Mannitol: properties, uses, pros, cons, safety

Mannitol is a polyol (sugar alcohol) widely used in the food, pharmaceutical, and cosmetic sectors. From a chemical point of view, it corresponds to D-mannitol, with the formula C₆H₁₄O₆ and a molecular weight of about 182.17 g/mol. It generally appears as a white crystalline powder, with a sweet taste that is less intense than sucrose. In the food sector it is also known as the additive E421, while in cosmetics it is mainly used for its humectant, moisturising, and skin conditioning properties.

Mannitol (D-Mannitol) is a natural alcohol found in the human body in the form of a sugar alcohol, where it is metabolically inert. It is also found in plants and fruits (such as olives and persimmons), as well as in some fungi and marine algae. 

Mannitol is a carbohydrate derived from the reduction of mannose or fructose and belongs to the polyol family. It may occur naturally in some plants, algae, fungi, and fruits, but industrially it is produced mainly by hydrogenation of suitable sugars or by fermentation, depending on the process and the commercial grade.

From a technological point of view, it is appreciated because it has a relatively stable profile, moderate sweetness, good compatibility with different matrices, and a lower tendency to absorb moisture compared with other polyols. In practice, this makes it interesting both in reduced-calorie food applications and in cosmetic formulations where a humectant ingredient is desired without excessive stickiness.

Production process

At the industrial level, Mannitol can be obtained by catalytic hydrogenation of suitable sugars or through fermentation processes. After production, the material is purified, concentrated, crystallized, dried, and subjected to the quality controls required for the intended grade.

For food use, what matters in particular is purity, compliance with the specifications of additive E421, contaminant control, and batch-to-batch consistency. For cosmetic use, in addition to chemical identity and purity, particle size, residual moisture, formulation compatibility, and microbiological quality are also considered.

Key constituents

In the case of Mannitol, the ingredient is essentially a single substance and not a complex mixture. The relevant compound is therefore D-mannitol itself. Any secondary components of the commercial grade are generally limited to traces of moisture, process impurities, or technological excipients, if present in the finished raw material.

Identification data and specifications

Physico-chemical properties (indicative)

Medical

In surgery, it is used to reduce intracranial pressure and facilitate brain retraction in cases of aneurysm rupture, as well as to reduce intraocular pressure (1).
Together with biotin, it can stimulate the accumulation of important lipids produced by microalgae (2).
It is a good diuretic.
It is used as a research tool in cell biology studies to control osmolarity and as a bacterial culture agent. It is also used for the determination of boron in chemical analysis.
It has both moisturizing and antioxidant properties, which make it a useful pharmaceutical excipient.

Food focus

In the food focus, Mannitol is used as a sweetener and bulking agent in reduced-calorie products, no-added-sugar products, or formulations designed for specific technological needs. Compared with sucrose, it provides less energy within the framework of European labeling and has lower sweetness, a feature that can be useful when the taste profile needs to be modulated without reaching the typical intensity of common sugar.

From a practical point of view, Mannitol is also appreciated for its lower tendency to retain moisture compared with other polyols. For this reason, it can be used in coatings, tablets, chewing gum, confectionery, powdered products, and other applications where physical stability and flowability are important. In addition, like other polyols, it is generally considered non-cariogenic or at least more favorable than sucrose from a dental perspective.

From a nutritional point of view, Mannitol should not be considered an essential nutrient, but rather a technological ingredient useful for partially replacing sugar. However, its use must be contextualized: a product with polyols is not automatically “healthy” overall, because the final profile always depends on the whole formulation. Another important point is gastrointestinal tolerance: like other polyols, if consumed in high quantities it may promote bloating, laxative effects, or osmotic diarrhea. In Europe, products containing more than 10% added polyols must carry the warning relating to possible laxative effects from excessive consumption.

Cosmetic focus

In the cosmetic focus, Mannitol is used mainly as a humectant, moisturising, skin conditioning, and, according to some classifications, also binding or masking ingredient. Its main role is to help retain water in the formula or on the skin surface, contributing to the maintenance of comfort and skin softness.

In skincare formulations it may appear in serums, gels, light creams, moisturizing products, and multi-active systems. Its presence is especially interesting when the goal is to combine a humectant function with good physical stability and a relatively light sensory profile. In some systems it may also be used as a technological support or carrier for other sensitive ingredients.

From a formulation point of view, Mannitol is generally fairly easy to incorporate into aqueous bases or light emulsions, but its real cosmetic usefulness depends on concentration, synergy with other humectants such as glycerin or hyaluronic acid, and the overall structure of the formula. In practice, it is rarely the “star” active, but it can be a good support ingredient.

Cosmetics - INCI Functions

Binder agent. Ingredient that is used in cosmetic, food and pharmaceutical products as an anti-caking agent with the function of making the product in which it is incorporated silky, compact and homogenous. The binder, either natural such as mucilage, gums and starches or chemical, may be in the form of a powder or liquid.

