Aspartame

1. What is aspartame?

• 1.1 What is the history of aspartame?
• 1.2 What are the uses and properties of aspartame?
• 1.3 Why is there concern about aspartame?

1.1 What is the history of aspartame?

The source document for this Digest states:

Aspartame was discovered in 1965 by a chemist working for the American company Searle and an initial marketing authorisation (MA) was granted in the United States by the Food and Drug Administration (US-FDA) in 1974. This MA was suspended a few months later following an appeal against the authorisation on the grounds that the toxic and carcinogenic effects on the brain of this compound and its metabolites had not been properly evaluated during the experimental studies. Following a reassessment of the studies on experimental animals and an examination of new data (including a study of carcinogenicity in the rat), the US-FDA granted this product a new MA in 1981 (US-FDA, FR 1981) for use in solid food. This authorisation was extended to soft drinks in 1983 (US-FDA, FR 1983) and for its use as a general sweetener in 1996. The safety of aspartame has been assessed and recognised by a number of other national and international organisations including the FAO/WHO Committee of Experts on Food Additives (JECFA) and, at EU level, by the Scientific Committee on Food. It was authorised by Directive 94/35/EC of the European Parliament and of the Council on sweeteners for use in foodstuffs (adopted on 30 June 1994) and its use is permitted in more than 90 countries. In France, aspartame has been permitted since 1988. The Acceptable Daily Intake (ADI) of aspartame for humans was fixed at 40 mg/kg body weight/day by the JECFA (1980).

In 1996, an article by J.W. Olney suggesting a link between an increased incidence of brain tumours in the United States and the marketing of aspartame relaunched the debate on the risks to human health posed by its consumption. The debate has been covered by the media, notably on the Internet where several thousand websites are devoted to the effects of aspartame. These contain allegations claiming that this additive is responsible for a large number of adverse effects (more than fifty), some of which are very serious, such as: multiple sclerosis, lupus erythematosus, Gulf War Syndrome, brain tumours, epileptic seizures, complications of diabetes, etc. At the same time, the health authorities in a number of countries have reacted by informing the public on the studies available or underway and on the data based on scientific evidence.

Following a recap of the physical and chemical properties of aspartame, this report will review, firstly, the available toxicological and epidemiological data on the effects of this additive on the nervous system (cancer and seizures) and secondly, the estimates of the consumption of this sweetener by the general population and by specific populations such as children and diabetic adolescents. For these specific populations, there may be a potential risk arising from heavy consumption, low body mass or finally, a special metabolic susceptibility.

Source & ©: AFSSA  Aspartame Assessment Report chap. 2: Introduction.

1.2 What are the uses and properties of aspartame?

The source document for this Digest states:

The E number of aspartame in France and Europe is E 951. It was first marketed by NutraSweet AG and more recently by Ajinomoto and Holland Sweetener Company. This sweetener is incorporated into a number of foodstuffs (drinks, desserts, sweets, etc.) and in table sweeteners, under the name Canderel, Pouss-suc and into some 600 medicines; this report does not consider the possible intake (very limited compared with dietary intake) of aspartame from this later source. Its sweetening power is 180 to 200 times greater than that of saccharose.

Aspartame is a dipeptide methyl ester of L-aspartyl-L-phenylalanine. It is a white, odourless, crystalline powder. Its molecular weight is 294.3 Daltons and its rotatory power [a]D22 = 2.3° in 1M HCl.

Its main impurity (approximately 2%) is diketopiperazine, a degradation product of aspartame which has no sweetening properties.

The solubility of aspartame in water is dependent on pH and temperature, the maximum solubility is reached at pH 2.2 (20 mg/ml at 25°C) and the minimum solubility at pH 5.2 (pHi) is 13.5 mg/ml at 25°C.

The stability of aspartame is dependent on time, temperature, pH and water activity (Dziezak, 1986; Bell et al., 1991; Tsoubeli et al., 1991; Homler, 1984; Graves et al., 1987; Huang et al., 1987; Neiderauer, 1998).

