Initial note

This article was previously published and is updated here following criteria of scientific rigor and clear communication. The purpose is to inform: it does not replace medical advice. The synthesis proposed here integrates experimental and clinical evidence published in the literature and clarifies limitations and contexts of application.

In brief

• Trehalose is a natural disaccharide with the ability to protect macromolecules and improve superficial skin hydration.
• In experimental models, it can activate cellular pathways related to autophagy and mitochondrial quality; this has also been observed in studies on the heart and nervous tissues.
• Its protective properties (stabilization of proteins and membranes) have solid biophysical bases, but clinical translations are still limited and depend on dose, administration route, and formulation.
• In cosmetics, trehalose is used as a humectant and conditioning ingredient: some clinical and human model studies suggest benefits for dry skin and the skin barrier, but caution is needed in therapeutic inferences.

Abstract: what does science say?

Trehalose is a natural disaccharide known for its ability to protect and stabilize proteins, biological membranes, and cellular structures under stress conditions. Experiments in cells and animals show that, in various tissues, trehalose can modulate cellular degradation and recycling pathways (autophagy) and promote the preservation of molecular structure. These actions explain its use as an additive in industry, as a stabilizing excipient, and as a cosmetic ingredient with humectant and protective functions. However, direct human evidence remains limited: many results derive from animal models or from topical applications/specific formulations. The validity of the benefits strongly depends on the method of use, concentration, formulation vehicle, and clinical context; interpretation requires attention to translational limitations and the distinction between observational associations and causal relationships.

What is trehalose and where is it found?

Trehalose is a disaccharide composed of two glucose units linked by an α,α-1,1 bond; it is naturally found in numerous organisms (fungi, yeasts, some plants, and invertebrates) where it functions as a protective molecule against dehydration and other environmental stresses. In industry, it is used as a food additive and as an excipient to preserve the stability of proteins and vaccines. At a biophysical level, trehalose can interact with water and with protein or lipid surfaces, contributing to forming a more stable state during desiccation or osmotic shock. This ability has led to the use of trehalose in skincare products, cosmetic formulations, and cryopreservation processes; however, practical efficacy varies depending on concentration, vehicle, and exposure time.

Relevant biological mechanisms

Autophagy and lysosomal regulation

In cellular and animal models, trehalose has been associated with an increase in autophagy markers and enhanced lysosomal biogenesis, with implications for the removal of aggregated proteins and mitochondrial quality. Studies on models of cardiac damage indicate that systemic administration of trehalose reduces post-infarction cardiac remodeling, an effect mediated by the activation of autophagy in cardiomyocytes. These results suggest that trehalose can support cellular maintenance mechanisms under stress conditions, although clinical translation remains to be validated. [1]

TFEB activation and action on macrophages

Some experimental work shows that trehalose can stimulate the transcription factor TFEB, a key regulator of lysosomal biogenesis and autophagy, particularly in macrophages; this pathway has been linked to protective effects in models of atherosclerosis and improved ability to degrade intracellular material. The activation of these genetic programs may explain part of the protective action observed in inflammatory or lipid tissues. [3]

Physico-chemical protection of proteins and membranes

The most established biophysical property is trehalose's ability to stabilize proteins and membranes during dehydration and freezing. By acting as an agent that modifies the hydration network and water mobility, trehalose helps preserve the native structure of macromolecules and limit protein aggregation. This action has been used in biotechnology and also explains the effects observed on exosomes and extracellular vesicles during storage. [8]

Experimental evidence and research areas

Research on trehalose spans multiple areas: neurodegenerative models, experimental cardiology, immunometabolism, and technological applications. In models of protein aggregation diseases, such as Huntington's disease, trehalose administration reduced aggregate formation and improved functional parameters in experimental animals; this orientation guided much subsequent research on trehalose's ability to modulate proteostasis. [2] In parallel, in experimental cardiology, the use of trehalose has shown benefits in limiting post-infarction remodeling through the promotion of autophagy and improved mitochondrial control. [1]

Despite promising data in preclinical models, the question of the precise mechanism remains open: some studies indicate that trehalose induces autophagy, while others report possible interference with autophagic flux or effects independent of autophagy itself. The scientific literature actively discusses this methodological and interpretive ambiguity. [4]

Applications for skin and cosmetics

Hydration, protective film, and skin barrier

In cosmetics, trehalose is used as a humectant and conditioning agent: due to its ability to bind water and contribute to the formation of a superficial film, it can increase the skin's capacity to retain moisture and reduce transepidermal water loss (TEWL) when included in appropriate formulations. Clinical studies on creams combining trehalose and ceramides have shown improvements in hydration and barrier parameters in subjects with dry skin, although results depend on the overall product composition and study design. [9]

Antioxidant potential and protection from environmental stress

Trehalose's ability to stabilize membranes and proteins makes a protective effect against oxidative stress and environmental aggressors at the epidermal level plausible. Research in cellular models of corneal epithelium and keratinocytes shows that trehalose can reduce the expression of proinflammatory mediators and promote autophagy markers under hyperosmotic stress conditions, suggesting a role in supporting superficial cellular homeostasis. However, the translation from in vitro models to systematic clinical benefits requires further controlled trials. [5]

