affinity to women’s fertility. It holds a dear place in my heart!

References:
1. Women’s Encyclopedia of Natural Medicine; Tori Hudson, ND. McGraw Hill Publishing, 2008

2. wikipedia.org/wiki/prostaglandin

3. Botanical Medicine for Women’s Health; Aviva Romm. Churchill Livingstone, 2010

4. Wise Woman Herbal for the Childbearing Year; Susun S. Weed. Ash Tree Publishing, 1986

Hardy ML. Herbs of special interest to women. J Am Pharm Assoc 200;40:234-42.

Wathes DC, Abayasekara DR, Aitken RJ. Polyunsaturated fatty acids in male and female reproduction. Biol Reprod. 2007 Aug;77(2):190-201. Epub 2007 Apr 18.

Dove D, Johnson P. Oral evening primrose oil: its effect on length of pregnancy and selected intrapartum outcomes in low-risk nulliparous women (abstract). J Nurse Midwifery 1999;44:320-4

Ford I, Cotter MA, Cameron NE, Greaves M. The effects of treatment with alpha-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow, and peripheral nerve conduction in the streptozotocin-diabetic rat. Metabolism. 2001 Aug;50(8):868-75.

GLA, EVENING PRIMROSE OIL, BORAGE OIL, Polyunsaturated fatty acids in male and female reproduction. REFERENCES

1 1 Minireview Polyunsaturated Fatty Acids in Male and ...

Herbal Monographs including Herbal Medicinal Products and Food Supplements

https://www.um.edu.mt/__data/assets/pdf_file/0007/148975/herbalmonographs.pdf

Polyunsaturated fatty acids in male and female reproduction.pdf - Google Search
Polyunsaturated fatty acids in male and female r... [Biol Reprod. 2007] - PubMed - NCBI Polyunsaturated fatty acids in male and female reproduction ...
Adequately powered trials that control for the ratios of different PUFAs consumed are required to determine the extent to which this aspect of our diets does influence our fertility. female reproductive tract, fertility, fish oil, gammalinolenic acid, parturition, prostaglandins, PUFAs, sperm, steroid hormones.

Polyunsaturated Fatty Acids in Male and Female Reproduction http://www.biolreprod.org/content/early/2007/04/18/biolreprod.107.060558.full.pdf
There is surprisingly little published data available to support the contention that GLA
consumption modulates aspects of reproduction. Our studies based on ovine uterine epithelial cells confirmed that addition of GLA in vitro increased both the absolute and proportional PGF1! production and slightly enhanced PGF2! generation, whereas supplemental AA increased PGF2! generation as expected [58]. Both GLA and AA increased overall PGF output significantly but prevented the cells from responding to oxytocin. GLA treatment of isolated rat uterine strips similarly enhanced the output of PGE1 but did not influence the generation of PGE2 or PGF2! [100]. As the PUFAs in both experiments were added directly to the uterine tissues, these data suggest indirectly that elongase activity is present in uterus but that FADS1 expression is low or absent. There is, however, little known about how much PGF1! is produced by normal reproductive tissues with or without GLA supplementation, or what the biological effects of PGF1! are in the context of reproduction. PGF1! was unable to decrease luteal progesterone concentrations in bovine corpora lutea in vitro [101] and it did not cause luteolysis in pregnant rats, although there was evidence of intrauterine growth retardation [102]. This is consistent with its lower affinity for the PGF receptor in comparison with PGF2! [20]. Endometrial biopsies from women taking a 6 month dietary supplement of GLA had a reduced ability to synthesize PGF2! and PGE2 in vitro, but 1-series PGs were not measured [103]. Intravenous infusion of PGF1! to one woman induced labor, but it was estimated to be 10 times less potent that PGE1 in this respect [104]. An evening primrose oil supplement was also evaluated in relation to fertility in the blue fox. It tended to improve the conception rate but the abortion rate also increased, so there was no overall effect on the number of females producing litters [105]. Further studies to determine the relevance of 1-series PGs to reproductive processes are thus urgently required.

REFERENCES
58. Cheng Z, Abayasekara DRE, Wathes DC. The effect of supplementation with n-6 polyunsaturated fatty acids on 1-, 2- and 3- series prostaglandin F production by ovine uterine epithelial cells. Biochim Biophys Acta 2005; 1736:128-135.

100. Chaud M, Franchi AM, Gimeno MF, Gimeno AL. Gamma-linolenic acid improves the constancy of contractions in uteri from sprayed rats and is metabolized to prostaglandin E1 but not to besenoic prostanoids. Prostaglandins 1988;35:95-106.

101. Heath E, Weinstein P, Merritt B, Shanks R, Hixon J. Effects of prostaglandins on the bovine corpus luteum: granules, lipid inclusions and progesterone secretion, Biol Reprod 1983; 29:977- 985.

102. Persaud, TV. Pregnancy and progeny in rats treated with prostaglandin F1!. Prostaglandins Med 1980; 4:101-106.

103. Graham J, Franks S, Bonney RC. In vivo and in vitro effects of gamma-linolenic acid and eicosapentaenoic acid on prostaglandin production and arachidonic acid uptake by human endometrium. Prostaglandins Leukot Essent Fatty Acids 1994; 50:321-329.

104. Caballero A, Garcia Albertos F, Corredera J, Alonso Magan JL, Prostaglandins PGF2!, E1 and F2! and delivery induction by intravenous infusion. Acta Ginecol (Madr) 1974; 25:23-54.

105. Tauson AH, Forsberg M. Effect of evening primrose oil as food supplement on reproduction in the blue fox. Acta Vet Scand 1991; 32:345-351.

106. Challis JR, Sloboda DM, Alfaidy N, Lye SJ, Gibb W, Patel FA, Whittle WL, Newnham JP. Prostaglandins and mechanisms of birth. Reproduction 2002; 124:1-17.

107. Challis JRG, Matthews SG, Gibb W, Lye SJ. Endocrine and paracrine regulation of birth at term and preterm. Endocr Rev 2000; 21:514-550.

4. Fight damage caused by multiple sclerosis. The essential fatty acids in Evening Primrose Oil may minimize inflammation caused by this progressive nerve disorder. Taken over time, the essential fatty acids may also help lead to healthy nerve development
Evening Primrose Oil - Rejuvenative Foods

SCIENTIFIC AND MEDICAL REFERENCE GUIDE FOR: GLA, EPO, EVENING PRIMROSE OIL HEALTH BENEFITS AND APPLICATIONS, FIGHTS INFLAMMATION, MULTIPLE SCLEROSIS, NERVE RELATED DAMAGE AND PROTECTION
Find patient medical information for EVENING PRIMROSE OIL on WebMD including its uses, effectiveness, side effects and safety, interactions, user ratings and ... Raynaud's syndrome, multiple sclerosis (MS), Sjogren's syndrome, cancer, high ... oil for chronic fatigue syndrome (CFS); asthma; nerve damage related to ... Evening primrose oil (EPO) contains an omega-6 essential fatty acid, ... These uses have been tested in humans or animals. ... Gamma-linolenic acid (GLA), one of the components of evening primrose oil, may be helpful ... Multiple sclerosis (MS) ... chemotherapy-induced neuropathy (nerve damage), Crohn's disease, cystic ..Evening Primrose (onethera biennis) is a biennial herb that has gained recognition in the scientific world - because of its precious seed oil. ... experimented with Evening Primrose Oil in treating 40 multiple sclerosis ... Later research has revealed that Evening Primrose Oil is effective for many diseases related .... References".These autoimmune disorders include: fibromyalgia, multiple sclerosis, ... The impact of a nerve fiber injury includes a change in nerve function both at the ... She had no medical insurance, but had been given diabetic testing supplies, insulin and ..... Evening Primrose oil in addition to alpha-linolenic acids (ALA), main source ...

