The truth about Artificial Sweetener Aspartame

 Aspartame

Aspartame is an intense low calorie sweetener used to replace sugar in foods and beverages in more than 100 countries. It is 200 times sweeter than sugar and generally labelled on foods as ‘E951’ (International Food Information Council Foundation, 2003). Aspartame is marketed as a table top sweetener, specifically branded aSweet. It is also part of numerous foods on the market throughout the world, including soft drinks, desserts, and sweets. Aspartame is placed in foods as a sweetener which contains no calories therefore a replacement sugar which is believed to promote weight loss.

Composition and break down metabolites.

Aspartame is made up of two amino acids, phenylalanine and aspartic acid. Aspartame can be metabolised in several ways, it can be hydrolysed in the intestinal lumen to form Aspartame, phenylalanine and methanol, these are then absorbed into the intestinal lumen and reach circulation in a way that amino acids do. Alternatively Aspartame can be absorbed into mucosal cells, and then hydrolysed to aspartate, phenylalanine and methanol.

(Stegink et al in Tschenz et al, 1996).

(i) Aspartic Acid:

Aspartic acid is a naturally occurring amino acid; Aspartame contains approximately 40% aspartic acid. Before the approval of Aspartame it was believed that when Aspartame was consumed with foods which contain monosodium glutamate (MSG), it might cause an increase in plasma levels of Aspartame and glutamate this could potentially cause focal brain damage (Stengink, 1987 cited in Leon, 1996). However studies performed on neonatal mice reported hypothalamic neuronal necrosis when plasma concentration exceeded 1110 mmol/L. In humans, Stengink failed to find increases plasma aspartic acid until Aspartame dosage reached 100 mg/kg body weight. Which is the equivalent of consuming 12 Litre of an Aspartame sweetened beverage by a 60 kg person (Stengink, 1987 cited in Leon, 1996).

(ii) Phenylalanine:

Phenylalanine is an essential dietary amino acid found in the brain. Phenylaline counts for approxamitely 50% of Aspartame. Persons with the genetic disorder called Phenylketonuria (PKU) cannot metabolise the amino acid phenylalanine. This leads to dangerously high levels of phenylalanine in the brain (Leon, 1996). Some scientists have made claims that Aspartame causes a dramatic increase in phenylalanine after ingestion, however no research backs up this theory, also numerous other studies have proven that phenylalanine does in fact not increase plasma phenylalanine significantly enough to effect health. One such test administered doses of Aspartame at approximately 30 mg/kg/day which did not increase plasma phenylalanine con/c above those observed after eating a protein meal (Stegink & Filer  (1989) cited in Butchko et al, 2001). Although the research proves that phenylalanine ingestion does not significantly raise Plasma levels, one account of a case study performed by John Cook disputes this research. In the study he consumed 6-8 diet drinks every day, gradually he began to show signs of memory loss, headaches, and extreme mood swings, also blood test showed phenylalanine level of 80 mg/L (Woodrow, Gold, 1995). Considering toxic levels of Phenylalanine are approxamiatly 1200milli[a1]  mole/L (Leon, 1996) After he stopped consuming Aspartame his conditions improved. This evidence is however not scientific proof and there is no data on the condition of the study for example other foods consumed, health status of the participant or the type of Aspartame food consumed.

(iii) Methanol:

