Factsheet
Type:
News
Type:
External Scientific Report
Aspartame is an intense, low-calorie, artificial sweetener. It is a white, odourless powder, approximately 200 times sweeter than sugar. In Europe, it is authorised to be used as a food additive in foodstuffs such as drinks, desserts, sweets, dairy, chewing gums, energy-reducing and weight control products and as a table-top sweetener.
Aspartame and its breakdown products have been the subject of extensive investigation for more than 30 years including experimental animal studies, clinical research, intake and epidemiological studies and post-marketing surveillance. It has been found to be safe and authorised for human consumption for many years and in many countries following thorough safety assessments.
In the EU the label on foodstuffs containing aspartame must state its presence, indicating either its name or its E number (E 951).
Milestones
2013
December
EFSA publishes its first full risk assessment of aspartame. The opinion concludes that aspartame and its breakdown products are safe for the general population (including infants, children and pregnant women).
The acceptable daily intake (ADI) of 40mg/kg bw/day is considered protective for the general population and consumer exposure to aspartame is estimated to be well below this ADI. For patients suffering from the medical condition phenylketonuria, the ADI is not applicable, as they require strict adherence to a diet low in phenylalanine (an amino acid making up proteins found in many foods).
January and April
EFSA holds an online public consultation on its draft scientific opinion on the safety of aspartame, followed by a meeting with interested parties to discuss the feedback received from the online public consultation.
2012
July
During its risk assessment of aspartame EFSA launches a call for data on 5-benzyl-3,6-dioxo-2-piperazine acetic acid (DKP) and other degradation products of aspartame, after experts find that there were insufficient data available on these substances that can form from aspartame in food and beverages when stored under certain conditions.
2011
September
Reaffirming its commitment to openness and transparency, EFSA publishes the full list of scientific studies received following a call for data and makes publicly available previously unpublished scientific data, including the 112 original documents on aspartame which were submitted to support the request for authorisation of aspartame in Europe in the early 1980s.
May
The European Commission asks EFSA to bring forward the full re-evaluation of aspartame, originally planned for completion by 2020 as part of the systematic re-evaluation of all food additives authorised in the EU prior to 20 January 2009.
February
EFSA concludes that two recent publications on artificial sweeteners do not give reason to reconsider previous safety assessments of aspartame or of other sweeteners currently authorised in the EU.
2009
April
EFSA’s experts assess new findings on the carcinogenicity of aspartame in rats and conclude that there is no indication that aspartame is genotoxic or carcinogenic and no reason to revise the ADI for aspartame of 40 mg/kg bw/day.
2006
May
After assessing a long-term carcinogenicity study on aspartame EFSA’s experts conclude that there is no reason to revise the ADI for aspartame of 40 mg/kg bw/day.
EFSA's role
EFSA’s main task in relation to the safety assessment of aspartame is to respond to requests from risk managers for scientific advice and to monitor scientific literature that may affect evaluation of the safety of this substance.
Under the programme for the re-evaluation by 2020 of all food additives authorised prior to 20 January 2009, EFSA is required to re-evaluate the safety of aspartame. This re-evaluation, originally scheduled to be finalised at the latest by 2020, was brought forward to 2013 following a request from the European Commission.
As part of its safety evaluations of food additives EFSA establishes, when possible (i.e. when sufficient scientific information is available), an acceptable daily intake (ADI) for each substance. The ADI is the amount of a substance that people can consume on a daily basis during their whole life without any appreciable risk to health. ADIs are usually expressed in mg per kg of body weight per day (mg/kg bw/day). The ADI can apply to a specific additive or a group of additives with similar properties. When re-evaluating previously authorised additives, EFSA may either confirm, amend or withdraw an existing ADI following review of all available evidence.
Since 2002, EFSA has kept the safety of aspartame under regular review and its scientific panels have issued several opinions on studies related to this sweetener.
EU framework
Aspartame is a food additive. The relevant EU legislation is detailed in the Topic: Food additives (see ‘EU framework’).
During the 1980s, aspartame was authorised for use in foods and as a table-top sweetener by several EU Member States. European legislation harmonising its use in foodstuffs was introduced in 1994 following thorough safety evaluations by the Scientific Committee on Food (SCF) in 1984 and 1988. Further reviews of aspartame data were carried out by the SCF in 1997 and 2002.