Multiple Sclerosis

In multiple sclerosis (MS), fatty layers around the myelin sheath of the nerves are degenerating. There is also evidence of abnormality in the immune function and EFA metabolism. If symptoms of an illness are relieved by the addition of a certain nutrient, then it can be assumed that the body was deficient in that particular substance. This is often apparent with MS - particularly if the disease is supplemented with oil of primrose early in its development. Deterioration usually stops, although the disease itself is not necessarily cured.

Gamma-linolenic acid (GLA) is an essential fatty acid in the family of Omega-6 fatty acids. “It can help play an important role in treatment of inflammatory conditions including exzema, psoriasis and rheumatoid arthritis (Shutes, n.d., p. 2-91).” Main sources of GLA are human breast milk, black currant seed oil, hemp seed oil, borage seed oil and evening primrose oil. Evening Primrose oil in addition to alpha-linolenic acids (ALA), main source is flax seed oil, and capsaicin have been shown to ease the pain of diabetic peripheral neuropathy as well (Halat & Dennehy, 2003, p. 47).

REFERENCES BORAGE AND EVENING PRIMROSE OIL, GLA. MINIMIZES INFLAMMATION IN MS (MULTIPLE SCLEROSIS) AND ENHANCES NEW NEURAL (NERVES - NEURONS) DEVELOPMENT

GLA, EVENING PRIMROSE OIL, BORAGE OIL, MULTIPLE SCLEROSIS MS,. REFERENCES

Gamma Linolenic Acid: A Natural Anti-inflammatory ... - ShiKai

http://www.shikai.com/publications/GLA-A%20Natural%20AntiInflammatoryAgent.pdf
Primrose (Oenothera biennis; 8 to 12% GLA), borage (Borago officinalis; 18 to 26 % ... diets that supply preformed AA, and by using vegetable oils rich in LA for cooking and ... Alzheimer's disease, cystic fibrosis, multiple sclerosis, ulcerative colitis, ..... Part II of this article, and the accompanying references, will appear in the ...

Gamma-linolenic acid, (GLA; cis-6, cis-9, cis-12-octadecatrienoic acid) is an omega-6 fatty acid that is naturally present in breast milk, beef, pork, chicken, and egg yolk. Over the past four decades, human and animal studies have confirmed anti-inflammatory properties of three commercialized sources of GLA: the oils of evening primrose (Oenothera biennis; 8 to 12% GLA), borage (Borago officinalis; 18 to 26% GLA), and black currant (Ribes nigrum; 13 to 17% GLA), for treating inflammatory conditions including arthritis and psoriasis; and for preventing diabetic neuropathy, high blood pressure, and skin disorders including itching, eczema, and dryness. During this same period, clinical trials have consistently found GLA to be a safe adjunct in the treatment of arthritis and several cancers. Although its exact mechanism of action is not well understood, GLA acts in several ways to exert its effects, including the modulation of eicosanoids (prostaglandins, leukotrienes) and cytokines, and by regulating genes that affect apoptosis and cell growth.

This two-part article reviews the current state of knowledge about the nutritional and health benefits of GLA.
GLA Metabolism
GLA is a functionally essential fatty acid (EFA) because it can correct the symptoms of EFA deficiency (1,2). It is produced endogenously in humans and animals as the first product of metabolism of linoleic acid (LA), an EFA of the omega-6 series. This reaction is catalyzed by the enzyme delta-6-desaturase (D6D) in what is the slowest and rate-limiting step in the metabolic pathway to GLA. Once synthesized, GLA is rapidly elongated to dihomogammalinolenic acid (DGLA) by the enzyme elongase (Fig. 1). Subsequently, DGLA is acetylated and incorporated into cell-membrane phospholipids. A small amount can be converted into arachidonic acid (AA) by the enzyme delta-5-desaturase (D5D).

The rate of formation of AA from DGLA is species- and tissue-specific. A rat metabolizes DGLA to AA in signifi- cant amounts, while humans and other species have limited capacity to form AA from DGLA. Cats are defi- cient in D6D and hence cannot synthesize GLA or the subsequent metabolites derived from from LA (3), and must therefore eat a meat-based diet to obtain DGLA. AA, and other longer-chain metabolites of LA, such as DGLA and AA.
GLA in the Balance of Pro-Versus Anti-inflammatory Cytokines
DGLA competes with AA for cyclooxygenase (COX) and lipoxygenase (LOX) enzymes, and the metabolites of DGLA and AA that are produced by these two types of enzymes—the prostaglandins and leukotrienes, respectively#have actions that oppose each other (Fig. 1). In humans, the activity of D6D declines with age and in various diseases including arthritis, diabetes, hypertension, eczema, and psoriasis. In addition to this, lifestyle factors such as stress; smoking; excessive consumption of alcohol, of linoleic acid, and of saturated and trans-fatty acids; as well as nutritional deficiencies of vitamin B6, zinc, and magnesium inhibit D6D. For example, the populations of industrialized Western nations obtain substantial amounts of LA and AA from their meat-based diets that supply preformed AA, and by using vegetable oils rich in LA for cooking and in salad dressings. The net result of all of the foregoing factors is diminished endogenous synthesis of GLA, with a functional deficit of DGLA that leads to an imbalance in prostaglandin/leukotriene production in which inflammatory prostaglandins derived from AA are produced in excess. Under such circumstances, supplementation with GLA restores balance to the system of inflammatory aversus anti-inflammatory cytokines, and may explain why such supplementation has been found beneficial in these populations.

REFERENCES
17. ZurierRB,RossettiRG,JacobsonEW,etal.gamma-Linolenicacidtreatmentofrheumatoid arthritis. A randomized, placebo-et al. Effects of altering dietary essential fatty acids on requirements for non- steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study. Ann Rheum Dis 47:96-104, 1988.
19. Pullman-MooarS,LaposataM,LemD,etal.Alterationofthecellularfattyacidprofileandthe production of eicosanoids in human monocytes by gamma-linolenic acid. Arthritis Rheum 33: 1526-1533, 1990.
20. SoekenKL.SelectedCAMtherapiesforarthritis-relatedpain:theevidencefromsystematic reviews. Clin J Pain 20:13-18, 2004.
21. ZilberbergM,LevineC,KomaroffE,etal.ClinicalUsesofGamma-LinolencAcid:ASystematic Review of the Literature. 2-22. 2000. Medford, MA, MetaWorks Inc. 10 Presidents Landing Medford, MA. Tel: 781-395-0700.
22. HansenTM,LercheA,KassisV,etal.TreatmentofrheumatoidarthritiswithprostaglandinE1 precursors cis-linoleic acid and gamma-linolenic acid. Scand J Rheumatol 12:85-88 (1983).
23. RemansPH,SontJK,WagenaarLW,etal.Nutrientsupplementationwithpolyunsaturatedfatty acids and micronutrients in rheumatoid arthritis: Clinical and biochemical effects. Eur J Clin Nutr 58:839-845,
2004.