Aspartame is made of about 10% methanol. Methanol is metabolised to formaldehyde and then to formic acid (Butchko et al, 2001). Formaldehyde is a toxin which is known to cause cancer, retinal damage, birth defects, and interferes with DNA replication (Barua, 1995). The FDA and NutraSweet say a serving of tomato juices contain up to six times more menthanol than the amount in an Aspartame sweetened beverage (International Food Information Council, 2003). Conversely some sources claim that menthanol is a cumulative toxin in the body. The absorption of methanol into the body is increased when free methanol is ingested. Free methanol is created from Aspartame when it is heated to above 86 degrees Fahrenheit. Free menthanol does not contain ethanol which is the antidote which prevents menthanol toxicity. Ethanol is present in all fruits which enables them to be consumed without causing harm (Diener, 2008). In a study conducted by Trocho, et al (1998) it was found that Aspartame may be hazardous because Formaldehyde accumulates in protein tissue and nucleic acid (Trocho et al, 1998 cited in Butchko et al, 2001). Formaldeyhde is considered a deadly neurotoxin. An EPA assessment of methanol considers the substance to be a cumulative poison due to its low rate of excretion (Gold, 1995). Yet other studies have found the amount of Methanol required to produce sufficient formic acid which would result in toxicity is 200 to 500 mg/kg body weight. Which is the same as a 60 kg person consuming the equivalent of 240 -600 Litres of an Aspartame sweetened beverage (Leon, 1996). These theories and studies highlight conflicting conclusion, which leave a level of ambiguity and concern about this substance safety.

  Discovery of Aspartame

 The sweet tasting chemical was first discovered in 1965, when James Schlatter, a chemist of G.D Searle company was testing an anti ulcer drug (0’brien & Gelardi, 1985 cited in Casely & Dixon 2001).  Aspartame was first approved as a sweetener in the United States by the FDA for use as a table top sweetener in 1981 and then in 1983 it was approved for use in carbonated drinks. In 1982 the UK also approved the sweetener for use in foods. Since then Aspartame has been used in numerous soft drinks and other low calorie and sugar free foods (Abbott laboratories, 1991).

  Consumption

According to The European Commissioners Report on Aspartame conducted by the Scientific Committee on Food, the consumption of Aspartame in Europe is reported as being approximately 21.3 mg/kg body weight per day for adults.  This is well below the ADI set by The International Committee of Experts of the Food and Agriculture Organisation (FAO) and The World Health Organisation (WHO) at 50mg/kg The FDA also established an ADI of 50 mg/kg body weight/day (European Commission, 2002).

Since its approval in 1983 Aspartame has become the most popular intense sweetener in the industry of low calorie products such as soft drinks and table top sweeteners. In 1981 when Saccharin was the only available intense sweetener on the market low calorie sweeteners made up only 5% of the soft drinks market. Now according to the American Calorie Control Council diet soft drinks account for 29% of America’s 200 million annual sales of soft drinks (The Food Institute, 2007). This significant increase is largely due to the introduction of Aspartame on to the market. The increasing consumption of Aspartame as the preferred intense sweetener is evident from the increasing uses of the product in low calorie foods particularly beverages. Between 1983 and 1987 the majority of diet carbonated drinks were sweetened with 50% saccharin and 50% Aspartame, each sweetener was present in approx 150mg/L. In recent years however two leading diet cola companies changed the mixture to 100% Aspartame formula. The change to using 100% Aspartame is due to its sweeter tasting quality. Other sectors of growth include desserts such as low calorie jelly, custards, low calorie hot chocolate, also sales of sugarfree chewing gum now exceed traditional sugar types (McQuillan, Heller, Corver, 1995).

  Controversy Surrounding Aspartame

To date numerous assessments and studies have been carried out on Aspartame evaluating its safety. Allegations from different sources claim that Aspartame is responsible for a large number of adverse health implications such as cancer, multiple sclerosis, epileptic seizures, headaches, and diabetes. An analysis of peer reviewed medical literature using medline was conducted in 1996 by Ralph G. Walton, MD Chairman, The Centre for Behavioural Medicine, North-Eastern Ohio University College of Medicine analyzed 164 studies on Aspartame, of those 164, 74 studies has Aspartame industry related sponsorship and 90 were funded without industry money. Of the 90 non industry related research, 83 illustrated one or more problems with Aspartame. Of the 7 studies which found no problems with Aspartame, 6 were conducted by the FDA. Given that a number of the FDA officials went to work for Aspartame after the approval including the former FDA commissioner, many would consider these research findings industry sponsored (Aspartame Toxicity Information Centre, 1996[a2] ). This research however have not been peer reviewed therefore cannot be considered as scientific. Under Freedom of Information the FDA are compelled to report all complaints they received from the public, in the report they admitted that Aspartame accounted for over 75% of complaints filed to the organisation. They claimed that over 7,000 complaints were filed since 1982 (Barua, 1995). Professor Alan Boob conducted a risk benefit analysis on the sweetener. The study began with the hypothesis that the substance is safe then used toxicity tests to reject the hypothesis. The conclusion of the data did not prove the compound was safe, but there was no data to prove it was unsafe (Renwick, 2007). This submits a level of ambiguity about the sweetener however the many substances on the market have been linked to a health ailment of some sort.   