FAQ
Background on aspartame:
1. What is aspartame?
Aspartame is a low-calorie, intense sweetener which is approximately 200 times sweeter than sugar.
2. In which food products is aspartame used?
Aspartame is authorised in the EU for use as a food additive to sweeten a variety of foods and beverages such as drinks, desserts, sweets, chewing gum, yogurt, low calorie and weight control products and as a table-top sweetener. Consumers can identify those foodstuffs containing aspartame by looking at the ingredients lists on product labelling. Like all food additives, aspartame has been assigned an “E-number” following authorisation. Its presence in foods can be indicated either by name (i.e. “aspartame”) or by its number E 951.
3. Is it safe to eat products containing aspartame?
Aspartame has been authorised for use in foods and as a table-top sweetener for almost 30 years in many countries throughout the world following thorough safety evaluations. The first safety assessment of aspartame carried out in Europe was published by the Scientific Committee on Food (SCF)[*] in 1984. Subsequent complementary assessments were made by the SCF in 1988, 1997 and 2002. The SCF established in 1984 an Acceptable Daily Intake (ADI) for aspartame of 40 mg/kg body weight. The ADI is an estimate of the amount of a food additive, expressed on a body weight basis that can be ingested daily over a lifetime without appreciable health risk.
EFSA’s Panel on Food Additives and Nutrient Sources Added to Food (ANS Panel) has carried out a full re-evaluation of the safety of aspartame and has concluded that aspartame does not pose a safety concern at current levels of exposure. The Panel considers that the ADI for aspartame set by the SCF is safe for the general population (including infants, children and pregnant women) and consumer exposure to aspartame is below this ADI. It is not applicable to people who suffer from PKU – see Question 4.
EFSA’s Panel on Food Additives and Nutrient Sources Added to Food (ANS Panel) has carried out a full re-evaluation of the safety of aspartame and has concluded that aspartame does not pose a safety concern at current levels of exposure. The Panel considers that the ADI for aspartame set by the SCF is safe for the general population (including infants, children and pregnant women) and consumer exposure to aspartame is below this ADI. It is not applicable to people who suffer from PKU – see Question 4.
[*] The Scientific Committee on Food (SCF) was the former scientific committee of the European Union before EFSA was established in 2002.
4. What is PKU?
Phenylketonuria (PKU) is an inherited disorder that causes high levels of phenylalanine and low levels of tyrosine in the blood. High blood phenylalanine levels are toxic to the brain and can, if left untreated, affect brain development and cause mental retardation, mood disorders and behavioural problems. Most treatment of PKU aims to keep blood phenylalanine at acceptable levels by restriction of foods rich in protein (meat, fish, eggs, dairy products, nuts and seeds), many starchy foods, including those containing flour (bread, pasta), as well as foods and drinks containing aspartame.
5. How much aspartame is it safe to consume?
When risk assessors like EFSA establish an ADI for a given substance, their scientific advice informs the decision-making of risk managers regarding the authorisation of specific proposed uses of the substance (i.e. the foods in which it can be used and the maximum proposed levels of use). For most products containing aspartame, consumption would need to be exceptionally high and regular over a person’s lifetime, in order to exceed the ADI. For instance, to reach the ADI for aspartame (40 mg/kg body weight), an adult weighing 60kg would have to drink 12 (330ml) cans of a diet soft drink (containing aspartame at the maximum permitted levels of use), every day for the rest of his/her life. However, in reality, aspartame is used at lower levels and amounts found in soft drinks can be 3 to 6 times less than the maximum permitted levels; this would increase the number of cans required to meet the ADI to 36 or more.
6. Has EFSA ever evaluated the safety of aspartame?
Since EFSA’s establishment in 2002, the Authority has kept the safety of aspartame under regular review; its scientific panels issued advice on new scientific studies related to this sweetener in 2006, 2009 and 2011, 2013. On all these occasions, the Authority has concluded that the new scientific data did not give reason to review the safety evaluation of aspartame or to revise the ADI.
