The Skin-Like Moisturiser: COSSMA

Cosmetic ingredients with moisturising properties are a key requirement in any skin care formulation. Formulators are continuously on the lookout for materials that are stable, easy to formulate while being efficacious. One such moisturising ingredient, saccharide isomerate has found place in many cosmetic and prescription products.

Stratum corneum, the topmost layer of the epidermis regulates skin hydration. The epidermis is known to have its own moisturizing factors (NMFs), a group of chemical compounds consisting of free amino acids and their derivatives, pyrrolidine carboxylic acid and its salts, urocanic acid, inorganic salts, sugars, lactic acid, glycerol, and urea. NMF components are hydrophilic and polar in nature and absorb water from the environment allowing the cells to maintain adequate moisturisation. They also assist the corneocytes in maintaining adequate osmotic pressure giving the skin a healthy and taut look. Due to their polar nature, NMFs form ionic bonds with the keratin fibers thereby enhancing skin’s elasticity.1

Daily washing of skin has been shown to reduce NMF levels. Long periods of exposure to water, hot water baths or disturbances in skin physiology can lead to reduction in NMF concentrations leading to the skin looking wrinkled, dry, or flaky. Exposure to UV light and aging are also known to negatively impact NMF levels in skin. A study published by Boireau et al 2021, showed that there are only marginal differences in NMF concentration on face vs other sites.2 Studies have shown reduced NMF levels or its complete absence in dry skin conditions such as atopic dermatitis, xerosis, psoriasis and ichthyosis.

Topical application of moisturisers has been advocated for management of skin dryness. An effective moisturiser has a balanced composition of humectants, emollients and occlusives to ensure hydration along with desirable sensory attributes. While there are an innumerable number of products available in the market, consumer acceptability and consistency of use is a key factor in ensuring product effectiveness. Lotions are the most popular product format with ease of application and spreadability, quick absorption and low greasiness compared to ointments. The latter are known to be most effective in dry skin conditions as they form an occlusive layer on the skin inhibiting epidermal water loss. (Xu, 2017)4–6. This drives the need for advanced moisturisation agents that can provide long lasting hydration while being easy to formulate and minimal impact on skin-feel.

Saccharide isomerate (SI) is formed by base catalyzed isomerization of D-glucose from plant sources such as corn or sugarcane resulting in a mixture of mono and disaccharides, mainly glucose and fructose.7 The molecular weight of SI ranges from 120–400 Da to 15-20 kDa; the maximum reported being > 1.4 MDa. In some cases, an assortment of sugars, rhamnose, glucose, galactose, along with galacturonic acid and N-acetylglucosamine have been reported in SI.8 Figure 1 shows the comparative profile of SI and human skin. Excipients such as water, citric acid, sodium citrate and preservatives or viscosity enhancers may also be present along with SI. The earliest known commercially available material is Pentavitin by DSM.

In DNA microarray studies, SI has shown stimulation of hyaluron synthase-3, one of the genes responsible for regulation of hyaluronan synthesis in the epidermis. SI was also demonstrated to increase loricrin gene expression resulting in enhanced cornification of stratum granulosum and a more protected skin barrier. Acid sphingomyelinase gene responsible for ceramide synthesis was also found to be upregulated upon exposure to SI.9, 10 Overall, SI has been shown to improve skin hydration levels by both increasing water retention due to its chemistry but also impact on several genes responsible for skin barrier strengthening.

Formulating with SI

SI is water soluble and easy to formulate.9 With only one product reported in 2000, one can find a surge in number of products containing SI in the last 5 years with nearly 500 products and variants in the years 2021 and 2022. (Figure 2A) Further, we tried to understand the distribution of SI across various categories. Based on secondary research, more than 3000 products were identified globally to contain SI across various products in personal care and beauty. (Figure 2B) While the major fraction continues to be skin care, followed by skin cleansing, it was remarkable to see the use of this material in color cosmetics, lip care and fragrances. This wide utilisation of SI further prompted our search to understand its clinical efficacy. In further sections, we will be discussing the study findings related to this material.

