Gamma-linolenic acid levels correlate with clinical efficacy of evening primrose oil in patients with atopic dermatitis

Dagmar Simon, Peter A Eng, Siegfried Borelli, Roland Kägi, Christian Zimmermann, Catherine Zahner, Jürgen Drewe, Lorenzo Hess, Giovanni Ferrari, Stephan Lautenschlager, Brunello Wüthrich, Peter Schmid-Grendelmeier, Dagmar Simon, Peter A Eng, Siegfried Borelli, Roland Kägi, Christian Zimmermann, Catherine Zahner, Jürgen Drewe, Lorenzo Hess, Giovanni Ferrari, Stephan Lautenschlager, Brunello Wüthrich, Peter Schmid-Grendelmeier

Abstract

Introduction: Atopic dermatitis (AD) has been related to a deficiency of delta-6-desaturase, an enzyme responsible for the conversion of linoleic acid to gamma-linolenic acid (GLA). Evening primrose oil (EPO) contains high amounts of GLA. Therefore, this study investigated whether EPO supplementation results in an increase in plasma GLA and its metabolite dihomo-gamma-linolenic acid (DGLA) correlating with clinical improvement of AD, assessed by the SCORing Atopic Dermatitis (SCORAD) index.

Methods: The open study included 21 patients with AD. EPO (4-6 g) was administered daily for 12 weeks. Before treatment, and 4 and 12 weeks after initiation of EPO supplementation, objective SCORAD was assessed and plasma concentrations of GLA and DGLA were determined by gas chromatography.

Results: A significant increase in plasma GLA and DGLA levels and a decrease in the objective SCORAD were observed 4 and 12 weeks after initiation of EPO treatment. In the per-protocol population (n = 14), a significant inverse correlation between the changes in plasma GLA levels and SCORAD was found (P = 0.008).

Conclusion: The clinical disease activity under EPO treatment correlates with the individual increase in plasma GLA levels. Thus, the results of this pilot study indicate that an increase in plasma GLA might be used as predictive parameter for responsiveness of AD to EPO therapy.

Trial registration: ClinicalTrials.gov NCT00878670.

Figures

Fig. 1
Fig. 1
Objective SCORAD (%, mean ± SEM) in the intention-to-treat population (n = 21) assessed at baseline and 4 and 12 weeks after initiation of EPO treatment (Wilcoxon Signed Rank Test). EPO evening primrose oil, SCORAD SCORing Atopic Dermatitis
Fig. 2
Fig. 2
Plasma GLA (a) and DGLA (b) levels (mean ± SEM) in the intention-to-treat population (n = 21) at baseline and 4 and 12 weeks after initiation of EPO treatment (Wilcoxon Signed Rank Test). DGLA dihomo-gamma-linolenic acid, EPO evening primrose oil, GLA gamma-linolenic acid
Fig. 3
Fig. 3
Correlation analysis on the per-protocol population (n = 14) between the change in objective SCORAD (%) and change of plasma GLA (%) from baseline versus last visit. GLA gamma-linolenic acid, SCORAD SCORing Atopic Dermatitis

References

    1. Bieber T. Atopic dermatitis. N Engl J Med. 2008;358(14):1483–1494. doi: 10.1056/NEJMra074081.
    1. Wuthrich B, Cozzio A, Roll A, Senti G, Kundig T, Schmid-Grendelmeier P. Atopic eczema: genetics or environment? Ann Agric Environ Med. 2007;14(2):195–201.
    1. Simon D, Kernland Lang K. Atopic dermatitis: from new pathogenic insights toward a barrier-restoring and anti-inflammatory therapy. Curr Opin Pediatr. 2011;23(6):647–652. doi: 10.1097/MOP.0b013e32834cad0a.
    1. Horrobin DF. Fatty acid metabolism in health and disease: the role of delta-6-desaturase. Am J Clin Nutr. 1993;57(5 Suppl):732S–6S (discussion 6S-7S).
    1. Ziboh VA, Miller CC, Cho Y. Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of antiinflammatory and antiproliferative metabolites. Am J Clin Nutr. 2000;71(1 Suppl):361S–366S.
    1. Yen CH, Dai YS, Yang YH, Wang LC, Lee JH, Chiang BL. Linoleic acid metabolite levels and transepidermal water loss in children with atopic dermatitis. Ann Allergy Asthma Immunol. 2008;100(1):66–73.
    1. Horrobin DF. Essential fatty acid metabolism and its modification in atopic eczema. Am J Clin Nutr. 2000;71(1 Suppl):367S–372S.
    1. Fan YY, Chapkin RS. Importance of dietary gamma-linolenic acid in human health and nutrition. J Nutr. 1998;128(9):1411–1414.
    1. Martens-Lobenhoffer J, Meyer FP. Pharmacokinetic data of gamma-linolenic acid in healthy volunteers after the administration of evening primrose oil (Epogam) Int J Clin Pharmacol Ther. 1998;36(7):363–366.
    1. Morse NL, Clough PM. A meta-analysis of randomized, placebo-controlled clinical trials of Efamol evening primrose oil in atopic eczema. Where do we go from here in light of more recent discoveries? Curr Pharm Biotechnol. 2006;7(6):503–524. doi: 10.2174/138920106779116946.
    1. 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(1):75–90.
    1. van Gool CJ, Zeegers MP, Thijs C. Oral essential fatty acid supplementation in atopic dermatitis-a meta-analysis of placebo-controlled trials. Br J Dermatol. 2004;150(4):728–740. doi: 10.1111/j.0007-0963.2004.05851.x.
    1. Williams HC. Evening primrose oil for atopic dermatitis. BMJ. 2003;327(7428):1358–1359. doi: 10.1136/bmj.327.7428.1358.
    1. Williams HC, Grindlay DJ. What’s new in atopic eczema? An analysis of the clinical significance of systematic reviews on atopic eczema published in 2006 and 2007. Clin Exp Dermatol. 2008;33(6):685–688. doi: 10.1111/j.1365-2230.2008.02906.x.
    1. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Arch Dermatol. 1980;113:663–670. doi: 10.1001/archderm.1977.01640050123023.
    1. Oranje AP, Glazenburg EJ, Wolkerstorfer A, de Waard-van der Spek FB. Practical issues on interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the three-item severity score. Br J Dermatol. 2007;157(4):645–8.
    1. Schulte E, Weber K. Fast generation of fatty acid methly esters from lipids using trimethyl sulfonium hydroxide or sodium methylate [German] Eur J Lipid Sci Technol. 1989;5:181–183.
    1. Focke M, Sesztak-Greinecker G, Brannath W, Gotz M, Jarisch R, Hemmer W. Plasma levels of polyunsaturated fatty acids in children with atopic dermatitis and in atopic and nonatopic controls. Wien Klin Wochenschr. 2005;117(13–14):485–491. doi: 10.1007/s00508-005-0394-z.
    1. van Gool CJ, Thijs C, Henquet CJ, et al. Gamma-linolenic acid supplementation for prophylaxis of atopic dermatitis–a randomized controlled trial in infants at high familial risk. Am J Clin Nutr. 2003;77(4):943–951.
    1. Henz BM, Jablonska S, van de Kerkhof PC, et al. Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema. Br J Dermatol. 1999;140(4):685–688. doi: 10.1046/j.1365-2133.1999.02771.x.

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