Aspartame

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    Thomas Solomon

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    Last Updated: April 2, 2024

    Aspartame is a nonnutritive artificial sweetener. It is used as a sugar substitute in soft drinks, candy, chewing gum, and low-calorie foods and is also available as a tabletop sweetener (e.g., Canderel, Hermesetas Gold, NutraSweet, and Pal Sweet).

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    What is aspartame?

    Aspartame is a nonnutritive artificial sweetener used as a food additive in foods, drinks, and some drugs. It is a dipeptide of the naturally occurring amino acids L-aspartic acid and L-phenylalanine.[15][16][3][2]

    Aspartame is most commonly used as a sugar substitute in soft drinks, candy, chewing gum, and low-calorie foods and is also available as a tabletop sweetener, sold under brand names like Canderel, Hermesetas Gold, NutraSweet, and Pal Sweet.

    How is aspartame made?

    What are aspartame’s main benefits?

    It is often claimed that aspartame (and other nonnutritive sweeteners) can suppress appetite, cause weight loss, and improve aspects of cardiometabolic health (e.g., blood glucose control and cholesterol). Because aspartame is a nonnutritive sweetener that is used to replace sugar in some foods and drinks, some people with weight loss goals use aspartame-containing foods and drinks as part of an energy restriction diet. Reducing sugar intake as a way to lower total daily energy intake can help support a weight loss strategy,[17][18][19][20] and some,[21][22][23] but not all,[24][25] studies show that a single dose of aspartame can acutely reduce food intake at the next meal. However, the current evidence does not show long-term health benefits of aspartame on energy intake, weight loss, or cardiometabolic health.[26][27] Consequently, there does not appear to be any direct benefit from ingesting aspartame.

    Do conflicts of interest influence findings from research studies on artificial sweeteners?

    What are aspartame’s main drawbacks?

    Some studies link aspartame with cancer risk, but the evidence is inconsistent. For example, some observational studies show an association between greater aspartame intake and increased cancer risk,[28] whereas others do not.[29] While observational studies can help evaluate the likelihood that a substance — a food additive, nutrient, pollutant, etc. — is involved in disease risk, they cannot prove causality. Observational studies also rely heavily on self-reported dietary intake data, which introduces recall bias. Other types of studies — cell experiments, animal studies, and randomized controlled trials — can help evaluate whether a substance causes a disease. Regulatory bodies then evaluate the strength of all known evidence to determine whether a substance can theoretically cause disease in humans.

    Accordingly, regulatory bodies such as the International Agency for Research on Cancer (IARC) and the Joint Food and Agriculture Organization and World Health Organisation Expert Committee on Food Additives (JECFA) have concluded that aspartame is “possibly carcinogenic” to humans — i.e., there is limited, but not convincing, evidence for aspartame causing cancer in humans and less than sufficient evidence for aspartame causing cancer in experimental animals.[2] Accordingly, food regulatory bodies including the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA), which determine whether foods (and additives) are safe to eat, currently conclude that aspartame is safe for human consumption at current exposure levels.[3] That said, given that some evidence suggests potential adverse effects, regulatory bodies also conclude that further high-quality studies are needed.

    So, in the amounts people are likely to consume, aspartame is unlikely to pose a major risk. However, if people want to reduce their exposure to any potential hazard that might be posed by aspartame, they can choose to avoid foods containing aspartame. For more information, read Does aspartame cause cancer in humans?.

    Does aspartame cause headaches?

    Does aspartame cause cancer in humans?

    How does aspartame work?

    When ingested, aspartame is broken down into its constituent amino acids, L-aspartic acid and L-phenylalanine. Further metabolism of these products produces methanol, formaldehyde, and formic acid in small quantities These chemicals can cause adverse effects in large doses and may, therefore, be implicated in some of the reported adverse effects of aspartame. However, the precise modes of action and fates of these metabolites in the body are not completely understood.[15][16][3][2]

    Like all nonnutritive artificial sweeteners, aspartame has a sweet taste because it activates taste receptors on the tongue.[30] This mechanism might influence sweet taste behavior and increase motivation for sweet foods, but the evidence is mixed and further work is needed to make a firm conclusion.[31][32] Some studies have also shown that a single dose of aspartame can acutely decrease food intake at the next meal.[21][22][23] The current evidence shows that this effect is not driven by changes in the secretion of appetite-regulating gut hormones,[33] but it has been suggested that the increase in blood phenylalanine concentrations following aspartame ingestion may regulate appetite because phenylalanine can cross the blood-brain barrier and can influence neurotransmitter synthesis.[34]