SI improves scalp conditions

In a comparative study conducted on 18 volunteers, 0.2% SI showed 2X reduced TEWL and improved barrier repair properties compared to solubilised 0.03% bisabolol in a simulated wash-off scalp treatment study.9

Another randomised, placebo controlled, single-blind study conducted by Martin et al, on 90 Chinese men and women (Mean = 39.51 yrs), recently showed dose-and time-dependent TEWL reduction in SI containing shampoos in 14 uses over 28 days. The researchers also reported decreased sebum levels and improved adherence scalp flaking score for sulphate containing test shampoos containing 0.2% and 0.5% SI compared to placebo. In undisclosed data, the team also discussed time-dependent growth inhibition of Malassezia furfur with SI.11 The study was further extended to demonstrate scalp hydration levels using 3D-modelling. Regulated usage of 0.5% SI containing shampoo showed well distributed and increased hydration and lowered sebum levels in a healthy scalp compared to placebo.12

SI imparts moisturisation in hand hygiene products

In spite of increasing use of alcohol-based sanitisers, there have been limited developments in the formulations due to WHO and regulatory compliances. Frequent hand-washing and sanitisation have become a norm. Exposure to alcohol rubs and frequent washing results in skin barrier disruption leading to atopic dermatitis and eczema.13,14 In one such clinical study, Imfield et al studied the benefits of SI in a hand hygiene product. 1% SI aqueous solution in 70% alcohol-based hand sanitiser formulation, retained skin moisture levels more effectively compared to placebo. SI boosted hydration by 9% more than the placebo in one hour post application and showed 14% increase than the placebo after three hours of sanitiser usage compared to standard formula.15

SI imparts moisturisation benefits in skin cleansers

SI has been reported to bind with the -amino group of lysine present in skin leading to longer retentivity and hydration. This is evident in a plethora of clinical assessments of skin cleansing formulations, where increased hydration was reported post rinsing.9 In a randomised, placebo-controlled study, in 50 Caucasian women aged 18–50 years, soap-free shower gels pH ~5 with 0.2% and 0.5% SI showed improved skin hydration for 24 hours post use. The difference was well perceived in the self-evaluation questionnaire where >70% volunteers reported that their skin felt softer, less tight and moisturised in 7-day usage.16 In a separate study, 33 Asian women aged 21–65 years and with dry skin evaluated 0.2% and 0.5% SI formulations in a soap-base product, pH ~9 for one week twice daily. The skin was reported to recover to its normal status within 1 hour of cleansing compared to the placebo; the hydration was maintained throughout one week of product use along with enhanced foam.16 While, both 0.2% and 0.5% doses showed significant changes in hydration compared to the baseline, 0.5% SI was found to be more promising on a longer period of use.

SI in combination with D-panthenol provided significant skin hydration with no impact on pH, microbiome, and barrier function in continued once-daily applications of a cleansing product pH 5.5 in subjects with dry skin for 4 weeks. The study compared the efficacy of the hydrating cleanser compared to water control in 44 adults aged 18-70 years predominantly of Fitzpatrick skin type III.17

In a placebo-controlled study conducted on 30 healthy Caucasian females (aged 25–45 years), the effect of 0.5% SI containing soap based cleanser on the skin microbiome was studied. Samples before and after 1-week treatment were collected from the volar forearm. Reduction in pathogenic bacteria, B. casei and R. mucilaginosa and increase in beneficial bacteria, P. marcusii were reported upon use of SI formulation suggesting development of a healthy skin microbiome.18

SI improves moisturisation in creams

In a pilot, no-treatment control study, with 12 women (aged 39–41), the effect of 1% SI application on skin barrier function was studied before and after a wash out period by TEWL and tape stripping techniques. Reduction in TEWL by 20% after 20 tape stripping compared to baseline and extended hydration up to 72 hours was reported. Enhanced aesthetics such as skin smoothness, firmness and reduced flaking and itching were also perceived by the consumers. The study confirms both binding of SI to stratum corneum as well as permeation into the deeper layers.9

In a double-arm study comprising of 30 subjects aged 30–35 years, Vlorensia et al compared the effectiveness of SI and ceramides in a moisturising formula across multiple body sites. Both the treatments resulted in improved skin hydration during and after the completion of the 1-week treatment period.19 The researchers also reported the effectiveness of a SI cream alone and in combination with ceramides in reducing TEWL in eczematous skin in 2 weeks in 48 subjects of Asian Indonesian origin aged 30–35 years.20

