Evening primrose oil for eczema: the Cochrane review that ended the debate

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Evening primrose oil was once a licensed prescription product in the UK for atopic eczema, sold under the brand Epogam. Today it is back on the supplement shelf with no eczema claim, because the clinical evidence collapsed under scrutiny. The 2013 Cochrane review — which pooled 27 randomized trials of evening primrose oil and borage oil — concluded that neither improves eczema beyond placebo. It is one of the cleaner "looked promising early, didn't survive proper trials" stories in supplement medicine, and a useful case study in why mechanism and small early studies are not enough.

The original mechanistic story

Evening primrose oil (Oenothera biennis) is rich in gamma-linolenic acid (GLA), an omega-6 fatty acid that sits just downstream of the delta-6-desaturase step in essential fatty acid metabolism. In the 1980s, researchers hypothesized that people with atopic dermatitis had reduced delta-6-desaturase activity, and that supplying GLA directly might restore downstream anti-inflammatory prostaglandin production and improve the skin barrier. It was a tidy, testable idea — and for a time the early data seemed to support it.

Early enthusiasm and Epogam

Several small early trials reported symptom improvements, and on that basis Epogam was licensed in the UK for atopic eczema and remained a prescribable product into the 1990s. But the supporting studies shared recurring weaknesses: small samples, inconsistent outcome measures, and a heavy reliance on industry-sponsored data. As independent groups began to test GLA with tighter methods, the signal faded. Berth-Jones and Graham-Brown's 1993 Lancet trial — a double-blind, placebo-controlled study in 123 patients receiving evening primrose oil, evening primrose plus fish oil, or placebo for 16 weeks — found no benefit from active treatment, and the authors pointedly noted that their design avoided the methodological problems of earlier positive studies [1].

The license is withdrawn

In 2002 the UK Medicines Control Agency (now the MHRA) withdrew the marketing authorizations for Epogam and the related product Efamast, having concluded that the accumulated evidence no longer supported efficacy in their licensed indications. The most rigorous independent eczema trial followed in 2003: Takwale and colleagues randomized 151 patients (of whom 140 were evaluable, including 69 children) to borage oil — a high-GLA oil — or placebo for 12 weeks [2]. The mean change in the standardized eczema severity (SASSAD) score actually favored placebo by a small, non-significant margin, and no secondary outcome favored GLA. Their conclusion was blunt: "Gamma linolenic acid is not beneficial in atopic dermatitis." Subset analysis showed the same null result in adults and in children.

The Cochrane review that settled it

The definitive synthesis came in 2013, when Bamford and colleagues published the Cochrane review "Oral evening primrose oil and borage oil for eczema" [3]. It pooled 27 studies (1,596 participants): 19 of evening primrose oil and 8 of borage oil. A meta-analysis of the evening primrose trials found no significant improvement in global eczema symptoms rated by either patients or doctors versus placebo, and the borage oil trials likewise showed no benefit. Adverse events were mild — mostly transient gastrointestinal upset — and similar between active and placebo arms. The reviewers concluded that oral evening primrose oil and borage oil are not effective treatments for eczema, and that because the confidence intervals were narrow enough to exclude a clinically useful effect, further trials would be hard to justify. A companion Cochrane review of other dietary supplements for eczema reached the same broad conclusion: no convincing evidence of benefit [4].

Why the early trials looked positive

The pattern here is familiar in evidence-based medicine. Small positive studies are easier to publish than small negative ones (publication bias), industry-funded trials of a sponsor's own product tend to report more favorable results, and dermatology is especially prone to large placebo responses because itch and self-rated severity are subjective and fluctuate. When better-powered, independent, blinded trials were finally run, the apparent effect disappeared. A defensible biological mechanism, in other words, did not survive contact with rigorous clinical testing.

Other proposed uses where the evidence is also thin

Evening primrose oil has been promoted for mastalgia (cyclical breast pain), premenstrual syndrome, rheumatoid arthritis, and menopausal hot flashes. The mastalgia story mirrors the eczema one: Goyal and Mansel's multicenter randomized trial in 555 women found that gamolenic acid (Efamast), with or without antioxidants, did not differ from placebo in reducing breast pain [5]. Across these indications the recurring pattern is small early-positive studies followed by larger negative ones; none has a stronger evidence base than the now-disproven eczema indication once did.

Safety considerations

Evening primrose oil is generally well tolerated; in the trials, adverse effects were mild and mostly gastrointestinal, occurring at rates similar to placebo [3]. The Cochrane authors noted a case report raising a theoretical concern about prolonged use (over a year) and another about increased bleeding in a patient taking warfarin, so caution with anticoagulants is reasonable, as is discussing prolonged use with a clinician. The short-term trials do not address long-term safety. None of this changes the central point: for eczema, the most useful interventions remain regular emollients, appropriate topical anti-inflammatory therapy, and trigger management — and evening primrose oil should not displace them.

Sources

1. Berth-Jones J, Graham-Brown RAC. "Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis." Lancet, 1993;341(8860):1557-60. PMID 8099640.
2. 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(7428):1385. PMID 14670885.
3. Bamford JTM, Ray S, Musekiwa A, et al. "Oral evening primrose oil and borage oil for eczema." Cochrane Database Syst Rev, 2013;(4):CD004416. PMID 23633319.
4. Bath-Hextall FJ, Jenkinson C, Humphreys R, Williams HC. "Dietary supplements for established atopic eczema." Cochrane Database Syst Rev, 2012;(2):CD005205. PMID 22336810.
5. Goyal A, Mansel RE. "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):41-7. PMID 15647077.