7. So if aspartame is safe, why has EFSA carried out a full re-evaluation?
By 2020, EFSA must re-evaluate all food additives which were authorised in the EU prior to 20 January 2009, as well as their permitted uses, as set down by Regulation EU 257/2010 on the re-evaluation of approved food additives. Given the enormity of this task, the European Commission established a schedule of priorities for this systematic re-evaluation programme. Most sweeteners, like aspartame, are scheduled for re-evaluation towards the end of the review period as their safety was evaluated more recently than many other additives authorised for use in the EU; for example, colours, many preservatives and emulsifiers were considered more urgent as many of these approved food additives were evaluated several years before sweeteners. However, any food additive can be re-prioritised at any time. In May 2011, EFSA was asked by the European Commission to bring forward the full re-evaluation of the safety of aspartame from 2020 to 2013 after concerns were raised by Members of the European Parliament.
8. Has EFSA finished its new safety review of aspartame?
EFSA published its scientific opinion on the safety of aspartame in December 2013. In January 2013, EFSA launched a online public consultation on its draft opinion, inviting all stakeholders and interested parties to comment by 15 February 2013. As part of this important process and the Authority’s commitment to actively engaging with its stakeholders, on 9 April EFSA held a follow-up meeting with interested parties to discuss its draft opinion and the feedback received from the online public consultation.
- Press release: EFSA wraps up aspartame consultation with public meeting
- Public consultation on the Draft scientific opinion on the re-evaluation of aspartame as a food additive
The re-evaluation of aspartame was carried out by EFSA’s Panel on Food Additives and Nutrient Sources Added to Food (ANS).
9. Why did EFSA have a public consultation for its scientific opinion on aspartame?
The importance of public consultations is set out in EFSA’s Founding Regulation. Alongside scientific excellence, independence and responsiveness, openness and transparency are key values at EFSA and help to underpin consumer confidence in the EU food safety system. In addition, consulting on draft scientific outputs is important to gather views, data sources and comments that can in turn ensure the completeness, clarity and effectiveness of the final outputs.
EFSA regularly consults the scientific community and other stakeholders on its guidance documents and, when compatible with the procedures and deadlines laid down in the relevant EU legislation, also on important scientific outputs of keen public interest such as its opinion on aspartame. This ensures that EFSA considers the widest possible range of views and scientific information. Feedback from the public consultation is then compiled in a report and, where appropriate, incorporated into the final scientific output.
EFSA regularly consults the scientific community and other stakeholders on its guidance documents and, when compatible with the procedures and deadlines laid down in the relevant EU legislation, also on important scientific outputs of keen public interest such as its opinion on aspartame. This ensures that EFSA considers the widest possible range of views and scientific information. Feedback from the public consultation is then compiled in a report and, where appropriate, incorporated into the final scientific output.
10. What were the main results of the public consultation?
During the public consultation, the Authority received a total of 219 comments on its draft opinion. The majority of these were submitted by NGOs and members of the public with most others originating from academia, national food safety agencies, the food industry and journalists. Comments were grouped according to the following main topics: scientific aspects of the opinion; toxicity of methanol (a breakdown product of aspartame) and formaldehyde (a metabolite of methanol); consumer exposure to aspartame; editorial changes; as well as related policy issues (for example, comments mistakenly directed at EFSA about the regulation of aspartame, such as requests to ban this sweetener which are not considered by EFSA given its role as scientific risk assessor).
The Panel considered all comments received. This has ensured that EFSA’s scientific advice fully integrates information received and that those with an interest in this work can easily understand how the Panel derived its conclusions.
11. Why have questions been raised about aspartame in the past?
Prior to its authorisation and since its market introduction, the safety of aspartame has sparked interest and at times controversy. Questions have primarily been raised about some of the early experimental animal studies utilised to evaluate the safety of aspartame. In 2013 EFSA published a full risk assessment of aspartame. Extensive reviews on aspartame have been carried out by many national and international regulatory and advisory bodies. All have concluded that the scientific evidence is sufficient to confirm that aspartame is safe for human consumption.
12. What information did EFSA look at? Has it reviewed the studies submitted with the original application for the authorisation of aspartame in Europe?
