Evening Primrose Oil

Scientific Name(s): Oenothera biennis L. Family: Onagraceae

Common Name(s): Evening primrose , common evening primrose

Uses

Evidence suggests that evening primrose oil may be effective for treating rheumatoid arthritis and diabetic neuropathy, but is lacking to support its place in the treatment of atopic dermatitis, menopausal vasomotor symptoms, mastalgia, or multiple sclerosis.

Dosing

Evening primrose oil has been administered orally in clinical trials at doses between 6 and 8 g/day in adults and 2 and 4 g/day in children. The typical content of gamma-linolenic acid (GLA) in the oil is 8% to 10%.

Contraindications

No contraindications have been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. A case report exists of transient petechiae in a newborn following oral and intravaginal use of evening primrose oil for cervical ripening for a week prior to the infant's birth. Both linoleic and GLA are normally present in breast milk, and it is reasonable to assume that evening primrose oil may be taken while breast-feeding.

Interactions

A case report exists of an interaction between evening primrose oil and lopinavir in which lopinavir plasma concentrations were elevated to toxic levels.

Adverse Reactions

Evening primrose oil was previously suspected to lower the seizure threshold in schizophrenic patients; however, this is now disputed.

Toxicology

No toxicity, carcinogenicity, or teratogenicity have been reported.

Botany

The evening primrose is a large, delicate wildflower native to North America with blooms usually lasting only 1 evening, but it is not a true primrose. Primrose is a yellow-flowered annual or biennial and can grow from 1 to 3 m in height. The fruit is a dry pod approximately 5 cm long that contains many small seeds. 1 , 2 , 3

Chemistry

Seeds from O. biennis contain 14% of a fixed oil known as evening primrose oil that can contain 50% to 70% cis -linoleic acid and 7% to 10% cis -GLA. Wild varieties of O. biennis contain highly variable amounts of linoleic acid and GLA; however, extensive crossbreeding has produced a commercial variety that consistently yields oil with 72% cis -linoleic acid and 9% GLA. 2 , 3 Also found are cis -6,9,12-octadecatrienoic acid; small amounts of oleic, palmitic, and stearic acids; steroids; campesterol; and beta-sitosterol. Mucilage and tannin in the plant parts have been analyzed. 2

Uses and Pharmacology

Essential fatty acids are important as cellular structural elements and as precursors of prostaglandins. Essential fatty acids are the biologically active parts of polyunsaturated fats that cannot be manufactured by the body and must be provided by the diet in relatively large amounts. 2 Recommended intake of linoleic acid and alpha-linolenic acid are 12 g and 1.1 g, respectively, for women 19 to 30 years of age. 4

In theory, the GLA provided by evening primrose oil can be converted directly to the prostaglandin precursor di-homo-gamma-linolenic acid and might be beneficial to individuals unable to metabolize cis -linoleic acid to GLA or those with low dietary intake of cis -linoleic acid. However, this relationship was not proven in a pharmacokinetic study in healthy participants. 5

Atopic dermatitis/Dermatologic disorders
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 show a lack of support for the use of evening primrose oil for atopic dermatitis. 6 , 7 , 8 , 9 Many of the trials are of poor quality and have apparent issues of bias. 9 , 10 , 11

While an older review suggested promising results, 12 the most comprehensive meta-analysis to date did not establish efficacy. 10 Clinical studies continue to be conducted, with a gradual time-dependent improvement suggested. 13

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.

Rheumatoid arthritis
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. A theoretical basis exists for the effect of GLA in inflammatory disease. 33

Clinical data

A Cochrane review of randomized trials comparing evening primrose oil with placebo suggests some benefit in using evening primrose oil for rheumatoid arthritis, despite the relative poor quality of the individual studies. A trend toward reduction of morning stiffness and joint tenderness, as well as pain relief, has been shown. The authors found the evidence to be sufficient to warrant further larger trials to provide conclusive results and define optimal dosage and duration of therapy. 34 These findings are supported by other reviews, especially with regard to effective duration of therapy. 35 , 36 A more recent randomized, double-blind, placebo-controlled study enrolling 90 patients with primary Sjögren syndrome found no statistically significant in patient fatigue with a higher dosage after 6 months of therapy. 37

