Aspartame

from Wikipedia, the free encyclopedia
Structural formula
Structure of aspartame
General
Surname Aspartame
other names
  • N - ( L -α-aspartyl) - L -phenylalanine methylester
  • ( S , S ) - N - (α-Aspartyl) phenylalanine methyl ester
  • H-Asp-Phe-OMe
  • E  951
  • ASPARTAME ( INCI )
Molecular formula C 14 H 18 N 2 O 5
Brief description

colorless, sweet-tasting crystals

External identifiers / databases
CAS number 22839-47-0
EC number 245-261-3
ECHA InfoCard 100.041.132
PubChem 134601
ChemSpider 118630
DrugBank DB00168
Wikidata Q182040
properties
Molar mass 294.31 g mol −1
Physical state

firmly

Melting point

248-250 ° C

solubility

bad in water and most organic solvents

safety instructions
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Aspartame ( E 951 ) is a synthetic sweetener that is used as a food additive . The permitted daily dose in the European Union is 40 milligrams per kilogram of body weight.

Aspartame is derived from the two natural α- amino acids L - aspartic acid and L - phenylalanine , which are linked to form a dipeptide . Aspartame is the methyl ester of the dipeptide L -aspartyl- L -phenylalanine.

Discovery and admission

Aspartame was discovered by accident in 1965 by James M. Schlatter, a chemist with the pharmaceutical company GD Searle & Company, while he was working on the synthesis of the peptide hormone gastrin .

Initial compatibility studies led to ambiguous results and led to a debate about possible carcinogenicity in rats. The US Food and Drug Administration (FDA), which is responsible for the approval of food additives , therefore refused approval of aspartame for several years. In 1980, an FDA investigative committee made up of independent advisors looked at whether aspartame could cause brain tumors . The committee denied this, but continued to refuse approval due to the open question of carcinogenicity in rats.

In 1981, GD Searle & Company received FDA approval for aspartame (NutraSweet). FDA chairman Arthur Hull Hayes, citing a Japanese study that was not yet available to the investigative committee, and statements from a group of experts, initially granted approval for dry products. In 1983 aspartame was also approved for carbonated beverages, and in 1993 as an additive in other beverages, baked goods and confectionery. It has not been used in the United States since 1996.

Searle held a patent on aspartame and marketed it under the trade name NutraSweet. In 1985, Searle was taken over by Monsanto , which continued the production of sweeteners under the name NutraSweet Company as an independent part of the company and sold it again in 2000. The NutraSweet Company then belonged to the private investment fund JW Childs Equity Partners II LP for a period. The patent expired in 1992, and today the global aspartame market is supplied by various competitors.

In Germany , aspartame was released on June 13, 1990 in accordance with the Additive Admissions Ordinance .

Manufacturing

Chemical and enzymatic processes for the production of aspartame are described. The starting material for chemical synthesis is ( S ) - aspartic acid , which is converted into a cyclic carboxylic acid anhydride by reaction with phosphorus oxychloride . Its reaction with ( S ) -phenylalanine methyl ester then yields aspartame:

Chemical synthesis of aspartame

This reaction sequence produces up to 20 percent of the undesired β isomer as a by-product . The purification is carried out by fractional crystallization .

properties

Aspartame is a chiral , colorless, sweet-tasting, crystalline substance that melts at 248–250 ° C and is only slightly soluble in water and most organic solvents. The isomeric L -aspartyl- D- phenylalanine methyl ester has a bitter taste.

Aspartame has an energy content of 17 kJ / g, comparable  to that of sugar . Due to its sweetening power 200 times higher than that of sugar , it is used in much smaller quantities, so that foods sweetened with aspartame have a significantly lower energy content. It is therefore used for low-energy diets and for diabetes mellitus nutrition . The formation of caries is not promoted by sugar substitutes or sweeteners, or is promoted to a significantly lesser extent.

use

Aspartame is a common sweetener in products such as soft drinks , confectionery , baked goods , dairy products , and baking icings , cereals , chewing gum , instant coffee , puddings, and ready meals .

Aspartame is marketed under the trade names "Canderel", "Equal" and "NutraSweet".

decomposition

Cyclization of aspartame to 2,5-dioxopiperazine with elimination of methanol

Aspartame is not heat resistant and decomposes at 196 ° C. At temperatures above 150 ° C, aspartame decomposes rapidly. In contrast, the degradation at 105 and 120 ° C is relatively slow. In mixtures with a water content of more than 8 percent, aspartame is broken down much more quickly.

Aspartame can into its individual components ( L - aspartic acid , L - phenylalanine and methanol ) decompose, or a 2,5-dioxo piperazine ( " diketopiperazine ") cyclize what happens in cooking and baking, and thereby losing the sweetness.

