Safety of aspartame (2014 Update)

Introduction

Aspartame is a dipeptide composed of two amino acids, phenylalanine and aspartic acid, and is used as a food additive for its very sweet taste. It gives food the same sweet taste as sugar, but in much smaller quantities. It allows for sweet-tasting food with a much lower caloric content than sugar. It is one of the most widely used sweetener and is found in a very wide range of ‘diet’ and low-calorie products. There have been over the years many claims on the toxicity of aspartame, in particular its carcinogenicity, and a very large number of studies evaluated in depth the safety of this food additive.

What happens to aspartame in the body?

Aspartame is rapidly and completely broken down in the gastrointestinal tract. It is broken down into the amino acids phenylalanine and aspartic acid (two amino acids that are part of natural proteins) as well as some methanol. The complete digestion of aspartame means that there is no detectable aspartame that enters the bloodstream.

How much aspartame are people exposed to?

This depends greatly on dietary habits. There are regulations that set the maximum amounts of aspartame that can be included in different types of food, but the amounts that are used by food producers can be different (and much lower) than these limits. For instance, in the case of edible ices, the limit is set at 800 mg/kg ice, but the food producers use only 50 mg/kg in it. By using the data of the industry and of food consumption surveys conducted in a number of European countries and using conservative assumptions, an estimated level of exposure was drawn up, as seen in table 8 of the EFSA report, that is copied below:

Table 8: Summary of anticipated exposure to aspartame (E 951) from its use as a food additive using MPLs and reported use levels or analytical data on use levels in five population groups (min-max across the dietary surveys in mg/kg bw/day). High level is defined as the top 5% of the population.

	Toddlers	Children	Adolescents	Adult	The elderly
	(12-35 months)	(3-9 years)	(10-17 years)	(18-64 years)	(>65 years)
Estimated exposure using MPLs
Mean	3.2-16.3	2.3-12.8	0.8-4.0	0.8-8.6	0.5-4.4
High level	11.8-36.9	7.1-32.9	2.3-13.3	2.5-27.5	1.5-23.5
Estimated exposure using reported use levels or analytical data
Mean	1.6-16.3	1.8-12.6	0.8-4.0	0.7-8.5	0.4-4.4
High Level	7.5-36.0	6.3-32.4	2.3-13.2	2.4-27.5	1.4-23.5

Is aspartame toxic and what is its maximal acceptable dose ?

The toxicity of aspartame itself was tested in animals and was found to be very low. From chronic toxicity studies in animals, no adverse effects, except possible developmental toxicity effects related to phenylalanine , which cannot be excluded, were observed at 4000 mg/kg bodyweight/day or below. Based on these observations, and using the common safety margin of 100 times lower than the dose that has no effect of animals, an acceptable daily consumption (Acceptable Daily Intake or ADI) of 40mg/kg bw/day was set for humans. This amount is the equivalent of the quantity of aspartame found in fifteen cans (or over 5L) of diet soda per day, and is well below the exposure of the high level group of consumption in the population as seen in table 8.

The Scientific Committee concluded that aspartame is not of safety concern at the current aspartame exposure estimates and at the ADI of 40 mg/kg bw/day. Regarding the possible developmental effects related to phenylalanine, the Opinion is that in human, the concentration reached in serum after a reasonable consumption of foods containing aspartame would never reach levels above recommended limits.

What happens with the breakdown products of aspartame ?

Since three main breakdown products of aspartame enter into the bloodstream, these have been evaluated for their potential adverse effects.

1. Phenylalanine ¹ at high concentration in the blood is known to cause development problems in humans. Some people suffer from a condition known as phenylketonuria (PKU), a genetic problem that interferes with the phenylalanine metabolism. These people have to follow a strict diet where phenylalanine intake is closely controlled, and these patients tend to suffer from developmental problems. Since it has been established that it is the excess in phenylalanine in the blood that is causing these developmental problems, it has been hypothesized that a large enough phenylalanine intake could also be a cause of development problems in people who do not have the genetic disorder. However, the blood level of phenylalanine needed to cause problems is much higher that what can be reached by a realistic food intake. In order to exceed a phenylalanine plasma concentration, which could cause concern in normal individuals, a repeated bolus administration of aspartame at 40 mg/kg bw (which is equivalent to the current ADI) would need to be given every hour, every day.
2. Methanol is broken down in the body into formaldehyde, then formate, and finally carbon dioxide. Methanol has a well-characterized toxicity, but the amount that people are exposed to, by eating or drinking food and drinks that contain aspartame is so small that it poses no health risk. By the way, methanol is a byproduct in the digestion of other natural molecules, the main one being the metabolism of pectin from fruits and vegetables, which produces a lot more methanol than the breakdown of aspartame.
3. Aspartic acid , another aspartame metabolite, is an amino acid which is itself a neurotransmitter and can be converted to the more potent excitatory neurotransmitter glutamate. However, at the current exposure estimates or at the ADI of 40 mg aspartame/kg bw/day, aspartic acid generated from aspartame is not of safety concern.

¹ The requirement of EU legislation is that products containing aspartame indicate through labeling that they contain a source of phenylalanine.

Could aspartame cause cancer?

Aspartame was shown to be non genotoxic and the results from three chronic toxicity and carcinogenicity studies conducted in rats and in mice revealed no aspartame-related increase in any type of neoplasms at all doses tested. Two more recent long term carcinogenicity studies on aspartame in rats and one in mice were published and made the headlines a few years ago but, when properly evaluated, were considered, including by the US-EPA, to have significant methodological flaws.

Furthermore there is no epidemiological evidence for possible associations of aspartame with various cancers in the human population.

Could aspartame cause reproductive diseases?

About 20 studies were made to study the potential of aspartame to produce reproductive disease. From the results, the Panel identified that a dose of 1000 mg aspartame/kg bw/day has no adverse effect for maternal (weight loss) and developmental toxicity (weight loss and malformations).

Conclusion

After its re-evaluation of aspartame (E 951) as a food additive, the EFSA Panel concluded that aspartame was not of safety concern related to its consumption at the current acceptable daily intake (ADI) of 40 mg/kg bw/day. Therefore, they concluded also that there was no reason to revise this current ADI for aspartame.

The Panel emphasized however that its evaluation of phenylalanine plasma levels from a dose of aspartame at the ensuing ADI is not applicable to patients suffering of phenylketonurea (PKU).

These individuals require total control of their global dietary phenylalanine intake to manage the risk from elevated phenylalanine plasma levels. The Panel underlined that the requirement of EU legislation is that products containing aspartame indicate through labeling that they contain a source of phenylalanine.