Neotame

What It Is

Neotame is a high-intensity sweetener made from aspartame: it is the aspartame molecule with a 3,3-dimethylbutyl group added. FDA puts it at about 7,000 to 13,000 times sweeter than table sugar. The range is wide because how sweet a high-intensity sweetener tastes depends on its concentration, so we do not narrow it to one number. That is roughly 40 to 60 times the potency of aspartame. In the EU it is E 961.

Two facts make it worth a page of its own. It carries no phenylketonuria (PKU) warning, although aspartame does. And regulators disagree about its acceptable daily intake more widely than for any other sweetener on this site.

Why There Is No PKU Warning

People with PKU cannot break down phenylalanine, and aspartame must carry the label warning “PHENYLKETONURICS: CONTAINS PHENYLALANINE”. Neotame still contains the same phenylalanine group, and is 44% phenylalanine by weight. Yet its regulation, 21 CFR 172.829, has no PKU warning requirement. The reason is quantitative, and FDA set out the arithmetic when it approved neotame in 2002:

• The added group stops the body’s enzymes from splitting the molecule, so only “approximately 13 to 17 percent of the total available phenylalanine in the ingested neotame is released into the plasma”. The rest leaves the body still bound in a breakdown product.
• At 7,000 to 13,000 times the sweetness of sugar, very little neotame is eaten. FDA estimated the 90th-percentile intake at 6 mg a day for a 60 kg adult and 3.4 mg a day for a 20 kg child aged 2 to 5. That gives 2.6 mg and 1.5 mg of phenylalanine a day.
• A healthy adult takes in 2.5 to 10 grams of phenylalanine a day from ordinary food, at least a thousand times more.

FDA’s conclusion for the group that matters most: “Even for the PKU homozygous child, the incremental amount of phenylalanine intake that can be expected from neotame is insignificant, i.e., equivalent to no more than 0.3 to 0.4 percent of the daily phenylalanine intake of the PKU homozygous child.” EFSA reached the same view on its own in 2025: at the ADI, phenylalanine from neotame would raise the body’s phenylalanine level by less than 1%, including in people who carry one copy of the PKU gene.

This does not mean neotame contains no phenylalanine. It means the amount is negligible at normal intakes. If you manage PKU, work from your own clinical plan and the ingredient list, not from this page.

Regulatory Status

In the US, neotame is an approved food additive, codified at 21 CFR 172.829. It went through the full petition process, like aspartame and advantame; it is not a GRAS notification. FDA approved it in 2002 as a general-purpose sweetener and flavour enhancer in foods, except in meat and poultry, after reviewing data from more than 110 animal and human studies.

In the EU, neotame is authorised as E 961, food category by food category, each with its own maximum level. EFSA re-evaluated it in an opinion published on 4 July 2025. It found “no concern for genotoxicity”, no cancer in mouse or rat studies at doses up to 1,000 mg/kg bw/day, and no population group whose intake exceeded the ADI, at the mean or the 95th percentile.

The ADI: A 33-Fold Spread

• FDA: 0.3 mg/kg of body weight per day
• JECFA (the joint FAO/WHO expert committee): 2 mg/kg bw/day
• EFSA: 10 mg/kg bw/day, since 2025

The highest figure is 33 times the lowest. For comparison, the regulators’ figures for sucralose span 3-fold and for aspartame 1.25-fold. Quoting “the ADI for neotame” without naming whose is off by more than an order of magnitude.

The difference can be traced. JECFA set its ADI of 0 to 2 mg/kg in 2003, from the no-effect level in a one-year dog study with a 100-fold safety factor (we have this derivation from secondary reports, not from JECFA’s own monograph). EFSA held the same 2 mg/kg until 2025, when it raised its ADI five-fold. The old figure rested on raised levels of a liver enzyme, alkaline phosphatase, in that dog study. EFSA concluded this “was not a marker of adverse effect in the absence of accompanying liver toxicity”, and based the new figure on long-term rat studies instead.

FDA’s 0.3 is the outlier, and we have not found how FDA derived it. FDA’s “Safe Levels of Sweeteners” chart states the figure without showing the study behind it. There is a further oddity. For neotame, FDA is about 6.7 times more cautious than JECFA. For advantame, another sweetener made from aspartame, FDA is about 6.6 times less cautious. We have found nothing that explains it.

Heat, Calories and Blood Glucose

FDA: neotame “is heat stable, meaning it stays sweet even when used at high temperatures during baking, making it suitable as a sugar substitute in baked goods.” This is the practical difference from aspartame, which loses its sweetness when heated.

Neotame is used in milligram amounts, so its calories and carbohydrate are effectively zero and it subtracts in full from net carbs. It adds no bulk, structure, browning or mouthfeel. Any tabletop product is almost entirely bulking agent by weight, commonly dextrose or maltodextrin, which are ordinary, fast-digesting carbohydrate. Count the carrier, not the neotame. Our record has no dedicated glucose, insulin or HbA1c trial for neotame, so it shows only that neotame itself adds no carbohydrate, not that it has any metabolic benefit.

Comparison Note

Against aspartame: far more potent, survives baking, and needs no PKU warning. Against advantame: the other sweetener made from aspartame, even more potent, with the FDA disagreement running the other way. Against acesulfame potassium and sucralose: all are heat-stable high-intensity sweeteners with full food-additive approval.

Regulators disagree about neotame more than about any other sweetener here, and it matters least in practice. EFSA moved its figure up, not down, and no regulator finds real intakes approaching even the most cautious limit.