The stability of aspartame in solutions is affected by time, temperature and pH . The optimum stability is achieved in the weakly acidic pH range in which most drinks move. In the range between pH 2.5 and 5.5, aspartame can be regarded as stable. The optimum stability is at pH 4.2.

Metabolism

The aspartate phenylalanine methyl ester is split into the dipeptide Asp-Phe and methanol by an intestinal esterase . Methanol is metabolized directly to carbon dioxide or formaldehyde . The dipeptide Asp-Phe is broken down by mucosal dipeptidases into the naturally occurring, proteinogenic amino acids phenylalanine and aspartic acid . Phenylalanine or the tyrosine produced from it by phenylalanine hydroxylase is largely incorporated into proteins . Aspartic acid is largely converted into oxaloacetate via a transaminase and used directly in the energy metabolism via the TCA cycle .

health

Aspartame should not be consumed by people with the inherited metabolic disease phenylketonuria . A study (screening report) from 2004 calculated a frequency of the disease of about 1: 8000 for Germany , which means that on average one in 8000 people has phenylketonuria. Therefore, aspartame-containing products in the EU must be labeled with the note “contains a source of phenylalanine” or “with phenylalanine”. Newborns are routinely tested for phenylketonuria. Any diet high in protein (especially milk, including breast milk) can harm people with phenylketonuria.

Another metabolite that arises when aspartame is metabolized is methanol , which is also produced when fresh citrus fruits , fruits and vegetables are digested. However, the human organism can easily detoxify a small amount. The article Sweetener deals with the effects of hunger and insulin release .

Scientific research

There is still a need for research into possible adverse effects from the use of aspartame.

Studies of the neurological or psychiatric effects

In 1993, Walton and colleagues reported for the first time, after a double-blind study with 13 test persons, that there was a connection between aspartame consumption and mental disorders , particularly in depressed people. A double-blind study with 40 test persons published in 2014 represents a conceptual replication of this: From an aspartame intake of 25 mg / kg body weight, a statistically significant deterioration in mood could be observed, which in some cases reached a clinically significant level. A review from 2013 summarizes the neuro-physiological effects of aspartame, which have been shown in numerous studies and which are now seen behind this connection. From a scientific point of view, further investigations into these aspartame effects are necessary, especially since earlier work no longer meets today's requirements due to inadequacies in their structure.

Previous research on headaches or migraines related to aspartame paints a mixed picture: In a double-blind cross-over study published by Schiffman and others in 1987 , 40 subjects who stated that aspartame consumption caused them repeated headaches were given either 30 milligrams of aspartame per kilogram Body weight or a placebo . During the study, however, more subjects had headaches when they were given the placebo. In addition, the incidence rate of headache after taking aspartame (35%) did not differ significantly from the rate after taking placebo (45%) ( P <0.5). Schiffman and colleagues concluded that there was no connection between headache and aspartame intake. In 1986 Johns described the case of a woman who developed migraines after consuming aspartame-containing foods. A survey of 171 patients with migraines in 1988 found that 8.2 percent of those surveyed believed that aspartame was a cause of their migraines. In a study by Koehler and Glaros from 1988, complaints of headaches were more common during aspartame intake than during the placebo phase; however, only 11 out of 25 participants completed this study. Interpretation of the data is difficult due to the high failure rate and the broad experimental setup.

More research is needed to assess the neurological and behavioral effects of aspartame and its breakdowns in the body.

Investigations of the mutagenic or carcinogenic effects

A study by John W. Olney published in 1996 suggested that aspartame could contribute to the development of cancer or even cause cancer itself. Thereupon the Scientific Committee for Food of the European Commission, after evaluating the scientific material in 1997, came to the conclusion that an increase in the rate of brain tumors had not been proven.

The Bologna-based Fondazione Europea di oncologia e scienze ambientali "Bernardino Ramazzini" (European Foundation for Oncology and Environmental Research "Bernardino Ramazzini") published the results of a study with rats in 2005; thereafter, there would be a direct connection between the consumption of the sweetener and certain cancers. The EFSA complained about the lack of data sets, contradictions to previous studies and the misinterpretation of the results: breast cancer is generally common in rats, the majority of the other tumors can be attributed to chronic pneumonia . The US National Cancer Institute also came to the conclusion in a publication from 2006 that the "hypothesis of leukemia - or brain tumor- promoting effects of aspartame [...] [is] not confirmed." At the end of 2010, the European Foundation for Oncology and Environmental Research published "Bernardino Ramazzini" another study, in which it is stated that a 16 mg / kg daily dose of aspartame causes a significant increase in the liver and 32 mg / kg daily dose causes a significant increase in the lung cancer rate in male mice. A study from the Middle East published in 2015, which examined the effects of aspartame and saccharine in rats, also came to the conclusion that there is a potentially higher risk of liver cancer, especially with long-term ingestion.

The American Food and Drug Administration and the European Food Safety Authority , however, come to the conclusion that there is no evidence in humans that aspartame causes an increased risk of cancer when used as a food additive.

