TABLE 1.

Structure, ADI, and biological effects of natural and synthetic sweeteners¹

Sweetener	ADI, mg · kg−1 · d−1	Structure	Biological effects
Acesulfame K (E-950)	15	C4H4KNO4S	Acesulfame K undergoes metabolization by the human body, which the majority of studies describe as innocuous. No effects on body weight or glucose tolerance.
Aspartame (E-951)	40	C14H18N2O5	Aspartame, a combination of amino acids, namely l-phenylalanine and l-aspartic acid, and connected through methyl ester bonds, is rapidly absorbed. This compound is safe and without toxicity in gene mutations.
Neotame (E-961)	2	C20H30N2O5	Neotame is a sweetener with a very similar structure to aspartame. It is safe for patients with phenylketonuria, but also safe for diabetics. With regard to its metabolization, half of the ingested neotame is not absorbed and excreted through the feces, whereas the other half is excreted in the urine as de-esterified neotame.
Advantame (E-969)	5	C24H30N2O7	Advantame is obtained through chemical synthesis from aspartame and isovanillin and is a source of phenylalanine. This compound is nontoxic or carcinogenic and there are no risks of its consumption as a food additive.
Cyclamate (E-952)	11	C6H12NNaO3S	Cyclamate is prepared by the sulfonation of cyclohexylamine (toxic compound). The EU has approved its use in food, although the FDA removed its GRAS status in 1969 and completely banned it in 1970. No effects on body weight or glucose tolerance.
Saccharin (E-954)	5	C7H5NO3S	Saccharin is excreted through urine and is not metabolized in the body, although it can cross the placenta and can be transferred through breast milk. Its consumption is not recommended for pregnant or breastfeeding women.
Sucralose (E-955)	5	C12H22O11	Sucralose is obtained by substitution of the 3-hydroxyl groups in sucrose. Approximately 11–27% of ingested sucralose is absorbed from the gut and is excreted in the kidneys. Sucralose is safe.
Steviol glucosides (E-960)	4	Variable	Steviol glycosides are molecules extracted from the leaves of Stevia rebaudiana Bertoni. Colonic bacteria converts them into steviol glucoronides to finally be excreted through urine. The consumption of these molecules is safe.
Glycyrrhizin	NA	C42H62O16	Glycyrrhizin is a triterpenoid saponin that is obtained from the roots and rhizome of Glycyrrhiza glabra. In the EU, its consumption is considered safe with a limit of 100 mg/d, given the glucocorticoid effects in the glycyrrhetinic acid present in the extract.
Neohesperidine dihydrochalcone (E-959)	4	C28H36O15	Neohesperidin dihydrochalcone is a seminatural sweetener that comes from the skin of the immature fruits of Citrus aurantium L. Approved in the EU since 1994 but not in the United States.
Thaumatin (E-957)	50	—	Thaumatin is a mixture of compounds extracted from the Thaumatococcus danielli Bennett plant. As a sweetener, it is approved both in the EU and the United States, where it is considered GRAS.

¹ADI, Acceptable Daily Intake; EU, European Union; GRAS, Generally Recognized As Safe; NA, not available.