Evening primrose oil (EPO) is benign. Evidence supports its use for diabetic neuropathy and rheumatoid arthritis; no benefit for psoriasis, hot flashes or premenstrual syndrome has been shown. Trials on eczema are mixed.

[LFDPKM ] Letter Key

Latin Name

Oenothera biennis L.

Family

Onagraceae

Description

• A biennial herb native to North America, evening primrose grows to 60 cm.
• Its yellow, four-petaled flowers open in the evening.

Part Used

Seed oil

Known Active Constituents

Seeds contain 24% fixed oil containing 65% to 80% linoleic acid and 7% to 14% gamma-linolenic, also called gamolenic acid (GLA) (1).

Mechanism/Pharmacokinetics

• GLA is metabolized to dihomo--linolenic acid (DGLA), which produces the antiinflammatory prostaglandin E₁.
• DGLA also may competitively inhibit 2 series prostaglandins and 4 series leukotrienes (2).

[Outline]

• LLatin Name
• FFamily
• DDescription
• PPart Used
• KKnown Active Constituents
• MMechanism/Pharmacokinetics

[CO ] Letter Key

Clinical Trials

• Labor induction
  • Midwives sometimes recommend oral or topical EPO to speed cervical ripening. A survey of the American College of Nurse-Midwives found that 90/172 certified nurse-midwives (CNMs) used herbal preparations to stimulate labor; of these, 60% used EPO (3). A retrospective study compared the medical records of 54 women prescribed EPO during pregnancy (500 mg p.o. t.i.d. × 1 week starting at week 37, then 500 mg p.o. q.d. until labor) with the records of 54 women not prescribed EPO (4). The two groups fared similarly on most outcome measures, but labor lasted an average of 3 hours longer in the EPO group. This study has several problems: there were significant differences between groups (infants in the EPO group were significantly larger; compliance was not assessed, etc.).
• Diabetic neuropathy
  • Two trials found a benefit of EPO in diabetic neuropathy. A randomized, double-blind, placebo-controlled 1-year study in 111 patients with mild diabetic neuropathy tested EF4 (12 capsules, each containing 40 mg of GLA) (5). EPO was significantly superior to placebo in 8/10 neurophysiologic parameters and 5 of 6 neurologic assessments. No adverse events were noted. Hemoglobin A_1c levels deteriorated in both groups during the trial.
  • Another double-blind placebo-controlled trial of 22 patients with distal diabetic polyneuropathy tested 360 mg GLA for 6 months on neuropathy symptoms and signs, nerve conduction studies, and thermal threshold measurements (6). Compared with placebo, the treated group had significantly improved neuropathy symptoms, motor nerve conduction velocity (MNCV), compound muscle action potential (CMAP), median and sensory nerve action potential (SNAP) amplitude, and heat and cold threshold.
• Rheumatoid arthritis
  • A study of 49 patients with rheumatoid arthritis compared placebo with EPO (540 mg GLA) or an EPO/fish oil product (450 mg GLA and 240 mg eicosapentaenoic acid) (2). Compared with placebo, significantly more patients in both treated groups reduced analgesic intake (2). A study of 37 patients with rheumatoid arthritis compared GLA with cottonseed oil; 24 weeks of treatment with GLA improved pain, ability to perform tasks, and physician global assessment (7).
  • Another double-blind placebo-controlled study of 40 patients with rheumatoid arthritis and nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal lesions compared 6 g daily of EPO (540 mg GLA) to olive oil for 6 months (8). Neither group improved much; morning stiffness was significantly less at 3 months in the GLA group; olive oil was significantly better than GLA in reducing pain and articular index at 6 months.
• Premenstrual syndrome
  • A systematic review of seven placebo-controlled trials of EPO for premenstrual syndrome identified seven trials; only two were properly randomized and controlled (9). Both enrolled 38 women and tested EPO (Efamol) capsules (8 or 12 capsules daily). Neither found a benefit for EPO.
• Mastalgia
  • EPO is approved for the treatment of mastalgia in the United Kingdom, but no randomized controlled trials were identified. Several case series claim a benefit for EPO (10–13).
• Breast cysts
  • A trial of 200 women (185 completed) with at least one aspirated breast cyst compared EPO (6 capsules daily) to placebo (paraffin) for 1 year (14). There was no difference in overall recurrence rate between the treated and placebo group.
• Hot flashes
