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Cosmeceutical Critique: Glycerol
 

Volume 37, Issue 9, Page 22 (September 2006)

Derived from the saponification of fats, glycerin (also spelled glycerine and usually referred to in the literature as glycerol) is a strong, nonvolatile trihydroxylated humectant that exhibits hygroscopic ability very similar to that associated with natural moisturizing factor (J. Soc. Cosmet. Chem. 1976;27:65; Acta Derm. Venereol. 1999;79:418–21). Natural moisturizing factor is found in corneocytes and can absorb large quantities of water, even when humidity levels are low, which allows the stratum corneum (SC) to maintain a sufficient hydration level in dry environments. Numerous ingredients have been used in moisturizing products to mimic the activity of natural moisturizing factor, and glycerol is one of the more successful.

Carl Wilhelm Scheele discovered glycerol in 1779, and since that time it has been widely incorporated into cosmetics. About 160,000 tons of the compound are used annually in the United States alone (J. Cosmet. Sci. 2002;53:229–36; Proc. Natl. Acad. Sci. USA 2003;100:7360–5). Glycerol is considered to be the most effective humectant (Skin Therapy Lett. 2005;10[5]:1–8), and has recently been shown to provide other benefits.



Mechanism of Action

It is known that skin xerosis is linked to incomplete desmosome degradation. In an in vitro study conducted a decade ago of moisturizers that facilitate desmosome digestion, investigators observed via electron microscopy that desmosomes treated with glycerol were in more advanced stages of degradation than was control tissue. In two other in vitro models evaluated by the same team, glycerol raised the corneocyte loss rate from the superficial surface of human skin biopsies and significantly reduced intercorneocyte forces (Arch. Dermatol. Res. 1995;287:457–64).

It has since been established that glycerol accelerates corneocyte maturation by inducing the activity of residual transglutaminase in the SC (Int. J. Cosmet. Sci. 2003;25:157–68; Skin Therapy Lett. 2005;10[5]:1–8). Glycerol diminishes xerotic scaling by contributing to desmosome digestion and then enhancing desquamation (Arch. Dermatol. Res. 1995;287:457–64).

In a 5-year study comparing two high-glycerol moisturizers with 16 other popular moisturizers in 394 patients with severe xerosis, the high-glycerol products outperformed the rest by more rapidly restoring normal hydration and preventing the resumption of dryness for a longer period—longer even than petrolatum. Glycerol also was shown to stabilize and fluidize cell membranes, as well as hydrate enzymes required for desmosome degradation (M. Loden and H. I. Maibach, eds. “Dry Skin and Moisturizers: Chemistry and Function,” 2000, Boca Raton, Fla.: CRC Press, p. 217). Ultrastructural analysis of skin treated with high-glycerol formulations has shown that glycerol expands not only corneocytes but also the space between layers of corneocytes, which results in expansion of the SC (Poster presentation, 53rd Annual Meeting of the American Academy of Dermatology, February 1995). These findings indicate that glycerol endows skin with the capacity to hold a reservoir of moisture that makes it more resistant to drying.

In a recent study of mice deficient in the epidermal water/glycerol transporter aquaporin-3 (AQP3), glycerol replacement ameliorated several defects, including diminished SC hydration and skin elasticity, as well as poor barrier recovery after SC removal. Notably, SC water content, which was measured as threefold lower in the AQP3-null mice than in wild-type mice, was restored by administration of topical or systemic glycerol, but administration of glycerol-like osmolytes, such as xylitol, erythritol, and propanediol, was unsuccessful. In addition to concluding that glycerol is an important determinant of SC water retention, the investigators suggested that their data provide a strong scientific foundation for the centuries-old practice of including glycerol in skin formulations for medicinal and cosmetic purposes (Proc. Natl. Acad. Sci. USA 2003;100:7360–5).

The authors also noted that when glycerol is added to SC lipids in vitro, it is thought to combine with lipid lamellae, foster water absorption, and hinder the conversion of lipid lamellar structures from liquid to solid crystal, thereby inhibiting or preventing water loss (J. Soc. Cosmet. Chem. 1990;41:51–65; Proc. Natl. Acad. Sci. USA 2003; 100:7360–5). This hypothesis, the data from this study, and the fact that pure glycerol absorbs its own weight in water in 3 days led the authors to speculate that glycerol likely improves SC water absorption and retention.

A recent study of asebia mice with profound sebaceous gland hypoplasia revealed that the topical application of glycerol (which is believed to be endogenously produced in sebaceous glands by triglyceride hydrolysis) restored normal SC hydration, whereas the endogenous humectant urea did not. The investigators also showed that glycerol from triglycerides in sebaceous glands contributes significantly to SC hydration (J. Invest. Dermatol. 2003;120:728–37).

In a more recent study, researchers found that endogenous glycerol, from the circulation into the epidermis via AQP3 and from triglyceride hydrolysis in sebaceous glands, is associated with SC hydration in humans. Indeed, they observed that glycerol from both sources forms a water reservoir that affects such hydration. The authors also noted that other findings in their study support the use of therapeutic moisturizers that contain glycerol (J. Invest. Dermatol. 2005;125:288–93).



Skin Barrier Stablilization

The capacity of glycerol as a barrier stabilizer and moisturizing compound is supported by two studies conducted by the same team in 1999. In the first study, barrier repair was found to be more rapid in glycerol-treated sites. Significant differences were noted 3 days after treatment between glycerol open vs. untreated and glycerol occluded vs. untreated sites, and SC hydration was superior in the glycerol plus occlusion sites.

In the second study, barrier repair was again more rapid in glycerol-treated areas, with significant differences, compared with untreated and base-treated areas at day 7, and SC hydration was superior in glycerol-treated areas after 3 days of treatment. The authors concluded that glycerol promotes barrier repair, notably after acute exogenous disturbance, and enhances hydration of the SC (Acta Derm. Venereol. 1999;79:418–21).

In a study of dermatologic vehicles and their effect on the horny layer, investigators found that adding glycerol to oil-in-water (O/W) emulsions eliminated the barrier-damaging effect of such formulations. O/W emulsions containing glycerol also decreased horny layer damage in stress tests with wash solutions, and were deemed to be appropriate for atopic dermatitis therapy (Skin Pharmacol. Physiol. 2004;17:267–73). More recently, combining glycerol with occlusive agents has been shown to confer a synergistic amelioration of xerotic symptoms (Skin Therapy Lett. 2005;10[5]:1–8; J. Soc. Cosmet. Chem. 1996;47:39).



On the Market

Glycerol, which helps condition the skin, is the most widely used hydrating agent and, as such, is a common ingredient in skin cleansers, creams, lotions, cosmetics, and cosmeceuticals. Its importance stems from its efficacy, long history of use (it has a veritable classic status among cosmetic raw materials), and pervasiveness in the skin care product market.

Recent research has indicated that glycerol exhibits multiple mechanisms of action, and its efficacy depends on the choice of vehicle and emulsifying agent. These considerations are especially important when making proper recommendations to patients and for helping consumers select over-the-counter products.

PII: S0037-6337(06)71517-0

doi:10.1016/S0037-6337(06)71517-0

© 2006 Elsevier Inc. All rights reserved.


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