32 healthy female subjects (22.5 ± 1.7 years old) of various ethnicities with normal non-photodamaged skin participated in the evaluation of a moisturising cream containing SI, niacinamide and glycerin for 28 days. Facial mapping showed improved skin hydration in the nasolabial and middle cheek area upon product use compared to baseline.21 In a blinded, vehicle-controlled study conducted in Chinese females (n = 62; 35.0 ± 0.9 years old, Fitzpatrick skin phototype II-IV, application of a 3% SI cream showed some improved hydration within 3 hours of application and extended hydration across all facial sites on prolonged use for 28 days, twice daily compared to the placebo.21  5% SI containing moisturising cream has also been found to improve skin hydration in 30 Asian Indonesian women (aged 30–45 years) within 2 weeks of application compared to a standard moisturiser. The SI cream was shown to maintain hydration even after discontinuation suggesting long lasting effects of the test material.22

In a group of 18 healthy people (age = 23–60 years) with Fitzpatrick type I-IV presenting dry skin, a comparative study showing the effectiveness of 3% w/w urea, SI or xylitol derivatives against a placebo control was conducted. Both SI and xylitol derivatives showed reduced skin roughness in a single application23.

Conclusion

In this review, we have evaluated and described the findings from various clinical studies. SI has been shown to be beneficial in both skin care and cleansing products. It is active at a low dose of 0.5% in cleansers in providing both instant and prolonged skin hydration, reducing surfactant and soap harshness, maintaining the microbiome, and improving scalp health. In skin care formulations, doses ranging from 1–5% have been shown to be effective in improving skin hydration with effects lasting up to  72 hours. Certain drawbacks have also been observed in study design. Most of the studies have been conducted on 30 and lesser volunteers raising concerns about the sample size and the power of the trial. Furthermore, no studies have been conducted on dry skin conditions except one report by Vlorensia et al19, where the requirements of such moisturizing materials are higher than normal healthy individuals. Due to the ease of formulation and hydrophilic nature, SI is expected to be a well sought material for products suited for all skin types. Thorough evaluation in atopic skin conditions will throw more light on the effectiveness of this molecule.

References:

1 Fowler J. Understanding the Role of Natural Moisturizing Factor in Skin Hydration. Pract Dermatol. 2012(Jul):36-40

2 Boireau-Adamezyk E, Baillet-Guffroy A, Stamatas GN. The stratum corneum water content and natural moisturization factor composition evolve with age and depend on body site. Int J Dermatol. 2021;60(7):834-839. doi:10.1111/ijd.15417

3 Sugawara T, Kikuchi K, Tagami H, Aiba S, Sakai S. Decreased lactate and potassium levels in natural moisturizing factor from the stratum corneum of mild atopic dermatitis patients are involved with the reduced hydration state. J Dermatol Sci. 2012;66(2):154-159.doi:10.1016/j.jdermsci.2012.02.011

4 Lodén M. The clinical benefit of moisturizers. J Eur Acad Dermatol Venereol. 2005;19:672-688. doi:10.1111/j.1468-3083.2005.01326.x

5 Xu S, Kwa M, Lohman ME, Evers-Meltzer R, Silverberg JI. Consumer Preferences, Product Characteristics, and Potentially Allergenic Ingredients in Best-selling Moisturizers. JAMA Dermatol.2017;153(11):1099-1105. doi:10.1001/jamadermatol.2017.3046

6 Kraft JN, Lynde CW. Moisturizers: what they are and a practical approach to product selection. Skin Ther Lett. 2005;10(5):1-8.

7 Konig J, Padberg G. Carbohydrate agent of high water retention power,process of making same,and composition containing same. Published online May 11, 1971. Accessed May 20, 2023. https://patents.google.com/patent/US3578655/en

8 Safety Assessment of Anhydrogalactose, Anhydroglucitol, Anhydroxylitol, Arabinose, Psicose, Saccharide Hydrolysate, and Saccharide Isomerate as Used in Cosmetics.

