Systematic (IUPAC) name
Clinical data
AHFS/ monograph
Pregnancy cat. C: (USA)
Legal status  ?
Routes Intravenous
Pharmacokinetic data
Bioavailability ~7%
Metabolism Hepatic, negligible.
Half-life 100 minutes
Excretion Renal: 90%
CAS number 69-65-8 YesY
ATC code A06AD16 B05BC01 B05CX04 R05CB16
PubChem CID 6251
DrugBank APRD01083
ChemSpider 6015 YesY
KEGG D00062 YesY
ChEBI CHEBI:16899 YesY
Chemical data
Formula C6H14O6 
Mol. mass 182.172
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Mannitol is a white, crystalline[1] organic compound with the formula (C6H8(OH)6). This polyol is used as an osmotic diuretic agent and a weak renal vasodilator. It was originally isolated from the secretions of the flowering ash, called manna after their resemblance to the Biblical food, and is also referred to as mannite and manna sugar.[2] In plants, it is used to induce osmotic stress.



Mannitol is a sugar alcohol; that is, it is derived from a sugar by reduction, with a molecular weight of 182.17 g/mol,[3] and a density of 1.52 g/mL.[4] Other sugar alcohols include xylitol and sorbitol. Mannitol and sorbitol are isomers, the only difference being the orientation of the hydroxyl group on carbon 2.[5] Aqueous solutions of mannitol are mildly acidic and sometimes such solutions are treated to lower the pH. Chemical Abstracts Registry Numbers for mannitol are 123897-58-5, 69-65-8 (D-Mannitol), 75398-80-0, 85085-15-0, and 87-78-5 (mannitol with unspecified stereochemistry). D-Mannitol (CAS# 69-65-8) has a solubility of 22g mannitol/ 100mL water (25°C), and a relative sweetness of 50 (sucrose=100).[3] It melts between 165°-169°C (7.6 torr), and boils at 295°C at 3.5 torr, indicating a greater boiling point at STP conditions.[4]

Similarity to sorbitol

Mannitol and sorbitol are isomers. Both are (C6H8(OH)6). The difference is the second carbon atom in the chain is chiral like, leading to physically different molecules.

Obtaining mannitol

Industrial synthesis

Mannitol is commonly formed via the hydrogenation of fructose, which is formed from either starch or sugar. Although starch is cheaper than sucrose, the transformation of starch is much more complicated. Eventually, it yields a syrup containing about 42% fructose, 52% dextrose, and 6% maltose. Sucrose is simply hydrolyzed into an invert sugar syrup, which contains about 50% fructose. In both cases, the syrups are chromatographically purified to contain 90-95% fructose. The fructose is then hydrogenated over a nickel catalyst into mixture of isomers sorbitol and mannitol. Yield is typically 50%:50%, although slightly alkaline reaction conditions can slightly increase mannitol yields.[5]

Biological syntheses

Mannitol is one of the most abundant energy and carbon storage molecules in nature, produced by a plethora of organisms, including bacteria, yeasts, fungi, algae, lichens, and many plants.[6] Fermentation by microorganisms is a possible alternative to traditional industrial synthesis, producing much higher yields of mannitol, with minimal to no side products. A fructose to mannitol metabolic pathway, known as the mannitol cycle in fungi, has been discovered in a type of red algae (Caloglossa leprieurii), and it is highly possible that other microorganisms employ similar such pathways.[7] A class of lactic acid bacteria,labeled heterofermentive because of their multiple fermentation pathways, convert either 3 fructose molecules or 2 fructose and 1 glucose molecule into 2 mannitol molecules, and one molecule each of lactic acid, acetic acid, and carbon dioxide. Feedstock syrups containing medium to large concentrations of fructose (for example, cashew apple juice, containing 55% fructose: 45% glucose) can produce yields 200g mannitol/ liter feedstock. Further research is being conducted, studying ways to engineer even more efficient mannitol pathways in lactic acid bacteria, and also studying the use of other microorganism, such as yeast[6] and E. coli bacteria in mannitol productions. When food grade strains of any of the aforementioned microorganisms are used, the mannitol and the organism itself are directly applicable to food products, avoiding the need for careful separation of microorganism and mannitol crystals. Although this is a promising method, steps are needed to scale it up to industrially needed quantities.[7]