The ANS Panel’s comprehensive review was made possible following two public calls for data. As part of its re-evaluation, EFSA launched a public call for scientific data as well as a thorough literature review. The Authority received access to over 600 both published and unpublished scientific studies and datasets following the call for data. Reaffirming its commitment to openness and transparency, EFSA published the full list of these scientific studies and also made publicly available on the EFSA website previously unpublished scientific data including the 112 original documents on aspartame which were submitted to support the request for authorisation of aspartame in Europe in the early 1980s. These studies have been critically evaluated and underpin the discussion points addressed in the opinion.
In the course of its scientific deliberations, the Panel found that there were too little data available on 5-benzyl-3,6-dioxo-2-piperazine acetic acid (DKP) and other potential degradation products that can be formed from aspartame in food and beverages when stored under certain conditions. EFSA therefore launched an additional call for data on DKP and other degradation products of aspartame. The Authority received over 140 studies and datasets as a result of this call.
The ANS Panel considered close to 2,000 studies and datasets during its risk assessment; some 800 of these were received as a result of its two calls for data. The Panel’s opinion references 365 published studies and 147 additional studies received during the calls for data.
Lists of published and unpublished studies and data files available for download:
13. Does EFSA only consider studies funded by industry? Can these studies be trusted?
EFSA considers all available scientific data and scientific literature in its risk assessments and takes account of all evidence that is produced to internationally recognised scientific standards. The Authority may also decide on a case-by-case basis to use data from studies not performed according to current standards when new data are lacking as long as the design of such studies and the reporting of the data are considered appropriate and sound. This holds true whether the source is industry, the public sector, academia or other scientific organisations.
It is a fundamental principle of EU legislation that the organisations or companies set to profit from food additives and other regulated substances and products (e.g. GMOs, active substances used in pesticides), must provide the evidence to prove that these substances are safe. Where new research on a specific substance is required to demonstrate its safety, manufacturers must bear the cost of producing the required data for the risk assessment. Regardless of the source, EFSA critically and rigorously evaluates all the data submitted as well as the design of the studies that produced them to ensure that they meet the standards required to ensure consumer protection. EFSA provides guidance which lays down the specific requirements for the risk assessment of regulated substances and products such as food additives, flavourings, GMOs and food contact materials.
14. The independence of scientific advice given on aspartame has at times been questioned. How does EFSA guarantee the independence of its scientific advice?
Opinions adopted by EFSA’s Scientific Committee and its Scientific Panels are always the outcome of collective deliberations and collective decisions. No one expert, including the Chair, can unduly influence the decisions of the Panels. In those cases where Panels cannot reach consensus on a subject, experts can express minority views which are recorded in the scientific opinions. EFSA is constantly vigilant to potential conflicts of interest whilst recognising that the top scientific experts in Europe can only gain their expertise by being active in their fields. The independence of scientific experts and all those involved in the activities of EFSA is ensured by one of the most rigorous Declaration of Interest policies in force in the world.
- Topic: Independence
15. What are EFSA’s scientists doing to make their decision-making as transparent as possible?
EFSA’s opinion on aspartame is a good example of how scientists are working to better explain and outline their risk assessment approaches in their scientific outputs. The ANS Panel has opted to use what is known as a “mode of action”, or “human relevance” approach in its risk assessment of the safety of aspartame. With this approach, by using the weight of evidence from experimental observations and scientific criteria, scientists identify ‘key events’ or ‘biological steps’ which are a sequence of reactions triggered by a chemical in a living organism (e.g. toxicity, effects on the hormonal system, increased/decreased cell growth). Observations of these key events in human and animal studies are compared to determine the relevance for human health. EFSA’s opinion on aspartame clearly describes the risk assessment approach to help facilitate understanding by risk managers, stakeholders and other interested parties and better inform risk management decisions.
16. Who regulates the use of aspartame within the EU? What is EFSA’s role?
EFSA’s role is to provide independent scientific advice to risk managers related to food and feed safety and to communicate its advice to the public at large. It is in this context that EFSA’s Scientific Committee and Scientific Panels carry out safety assessments and review new evidence.
The Authority neither authorises nor bans the use of substances in foods. It is the responsibility of risk managers in the European Commission, the European Parliament and the EU Member States to define and agree measures as and where required, taking into account scientific advice and other considerations.
