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Clin Cosmet Investig Dermatol. 2017 Oct 5;10:403-411. doi: 10.2147/CCID.S146760. eCollection 2017.

Feeding filaggrin: effects of l-histidine supplementation in atopic dermatitis.

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


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.


amino acid; atopic dermatitis; eczema; filaggrin; l-histidine; nutritional supplement; skin barrier

Conflict of interest statement

Disclosure CEMG reports grants from Zymogenetics, Stiefel, and Regeneron, grants and personal fees from Novartis and Pfizer. NKG is a founding director of Curapel, a University of Manchester spin-out company owning patents in this field. The other authors report no conflicts of interest in this work.

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