Nevertheless Aspartame has undergone numerous scientific studies before its approval. It has also been approved for use in over 100 countries worldwide including the U.K, Germany, Canada, U.S, and Japan. It has been reviewed by numerous scientific committees around the world including, the Joint Expert Committee on Food Additives (JECFA) of the United Nation Food and Agricultural Organization, the World Health Organisation and also the Scientific Committee on Food of the European Union (International food Information Council Foundation, 2006).

 Aspartames association with cancer

The components of Aspartame have been related to a wide variety of ailments, One which has attracted a considerable amount of attention in the media and also in the scientific community is the link between Aspartame and cancer. Both sides of the argument have conducted numerous research projects however each have conflicting results and questions have been raised about the conduction of some research studies.

One study which attracted a considerable amount of attention and criticism was performed by the European Ramazzini Foundation of Oncology and Environmental Science. They investigated the relationship Aspartame has with the development of lymphomas and leukaemias in rats. In the tests they added Aspartame to a standard diet for rats. They used Aspartame at concentration of 100,000 ppm (5,000 mg/kg), 50,000 ppm (2,500 mg/kg), 10,000 ppm (500 mg/kg), 2,000 ppm (100 mg/kg), 400 ppm (20mg/kg), 80 ppm (4 mg/kg), 0 ppm. The Aspartame treated feed was given to 100-150 Sprague-dawley rats in each group at different doses. The results show that Aspartame causes a statistically significant increase in the incidence of Lymphomas and Leukaemia at concentration of 100,000 ppm (p<_ 0.01) 50,000 ppm (p<_0.01) 10,000 ppm (p<_ 0.05) 2,000 ppm (p<_ 0.01) and 400 ppm (p<_0.01). The results also illustrate that at the lowest exposure of 80ppm or 4mg/kg (considering the ADI for Aspartame is 40mg/kg) there was a 62% increase in Lymphomas and Leukaemia’s compared to controls. The study hypothesises the link with cancer maybe due to a metabolic component of Aspartame called methanol (Soffritti, et al 2006).

The FDA and other association funded by NutraSweet have spoke out against this study stating the research was an unusual design; the animals were from an inbred colony with a high incidence of respiratory and other infections, they also said the protocol did not comply with testing guidelines such as those set out by Organisation for Economic Co-Operation (OECO) (Renwick, 2007). However details of the study provide in-depth information on testing conditions the components of feed administered, temperature of the cages, living condition of the animals, how the animals were preserved after death and how the biopsies were performed. Never the less the EFSA (European Food Safety Authority) provided comprehensive evaluation of the study which reached the conclusion that the data does not prove evidence of carcinogenic potential of Aspartame and there was no reason to revise the previously established ADI for Aspartame (Renwick, 2007).

The European Ramazzini Foundation of Oncology and Environmental Science preformed another study in 2007 which researched ‘Life-Span Exposure to Low Doses of Aspartame Beginning during Prenatal Life Effect on Cancer in Rats’. This test also confirmed an association between Aspartame and cancer. They studied groups of 70–95 male and female Sprague-Dawley rats which were given Aspartame doses of 2,000 ppm, 400 ppm, 0 ppm (100, 20, 0 mg/kg body weight, respectively). Treatment began during foetal life, with administration of Aspartame in feed to female breeders from the 12th day of pregnancy. The results showed that Aspartame causes a significant, dose-related increased in incidence of Lymhomas. When compared with the untreated control group, the increased occurrence of lymphomas/leukemias in treated males and females was significant at 2,000 ppm (p ? 0.05 males and p ? 0.01 females) the incidence of lymphomas/leukemias in the control was 9.5%, and the incidence of lymphomas/leukemias in the group treated at the highest dose 17.1%. This is close to double the control (Soffritti et al, 2007).

