Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Aspartame: Difference between pages

{{Short description|Artificial non-saccharide sweetener}}

{{Redirect|E951|the road in Greece|European route E951}}

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| verifiedrevid = 477164885

| Name = Aspartame

| pronounce = {{IPAc-en|ˈ|æ|s|p|ər|t|eɪ|m}} or <br />{{IPAc-en|ə|ˈ|s|p|ɑr|t|eɪ|m}}

| Reference = <ref>{{cite book | veditors = Budavari S |title=The Merck Index |edition=11th |year=1989 |publisher=Merck & Co. |location=Rahway, NJ |isbn=978-0-911910-28-5 |chapter=861. Aspartame |page=[https://archive.org/details/merckindexency00buda/page/859 859] |chapter-url=https://archive.org/details/merckindexency00buda/page/859 }}</ref>

| ImageFile = Aspartame.svg

| ImageFile1 = Aspartame-from-hydrate-xtal-2000-3D-balls.png

| ImageName1 = Ball-and-stick model of aspartame

| ImageFile2 = Aspartame sample.jpg

| IUPACName = Methyl <small>L</small>-α-aspartyl-<small>L</small>-phenylalaninate

| SystematicName =(3S)-3-amino-4-「[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino」-4-oxobutanoic acid

| OtherNames = {{Unbulleted list|''N''-(<small>L</small>-α-Aspartyl)-<small>L</small>-phenylalanine,<br />1-methyl ester}}

| Section1 = {{Chembox Identifiers

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo = 22839-47-0

| Beilstein = 2223850

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 2877

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 171679

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 118630

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00168

| PubChem = 134601

| EC_number = 245-261-3

| Section2 = {{Chembox Properties

| C=14 | H=18 | N=2 | O=5

| MeltingPtC = 246.5

| MeltingPt_ref = <ref>{{cite book |ref=Haynes| editor= Haynes WM | date = 2016| title = [[CRC Handbook of Chemistry and Physics]] | edition = 97th | publisher = [[CRC Press]] | isbn = 978-1498754293|page=3.30}}</ref>

| BoilingPt = Decomposes

| Density = 1.347{{nbsp}}g/cm³

| Solubility = Sparingly soluble

| SolubleOther = Slightly soluble in [[ethanol]]

| pKa = 4.5–6.0<ref>{{Cite book| vauthors = Rowe RC | chapter = Aspartame | title = Handbook of Pharmaceutical Excipients | year = 2009 | pages = 11–12 | publisher = Pharmaceutical Press | isbn = 978-1-58212-058-4}}</ref>

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| Section7 = {{Chembox Hazards

| Hazards_ref =<ref name="pubch">{{cite web|title=Aspartame|url=https://pubchem.ncbi.nlm.nih.gov/compound/134601|publisher=PubChem, National Library of Medicine, US National Institutes of Health|date=27 May 2023|access-date=2 June 2023|archive-date=17 August 2017|archive-url=https://web.archive.org/web/20170817163923/https://pubchem.ncbi.nlm.nih.gov/compound/134601|url-status=live}}</ref>

'''Aspartame''' is an [[chemical synthesis|artificial]] non-[[saccharide]] sweetener 200&nbsp;times [[sweeter]] than [[sucrose]] and is commonly used as a [[sugar substitute]] in foods and beverages.<ref name="pubch" /> It is a methyl [[ester]] of the [[aspartic acid]]/[[phenylalanine]] [[dipeptide]] with [[brand name]]s NutraSweet, Equal, and Canderel.<ref name=pubch/> Aspartame was approved by the US [[Food and Drug Administration]] (FDA) in 1974, and then again in 1981, after approval was revoked in 1980.<ref name=pubch/><ref name="fda-timeline" /><ref name=EFSAExperts/>

<!-- Health effects and safety -->

Aspartame is one of the most studied food additives in the human food supply.<ref name="fda7-14">{{cite web |date=14 July 2023 |title=Aspartame and Other Sweeteners in Food |url=https://www.fda.gov/food/food-additives-petitions/aspartame-and-other-sweeteners-food |access-date=14 July 2023 |publisher=US Food and Drug Administration |archive-date=29 June 2023 |archive-url=https://web.archive.org/web/20230629234038/https://www.fda.gov/food/food-additives-petitions/aspartame-and-other-sweeteners-food |url-status=live }}</ref><ref name="Mitchell 2006 943">{{Cite book |title=Sweeteners and sugar alternatives in food technology |author=Kay O'Donnel |editor=Mitchell H |publisher=Wiley-Blackwell |year=2012 |place=Oxford, UK |page=126}}</ref> Reviews by over 100 governmental regulatory bodies found the ingredient safe for consumption at the normal [[acceptable daily intake]] limit.<ref name=EFSAExperts/><ref name="fda7-14" /><ref name=cfr/><ref name="Magnuson">{{cite journal | vauthors = Magnuson BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW, Spencer PS, Waddell WJ, Walker R, Williams GM | title = Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies | journal = Critical Reviews in Toxicology | volume = 37 | issue = 8 | pages = 629–727 | year = 2007 | pmid = 17828671 | doi = 10.1080/10408440701516184 | s2cid = 7316097 }}</ref><ref name=FSANZ2>Food Standards Australia New Zealand: {{cite web |title=Food Standards Australia New Zealand: Aspartame – what it is and why it's used in our food |access-date=9 December 2008|url= http://www.nzfsa.govt.nz/consumers/chemicals-nutrients-additives-and-toxins/aspartame/|archive-url= https://web.archive.org/web/20081216093929/http://www.nzfsa.govt.nz/consumers/chemicals-nutrients-additives-and-toxins/aspartame/|archive-date= 16 December 2008}}</ref><ref name=Butchko>{{cite journal | vauthors = Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL, de Sonneville LM, Geha RS, Hertelendy Z, Koestner A, Leon AS, Liepa GU, McMartin KE, Mendenhall CL, Munro IC, Novotny EJ, Renwick AG, Schiffman SS, Schomer DL, Shaywitz BA, Spiers PA, Tephly TR, Thomas JA, Trefz FK | title = Aspartame: review of safety | journal = Regulatory Toxicology and Pharmacology | volume = 35 | issue = 2 Pt 2 | pages = S1–93 | date = April 2002 | pmid = 12180494 | doi = 10.1006/rtph.2002.1542 }}</ref><ref>{{cite report | vauthors=Rios-Leyvraz M, Montez J | title=Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis | publisher=[[World Health Organization]] (WHO) | date=12 April 2022 | url=https://www.who.int/publications/i/item/9789240046429 | isbn=978-92-4-004642-9 | hdl=10665/353064 | hdl-access=free }}</ref>

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==Uses==

Aspartame is about 180 to 200&nbsp;times sweeter than [[sucrose]] (table sugar). Due to this property, even though aspartame produces roughly the same energy per gram when metabolized as sucrose does, {{cvt|4|kcal|kJ}}, the quantity of aspartame needed to produce the same sweetness is so small that its caloric contribution is negligible.<ref name=Magnuson/> The sweetness of aspartame lasts longer than that of sucrose, so it is often blended with other artificial sweeteners such as [[acesulfame potassium]] to produce an overall taste more like that of sugar.<ref>{{cite web|url=http://www.foodproductdesign.com/articles/2007/05/new-products-weigh-in.aspx |title=New Products Weigh In |publisher=foodproductdesign.com |access-date=19 June 2010 |archive-date=11 July 2011 |archive-url=https://web.archive.org/web/20110711015222/http://www.foodproductdesign.com/articles/2007/05/new-products-weigh-in.aspx |url-status=live }}</ref>

