Aspartame

Chemistry
Aspartame is an artificial, non-saccharide sweetener used as a sugar substitute in some foods and beverages. In the European Union, it is codified as E951. Aspartame is a methyl ester of the aspartic acid/phenylalanine dipeptide. It was first sold under the brand nameNutraSweet; since 2009 it also has been sold under the brand name AminoSweet. It was first synthesized in 1965 and the patent expired in 1992. The safety of aspartame has been the subject of several political and medical controversies, congressional hearings and internet hoaxes[3][4][5] since its initial approval for use in food products by the U.S. Food and Drug Administration (FDA) in 1974. A 2007 medical review on the subject concluded that "the weight of existing scientific evidence indicates that aspartame is safe at current levels of consumption as a non-nutritive sweetener".[6] However, because its breakdown products include phenylalanine, aspartame must be avoided by people with the genetic condition phenylketonuria (PKU).

Properties and use
   Beta-aspartame differs from aspartame based upon which carboxyl group of aspartate binds to the nitrogen of phenylalanine.

Aspartame, an artificial sweetener, is approximately 200 times sweeter than sucrose, or table sugar. Due to this property, even though aspartame produces four kilocalories of energy per gram when metabolized, the quantity of aspartame needed to produce a sweet taste is so small that its caloric contribution is negligible.[6] The taste of aspartame and other artificial sweeteners differs from that of table sugar in the times of onset and how long the sweetness lasts, though aspartame comes closest to sugar's taste profile among approved artificial sweeteners.[8]The sweetness of aspartame lasts longer than sucrose, so it is often blended with other artificial sweeteners such as acesulfame potassium to produce an overall taste more like sugar.[10] Aspartame can be synthesized from its constituent amino acids, L-phenylalanine and L-aspartate. Like many other peptides, aspartame may hydrolyze (break down) into its constituent amino acids under conditions of elevated temperature or high pH. This makes aspartame undesirable as a baking sweetener, and prone to degradation in products hosting a high pH, as required for a long shelf life. The stability of aspartame under heating can be improved to some extent by encasing it in fats or in maltodextrin. The stability when dissolved in water depends markedly on pH. At room temperature, it is most stable at pH 4.3, where its half-life is nearly 300 days. At pH 7, however, its half-life is only a few days. Most soft-drinks have a pH between 3 and 5, where aspartame is reasonably stable. In products that may require a longer shelf life, such as syrups for fountain beverages, aspartame is sometimes blended with a more stable sweetener, such as saccharin.[11] Aspartame's major decomposition products are its cyclic dipeptide (diketopiperazine form), the de-esterified dipeptide (aspartyl-phenylalanine), and its constituent components, phenylalanine,[12] aspartic acid,[13] and methanol.[14] At 180°C, aspartame undergoes decomposition to form a diketopiperazine (DKP) derivative.[15] In products such as powdered beverages, the amine in aspartame can undergo a Maillard reaction with the aldehyde groups present in certain aroma compounds. The ensuing loss of both flavor and sweetness can be prevented by protecting the aldehyde as an acetal. Descriptive analyses of solutions containing aspartame report a sweet aftertaste as well as bitter and off-flavor aftertastes.[16]

