Formulating Dead Sea Mud in Cosmetic Products, Its Effects on Skin, and the Underlying Biological Mechanism: A Review

Research Background: The marketing of cosmetic products derived from Dead Sea (DS) mud has undergone significant evolution, transforming from simple souvenirs into a large-scale cosmetic industry offering a diverse array of products. DS mud is utilized both as pure mud for home spa treatments and as an active ingredient in cosmetic and cosmeceutical formulations. Its global appeal is largely due to its natural, health-oriented image, which aligns with consumer preferences and provides assurance regarding its use in skincare. Research Objectives: This review examines the published data related to the rationale for formulating DS mud in cosmetics, the biological and cosmetic effects of DS mud on the skin, and the speculated bio-mechanisms underlying these effects. Methods: We screened relevant literature on DS mud collected from the shores of the Dead Sea in Jordan and Israel. Publications on mineral muds excavated in different locations around the globe, as well as studies on the biological mechanisms of other DS minerals, were also reviewed as indications and supportive recommendations. Summarizing the vast collected data into a comprehensive review was undertaken to expose readers to the various aspects of DS mud in cosmetics. Results: The primary reason for formulating DS mud in skincare products is its deep cleansing and skin detoxification properties. Consequently, it is often incorporated into rinse-off masks, soaps, and scrubbing products. Additionally, DS mud is used in leave-on products and sheet masks. Cosmeceutical applications of DS mud, recommended for various skin conditions, offer complementary treatments to improve the quality of life for people with skin diseases. The physicochemical and biological effects of DS mud are driven by its rich mineral ion composition, including magnesium, calcium, sodium, potassium, zinc, and strontium—elements known to improve skin barrier function, enhance hydration, and reduce inflammation. The high salt concentration induces moderate ionic osmotic stress, stimulating cellular growth and hydration pathways. Moreover, DS mud’s anti-microbial properties further contribute to its therapeutic potential. Ongoing innovations in formulation techniques continue to expand the applications of DS mud, including blending it with other active ingredients, developing novel application methods, and refining manufacturing processes to improve product quality and efficacy. Conclusions: DS mud remains a valuable ingredient in modern skincare due to its rich mineral content and therapeutic properties. Ongoing research and technological advancements promise further innovations, reinforcing its status as a natural and effective component in the global cosmetics industry.

A Dead Sea Water-Enriched Body Cream Improves Skin Severity Scores in Children with Atopic Dermatitis

Dead Sea (DS) mud and water are known for their unique composition of minerals, and for their therapeutic properties on inflammatory skin diseases. The objective of the study was to evaluate the efficacy of an emollient cream enriched with DS water in children with atopic dermatitis (AD). Eighty six AD children were randomized in a double-blind controlled study to receive twice-daily topical treatment with a body cream enriched with DS minerals (TP) compared to two types of control: 1) DM, DS minerals with lower DS water concentrations than TP, and 2) an emollient (E) with no DS minerals. Efficacy was assessed by a change in clinical skin severity scores: SCORing Atopic Dermatitis (SCORAD), investigator’s global assessment (IGA) and patient global assessment (PGA) as well as by objective physiological parameters: transepidermal water loss (TEWL), stratum corneum hydration (SCH), affected body surface area (BSA) and Objective Severity Assessment of Atopic Dermatitis (OSAAD). The total length of the trial was 12 weeks divided to 6 visits at weeks 0, 2, 4, 6, 8, 12. The study showed that both TP and DM creams improved OSAAD scores. Only TP improved TEWL and SCH. TP was the most effective regarding TEWL, SCH and OSAAD compared to DM and E. Treatment with E decreased more significantly IGA score compared to TP. Although within each treatment group significant improvements in SCH, BSA, SCORAD, IGA and PGA were observed, the reduction in BSA, SCORAD and PGA was not significantly different among the groups. Our results clearly show the benefits of TP as a leave on-skin emulsion enrich with DS water in terms of skin barrier function. Thus, TP can serve as an effective adjuvant treatment for AD skin as well as for its maintenance.

Protective Effects of a Novel Preparation Consists of Concentrated Dead Sea Water and Natural Plants Extracts against Skin Photo-Damage

