Aspartame

{{Chembox new
| Name = Aspartame
| Reference =<ref>''Merck Index'', 11th Edition, '''861'''.</ref>
| ImageFile = aspartame structure.png

| ImageName = Aspartame
| ImageFile1 = Aspartame-3D-balls.png

| ImageName1 = Ball-and-stick model of aspartame
| IUPACName = ''N''-(L-α-Aspartyl)-L-phenylalanine, 1-methyl ester
| OtherNames = [[NutraSweet]] [[Canderel]] [[Equal (sweetener)|Equal]]
| Section1 = {{Chembox Identifiers
| CASNo = 22839-47-0
| SMILES = [NH3+] [C@@H](CC([O-])=O)C(N[C@@H] (CC1=CC=CC=C1)C(OC)=O)=O
}}
| Section2 = {{Chembox Properties
| Formula = C14H18N2O5
| MolarMass = 294.301 g/mol
| MeltingPt = 246-247 °C
| BoilingPt = decomposes
}}
| Section7 = {{Chembox Hazards
| NFPA-H = 1
| NFPA-F = 1
| NFPA-R = 0
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}}

'''Aspartame''' (or '''APM''') ({{pronEng|ˈæspɚteɪm}} or {{IPA|/əˈspɑrteɪm/}}) is the name for an artificial, non-[[saccharide]] [[sweetener]], ''aspartyl-phenylalanine-1-methyl ester''; i.e., the methyl [[ester]] of the [[dipeptide]] of the [[amino acid]]s [[aspartic acid]] and [[phenylalanine]].

This sweetener is marketed under a number of trademark names, including [[Equal (sweetener)|Equal]], [[NutraSweet]], and [[Canderel]], and is an ingredient of approximately 6,000 consumer foods and beverages sold worldwide. It is commonly used in diet [[soft drink]]s, and is often provided as a table condiment. It is also used in some brands of chewable [[vitamin]] supplements and common in many sugar-free chewing gums. However, aspartame is not always suitable for [[baking]] because it often [[chemical decomposition|breaks down]] when heated and loses much of its sweetness. In the European Union, it is also known under the [[E number]] (additive code) '''E951'''. Aspartame is also one of the sugar substitutes used by people with [[diabetes mellitus|diabetes]].

Aspartame is a subject of public controversy due to possible health risks. See [[Aspartame controversy]]. It has lost market share in recent years to [[sucralose]] (Splenda, Altern, or [[E number]] E955).<ref>{{cite news | author = John Schmeltzer | url =
http://www.chicagotribune.com/business/chi-0412020391dec02,1,2234783.story?coll=chi-business-hed | title = Equal fights to get even as Splenda looks sweet] | publisher = [[Chicago Tribune]] |date=2 December 2004 | accessdate = 2007-07-04 | format = subscription required}}</ref>

==Chemistry==
Aspartame is the [[methyl]] [[ester]] of the [[dipeptide]] of the natural [[amino acid]]s L-[[aspartic acid]] and L-[[phenylalanine]]. Under strongly [[acid]]ic or [[Base (chemistry)|alkaline]] conditions, aspartame first generates [[methanol]] by [[hydrolysis]]. Under more severe conditions, the [[peptide bond]]s are also [[hydrolyzed]], resulting in the free amino acids. It is a nonpolar molecule.<ref>
{{cite journal
| author = David J. Ager, David P. Pantaleone, Scott A. Henderson, Alan R. Katritzky, Indra Prakash, D. Eric Walters
| title = Commercial, Synthetic Nonnutritive Sweeteners
| journal = [[Angewandte Chemie International Edition]]
| year = 1998
| volume = 37
| issue = 13-24
| pages = 1802-1817
| doi = 10.1002/(SICI)1521-3773(19980803)37:13/14%3C1802::AID-ANIE1802%3E3.0.CO;2-9}}</ref>

==Properties and use==
Aspartame is an attractive sweetener because it is 180 times as sweet as [[sugar]] in typical [[concentration]]s, without the high energy value of [[sugar]]. While aspartame, like other [[peptide]]s, has a caloric value of 4 kilocalories (17 kilojoules) per [[gram]], the quantity of aspartame needed to produce a sweet taste is so small that its caloric contribution is negligible, which makes it a popular sweetener for those trying to avoid calories from sugar. The taste of aspartame is not identical to that of sugar: the sweetness of aspartame has a slower onset and longer duration than that of sugar, and some consumers find it unappealing. Blends of aspartame with [[acesulfame potassium]] — usually listed in ingredients as [[acesulfame potassium|acesulfame K]] — are alleged to taste more like sugar, and to be sweeter than either substitute used alone.

