Aspartame: Difference between revisions
Novangelis (talk | contribs) Undid revision 368797351 by Henri Hudson (talk) avoid weasel words |
Not Nutrasweet but Ajinomoto. Also restoring edits removed by Verbal. Will investigate Snopes source for inclusion and if good, will restore "hoax" material |
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Aspartame was first synthesized in 1965. Its use in food products was first approved by the [[Food and Drug Administration (United States)|United States Food and Drug Administration]] in 1974. Because its breakdown products include [[phenylalanine]], aspartame is among the many substances that must be avoided by people with [[phenylketonuria]] (PKU), a rare genetic condition. |
Aspartame was first synthesized in 1965. Its use in food products was first approved by the [[Food and Drug Administration (United States)|United States Food and Drug Administration]] in 1974. Because its breakdown products include [[phenylalanine]], aspartame is among the many substances that must be avoided by people with [[phenylketonuria]] (PKU), a rare genetic condition. |
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A |
A study funded by Ajinomoto Company Inc.,<ref>{{cite web |url=http://www.webmd.com/food-recipes/news/20070911/expert-panel-aspartame-sweetener-safe |title=Expert Panel: Aspartame Sweetener Safe |publisher=www.webmd.com |accessdate=2010-06-18 }}</ref> a major maker of aspartame, concluded that "the weight of existing scientific evidence indicates that aspartame is safe at current levels of consumption as a non-nutritive sweetener".<ref name=CritReview>{{cite journal |author=Magnuson BA, Burdock GA, Doull J, ''et al.'' |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}}</ref> |
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The [[Aspartame controversy|safety of aspartame]] has been the subject of several political and medical controversies, [[Congressional hearing|Congressional Hearings]] |
The [[Aspartame controversy|safety of aspartame]] has been the subject of several political and medical controversies, as well as the subject of [[Congressional hearing|Congressional Hearings]], since its initial approval by the [[U.S. Food and Drug Administration]] (FDA) in 1974. |
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== Marketing == |
== Marketing == |
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[[Equal]], [[NutraSweet]], and [[Canderel]] are ingredients of 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 vitamins supplements, milk drinks, pharmaceutical drugs and supplements, shake mixes, tabletop sweeteners, teas, instant coffees, topping mixes, wine coolers and yogurt. It is provided as a table [[condiment]] in some countries. However, aspartame is not always suitable for [[baking]] because it often [[chemical decomposition|breaks down]] when heated and loses much of its sweetness. Aspartame is also one of the main sugar substitutes used by people with [[diabetes mellitus|diabetes]]. |
[[Equal]], [[NutraSweet]], and [[Canderel]] are ingredients of 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 vitamins supplements, milk drinks, pharmaceutical drugs and supplements, shake mixes, tabletop sweeteners, teas, instant coffees, topping mixes, wine coolers and yogurt. It is provided as a table [[condiment]] in some countries. However, aspartame is not always suitable for [[baking]] because it often [[chemical decomposition|breaks down]] when heated and loses much of its sweetness. Aspartame is also one of the main sugar substitutes used by people with [[diabetes mellitus|diabetes]]. |
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Leading aspartame producer [[Ajinomoto]] has a new |
Leading aspartame producer [[Ajinomoto]] has a new brand name for its aspartame sweetener called AminoSweet.<ref>http://www.foodnavigator.com/Financial-Industry/Ajinomoto-brands-aspartame-AminoSweet</ref><ref>http://www.foodbev.com/news/ajinomoto-brands-aspartame-aminosweet</ref> |