Like many other [[peptide]]s, 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&nbsp;4.3, where its [[half-life]] is nearly 300&nbsp;days. At pH&nbsp;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 [[syrup]]s for [[fountain beverage]]s, 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 |url-status=dead |archive-url=https://web.archive.org/web/20090320175404/http://www.thecoca-colacompany.com/mail/goodanswer/us_fountain_beverages.pdf |archive-date=20 March 2009 }}</ref>

[[Descriptive statistics|Descriptive analyses]] of solutions containing aspartame report a sweet aftertaste as well as bitter and off-flavor aftertastes.<ref>{{cite journal | vauthors = Nahon DF, Roozen JP, de Graaf C | title = Sensory evaluation of mixtures of maltitol or aspartame, sucrose and an orange aroma | journal = Chemical Senses | volume = 23 | issue = 1 | pages = 59–66 | date = February 1998 | pmid = 9530970 | doi = 10.1093/chemse/23.1.59 | doi-access = free }}</ref>

==Acceptable levels of consumption==

The [[acceptable daily intake]] (ADI) value for food additives, including aspartame, is defined as the "amount of a food additive, expressed on a body weight basis, that can be ingested daily over a lifetime without appreciable health risk".<ref name=WHO1987>{{Cite journal | last = WHO | title = Principles for the safety assessment of food additives and contaminants in food | journal = Environmental Health Criteria 70 | year = 1987 | url = http://www.inchem.org/documents/ehc/ehc/ehc70.htm | url-status = live | archive-url = https://web.archive.org/web/20150430035319/http://www.inchem.org/documents/ehc/ehc/ehc70.htm | archive-date = 30 April 2015 }}</ref> The [[Joint FAO/WHO Expert Committee on Food Additives]] (JECFA) and the [[European Commission]]'s [[Scientific Committee on Food]] (later becoming [[European Food Safety Authority|EFSA]]) have determined this value is 40&nbsp;mg/kg of body weight per day for aspartame,<ref name=efsa2013/><ref name=Renwick>{{cite journal | vauthors = Renwick AG | title = The intake of intense sweeteners – an update review | journal = Food Additives and Contaminants | volume = 23 | issue = 4 | pages = 327–338 | date = April 2006 | pmid = 16546879 | doi = 10.1080/02652030500442532 | s2cid = 27351427 | url = https://hal.archives-ouvertes.fr/hal-00577562/file/PEER_stage2_10.1080%252F02652030500442532.pdf | access-date = 22 April 2022 | archive-date = 23 August 2022 | archive-url = https://web.archive.org/web/20220823075508/https://hal.archives-ouvertes.fr/hal-00577562/file/PEER_stage2_10.1080%252F02652030500442532.pdf | url-status = live }}</ref> while the FDA has set its ADI for aspartame at 50&nbsp;mg/kg per day {{ndash}} an amount equated to consuming 75 packets of commercial aspartame sweetener per day to be within a safe upper limit.<ref name=fda7-14/>

The primary source for exposure to aspartame in the US is diet [[soft drink]]s, though it can be consumed in other products, such as pharmaceutical preparations, fruit drinks, and chewing gum among others in smaller quantities.<ref name=Magnuson/> A {{Convert|12|USoz|ml impoz|adj=on}} can of diet soda contains {{convert|0.18|g|oz}} of aspartame, and, for a {{convert|75|kg|lb|adj=on}} adult, it takes approximately 21&nbsp;cans of diet soda daily to consume the {{convert|3.7|g|oz}} of aspartame that would surpass the FDA's 50&nbsp;mg/kg of body weight ADI of aspartame from diet soda alone.<ref name=NCIFAQ>{{cite web | title = Aspartame and Cancer: Questions and Answers | publisher=[[National Cancer Institute]] | date = 12 September 2006 | url = http://www.cancer.gov/cancertopics/factsheet/AspartameQandA|archive-url=https://web.archive.org/web/20090212130028/http://cancer.gov/cancertopics/factsheet/AspartameQandA|archive-date=12 February 2009|access-date = 29 August 2011}}</ref><ref>{{cite web | title=Artificial Sweeteners and Cancer | website=NCI | date=29 August 2023 | url=https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet | access-date=17 June 2024 | archive-date=8 December 2015 | archive-url=https://web.archive.org/web/20151208135059/https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet | url-status=live }}</ref><ref>{{cite web | title=Aspartame and Cancer Risk | website=American Cancer Society | date=6 July 2023 | url=https://www.cancer.org/cancer/risk-prevention/chemicals/aspartame.html | access-date=17 June 2024}}</ref>

Reviews have analyzed studies which have looked at the consumption of aspartame in countries worldwide, including the US, countries in Europe, and Australia, among others. These reviews have found that even the high levels of intake of aspartame, studied across multiple countries and different methods of measuring aspartame consumption, are well below the ADI for safe consumption of aspartame.<ref name=EFSAExperts/><ref name=Magnuson/><ref name=Renwick/> Reviews have also found that populations that are believed to be especially high consumers of aspartame, such as children and diabetics, are below the ADI for safe consumption, even considering extreme worst-case scenario calculations of consumption.<ref name=EFSAExperts/><ref name=Magnuson/>

In a report released on 10 December 2013, the EFSA said that, after an extensive examination of evidence, it ruled out the "potential risk of aspartame causing damage to genes and inducing cancer" and deemed the amount found in diet sodas safe to consume.<ref>{{cite news|title=Aspartame in Soda is Safe: European Review|url=http://www.newsmaxhealth.com/Health-News/artificial-sweeteners-aspartame-food-safety-diet-soft-drinks/2013/12/10/id/541046|agency=Associated Press|access-date=16 December 2013|url-status=live|archive-url=https://web.archive.org/web/20131217041236/http://www.newsmaxhealth.com/Health-News/artificial-sweeteners-aspartame-food-safety-diet-soft-drinks/2013/12/10/id/541046|archive-date=17 December 2013}}</ref>

== Safety and health effects ==

{{See also|Aspartame controversy}}

The safety of aspartame has been studied since its discovery,<ref name="EFSAExperts">{{cite journal | author = EFSA National Experts | title = Report of the meetings on aspartame with national experts | journal = EFSA Supporting Publications | publisher = EFSA | date = May 2010 | volume = 7 | issue = 5 | doi = 10.2903/sp.efsa.2010.ZN-002 | url = https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/sp.efsa.2010.ZN-002 | access-date = 9 January 2011 | archive-date = 3 February 2021 | archive-url = https://web.archive.org/web/20210203195313/https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/sp.efsa.2010.ZN-002 | url-status = live }}</ref> and it is a rigorously tested food ingredient.<ref name="fda7-14" /><ref name="Mitchell 2006 94">{{Cite book |title=Sweeteners and sugar alternatives in food technology |vauthors=Mitchell H |publisher=Wiley-Blackwell |year=2006 |isbn=978-1-4051-3434-7 |place=Oxford, UK |page=94}}</ref> Aspartame has been deemed safe for human consumption by over 100 regulatory agencies in their respective countries, including the US [[Food and Drug Administration]] (FDA),<ref name="fda7-14" /><ref name="cfr">{{cite web|url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=172.804|title=CFR – Code of Federal Regulations, Title 21, Part 172: Food additives permitted for direct addition to food for human consumption. Subpart I – Multipurpose Additives; Sec. 172.804 Aspartame|date=1 April 2018|publisher=US Food and Drug Administration|access-date=22 August 2019|archive-date=20 September 2018|archive-url=https://web.archive.org/web/20180920072605/https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=172.804|url-status=live}}</ref> UK [[Food Standards Agency]],<ref>{{cite web | title = Aspartame | publisher=UK FSA | date = 17 June 2008 |url = https://www.food.gov.uk/science/additives/aspartame/ | access-date = 23 September 2010| archive-url= https://web.archive.org/web/20101007120121/http://www.food.gov.uk/safereating/chemsafe/additivesbranch/sweeteners/55174| archive-date= 7 October 2010 | url-status= live}}</ref> the [[European Food Safety Authority]] (EFSA),<ref name="efsa2013">{{cite journal |author1=EFSA Panel On Food Additives And Nutrient Sources Added To Food |title=Scientific Opinion on the re-evaluation of aspartame (E 951) as a food additive |journal=EFSA Journal |date=10 December 2013 |volume=11 |issue=12 |page=3496 |doi=10.2903/j.efsa.2013.3496 |url=https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2013.3496 |access-date=30 June 2023 |archive-date=30 June 2023 |archive-url=https://web.archive.org/web/20230630044532/https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2013.3496 |url-status=live }}</ref><ref>{{cite web|title=Aspartame |publisher=EFSA |url=https://www.efsa.europa.eu/en/topics/topic/aspartame |access-date=23 September 2010 |url-status=dead |archive-url=https://web.archive.org/web/20110310160411/https://www.efsa.europa.eu/en/topics/topic/aspartame |archive-date=10 March 2011 }}</ref> [[Health Canada]],<ref>{{cite web | title = Aspartame | publisher=Health Canada | url = http://www.hc-sc.gc.ca/fn-an/securit/addit/sweeten-edulcor/aspartame-eng.php | access-date = 23 September 2010| archive-url= https://web.archive.org/web/20100922181732/http://www.hc-sc.gc.ca/fn-an/securit/addit/sweeten-edulcor/aspartame-eng.php| archive-date= 22 September 2010 | url-status= live| date=5 November 2002 }}</ref> and [[Food Standards Australia New Zealand]].<ref name="FSANZ2" />

