NNNS: Adverse Effects (2011)
Aspartame and Adverse Effects
- General Population
- Special Populations
Only non-nutritive sweeteners approved by the FDA and considered to be safe for human consumption are included in the N&NNS evidence analysis project. These include: acesulfame-K, aspartame, neotame, saccharin, stevia, and sucrolose.
The Academy does not evaluate safety; however we do summarize the human subject research published in peer-reviewed journals regarding adverse effects.
-
Assessment
What is the evidence from human subjects research that aspartame consumption is associated with adverse effects in the general population?
-
Conclusion
Aspartame consumption is not associated with adverse effects in the general population. Studies have found no evidence of a wide range of adverse effects of aspartame including hypersensitivity reactions, elevated blood methanol or formate levels and hematopoeitic or brain cancers. Neurological changes tested included cognitive functions, seizures, headaches and changes in memory or mood.
The 2009 update did not find new studies meeting the inclusion criteria for this question and the N&NNS workgroup (2009) concurs with the conclusion above formulated by the Aspartame workgroup (2008).
-
Grade: I
- Grade I means there is Good/Strong evidence supporting the statement;
- Grade II is Fair;
- Grade III is Limited/Weak;
- Grade IV is Expert Opinion Only;
- Grade V is Not Assignable.
- High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
- Moderate (B) means we are moderately confident in the effect estimate;
- Low (C) means our confidence in the effect estimate is limited;
- Very Low (D) means we have very little confidence in the effect estimate.
- Ungraded means a grade is not assignable.
-
Evidence Summary: What is the evidence from human subjects research that aspartame consumption is associated with adverse effects in the general population?
- Detail
- Quality Rating Summary
For a summary of the Quality Rating results, click here.
- Worksheets
- Butchko HH, Stargel WW. Aspartame: scientific evaluation in the postmarketing period. Regul Toxicol Pharmacol. 2001 Dec; 34 (3): 221-233. PMID: 11754527.
- Butchko HH, Stargel WW. Aspartame: scientific evaluation in the postmarketing period. Regul Toxicol Pharmacol. 2001 Dec; 34 (3): 221-233. PMID: 11754527.
- Garriga MM, Berkebile C, Metcalfe DD. A combined single-blind, double-blind, placebo-controlled study to determine the reproducibility of hypersensitivity reactions to aspartame. J Allergy Clin Immunol. 1991 Apr; 87 (4): 821-827.
- Garriga MM, Berkebile C, Metcalfe DD. A combined single-blind, double-blind, placebo-controlled study to determine the reproducibility of hypersensitivity reactions to aspartame. J Allergy Clin Immunol. 1991 Apr; 87 (4): 821-827.
- Geha R, Buckley CE, Greenberger P, Patterson R, Polmar S, Saxon A, Rohr A, Yang W, Drouin M. Aspartame is no more likely than placebo to cause urticaria/angioedema: Results of a multicenter, randomized, double-blind, placebo-controlled, crossover study. J Allergy Clin Immunol. 1993 Oct; 92 (4): 513-520.
- Geha R, Buckley CE, Greenberger P, Patterson R, Polmar S, Saxon A, Rohr A, Yang W, Drouin M. Aspartame is no more likely than placebo to cause urticaria/angioedema: Results of a multicenter, randomized, double-blind, placebo-controlled, crossover study. J Allergy Clin Immunol. 1993 Oct; 92 (4): 513-520.
- Knopp RH, Brandt K, Arky RA. Effects of aspartame in young persons during weight reduction. J Toxicol Environ Health. 1976 Nov; 2 (2): 417-428.
- Knopp RH, Brandt K, Arky RA. Effects of aspartame in young persons during weight reduction. J Toxicol Environ Health. 1976 Nov; 2 (2): 417-428.
- Lapierre KA, Greenblatt DJ, Goddard JE, Harmatz JS, Shader RI. The neuropsychiatric effects of aspartame in normal volunteers. J Clin Pharmacol. 1990; 30 (5): 454-460.
- Lapierre KA, Greenblatt DJ, Goddard JE, Harmatz JS, Shader RI. The neuropsychiatric effects of aspartame in normal volunteers. J Clin Pharmacol. 1990; 30 (5): 454-460.
- Leon AS, Hunninghake DB, Bell C, Rassin DK, Tephly TR. Safety of long-term large doses of aspartame. Arch Intern Med. 1989 Oct; 149 (10): 2,318-2,324.
- Leon AS, Hunninghake DB, Bell C, Rassin DK, Tephly TR. Safety of long-term large doses of aspartame. Arch Intern Med. 1989 Oct; 149 (10): 2,318-2,324.