  • In a randomized double-blind controlled trial, 56 menopausal women (35 completed) with at least three hot flashes daily received EPO (2,000 mg with 40 mg vitamin E b.i.d. × 6 months) or control (paraffin) (15). EPO was not superior to placebo in any measure. Both groups experienced decreased nighttime hot flashes; only the placebo group improved in daytime hot flashes.
• Hepatitis B
  • A randomized controlled trial (no mention is made of blinding) of 24 patients (20 completed) with hepatitis B showed no benefit for EPO (4 g daily × 12 months) against placebo (16). There was no evidence of histologic benefit, and no patient’s blood became negative for surface antigen. At 12 months, mean serum alanine transaminase (ALT) level was similar between the two groups; at 6 months ALT levels were statistically higher in the EPO group than in the placebo group.
• Psoriasis
  • A double-blind, placebo-controlled, 28-week trial tested 12 capsules daily of a mixed product (each capsule contained EPO 430 mg, fish oil 107 mg, and vitamin E 10 mg) for psoriasis. No benefit of treatment was seen in psoriasis severity or transepidermal water loss (17). A 9-month trial tested a similar product (Efamol Marine), providing a total daily dose of 480 mg GLA, 240 mg eicosapentaenoic acid (EPA), and 132 mg docosahexaenoic acid (DHA) in 38 patients with psoriatic arthritis. During the third month of the study, patients attempted to reduce their intake of NSAIDs (18). Severity, percentage of body affected, and itch were unchanged; NSAID requirements remained the same and there was no change in arthritis activity. Serum thromboxane B₂ rose and leukotriene B₄ fell in the treated group, indicating a possible effect on prostaglandin metabolism.
• Atopic dermatitis
  • A 16-week, double-blind, placebo-controlled trial of 60 children with atopic dermatitis found no benefit for EPO (Epogam, with 40 mg GLA and 10 mg vitamin E per capsule, 8 to 12 capsules daily) (19). Over 16 weeks, both groups improved significantly; there was no significant difference between the two groups.
  • Another double-blind placebo-controlled trial in patients with atopic eczema tested EPO (eight capsules daily of Efamol—each capsule contained 360 mg linoleic acid, 50 mg oleic acid, and 45 mg GLA) in 25 patients (20). Inflammation decreased in both groups; EPO-treated patients had significantly less inflammation than those receiving placebo.
  • In 17 children and 15 adults, a randomized double-blind crossover trial found that 3 weeks of treatment with Efamol (four capsules b.i.d. for adults, two capsules b.i.d. for children) resulted in modest but significant improvement on both physician and patient assessments (21).
  • A double-blind controlled crossover study in 99 adults and children with atopic eczema compared three doses of Efamol; only the highest dose (six capsules b.i.d.) showed a significant clinical improvement (22).
  • A meta-analysis of nine controlled trials (four parallel, five crossover) of Epogam (not including trials mentioned previously) found that parallel trials favored EPO over placebo; there was no significant difference between EPO and placebo in the crossover trials (23).
  • A double-blind placebo-controlled trial in 39 patients with stable hand dermatitis tested Epogam (600 mg GLA daily × 16 weeks; patients were observed for another 8 weeks) (24). Clinical parameters improved in both groups, with no significant difference between groups. No changes in lipid composition of plasma red cells or epidermis were noted, and no changes were seen in biopsied skin.
  • EPO is approved to treat atopic dermatitis in the United Kingdom.
• Pruritis in dialysis patients
  • A study of 16 dialysis patients compared EPO to linoleic acid (2 g/day × 6 weeks) (25). The EPO-treated group experienced significantly increased DGLA (a precursor of antiinflammatory prostaglandin E₁) with no concomitant change in arachidonic acid (a proinflammatory precursor of prostaglandin E₂). Although the EPO-treated group improved significantly in three uremic skin symptoms, pruritus was not significantly affected.

Other Claimed Benefits/Actions

• Cancer
• Attention deficit/Hyperactivity disorder

[Outline]

• CClinical Trials
  • Labor induction
  • Diabetic neuropathy
  • Rheumatoid arthritis
  • Premenstrual syndrome
  • Mastalgia
  • Breast cysts
  • Hot flashes
  • Hepatitis B
  • Psoriasis
  • Atopic dermatitis
  • Pruritis in dialysis patients
• OOther Claimed Benefits/Actions

Adverse Reactions

• No serious adverse events have been reported.
• Side effects reported in trials include nausea, indigestion, softening of stools, and headache.

• Adults: 3 to 8 g
• Children: 2 to 4 g

Q: Doesn’t EPO cause seizures?

