D-mannitol 1-phosphate
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Mannitol is a type of
sugar alcohol Sugar alcohols (also called polyhydric alcohols, polyalcohols, alditols or glycitols) are organic compounds, typically derived from sugars, containing one hydroxyl group attached to each carbon atom. They are white, water-soluble solids that c ...
used as a
sweetener A sweetener is a substance added to food or drink to impart the flavor of sweetness, either because it contains a type of sugar, or because it contains a sweet-tasting sugar substitute. Various natural non-sugar sweeteners (NSS) and artificial s ...
and medication. It is used as a low calorie sweetener as it is poorly absorbed by the
intestines The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...
. As a medication, it is used to decrease pressure in the eyes, as in
glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...
, and to lower
increased intracranial pressure Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 mmHg for a supine adult. ...
. 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 Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function ...
and
dehydration In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...
. Other serious side effects may include worsening
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...
and
kidney problems Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...
. It is unclear if use is safe in
pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...
. Mannitol is in the
osmotic diuretic An osmotic diuretic is a type of diuretic that inhibits reabsorption of water and sodium (Na). They are pharmacologically inert substances that are given intravenously. They increase the osmolarity of blood and renal filtrate. This fluid eventually ...
family of medications and works by pulling fluid from the brain and eyes. The discovery of mannitol is attributed to
Joseph Louis Proust Joseph Louis Proust (26 September 1754 – 5 July 1826) was a French chemist. He was best known for his discovery of the law of definite proportions in 1797, stating that chemical compounds always combine in constant proportions. Life Joseph-Lo ...
in 1806. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
. It was originally made from the flowering ash and called
manna Manna (, ; ), sometimes or archaically spelled Mahna or Mana, is described in the Bible and the Quran as an edible substance that God in Abrahamic religions, God bestowed upon the Israelites while they were wandering the desert during the 40-year ...
due to its supposed resemblance to the Biblical food. Mannitol is on the
World Anti-Doping Agency The World Anti-Doping Agency (WADA; , AMA) is an international organization co-founded by the governments of over 140 nations along with the International Olympic Committee based in Canada to promote, coordinate, and monitor the fight against d ...
's banned substances list due to concerns that it may mask prohibited drugs.


Uses


Medical uses


Injected

In the United States, injected mannitol is
indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
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 A head injury is any injury that results in trauma to the skull or brain. The terms ''traumatic brain injury'' and ''head injury'' are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of inj ...
. While mannitol injection is the mainstay for treating high pressure in the skull after a bad 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, decreasing 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 Cardiopulmonary bypass (CPB) or heart-lung machine, also called the pump or CPB pump, is a machine that temporarily takes over the function of the heart and lungs during open-heart surgery by maintaining the circulation of blood and oxygen throu ...
during
cardiopulmonary bypass Cardiopulmonary bypass (CPB) or heart-lung machine, also called the pump or CPB pump, is a machine that temporarily takes over the function of the heart and lungs during open-heart surgery by maintaining the circulation of blood and oxygen throug ...
. 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 cell The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...
s in the kidney, which may have otherwise reduced blood flow to this area and resulted in cell damage. Mannitol can also be used to temporarily encapsulate a sharp object (such as a helix on a lead for an
artificial pacemaker A pacemaker, also known as an artificial cardiac pacemaker, is an Implant (medicine), implanted medical device that generates Pulse (signal processing), electrical pulses delivered by electrodes to one or more of the Heart chamber, chambers of ...
) 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 The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...
by disrupting
tight junctions Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes between epithelial cells, sealing and preventing leakage of solutes and water. They also play a ...
. Mannitol is also the first drug of choice to treat acute
glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...
(high eye pressure) in veterinary medicine. It is administered as a 20% solution intravenously. It dehydrates the
vitreous humor The vitreous body (''vitreous'' meaning "glass-like"; , ) is the clear gel that fills the space between the lens and the retina of the eyeball (the vitreous chamber) in humans and other vertebrates. It is often referred to as the vitreous humo ...
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 Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
(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 Exercise-induced bronchoconstriction (EIB) occurs when the airways narrow as a result of exercise. This condition has been referred to as exercise-induced asthma (EIA); however, this term is no longer preferred. While exercise does not cause asth ...
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 Laxatives, purgatives, or aperients are substances that loosen stools and increase bowel movements. They are used to treat and prevent constipation. Laxatives vary as to how they work and the side effects they may have. Certain stimulant, lubri ...
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 Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula . For human consumption, sucrose is extracted and refined ...
(thus having a relatively low
glycemic index The glycemic (glycaemic) index (GI; ) is a number from 0 to 100 assigned to a food, with pure glucose arbitrarily given the value of 100, which represents the relative rise in the blood glucose level two hours after consuming that food. The GI of ...
) so is used as a
sweetener A sweetener is a substance added to food or drink to impart the flavor of sweetness, either because it contains a type of sugar, or because it contains a sweet-tasting sugar substitute. Various natural non-sugar sweeteners (NSS) and artificial s ...
for people with
diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
, and in
chewing gum Chewing gum is a soft, cohesive substance designed to be chewed without being swallowed. Modern chewing gum is composed of gum base, sweeteners, softeners/plasticizers, flavors, colors, and, typically, a hard or powdered polyol coating. Its tex ...
s. Although mannitol has a higher
heat of solution In thermochemistry, the enthalpy of solution (heat of solution or enthalpy of solvation) is the enthalpy change associated with the dissolution of a substance in a solvent at constant pressure resulting in infinite dilution. The enthalpy of sol ...
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 Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substance ...
– 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 An excipient is a substance formulated alongside the active ingredient of a medication. They may be used to enhance the active ingredient’s therapeutic properties; to facilitate drug absorption; to reduce viscosity; to enhance solubility; to i ...
for chewable tablets.