- Lim U, Subar AF, Mouw T, Hartge P, Morton LM, Stolzenberg-Solomon R, Campbell D, Hollenbeck AR, Schatzkin A. Consumption of aspartame-containing beverages and incidence of hematopoietic and brain malignancies. Cancer Epidemiol Biomarkers Prev. 2006 Sep; 15 (9): 1,654-1,659.
- Lim U, Subar AF, Mouw T, Hartge P, Morton LM, Stolzenberg-Solomon R, Campbell D, Hollenbeck AR, Schatzkin A. Consumption of aspartame-containing beverages and incidence of hematopoietic and brain malignancies. Cancer Epidemiol Biomarkers Prev. 2006 Sep; 15 (9): 1,654-1,659.
- London RS. Saccharin and aspartame. Are they safe to consume during pregnancy? J Reprod Med. 1988 Jan; 33 (1): 17-21.
- London RS. Saccharin and aspartame. Are they safe to consume during pregnancy? J Reprod Med. 1988 Jan; 33 (1): 17-21.
- Pivonka EEA, Grunewald KK. Aspartame- or sugar-sweetened beverages: effects on mood in young women. J Am Diet Assoc. 1990; 90: 250-254.
- Pivonka EEA, Grunewald KK. Aspartame- or sugar-sweetened beverages: effects on mood in young women. J Am Diet Assoc. 1990; 90: 250-254.
- Rowan AJ et al. Aspartame and seizure susceptibility: results of a clinical study in reportedly sensitive individuals. Epilepsia. 1995 Mar; 36 (3): 270-275.
- Rowan AJ et al. Aspartame and seizure susceptibility: results of a clinical study in reportedly sensitive individuals. Epilepsia. 1995 Mar; 36 (3): 270-275.
- Ryan-Harshman M, Leiter LA, Anderson H. Phenylalanine and aspartame fail to alter feeding behavior, mood and arousal in men. Physiology and Behavior. 1987; 39(2): 247-253.
- Ryan-Harshman M, Leiter LA, Anderson H. Phenylalanine and aspartame fail to alter feeding behavior, mood and arousal in men. Physiology and Behavior. 1987; 39(2): 247-253.
- Schiffman SS, Buckley CE III, Sampson HA, Massey EW, Baraniuk JN, Follett JV, Warwick ZS. Aspartame and susceptibility to headache. N Engl J Med. 1987 Nov 5; 317(19): 1,181-1,185.
- Schiffman SS, Buckley CE III, Sampson HA, Massey EW, Baraniuk JN, Follett JV, Warwick ZS. Aspartame and susceptibility to headache. N Engl J Med. 1987 Nov 5; 317(19): 1,181-1,185.
- Spiers PA et al, Aspartame: neuropsychologic and neurophysiologic evaluation of acute and chronic effects. Am J Clin Nutr. 1998 Sep; 68 (3): 531-537.
- Spiers PA et al, Aspartame: neuropsychologic and neurophysiologic evaluation of acute and chronic effects. Am J Clin Nutr. 1998 Sep; 68 (3): 531-537.
- Stokes AF, Belger A, Banich MT, Taylor H. Effects of acute aspartame and acute alcohol ingestion upon the cognitive performance of pilots. Aviat Space Environ Med. 1991; 62: 648-653.
- Stokes AF, Belger A, Banich MT, Taylor H. Effects of acute aspartame and acute alcohol ingestion upon the cognitive performance of pilots. Aviat Space Environ Med. 1991; 62: 648-653.
- Stokes AF, Belger A, Banich MT, Bernadine E. Effects of alcohol and chronic aspartame consumption upon performance in aviation relevant cognitive tasks. Aviation, Space and Environmental Medicine. 1994; 65(1): 7-15.
- Stokes AF, Belger A, Banich MT, Bernadine E. Effects of alcohol and chronic aspartame consumption upon performance in aviation relevant cognitive tasks. Aviation, Space and Environmental Medicine. 1994; 65(1): 7-15.
- Weihrauch MR, Diehl V. Artificial sweeteners-do they bear a carcinogenic risk? Annals of Oncology, 2004, 15: 1,460-1,465.
- Weihrauch MR, Diehl V. Artificial sweeteners-do they bear a carcinogenic risk? Annals of Oncology, 2004, 15: 1,460-1,465.