Background: Exposure to solar UV rays has deleterious effects on skin appearance through physiological and structural alterations that eventually lead to skin photo-damage. Aims: To test the photo-protective effect of a novel preparation, Dead Sea Osmoter Concentrate (DSOC), containing high concentration of Dead Sea water. Methods: Human skin organ culture was used as a model to assess the biological effects of UVB irradiation and the protective effect of topical application of DSOC preparation. Skin pieces were analyzed for mitochondrial activity by Alamar blue (resazurin) assay, for apoptosis by caspase 3 assay, for detoxification by proteasome 20S sub-unit activity and for skin hydration by aquaporin 3 (AQP3) membrane channels expression. Human subjects were tested to evaluate the effect of DSOC Serum, a topical formula for facial skin, on skin hydration by a corneometer. Results: UVB irradiation induced cell apoptosis in the epidermis of skin organ cultures and decreased their proteasome activity and AQP3 expression. Topical application of DSOC significantly attenuated all these effects. In human subjects, an elevation in the intense skin moisture, which was higher relatively to subjects’ regular moisturizer, was observed. Moreover, DSOC Serum boosted the hydration effect together with regular moisturizer. Conclusions: The results clearly demonstrate that DSOC preparation can significantly improve the skin capability in coping with UVB rays stress in different cellular functions such as anti-apoptotic properties as well as detoxification and hydration recovery that can attenuate biological effects of skin photo-damage. Topical application of DSOC Serum had contributed to skin appearance by a strong hydration impact, also as a booster.

Safe Retinol-Like Skin Biological Effect by a New Complex, Enriched with Retinol Precursors

Background: Retinol (RE) is deeply involved in skin processes, therefore it is widely formulated in cosmetics, primarily as an anti-aging ingredient. Despite its efficacy, the safety profile of RE is controversial. Objectives: Pretinol (PRE) complex was formulated with two RE precursors, β-Carotene and Niacinamide, in order to deliver retinol-like skin benefits with healthier characteristics, assuming that skin enzymes will enable safe RE supply on spot. Methods: The expression levels of hyaluronic acid, Tumor Necrosis Factor alpha (TNFα) and Interleukin 1 alpha (IL-1α), were measured using various skin models before and after exposure to PRE and RE. Full genome microarray was performed and the affected genes and pathways were analyzed. Results: Following fibroblasts exposure to PRE, the natural synthesis of hyaluronic acid is significantly elevated. Skin safety, demonstrated via cytokines expression on ex-vivo skin, results with TNFα and IL-1α elevation by RE application. In contrary PRE significantly reduces TNFα while IL-1α is not affected. These results establish skin safety advantage of PRE vs RE. Microarray results examined on skin equivalents reveal the involvement of PRE in inflammatory attenuation. Conclusions: Formulating RE precursors as a safe source for RE is partially supported. PRE presents a skin benefit in parallel to RE, while PRE characteristics are suggested to be safer to skin.

Topical Application of Synbiotic Bacillus Preparations Positively Affects Skin (Micro) Biology

Alteration in skin microbiome profile is involved in many skin conditions, therefore, microbiome modulation is a reasonable target for skin health. Probiotic skincare was suggested, and leave-on synbiotic skincare preparation, blending bacillus spores, as probiotic active ingredient, and inulin sugar, as prebiotic booster, is evaluated, using microarray, 16S gene sequencing, and clinical skin analyses. Topical application of leave-on synbiotic skincare on skin model activates a profound effect on skin biology, expressed in the transcriptome level, with higher than 10% affected genes. The significance of the synbiotic preparation on skin biology was assured, indicating the involvement of major biological pathways. Blending probiotic with Polygonum aviculare plant extract, had triggered a distinct gene expression alteration, demonstrating the sensitivity of skin responses to different active substances. A synbiotic skincare application, had successfully introduced live and active Bacillus probiotics on human skin, detectable days after application was finalized. Following synbiotic application, the microbial content of several microorganisms, related to skin pathologies, was reduced, while the content of bacillus species, representing a healthier microbiome status, was increased, suggesting that frequent application may lead to overall healthier skin microbiome. Acne vulgaris involves unbalanced skin microbiome, with expansion of Cutibacterium acnes. The efficacy of a synbiotic skin cream was assessed to improve acne symptoms, including IGA dermatologist acne severity score, the number of counted acne lesions, measured skin oiliness and skin redness, visual appearance of skin-pores, skin smoothness and softness, and Acne Quality of Life Index.

How to Predict AGEs Accumulation Slowdown Effect of a Cosmetic Ingredient? Two Steps <i>In-Vitro</i>System for Evaluating the Anti-AGE Impact of a New Blend

Advanced Glycation End-Products (AGEs), play a crucial part in advancing the process of cellular skin aging and its link to chronological age was re-assessed. AGEs accumulation alters cell structure and function of most types of skin cells, affecting skin’s mechanical and physiological properties, following the molecular transformations. Slowdown AGEs accumulation rate in skin, although a potent anti-aging strategy, is difficult and tricky. The lack of working methods for In-Vitro and In-Vitro measuring AGEs level complicates the evaluation and prediction of active ingredients’ ability to affect cellular AGEs accumulation. A two-step In-Vitro systematic screening method is proposed and three different cosmetic active ingredients were selected for its demonstration, using BSA-Glucose and Collagen-Glucose predicting models. Candidates’ effects on AGEs accumulation were evaluated as standalone, and when formulated in a blend. Additionally, the potency of non-invasive auto-fluorescence in-vivo measurement to detect AGEs levels among subjects of different ages was demonstrated. The results are presented in this work and the potential contribution of the proposed system to assist the desired inhibition of AGEs accumulation in skin is discussed.

