Mannitol

Table of Contents

Definition

noun
plural: mannitols
man·ni·tol, ˈmæn ɪˌtɔl
A sugar alcohol with a sweetish taste, occurs naturally in certain plants and algae, and manufactured chemically via reduction of mannose, for use as a low-calorie sweetener in the food industry, and medically, as a diuretic

Details

Overview

Mannitol is one of the sugar alcohols. Sugar alcohols belong to a class of polyols characterized by being white, water-soluble, organic compounds with a general chemical formula of (CHOH)_nH_{2</sub. Sugar alcohols may be produced by the hydrogenation of sugars.}

History

The discovery of mannitol is attributed to Joseph Louis Proust 1754 – 1826 in 1806. He was a French chemist. He was also credited for the discovery of leucine in 1819.¹ The chemical structure of mannitol was elucidated by the Croatian chemist Julije Domac 1853-1928. He obtained the mannitol from manna, a natural sweet secretion from the manna ash. Today, mannitol is produced chemically via the hydrogenation of fructose (hydrolyzed from starch or sucrose) over a nickel catalyst. Similar to sorbitol (another sugar alcohol), mannitol has been affirmed as generally safe by the U.S. Food and Drug Administration.

Properties

Mannitol is a polyol with a chemical formula of C₆H₁₄O₆, which is the same as that of sorbitol. Mannitol and sorbitol are isomers of each other. Their structural difference is the orientation of the hydroxyl group on C-2. They also have different melting points. The melting point of sorbitol is at 94–96 °C whereas that of mannitol is at 166-168 °C. Both of them occur naturally in plants. They are also produced chemically. They are used as alternative sweetening agents for their sweet-tasting properties. However, they are used differently in medicine. As a treatment, mannitol is used chiefly as a diuretic whereas sorbitol is used largely as a laxative. Sorbitol is hygroscopic whereas mannitol is considered non-hygroscopic. Mannitol does not undergo Mallard reactions.²
Similar to sorbitol, mannitol is used as an alternative to sucrose (table sugar). Mannitol is less sweet than sucrose. It has about 50-60% sweetness relative to sucrose and with a strong cooling effect. It has a glycemic index of 0; sucrose has a glycemic index of 65.

Biological activities

D-mannitol is regarded as the most abundant natural polyol. It is biosynthesized by many organisms such as bacteria, fungi, algae, lichens, and vascular plants^3,4,5 but not by Archaea and animals ⁵. It is one of the major photosynthetic products of many plants, such as celery and privet.^3,4 In bacteria, mannitol is biosynthesized via different fermentation pathways. For instance, certain lactic acid bacteria can convert three fructose molecules (or 2 fructose and 1 glucose) into two mannitol molecules, one lactic acid, one acetic acid, and one CO₂. In algae and Apicomplexa, mannitol biosynthesis is a two-step process: the first step is the conversion of fructose-6-phosphate into mannitol-1-phosphate by the enzyme mannitol-1-phosphate dehydrogenase and the second step is the conversion of mannitol-1-phosphate into D-mannitol by the enzyme mannitol-1-phosphatase. This was also described to occur in fungi ⁵. The mannitol biosynthetic pathway in fungi is also referred to as the “mannitol cycle”. In vascular plants, mannitol biosynthesis is a three-step process. In the first step, fructose-6-phosphate is isomerized to mannose-6-phosphate by an isomerase enzyme. The second step is the conversion of mannose-6-phosphate into mannitol-1-phosphate via the NADPH-dependent enzyme mannose-6-phosphate reductase. The final step (which is irreversible) is the conversion of mannitol-1-phosphate into D-mannitol ³.

Biological activities

Mannitol, aside from being produced naturally, can be chemically produced. For example, the hydrogenation of fructose over a nickel catalyst will produce mannitol (along with sorbitol). Similar to sorbitol, mannitol is used as a low-calorie sweetening agent in foods and special dietary products. In humans, the absorption of mannitol in the intestine occurs at a relatively slower rate. When absorbed, it is released into the bloodstream to be picked up especially by the liver cells where it is converted into fructose to be metabolized (just as sorbitol can be converted into fructose as well) via dehydrogenases.^2,6 However, dehydrogenases are more efficient at converting sorbitol than mannitol. Thus, a large part of mannitol may not be metabolized but excreted in the urine. ⁶.