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Because [[sucralose]], unlike aspartame, retains its sweetness after being heated, it has become more popular as an ingredient.{{Citation needed|date=February 2010}} This, along with differences in marketing and changing consumer preferences, has caused aspartame to lose market share to sucralose.<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=2004-12-02 | accessdate = 2007-07-04 | format = subscription required}}</ref><ref>{{Cite news | last = Carney | first = By Beth | title = It's Not All Sweetness for Splenda | work = BusinessWeek: Daily Briefing | accessdate = 2008-09-05 | date = 2005-01-19 | url = http://www.businessweek.com/bwdaily/dnflash/jan2005/nf20050119_5391_db014.htm }}</ref> |
Because [[sucralose]], unlike aspartame, retains its sweetness after being heated, it has become more popular as an ingredient.{{Citation needed|date=February 2010}} This, along with differences in marketing and changing consumer preferences, has caused aspartame to lose market share to sucralose.<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=2004-12-02 | accessdate = 2007-07-04 | format = subscription required}}</ref><ref>{{Cite news | last = Carney | first = By Beth | title = It's Not All Sweetness for Splenda | work = BusinessWeek: Daily Briefing | accessdate = 2008-09-05 | date = 2005-01-19 | url = http://www.businessweek.com/bwdaily/dnflash/jan2005/nf20050119_5391_db014.htm }}</ref> |
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{{Main|Aspartame controversy}} |
{{Main|Aspartame controversy}} |
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Aspartame has been linked to [[headache]] and [[migraine]] in susceptible individuals.<ref name="Newman-2001">{{Cite journal | last1 = Newman | first1 = LC. | last2 = Lipton | first2 = RB. | title = Migraine MLT-down: an unusual presentation of migraine in patients with aspartame-triggered headaches. | journal = Headache | volume = 41 | issue = 9 | pages = 899-901 | month = Oct | year = 2001 | doi = | PMID = 11703479 }}</ref><ref name="Jacob-">{{Cite journal | last1 = Jacob | first1 = SE. | last2 = Stechschulte | first2 = S. | title = Formaldehyde, aspartame, and migraines: a possible connection. | journal = Dermatitis | volume = 19 | issue = 3 | pages = E10-1 | month = | year = | doi = | PMID = 18627677 }}</ref><ref name="Sun-Edelstein-2009">{{Cite journal | last1 = Sun-Edelstein | first1 = C. | last2 = Mauskop | first2 = A. | title = Foods and supplements in the management of migraine headaches. | journal = Clin J Pain | volume = 25 | issue = 5 | pages = 446-52 | month = Jun | year = 2009 | doi = 10.1097/AJP.0b013e31819a6f65 | PMID = 19454881 }}</ref><ref name="Millichap-2003">{{Cite journal | last1 = Millichap | first1 = JG. | last2 = Yee | first2 = MM. | title = The diet factor in pediatric and adolescent migraine. | journal = Pediatr Neurol | volume = 28 | issue = 1 | pages = 9-15 | month = Jan | year = 2003 | doi = | PMID = 12657413 }}</ref><ref name="Lipton-1989">{{Cite journal | last1 = Lipton | first1 = RB. | last2 = Newman | first2 = LC. | last3 = Cohen | first3 = JS. | last4 = Solomon | first4 = S. | title = Aspartame as a dietary trigger of headache. | journal = Headache | volume = 29 | issue = 2 | pages = 90-2 | month = Feb | year = 1989 | doi = | PMID = 2708042 }}</ref> |
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| ⚫ | Aspartame has been the subject of several controversies since its initial approval by the [[U.S. Food and Drug Administration]] (FDA) in 1974. Critics allege that [[Conflict of interest|conflicts of interest]] marred the FDA's approval of aspartame, question the quality of the initial research supporting its safety,<ref name=GAO87/><!--First sentence of this document: "Since 1974, aspartame, a food additive marketed under the brand name NutraSweetB, has been the subject of controversy."