Safety, formulations, and limits of use

Trehalose is generally considered well-tolerated as a cosmetic ingredient and food additive; its topical safety is supported by current use evaluations. However, efficacy strongly depends on concentration, chemical form (e.g., trehalose vs. sulfated derivatives), and the formulation vehicle that determines its penetration and skin permanence. Furthermore, when administered systemically in experimental models, the enzyme trehalase present in many organisms can reduce bioavailability just as quickly: this affects the interpretation of observed effects in animal studies compared to possible clinical applications. [6]

What it means in practice

For the general public: trehalose is an ingredient with real scientific bases for some functions useful for the skin, especially as a humectant and stabilizing agent in cosmetic products. Daily use in creams, serums, or sprays can provide hydration support and contribute to the feeling of softer, more protected skin. However, there is currently no robust evidence that trehalose, alone, stops or "reverses" skin aging or treats complex skin conditions. Possible clinical benefits observed in animal or cell studies—for example, effects related to autophagy—do not automatically translate into therapeutic recommendations for people. In practice, evaluating the overall quality of the formulation and specific clinical evidence remains fundamental: a product containing trehalose can be useful in a skincare strategy, but it should not be considered a definitive treatment for diseases or deep skin conditions.

Limitations of evidence

Distinguishing between observational results, preclinical data, and causal evidence is essential. Much of the evidence on trehalose comes from in vitro or animal model studies showing plausible biological mechanisms, but demonstrating a clear clinical effect in humans requires randomized, controlled, and replicated trials. Several methodological limitations emerge in the literature: differences in doses used in experiments compared to realistic concentrations in commercial products, variability in formulations that affect penetration and stability, and sometimes surrogate measurements of outcomes (molecular markers) instead of relevant clinical outcomes. Furthermore, some works report conflicting results on the exact way trehalose influences autophagy (whether it induces it or interferes with autophagic flux), which requires further mechanistic and experimental studies. [4]

Key takeaways

• Trehalose stabilizes proteins and membranes: it is used as a protective and cryoprotective agent in biotechnology. [8]
• In experimental models, it can activate pathways related to autophagy and improve cellular quality in various tissues; clinical translation is still partial. [1][3]
• In cosmetics, it acts as a humectant and film-forming agent; some clinical studies of formulations with trehalose report improvements in skin hydration. [9]
• Positive effects observed in the laboratory do not justify therapeutic claims: controlled clinical studies are needed to confirm benefits for specific skin conditions. [4]

Editorial conclusion

Trehalose is an interesting molecule from both a biophysical and biological perspective. Its properties of protecting and stabilizing macromolecules are well-established and explain its widespread use in industry and cosmetics. More recent research adds insights into its possible role in regulating autophagy and its ability to support cellular responses to various stresses; preclinical studies indicate promising effects in disease models. However, caution is needed in translating these results to clinical practice or making therapeutic claims. For the consumer, the most immediate practical value remains the use of trehalose as an ingredient in moisturizing and protective formulas: a potential aid for the skin when used in well-formulated products, without expectations of miracles. Future research will need to clarify effective doses, administration routes, and real clinical benefits in humans.

Editorial note

This article has been updated following bibliographic verification and transparency criteria: the cited research has been selected for direct relevance, peer-review, and accessibility via DOI. This content is for informational purposes only and does not replace personalized medical or dermatological advice.

SCIENTIFIC RESEARCH

1. Sciarretta S., Yee D., Nagarajan N., et al. Trehalose‑Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction. Journal of the American College of Cardiology. 2018;71(18):1999–2010. https://doi.org/10.1016/j.jacc.2018.02.066 [1]
2. Tanaka M., Machida Y., Niu S., et al. Trehalose alleviates polyglutamine‑mediated pathology in a mouse model of Huntington disease. Nature Medicine. 2004;10:148–154. https://doi.org/10.1038/nm985 [2]
3. Sergin I., Evans T.D., Zhang X., et al. Exploiting macrophage autophagy‑lysosomal biogenesis as a therapy for atherosclerosis. Nature Communications. 2017;8:15750. https://doi.org/10.1038/ncomms15750 [3]
4. Lee J.H., et al. Is trehalose an autophagic inducer? Unraveling the roles of non‑reducing disaccharides on autophagic flux and alpha‑synuclein aggregation. Cell Death & Disease. 2017;8:e3091. https://doi.org/10.1038/cddis.2017.501 [4]
5. Bao H., et al. Trehalose Induces Autophagy Against Inflammation by Activating TFEB Signaling Pathway in Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress. Investigative Ophthalmology & Visual Science. 2020;61(10):26. https://doi.org/10.1167/iovs.61.10.26 [5]
6. Wang Y., et al. Trehalose restores functional autophagy suppressed by high glucose. (Reproductive Toxicology / other journal). 2019; doi:10.1016/j.reprotox.2019.02.005. https://doi.org/10.1016/j.reprotox.2019.02.005 [6]
7. Holler C.J., et al. Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia. Molecular Neurodegeneration. 2016;11:46. https://doi.org/10.1186/s13024-016-0114-3 [7]
8. Yuyama K., et al. Trehalose prevents aggregation of exosomes and cryodamage. Scientific Reports. 2016;6:36162. https://doi.org/10.1038/srep36162 [8]
9. Greco M., et al. Evaluation of the filming and protective properties of a new trehalose and ceramides based ingredient. Cosmetics (MDPI). 2019;6(4):62. https://doi.org/10.3390/cosmetics6040062 [9]

Note: the listed research has been selected for direct relevance to the topic. The verifiable DOI is provided for each entry.