Evening Primrose Oil | University of Michigan Health System
Evening primrose oil (EPO), comes from the seeds of the evening primrose ... Like black currant seed oil and borage oil, EPO contains gamma linolenic acid ( GLA), ..... Linoleic acid and multiple sclerosis: a reanalysis of three double-blind trials. ... in diseases of connective tissue with special reference to scleroderma and to ...

Nutritional Management of Multiple Sclerosis - Consortium ... Nutritional Management of Multiple Sclerosis https://c.ymcdn.com/sites/www.mscare.org/resource/resmgr/Articles/

Article0004_NutritionMgmtMS.pdf
Multiple Sclerosis (MS) is an autoimmune neurological disease .... genated oils may be involved in the etiology and .... Gamma-linolenic acid. Dietary sources: evening primrose oil, borage oil .... refer to a comprehensive reference such as MS mainly affects young adults, with peak incidence at age 30. Although the incidence in women is higher than in men (3:2 ratio), men tend to experience a more debilitating form of the disease. Additionally, MS is twice as likely to occur in Caucasians than Blacks, while the disease is rarely reported in populations of oriental origin.4,5 Of the various types of MS, relapsing-remitting MS (RRMS) affects approximately 85% of all patients.5 Patients diagnosed with RRMS display a characteristic cyclical pattern of the disease characterized by periods of remission, followed by intervals of relapses that present as an acute ‘flare-up’ or ‘exacerbation’. The course of RRMS varies greatly between individuals, however up to 75% of these patients can progress to the secondary progressive form of the disease (SPMS). SPMS is a more debilitating form of the disease defined by a gradual, continuous decline in neurological function, with or without further relapses.6

Multiple Sclerosis: Oils rich in essential fatty acids, such as evening primrose oil, have been investigated in the treatment of multiple sclerosis [Ref 68. Multiple sclerosis patients taking safflower oil supplements for two years had less frequent and less severe relapses compared to a control group taking olive oil [Ref 17. improved mitogenic response was noted in lymphocytes from multiple sclerosis patients receiving evening primrose oil supplements for 85 days [Ref 17.

REFERENCES
1. E J Field & G Joyce, (1978), Effect of prolonged ingestion of y-linolenic acid by multiple scelrosis patients. Eur. Neurol., l7, p67
2. JECFA, FAO food and nutrition paper No 57 - Fats and oils in human nutrition report of a joint expert consultation, WHO, Geneva pp 3-7, 49-55, 81-88 & 89-94
Gamma-linolenic Acid - Willis-Knighton Health System http://healthlibrary.epnet.com/print.aspx?token=d168334d-e19b-432f-a759- e5d7d5fc1440&chunkiid=21587
References ... Borage oil is the richest supplemental source (17% to 25% GLA), followed by black currant oil ... Borage and evening primrose are the most common sources used in studies. ... way),25, 26weight loss,27,28ulcerative colitis,30,82kidney stones,19,20,31,32multiple sclerosis, 33 ...
Supplement Forms/Alternate Names
Omega-6 Oil(s); Omega-6 Fatty Acids; Sources of GLA Include: Black Currant Seed Oil, Borage Oil, Evening Primrose Oil

Supplement Forms/Alternate Names

• Omega-6 Oil(s); Omega-6 Fatty Acids; Sources of GLA Include: Black Currant Seed Oil, Borage Oil, Evening Primrose Oil Principal Proposed Uses
• Diabetic Neuropathy
Other Proposed Uses • 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 Probably Not Effective Uses

• Eczema

33. Horrobin DF. Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil. Med Hypotheses. 1979;5:365-378. 34. Field EJ, Joyce G. Effect of prolonged ingestion of gamma-linolenate by MS patients. Eur Neurol.

1978;17:67-76. 35. Bates D. Dietary lipids and multiple sclerosis. Ups J Med Sci Suppl. 1990;48:173-187. 36. Horrobin DF. Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil. Med Hypotheses. 1979;5:365-378.

Evening Primrose - Campbell University
Studies have shown that evening primrose oil can help lower blood .... No side effects were registered with the applied doses.22 Earlier, in a similar study using borage oil as a source of GLA for 12 weeks at 1.1 g/day, GLA ... Multiple Sclerosis : Some studies have shown an improvement in MS patients whose ... References
Multiple Sclerosis: Some studies have shown an improvement in MS patients whose diet was supplemented with EFAs. MS is associated with abnormalities in EFA metabolism and lymphocyte function.29 Patients with MS have low EFAs in their blood cells, a deficiency in PGE1 synthesis and abnormal activation of T lymphocytes against self proteins. Although a primrose oil- or linolenic acid-rich diet improved symptoms of some patients, it was more effective in combination with colchicine. In France, the effects of EPO were studied on platelets of MS patients. While there was not a significant effect on platelets, thrombin-induced platelet aggregation was higher in MS patients after oil treatment.30 It is too early to conclude that MS patients cannot be helped by EPO treatment. Most studies suggest that combined drug therapy including EPO may benefit MS patients.

REFERENCES

29. Horrobin, D.F. Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil. Med. Hypothesis 1979;5(3):365-378.
30. Mcgregor, L., Smith, A.D. et al. Effects of dietary linoleic acid and gamma linolenic acid on platelets with multiplesclerosis. Acta Neurol. Scand. 1989;80(1):23-27.

Nutritional Approach to Support MS - Brighter Day Natural Foods
Multiple Sclerosis Society ... nervous system and in addition causes damage to the actual nerve body (axon). ... DGLA (GLA from Primrose Oil, Borage Oil or Black Currant Oil is ... 5- It decreased inflammation response, helping to control arthritis ..... References:.
Some facts about MS – Statistics show that the occurrence rate of MS is much higher in the higher latitudes north and south of the equator, where the occurrence rate is 50 – 100 per 100,000 vs. in the tropics the occurrence rate is only 5 to 10 per 100,000. Japan is one exception to the rule where it is uncommon. In Japan the diet is high in Fish, seaweed, seeds, and soy foods. Because of the environmental relationship between latitude and MS, it is hypothesized that a crucial factor is lack of ultraviolet light-induced vitamin D3 synthesis in the skin, and that vitamin D3 acts as a selective immune system regulator that works to inhibit autoimmune disease; therefore in low sunlight conditions, insufficient protective amounts of D3 are manufactured. The authors of the research about vitamin D suggest that further research in this area may suggest the possibility that MS could be prevented in genetically susceptible people through the use of supplemental vitamin D3. (D3 is the natural vitamin D found in fish oil).
The direct relationship between MS mortality and dietary fat, especially saturated fats and animal fats was eloquently described in an extensive study involving 36 countries appearing in the American Journal of Epidemiology in 1995. The MS rate was significantly correlated repeatedly with one or another parameter reflecting the consumption of animal fat, animal protein, and meat from non-marine mammals. These deficiencies in polyunsaturated fats were thought to interfere with the elongation of fats that compose the nerve cell membrane and impair formation of normal myelin. Swanks 1952 study of the direct correlation between the incidence of MS in various districts of Norway and the amount of dairy products consumed by the populations of those specific regions also pointed in the same direction.
MS, like many other diseases of modern civilization, is a disease quite simply caused by an overactive and misdirected immune system. The immune system reacts against protective insulating cover (myelin) of the nerves of the central nervous system and in addition causes damage to the actual nerve body (axon). White blood cells called lymphocytes attack myelin as if it were some invading organisms or foreign substance.