--><ref>{{cite news |url=http://pqasb.pqarchiver.com/washingtonpost_historical/access/125899752.html?dids=125899752:125899752&FMT=ABS&FMTS=ABS:FT| publisher= ''[[Washington Post]]''|title=Controversy Surrounds Sweetener|first=Carole | last=Sugarman|date=1983-07-03|accessdate = 2008-11-25|pages=D1–2}}</ref><ref>{{cite journal|journal=FDA Consumer Magazine|author=Henkel J|title=Sugar substitutes. Americans opt for sweetness and lite|year=1999|volume=33|issue=6|pmid=10628311|url=http://books.google.com/?id=bLuA-9PPe7gC&pg=PA1|pages=12–6|publisher=DIANE Publishing|isbn=9781422326909}}</ref> and postulate that numerous health risks may be associated with aspartame. |
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| ⚫ | In 1987, the U.S. [[Government Accountability Office]] concluded that the food additive approval process had been followed properly for aspartame.<ref name=GAO87>GAO 1987. [http://www.gao.gov/docdblite/info.php?rptno=HRD-87-46 "Food Additive Approval Process Followed for Aspartame"] [http://archive.gao.gov/d28t5/133460.pdf Full GAO Report] United States General Accounting Office, GAO/HRD-87-46, June 18, 1987</ref><ref name=GAO86>GAO 1986. [http://archive.gao.gov/d4t4/130780.pdf "Six Former HHS Employees' Involvement in Aspartame's Approval."] United States General Accounting Office, GAO/HRD-86-109BR, July 1986.</ref> Aspartame has been found to be safe for human consumption by more than ninety countries worldwide,<ref name="Health Canada">[[Health Canada]]: {{cite web |url=http://www.hc-sc.gc.ca/fn-an/securit/addit/sweeten-edulcor/aspartame-eng.php |title=Aspartame - Artificial Sweeteners |accessdate=2008-11-08}}</ref><ref name=FSANZ>[[Food Standards Australia New Zealand]]: {{cite web |url=http://www.foodstandards.gov.au/newsroom/factsheets/factsheets2007/aspartameseptember203703.cfm |title=Food Standards Australia New Zealand: Aspartame (September 2007) |accessdate=2008-11-08}}</ref> with FDA officials describing aspartame as "one of the most thoroughly tested and studied food additives the agency has ever approved" and its safety as "clear cut".<ref>{{cite news | url = http://web.archive.org/web/20071214170430/www.fda.gov/fdac/features/1999/699_sugar.html | title = Sugar Substitutes: Americans Opt for Sweetness and Lite | work = [[FDA Consumer]] | date = November–December 1999 | accessdate = January 29, 2009 | first = John | last = Henkel}}</ref> A study funded by the Nutrasweet Company concluded that the weight of existing scientific evidence indicates that aspartame is safe at current levels of consumption as a non-nutritive sweetener.<ref name=CritReview>{{cite journal |author=Magnuson BA, Burdock GA, Doull J, ''et al.'' |title=Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies |journal=Crit. Rev. Toxicol. |volume=37 |issue=8 |pages=629–727 |year=2007 |pmid=17828671 |doi=10.1080/10408440701516184 |url=}}</ref> |
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== Compendial status == |
== Compendial status == |
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Revision as of 14:17, 18 June 2010
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| Names | |
|---|---|
| IUPAC names
N-(L-α-Aspartyl)-L-phenylalanine,
1-methyl ester | |
| Identifiers | |
3D model (JSmol)
|
|
| ChemSpider | |
| ECHA InfoCard | 100.041.132 |
| E number | E951 (glazing agents, ...) |
CompTox Dashboard (EPA)
|
|
| |
| |
| Properties | |
| C14H18N2O5 | |
| Molar mass | 294.307 g·mol−1 |
| Density | 1.347 g/cm3 |
| Melting point | 246–247 °C |
| Boiling point | decomposes |
| sparingly soluble | |
| Solubility | slightly soluble in ethanol |
| Acidity (pKa) | 4.5-6.0 [2] |
| Hazards | |
| NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
| |
Aspartame (or APM) (Template:PronEng or /əˈspɑrteɪm/) is the name for an artificial, non-saccharide sweetener used as a sugar substitute in many foods and beverages. In the European Union, it is known under the E number (additive code) E951. Aspartame is the methyl ester of a phenylalanine/aspartic acid dipeptide.