- Detail
-
Search Plan and Results: NNNS: Aspartame and Adverse Effects 2009
What is the evidence from human subjects research that aspartame consumption is associated with adverse effects in special populations including children?-
Conclusion
A limited number of human studies published in peer-reviewed journals that involved children or special adult populations were available for this question.
Limited evidence from human studies suggests that aspartame consumption is not associated with detrimental effect on blood methanol, eye problems, acne, blood pressure, seizure disorder or attention deficit disorder in children.
There is limited evidence from human studies for three special adult populations. In people with diabetes, aspartame consumption is not associated with elevated plasma phenylalanine and tyrosine levels, fasting glucose control, intolerance to aspartame, opthalmologic effects, heart rhythm or weight. In people with chronic alcoholic liver disease, portal systemic encephalopathy index was unchanged. Levodopa levels were not significantly different in individuals with Parkinson's disease.
The 2009 update did not find new studies meeting the inclusion criteria for this question and the N&NNS workgroup (2009) concurs with the conclusion above formulated by the Aspartame workgroup (2008).
-
Grade: III
- Grade I means there is Good/Strong evidence supporting the statement;
- Grade II is Fair;
- Grade III is Limited/Weak;
- Grade IV is Expert Opinion Only;
- Grade V is Not Assignable.
- High (A) means we are very confident that the true effect lies close to that of the estimate of the effect;
- Moderate (B) means we are moderately confident in the effect estimate;
- Low (C) means our confidence in the effect estimate is limited;
- Very Low (D) means we have very little confidence in the effect estimate.
- Ungraded means a grade is not assignable.
-
Evidence Summary: What is the evidence from human subjects research that aspartame consumption is associated with adverse effects in special populations including children?
- Detail
- Quality Rating Summary
For a summary of the Quality Rating results, click here.
- Worksheets
- Bunin GR, Kushi LH, Gallagher PR, Rorke-Adams LB, McBride ML, Cnaan A. Maternal diet during pregnancy and its association with medulloblastoma in children: a children's oncology group study (United States). Cancer Causes Control. 2005 Sep; 16 (7): 877-891.
- Bunin GR, Kushi LH, Gallagher PR, Rorke-Adams LB, McBride ML, Cnaan A. Maternal diet during pregnancy and its association with medulloblastoma in children: a children's oncology group study (United States). Cancer Causes Control. 2005 Sep; 16 (7): 877-891.
- Butchko HH, Stargel WW. Aspartame: scientific evaluation in the postmarketing period. Regul Toxicol Pharmacol. 2001 Dec; 34 (3): 221-233. PMID: 11754527.
- Butchko HH, Stargel WW. Aspartame: scientific evaluation in the postmarketing period. Regul Toxicol Pharmacol. 2001 Dec; 34 (3): 221-233. PMID: 11754527.
- Camfield PR, Camfield CS, Dooley JM, Gordon K, Jollymore S, Weaver DF. Aspartame exacerbates EEG spike-wave discharge in children with generalized absence epilepsy: a double-blind controlled study. Neurology, 1992 May; 42 (5): 1,000-1,003.
- Camfield PR, Camfield CS, Dooley JM, Gordon K, Jollymore S, Weaver DF. Aspartame exacerbates EEG spike-wave discharge in children with generalized absence epilepsy: a double-blind controlled study. Neurology, 1992 May; 42 (5): 1,000-1,003.
- Frey GH. Use of aspartame by apparently healthy children and adolescents. J Toxicol Environ Health. 1976 Nov; 2 (2): 401-415.
- Frey GH. Use of aspartame by apparently healthy children and adolescents. J Toxicol Environ Health. 1976 Nov; 2 (2): 401-415.
- Gupta V, Cochran C, Parker TF, Long DL, Ashby J, Gorman MA, Liepa GU. Effect of aspartame on plasma amino acid profiles of diabetic patients with chronic renal failure. Am J Clin Nutr. 1989 Jun; 49 (6): 1,302-1,306.
- Gupta V, Cochran C, Parker TF, Long DL, Ashby J, Gorman MA, Liepa GU. Effect of aspartame on plasma amino acid profiles of diabetic patients with chronic renal failure. Am J Clin Nutr. 1989 Jun; 49 (6): 1,302-1,306.
- Hertelendy ZI, Mendenhall CL, Rouster SD, Marshall L, Weesner R. Biochemical and clinical effects of aspartame in patients with chronic, stable alcoholic liver disease. Am J Gastroenterol. 1993 May; 88(5): 737-743.
- Hertelendy ZI, Mendenhall CL, Rouster SD, Marshall L, Weesner R. Biochemical and clinical effects of aspartame in patients with chronic, stable alcoholic liver disease. Am J Gastroenterol. 1993 May; 88(5): 737-743.