Natural product extraction

As stated above, mannitol is found in a wide variety of natural products, including almost all plants. This allows for direct extraction from natural products, rather than chemical or biological syntheses. In fact, in China, isolation from seaweeds is the most common form of mannitol production.[1] Mannitol concentrations of plant exudates can range from 20% in seaweeds to 90% in the plane tree. Traditionally, mannitol is extracted by the Soxhlet extraction, utilizing ethanol, water, and methanol to steam and then hydrolyze the crude material. The mannitol is then recrystallized from the extract, generally resulting in yields of about 18% of the original natural product. Another up and coming method of extraction is by using supercritical and subcritical fluids. These fluids are at such a stage that there is no difference between the liquid and gas stages, and are therefore more diffusive than normal fluids. This is considered to make them much more effective mass transfer agents than normal liquids. The super/sub critical fluid is pumped through the natural product, and the mostly mannitol product is easily separated from the solvent and minute amount of byproduct. Supercritical carbon dioxide extraction of olive leaves has been shown to require less solvent per grams of leaf than a traditional extraction (141.7 g CO2 vs. 194.4 g ethanol/ 1 g olive leaf). Heated, pressurized, subcritical water is even cheaper, and is shown to have dramatically greater results than traditional extraction. It requires only 4.01 g water/ 1 g olive leaf, and gives a yield of 76.75% mannitol. Both super- and sub-critical extractions are cheaper, faster, purer, and more environmentally friendly than the traditional extraction. However, the high required operating temperatures and pressures are cause for hesitancy in the industrial use of this technique.[7]


Medical applications

Mannitol is used clinically in osmotherapy to reduce acutely raised intracranial pressure until more definitive treatment can be applied, e.g., after head trauma. It is also used to treat patients with oliguric renal failure. It is administered intravenously, and is filtered by the glomeruli of the kidney, but is incapable of being resorbed from the renal tubule, resulting in decreased water and Na+ reabsorption via its osmotic effect. Consequently, mannitol increases water and Na+ excretion, thereby decreasing extracellular fluid volume.

Mannitol can also be used as a facilitating agent for the transportation of pharmaceuticals directly into the brain. The arteries of the blood-brain barrier are much more selective than normal arteries. Normally, molecules can diffuse into tissues through gaps between the endothelial cells of the blood vessels. However, what enters the brain must be much more rigorously controlled. The endothelial cells of the blood-brain barrier are connected by tight junctions, and simple diffusion through them is impossible. Rather, active transport is necessary, requiring energy, and only transporting molecules that the arterial endothelial cells have receptor signals for. Mannitol is capable of opening this barrier by temporarily shrinking the endothelial cells, simultaneously stretching the tight junctions between them.[8] An intracarotid injection of high molarity mannitol (1.4-1.6M), causes the contents of the artery to be hyperosmotic to the cell. Water leaves the cell and enters the artery in order to recreate an osmotic equilibrium. This loss of water causes the cells to shrivel and shrink, stretching the tight junctions between the cells.[9] The newly formed gap reaches its peak width five minutes after mannitol injection, and stays widely open for thirty minutes. During this timespan, drugs injected into the artery can easily diffuse though the gaps between cells directly into the brain.[10] This makes mannitol indispensable for delivering various drugs directly to the brain (e.g., in the treatment of Alzheimer's disease, or in chemotherapy for brain tumors.[11]

Mannitol is commonly used in the circuit prime of a heart lung machine during cardiopulmonary bypass. The presence of mannitol preserves renal function during the times of low blood flow and pressure, while the patient is on bypass. The solution prevents the swelling of endothelial cells in the kidney, which may have otherwise reduced blood flow to this area and resulted in cell damage.

Mannitol is also being developed by an Australian pharmaceutical company as a treatment for cystic fibrosis and bronchiectasis and as a diagnostic test for airway hyperresponsiveness. The mannitol is orally inhaled as a dry powder through what is known as an osmohaler and osmotically draws water into the lungs to thin the thick, sticky mucus characteristic of cystic fibrosis. This is intended to make it easier for the sufferer to cough the mucus up during physiotherapy. The critical characteristic of the mannitol is its particle size distribution.