European and international assessments

  • The permitted daily dose in the EU was set at 40 mg / kg body weight / day. In practical terms, 40 mg / kg body weight means about 266 sweetener tablets for a person weighing 70 kg or - for a person weighing 60 kg - sometimes more than 12 l (36 doses of 330 ml) of a diet lemonade sweetened with aspartame. For a diet drink that contains aspartame in the maximum permitted use, 4 l (12 cans of 330 ml) would be required to exceed the ETD value (permitted daily dose). However, the lemonades available on the food market are well below the permitted maximum values.
  • The Food and Drug Administration (FDA) evaluated a large number of toxicological and clinical studies on aspartame and declared its use safe in 1981, provided that a daily dose of 50 mg / kg body weight was not exceeded. In April 2007, on the basis of the test data made available by the Fondazione Europea di oncologia e scienze ambientali "Bernardino Ramazzini", she found that the results of this study could not be confirmed. It was criticized that not all data had been made available. The FDA saw no reason to question the safety of aspartame.
  • The European Food Safety Authority (EFSA) has been speaking about the safety of aspartame since 2002 and stated that "there is currently no scientific basis for rethinking previous safety assessments for aspartame". Due to the decision of the European Commission, however, the EFSA had to re-examine the artificial sweetener aspartame (E 951) by 2012, as two studies were published in 2010 that found a connection between aspartame consumption and premature birth (Halldorsson et al., 2010) and cancer (Soffritti et al., 2010 ) pointed out. This was done as part of a complete re-evaluation, the draft was published in January 2013 and comments could be made until February 15, 2013. The comments were discussed in a public event on April 9, 2013, the participants and the presentations were made public. The final reassessment was published on December 10, 2013, in which the permitted EU daily dose of 40 milligrams of aspartame per kilogram of body weight is declared to be harmless.
  • The Federal Institute for Risk Assessment was a link between the costs incurred by the metabolism of aspartame substances in 2003, aspartic acid , phenylalanine and methanol and headaches, allergies, neuroendocrine changes, epilepsy or brain tumors not confirm.

Related substances

Superaspartame is a derivative of aspartame that is around 14,000 times sweeter than sucrose . In superaspartame, the free amino group is substituted by a ( p- cyanophenyl) carbamoyl radical. Superaspartame was discovered in 1982 by chemists at the University of Claude Bernard Lyon while searching for aspartame-based sweeteners. By replacing the oxygen atom in the urea unit with a sulfur atom, they received thio-superaspartame in 1985 with 50,000 times the sweetening power. In 1991 they also synthesized neotame , also an aspartame-based sweetener. Another related sweetener is alitame , which, as a dipeptide amide, is considerably more heat-stable than the aspartame-type dipeptide esters.

  • Superaspartame , ( p -cyanophenyl) carbamoyl- L -aspartyl- L -phenylalanine ester

  • Neotame , N - ( N - (3,3-dimethylbutyl) - L -α-aspartyl) - L -phenylalanine 1-methyl ester

  • Alitame , L -aspartyl- D -alanyl
    tetramethyl thiethanylamide

Web links

Wiktionary: Aspartame  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. ↑ Entry on E 951: Aspartame in the European database on food additives, accessed on June 27, 2020.
  2. ↑ entry to ASPARTAME in CosIng database of the European Commission, called on August 6, 2020th
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  4. ↑ a b Data sheet aspartame from Acros, accessed March 30, 2007.
  5. ↑ a b Data sheet aspartame from Sigma-Aldrich , accessed on November 7, 2012 ( PDF ).Template: Sigma-Aldrich / name not given
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  18. ↑ Hellmut Mehnert among others: Diabetology in clinics and practices. 5th edition. Thieme, Stuttgart 2003, ISBN 3-13-512805-9 .
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  27. ↑ Screening report of the German Society for Newborn Screening ( Memento of the original from January 24, 2013 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.  @1@ 2Template: Webachiv / IABot / www.screening-dgns.de
  28. ↑ ZZulV - single standard - § 9 identification .
  29. ↑ BA Magnuson et al .: Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies . In: Critical Reviews in Toxicology . tape 37 , no. 8 , 2007, p. 629-727 , doi : 10.1080 / 10408440701516184 .
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  54. ↑ EFSA press release of January 8, 2013 , accessed on January 12, 2013.
  55. ↑ EFSA's invitation to comment ( memento of the original of 16 May 2018 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. , dated January 8, 2013, accessed January 12, 2013. @1@ 2Template: Webachiv / IABot / www.efsa.europa.eu
  56. ↑ EFSA communication of 9 April 2013 .
  57. ↑ EFSA press release of December 10, 2013 .
  58. ↑ spiegel.de: Sweetener: EU food authority declares aspartame to be harmless from December 10, 2013.
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