This research conclusion would lead to the assumption that Aspartame is responsible for the development of the cancers . The FDA still deny this association, in doing so and allowing the sweetener to remain on the market without any further test ultimately undermines the law, as the Delaney Clause states that any additive which is found to cause cancer in animals or rats should be prohibited from approval (Food and Drug Administration/International Food Information Council, 1992). Thus technically the FDA are breaking the law in refusing to perform further testing.

Nevertheless the Ramazzini researchers failed/refused to provide slides of their study to regulatory agencies subjecting them to internationally recognised standardized review, such as The National Toxicology Program (NTP) which has established guidelines for pathology peer review in order to provide scientific consensus that ensure study conclusion are valid (Renwick, 2007). This leads us to wonder are they hiding critical information in order to gain media attention.

 Research performed by the sweetening company Searle has also provided invalid and incoherent results on studies testing Aspartame safety. The extent of uncertainity about their tests posed so much controversy that a report was compiled by the FDA into their research and testing methods which was called the Bressler report. This report pointed out many discrepancies concerning their studies into Aspartame. It found the design of the studies were flawed, the stability and exact diet mixture were not recorded, also no reserve samples of the  mixture were retained, they also found conflicting comparison between the Searle submission statements on their research and the independent FDA analysis. The report also found inconsistency in records of deaths of animals, how they died, and result of autopsy’s (FDA Bressler report, 1977).

               In other studies involved in researching the possible link between Aspartame and cancer results again illustrated inconsistencies. One study by Lim, et al (2006) examined the consumption of Aspartame containing beverages and the incidence of hematopoietic and brain malignancies. They examined 285,079 men and 188,905 women aged 50 to 71 years. Daily Aspartame intakes were found from a self administered food frequency questionnaire that queried four Aspartame containing beverages (Soda, fruit drinks, sweetened ice tea, and Aspartame added to coffe and tea) during the last year. Multivariable adjusted relative risks and 95% confidence intervals were estimated using Cox proportional hazards regression which adjusted for age, sex, ethnicity, body mass and history of diabetes. During the 5 years (1995-2000) 1,888 hematopoietic cancers and 315 malignant gliomas were found. Higher levels of Aspartame consumption were not associated with increased incidence of cancer (Lim et al, 2006). This type of testing however could contain many human errors, such as inaccurate estimates of consumption of Aspartame and also between 1995 and 2000 Aspartame was introduced in to numerous other diet products, confectionary foods and pharmaceutical drugs which would alter consumption patterns of Aspartame in the tested group.

Professor John Olney of Washington University St Louis and his colleagues alternatively hypothesised that Aspartame did have a link with cancer. They based their hypothesis on several sets of considerations. Firstly they looked at cancer statistics gathered by the US National Cancer Institute since 1975. They found the introduction of Aspartame into dry goods in 1981 and soft drinks in 1983 was followed by an unprecedented increase in the incidence of brain tumours by approximate 10%. This accounts for an extra 1,500 extra cases of brain cancer per year in the USA (Millstone, 1996). However major criticisms have been made from numerous scientists; one major criticism is that he only took into account the frequency of brain tumours during a selected period i.e. 1975- 1992. If all the epidemiological data were used from 1973-1992 a different conclusion is thought to be found, as the frequency of brain tumours began to increase in 1973 and stabilised in the mid 1980 (levey et al, 1996, cited in Opinion of the scientific committee on food, 2007). In addition there was never a proven quantitative or qualitative link between the exposure of the population to Aspartame and the observed frequency of brain tumours (Moden et al, 1992, by European Commissioner, 2007). For example Professor Onley has no information that those who developed brain tumours consumed Aspartame as the incidence of cancer could be related to numerous other factors such as improvements in diagnostic technology, or the increased use of other substances which are also thought to cause cancer i.e mobile phones, radiation, depletion of the ozone (Muir et al (1994) cited in Harriett et al, 2001).