- Karstaedt PJ, Pincus JH. Aspartame use in Parkinson's disease. Neurology, 1993 Mar; 43 (3 Pt 1): 611-613.
- Karstaedt PJ, Pincus JH. Aspartame use in Parkinson's disease. Neurology, 1993 Mar; 43 (3 Pt 1): 611-613.
- London RS. Saccharin and aspartame. Are they safe to consume during pregnancy? J Reprod Med. 1988 Jan; 33 (1): 17-21.
- London RS. Saccharin and aspartame. Are they safe to consume during pregnancy? J Reprod Med. 1988 Jan; 33 (1): 17-21.
- Nehrling JK, Kobe P, McLane MP, Olson RE, Kamath S, Horwitz DL. Aspartame use by persons with diabetes. Diabetes Care. 1985, Sep-Oct; 8 (5): 415-417.
- Nehrling JK, Kobe P, McLane MP, Olson RE, Kamath S, Horwitz DL. Aspartame use by persons with diabetes. Diabetes Care. 1985, Sep-Oct; 8 (5): 415-417.
- Saravis S, Schachar R, Zlotkin S, Leiter LA, Anderson GH. Aspartame: effects on learning, behavior and mood. Pediatrics. 1990; 86 (1): 75-83.
- Saravis S, Schachar R, Zlotkin S, Leiter LA, Anderson GH. Aspartame: effects on learning, behavior and mood. Pediatrics. 1990; 86 (1): 75-83.
- Shaywitz BA, Sullivan CM, Anderson GM, Gillespie SM, Sullivan B, Shaywitz SE. Aspartame, behavior, and cognitive function in children with attention deficit disorder. Pediatrics. 1994; 93: 70-75.
- Shaywitz BA, Sullivan CM, Anderson GM, Gillespie SM, Sullivan B, Shaywitz SE. Aspartame, behavior, and cognitive function in children with attention deficit disorder. Pediatrics. 1994; 93: 70-75.
- Stegink LD, Lindgren SD, Brummel MC, Stumbo PJ, Wolraich ML. Erythrocyte L-aspartyl-L-phenylalanine hydrolase activity and plasma phenylalanine and aspartate concentrations in children consuming diets high in aspartame. Am J Clin Nutr. 1995 Dec; 62 (6): 1,206-1,211.
- Stegink LD, Lindgren SD, Brummel MC, Stumbo PJ, Wolraich ML. Erythrocyte L-aspartyl-L-phenylalanine hydrolase activity and plasma phenylalanine and aspartate concentrations in children consuming diets high in aspartame. Am J Clin Nutr. 1995 Dec; 62 (6): 1,206-1,211.
- Stern SB, Bleicher SJ, Flores A, Gombos G, Recitas D, Shu J. Administration of aspartame in non-insulin-dependent diabetics. J Toxicol Environ Health. 1976 Nov; 2 (2): 429-439.
- Stern SB, Bleicher SJ, Flores A, Gombos G, Recitas D, Shu J. Administration of aspartame in non-insulin-dependent diabetics. J Toxicol Environ Health. 1976 Nov; 2 (2): 429-439.
- Stokes AF, Belger A, Banich MT, Taylor H. Effects of acute aspartame and acute alcohol ingestion upon the cognitive performance of pilots. Aviat Space Environ Med. 1991; 62: 648-653.
- Stokes AF, Belger A, Banich MT, Taylor H. Effects of acute aspartame and acute alcohol ingestion upon the cognitive performance of pilots. Aviat Space Environ Med. 1991; 62: 648-653.
- Stokes AF, Belger A, Banich MT, Bernadine E. Effects of alcohol and chronic aspartame consumption upon performance in aviation relevant cognitive tasks. Aviation, Space and Environmental Medicine. 1994; 65(1): 7-15.
- Stokes AF, Belger A, Banich MT, Bernadine E. Effects of alcohol and chronic aspartame consumption upon performance in aviation relevant cognitive tasks. Aviation, Space and Environmental Medicine. 1994; 65(1): 7-15.
- Weihrauch MR, Diehl V. Artificial sweeteners-do they bear a carcinogenic risk? Annals of Oncology, 2004, 15: 1,460-1,465.
- Weihrauch MR, Diehl V. Artificial sweeteners-do they bear a carcinogenic risk? Annals of Oncology, 2004, 15: 1,460-1,465.
- Detail
-
Search Plan and Results: NNNS: Aspartame and Adverse Effects 2009
-
Conclusion