===Metabolism and body weight===

{{as of|2017|post=,}} reviews of [[clinical trial]]s showed that using aspartame (or other non-nutritive sweeteners) in place of sugar reduces calorie intake and body weight in adults and children.<ref name=Az2017>{{cite journal | vauthors = Azad MB, Abou-Setta AM, Chauhan BF, Rabbani R, Lys J, Copstein L, Mann A, Jeyaraman MM, Reid AE, Fiander M, MacKay DS, McGavock J, Wicklow B, Zarychanski R | title = Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies | journal = CMAJ | volume = 189 | issue = 28 | pages = E929–E939 | date = July 2017 | pmid = 28716847 | pmc = 5515645 | doi = 10.1503/cmaj.161390 }}</ref><ref name="Rogers2016">{{cite journal | vauthors = Rogers PJ, Hogenkamp PS, de Graaf C, Higgs S, Lluch A, Ness AR, Penfold C, Perry R, Putz P, Yeomans MR, Mela DJ | title = Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies | journal = International Journal of Obesity | volume = 40 | issue = 3 | pages = 381–394 | date = March 2016 | pmid = 26365102 | pmc = 4786736 | doi = 10.1038/ijo.2015.177 }}</ref><ref name="Miller2014">{{cite journal | vauthors = Miller PE, Perez V | title = Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies | journal = The American Journal of Clinical Nutrition | volume = 100 | issue = 3 | pages = 765–777 | date = September 2014 | pmid = 24944060 | pmc = 4135487 | doi = 10.3945/ajcn.113.082826 }}</ref> A 2017 review of [[metabolism|metabolic effects]] by consuming aspartame found that it did not affect [[blood glucose]], [[insulin]], [[total cholesterol]], [[triglyceride]]s, calorie intake, or body weight. While [[high-density lipoprotein]] levels were higher compared to control, they were lower compared to sucrose.<ref name=San2017>{{cite journal | vauthors = Santos NC, de Araujo LM, De Luca Canto G, Guerra EN, Coelho MS, Borin MF | title = Metabolic effects of aspartame in adulthood: A systematic review and meta-analysis of randomized clinical trials | journal = Critical Reviews in Food Science and Nutrition | volume = 58 | issue = 12 | pages = 2068–2081 | date = April 2017 | pmid = 28394643 | doi = 10.1080/10408398.2017.1304358 | s2cid = 43863824 }}</ref>

In 2023, the [[World Health Organization]] recommended against the use of common non-sugar sweeteners (NSS), including aspartame, to control body weight or lower the risk of [[non-communicable disease]]s, stating: "The recommendation is based on the findings of a systematic review of the available evidence which suggests that use of NSS does not confer any long-term benefit in reducing body fat in adults or children. Results of the review also suggest that there may be potential undesirable effects from long-term use of NSS, such as an increased risk of type 2 diabetes, cardiovascular diseases, and mortality in adults."<ref>{{cite press release | title = WHO advises not to use non-sugar sweeteners for weight control in newly released guideline | date = 15 May 2023 | publisher = [[World Health Organization]] (WHO) | url = https://www.who.int/news/item/15-05-2023-who-advises-not-to-use-non-sugar-sweeteners-for-weight-control-in-newly-released-guideline | access-date = 30 June 2023 | archive-date = 30 June 2023 | archive-url = https://web.archive.org/web/20230630105256/https://www.who.int/news/item/15-05-2023-who-advises-not-to-use-non-sugar-sweeteners-for-weight-control-in-newly-released-guideline | url-status = live }}</ref><ref>{{cite tech report | title=Use of non-sugar sweeteners: WHO guideline | publisher=[[World Health Organization]] (WHO) | location=Geneva | date=15 May 2023 | url=https://www.who.int/publications/i/item/9789240073616 | isbn=978-92-4-007361-6 | hdl=10665/367660 | hdl-access=free }}</ref>

===Phenylalanine===

High levels of the naturally occurring [[essential amino acid]] [[phenylalanine]] are a health hazard to those born with [[phenylketonuria]] (PKU), a rare inherited disease that prevents phenylalanine from being properly metabolized.<ref name="phenyl">{{cite web |title=Phenylalanine |url=https://pubchem.ncbi.nlm.nih.gov/compound/Phenylalanine |publisher=PubChem, National Library of Medicine, US National Institutes of Health |access-date=2 June 2023 |date=27 May 2023 |archive-date=22 April 2023 |archive-url=https://web.archive.org/web/20230422081636/https://pubchem.ncbi.nlm.nih.gov/compound/Phenylalanine |url-status=live }}</ref> Because aspartame contains phenylalanine, foods containing aspartame sold in the US must state: "Phenylketonurics: Contains Phenylalanine" on product labels.<ref name=cfr/>

In the UK, foods that contain aspartame are required by the [[Food Standards Agency]] to list the substance as an ingredient, with the warning "Contains a source of phenylalanine". Manufacturers are also required to 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".<ref name="FSA2015">{{cite web |url=https://www.food.gov.uk/science/additives/aspartame |title=Aspartame |author=<!--Not stated--> |date=19 March 2015 |website=UK Food Standards Agency |access-date=28 June 2017 |url-status=live |archive-url=https://web.archive.org/web/20170711201731/https://www.food.gov.uk/science/additives/aspartame |archive-date=11 July 2017 }}</ref>

In Canada, foods that contain aspartame are required to list aspartame among the ingredients, include the amount of aspartame per serving, and state that the product contains phenylalanine.<ref name="hc2018">{{cite web |title=Mandatory Labelling of Sweeteners |url=http://www.inspection.gc.ca/food/requirements-and-guidance/labelling/industry/sweeteners/eng/1387749708758/1387750396304?chap=2 |publisher=Canadian Food Inspection Agency, Health Canada |access-date=23 August 2019 |date=11 May 2018 |archive-date=6 July 2023 |archive-url=https://web.archive.org/web/20230706042715/https://inspection.canada.ca/food-labels/labelling/industry/sweeteners/eng/1387749708758/1387750396304?chap=2 |url-status=live }}</ref>