Analytical chemistry

Mannitol forms stable complexes with
boric acid Boric acid, more specifically orthoboric acid, is a compound of boron, oxygen, and hydrogen with formula . It may also be called hydrogen orthoborate, trihydroxidoboron or boracic acid. It is usually encountered as colorless crystals or a white ...
. 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 p''K''a 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 Cutting is the separation or opening of a physical object, into two or more portions, through the application of an acutely directed force. Implements commonly used for cutting are the knife and saw, or in medicine and science the scalpel and m ...
in various drugs that are used intranasally ( snorted), such as
heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a morphinan opioid substance synthesized from the Opium, dried latex of the Papaver somniferum, opium poppy; it is mainly used as a recreational drug for its eupho ...
and
cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...
. A mixture of mannitol and
fentanyl Fentanyl is a highly potent synthetic piperidine opioid primarily used as an analgesic (pain medication). It is 30 to 50 times more Potency (pharmacology), potent than heroin and 50 to 100 times more potent than morphine. Its primary Medici ...
(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 Anuria is nonpassage of urine, in practice is defined as passage of less than 100 milliliters of urine in a day. Anuria is often caused by failure in the function of kidneys. It may also occur because of some severe obstruction like kidney stone ...
, severe
hypovolemia Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt and water or a decrease in blood volume. Hypovolemia refers to the loss ...
, pre-existing severe pulmonary vascular congestion or pulmonary edema, irritable bowel syndrome (IBS), and active intracranial bleeding except during craniotomy. Adverse effects include
hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the Serum (blood), blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symp ...
and volume depletion leading to
metabolic acidosis Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidn ...
.


Chemistry

Mannitol is an
isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...
of
sorbitol Sorbitol (), less commonly known as glucitol (), is a sugar alcohol with a sweet taste which the human body metabolizes slowly. It can be obtained by reduction of glucose, which changes the converted aldehyde group (−CHO) to a primary alco ...
, another sugar alcohol; the two differ only in the orientation of the
hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
group on carbon 2. While similar, the two sugar alcohols have very different sources in nature,
melting point The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state of matter, state from solid to liquid. At the melting point the solid and liquid phase (matter), phase exist in Thermodynamic equilib ...
s, and uses.