    Although a direct causal effect of aspartame on cancer in humans is unlikely at the current exposure levels, it has been associated with cancer in some observational studies, so it is important to explore the plausible mechanistic bases for a causal link. One possibility is that L-aspartic acid and L-phenylalanine (breakdown products of aspartame) could enter cellular protein synthesis pathways and affect mTOR signaling, which is known to regulate cell growth.[35] L-aspartic acid (aka aspartate) has also been shown to directly regulate cancer cell growth.[36][37] However, these are speculations, and evidence for this comes mainly from in vitro cell experiments.[36][37] Furthermore, humans are exposed to L-aspartic acid and L-phenylalanine every time protein is eaten, and cancer cell metabolism is also regulated by many other metabolites — other amino acids, glucose, etc. — that are essential for life.[35][36][37] This does not mean that such metabolites cause cancer.

    What are other names for Aspartame

    Note that Aspartame is also known as:
    • Methyl aspartylphenylalanine
    • Canderel
    • Hermestas Gold
    • Milisucre
    • Tri-Sweet
    • Nozucar
    • NutraSweet
    • Pal Sweet

    Dosage information

    Dosage Information

    In the US, aspartame and other artificial sweeteners are regulated by the FDA, and products containing aspartame must be approved before they can be used. Because of the potential health risks of aspartame consumption, the FDA has set an acceptable daily intake, which is the maximum amount considered safe to consume each day over a person's lifetime.

    In the US, the FDA has set the acceptable daily intake for aspartame at 50 milligrams per kilogram of body weight per day (mg/kg/day). Meanwhile, the EFSA and the Joint Food and Agriculture Organization and World Health Organisation Expert Committee on Food Additives (JECFA) have set the acceptable daily intake for aspartame at 40 mg/kg/day.[2][3]

    To put these acceptable daily intake values into context, a person weighing 70 kg would have to consume approximately 9–14 cans of diet soda per day to exceed an intake level of 40 mg/kg/day.

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    Frequently asked questions

    What is aspartame?

    Aspartame is a nonnutritive artificial sweetener used as a food additive in foods, drinks, and some drugs. It is a dipeptide of the naturally occurring amino acids L-aspartic acid and L-phenylalanine.[15][16][3][2]

    Aspartame is most commonly used as a sugar substitute in soft drinks, candy, chewing gum, and low-calorie foods and is also available as a tabletop sweetener, sold under brand names like Canderel, Hermesetas Gold, NutraSweet, and Pal Sweet.

    How is aspartame made?

    Aspartame was discovered in 1965 by James Schlatter[40] and can be made using either chemical or enzymatic synthesis methods.[3][41][42]

    Chemical synthesis methods couple the two amino acids that aspartame is composed of, L-aspartic acid and L-phenylalanine. However, chemical synthesis has the limitation that it produces a bitter isomer (β-aspartame) as well as the sweet isomer (α-aspartame) used in aspartame products. These isomers then have to be separated.

    Enzymatic methods are preferable because they use Thermolysin, an enzyme derived from a bacterium called Bacillus thermoproteolyticus, which only produces the sweet isomer (α-aspartame).[43][44][45]

    Due to a lack of information on different manufacturers’ websites, it is unclear exactly which methods are used to produce aspartame by different manufacturers (Canderel, Hermesetas Gold, NutraSweet, Pal Sweet, etc.).

    What are aspartame’s main benefits?

    It is often claimed that aspartame (and other nonnutritive sweeteners) can suppress appetite, cause weight loss, and improve aspects of cardiometabolic health (e.g., blood glucose control and cholesterol). Because aspartame is a nonnutritive sweetener that is used to replace sugar in some foods and drinks, some people with weight loss goals use aspartame-containing foods and drinks as part of an energy restriction diet. Reducing sugar intake as a way to lower total daily energy intake can help support a weight loss strategy,[17][18][19][20] and some,[21][22][23] but not all,[24][25] studies show that a single dose of aspartame can acutely reduce food intake at the next meal. However, the current evidence does not show long-term health benefits of aspartame on energy intake, weight loss, or cardiometabolic health.[26][27] Consequently, there does not appear to be any direct benefit from ingesting aspartame.

