Open Access Articles- Top Results for Mannitol


File:Mannitol structure.png
File:D-Mannitol 3d space fill.png
Systematic (IUPAC) name
Clinical data
Trade names Osmitrol
AHFS/ monograph
Pharmacokinetic data
Bioavailability ~7%
Metabolism Hepatic, negligible.
Half-life 100 minutes
Excretion Renal: 90%
69-65-8 7pxY
A06AD16 B05BC01 B05CX04 R05CB16
PubChem CID 6251
DrugBank DB00742 7pxY
ChemSpider 6015 7pxY
UNII 3OWL53L36A 7pxY
KEGG D00062 7pxY
ChEBI CHEBI:16899 7pxY
Chemical data
Formula C6H14O6
 14pxY (what is this?)  (verify)
Mannitol structure
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IUPAC name
Other names
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ChemSpider 6015
DrugBank DB00742
Jmol-3D images Image
KEGG D00062
PubChem Template:Chembox PubChem/format
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Molar mass 182.172
Appearance white crystalline solid
Density 1.52 g/cm3
Melting point Script error: No such module "convert".
Boiling point Script error: No such module "convert".
216 g/L
Acidity (pKa) 13.50 @ 18 °C
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1700 mg/kg (rat oral)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Mannitol (also referred to as mannite or manna sugar)[1] is a white, crystalline solid[2] that looks and tastes sweet like sucrose. It was originally isolated from the secretions of the flowering ash and called manna after its resemblance to the Biblical food. In plants it is used to alleviate osmotic stress. Mannitol has several industrial uses, but is mainly used to produce tablets of medicine. Its fetal safety is "C" (FDA pregnancy category: risk not ruled out) in Briggs' Reference Guide to Fetal and Neonatal Risk.[3] Mannitol is classified as a sugar alcohol; that is, it is derived from a sugar (mannose) by reduction. 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.[4]

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[5]


Medical uses

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. 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.[6] 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.[7] 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.[8] 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.[7])

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 the basis of Bronchitol which was developed by the Australian pharmaceutical company Pharmaxis as a treatment for cystic fibrosis and bronchiectasis. 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. Pharmaxis has also developed Aridol – a diagnostic test for airway hyperresponsiveness based on mannitol.

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, therefore, lowers the intraocular pressure. However, it requires an intact blood-ocular barrier to work.[9]

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.

Mannitol acts as an osmotic laxative[10] in oral doses larger than 20 g[11] and is sometimes sold as a laxative for children[citation needed].

The use of mannitol, when inhaled, as a bronchial irritant as an alternative method of diagnosis of exercise induced asthma has been proposed. A 2013 systematic review concluded there is insufficient evidence to support its use for this purpose at this time.[12]


Mannitol increases blood glucose to a lesser extent than sucrose (thus having a relatively low glycemic index[13]) and is therefore used as a sweetener for people with diabetes, and in chewing gums. 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.[4] 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.[2] The pleasant taste and mouthfeel of mannitol also makes it a popular excipient for chewable tablets.[14]

Analytical chemistry

Mannitol can be used to form a complex with boric acid. This increases the acid strength of the boric acid permitting better precision in volumetric analysis of this acid.

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]


Industrial synthesis

Mannitol is commonly produced via the hydrogenation of fructose, which is formed from either starch or sucrose (common table sugar). Although starch is a cheaper source 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.[4]


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.[16] Fermentation by microorganisms is an alternative to the traditional industrial synthesis. 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.[17] A class of lactic acid bacteria, labeled heterofermentive because of their multiple fermentation pathways, convert either three fructose molecules or two fructose and one glucose molecule into two 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 Script error: No such module "convert". mannitol per liter of feedstock. Further research is being conducted, studying ways to engineer even more efficient mannitol pathways in lactic acid bacteria, as well as the use of other microorganisms such as yeast[16] and E. coli in mannitol production. 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.[17]