When the body’s immune system fails to control itself and lymphocytes attack normal body tissue, the disease process that ensues is called an autoimmune disease.
In MS, lymphocytes somehow receive inappropriate signals directing them to attack the brain and spinal cord. The activity of the lymphocytes is regulated by a group of chemicals called prostaglandins. Prostaglandins (PGs) - Prostaglandins (PGs) are extremely powerful, they affect every aspect of our health through their hormone-like effects, and our body makes them from essential fatty acids (EFAs). Functionally, PGs are short-lived, hormone-like chemicals that regulate cellular activities on a moment-to-moment basis. Prostaglandins fall into 3 families or series - PG-1, PG-2, & PG-3, depending on which fatty acid they were made from. Series 1 and 2 prostaglandins come from the omega 6 family of fats, with the EFA linoleic acid (LA) as the starting material. Series 3 prostaglandins comes from omega 3 fatty acids –the most important being EPA from Fish Oils. DHA from fish oils are also important. It may be possible to reduce the over activity of immune function in MS by providing dietary sources of the essential fats - part from the omega 6 and omega 3 fatty acid groups so the body has the ability to produce more of the “good prostaglandins” – groups 1 and 3 and thus, control of lymphocyte activity, which plays a critical role in MS.

Functions of Prostaglandins: The role of prostaglandins from groups 1 is to moderate or tone down immune activity and inflammation. Prostaglandins in group 2 on the other hand signal the lymphocytes to become more active in the immune response and induce inflammatory activity. In normal situationsprostaglandins in group 2 activate the white blood cells, but this activity is kept in check by prostaglandins from groups 1 and 3. Series 1 – prostaglandins made from DGLA (GLA from Primrose Oil, Borage Oil or Black Currant Oil is the direct precursor to DGLA)– the most famous member of the series is prostaglandin E1, or PGE1. PGE1 has important functions in several tissues in our body:

1- It keeps blood platelets from sticking together, and thereby helps prevent heart attacks and strokes caused by blood clots in our arteries.

2. 2-  In our kidneys it helps remove sodium and excess fluid from our body.

3. 3-  It relaxes blood vessels, improving circulation, lowering blood pressure and relieving angina.

4. 4-  It may slow down cholesterol production.

5. 5-  It decreased inflammation response, helping to control arthritis

6. 6-  It makes insulin work more effectively, helping diabetics

7. 7-  It improves nerve function, producing a sense of well-being.

8. 8-  It regulates calcium metabolism.

9. 9-  It improves the functioning of T-cells in our immune system, which destroy foreign molecules and cells.

10- It prevents the release of AA (Arachidonic Acid) from our cell membranes.

The cerebrospinal fluid, a liquid covering the brain and spinal cord, has been shown to contain significalntly less linoleic acid in MS patients compared to controls. Linoleic acid (GLA-Gamma Linoleic Acid is derived from this) is the precursor to the prostaglandin 1 group, so its deficiency could allow overactivation of the immune system. Prostaglandins 1 and 3 calm the immune system while prostaglandin 2 is pro-inflammatory. This follows the epidemiological studies describing diet and risk for MS.

Diets based on animal fats, dairy products and animal proteins and alcohol favor prostaglandin 2 formation and are associated with higher rates of MS, more frequent exacerbations, and higher MS-related mortality rates. Diets rich in vegetables, nuts seeds and fish favor the production of prostaglandins 1 and 3, and are associated with lower rates of MS.

Doctors who analyzed the data on linoleic acid supplementation stated in the journal Neurology. We have reanalyzed the data from 3 double-blind trials of linoleic acid in the treatment of MS. Our most important finding is that patients with minimal or no disability at entry had a significantly smaller increase in disability over the course of the trials than did control patients. Patients treated with linoleic acid did not have a significant change from the beginning of treatment to the end of the trial, whereas control patients had a significant increase in disability.

The most important precursor of prostaglandin 1 – critically important in controlling the immune system is GLA – Gamma linoleic acid. It is the critical precursor and is found in Evening Primrose Oil, Black Currant Oil and Borage Oil. GLA directly influences the production of prostaglandin 1.
Prostaglandin 3 is also very important in reducing the overactive immune response in MS. While much less potent than prostaglandin 1, it nevertheless plays and important role by reducing the activity of inflammation enhancing prostaglandin 2. Flaxseed Oil is 50 – 60 % linolenic acid – but it must be converted into EPA and DHA which is a fairly inefficient process. Under the best of circumstances humans convert only about 2.7% of linolenic acid to EPA/DHA. Vit C, B3, B6, Magnesium and Zinc must be present to convert it. Consumption of Fish Oils is the most effective way to get EPA/DHA in the diet. These essential fatty acids should be kept refrigerated to prevent rancidity. The risk of consuming more fish increases the potential for mercury toxicity (mercury is a neurotoxic heavy metal). So consuming high quality purified fish oils that are mercury free is the safest way to get these essential fats in the diet. The fish that are lowest in mercury according to research done by the EPA and U.S. Department of Health and Human Services and higher in the Omega 3 fatty acids EPA/DHA are Anchovies, Salmon – canned, fresh and frozen (wild salmon are lower in pesticide residues and higher in the beneficial essential fatty acids EPA/DHA look for the word wild on all canned salmon, the vast majority of fresh salmon is farmed), Sardines, Cod, Croaker, Haddock, Herring, Atlantic Mackerel, Pollack, light canned tuna – not albacore-fresh tuna is high. Other fish rated high in mercury are Gulf of Mexico Mackerel, King Mackerel, Swordfish, Shark and Tile Fish. www.cfsan.fda.gov/ ~frf/sea-mehg.html)

Essential Fatty Acid Supplement – Udo’s Choice Essential Fatty Acid Blend is a blend of Omega 6 and 3’s with trace amounts of 9 – the oils are produced without damaging any of the essential fatty acids. Used in Salads, smoothies, soups (added after cooking) are a way to get the highest quality oils in the diet.
Alpha Lipoic Acid – is emerging as one of the most powerful brain antioxidants available. Readily passing the blood brain barrier, lipoic acid is a key nutrient in all the neurodegenerative disorders. Is a key nutrient in his protocol for MS.

Ginkgo Biloba – Ginkgo is useful in virtually all the neurodegenerative conditions due not only to its ability to reduce the activity of free radicals, but also because of its potent effects enhancing neurotransmission, the process by which neurons are able to communicate with each other. NAC – N-acetyl-cysteine - enhances the production of glutathione, one of the most important brain antioxidants, NAC is a key supplement in MS and all other neurodegenerative conditions. Phosphatidylserine PS – plays a major role in preserving function of the membrane surrounding the energy producing mitochondria. It enhances the ability of nerves to transmit information.

CoQ10 – the critical role of adequate CoQ10 in facilitating cellular energy production.

GLA –(Gamma Linolenic Acid) from Borage, Black Currant or Primrose Oil should be 300mg a day.

Gamma-Linolenic Acid (GLA) - NYU Langone Medical Center

Borage and evening primrose are the most common sources used in studies. ... 19,20,31,32multiple sclerosis , 33,36 and increasing the effectiveness of the ..

