Aspartame, updated assessment of risks on health, cancer and pregnancy

Introduction

In 2011 and 2013, EFSA updated its opinion on the basis of the most recent studies on aspartame.

Original reports, previous evaluations, additional literature and data made available following a public call were evaluated. The present includes the assessment of all unpublished studies, together with the published literature identified until the end of November 2012.

The Scientific Panel on food Additives and Nutrient Sources (ANS) of the European Food Safety Authority (EFSA) is comprised of experts in risk assessment of various European nationalities highly skilled and with expertise in all relevant areas.

What is aspartame?

Aspartame (L-aspartyl-L-phenylalanine methyl ester) (E 951) is a dipeptide of L-phenylalanine methyl ester and L-aspartic acid, which are two amino acids usually found in proteins. It is used as an artificial sweetener authorised as a food additive in the EU. After oral ingestion, aspartame is rapidly and completely hydrolysed in the gastrointestinal tract to its degradation products, which are mostly phenylalanine, aspartic acid, and methanol.

The exposure to these degradation products was taken into account in the safety evaluation and, as a whole, the total estimated uncertainty from all sources generally lead to an overestimation of the calculated exposures, thus providing conservative estimates.

What is phenylketonuria and what is its relationship with aspartame?

Some humans show a slightly reduced capacity to eliminate phenylalanine compared to normal individuals, and some (the so-called phenylketonuria (PKU) patients) have a markedly reduced capacity for phenylalanine elimination or “metabolism”. In particular, PKU mothers with poorly controlled phenylalanine intake in their diet during pregnancy may give birth to babies with congenital heart diseases, microcephaly and impaired neurological function. If their phenylalanine intake via the diet is not strictly controlled, PKU babies may show severe impairment in development and cognition.

This is why it is recommended to persons suffering from phenylketonuria to not consume aspartame, which is a source of phenylalanine. Most of the food items in which aspartame is authorised are subject to limitations.

Is aspartame representing a health risk and where the EFSA conclusions of its previous risk evaluation of aspartame modified?

The toxicity of aspartame was tested in mice, rats, rabbits and dogs and was found to be very low. The possibility of developmental toxicity occurring at doses lower than 4000 mg/kg in animals could not be excluded but was mainly attributable to phenylalanine. Meanwhile, in calculating a safe level of aspartame exposure (based on plasma phenylalanine concentrations), the expert Panel of EFSA assumed the worst-case scenario, and concluded that aspartame consumption was not of safety concern at the current aspartame and its degradation products exposure estimates, which are below their respective Acceptable Daily Intake (ADI) recommended in 2006 (40 mg/kg bw/day for aspartame). In calculating a safe level of aspartame exposure (based on plasma phenylalanine concentrations), the Panel assumed the worst-case scenario. Therefore, there was no reason to revise the ADI of aspartame, which however is not applicable to PKU patients who should limit as much as possible their exposure to any source of phenylalanine, including in their regular diet.

The Panel noted that in all the repeat aspartame administration studies, where human healthy adults, children or patients suffering various diseases, including PKU individuals, received daily dose of aspartame above the current ADI of 40 mg/kg/day for periods up to 6 months, no significant increase in plasma phenylalanine concentration was observed. Therefore, that there is no risk of phenylalanine accumulation in such human populations with normal uses levels of aspartame (at or below the ADI). Conservative estimates of exposure to aspartame made by the Panel for the general population were up to 36 mg/kg bw/day at the 95th percentile (the highest consumers), thus below the ADI.

What about the results of the carcinogenicity studies not considered in the previous evaluation?

The Panel noted there was no epidemiological evidence for possible association of aspartame with various cancers in the human population. Furthermore, no new data demonstrated a genotoxic or carcinogenic potential of aspartame. In particular the results of the carcinogenicity study on aspartame conducted in mice in 2010 did not provide a sufficient basis to reconsider the previous evaluations by EFSA. Regarding the lymphomas and leukemias observed in a 2007 study, these changes were not considered as related to the aspartame treatment due to weaknesses in the study protocol. Similarly, the reported increased incidence of breast carcinomas in animal experiments had also not been considered to indicate a carcinogenic potential of aspartame.

The Panel also noted there was no epidemiological evidence for possible associations of aspartame with various cancers in the human population.

Are there risks of developmental effects on the foetus or premature delivery?

Many experimental studies were conducted on the potential toxicity of aspartame on reproduction and development. For the risk of developmental toxicity, EFSA concluded that human data were more appropriate for the risk assessment, and concluded that developmental toxicity in animals was attributable to phenylalanine. Phenylalanine at high plasma levels is known to cause developmental toxicity in humans.

The Panel considered that, in addition to exposure to phenylalanine from the regular diet, a realistic dietary intake of aspartame up to the ADI of 40 mg/kg bw/day would not result in peak plasma phenylalanine levels exceeding 240 µM in normal or PKU heterozygous individuals, that is well below the concentrations at which adverse effects in the foetus are reported. This is also below the current clinical guideline (360 µM) for prevention of effects in the foetuses of pregnant PKU patients.

Regarding a risk of premature delivery, EFSA also considered an epidemiological study (study based on human exposure data) on its relationship with consumption of artificially sweetened soft drinks and concluded that there was no evidence from this study to support a causal relationship. However, additional studies are required to definitively conclude on such an association.

What were the conclusions of other evaluations of aspartame made by European and US health authorities?

During the 1980s, the use of aspartame was allowed for use in foods and as a tabletop sweetener by several member states and through the European legislation introduced in 1994 to harmonize its use in foods, this after thorough evaluations made by the Scientific Committee for Food (SCF) in 1984 and 1988. Further reviews of data on aspartame were also conducted by the SCF in 1997 and 2002. In 2006, based on all available evidence, studies and previous evaluations, EFSA had already considered there was no reason to revise the previously established ADI for aspartame (EFSA, 2006).

Similarly, the US Food and Drug Administration (FDA) reviewed in 2007 the data made available to them by the authors of a new carcinogenicity study and identified significant shortcomings in the design, conduct, reporting, and interpretation of this study. The FDA found that the reliability and interpretation of the study outcome was compromised by these shortcomings and uncontrolled variables, such as the presence of infection in the test animals. On this basis, the FDA found that it did not support the conclusion of the authors of the study that aspartame is a carcinogen. Additionally, these data did not provide evidence to alter FDA’s previous conclusion that the use of aspartame is safe.

http://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/ucm208580.htm 

There was no significant and more recent risk assessment published on aspartame