Natural product extraction

Since mannitol is found in a wide variety of natural products, including almost all plants, it can be directly extracted from natural products, rather than chemical or biological syntheses. In fact, in China, isolation from seaweed is the most common form of mannitol production.[2] Mannitol concentrations of plant exudates can range from 20% in seaweeds to 90% in the plane tree. It is a constituent of saw palmetto (Serenoa).[18] 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 measure of leaf than a traditional extraction — Script error: No such module "convert". CO2 versus Script error: No such module "convert". ethanol per Script error: No such module "convert". olive leaf. Heated, pressurized, subcritical water is even cheaper, and is shown to have dramatically greater results than traditional extraction. It requires only Script error: No such module "convert". water per Script error: No such module "convert". of 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 required high operating temperatures and pressures are causes for hesitancy in the industrial use of this technique.[17]

Controversy over severe head injury treatment

The three studies[19][20][21] that initially found that high-dose mannitol was effective in cases of severe head injury have been the subject of a recent investigation.[22] 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. As a result of doubt surrounding Cruz's work, an updated version of the Cochrane review excludes all studies by Julio Cruz, leaving only 4 studies.[23] Due to vast differences in selection of control groups, a conclusion about the clinical use of mannitol could not be reached. There is some evidence that mannitol may worsen cerebral edema.[24]


Mannitol is contraindicated in patients with anuria, congestive heart failure and active cerebral haemorrhage (except during craniotomy).[citation needed]


  • Parkinson disease:

Researchers from Tel Aviv University describe experiments that could lead to a new approach for treating Parkinson's disease (PD) using a common sweetener, mannitol.[25]

These findings were confirmed by a second study which measured the impact of mannitol on mice engineered to produce human α-synuclein, developed by Dr. Eliezer Masliah of the University of San Diego. After four months, the researchers found that the mice injected with mannitol also showed a dramatic reduction of α-synuclein in the brain.[26][27]