Aspartame is very stable in the dry state: at 105°C a loss of approximately 5% (formation of diketopiperazine) is observed after 100 hours of treatment. At 120°C, a 50% loss is obtained after 80 hours of treatment.

In solution, when stored at temperatures ranging from 30 to 80°C, aspartame is progressively degraded into diketopiperazine (Pattanaargson et al., 2000). It is therefore not usable in foods heated at higher temperature (cooking, sterilisation, etc.). At room temperature its stability is good at pH values of between 3.4 and 5 and it is maximum at pH 4.3. At pH below 3.4 the dipeptide is hydrolysed and at a pH greater than 5, cyclisation occurs with the formation of diketopiperazine. In both cases, this transformation results in the loss of sweetness.

In foods with a low or moderate water content (water activities between 0.34 and 0.66), the maximum stability is observed at pH 5.0.

Aspartame has good stability in deep frozen products.

Source & ©: AFSSA  Aspartame Assessment Report
chap. 3: Identity, physical and chemical properties and stability of aspartame.

1.3 Why is there concern about aspartame?

The source document for this Digest states:

The Scientific Committee for Food (EEA) initially evaluated aspartame (L-aspartyl- L-phenylalanine methyl ester) during 1984 (EEA, 1985) and subsequently during 1988 (EEA, 1989). At its 107^th meeting in June 1997, the EEA also examined the issue of an alleged connection between aspartame and increase in incidence of brain tumours in the USA (EEA, 1997).

Aspartame has also been considered by other bodies including the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 1980) the US Food and Drug Administration (US-FDA, 1984), and the UK Committee on Toxicity (COT, 1992). The toxicity data on aspartame were used by the JECFA, EEA and COT to establish an Acceptable Daily Intake (ADI) of 40 mg/kg body weight/day and an ADI of 50 mg/kg bw/d was established by the US-FDA. An ADI of 7.5 mg/kg bw/d was also established for a minor cyclic dipeptide derivative of aspartame, a diketopiperazine (DKP), which is formed in some aqueous solutions (JECFA, 1980; EEA, 1985).

The safety issues that have been raised in the past about aspartame have included: (1) the possibility of toxicity from methanol, one of the breakdown products of aspartame; (2) elevations in plasma concentrations of phenylalanine (Phe) and aspartic acid, which could result in increased transport of these amino acids into the brain, altering the brain's neurochemical composition; (3) the possibility of neuroendocrine changes, particularly increased concentrations in the brain, synaptic ganglia and adrenal medulla of catecholamines derived from Phe and its hydroxylation product, tyrosine; and (4) a postulated link with epilepsy and brain tumours. All these areas have been addressed in the pre-1988 literature and in more recent reviews (Meldrum, 1993; Lajtha et al., 1994; Tschanz et al., 1996).

The safety of aspartame and its metabolic breakdown products (phenylalanine, aspartic acid and methanol) has been assessed in humans generally and in several subgroups, including healthy infants, children, adolescents, adults, obese individuals, diabetics, lactating women, and individuals heterozygous for the genetic disease, phenylketonuria (PKU), who have a compromised ability to metabolise the essential amino acid, Phe.

Since its approval, aspartame has undergone further investigation through clinical and laboratory research, intake studies and postmarketing surveillance of anecdotal reports of adverse health effects.

The present review updates the previous EEA opinions in the light of new reports on the consumption of aspartame in relation to the onset of brain tumours and seizures, headaches, allergies, and changes in behaviour and cognitive function. Information on the safety of aspartame was available from a variety of sources including scientific papers, conference proceedings, abstracts and magazine articles. This review focuses on papers published in the open scientific literature from 1988 to 2001 and draws on the recent extensive review by the Agence Française de Sécurité Sanitaire des Aliments (AFSSA, 2002), which covered mutagenic, carcinogenic and neurological effects.

Source & ©: EC-SCF  Update on the Safety of Aspartame