    Do conflicts of interest influence findings from research studies on artificial sweeteners?

    In 2016, an “umbrella” systematic review compiled all known reviews examining the effects of artificially sweetened beverages on weight outcomes.[39] The systematic review sought to determine whether study findings were influenced by authors’ conflicts of interest, finding that reviews sponsored by the artificial sweetener industry were seventeen times more likely to have favorable results and two times more likely to have favorable conclusions than non-industry-sponsored reviews. Furthermore, reviews performed by authors with a food industry-related financial conflict of interest were seven times more likely to have favorable conclusions than reviews performed by authors without conflicts of interest.

    What are aspartame’s main drawbacks?

    Some studies link aspartame with cancer risk, but the evidence is inconsistent. For example, some observational studies show an association between greater aspartame intake and increased cancer risk,[28] whereas others do not.[29] While observational studies can help evaluate the likelihood that a substance — a food additive, nutrient, pollutant, etc. — is involved in disease risk, they cannot prove causality. Observational studies also rely heavily on self-reported dietary intake data, which introduces recall bias. Other types of studies — cell experiments, animal studies, and randomized controlled trials — can help evaluate whether a substance causes a disease. Regulatory bodies then evaluate the strength of all known evidence to determine whether a substance can theoretically cause disease in humans.

    Accordingly, regulatory bodies such as the International Agency for Research on Cancer (IARC) and the Joint Food and Agriculture Organization and World Health Organisation Expert Committee on Food Additives (JECFA) have concluded that aspartame is “possibly carcinogenic” to humans — i.e., there is limited, but not convincing, evidence for aspartame causing cancer in humans and less than sufficient evidence for aspartame causing cancer in experimental animals.[2] Accordingly, food regulatory bodies including the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA), which determine whether foods (and additives) are safe to eat, currently conclude that aspartame is safe for human consumption at current exposure levels.[3] That said, given that some evidence suggests potential adverse effects, regulatory bodies also conclude that further high-quality studies are needed.

    So, in the amounts people are likely to consume, aspartame is unlikely to pose a major risk. However, if people want to reduce their exposure to any potential hazard that might be posed by aspartame, they can choose to avoid foods containing aspartame. For more information, read Does aspartame cause cancer in humans?.

    Does aspartame cause headaches?

    Some case studies of individual people have reported headaches or migraine occurring after aspartame ingestion.[4][5][6] Furthermore, the Center for Disease Control (CDC) found that 67% (346/517) of people submitting a complaint about aspartame reported neurological/behavioral symptoms, including headaches, dizziness, and mood alterations after consuming aspartame-containing products.[7] Therefore, headaches are among the complaints about aspartame, but neither the data from the CDC nor observations from isolated case studies prove that aspartame causes headaches in all people.

    To explore whether there is a causal link between aspartame and headaches, some randomized controlled trials have been completed. They show that the incidence of headaches after a single dose of aspartame does not differ from that after a placebo.[8] Meanwhile, daily administration of aspartame has increased headache frequency in some[9][10] but not all studies.[11] However, it is important to note that these studies include a small number of participants and the quality of their design and statistical approaches have been debated.[12][13][14]

    Consequently, the low number of case studies and complaints suggests that aspartame-associated headaches are rare in the general population, and it is currently unclear whether aspartame consumption directly causes headaches or not. Further high-quality clinical trials would help remedy that lack of clarity. In the meantime, people who are susceptible to headaches following consumption of aspartame or aspartame-containing foods can choose to avoid such products.

    Does aspartame cause cancer in humans?

    The clinical evidence is mixed: Some observational studies show that higher levels of dietary aspartame intake are associated with an increased risk of some cancers,[28] while other observational studies do not support that relationship.[29] The current evidence also doesn’t show a dose response between aspartame intake and cancer risk,[28][29] and no long-term randomized controlled trials of aspartame intake have investigated cancer outcomes. Therefore, the direct causality between aspartame exposure and cancer cannot yet be determined.