9 Klock J, Rosenberger V. Saccharide Isomerate to Deeply Hydrate Skin and Scalp. Cosmetics & Toiletries. Published September 11, 2013. Accessed May 20, 2023. https://www.cosmeticsandtoiletries.com/cosmetic-ingredients/article/21835968/saccharide-isomerate-todeeply-hydrate-skin-and-scalp

10 Nunes S, Vieira JC, Melo CSA. Evaluation of the moisturizing and protective activity of a topical product containing saccharide isomerate and hydroxyethyl urea, on the skin barrier. Surg Cosmet Dermatol. 2018;10(3):19-26. doi:10.5935/scd1984-8773.201810311039

11 Martin E, Zhang A, Campiche R. Saccharide isomerate ameliorates cosmetic scalp conditions in a Chinese study population. J Cosmet Dermatol. 2023;22(1):262-266. doi:10.1111/jocd.14913

12 Martin E, Campiche R, Gourion-Arsiquaud S, Jomier M, Waeckel M, Guillemard F. On the Map – Skin Actives for Scalp Care. SOFW. 2023(5). Accessed May 29, 2023. https://www.sofw.com/en/sofw-journal/articles-en/48-personal-care/3794-on-the-map-skin-actives-for-scalp-care

13 Beiu C, Mihai M, Popa L, et al. Frequent Hand Washing for COVID-19 Prevention Can Cause Hand Dermatitis: Management Tips. Cureus. 2020;12(4). doi:10.7759/cureus.7506

14 Singh M, Pawar M, Bothra A, Choudhary N. Overzealous hand hygiene during the COVID 19 pandemic causing an increased incidence of hand eczema among general population. J Am Acad Dermatol. 2020;83(1):e37-e41. doi:10.1016/j.jaad.2020.04.047

15 Imfield D, Laurent G, Rosenberger V, Adamietz S, Guillemard F, Zhang A. Moisturising care and hygiene go hand in hand. Pers Care Mag. 2021(Feb):1-3.

16 Rosenberger V, Sfriso R, Laurent G, Adamietz S. No more skin dryness after cleansing. Pers Care Mag. 2021(Jul):55-56

17 Peltier E, Trapp S, de Salvo R, et al. A new dexpanthenol-containing liquid cleanser for atopic-prone skin: Results from two prospective clinical studies evaluating cutaneous tolerability, moisturization potential, and effects on barrier function. J Cosmet Dermatol. 2022;21(9):3859-3866. doi:10.1111/jocd.15252

18 Sfriso R, Claypool J. Microbial Reference Frames Reveal Distinct Shifts in the Skin Microbiota after Cleansing. Microorganisms. 2020;8(11):1634. doi:10.3390/microorganisms8111634

19 Vlorensia, Hartini H, Abdullah H, Raif Martinus A, Ikhtiari R. The Effect of a Moisturizing Cream with Saccharide Isomerate and Ceramide on Increasing Skin Hydration. In: Proceedings of the International Conference on Health Informatics and Medical Application Technology; 2019:428-475

20 Hartini H, Vlorensia, Abdullah H, Raif Martinus A, Ikhtiari R. The Effect of a Moisturizing Cream Containing Saccharide Isomerate and Ceramide on Reducing Transepidermal Water Loss in Eczema. In: Proceedings of the International Conference on Health Informatics and Medical Application Technology; 2019:411-417

21 Voegeli R, Gierschendorf J, Summers B, Rawlings AV. Facial skin mapping: from single point bio-instrumental evaluation to continuous visualization of skin hydration, barrier function, skin surface pH, and sebum in different ethnic skin types. Int J Cosmet Sci. 2019;41(5):411-424. doi:10.1111/ics.12562

22 Dewi DAR, Pangkahila W. Addition of 5% Saccharide Isomerates in Moisturizing Formulation Increases Skin Hydration Higher than Regular Moisturizers. Eduvest - J Univers Stud. 2022;2(8):1.536-1.551. doi:10.59188/eduvest.v2i8.562

23 Gougeon S, Hernandez E, Chevrot N, et al. Evaluation of a new connected portable camera for the analysis of skin microrelief and the assessment of the effect of skin moisturisers. Skin Res Technol. 29:1-15