Like many other [[peptide]]s, aspartame may [[hydrolise]] (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 [[fat]]s 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 [[soda fountain|fountain beverages]], aspartame is sometimes blended with a more stable sweetener, such as [[saccharin]].<ref>{{cite web | url = http://www.thecoca-colacompany.com/mail/goodanswer/us_fountain_beverages.pdf | publisher = [[The Coca-Cola Company]] | title = Fountain Beverages in the US |date=May 2007}}</ref>

In products such as [[powder]]ed beverages, the [[amine]] in aspartame can undergo a [[Maillard reaction]] with the [[aldehyde]] groups present in certain [[aroma compound]]s. The ensuing loss of both flavor and sweetness can be prevented by protecting the aldehyde as an [[acetal]].

==Discovery and approval==
Aspartame was discovered in [[1965]] by James M. Schlatter, a chemist working for [[Searle (company)|G.D. Searle & Company]]. Schlatter had [[Chemical synthesis|synthesized]] aspartame in the course of producing an anti-[[ulcer]] drug candidate. He discovered its sweet taste serendipitously when he licked his finger, which had accidentally become contaminated with aspartame.<ref>[http://science.enotes.com/how-products-encyclopedia/aspartame How Products Are Made: Aspartame]</ref>

Following initial safety testing, there was debate as to whether these tests had indicated that aspartame may cause cancer in rats{{Fact|date=October 2007}}; as a result, the [[Food and Drug Administration|U.S. Food and Drug Administration]] (FDA) did not approve its use as a food additive in the [[United States]] for many years{{Fact|date=October 2007}}. 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]]{{Fact|date=October 2007}}. The PBOI concluded that aspartame does not cause [[brain]] damage, but it recommended against approving aspartame at that time, citing unanswered questions about [[cancer]] in laboratory rats{{Fact|date=October 2007}}. At that point in time, there was no requirement in place in FDA regulations to include brain research in the approval process, only cancer research. Searle's [[Chief Operating Officer]], [[Donald Rumsfeld]], reapplied for FDA certification immediately after U.S. President [[Ronald Reagan]] took office.<ref>{{cite web
|url=http://www.salon.com/mwt/feature/2007/10/08/cancer_q_a/print.html
|title=Life will kill you: Can diet soda, cellphones and makeup give you cancer? The author of "The Secret History of the War on Cancer" discusses the health risks of, well, living.
|first=Katharine
|last=Mieszkowski
|publisher=Salon
|date=2007-10-08}}</ref> In 1981, Reagan appointed Arthur Hull Hayes as FDA commissioner. Citing data from a Japanese study that had not been available to the members of the PBOI{{Fact|date=October 2007}}, Hayes approved aspartame for use in dry goods.<ref name="http://archive.gao.gov/d28t5/133460.pdf">[http://archive.gao.gov/d28t5/133460.pdf http://archive.gao.gov/d28t5/133460.pdf]</ref> In 1983 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.

In 1985, [[Monsanto]] bought G.D. Searle — and the aspartame business became a separate Monsanto subsidiary, the [[NutraSweet|NutraSweet Company]]. On [[May 25]] [[2000]] Monsanto sold it to J.W. Childs Equity Partners II L.P.<ref name="http://www.findarticles.com/p/articles/mi_m0EUY/is_22_6/ai_62920821">[http://www.findarticles.com/p/articles/mi_m0EUY/is_22_6/ai_62920821 http://www.findarticles.com/p/articles/mi_m0EUY/is_22_6/ai_62920821]</ref> The U.S. [[patent]] on aspartame expired in 1992. Since then the company has faced hot competition in market for aspartame from other manufacturers, including [[Ajinomoto]], Merisant and the Holland Sweetener Company, which stopped making the chemical in late 2006 because "global aspartame markets are facing structural oversupply, which has caused worldwide strong price erosion over the last 5 years" making the business "persistently unprofitable”.<ref name="http://www.marketwire.com/mw/release_html_b1?release_id=115447">[http://www.marketwire.com/mw/release_html_b1?release_id=115447 http://www.marketwire.com/mw/release html b1?release id=115447]</ref>

Several European Union states 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 Adequate Daily Intake was appropriate, after reviewing yet another set of studies.<ref>http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620765743.htm</ref>

It has also been investigated and approved by the Joint Expert Committee on Food Additives of the [[United Nations Food and Agricultural Organization]] and [[World Health Organization]].<ref>http://www.dorway.com/offasprt.html</ref>