    For these reasons, aspartame has been classified by the International Agency for Research on Cancer (IARC) and the Joint Food and Agriculture Organization and World Health Organisation Expert Committee on Food Additives (JECFA) as a “Group 2B” (possibly carcinogenic) compound in a four-group classification system.[2]

    To help put this classification in context, Group 1 means “carcinogenic to humans”, and includes things like solar radiation, processed meat, tobacco smoking, and air pollution. Group 2A means “probably carcinogenic to humans”, and includes eating red meat, anabolic steroids, indoor fireplace emissions, etc. Group 3 means “not classifiable regarding its carcinogenicity to humans”. Interestingly, the classification for aspartame — Group 2B — contains other common foods and supplements including pickled vegetables, aloe vera, kava extract, and caffeic acid (which is found in all plants, including coffee), and many other substances humans are exposed to daily.

    Consequently, while aspartame is “possibly carcinogenic” (has the potential to cause cancer), aspartame intake in the amounts that are typically consumed is unlikely to cause cancer in humans (a person weighing 70 kg would have to consume approximately 9–14 cans of diet soda per day to exceed the acceptable daily intake level of 40 mg/kg/day). This is the current message conveyed by food regulatory bodies in the US — the FDA — and in Europe — the EFSA.[3] However, this message might change when more high-quality clinical studies are completed.

    It’s also important to note that it is challenging to prove that foods cause cancer in humans, because much of the evidence relies on observational studies that are unable to prove causality. For example, observational studies have shown that most common food ingredients are associated with both an increased and a decreased cancer risk, whereas meta-analyses of such studies find that the claimed benefits of such foods are nonexistent.[38]

    To summarize, the current evidence does not show that aspartame causes cancer in humans but the evidence doesn’t rule out that it can — absence of evidence is not evidence of absence. While aspartame is unlikely to pose a major risk, it is a food additive and not an essential nutrient; therefore, people can choose to avoid foods that contain aspartame to remove the exposure to any potential hazard.

    How does aspartame work?

    When ingested, aspartame is broken down into its constituent amino acids, L-aspartic acid and L-phenylalanine. Further metabolism of these products produces methanol, formaldehyde, and formic acid in small quantities These chemicals can cause adverse effects in large doses and may, therefore, be implicated in some of the reported adverse effects of aspartame. However, the precise modes of action and fates of these metabolites in the body are not completely understood.[15][16][3][2]

    Like all nonnutritive artificial sweeteners, aspartame has a sweet taste because it activates taste receptors on the tongue.[30] This mechanism might influence sweet taste behavior and increase motivation for sweet foods, but the evidence is mixed and further work is needed to make a firm conclusion.[31][32] Some studies have also shown that a single dose of aspartame can acutely decrease food intake at the next meal.[21][22][23] The current evidence shows that this effect is not driven by changes in the secretion of appetite-regulating gut hormones,[33] but it has been suggested that the increase in blood phenylalanine concentrations following aspartame ingestion may regulate appetite because phenylalanine can cross the blood-brain barrier and can influence neurotransmitter synthesis.[34]

    Although a direct causal effect of aspartame on cancer in humans is unlikely at the current exposure levels, it has been associated with cancer in some observational studies, so it is important to explore the plausible mechanistic bases for a causal link. One possibility is that L-aspartic acid and L-phenylalanine (breakdown products of aspartame) could enter cellular protein synthesis pathways and affect mTOR signaling, which is known to regulate cell growth.[35] L-aspartic acid (aka aspartate) has also been shown to directly regulate cancer cell growth.[36][37] However, these are speculations, and evidence for this comes mainly from in vitro cell experiments.[36][37] Furthermore, humans are exposed to L-aspartic acid and L-phenylalanine every time protein is eaten, and cancer cell metabolism is also regulated by many other metabolites — other amino acids, glucose, etc. — that are essential for life.[35][36][37] This does not mean that such metabolites cause cancer.

    Update History

    Full FAQ and database update

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    We fully updated this page, and have added a number of new FAQs, including ones about how aspartame is made, whether it causes headaches and cancer, and how industry involvement may influence the findings of the studies we cite.

