l-Histidine Supplementation in Adults and Young Children with Atopic Dermatitis (Eczema).

2020-10
The Journal of nutrition 150
- Neil K Gibbs

PubMed: 33000160
DOI: 10.1093/jn/nxaa200

Study Design

Type: Review
Sample size: n = 98
Population: adult subjects (n = 24) with AD; young children with AD (n = 49; mean age 3.5 y)
Methods: placebo-controlled clinical pilot study; oral l-histidine supplementation at 4 g daily for 8 wk (adults) and 0.8 g daily for 12 wk (children)
Blinding: Open-label
Duration: 8 wk (adults) and 12 wk (children)

Atopic dermatitis (AD) is an incurable, inflammatory skin condition that is prevalent (∼20%) in young children. There is an unmet clinical need, particularly in children, for safe interventions that target the etiology of the disease. Deficiencies in the skin barrier protein, filaggrin (FLG) have been identified as major predisposing factors in AD. In mammals, l-histidine is rapidly incorporated into epidermal FLG and subsequent FLG proteolysis releases l-histidine as an important natural moisturizing factor (NMF). It has therefore been hypothesized that l-histidine supplementation would be a safe approach to augment both FLG and the NMF, enhance skin barrier function, and reduce AD severity. In a clinical pilot study, adult subjects (n = 24) with AD took either a placebo or 4 g oral l-histidine daily for 8 wk. Unlike the placebo, l-histidine reduced AD (34% reduction in SCORing Atopic Dermatitis scores; P < 0.003) after 4 wk. Nine and 8 adverse events (AEs), and 1 and 0 severe AEs were recorded in the l-histidine or placebo groups, respectively, with no AE being causally related to l-histidine ingestion. A survey of adults (n = 98) taking 4 g l-histidine daily reiterated a lack of causal AEs and also reported a 33% reduction in topical corticosteroid use. A placebo-controlled, clinical pilot study conducted in young children with AD (n = 49; mean age 3.5 y) taking 0.8 g l-histidine daily, showed that eczema area and severity index scores were reduced by 49% (P < 0.02) at 12 wk, whereas a placebo had no effect. The children taking l-histidine had 50 minor AEs (compared with 39 on placebo), with 78% considered as "not," 18% "unlikely," and 4% "possibly" related to l-histidine ingestion. These studies indicate that at the levels reported, oral l-histidine supplementation is well tolerated and has potential as a safe intervention for long-term use in the management of AD in all age groups.

Research Insights

L-Histidine→Reduced Atopic Dermatitis Severity
l-histidine reduced AD (34% reduction in SCORing Atopic Dermatitis scores; P < 0.003) after 4 wk.
Effect
Beneficial
Effect size
Moderate
Dose
4 g oral l-histidine daily
L-Histidine→Reduced Eczema Area and Severity Index
eczema area and severity index scores were reduced by 49% (P < 0.02) at 12 wk, whereas a placebo had no effect.
Effect
Beneficial
Effect size
Moderate
Dose
0.8 g oral l-histidine daily
L-Histidine→Reduced Eczema Area and Severity Index Score
eczema area and severity index scores were reduced by 49% (P < 0.02) at 12 wk, whereas a placebo had no effect.
Effect
Beneficial
Effect size
Moderate
Dose
0.8 g oral l-histidine daily
L-Histidine→Reduced Topical Corticosteroid Use
A survey of adults (n = 98) taking 4 g l-histidine daily reiterated a lack of causal AEs and also reported a 33% reduction in topical corticosteroid use.
Effect
Beneficial
Effect size
Moderate
Dose
4 g oral l-histidine daily

Adverse Events Reported

L-Histidine→Overall tolerability
These studies indicate that at the levels reported, oral l-histidine supplementation is well tolerated and has potential as a safe intervention for long-term use in the management of AD in all age groups.
Finding
Reported
L-Histidine→adverse events (causal relationship)
with no AE being causally related to l-histidine ingestion.
Finding
Reported
Magnitude
no AE was causally related to l-histidine ingestion
L-Histidine→adverse events (general)
Nine and 8 adverse events (AEs), and 1 and 0 severe AEs were recorded in the l-histidine or placebo groups, respectively, with no AE being causally related to l-histidine ingestion.
Finding
Reported
Magnitude
9 adverse events in l-histidine group vs 8 in placebo group; 1 severe AE in l-histidine vs 0 in placebo
L-Histidine→adverse events (unspecified)
Nine and 8 adverse events (AEs), and 1 and 0 severe AEs were recorded in the l-histidine or placebo groups, respectively, with no AE being causally related to l-histidine ingestion.
Finding
Reported
L-Histidine→severe adverse events
Nine and 8 adverse events (AEs), and 1 and 0 severe AEs were recorded in the l-histidine or placebo groups, respectively, with no AE being causally related to l-histidine ingestion.
Finding
Reported
Severity
Serious adverse event
Grade
severe