Currently, evening primrose seed oil (EPO) is used to treat atopic dermatitis and cyclical/noncyclical mastalgia. It is also considered to be potentially useful for the treatment of premenstrual syndrome and many other inflammatory conditions. The plant that the seed oil comes from, evening primrose, has served as both food and medicine at previous times in history. Native Americans ate the boiled, nutty-flavored root, and used leaf poultices from the plant for bruises and hemorrhoids. European settlers took the root back to England and Germany, where it was introduced as food and became known as German rampion. The plant was also a Shaker medicine, sold commercially.

Recent investigation of dietary fatty acids and their roles in health stimulated interest in evening primrose. EPO contains the essential fatty acids linoleic acid (LA) and gamma-linolenic acid (GLA). GLA, an omega-6 series fatty acid, normally forms in the body during the desaturation of LA. Both GLA and its break-down product, dihomogamma-linolenic acid (DGLA), are involved with the formation of prostaglandins E₁ (PGE₁) and E₂ (PGE₂). PGE₁ are vasodilatory, immune-modulating, and anti-inflammatory prostaglandins. They also inhibit platelet aggregation and phospholipase A₂, block cholesterol synthesis, and lower blood pressure. PGE₂ prostaglandins, on the other hand, tend toward the opposite of these actions.

EPO ingestion, and subsequent GLA and DGLA formation, may result in reductions to PGE₂ stimulation by arachiadonic acid. Tests demonstrate that DGLA-stimulated PGE₁ reduces PGE₂. EPO delivers GLA, bypasses conversion, and favors PGE₁ formation over PGE₂. The many potential uses of EPO include atopic eczema, diabetes, cardiovascular disease, high cholesterol, chronic fatigue syndrome, and cancer. Patients with some of these illnesses have demonstrated a slower LA-GLA conversion rate, as well as, in some cases, deficient levels of LA due to poor diet. Please see monograph on GLA for additional information.

Biennial plant native to North America, evening primrose grows a rosette of leaves in the first year, and creamy yellow or bright yellow flowers in the second. Flowers bloom after sunset, June through September, or on overcast days. Stems are branched, with alternate, lanceolate leaves; flowers contain a predominant X-shaped stamen and seeds. This monograph focuses on the seed from which the oil is extracted.

• Flower
• Leaves
• Roots
• Seed oil

Seed oil contains up to 25% fatty oil, which is extracted with hexane (except in the case of products labeled "hexane free") to produce a 60% to 80% LA–8 % to 14% GLA product.

Standardized preparations (8% GLA), in capsules or as oil.

Traditional actions of the leaf, flower, and root bark include vulnerary, stomachic, demulcent, and anti-inflammatory. Oil is used topically for infantile eczema. Conditions for which it is used clinically today include bruises, wounds, obesity, hemorrhoids, infantile eruptions.

In clinical applications, there are two categories of potential indications.

• Conditions associated with essential fatty acid deficiency or imbalance: acne, arthritis, rheumatoid arthritis, asthma, chronic fatigue syndrome, platelet aggregation and high blood pressure relative to congestive heart failure, diabetic neuropathy, developmental disorders, diabetes, dry scaly skin, eczema, fibrocystic breast disease, inflammation, intermittent claudication, hypercholesterolemia, mastalgia, metabolic disorders, migraine, multiple sclerosis, premenstrual syndrome, psoriasis, psychological disorders, Raynaud's syndrome, Sjogren's syndrome
• Conditions associated with difficulty or inability to convert cis-linoleic acid to prostaglandin E₁: aging-related disorders, alcoholism, cancer, poor nutrition, radiation damage

Anti-inflammatory and relaxed smooth muscle response may result from alterations in prostaglandin biosynthesis. Effects of EPO vary and indicate a need for future research.

Placebo-controlled studies show positive effects for EPO in: rheumatoid arthritis patients (resulting in a lesser need for NSAIDs in 60% of RA patients despite the lack of changes in biochemical indicators); Sjogren's syndrome (mild increase in tear flow); irritable bowel syndrome (symptom improvement); chronic fatigue syndrome (symptom improvement); kidney transplant graft survival rate; endometriosis (90% symptom reduction in EPO group, versus 10% symptom reduction in placebo group); schizophrenic symptoms (EPO/zinc/B₆/C/niacin combination, also improved tardive dyskenesia, memory loss); alcohol withdrawal; Alzheimer's disease.

Two large double-blind, placebo-controlled trials showed no effect of EPO on atopic dermatitis. Smaller studies, with severe cases, showed positive results.

Most studies support EPO in the treatment of noncyclic breast pain and inflammation. A daily dosage of 3 g EPO had an equal effect to bromocriptine. Neither EPO nor bromocriptine were as effective as danazol, but the EPO recipients had significantly fewer side effects (4%) than did the pharmaceutical recipients (danazol: 30%; bromocriptine: 35%).

Both positive results and no results have been demonstrated in studies on the effects of EPO on premenstrual syndrome, and studies on EPO in multiple sclerosis also yield conflicting results; patients in early or less severe stages of the disease showed the greatest benefit.

Effects of EPO and GLA on human cancers are currently under study.

Products are standardized to contain 8% GLA. A three-month treatment period may be necessary in order to achieve a clinical response. The recommended doses are as follows.

• Atopic dermatitis: 6 to 8 g (adult); 2 to 4 g (child)
• Cyclical and noncyclical mastalgia: 3 to 4 g daily
• Premenstrual syndrome: 3 g daily

American Herbal Products Association (AHPA) safety rating: class 1 (safe with appropriate use). Reported side effects are rare and mild, and include nausea, stomach pain, headache. Soft stool and abdominal pain indicate excess dosage.

EPO may trigger latent temporal lobe epilepsy. Schizophrenics receiving phenothiazines are at greatest risk; occurrence not yet observed in non-phenothiazine therapy.

Breast milk contains LA and GLA; EPO safety while breast-feeding is inferred. During pregnancy, use with caution as for any herbal preparation or dietary supplement.

In rat studies, evening primrose oil (EPO) offered protection from cyclosporine-induced renal dysfunction (Morphake et al. 1994). Rats fed standard chow containing 10 mL/kg EPO (representing 9% gamma-linolenic acid and 72% cis-linolenic acid) developed fewer lesions than untreated animals following 7 days of treatment with cyclosporine (45 mg/kg/day intraperitoneally).

A double-blind cross-over study involving 13 chronic inpatients or day patients with schizophrenia evaluated the effects of EPO (4 g) as an adjunct to treatment (Holman and Bell 1983). No significant therapeutic effects were associated with EPO. However, grand mal seizures occurred in two patients, indicating that EPO may enhance the epileptogenic properties of phenothiazines. EPO is contraindicated in patients taking phenothiazines because of the potential for lowering the seizure threshold and increasing the risk of seizures in this patient population (Shaw et al. 1991).

In the Unites States, EPO is a dietary supplement. In England, a proprietary evening primrose oil is licensed for use in atopic eczema and mastalgia. Germany has approved evening primrose as a food, but the oil is not included in the Commission E monographs.

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