Aspartame was first synthesized in 1965. Its use in food products was first approved by the United States Food and Drug Administration in 1974. Because its breakdown products include phenylalanine, aspartame is among the many substances that must be avoided by people with phenylketonuria (PKU), a rare genetic condition.
A study funded by Ajinomoto Company Inc.,[3] a major maker of aspartame, concluded that "the weight of existing scientific evidence indicates that aspartame is safe at current levels of consumption as a non-nutritive sweetener".[4]
The safety of aspartame has been the subject of several political and medical controversies, as well as the subject of Congressional Hearings, since its initial approval by the U.S. Food and Drug Administration (FDA) in 1974.
Marketing
Equal, NutraSweet, and Canderel are ingredients of 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 vitamins supplements, milk drinks, pharmaceutical drugs and supplements, shake mixes, tabletop sweeteners, teas, instant coffees, topping mixes, wine coolers and yogurt. It is provided as a table condiment in some countries. However, aspartame is not always suitable for baking because it often breaks down when heated and loses much of its sweetness. Aspartame is also one of the main sugar substitutes used by people with diabetes.
Leading aspartame producer Ajinomoto has a new brand name for its aspartame sweetener called AminoSweet.[5][6]
Because sucralose, unlike aspartame, retains its sweetness after being heated, it has become more popular as an ingredient.[citation needed] This, along with differences in marketing and changing consumer preferences, has caused aspartame to lose market share to sucralose.[7][8]
Chemistry
Aspartame is the methyl ester of the dipeptide of the natural amino acids L-aspartic acid and L-phenylalanine. Under strongly acidic or alkaline conditions, aspartame may generate methanol by hydrolysis. Under more severe conditions, the peptide bonds are also hydrolyzed, resulting in the free amino acids.[9]
In certain markets aspartame is manufactured using a genetically modified variation of E. coli.[10][11]
Properties and use
Aspartame is an artificial sweetener. It is 200 times sweeter than sugar in typical concentrations, without the high energy value of sugar.[citation needed] While aspartame, like other peptides, 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. 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. Blends of aspartame with acesulfame potassium—usually listed in ingredients as acesulfame K—are alleged[who?] to taste more like sugar, and to be sweeter than either substitute used alone.
Like many other peptides, aspartame may hydrolyze (break down) into its constituent amino acids under conditions of elevated temperature or high pH. This makes aspartame undesirable as a baking sweetener, and prone to degradation in products hosting a high-pH, as required for a long shelf life. The stability of aspartame under heating can be improved to some extent by encasing it in fats or in maltodextrin. The stability when dissolved in water depends markedly on pH. At room temperature, it is most stable at pH 4.3, where its half-life is nearly 300 days. At pH 7, however, its half-life is only a few days. Most soft-drinks have a pH between 3 and 5, where aspartame is reasonably stable. In products that may require a longer shelf life, such as syrups for fountain beverages, aspartame is sometimes blended with a more stable sweetener, such as saccharin.[12]
In products such as powdered beverages, the amine in aspartame can undergo a Maillard reaction with the aldehyde groups present in certain aroma compounds. The ensuing loss of both flavor and sweetness can be prevented by protecting the aldehyde as an acetal.
Some claim that aspartame leaves an odd after-taste, while others describe it as a non-flavor or watery after-taste.[13]
Discovery and approval
Aspartame was discovered in 1965 by James M. Schlatter, a chemist working for G.D. Searle & Company. Schlatter had synthesized aspartame in the course of producing an anti-ulcer drug candidate. He accidentally discovered its sweet taste when he licked his finger, which had become contaminated with aspartame.[14]
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 that aspartame does not cause brain damage, but it recommended against approving aspartame at that time, citing unanswered questions about cancer in laboratory rats. A U.S. FDA task force teams investigated allegations of errors in the pre-approval research conducted by the manufacturer and found only minor discrepancies that did not affect the study outcomes.[15][16] On January 21, 1981, the day after Ronald Reagan's inauguration, Searle, led by then CEO Donald Rumsfeld, re-applied to the FDA for approval to use aspartame in food sweetener, and Reagan's new FDA commissioner, Arthur Hull Hayes, Jr., appointed a 5-person Scientific Commission to review the board of inquiry's decision.