Phenylalanine is one of the [[essential amino acid]]s and is required for normal growth and maintenance of life.<ref name=phenyl/> Concerns about the safety of phenylalanine from aspartame for those without phenylketonuria center largely on hypothetical changes in [[neurotransmitter]] levels as well as ratios of neurotransmitters to each other in the blood and brain that could lead to neurological symptoms. Reviews of the literature have found no consistent findings to support such concerns,<ref name=EFSAExperts/><ref name=Butchko/> and, while high doses of aspartame consumption may have some biochemical effects, these effects are not seen in toxicity studies to suggest aspartame can adversely affect neuronal function.<ref name=phenyl/> As with methanol and aspartic acid, common foods in the typical diet, such as milk, meat, and fruits, will lead to ingestion of significantly higher amounts of phenylalanine than would be expected from aspartame consumption.<ref name=Butchko/>

===Cancer===

{{As of|2023}}, regulatory agencies, including the FDA<ref name="fda-timeline">{{cite web|title=Timeline of Selected FDA Activities and Significant Events Addressing Aspartame|publisher=US Food and Drug Administration|url=https://www.fda.gov/food/food-additives-petitions/timeline-selected-fda-activities-and-significant-events-addressing-aspartame|access-date=1 July 2023|date=30 May 2023|archive-date=1 July 2023|archive-url=https://web.archive.org/web/20230701215649/https://www.fda.gov/food/food-additives-petitions/timeline-selected-fda-activities-and-significant-events-addressing-aspartame|url-status=live}}</ref> and EFSA,<ref name=efsa2013/> and the US [[National Cancer Institute]], have concluded that consuming aspartame is safe in amounts within acceptable daily intake levels and does not cause cancer.<ref name="nci">{{cite web |title=Artificial sweeteners and cancer |url=https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet |publisher=National Cancer Institute, US National Institutes of Health |access-date=1 July 2023 |date=12 January 2023 |archive-date=8 December 2015 |archive-url=https://web.archive.org/web/20151208135059/https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet |url-status=live }}</ref> These conclusions are based on various sources of evidence,<ref name=fda-timeline/> such as reviews and [[epidemiology|epidemiological]] studies finding no association between aspartame and cancer.<ref>{{cite journal | vauthors = Marinovich M, Galli CL, Bosetti C, Gallus S, La Vecchia C | title = Aspartame, low-calorie sweeteners and disease: regulatory safety and epidemiological issues | journal = Food and Chemical Toxicology | volume = 60 | pages = 109–115 | date = October 2013 | pmid = 23891579 | doi = 10.1016/j.fct.2013.07.040 }}</ref><ref>{{cite journal | vauthors = Kirkland D, Gatehouse D | title = Aspartame: A review of genotoxicity data | journal = Food and Chemical Toxicology | volume = 84 | pages = 161–168 | date = October 2015 | pmid = 26321723 | doi = 10.1016/j.fct.2015.08.021 | doi-access = free }}</ref><ref>{{Cite journal |last1=Haighton |first1=Lois |last2=Roberts |first2=Ashley |last3=Jonaitis |first3=Tomas |last4=Lynch |first4=Barry |date=1 April 2019 |title=Evaluation of aspartame cancer epidemiology studies based on quality appraisal criteria |journal=Regulatory Toxicology and Pharmacology |language=en |volume=103 |pages=352–362 |doi=10.1016/j.yrtph.2019.01.033 |pmid=30716379 |s2cid=73442105 |issn=0273-2300 |doi-access=free }}</ref>

In July 2023, scientists for the [[International Agency for Research on Cancer]] (IARC) concluded that there was "limited evidence" for aspartame causing cancer in humans, classifying the sweetener as [[IARC group 2B|Group 2B]] (possibly carcinogenic).<ref>{{cite journal |url=https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00341-8/fulltext |title=Carcinogenicity of aspartame, methyleugenol, and isoeugenol |vauthors=Riboli E, Beland FA, Lachenmeier DW, Marques MM, Phillips DH, Schernhammer E, Afghan A, Assunção R, Caderni G, Corton JC, de Aragão Umbuzeiro G, de Jong D, Deschasaux-Tanguy M, Hodge A, Ishihara J, Levy DD, Mandrioli D, McCullough ML, McNaughton SA, Morita T, Nugent AP, Ogawa K, Pandiri AR, Sergi CM, Touvier M, Zhang L, Benbrahim-Tallaa L, Chittiboyina S, Cuomo D, DeBono NL, Debras C, de Conti A, El Ghissassi F, Fontvieille E, Harewood R, Kaldor J, Mattock H, Pasqual E, Rigutto G, Simba H, Suonio E, Viegas S, Wedekind R, Schubauer-Berigan MK, Madia F |journal=The Lancet Oncology |volume=24 |issue=8 |date=August 2023 |pages=848–850 |doi=10.1016/S1470-2045(23)00341-8 |pmid=37454664 |s2cid=259894482 |hdl=2158/1320996 |hdl-access=free |access-date=14 July 2023 |archive-date=14 July 2023 |archive-url=https://web.archive.org/web/20230714071015/https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00341-8/fulltext |url-status=live }}</ref><ref name="who7-13">{{cite web |title=Aspartame hazard and risk assessment results released (news release) |url=https://www.who.int/news/item/14-07-2023-aspartame-hazard-and-risk-assessment-results-released |publisher=World Health Organization |access-date=14 July 2023 |date=13 July 2023 |archive-date=13 July 2023 |archive-url=https://web.archive.org/web/20230713230948/https://www.who.int/news/item/14-07-2023-aspartame-hazard-and-risk-assessment-results-released |url-status=live }}</ref><ref>{{cite web | title=Aspartame hazard and risk assessment results released | website=International Agency for Research on Cancer | url=https://www.iarc.who.int/featured-news/aspartame-hazard-and-risk-assessment-results-released | access-date=17 June 2024}}</ref> The lead investigator of the IARC report stated that the classification "shouldn't really be taken as a direct statement that indicates that there is a known cancer hazard from consuming aspartame. This is really more of a call to the research community to try to better clarify and understand the carcinogenic hazard that may or may not be posed by aspartame consumption."<ref name="naddaf">{{cite journal |last1=Naddaf |first1=Miryam |title=Aspartame is a possible carcinogen: the science behind the decision |journal=Nature |date=14 July 2023 |doi=10.1038/d41586-023-02306-0 |pmid=37452160 |s2cid=259904544 |url=https://www.nature.com/articles/d41586-023-02306-0 |access-date=14 July 2023 |archive-date=30 July 2023 |archive-url=https://web.archive.org/web/20230730220902/https://www.nature.com/articles/d41586-023-02306-0 |url-status=live }}</ref>

The [[Joint FAO/WHO Expert Committee on Food Additives]] (JECFA) added that the limited cancer assessment indicated no reason to change the recommended acceptable daily intake level of 40 mg per kg of body weight per day, reaffirming the safety of consuming aspartame within this limit.<ref name=who7-13/>

The FDA responded to the report by stating: {{blockquote|Aspartame being labeled by IARC as "possibly carcinogenic to humans" does not mean that aspartame is actually linked to cancer. The FDA disagrees with IARC's conclusion that these studies support classifying aspartame as a possible carcinogen to humans. FDA scientists reviewed the scientific information included in IARC's review in 2021 when it was first made available and identified significant shortcomings in the studies on which IARC relied.<ref name=fda7-14/>}}

