Neotame

In US and EU, the acceptable daily intake (ADI) of neotame for humans is 0.3 and 2 mg per kg of bodyweight (mg/kg bw), respectively. NOAEL for humans is 200 mg/kg bw per day within EU. ==Sweetness==

Water solutions of neotame that are equivalent in sweetness to sucrose water solutions increase logarithmically in relative sweetness as the sucrose concentration of a comparably sweet sucrose solution increases until a plateau is reached. Maximum sweetness is reached at neotame solution concentrations that are relatively as sweet as a water solution that is 15.1 percentage sucrose by weight, i.e., at 15.1 sucrose equivalence % (SE%). For comparison, acesulfame K, cyclamate and saccharin reach their maximum sweetness at 11.6 SE%, 11.3 SE% and 9 SE%, respectively. ==Chemistry==

Structure Neotame is formally a secondary amine of 3,3-dimethylbutanal and aspartame. The latter is a dipeptide of phenylalanine and aspartic acid. Neotame has 2 stereocenters and 4 stereoisomers. Sweetness is due to the (2S),(3S)-stereoisomer. Spectroscopy Neotame NMR spectroscopy identifies its structure with a peak at 0.84 ppm indicating the three methyl groups on the carbon chain bonded to the nitrogen. Neotame has similar stability as aspartame, but has greater stability especially in heated and dairy foods. Increased temperature, moisture or pH increase losses, and are the main relevant properties of a food when considering the stability of neotame. For example, about 90% of original neotame remains after 8 weeks of storage in pH 3.2 beverages. Neotame is especially stable as a dry powder at room temperature and humidity even if mixed with glucose or maltodextrin, and is relatively inert in foods with reducing sugars like fructose. Unlike aspartame, neotame doesn't form diketopiperazines via intra-molecular cyclization due to its N-alkyl substitution with 3,3-dimethylbutyl. This increases its heat stability. Over 1000 g of neotame dissolves in 1 kg of ethanol at 15 °C. At 15 °C the solubility of neotame is 10.6 g/kg in water and 43.6 g/kg in ethyl acetate. At 25 °C the solubilities are 12.6 g/kg and 77.0 g/kg, respectively. At 40 °C the solubilities are 18.0 g/kg and 238 g/kg, respectively. At 50 °C the solubilities are 25.2 g/kg and 872 g/kg, respectively. Neotame is acidic and its 0.5 wt% solution has a pH of 5.80. Manufacture Industrially neotame is made from 3,3-dimethylbutanal and aspartame via reductive amination. They are dissolved in methanol, palladium on carbon catalyst is added, air is replaced with hydrogen and the reaction is carried out in room temperature under pressure for a few hours. Catalyst is filtered out. This can be aided with diatomaceous earth. Methanol is distilled followed by addition of water. The mixture is cooled for a few hours, neotame is isolated via centrifugation, washed with water and vacuum dried. Neotame is milled to suitable size. ==Metabolism==

. CH3OH is methanol. In humans and many other animals like dogs, rats and rabbits, neotame is rapidly but incompletely absorbed. Its metabolites are not retained or concentrated in specific tissues. In humans at oral doses of about 0.25 mg per kg of bodyweight (mg/kg bw), about 34% is absorbed into blood. Pharmacokinetics of oral doses of 0.1–0.5 mg/kg bw are somewhat linear, and at such doses, maximum neotame concentration in blood plasma is reached after about 0.5 hours with a half-life of about 0.75 hours. In blood and in body in general, non-specific esterases degrade neotame to de-esterified neotame and methanol, which is the main metabolic pathway in humans. De-esterified neotame has a plasma half-life of about 2 hours, and is the main metabolite in plasma. Methanol from neotame metabolism is insignificant at regulated levels used in foods and in comparison to methanol naturally found in foods. ==Patent==

The patent covering the neotame molecule in the US, 5,480,668, ==References==