Gamma-linolenic acid (GLA) found in evening primrose oil and borage oil 30-33,94 EVENING PRIMROSE OIL: Uses, Side Effects, Interactions ...
FPO IP Research & Communities http://www.thorne.com/altmedrev/.fulltext/9/1/70.pdf

Diabetic Neuropathy

GLA has shown promising results in the treatment of diabetic complications in several human and animal studies.52-55 In a double-blind, placebo-controlled, parallel trial of 111 patients with mild diabetic neuropathy, patients were given either 480 mg GLA or placebo daily.56 After one year, GLA-treated patients showed favorable improvement in all parameters, including hot and cold threshold, sensation, tendon reflexes, and muscle strength compared to placebo.

In a smaller, double-blind, placebo-con- trolled trial of 22 patients with distal diabetic neuropathy, similar results were achieved at a dose of 360 mg GLA daily for six months.57

Evening Primrose Oil Uses, Benefits & Dosage - Drugs.com Herbal Database
27. Namaka M, Crook A, Doupe A, et al. Examining the evidence: complementary adjunctive therapies for multiple sclerosis. Neurol Res . 2008;30(7):710-719.

28. Schwarz S, Leweling H. Multiple sclerosis and nutrition. Mult Scler . 2005:11(1): 24-32.

29. Dworkin RH, Bates D, Millar JH, Paty DW. Linoleic acid and multiple sclerosis: a reanalysis of three double-blind trials. Neurology . 1984;34(11):1441-1445.

30. McGregor L, Smith AD, Sidey M, Belin J, Zilkha KJ, McGregor JL. Effects of dietary linoleic acid and gamma linolenic acid on platelet of patients with multiple sclerosis. Acta Neuro Scand . 1989;80(1):23-27.

31. Horrobin DF. Multiple sclerosis: the rational basis for treatment with colchicine and evening primrose oil. Med Hypothesis . 1979;5(3):365-378.

32. Namazi MR. The beneficial and detrimental effects of linoleic acid on autoimmune disorders. Autoimmunity . 2004;37(1):73-75.

These autoimmune disorders include: fibromyalgia, multiple sclerosis, ... The impact of a nerve fiber injury includes a change in nerve function both at the ... She had no medical insurance, but had been given diabetic testing supplies, insulin and ..... Evening Primrose oil in addition to alpha-linolenic acids (ALA), main source ...

Belch J, Hill A. Evening primrose oil and borage oil in rheumatologic conditions. Am J Clin Nutr 2000;71:352S-6S.

Belch JJ, Ansell D, Madhok R, et al. Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: A double blind placebo controlled study. Ann Rheum Dis 1988;47:96-104.

Erasmus, Udo Fats and Oils, (Alive books, 1986)
Horrobin, David F. Essential Fatty Acids: A Review (Clinical Uses of Essential Fatty

Acids, 1982)

Moore, Michael Medicinal Plants of the Mountain West, (The museum of New Mexico Press, 1979)

Susan G. Komen® | Understanding Breast Cancer | Evening primrose oil
Multiple sclerosis (MS)
It is theorized that primrose oil may be helpful in patients with MS based on laboratory studies. Limited evidence is available in humans.

OTHER VALUED REFERENCES FOR EPO - EVENING PRIMROSE OIL APPLICATIONS AND BENEFITS
MEDICAL AND SCIENTIFIC REFERENCES RESEARCH OF THE BENEFITS AND APPLICATIONS OF EPO , EVENING PRIMROSE OIL, GLA

Mastalgia
Animal data
The widespread consumption of evening primrose oil as a supplement and the availability of clinical data make data from animal studies largely irrelevant.

Clinical data

There is little evidence to support the efficacy of evening primrose oil in treatment of mastalgia, with most trials finding no advantage over placebo. 14 , 15 , 16 , 17 A meta- analysis of clinical trials found no evidence of effect in pain relief, with a mean pain score difference of -2.78 (95% confidence interval, -7.97 to 2.4). 18

Menopause-associated vasomotor symptoms/premenstrual syndrome Animal data
The widespread consumption of evening primrose oil as a supplement and the availability of clinical data make data from animal studies largely irrelevant.

Clinical data

A number of reviews and randomized clinical trials found no evidence of benefit with evening primrose oil use for menopausal vasomotor symptoms or premenstrual syndrome. 19 , 20 , 21 , 22 , 23 , 24 , 25 In 2004, the North American Menopause Society did not support the use of evening primrose oil for menopausal vasomotor symptoms given the lack of efficacy data, but this has not been recently reviewed. 26

Multiple sclerosis
Animal data
The widespread consumption of evening primrose oil as a supplement and the availability of clinical data make data from animal studies largely irrelevant.

Clinical data

Despite a seemingly valid theoretical basis for the use of evening primrose oil in multiple sclerosis, there is a lack of evidence to substantiate its use. 27 A review of 3 trials suggested an effect with a slower progression of disability and improved relapse (severity and duration) scores, but a randomized, controlled trial, not included in the review, showed no effect. 28 , 29 , 30 , 31 , 32 No new trials have been published since the 1980s.

McKendry RJ. Treatment of Sjogren's syndrome with essential fatty acids, pyridoxine and vitamin C. Prostaglandins Leukot Med 1982;8:403-8.

Menendez JA, Colomer R, Lupu R. Omega-6 polyunsaturated fatty acid gamma- linolenic acid (18:3n-6) is a selective estrogen-response modulator in human breast cancer cells: gamma-Linolenic acid antagonizes estrogen receptor-dependent transcriptional activity, transcriptionally represses estrogen receptor expression and synergistically enhances tamoxifen and ICI 182,780 (Faslodex) efficacy in human breast cancer cells. Int J Cancer 2004;10;109:949-54.

Menendez JA, del Mar Barbacid M, Montero S, et al. Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells. Eur J Cancer 2001;37:402-13.

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.

Oxholm P, Manthorpe R, Prause JU, Horrobin D. Patients with primary Sjogren's syndrome treated for two months with evening primrose oil. Scan J Rheumatol 1986;15:103-8.

Pye JK, Mansel RE, Hughes LE. Clinical experience of drug treatments for mastalgia. Lancet 1985;2:373-7.

Rose DP, Connolly JM, Liu XH. Effects of linoleic acid and gamma-linolenic acid on the growth and metastasis of a human breast cancer cell line in nude mice and on its growth and invasive capacity in vitro. Nutr Cancer 1995;24:33-45.

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. Br J Dermatol 1987;117:11-9.

Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements: a 5- year toxicological study (1991-1995). Drug Saf 1997;17:342-56.

Shuster J. Black cohosh root? Chasteberry Tree? Seizures! Hosp Pharm 1996;31:1553-4.

Sinn N, Bryan J. Effect of Supplementation with Polyunsaturated Fatty Acids and

Micronutrients on Learning and Behavior Problems Associated with Child ADHD. J Dev Behav Pediatr 2007;28:82-91.

Stordy BJ. Dark adaptation, motor skills, docosahexaenoic acid, and dyslexia. Am J Clin Nutr 2000;71:323S-6S.

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.

Verhoeven MO, van der Mooren MJ, van de Weijer PH, et al. CuraTrial Research Group. Effect of a combination of isoflavones and Actaea racemosa Linnaeus on climacteric symptoms in healthy symptomatic perimenopausal women: a 12-week randomized, placebo-controlled, double-blind study. Menopause 2005;12:412-20.

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;99:112-6.

Wedig KE, Whitsett JA. Down the primrose path: petechiae in a neonate exposed to herbal remedy for parturition. J Pediatr 2008;152:140, 140.e1.

