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Research Article

Aspartame: A Safety Evaluation Based on Current Use Levels, Regulations, and Toxicological and Epidemiological Studies

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Pages 629-727 | Published online: 10 Oct 2008
 

Abstract

Aspartame is a methyl ester of a dipeptide used as a synthetic nonnutritive sweetener in over 90 countries worldwide in over 6000 products. The purpose of this investigation was to review the scientific literature on the absorption and metabolism, the current consumption levels worldwide, the toxicology, and recent epidemiological studies on aspartame. Current use levels of aspartame, even by high users in special subgroups, remains well below the U.S. Food and Drug Administration and European Food Safety Authority established acceptable daily intake levels of 50 and 40 mg/kg bw/day, respectively. Consumption of large doses of aspartame in a single bolus dose will have an effect on some biochemical parameters, including plasma amino acid levels and brain neurotransmitter levels. The rise in plasma levels of phenylalanine and aspartic acid following administration of aspartame at doses less than or equal to 50 mg/kg bw do not exceed those observed postprandially. Acute, subacute and chronic toxicity studies with aspartame, and its decomposition products, conducted in mice, rats, hamsters and dogs have consistently found no adverse effect of aspartame with doses up to at least 4000 mg/kg bw/day. Critical review of all carcinogenicity studies conducted on aspartame found no credible evidence that aspartame is carcinogenic. The data from the extensive investigations into the possibility of neurotoxic effects of aspartame, in general, do not support the hypothesis that aspartame in the human diet will affect nervous system function, learning or behavior. Epidemiological studies on aspartame include several case-control studies and one well-conducted prospective epidemiological study with a large cohort, in which the consumption of aspartame was measured. The studies provide no evidence to support an association between aspartame and cancer in any tissue. The weight of existing evidence is that aspartame is safe at current levels of consumption as a nonnutritive sweetener.

Notes

1The sterilization process involves heat treatment at 105°C for 5 s using a heat plate exchanger (personal communication).

2 Water activity is a measure of the amount of water available for microbial growth. It is defined as the ratio of the vapor pressure of water in a solution to the vapor pressure of pure water (Vaclavik and Christian, Citation2003).

3 Fruit cream is a custard dessert containing fruit and cream.

7 http://www.ers.usda.gov/ (site visited May 10, 2006).

8CSFII data from 1996 was used for the analysis (U.S. population of 265,462,901 taken from the U.S. Census Bureau, Department of Commerce, www.census.gov/cgi-bin/ipc/idbrank.pl).

9 Not all food products have been reported to be consumed in the CSFII survey database. Therefore, the “Eaters only” consumption may be based on a subset of the foods found in Appendix II.

10 ip = intraperitoneal or within the peritoneal cavity (Stedman's Medical Dictionary, 1995c).

11 Phenylketonuria (PKU) is also called Folling's disease. It is congenital deficiency of phenylalanine 4-monooxygenase causing inadequate formation of L-tyrosine, elevation of serum L-phenylalanine, urinary excretion of phenylpyruvic acid and other derivatives, and accumulation of phenylalanine and its metabolites, which can produce brain damage resulting in severe mental retardation, often with seizures, other neurologic abnormalities such as retarded myelination, and deficient melanin formation leading to hypopigmentation of the skin and eczema; it follows autosomal recessive inheritance (Stedman's Medical Dictionary, 1995k).

12 Shelley Case, a registered dietitian, is a leading North American nutrition expert on celiac disease and the gluten-free diet. She is the author of The Gluten-Free Diet, and a member of the Medical Advisory Boards of the Celiac Disease Foundation and Gluten Intolerance Group in the United States and the Professional Advisory Board of the Canadian Celiac Association. http://www.glutenfreediet.ca, Site visited October 1, 2006.

13 HPLC, high-performance liquid chromatography.

14 LDL, low-density lipoprotein.

15 VLDL, very-low-density lipoprotein.

16 The Corticella diet is used exclusively by the European Ramazzini Foundation of Oncology and Environmental Sciences. The composition was not reported.

17 Pyelonephritis = inflammation of the renal parenchyma, calyces, and pelvis, particularly due to local bacterial infection (Stedman's Medical Dictionary, 1995m).

18 Pleuritis = inflammation of the pleura (Stedman's Medical Dictionary, 1995l).

19 Peritonitis = inflammation of the peritoneum (Stedman's Medical Dictionary, 1995j).

20 Pericarditis = inflammation of the pericardium (Stedman's Medical Dictionary, 1995i).

21 Meningitis = inflammation of the membranes of the brain or spinal cord (Stedman's Medical Dictionary, 1995e).

24Metrazol is a convulsant which induces clonic-tonic convulsions (Guiso et al., Citation1988).

25 Quinolinic acid is 2,3-pyridinedicarboxylic acid; a catabolite of tryptophan and a precursor of nicotinic acid. When administered into the hippocampus, this compound causes as seizure similar to human epilepsy of the temporal lobe (Guiso et al., Citation1988; Stedman's Medical Dictionary, 1995n).

26 ED50 = dose that induced convulsions or seizures in 50% of the animals.

27 Pentylenetetrozole is a powerful stimulant to the central nervous system; used to cause generalized convulsion in the shock treatment of emotional states and as a respiratory stimulant (Stedman's Medical Dictionary, 1995h).

28 Fluorothyl is bis (2,2,2-trifluoroethyl) ether; a convulsant primarily used in experimental animals. It was formerly used to induce convultions as a alternative to electroshock therapy; http://www.online-medical-dictionary.org/omd.asp? = Fluorothyl.

29 CD50 is the dose that induces convulsions in 50% of the animals (Pinto and Maher, Citation1988a).

30 Kindling is long-lasting epileptogenic changes induced by daily subthreshold electrical brain stimulation without apparent neuronal damage (Stedman's Medical Dictionary, 1995d).

31 Clonic = a rapid succession of alternating contractions and partial relaxations of a muscle occurring in some nervous diseases (Merriam Webster, 2006a).

32 Tonic = marked by prolonged muscular contraction (Merriam Webster, 2006b).

33 Myoclonus is clonic spasm or twitching of a muscle or group of muscles (Stedman's Medical Dictionary, 1995f).

34 Coloboma: Any defect, congenital, pathologic, or artificial, especially of the eye (Stedman's Medical Dictionary, 1995a).

35 Microphthalmos: Abnormal smallness of one or both eyeballs.

36 Anophthalmos: Congenital absence of all tissues of the eyes.

37 Anarchic globes: Globes of the eye lacking order, regularity, or definiteness.

38 Urticaria: An allergic disorder marked by raised edematous patches of skin or mucous membrane and usually intense itching and caused by contact with a specific precipitating factor (as a food, drug, or inhalant) either externally or internally (Stedman's Medical Dictionary, 1995o).

39 Panniculitis: Inflammation of subcutaneous adipose tissue (Stedman's Medical Dictionary, 1995g).

40 EEG = electroencephalogram (Stedman's Medical Dictionary, 1995b).

41 The food categories contained in this report were identified by the client and the most reasonable food codes fitting these categories were selected by the Burdock Group.

42 Source: HHS What We Eat in America, National Health and Nutrition Examination Survey (NHANES) 2001–2002, USDA.

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