Editing Aspartame (section)

== 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/>}}

=== Neurological safety ===
Reviews found no evidence that low doses of aspartame had [[Neurotoxicity|neurotoxic]] effects.<ref name=EFSAExperts/><ref name=Magnuson/><ref name=Butchko/> A 2019 policy statement by the [[American Academy of Pediatrics]] concluded that there were no safety concerns about aspartame in fetal or childhood development or as a factor in [[attention deficit hyperactivity disorder]].<ref name="baker">{{cite journal |vauthors=Baker-Smith CM, de Ferranti SD, Cochran WJ, etal |title=Policy Statement: The Use of Nonnutritive Sweeteners in Children |journal=Pediatrics |volume=144 |issue=5 |pages= |date=November 2019 |pmid=31659005 |doi=10.1542/peds.2019-2765 |url=https://publications.aap.org/pediatrics/article/144/5/e20192765/38183/The-Use-of-Nonnutritive-Sweeteners-in-Children}}</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>