Health risks

Mannitol is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. When ingested in amounts greater than the recommended 50 mg/kg body weight, it may cause abdominal pain, excessive gas (flatulence), loose stools or diarrhea.⁷

Biological importance

Mannitol serves as an essential carbon source especially by organisms capable of synthesizing it naturally. In plants, it is one of the major products derived from the hydrogenation of fructose. Mannitol-producing plants are capable of tolerating saline habitats. Mannitol apparently helps prevent water loss and balance salt accumulation without interfering normal metabolism. It also has been postulated to act as scavengers of reactive oxygen species and therefore may be helpful in preventing lipid peroxidation that causes cell damage.³
Mannitol has been extracted and processed for use in the food industry. It has been used as sweetener, anti-caking agent, thickener, or emulsifier in foods such as ice cream, confections, chewing gum, butter, pre-cooked pasta, and infant formula.⁷ Mannitol as substitute to sugars provides benefits by not causing spikes in blood sugar and not promoting tooth decay. Just as the other sugar alcohols, mannitol is not usually fermented or metabolized by oral bacteria, and therefore is not converted into acids or other byproducts that contribute to tooth decay. It has a very low glycemic index (GI), which is 0, as opposed to sucrose that has GI of 65. Glucose has GI of 100 and fructose has 25. A high GI means that it can raise blood glucose levels. A consistently high blood glucose level is implicated in diabetes mellitus and obesity. As for the dietary energy, mannitol provides 1.6 kilocalories per gram, which is also less than that of sucrose. Similar to other sugar alcohols, mannitol also has laxative effects, particularly when consumed in excess.
In medicine, mannitol is used to treat or manage certain conditions. Some of its FDA-approved medical uses are for temporarily disrupting the blood-brain barrier prior to some forms of chemotherapy and for promoting diuresis. Mannitol can be used to help excretion of toxic metabolites or substances. It helps in reducing intracranial pressure and intraocular pressure (e.g. as in glaucoma) by pulling away the accumulating fluid from the brain and eyes. It is administered by injection.
Sorbitol is also used as a growth substrate in some tests for bacteria and is sometimes used to maintain the tonicity of low ionic strength media.

Supplementary

Etymology

mannose + –itol (referring to polyhydric alcohols)

IUPAC

(2R,3R,4R,5R)-Hexane-1,2,3,4,5,6-hexol

Chemical formula

C₆H₁₄O₆

Synonym(s)

D-Mannitol

mannite

manna sugar

Derived term(s)

Mannitol dehydrogenase
Mannitol hexanitrate

Reference

Kremers, E., Urdang, G. & Sonnedecker, G. (1986). Kremers and Urdang’s history of pharmacy. Madison, Wis: American Institute of the History of Pharmacy. p.481
Nabors, L. (2001). Alternative sweeteners. New York: M. Dekker.
Tissier, C. (2005). MetaCyc mannitol biosynthesis. Retrieved from ://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-3881 Link
Loescher, W. H., Tyson, R. H., Everard, J. D., Redgwell, R. J., & Bieleski, R. L. (1992). Mannitol Synthesis in Higher Plants : Evidence for the Role and Characterization of a NADPH-Dependent Mannose 6-Phosphate Reductase. Plant Physiology, 98(4), 1396–402. Retrieved from ://www.ncbi.nlm.nih.gov/pmc/articles/PMC1080363/ Link
Tonon, T., Li, Y. & McQueen-Mason, S. (2016). Mannitol biosynthesis in algae: more widespread and diverse than previously thought. New Phytologist, 213(4), 1573–1579. ://doi.org/10.1111/nph.14358 Link
Marie, S. & Piggott, J. (1991). Handbook of sweeteners. Glasgow England: Blackie Avi.
A Sweetener Mannitol: Nutrition Facts, Side Effects, Dangers. (2016, June 4). Retrieved from ://www.nutrientsreview.com/carbs/sugar-alcohol-mannitol.html Link