The Authority neither authorises nor bans the use of substances in foods. It is the responsibility of risk managers in the European Commission, the European Parliament and the EU Member States to define and agree measures as and where required, taking into account scientific advice and other considerations.
Questions on EFSA’s 2013 opinion:
17. What are the main conclusions of the opinion?
Following a detailed and methodical analysis, EFSA’s scientific experts have concluded in this opinion that aspartame and its breakdown products (phenylalanine, aspartic acid and methanol) are safe for human consumption at current levels of exposure. The current ADI is considered to be safe for the general population (including infants, children and pregnant women) and consumer exposure to aspartame is below this ADI. It is not applicable to people who suffer from PKU – see Question 4.
18. Given EFSA is not proposing any change to the ADI, what is different about this scientific opinion?
This new piece of scientific work has involved the a rigorous review of all available scientific research on aspartame and its breakdown products, covering data and studies from the 1960s to the present. More recent scientific literature and data have been critically analysed and interpreted alongside the information that was first evaluated prior to aspartame’s authorisation. In addition, EFSA’s new risk assessment has benefitted from the latest scientific thinking and methodological approaches to the risk assessment of chemical substances used in foods. Also, while previous safety evaluations of aspartame derived the ADI from long-term toxicity studies in animals, the new risk assessment also uses information from studies in humans.
19. Does the scientific opinion specifically address all aspects relating to the safety of aspartame?
The opinion explores the potential safety concerns relating to toxicity, carcinogenicity and genotoxicity as well as possible reproductive and developmental effects related to aspartame, its breakdown products. Based on its comprehensive review, EFSA concludes that aspartame and its breakdown products pose no safety concern for consumers at current levels of exposure. The current Acceptable Daily Intake (ADI) is considered to be safe for the general population and consumer exposure to aspartame is below this ADI.
The Panel also confirmed that the ADI, while protective of the general population (including infants, children and pregnant women), is not applicable to people who suffer from PKU, as they require strict adherence to a diet low in phenylalanine (PKU is an inherited disorder which increases blood phenylalanine concentrations to levels toxic to the developing brain).
The Panel also confirmed that the ADI, while protective of the general population (including infants, children and pregnant women), is not applicable to people who suffer from PKU, as they require strict adherence to a diet low in phenylalanine (PKU is an inherited disorder which increases blood phenylalanine concentrations to levels toxic to the developing brain).
20. What are the Panel’s conclusions regarding specific safety concerns?
The Panel’s conclusions in relation to potential safety concerns in humans are as follows:
- Studies do not suggest an increased risk associated with aspartame consumption for pre-term delivery in pregnant women, leukaemia, brain tumours or a variety of cancers, including brain, lymphatic and haematopoietic (blood) cancers.
- The weight of evidence suggests that aspartame ingestion has no effect on behaviour or cognitive function.
- There is no evidence that consuming aspartame causes seizures.
- There is no convincing evidence that consuming aspartame causes headaches.
- The weight of evidence shows that aspartame is not associated with allergic type reactions.
- Methanol derived from aspartame is a small portion of total exposure to methanol from all sources.
- The contribution of breakdown products of aspartame (phenylalanine, methanol and aspartic acid) to the overall dietary exposure to these substances is low.
21. Do these conclusions also take into consideration EFSA’s recent scientific work on aspartame?
Yes. In 2010, publication of two studies influenced the timing of the re-evaluation of aspartame. The studies looked at possible health risks related to the consumption of artificial sweeteners including aspartame: namely an epidemiological study on the association between intakes of artificially sweetened soft drinks and increased incidence of preterm delivery (Halldorsson et al., 2010); and a carcinogenicity study in mice exposed to aspartame through feed conducted by the European Ramazzini Foundation (ERF) (Soffritti et al., 2010).
For EFSA’s 2013 risk assessment, the ANS Panel has re-examined these studies in full.
For EFSA’s 2013 risk assessment, the ANS Panel has re-examined these studies in full.
22. Is there scientific evidence that pregnant women should not consume products containing aspartame?
The ANS Panel assessed potential risks of aspartame for pregnant women by evaluating the safety of concentrations of the breakdown product phenylalanine in blood following the consumption of aspartame-containing products. Phenylalanine is known to be toxic at high intake levels, in particular to the developing foetus in women suffering from the medical condition phenylketonuria (PKU). The Panel concluded there is no safety concern for pregnant women at current levels of exposure.
