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Feeding filaggrin: effects of L-histidine supplementation in atopic dermatitis

Authors Tan SP, Brown SB, Griffiths CEM, Weller RB, Gibbs NK

Received 21 July 2017

Accepted for publication 5 September 2017

Published 5 October 2017 Volume 2017:10 Pages 403—411

DOI https://doi.org/10.2147/CCID.S146760

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 4

Editor who approved publication: Dr Jeffrey Weinberg

Siao Pei Tan,1,2 Simon B Brown,1,2 Christopher EM Griffiths,3 Richard B Weller,1,2 Neil K Gibbs3,4

1MRC Centre for Inflammation Research, 2Department of Dermatology, The University of Edinburgh, Edinburgh, 3Dermatology Centre, Division of Musculoskeletal and Dermatological Sciences, Salford Royal NHS Foundation Trust, University of Manchester, Manchester, 4Curapel, Life Sciences Hub Wales, Cardiff, UK

Abstract: Atopic dermatitis (AD), also known as eczema, is one of the most common chronic skin conditions worldwide, affecting up to 16% of children and 10% of adults. It is incurable and has significant psychosocial and economic impacts on the affected individuals. AD etiology has been linked to deficiencies in the skin barrier protein, filaggrin. In mammalian skin, l-histidine is rapidly incorporated into filaggrin. Subsequent filaggrin proteolysis releases l-histidine as an important natural moisturizing factor (NMF). In vitro studies were conducted to investigate the influence of l-histidine on filaggrin processing and barrier function in human skin-equivalent models. Our further aim was to examine the effects of daily oral l-histidine supplementation on disease severity in adult AD patients. We conducted a randomized, double-blind, placebo-controlled, crossover, nutritional supplementation pilot study to explore the effects of oral l-histidine in adult AD patients (n=24). In vitro studies demonstrated that l-histidine significantly increased both filaggrin formation and skin barrier function (P<0.01, respectively). Data from the clinical study indicated that once daily oral l-histidine significantly reduced (P<0.003) AD disease severity by 34% (physician assessment using the SCORingAD tool) and 39% (patient self-assessment using the Patient Oriented Eczema Measure tool) after 4 weeks of treatment. No improvement was noted with the placebo (P>0.32). The clinical effect of oral l-histidine in AD was similar to that of mid-potency topical corticosteroids and combined with its safety profile suggests that it may be a safe, nonsteroidal approach suitable for long-term use in skin conditions that are associated with filaggrin deficits such as AD.

Keywords: atopic dermatitis, eczema, filaggrin, l-histidine, amino acid, skin barrier, nutritional supplement

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