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    References

    1. ^van Spronsen FJ, Blau N, Harding C, Burlina A, Longo N, Bosch AMPhenylketonuria.Nat Rev Dis Primers.(2021-May-20)
    2. ^Joint FAO/WHO Expert Committee on Food Additives (JECFA)Joint IARC and JECFA summary of findings of the evaluation of aspartame including Q&A. World Health Organization(2023 July)
    3. ^EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS)Scientific Opinion on the re-evaluation of aspartame (E 951) as a food additiveEFSA Journal.(2013 Dec)
    4. ^Johns DRMigraine provoked by aspartame.N Engl J Med.(1986-Aug-14)
    5. ^Jacob SE, Stechschulte SFormaldehyde, aspartame, and migraines: a possible connection.Dermatitis.(2008)
    6. ^Newman LC, Lipton RBMigraine MLT-down: an unusual presentation of migraine in patients with aspartame-triggered headaches.Headache.(2001-Oct)
    7. ^Centers for Disease Control (CDC)Evaluation of consumer complaints related to aspartame use.MMWR Morb Mortal Wkly Rep.(1984 Nov 2)
    8. ^Schiffman SS, Buckley CE, Sampson HA, Massey EW, Baraniuk JN, Follett JV, Warwick ZSAspartame and susceptibility to headache.N Engl J Med.(1987-Nov-05)
    9. ^Koehler SM, Glaros AThe effect of aspartame on migraine headache.Headache.(1988-Feb)
    10. ^Van den Eeden SK, Koepsell TD, Longstreth WT, van Belle G, Daling JR, McKnight BAspartame ingestion and headaches: a randomized crossover trial.Neurology.(1994-Oct)
    11. ^Lindseth GN, Coolahan SE, Petros TV, Lindseth PDNeurobehavioral effects of aspartame consumption.Res Nurs Health.(2014-Jun)
    12. ^Schiffman SAspartame and headache.Neurology.(1995-Aug)
    13. ^Roberts HJAspartame and headache.Neurology.(1995-Aug)
    14. ^Levy PS, Hedeker D, Sanders PGAspartame and headache.Neurology.(1995-Aug)
    15. ^Choudhary AK, Pretorius ERevisiting the safety of aspartameNutr Rev.(2017 Sep 1)
    16. ^National Library of Medicine (US), National Center for Biotechnology InformationPubChem Compound Summary for CID 134601, AspartamePubChem.(2024 Feb)
    17. ^Tobiassen PA, Køster-Rasmussen RSubstitution of sugar-sweetened beverages with non-caloric alternatives and weight change: A systematic review of randomized trials and meta-analysis.Obes Rev.(2024-Feb)
    18. ^Néma D McGlynn, Tauseef Ahmad Khan, Lily Wang, Roselyn Zhang, Laura Chiavaroli, Fei Au-Yeung, Jennifer J Lee, Jarvis C Noronha, Elena M Comelli, Sonia Blanco Mejia, Amna Ahmed, Vasanti S Malik, James O Hill, Lawrence A Leiter, Arnav Agarwal, Per B Jeppesen, Dario Rahelic, Hana Kahleová, Jordi Salas-Salvadó, Cyril W C Kendall, John L SievenpiperAssociation of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysisJAMA Netw Open.(2022 Mar 1)
    19. ^Chen L, Appel LJ, Loria C, Lin PH, Champagne CM, Elmer PJ, Ard JD, Mitchell D, Batch BC, Svetkey LP, Caballero BReduction in consumption of sugar-sweetened beverages is associated with weight loss: the PREMIER trial.Am J Clin Nutr.(2009-May)
    20. ^Blackburn GL, Kanders BS, Lavin PT, Keller SD, Whatley JThe effect of aspartame as part of a multidisciplinary weight-control program on short- and long-term control of body weight.Am J Clin Nutr.(1997-Feb)
    21. ^Rogers PJ, Burley VJ, Alikhanizadeh LA, Blundell JEPostingestive inhibition of food intake by aspartame: importance of interval between aspartame administration and subsequent eating.Physiol Behav.(1995-Mar)
    22. ^Rogers PJ, Blundell JEReanalysis of the effects of phenylalanine, alanine, and aspartame on food intake in human subjects.Physiol Behav.(1994-Aug)
