What are the different types of trehalose?

December 23, 2025 •

4 min read

Trehalose, a disaccharide sugar, is produced by many organisms to survive extreme environmental stresses like desiccation and freezing. However, this cryoprotective molecule exists not as a single entity but as distinct types with different structural and physical properties. What are the different types of trehalose and how do these variations define its wide range of applications?

Quick Summary

Trehalose exists as three stereoisomers: alpha,alpha-; alpha,beta- (neotrehalose); and beta,beta- (isotrehalose), with only the alpha,alpha- form being common in nature. It also appears in various physical states, such as a crystalline dihydrate and an amorphous glass, each offering unique stabilizing properties for commercial use.

Key Points

Isomeric Variety: Trehalose exists in three main isomeric forms—the natural α,α-trehalose and the synthetic isomers neotrehalose (α,β-) and isotrehalose (β,β-), differing by their glycosidic bond configurations.
Natural Dominance: The α,α-trehalose isomer is the only form produced by organisms in nature and is valued for its exceptional stability and non-reducing properties.
Physical Forms: Trehalose is available in several physical states, including a stable crystalline dihydrate, a glassy amorphous solid, and a water-free anhydrous powder.
Application Dependency: Different types and forms of trehalose are utilized for specific applications; for example, the amorphous form is crucial for cryopreservation, while the crystalline dihydrate is common in food and pharmaceuticals.
Enhanced Stability: The non-reducing nature of α,α-trehalose makes it resistant to degradation and reaction with proteins, which is why it is used as a stabilizer in food and pharmaceuticals.
Hydrating Properties: The anhydrous and dihydrate forms of trehalose are leveraged in the cosmetics industry for their moisturizing capabilities, which help bind water to the skin.
Biopreservation Role: The glassy amorphous state is critical for protecting biological macromolecules like proteins and cell membranes against damage from dehydration and freezing, a process known as anhydrobiosis.

Trehalose Isomers: A Matter of Molecular Structure

At its core, trehalose is a disaccharide formed from two glucose molecules. The specific glycosidic bond linking these two units determines the sugar's isomeric type and dictates many of its properties. There are three possible stereoisomers of trehalose, distinguished by the configuration of the 1,1-glycosidic bond.

Alpha,Alpha-Trehalose

This is the most common and naturally occurring form of trehalose, widely found in bacteria, fungi, insects, and plants. The name comes from the alpha-1,1-glycosidic bond that links the two alpha-glucose units. This symmetrical, non-reducing structure is exceptionally stable and highly resistant to acid hydrolysis and enzymatic degradation. It is the form primarily responsible for the cryoprotective and desiccation-protective properties observed in nature, and the one most used commercially.

Alpha,Beta-Trehalose (Neotrehalose)

Also known as neotrehalose, this isomer features an alpha,beta-1,1-glycosidic bond. This asymmetry gives it different chemical properties compared to the natural alpha,alpha- form. While it has been synthesized chemically, it has not been isolated from living organisms. Its distinct structure also means it is hydrolyzed by different enzymes, specifically beta-glycosidase enzymes, unlike the natural form.

Beta,Beta-Trehalose (Isotrehalose)

Referred to as isotrehalose, this isomer has a beta,beta-1,1-glycosidic bond. Like neotrehalose, this form is not naturally found in organisms but has been produced through chemical synthesis. Isotresalose is unique because it can be hydrolyzed by both alpha- and beta-glycosidase enzymes, reflecting the presence of both types of anomeric linkages in its structure.

Trehalose Physical Forms: Crystalline, Amorphous, and Anhydrous

Beyond its isomeric structure, trehalose can also be classified by its physical state, which is particularly relevant for its industrial applications. The presence of water and the manufacturing process determine whether trehalose exists as a crystal or an amorphous solid.

Crystalline Trehalose Dihydrate

The most common commercial form is trehalose dihydrate, a crystalline solid that contains two molecules of water.

Properties: It is a stable, non-hygroscopic powder that is easily handled and incorporated into various formulations.
Uses: Used as an excipient for protein stabilization, a mild sweetener in foods, and a bulking agent.

Amorphous (Glassy) Trehalose

When trehalose is rapidly dried, such as through freeze-drying, it forms a non-crystalline, glassy, or amorphous state.

Properties: In this state, trehalose has a high glass transition temperature, making it highly effective at immobilizing and protecting biological structures, such as proteins and cell membranes.
Uses: Vital for the long-term preservation of vaccines, biopharmaceuticals, and cells through lyophilization (freeze-drying).

Anhydrous Trehalose

This is the water-free crystalline form of trehalose, which can be created by heating the dihydrate form.

