Evening primrose oil in the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema. Epogam evening primrose oil treatment in atopic dermatitis and asthma. Evening primrose oil is effective in atopic dermatitis: a randomized placebo-controlled trial. Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial. 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. A double-blind placebo controlled trial of Efamol Marine on skin and joint symptoms of psoriatic arthritis. Atopic eczema unresponsive to evening primrose oil (linoleic and gamma-linolenic acids). [Gamma-linolenic-acid-rich borage seed oil capsules in children with atopic dermatitis. A placebo-controlled double-blind study].
In a double-blind trial patients with atopic eczema received either oral evening primrose oil (EPO) (n = 14) or placebo (n = 11) for 12 weeks. In the EPO group a statistically significant improvement was observed in the overall severity and grade of inflammation and in the percentage of the body surface involved by eczema as well as in dryness and itch. Patients in the placebo group showed a significant reduction in inflammation. The patients receiving EPO showed a significantly greater reduction in inflammation than those receiving placebo. Evening primrose oil caused a significant rise in the amount of dihomogammalinolenic acid in the plasma phospholipid fatty acids. Plasma levels of TXB2, 6-keto-PGF1 alpha and PGE1, and the amount of TXB2 released into serum during clotting were not altered by evening primrose oil. Although gamma-linolenic acid (GLA) has been shown to correct deficiencies in skin lipids associated with reduced delta-6-desaturase activity which should result in improvement of dysregulation of inflammation and immunity in atopic eczema, clinical studies with evening primrose oil containing 10% GLA have yielded contradictory results. We have therefore examined the effect of a higher percentage (at least 23%) GLA-containing borage oil in adults with stable atopic eczema of moderate severity in a double-blind, multicentre study. One hundred and sixty patients were randomized to take daily either 500 mg of borage oil-containing capsules or the bland lipid miglyol as a placebo over a 24-week period. Use of topical diflucortolone-21-valerate cream was allowed as rescue medication, with the amount used until response being defined as primary, and clinical improvement as secondary efficacy criteria. Although several clinical symptoms improved compared with placebo, the overall response to borage oil did not reach statistical significance. Significant differences in favour of borage oil were, however, observed in a subgroup excluding patients who failed to show increased erythrocyte dihomo-gamma-linolenic acid levels and in whom adherence to inclusion criteria and the study protocol were questionable. GLA metabolites increased in borage oil-treated patients only, and serum IgE showed a trend to decrease on overall and subgroup analysis. No substance-related adverse effects were observed. This study shows no overall efficacy of GLA-containing borage oil in atopic eczema, with steroid use being the primary response parameter, although it suggests that a subgroup of patients may benefit from this well-tolerated treatment. Essential fatty acids are claimed to have positive effects in atopic diseases. In a double blind, placebo controlled, parallel group study 58 out of 60 children, with atopic dermatitis and the need for regular treatment with topical skin steroids, completed a 16 weeks' treatment period with either Epogam evening primrose oil or placebo capsules. Twenty two of these subjects also had asthma. The parents used diaries to record symptom scores and concomitant medication. Peak expiratory flow was measured and disease activity was monitored by the clinician every four weeks. The plasma concentrations of essential fatty acids increased significantly in the group treated with Epogam capsules. The study demonstrated significant improvements of the eczema symptoms but no significant difference was found between the placebo and the Epogam groups. No therapeutic effect was shown on asthma symptoms or fidget. Atopic dermatitis (AD) is a chronic, relapsing, itchy dermatosis of multifactorial origin, which commonly starts in childhood. Defective metabolism of essential fatty acids leading to relative dominance of pro-inflammatory prostaglandins (PGE2 and PGF2) has been reported as an important factor in the pathogenesis of AD. Evening primrose oil (EPO) as a source of gamma-linolenic acid (GLA) has been of interest in the management of AD.
                To evaluate the efficacy and safety of EPO in atopic dermatitis in our patients.
                Consecutive new out-patient department (OPD) patients of a referral hospital in Kolkata clinically diagnosed as having AD were randomly allocated to two groups. To the first group, evening primrose oil was supplied as 500-mg oval clear unmarked capsules, while placebo capsules identical in appearance and containing 300 mg of sunflower oil were given to the other group. Treatment continued for a period of 5 months. With pre-designed scoring system (based on four major parameters: extent, intensity, itching, and dryness), clinical evaluation was done at baseline and subsequent monthly visits. Data of the first 25 patients from each group who completed the 5 months of trial were compiled and analyzed.
                At the end of the fifth month, 24 (96%) patients of EPO group and 8 (32%) patients of placebo group showed improvement. There was significant difference in outcome of treatment between two groups (P<0.00001). No significant adverse effect was reported by any patient/guardian at any point of assessment.
                Evening primrose oil is a safe and effective medicine in management of AD. However, since not all researchers across the world have found the same good result, further large trials on Indian patients are needed. To study the efficacy and tolerability of borage oil, which contains a high concentration of gamma linolenic acid, in children and adults with atopic eczema.
                Single centre, randomised, double blind, placebo controlled, parallel group trial.
                Acute district general hospital in Nuneaton, England.
                151 patients, of whom 11 failed to return for assessment, leaving an evaluable population of 140 (including 69 children).
                Adults received four capsules of borage oil twice daily (920 mg gamma linolenic acid), and children received two capsules twice daily, for 12 weeks.