Whitaker DK, Cilliers J, de Beer C. Evening primrose oil (Epogam) in the treatment of chronic hand dermatitis: disappointing therapeutic results. Dermatology 1996;193:115-20.

Williams HC. Evening primrose oil for atopic dermatitis. BMJ 2003;327:1358-9.

BREAST MASTALGIA
14. Goyal A, Mansel RE, Efamast Study Group. A randomized multicenter study of gamolenic acid ( Efamast ) with and without antioxidant vitamins and minerals in the management of mastalgia. Breast J . 2005;11(1):41-47.

15. Qureshi S, Sultan N. Topical nonsteroidal anti-inflammatory drugs versus oil of evening primrose in the treatment of mastalgia. Surgeon . 2005;3(1):7-10.

16. Blommers J, de Lange-de Klerk ES, Kuik DJ, Bezemer PD, Meijer S. Evening primrose oil and fish oil for severe chronic mastalgia: a randomized, double-blind, controlled trial. Am J Obstet Gynecol . 2002;187(5):1389-1394.

17. Pruthi S, Wahner-Roedler DL, Torkelson CJ, et al. Vitamin E and evening primrose oil for management of cyclical mastalgia: a randomized pilot study. Altern Med Rev . 2010;15(1):59-67.

18. Srivastava A, Mansel RE, Arvind N, et al. Evidence-based management of mastalgia: a meta-analysis of randomised trials. Breast . 2007;16(5):503-512.

Bamford JT, Gibson RW, Renier CM. Atopic eczema unresponsive to evening primrose oil (linoleic and gamma-linolenic acids). J Am Acad Dermatol 13.6 (1985): 959–65. Barcelli UO et al. Beneficial effects of polyunsaturated fatty acids in partially nephrectomized rats. Prostaglandins 32.2 (1986): 211–19.

Barcelli UO et al. A diet containing n-3 and n-6 fatty acids favorably alters the renal phospholipids, eicosanoid synthesis and plasma lipids in nephrotic rats. Lipids 23.11 (1988): 1059–63.
Barcelli UO et al. High linoleic acid diets ameliorate diabetic nephropathy in rats. Am J Kidney Dis 16.3 (1990): 244–51.

Belch JJ, Hill A. Evening primrose oil and borage oil in rheumatologic conditions. Am J Clin Nutr 71 (Suppl 1) (2000): 352S–6S.
Belch JJ et al. Evening primrose oil (Efamol) in the treatment of Raynaud’s phenomenon: a double blind study. Thromb Haemost 54.2 (1985): 490–4.

Belch JJ et al. Effects of altering dietary essential fatty acids on requirements for non- steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study. Ann Rheum Dis 47.2 (1988): 96–104.
Berth-Jones J, Graham-Brown RA. Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis. Lancet 341.8860 (1993): 1557–60.

Blommers J et al. Evening primrose oil and fish oil for severe chronic mastalgia: a randomized, double-blind, controlled trial. Am J Obstet Gynecol 187.5 (2002): 1389– 94.
Brush MG et al. Abnormal essential fatty acid levels in plasma of women with premenstrual syndrome. Am J Obstet Gynecol 150.4 (1984): 363–6.

Brzeski M, Madhok R, Capell HA. Evening primrose oil in patients with rheumatoid arthritis and side-effects of non-steroidal anti-inflammatory drugs. Br J Rheumatol 30.5 (1991): 370–2.
Budeiri D, Li Wan PA, Dornan JC. Is evening primrose oil of value in the treatment of premenstrual syndrome? Control Clin Trials 17.1 (1996): 60–8.
Businco L et al. Breast milk from mothers of children with newly developed atopic eczema has low levels of long chain polyunsaturated fatty acids. J Allergy Clin Immunol 91.6 (1993): 1134–9.
Charnock JS. Gamma-linolenic acid provides additional protection against ventricular fibrillation in aged rats fed linolenic acid rich diets. Prostaglandins Leukot Essent Fatty Acids 62.2 (2000): 129–34.
Chen YC, Chiu WT, Wu MS. Therapeutic effect of topical gamma-linolenic acid on refractory uremic pruritis. Am J Kidney Dis 48.1 (2006): 69–76.
Chenoy R et al. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ 308.6927 (1994): 501–3.
Claassen N et al. Supplemented gamma-linolenic acid and eicosapentaenoic acid influence bone status in young male rats: effects on free urinary collagen crosslinks, total urinary hydroxyproline, and bone calcium content. Bone 16 (Suppl 4) (1995): 385S–92S.
D’Almeida A et al. Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, and versus placebo in preventing pre-eclampsia. Women Health 19.2–3 (1992): 117–31. Das UN. A defect in delta 6 and delta 5 desaturases may be a factor in the initiation and progression of atherosclerosis. Prostaglandins Leukot Essent Fatty Acids 76 (2007): 251–68.

Dasgupta S, Bhattacharyya DK. Dietary effect of gamma-linolenic acid on the lipid profile of rat fed erucic acid rich oil. J Oleo Sci 56.11 (2007): 569–77.

Deferne J, Leeds A. The antihypertensive effect of dietary supplementation with a 6- desaturated essential fatty acid concentrate as compared with sunflower seed oil. J Hum Hypertens 6.2 (1992): 113–19.
Everett DJ, Perry CJ, Bayliss P. Carcinogenicity studies of Efamol evening primrose oil in rats and mice. Med Sci Res 16.16 (1988): 865–6.

Fan Y-Y, Chapkin RS. Mouse peritoneal macrophage prostaglandin E1 synthesis is altered by dietary !-linolenic acid. J Nutr 122 (1992): 1600–6.
Fan Y-Y, Chapkin RS. Importance of dietary !-linolenic acid in human health and nutrition. J Nutr 128.9 (1998): 1411–14.

Fan Y-Y, Ramos KS, Chapkin RS. Dietary !-linolenic acid suppresses aortic smooth muscle cell proliferation and modifies atherosclerotic lesions in apolipoprotein E knockout mice. J Nutr 131 (2001): 1675–81.
Ford I et al. The effects of treatment with alpha-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow and peripheral nerve conduction in the streptozotocin-diabetic rat. Metabolism 50.8 (2001): 868–75.

Fukushima M et al. Comparative hypocholesterolemic effects of six dietary oils in cholesterol-fed rats after long-term feeding. Lipids 32.10 (1997): 1069–74.
Fukushima et al. Effects of diets enriched in n-6 or n-3 fatty acids on cholesterol metabolism in older rats chronically fed a cholesterol-enriched diet. Lipids 36.3 (2001): 261–6.

Gateley CA et al. Drug treatments for mastalgia: 17 years experience in the Cardiff Mastalgia Clinic. J R Soc Med 85.1 (1992a): 12–15.
Gateley CA et al. Plasma fatty acid profiles in benign breast disorders. Br J Surg 79.5 (1992b): 407–9.

Geppert J et al. Co-supplementation of healthy women with fish oil and evening primrose oil increases plasma docosahexaenoic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid levels without reducing arachidonic acid concentrations. Br J Nutr 99.2 (2008): 360–9.

Godfrey DG et al. Effects of dietary supplementation on autoimmunity in the MRL/LPR mouse: a preliminary investigation. Ann Rheum Dis 45.12 (1986): 1019–24.
Halat KM, Dennehy CE. Botanicals and dietary supplements in diabetic peripheral neuropathy. J Am Board Fam Pract 16 (2003): 47–57.