Compendial status

See also

Notes and references

  1. ^ Cooley's Cyclopaedia of Practical Receipts, 6th ed. (1880)
  2. ^ a b c Lawson, P. (2007) Mannitol. Blackwell Publishing Ltd. pp 219–225.
  3. ^ Briggs GG, Freeman RK, Yaffe SJ. (2008) Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition. Lippincott Williams & Wilkins.
  4. ^ a b c Kearsley, M. W.; Deis, R. C. (2006) "Sorbitol and Mannitol", pp. 249–261 in Sweeteners and Sugar Alternatives in Food Technology. Wiley-Blackwell. ISBN 0470659688
  5. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  6. ^ Best, B. Perfusion & Diffusion in Cryonics Protocol.
  7. ^ a b Ikeda, M.; Bhattacharjee, A. K.; Kondoh, T.; Nagashima, T.; Tamaki, N. (2002). "Synergistic Effect of Cold Mannitol and Na+/Ca2+ Exchange Blocker on Blood–Brain Barrier Opening". Biochemical and Biophysical Research Communications 291 (3): 669. PMID 11855842. doi:10.1006/bbrc.2002.6495.  edit
  8. ^ Wang, M; Etu, J; Joshi, S (2007). "Enhanced disruption of the blood brain barrier by intracarotid mannitol injection during transient cerebral hypoperfusion in rabbits". Journal of Neurosurgical Anesthesiology 19 (4): 249–56. PMID 17893577. doi:10.1097/ANA.0b013e3181453851.  edit
  9. ^ Veterinary Class Notes, Ophthalmology, The Ohio State University, provided by David Wilkie, DVM, DACVO
  10. ^ "Select Committee on GRAS Substances (SCOGS) Opinion: Mannitol". April 2013. Retrieved October 2014. 
  11. ^ Ellis, F.W.; Krantz, J.C. Jr. (1941). "Sugar alcohols: XXII. Metabolism and toxicity studies with mannitol and sorbitol in man and animals". J. Biol. Chem. 141: 147–154. 
  12. ^ Stickland, MK; Rowe, BH; Spooner, CH; Vandermeer, B; Dryden, DM (September 2011). "Accuracy of eucapnic hyperpnea or mannitol to diagnose exercise-induced bronchoconstriction: a systematic review.". Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 107 (3): 229–34.e8. PMID 21875541. doi:10.1016/j.anai.2011.06.013. 
  13. ^ Grenby, T.H (2011) Advances in Sweetners. Springer. ISBN 1461285224. p. 66
  14. ^ Weiner, Myra L.; Lois A. Kotkoskie (1999). Excipient Toxicity and Safety. p. 370. ISBN 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. ^ a b Song, S. H.; Vieille, C. (2009). "Recent advances in the biological production of mannitol". Applied Microbiology and Biotechnology 84 (1): 55–62. PMID 19578847. doi:10.1007/s00253-009-2086-5.  edit
  17. ^ a b c Ghoreishi, S. M.; Shahrestani, R. G. (2009). "Innovative strategies for engineering mannitol production". Trends in Food Science & Technology 20 (6–7): 263. doi:10.1016/j.tifs.2009.03.006.  edit
  18. ^ Wagner, H; Flachsbarth, H; Vogel, G (Mar 1981). "[A New Antiphlogistic Principle from Sabal serrulata, II].". Planta medica 41 (3): 252–8. PMID 17401849. doi:10.1055/s-2007-971711. 
  19. ^ Cruz, J.; Minoja, G.; Okuchi, K. (2001). "Improving Clinical Outcomes from Acute Subdural Hematomas with the Emergency Preoperative Administration of High Doses of Mannitol: A Randomized Trial". Neurosurgery 49 (4): 864. PMID 11564247. doi:10.1097/00006123-200110000-00016.  edit
  20. ^ Cruz, J.; Minoja, G.; Okuchi, K. (2002). "Major Clinical and Physiological Benefits of Early High Doses of Mannitol for Intraparenchymal Temporal Lobe Hemorrhages with Abnormal Pupillary Widening: A Randomized Trial". Neurosurgery 51 (3): 628. PMID 12188940. doi:10.1097/00006123-200209000-00006.  edit
  21. ^ Cruz, J.; Minoja, G.; Okuchi, K.; Facco, E. (2004). "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". Journal of Neurosurgery 100 (3): 376. PMID 15035271. doi:10.3171/jns.2004.100.3.0376.  edit
  22. ^ Roberts, I.; Smith, R.; Evans, S. (2007). "Doubts over head injury studies". BMJ 334 (7590): 392. PMID 17322250. doi:10.1136/bmj.39118.480023.BE.  edit PMID 17322250
  23. ^ Wakai, Abel; Aileen McCabe; Ian Roberts; Gillian Schierhout (2013). "Mannitol for acute traumatic brain injury". The Cochrane Database of Systematic Reviews 8: –001049. ISSN 1469-493X. PMID 23918314. doi:10.1002/14651858.CD001049.pub5. 
  24. ^ Kaufmann AM, Cardoso ER. Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg. 1992 Oct;77(4):584–9. PMID 1527619
  25. ^ "Flies model a potential sweet treatment for Parkinson's disease", Genetics Society of America's 54th Annual Drosophila Research Conference, Washington D.C., April 3–7, 2013.
  26. ^ Artificial sweetener a potential treatment for Parkinson's disease. Science Daily. June 17, 2013
  27. ^ Shaltiel-Karyo, R.; Frenkel-Pinter, M.; Rockenstein, E.; Patrick, C.; Levy-Sakin, M.; Schiller, A.; Egoz-Matia, N.; Masliah, E.; Segal, D.; Gazit, E. (2013). "A BBB Disrupter is also a Potent α-Synuclein (α-syn) Aggregation Inhibitor: A Novel Dual Mechanism of Mannitol for the Treatment of Parkinson's Disease (PD)". Journal of Biological Chemistry 288 (24): 17579–17588. PMC 3682557. PMID 23637226. doi:10.1074/jbc.M112.434787.  edit
  28. ^ British Pharmacopoeia Commission Secretariat (2009). "Index, BP 2009" (PDF). Retrieved 31 January 2010. 
  29. ^ "Japanese Pharmacopoeia, Fifteenth Edition" (PDF). 2006. Retrieved 31 January 2010. 
  30. ^ USP 32 (2008). "Mannitol Injection" (PDF). Retrieved 31 January 2010. 

External links