It soon became clear that the panel would uphold the ban by a 3-2 decision, but Hayes then installed a sixth member on the commission, and the vote became deadlocked. He then personally broke the tie in aspartame's favor. Hayes later left the FDA under allegations of impropriety, served briefly as Provost at New York Medical College, and then took a position with Burston-Marsteller, the chief public relations firm for both Monsanto and GD Searle. Since that time he has never spoken publicly about aspartame. Citing data from a Japanese study that had not been available to the members of the PBOI,[17] and after seeking advice from an expert panel that found fault with statistical analyses underlying the PBOI's hesitation,[18] FDA commissioner Hayes approved aspartame for use in dry goods.[19] In 1983, the FDA further approved aspartame for use in carbonated beverages, and for use in other beverages, baked goods, and confections in 1993. In 1996, the FDA removed all restrictions from aspartame allowing it to be used in all foods.
In 1984, Monsanto Company bought G.D. Searle—and the aspartame business became a separate Monsanto subsidiary, the NutraSweet Company. On May 25, 2000, Monsanto sold it to J.W. Childs Equity Partners II L.P.[20] The U.S. patent on aspartame expired in 1992. Since then, the company has competed for market share with other manufacturers, including Ajinomoto, Merisant and the Holland Sweetener Company. The latter 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 five years", making the business "persistently unprofitable".[21]
Several European Union countries approved aspartame in the 1980s, with EU-wide approval in 1994. The European Commission Scientific Committee on Food reviewed subsequent safety studies and reaffirmed the approval in 2002. The European Food Safety Authority reported in 2006 that the previously established Acceptable Daily Intake was appropriate, after reviewing yet another set of studies.[22]
Metabolism and phenylketonuria
Upon ingestion, aspartame breaks down into natural residual components, including aspartic acid, phenylalanine, methanol,[23] and further breakdown products including formaldehyde,[24] known to have a number[which?] of detrimental effects on the human body,[citation needed] formic acid, and a DKP - Aspartylphenylalanine diketopiperazine.[25]
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. 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.[citation needed]
In the UK, foods that contain aspartame are legally required by the country's Food Standards Agency to 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 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".[26]
Studies have also been conducted regarding aspartame's effect on the production of Leptin which controls food intake and energy expenditure by acting on receptors in the mediobasal hypothalamus.[27] These studies[28] have shown that leptin was "significantly reduced by 34%" after "chronic ingestion of aspartame (ASP)".
Further studies have shown that a metabolite of aspartame inhibits angiotensin converting enzyme.[29]
Safety controversy
Aspartame has been linked to headache and migraine in susceptible individuals.[30][31][32][33][34]
Aspartame has been the subject of several controversies since its initial approval by the U.S. Food and Drug Administration (FDA) in 1974. Critics allege that conflicts of interest marred the FDA's approval of aspartame, question the quality of the initial research supporting its safety,[35][36][37] and postulate that numerous health risks may be associated with aspartame.
In 1987, the U.S. Government Accountability Office concluded that the food additive approval process had been followed properly for aspartame.[35][38] Aspartame has been found to be safe for human consumption by more than ninety countries worldwide,[39][40] with FDA officials describing aspartame as "one of the most thoroughly tested and studied food additives the agency has ever approved" and its safety as "clear cut".[41] A study funded by the Nutrasweet Company concluded that the weight of existing scientific evidence indicates that aspartame is safe at current levels of consumption as a non-nutritive sweetener.[4]
Compendial status
- British Pharmacopoeia [42] [clarification needed]
- United States Pharmacopeia [43] [clarification needed]
References
Parameter error in {{ISBN}}: Missing ISBN.
- ^ Merck Index, 11th Edition, 861.
- ^ Rowe, Raymond C. (2009). "Aspartame". Handbook of Pharmaceutical Excipients. pp. 11–12. ISBN 1582120587.