=== Neurotoxicity symptoms ===

Reviews found no evidence that low doses of aspartame would plausibly lead to neurotoxic effects.<ref name=EFSAExperts/><ref name=Magnuson/><ref name=Butchko/> A review of studies on children did not show any significant findings for safety concerns with regard to neuropsychiatric conditions such as [[panic attack]]s, mood changes, [[hallucination]]s, [[attention deficit hyperactivity disorder]] (ADHD), or seizures by consuming aspartame.<ref name="PediatricsReview">{{cite journal |vauthors= |date=February 1997 |title='Inactive' ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs |journal=Pediatrics |volume=99 |issue=2 |pages=268–278 |doi=10.1542/peds.99.2.268 |pmid=9024461 |doi-access=free}}</ref>

===Headaches===

Reviews have found little evidence to indicate that aspartame induces headaches, although certain subsets of consumers may be sensitive to it.<ref name=pubch/><ref name=EFSAExperts/><ref>{{cite journal | vauthors = Sun-Edelstein C, Mauskop A | title = Foods and supplements in the management of migraine headaches | journal = The Clinical Journal of Pain | volume = 25 | issue = 5 | pages = 446–452 | date = June 2009 | pmid = 19454881 | doi = 10.1097/AJP.0b013e31819a6f65 | s2cid = 3042635 | citeseerx = 10.1.1.530.1223 }}</ref>

===Water quality===

Aspartame passes through [[wastewater treatment plant]]s mainly unchanged.<ref name="nature-2018-Removal-artificial-sweeteners">{{cite journal | vauthors = Li S, Geng J, Wu G, Gao X, Fu Y, Ren H |title=Removal of artificial sweeteners and their effects on microbial communities in sequencing batch reactors |journal=Scientific Reports |date=February 2018 |volume=8 |issue=1 |pages=3399 |doi=10.1038/s41598-018-21564-x |pmid=29467367 |pmc=5821853 |bibcode=2018NatSR...8.3399L |s2cid=3384839 |doi-access=free }}</ref><ref name="Lange-2012-environmental-contaminants">{{cite journal | vauthors = Lange FT, Scheurer M, Brauch HJ |title=Artificial sweeteners – a recently recognized class of emerging environmental contaminants: a review |journal=Analytical and Bioanalytical Chemistry |date=July 2012 |volume=403 |issue=9 |pages=2503–2518 |doi=10.1007/s00216-012-5892-z|pmid=22543693 |s2cid=33178173 }}</ref>

==Mechanism of action==

The perceived sweetness of aspartame (and other sweet substances like [[acesulfame&nbsp;potassium]]) in humans is due to its binding of the heterodimer [[G&nbsp;protein-coupled receptor]] formed by the proteins [[TAS1R2]] and [[TAS1R3]].<ref>{{cite journal | vauthors = Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E | title = Human receptors for sweet and umami taste | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 7 | pages = 4692–4696 | date = April 2002 | pmid = 11917125 | pmc = 123709 | doi = 10.1073/pnas.072090199 | doi-access = free | bibcode = 2002PNAS...99.4692L }}</ref> Rodents do not experience aspartame as sweet-tasting, due to differences in their taste receptors.<ref>{{cite journal | vauthors = Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJ, Zuker CS | title = An amino-acid taste receptor | journal = Nature | volume = 416 | issue = 6877 | pages = 199–202 | date = March 2002 | pmid = 11894099 | doi = 10.1038/nature726 | s2cid = 1730089 | bibcode = 2002Natur.416..199N }}</ref>

=== Metabolites ===

Aspartame is rapidly [[hydrolyzed]] in the [[small intestine]] by [[digestive enzyme]]s which break aspartame down into [[methanol]], [[phenylalanine]], [[aspartic acid]], and further metabolites, such as [[formaldehyde]] and [[formic acid]].<ref name=Magnuson/><ref name="ahmad">{{cite journal | vauthors = Ahmad SY, Friel JK, Mackay DS | title=Effect of sucralose and aspartame on glucose metabolism and gut hormones | journal=Nutrition Reviews| volume=78 | issue=9 | date=September 2020 | pmid=32065635 | doi=10.1093/nutrit/nuz099 | pages=725–746 | doi-access=free }}</ref><ref name="Lin-2000">{{cite journal | vauthors = Lin SY, Cheng YD | title = Simultaneous formation and detection of the reaction product of solid-state aspartame sweetener by FT-IR/DSC microscopic system | journal = Food Additives and Contaminants | volume = 17 | issue = 10 | pages = 821–827 | date = October 2000 | pmid = 11103265 | doi = 10.1080/026520300420385 | s2cid = 10065876 }}</ref> Due to its rapid and complete metabolism, aspartame is not found in circulating blood, even following ingestion of high doses over 200&nbsp;mg/kg.<ref name=Magnuson/><ref name=ahmad/>

====Aspartic acid====

Aspartic acid (aspartate) is one of the most common [[amino acid]]s in the typical diet. As with methanol and phenylalanine, intake of aspartic acid from aspartame is less than would be expected from other dietary sources.<ref name=Magnuson/><ref name=ahmad/> At the 90th percentile of intake, aspartame provides only between 1% and 2% of the daily intake of aspartic acid.<ref name=Magnuson/>

====Methanol====

The methanol produced by aspartame metabolism is unlikely to be a safety concern for several reasons. The amount of methanol produced from aspartame-sweetened foods and beverages is likely to be less than that from food sources already in diets.<ref name=Magnuson/> With regard to formaldehyde, it is rapidly converted in the body, and the amounts of formaldehyde from the metabolism of aspartame are trivial when compared to the amounts produced routinely by the human body and from other foods and drugs.<ref name=Magnuson/> At the highest expected human doses of consumption of aspartame, there are no increased blood levels of methanol or formic acid,<ref name=Magnuson/> and ingesting aspartame at the 90th percentile of intake would produce 25 times less methanol than what would be considered toxic.<ref name=Butchko/>

==Chemistry==

Aspartame is a [[methyl ester]] of the [[dipeptide]] of the natural [[amino acid]]s <small>L</small>-[[aspartic acid]] and <small>L</small>-[[phenylalanine]].<ref name=pubch/> Under strongly [[acid]]ic or [[Base (chemistry)|alkaline]] conditions, aspartame may generate [[methanol]] by [[hydrolysis]]. Under more severe conditions, the [[peptide bond]]s are also hydrolyzed, resulting in free amino acids.<ref>

{{Cite journal| vauthors = Ager DJ, Pantaleone DP, Henderson SA, Katritzky AR, Prakash I, Walters DE | title = Commercial, Synthetic Non-nutritive Sweeteners| journal = [[Angewandte Chemie International Edition]]| year = 1998| volume = 37| issue = 13–24| pages = 1802–8117| doi = 10.1002/(SICI)1521-3773(19980803)37:13/14<1802::AID-ANIE1802>3.0.CO;2-9 }}</ref>

[[File:Beta aspartame.png|thumb|right|alt= Beta aspartame differs from aspartame based on which carboxyl group binds to phenylalanine|Beta-aspartame differs from aspartame based upon which carboxyl group of aspartate binds to the nitrogen of phenylalanine.]]