    23. ^Rogers PJ, Keedwell P, Blundell JEFurther analysis of the short-term inhibition of food intake in humans by the dipeptide L-aspartyl-L-phenylalanine methyl ester (aspartame).Physiol Behav.(1991-Apr)
    24. ^Anton SD, Martin CK, Han H, Coulon S, Cefalu WT, Geiselman P, Williamson DAEffects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levelsAppetite.(2010 Aug)
    25. ^Lavin JH, French SJ, Read NWThe effect of sucrose- and aspartame-sweetened drinks on energy intake, hunger and food choice of female, moderately restrained eatersInt J Obes Relat Metab Disord.(1997 Jan)
    26. ^Santos NC, de Araujo LM, De Luca Canto G, Guerra ENS, Coelho MS, Borin MFMetabolic effects of aspartame in adulthood: A systematic review and meta-analysis of randomized clinical trialsCrit Rev Food Sci Nutr.(2018)
    27. ^Higgins KA, Considine RV, Mattes RDAspartame Consumption for 12 Weeks Does Not Affect Glycemia, Appetite, or Body Weight of Healthy, Lean Adults in a Randomized Controlled TrialJ Nutr.(2018 Apr 1)
    28. ^Charlotte Debras, Eloi Chazelas, Bernard Srour, Nathalie Druesne-Pecollo, Younes Esseddik, Fabien Szabo de Edelenyi, Cédric Agaësse, Alexandre De Sa, Rebecca Lutchia, Stéphane Gigandet, Inge Huybrechts, Chantal Julia, Emmanuelle Kesse-Guyot, Benjamin Allès, Valentina A Andreeva, Pilar Galan, Serge Hercberg, Mélanie Deschasaux-Tanguy, Mathilde TouvierArtificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort studyPLoS Med.(2022 Mar 24)
    29. ^Ingrid Toews, Szimonetta Lohner, Daniela Küllenberg de Gaudry, Harriet Sommer, Joerg J MeerpohlAssociation Between Intake of Non-Sugar Sweeteners and Health Outcomes: Systematic Review and Meta-Analyses of Randomised and Non-Randomised Controlled Trials and Observational StudiesBMJ.(2019 Jan 2)
    30. ^Sukumaran SK, Palayyan SRSweet Taste Signaling: The Core Pathways and Regulatory Mechanisms.Int J Mol Sci.(2022-Jul-26)
    31. ^Wilk K, Korytek W, Pelczyńska M, Moszak M, Bogdański PThe Effect of Artificial Sweeteners Use on Sweet Taste Perception and Weight Loss Efficacy: A Review.Nutrients.(2022-Mar-16)
    32. ^Yunker AG, Patel R, Page KAEffects of Non-nutritive Sweeteners on Sweet Taste Processing and Neuroendocrine Regulation of Eating Behavior.Curr Nutr Rep.(2020-Sep)
    33. ^Zhang R, Noronha JC, Khan TA, McGlynn N, Back S, Grant SM, Kendall CWC, Sievenpiper JLThe Effect of Non-Nutritive Sweetened Beverages on Postprandial Glycemic and Endocrine Responses: A Systematic Review and Network Meta-Analysis.Nutrients.(2023-Feb-20)
    34. ^Hall WL, Millward DJ, Rogers PJ, Morgan LMPhysiological mechanisms mediating aspartame-induced satiety.Physiol Behav.(2003-Apr)
    35. ^Jiajun Zhu, Craig B ThompsonMetabolic regulation of cell growth and proliferationNat Rev Mol Cell Biol.(2019 Jul)
    36. ^Lucas B Sullivan, Alba Luengo, Laura V Danai, Lauren N Bush, Frances F Diehl, Aaron M Hosios, Allison N Lau, Sarah Elmiligy, Scott Malstrom, Caroline A Lewis, Matthew G Vander HeidenAspartate is an endogenous metabolic limitation for tumour growthNat Cell Biol.(2018 Jul)
    37. ^Garcia-Bermudez J, Baudrier L, La K, Zhu XG, Fidelin J, Sviderskiy VO, Papagiannakopoulos T, Molina H, Snuderl M, Lewis CA, Possemato RL, Birsoy KAspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours.Nat Cell Biol.(2018-Jul)
    38. ^Schoenfeld JD, Ioannidis JPIs everything we eat associated with cancer? A systematic cookbook reviewAm J Clin Nutr.(2013 Jan)
    39. ^Mandrioli D, Kearns CE, Bero LARelationship between Research Outcomes and Risk of Bias, Study Sponsorship, and Author Financial Conflicts of Interest in Reviews of the Effects of Artificially Sweetened Beverages on Weight Outcomes: A Systematic Review of Reviews.PLoS One.(2016)