Mannitol is also the first drug of choice for the treatment of acute glaucoma in veterinary medicine. It is administered as a 20% solution IV. It dehydrates the vitreous humor and, thus, lowers the intraocular pressure. However, it requires an intact blood-ocular barrier to work.[12]

Mannitol can also be used to temporarily encapsulate a sharp object (such as a helix on a lead for an artificial pacemaker) while it is passed through the venous system. Because the mannitol dissolves readily in blood, the sharp point will become exposed at its destination.

Mannitol may be administered in cases of severe Ciguatera poisoning. Severe ciguatoxin, or "tropical fish poisoning" can produce stroke-like symptoms.

Mannitol is the primary ingredient of Mannitol Salt Agar, a bacterial growth medium, and is used in others.

In oral doses larger than 20 g, mannitol acts as an osmotic laxative, and is sometimes sold as a laxative for children[citation needed].

In foods

Mannitol does not stimulate an increase in blood glucose, and is therefore used as a sweetener for people with diabetes, and in chewing gums. It also has a low glycemic index, making it a low carb food. Although mannitol has a higher heat of solution than most sugar alcohols, its comparatively low solubility reduces the cooling effect usually found in mint candies and gums. However, when mannitol is completely dissolved in a product, it induces a strong cooling effect.[5] Also, it has a very low hygroscopicity- it does not pick up water from the air until the humidity level is 98%. This makes mannitol very useful as a coating for hard candies, dried fruits, and chewing gums, and it is often included as an ingredient in candies and chewing gum.[13] The pleasant taste and mouthfeel of mannitol also makes it a popular excipient for chewable tablets.[14]

In illicit drugs

Mannitol is sometimes used as an adulterant or cutting agent for heroin, methamphetamines, cocaine, or other illicit drugs. In popular culture, when it is used in this manner, it is often referred to as baby laxative.[15]


The three studies[16][17][18] that initially found that high-dose mannitol was effective in cases of severe head injury have been the subject of a recent investigation.[19] Although several authors are listed with Dr. Julio Cruz, it is unclear whether the authors had knowledge of how the patients were recruited. Further, the Federal University of São Paulo, which Dr. Cruz gave as his affiliation, has never employed him. Currently, therefore, the Cochrane review recommending high-dose mannitol[20] has been withdrawn pending re-evaluation, as there is some evidence that mannitol may worsen cerebral edema.[21]


Mannitol is contraindicated in patients with anuria and congestive heart failure.[citation needed]

