Mannitol is a type of sugar alcohol used as a sweetener and medication. It is used as a low-calorie sweetener as it is poorly absorbed by the intestines. As a medication, it is used to decrease pressure in the eyes, as in glaucoma, and to lower increased intracranial pressure. Medically, it is given by injection or inhalation. Effects typically begin within 15 minutes and last up to 8 hours. Common side effects from medical use include electrolyte problems and dehydration. Other serious side effects may include worsening heart failure and kidney problems. It is unclear if use is safe in pregnancy. Mannitol is in the osmotic diuretic family of medications and works by pulling fluid from the brain and eyes. The discovery of mannitol is attributed to Joseph Louis Proust in 1806. It is on the World Health Organization's List of Essential Medicines. It was originally made from the flowering ash and called manna due to its supposed resemblance to the Biblical food. Mannitol is on the World Anti-Doping Agency's banned substances list due to concerns that it may mask prohibited drugs. Mannitol is a natural constituent of most microorganisms and plants, having an essential role in maintaining cell and tissue water balance, and responding to environmental stresses, such as drought or low temperature.
Uses
Medical uses
Injected In the United States, injected mannitol is indicated for the reduction of intracranial pressure and treatment of cerebral edema and elevated intraocular pressure. Mannitol is used intravenously to reduce acutely raised intracranial pressure until more definitive treatment can be applied, e.g., after head trauma. While mannitol injection is the mainstay for treating high pressure in the skull after a serious brain injury, it is no better than hypertonic saline as a first-line treatment. In treatment-resistant cases, hypertonic saline works better. It may also be used for certain cases of kidney failure with low urine output, to decrease pressure in the eye, to increase the elimination of certain toxins, and to treat fluid build up. Intraoperative mannitol prior to vessel clamp release during renal transplant has been shown to reduce post-transplant kidney injury, but has not been shown to reduce graft rejection. 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 resultant cell damage. Mannitol can also be used to temporarily encapsulate a sharp object (such as a helix on a lead for an artificial pacemaker) while it passes through the venous system. Because the mannitol dissolves readily in blood, the sharp point becomes exposed at its destination. Intra-arterial infusions of mannitol can transiently open the blood–brain barrier by disrupting tight junctions. Mannitol is also the first drug of choice to treat acute glaucoma (high eye pressure) in veterinary medicine. It is administered as a 20% solution intravenously. It dehydrates the vitreous humor and, therefore, lowers the intraocular pressure. However, it requires an intact blood-ocular barrier to work.
Inhaled In the European Union, inhaled mannitol is indicated for the treatment of cystic fibrosis (CF) in adults aged 18 years and above as an add-on therapy to best standard of care. 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 evidence to support its use for this purpose at this time is insufficient.
Oral Mannitol acts as an osmotic laxative in oral doses larger than 20 g, and is sometimes sold as a laxative for children.
Food Mannitol increases blood glucose to a lesser extent than sucrose (thus having a relatively low glycemic index) so is 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. 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. The pleasant taste and mouthfeel of mannitol also makes it a popular excipient for chewable tablets.
Analytical chemistry Mannitol forms stable complexes with boric acid. This considerably enhances the acidity of boric acid, allowing for greater precision in the volumetric titration of this acid. The stability of the mannitoborate ester anions shifts the acid dissociation equilibrium to the right, thereby increasing the solution's acidity by five orders of magnitude compared to that of pure boric acid. This lowers the pKa from 9 to below 4 for a sufficient concentration of mannitol. The resulting solution is referred to as mannitoboric acid.
Other Mannitol is the primary ingredient of mannitol salt agar, a bacterial growth medium, and is used in others. Mannitol is used as a cutting agent in various drugs that are used intranasally (snorted), such as heroin and cocaine. A mixture of mannitol and fentanyl (or fentanyl analogs) in ratio 1:10 is labeled and sold as "China white", a popular heroin substitute. Mannitol is a sugar alcohol with "50–70 percent of the relative sweetness of sugar, which means more must be used to equal the sweetness of sugar. Mannitol lingers in the intestines for a long time and therefore often causes bloating and diarrhea."
Contraindications Mannitol is contraindicated in people with anuria, severe hypovolemia, pre-existing severe pulmonary vascular congestion or pulmonary edema, irritable bowel syndrome (IBS), and active intracranial bleeding except during craniotomy. Adverse effects include hyponatremia and volume depletion leading to metabolic acidosis.
Chemistry Mannitol is an isomer of sorbitol, another sugar alcohol; the two differ only in the orientation of the hydroxyl group on carbon 2. While similar, the two sugar alcohols have very different sources in nature, melting points, and uses.
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