Discovery and approval
Aspartame was discovered in 1965 by James M. Schlatter, a chemist working for [|G.D. Searle & Company]. Schlatter had [|synthesized] aspartame in the course of producing an anti- [|ulcer] drug candidate. He accidentally discovered its sweet taste when he licked his finger, which had become contaminated with aspartame, to lift up a piece of paper. [|[17]][|[18]] In 1975, prompted by issues regarding [|Flagyl] and [|Aldactone], a U.S. FDA task force team reviewed 25 studies submitted by the manufacturer, including 11 on aspartame. The team reported “serious deficiencies in Searle’s operations and practices". [|[19]] The FDA sought to authenticate 15 of the submitted studies against the supporting data. In 1979, the [|Center for Food Safety and Applied Nutrition] (CFSAN) concluded, since many problems with the aspartame studies were minor and did not affect the conclusions, the studies could be used to assess aspartame's safety. [|[19]]  In 1980, the FDA convened a Public Board of Inquiry (PBOI) consisting of independent advisors charged with examining the purported relationship between aspartame and [|brain cancer] . The PBOI concluded aspartame does not cause [|brain] damage, but it recommended against approving aspartame at that time, citing unanswered questions about [|cancer] in laboratory rats. [|[19]][|[20]] Citing data from a Japanese study that had not been available to the members of the PBOI, [|[21]] and after seeking advice from an expert panel that found fault with statistical analyses underlying the PBOI's hesitation, yet argued against approval, [|[22]] FDA commissioner Hayes approved aspartame for use in dry goods. [|[23]] In 1983, the FDA further approved aspartame for use in carbonated beverages, and for use in other beverages, baked goods, and confections in 1993. In 1996, the FDA removed all restrictions from aspartame, allowing it to be used in all foods. Several European Union countries approved aspartame in the 1980s, with EU-wide approval in 1994. The European Commission [|Scientific Committee on Food] reviewed subsequent safety studies and reaffirmed the approval in 2002. The [|European Food Safety Authority] reported in 2006 that the previously established [|Acceptable Daily Intake] was appropriate, after reviewing yet another set of studies. [|[24]]
 * [|IUPAC name] [|[hide]] //N//-( L -α-Aspartyl)- L -phenylalanine,

1-methyl ester || [|[show]] || [|[show]] ||
 * ~ Identifiers ||
 * [|CAS number] || [|22839-47-0]  [[image:http://upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png width="7" height="7" caption="Yes"]] ||
 * [|ChemSpider] || [|118630]  [[image:http://upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png width="7" height="7" caption="Yes"]] ||
 * [|UNII] || [|Z0H242BBR1]  [[image:http://upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png width="7" height="7" caption="Yes"]] ||
 * [|DrugBank] || [|DB00168]  ||
 * [|KEGG] || [|C11045]  [[image:http://upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png width="7" height="7" caption="Yes"]] ||
 * [|ChEBI] || [|CHEBI:2877]  [[image:http://upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png width="7" height="7" caption="Yes"]] ||
 * [|ChEMBL] || [|CHEMBL171679]  [[image:http://upload.wikimedia.org/wikipedia/en/thumb/f/fb/Yes_check.svg/7px-Yes_check.svg.png width="7" height="7" caption="Yes"]] ||
 * [|Jmol] -3D images || [|Image 1] ||
 * [|SMILES]
 * [|InChI]
 * ~ Properties ||
 * [|Molecular formula] || C14H18N2O5 ||
 * [|Molar mass] || 294.3 g mol−1 ||
 * [|Density] || 1.347 g/cm3 ||
 * [|Melting point] || 246–247 °C ||
 * [|Boiling point] || decomposes ||
 * [|Solubility] in [|water] || sparingly soluble ||
 * [|Solubility] || slightly soluble in [|ethanol] ||
 * [|Acidity] (p//K//a) || 4.5-6.0 [|[2]] ||
 * ~ Hazards ||
 * [|NFPA 704] ||  ||





Aspartame has been found to be safe for human consumption by more than ninety countries worldwide, [|[49]][|[50]] with FDA officials describing aspartame as "one of the most thoroughly tested and studied food additives the agency has ever approved" and its safety as "clear cut", [|[51]] but has been the subject of several controversies, hoaxes [|[3]] and health scares. [|[52]] Problems with safety tests were found following the initial approval by the [|U.S. Food and Drug Administration] (FDA) in 1974. Approval was rescinded the following year and after reviews and additional testing, final approval was granted in 1981. Allegations of [|conflicts of interest] marred the FDA's approval of aspartame; question the quality of the initial research supporting its safety; [|[53]][|[54]][|[55]] The U.S. [|Government Accountability Office] conducted reviews of the actions of involved officials in 1986 and the approval process in 1987; neither the allegations of conflict of interest nor problems in the final approval process were substantiated. [|[53]][|[56]] A widely circulated email hoax cited aspartame as the cause of numerous diseases. [|[57]] The Center for Disease Control investigated and was unable to find any [|epidemiological] associations. and postulate that numerous health risks may be associated with aspartame. [|[58]] The weight of existing scientific evidence indicates that aspartame is safe at current levels of consumption as a non-nutritive sweetener. [|[6]] Reviews conducted by regulatory agencies decades after aspartame was first approved have supported its continued availability. [|[59]]