Two approaches to synthesis are used commercially. In the chemical synthesis, the two carboxyl groups of aspartic acid are joined into an anhydride, and the amino group is [[Protecting group|protected]] with a [[formyl group]] as the formamide, by treatment of aspartic acid with a mixture of formic acid and acetic anhydride.<ref>{{Cite patent|title=Process for producing N-formylamino acid and use thereof|country=US|number=20040137559|issue-date=2003-10-20}}</ref> Phenylalanine is converted to its methyl ester and combined with the ''N''-formyl aspartic anhydride; then the protecting group is removed from aspartic nitrogen by acid hydrolysis. The drawback of this technique is that a byproduct, the bitter-tasting β-form, is produced when the wrong carboxyl group from aspartic acid anhydride links to phenylalanine, with desired and undesired isomer forming in a 4:1 ratio.<ref>{{cite web|url=https://www.chemistryviews.org/details/ezine/9138171/The_Saccharin_Saga__Part_6.html|title=The Saccharin Saga – Part 6|work=ChemViews Magazine|date=5 April 2016|access-date=18 March 2019|archive-date=2 June 2018|archive-url=https://web.archive.org/web/20180602151924/http://www.chemistryviews.org/details/ezine/9138171/The_Saccharin_Saga__Part_6.html|url-status=live}}</ref> A process using an [[Thermolysin|enzyme from ''Bacillus thermoproteolyticus'']] to catalyze the condensation of the chemically altered amino acids will produce high yields without the β-form byproduct. A variant of this method, which has not been used commercially, uses unmodified aspartic acid but produces low yields. Methods for directly producing aspartyl-phenylalanine by enzymatic means, followed by chemical methylation, have also been tried but not scaled for industrial production.<ref>{{cite journal | vauthors = Yagasaki M, Hashimoto S | title = Synthesis and application of dipeptides; current status and perspectives | journal = Applied Microbiology and Biotechnology | volume = 81 | issue = 1 | pages = 13–22 | date = November 2008 | pmid = 18795289 | doi = 10.1007/s00253-008-1590-3 | s2cid = 10200090 }}</ref>

==History==

Aspartame was discovered in 1965 by James M. Schlatter, a chemist working for [[G.D. Searle & Company]]. Schlatter had [[Chemical synthesis|synthesized]] aspartame as an intermediate step in generating a tetrapeptide of the hormone [[gastrin]], for use in assessing an anti-[[Peptic ulcer disease|ulcer]] drug candidate.<ref>{{cite book | vauthors = Mazur RH | veditors = Inglett GE |title= Symposium: sweeteners |year= 1974 |publisher= AVI Publishing |location= Westport, CT |isbn= 978-0-87055-153-6 |lccn= 73-94092 |pages= [https://archive.org/details/symposiumsweeten0000unse/page/159 159–63] |chapter= Aspartic acid-based sweeteners |chapter-url= https://archive.org/details/symposiumsweeten0000unse/page/159 }}</ref> He discovered its sweet taste when he licked his finger, which had become contaminated with aspartame, to lift up a piece of paper.<ref name=Magnuson/><ref name="isbn0-632-04452-7">{{cite book | vauthors = Lewis R |title=Discovery: windows on the life sciences | url = https://archive.org/details/discoveryscience00lewi | url-access = limited |publisher=Blackwell Science |location=Oxford |year=2001 |page=[https://archive.org/details/discoveryscience00lewi/page/n16 4] |isbn=978-0-632-04452-8 }}</ref> [[Torunn Atteraas Garin]] participated in the development of aspartame as an [[artificial sweetener]].<ref>{{cite news|title=Torunn A. Garin, 54, Noted Food Engineer|url=https://www.nytimes.com/2002/05/01/nyregion/torunn-a-garin-54-noted-food-engineer.html|work=The New York Times|date=1 May 2002|url-status=live|archive-url=https://web.archive.org/web/20160306051959/http://www.nytimes.com/2002/05/01/nyregion/torunn-a-garin-54-noted-food-engineer.html|archive-date=6 March 2016}}</ref>

In 1975, prompted by issues regarding [[Flagyl]] and [[Aldactone]], an FDA task force team reviewed 25&nbsp;studies submitted by the manufacturer, including 11 on aspartame. The team reported "serious deficiencies in Searle's operations and practices".<ref name="GAO87">{{cite web|url=https://www.gao.gov/assets/hrd-87-46.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://www.gao.gov/assets/hrd-87-46.pdf |archive-date=9 October 2022 |url-status=live|title=Food additive approval process followed for Aspartame|publisher=US Food and Drug Administration|date=18 June 1987|access-date=14 July 2022 }}</ref> 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.<ref name="GAO87" />

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 [[Human brain|brain]] damage, but it recommended against approving aspartame at that time, citing unanswered questions about cancer in laboratory rats.<ref name="GAO87"/>{{rp|94–96}}<ref>Testimony of Dr. Adrian Gross, Former FDA Investigator to the US Senate Committee on Labor and Human Resources, 3 November 1987. Hearing title: "NutraSweet Health and Safety Concerns." Document # Y 4.L 11/4:S.HR6.100, pp.&nbsp;430–39.</ref>

In 1983, the FDA approved aspartame for use in carbonated beverages and for use in other beverages, baked goods, and confections in 1993.<ref name =cfr/> In 1996, the FDA removed all restrictions from aspartame, allowing it to be used in all foods.<ref name=cfr/><ref name=FDA1996>[https://web.archive.org/web/20041128020903/https://www.fda.gov/bbs/topics/answers/ans00772.html FDA Statement on Aspartame], 18 November 1996</ref> As of May 2023, the FDA stated that it regards aspartame as a safe food ingredient when consumed within the acceptable daily intake level of 50 mg per kg of body weight per day.<ref name=fda7-14/>

Several European Union countries approved aspartame in the 1980s, with EU-wide approval in 1994. The [[Scientific Committee on Food]] (SCF) reviewed subsequent safety studies and reaffirmed the approval in 2002. The [[European Food Safety Authority]] (EFSA) reported in 2006 that the previously established [[Acceptable daily intake]] (ADI) was appropriate, after reviewing yet another set of studies.<ref name="EFSAreport">{{cite journal |author=Panel on Food Additives and Nutrient Sources added to Food |year=2006 |title=Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to a new long-term carcinogenicity study on aspartame |journal=The EFSA Journal |volume=356 |issue=5 |pages=1–44 |doi=10.2903/j.efsa.2006.356 |doi-access=free}}</ref>

===Compendial status===

* [[British Pharmacopoeia]]<ref name=ibp>{{cite web |author=British Pharmacopoeia Commission Secretariat |title=Index (BP) |url=http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf |access-date=16 January 2010 |url-status=dead |archive-url=https://web.archive.org/web/20090411071437/http://www.pharmacopoeia.co.uk/pdf/2009_index.pdf |archive-date=11 April 2009 }}</ref>

* [[United States Pharmacopeia]]<ref name=firs>{{cite web|author=United States Pharmacopeia|author-link=United States Pharmacopeia|title=Food Ingredient Reference Standards |url=http://www.usp.org/pdf/EN/fccRefStandards.pdf |access-date=16 January 2010 |url-status=dead |archive-url=https://web.archive.org/web/20100331163714/http://www.usp.org/pdf/EN/fccRefStandards.pdf |archive-date=31 March 2010 }}</ref>

==Commercial uses==

Under the brand names [[Equal (sweetener)|Equal]], [[NutraSweet]], and [[Canderel]], aspartame is an ingredient in approximately 6,000 consumer foods and beverages sold worldwide, including (but not limited to) diet sodas and other soft drinks, instant breakfasts, breath mints, cereals, sugar-free chewing gum, cocoa mixes, frozen desserts, gelatin desserts, juices, laxatives, chewable vitamin supplements, milk drinks, pharmaceutical drugs and supplements, shake mixes, tabletop sweeteners, teas, [[instant coffee]]s, topping mixes, wine coolers, and yogurt. It is provided as a table [[condiment]] in some countries. Aspartame is less suitable for [[baking]] than other sweeteners because it [[chemical decomposition|breaks down]] when heated and loses much of its sweetness.<ref>{{cite web|url=https://news.nationalgeographic.com/news/2013/07/130717-sugar-substitutes-nutrasweet-splenda-stevia-baking/|title=How Sugar Substitutes Stack Up|date=17 July 2013|website=National Geographic News|access-date=21 February 2019|archive-date=22 February 2019|archive-url=https://web.archive.org/web/20190222041958/https://news.nationalgeographic.com/news/2013/07/130717-sugar-substitutes-nutrasweet-splenda-stevia-baking/|url-status=dead}}</ref><ref>{{Cite journal| vauthors = Struck S, Jaros D, Brennan CS, Rohm H |date=2014|title=Sugar replacement in sweetened bakery goods|journal=International Journal of Food Science & Technology|volume=49|issue=9|pages=1963–1976|doi=10.1111/ijfs.12617}}</ref>