Production

Mannitol is classified as a
sugar alcohol Sugar alcohols (also called polyhydric alcohols, polyalcohols, alditols or glycitols) are organic compounds, typically derived from sugars, containing one hydroxyl group attached to each carbon atom. They are white, water-soluble solids that c ...
; that is, it can be derived from a sugar (
mannose Mannose is a sugar with the formula , which sometimes is abbreviated Man. It is one of the monomers of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylatio ...
) by reduction. Other sugar alcohols include
xylitol Xylitol is a chemical compound with the formula , or HO(CH2)(CHOH)3(CH2)OH; specifically, one particular Stereoisomerism, stereoisomer with that structural formula. It is a colorless or white crystalline solid. It is classified as a polyalcoho ...
and
sorbitol Sorbitol (), less commonly known as glucitol (), is a sugar alcohol with a sweet taste which the human body metabolizes slowly. It can be obtained by reduction of glucose, which changes the converted aldehyde group (−CHO) to a primary alco ...
.


Industrial synthesis

Mannitol is commonly produced via the
hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to redox, reduce or Saturated ...
of fructose, which is formed from either
starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human diet ...
or
sucrose Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula . For human consumption, sucrose is extracted and refined ...
(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 Fructose (), or fruit sugar, is a Ketose, ketonic monosaccharide, simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and gal ...
, 52%
glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
, and 6%
maltose } Maltose ( or ), also known as maltobiose or malt sugar, is a disaccharide formed from two units of glucose joined with an α(1→4) bond. In the isomer isomaltose, the two glucose molecules are joined with an α(1→6) bond. Maltose is the tw ...
. 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 Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...
into a mixture of isomers
sorbitol Sorbitol (), less commonly known as glucitol (), is a sugar alcohol with a sweet taste which the human body metabolizes slowly. It can be obtained by reduction of glucose, which changes the converted aldehyde group (−CHO) to a primary alco ...
and mannitol. Yield is typically 50%:50%, although slightly
alkaline In chemistry, an alkali (; from the Arabic word , ) is a basic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a soluble base has a pH greater than 7.0. The ...
reaction conditions can slightly increase mannitol yields.


Biosyntheses

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.
Fermentation Fermentation is a type of anaerobic metabolism which harnesses the redox potential of the reactants to make adenosine triphosphate (ATP) and organic end products. Organic molecules, such as glucose or other sugars, are catabolized and reduce ...
by microorganisms is an alternative to the traditional industrial synthesis. A fructose to mannitol
metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are ...
, 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. A class of
lactic acid bacteria Lactobacillales are an order of gram-positive, low-GC, acid-tolerant, generally nonsporulating, nonrespiring, either rod-shaped (bacilli) or spherical ( cocci) bacteria that share common metabolic and physiological characteristics. These bact ...
, 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 Lactic acid is an organic acid. It has the molecular formula C3H6O3. It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as wel ...
,
acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main compone ...
, and
carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...
.
Feedstock A raw material, also known as a feedstock, unprocessed material, or primary commodity, is a basic material that is used to produce goods, finished goods, energy, or intermediate materials/Intermediate goods that are feedstock for future finishe ...
syrups containing medium to large concentrations of fructose (for example, cashew apple juice, containing 55% fructose: 45%
glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
) can produce yields 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 Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...
and ''
E. coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly foun ...
'' 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.