==Metabolism==
Upon ingestion, aspartame breaks down into several residual chemicals, including [[aspartic acid]], [[phenylalanine]], [[methanol]], and further breakdown products including [[formaldehyde]].<ref>{{cite journal | author = C. Trocho, R. Pardo, I. Rafecas, J. Virgili, X. Remesar, J. A. Fernandez-Lopez and M. Alemany | title = Formaldehyde derived from dietary aspartame binds to tissue components in vivo | year = 1998 | journal = [[Life Sciences]] | volume = 63 | issue = 5 | pages = 337-349 | doi = 10.1016/S0024-3205(98)00282-3}}</ref> and [[formic acid]]. There is some controversy surrounding the rate of breakdown into these various products and the effects that they have on those that consume aspartame-sweetened foods. (See [[Aspartame controversy]])

The naturally-occurring [[essential amino acid]] [[phenylalanine]] is a health hazard to those born with [[phenylketonuria]] (PKU), a rare inherited disease that prevents phenylalanine from being properly metabolized. Since individuals with PKU must consider aspartame as an additional source of phenylalanine, foods containing aspartame sold in the [[United States]] must state "Phenylketonurics: Contains Phenylalanine" on their product labels.

In the [[United Kingdom|UK]], foods that contain aspartame must list the chemical among the product's ingredients and carry the warning 'Contains a source of phenylalanine' – this is usually at the foot of the list of ingredients. Manufacturers should print '"with sweetener(s)" on the label close to the main product name' on foods that contain 'sweeteners such as aspartame' or "with sugar and sweetener(s)" on 'foods that contain both sugar and sweetener'. 'This labelling is a legal requirement,'says the country's Food Standards Agency.<ref>[http://www.food.gov.uk/safereating/chemsafe/additivesbranch/sweeteners/55174#h_5/ ''Aspartame - Labelling'', UK Food Standards Agency, 18 July 2006].Retrieved on [[2007-07-22]].</ref>

==Health Concerns==
{{main|Aspartame controversy}}

Aspartame has been the subject of controversy regarding its safety and the circumstances of its approval by the American FDA and European FSA. Some studies have also recommended further investigation into possible connections between aspartame and negative effects such as headaches, [[brain tumor]]s, [[lesion|brain lesions]], and [[lymphoma]].<ref>Olney, J.W., N.B. Farber, E. Spitznagel, L.N. Robins, 1996. "Increasing Brain Tumor Rates: Is There a Link to Aspartame?" Journal of Neuropathology and Experimental Neurology, Volume 55, pages 1115-1123.</ref><ref name = soffritti>{{cite journal | author = Morando Soffritti, Fiorella Belpoggi, Davide Degli Esposti, Luca Lambertini, Eva Tibaldi, and Anna Rigano | title = First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats | journal = [[Environmental Health Perspectives]] | volume = 114 | issue = 3 | pages = 379-385 | year = 2006 | doi = 10.1289/ehp.8711 | url = http://www.ramazzini.it/fondazione/pdfUpload/Environ%20Health%20Perspect%20114%20379-385_2006.pdf | format = reprint}}</ref><ref>Roberts, H.J., "Does Aspartame Cause Human Brain Cancer," Journal of Advancement in Medicine, Volume 4(4):231-241, 1991.</ref> These findings, combined with possible [[Conflict of interest|conflicts of interest]] involving CEO [[Donald Rumsfeld]] in the approval process, have engendered vocal activism regarding the possible risks of aspartame.<ref>GAO 1986. "Six Former HHS Employees' Involvement in Aspartame's Approval," United States General Accounting Office, GAO/HRD-86-109BR, July 1986. http://archive.gao.gov/d4t4/130780.pdf</ref><ref>Gordon, Gregory, United Press International Investigation, "NutraSweet: Questions Swirl," 1987. http://www.dorway.com/upipaper.txt</ref>

==References==
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==Further reading==
* {{cite journal | title = Lifespan Exposure to Low Doses of Aspartame Beginning During Prenatal Life Increases Cancer Effects in Rats | author = Morando Soffritti, Fiorella Belpoggi, Eva Tibaldi, Davide Degli Esposti, Michela Lauriola |date=13 June 2007 | doi = 10.1289/ehp.10271 | format = article in press}}

* side effects of the Aspartame [http://www.sweetpoison.com/aspartame-side-effects.html]

{{E number infobox 950-969}}

[[Category:Carboxylate esters]]
[[Category:Sweeteners]]

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