===NutraSweet Company===

In 1985, [[Monsanto]] bought G.D.{{nbsp}}Searle,<ref>{{cite news |title=Monsanto to Acquire G.D. Searle |date=18 July 1985 | vauthors = Greenhouse S |url=https://www.nytimes.com/1985/07/19/business/monsanto-to-acquire-g-d-searle.html |newspaper=The New York Times |url-status=live |archive-url=https://web.archive.org/web/20171126033525/http://www.nytimes.com/1985/07/19/business/monsanto-to-acquire-g-d-searle.html |archive-date=26 November 2017 }}</ref> and the aspartame business became a separate Monsanto subsidiary, [[NutraSweet]]. In March 2000, Monsanto sold it to [[J.W. Childs Associates]] 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 J.W. Childs Equity Partners II, L.P] {{webarchive|url=https://web.archive.org/web/20070514184641/http://findarticles.com/p/articles/mi_m0EUY/is_22_6/ai_62920821 |date=14 May 2007 }}, ''Food & Drink Weekly'', 5 June 2000</ref><ref>{{cite web | title=JW Childs Acquires Monsanto's NutraSweet Sweetener Business | website=Chemical Online | date=28 March 2000 | url=https://www.chemicalonline.com/doc/jw-childs-acquires-monsantos-nutrasweet-sweet-0001 | access-date=1 July 2023 | archive-date=21 January 2022 | archive-url=https://web.archive.org/web/20220121022446/https://www.chemicalonline.com/doc/jw-childs-acquires-monsantos-nutrasweet-sweet-0001 | url-status=live }}</ref> European use patents on aspartame expired beginning in 1987, with the US patent following suit in 1992.<ref>{{Cite news |date=19 November 1989 |title=Nutrasweet's Bitter Fight |url=https://www.nytimes.com/1989/11/19/business/nutrasweet-s-bitter-fight.html |url-status=live |archive-url=https://web.archive.org/web/20170210231151/http://www.nytimes.com/1989/11/19/business/nutrasweet-s-bitter-fight.html |archive-date=10 February 2017 |newspaper=[[The New York Times]] |vauthors=Shapiro E}}</ref>

===Ajinomoto===

In 2004, the market for aspartame, in which [[Ajinomoto]], the world's largest aspartame manufacturer, had a 40% share, was {{Convert|14000|t|ST LT|sp=us}} a year, and consumption of the product was rising by 2% a year.<ref>{{Cite news |url=https://www.bloomberg.com/apps/news?pid=newsarchive&sid=a1rBnsdDJnM8 |title=Ajinomoto May Exceed Full-Year Forecasts on Amino Acid Products |publisher=Bloomberg L.P.access-date=23 June 2010 |date=18 November 2004 |url-status=live |archive-url=https://archive.today/20130620035625/http://www.bloomberg.com/apps/news?pid=newsarchive&sid=a1rBnsdDJnM8 |archive-date=20 June 2013 }}</ref> Ajinomoto acquired its aspartame business in 2000 from [[Monsanto]] for $67&nbsp;million (equivalent to ${{Formatprice|{{inflation|US-GDP|67000000|2000}}}} in {{Inflation/year|index=US-GDP}}{{Inflation/fn|index=US-GDP}}).<ref>{{cite web |url=http://www.icis.com/Articles/2000/06/05/114953/sweetener-sale.html |title=Sweetener sale-05/06/2000-ECN |publisher=icis.com |access-date=9 July 2010 |archive-date=13 July 2011 |archive-url=https://web.archive.org/web/20110713001707/http://www.icis.com/Articles/2000/06/05/114953/sweetener-sale.html |url-status=live }}</ref>

In 2007, [[Asda]] was the first British supermarket chain to remove all artificial flavourings and colours in its [[store brand]] foods.<ref name="standard/6582564">{{cite news |title=Asda becomes first supermarket to axe all artificial flavourings and colours in own brand foods |url=https://www.standard.co.uk/hp/front/asda-becomes-first-supermarket-to-axe-all-artificial-flavourings-and-colours-in-own-brand-foods-6582564.html |access-date=23 October 2022 |work=[[Evening Standard]] |date=12 April 2012 |archive-date=23 October 2022 |archive-url=https://web.archive.org/web/20221023050121/https://www.standard.co.uk/hp/front/asda-becomes-first-supermarket-to-axe-all-artificial-flavourings-and-colours-in-own-brand-foods-6582564.html |url-status=live }}</ref> In 2008, Ajinomoto sued Asda, part of [[Walmart]], for a malicious falsehood action concerning its aspartame product when the substance was listed as excluded from the chain's product line, along with other "nasties". In July 2009, a British court ruled in favor of Asda.<ref name="independent/1747827">{{cite news |last1=Howard |first1=Stephen |title=Asda wins fight over 'nasty' sweetener |url=https://www.independent.co.uk/news/uk/home-news/asda-wins-fight-over-nasty-sweetener-1747827.html |access-date=23 October 2022 |work=[[The Independent]] |agency=[[Press Association]] |date=15 July 2009 |archive-date=23 October 2022 |archive-url=https://web.archive.org/web/20221023051220/https://www.independent.co.uk/news/uk/home-news/asda-wins-fight-over-nasty-sweetener-1747827.html |url-status=live }}</ref><ref>{{cite web |url=http://www.foodanddrinkeurope.com/Products-Marketing/Asda-claims-victory-in-aspartame-nasty-case |title=Asda claims victory in aspartame 'nasty' case |publisher=foodanddrinkeurope.com |access-date=23 June 2010 |url-status=live |archive-url=https://web.archive.org/web/20100103050234/http://www.foodanddrinkeurope.com/Products-Marketing/Asda-claims-victory-in-aspartame-nasty-case |archive-date=3 January 2010 }}</ref> In June 2010, an appeals court reversed the decision, allowing Ajinomoto to pursue a case against Asda to protect aspartame's reputation.<ref name="confectionerynews/2010-Ajinomoto-Asda">{{cite news |last1=Watson |first1=Elaine |title=Radical new twist in Ajinomoto vs Asda 'nasty' battle |url=https://www.confectionerynews.com/Article/2010/06/03/Radical-new-twist-in-Ajinomoto-vs-Asda-nasty-battle |access-date=23 October 2022 |work=confectionery news |publisher= [[William Reed Ltd]] |date=2 June 2010 |archive-url=https://web.archive.org/web/20221023040631/https://www.confectionerynews.com/Article/2010/06/03/Radical-new-twist-in-Ajinomoto-vs-Asda-nasty-battle |archive-date=23 October 2022}}</ref><ref>{{cite web |url=http://www.foodbev.com/news/court-of-appeal-rules-in-ajinomotoasda-aspartame-case |title=FoodBev.com |publisher= |access-date=23 June 2010 |quote=Court of Appeal rules in Ajinomoto/Asda aspartame case |url-status=live |archive-url=https://web.archive.org/web/20110711015104/http://www.foodbev.com/news/court-of-appeal-rules-in-ajinomotoasda-aspartame-case |archive-date=11 July 2011 |date=3 June 2010 }}</ref> Asda said that it would continue to use the term "no nasties" on its own-label products,<ref>{{cite web|url=http://www.foodnavigator.com/Legislation/Radical-new-twist-in-Ajinomoto-vs-Asda-nasty-battle |title=Radical new twist in Ajinomoto vs Asda 'nasty' battle |publisher= [[William Reed Ltd]] |work=foodnavigator.com |date=2 June 2010 |access-date=23 June 2010 | archive-url= https://web.archive.org/web/20100606185621/http://www.foodnavigator.com/Legislation/Radical-new-twist-in-Ajinomoto-vs-Asda-nasty-battle| archive-date= 6 June 2010 | url-status= live}}</ref> but the suit was settled in 2011 with Asda choosing to remove references to aspartame from its packaging.<ref>{{cite news |title= Asda settles 'nasty' aspartame legal battle with Ajinomoto | vauthors = Bouckley B |url= http://www.foodnavigator.com/Financial-Industry/Asda-settles-nasty-aspartame-legal-battle-with-Ajinomoto |work=FoodNavigator.com |publisher= [[William Reed Ltd]] |date= 18 May 2011 |access-date= 18 July 2011 |url-status= live |archive-url= https://web.archive.org/web/20110731051352/http://www.foodnavigator.com/Financial-Industry/Asda-settles-nasty-aspartame-legal-battle-with-Ajinomoto |archive-date= 31 July 2011 }}</ref><ref name="foodmanufacture/2011-Asda-settles">{{cite news |last1=Bouckley |first1=Ben |title=Asda settles 'nasty' legal spat with Ajinomoto over sweetener aspartame |url=https://www.foodmanufacture.co.uk/Article/2011/05/17/Asda-settles-nasty-legal-spat-with-Ajinomoto-over-sweetener-aspartame |access-date=23 October 2022 |work=foodmanufacture.co.uk |publisher= [[William Reed Ltd]] |date=16 May 2011 |archive-url=https://web.archive.org/web/20221023040648/https://www.foodmanufacture.co.uk/Article/2011/05/17/Asda-settles-nasty-legal-spat-with-Ajinomoto-over-sweetener-aspartame |archive-date=23 October 2022}}</ref>