Fragrance. It plays a decisive and important role in the formulation of cosmetic products as it provides the possibility of enhancing, masking or adding fragrance to the final product, increasing its marketability.  The consumer always expects to find a pleasant or distinctive scent in a cosmetic product.

Humectant. Hygroscopic compound used to minimise water loss in the skin and to prevent it from drying out by facilitating faster and greater absorption of water into the stratum corneum of the epidermis.  The epidermis is the most superficial of the three layers that make up human skin (epidermis, dermis and hypodermis) and is the layer that maintains hydration in all three layers. In turn, the epidermis is composed of five layers: horny, the most superficial, granular, spinous, shiny, and basal. Humectants have the ability to retain the water they attract from the air in the stratum corneum and have the function of moisturising the skin. They are best used before emollients, which are oil-based.

Moisturizing. This ingredient is responsible for preventing the evaporation of moisture from the skin and improving cellular activity. When exposed to cold or hot air currents, the skin absorbs water from its inner layer to compensate for the evaporated water. If the draught phenomenon persists, the stratum corneum is dry and, if at all, damaged.

Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.

Other uses

Plastics industry to produce artificial glycerine resins and rosin esters.

Explosives and as nitrified mannitol to produce detonators.

Pros

• It is a well-known and technically versatile polyol.

• In food applications it allows a reduction in energy intake compared with sucrose.

• It has low hygroscopicity compared with other polyols, which is useful in some technological applications.

• It is suitable for formulations where physical stability, flowability, or moisture control are needed.

• In cosmetics it works well as a humectant and as an ingredient supporting skin conditioning.

Cons

• It is less sweet than sucrose, so it is not always sufficient on its own from a sensory point of view.

• High consumption may cause gastrointestinal disturbances and laxative effects.

• The fact that a product is “sugar-free” or “with polyols” does not automatically make its overall profile better.

• In cosmetics it often plays a more complementary than central role.

• In complex formulas, compatibility with the preservative system, pH, and other humectants should still be verified.

Safety, regulatory aspects and environment

From a food safety point of view, Mannitol is authorized in the European Union as additive E421, with defined specifications for conventional mannitol and mannitol obtained by fermentation. The main practical critical point is not toxicity at normal use levels, but rather intestinal tolerance at high consumption.

In cosmetics, Mannitol is among the ingredients generally considered safe under normal conditions of use, especially when included in properly designed formulations. It is not a classic fragrance allergen; however, as with any ingredient, tolerability should always be referred to the finished product.

From an industrial and environmental point of view, fermentation processes may offer an interesting profile in terms of production selectivity, but the real impact depends on the specific process, purification, raw materials used, and the energy management of the production site.

Conclusion

Mannitol is a solid, versatile, and well-established ingredient, with a primary role in the food focus as a polyol with reduced energy contribution compared with sugar and with useful technological applications in many product categories. In the cosmetic focus it acts mainly as a humectant and skin conditioning ingredient, with a supporting technical role rather than that of a leading active.

Overall, its value emerges above all when it is used in the correct context: in foods where specific technological properties and partial calorie reduction are needed, and in cosmetics where hydration, stability, and good formulation compatibility are desired.

The most relevant studies on this ingredient have been selected with a summary of their contents:

"Mannitol, studies"

Typical commercial product characteristics Mannitol

• Molecular Formula    C₆H₁₄O₆
• Molecular Weight  182.172 g/mol
• Exact Mass   182.079041
• CAS   69-65-8  87-78-5
• EC Number: 200-711-8  201-770-2
• UNII: 3OWL53L36A
• PubChem Substance ID 329823038
• MDL number MFCD00064287
• Beilstein Registry Number 1721898
• DSSTox Substance ID  DTXSID1023235
• IUPAC  (2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexol
• InChI=1S/C6H14O6/c7-1-3(9)5(11)6(12)4(10)2-8/h3-12H,1-2H2/t3-,4-,5-,6-/m1/s1  
• InChl Key      FBPFZTCFMRRESA-KVTDHHQDSA-N
• SMILES   C(C(C(C(C(CO)O)O)O)O)O
• ChEBI  16899
• NCI   C625  
• RXCUI   6628   
• RTECS   OP2060000

Synonyms:

• Mannite
• D-mannitol
• Osmitrol
• Mannitol, D-
• Manna sugar
• Invenex
• Osmofundin
• Osmosal
• Cordycepic acid
• Mannidex 16700
• Mannit 

References__________________________________________________________________________

(1) Karamian A, Seifi A, Lucke-Wold B. Comparing the effects of mannitol and hypertonic saline in severe traumatic brain injury patients with elevated intracranial pressure: a systematic review and meta-analysis. Neurol Res. 2024 Sep;46(9):883-892. doi: 10.1080/01616412.2024.2360862. 

