Neotame – guide to artificial sweeteners

Neotame (E 961) is the ‘perfect’ sweetener. At least it was meant to be when the search for a better version of aspartame began thirty years ago. The result is an artificial sweetener with extreme sweetness, sugary taste and no off-flavours. It has no known health problems. And it is more stable than aspartame. Maybe it’s perfect. Or? In this article, you will learn more about this update of a proven sweetener.

1 December 2020 •

The pre­vi­ous arti­cle in our guide to arti­fi­cial sweet­en­ers focused the spot­light on a sweet­en­er that is a bet­ter ver­sion of aspar­tame. There is anoth­er arti­fi­cial sweet­en­er that claims the same thing: Neotame. In this arti­cle, we put our teeth into this sweetie.

The hunt for a new sweet

The com­pa­ny that acci­den­tal­ly dis­cov­ered aspar­tame in the mid-1960s decid­ed 25 years lat­er to find the ‘per­fect’ sweet­en­er. This time, noth­ing was left to chance. The US com­pa­ny devot­ed sev­en years of inten­sive research to the task, plough­ing down $ 80 mil­lion, and test­ing 2,500 can­di­dates, before one day find­ing its winner:

(S)-3-((3,3-Dimethylbutyl)amino)-4-(((S)-1-methoxy-1-oxo-3-phenylpropan-2-yl)amino)-4-oxobutanoic acid

Maybe not the ‘per­fect’ name for some­thing you want con­sumers to put in their mouth. So the sweet sub­stance also got a sweet­er name: Neotame.

formeln för neotam

Benefits of neotame

Neotame is sweet. 7,000 to 13,000 times sweet­er than sugar.

It has no unwant­ed off-taste or after­taste that many oth­er sweet­en­ers is bur­den with.

Neotame does not con­tribute ener­gy (0 kcal), does not affect blood sug­ar lev­els (gly­caemic index GI is 0) and does not cause caries.

Compared to aspar­tame, it is cheap­er and has sev­er­al food tech­nol­o­gy advan­tages, which we will return to.

How about the health impact? We will return to that too.

But let’s start from the beginning.

NutraSweet’s investment

In the ear­ly 1990s, the com­pa­ny NutraSweet launched a com­pre­hen­sive invest­ment in find­ing opti­mal sweet­en­er. It was a com­pe­ti­tion between two research groups. One was based in Illinois, USA, and was led by NutraSweet’s President, Robert Shapiro. The oth­er was based in France and was led by the chemists Claude Nofre and Jean-Marie Tinti.

After sev­en years, the American group had found 500 new arti­fi­cial sweet­en­ers. At the same time, the group in France had found 2,000 new sweet­en­ers, one of which was neotame.

The entire devel­op­ment project cost NutraSweet $ 80 mil­lion. No won­der if they saw stevia’s inroads to the sweet­en­ing mar­ket as a threat.

Manufacturing of neotame

Simplified, neo­tame can be described as a com­po­si­tion of aspar­tame and 3,3-dimethylbutyraldehyde.

Aspartame is, as you know, a sweet­en­er pro­duced by allow­ing the bac­te­rias Brevibacterium flavum and Corynebacterium glu­tam­icum to form amino acids in a fer­men­ta­tion process. These amino acids are then syn­the­sised into aspartame.

3,3-dimethylbutyraldehyde is a clear, light yel­low liq­uid that is high­ly flam­ma­ble and irri­tates the eyes, res­pi­ra­to­ry sys­tem and skin. If there is any con­so­la­tion, it is man­u­fac­tured from 3,3-dimethyl-1-butanol, which is found nat­u­ral­ly in bal­sam­ic vine­gar and some cold-pressed oils. On the oth­er hand, the oth­er sub­stances used in the man­u­fac­tur­ing process are not as natural:

  • Oxalyl chlo­ride which decom­pos­es into hydrochlo­ric acid and oxal­ic acid in con­tact with air.
  • Dimethyl sul­fox­ide is a by-prod­uct of pulp production.
  • Triethylamine pro­duced by alky­la­tion of gasi­fied ammo­nia with ethanol.

Anyway: With aspar­tame and 3,3-dimethylbutyraldehyde in place, neo­tame can be pre­pared in a sin­gle step. Equal parts (in molar mass) of aspar­tame and 3,3-dimethylbutyraldehyde are dis­solved in methanol, after which hydro­gen gas is added under pres­sure in the pres­ence of metal.

The met­al, which is often plat­inum or pal­la­di­um, acts as a land­ing site where an aspar­tame mol­e­cule and a 3,3-dimethylbutyraldehyde mol­e­cule can set­tle before join­ing and becom­ing neo­tame. The method is called reduc­tive alky­la­tion.

Methanol is just a sol­vent. Most of it is removed by dis­til­la­tion, and what remains are sep­a­rat­ed from the crys­tals by cen­trifu­ga­tion. The neo­tame crys­tals are dried and final­ly ground to a powder.


In the body, neo­tame is bro­ken down rapid­ly and completely.

The resid­ual prod­ucts are de-ester­i­fied neo­tame (92 per cent) and methanol (8 per cent).

80 per cent have left the body the nat­ur­al way with­in two days. The rest will fol­low. 64 per cent via fae­ces. The rest via urine. Nothing accu­mu­lates in the body.

Is neotame safe?

Given that neo­tame is pro­duced by aspar­tame, which has a bad rep­u­ta­tion, and that the man­u­fac­tur­ing process involves many chem­i­cals, you might won­der if it is safe to eat.