In November 2009, Ajinomoto announced a new brand name for its aspartame sweetener—AminoSweet.<ref name="rebrand">

*{{cite web |url=http://www.foodnavigator.com/Financial-Industry/Ajinomoto-brands-aspartame-AminoSweet |title=Ajinomoto brands aspartame AminoSweet |publisher= [[William Reed Ltd]] |work=Foodnavigator.com |date=25 November 2009 |access-date=7 July 2010 |url-status=live |archive-url=https://web.archive.org/web/20100830014645/http://www.foodnavigator.com/Financial-Industry/Ajinomoto-brands-aspartame-AminoSweet |archive-date=30 August 2010 }}

* {{cite web |url=http://www.foodbev.com/news/ajinomoto-brands-aspartame-aminosweet |title=Ajinomoto brands aspartame 'AminoSweet' |publisher=FoodBev.com |date=17 November 2009 |access-date=7 July 2010 |url-status=live |archive-url=https://web.archive.org/web/20100330163628/http://www.foodbev.com/news/ajinomoto-brands-aspartame-aminosweet |archive-date=30 March 2010 }}</ref>

===Holland Sweetener Company===

A joint venture of [[DSM (company)|DSM]] and [[Tosoh]], the Holland Sweetener Company manufactured aspartame using the enzymatic process developed by Toyo Soda (Tosoh) and sold as the brand Sanecta.<ref>{{cite book | vauthors = Lee TD |title= Kirk-Othmer Encyclopedia of Chemical Technology |edition= 5th |volume= 24 |year= 2007 |publisher= Wiley |isbn= 978-0-471-48496-7 |pages= 224–252 |chapter= Sweetners |doi=10.1002/0471238961.19230505120505.a01.pub2}}</ref> Additionally, they developed a combination [[aspartame-acesulfame salt]] under the brand name Twinsweet.<ref>{{cite news |title= Holland Sweetener rolls out Twinsweet |url= http://www.bakeryandsnacks.com/Processing-Packaging/Holland-Sweetener-rolls-out-Twinsweet |access-date= 29 July 2011 |newspaper= BakeryAndSnacks.com |publisher= William Reed Business Media |date= 19 November 2003 |url-status= live |archive-url= https://web.archive.org/web/20110929113951/http://www.bakeryandsnacks.com/Processing-Packaging/Holland-Sweetener-rolls-out-Twinsweet |archive-date= 29 September 2011 }}</ref> They left the sweetener industry in 2006, because "global aspartame markets are facing structural oversupply, which has caused worldwide strong price erosion over the last five years", making the business "persistently unprofitable".<ref>[https://www.sec.gov/Archives/edgar/vprr/06/9999999997-06-013522 "Holland Sweetener Company to exit from aspartame business"] {{webarchive |url=https://web.archive.org/web/20130507075849/http://www.sec.gov/Archives/edgar/vprr/06/9999999997-06-013522 |date=7 May 2013 }}. DSM press release, [[US Securities and Exchange Commission]]. 30 March 2006.</ref>

===Competing products===

Because [[sucralose]], unlike aspartame, retains its sweetness after being heated, and has at least twice the shelf life of aspartame, it has become more popular as an ingredient.<ref>{{cite news|url=https://www.nytimes.com/2004/12/22/business/a-something-among-the-sweet-nothings.html|title=A Something Among the Sweet Nothings; Splenda Is Leaving Other Sugar Substitutes With That Empty Feeling|newspaper=The New York Times | vauthors = Warner M |date=22 December 2004|url-status=live|archive-url=https://web.archive.org/web/20170421130808/http://query.nytimes.com/gst/fullpage.html?res=9402E6DC1030F931A15751C1A9629C8B63|archive-date=21 April 2017}}</ref> This, along with differences in marketing and changing consumer preferences, caused aspartame to lose market share to sucralose.<ref>{{Cite news | vauthors = Schmeltzer J | url = http://articles.chicagotribune.com/2004-12-02/business/0412020391_1_splenda-merisant-worldwide-equal | title = Equal fights to get even as Splenda looks sweet | work = Chicago Tribune | date = 2 December 2004 | access-date = 4 July 2007 | url-status = live | archive-url = https://web.archive.org/web/20101204063027/http://articles.chicagotribune.com/2004-12-02/business/0412020391_1_splenda-merisant-worldwide-equal | archive-date = 4 December 2010 }}</ref><ref>{{Cite news| vauthors = Carney B | title = It's Not All Sweetness for Splenda | work = BusinessWeek: Daily Briefing | access-date =5 September 2008 | date = 19 January 2005 | url = http://www.businessweek.com/bwdaily/dnflash/jan2005/nf20050119_5391_db014.htm | archive-url= https://web.archive.org/web/20081007062929/http://www.businessweek.com/bwdaily/dnflash/jan2005/nf20050119_5391_db014.htm| archive-date= 7 October 2008 | url-status= dead}}</ref> In 2004, aspartame traded at about {{Convert|30|$/kg|$/lb}} and sucralose, which is roughly three times sweeter by weight, at around {{Convert|300|$/kg|$/lb}}.<ref>{{cite web |url=http://www.beveragedaily.com/Markets/Aspartame-defence-courts-reaction |title=Aspartame defence courts reaction |publisher=beveragedaily.com |date=7 October 2004 |url-status=live |archive-url=https://web.archive.org/web/20110707231126/http://www.beveragedaily.com/Markets/Aspartame-defence-courts-reaction |archive-date=7 July 2011 }}</ref>

== References ==

{{reflist}}

== External links ==

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