               Although extensive research has been done in relation to the link between Aspartame and cancer, there is still apprehension about the sweetener. The fact of the matter is that research which has been conducted and found no correlation between Aspartame and cancer has been peer review and widely accepted within the scientific community, while research which finds a link has only been accepted by a minority of scientists, and is widely criticised by the scientific community.

 Aspartame association with neurological disorders

The link between Aspartame and neurological disorders has been given a significant amount of attention, considering the large majority of anecdotal complaints that were issued to the FDA were in relation to the neurological side effects of Aspartame. Numerous studies have draw attention to this association, one study conducted on ‘The effect of Aspartame metabolites on human erythrocyte membrane acetylcholinesterase’, in which human erythrocyte membranes were incubated with Aspartame metabolites, phenylalanine, methanol and aspartic acid. The erythrocytes were obtained from 12 people. The erythrocyte were incubated for 1 hour, the concentration of Aspartame were 34 mg/kg, 150 mg/kg, and 200 mg/kg. The results showed that Aspartame consumption caused a reduction in enzyme activity of 33% (34 mg/kg), 41% (150 mg/kg), 57% (200 mg/kg). It concluded that high levels of Aspartame showed a decrease in membrane AChE activity. The results did also state that Aspartame concentration found in beverages had no effect on AChE activity and the levels which did find negatives effects on enzyme activity were well above the ADI (Acceptable Daily Intake) of 50 mg/kg per day (Tsakiris, 2005). It believed these alteration are the cause of numerous nuerological disorders such as headaches, mood alterations, and seizures.

It is believed that the alterations in blood chemistry may be the cause of numerous complaints which have linked Aspartame with the occurrence of seizures, memory loss, headaches and hypersensitivity reactions. In 1983, when Aspartame was first brought onto the market it received approx 517 complaints by June 1984, the most predominant illnesses reported were related to headaches dizziness and mood alteration. The Centre of Disease Control (CDC) investigated the complaints in order to find a descriptive analysis of the symptoms reported and determine what illnesses were predominant. It found of the 231 which were analyzed, 13% reported that symptoms returned after consuming more than one product, and another 15% reported that symptoms reappear on second use of the same product. The conclusion of the study found that a wide variety of complaints were made. However they found no evidence that proves Aspartame causes extensive serious adverse effects to health, and that the reaction some people developed may be due to sensitivity towards the product (Centre of Disease Control, 1984).

Taking this into account the fact that Aspartame has the potential to cause alteration in the concentrations of neurotransmitters at high doses; we must consider the effect of additives like Aspartame being mixed with other additives. Researchers at the University of Liverpool in 2005 examined the effect of a mixture of additives on nerve cells; additives mixed were Aspartame and quinoline yellow. The mixture of the additives illustrated a very potent effect on nerve cells compared to the additive on their own, stating that the toxic effect on cells could be up to seven times greater when the substances were mixed. The Food Standards Agency said ‘it needs more information on the research before they can make an assessment’ and The Aspartame Information Service who represent the sweetener industry stated ‘the research did not prove meaningful information’ (Lawrence, 2005). Nevertheless, the sweetening industry never proved the research was invalid or confirmed the safety of Aspartame when mixed with other food additives. This discloses an air of uncertainty about not only Aspartame but all additives, as the safety of additives mixed together has an unidentified toxic potential. Also the licensing laws of additives only approve  additives for use one at a time, while in the modern diet people consume hundreds of additives a day, this could produce a deadly cocktail of chemicals, in which the toxic potential is unknown (Lawrence, 2005).