- ^ "Expert Panel: Aspartame Sweetener Safe". www.webmd.com. Retrieved 2010-06-18.
- ^ a b Magnuson BA, Burdock GA, Doull J; et al. (2007). "Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies". Critical Reviews in Toxicology. 37 (8): 629–727. doi:10.1080/10408440701516184. PMID 17828671.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) Cite error: The named reference "CritReview" was defined multiple times with different content (see the help page). - ^ http://www.foodnavigator.com/Financial-Industry/Ajinomoto-brands-aspartame-AminoSweet
- ^ http://www.foodbev.com/news/ajinomoto-brands-aspartame-aminosweet
- ^ John Schmeltzer (2004-12-02). "Equal fights to get even as Splenda looks sweet]" (subscription required). Chicago Tribune. Retrieved 2007-07-04.
- ^ Carney, By Beth (2005-01-19). "It's Not All Sweetness for Splenda". BusinessWeek: Daily Briefing. Retrieved 2008-09-05.
- ^
David J. Ager, David P. Pantaleone, Scott A. Henderson, Alan R. Katritzky, Indra Prakash, D. Eric Walters (1998). "Commercial, Synthetic Non-nutritive Sweeteners". Angewandte Chemie International Edition. 37 (13–24): 1802–1817. doi:10.1002/(SICI)1521-3773(19980803)37:13/14<1802::AID-ANIE1802>3.0.CO;2-9.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ The Independent, Sunday, 20 June 1999
- ^ Method for production of L-phenylalanine by recombinant E. coli ATCC 67460
- ^ "Fountain Beverages in the US" (PDF). The Coca-Cola Company. 2007.
{{cite web}}: Unknown parameter|month=ignored (help) - ^ "Has aspartame an aftertaste". Institute of Food Technologists. 1985.
{{cite web}}: Unknown parameter|month=ignored (help) - ^ Magnuson BA, Burdock GA, Doull J (2007). "Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies". Crit. Rev. Toxicol. 37 (8): 629–727. doi:10.1080/10408440701516184. PMID 17828671.
{{cite journal}}: CS1 maint: multiple names: authors list (link) Citing: Mazur, R.H. (1984). Discovery of aspartame. In Aspartame: Physiology and Biochemistry (L. D. Stegink and L. J. Filer Jr., Eds.). Marcel Dekker, New York, pp. 3–9. - ^ "U.S. GAO - HRD-87-46 Food and Drug Administration: Food Additive Approval Process Followed for Aspartame, June 18, 1987". pp. 94–96. Retrieved 2008-09-05.
- ^ Testimony of Dr. Adrian Gross, Former FDA Investigator to the U.S. Senate Committee on Labor and Human Resources, November 3, 1987. Hearing title: "NutraSweet Health and Safety Concerns." Document # Y 4.L 11/4:S.HR6.100, page 430-439.
- ^ FDA Statement on Aspartame, November 18, 1996
- ^ "U.S. GAO - HRD-87-46 Food and Drug Administration: Food Additive Approval Process Followed for Aspartame, June 18, 1987". p. 53. Retrieved 2008-09-05.
- ^ Food Additive Approval Process Followed for Aspartame, Food and Drug Administration, June 1987
- ^ J.W. Childs Equity Partners II, L.P, Food & Drink Weekly, June 5, 2000
- ^ html b1?release id=115447
- ^ EFSA ::. 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
- ^ Roberts HJ (2004). "Aspartame disease: a possible cause for concomitant Graves' disease and pulmonary hypertension". Texas Heart Institute Journal. 31 (1): 105, author reply 105–6. PMC 387446. PMID 15061638.
- ^ Trocho C, Pardo R, Rafecas I; et al. (1998). "Formaldehyde derived from dietary aspartame binds to tissue components in vivo". Life Sciences. 63 (5): 337–49. doi:10.1016/S0024-3205(98)00282-3. PMID 9714421.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Gaines, Susan M.; Bada, Jeffrey L. (1988). "Aspartame decomposition and epimerization in the diketopiperazine and dipeptide products as a function of pH and temperature". The Journal of Organic Chemistry. 53: 2757–64. doi:10.1021/jo00247a018.