Furthermore, in relation to EFSA’s previous work the Panel’s new assessment of the Halldorsson et al. (2010) publication concluded that there is no evidence available in this study to support a causal relationship between the consumption of artificially sweetened soft drinks and preterm delivery and that additional studies would be required either to confirm or reject such an association, as indicated by the authors. In an additional study conducted in Norway by Englund-Ögge et al. (2012), there was a barely discernible association of pre-term delivery with artificially sweetened soft drinks. In fact, this was not as strong as the association with sugar-sweetened soft drinks.
Furthermore, in relation to EFSA’s previous work the Panel’s new assessment of the Halldorsson et al. (2010) publication concluded that there is no evidence available in this study to support a causal relationship between the consumption of artificially sweetened soft drinks and preterm delivery and that additional studies would be required either to confirm or reject such an association, as indicated by the authors. In an additional study conducted in Norway by Englund-Ögge et al. (2012), there was a barely discernible association of pre-term delivery with artificially sweetened soft drinks. In fact, this was not as strong as the association with sugar-sweetened soft drinks.
23. What about the second study that looked at long-term carcinogenic effects?
The ANS Panel considered findings from long-term studies conducted in experimental animals related to toxicity and carcinogenicity on the developing foetus. In its review of the Soffritti et al. (2010) publication, EFSA’s scientists concluded that, on the basis of the information available in the publication, the validity of the study and its statistical approach cannot be assessed and its results cannot be interpreted. Regarding the design of the study, and in line with the global scientific consensus, EFSA advised that experimental studies carried out over animals’ lifetimes can lead to erroneous conclusions. Older animals for instance are more susceptible to illness and when a carcinogenicity study in mice is extended beyond the recommended 104 weeks, age-related pathological changes (such as spontaneous tumours) can appear which may confound the interpretation of any compound-related effects. Furthermore, EFSA noted that Swiss mice (used in this study) are known to have a high incidence of spontaneous hepatic and pulmonary tumours and that the increased incidence of these tumours reported in the study fall within the historical control range recorded in this laboratory for these tumours in these mice.
24. What happens to aspartame in the body once it is ingested?
Following ingestion, aspartame breaks down in the gut into its three constituent parts: aspartic acid, phenylalanine and methanol. Aspartame itself does not enter the bloodstream nor does it accumulate in the body.
Aspartic acid, phenylalanine and methanol are also present naturally in other foods including fruit and vegetables and, for foods containing aspartame, are processed by the body in the same way as those derived from other dietary sources. By comparison, the amounts of these components ingested from foods and drinks containing aspartame are small. For example, a serving of non-fat milk provides about six times more phenylalanine and 13 times more aspartic acid compared to an equivalent amount of a diet beverage sweetened only with aspartame.
Aspartic acid, phenylalanine and methanol are also present naturally in other foods including fruit and vegetables and, for foods containing aspartame, are processed by the body in the same way as those derived from other dietary sources. By comparison, the amounts of these components ingested from foods and drinks containing aspartame are small. For example, a serving of non-fat milk provides about six times more phenylalanine and 13 times more aspartic acid compared to an equivalent amount of a diet beverage sweetened only with aspartame.
25. Are there any safety concerns related to aspartic acid?
Aspartic acid is an amino acid found in proteins. The body may convert aspartic acid into the neurotransmitter glutamate which at very high levels can have harmful effects on the nervous system. However, EFSA’s experts did not see any evidence of neurotoxicity associated with aspartame and therefore concluded that aspartic acid derived from aspartame does not raise any safety concerns for consumers.
26. Is methanol from aspartame a safety concern?
Methanol is present in or can be released from foods such as fruit and vegetables and is also naturally produced by the body. It becomes toxic when exposure is extremely high, such as from consumption of some home-distilled alcoholic spirits. Methanol derived from aspartame is a small portion of total exposure to methanol from all sources.
Based on the available scientific evidence, EFSA’s experts concluded that dietary exposure to methanol from aspartame does not pose a safety concern. The same applies to formaldehyde, a metabolite of methanol.