Natural 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 Seaweed, or macroalgae, refers to thousands of species of macroscopic, multicellular, marine algae. The term includes some types of ''Rhodophyta'' (red), '' Phaeophyta'' (brown) and ''Chlorophyta'' (green) macroalgae. Seaweed species such as ...
is the most common form of mannitol production. Mannitol concentrations of plant
exudate An exudate is a fluid released by an organism through pores or a wound, a process known as exuding or exudation. ''Exudate'' is derived from ''exude'' 'to ooze' from Latin language, Latin 'to (ooze out) sweat' (' 'out' and ' 'to sweat'). Medi ...
s can range from 20% in seaweeds to 90% in the
plane tree ''Platanus'' ( ) is a genus consisting of a small number of tree species native to the Northern Hemisphere. They are the sole living members of the family Platanaceae. All mature members of ''Platanus'' are tall, reaching in height. The type ...
. It is a constituent of saw palmetto (''
Serenoa ''Serenoa repens'', commonly known as saw palmetto, is a small palm, growing to a maximum height around . Taxonomy It is the sole species in the genus ''Serenoa''. The genus name honors American botanist Sereno Watson. Distribution and ...
''). Traditionally, mannitol is extracted by the Soxhlet extraction, using
ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...
, water, and
methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical compound and the simplest aliphatic Alcohol (chemistry), alcohol, with the chemical formula (a methyl group linked to a hydroxyl group, often ab ...
to steam and then hydrolysis of the crude material. The mannitol is then recrystallized from the extract, generally resulting in yields of about 18% of the original natural product. Another method of extraction is using supercritical and
subcritical In the operation of a nuclear reactor, criticality or critical state is the state in which a nuclear chain reaction is self-sustaining but not growing. Subcriticality or subcritical state is the state in which a nuclear chain reaction is not self ...
fluids. These fluids are at such a stage that no difference exists between the liquid and gas stages, so are more diffusive than normal fluids. This is considered to make them much more effective mass transfer agents than normal liquids. The super- or subcritical 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 Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...
extraction of olive leaves has been shown to require less solvent per measure of leaf than a traditional extraction – CO2 versus ethanol per olive leaf. Heated, pressurized, subcritical water is even cheaper, and is shown to have dramatically greater results than traditional extraction. It requires only water per of olive leaf, and gives a yield of 76.75% mannitol. Both super- and subcritical 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.


History

In the early 1880s, Julije Domac elucidated the structure of hexene and mannitol obtained from Caspian manna. He determined the place of the double bond in hexene obtained from mannitol and proved that it is a derivative of a normal hexene. This also solved the structure of mannitol, which was unknown until then.


Controversy

The three studies that originally found high-dose mannitol effective in treating severe head injury were the subject of an investigation. Published in 2007 after the lead author Dr Julio Cruz's death, the investigation questioned whether the studies had actually taken place. The co-authors of the paper were not able to confirm the existence of the study patients, and the Federal University of São Paulo, which Cruz gave as his affiliation, had never employed him. As a result of doubt surrounding Cruz's work, an updated version of the
Cochrane review Cochrane is a British international charitable organisation formed to synthesize medical research findings to facilitate evidence-based choices about health interventions involving health professionals, patients and policy makers. It includes ...
excludes all studies by Julio Cruz, leaving only four studies. Due to differences in selection of control groups, a conclusion about the clinical use of mannitol has not been reached.


Compendial status

*
British Pharmacopoeia The ''British Pharmacopoeia'' (''BP'') is the national pharmacopoeia of the United Kingdom. It is an annually published collection of quality standards for medicinal substances in the UK, which is used by individuals and organisations involve ...
*
Japanese Pharmacopoeia The is the official pharmacopoeia of Japan. It is published by the . The first edition was published on 25 June 1886, with revisions being issued from time to time. The current revision is number 18, issued electronically on 7 June 2021. An off ...
*
United States Pharmacopeia The ''United States Pharmacopeia'' (''USP'') is a pharmacopeia (compendium of drug information) for the United States published annually by the over 200-year old United States Pharmacopeial Convention (usually also called the USP), a nonprofi ...


See also

* -mannitol oxidase *
E number E numbers, short for Europe numbers, are codes for substances used as food additives, including those found naturally in many foods, such as vitamin C, for use within the European Union (EU) and European Free Trade Association (EFTA). Commonly ...
* Mannitol dehydrogenase * Mannitol dehydrogenase (cytochrome) * Mannitol-1-phosphatase * Mannitol 2-dehydrogenase * Mannitol 2-dehydrogenase (NADP+) * Mannitol-1-phosphate 5-dehydrogenase


References


External links

* {{Portal bar, Medicine E-number additives Excipients Glycerols Nephrotoxins Osmotic diuretics Wikipedia medicine articles ready to translate Sugar alcohols Sugar substitutes World Anti-Doping Agency prohibited substances World Health Organization essential medicines