Properties: Anhydrous trehalose readily regains moisture to revert to its dihydrate form, a property that makes it useful in cosmetics and other applications where controlled rehydration is desired.

Comparing Trehalose Isomers and Forms


Feature	Alpha,Alpha-Trehalose	Alpha,Beta-Trehalose (Neotrehalose)	Beta,Beta-Trehalose (Isotrehalose)
Glycosidic Bond	α,α-1,1-bond	α,β-1,1-bond	β,β-1,1-bond
Natural Occurrence	Widespread	Not naturally isolated	Not naturally isolated
Stability	Most stable, non-reducing	Lower stability	Lower stability
Hydrolysis	Cleaved by trehalase	Cleaved by β-glycosidase	Cleaved by both α- and β-glycosidases

Comparison of Physical Forms

Crystalline Dihydrate: A stable, easy-to-handle powder used for bulk applications, providing mild sweetness and stabilization.
Amorphous Glass: A highly protective, non-crystalline form essential for biopreservation and cryoprotection in pharmaceuticals.
Anhydrous Crystal: The water-free form, used in cosmetics for its rehydration properties and moisture-binding capabilities.

The Commercial and Biological Significance of Trehalose Diversity

Understanding the distinct types of trehalose is vital for optimizing its use across various industries. In the food industry, the stability and mild sweetness of alpha,alpha-trehalose allow it to function as a preservative, texturizer, and low-intensity sweetener. Its ability to stabilize ingredients under heat and prevent starch staling is highly valued. In the pharmaceutical industry, the amorphous and crystalline forms are utilized for preserving sensitive biologicals, such as vaccines and antibodies. Its use as an excipient ensures the long-term stability and efficacy of these complex drugs. Trehalose also shows promise in medical applications for treating conditions like dry eye syndrome, utilizing its protective and hydrating properties on the ocular surface. For the cosmetics industry, the moisture-retaining properties of anhydrous and crystalline trehalose make it an excellent humectant, protecting skin from desiccation and oxidative stress.

Trehalose's unique properties are an object of ongoing research, with new applications in biopharma and human health constantly being explored. To learn more about its therapeutic potential, explore the research on its use for medical applications in ophthalmology and neuroprotection, such as this article from PMC: https://pmc.ncbi.nlm.nih.gov/articles/PMC3102588/.

Conclusion

Trehalose is more than a simple sugar; its classification into different isomeric and physical types reveals a nuanced molecule with a broad range of applications. The naturally abundant and highly stable alpha,alpha-trehalose is complemented by its synthetically produced stereoisomers, neotrehalose and isotrehalose, each possessing distinct chemical characteristics. Furthermore, its ability to exist in crystalline dihydrate, amorphous glass, and anhydrous forms allows for tailored uses in fields ranging from food and cosmetics to advanced biopharmaceutical preservation. The remarkable versatility of trehalose stems directly from the specific type and form of the molecule being utilized, underscoring its importance in science and industry.

Frequently Asked Questions

Alpha,alpha-trehalose has a symmetrical alpha-1,1-glycosidic bond between two glucose units and is the most stable, naturally occurring form. Its isomers, neotrehalose (alpha,beta-) and isotrehalose (beta,beta-), have different bond configurations, are synthetically produced, and are less stable.

Trehalose is a non-reducing sugar because its glucose units are linked via their anomeric carbons (the C1 carbons) in a 1,1-glycosidic bond. This bond configuration prevents the exposure of the aldehyde or ketone functional groups that are necessary for reducing activity.

Amorphous trehalose is a non-crystalline, glassy form of the sugar that is created by rapidly drying it. This state is excellent for immobilizing and protecting sensitive biological materials like proteins, enzymes, and cells, making it crucial for biopharmaceutical preservation.

In the food industry, trehalose, primarily in its crystalline dihydrate form, is used as a mild sweetener, texturizer, and stabilizer. It prevents starch staling in baked goods, controls moisture, and can be used in frozen foods to inhibit ice crystal formation.

Yes, trehalose is considered generally recognized as safe (GRAS) by the FDA and has been used in foods for many years. It is digested and absorbed similar to other sugars by the enzyme trehalase in the small intestine.

Trehalose protects cells and organisms from dehydration by a "water replacement" mechanism. It forms hydrogen bonds with cellular components like proteins and membranes, replacing water molecules and stabilizing the structures in a dry state.

The primary distinction is their physical structure and water content. Crystalline trehalose (typically the dihydrate) has an ordered molecular lattice, while amorphous trehalose is a disordered, glassy solid. The amorphous form is more effective for high-level stabilization, while the crystalline form is more stable for bulk handling.