Based on the available scientific evidence, EFSA’s experts concluded that dietary exposure to methanol from aspartame does not pose a safety concern. The same applies to formaldehyde, a metabolite of methanol.
27. What about the safety of phenylalanine?
Phenylalanine is an amino acid making up protein found in many foods. It can also be converted by the body into tyrosine, which is another amino acid used in protein synthesis and for the formation of some hormones and neurotransmitters. Phenylalanine is a so-called essential amino acid as it cannot be produced by the body and must be supplied through the diet.
Phenylketonuria (PKU) is a hereditary human disorder that causes high levels of phenylalanine and low levels of tyrosine in the blood. High phenylalanine concentrations in blood are toxic to the brain and can, if left untreated, affect brain development and cause mental retardation, mood disorders and behavioural problems. This is especially critical to the developing foetus in women suffering from PKU. Most PKU treatment aims to keep blood phenylalanine at acceptable levels by restriction of foods rich in protein (meat, fish, eggs, bread, dairy products, nuts and seeds), as well as foods and drinks containing aspartame.
The Panel confirmed that the ADI, while protective of the general population, is not applicable to people who suffer from PKU, as they require strict adherence to a diet low in phenylalanine. In regulating the use of aspartame in foods, EU risk managers have recognised the need to ensure that PKU sufferers are made aware of the presence of aspartame in foods so that they can avoid exposure to this substance. In the European Union, because they are a source of phenylalanine, all products containing aspartame must be labelled “Contains a source of phenylalanine”.
Phenylketonuria (PKU) is a hereditary human disorder that causes high levels of phenylalanine and low levels of tyrosine in the blood. High phenylalanine concentrations in blood are toxic to the brain and can, if left untreated, affect brain development and cause mental retardation, mood disorders and behavioural problems. This is especially critical to the developing foetus in women suffering from PKU. Most PKU treatment aims to keep blood phenylalanine at acceptable levels by restriction of foods rich in protein (meat, fish, eggs, bread, dairy products, nuts and seeds), as well as foods and drinks containing aspartame.
The Panel confirmed that the ADI, while protective of the general population, is not applicable to people who suffer from PKU, as they require strict adherence to a diet low in phenylalanine. In regulating the use of aspartame in foods, EU risk managers have recognised the need to ensure that PKU sufferers are made aware of the presence of aspartame in foods so that they can avoid exposure to this substance. In the European Union, because they are a source of phenylalanine, all products containing aspartame must be labelled “Contains a source of phenylalanine”.
28. How did EFSA use human studies in its review of the current ADI for aspartame?
In previous risk assessments of aspartame the ADI was derived directly from animal data. In reviewing the current ADI, the ANS Panel considered findings from long-term studies conducted in experimental animals related to chronic toxicity including carcinogenicity and possible adverse health effects of phenylalanine on the developing foetus. The Panel identified ‘No observable adverse effect levels’ (NOAELs) for a series of endpoints (for instance, the presence of tumours) on the basis of the animal data. However, with respect to the evaluation of reproductive and developmental toxicity, EFSA’s experts decided that it was more appropriate to utilise human data.
The Panel compared blood phenylalanine levels in humans following consumption of aspartame, with blood phenylalanine levels associated with developmental effects in children born from PKU mothers. Current clinical guidelines recommend that levels of phenylalanine in blood are maintained below 6 mg/dl. By comparison, for PKU patients, mild effects have been associated with levels of 10-13mg/dl, whilst significant detrimental effects have been associated with levels exceeding 20mg/dl of phenylalanine in the blood. In calculating a safe level of aspartame exposure (based on blood phenylalanine concentrations), the ANS Panel assumed a worst-case scenario that intake of aspartame occurs in combination with an everyday meal (containing naturally occurring sources of phenylalanine). The Panel estimated that even an hourly dose of aspartame equal to the current ADI would result in peak blood phenylalanine concentrations of 240 µM, well below the current clinical guidelines. This implies that an adult weighing 60kg would have to drink 12 (330ml) cans of a diet soft drink (containing aspartame at the maximum permitted levels of use), every hour to reach this blood phenylalanine concentration.