Nrf2 Pathway Involvement in the Beneficial Skin Effects of Moderate Ionic Osmotic Stress—The Case of The Dead Sea Water

Objectives: Exposing skin to moderate ionic osmotic stress (MIOS) triggers several biochemical responses. The objective of this work is to reveal the mechanism triggered by MIOS on the skin surface. Furthermore, this work aims to study the involvement of the Nrf2 (nuclear factor erythroid-2-related factor 2) pathway, activated by MIOS, and its beneficial effect in protecting skin against stress via the stimulation of phase II enzymes. Methods: HaCaT cells and human skin organ culture were exposed to Dead Sea Water (DSW) as MIOS inducers and the induction of internal ROS elevation, Nrf2 translocation, mRNA gene expressions of the phase II enzymes, heme-oxygenase 1 (HO1), and Catalase (CAT) were determined. Results: Skin exposure to MIOS increases Nrf2 translocation to the nucleus, leading to increased levels of ROS, HO1, and CAT. Furthermore, exposing skin to MIOS promotes protection against UVB-related risks. This is demonstrated by attenuation of the expression of biomarkers, related to UVB-induced damage, Caspase-3, IL-8, and IL-1β. Conclusions: Skin exposure to MIOS leads to the activation of Nrf2 skin defense pathway and, therefore, could present beneficial advantages to human skin health, as demonstrated on human skin models. The beneficial effects of MIOS, induced by DSW are significantly superior to eq. NaCl brine, suggests that MIOS protection of skin against stress is partially related to specific mineral combinations.

Apple of Sodom (<em>Calatropis procera</em>) Callus Extract, a Novel Skincare Active and Its Biological Activity in Skin Models When Combined with Dead Sea Water

Background: Calotropis procera (C. procera), is an authentic plant naturally grown in the flora of Dead Sea region. Despite its toxicity, C. procera presents healing properties. However, it has not been implemented yet in cosmetics as an active ingredient. Objective: The biological effects of C. procera callus extract on skin were elucidated solely and in combination with Dead Sea water (DSW). Methods: The capability of C. procera extract to protect against skin inflammation and irritation was tested on ex vivo human skin organ culture by LPS and SDS addition respectively. Viability and cytokine secretion were evaluated. The combination of C. procera extract with Dead Sea water was tested on full thickness skin equivalents. Gene expression and relevant biochemical markers for glycolysis, hypoxia and extracellular matrix balance were tested. Results: C. procera extract exhibits a protective biological activity against skin irritation and inflammation at the biochemical level. Furthermore, a combination of C. procera extract and DSW demonstrates a potential contribution for skin wellbeing via enhance energy production, resistance to hypoxia and extracellular matrix balance. Conclusions: Topical application of C. procera callus extract might support skin balance and wellbeing at the molecular level. Hence, it is recommended for new cosmetic formulae as standalone or in combination with Dead Sea water, in the effort to achieve anti-aging bio-activity that is working beyond skin aging symptoms, especially via skin calming effects and skin energy enhancement.

Dead Sea Minerals-Induced Positive Stress as an Innovative Resource for Skincare Actives

Objective: Exposure to certain stresses in small doses might lead to a protective effect by improving resistance to other stressors. Dead Sea (DS) minerals can be a relevant source to induce positive stress due to their high salinity and unique mineral combination. This concept could be further optimized using advanced unique cell biotechnology. The purpose of this study was to elucidate the innovative concept of DS minerals (water extract and black mud) supplementation in small amount to Pichia pastoris yeast growth media as a positive stress by testing the capability of accepted fermentation compounds to affect the appearance of skin. Methods: Skin equivalents were topically applied with different Pichia pastoris fermentations (Metabiotics?). Skin elasticity biomarkers were tested, since loss of elasticity and suppleness is a natural skin aging process leading to deeper wrinkles and loss of firmness. A preliminary screening at the gene level using DNA microarray was performed and subsequently, the following proteins were detected using ELISA or immunoblotting assays: elastin, fibulin-1, lysyl oxidase (LOX), metalloproteinase 3 (MMP-3), E-cadherin, claudin 4, tight junction protein (TJP)-1 and TJP-2. UVB irradiation was selected as a stressor. Results: Fermentation compounds generated in the presence of small doses of DS minerals affected the expression of various elasticity-related genes in skin. Moreover, they significantly attenuated the abnormal UVB-induced alterations, the proteins elastin, fibulin-1, LOX, MMP-3, E-cadherin and TJP-2. Conclusions: The observations clearly demonstrate that when DS Metabiotics? compounds are topically applied, significant alterations in several biomarkers that contribute to skin elasticity occur. Thus, these novel compounds have the potential to serve as skincare actives.