A: Although the assertion that EPO causes seizures or decreases seizure threshold in phenothiazine-treated patients has been repeated in many publications, there have been no reliable published reports of such an effect. EPO was briefly used to differentiate temporal lobe epilepsy from schizophrenia. A report of new-onset nocturnal seizures has been reported in a 45-year-old woman, beginning about a month after consuming capsules containing EPO, black cohosh, and vitex (26). Products were not analyzed, and the case is sketchily presented. The only reference for an EPO-phenothiazine interaction is an anonymous entry in the Data Sheet Compendium 1994–1995 (27), for which details are unavailable. Phenothiazines decrease seizure threshold on their own, so an interaction report would have to be well-documented to be credible.

1. De Wick PM. Medicinal natural products: a biosynthetic approach. West Sussex, England: John Wiley and Sons, 1997:42.
2. Belch JJF, 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. Ann Rheum Dis 1988;47:96–104.
3. McFarlin BL, Gibson MH, O’Rear J et al. 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;44:205–216.
4. Dove D, Johnson P. Oral evening primrose oil: its effect on length of pregnancy and selected intrapartum outcomes in low-risk nulliparous women. J Nurse Midwifery 1999;44:320–324.
5. Gamma-Linolenic Multicenter Trial Group (Keen H, Payan J, Allawi J et al.) Treatment of diabetic neuropathy with -linolenic acid. Diabetes Care 1993;16:8–15.
6. Jamal GA, Carmichael H. The effect of gamma-linolenic acid on human diabetic peripheral neuropathy: a double-blind placebo-controlled trial. Diabet Med 1990;7:319–323.
7. Leventhal LJ, Boyce EG, Zurier RB. Treatment of rheumatoid arthritis with gammalinolenic acid. Ann Int Med 1993;119:867–873.
8. 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 1991;30:370–372.
9. 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.
10. Gately CA, Miers M, Mansel RE et al. Drug treatments for mastalgia: 17 years experience in the Cardiff mastalgia clinic. J R Soc Med 1992;85:12–15.
11. Pye JK, Mansel RE, Hughes LE. Clinical experience of drug treatments for mastalgia. Lancet 1985;2:373–377.
12. Harding C, Harvey J, Kirkman R et al. Hormone replacement therapy-induced mastalgia responds to evening primrose oil. Br J Surg 1996;83(Suppl 1):24.
13. Wetzig S, Burton JL. Oral evening-primrose-seed oil improves atopic eczema. Lancet 1982;2:1120–1122.
14. Mansel RE, Harrison BJ, Melhuish J et al. A randomized trial of dietary intervention with essential fatty acids in patients with categorized cysts. Ann N Y Acad Sci 1990;586:288–294.
15. 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.
16. Jenkins AP, Green AT, Thompson RPH. Essential fatty acid supplementation in chronic hepatitis B. Aliment Pharmacol Ther 1996;10:665–668.
17. Oliwiecki S, Burton JL. Evening primrose oil and marine oil in the treatment of psoriasis. Clin Exp Dermatol 1994;19:127–129.
18. Veale DJ, Torley HI, Richards IM et al. A double-blind placebo controlled trial of Efamol marine on skin and joint symptoms of psoriatic arthritis. Br J Rheumatol 1994;33:954–958.
19. Hederos C-A, Berg A. Epogam evening primrose oil treatment in atopic dermatitis and asthma. Arch Dis Child 1996;75:494–497.
20. Schalin-Karrila M, Mattila L, Jansen CT et al. Evening primrose oil in the treatment of atopic eczema: affect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol 1987;117:11–19.
21. Lovell CR, Burton JL, Horrobin DF. Treatment of atopic eczema with evening primrose oil. Lancet 1981;1:278.
22. Wright S, Burton JL. Oral evening-primose-seed oil improves atopic eczema. Lancet 1982;2:1120–1122.
23. 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.
24. Whitaker DK, Cilliers J, de Beer C. Evening primrose oil (Epogam) in the treatment of chronic hand dermatitis: disappointing therapeutic results. Dermatology 1996;193:115–120.
25. Yoshimoto-Furuie K, Yoshimoto K, Tanaka T et al. Effects of oral supplementation with evening primrose oil for six weeks on plasma essential fatty acids and uremic skin symptoms in hemodialysis patients. Nephron 1999;81:151–159.
26. Shuster J. Black cohosh root? Chasteberry tree? Seizures!. Hosp Pharm 1998;31:1553–1554.
27. Data Sheet Compendium 1994–1995, 1520–1521. Efamast, Epogam (Searle).