Hansen TM et al. Treatment of rheumatoid arthritis with prostaglandin E1 precursors cis-linoleic acid and gamma-linolenic acid. Scand J Rheumatol 12.2 (1983): 858. Henz BM et al. Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema. Br J Dermatol 140.4 (1999): 685–8.

Hoare C et al. Systematic review of treatments for atopic eczema. Health Technol Assess 4.37 (2000): 25–8.
Hoffmann P et al. Cardiovascular effects of antihypertensive drugs as affected by dietary polyunsaturates. Biomedica Biochimica Acta 43.8–9 (1984): S195–8. Horrobin DF. The role of essential fatty acids and prostaglandins in the premenstrual syndrome. J Reprod Med 28.7 (1983): 465–8.

Horrobin DF. Essential fatty acids, prostaglandins, and alcoholism: an overview.

Alcohol Clin Exp Res 11.1 (1987): 2–9.
Horrobin DF. Gamma linolenic acid. Rev Contemp Pharmacother 1.1 (1990): 1–45. Horrobin DF. Essential fatty acid metabolism and its modification in atopic eczema. Am J Clin Nutr 71 (Suppl 1) (2000): 367S–72S.
Jamal GA, Carmichael H. The effect of gamma-linolenic acid on human diabetic peripheral neuropathy: a double-blind placebo-controlled trial. Diabet Med 7.4 (1990): 319–23.
Jantti J et al. Evening primrose oil and olive oil in treatment of rheumatoid arthritis. Clin Rheumatol 8.2 (1989): 238–44.
Joy CB, Mumby-Croft R, Joy LA. Polyunsaturated fatty acid (fish or evening primrose oil) for schizophrenia. Cochrane Database Syst Rev 2 (2000): CD001257.
Julu PO. Latency of neuroactivity and optimum period of treatment with evening primrose oil in diabetic rats. J Lipid Mediat Cell Signal 13.2 (1996): 99–113.
Khan F et al. The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects. Cardiovasc Res 59.4 (2003): 955–62.
Khoo SK, Munro C, Battistutta D. Evening primrose oil and treatment of premenstrual syndrome. Med J Aust 153.4 (1990): 189–92.
Kitz R et al. Impact of early dietary gamma-linolenic acid supplementation on atopic eczema in infancy. Pediatr Allergy Immunol 17.2 (2006): 112–17.
Kollias J et al. Effect of evening primrose oil on clinically diagnosed fibroadenomas. Breast 9.1 (2000): 35–6.
Kunkel SL et al. Suppression of chronic inflammation by evening primrose oil. Prog Lipid Res 20 (1981a): 885–8.
Kunkel SL et al. Modulation of inflammatory responses by prostaglandins and essential fatty acids. Fed Proc 40.3 (1981b): 632.
Leeds A, Gray I, Ahmad M. Effects of n-6 essential fatty acids as evening primrose oil in mild hypertension. In: Horrobin D (ed). Omega-6 essential fatty acids: pathophysiology and roles in clinical medicine. New York: Alan R Liss, 1990, pp 157– 71.
Mertin J. Omega-6 and omega-3 polyunsaturates and the immune system. Br J Clin Pract Suppl 31 (1984): 111–14.
Mills DE et al. Dietary N-6 and N-3 fatty acids and salt-induced hypertension in the borderline hypertensive rat. Lipids 24.1 (1989): 17–24.
Morse PF 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 121.1 (1989): 75–90.
National Health and Medical Research Council. Nutrient Reference Values for Australia and New Zealand. Canberra: Department of Health and Ageing, 2005, pp 87–94.
North American Menopause Society. Treatment of menopause-associated vasomotor symptoms: position statement. Menopause 11.1 (2004): 11–33.
Nyalala JO et al. Hypertriglyceridemia and hypercholesterolemia: effects of drug treatment on fatty acid composition of plasma lipids and membranes. Prostaglandins Leukot Essent Fatty Acids 78.4–5 (2008): 271–80.
Oliwiecki S, Burton JL. Evening primrose oil and marine oil in the treatment of psoriasis. Clin Exp Dermatol 19.2 (1994): 127–9.
Papanikolaou N. Alteration of mercuric chloride-induced autoimmune glomerulonephritis in brown-Norway rats by herring oil, evening primrose oil and

OKY-046 a selective TXA-synthetase inhibitor. Prostaglandins Leukot Med 27.2–3 (1987): 129–49.
Pritchard GA, Jones DL, Mansel RE. Lipids in breast carcinogenesis. Br J Surg 76.10 (1989): 1069–73.

Qureshi S, Sultan N. Topical nonsteroidal anti-inflammatory drugs versus oil of evening primrose in the treatment of mastalgia. Surgeon 3.1 (2005): 7–10.
Soeken KL. Selected CAM therapies for arthritis-related pain: the evidence from systematic reviews. Clin J Pain 20.1 (2004): 13–18.

Spinella M. Herbal medicines and epilepsy: the potential for benefit and adverse effects. Epilepsy Behav 2.6 (2001): 524–32.
Srivastava A et al. Evidence-based management of mastalgia: a meta-analysis of randomized trials. The Breast 16 (2007): 503–12.

Stolyhwo Gofron M et al. Two weeks supplementation with olive oil and evening primrose oil similarly affect plasma lipid level in men with coronary artery disease. Conference abstract (2006).
Stonemetz D. A review of the clinical efficacy of evening primrose. Holist Nurs Pract 22.3 (2008): 171–4.

Takwale A et al. Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial. BMJ 327 (2003): 1385–7.
Tate GA et al. Suppression of monosodium urate crystal-induced acute inflammation by diets enriched with gamma-linolenic acid and eicosapentaenoic acid. Arthritis Rheum 31.12 (1988): 1543–51.

Tomlinson DR et al. Essential fatty acid treatment-effects on nerve conduction, polyol pathway and axonal transport in streptozotocin diabetic rats. Diabetologia 32.9 (1989): 655–9.
Ty-Torredes KA. The effect of oral evening primrose oil on Bishop score and cervical length among term gravidas. Conference Abstract. 2006

Vaddadi KS. The use of gamma-linolenic acid and linoleic acid to differentiate between temporal lobe epilepsy and schizophrenia. Prostaglandins Med 6.4 (1981): 375–9. Van Gool 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 77.4 (2003): 943–51.

Van Gool CJ, Zeegers MP, Thijs C. Oral essential fatty acid supplementation in atopic dermatitis – a meta-analysis of placebo-controlled trials. Br J Dermatol 150.4 (2004): 728–40.
Varma PK, Persaud TV. Protection against ethanol-induced embryonic damage by administering gamma-linolenic and linoleic acids. Prostaglandins Leukot Med 8.6 (1982): 641–5.

Veale DJ et al. A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis. Br J Rheumatol 33.10 (1994): 954–8.
Venter CP, Joubert PH, Booyens J. Effects of essential fatty acid on mild to moderate essential hypertension. Prostaglandins Leukot Essent Fatty Acids 33.1 (1988): 49–51. Wagner W, Nootbaar-Wagner U. Prophylactic treatment of migraine with gamma- linolenic and alpha-linolenic acid. Cephalalgia 17.2 (1997): 127–30.

References:

Aman MG, Mitchell EA, Turbott SH. The effects of essential fatty acid supplementation by Efamol in hyperactive children. J Abnorm Child Psychol 1987;15:75-90.

