Aspartame

• N-( L- α -aspartyl ) - L- phenylalanine methyl ester
• (S, S )-N- ( α -aspartyl ) phenylalanine methyl ester
• H -Asp -Phe- OMe
• E951

Colorless, sweet-tasting crystals

Fixed

248-250 ° C

Poorly in water and most organic solvents

• > 10,000 mg · kg -1 ( LD50, mouse, oral)
• > 5000 mg · kg -1 ( LD50, mouse, rat, ip)
• 3.71 mg · kg -1 ( TDLo, wife, oral)

Template: Infobox chemical / molecular formula search available

Aspartame is a sweetener produced synthetically. It is derived from both the 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.

As a food additive it is declared as E951 that permitted daily dose is in the European Union 40 milligrams per kilogram of body weight. Aspartame is a common ingredient in many products such as soft drinks, confectionery, bakery and dairy products.

• 6.1 studies
• 6.2 Official Rating

Discovery and registration

Aspartame in 1965 GD by accident by James M. Schlatter, a chemist at the pharmaceutical company Searle & Company discovered when he worked on the synthesis of the peptide hormone gastrin.

First compatibility tests led to ambiguous results and led to a debate about a possible carcinogenicity in rats. Therefore responsible for the authorization of food additives U.S. Food and Drug Administration ( FDA) rejected an approval of aspartame from several years. In 1980, an FDA investigation committee composed of independent consultants dealt with the question of whether aspartame brain tumors could trigger. The Committee denied this, however, refused admission due to the open question of carcinogenicity in rats continues to decrease.

In 1981 the G. D. Searle & Company from the FDA approval for aspartame ( NutraSweet ). The FDA chairman Arthur Hull Hayes, who cited a Japanese study that had not yet become the committee of inquiry available, as well as statements of an expert group, the authorization granted initially for dry products. 1983 aspartame was approved for carbonated beverages in 1993 as an additive in other beverages, baked goods and sweets. Since 1996, it is subject to in the United States no longer any restriction on use.

Searle held a patent on Aspartame and marketed it under the trade name NutraSweet. 1985 Searle was acquired by Monsanto, which continued the sweetener production under the name NutraSweet Company as a separate part of the business and repelled again in 2000. The NutraSweet Company is today one of the private investment funds JW Childs Equity Partners II L.P. The patent has already expired in 1992, the worldwide aspartame market is supplied by various competitors.

In Germany, aspartame has been released in accordance with the additive approval Regulation on 13 June 1990.

Production

There are described chemical and enzymatic methods for the production of aspartame. Starting material of the chemical synthesis of (S) - aspartic acid, which is converted by the reaction with phosphorus oxychloride in a cyclic carboxylic anhydride. Reacting it with (S) -phenylalanine methyl ester then provides Aspartame:

As a by- product formed in this reaction sequence up to 20 percent of the undesired β - isomer. The cleaning is done by fractional crystallization.

Properties

Aspartame is a chiral, colorless, sweet-tasting, crystalline substance, melting 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, which is comparable with sugar energy content of 17 kJ / g Due to its relative to 200 times higher sweetening power of sugar, it is used in much lower amounts, so that aspartame sweetened food have a much lower energy content. Therefore, it is suitable for low-energy diets and the diet in diabetes mellitus. The formation of caries is not or much less heavily promoted by sugar substitutes or sweeteners.

Use

Aspartame is a common sweetener that is used in many products such as baked goods and bakery glazes, breakfast cereals, chewing gum, dry mixes for beverages, instant coffee, soft drinks, tea and milk drinks, puddings, confectionery, dairy products and ready meals. Aspartame is marketed under the trade name " Canderel ", " Equal" and " NutraSweet ".

Restriction of use by decomposition

Aspartame is not heat resistant and decomposes in the dry state at 196 ° C. Already at temperatures above 150 ° C there is a rapid disintegration of the aspartame. The degradation at 105 and 120 ° C runs in contrast, is relatively slow. In mixtures with a water content of more than 8 percent aspartame is broken down much more quickly.

In addition, aspartame into its individual components (L- aspartic acid, L- phenylalanine, and methanol) can decompose or cyclizing to a 2.5 - dioxopiperazine ( " diketopiperazine " ), which happens mainly in cooking and baking and thereby losing the sweetening power.

The stability of aspartame in solutions is considerably influenced by the three factors of time, temperature and pH. At constant temperature and pH of the sweetener content decreases slowly. The optimum stability is achieved in the weakly acidic pH range, where most drinks move anyway. In the range between pH 2.5 and 5.5 Aspartame can be considered relatively stable. The stability optimum is at pH 4.2.

Metabolism

Aspartate -phenylalanine methyl ester is cleaved by an esterase in the intestinal dipeptide Asp-Phe and methanol. Methanol is metabolized directly to carbon dioxide or formaldehyde. The dipeptide Asp -Phe disassembled by mucosaen dipeptidases in the naturally occurring proteinogenic amino acids phenylalanine and aspartic acid. Phenylalanine, or arise therefrom by phenylalanine, tyrosine is incorporated in large part into proteins. Aspartic acid is mainly converted via a transaminase in oxaloacetate and used via the TCA cycle directly in energy metabolism.

Health issues

Aspartame should not be consumed by people with congenital metabolic disease phenylketonuria. A study ( Screening Report) in 2004 calculated for Germany a frequency of illness of about 1:8000, ie average is one of 8,000 people with phenylketonuria before. Therefore, aspartame products in the EU with regard to " contains a source of phenylalanine " or be marked " phenylalanine ". Newborn babies are routinely tested for phenylketonuria. Each protein-rich food ( especially milk, including breast milk) can harm people with phenylketonuria.