Compendial status

See also

Notes and references

  1. ^ a b Lawson, P. In In Mannitol; Blackwell Publishing Ltd: 2007; pp 219-225.
  2. ^ Cooley's Cyclopaedia of Practical Receipts, 6th ed. (1880)
  3. ^ a b Lawson, P. In In Mannitol; Blackwell Publishing Ltd: 2007; pp 219-225
  4. ^ a b Anonymous. D-Mannitol. (accessed November 11, 2010).
  5. ^ a b c Kearsley, M. W.; Deis, R. C. Sorbitol and Mannitol. In Sweeteners and Sugar Alternatives in Food Technology; Ames: Oxford, 2006; pp 249-249-261.
  6. ^ a b Song, S. H.; Vieille, C. Recent advances in the biological production of mannitol. Appl. Microbiol. Biotechnol. 2009, 84, 55-62.
  7. ^ a b c Ghoreishi, S. M.; Shahrestani, R. G. Innovative strategies for engineering mannitol production. Trends Food Sci. Technol. 2009, 20, 263-270.
  8. ^ Best, B. . Perfusion & Diffusion in Cryonics Protocol. (accessed November 10, 2010).
  9. ^ Ikeda, M.; Bhattacharjee, A. K.; Kondoh, T.; Nagashima, T.; Tamaki, N. Synergistic Effect of Cold Mannitol and Na+/Ca2+ Exchange Blocker on Blood-Brain Barrier Opening. Biochem. Biophys. Res. Commun. 2002, 291, 669-674.
  10. ^ Wang, M.; Etu, J.; Joshi, S. Enhanced disruption of the blood brain barrier by intracarotid mannitol injection during transient cerebral hypoperfusion in rabbits. J. Neurosurg. Anesthesiol. 2007, 19, 249-256.
  11. ^ Ikeda, M.; Bhattacharjee, A. K.; Kondoh, T.; Nagashima, T.; Tamaki, N. Synergistic Effect of Cold Mannitol and Na+/Ca2+ Exchange Blocker on Blood-Brain Barrier Opening. Biochem. Biophys. Res. Commun. 2002, 291, 669-674
  12. ^ Veterinary Class Notes, Ophthalmology, The Ohio State University, provided by David Wilkie, DVM, DACVO
  13. ^ Lawson, P. In In Mannitol; (1); Blackwell Publishing Ltd: 2007; pp 219-225.
  14. ^ Weiner, Myra L.; Lois A. Kotkoskie (1999). Excipient Toxicity and Safety. pp. 370. ISBN 0824782100, 9780824782108. 
  15. ^ An interview on the History Channel show Gangland showed a man claiming to be the chief methamphetamine "cooker" for the Pagans MC in Philadelphia, who stated that he used mannitol, a "baby laxative", as a "cut" for methamphetamine. He stated that in his hands the drug began as a purple color, and became first dark pink, then light pink, finally white as successive adulterations were done with mannitol. In the interview he stated that people snorting a line of the powder would need to go to the bathroom as a result of using it. He said that they incorrectly believed that this was the result of the potency of the drug, but it was actually caused by the added mannitol.
  16. ^ Cruz J, Minoja G, Okuchi K. Improving clinical outcomes from acute subdural hematomas with the emergency preoperative administration of high doses of mannitol: a randomized trial. Neurosurgery. 2001 Oct;49(4):864-71. doi:10.1097/00006123-200110000-00016 PMID 11564247
  17. ^ Cruz J, Minoja G, Okuchi K. Major clinical and physiological benefits of early high doses of mannitol for intraparenchymal temporal lobe hemorrhages with abnormal pupillary widening: a randomized trial. Neurosurgery. 2002 Sep;51(3):628-37; discussion 637-8. doi:10.1097/00006123-200209000-00006 PMID 12188940
  18. ^ Cruz J, Minoja G, Okuchi K, Facco E. Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial. J Neurosurg. 2004 Mar;100(3):376-83. doi:10.3171/jns.2004.100.3.0376 PMID 15035271
  19. ^ Roberts I, Smith R, Evans S. Doubts over head injury studies. BMJ. 2007 Feb 24;334(7590):392-4. doi:10.1136/bmj.39118.480023.BE PMID 17322250
  20. ^ Wakai A, Roberts I, Schierhout G. Mannitol for acute traumatic brain injury. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD001049. PMID 16235278
  21. ^ Kaufmann AM, Cardoso ER. Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg. 1992 Oct;77(4):584-9. PMID 1527619
  22. ^ British Pharmacopoeia Commission Secretariat (2009). "Index, BP 2009". Retrieved 31 January 2010. 
  23. ^ "Japanese Pharmacopoeia, Fifteenth Edition". 2006. Retrieved 31 January 2010. 
  24. ^ USP 32 (2008). "Mannitol Injection". Retrieved 31 January 2010. 

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  • mannitol — man ni*tol, n. [Mannite + ol.] 1. (Chem.) A white crystalline hexose ({HO.CH2.(CHOH)4.CH2.OH}) of a sweet taste obtained from a so called manna, the dried sap of the flowering ash ({Fraxinus ornus}); called also {mannite}, and {hydroxy hexane}.… …   The Collaborative International Dictionary of English

  • mannitol — [man′ə tôl΄, man′ətōl΄] n. [< MANNITE + OL1] a colorless, crystalline sugar alcohol, C6H8 (OH) 6, occurring in various plants and animals …   English World dictionary

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  • mannitol — /man i tawl , tol /, n. 1. Chem. a white, crystalline, sweetish, water soluble, carbohydrate alcohol, C6H8(OH)6, occurring in three optically different forms, the common one being found in the manna of the ash Fraxinus ornus and in other plants:… …   Universalium

  • mannitol — The hexahydric alcohol, widespread in plants, derived by reduction of fructose; used in renal function testing to measure glomerular filtration, and intravenously as an osmotic diuretic. SYN: manna s …   Medical dictionary

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