Other uses
Cardiovascular disease

There is no recent evidence to support older studies, 38 , 39 , 40 suggesting that evening primrose oil reduced platelet aggregation. An observational study suggests serum linoleic acid may protect against ischemic stroke. 41 Despite limited older trials in humans and numerous studies using rats and rabbits, there are no recent randomized, controlled trials demonstrating a beneficial effect of evening primrose oil on cholesterol levels or serum lipids. A more recent randomized, controlled trial found no effect on endothelial function or vascular tone with evening primrose oil supplementation. 42

Diabetic neuropathy

A review of 3 randomized, controlled trials suggested evening primrose oil might improve symptoms of diabetic neuropathy. Dosages in these trials ranged from 360 to 480 mg GLA daily. Few adverse effects were noted in these trials, and there was no increase in blood glucose levels. 43 , 44

Dyslexia/Brain development

Current interest in the use of evening primrose oil for enhancing intellectual performance in children is yet to be validated by rigorous research. Studies conducted in children with dyslexia suggest improved reading, spelling, and behavior, 45 , 46 while a Cochrane systematic review and a long-term study (39 months) showed no long-term benefit in infants fed formula supplemented with long-chain polyunsaturated fatty acids. 47 , 48 An open study found benefit with the use of a fish oil and evening primrose oil combination in children with dyslexia. 49

Eye conditions

Study results disagree as to the effect of evening primrose oil on dry eye syndrome, 37 , 50 , 51 and there is concern regarding high intake of linoleic and linolenic acid and the risk of cataract development. 52 , 53

Hyperpigmentation

Topical application of saponified evening primrose oil reduced ultraviolet B-induced hyperpigmentation, while a decrease in melanin production has been demonstrated in vivo with the saponified oil. 54

Inflammation

Local injection-site reactions after subcutaneous injections of 5-azacitidine have been reduced with topical application of evening primrose oil. 55

Myalgic encephalomyelitis (chronic fatigue syndrome)

A theoretical model has been proposed for a place in therapy for evening primrose oil in this condition. Clinical trials are lacking. 56

Urolithiasis

An exploratory study found an increase in urinary citrate excretion following 1,000 mg/day of evening primrose oil. 57

Dosage

Evening primrose oil has been administered orally in clinical trials at doses between 6 and 8 g/day in adults and 2 and 4 g/day in children. Wide-ranging doses of 0.27 g to 6.48 g GLA per day have been used in clinical studies in mastalgia. 24 The typical content of GLA in the oil is 8% to 10%. 2

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Both linoleic and GLA are normally present in breast milk, and it is reasonable to assume that evening primrose oil may be taken while breast-feeding. A case report exists of transient petechiae in a newborn following oral and intravaginal use of evening primrose oil for a week prior to the infant's birth for cervical ripening. In vitro and in vivo animal studies suggest inhibition of platelet function in the newborn may have been caused by exposure to evening primrose oil. 58

Interactions

A case report exists of an interaction between evening primrose oil and lopinavir. Toxic lopinavir levels and diarrhea were reported. 59 A class effect with other protease inhibitors has not been established, but caution is warranted.

Adverse Reactions

Two clinical studies conducted in the 1980s among individuals with schizophrenia led to a concern that evening primrose oil might lower the seizure threshold. However, other factors may account for the observed seizures: the few participants who developed seizures were taking concomitant medicines (phenothiazines) known to lower the seizure threshold, and also a link has been described between schizophrenia and epilepsy. There are no further reports of seizures related to evening primrose oil, which may have a protective effect. 60

A case report of lipoid pneumonia secondary to chronic evening primrose oil use exists. 61

Toxicology

Animal toxicological studies and extensive use of evening primrose oil over many years revealed no data of concern. As a nutritional supplement, the maximum label-recommended daily dose of evening primrose oil is approximately 4 g, containing 300 to 360 mg of GLA. There is little concern about the safety of evening primrose oil as a dietary supplement in the recommended dosage range. 2

Bibliography

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