Another arising during metabolizing metabolite of aspartame is methanol, which is also produced in the digestion of fresh citrus fruit, fruits and vegetables. However, a small amount of the organism can detoxify easily.

Regarding the impact on hunger and insulin release, see the article sweetener.

Studies

About other possible health hazards associated with the use of aspartame, there are several controversial studies:

• In one of Schiffman and others published in 1987 double-blind cross-over study was 40 subjects who reported that Aspartame caused repeated headaches with them, either administered 30 milligrams of aspartame per kilogram of body weight or a placebo. But while the study subjects had more headaches when they were given the placebo. The incidence rate of headache after aspartame (35%) did not differ significantly from the rate after placebo ingestion ( 45 %) ( P < 0.5). Schiffman and colleagues concluded that no relationship between headache and Aspartamaufnahme there.
• JR Johns described in 1986 a case study of a woman who got migraines after drinking aspartame - containing foods. A survey of 171 patients with migraine in 1988 showed that 8.2 percent of respondents aspartame held for a trigger their migraine. In a study by Koehler and Glaros 1988 was frequently complained of headaches during the Aspartamaufnahme than during the placebo phase; However, finished only 11 of 25 participants this study. Due to the high failure rate and the broad experimental setup an exact interpretation of the data is difficult.
• In one of Ralph G. Walton and others carried out in 1993 with 13 people double-blind study was an association between aspartame consumption and mood disorders, especially in depressed people, states. After already träten at a dose of 30 mg per kg body weight significantly more common headaches.
• A study published in 1996 by John W. Olney suggested aspartame could contribute to carcinogenesis or even act itself carcinogenic. The Scientific Committee on Food of the European Commission came to the evaluation of the scientific material in June 1997 to the conclusion that it did not demonstrate an alleged increase in brain tumor rates.
• In July 2005, published Headquartered in Bologna, Fondazione Europea di oncologia e scienze ambientali " Bernardino Ramazzini " ( European Foundation of Oncology and Environmental Research " Bernardo Ramazzini " ) the results of a study with rats, which apparently is a direct correlation between the intake of the sweetener and the disease to cancer occupy. EFSA criticized in the study missing records or objections to the previous studies and the misinterpretation of results. Breast cancer in rats would generally common. The remaining tumors were mainly attributed to chronic lung inflammation.
• In April 2006, the U.S. National Cancer Institute published a recent study with the results: " The hypothesis of leukemia or brain tumor -promoting effect of aspartame is not confirmed ."

Official Rating

• The EU limit value was set at 40 mg / kg body weight / day. Practically mean 40 mg / kg body weight for a 70 -kilogram man about 266 sweetener tablets or - for a 60 kg person - sometimes more than 36 doses (à 330 ml) of aspartame-sweetened diet soda, which would have to be taken in one day. With a diet drink containing aspartame in the permissible maximum usable dose, 12 doses were à 330 ml needed to exceed the ADI. However, the soft drinks available on the food market is below the permitted maximum levels.
• The Food and Drug Administration ( FDA) evaluated a large number of toxicological and clinical studies on aspartame and declared 1981 the use of safe, provided a daily dose of 50 mg / kg body weight is not exceeded. In April 2007, she presented on the basis of scienze by Fondazione Europea di oncologia e ambientali " Bernardino Ramazzini " provided experimental data found that the results of this study can not be confirmed. It has been criticized that not all data had been made ​​available. The FDA saw no reason to question the safety of aspartame in question.
• The European Food Safety Authority (EFSA ) since 2002 speaks of a safety of aspartame and concluded that " there is currently no scientific basis to reconsider previous safety assessments of aspartame ". Through the European Commission's decision, the EFSA but the artificial sweetener aspartame had to check new to 2012 (951 E), since 2010, two studies were published that a connection between Aspartame and prematurity ( Halldorsson et al, 2010) and cancer ( Soffritti et al, 2010) aufzeigten. This was part of a complete re-evaluation, the draft was published in January 2013 and was commented on by 15 February 2013. The comments were discussed at a public event on April 9, 2013, the participants and the presentations were published. The final re-evaluation was published on December 10, 2013, in which the allowed EU - daily dose of 40 milligrams of aspartame per kilogram of body weight is explained as harmless.
• The Federal Institute for Risk Assessment could not confirm a link between the lower metabolism of aspartame resulting materials aspartic acid, phenylalanine and methanol with unwanted effects such as headaches, allergies, neuroendocrine changes, epilepsy or brain tumors in 2003.

Related substances

Superaspartame is a derivative of aspartame, which is about 14,000 times sweeter than sucrose. Superaspartame at the free amino group is substituted by a (p- cyanophenyl ) carbamoyl. Superaspartame was discovered in 1982 by chemists from the University Claude Bernard Lyon in finding sweeteners aspartame basis. By replacing the oxygen atom in the urea moiety through a sulfur atom they received in 1985, the thio- superaspartame with a 50,000 -fold sweetening power. They also synthesized in 1991 neotame, another sweetener aspartame basis. Another related sweetener is alitame, which is much more heat stable than those of the dipeptide as Aspartamtyp dipeptide amide.

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

Alitame, L -aspartyl- D- alanyltetramethylthiethanylamid