Abstract. Objectives: Controlling elevated intracranial pressure following brain injury with hyperosmolar agents is one of the mainstay treatments in traumatic brain injury patients. In this study, we compared the effects of hypertonic saline (HS) and mannitol in reducing increased intracranial pressure. Methods: A total of 637 patients from 15 studies were included in our meta-analysis. The primary outcomes were mortality, the length of stay in the hospital and ICU, and the Glasgow Outcome Scale at follow-up.....Discussion: The results showed that HS and mannitol had similar effects in reducing ICP. Although the HS was associated with a longer duration of effect and shorter ICU stay, other secondary outcomes including mortality rate and favorable neurological outcomes were similar between the two drugs. In conclusion, considering the condition of each patient individually, HS could be a reasonable option than mannitol to reduce ICP in TBI patients.

(2) Ali MK, Sen B, He Y, Bai M, Wang G. Media Supplementation with Mannitol and Biotin Enhances Squalene Production of Thraustochytrium ATCC 26185 through Increased Glucose Uptake and Antioxidative Mechanisms. Molecules. 2022 Apr 11;27(8):2449. doi: 10.3390/molecules27082449.

Abstract. Media supplementation with exogenous chemicals is known to stimulate the accumulation of important lipids produced by microalgae and thraustochytrids. However, the roles of exogenous chemicals in promoting and preserving the terpenoids pool of thraustochytrids have been rarely investigated. Here, we realized the effects of two media supplements-mannitol and biotin-on the biomass and squalene production by a thraustochytrid strain (Thraustochytrium sp. ATCC 26185) and elucidated their mechanism of action. A significant change in the biomass was not evident with the exogenous addition of these supplements. However, with mannitol (1 g/L) supplementation, the ATCC 26185 culture achieved the best concentration (642 ± 13.6 mg/L) and yield (72.9 ± 9.6 mg/g) of squalene, which were 1.5-fold that of the control culture (non-supplemented). Similarly, with biotin supplementation (0.15 mg/L), the culture showed 459 ± 2.9 g/L and 55.7 ± 3.2 mg/g of squalene concentration and yield, respectively. The glucose uptake rate at 24 h of fermentation increased markedly with mannitol (0.31 g/Lh-1) or biotin (0.26 g/Lh-1) supplemented culture compared with non-supplemented culture (0.09 g/Lh-1). In addition, the reactive oxygen species (ROS) level of culture supplemented with mannitol remained alleviated during the entire period of fermentation while it alleviated after 24 h with biotin supplementation. The ∆ROS with mannitol was better compared with biotin supplementation. The total antioxidant capacity (T-AOC) of the supplemented culture was more than 50% during the late stage (72-96 h) of fermentation. Our study provides the potential of mannitol and biotin to enhance squalene yield and the first lines of experimental evidence for their protective role against oxidative stress during the culture of thraustochytrids.

Martău GA, Coman V, Vodnar DC. Recent advances in the biotechnological production of erythritol and mannitol. Crit Rev Biotechnol. 2020 Aug;40(5):608-622. doi: 10.1080/07388551.2020.1751057.

Abstract. Dietary habits that include an excess of added sugars have been strongly associated with an increased risk of obesity, heart disease, diabetes, and tooth decay. With this association in view, modern food systems aim to replace added sugars with low calorie sweeteners, such as polyols. Polyols are generally not carcinogenic and do not trigger a glycemic response. Furthermore, owing to the absence of the carbonyl group, they are more stable compared to monosaccharides and do not participate in Maillard reactions. As such, since polyols are stable at high temperatures, and they do not brown or caramelize when heated. Therefore, polyols are widely used in the diets of hypocaloric and diabetic patients, as well as other specific cases where controlled caloric intake is required. In recent years, erythritol and mannitol have gained increased importance, especially in the food and pharmaceutical industries. In these areas, research efforts have been made to improve the productivity and yield of the two polyols, relying on biotechnological manufacturing methods. The present review highlights the recent advances in the biotechnological production of erythritol and mannitol and summarizes the benefits of using the two polyols in the food and pharmaceutical industries.

The addition of Mannitol to hyaluronic acid fillers is a valid and safe option to improve both the short and long term effects of hyaluronic acid (1).

Used, together with trehalose, in nanoparticles for the transport of medicines (2).

As an option in intradialytic hypotension which is a common complication at the beginning of hemodialysis therapy (3).

References___________________________________

(1) Free-radical scavenging properties of mannitol and its role as a constituent of hyaluronic acid fillers: a literature review.
André P, Villain F.
Int J Cosmet Sci. 2016 Dec 27. doi: 10.1111/ics.12386.

(2) Chitosan-Based Nano-Embedded Microparticles: Impact of Nanogel Composition on Physicochemical Properties.
Islam P, Water JJ, Bohr A, Rantanen J.
Pharmaceutics. 2016 Dec 22;9(1). pii: E1. doi: 10.3390/pharmaceutics9010001.

(3) Hypertonic Mannitol for the Prevention of Intradialytic Hypotension: A Randomized Controlled Trial.
Mc Causland FR, Claggett B, Sabbisetti VS, Jarolim P, Waikar SS.
Am J Kidney Dis. 2019 Apr 27. pii: S0272-6386(19)30640-7. doi: 10.1053/j.ajkd.2019.03.415.