    40. ^Mazur RH, Goldkamp AH, James PA, Schlatter JMStructure-taste relationships of aspartic acid amides.J Med Chem.(1970-Nov)
    41. ^Chattopadhyay S, Raychaudhuri U, Chakraborty RArtificial sweeteners - a reviewJ Food Sci Technol.(2014 Apr)
    42. ^Marie K. WalshImmobilized enzyme technology for food applicationsNovel Enzyme Technology for Food Applications.(2007)
    43. ^Yagasaki M, Hashimoto SSynthesis and application of dipeptides; current status and perspectives.Appl Microbiol Biotechnol.(2008-Nov)
    44. ^Richard J. PrankerdAspartameAnalytical Profiles of Drug Substances and Excipients.(2002)
    45. ^Ager et al.Commercial, Synthetic Nonnutritive SweetenersAngew Chem Int Ed.(2004 Feb)
    46. ^Maersk M, Belza A, Stødkilde-Jørgensen H, Ringgaard S, Chabanova E, Thomsen H, Pedersen SB, Astrup A, Richelsen BSucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention studyAm J Clin Nutr.(2011 Dec 28. {Epub ahead of print}di)
    47. ^Tate DF, Turner-McGrievy G, Lyons E, Stevens J, Erickson K, Polzien K, Diamond M, Wang X, Popkin BReplacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trialAm J Clin Nutr.(2012 Mar)
    48. ^Wang YC, Ludwig DS, Sonneville K, Gortmaker SLImpact of change in sweetened caloric beverage consumption on energy intake among children and adolescentsArch Pediatr Adolesc Med.(2009 Apr)
    49. ^Chen L, Appel LJ, Loria C, Lin PH, Champagne CM, Elmer PJ, Ard JD, Mitchell D, Batch BC, Svetkey LP, Caballero BReduction in consumption of sugar-sweetened beverages is associated with weight loss: the PREMIER trialAm J Clin Nutr.(2009 May)
    50. ^Davidson TL, Swithers SEA Pavlovian approach to the problem of obesityInt J Obes Relat Metab Disord.(2004 Jul)
    51. ^Nettleton JA, Lutsey PL, Wang Y, Lima JA, Michos ED, Jacobs DR JrDiet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)Diabetes Care.(2009 Apr)
    52. ^Dhingra R, Sullivan L, Jacques PF, Wang TJ, Fox CS, Meigs JB, D'Agostino RB, Gaziano JM, Vasan RSSoft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the communityCirculation.(2007 Jul 31)
    53. ^Gardener H, Rundek T, Markert M, Wright CB, Elkind MS, Sacco RLDiet Soft Drink Consumption is Associated with an Increased Risk of Vascular Events in the Northern Manhattan StudyJ Gen Intern Med.(2012 Jan 27)
    54. ^Kaplowitz GJAn update on the dangers of soda popDent Assist.(2011 Jul-Aug)
    55. ^Cheng R, Yang H, Shao MY, Hu T, Zhou XDDental erosion and severe tooth decay related to soft drinks: a case report and literature reviewJ Zhejiang Univ Sci B.(2009 May)
    56. ^Shenkin JD, Heller KE, Warren JJ, Marshall TASoft drink consumption and caries risk in children and adolescentsGen Dent.(2003 Jan-Feb)

    Examine Database References

    1. Fasting Glucose - Santos NC, de Araujo LM, De Luca Canto G, Guerra ENS, Coelho MS, Borin MFMetabolic effects of aspartame in adulthood: A systematic review and meta-analysis of randomized clinical trialsCrit Rev Food Sci Nutr.(2018)
    2. Fasting Glucose - Ingrid Toews, Szimonetta Lohner, Daniela Küllenberg de Gaudry, Harriet Sommer, Joerg J MeerpohlAssociation Between Intake of Non-Sugar Sweeteners and Health Outcomes: Systematic Review and Meta-Analyses of Randomised and Non-Randomised Controlled Trials and Observational StudiesBMJ.(2019 Jan 2)
    3. Insulin - Zhang R, Noronha JC, Khan TA, McGlynn N, Back S, Grant SM, Kendall CWC, Sievenpiper JLThe Effect of Non-Nutritive Sweetened Beverages on Postprandial Glycemic and Endocrine Responses: A Systematic Review and Network Meta-Analysis.Nutrients.(2023-Feb-20)