 Aspartames association with weight control

Aspartame is primarily promoted as an alternative to sugar sweetened drinks as its calorie free, therefore beneficial for people who want to lose weight but still need the sweet taste. Some anecdotal research have made claims that Aspartame causes an increase in appetite for sugary food and in the long term causes an increase in body weight, however these reports have been proven invalid, while numerous other research studies have proven and confirmed that Aspartame beverages have no effect on appetite. Dr. Margaret Ashwell performed a systematic review of average body weight in the past ten years. She found that the replacements of sucrose with Aspartame can reduce body weight by approx 0.2 kg/week. According to Dr. Ashwell people in England have gained an average of 3.5kg from 1993-2003 which could also be seen as an increase of 0.35kg/year, which equates to 10kg per year. (Renwick, 2007). In a long term clinical trial conducted by Kanders 59 obese, men and women were randomly placed on a balanced diet which either contained Aspartame products or not. The subject were also given behaviour modification and exercise instructions. The results showed males loss a significant amount of weight in both groups, while women lost more weight in the Aspartame supplement group approximately 16.5lb compared to 12.8 lb (Kander et al, (1988) cited in Rolls et al 1996). Few studies have shown that Aspartame increases hunger while the majority of evidence illustrates that use of Aspartame is associated with reduced energy intake. Therefore current evidence illustrates that Aspartame foods do not effect eating behaviour and have the potential to promote weight loss and weight maintance.

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 Recommendations

  • Food additives do play a major role in society and have numerous functions; however food in modern society contains hundreds of additives. This has undoubtedly had an effect of the health of society. As most additives contain little nutritional value and many questions have been raised about numerous additives which are believed to cause health problems. More emphasis should be placed on producing and consuming foods which contain fewer additives. Also parents and children should be educated on consuming nutritious foods instead of processed convenience foods which contain a large majority of additives, as the combined effect of some many additives in the diet has unknown toxic effects on the body over time.
  • Although America and Europe have strict regulating laws in relation to approval of food additives, they have failed to take into account the use of food additives when mixed with other substances. As additives are only approved for use one at a time and not mixed with other additives. Research has proven some additives such as Aspartame become increasingly more toxic when mixed with other additives. This research is very worrying considering the majority of food on the market contains many mixtures of additives. Regulation authority should consider evaluating mixed additives effect on health.
  • Allegations which were made in relation to the revolving doors of the FDA and NutraSweet, have also raised questions about the safety of the sweetener, however these allegations were never proved in a court of law. Therefore cannot be taken into account when reviewing the approval of Aspartame, although the allegations illustrate a corrupt partnership which cast doubt on the validity of research conducted by the FDA, if people choose to believe the allegations.
  • According to Dietary guidelines sugar should be consumed in moderation as it promotes obesity. Therefore the use of Aspartame is beneficial as it’s an alternative to sugar. Also considering recent research illustrated that 20% of energy is obtained from sugar in adolescents diet, while it’s recommended that only 6%-10% of energy should be consuming from sugars. In this instance Aspartame products would help reduce energy intake from sugar.
  • Although Aspartame is beneficial for reducing weight gain, the product metabolites raises suspect about the toxicity of the substance, as its by products have been proven to cause changes in neurotransmitter in the body. These changes only occur at high doses; therefore considering Aspartame is in over 600 foods on the market over consumption of the product is very possible. Regulatory agencies should look into limiting the amount of food Aspartame is approved to be used in.
  • The fact that Aspartame is still on the market after research has proven it causes lymophamias in rats is a crime. Also that the FDA dismissed the research without conducting further test to prove its safety undermines the credibility of the Regulatory Authority. The introduction of the Bressler report also raises suspicions about the conduct of research done by The Searle Company. Due to incoherence’s in results of tests the issue needs to be reassessed by independent researchers in order to finally prove its saf
  • All articles or books on the issue are against or for the sweetener which makes it difficult to identify which information is true. The issue needs to be assessed by independent researchers which can provide information to the public about the true effects of Aspartame good or bad.
  • One statements which summed up the prevailing question of Aspartames safety was stated in a European Conference when Professor Alan Boois who conducted a risk benefit analysis on Aspartame  stated ‘The Data does not prove that the compound is safe, but there is no data to support the conclusion that its unsafe’(Renwick, 2007). This statement highlights the need for further data to be produced to confirm its safety or hazard.

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