Anon. EPOGAM Capsules. G.D. Searle (South Africa) (Pty) Ltd. January 1990. Available at: http://home.intekom.com/pharm/searle/epogm.html

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;25:222-8.

Behan PO, Behan WM, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand 1990;82:209-16.

Belch J, Hill A. Evening primrose oil and borage oil in rheumatologic conditions. Am J Clin Nutr 2000;71:352S-6S.

Belch JJ, Ansell D, Madhok R, et al. Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: A double blind placebo controlled study. Ann Rheum Dis 1988;47:96-104.

Bendich A. The potential for dietary supplements to reduce premenstrual syndrome (PMS) symptoms. J Am Coll Nutrition 2000;19:3-12.

Berth-Jones J, Graham-Brown RA. Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis. Lancet 1993;341:1557-60.

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.

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;187:1389-94.

Bordoni A, Biagi PL, Masi M, et al. Evening primrose oil (Efamol) in the treatment of children with atopic eczema. Drugs Exp Clin Res 1988;14:291-7.

Budeiri D, Li Wan Po A, Dornan JC. Is evening primrose oil of value in the treatment of premenstrual syndrome? Control Clin Trials 1996;17:60-8.

Cant A, Shay J, Horrobin DF. The effect of maternal supplementation with linoleic and gamma- linolenic acids on the fat composition and content of human milk: a placebo- controlled trial. J Nutr Sci Vitaminol (Tokyo) 1991;37:573-9.

Chenoy R, Hussain S, Tayob Y, et al. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing (abstract). BMJ 1994;308:501-3.

Cheung KL. Management of cyclical mastalgia in oriental women: pioneer experience of using gamolenic acid (Efamast) in Asia. Aust N Z J Surg 1999;69:492-4.

Das UN. The lipids that matter from infant nutrition to insulin resistance. Prostaglandins Leukot Essent Fatty Acids 2002;67:1-12.

Dove D, Johnson P. Oral evening primrose oil: its effect on length of pregnancy and selected intrapartum outcomes in low-risk nulliparous women (abstract). J Nurse Midwifery 1999;44:320-4.

Furse RK, Rossetti RG, Seiler CM, Zurier RB. Oral administration of gammalinolenic acid, an unsaturated fatty acid with anti-inflammatory properties, modulates interleukin-1beta production by human monocytes. J Clin Immunol 2002;22:83-91.

Guivernau M, Meza N, Barja P, Roman O. Clinical and experimental study on the long- term effect of dietary gamma-linolenic acid on plasma lipids, platelet aggregation, thromboxane formation, and prostacyclin production. Prostaglandins Leukot Essent Fatty Acids 1994;51:311-6.

Hansen TM, Lerche A, Kassis V, et al. Treatment of rheumatoid arthritis with prostaglandin E1 precursors cis-linoleic acid and gamma-linolenic acid. Scand J Rheumatol 1983;12:85-8.

Hardy ML. Herbs of special interest to women. J Am Pharm Assoc 200;40:234-42.

Head RJ, McLennan PL, Raederstorff D, et al. Prevention of nerve conduction deficit in diabetic rats by polyunsaturated fatty acids. Am J Clin Nutr 2000;71:386S-392S.

Hederos CA, Berg A. Epogam evening primrose oil treatment in atopic dermatitis and asthma. Arch Dis Child 1996;75:494-7.

Horrobin DF. Evening primrose oil and premenstrual syndrome. Med J Aust 1990;153:630-1.

Kenny FS, Pinder SE, Ellis IO, et al. Gamma linolenic acid with tamoxifen as primary therapy in breast cancer. Int J Cancer 2000;85:643-8.

Khoo SK, Munro C, Battistutta D. Evening primrose oil and treatment of premenstrual syndrome. Med J Aust 1990;153:189-92.

Kleijnen J. Evening primrose oil. BMJ 1994;309:824-825.

Kruger MC, Coetzer H, de Winter R, et al. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano) 1998;10:385-94.

Laivuori H, Hovatta O, Viinikka L, et al. Dietary supplementation with primrose oil or fish oil does not change urinary excretion of prostacyclin and thromboxane metabolites in pre-eclamptic women. Prostaglandins Leukot Essent Fatty Acids 1993;49:691-4.

McKendry RJ. Treatment of Sjogren's syndrome with essential fatty acids, pyridoxine and vitamin C. Prostaglandins Leukot Med 1982;8:403-8.

Menendez JA, Colomer R, Lupu R. Omega-6 polyunsaturated fatty acid gamma- linolenic acid (18:3n-6) is a selective estrogen-response modulator in human breast cancer cells: gamma-Linolenic acid antagonizes estrogen receptor-dependent transcriptional activity, transcriptionally represses estrogen receptor expression and synergistically enhances tamoxifen and ICI 182,780 (Faslodex) efficacy in human breast cancer cells. Int J Cancer 2004;10;109:949-54.

Menendez JA, del Mar Barbacid M, Montero S, et al. Effects of gamma-linolenic acid and oleic acid on paclitaxel cytotoxicity in human breast cancer cells. Eur J Cancer 2001;37:402-13.

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.

Oxholm P, Manthorpe R, Prause JU, Horrobin D. Patients with primary Sjogren's syndrome treated for two months with evening primrose oil. Scan J Rheumatol 1986;15:103-8.

Pye JK, Mansel RE, Hughes LE. Clinical experience of drug treatments for mastalgia. Lancet 1985;2:373-7.

Rose DP, Connolly JM, Liu XH. Effects of linoleic acid and gamma-linolenic acid on the growth and metastasis of a human breast cancer cell line in nude mice and on its growth and invasive capacity in vitro. Nutr Cancer 1995;24:33-45.

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. Br J Dermatol 1987;117:11-9.

Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements: a 5- year toxicological study (1991-1995). Drug Saf 1997;17:342-56.

Shuster J. Black cohosh root? Chasteberry Tree? Seizures! Hosp Pharm 1996;31:1553-4.

Sinn N, Bryan J. Effect of Supplementation with Polyunsaturated Fatty Acids and Micronutrients on Learning and Behavior Problems Associated with Child ADHD. J Dev Behav Pediatr 2007;28:82-91.

Stordy BJ. Dark adaptation, motor skills, docosahexaenoic acid, and dyslexia. Am J Clin Nutr 2000;71:323S-6S.

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.

The Medicines Control Agency (MCA), Epogam and Efamast (gamolenic acid) - withdrawal of marketing authorizations. http://www.mca.gov.uk/whatsnew/epogam.htm. (Accessed 2 June 2003).

Verhoeven MO, van der Mooren MJ, van de Weijer PH, et al. CuraTrial Research Group. Effect of a combination of isoflavones and Actaea racemosa Linnaeus on climacteric symptoms in healthy symptomatic perimenopausal women: a 12-week randomized, placebo-controlled, double-blind study. Menopause 2005;12:412-20.

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;99:112-6.

Wedig KE, Whitsett JA. Down the primrose path: petechiae in a neonate exposed to herbal remedy for parturition. J Pediatr 2008;152:140, 140.e1.

Whitaker DK, Cilliers J, de Beer C. Evening primrose oil (Epogam) in the treatment of chronic hand dermatitis: disappointing therapeutic results. Dermatology 1996;193:115-20.

Williams HC. Evening primrose oil for atopic dermatitis. BMJ 2003;327:1358-9.