                Change in total sign score at 12 weeks measured with the six area, six sign, atopic dermatitis (SASSAD) score (primary endpoint); symptom scores, assessed on visual analogue scales; topical corticosteroid requirement, assessed on a five point scale; global assessment of response by participants; adverse events and tolerability.
                The mean SASSAD score fell from 30 to 27 in the borage oil group and from 28 to 23 in the placebo group. The difference between the mean improvements in the two groups was 1.4 (95% confidence interval -2.2 to 5.0) points in favour of placebo (P = 0.45). No significant differences occurred between treatment groups in the other assessments. Subset analysis of adults and children did not indicate any difference in response. The treatments were well tolerated.
                Gamma linolenic acid is not beneficial in atopic dermatitis. In rheumatoid arthritis (RA) benefit from non-steroidal anti-inflammatory drugs (NSAIDs) is mediated through inhibition of the cyclo-oxygenase enzyme, thereby decreasing production of the 2 series prostaglandins (PGs). The lipoxygenase enzyme is intact, however, allowing leucotriene (LT) production, e.g., LTB4 (an inflammatory mediator). Treatment with evening primrose oil (EPO) which contains gamma-linolenic acid (GLA) leads to production of the 1 series PGs, e.g., PGE1, which has less inflammatory effects. Also LT production is inhibited. Eicosapentaenoic acid (EPA, fish oil) treatment provides a substrate for PGs and LTs, which are also less inflammatory. In this study 16 patients with RA were given 540 mg GLA/day (EPO), 15 patients 240 mg EPA and 450 mg GLA/day (EPO/fish oil), and 18 patients an inert oil (placebo). The aim of this study was to determine if EPO or EPO/fish oil could replace NSAID treatment in RA. The initial 12 month treatment period was followed by three months of placebo for all groups. Results at 12 months showed a significant subjective improvement for EPO and EPO/fish oil compared with placebo. In addition, by 12 months the patients receiving EPO and EPO/fish oil had significantly reduced their NSAIDs. After 3 months of placebo those receiving active treatment had relapsed. Despite the decrease in NSAIDs, measures of disease activity did not worsen. It is suggested that EPO and EPO/fish oil produce a subjective improvement and allow some patients to reduce or stop treatment with NSAIDs. There is, however, no evidence that they act as disease modifying agents. Fish oil may be beneficial in the treatment of psoriasis and in RA. We examined the potential benefit of Efamol Marine, a combination of evening primrose oil and fish oil in the treatment of 38 patients with PsA. Patients with PsA were entered in a double-blind placebo controlled study and received either 12 Efamol Marine capsules or 12 placebo capsules daily for 9 months. All patients received placebo capsules for a further 3 months. At month 3 of the study patients were asked to reduce their intake of NSAIDs and maintain that decrease provided there was no worsening of their joint symptoms. Clinical assessments of skin and joint disease severity and activity were performed at 0, 1, 3, 6, 9 and 12 months. All measures of skin disease activity including severity, percentage body affected and itch were unchanged by Efamol Marine. The NSAID requirement remained the same between both treatment groups. In addition, there was no change demonstrated in the activity of arthritis as measured by duration of morning stiffness. Ritchie articular index, number of active joints, ESR and CRP. However, a rise in serum TXB2 was observed in the active group during the placebo phase; in addition a fall in leukotriene B4 production occurred during the active phase period followed by a marked rise during the placebo phase suggesting some laboratory documented anti-inflammatory effect. In conclusion, this study suggests that Efamol Marine may alter prostaglandin metabolism in patients with PsA, although it did not produce a clinical improvement and did not allow reduction in NSAID requirement. A larger dose of essential fatty acid may be needed to produce a clinical benefit. This study was designed to look at the effect of evening primrose oil (linoleic and gamma-linolenic acids) as an oral supplement for patients with atopic eczema. We used a double-blind, blocked crossover design with random assignment of patients to treatment groups. We used Wilcoxon's signed-ranks method of comparing changes during the trial. We observed no significant effect on erythema, scale, excoriation, lichenification, or overall severity in 123 patients with atopic eczema of average severity while they took oral doses of evening primrose oil (2 or 4 gm in children, 6 or 8 gm in adults). We investigated the effect of gamma-linolenic-acid from borage seed on atopic dermatitis of children. In a placebo-controlled, double-blind manner we studied 24 patients, 3-17 years old. Every patient received 360 mg of gamma-linolenic acid daily, independent from sex and age; the same amount of corn seed-oil served as placebo. After 10 to 14 weeks of treatment there was no improvement of the eczema in the verum phase compared to placebo. Both groups showed improvement while taking placebo. This result could be seen in the objective investigations (Costa-Score, 3 times per treatment period) as well as in the daily patients documentation. The patients whose eczema has improved under borage seed-oil (n = 10) had no special characteristics, so that we could not identify any responder-type.
Implications for practice  

Oral borage oil and evening primrose oil lack effect on eczema; improvement was similar to respective placebos used in trials. Oral BO and EPO are not effective treatments for eczema.
In these studies, along with the placebos, EPO and BO have the same, fairly common, mild, transient adverse effects, which are mainly gastrointestinal.
The short-term studies included here do not examine possible adverse effects of long-term use of EPO or BO. A case report warned that if EPO is taken for a prolonged period of time (more than one year), there is a potential risk of inflammation, thrombosis, and immunosuppression; another study found that EPO may increase bleeding for people on Coumadin® (warfarin) medication.

Implications for research 

Noting that the confidence intervals between active and placebo treatment are narrow, to exclude the possibility of any clinically useful difference, we concluded that further studies on EPO or BO for eczema would be hard to justify.
This review does not provide information about long-term use of these products.