- ^ Aspartame - Labelling, UK Food Standards Agency, 18 July 2006. Retrieved on 2007-07-22.
- ^ Williams KW, Scott MM, Elmquist JK (2009). "From observation to experimentation: leptin action in the mediobasal hypothalamus". The American Journal of Clinical Nutrition. 89 (3): 985S–990S. doi:10.3945/ajcn.2008.26788D. PMC 2667659. PMID 19176744.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Beck B, Burlet A, Max JP, Stricker-Krongrad A (2002). "Effects of long-term ingestion of aspartame on hypothalamic neuropeptide Y, plasma leptin and body weight gain and composition". Physiology & Behavior. 75 (1–2): 41–7. doi:10.1016/S0031-9384(01)00654-0. PMID 11890951.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Grobelny D, Galardy RE (1985). "A metabolite of aspartame inhibits angiotensin converting enzyme". Biochemical and Biophysical Research Communications. 128 (2): 960–4. doi:10.1016/0006-291X(85)90140-8. PMID 2986632.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Newman, LC.; Lipton, RB. (2001). "Migraine MLT-down: an unusual presentation of migraine in patients with aspartame-triggered headaches". Headache. 41 (9): 899–901. PMID 11703479.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Jacob, SE.; Stechschulte, S. "Formaldehyde, aspartame, and migraines: a possible connection". Dermatitis. 19 (3): E10-1. PMID 18627677.
{{cite journal}}: Cite has empty unknown parameter:|month=(help) - ^ Sun-Edelstein, C.; Mauskop, A. (2009). "Foods and supplements in the management of migraine headaches". Clin J Pain. 25 (5): 446–52. doi:10.1097/AJP.0b013e31819a6f65. PMID 19454881.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Millichap, JG.; Yee, MM. (2003). "The diet factor in pediatric and adolescent migraine". Pediatr Neurol. 28 (1): 9–15. PMID 12657413.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Lipton, RB.; Newman, LC.; Cohen, JS.; Solomon, S. (1989). "Aspartame as a dietary trigger of headache". Headache. 29 (2): 90–2. PMID 2708042.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ a b GAO 1987. "Food Additive Approval Process Followed for Aspartame" Full GAO Report United States General Accounting Office, GAO/HRD-87-46, June 18, 1987
- ^ Sugarman, Carole (1983-07-03). "Controversy Surrounds Sweetener". Washington Post. pp. D1–2. Retrieved 2008-11-25.
{{cite news}}: Italic or bold markup not allowed in:|publisher=(help) - ^ Henkel J (1999). "Sugar substitutes. Americans opt for sweetness and lite". FDA Consumer Magazine. 33 (6). DIANE Publishing: 12–6. ISBN 9781422326909. PMID 10628311.
- ^ GAO 1986. "Six Former HHS Employees' Involvement in Aspartame's Approval." United States General Accounting Office, GAO/HRD-86-109BR, July 1986.
- ^ Health Canada: "Aspartame - Artificial Sweeteners". Retrieved 2008-11-08.
- ^ Food Standards Australia New Zealand: "Food Standards Australia New Zealand: Aspartame (September 2007)". Retrieved 2008-11-08.
- ^ Henkel, John (November–December 1999). "Sugar Substitutes: Americans Opt for Sweetness and Lite". FDA Consumer. Retrieved January 29, 2009.
{{cite news}}: Check date values in:|date=(help) - ^ British Pharmacopoeia Commission Secretariat. "Index (BP)" (PDF). Retrieved 16 January 2010.
{{cite web}}: Cite has empty unknown parameter:|coauthors=(help) - ^ United States Pharmacopeia. "Food Ingredient Reference Standards" (PDF). Retrieved 16 January 2010.
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