Trehalose
Also known as Trehalose, Mycose, Tremalose, alpha,alpha-trehalose, alpha-D-glucopyranosyl-alpha-D-glucopyranoside
“CIR Expert Panel says: safe as used in cosmetics.”
Trehalose (CAS 99-20-7) is a non-reducing disaccharide composed of two alpha-D-glucose units linked α(1→1), functioning as a humectant and skin conditioning agent. The CIR Expert Panel's 2014 group safety assessment (published IJT 38(1_suppl):5S-38S, 2019; PMID 31170840) explicitly concluded trehalose is 'safe in the present practices of use and concentration in cosmetics.' The assessment noted 474 VCRP-reported cosmetic uses for trehalose, second only to sucrose among the 25 saccharide ingredients reviewed. The Panel assessed trehalose as not genotoxic in vitro; genotoxic potential was also evaluated in vivo with negative results, making it one of the few ingredients in the group for which both in vitro and in vivo genotoxicity data were available and negative. Because trehalose is listed in the Food Chemical Codex and is a common dietary sugar metabolized by intestinal trehalase, the Panel focused safety review on dermal effects; no dermal irritation or sensitization concerns were identified. Recent literature adds mechanistic context: Muto et al. (Commun Biol 2023; PMID 36609486) showed highly concentrated trehalose (100 mg/mL) promotes epidermal spread in engineered skin models without deleterious effects and accelerates wound healing via a CDKN1A/p21 prohealing senescence-like state in fibroblasts — a notable cryoprotective mechanism relevant to its biological reputation. Chmielewski and Lesiak (Clin Cosmet Investig Dermatol 2024; PMID 39624066) reviewed trehalose's role in mitigating glycation and oxidative stress in skin aging, noting anti-AGE and photoprotective effects when combined with hyaluronic acid.
Humectant: attracts and retains water in the stratum corneum through its multiple hydroxyl groups and hygroscopic α,α-1,1-glycosidic structure (CIR 2014; 474 reported cosmetic uses in VCRP data).
Unique cryoprotective/desiccation-tolerance mechanism: trehalose forms an amorphous glass ('vitrification') that stabilizes cell membranes and proteins against desiccation stress — the basis for its widespread use in dried/lyophilized cosmetic and pharmaceutical formulations.
Pro-healing: highly concentrated trehalose promotes wound closure and neo-vascularization in mouse models via a transient CDKN1A/p21-mediated senescence-like state in dermal fibroblasts without cytotoxicity (Muto et al. 2023, PMID 36609486).
Anti-glycation and photoprotective: trehalose inhibits formation of advanced glycation end-products (AGEs) and provides UVB photoprotection in skin models, with synergistic anti-aging effects when combined with hyaluronic acid (Chmielewski & Lesiak 2024, PMID 39624066).
Genotoxicity: negative in both in vitro and in vivo assays — one of few saccharides in the 2014 CIR group assessment with both test types completed (CIR FR 2014).
Long history of food and cosmetic use; metabolized endogenously by intestinal trehalase to glucose.
Group (class-level) safety assessment: trehalose was included as one of 25 saccharide ingredients; dedicated individual CIR report does not exist as of the QRT date (2018). Evidence basis is robust for the class but trehalose-specific dermal data are limited.
Trehalose is listed in the Food Chemical Codex but is NOT listed as a GRAS food substance under 21 CFR 184 at the time of the 2014 CIR assessment (lacks '#' designation in the CIR FR); a subsequent GRAS Notice (GRN 912) was filed for food use but does not constitute a cosmetic regulatory determination.
The biological mechanism of cellular cryoprotection (vitrification, desiccation tolerance) is well established for trehalose but is an efficacy mechanism, not a safety concern; no adverse effects associated with this mechanism were identified in the cosmetic concentration range.
CIR Quick Reference Table (12/2017, revised 07/2018) — Trehalose row: Finding=S (Safe), Citation='Final report 03/2014 available from CIR'
“Trehalose | S | | Final report 03/2014 available from CIR”— QRT-122017revised072018.pdf, p. 134