Since neo­tame is mod­i­fied aspar­tame, it’s rea­son­able to believe that neo­tame, like aspar­tame, is a source of pheny­lala­nine. Phenylalanine is harm­ful to peo­ple with the dis­ease phenylke­tonuria (PKU). This is why food and bev­er­ages with a pheny­lala­nine source must car­ry a warn­ing text. However, the 3,3-dimethylbutyraldehyde group pre­vents the release of pheny­lala­nine in more than neg­li­gi­ble amounts.

But the amounts of methanol pro­duced when neo­tame is bro­ken down in the body are not insignif­i­cant. Fortunately, because neo­tame is used in such small amounts, due to its sweet­ness, the con­tri­bu­tion becomes neg­li­gi­ble com­pared to the quan­ti­ties of methanol that are nat­u­ral­ly present in oth­er food.

So is neo­tame safe? Yes.

Accepted Daily Intake (ADI)

Neotame was approved for use in food and drink as ear­ly as 2002 in the United States. But it was not until 2010 that the European Food Safety Authority (EFSA) was con­vinced and grant­ed neo­tame with the E-num­ber 961.

As always, EFSA’s approval comes with strict rules on use and quan­ti­ties. These are based on an accept­able dai­ly intake (ADI) of 2 mil­ligrams per kilo­gram of body weight. It sounds lit­tle, but it is prac­ti­cal­ly impos­si­ble to get close to because neo­tame is so sweet that only small amounts can be used.

Neotame adds flavour to life

Neotame is a white pow­der that is 7,000 to 13,000 times sweet­er than reg­u­lar sug­ar, and 30 to 70 times sweet­er than aspartame.

It has a sweet­ness that comes with a lit­tle delay but stays the longer. It is per­ceived as clear and sug­ar-like, with­out off-taste or unwant­ed aftertaste.

Neotame can even reduce the bit­ter­ness of oth­er ingre­di­ents – such as caf­feine and soy.

In addi­tion, neo­tame can enhance the flavours of ingre­di­ents such as mint, vanillin, cocoa and yoghurt.

Sweet plus sweet becomes more than extra sweet

In an exper­i­ment, neo­tame was blend­ed with sac­cha­rin. The blend gave a sweet­ness that was as much as 14 to 24 times greater than what can be pre­dict­ed from the indi­vid­ual sweet­en­ers’ own sweet­ness. Sweet plus neo­tame sim­ply becomes more than extra sweet.

Neotame can also be used in this way with oth­er sweet­en­ers, for exam­ple, aspar­tame, ace­sul­fame K and sucralose.

Godis i olika färger i vita skålar

Neotame compared to aspartame

Neotame can be thought of as aspar­tame minus the dis­ad­van­tages plus many new ben­e­fits. Therefore, it is nat­ur­al to com­pare the two. How does neo­tame com­pare to aspar­tame? Very well, it turns out.

In addi­tion to the high sweet­ness, sug­ar-like taste and lack of known health dis­ad­van­tages, neo­tame has sev­er­al food tech­nol­o­gy advan­tages over aspartame.

Neotame is more sta­ble than aspar­tame; it with­stands heat, mois­ture and acidic envi­ron­ments bet­ter than aspar­tame. An exam­ple: After eight weeks, 90 per cent of neo­tame remains in bev­er­ages with a pH of 3.2. As a dry pow­der, neo­tame excels, even in mix­tures with oth­er ingre­di­ents such as glu­cose and maltodextrin.

Neotame dis­solves sim­i­lar to aspar­tame, but at a much faster pace.

Benefits of neotame

Let’s sum­marise the ben­e­fits of neotame:

  • It is 7,000 to 13,000 times sweet­er than reg­u­lar sugar
  • It adds no ener­gy (0 kcal)
  • It has no effect on blood sug­ar lev­el (GI = 0)
  • It does not cause caries
  • It’s cheap. The cost of neo­tame is 1 per cent of the cost of the amount of sug­ar required to pro­vide the same sweetness.
  • The taste is pure and sug­ar-like, with­out off-taste or unwant­ed aftertaste.
  • It can han­dle heat, mois­ture and acid bet­ter than aspartame.
  • It dis­solves quick­ly in liquid.

Disadvantages of neotame

However, neo­tame is not entire­ly with­out disadvantages:

  • Its extreme sweet­ness makes it dif­fi­cult to dose correctly.
  • Its aspar­tame her­itage gives neg­a­tive associations.
  • Its sweet­ness is delayed com­pared to sugar.
  • Its sweet­ness lingers longer than sugar.

Alternatives of natural origin to neotame

Neotame is in many respects a bet­ter sweet­en­er than aspar­tame, from which it is derived and intend­ed to replace. But the asso­ci­a­tion with aspar­tame is also its Achilles heel.

More and more con­sumers are pay­ing more and more atten­tion to the con­tent of food and drink they con­sume. Then the rela­tion­ship with aspar­tame is a bur­den, as are the chem­i­cal process­es used to make the arti­fi­cial sweetener.

For food pro­duc­ers who pro­tect their brand, it may be bet­ter to choose a sweet­en­er of nat­ur­al ori­gin. In prac­tice, it means ste­vi­ol gly­co­sides that are extract­ed from the ste­via plant in a way that is rem­i­nis­cent of how reg­u­lar sug­ar is extract­ed from sug­ar beets.

When ste­vi­ol gly­co­side was approved in the EU, the year after neo­tame, the notice­able bit­ter off-taste and liquorice-like after­taste of the first ste­via extracts was putting off some buy­ers. Since then, plant breed­ing and improved extrac­tion tech­nol­o­gy have giv­en us ste­via extracts with very lit­tle off-taste, or no at all. In par­tic­u­lar, Reb M has a pure and sug­ar-like taste as neotame.

Contact us if you want a sam­ple of Reb M or want to dis­cuss how we can help you reduce sug­ar in your food.

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