The Panel compared blood phenylalanine levels in humans following consumption of aspartame, with blood phenylalanine levels associated with developmental effects in children born from PKU mothers. Current clinical guidelines recommend that levels of phenylalanine in blood are maintained below 6 mg/dl. By comparison, for PKU patients, mild effects have been associated with levels of 10-13mg/dl, whilst significant detrimental effects have been associated with levels exceeding 20mg/dl of phenylalanine in the blood. In calculating a safe level of aspartame exposure (based on blood phenylalanine concentrations), the ANS Panel assumed a worst-case scenario that intake of aspartame occurs in combination with an everyday meal (containing naturally occurring sources of phenylalanine). The Panel estimated that even an hourly dose of aspartame equal to the current ADI would result in peak blood phenylalanine concentrations of 240 µM, well below the current clinical guidelines. This implies that an adult weighing 60kg would have to drink 12 (330ml) cans of a diet soft drink (containing aspartame at the maximum permitted levels of use), every hour to reach this blood phenylalanine concentration.
29. Is Di-ketopiperazine (DKP) from aspartame a safety concern?
Moisture, pH, temperature and storage time can all affect the stability of aspartame, causing it to break down into impurities including the substance 5-benzyl-3,6-dioxo-2-piperazine acetic acid (also known as ‘Di-ketopiperazine’ or DKP). Conversion of aspartame to DKP results in the loss of the sweet taste for which aspartame is used.
The EU has set an Acceptable Daily Intake for DKP of 7.5 milligrams per kilogram body weight per day (mg/kg bw/day) to protect consumers against possible harmful effects of this substance in food. Based on exposure levels for aspartame, exposure to DKP from all food and drink using the sweetener would on average be approximately 0.1 to 1.9 mg/kg bw/day for all population groups.
Given these findings, EFSA’s experts concluded that consumer safety is not at risk from exposure to DKP from aspartame in foods and drinks.
The EU has set an Acceptable Daily Intake for DKP of 7.5 milligrams per kilogram body weight per day (mg/kg bw/day) to protect consumers against possible harmful effects of this substance in food. Based on exposure levels for aspartame, exposure to DKP from all food and drink using the sweetener would on average be approximately 0.1 to 1.9 mg/kg bw/day for all population groups.
Given these findings, EFSA’s experts concluded that consumer safety is not at risk from exposure to DKP from aspartame in foods and drinks.
30. Does the opinion highlight any uncertainties?
EFSA’s opinion recognises that many of the studies considered in its risk assessment were not performed according to current standards (for example, Good Laboratory Practice (GLP) and/or Organisation for Economic Co-operation and Development (OECD) guidelines), see Question 10 above. However, EFSA’s experts decided that they could be considered on a case-by-case basis as long as the design of such studies and the reporting of the data were considered acceptable or of a sufficiently high calibre. Also, it is worth mentioning that many of the older studies on aspartame could not now be repeated because of the need for fewer or more refined animal tests that benefit animal welfare.
In addition, the opinion discusses potential uncertainties related mainly to the difficulties associated with using different sources of data, both on consumption and on the levels of aspartame in foods. In many cases, these are the result of national differences in terms of reporting methodologies and standards, or other technical difficulties experienced in adequately assessing exposure. For example, data may refer to acute (one-off) exposure when chronic (long-term) information is needed. Food and drink categories and portion sizes may also differ. Overall, most of these uncertainties are likely to have led to an overestimation of consumer exposure, however in some cases there could be an underestimation (mainly on consumption data and actual use levels of aspartame in foods). (See Table 18 of the opinion for an overview.)
In addition, the opinion discusses potential uncertainties related mainly to the difficulties associated with using different sources of data, both on consumption and on the levels of aspartame in foods. In many cases, these are the result of national differences in terms of reporting methodologies and standards, or other technical difficulties experienced in adequately assessing exposure. For example, data may refer to acute (one-off) exposure when chronic (long-term) information is needed. Food and drink categories and portion sizes may also differ. Overall, most of these uncertainties are likely to have led to an overestimation of consumer exposure, however in some cases there could be an underestimation (mainly on consumption data and actual use levels of aspartame in foods). (See Table 18 of the opinion for an overview.)